practice guidelines for central venous access fiscal year/fy2013clinicaltopics.pdfhickman ®,...

Practice Guidelines for Central Venous Access

A Report by the American Society of Anesthesiologists TaskForce on Central Venous Access

P RACTICE Guidelines are systematically developed rec-ommendations that assist the practitioner and patient

in making decisions about health care. These recommenda-tions may be adopted, modified, or rejected according toclinical needs and constraints, and are not intended to re-place local institutional policies. In addition, Practice Guide-lines developed by the American Society of Anesthesiologists(ASA) are not intended as standards or absolute require-ments, and their use cannot guarantee any specific outcome.Practice Guidelines are subject to revision as warranted bythe evolution of medical knowledge, technology, and prac-tice. They provide basic recommendations that are sup-ported by a synthesis and analysis of the current literature,expert and practitioner opinion, open forum commentary,and clinical feasibility data.

Methodology

A. Definition of Central Venous AccessFor these Guidelines, central venous access is defined asplacement of a catheter such that the catheter is inserted intoa venous great vessel. The venous great vessels include thesuperior vena cava, inferior vena cava, brachiocephalic veins,

internal jugular veins, subclavian veins, iliac veins, and com-mon femoral veins.* Excluded are catheters that terminate ina systemic artery.

B. Purposes of the GuidelinesThe purposes of these Guidelines are to (1) provide guid-ance regarding placement and management of central ve-nous catheters, (2) reduce infectious, mechanical, throm-botic, and other adverse outcomes associated with centralvenous catheterization, and (3) improve management ofarterial trauma or injury arising from central venous cath-eterization.

C. FocusThese Guidelines apply to patients undergoing elective cen-tral venous access procedures performed by anesthesiologistsor health care professionals under the direction/supervisionof anesthesiologists. The Guidelines do not address (1) clin-ical indications for placement of central venous catheters, (2)emergency placement of central venous catheters, (3) pa-tients with peripherally inserted central catheters, (4) place-ment and residence of a pulmonary artery catheter, (5) inser-tion of tunneled central lines (e.g., permacaths, portacaths,

Developed by the American Society of Anesthesiologists TaskForce on Central Venous Access: Stephen M. Rupp, M.D., Seattle,Washington (Chair); Jeffrey L. Apfelbaum, M.D., Chicago, Illinois;Casey Blitt, M.D., Tucson, Arizona; Robert A. Caplan, M.D., Seattle,Washington; Richard T. Connis, Ph.D., Woodinville, Washington;Karen B. Domino, M.D., M.P.H., Seattle, Washington; Lee A. Fleisher,M.D., Philadelphia, Pennsylvania; Stuart Grant, M.D., Durham, NorthCarolina; Jonathan B. Mark, M.D., Durham, North Carolina; Jeffrey P.Morray, M.D., Paradise Valley, Arizona; David G. Nickinovich, Ph.D.,Bellevue, Washington; and Avery Tung, M.D., Wilmette, Illinois.

Received from the American Society of Anesthesiologists, ParkRidge, Illinois. Submitted for publication October 20, 2011. Acceptedfor publication October 20, 2011. Supported by the American Society ofAnesthesiologists and developed under the direction of the Committeeon Standards and Practice Parameters, Jeffrey L. Apfelbaum, M.D.(Chair). Approved by the ASA House of Delegates on October 19,2011. Endorsed by the Society of Cardiovascular Anesthesiologists,October 4, 2010; the Society of Critical Care Anesthesiologists March 16,2011; the Society of Pediatric Anesthesia March 29, 2011. A completelist of references used to develop these updated Guidelines, arrangedalphabetically by author, is available as Supplemental Digital Content 1,http://links.lww.com/ALN/A783.

Address correspondence to the American Society of Anesthesi-ologists: 520 North Northwest Highway, Park Ridge, Illinois 60068-2573. These Practice Guidelines, as well as all ASA Practice Param-eters, may be obtained at no cost through the Journal Web site,www.anesthesiology.org.

* This description of the venous great vessels is consistent withthe venous subset for central lines defined by the National Health-care Safety Network (NHSN).

Copyright © 2012, the American Society of Anesthesiologists, Inc. LippincottWilliams & Wilkins. Anesthesiology 2012; 116:539–73

• What other guideline statements are available on this topic?X Several major organizations have produced practice guide-

lines on central venous access128–132

• Why was this Guideline developed?X The ASA has created this new Practice Guideline to provide

updated recommendations on some issues and new rec-ommendations on issues that have not been previously ad-dressed by other guidelines. This was based on a rigorousevaluation of recent scientific literature as well as findingsfrom surveys of expert consultants and randomly selectedASA members

• How does this statement differ from existing guidelines?X The ASA Guidelines differ in areas such as insertion site

selection (e.g., upper body site) guidance for catheter place-ment (e.g., use of real-time ultrasound) and verification ofvenous location of the catheter

• Why does this statement differ from existing guidelines?X The ASA Guidelines differ from existing guidelines because

it addresses the use of bundled techniques, use of an as-sistant during catheter placement, and management of ar-terial injury

� Supplemental digital content is available for this article. DirectURL citations appear in the printed text and are available inboth the HTML and PDF versions of this article. Links to thedigital files are provided in the HTML text of this article on theJournal’s Web site (www.anesthesiology.org).

Anesthesiology, V 116 • No 3 March 2012539

http://links.lww.com/ALN/A783

Hickman®, Quinton®, (6) methods of detection or treat-ment of infectious complications associated with central ve-nous catheterization, or (7) diagnosis and management ofcentral venous catheter-associated trauma or injury (e.g.,pneumothorax or air embolism), with the exception of ca-rotid arterial injury.

D. ApplicationThese Guidelines are intended for use by anesthesiologistsand individuals who are under the supervision of an anes-thesiologist. They also may serve as a resource for otherphysicians (e.g., surgeons, radiologists), nurses, or healthcare providers who manage patients with central venouscatheters.

E. Task Force Members and ConsultantsThe ASA appointed a Task Force of 12 members, includinganesthesiologists in both private and academic practice fromvarious geographic areas of the United States and two con-sulting methodologists from the ASA Committee on Stan-dards and Practice Parameters.

The Task Force developed the Guidelines by means of aseven-step process. First, they reached consensus on the cri-teria for evidence. Second, original published research stud-ies from peer-reviewed journals relevant to central venousaccess were reviewed and evaluated. Third, expert consul-tants were asked to (1) participate in opinion surveys on theeffectiveness of various central venous access recommenda-tions and (2) review and comment on a draft of the Guide-lines. Fourth, opinions about the Guideline recommenda-tions were solicited from a sample of active members of theASA. Opinions on selected topics related to pediatric pa-tients were solicited from a sample of active members of theSociety for Pediatric Anesthesia (SPA). Fifth, the Task Forceheld open forums at three major national meetings† to solicitinput on its draft recommendations. Sixth, the consultantswere surveyed to assess their opinions on the feasibility ofimplementing the Guidelines. Seventh, all available informa-tion was used to build consensus within the Task Force tofinalize the Guidelines. A summary of recommendationsmay be found in appendix 1.

F. Availability and Strength of EvidencePreparation of these Guidelines followed a rigorous meth-odologic process. Evidence was obtained from two principalsources: scientific evidence and opinion-based evidence.

Scientific Evidence

Study findings from published scientific literature were ag-gregated and are reported in summary form by evidence cat-egory, as described in the following paragraphs. All literature(e.g., randomized controlled trials, observational studies, casereports) relevant to each topic was considered when evaluat-ing the findings. However, for reporting purposes in thisdocument, only the highest level of evidence (i.e., level 1, 2,or 3 within category A, B, or C, as identified in the followingparagraphs) is included in the summary.

Category A: Supportive LiteratureRandomized controlled trials report statistically significant(P � 0.01) differences between clinical interventions for aspecified clinical outcome.

Level 1: The literature contains multiple randomized con-trolled trials, and aggregated findings are supportedby meta-analysis.‡

Level 2: The literature contains multiple randomized con-trolled trials, but the number of studies is insuffi-cient to conduct a viable meta-analysis for the pur-pose of these Guidelines.

Level 3: The literature contains a single randomized con-trolled trial.

Category B: Suggestive LiteratureInformation from observational studies permits inference ofbeneficial or harmful relationships among clinical interven-tions and clinical outcomes.

Level 1: The literature contains observational comparisons(e.g., cohort, case-control research designs) of clin-ical interventions or conditions and indicates statis-tically significant differences between clinical inter-ventions for a specified clinical outcome.

Level 2: The literature contains noncomparative observa-tional studies with associative (e.g., relative risk,correlation) or descriptive statistics.

Level 3: The literature contains case reports.

Category C: Equivocal LiteratureThe literature cannot determine whether there are beneficialor harmful relationships among clinical interventions andclinical outcomes.

Level 1: Meta-analysis did not find significant differences(P � 0.01) among groups or conditions.

Level 2: The number of studies is insufficient to conductmeta-analysis, and (1) randomized controlled trialshave not found significant differences amonggroups or conditions or (2) randomized controlledtrials report inconsistent findings.

Level 3: Observational studies report inconsistent findingsor do not permit inference of beneficial or harmfulrelationships.

† Society for Pediatric Anesthesia Winter Meeting, April 17, 2010,San Antonio, Texas; Society of Cardiovascular Anesthesia 32ndAnnual Meeting, April 25, 2010, New Orleans, Louisiana, and Inter-national Anesthesia Research Society Annual Meeting, May 22, 2011,Vancouver, British Columbia, Canada.

‡ All meta-analyses are conducted by the ASA methodologygroup. Meta-analyses from other sources are reviewed but notincluded as evidence in this document.

Practice Guidelines

Anesthesiology 2012; 116:539 –73 Practice Guidelines540

Category D: Insufficient Evidence from LiteratureThe lack of scientific evidence in the literature is described bythe following terms:

Inadequate: The available literature cannot be used to assessrelationships among clinical interventions andclinical outcomes. The literature either does notmeet the criteria for content as defined in the “Fo-cus” of the Guidelines or does not permit a clearinterpretationof findingsdue tomethodologic con-cerns (e.g., confounding in study design or imple-mentation).

Silent: No identified studies address the specified relation-ships among interventions and outcomes.

Opinion-based Evidence

All opinion-based evidence relevant to each topic (e.g., survey data,open-forum testimony, Internet-based comments, letters, editori-als) is considered in thedevelopmentof theseGuidelines.However,only the findings obtained from formal surveys are reported.

Opinion surveys were developed by the Task Force toaddress each clinical intervention identified in the docu-ment. Identical surveys were distributed to expert consul-tants and ASA members, and a survey addressing selectedpediatric issues was distributed to SPA members.

Category A: Expert OpinionSurvey responses from Task Force-appointed expert consultantsare reported in summary form in the text, with a completelisting of consultant survey responses reported in appendix 5.

Category B: Membership OpinionSurvey responses from active ASA and SPA members are re-ported in summary form in the text, with a complete listing ofASA and SPA member survey responses reported in appendix 5.

Survey responses are recorded using a 5-point scale andsummarized based on median values.§

Strongly Agree. Median score of 5 (at least 50% of theresponses are 5).

Agree. Median score of 4 (at least 50% of the responses are4 or 4 and 5).

Equivocal. Median score of 3 (at least 50% of the responsesare 3, or no other response category or com-bination of similar categories contain atleast 50% of the responses).

Disagree. Median score of 2 (at least 50% of responses are 2or 1 and 2).

Strongly Disagree. Median score of 1 (at least 50% of re-sponses are 1).

Category C: Informal OpinionOpen-forum testimony, Internet-based comments, letters,and editorials are all informally evaluated and discussed dur-ing the development of Guideline recommendations. Whenwarranted, the Task Force may add educational informationor cautionary notes based on this information.

Guidelines

I. Resource PreparationResource preparation includes (1) assessing the physical envi-ronment where central venous catheterization is planned to de-termine the feasibility of using aseptic techniques, (2) availabil-ity of a standardized equipment set, (3) use of an assistant forcentral venous catheterization, and (4) use of a checklist or pro-tocol for central venous catheter placement and maintenance.

The literature is insufficient to specifically evaluate theeffect of the physical environment for aseptic catheter inser-tion, availability of a standardized equipment set, or the useof an assistant on outcomes associated with central venouscatheterization (Category D evidence). An observational studyreports that the implementation of a trauma intensive careunit multidisciplinary checklist is associated with reducedcatheter-related infection rates (Category B2 evidence).1 Ob-servational studies report reduced catheter-related blood-stream infection rates when intensive care unit-wide bundledprotocols are implemented (Category B2 evidence).2–7 Thesestudies do not permit the assessment of the effect of anysingle component of a checklist or bundled protocol on out-come. The Task Force notes that the use of checklists in otherspecialties or professions has been effective in reducing theerror rate for a complex series of activities.8,9

The consultants and ASA members strongly agree that cen-tral venous catheterization should be performed in a locationthat permits the use of aseptic techniques. The consultants andASA members strongly agree that a standardized equipment setshould be available for central venous access. The consultantsand ASA members agree that a trained assistant should be usedduring the placement of a central venous catheter. The ASAmembers agree and the consultants strongly agree that a check-list or protocol should be used for the placement and mainte-nance of central venous catheters.

Recommendations for Resource Preparation. Central ve-nous catheterization should be performed in an environ-ment that permits use of aseptic techniques. A standard-ized equipment set should be available for central venousaccess.� A checklist or protocol should be used for place-ment and maintenance of central venous catheters.# Anassistant should be used during placement of a centralvenous catheter.**

§ When an equal number of categorically distinct responses areobtained, the median value is determined by calculating the arith-metic mean of the two middle values. Ties are calculated by apredetermined formula.

� Refer to appendix 2 for an example of a list of standardizedequipment for adult patients.

# Refer to appendix 3 for an example of a checklist or protocol.

** Refer to appendix 4 for an example of a list of duties per-formed by an assistant.

SPECIAL ARTICLES


II. Prevention of Infectious ComplicationsInterventions intended to prevent infectious complica-tions associated with central venous access include, but arenot limited to (1) intravenous antibiotic prophylaxis, (2)aseptic techniques (i.e., practitioner aseptic preparationand patient skin preparation), (3) selection of coated orimpregnated catheters, (4) selection of catheter insertionsite, (5) catheter fixation method, (6) insertion site dress-ings, (7) catheter maintenance procedures, and (8) aseptictechniques using an existing central venous catheter forinjection or aspiration.Intravenous Antibiotic Prophylaxis. Randomized con-trolled trials indicate that catheter-related infections andsepsis are reduced when prophylactic intravenous antibi-otics are administered to high-risk immunosuppressedcancer patients or neonates. (Category A2 evidence).10,11

The literature is insufficient to evaluate outcomes associ-ated with the routine use of intravenous antibiotics (Cat-egory D evidence).

The consultants and ASA members agree that intrave-nous antibiotic prophylaxis may be administered on acase-by-case basis for immunocompromised patients orhigh-risk neonates. The consultants and ASA membersagree that intravenous antibiotic prophylaxis should notbe administered routinely.Recommendations for Intravenous Antibiotic Prophylaxis.For immunocompromised patients and high-risk neonates,administer intravenous antibiotic prophylaxis on a case-by-case basis. Intravenous antibiotic prophylaxis should not beadministered routinely.

Aseptic Preparation and Selection of Antiseptic SolutionAseptic preparation of practitioner, staff, and patients: A ran-domized controlled trial comparing maximal barrier precau-tions (i.e., mask, cap, gloves, gown, large full-body drape)with a control group (i.e., gloves and small drape) reportedequivocal findings for reduced colonization (P � 0.03) andcatheter-related septicemia (P � 0.06) (Category C2 evi-dence).12 The literature is insufficient to evaluate the efficacyof specific aseptic activities (e.g., hand washing) or barrierprecautions (e.g., sterile full-body drapes, sterile gown,gloves, mask, cap) (Category D evidence). Observational stud-ies report hand washing, sterile full-body drapes, sterilegloves, caps, and masks as elements of care “bundles” thatresult in reduced catheter-related bloodstream infections(Category B2 evidence).2–7 However, the degree to which eachparticular element contributed to improved outcomes couldnot be determined.

Most consultants and ASA members indicated that thefollowing aseptic techniques should be used in preparationfor the placement of central venous catheters: hand washing(100% and 96%); sterile full-body drapes (87.3% and73.8%); sterile gowns (100% and 87.8%), gloves (100% and

100%), caps (100% and 94.7%), and masks covering boththe mouth and nose (100% and 98.1%).

Selection of Antiseptic SolutionChlorhexidine solutions: A randomized controlled trial com-paring chlorhexidine (2% aqueous solution without alcohol)with 10% povidone iodine (without alcohol) for skin prep-aration reports equivocal findings regarding catheter coloni-zation (P � 0.013) and catheter-related bacteremia (P �0.28) (Category C2 evidence).13 The literature is insufficientto evaluate chlorhexidine with alcohol compared with povi-done-iodine with alcohol (Category D evidence). The litera-ture is insufficient to evaluate the safety of antiseptic solu-tions containing chlorhexidine in neonates, infants andchildren (Category D evidence).

Solutions containing alcohol: Comparative studies are in-sufficient to evaluate the efficacy of chlorhexidine with alco-hol in comparison with chlorhexidine without alcohol forskin preparation during central venous catheterization (Cat-egory D evidence). A randomized controlled trial of povidone-iodine with alcohol indicates that catheter tip colonization isreduced when compared with povidone-iodine alone (Cate-gory A3 evidence); equivocal findings are reported for cathe-ter-related infection (P � 0.04) and clinical signs of infection(P � 0.09) (Category C2 evidence).14

The consultants and ASA members strongly agree thatchlorhexidine with alcohol should be used for skin prep-aration. SPA members are equivocal regarding whetherchlorhexidine-containing solutions should be used forskin preparation in neonates (younger than 44 gestationalweeks); they agree with the use of chlorhexidine in infants(younger than 2 yr) and strongly agree with its use inchildren (2–16 yr).

Recommendations for Aseptic Preparation and Selectionof Antiseptic SolutionIn preparation for the placement of central venous catheters,use aseptic techniques (e.g., hand washing) and maximal bar-rier precautions (e.g., sterile gowns, sterile gloves, caps, maskscovering both mouth and nose, and full-body patientdrapes). A chlorhexidine-containing solution should be usedfor skin preparation in adults, infants, and children; for ne-onates, the use of a chlorhexidine-containing solution forskin preparation should be based on clinical judgment andinstitutional protocol. If there is a contraindication to chlo-rhexidine, povidone-iodine or alcohol may be used. Unlesscontraindicated, skin preparation solutions should containalcohol.Catheters Containing Antimicrobial Agents. Meta-analysisof randomized controlled trials15–19 comparing antibiotic-coated with uncoated catheters indicates that antibiotic-coated catheters reduce catheter colonization (Category A1evidence). Meta-analysis of randomized controlled trials20–24

Practice Guidelines


comparing silver-impregnated catheters with uncoated cath-eters report equivocal findings for catheter-related blood-stream infection (Category C1 evidence); randomized con-trolled trials were equivocal regarding catheter colonization(P � 0.16–0.82) (Category C2 evidence).20–22,24 Meta-anal-yses of randomized controlled trials25–36 demonstrate thatcatheters coated with chlorhexidine and silver sulfadiazinereduce catheter colonization (Category A1 evidence); equivo-cal findings are reported for catheter-related bloodstream in-fection (i.e., catheter colonization and corresponding posi-tive blood culture) (Category C1 evidence).25–27,29–35,37,38

Cases of anaphylactic shock are reported after placement of acatheter coated with chlorhexidine and silver sulfadiazine(Category B3 evidence).39–41

Consultants and ASA members agree that catheters coatedwith antibiotics or a combination of chlorhexidine and silversulfadiazine may be used in selected patients based on infectiousrisk, cost, and anticipated duration of catheter use.Recommendations for Use of Catheters Containing Anti-microbial Agents. Catheters coated with antibiotics or acombination of chlorhexidine and silver sulfadiazine shouldbe used for selected patients based on infectious risk, cost,and anticipated duration of catheter use. The Task Forcenotes that catheters containing antimicrobial agents are not asubstitute for additional infection precautions.Selection of Catheter Insertion Site. A randomized con-trolled trial comparing the subclavian and femoral insertionsites report higher levels of catheter colonization with thefemoral site (Category A3 evidence); equivocal findings arereported for catheter-related sepsis (P � 0.07) (Category C2evidence).42 A randomized controlled trial comparing the in-ternal jugular insertion site with the femoral site reports nodifference in catheter colonization (P � 0.79) or catheterrelated bloodstream infections (P � 0.42) (Category C2 evi-dence).43 Prospective nonrandomized comparative studiesare equivocal (i.e., inconsistent) regarding catheter-relatedcolonization44–46 and catheter related bloodstream infec-tion46–48 when the internal jugular site is compared with thesubclavian site (Category C3 evidence). A nonrandomizedcomparative study of burn patients reports that catheter col-onization and bacteremia occur more frequently the closerthe catheter insertion site is to the burn wound (Category B1evidence).49

Most consultants indicate that the subclavian insertionsite is preferred to minimize catheter-related risk of infec-tion. Most ASA members indicate that the internal jugularinsertion site is preferred to minimize catheter-relatedrisk of infection. The consultants and ASA members agreethat femoral catheterization should be avoided when pos-sible to minimize the risk of infection. The consultantsand ASA members strongly agree that an insertion siteshould be selected that is not contaminated or potentiallycontaminated.

Recommendations for Selection of Catheter Insertion Site.Catheter insertion site selection should be based on clin-ical need. An insertion site should be selected that is notcontaminated or potentially contaminated (e.g., burned orinfected skin, inguinal area, adjacent to tracheostomy oropen surgical wound). In adults, selection of an upperbody insertion site should be considered to minimize therisk of infection.

Catheter Fixation. The literature is insufficient to evaluatewhether catheter fixation with sutures, staples or tape is as-sociated with a higher risk for catheter-related infections(Category D evidence).

Most consultants and ASA members indicate that use ofsutures is the preferred catheter fixation technique to mini-mize catheter-related infection.

Recommendations for Catheter Fixation. The use of su-tures, staples, or tape for catheter fixation should be deter-mined on a local or institutional basis.

Insertion Site Dressings. The literature is insufficient to

evaluate the efficacy of transparent bio-occlusive dressingsto reduce the risk of infection (Category D evidence). Ran-domized controlled trials are equivocal (P � 0.04 – 0.96)regarding catheter tip colonization50,51 and inconsistent(P � 0.004 – 0.96) regarding catheter-related blood-stream infection50,52 when chlorhexidine sponge dressingsare compared with standard polyurethane dressings (Cate-gory C2 evidence). A randomized controlled trial is also equiv-ocal regarding catheter tip colonization for silver-impreg-nated transparent dressings compared with standarddressings (P � 0.05) (Category C2 evidence).53 A randomizedcontrolled trial reports a greater frequency of severe localizedcontact dermatitis when neonates receive chlorhexidine-im-pregnated dressings compared with povidone-iodine im-pregnated dressings (Category A3 evidence).54

The ASA members agree and the consultants stronglyagree that transparent bio-occlusive dressings should be usedto protect the site of central venous catheter insertion frominfection. The consultants and ASA members agree thatdressings containing chlorhexidine may be used to reduce therisk of catheter-related infection. SPA members are equivocalregarding whether dressings containing chlorhexidine maybe used for skin preparation in neonates (younger than 44gestational weeks); they agree that the use of dressings con-taining chlorhexidine may be used in infants (younger than 2yr) and children (2–16 yr).

Recommendations for Insertion Site Dressings. Transpar-

ent bio-occlusive dressings should be used to protect thesite of central venous catheter insertion from infection.Unless contraindicated, dressings containing chlorhexi-dine may be used in adults, infants, and children. Forneonates, the use of transparent or sponge dressings con-taining chlorhexidine should be based on clinical judg-ment and institutional protocol.

SPECIAL ARTICLES


Catheter Maintenance. Catheter maintenance consists of (1)

determining the optimal duration of catheterization, (2) con-ducting catheter site inspections, (3) periodically changingcatheters, and (4) changing catheters using a guidewire in-stead of selecting a new insertion site.

Nonrandomized comparative studies indicate that longercatheterizations are associated with higher rates of cathetercolonization, infection, and sepsis (Category B2 evi-dence).45,55 The literature is insufficient to evaluate whetherspecified time intervals between catheter site inspections areassociated with a higher risk for catheter-related infection(Category D evidence). Randomized controlled trials reportequivocal findings (P � 0.54–0.63) regarding differences incatheter tip colonizations when catheters are changed at 3-versus 7-day intervals (Category C2 evidence).56,57 Meta-anal-ysis of randomized controlled trials58–62 report equivocalfindings for catheter tip colonization when guidewires areused to change catheters compared with the use of new in-sertion sites (Category C1 evidence).

The ASA members agree and the consultants stronglyagree that the duration of catheterization should be based onclinical need. The consultants and ASA members stronglyagree that (1) the clinical need for keeping the catheter inplace should be assessed daily; (2) catheters should bepromptly removed when deemed no longer clinically neces-sary; (3) the catheter site should be inspected daily for signs ofinfection and changed when infection is suspected; and (4)when catheter infection is suspected, replacing the catheterusing a new insertion site is preferable to changing the cath-eter over a guidewire.

Recommendations for Catheter Maintenance. The dura-

tion of catheterization should be based on clinical need. Theclinical need for keeping the catheter in place should be as-sessed daily. Catheters should be removed promptly when nolonger deemed clinically necessary. The catheter insertionsite should be inspected daily for signs of infection, and thecatheter should be changed or removed when catheter inser-tion site infection is suspected. When a catheter related in-fection is suspected, replacing the catheter using a new inser-tion site is preferable to changing the catheter over aguidewire.

Aseptic Techniques Using an Existing Central VenousCatheter for Injection or AspirationAseptic techniques using an existing central venous catheterfor injection or aspiration consist of (1) wiping the port withan appropriate antiseptic, (2) capping stopcocks or accessports, and (3) use of needleless catheter connectors or accessports.

The literature is insufficient to evaluate whether wipingports or capping stopcocks when using an existing centralvenous catheter for injection or aspiration is associated with areduced risk for catheter-related infections (Category D evi-dence). Randomized controlled trials comparing needleless

connectors with standard caps indicate decreased levels ofmicrobial contamination of stopcock entry ports withneedleless connectors (Category A2 evidence);63,64 no differ-ences in catheter-related bloodstream infection are reported(P � 0.3–0.9) (Category C2 evidence).65,66

The consultants and ASA members strongly agree thatcatheter access ports should be wiped with an appropriateantiseptic before each access. The consultants and ASA mem-bers agree that needleless ports may be used on a case-by-casebasis. The consultants and ASA members strongly agree thatcentral venous catheter stopcocks should be capped when notin use.Recommendations for Aseptic Techniques Using an Ex-isting Central Line. Catheter access ports should be wipedwith an appropriate antiseptic before each access when usingan existing central venous catheter for injection or aspiration.Central venous catheter stopcocks or access ports should becapped when not in use. Needleless catheter access ports maybe used on a case-by-case basis.

III. Prevention of Mechanical Trauma or InjuryInterventions intended to prevent mechanical trauma orinjury associated with central venous access include, butare not limited to (1) selection of catheter insertion site,(2) positioning the patient for needle insertion and cath-eter placement, (3) needle insertion and catheter place-ment, and (4) monitoring for needle, guidewire, and cath-eter placement.1. Selection of Catheter Insertion Site. A randomized con-trolled trial comparing the subclavian and femoral insertionsites reports that the femoral site had a higher frequency ofthrombotic complications in adult patients (Category A3 ev-idence).42 A randomized controlled trial comparing the in-ternal jugular insertion site with the femoral site reportsequivocal findings for arterial puncture (P � 0.35), deepvenous thrombosis (P � 0.62) or hematoma formation (P �0.47) (Category C2 evidence).43 A randomized controlled trialcomparing the internal jugular insertion site with the subcla-vian site reports equivocal findings for successful veni-puncture (P � 0.03) (Category C2 evidence).67 Nonran-domized comparative studies report equivocal findings forarterial puncture, pneumothorax, hematoma, hemotho-rax, or arrhythmia when the internal jugular insertion siteis compared with the subclavian insertion site (CategoryC3 evidence).68 –70

Most consultants and ASA members indicate that theinternal jugular insertion site is preferred to minimizecatheter cannulation-related risk of injury or trauma.Most consultants and ASA members also indicate that theinternal jugular insertion site is preferred to minimizecatheter-related risk of thromboembolic injury or trauma.

Recommendations for Catheter Insertion Site Selection.Catheter insertion site selection should be based onclinical need and practitioner judgment, experience, and

Practice Guidelines


skill. In adults, selection of an upper body insertion siteshould be considered to minimize the risk of thromboticcomplications.

2. Positioning the Patient for Needle Insertion and Cath-eter Placement. Nonrandomized studies comparing the Tren-

delenburg (i.e., head down) position with the normal supineposition indicates that the right internal jugular vein increases indiameter and cross-sectional area to a greater extent when adultpatients are placed in the Trendelenburg position (Category B2evidence).71–76 One nonrandomized study comparing the Tren-delenburg position with the normal supine position in pediatricpatients reports an increase in right internal jugular vein diam-eter only for patients older than 6 yr (Category B2 evidence).77

The consultants and ASA members strongly agree that,when clinically appropriate and feasible, central vascular ac-cess in the neck or chest should be performed with the patientin the Trendelenburg position.

Recommendations for Positioning the Patient for NeedleInsertion and Catheter PlacementWhen clinically appropriate and feasible, central venous ac-cess in the neck or chest should be performed with the patientin the Trendelenburg position.

3. Needle Insertion, Wire Placement, and Catheter Place-ment. Needle insertion, wire placement, and catheter place-

ment includes (1) selection of catheter size and type, (2) use of awire-through-thin-wall needle technique (i.e., Seldinger tech-nique) versus a catheter-over-the-needle-then-wire-through-the-catheter technique (i.e., modified Seldinger technique), (3)limiting the number of insertion attempts, and (4) introducingtwo catheters in the same central vein.

Case reports describe severe injury (e.g., hemorrhage, he-matoma, pseudoaneurysm, arteriovenous fistula, arterial dis-section, neurologic injury including stroke, and severe orlethal airway obstruction) when there is unintentional ar-terial cannulation with large bore catheters (Category B3evidence).78 – 88 The literature is insufficient to evaluatewhether the risk of injury or trauma is associated with theuse of a thin-wall needle technique versus a catheter-over-the needle technique (Category D evidence). The literatureis insufficient to evaluate whether the risk of injury ortrauma is related to the number of insertion attempts(Category D evidence). One nonrandomized comparativestudy reports a higher frequency of dysrhythmia when twocentral venous catheters are placed in the same vein (rightinternal jugular) compared with placement of one cathe-ter in the vein (Category B2 evidence); no differences incarotid artery puncture (P � 0.65) or hematoma (P �0.48) were noted (Category C3 evidence).89

The consultants agree and the ASA members stronglyagree that the selection of catheter type (i.e., gauge,length, number of lumens) and composition (e.g., poly-urethane, Teflon) should be based on the clinical situa-

tion, and the skill and experience of the operator. Theconsultants and ASA members agree that the selection of amodified Seldinger technique versus a Seldinger techniqueshould be based on the clinical situation and the skill andexperience of the operator. The consultants and ASAmembers agree that the number of insertion attemptsshould be based on clinical judgment. The ASA membersagree and the consultants strongly agree that the decisionto place two central catheters in a single vein should bemade on a case-by-case basis.Recommendations for Needle Insertion, Wire Placement,and Catheter Placement. Selection of catheter size (i.e.,outside diameter) and type should be based on the clinicalsituation and skill/experience of the operator. Selection ofthe smallest size catheter appropriate for the clinical situ-ation should be considered. Selection of a thin-wall needle(i.e., Seldinger) technique versus a catheter-over-the-nee-dle (i.e., modified Seldinger) technique should be basedon the clinical situation and the skill/experience of theoperator. The decision to use a thin-wall needle techniqueor a catheter-over-the-needle technique should be based atleast in part on the method used to confirm that the wireresides in the vein before a dilator or large-bore catheter isthreaded (fig. 1). The Task Force notes that the catheter-over-the-needle technique may provide more stable ve-nous access if manometry is used for venous confirmation.The number of insertion attempts should be based onclinical judgment. The decision to place two catheters in asingle vein should be made on a case-by-case basis.4. Guidance and Verification of Needle, Wire, and CatheterPlacement. Guidance for needle, wire, and catheter placementincludes ultrasound imaging for the purpose of prepuncturevessel localization (i.e., static ultrasound) and ultrasound forvessel localization and guiding the needle to its intended venouslocation (i.e., real time or dynamic ultrasound). Verification ofneedle, wire, or catheter location includes any one or more of thefollowing methods: (1) ultrasound, (2) manometry, (3) pressurewaveform analysis, (4) venous blood gas, (5) fluoroscopy, (6)continuous electrocardiography, (7) transesophageal echocardi-ography, and (8) chest radiography.

GuidanceStatic Ultrasound. Randomized controlled trials comparingstatic ultrasound with the anatomic landmark approach for lo-cating the internal jugular vein report a higher first insertionattempt success rate for static ultrasound (Category A3 evi-dence);90 findings are equivocal regarding overall successful can-nulation rates (P � 0.025–0.57) (Category C2 evidence).90–92 Inaddition, the literature is equivocal regarding subclavian veinaccess (P � 0.84) (Category C2 evidence) 93 and insufficient forfemoral vein access (Category D evidence).

The consultants and ASA members agree that static ultra-sound imaging should be used in elective situations for pre-puncture identification of anatomy and vessel localization

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when the internal jugular vein is selected for cannulation;they are equivocal regarding whether static ultrasound imag-ing should be used when the subclavian vein is selected. Theconsultants agree and the ASA members are equivocal re-garding the use of static ultrasound imaging when the fem-oral vein is selected.

Real-time Ultrasound. Meta-analysis of randomized con-trolled trials94–104 indicates that, compared with the ana-tomic landmark approach, real-time ultrasound guided ve-nipuncture of the internal jugular vein has a higherfirst insertion attempt success rate, reduced access time,higher overall successful cannulation rate, and decreased

Fig. 1. Algorithm for central venous insertion and verification. This algorithm compares the thin-wall needle (i.e., Seldinger)technique versus the catheter-over-the needle (i.e., Modified-Seldinger) technique in critical safety steps to prevent uninten-tional arterial placement of a dilator or largebore catheter. The variation between the two techniques reflects mitigation stepsfor the risk that the thin-wall needle in the Seldinger technique could move out of the vein and into the wall of an artery betweenthe manometry step and the threading of the wire step. ECG � electrocardiography; TEE � transesophageal echocardiography.

Practice Guidelines


rates of arterial puncture (Category A1 evidence).Randomized controlled trials report fewer number ofinsertion attempts with real-time ultrasound guidedvenipuncture of the internal jugular vein (Category A2evidence).97,99,103,104

For the subclavian vein, randomized controlled trials reportfewer insertion attempts with real-time ultrasound guided veni-puncture (Category A2 evidence),105,106 and one randomizedclinical trial indicates a higher success rate and reduced accesstime, with fewer arterial punctures and hematomas comparedwith the anatomic landmark approach (Category A3 evi-dence).106

For the femoral vein, a randomized controlled trial re-ports a higher first-attempt success rate and fewer needlepasses with real-time ultrasound guided venipuncture com-pared with the anatomic landmark approach in pediatricpatients (Category A3 evidence).107

Theconsultants agree and theASAmembers are equivocal that,when available, real time ultrasound should be used forguidance during venous access when either the internaljugular or femoral veins are selected for cannulation. Theconsultants and ASA members are equivocal regarding theuse of real time ultrasound when the subclavian vein isselected.

Verification

Confirming that the Catheter or Thin-wall Needle Residesin the Vein. A retrospective observational study reports thatmanometry can detect arterial punctures not identified by bloodflow and color (Category B2 evidence).108 The literature is insuf-ficient to address ultrasound, pressure-waveform analysis, bloodgas analysis, blood color, or the absence of pulsatile flow aseffective methods of confirming catheter or thin-wall needlevenous access (Category D evidence).

Confirming Venous Residence of the Wire. An observationalstudy indicates that ultrasound can be used to confirm venousplacement of the wire before dilation or final catheterization(Category B2 evidence).109 Case reports indicate that transesoph-ageal echocardiography was used to identify guidewire position(Category B3 evidence).110–112 The literature is insufficient toevaluate the efficacy of continuous electrocardiography in con-firming venous residence of the wire (Category D evidence), al-though narrow complex electrocardiographic ectopy is recog-nized by the Task Force as an indicator of venous location of thewire. The literature is insufficient to address fluoroscopy as aneffective method to confirm venous residence of the wire (Cat-egory D evidence); the Task Force believes that fluoroscopy maybe used.Confirming Residence of the Catheter in the Venous Sys-tem. Studies with observational findings indicate that fluo-roscopy113,115 and chest radiography115–125 are useful in

identifying the position of the catheter tip (Category B2 evi-dence). Randomized controlled trials indicate that continu-ous electrocardiography is effective in identifying propercatheter tip placement compared with not using electrocar-diography (Category A2 evidence).115,126,127

The consultants and ASA members strongly agree thatbefore insertion of a dilator or large- bore catheter over awire, venous access should be confirmed for the catheter orthin-wall needle that accesses the vein. The Task Force be-lieves that blood color or absence of pulsatile flow should notbe relied upon to confirm venous access. The consultantsagree and ASA members are equivocal that venous accessshould be confirmed for the wire that subsequently resides inthe vein after traveling through a catheter or thin-wall needlebefore insertion of a dilator or large-bore catheter over a wire.The consultants and ASA members agree that, when feasible,both the location of the catheter or thin-wall needle and wireshould be confirmed.

The consultants and ASA members agree that a chestradiograph should be performed to confirm the location ofthe catheter tip as soon after catheterization as clinically ap-propriate. They also agree that, for central venous cathetersplaced in the operating room, a confirmatory chest radio-graph may be performed in the early postoperative period.The ASA members agree and the consultants strongly agreethat, if a chest radiograph is deferred to the postoperativeperiod, pressure waveform analysis, blood gas analysis, ultra-sound, or fluoroscopy should be used to confirm venouspositioning of the catheter before use.

Recommendations for Guidance and Verification ofNeedle, Wire, and Catheter PlacementThe following steps are recommended for prevention of me-chanical trauma during needle, wire, and catheter placementin elective situations:

● Use static ultrasound imaging before prepping anddraping for prepuncture identification of anatomy todetermine vessel localization and patency when the in-ternal jugular vein is selected for cannulation. Staticultrasound may be used when the subclavian or femoralvein is selected.

● Use real time ultrasound guidance for vessel localizationand venipuncture when the internal jugular vein is selectedfor cannulation (see fig. 1). Real-time ultrasound may beused when the subclavian or femoral vein is selected. TheTask Force recognizes that this approach may not be fea-sible in emergency circumstances or in the presence ofother clinical constraints.

● After insertion of a catheter that went over the needle or athin-wall needle, confirm venous access.†† Methods forconfirming that the catheter or thin-wall needle resides inthe vein include, but are not limited to, ultrasound, ma-nometry, pressure-waveform analysis, or venous blood gasmeasurement. Blood color or absence of pulsatile flow

†† For neonates, infants, and children, confirmation of venousplacement may take place after the wire is threaded.

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should not be relied upon for confirming that the catheteror thin-wall needle resides in the vein.

● When using the thin-wall needle technique, confirmvenous residence of the wire after the wire is threaded.When using the catheter-over-the-needle technique,confirmation that the wire resides in the vein may not beneeded (1) when the catheter enters the vein easily andmanometry or pressure waveform measurement pro-vides unambiguous confirmation of venous location ofthe catheter; and (2) when the wire passes through thecatheter and enters the vein without difficulty. If there isany uncertainty that the catheter or wire resides in thevein, confirm venous residence of the wire after the wireis threaded. Insertion of a dilator or large-bore cathetermay then proceed. Methods for confirming that the wireresides in the vein include, but are not limited to, ultra-sound (identification of the wire in the vein) or trans-esophageal echocardiography (identification of the wirein the superior vena cava or right atrium), continuouselectrocardiography (identification of narrow-complexectopy), or fluoroscopy.

● After final catheterization and before use, confirm resi-dence of the catheter in the venous system as soon asclinically appropriate. Methods for confirming that thecatheter is still in the venous system after catheterizationand before use include manometry or pressure wave-form measurement.

● Confirm the final position of the catheter tip as soon asclinically appropriate. Methods for confirming the position ofthe catheter tip include chest radiography, fluoroscopy, orcontinuous electrocardiography. For central venous cathetersplaced in the operating room, perform the chest radiographno later than the early postoperative period to confirm theposition of the catheter tip.

IV. Management of Arterial Trauma or Injury Arisingfrom Central Venous CatheterizationCase reports of adult patients with arterial puncture by alarge bore catheter/vessel dilator during attempted centralvenous catheterization indicate severe complications (e.g.,cerebral infarction, arteriovenous fistula, hemothorax) af-ter immediate catheter removal; no such complicationswere reported for adult patients whose catheters were leftin place before surgical consultation and repair (CategoryB3 evidence).80,86

The consultants and ASA members agree that, when unin-tended cannulation of an arterial vessel with a large-bore cathe-ter occurs, the catheter should be left in place and a generalsurgeon or vascular surgeon should be consulted. When unin-tended cannulation of an arterial vessel with a large-bore cathe-ter occurs, the SPA members indicate that the catheter should beleft in place and a general surgeon, vascular surgeon, or inter-ventional radiologist should be immediately consulted beforedeciding on whether to remove the catheter, either surgically or

nonsurgically, as follows: 54.9% (for neonates), 43.8% (for in-fants), and 30.0% (for children). SPA members indicating thatthe catheter may be nonsurgically removed without consulta-tion is as follows: 45.1% (for neonates), 56.2% (for infants), and70.0% (for children). The Task Force agrees that the anesthesi-ologist and surgeon should confer regarding the relative risksand benefits of proceeding with elective surgery after an arterialvessel has sustained unintended injury by a dilator or large-borecatheter.

Recommendations for Management of Arterial Trauma orInjury Arising from Central Venous Access. When unin-tended cannulation of an arterial vessel with a dilator orlarge-bore catheter occurs, the dilator or catheter shouldbe left in place and a general surgeon, a vascular surgeon,or an interventional radiologist should be immediatelyconsulted regarding surgical or nonsurgical catheter re-moval for adults. For neonates, infants, and children thedecision to leave the catheter in place and obtain consul-tation or to remove the catheter nonsurgically should bebased on practitioner judgment and experience. After theinjury has been evaluated and a treatment plan has beenexecuted, the anesthesiologist and surgeon should conferregarding relative risks and benefits of proceeding with theelective surgery versus deferring surgery to allow for a pe-riod of patient observation.

Appendix 1: Summary ofRecommendations

Resource Preparation

● Central venous catheterization should be performed in an envi-ronment that permits use of aseptic techniques.

● A standardized equipment set should be available for central ve-nous access.

● A checklist or protocol should be used for placement and main-tenance of central venous catheters.

● An assistant should be used during placement of a central venouscatheter.

Prevention of Infectious Complications• For immunocompromised patients and high-risk neonates,

administer intravenous antibiotic prophylaxis on a case-by-case basis.

� Intravenous antibiotic prophylaxis should not be adminis-tered routinely.

• In preparation for the placement of central venous catheters, useaseptic techniques (e.g., hand washing) and maximal barrier pre-cautions (e.g., sterile gowns, sterile gloves, caps, masks coveringboth mouth and nose, and full-body patient drapes).

• A chlorhexidine-containing solution should be used for skinpreparation in adults, infants, and children.

� For neonates, the use of a chlorhexidine-containing solutionfor skin preparation should be based on clinical judgment andinstitutional protocol.

Practice Guidelines


� If there is a contraindication to chlorhexidine, povidone-io-dine or alcohol may be used as alternatives.

� Unless contraindicated, skin preparation solutions shouldcontain alcohol.

• If there is a contraindication to chlorhexidine, povidone-iodineor alcohol may be used. Unless contraindicated, skin preparationsolutions should contain alcohol.

• Catheters coated with antibiotics or a combination of chlo-rhexidine and silver sulfadiazine should be used for selectedpatients based on infectious risk, cost, and anticipated dura-tion of catheter use.

� Catheters containing antimicrobial agents are not a substi-tute for additional infection precautions.

• Catheter insertion site selection should be based on clinicalneed.

� An insertion site should be selected that is not contami-nated or potentially contaminated (e.g., burned or infectedskin, inguinal area, adjacent to tracheostomy or open sur-gical wound).

� In adults, selection of an upper body insertion site shouldbe considered to minimize the risk of infection.

• The use of sutures, staples, or tape for catheter fixation should bedetermined on a local or institutional basis.

• Transparent bio-occlusive dressings should be used to protectthe site of central venous catheter insertion from infection.

� Unless contraindicated, dressings containing chlorhexidinemay be used in adults, infants, and children.

� For neonates, the use of transparent or sponge dressingscontaining chlorhexidine should be based on clinical judg-ment and institutional protocol.

• The duration of catheterization should be based on clinicalneed.

� The clinical need for keeping the catheter in place should beassessed daily.

� Catheters should be removed promptly when no longerdeemed clinically necessary.

• The catheter insertion site should be inspected daily for signs ofinfection.

� The catheter should be changed or removed when catheterinsertion site infection is suspected.

• When a catheter-related infection is suspected, replacing thecatheter using a new insertion site is preferable to changing thecatheter over a guidewire.

• Catheter access ports should be wiped with an appropriate anti-septic before each access when using an existing central venouscatheter for injection or aspiration.

• Central venous catheter stopcocks or access ports should becapped when not in use.

• Needleless catheter access ports may be used on a case-by-casebasis.

Prevention of Mechanical Trauma or Injury• Catheter insertion site selection should be based on clinical need

and practitioner judgment, experience, and skill.

� In adults, selection of an upper body insertion site shouldbe considered to minimize the risk of thromboticcomplications.

• When clinically appropriate and feasible, central venous access inthe neck or chest should be performed with the patient in theTrendelenburg position.

• Selection of catheter size (i.e., outside diameter) and typeshould be based on the clinical situation and skill/experienceof the operator.

� Selection of the smallest size catheter appropriate for theclinical situation should be considered.

• Selection of a thin-wall needle (a wire-through-thin-wall-needle,or Seldinger) technique versus a catheter-over-the-needle (a cath-eter-over-the-needle-then-wire-through-the-catheter, or Modi-fied Seldinger) technique should be based on the clinical situationand the skill/experience of the operator.

� The decision to use a thin-wall needle technique or a cath-eter-over-the-needle technique should be based at least inpart on the method used to confirm that the wire resides inthe vein before a dilator or large-bore catheter isthreaded.

� The catheter-over-the-needle technique may providemore stable venous access if manometry is used for venousconfirmation.

• The number of insertion attempts should be based on clinicaljudgment.

• The decision to place two catheters in a single vein should bemade on a case-by-case basis.

• Use static ultrasound imaging in elective situations before prep-ping and draping for prepuncture identification of anatomy todetermine vessel localization and patency when the internal jug-ular vein is selected for cannulation.

� Static ultrasound may be used when the subclavian or femoralvein is selected.

• Use real-time ultrasound guidance for vessel localization andvenipuncture when the internal jugular vein is selected forcannulation.

� Real-time ultrasound may be used when the subclavian orfemoral vein is selected.

� Real-time ultrasound may not be feasible in emergencycircumstances or in the presence of other clinicalconstraints.

• After insertion of a catheter that went over the needle or athin-wall needle, confirm venous access.††

� Methods for confirming that the catheter or thin-wall nee-dle resides in the vein include, but are not limited to: ultra-sound, manometry, pressure-waveform analysis, or venousblood gas measurement.

� Blood color or absence of pulsatile flow should not be reliedupon for confirming that the catheter or thin-wall needleresides in the vein.

• When using the thin-wall needle technique, confirm venous res-idence of the wire after the wire is threaded.

• When using the catheter-over-the-needle technique, confir-mation that the wire resides in the vein may not be needed (1)when the catheter enters the vein easily and manometry orpressure waveform measurement provides unambiguous con-

SPECIAL ARTICLES


firmation of venous location of the catheter, and (2) when thewire passes through the catheter and enters the vein withoutdifficulty.

� If there is any uncertainty that the catheter or wire resides in thevein, confirm venous residence of the wire after the wire isthreaded. Insertion of a dilator or large-bore catheter may thenproceed.

� Methods for confirming that the wire resides in the veininclude, but are not limited to surface ultrasound (identifi-cation of the wire in the vein) or transesophageal echocar-diography (identification of the wire in the superior venacava or right atrium), continuous electrocardiography(identification of narrow-complex ectopy), or fluoroscopy.

• After final catheterization and before use, confirm residence ofthe catheter in the venous system as soon as clinicallyappropriate.

� Methods for confirming that the catheter is still in thevenous system after catheterization and before use includewaveform manometry or pressure measurement.

• Confirm the final position of the catheter tip as soon as clin-ically appropriate.

� Methods for confirming the position of the catheter tipinclude chest radiography, fluoroscopy, or continuouselectrocardiography.

• For central venous catheters placed in the operating room, per-form the chest radiograph no later than the early postoperativeperiod to confirm the position of the catheter tip.

Management of Arterial Trauma or Injury Arising fromCentral Venous Catheterization• When unintended cannulation of an arterial vessel with a dilator

or large-bore catheter occurs, the dilator or catheter should be leftin place and a general surgeon, a vascular surgeon, or an interven-tional radiologist should be immediately consulted regarding sur-gical or nonsurgical catheter removal for adults.

� For neonates, infants, and children, the decision to leave thecatheter in place and obtain consultation or to remove thecatheter nonsurgically should be based on practitioner judg-ment and experience.

• After the injury has been evaluated and a treatment planhas been executed, the anesthesiologist and surgeon shouldconfer regarding relative risks and benefits of proceeding withthe elective surgery versus deferring surgery for a period ofpatient observation.

Appendix 2. Example of a Standardized EquipmentCart for Central Venous Catheterization for AdultPatients

Item Description Quantity

First Drawer

Bottles Alcohol-based Hand Cleanser 2Transparent bio-occlusive dressings with catheter

stabilizer devices2

Transducer kit: NaCL 0.9% 500 ml bag; single-line transducer, pressure bag

1

Needle Holder, Webster Disposable 5 inch 1Scissors, 4 1/2 inchSterile 1Vascular Access Tray(Chloraprep, Sponges,

Labels)1

Disposable pen with sterile labels 4Sterile tubing, arterial line pressure-rated (for

manometry)2

Intravenous connector with needleless valve 4

Second Drawer

Ultrasound Probe Cover, Sterile 3 � 96 2Applicator, chloraprep 10.5 ml 3Surgical hair clipper blade 3Solution, NaCl bacteriostatic 30 ml 2

Third Drawer

Cap, Nurses Bouffant 3Surgeon hats 6Goggles 2Mask, surgical fluidshield 2Gloves, sterile sizes 6.0–8.0 (2 each size) 10Packs, sterile gowns 2

Fourth Drawer

Drape, Total Body (with Femoral Window) 1Sheet, central line total body (no window) 1

Fifth Drawer

Dressing, Sterile Sponge Packages 4Catheter kit, central venous pressure single

lumen14 gauge1

Catheter kits, central venous pressure twolumens 16 cm 7 French

2

Sixth Drawer

Triple Lumen Centravel Venous Catheter Sets,7 French Antimicrobial Impregnated

2

Introducer catheter sets, 9 French with sideport 2

Practice Guidelines


Appendix 3. Example of a Central Venous Catheterization Checklist

Central Line Insertion Standard Work & Safety (Bundle) Checklist for OR and CCU

Date: __________________________ Start Time: ________________ End Time: _______________

Procedure Operator: ______________________ Person Completing Form: ______________________

Catheter Type: � Central Venous � PA/Swan-Ganz

French Size of catheter: _______________ . Catheter lot number: _______________

Number of Lumens: � 1 � 2 � 3 � 4

Insertion Site: � Jugular � Upper Arm � Subclavian � Femoral

Side of Body: � Left � Right � Bilateral

Clinical Setting: � Elective � Emergent

1. Consent form complete and in chart Exception: Emergent procedure �

2. Patient’s Allergy Assessed (especially to Lidocaine or Heparin) �

3. Patient’s Latex Allergy Assessed (modify supplies) �

4. Hand Hygiene: � Operator and Assistant cleanse hands (ASK, if not witnessed) �

5. Optimal Catheter Site Selection:

� In adults, Consider Upper Body Site � Check / explain why femoral site used:

________________________________

� Anatomy – distorted, prior surgery/rad. Scar � Chest wall infection or burn � Coagulopathy � COPD severe/ lung disease � Emergency / CPR � Pediatric

��

ORException(s)

checked to left

6. Pre-procedure Ultrasound Check of internal jugular location and patency if IJ �7. Skin Prep Performed (Skin Antisepsis):

� Chloraprep 10.5 ml applicator used

� Dry technique (normal, unbroken skin): 30 second scrub + 30 second dry time

� Wet technique (abnormal or broken skin): 2 minute scrub + 1 minute dry time

�

� DRY� WET

8. MAXIMUM Sterile Barriers:

� Operator wearing hat, mask, sterile gloves, and sterile gown � Others in room, (except patient) wearing mask � Patient’s body covered by sterile drape

��

9. Procedural “Time out” performed: � Patient ID X 2 � Procedure to be performed has been announced � Insertion site marked � Patient positioned correctly for procedure (Supine or Trendelenburg) � Assembled equipment/ supplies including venous confirmation method verified � Labels on all medication & syringes are verified

��

(continued)

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Appendix 3. Continued

10. Ultrasound Guidance Used for Elective Internal Jugular insertions (sterile probe cover in place)

� Used for IJ � Not used (Other site used)

11. Confirmation of Venous Placement of Access Needle or Catheter: (do not rely on blood color or presence/absence of pulsatility)

� Manometry � Ultrasound � Transducer � Blood Gas

12. Confirmation of Venous Placement of the Wire:

� Access catheter easily in vein & confirmed (catheter-over needle technique)

� Access via thin-wall needle (confirmation of wire recommended) � or ambiguous catheter or wire placement when using catheter-over-the-needle

technique

� Not Needed

� Ultrasound� TEE� Fluoroscopy� ECG

13. Confirmation of Final Catheter in Venous System Prior to Use: � Manometry� Transducer

14. Final steps:

� Verify guidewire not retained � Type and Dosage (ml / units) of Flush: _____________ � Catheter Caps Placed on Lumens� Tip position confirmation:

Fluoroscopy Chest radiograph ordered

� Catheter Secured / Sutured in place

�

��

��

�

15. Transparent Bio-occlusive dressing applied �

16. Sterile Technique Maintained when applying dressing �

17. Dressing Dated �

18. Confirm Final Location of Catheter Tip � CXR

� Fluoroscopy � Continuous

ECG

19. After tip location confirmed, “Approved for use” Written on Dressing �

20. Central line (maintenance) Order Placed �

Comments:

Tip location:

Practice Guidelines


Appendix 5: Methods and Analyses

State of the LiteratureFor these Guidelines, a literature review was used in combinationwith opinions obtained from expert consultants and other sources(e.g., ASA members, SPA members, open forums, Internet post-ings). Both the literature review and opinion data were based onevidence linkages, or statements regarding potential relationshipsbetween clinical interventions and outcomes. The interventionslisted below were examined to assess their effect on a variety ofoutcomes related to central venous catheterization.

Resource PreparationSelection of a Sterile EnvironmentAvailability of a standardized equipment setUse of a checklist or protocol for placement and maintenanceUse of an assistant for placement

Prevention of Infectious ComplicationsIntravenous antibiotic prophylaxisAseptic techniquesAseptic preparation

Hand washing, sterile full-body drapes, sterile gown, gloves,mask, cap

Skin preparationChlorhexidine versus povidone-iodine

Aseptic preparation with versus without alcoholSelection of catheter coatings or impregnation

Antibiotic-coated catheters versus no coating

Silver-impregnated catheters versus no coatingChlorhexidine combined with silver sulfadiazine cathetercoating versus no coating

Selection of catheter insertion siteInternal jugularSubclavianFemoralSelecting a potentially uncontaminated insertion site

Catheter fixationSuture, staple, or tape

Insertion site dressingsClear plastic, chlorhexidine, gauze and tape, cyanoacrylate,antimicrobial dressings, patch, antibiotic ointment

Catheter maintenanceLong-term versus short-term catheterizationFrequency of insertion site inspection for signs of infection

Changing cathetersSpecified time intervalsSpecified time interval versus no specified time interval (i.e., asneeded)One specified time interval versus another specified time intervalChanging a catheter over a wire versus a new site

Aseptic techniques using an existing central line for injection oraspiration

Wiping ports with alcoholCapping stopcocksNeedleless connectors or access ports

Prevention of Mechanical Trauma or InjurySelection of catheter insertion site

Internal jugularSubclavianFemoral

Trendelenburg versus supine positionNeedle insertion and catheter placement

Selection of catheter type (e.g., double lumen, triple lumen,Cordis)Selection of a large-bore catheterPlacement of two catheters in the same veinUse of a Seldinger technique versus a modified SeldingertechniqueLimiting number of insertion attempts

Guidance of needle, wire and catheter placementStatic ultrasound versus no ultrasound (i.e., anatomiclandmarks)Real-time ultrasound guidance versus no ultrasound

Verification of placementManometry versus direct pressure measurement (via pressuretransducer)Continuous electrocardiogramFluoroscopyVenous blood gasTransesophageal echocardiographyChest radiography

Management of Trauma or Injury Arising from Central VenousCatheterization

Not removing versus removing central venous catheter onevidence of arterial puncture.

Appendix 4. Example Duties Performed by anAssistant for Central Venous Catheterization

Reads prompts on checklist to ensure that no safetystep is forgotten or missed. Completes checklist astask is completed

Verbally alerts anesthesiologist if a potential error ormistake is about to be made.

Gathers equipment/supplies or brings standardizedsupply cart.

Brings the ultrasound machine, positions it, turns it on,makes adjustments as needed.

Provides moderate sedation (if registered nurse) ifneeded.

Participates in “time-out” before procedure.Washes hands and wears mask, cap, and nonsterile

gloves (scrubs or cover gown required if in the sterileenvelope).

Attends to patient requests if patient awake duringprocedure.

Assists with patient positioning.Assists with draping.Assists with sterile field setup; drops sterile items into

field as needed.Assists with sterile ultrasound sleeve application to

ultrasound probe.Assists with attachment of intravenous lines or

pressure lines if needed.Assists with application of a sterile bandage at the end

of the procedure.Assists with clean-up of patient, equipment, and

supply cart; returns items to their proper location.

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For the literature review, potentially relevant clinical studies wereidentified via electronic and manual searches of the literature. Theelectronic and manual searches covered a 44-yr period from 1968through 2011. More than 2,000 citations were initially identified,yielding a total of 671 nonoverlapping articles that addressed topicsrelated to the evidence linkages. After review of the articles, 383studies did not provide direct evidence, and were subsequentlyeliminated. A total of 288 articles contained direct linkage-relatedevidence. A complete bibliography used to develop these Guide-lines, organized by section, is available as Supplemental DigitalContent 2, http://links.lww.com/ALN/A784.

Initially, each pertinent outcome reported in a study was classi-fied as supporting an evidence linkage, refuting a linkage, or equiv-ocal. The results were then summarized to obtain a directionalassessment for each evidence linkage before conducting formalmeta-analyses. Literature pertaining to five evidence linkages con-tained enough studies with well-defined experimental designs andstatistical information sufficient for meta-analyses (table 1). Theselinkages were (1) antimicrobial catheters, (2) silver sulfadiazinecatheter coatings, (3) chlorhexidine and silver sulfadiazine cathetercoatings, (4) changing a catheter over a wire versus a new site, and(5) ultrasound guidance for venipuncture.

General variance-based effect-size estimates or combined prob-ability tests were obtained for continuous outcome measures, andMantel-Haenszel odds-ratios were obtained for dichotomous out-come measures. Two combined probability tests were employed asfollows: (1) the Fisher combined test, producing chi-square valuesbased on logarithmic transformations of the reported P values fromthe independent studies, and (2) the Stouffer combined test, pro-viding weighted representation of the studies by weighting each ofthe standard normal deviates by the size of the sample. An odds-ratio procedure based on the Mantel-Haenszel method for combin-ing study results using 2 � 2 tables was used with outcome fre-quency information. An acceptable significance level was set at P �0.01 (one-tailed). Tests for heterogeneity of the independent stud-ies were conducted to assure consistency among the study results.DerSimonian-Laird random-effects odds ratios were obtainedwhen significant heterogeneity was found (P � 0.01). To controlfor potential publishing bias, a “fail-safe n ” value was calculated.No search for unpublished studies was conducted, and no reliabilitytests for locating research results were done. To be accepted assignificant findings, Mantel-Haenszel odds ratios must agree withcombined test results whenever both types of data are assessed. Inthe absence of Mantel-Haenszel odds-ratios, findings from both theFisher and weighted Stouffer combined tests must agree with eachother to be acceptable as significant.

Interobserver agreement among Task Force members and twomethodologists was established by interrater reliability testing.Agreement levels using a kappa (�) statistic for two-rater agreementpairs were as follows: (1) type of study design, � � 0.70–1.00l; (2)type of analysis, � � 0.60–0.84; (3) evidence linkage assignment,� � 0.91–1.00; and (4) literature inclusion for database, � � 0.65–1.00. Three-rater chance-corrected agreement values were (1) studydesign, Sav � 0.80, Var (Sav) � 0.006; (2) type of analysis, Sav �

0.70, Var (Sav) � 0.016; (3) linkage assignment, Sav � 0.94, Var(Sav) � 0.002; (4) literature database inclusion, Sav � 0.65, Var(Sav) � 0.034. These values represent moderate to high levels ofagreement.

Consensus-based EvidenceConsensus was obtained from multiple sources, including (1) sur-vey opinion from consultants who were selected based on theirknowledge or expertise in central venous access, (2) survey opinionssolicited from active members of the ASA and SPA, (3) testimonyfrom attendees of publicly-held open forums at two national anes-thesia meetings, (4) Internet commentary, and (5) task force opin-ion and interpretation. The survey rate of return was 41.0% (n � 55of 134) for the consultants (table 2), 530 surveys were received fromactive ASA members (table 3), and 251 surveys were received fromactive SPA members (table 4).

An additional survey was sent to the expert consultants askingthem to indicate which, if any, of the evidence linkages wouldchange their clinical practices if the Guidelines were instituted. Therate of return was 16% (n � 22 of 134). The percentage of respond-ing consultants expecting no change associated with each linkagewere as follows: (1) availability of a standardized equipment set �91.8%, (2) use of a trained assistant � 83.7%, (3) use of a checklist orprotocol for placement and maintenance � 75.5%, (4) use of bundlesthat include a checklist or protocol � 87.8%, (5) intravenous antibioticprophylaxis � 93.9%, (6) aseptic preparation (e.g., hand washing, caps,masks) � 98.0%, (8) skin preparation � 98.0%, (9) selection of cath-eters with antibiotic or antiseptic coatings/impregnation � 89.8%,(10) selection of catheter insertion site for prevention of infection �100%, (11) catheter fixation methods � 89.8%, (12) insertion sitedressings � 100%, (13) catheter maintenance � 100%, (14) aseptictechniques using an existing central line for injection or aspiration �95.9%, (15) selection of catheter insertion site for prevention of me-chanical trauma or injury � 100%, (16) Trendelenburg versus supinepatient positioning for neck or chest venous access � 100%, (17)needle insertion and catheter placement � 100%, (18) guidanceof needle, wire, and catheter placement � 89.8%, (19) verification ofneedle puncture and placement � 98.0%, (20) management of traumaor injury � 100%.

Fifty-seven percent of the respondents indicated that the Guide-lines would have no effect on the amount of time spent on a typicalcase, and 43% indicated that there would be an increase of theamount of time spent on a typical case with the implementation ofthese Guidelines. Seventy-four percent indicated that new equip-ment, supplies, or training would not be needed to implement theGuidelines, and 78% indicated that implementation of the Guide-lines would not require changes in practice that would affect costs.

Combined Sources of EvidenceEvidence for these Guidelines was formally collected from multiplesources, including randomized controlled trials, observational liter-ature, surveys of expert consultants, and randomly selected samplesof ASA and SPA members. This information is summarized in table5, with a brief description of each corresponding recommendation.

Practice Guidelines



Table 1. Meta-analysis Summary

Evidence Linkages NFisher

Chi-squareP

Value

WeightedStouffer

ZcP

ValueEffectSize

OddsRatio

ConfidenceInterval

Heterogeneity

PValues

EffectSize

Antibiotic-coated cathetersvs. no coating

Catheter colonization 5 0.35 0.23–0.55 nsSilver sulfadiazine catheter

coating vs. no coatingCatheter-related

bloodstream infection5 0.70 0.45–1.10 ns

Chlorhexidine � silversulfadiazine cathetercoating vs. no coating

Catheter colonization 12 0.43 0.34–0.54 nsCatheter-related

bloodstream infection12 0.70 0.47–1.03 ns

Changing a catheter overa wire vs. a new site

Catheter colonization 5 1.18 0.66–2.09 nsReal-time ultrasound

guidance vs. noultrasound*

Successful insertion/cannulation

11 7.15† 1.33–18.27 0.005

First attempt success 5 3.24 1.93–5.45 nsTime to insertion 6 70.67 0.001 �7.15 0.001 �0.23 ns nsArterial puncture 10 0.24 0.15–0.38 ns

* Findings represent studies addressing internal jugular access. † Random-effects odds ratio.ns � P � 0.01.

Table 2. Consultant Survey Responses*

Percent Responding to Each Item

NStronglyAgree Agree Equivocal Disagree

StronglyDisagree

I. Resource preparation1. Central venous catheterization should be

performed in a location that permits the use ofaseptic techniques

54 92.6* 7.4 0.0 0.0 0.0

2. A standardized equipment set should beavailable for central venous access

55 78.2* 16.4 5.4 0.0 0.0

3. A trained assistant should be present duringplacement of a central venous catheter

54 33.3 29.6* 16.7 18.4 1.9

4. A checklist or protocol should be used for theplacement and maintenance of central venouscatheters

54 59.3* 20.4 9.3 9.3 1.8

II. Prevention of infectious complications5. Intravenous antibiotic prophylaxis should not be

administered routinely55 43.6 32.7* 12.7 7.3 3.6

6. For immunocompromised patients and high-riskneonates, intravenous antibiotic prophylaxis maybe administered on a case-by-case basis

55 23.6 36.4* 27.3 10.9 1.8

7. The practitioner should use the following aseptictechniques in preparation for the placement ofcentral venous catheters (check all that apply) 55 Percentage

Hand washing 100.0Sterile full-body drapes 87.3Sterile gowns 100.0Gloves 100.0Caps 100.0Masks covering both mouth and nose 100.0

(continued)

SPECIAL ARTICLES


Table 2. Continued



StronglyDisagree

8. Chlorhexidine with alcohol should be used forskin preparation

55 72.7* 27.3 0.0 0.0 0.0

9. Catheters coated with antibiotics or acombination of chlorhexidine and silversulfadiazine may be used in selected patientsbased on infectious risk, cost, and anticipatedduration of catheter use

55 38.2 45.5* 16.3 0.0 0.0

10. Please indicate your preferred central venouscatheter insertion site to minimize catheter-related risk of infection (check one) 55 Percentage

Internal jugular 41.8Subclavian 52.7Femoral 0.0No preference 5.5

11. Femoral catheterization should be avoided whenpossible to minimize the risk of infection

54 37.0 53.7* 3.7 3.7 1.9

12. An insertion site should be selected that is notcontaminated or potentially contaminated (e.g.,burned or infected skin, inguinal area, adjacentto tracheostomy or open surgical wound)

53 71.7* 24.5 7.8 0.0 0.0

13. Please indicate your preferred catheter fixationtechnique to minimize catheter-related risk ofinfection (check one) 54 Percentage

Sutures 70.4Staples 3.7Tape 5.5No preference 20.4

14. Transparent bio-occlusive dressings should beused to protect the site of central venouscatheter insertion from infection

55 52.7* 41.8 3.6 1.8 0.0

15. Dressings containing chlorhexidine may be usedto reduce the risk of catheter-related infection

55 20.0 34.6* 45.4 0.0 0.0

16. The duration of catheterization should be basedon clinical need

55 61.8* 30.9 0.0 7.3 0.0

17. The clinical need for keeping a catheter in placeshould be assessed daily

53 90.6* 9.4 0.0 0.0 0.0

18. Catheters should be promptly removed whendeemed no longer clinically necessary

54 88.9* 11.1 0.0 0.0 0.0

19. The catheter site should be inspected daily forsigns of infection

54 88.9* 11.1 0.0 0.0 0.0

20. The catheter should be changed or removedwhen infection is suspected

55 74.6* 20.0 3.6 1.8 0.0

21. When catheter-related infection is suspected,replacing the catheter using a new insertion siteis preferable to changing the catheter over aguidewire

55 70.9* 27.3 1.8 0.0 0.0

22. Catheter access ports should be wiped with anappropriate antiseptic before each access

55 69.1* 21.8 7.3 1.8 0.0

23. Needleless catheter access ports may be usedon a case-by-case basis

55 30.9 47.3* 12.7 3.6 5.5

24. Central venous catheter stopcocks should becapped when not in use

54 81.5* 18.5 0.0 0.0 0.0

(continued)

Practice Guidelines


Table 2. Continued



StronglyDisagree

III. Prevention of mechanical trauma or injury25. Please indicate your preferred central venous

catheter insertion site to minimize cathetercannulation-related risk of injury or trauma(check one) 55 Percentage


26. Please indicate your preferred central venouscatheter insertion site to minimize catheter-related risk of thromboembolic injury or trauma(check one) 55 Percentage


27. When clinically appropriate and feasible, centralvenous access in the neck or chest should beperformed in the Trendelenburg position

54 51.9* 33.3 9.6 5.6 0.0

28. Selection of catheter type (i.e., gauge, length,number of lumens) and composition (e.g.,polyurethane, Teflon) should be based on theclinical situation and skill/experience of theoperator

55 49.1 38.2* 9.1 3.6 0.0

29. Selection of a modified Seldinger technique vs.a Seldinger technique should be based on theclinical situation and the skill/experience of theoperator

55 36.4 49.1* 5.4 7.3 1.8

30. The number of insertion attempts should bebased on clinical judgment

55 45.5 32.7* 3.6 16.4 1.8

31. The decision to place two catheters in a singlevein should be made on a case-by-case basis

55 55.6* 40.0 3.6 1.8 0.0

32. Ultrasound imaging (i.e., static) should be usedin elective situations for pre-punctureidentification of anatomy and vessel localizationwhen the internal jugular vein is selected forcannulation

53 49.1 26.4* 11.3 9.4 3.8

33. Ultrasound imaging (i.e., static) should be used inelective situations for pre-puncture identification ofanatomy and vessel localization when the subclavianvein is selected for cannulation

55 12.7 18.2 32.7* 25.5 10.9

34. Ultrasound imaging (i.e., static) should be usedin elective situations for pre-punctureidentification of anatomy and vessel localizationwhen the femoral vein is selected forcannulation

55 18.2 32.7* 21.8 23.6 3.6

35. When available, real-time ultrasound should beused for guidance during venous access whenthe internal jugular vein is selected forcannulation

54 44.4 33.3* 13.0 9.3 0.0

36. When available, real-time ultrasound should beused for guidance during venous access whenthe subclavian vein is selected for cannulation

53 11.3 17.0 37.7* 28.3 5.7

(continued)

SPECIAL ARTICLES


Table 2. Continued



StronglyDisagree

37. When available, real-time ultrasound should beused for guidance during venous access whenthe femoral vein is selected for cannulation

54 14.8 35.2* 33.3 14.8 1.9

38. Before insertion of a dilator or large borecatheter over a wire, venous access should beconfirmed for the catheter or thin-wall needlethat accesses the vein

54 57.4* 25.9 7.4 9.3 0.0

39. Before insertion of a dilator or large borecatheter over a wire, venous access should beconfirmed for the wire that subsequently residesin the vein after traveling through a catheter orthin-wall needle

55 29.1 29.1* 25.5 12.7 3.6

40. When feasible, both the location of the catheteror thin-wall needle and wire should beconfirmed

55 25.4 38.2* 18.2 15.6 3.6

41. A chest radiograph should be performed toconfirm the location of the catheter tip as soonafter catheterization as clinically appropriate

55 30.9 41.8* 9.1 14.5 3.6

42. For central venous catheters placed in theoperating room, a confirmatory chest radiographmay be performed in the early postoperativeperiod

55 47.3 50.9* 0.0 1.8 0.0

43. If a chest radiograph will be deferred to thepostoperative period, pressure/waveformanalysis, blood gas analysis, ultrasound orfluoroscopy should be used to confirm venouspositioning of the catheter before use

55 56.4* 30.9 5.4 7.3 0.0

IV. Management of arterial trauma or injury arisingfrom central venous

44. When unintended cannulation of an arterialvessel with a large bore catheter occurs, thecatheter should be left in place and a general orvascular surgeon should be consulted

55 45.4 36.4* 7.3 9.1 1.8

* N � number of consultants who responded to each item. An asterisk next to a percentage score indicates the median.

Practice Guidelines


Table 3. ASA Member Survey Responses*



StronglyDisagree

I. Resource preparation1. Central venous catheterization should be

performed in a location that permits theuse of aseptic techniques

529 78.1* 19.1 2.1 0.8 0.0

2. A standardized equipment set should beavailable for central venous access

530 64.5* 30.0 4.2 0.9 0.4

3. A trained assistant should be present duringplacement of a central venous catheter

526 24.1 35.6* 24.0 13.1 3.2

4. A checklist or protocol should be used forThe placement and maintenance of centralvenous catheters

528 35.6 37.5* 16.3 8.9 1.7

II. Prevention of infectious complications5. Intravenous antibiotic prophylaxis should

not be administered routinely526 29.7 44.5* 16.9 7.0 1.9

6. For immunocompromised patients andhigh-risk neonates, intravenous antibioticprophylaxis may be administered on acase-by-case basis

523 25.0 54.1* 15.9 4.2 0.8

7. The practitioner should use the followingaseptic techniques in preparation for theplacement of central venous catheters(check all that apply) 524 Percentage

Hand washing 96.0Sterile full-body drapes 73.8Sterile gowns 87.8Gloves 100.0Caps 94.7

Masks covering both mouth and nose 98.18. Chlorhexidine with alcohol should be used

for skin preparation522 57.3* 34.1 7.8 0.8 0.0

9. Catheters coated with antibiotics or acombination of chlorhexidine and silversulfadiazine may be used in selectedpatients based on infectious risk, cost,and anticipated duration of catheter use

526 24.3 54.8* 19.2 1.7 0.0

10. Please indicate your preferred central venouscatheter insertion site to minimize catheter-related risk of infection (check one) 524 Percentage


11. Femoral catheterization should be avoidedwhen possible to minimize the risk ofinfection

525 33.9 49.7* 9.3 4.7 2.3

12. An insertion site should be selected that isnot contaminated or potentiallycontaminated (e.g., burned or infectedskin, inguinal area, adjacent totracheostomy or open surgical wound)

523 58.9* 37.9 2.5 0.7 0.0

(continued)

SPECIAL ARTICLES


Table 3. Continued



StronglyDisagree

13. Please indicate your preferred catheterfixation technique to minimize catheter-related risk of infection (check one) 524 Percentage

Sutures 80.2Staples 5.7Tape 3.6No preference 10.5

14. Transparent bio-occlusive dressingsshould be used to protect the site ofcentral venous catheter insertion frominfection

522 46.9 44.4* 6.5 1.3 0.8

15. Dressings containing chlorhexidine may beused to reduce the risk of catheter-relatedinfection

525 18.7 37.9* 41.3 1.9 0.2

16. The duration of catheterization should bebased on clinical need

523 49.5 44.5* 3.1 2.5 0.4

17. The clinical need for keeping a catheter inplace should be assessed daily

523 65.8* 32.5 1.3 0.4 0.0

18. Catheters should be promptly removedwhen deemed no longer clinicallynecessary

521 78.7* 20.9 0.4 0.0 0.0

19. The catheter site should be inspecteddaily for signs of infection

521 79.1* 19.6 1.1 0.2 0.0

20. The catheter should be changed orremoved when infection is suspected

524 72.7* 24.4 2.5 0.2 0.2

21. When catheter-related infection issuspected, replacing the catheter using anew insertion site is preferable tochanging the catheter over a guidewire

525 64.8* 30.7 3.8 0.8 0.0

22. Catheter access ports should be wipedwith an appropriate antiseptic before eachaccess

522 64.6* 31.0 3.4 1.0 0.0

23. Needleless catheter access ports may beused on a case-by-case basis

522 33.9 51.3* 12.3 1.7 0.8

24. Central venous catheter stopcocks shouldbe capped when not in use

527 70.6* 26.2 2.6 0.6 0.0

III. Prevention of mechanical trauma or injury25. Please indicate your preferred central

venous catheter insertion site to minimizecatheter cannulation-related risk of injuryor trauma (check one) 525 Percentage


26. Please indicate your preferred centralvenous catheter insertion site to minimizecatheter-related risk of thromboembolicinjury or trauma (check one) 525 Percentage


(continued)

Practice Guidelines


Table 3. Continued



StronglyDisagree

27. When clinically appropriate and feasible,central venous access in the neck orchest should be performed in theTrendelenburg position

528 57.0* 37.7 3.0 1.9 0.4

28. Selection of catheter type (i.e., gauge,length, number of lumens) andcomposition (e.g., polyurethane, Teflon)should be based on the clinical situationand skill/experience of the operator

530 52.1* 38.1 6.2 3.4 0.0

29. Selection of a modified Seldingertechnique vs. a Seldinger techniqueshould be based on the clinical situationand the skill/experience of the operator

531 47.8 36.9* 9.8 4.7 0.8

30. The number of insertion attempts shouldbe based on clinical judgment

528 47.3 43.6* 4.2 3.8 1.1

31. The decision to place two catheters in asingle vein should be made on a case-by-case basis

527 45.9 36.2* 12.1 4.4 1.3

32. Ultrasound imaging (i.e., static) should beused in elective situations for pre-punctureidentification of anatomy and vessellocalization when the internal jugular veinis selected for cannulation

526 28.9 25.1* 21.3 18.8 5.9

33. Ultrasound imaging (i.e., static) should beused in elective situations for pre-punctureidentification of anatomy and vessellocalization when the subclavian vein isselected for cannulation

528 9.7 14.2 41.5* 26.5 8.1

34. Ultrasound imaging (i.e., static) should beused in elective situations for pre-punctureidentification of anatomy and vessellocalization when the femoral vein isselected for cannulation

527 11.9 29.8 30.6* 21.4 6.3

35. When available, real time ultrasoundshould be used for guidance duringvenous access when the internal jugularvein is selected for cannulation

525 24.0 24.2 23.2* 21.5 7.1

36. When available, real time ultrasoundshould be used for guidance duringvenous access when the subclavian vein isselected for cannulation

530 8.1 13.4 42.1* 27.9 8.5

37. When available, real-time ultrasoundshould be used for guidance duringvenous access when the femoral vein isselected for cannulation

528 13.5 23.5 31.4* 25.0 6.6

38. Before insertion of a dilator or large borecatheter over a wire, venous accessshould be confirmed for the catheter orthin-wall needle that accesses the vein

524 52.9* 32.1 8.4 6.3 0.4

39. Before insertion of a dilator or large borecatheter over a wire, venous access shouldbe confirmed for the wire that subsequentlyresides in the vein after traveling through acatheter or thin-wall needle

524 24.0 25.4 25.6* 22.9 2.1

(continued)

SPECIAL ARTICLES


Table 3. Continued



StronglyDisagree

40. When feasible, both the location of thecatheter or thin-wall needle and wireshould be confirmed

526 23.8 32.5* 22.1 19.4 2.3

41. A chest radiograph should be performedto confirm the location of the catheter tipas soon following catheterization asclinically appropriate

525 39.8 45.5* 7.1 7.0 0.6

42. For central venous catheters placed in theoperating room, a confirmatory chestradiograph may be performed in the earlypostoperative period

524 46.8 48.1* 2.5 1.9 0.8

43. If a chest radiograph will be deferred tothe postoperative period,pressure/waveform analysis, blood gasanalysis, ultrasound or fluoroscopy shouldbe used to confirm venous positioning ofthe catheter before use

527 33.0 35.3* 12.7 16.7 2.3

IV. Management of arterial trauma or injuryarising from central venous

44. When unintended cannulation of anarterial vessel with a large bore catheteroccurs, the catheter should be left inplace and a general or vascular surgeonshould be consulted

526 28.5 35.6* 16.3 17.9 1.7

* Number of ASA members who responded to each item. An asterisk next to a percentage score indicates the median.

Practice Guidelines


Table 4. SPA Member Survey Responses*



StronglyDisagree

1. A chlorhexidine-containing solution shouldbe used for skin preparation in neonates†

250 17.2 26.0 31.6* 17.2 8.0

2. A chlorhexidine-containing solution shouldbe used for skin preparation in infants‡

248 46.0 40.3* 11.3 2.4 0.0

3. A chlorhexidine-containing solution shouldbe used for skin preparation in children§

249 62.7* 30.9 5.2 1.2 0.0

4. Dressings containing chlorhexidine may beused in neonates

243 7.0 14.0 52.2* 20.2 6.6

5. Dressings containing chlorhexidine may beused in infants

249 22.5 36.6* 35.3 4.8 0.8

6. Dressings containing chlorhexidine may beused in children

249 38.6 35.3* 24.5 1.2 0.4

7. When unintended cannulation of an arterialvessel with a large bore catheter occurs inneonates (check one) 244 Percentage

The catheter should be left in place5 54.9The catheter may be nonsurgically

removed�45.1

8. When unintended cannulation of an arterialvessel with a large-bore catheter occurs ininfants (check one) 249 Percentage

The catheter should be left in place 43.8The catheter may be nonsurgically

removed56.2

9. When unintended cannulation of an arterialvessel with a large bore catheter occurs inchildren (check one) 244 Percentage

The catheter should be left in place 30.0The catheter may be nonsurgically

removed70.0

* Number of SPA members who responded to each item. An asterisk beside a percentage score indicates the median response.† Younger than 44 gestational weeks. ‡ Younger than 2 yr. § 2–16 yr of age. � The complete wording of the response category is:The catheter should be left in place and a general surgeon, vascular surgeon, or interventional radiologist should be immediatelyconsulted before deciding on whether to remove the catheter, either surgically or nonsurgically. # The complete wording of theresponse category is: The catheter may be nonsurgically removed without consulting a general surgeon, vascular surgeon, orinterventional radiologist.

SPECIAL ARTICLES


Table 5. Evidence Summary*

InterventionsEvidenceCategory1

ConsultantSurvey2

ASA MemberSurvey2

SPA MemberSurvey2

GuidelineRecommendation

I. Resource preparationCatheterization in environment

that permits use ofaseptic techniques

D Strongly agree Strongly agree Should be performed

Standardized equipment set D Strongly agree Strongly agree Should be availableAn assistant D Agree (trained) Agree (trained) Should be usedA checklist or protocol B23 Strongly agree Agree Should be used

II. Prevention of infectiouscomplications

Intravenous antibioticprophylaxis

Prophylactic intravenousantibiotics shouldnot be administeredroutinely

D Agree Agree Should not be routinelyadministered

Prophylactic intravenousantibiotics should beadministered toimmunocompromisedpatients and high-risk neonates

A24 Agree Agree Administer on a case-by-case basis

Aseptic techniques andbarrier precautions:

Maximal barrier vs. glovesand small drapeonly

C25,6

�Bundled� elements:hand-washing,sterile full bodydrapes, sterile,gloves, caps, andmasks

B23

Specific activities:Hand washing D 100% agreement 96% agreement UseSterile full-body drape D 87% agreement 74% agreement UseSterile gown D 100% agreement 88% agreement UseSterile gloves D 100% agreement 100% agreement UseCaps D 100% agreement 95% agreement UseMasks covering both

mouth and noseD 100% agreement 98% agreement Use

Skin preparation:Solutions containing

chlorhexidine:Chlorhexidine with

alcohol (patient agenot specified)

D Strongly agree Strongly agree Should be used for adults,infants and children

Antiseptic solutionscontainingchlorhexidine for:

Neonates D Equivocal Should be based on clinicaljudgment andInstitutional protocol

Infants D Agree Should be usedChildren D Strongly agree Should be used

Solutions containingalcohol:

Chlorhexidine withoutalcohol vs.povidone-iodinewithout alcohol

C25,7

Chlorhexidine withalcohol vs.Povidone-iodinewith alcohol

D

Skin preparation solutionswith vs. withoutalcohol:

Chlorhexidine D(continued)

Practice Guidelines


Table 5. Continued


ConsultantSurvey2

ASA MemberSurvey2

SPA MemberSurvey2


Povidone-iodine A35/C28

Skin preparation solutionscontaining alcohol

Use unless contraindicated

Catheters containingantimicrobial agents:

Antibiotic-coatedcatheters

A15 Agree (selectedpts)

Agree (selectedpts)

Should be used forselected patients

Silver-impregnatedcatheters

C13/C25 No recommendation

Chlorhexidine and silversulfadiazine coatedcatheters

A15/B39/C13 Agree (selectedpts)

Agree (selectedpts)

Should be used forselected patients

Selection of catheterinsertion site:

Internal jugular vs.subclavian

C23,5/C33,5 Majority prefersubclavian site

Majority preferinternal jugular

site

Site selection should bebased on clinical need tominimize risk of catheter-related infection

Subclavian vs. femoral A35/C24 Agree (avoidfemoral)

Agree (avoidfemoral)

Site selection should bebased on clinical need.In adults, upper bodysite should beconsidered to minimizerisk of infection

Catheter fixation:Risk of catheter-related

infections withsuture, staple, tape

D Majority prefersuture

Majority prefersuture

Should be determined on alocal or institutional basis

Catheter insertion sitedressings:

Transparent bio-occlusive D Strongly agree Strongly agree Should be usedChlorhexidine sponge

dressings (patientage not specified)

C23,5 Agree Agree May be used unlesscontraindicated

Chlorhexidine-impregnatedtransparentdressings forneonates

A310 Should be based on clinicaljudgment and institutionalprotocol

Chlorhexidine spongedressings

For neonates Equivocal Should be based on clinicaljudgment andinstitutional protocol

For infants Agree May be used, unlesscontraindicated

For children Agree May be used, unlesscontraindicated

Silver-impregnatedtransparentdressings

C25 No recommendation

Catheter maintenance:Duration of catheterization

related to highercolonization/infectionrates

B24,5

Duration of catheterizationshould be based onclinical need

Strongly agree Agree Duration should be basedon clinical need

Specific time intervalsbetween insertionsite inspections

D

Catheter change interval3-days vs. 7-days

C25

Daily assessment ofclinical need forcontinuingcatheterization

Strongly agree Strongly agree Clinical need for keepingcatheter in place shouldbe assessed daily

(continued)

SPECIAL ARTICLES


Table 5. Continued


ConsultantSurvey2

ASA MemberSurvey2

SPA MemberSurvey2


Conduct daily cathetersite inspections

Strongly agree Strongly agree Catheter insertion siteshould be inspecteddaily for signs ofinfection

Change or removecatheter wheninfection issuspected

Strongly agree Strongly agree Catheter should bechanged or removedwhen Catheter insertionsite infection issuspected

When catheter-relatedinfection issuspected, replacecatheter using newinsertion site vs.catheter changeover a guidewire

C15 Strongly agree(Suspectedinfection)

Strongly agree(Suspectedinfection)

When catheter-relatedinfection is suspected,replacing the catheterusing a new insertion siteis preferred

Promptly remove catheterwhen deemed nolonger clinicallynecessary

Strongly agree Strongly agree Promptly remove catheterwhen deemed no longerclinically necessary

Aseptic techniques using anexisting centralvenous catheter:

Wipe port with anappropriateantiseptic beforeaccess

D Strongly agree Strongly agree Catheter access portsshould be wiped with anappropriate antisepticbefore each access

Cap stopcocks or accessports when not inuse

Strongly agree Strongly agree Central venous catheterstopcocks or accessports should be cappedwhen not in use

Needleless catheterconnectors/accessports vs. standardcaps

Needleless catheterconnectors/ports vs.standard caps

A211/C23 Agree(case-by case

basis)

Agree(case-by case

basis)

Needless catheter accessports may be used on acase-by-case basis

III. Prevention of mechanicaltrauma or injury

Selection of catheterinsertion site:

Internal jugular vs.subclavian

C213,14,15,16/C317

Subclavian vs. femoral A312

Preferred catheterinsertion site



Insertion site selectionshould be based onclinical need andpractitioner judgment,experience and skill. Inadults, selection of anupper body insertion siteshould be considered tominimize the risk ofthromboembolic injury ortrauma

Positioning the patient forneedle insertion andcatheter placement:

Trendelenburg vs. normalsupine

B218 Strongly agree Strongly agree When clinically appropriateand feasible, centralvenous access in the neckor chest should beperformed with the patientin the Trendelenburgposition

(continued)

Practice Guidelines


Table 5. Continued


ConsultantSurvey2

ASA MemberSurvey2

SPA MemberSurvey2


Needle insertion, wire andcatheter placement:

Selection of catheter sizeand type

Strongly agree Strongly agree Should be based on theclinical situation and theskill and experience ofthe practitioner; selectionof the smallest sizecatheter appropriate forthe clinical situationshould be considered

Large-bore cathetersassociated withunintentional arterialcannulation

B319 Select the smallest sizecatheter appropriate forthe clinical situation

Modified Seldinger vs.Seldinger technique

D Agree Agree Should be based on theclinical situation and theskill and experience ofthe operator; thedecision to use acatheter-over-the- needle(modified Seldinger)technique or a thin-wallneedle (Seldinger)technique should bebased at least in part onthe method used toconfirm that the wireresides in the vein beforea dilator or large-borecatheter is threaded

Limiting the number ofinsertion attempts

D Agree Agree Should be based on clinicaljudgment

Introducing two cathetersin the same centralvein

B220/C313,15 Strongly agree(case-by-case)

Agree(case-by-case)

Should be decided on acase-by-case basis

Guidance of needleplacement inelective situations:

Static ultrasound forpreproceduralvessel localizationvs. landmarkapproach:

Internal jugular veinaccess

A321/C222 Agree(elective

situations)

Agree(elective

situations)

Use

Subclavian vein access C222 Equivocal(elective

situations)

Equivocal(elective

situations)

May be used

Femoral vein access D Agree(elective

situations)

Equivocal(elective

situations)

May be used

Real-time ultrasound forguiding needle vs.landmark approach:

Internal jugular veinaccess

A113,21,22,23/A224 Agree(when available)

Equivocal(when available)

Use

Subclavian vein access A224/A313,15,16,23 Equivocal(when available)


May be used

Femoral vein access A321,24 Agree(when available)


May be used

(continued)

SPECIAL ARTICLES


Table 5. Continued


ConsultantSurvey2

ASA MemberSurvey2

SPA MemberSurvey2


Verification of venousaccess:

Confirm that catheter orthin-wall needle is ina vein

Strongly agree Strongly agree Confirm venous accessafter insertion of catheterthat went over theneedle or a thin-wallneedle

Ultrasound D An identified methodManometry B213 An identified methodPressure waveform

analysisD An identified method

Venous blood gas D An identified methodAbsence of pulsatility,

blood colorD Should not be relied upon

to confirm venousaccess (based on TaskForce opinion)

Confirm venous residenceof the wire

Agree Equivocal When using the thin-wallneedle technique,confirm venousresidence of the wireafter the wire is threaded

Ultrasound B225 An identified methodTransesophageal

ultrasoundB325 An identified method

Continuouselectrocardiography

D An identified method (basedon Task Force opinion)

Fluoroscopy D An identified method (basedon Task Force opinion)

Confirm both the locationof the catheter orthin-wall needle andwire

Agree(when feasible)

Agree(when feasible)

Confirm if there is anyuncertainty that thecatheter or wire residesin the vein

Verification of catheterplacement:

Confirmation of finalposition of tip ofcatheter

Confirm the final position ofthe catheter tip as soon asclinically appropriate (basedon Task Force opinion)

Fluoroscopy B226 Strongly agree Agree An identified methodChest radiograph B226 Agree Agree An identified methodContinuous

electrocardiographyA226 An identified method

Unintended cannulation ofan arterial vesselwith a large borecatheter:

Leave catheter in place(patient age notspecified)

B327 Agree Agree For adults, the cathetershould be left in placeand a general surgeon, avascular surgeon, or aninterventional radiologistshould be immediatelyconsulted

For neonates Majority preferleaving in place

Should be based on clinicaljudgment

For infants Majority prefernonsurgical

removal


(continued)

Practice Guidelines


References‡‡1. Chua C, Wisniewski T, Ramos A, Schlepp M, Fildes JJ,

Kuhls DA: Multidisciplinary trauma intensive care unit check-list: Impact on infection rates. J Trauma Nurs 2010; 17:163–6

2. Berenholtz SM, Pronovost PJ, Lipsett PA, Hobson D, EarsingK, Farley JE, Milanovich S, Garrett-Mayer E, Winters BD,Rubin HR, Dorman T, Perl TM: Eliminating catheter-relatedbloodstream infections in the intensive care unit. Crit CareMed 2004; 32:2014 –20

3. Higuera F, Rosenthal VD, Duarte P, Ruiz J, Franco G, Safdar N:The effect of process control on the incidence of central venouscatheter-associated bloodstream infections and mortality in inten-sive care units in Mexico. Crit Care Med 2005; 33:2022–7

4. Miller MR, Griswold M, Harris JM 2nd, Yenokyan G, HuskinsWC, Moss M, Rice TB, Ridling D, Campbell D, Margolis P,Muething S, Brilli RJ: Decreasing PICU catheter-associatedbloodstream infections: NACHRI’s quality transformationefforts. Pediatrics 2010; 125:206 –13

5. Pronovost P, Needham D, Berenholtz S, Sinopoli D, Chu H,Cosgrove S, Sexton B, Hyzy R, Welsh R, Roth G, Bander J,Kepros J, Goeschel C: An intervention to decrease catheter-related bloodstream infections in the ICU. N Engl J Med2006; 355:2725–32

6. Schulman J, Stricof R, Stevens TP, Horgan M, Gase K,Holzman IR, Koppel RI, Nafday S, Gibbs K, Angert R, Sim-monds A, Furdon SA, Saiman L, New York State RegionalPerinatal Care Centers: Statewide NICU central-line-associ-

ated bloodstream infection rates decline after bundles andchecklists. Pediatrics 2011; 127:436 – 44

7. Warren DK, Cosgrove SE, Diekema DJ, Zuccotti G, ClimoMW, Bolon MK, Tokars JI, Noskin GA, Wong ES, SepkowitzKA, Herwaldt LA, Perl TM, Solomon SL, Fraser VJ, Preven-sion Epicenter Program: A multicenter intervention to pre-vent catheter-associated bloodstream infections. InfectControl Hosp Epidemiol 2006; 27:662–9

8. Boorman D: Today’s electronic checklists reduce likelihoodof crew errors and help prevent mishaps. ICAO J 2001:17–20-36

9. Karl R: Briefings, checklists, geese, and surgical safety. AnnSurg Oncol 2010; 17:8 –11

10. Spafford PS, Sinkin RA, Cox C, Reubens L, Powell KR:Prevention of central venous catheter-related coagulase-negative staphylococcal sepsis in neonates. J Pediatr 1994;125:259 – 63

11. Vassilomanolakis M, Plataniotis G, Koumakis G, Hajichras-tou H, Skouteri H, Dova H, Efremidis AP: Central venouscatheter-related infections after bone marrow transplanta-tion in patients with malignancies: A prospective study ofshort-course vancomycin prophylaxis. Bone Marrow Trans-plant 1995; 15:77– 80

12. Raad II, Hohn DC, Gilbreath BJ, Suleiman N, Hill LA, BrusoPA, Marts K, Mansfield PF, Bodey GP: Prevention of centralvenous catheter-related infections by using maximal sterilebarrier precautions during insertion. Infect Control HospEpidemiol 1994; 15:231– 8

13. Maki DG, Ringer M, Alvarado CJ: Prospective randomisedtrial of povidone-iodine, alcohol, and chlorhexidine forprevention of infection associated with central venous andarterial catheters. Lancet 1991; 338:339 – 43

‡‡ A complete bibliography used to develop these Guidelines,arranged alphabetically by author, is available as SupplementalDigital Content 1, http://links.lww.com/ALN/A783.

Table 5. Continued


ConsultantSurvey2

ASA MemberSurvey2

SPA MemberSurvey2


For children Majority preferNonsurgical removal


* Categories of evidence for literature: Category A: Supportive Literature. Randomized controlled trials report statistically significant(P � 0.01) differences between clinical interventions for a specified clinical outcome. Level 1: The literature contains multiplerandomized controlled trials, and aggregated findings are supported by meta-analysis. † Level 2: The literature contains multiplerandomized controlled trials, but the number of studies is insufficient to conduct a viable meta-analysis for the purpose of theseGuidelines. Level 3: The literature contains a single randomized controlled trial. Category B: Suggestive Literature. Information fromobservational studies permits inference of beneficial or harmful relationships among clinical interventions and clinical outcomes. Level1: The literature contains observational comparisons (e.g., cohort, case-control research designs) of clinical interventions or conditionsand indicates statistically significant differences between clinical interventions for a specified clinical outcome. Level 2: The literaturecontains noncomparative observational studies with associative (e.g., relative risk, correlation) or descriptive statistics. Level 3: Theliterature contains case reports. Category C: Equivocal Literature. The literature cannot determine whether there are beneficial orharmful relationships among clinical interventions and clinical outcomes. Level 1: Meta-analysis did not find significant differences (P �0.01) among groups or conditions. Level 2: The number of studies is insufficient to conduct meta-analysis, and (1) randomizedcontrolled trials have not found significant differences among groups or conditions or (2) randomized controlled trials report inconsistentfindings. Level 3: Observational studies report inconsistent findings or do not permit inference of beneficial or harmful relationships.Category D: Insufficient Evidence from Literature. The lack of scientific evidence in the literature is described by the following terms.Inadequate: The available literature cannot be used to assess relationships among clinical interventions and clinical outcomes. Theliterature either does not meet the criteria for content as defined in the “Focus” of the Guidelines or does not permit a clear interpretationof findings due to methodological concerns (e.g., confounding in study design or implementation). Silent: No identified studies addressthe specified relationships among interventions and outcomes. 1 All meta-analyses are conducted by the ASA methodology group.Meta-analyses from other sources are reviewed but not included as evidence in this document. 2 Survey data recorded on a 5-pointscale: strongly agree - agree - equivocal - disagree - strongly disagree; reported findings represent the median survey response.3 Catheter-related bloodstream infection. 4 Catheter-related infection and sepsis. 5 Catheter colonization. 6 Catheter-related septice-mia. 7 Catheter-related bacteremia. 8 Catheter-related infection and clinical signs of infection. 9 Anaphylactic shock. 10 Localizedcontact dermatitis. 11 Microbial contamination of stopcock entry ports. 12 Thrombotic complications. 13 Arterial puncture. 14 Deep veinthrombosis. 15 Hematoma. 16 Successful venipuncture. 17 Pneumothorax, hemothorax, or arrhythmia. 18 Diameter and cross sectionalarea of right internal jugular vein for patients older than 6 yr. 19 Severe injury (e.g., hemorrhage, hematoma, pseudoaneurysm,arteriovenous fistula, arterial dissection, neurologic injury including stroke, and severe or lethal airway obstruction) may occur.20 Dysrhythmia. 21 First insertion attempt success rate. 22 Overall successful cannulation rate. 23 Access time. 24 Number of insertionattempts. 25 Confirmation of venous placement of wire. 26 Identifying the position of the catheter tip. 27 Fewer severe complications inadult patients.

SPECIAL ARTICLES



14. Parienti JJ, du Cheyron D, Ramakers M, Malbruny B, LeclercqR, Le Coutour X, Charbonneau P, Members of the NACREStudy Group: Alcoholic providone-iodine to prevent centralvenous catheter colonization: A randomized unit crossoverstudy. Crit Care Med 2004; 32:708–13

15. Bach A, Darby D, Bottiger B, Bohrer H, Motsch J, Martin E:Retention of the antibiotic teicoplanin on a hydromer-coated central venous catheter to prevent bacterial coloni-zation in postoperative surgical patients. Intensive CareMed 1996; 22:1066 –9

16. Kamal GD, Pfaller MA, Rempe LE, Jebson PJ: Reducedintravascular catheter infection by antibiotic bonding: Aprospective, randomized, controlled trial. JAMA 1991; 265:2364 – 8

17. Len C, Ruiz-Santana S, Rello J, de la Torre MV, Valls J, Alvarez-Lerma F, Sierra R, Saavedra P, Alvarez-Salgado F: Benefits ofminocycline and rifampin-impregnated central venous catheters:A prospective, randomized, double-blind, controlled, multicentertrial. Intensive Care Med 2004; 30:1891–9

18. Thornton J, Todd NJ, Webster NR: Central venous linesepsis in the intensive care unit: A study comparing antibi-otic coated catheters with plain catheters. Anaesthesia1996; 51:1018 –20

19. Raad I, Darouiche R, Dupuis J, Abi-Said D, Gabrielli A,Hachem R, Wall M, Harris R, Jones J, Buzaid A, Robertson C,Shenaq S, Curling P, Burke T, Ericsson C: Central venouscatheters coated with minocycline and rifampin for theprevention of catheter-related colonization and blood-stream infections: A randomized, double-blind trial. TheTexas Medical Center Catheter Study Group. Ann InternMed 1997;127:267–74

20. Bong JJ, Kite P, Wilco MH, McMahon MJ: Prevention ofcatheter related bloodstream infection by silver iontopho-retic central venous catheters: A randomised controlledtrial. J Clin Pathol 2003; 56:731–5

21. Boswald M, Lugauer S, Regenfus A, Braun GG, Martus P,Geis C, Scharf J, Bechert T, Greil J, Guggenbichler J-P:Reduced rates of catheter-associated infection by use of anew silver-impregnated central venous catheter. Infection1999;27:56 – 60

22. Hagau N, Studnicska D, Gavrus RL, Csipak G, Hagau R, Slav-covici AV: Central venous catheter colonization and catheter-related bloodstream infections in critically ill patients: A com-parison between standard and silver-integrated catheters. EurJ Anaesthesiol 2009; 26:752–8

23. Harter C, Salwender HJ, Bach A, Egerer G, Goldschmidt H, HoAD: Catheter-related infection and thrombosis of the internaljugular vein in hematologic-oncologic patients undergoingchemotherapy: A prospective comparison of silver-coated anduncoated catheters. Cancer 2002; 94:245–51

24. Kalfon P, de Vaumas C, Samba D, Boulet E, Lefrant JY,Eyraud D, Lherm T, Santoli F, Naija W, Riou B: Comparisonof silver-impregnated with standard multi-lumen centralvenous catheters in critically ill patients. Crit Care Med2007; 35:1032–9

25. Bach A, Schmidt H, Bttiger B, Schreiber B, Bhrer H, Motsch J,Martin E, Sonntag HG: Retention of antibacterial activity andbacterial colonization of antiseptic-bonded central venouscatheters. J Antimicrob Chemother 1996; 37:315–22

26. Brun-Buisson C, Doyon F, Sollet JP, Cochard JF, Cohen Y,Nitenberg G: Prevention of intravascular catheter-relatedinfection with newer chlorhexidine-silver sulfadiazine-coated catheters: A randomized controlled trial. IntensiveCare Med 2004; 30:837– 43

27. Ciresi DL, Albrecht RM, Volkers PA, Scholten DJ: Failure ofantiseptic bonding to prevent central venous catheter-relatedinfection and sepsis. Am Surg 1996; 62:641–6

28. Collin GR: Decreasing catheter colonization through the useof an antiseptic-impregnated catheter: A continuous qualityimprovement project. Chest 1999; 115:1632–40

29. George SJ, Vuddamalay P, Boscoe MJ: Antiseptic-impreg-nated central venous catheters reduce the incidence ofbacterial colonization and associated infection in immuno-compromised transplant patients. Eur J Anaesthesiol 1997;14:428 –31

30. Hannan M, Juste RN, Umasanker S, Glendenning A, Night-ingale C, Azadian B, Soni N: Antiseptic-bonded central ve-nous catheters and bacterial colonisation. Anaesthesia1999; 54:868 –72

31. Heard SO, Wagle M, Vijayakumar E, McLean S, Bruegge-mann A, Napolitano LM, Edwards LP, O’Connell FM, PuyanaJC, Doern GV: Influence of triple-lumen central venouscatheters coated with chlorhexidine and silver sulfadiazineon the incidence of catheter-related bacteremia. Arch In-tern Med 1998; 158:81–7

32. Maki DG, Stolz SM, Wheeler S, Mermel LA: Prevention ofcentral venous catheter-related bloodstream infection by useof an antiseptic-impregnated catheter. A randomized, con-trolled trial. Ann Intern Med 1997; 127:257–66

33. Ostendorf T, Meinhold A, Harter C, Salwender H, Egerer G,Geiss HK, Ho AD, Goldschmidt H: Chlorhexidine and silver-sulfadiazine coated central venous catheters in haematologicalpatients–a double-blind, randomised, prospective, controlledtrial. Support Care Cancer 2005; 13:993–1000

34. Rupp ME, Lisco SJ, Lipsett PA, Perl TM, Keating K, CivettaJM, Mermel LA, Lee D, Dellinger EP, Donahoe M, Giles D,Pfaller MA, Maki DG, Sherertz R: Effect of a second-gener-ation venous catheter impregnated with chlorhexidine andsilver sulfadiazine on central catheter-related infections: Arandomized, controlled trial. Ann Intern Med 2005; 143:570 – 80

35. Tennenberg S, Lieser M, McCurdy B, Boomer G, HowingtonE, Newman C, Wolf I: A prospective randomized trial of anantibiotic- and antiseptic-coated central venous catheter inthe prevention of catheter-related infections. Arch Surg1997; 132:1348 –51

36. van Heerden PV, Webb SAR, Fong S, Golledge CL, RobertsBL: Central venous catheters revisited: Infection rates andan assessment of the new fibrin analysing system brush.Anaesth Intens Care 1996; 24:330 –3

37. Logghe C, Van Ossel C, D’Hoore W, Ezzedine H, Wauters G,Haxhe JJ: Evaluation of chlorhexidine and silver-sulfadiazineimpregnated central venous catheters for the prevention ofbloodstream infection in leukaemic patients: A randomizedcontrolled trial. J Hosp Infect 1997; 37:145–56

38. Pemberton LB, Ross V, Cuddy P, Kremer H, Fessler T,McGurk E: No difference in catheter sepsis between stan-dard and antiseptic central venous catheters. A prospectiverandomized trial. Arch Surg 1996; 131:986 –9

39. Oda T, Hamasaki J, Kanda N, Mikami K: Anaphylactic shockinduced by an antiseptic-coated central venous catheter.ANESTHESIOLOGY 1997; 87:1242– 4

40. Stephens R, Mythen M, Kallis P, Davies DW, Egner W, RickardsA: Two episodes of life-threatening anaphylaxis in the samepatient to a chlorhexidine-sulphadiazine-coated central ve-nous catheter. Br J Anaesth 2001; 87:306–8

41. Terazawa E, Shimonaka H, Nagase K, Masue T, Dohi S:Severe anaphylactic reaction due to a chlorhexidine-im-pregnated central venous catheter. ANESTHESIOLOGY 1998;89:1296 – 8

42. Merrer J, De Jonghe B, Golliot F, Lefrant JY, Raffy B, BarreE, Rigaud JP, Casciani D, Misset B, Bosquet C, Outin H,Brun-Buisson C, Nitenberg G, French Catheter Study Groupin Intensive Care: Complications of femoral and subclavianvenous catheterization in critically ill patients: A random-ized controlled trial. JAMA 2001; 286:700 –7

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Practice Guidelines


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46. Gowardman JR, Robertson IK, Parkes S, Rickard CM: Influ-ence of insertion site on central venous catheter coloniza-tion and bloodstream infection rates. Intensive Care Med2008; 34:1038 – 45

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48. McKinley S, Mackenzie A, Finfer S, Ward R, Penfold J:Incidence and predictors of central venous catheter relatedinfection in intensive care patients. Anaesth Intensive Care1999; 27:164 –9

49. Ramos GE, Bolgiani AN, Patio O, Prezzavento GE,Guastavino P, Durlach R, Fernandez Canigia LB, Benaim F:Catheter infection risk related to the distance betweeninsertion site and burned area. J Burn Care Rehabil 2002;23:266 –71

50. Levy I, Katz J, Solter E, Samra Z, Vidne B, Birk E, AshkenaziS, Dagan O: Chlorhexidine-impregnated dressing for pre-vention of colonization of central venous catheters in in-fants and children: A randomized controlled study. PediatrInfect Dis J 2005; 24:676 –9

51. Roberts B, Cheung D: Biopatch: A new concept in antimi-crobial dressings for invasive devices. Aust Crit Care 1998;11:16 –9

52. Timsit JF, Schwebel C, Bouadma L, Geffroy A, Garrouste-Orgeas M, Pease S, Herault MC, Haouache H, Calvino-Gunther S, Gestin B, Armand-Lefevre L, Leflon V, ChaplainC, Benali A, Francais A, Adrie C, Zahar JR, Thuong M,Arrault X, Croize J, Lucet JC, Dressing Study Group: Chlo-rhexidine-impregnated sponges and less frequent dressingchanges for prevention of catheter-related infections incritically ill adults: A randomized controlled trial. JAMA2009; 301:1231– 41

53. Madeo M, Martin CR, Turner C, Kirkby V, Thompson DR: Arandomized trial comparing Arglaes (a transparent dressingcontaining silver ions) to Tegaderm (a transparent polyure-thane dressing) for dressing peripheral arterial cathetersand central vascular catheters. Intensive Crit Care Nurs1998; 14:187–91

54. Garland JS, Alex CP, Mueller CD, Otten D, Shivpuri C, HarrisMC, Naples M, Pellegrini J, Buck RK, McAuliffe TL, GoldmannDA, Maki DG: A randomized trial comparing povidone-iodineto a chlorhexidine gluconate-impregnated dressing for preven-tion of central venous catheter infections in neonates. Pediat-rics 2001; 107:1431–6

55. Moro ML, Vigano EF, Cozzi Lepri A: Risk factors for centralvenous catheter-related infections in surgical and intensivecare units: The Central Venous Catheter-Related InfectionsStudy Group. Infect Control Hosp Epidemiol 1994; 15:253– 64

56. Bonawitz SC, Hammell EJ, Kirkpatrick JR: Prevention ofcentral venous catheter sepsis: A prospective randomizedtrial. Am Surg 1991; 57:618 –23

57. Kowalewska-Grochowska K, Richards R, Moysa GL, Lam K,Costerton JW, King EG: Guidewire catheter change in cen-tral venous catheter biofilm formation in a burn population.Chest 1991; 100:1090 –5

58. Cobb DK, High KP, Sawyer RG, Sable CA, Adams RB, Lindley

DA, Pruett TL, Schwenzer KJ, Farr BM: A controlled trial ofscheduled replacement of central venous and pulmonary-ar-tery catheters. N Engl J Med 1992; 327:1062–8

59. Eyer S, Brummitt C, Crossley K, Siegel R, Cerra F: Catheter-related sepsis: Prospective, randomized study of threemethods of long-term catheter maintenance. Crit Care Med1990; 18:1073–9

60. Kealey GP, Chang P, Heinle J, Rosenquist MD, Lewis RW:Prospective comparison of two management strategies ofcentral venous catheters in burn patients. J Trauma 1995;38:344 –9

61. Michel LA, Bradpiece HA, Randour P, Pouthier F: Safety ofcentral venous catheter change over guidewire for sus-pected catheter-related sepsis. A prospective randomizedtrial. Int Surg 1988; 73:180 – 6

62. Snyder RH, Archer FJ, Endy T, Allen TW, Condon B, KaiserJ, Whatmore D, Harrington G, McDermott CJ: Catheterinfection: A comparison of two catheter maintenance tech-niques. Ann Surg 1988; 208:651–3

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65. Lucet JC, Hayon J, Bruneel F, Dumoulin JL, Joly-Guillou ML:Microbiological evaluation of central venous catheter ad-ministration hubs. Infect Control Hosp Epidemiol 2000;21:40 –2

66. Ybenes JC, Vidaur L, Serra-Prat M, Sirvent JM, Batlle J, MotjeM, Bonet A, Palomar M: Prevention of catheter-relatedbloodstream infection in critically ill patients using a disin-fectable, needle-free connector: A randomized controlledtrial. Am J Infect Control 2004; 32:291–5

67. Kaiser CW, Koornick AR, Smith N, Soroff HS: Choice ofroute for central venous cannulation: Subclavian or internaljugular vein? A prospective randomized study. J Surg Oncol1981; 17:345–54

68. Eisenhauer ED, Derveloy RJ, Hastings PR: Prospective eval-uation of central venous pressure (CVP) catheters in a largecity-county hospital. Ann Surg 1982; 196:560

69. Molgaard O, Nielsen MS, Handberg BB, Jensen JM, Kjaer-gaard J, Juul N: Routine X-ray control of upper centralvenous lines: Is it necessary? Acta Anaesthesiol Scand 2004;48:685–9

70. Sznajder JI, Zveibil FR, Bitterman H, Weiner P, Bursztein S:Central vein catheterization: Failure and complication ratesby three percutaneous approaches. Arch Intern Med 1986;146:259 – 61

71. Armstrong PJ, Sutherland R, Scott DH: The effect of posi-tion and different manoeuvres on the internal jugular veindiameter size. Acta Anaesth Scand 1994; 38:229 –31

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73. Modeliar SS, Sevestre MA, de Cagny B, Slama M: Ultrasoundevaluation of central veins in the intensive care unit: Effects ofdynamic manoeuvres. Intensive Care Med 2008; 34:333–8

74. Parry G: Trendelenburg position, head elevation and a mid-line position optimize right internal jugular vein diameter.Can J Anaesth 2004; 51:379 – 81

75. Suarez T, Baerwald JP, Kraus C: Central venous access: Theeffects of approach, position, and head rotation on internaljugular vein cross-sectional area. Anesth Analg 2002; 95:1519 –24

76. Tugrul M, Camci E, Pembeci K, Al-Darsani A, Telci L: Relation-

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ship between peripheral and central venous pressures in dif-ferent patient positions, catheter sizes, and insertion sites.J Cardiothorac Vasc Anesthesia 2004; 18:446–50

77. Sayin MM, Mercan A, Koner O, Ture H, Celebi S, Sozubir S,Aykac B: Internal jugular vein diameter in pediatric pa-tients: Are the J-shaped guidewire diameters bigger thaninternal jugular vein? An evaluation with ultrasound Paedi-atr Anaesth 2008; 18:745–51

78. Brown CQ: Inadvertent prolonged cannulation of the ca-rotid artery. Anesth Analg 1982; 61:150 –2

79. Digby S: Fatal respiratory obstruction following insertion ofa central venous line. Anaesthesia 1994; 49:1013– 4

80. Guilbert MC, Elkouri S, Bracco D, Corriveau MM, BeaudoinN, Dubois MJ, Bruneau L, Blair JF: Arterial trauma duringcentral venous catheter insertion: Case series, review andproposed algorithm. J Vasc Surg 2008; 48:918 –25, discus-sion 925

81. Farhat K, Nakhjavan K, Cope C, Yazdanfar S, Fernandez J,Gooch A, Goldberg H: Iatrogenic arteriovenous fistula: Acomplicaton of percutaneous subclavian vein puncture.Chest 1975; 67:480 –2

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93. Mansfield PF, Hohn DC, Fornage BD, Gregurich MA, OtaDM: Complications and failures of subclavian-vein catheter-ization. N Engl J Med 1994; 331:1735– 8

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95. Cajozzo M, Quintini G, Cocchiera G, Greco G, Vaglica R,Pezzano G, Barbera V, Modica G: Comparison of centralvenous catheterization with and without ultrasound guide.Transfus Apher Sci 2004; 31:199 –202

96. Grebenik CR, Boyce A, Sinclair ME, Evans RD, Mason DG,Martin B: NICE guidelines for central venous catheterizationin children. Is the evidence base sufficient? Br J Anaesth2004; 92:827–30

97. Karakitsos D, Labropoulos N, De Groot E, Patrianakos AP,Kouraklis G, Poularas J, Samonis G, Tsoutsos DA, Konsta-doulakis MM, Karabinis A: Real-time ultrasound-guided cath-eterisation of the internal jugular vein: A prospective com-parison with the landmark technique in critical carepatients. Crit Care 2006; 10:R162

98. Koroglu M, Demir M, Koroglu BK, Sezer MT, Akhan O,Yildiz H, Yavuz L, Baykal B, Oyar O: Percutaneous place-ment of central venous catheters: Comparing the anatomi-cal landmark method with the radiologically guided tech-nique for central venous catheterization through theinternal jugular vein in emergency hemodialysis patients.Acta Radiol 2006; 47:43–7

99. Mallory DL, McGee WT, Shawker TH, Brenner M, Bailey KR,Evans RG, Parker MM, Farmer JC, Parillo JE: Ultrasoundguidance improves the success rate of internal jugular veincannulation: A prospective, randomized trial. Chest 1990;98:157– 60

100. Slama M, Novara A, Safavian A, Ossart M, Safar M, Fagon JY:Improvement of internal jugular vein cannulation using anultrasound-guided technique. Intensive Care Med 1997; 23:916 –9

101. Teichgrber UKM, Benter T, Gebel M, Manns MP: A sono-graphically guided technique for central venous access. AJRAm J Roentgenol 1997; 169:731–3

102. Troianos CA, Jobes DR, Ellison N: Ultrasound-guided can-nulation of the internal jugular vein: A prospective, ran-domized study. Anesth Analg 1991; 72:823– 6

103. Verghese ST, McGill WA, Patel RI, Sell JE, Midgley FM,Ruttimann UE: Comparison of three techniques for internaljugular vein cannulation in infants. Paediatr Anaesth 2000;10:505–11

104. Verghese ST, McGill WA, Patel RI, Sell JE, Midgley FM,Ruttimann UE: Ultrasound-guided internal jugular venouscannulation in infants: A prospective comparison with thetraditional palpation method. ANESTHESIOLOGY 1999; 91:71–7

105. Gualtieri E, Deppe SA, Sipperly ME, Thompson DR: Subcla-vian venous catheterization: Greater success rate for lessexperienced operators using ultrasound guidance. Crit CareMed 1995; 23:692–7

106. Fragou M, Gravvanis A, Dimitriou V, Papalois A, Kouraklis G,Karabinis A, Saranteas T, Poularas J, Papanikolaou J, DavlourosP, Labropoulos N, Karakitsos D: Real-time ultrasound-guidedsubclavian vein cannulation versus the landmark method incritical care patients: A propsective randomized study. CritCare Med 2011; 39:1607–12

107. Aouad MT, Kanazi GE, Abdallah FW, Moukaddem FH, Tur-bay MJ, Obeid MY, Siddik-Sayyid SM: Femoral vein cannu-lation performed by residents: A comparison between ul-trasound-guided and landmark technique in infants andchildren undergoing cardiac surgery. Anesth Analg 2010;111:724 – 8

108. Ezaru CS, Mangione MP, Oravitz TM, Ibinson JW, Bjerke RJ:Eliminating arterial injury during central venous catheteriza-tion using manometry. Anesth Analg 2009; 109:130–4

109. Gillman LM, Blaivas M, Lord J, Al-Kadi A, Kirkpatrick W:Ultrasound confirmation of guidewire position may elimi-nate accidental arterial dilatation during central venouscannulation. Scand J Trauma 2010; 18:39

110. Gu X, Paulsen W, Tisnado J, He Y, Li Z, Nixon JV: Malpo-

Practice Guidelines


sition of a central venous catheter in the right main pulmo-nary artery detected by transesophageal echocardiography.J Am Soc Echocardiogr 2009; 22:1420

111. Mahmood F, Sundar S, Khabbaz K: Misplacement of a guide-wire diagnosed by transesophageal echocardiography.J Cardiothorac Vasc Anesth 2007; 21:420 –1

112. Sawchuk C, Fayad A: Confirmation of internal jugular guidewire position utilizing transesophageal echocardiography.Can J Anaesth 2001; 48:688 –90

113. Janik JE, Cothren CC, Janik JS, Hendrickson RJ, Bensard DD,Partrick DA, Karrer FM: Is a routine chest x-ray necessaryfor children after fluoroscopically assisted central venousaccess? J Pediatr Surg 2003; 38:1199 –202

114. Lucey B, Varghese JC, Haslam P, Lee MJ: Routine chestradiographs after central line insertion: Mandatory postpro-cedural evaluation or unnecessary waste of resources? Car-diovasc Intervent Radiol 1999; 22:381– 4

115. Gebhard RE, Szmuk P, Pivalizza EG, Melnikov V, Vogt C,Warters RD: The accuracy of electrocardiogram-controlledcentral line placement. Anesth Analg 2007; 104:65–70

116. Abood GJ, Davis KA, Esposito TJ, Luchette FA, Gamelli RL:Comparison of routine chest radiograph versus clinicianjudgment to determine adequate central line placement incritically ill patients. J Trauma 2007; 63:50–6

117. Amshel CE, Palesty JA, Dudrick SJ: Are chest X-rays mandatoryfollowing central venous recatheterization over a wire? AmSurg 1998; 64:499–501; discussion 501–2

118. Bailey SH, Shapiro SB, Mone MC, Saffle JR, Morris SE, BartonRG: Is immediate chest radiograph necessary after centralvenous catheter placement in a surgical intensive care unit?Am J Surg 2000; 180:517–21; discussion 521–2

119. Cullinane DC, Parkus DE, Reddy VS, Nunn CR, RutherfordEJ: The futility of chest roentgenograms following routinecentral venous line changes. Am J Surg 1998; 176:283–5

120. Frassinelli P, Pasquale MD, Cipolle MD, Rhodes M: Utilityof chest radiographs after guidewire exchanges ofcentral venous catheters. Crit Care Med 1998; 26:611–5

121. Lessnau KD: Is chest radiography necessary after uncom-plicated insertion of a triple-lumen catheter in the rightinternal jugular vein, using the anterior approach? Chest2005; 127:220 –3

122. Maury E, Guglielminotti J, Alzieu M, Guidet B, Offenstadt G:Ultrasonic examination: An alternative to chest radiography

after central venous catheter insertion? Am J Respir CritCare Med 2001; 164:403–5

123. Riblet JL, Shillinglaw W, Goldberg AJ, Mitchell K, SedaniKH, Davis FE, Reynolds HN: Utility of the routine chestX-ray after “over-wire” venous catheter changes. Am Surg1996; 62:1064 –5

124. Weil BR, Ladd AP, Yoder K: Pericardial effusion and cardiactamponade associated with central venous catheters in chil-dren: An uncommon but serious and treatable condition.J Pediatr Surg 2010; 45:1687–92

125. Wirsing M, Schummer C, Neumann R, Steenbeck J, SchmidtP, Schummer W: Is traditional reading of the bedside chestradiograph appropriate to detect intraatrial central ve-nous catheter position? Chest 2008; 134:527–33

126. Francis KR, Picard DL, Fajardo MA, Pizzi WF: Avoidingcomplications and decreasing costs of central venous cath-eter placement utilizing electrocardiographic guidance.Surg Gynecol Obstet 1992; 175:208 –11

127. McGee WT, Ackerman BL, Rouben LR, Prasad VM, Bandi V,Mallory DL: Accurate placement of central venous cathe-ters: A prospective, randomized, multicenter trial. Crit CareMed 1993; 21:1118 –23

128. O’Grady NP, Alexander M, Burns LA, Dellinger EP, Garland J,Heard SO, Lipsett PA, Masur H, Mermel LA, Pearson ML, RaadII, Randolph AG, Rupp ME, Saint S, Healthcare Infection Con-trol Practices Advisory Committee. Guidelines for the preven-tion of intravascular catheter related infections. Am J InfectControl 2011; 39(4 Suppl 1):S1–34

129. Marschall J, Mermel LA, Classen D, Arias KM, Podgorny K, An-derson DJ, Burstin H, Calfee DP, Coffin SE, Dubberke ER, FraserV, Gerding DN, Griffin FA, Gross P, Kaye KS, Klompas M, Lo E,Nicolle L, Pegues DA, Perl TM, Saint S, Salgado CD, Weinstein RA,Wise R, Yokoe DS: Strategies to prevent central line-associatedbloodstream infections in acute care hospitals. Infect ControlHosp Epidemiol 2008; 29(Suppl 1):S22–30

130. Institute for Healthcare Improvement: Prevent Central LineInfections How-to Guide. Cambridge, MA; 2008

131. The Joint Commission Accreditation Program: Hospital: Na-tional patient safety goals. http://www.jointcommission.org/assets/1/6/2011_NPSGs_HAP.pdf. Accessed January 1,2011

132. National Institute for Clinical Excellence: Guidance on the use ofultrasound locating devices for placing central venous catheters.http://www.nice.org.uk/nicemedia/pdf/49_English_patient.pdf. Accessed September 2012

SPECIAL ARTICLES


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European Journal of Radiology 76 (2010) 20–23

Contents lists available at ScienceDirect

European Journal of Radiology

journa l homepage: www.e lsev ier .com/ locate /e j rad

adiation protection of medical staff

ohn Le Herona,∗, Renato Padovanib, Ian Smithc, Renate Czarwinskia

Radiation Safety & Monitoring Section, Division of Radiation, Transport and Waste Safety,nternational Atomic Energy Agency, Wagramer Strasse 5, P.O. Box 100, 1400 Vienna, AustriaMedical Physics Department, University Hospital, Udine, ItalySt Andrew’s Medical Institute, St Andrew’s War Memorial Hospital, Brisbane, Australia

r t i c l e i n f o

rticle history:eceived 14 June 2010ccepted 15 June 2010

eywords:adiation protection

a b s t r a c t

The continuing increase in the worldwide use of X-ray imaging has implications for radiation protection ofmedical staff. Much of the increased usage could be viewed as simply a workload issue with no particularnew challenges. However, advances in technology and developments in techniques have seen an increasein the number of X-ray procedures in which medical personnel need to maintain close physical contactwith the patient during radiation exposures. The complexity of many procedures means the potential

ccupational exposuremage-guided interventional proceduresrotective toolsrotective clothingonitoring

for significant occupational exposure is high, and appropriate steps must be taken to ensure that actualoccupational exposures are as low as reasonably achievable. Further attention to eye protection may benecessitated if a lowering of the dose limit for the lens of the eye is implemented in the near future.

Education and training in radiation protection as it applies to specific situations, established workingprocedures, availability and use of appropriate protective tools, and an effective monitoring programmeare all essential elements in ensuring that medical personnel in X-ray imaging are adequately and accept-
ably protected.
. Introduction

The use of radiation in medical applications continues toncrease worldwide. Latest UNSCEAR estimates suggest that therere about 4 billion X-ray examinations per year, worldwide [1]. Allhese procedures need to be performed by medical personnel withhe accompanying potential for occupational radiation exposure.oes the increasing demand for X-ray imaging have implications

or radiation protection of medical staff? The increasing usage coulde viewed as simply a workload issue with no particular new chal-

enges. However, there is also a change in the types of X-ray imagingrocedures being performed and by whom – procedures requiringersonnel to be close to the patient, and these procedures presentchallenge to ensure appropriate radiation protection of medical

taff.The term X-ray imaging is used in this paper to cover both

iagnostic radiology and image-guided interventional procedures.
ccupational radiation protection is achieved by application of the
hree ICRP principles of justification, optimization and dose lim-tation [2]. In practice, to afford radiation protection for medicaltaff in X-ray imaging, it is the application of optimization and

∗ Corresponding author. Tel.: +43 1 2600 21416.E-mail addresses: [email protected] (J. Le Heron),

[email protected] (R. Padovani), [email protected]. Smith), [email protected] (R. Czarwinski).

720-048X/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved.oi:10.1016/j.ejrad.2010.06.034

© 2010 Elsevier Ireland Ltd. All rights reserved.

dose limitation that is arguably the most important. However, itshould be recognized that the lack of rigorous application of thejustification principle is resulting in the performance of significantnumbers of unnecessary X-ray imaging examinations, and theseadd to occupational exposure.

This paper cannot cover all the aspects of radiation protectionof medical staff, but instead focuses more on the challenges in thenever ending story of occupational radiation protection, includinga brief discussion of factors that determine the level of occupationalexposure in X-ray imaging, the implications of recent trends in X-ray imaging for occupational radiation protection, and the basis forensuring effective radiation protection of medical staff in the lightof these new developments.

2. What determines the level of occupational exposure inX-ray imaging?

The level of occupational exposure associated with X-ray imag-ing procedures is highly variable and ranges from potentiallynegligible in the case of simple chest X-rays, to significant for com-plex interventional procedures. What are the reasons for this? From
the occupational perspective, there are two “sources” of radiationexposure. Clearly the X-ray tube is the true source of radiation,but in practice there should be very few situations in which per-sonnel have the potential to be directly exposed to the primarybeam. This leaves the other “source”, which is the patient. Interac-
dx.doi.org/10.1016/j.ejrad.2010.06.034

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ion of the primary X-ray beam with the part of the patient’s bodyeing imaged produces scattered radiation, which emanates fromhe patient in all directions. So, in most cases, the main determinantor occupational exposure is proximity of personnel to the patienthen exposures are being made. Furthermore, the level of scat-

er is determined largely by the dose to the patient, resulting in anmportant corollary that reducing the patient dose to the minimumecessary to achieve the required medical outcome also lowersotential occupational exposures. A common and useful maxim ishat when personnel take care of the patient, they will also takeare of their occupational exposure.

.1. Working at some distance from the patient

For many situations, such as radiography, mammography andeneral CT, there is usually no need for personnel to be physi-ally close to the patient. This provides two opportunities to affordood occupational radiation protection. First, being distant from theatient reduces the levels of scatter reaching personnel. Divergencef the scattered X-rays from the patient results in radiation inten-ities falling off rapidly with distance. This is the so-called “inversequare law” where, for example, a doubling of the distance resultsn a four-fold reduction in radiation intensity.

The second factor is that structural shielding can be placedetween the patient and personnel. For example, shielding maye incorporated into the wall and window of the control roomarrier, resulting in negligible levels of scatter reaching personnel.ppropriate room design with shielding specification by a medicalhysicist or radiation protection expert (RPE) also should ensurehat occupational exposure will be essentially zero for these X-raymaging situations.

.2. Working close to the patient

There are some situations, typically in fluoroscopic examina-ions and in image-guided interventional procedures, where it isecessary to maintain close physical contact with the patient whenadiation is being used. Distance and structural shielding are notptions, so what can be done for these personnel?

Scattered radiation can be attenuated by protective cloth-ng worn by personnel, such as aprons, spectacles, and thyroidhields, and by protective tools, such as ceiling-suspended pro-ective screens or table-mounted protective curtains or wheeledcreens, which are able to be placed between the patient and per-onnel. Depending on its lead equivalence and the energy of the-rays, an apron will attenuate 90% or more of the incident scat-

ered radiation. Protective aprons come in different thicknesses andhapes, ranging from the simple front-only apron to a full coat: theormer being effective only if the wearer is always facing the sourcef the scattered radiation.

The lens of the eye is highly radiation sensitive. For per-ons working close to the patient, doses to the eyes can becomenacceptably high. Wearing protective eyewear, particularly those

ncorporating side protection, can reduce the dose to the eyes fromcatter by 90%, but to achieve maximum effectiveness, careful con-ideration needs to be given to issues such as the placement of theiewing monitor to ensure the eyewear intercepts the scatter fromhe patient. It is likely that measures to protect the eyes will receiveurther attention if the dose limit for the lens of the eye is lowereds a result of a review of current scientific evidence [2].

There are some situations, usually associated with image-
uided interventional procedures, when the hands of the operatoray inadvertently be placed in the primary X-ray beam. Protective
loves may appear to be indicated, but such gloves can prove toe counter-productive as their presence in the primary beam leadso an automatic increase in the radiation dose rate, offsetting any

of Radiology 76 (2010) 20–23 21

protective value. Gloves also may slow down the procedure andengender a false sense of safety: it is much better to train person-nel to keep their hands out of the primary beam. Ensuring the X-raytube is under the table provides the best protection when the handsmust be near the X-ray field, as the primary beam is then attenuatedby the patient’s body.

Ceiling-suspended protective screens can provide significantprotection, but their effectiveness depends on them being posi-tioned correctly. Screens provide protection to only part of the body(typically the upper body, head and eyes) and their use is additionalto wearing protective clothing. Sometimes a protective screen can-not be deployed for clinical reasons. Table-mounted protectivecurtains also provide additional shielding, typically to the lowerbody and legs. A further option for complex image-guided inter-ventional procedures is the use of disposable protective patientdrapes. These are attenuating drapes placed on the patient afterthe operative site has been prepared.

Because radiological workloads can be very different for the dif-ferent specialties, the necessary protective tools should be specifiedby a medical physicist or a RPE. For example, a person with a highworkload in a cardiac laboratory should use all the described pro-tective tools, while a person in an orthopedic suite may need onlya simple front-only protective apron.

Many factors can influence how fluoroscopic examinations andimage-guided interventional procedures are performed, and hencethe patient dose and occupational exposure. It is therefore essen-tial that personnel performing such procedures have had effectivetraining in radiation protection so they understand the implicationsof these factors. Moreover, because of the wide variability in poten-tial occupational exposures from these procedures, it is also crucialthat personal monitoring is performed continuously and correctly.Both these aspects are discussed in this chapter.

3. Implications of recent trends in X-ray imaging formedical staff

In the area of radiography, including mammography, there hasbeen a shift from film-based to digital systems. Patient dosesremain broadly similar, but patient throughput for a given imagingroom may have increased. Overall, the implications for occupa-tional radiation protection have been minimal.

CT imaging has seen the advent of multi-detector CT scanners(MDCT). Again, depending on how well imaging protocols havebeen optimized, patient doses are broadly similar to their singleslice antecedents and future trend are likely to lower patient dosesas manufacturers continue to introduce more dose-saving features.Image acquisition is considerably faster and usage of CT is increas-ing, resulting in higher workloads in the CT room. This has oftenresulted in a need for increased structural shielding to maintainacceptable standards of occupational radiation protection.

New technologies and techniques have also allowed the per-formance of complex diagnostic and interventional procedureswith the advantage of avoiding more risky surgical interventionsin several cases. These procedures present several challenges forradiation protection of medical staff.

3.1. CT-fluoroscopy

CT-fluoroscopy facilitates the performance of biopsies by gen-erating live tomographic images to better guide the intervention.
However, as the interventionalist is very near to the patient, thereis the potential for the hands to be exposed to the primary beamand hand doses of up to 0.6 mSv for a procedure lasting only 20 shave been reported [3]. Without protective measures, dose limits(see Table 1) for the hands could easily be exceeded.

22 J. Le Heron et al. / European Journal

Table 1Recommended dose limits for occupational exposure in X-ray imaging (adaptedfrom ICRP[2]).

Dose quantity Occupational dose limita

Effective dose 20 mSv per year averaged over 5 consecutiveyears (100 mSv in 5 years), and 50 mSv in anysingle year

Equivalent dose in:Lens of the eyeb 150 mSv in a yearSkinc 500 mSv in a yearHands and feet 500 mSv in a year

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a Dose limits can be different in national regulations.b This limit is currently being reviewed by an ICRP Task Group.c Averaged over 1 cm2 of the most highly irradiated area of the skin.

.2. Interventional radiology and cardiology

In interventional radiology or cardiology the main operatorstay very close to the patient table where the intensity of scatteredadiation can be very high. For example, in a cardiology procedurehen the X-ray tube is under the table, the dose rate of incident

cattered radiation at the position of the operator can typicallyange from around 0.5 to 10 mSv/h, from head height down towardshe legs. It is easy to see how cumulative doses can exceed doseimits and reach hundreds of mSv per year if protective measures

ere not taken, as described briefly in Section 2.2. This is describedore comprehensively, in the case of interventional radiology, in

he recent guidelines on occupational radiation protection pub-ished by the Cardiovascular and Interventional Radiology Societyf Europe and the Society of Interventional Radiology [4].

.3. Image-guided procedures outside radiology departments

Many fluoroscopy-guided procedures today are performed out-ide radiology departments, using mobile C-arm or O-arm unitsn, for example, orthopaedic, gastroenterology, urology, and vas-ular operating theatres. The use of radiation in these proceduresan range from very short fluoroscopy times (<0.5 min for a typi-al orthopaedic procedure) to very long fluoroscopy times, such as0–90 min for an aortic aneurysm treatment. The main issue is thathe non-radiologist specialists and nurses involved in these proce-ures are often outside the umbrella of the radiology department,nd hence may not receive adequate training (including training inadiation protection) in the use of modern equipment, which allowsot only simple fluoroscopy, but also pulsed fluoroscopy, digitalcquisition, angiography and digital subtraction angiography.

. Ensuring effective radiation protection of medical staff

A radiation protection programme (RPP) is one means ofmplementing occupational radiation protection by the adoptionf appropriate management structures, policies, procedures andrganizational arrangements. For medical staff in X-ray imaging,opics would include the need for local rules and procedures forersonnel to follow, arrangements for the provision of personalrotective equipment, a programme for education and training inadiation protection, arrangements for individual monitoring, andethods for periodically reviewing and auditing the performance

f the RPP. The following sections describe aspects of two of theseopics. Further details on RPPs can be found in the BSS [5], andAEA SRS No 39 [6].

.1. Radiation protection training

Education and training underpin the implementation of radi-tion protection in practice, and most countries have regulatory

of Radiology 76 (2010) 20–23

requirements for such training. In X-ray imaging, personnel needtraining not only in occupational radiation protection, but also inpatient radiation protection as the latter can influence occupationalexposure. Guidance has been published on what the training formedical staff should cover, such as by the European Commission [7].Several resources for training are freely available, including IAEAmaterial for diagnostic and interventional radiology and cardiology[8], and the MARTIR project (multimedia tool for training in inter-ventional radiology) [9], which is particularly useful for distancelearning purposes.

For the reasons noted previously, it is crucial that programmesfor radiation protection training in hospital settings include thosemedical personnel who are outside the radiology department butwho are involved in X-ray imaging procedures.

4.2. Monitoring of occupational exposure in X-ray imaging

Occupational exposure is subject to dose limits as given inTable 1, established to ensure that the risks arising from occupa-tional exposure are not unacceptable [2]. The dose limit expressedas effective dose addresses cancers and hereditary effects, while theother dose limits (in terms of equivalent dose) are to prevent radi-ation effects in particular tissues or areas of the body. In addition,the application of the principle of optimization of protection shouldensure that occupational doses to medical staff in X-ray imaging areas low as reasonably achievable (ALARA principle), and typicallywell below the dose limits.

The purpose of individual radiation monitoring is to ensure thedose limits are not exceeded. Further, through regular review, theresults of individual monitoring are used to assess the effectivenessof strategies for optimization. It is always hoped that the monitor-ing results confirm that good practice is taking place.

Estimates of effective dose and equivalent dose can be madeusing appropriately designed and calibrated dosimeters, such asthose provided by an accredited individual monitoring service,worn by medical personnel when performing X-ray imaging. It isimportant that personal dosimeters are worn correctly. In X-rayimaging this can become complicated, depending on the roles ofthe person being monitored and whether they are sometimes oreven always wearing protective clothing. If a person is normally dis-tant from the patient and is being protected by structural shielding,then wearing a single dosimeter on the front of the torso, betweenthe shoulders and the waist, would normally suffice. However, ifa person is working close to the patient during imaging and iswearing a protective apron, then a single dosimeter worn underthe apron will provide a good estimate of exposure to the shieldedparts of the body, but will underestimate exposure to the organsand tissue outside the apron. In these cases, as dose to the eyes isoften of most concern, it is recommended that two dosimeters areworn, one under the apron and the other outside the apron, oftenat shoulder or collar level. The results of the two dosimeters canbe combined to give a better estimate of effective dose, as well asproviding an estimate for the dose to the eyes.

In some cases in X-ray imaging, monitoring of the fingers andhands may be indicated. This requires special dosimeters, such asring or bracelet dosimeters. It is important to position the dosime-ter in the position most likely to receive the highest exposure. Thismay not be the dominant hand. In all cases of individual monitoring,specific advice from a medical physicist or RPE should be obtained.One of the practical difficulties in individual monitoring is ensuringthat monitored personnel actually always wear their dosimeters
when working with radiation. Incomplete compliance means thata person’s occupational exposure is underestimated and, if this lackof compliance with monitoring is widespread, then doses to thatoccupational group as a whole would also be underestimated. Thereality is that many medical personnel do not always wear their

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osimeters, for a variety of reasons that range from simple neg-igence to deliberate avoidance to ensure that monitored resultsemain below the threshold for administrative or regulatory inves-igation. It is important that monitoring is not viewed negatively,ut rather as a means for adding value to occupational radiationrotection by confirming good practice when this is the case, andor improvement through corrective actions when problems aredentified.

Developments in individual dosimetry may help solve theonitoring compliance issue. For example, technology is being

eveloped that utilises compact personal electronic monitoringevices that wirelessly connect to a base station. Multiple devicesan be monitored simultaneously, so all staff involved in a com-lex imaging procedure can monitor their doses and dose rates ineal-time and use this information to modify their practice if indi-ated. Future technology may even negate the need for dosimetersr devices to be worn by personnel. It is feasible that a person’s loca-ion in a room can be monitored in real-time, and their real-timeccupational exposure calculated from the real-time knowledge ofhe X-ray equipment and how it is being used.

.3. Current occupational doses to medical staff

There is a large number of publications giving occupationaloses per given procedure in X-ray imaging in a given facility,nd others that estimate likely annual doses. UNSCEAR provides aomprehensive source of information on occupational doses world-ide, and in its 2010 report (covering the period 2002–2006) it

oncludes that over 80% of general and CT radiographers did noteceive measurable doses [1], confirming that for personnel whore protected by structural shielding, doses are very low. The reportotes that only a few countries were able to provide data that distin-uished between conventional techniques in diagnostic radiologynd interventional procedures. From these limited data, for con-entional diagnostic radiology the reported mean annual effectiveose was about 0.5 mSv for monitored personnel, while for inter-entional procedures it was about 1.6 mSv. A recent study with data
rom 23 countries gave an average median effective dose for inter-entional cardiologists of 0.7 mSv, averaged per country (Padovanit al., unpublished results). These figures would seem to be under-stimates when compared with published facility-specific data,gain raising the issues of monitoring compliance.
[

[

of Radiology 76 (2010) 20–23 23

5. Conclusions

The continuing increase in the worldwide use of X-ray imagingis creating new challenges for occupational radiation protection ofmedical staff. Advances in technology and developments in tech-niques have seen an increase in the number of X-ray proceduresin which medical personnel must maintain close physical contactwith the patient during radiation exposures. The complexity ofmany procedures means the potential for significant occupationalexposure is high, and appropriate steps must be taken to ensureactual occupational exposures are as low as reasonably achievable.Further attention to eye protection may be necessitated if a low-ering of the dose limit for the lens of the eye is implemented inthe near future. Education and training in radiation protection as itapplies to specific situations, plus established working procedures,availability and use of appropriate protective tools, and an effec-tive monitoring programme are all essential elements in ensuringthat medical staff in X-ray imaging are adequately and acceptablyprotected.

References

1] UNSCEAR 2008 Report: Sources of ionizing radiation, vols. I & II; in press.2] International Commission on Radiological Protection. The 2007 recommen-

dations of the International Commission on Radiological Protection. ICRPPublication 103. Ann ICRP 2007;37:1–332.

3] Stoeckelhuber Beate M, Leibecke T, Schulz E, et al. Radiation dose to the radiol-ogists hand during continuous CT fluoroscopy-guided interventions. CardiovascIntervent Radiol 2005;28:589–94.

4] Miller DL, Vano E, Bartal G, et al. Occupational radiation protection in inter-ventional radiology: a joint guideline of the Cardiovascular and InterventionalRadiology Society of Europe and the Society of Interventional Radiology. Cardio-vasc Intervent Radiol 2010;33:230–9.

5] Food and Agricultural Organization of the United Nations, International AtomicEnergy Agency, International Labour Organization, OECD Nuclear EnergyAgency, Pan American Health Organization, World Health Organization. Inter-national basic safety standards for protection against ionizing radiation and forthe safety of radiation sources. In: Safety Series No. 115. Vienna: IAEA; 1996.

6] International Atomic Energy Agency. Applying radiation safety standards indiagnostic radiology and interventional procedures using X rays. In: SafetyReport Series No. 39. Vienna: IAEA; 2006.

7] European Commission. Radiation protection 116. Guidelines on educationand training in radiation protection for medical exposures. Luxembourg:
Directorate-General for the Environment, European Commission; 2000.
8] Accessible at: http://rpop.iaea.org/RPOP/RPoP/Content/AdditionalResources/Training/1 TrainingMaterial/index.htm.

9] MARTIR. Multimedia and audio-visual radiation protection training in inter-ventional radiology, radiation protection 119. Luxembourg: Office for OfficialPublications of the European Communities; 2002.

http://rpop.iaea.org/RPOP/RPoP/Content/AdditionalResources/Training/1_TrainingMaterial/index.htm

Anesthesiology 2001; 94:239–44 © 2001 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Chlorhexidine versus Povidone Iodine in PreventingColonization of Continuous Epidural Catheters inChildren

A Randomized, Controlled TrialBrian Kinirons, M.D.,* Olivier Mimoz, M.D., Ph.D.,† Leila Lafendi, Pharm.D.,‡ Thierry Naas, Ph.D.,§Jean-François Meunier, M.D.,* Patrice Nordmann, M.D., Ph.D.i

Background: Chlorhexidine is better than povidone iodinefor skin preparation before intravascular device insertion orblood culture collection, but it is not known whether chlorhexi-dine is superior in reducing colonization of continuous epi-dural catheters.

Methods: Children requiring an epidural catheter for postop-erative analgesia longer than 24 h were randomly assigned toreceive skin preparation with an alcoholic solution of 0.5%chlorhexidine or an aqueous solution of 10% povidone iodinebefore catheter insertion. Using surgical aseptic techniques,catheters were inserted into either the lumbar or the thoracicepidural space based on the preferences of the anesthesia team,on clinical indication, or both. Immediately before epiduralcatheter removal, their insertion site and hub were qualitativelycultures. After their removal, the catheter tips were quantita-tively cultured. Catheters were classified as colonized whentheir tips yielded 1,000 or more colony-forming units/ml incultures.

Results: Of 100 randomly assigned patients, 96 were evalu-able. The clinical characteristics of the patients and the riskfactors for infection were similar in the two groups. Catheterswere kept in place for a median (range) duration of 50 (range,21–100) h. Catheters inserted after skin preparation with chlo-rhexidine were one sixth as likely and less quickly to be colo-nized as catheters inserted after skin preparation with povi-done iodine (1 of 52 catheters [0.9 per 100 catheter days] vs. 5 of44 catheters [5.6 per 100 catheter days]; relative risk, 0.2 [95%confidence interval, 0.1–1.0]; P 5 0.02). Coagulase-negativestaphylococci were the only colonizing microorganisms recov-ered, and the skin surrounding the catheter insertion site wasthe origin of all the colonizing microorganisms.

Conclusions: Compared with aqueous povidone iodine, theuse of alcoholic chlorhexidine for cutaneous antisepsis beforeepidural catheter insertion reduces the risk of catheter coloni-zation in children.

THE use of epidural catheters to infuse analgesic agentscontinuously for pain management during the perioper-ative period has becoming an increasingly popular treat-ment method in the pediatric population. Epidural ab-

scess is a recognized complication of the use of suchcatheters. Although rare, epidural abscess can progressrapidly to meningitis, paralysis, or death.1–3

Catheters kept in place for a short time are generallycolonized by skin flora present on the insertion sites,mostly during catheter placement.4 Colonization riskincreases after a threshold level of skin colonizationoccurs.5,6 Thus, effective cutaneous antisepsis beforeepidural insertion may reduce catheter colonization, epi-dural catheter sepsis, and, ultimately, deep spaceinfection.

The French Society for Anesthesiology recommendsthe use of either povidone iodine or chlorhexidine forskin preparation before epidural catheter placement inchildren.7 Iodine tincture is not used in this settingbecause of its possible toxic effects, particularly on thethyroid gland. Although chlorhexidine has been found tobe superior to povidone iodine for skin preparationbefore intravascular catheter insertion8–10 or blood cul-ture collection,11 its value in preventing epidural cathe-ter colonization remains unknown.

The goal of this prospective trial therefore was todetermine if an alcoholic solution of 0.5% chlorhexidineis more effective than an aqueous solution of 10% povi-done iodine in reducing catheter colonization associatedwith short-term epidural catheter placement in children.

Methods

PatientsThe study was conducted between December, 4, 1998

and December 20, 1999 in a 1,000-bed, university-affili-ated hospital in France (Hopital de Bicetre, Le KremlinBicetre). After ethics committee approval (Comite Con-sultatif de Protection des Personnes dans la RechereBiomedicale de l’hopital Ambroise Pare a Boulogne Bil-lancourt) and informed parental written consent, pa-tients younger than 15 yr of age who were to have anepidural catheter placed during surgery for abdominal,lower extremity, or urologic surgical procedures wereeligible to be included in the study.

Exclusion criteria included patients with history ofallergy to one of the antiseptic solutions used, the pres-ence of a clotting defect, neutropenia, neurologic dis-ease, local or generalized infection, and those receivingimmunosuppressive therapy. No antimicrobial prophy-

* Fellow of Anesthesiology, † Assistant Professor of Anesthesiology, ‡ StaffMicrobiologist, § Assistant Professor of Microbiology, i Chairman, Department ofMicrobiology, University Paris XI.

Received from the Department of Anesthesia and Intensive Care, Hôpital deBicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicêtre, France. Sub-mitted for publication June 20, 2000. Accepted for publication September 18,2000. Supported by a grant from Laboratoires Zeneca Pharma, Cergy, France. Thefunding agency was not involved in the design, conduct, or reporting of thisstudy or in the decision to submit the manuscript for publication.

Address correspondence to Dr. Mimoz: Département d’ Anesthésie-Réanima-tion, CHU la Milétrie, BP 577, 86021 Poitiers Cedex, France. Address electronicmail to: [email protected]. Reprints will not be available from the au-thors. Individual article reprints may be purchased through the Journal Web site,www.anesthesiology.org.

Anesthesiology, V 94, No 2, Feb 2001 239

laxis was administered specifically for the epidural cath-eter insertion. However, most of the patients receivedantibiotics during the operative period that werestopped at the end of surgery (aminopenicillins or ceph-alosporins given mostly alone, but sometimes in combi-nation with aminoglycosides), according to the Frenchguidelines on antibiotic prophylaxis during surgery.12

Insertion and Maintenance of CathetersPatients were randomized to receive either 0.5%

chlorhexidine gluconate (Hibitane Champ; ZenecaPharma, Cergy, France) or 10% povidone iodine (Béta-dine; Asta Médica, Marignane, France) for cutaneousantisepsis before epidural catheter insertion usingcomputerized randomization lists. Catheters were in-serted using the maximal sterile-barrier precautionsinto either the lumbar or the thoracic epidural space,based on the preferences of the anesthesia team, onclinical indication, or both. After surgical hand wash-ing, fellow or resident anesthesiologists were gowned,gloved, and masked. The skin was cleaned twice (be-fore and after placement of sterile disposable drapes)by vigorously applying the designed antiseptic solu-tion on an area more than 300 cm2 for at least 10 s andallowing the area to dry between each antiseptic ap-plication. Epidural catheters were located using theloss-of-resistance technique with either saline solutionor air (Tuohy 20-gauge needle). A 22-gauge polyamideepidural catheter (Portex, Berck, France) was ad-vanced 3– 4 cm into the epidural space to ensuresecure placement without subcutaneous tunneling.All catheters were fixed in place with a sterile occlu-sive dressing (Opsite; Smith and Nephew Medical Ltd.,Hull, UK). The proximal portion of the catheter wasthen directed cephalad and fixed on the back usingtape (Albupore; Smith and Nephew Medical Ltd.).Continuous infusions of 0.1% bupivacaine with orwithout preservative-free morphine chlorhydrate(30 –50 mg/kg) or clonidine (1 mg/kg) were adminis-tered through the catheters using an antimicrobialfilter. The anesthetic solutions were changed at leastevery 24 h, and the connections were manipulatedwith gauze soaked with 70% isopropyl alcohol. Topi-cal antibiotic or antiseptic ointments were not used onany catheter. The dressings were not changed untilthe catheters were removed to avoid catheter migra-tion out of the epidural space. The following informa-tion was recorded when the epidural catheters wereinserted: age, sex, weight, American Society of Anes-thesiologists classification score, Altemeir class13 andduration of surgery, status of doctor performing theepidural (resident or fellow), epidural solution used,perioperative antimicrobial prophylaxis administra-tion, and duration of epidural infusion.

The insertion site and the dressing were inspecteddaily by nursing staff and the patient’s physician, who

were blind to the antiseptic solution used, to search forsigns of infection (pus), inflammation (erythema, heat,tenderness), or cutaneous allergic events to the disinfec-tant (edema, erythema). The decision to remove thecatheter was made solely by the patient’s physician, whokept the catheter in place until it was no longer requiredor until an adverse event, such catheter-related infectionor catheter migration out of the epidural space, necessi-tated its removal. Catheter-related infection was sus-pected in a patient who became febrile without anyother cause.

CulturesAfter removal of the occlusive dressing, dry swabs

were taken at the site surrounding catheter insertion andat the catheter hub to help identify the sources of mi-croorganisms that may colonize catheters. The skin wasthen cleaned with 70% isopropyl alcohol. After the alco-hol was allowed to dry, the catheter was removed asep-tically, and its tip (3–4 cm distal segment) was cut andcultured quantitatively by a method previously describedfor vascular catheters.14 The laboratory technicians wereunaware of the antiseptic solution used for skin prepa-ration. Standard microbiologic methods and criteriaidentified recovered microorganisms. If a same bacterialspecies was isolated from different sites in a given pa-tient, their Sma-I-restricted pulse-field gel electrophore-sis patterns were visually analyzed for similarity.15 Bac-terial isolates were considered similar when pulse-fieldgel electrophoresis patterns differed by no more thanone band, according to Tenover criteria.15

DefinitionsWe adapted the definition of catheter colonization

proposed by the Centers for Disease Control and Preven-tion for intravascular devices.16 Epidural catheter colo-nization was defined as the growth of 1,000 or morecolony-forming units/ml in cultures from the cathetertip. Colonization of the catheter was related to the skinwhen the same bacterial isolate yielded from the cathe-ter tip and the skin surrounding the insertion site, andwas related to the catheter hub when the same bacterialisolate yielded from the catheter tip and the catheter hub.

Statistical AnalysisBefore undertaking this study, we estimated the num-

ber of catheters that would be required for an adequateexamination of the hypothesis that epidural cathetersinserted after skin preparation with chlorhexidine aretwo thirds less likely to be colonized than cathetersinserted after skin preparation with povidone iodine.This was based on our experience with intravasculardevices.9 Supposing that the use of povidone iodine willbe associated with a 20% incidence of catheter coloni-zation, randomly assigning approximately a total of 96catheters would have allowed us to detect, with 80%

240 KINIRONS ET AL.

Anesthesiology, V 94, No 2, Feb 2001

power, a significant difference in the rates of coloniza-tion between the two types of antiseptic solutions at aone-tailed significance level of 5%.

Data are expressed as medians with range for contin-uous variables or percentages for categorical variables.The significance of the differences between the twostudy groups was determined with the Mann–Whitney Utest for continuous variables and the Fisher exact test orthe chi-square test for categorical variables. The propor-tions of catheters that were free of colonization as afunction of time they had been in place were comparedbetween the groups with use of a log-rank test onKaplan-Meier estimates. All P values were based on two-tailed tests of significance with P , 0.05 used to deter-mine significance. All computations were performedwith SPSS 10.0 for Windows software (SPSS Inc. Head-quarters, Chicago, IL).17

Results

A total of 100 patients requiring an epidural catheterwere enrolled in the trial and randomly assigned (48 inthe povidone iodine group and 52 in the chlorhexidinegroup). Completed data could be evaluated for 96 cath-eters (44 in the povidone iodine group and 52 in thechlorhexidine group). The remaining four catheterssited after povidone iodine skin preparation were notcultured (three were not inserted as a result of failure tocatheterize the epidural space and one migrated outsidethe skin and was grossly contaminated before catheterculture). The two groups of catheters were similar withrespect to characteristics of patients and catheters, al-though the duration of surgery was not significantlyhigher in the chlorhexidine group (table 1). Neitherlocal nor systemic hypersensitivity reactions were ob-served with the use of either antiseptic solution.

Twenty cultures of catheter tips yielded microorganisms(table 2). The bacterial species isolated were coagulase-negative staphylococci (mainly methicillin resistant) in 19cases and Enterococcus faecalis in one case. Cultures ofcatheter tips in the chlorhexidine group were significantlyless likely to yield microorganisms on removal (five events[4.3 per 100 catheter days]) than were catheter tips in thepovidone iodine group (15 events [16.7 per 100 catheterdays]; relative risk, 0.2 [95% confidence interval, 0.1–0.7];P , 0.001, log-rank test).

Six of the 20 catheters tips yielding microorganisms inculture yielded more than 1,000 colony-forming units/ml,and the corresponding catheters were considered ascolonized (table 2). As shown in figure 1, catheter colo-nization occurred less frequently and less quickly whenchlorhexidine was used for skin preparation (one event[0.9 per 100 catheter days]) than when povidone iodinewas used (five events [5.6 per 100 catheter days]; rela-tive risk, 0.2 [95% confidence interval, 0.1–1.0]; P 5

0.02, log-rank test). None of the catheters colonizedwassuspected of being infected before catheter removal.The presence of signs of inflammation (mainly ery-thema) at the insertion site was not more frequent whenthe catheter was colonized (one catheter colonizedamong the 11 patients [9%] with signs of inflammationvs. five catheters colonized among the 85 patients [6%]without signs of inflammation; relative risk, 1.5 [95%confidence interval, 0.2–11.8]; P 5 0.54, Fisher exacttest). Methicillin-resistant coagulase-negative staphylo-cocci were the only colonizing microorganisms recov-ered. In no patient did an epidural abscess, meningitis,or any serious local or systemic infection develop.

Cultures of the sites surrounding catheter insertion in thechlorhexidine group were less likely to yield microorgan-isms at catheter removal than were insertion sites in thepovidone iodine group (table 2), whereas the number ofcatheter hubs contaminated were similar between the twostudy groups. The skin surrounding the catheter insertionsite was the origin of all the colonizing microorganisms.

Table 1. Characteristics of the Patients and Epidural Catheters*

Povidoneiodine

(n 5 44)Chlorhexidine

(n 5 52) P Value

No. of patients 44 52Male sex, n (%) 17 (39) 29 (56) 0.11Age (months) 22 (1–180) 24 (1–180) 0.87Weight (kg) 12 (3–56) 12 (2–42) 0.81ASA score, n (%) 0.79

I 15 (34) 20 (38)II 27 (61) 29 (56)III 2 (5) 3 (6)

Altemeier class, n (%) 0.32Clean 33 (75) 33 (63)Clean–contaminated 9 (20) 18 (35)Contaminated 2 (5) 1 (2)

Antibioprophylaxis, n (%)Yes 39 (89) 50 (96) 0.26Amino-penicillin 23 (52) 30 (58) 0.28Cephalosporin 9 (36) 20 (38) 0.56Aminoglycoside 2 (5) 1 (2) 0.59

Type of clinician, n (%) 0.96Resident 25 (57) 29 (56)Fellow 19 (43) 23 (44)

Insertion site levels, n (%) 0.22Thoracic 2 (5) 1 (2)L2–L3 11 (25) 11 (22)L3–L4 21 (47) 19 (36)L4–L5 8 (18) 19 (36)L5–S1 2 (5) 2 (4)

Duration of surgery (min) 180 (80–550) 240 (90–840) 0.12Duration of placement (h) 50 (21–74) 50 (24–100) 0.59Reason for removal, n (%) 0.53

Catheter no longer needed 41 (93) 49 (94)Suspected catheter infection 2 (5) 1 (2)Catheter displacement 1 (2) 2 (4)

* Continuous variables are expressed as medians with ranges and comparedwith the Mann–Whitney U test. Categorical variables are expressed as num-bers with percentages and compared with the Fisher exact test or the chi-square test.

ASA 5 American Society of Anesthesiologists.

241CONTINUOUS EPIDURAL CATHETER COLONIZATION IN CHILDREN


Discussion

Our study demonstrates that in the pediatric popula-tion studied, an alcohol solution of 0.5% chlorhexidineused for skin disinfection before short-term epiduralcatheter insertion was more effective than an aqueoussolution of 10% povidone iodine in preventing cathetercolonization. No patient had an epidural space infection.

Although there are several studies assessing coloniza-tion of epidural catheters in the pediatric population,interstudy comparisons are difficult to make because ofdifferences in definition of catheter colonization, routeof epidural used (caudal versus lumbar) and differencesin the choice of antiseptic solution used before epiduralcatheter insertion. The presence or absence of prophy-lactic antibiotics and the varying duration of epiduralcatheterization also make interstudy comparisons diffi-cult. Colonization of epidural catheters is common in the

pediatric population, with incidences varying from 12 to35%.1–3 Our results suggest that despite high coloniza-tion, the risk of epidural space infection in this popula-tion is low. This finding is consistent with previousreports. Strafford et al.,18 in a study of 1,620 childrenwho received epidural analgesia, reported only one tho-racic epidural infection occurring with very prolongeduse in palliative care of a patient with immunosuppres-sion. Likewise, Kost-Byerly et al.,2 in a study of 210children who received caudal or lumbar epidural anal-gesia, demonstrated that despite a 35% colonization rate,no serious systemic infection occurred. McNeely et al.1

reported an overall colonization rate of 20% in caudalepidurals and similarly reported no deep tissue infec-tions. Although rare, catheter infection can rapidlyprogress to epidural abscess, meningitis, paralysis, ordeath.1–3 Such complications are unacceptable in thissetting.

Although the precise mechanism of epidural infectionassociated with epidural block has yet to be defined,several possible mechanisms have been proposed. Con-tamination of drug or material may be a factor. Raedler etal.19 assessed bacterial contamination of 114 spinal and20 epidural needles after subarachnoid or epidural blockperformed under strict aseptic guidelines. Bacterial con-tamination occurred in 18% of the needles, suggestingthan even when following strict aseptic guidelines, nee-dle contamination by skin pathogens is common. Simi-larly, skin flora introduced either at the time of punctureor as a result of bacterial migration along a catheter orneedle tract has been implicated as a potential source ofepidural abscess. Sato et al.4 assessed 69 paired skinspecimens that had been excised from the incisional site(laminectomies) after disinfection with 10% povidoneiodine or an alcoholic solution of 0.5% chlorhexidine.They found viable microorganisms in 13 biopsies, mainlyin the povidone iodine group (32% versus 6%; P , 0.01).They explained the superior performance of chlorhexi-dine by its more potent bactericidal activity and its highpermeability into the hair follicles. Hematogenousspread from another site of infection has been postu-lated as another potential source of epidural infection.Darchy et al.20 reviewed infectious complications in 75intensive care patients who received epidural analgesia.Twenty-four other site infections occurred in 21 pa-tients. The microorganisms isolated were different fromthose isolated from swab or catheter cultures. Theystated that the presence of other infection sites did notincrease the incidence of epidural infection. Finally,catheter colonization can arises from clinicians’ andnurses’ handling of syringes and solutions, via the cath-eter hub. To determine if catheter colonization was theresult of unsatisfactory skin antisepsis or septic manipu-lation of the catheter line, we cultured the insertion siteand the catheter hub at catheter removal.

Fig. 1. Kaplan-Meier curves for freedom from catheter coloni-zation after skin preparation with either chlorhexidine or po-vidone iodine. The number of catheters in each group that wereat risk to be colonized at various times are shown below thefigure. The risk of catheter colonization was significantly lowerwhen skin preparation was performed with chlorhexidine so-lution than with povidone iodine (P 5 0.02, log-rank test).

Table 2. Positive Bacteriologic Cultures

Povidone Iodine(n 5 44)

Chlorhexidine(n 5 52) P Value

Catheter tip, n (%),1,000 cfu/ml 10 (23) 4 (8) 0.04$1,000 cfu/ml 5 (11) 1 (2) 0.07

Catheter hub, n (%) 1 (2) 4 (8) 0.4Insertion site, n (%) 20 (45) 12 (23) 0.03

cfu 5 colony-forming units.

242 KINIRONS ET AL.


There are few studies comparing the efficacy of chlo-rhexidine versus povidone iodine used as skin disinfec-tant in reducing epidural catheter colonization. Adam etal.,21 in a study of 294 obstetric epidurals, were unableto demonstrate any benefit of chlorhexidine over povi-done iodine. Methodologic deficiencies of this studyinclude lack of randomization and the fact that the skinwas not cleaned before catheter removal. Thus, bias andunavoidable contamination may have altered the results.In contrast, Shapiro et al.22 demonstrated that use of achlorhexidine dressing reduced microbial colonizationof epidural catheters. The chlorhexidine group was oneseventh as likely to be colonized as those in the controlgroup.

Our study supports these findings. Catheters insertedafter skin preparation with chlorhexidine were one sixthas likely and less quickly colonized as catheters insertedafter skin preparation with povidone iodine. Our resultsare in accordance with those from the previously quotedstudy of Sato et al.,4 indicating that fewer viable micro-organisms were cultured from skin biopsies after cuta-neous disinfection with chlorhexidine. Chlorhexidinegluconate is a potent broad-spectrum germicide, whichis effective against nearly all nosocomial bacteria andyeasts.8,9,11 In addition, chlorhexidine has a low skinirritancy and sensitization potential. It has a strong affin-ity for the skin and demonstrates prolonged duration ofantimicrobial effect. Unlike povidone iodine, the anti-bacterial activity of chlorhexidine persists for hours aftertopical application. In contrast to iodine-containing com-pounds, chlorhexidine is not neutralized by contact withproteinous solutions. Iodine-containing compounds lackpersistence and may induce allergic reactions in sensi-tive individuals. Finally, bacterial resistance to chlorhexi-dine is rare.

Coagulase-negative staphylococci were the only colo-nizing microorganisms recovered in our study. This con-curs with previous studies indicating that coagulase-negative staphylococci, the predominant species on thehuman skin, are the most common agents of cannula-related infections.1,9,19 The superiority of chlorhexidineover povidone iodine in preventing catheter coloniza-tion and catheter-related sepsis as a result of Gram-positive bacteria has already been noted in various stud-ies,9,23 and was reported to be the result of a moreprolonged activity of chlorhexidine against staphylococ-ci.23 This superiority may explain, at least in part, thelower epidural catheter colonization rate that we ob-served after chlorhexidine disinfection.

Our trial had several limitations. Because color differ-ences between the two solutions used, the physicianwas not blinded, and this may have introduced bias intothe study. However, both solutions are in common use,and we do not believe that physicians knew that onesolution was better than the other. Furthermore, themicrobiologists who performed the cultures as well as

the patient’s physician who decided to remove the cath-eters were not aware of the antiseptic solutions used.The duration of epidural use was short, with a median of50 h in both groups. Although a short duration maymitigate against colonization, this duration representscurrent practice in our unit. We did not evaluatewhether the use of chlorhexidine reduces colonizationof caudal catheters, despite the fact that caudal cathetersare frequently placed in the pediatric population andthat the incidence of catheter colonization is higher aftercaudal than lumbar catheter placement, because of thefew number of caudal catheters inserted in our unit. Thewidespread use of antibiotics in this study may haveinfluenced culture results. However, prophylactic anti-biotic use was guided by national guidelines, and theiruse was similar in both groups. Moreover, no patientreceived antibiotic potent against methicillin-resistantcoagulase-negative staphylococci, the causative agent forcatheter colonization. Finally, we could not evaluate ifthe use of chlorhexidine reduces the risk of lumbarcatheter infection because of the very low incidence ofsubcutaneous or epidural space infection with short-term catheterization. However, the use of catheter col-onization as a surrogate marker of true risk of infectionis reasonable, because colonization generally precedesinfection.

In conclusion, the use of chlorhexidine solution ratherthan povidone iodine may be a better choice for cuta-neous antisepsis before short-term epidural catheterplacement in children. Whether this antiseptic agentreduces colonization for longer lumbar catheterizationor of caudal catheters requires further investigation.

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3. Abouleish E, Orig T, Amortegui AJ: Bacterial comparisons between epiduraland caudal techniques. ANESTHESIOLOGY 1980; 53:511–4

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243CONTINUOUS EPIDURAL CATHETER COLONIZATION IN CHILDREN


10. Garland JS, Buck RK, Maloney P, Durkin DM, Toth-Lloyd S, Duffy M, SzocikP, Mcauliffe TL, Goldman D: Comparison of 10% povidone iodine and 0.5%chlorhexidine gluconate for the prevention of peripheral intravenous cathetercolonization in neonates: a prospective trial. Pediatr Infect Dis J 1995; 14:510–6

11. Mimoz O, Karim A, Mercat A, Cosseron M, Falissard B, Parker F, Richard C,Samii K, Nordmann P: Chlorhexidine compared with povidone iodine as skinpreparation before blood culture. Ann Intern Med 1999; 131:834–7

12. Société Française d’Anesthésie et de Réanimation, Consensus Conference:‘Antibioprophylaxis in a surgical setting.’ Réactualisation 1999. Ann Fr AnesthRéanim 1999; 18: fi 75–85

13. Altemeir WA, Culbertson WR: Surgical infections, Surgery Principles andPractice. Edited by Moyer CR, Disterhoft JF. Philadelphia, JB Lippincott, 1965, pp185–218

14. Brun-Buisson C, Abrouk F, Legrand P, Huet Y, Larabi S, Rapin M: Diagnosisof central venous catheter-related sepsis. Critical level of quantitative tip cultures.Arch Intern Med 1987; 147:873–7

15. Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE, Persing DH,Swaminathan B: Interpreting chromosomal DNA restriction patterns producedby pulse-field gel electrophoresis criteria for bacterial strain typing. J Clin Micro-biol 1995; 33:2233–9

16. Pearson ML: Hospital Infection Control Practices Advisory Committee.

Guidelines for prevention of intravascular device-related infections. I. Intravas-cular device-infection overview. Am J Infect Control 1996; 24:277–93

17. SPSS Inc.: SPSS Users Guide: Statistics, Version 10.0. Chicago, SPSS Inc., 199918. Strafford MA, Wilder RT, Berde CB: The risk of infection from epidural

analgesia in children: A review of 1620 cases. Anesth Analg 1995; 80:234–819. Raedler C, Lass-Flörl C, Pühringer F, Kolbitsch Ch, Lingnau W, Benzer A:

Bacterial contamination of needles used for spinal and epidural anaesthesia. Br JAnaesth 1999; 83:657–8

20. Darchy B, Forceville X, Bavoux E, Soriot F, Domart Y: Clinical and bacte-riologic survey of epidural analgesia in patients in the intensive care unit.ANESTHESIOLOGY 1996; 85:988–98

21. Adam MN, Dinulescu T, Mathieu P, Giacomini T, Le Pennec MP: Com-paraison de l’efficacité de deux antiseptiques dans la prévention de l’infectionliée aux cathéters périduraux. Cah Anesth 1996; 44:465–7

22. Shapiro JM, Bond EL, Garman JK: Use of a chlorhexidine dressing toreduce microbial colonization of epidural catheters. ANESTHESIOLOGY 1990; 73:625–31

23. Shelton DM: A comparison of the effects of two antiseptic agents onStaphylococcus epidermidis colony forming units at the peritoneal dialysis cath-eter exit site. Adv Perit Dial 1991;7:120–4

244 KINIRONS ET AL.


Anesthesiology, V 118 • No 6 1466 June 2013

ABSTRACT

Managing patients in the perioperative setting receiving novel oral anticoagulation agents for thromboprophylaxis or stroke prevention with atrial fibrillation is an important consideration for clinicians. The novel oral anticoagulation agents include direct Factor Xa inhibitors rivaroxaban and apixaban, and the direct thrombin inhibitor dabigatran. In elective surgery, dis-continuing their use is important, but renal function must also be considered because elimination is highly dependent on renal elimination. If bleeding occurs in patients who have received these agents, common principles of bleeding management as with any anticoagulant (including the known principles for

warfarin) should be considered. This review summarizes the available data regarding the management of bleeding with novel oral anticoagulation agents. Hemodialysis is a therapeu-tic option for dabigatran-related bleeding, while in vitro studies showed that prothrombin complex concentrates are reported to be useful for rivaroxaban-related bleeding. Additional clini-cal studies are needed to determine the best method for reversal of the novel oral anticoagulation agents when bleeding occurs.

ANTICOAGULATION is routinely used in diverse clini-cal settings, including perioperative venous thromboem-

bolism (VTE) prophylaxis and stroke prevention in patients with atrial fibrillation (AF). Unfractionated heparin, low-molecular-weight heparin, and vitamin K antagonists such as warfarin are widely used but have disadvantages. Although there is no “ideal” anticoagulant, an optimal profile includes, in addition to established efficacy and safety, oral adminis-tration, no routine monitoring requirement, a predictable anticoagulant effect, a rapid onset and offset of action, and reversibility.1 Only a few anticoagulants are acutely reversible, including unfractionated heparin with protamine and vita-min K antagonists with four-component prothrombin com-plex concentrates. The newer oral anticoagulants (NOACs) include the direct thrombin inhibitor dabigatran etexilate (Pradaxa®, Boehringer-Ingelheim Pharma GmbH, Ingelheim am Rhein, Germany) and the direct factor Xa inhibitors riva-roxaban (Xarelto, Johnson and Johnson/Bayer HealthCare AG, Leverkusen, Germany) and apixaban (Eliquis, Bristol Myers Squibb/Pfizer, Bristol-Myers Squibb House, Uxbridge, United Kingdom).2 Advantages of these new agents include their relatively rapid onset and offset of action and predict-able anticoagulant effect so that routine coagulation moni-toring is not required. However, laboratory monitoring may be relevant in certain clinical situations, where an assessment of the anticoagulation status is needed. As the NOACs are

David S. Warner, M.D., Editor

Managing New Oral Anticoagulants in the Perioperative and Intensive Care Unit Setting

Jerrold H. Levy, M.D., F.A.H.A., F.C.C.M.,* David Faraoni, M.D.,† Jenna L. Spring, M.S.,‡ James D. Douketis, M.D.,§ Charles M. Samama, M.D., Ph.D., F.C.C.P.||

* Professor, Department of Anesthesiology/Critical Care, Duke University School of Medicine, Durham, North Carolina. † Assistant Professor, Queen Fabiola Children’s University Hospital, Brussels, Belgium. ‡ Medical Student, Emory University School of Medicine, Atlanta, Georgia. § Professor of Medicine, Division of Hematology and Thromboembolism, McMaster University, Hamilton, Ontario, Canada. || Professor, Department of Anesthesiology and Intensive Care, Hotel-Dieu University Hospital, Paris, France.

Received from the Department of Anesthesiology, Emory Uni-versity School of Medicine, Atlanta, Georgia. Submitted for publi-cation July 30, 2012. Accepted for publication December 20, 2012. Support was provided solely from institutional and/or departmen-tal sources. JHL serves on Steering Committees for Boehringer-Ingelheim, Ingelheim am Rhein, Germany; CSL Behring, King of Prussia, Pennsylvania; and Johnson and Johnson, New Brunswick, New Jersey. Figures 1 and 2 were created by Annemarie B. John-son, C.M.I., Medical Illustrator, Wake Forest University School of Medicine Creative Communications, Wake Forest University Medi-cal Center, Winston-Salem, North Carolina.

Address correspondence to Dr. Levy: Duke University Medi-cal Center, 2301 Erwin Rd., 5691H, HAFS, Box 3094, Durham, North Carolina 27710. [email protected]. This article may be accessed for personal use at no charge through the Journal Web site, www.anesthesiology.org.

Perioperative Management of New Oral Anticoagulants

Levy et al.

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Review Article

REVIEW ARTICLE Anesthesiology 2010; 112:473–92

Copyright © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins

David S. Warner, M.D., and Editor

Ultrasound Imaging for Regional Anesthesia in Infants,Children, and Adolescents

A Review of Current Literature and Its Application in the Practice of Extremity andTrunk Blocks

Ban C. H. Tsui, M.D., F.R.C.P.C.,* Santhanam Suresh, M.D., F.A.A.P.†

This article has been selected for the ANESTHESIOLOGY CME Program. Learningobjectives and disclosure and ordering information can be found in the CMEsection at the front of this issue.

ABSTRACTThe use of ultrasound guidance has provided an opportunity to

perform many peripheral nerve blocks that would have been difficultto perform in children based on pure landmark techniques due to thepotential for injection into contiguous sensitive vascular areas. Thisreview article provides the readers with techniques on ultrasound-guided peripheral nerve blocks of the extremities and trunk withcurrently available literature to substantiate the available evidence forthe use of these techniques. Ultrasound images of the blocks withcorresponding line diagrams to demonstrate the placement of theultrasound probe have been provided for all the relevant nerve blocksin children. The authors hope that this review will stimulate furtherresearch into ultrasound-guided regional anesthesia in infants, chil-dren, and adolescents and stimulate more randomized controlledtrials to provide a greater understanding of the anatomy and physi-ology of regional anesthesia in pediatrics.

ONE of the most exciting recent advances in technology inpediatric regional anesthesia has been the introduction of

anatomically based ultrasound imaging for facilitating nerve lo-calization. This is because regional anesthesia techniques in chil-dren have been considered challenging due to (1) target neuralstructures that often course very close to critical structures (e.g.,nerves of the brachial plexus run close to the pleura as theytraverse the supraclavicular region), and particularly during cen-tral neuraxial blocks where the safety margin is narrow for needleplacement particularly close to the spinal cord, (2) the prerequi-site for sedation or general anesthesia masking potential warningsigns (paresthesia), and (3) the need for limiting the volume oflocal anesthetic solution below toxic levels. With the possibilityof visualizing the target structures, ultrasound technology mayencourage many anesthesiologists who had previously aban-doned regional techniques to resume or increase their use ofregional anesthesia in children.

Although literature evaluating the evidence for successand safety of ultrasound in regional anesthesia has begun toemerge, a comprehensive narrative review of the literaturepertaining to techniques described and outcomes evaluatingultrasound guidance in pediatric regional anesthesia was notavailable at the time of writing this article. This review aimsto provide the pediatric anesthesiologist with an overall sum-mary of the techniques used and of the outcomes found(based on controlled or comparative studies) as described inthe literature on ultrasound guidance of peripheral nerveblocks of the extremities and trunk in pediatrics. A compan-ion article with similar objectives related to neuraxial blockswill be published in the next issue of ANESTHESIOLOGY.1 Inaddition to case series and clinical studies, descriptions from

* Professor, Department of Anesthesiology and Pain Medicine,University of Alberta. † Professor, Department of Pediatric Anesthe-siology and Pediatrics, Children’s Memorial Hospital, NorthwesternUniversity, Feinberg School of Medicine.

Received from Department of Anesthesiology and Pain Medicine,University of Alberta, Edmonton, Alberta, Canada, and the Depart-ment of Pediatric Anesthesiology, Northwestern University, Fein-berg School of Medicine, Chicago, Illinois. Submitted for publica-tion April 17, 2009. Accepted for publication September 30, 2009.Supported by a Career Scientist Award in Anesthesia (to Dr. Tsui),Canadian Anesthesiologists’ Society-Abbott Laboratories Ltd., To-ronto, Ontario, Canada, a Clinical Scholar Award (to Dr. Tsui) fromthe Alberta Heritage Foundation for Medical Research, Edmonton,Alberta, Canada, and Foundation for Anesthesia Education andResearch (FAER) Research in Education grant (to Dr. Suresh).

Mark A. Warner, M.D., served as Handling Editor for this article.

Address correspondence to Dr. Suresh: Department of PediatricAnesthesiology, Children’s Memorial Hospital, 2300 Children’s Plaza,P. O. Box 19, Chicago, Illinois 60614. [email protected] article may be accessed for personal use at no charge through theJournal Web site, www.anesthesiology.org.

Anesthesiology, V 112 • No 2 473 February 2010

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Anesthesiology 2013; 118:1466-74 1467 Levy et al.

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increasingly replacing older parenteral agents and vitamin K antagonists in clinical practice, it is important to consider that patients treated with these agents will be exposed to differ-ent clinical situations (spontaneous or postoperative bleeding, overdose, trauma, and elective or emergent surgical proce-dures) that require an intervention. There are also increasing concerns about managing patients on these therapeutic agents following trauma or in a perioperative setting. The purpose of this review is (1) to examine the NOACs, focusing on key pharmacologic properties, and (2) to provide management approaches for users of NOACs in the perioperative and criti-cal care settings based on the available literature.

Oral Direct Thrombin InhibitorsThrombin has a pivotal role in hemostasis, making it an appealing target for anticoagulant drugs. When thrombin is activated from prothrombin, it converts soluble fibrinogen to insoluble fibrin; activates coagulation factors V, VIII, and XI (which generate more thrombin); and activates platelets (fig. 1).3 Dabigatran is a reversible direct thrombin inhibitor that directly inhibits free and fibrin-bound thrombin without the need for antithrombin. Dabigatran etexilate is a prodrug that has a rapid onset of action, no reported food interactions, few drug interaction, and does not require routine coagulation monitoring. The peak plasma concentration is reached 1.25–3 h after administration, and it has a half-life of 12–14 h in healthy volunteers.4 Dabigatran is 35% bound to plasma proteins and undergoes renal excretion, with 80% of the drug entering the urine unchanged. The anticoagulant effect of dabigatran accumulates in the setting of renal insufficiency, and such bioaccumulation correlates well with the degree of renal dysfunction.5 In contrast to

other NOACs that are highly protein bound, the relatively low protein binding of dabigatran allows it to be eliminated to a large extent by hemodialysis.6 In cases of moderate hepatic impairment, dabigatran can be administered safely and no dose adjustment is necessary.7

Dabigatran is approved in the United States, Canada, Europe, and Japan for stroke prevention in patients with non-valvular AF based on the results of the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial in which 150 mg of dabigatran twice-daily was superior to dose-adjusted warfarin with a similar rate of major bleed-ing.8 Dabigatran, 75 mg twice-daily, is approved for use in the United States for patients with severe renal insufficiency (CrCl 15–30 ml/min), based on indirect pharmacokinetic modeling and the assumed anticoagulant effect with this level of renal dysfunction. In Europe and Canada, the 75-mg dose is not approved for clinical use and dabigatran is con-traindicated in patients with a CrCl < 30 ml/min. Dabiga-tran is also is approved for VTE prophylaxis following total hip or knee replacement surgery in Europe and Canada, but not the United States. A recent indirect network meta-analy-sis suggests that treatment with dabigatran offers benefit for the prevention of stroke, systemic embolism, and mortality over antiplatelets and placebo without increased intracranial or extracranial hemorrhage compared to antiplatelet agents.9 Further investigations are needed to confirm these results.

Oral Direct Factor Xa InhibitorsFactor Xa is another important target for anticoagulant drugs due to its role as the rate-limiting factor in throm-bin generation and amplification, generating the Xa com-plex that converts prothrombin to thrombin (fig. 1).2 The direct factor Xa inhibitors inhibit free Factor Xa, Factor Xa in the prothrombinase complex, and Factor Xa found in clots, independent of an antithrombin cofactor.2,10 This is in contrast to low-molecular-weight heparin, unfractionated heparin, and fondaparinux, which all are dependent on anti-thrombin to inhibit Factor Xa.

RivaroxabanRivaroxaban is an oral, direct Factor Xa inhibitor that has good bioavailability (80%), is highly protein-bound, and has few drug interactions. Peak plasma concentrations occur within 2–4 h of administration, and rivaroxaban has a half-life of 5–9 h in healthy subjects and 11–13 h in the elderly.10 It is selective for Factor Xa in relation to other serine prote-ases.2 Clearance of rivaroxaban may be decreased to some extent in patients with renal impairment,11 but its primary mode of clearance is by non-renal mechanisms. It should be noted that although some reports may indicate that approxi-mately 67% of rivaroxaban is eliminated by the kidney, such total renal clearance reflects 33% clearance of active drug and 33% clearance of inactive rivaroxaban, which is not clin-ically important. Thus, two-thirds of the active rivaroxaban

Fig. 1. Effect sites of anticoagulation agents. The new oral an-ticoagulation agents directly inhibit one of two major targets in the coagulation cascade. Rivaroxaban and apixaban directly inhibit factor Xa, and dabigatran directly inhibits thrombin. The parenteral anticoagulants that inhibit factor Xa include low-molecular-weight heparin (LMWH) and fondaparinux by antithrombin (AT)-dependent binding. Parenteral direct thrombin inhibitors include argatroban, bivalirudin, and de-sirudin that also directly inhibit thrombin independent of AT.



are cleared by nonrenal mechanisms. Based on pharmaco-kinetic study, 10-mg rivaroxaban administered once daily offers the best efficacy profile while avoiding excessive bleed-ing complications.12 In patients with AF, the recommended rivaroxaban dose is 20 mg daily, although a reduced dose (15 mg daily) is recommended in patients with a CrCl 15–30 ml/min.13 Due to high plasma protein binding (>90%), rivaroxaban cannot be eliminated during hemodialysis.

Rivaroxaban is approved in the United States, Canada, and Europe for VTE prophylaxis after hip or knee replacement surgery and for stroke prevention in patients with non-valvular AF. Rivaroxaban was recently approved for treatment of deep vein thrombosis, pulmonary embolism, and reduction in the risk of recurrence. In the Regulation of Coagulation in Orthopedic surgery to pRevent Deep venous thrombosis and pulmonary embolism (RECORD) trials, rivaroxaban, 10 mg daily, was superior to enoxaparin 30 mg twice-daily, and 40 mg once-daily for the prevention of VTE after knee and hip replacement, respectively, without a significant increase in the rate of major bleeding.14–17 In terms of stroke prevention, the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial randomly allocated (in a double-blind manner) 14,264 patients with AF to rivaroxaban 20 mg daily (15 mg daily if CrCl 15–50 ml/min) compared to dose-adjusted warfarin and found that rivaroxaban was not inferior to warfarin in efficacy, with no significant difference in major bleeding events.18 In patients with an acute coronary syndrome, the Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome–Thrombolysis in Myocardial Infarction 51 (ATLAS ACS2–TIMI 51) compared rivaroxaban, 2.5 mg or 5 mg daily, to placebo in patients who were receiving aspirin and a thienopyridine (usually clopidogrel). Although the 2.5-mg dose regimen conferred a significant reduction in cardiovascular and all-cause mortality (and also led to more bleeding), the Food and Drug Administration issued a “complete response letter” and requested additional data.19

ApixabanApixaban is another oral, direct Factor Xa inhibitor with good oral bioavailability (80%), is highly protein bound, reaches peak plasma concentration within 2–3 h after intake, and has limited potential for drug interactions.10 Apixaban 2.5 mg twice-daily is the recommended dose for VTE pro-phylaxis based on pharmacokinetic study.20 In patients who received apixaban 2.5 mg twice-daily for VTE prophylaxis, the risk of major bleeding was not influenced by renal func-tion.21 Moreover, in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, assessing apixaban 5 mg twice-daily for stroke prevention, patients were excluded only if they had a CrCl < 25 ml/min. For these reasons, no dose adjustment is

recommended in patients with mild (CrCl, 50–80 ml/min) or moderate (CrCl, 30–50 ml/min) renal impairment. The half-life in healthy subjects is 8–15 h.10 Apixaban has been approved in Canada and Europe for VTE prophylaxis after total hip and knee replacement surgery based on the results of the ADVANCE trials.22,23 Apixaban is currently under Food and Drug Administration review in the United States for this indication. In the ARISTOLE trial, apixaban was superior to dose-adjusted warfarin in preventing stroke and systemic embolism, with a decrease in bleeding complica-tions, and a lower mortality.24 The Apixaban Versus Acetyl-salicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antago-nist Treatment (AVERROES) study is noteworthy as it is the only trial comparing treatment with a NOAC, in this case apixaban 5 mg twice-daily, against aspirin (81–325 mg) for stroke prevention in AF.25 Although it would be expected that apixaban conferred a lower risk for stroke, what is sur-prising, perhaps, is that this treatment was not associated with more bleeding compared with aspirin.25

Monitoring Anticoagulation with the NOACsAlthough routine laboratory testing is not required in NOAC-treated patients, except for periodic monitoring of renal function (especially in patients with preexisting renal impairment), coagulation function tests should be ordered for any anticoagulated patient presenting with an acute bleed, suspected overdose, or requiring emergency surgery.26 Due to the effect of dabigatran on thrombin-mediated con-version of fibrinogen to fibrin, most of the routine coagula-tion assays will be prolonged except the prothrombin time.27 The maximum effect of dabigatran on coagulation param-eters occurs at the same time as peak plasma concentration. For this reason, the delay between the last dabigatran dose and the time of blood sampling is needed to interpret the tests. The effects of dabigatran can be best measured using the thrombin time or a dilute thrombin time, available as the Hemoclot assay.28 Other assays that have been studied include the ecarin clotting time, although this test is not widely available.2,29 The thrombin time provides a direct assessment of thrombin activity and increases linearly with increasing dabigatran concentration; however, experience with this assay indicates that it is overly sensitive to dabiga-tran levels and, consequently, the thrombin time may be pro-longed in the setting of a clinically insignificant dabigatran effect.28 The Hemoclot assay has better linear correlation to plasma levels of dabigatran and is probably the most reliable method to measure the anticoagulant effect of dabigatran.28 In the ecarin clotting time assay, prothrombin is converted to meizothrombin, a prothrombin–thrombin intermediate, by the snake venom ecarin, and dabigatran directly inhibits this meizothrombin intermediate in a dose-dependent fash-ion but this assay is not frequently used.30 A more universally available test, the activated partial thromboplastin time, can also be used; however, the relationship between dabigatran


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concentration and partial thromboplastin time is curvilinear, resulting in decreased precision of the assay as plasma dabi-gatran concentrations increase,29 and there may be interassay variability in measurements. Nonetheless, the partial throm-boplastin time provides a reasonable alternative if other tests are not available and a normal partial thromboplastin time will likely indicate the absence of a clinically important anti-coagulant effect. Additional laboratory studies are urgently needed to correlate coagulation assay results with varying plasma levels of dabigatran.

Rivaroxaban and apixaban inhibit factor Xa directly, which is in complex with FVa and independ of antithrombin.2 Rivaroxaban causes a prolongation of the prothrombin time, although there may be considerable inter-assay variability in such measurements, and has less of an effect on the partial thromboplastin time. However, these tests are not useful for measuring the pharmacodynamic effects of oral factors Xa inhibitors.31 More recently, a specific assay has been developed for the direct Xa inhibitors that is different from an antiXa assay used to monitor low-molecular-weight heparin, and may provide the optimal method for determining the effect of rivaroxaban, although further studies are needed.2,32,33 Rivaroxaban produces a concentration-dependent prolongation of clotting parameters on thromboelastometry, including R and K time without significant modification of maximal amplitude, making this assay not useful for routine monitoring.31 Until now, the lack of readily available means for assessing the degree of anticoagulation remains a notable concern, especially in a life-threatening bleed where

point-of-care monitoring or rapid laboratory assays might be required.

Temporary Discontinuation before Surgery and Neuraxial AnesthesiaBefore discontinuing any anticoagulant medication, the risk of bleeding must be carefully weighed against the risk of thrombosis. For dabigatran, which is eliminated primarily by renal mechanisms, the timing of discontinuation should be based on patients’ CrCl and the bleeding risk associated with the procedure (table 1).34,35 Renal impairment may be less important in patients taking rivaroxaban, in which a decreased creatinine clearance appears to have a limited effect on the half-life of the drug. In a study of patients with renal impairment who are receiving a single 10-mg dose of rivaroxaban, the mean half-life only increased very slightly from 8.3 h in healthy controls to 9.5 h in patients with severe renal impairment (CrCl < 30 ml/min).11

The Working Group on perioperative hemostasis and the French Study Group on thrombosis and hemostasis published recommendations about the perioperative man-agement of NOACs.36,37 For scheduled surgery or invasive procedures with low risk of bleeding, they recommend interruption 24 h (≈2 half-lives) before the procedure and to restart 24 h after. In case of scheduled surgery or invasive procedures at moderate or high risk of bleeding, a 5 days interruption before surgery is recommended, while treat-ment should be restarted according to the bleeding risk. For patients at higher thrombosis risk, unfractionated heparin or low-molecular-weight heparin at curative dose should be initiated 12 h after the last dose of oral anticoagulants. Although these recommendations are easy to use and appear sensible, there is a need for prospective studies assessing the efficacy and safety of these (and other) perioperative man-agement protocols for NOAC-treated patients who require an elective surgery/procedure.

The safety of neuraxial anesthesia for patients treated with NOACs will be based on the pharmacokinetic properties of the anticoagulant (table 2).36 Catheter placement and, to a lesser extent, removal should be considered when anticoagu-lant concentrations are at their lowest, and patients should be monitored closely for signs of hematoma in the initial days after catheter removal. Specific recommendations for

Table 1. Preoperative Discontinuation of Dabigatran Based on Renal Function

Renal Function (CrCl, ml/min) Half-life, h

Timing of Last Dose before Surgery

Normal Bleeding

Risk

High Bleeding

Risk

>80 13 (11–12) 1 d 2–4 d50–80 15 (12–34) 1 d 2–4 d30–50 18 (13–23) >2 d >4 d<30 27 (22–35) 2–5 d >5 d

CrCl = creatinine clearance (ml/min); d = days.

Table 2. Pharmacokinetics of the New Oral Anticoagulation Agents

Dabigatran Rivaroxaban Apixaban

Route of administration Oral twice daily Oral once daily Oral twice dailyBioavailability 6.5% 80% 66%Time to maximal concentration (Tmax) 1.25–3 h 2–4 h 1–3 hHalf-life 12–14 h 5–13 h 8–15 hRenal excretion 80% 66% 25%Plasma protein binding 35% >90% 87%



managing these agents for venous thromboembolic prophy-laxis in the setting of peridural/regional anesthesia are listed in table 3. Rosencher38 suggests allowing at least two half-lives to pass before catheter removal, at which point only 25% of the drug remains active. Allowing a longer interval would only slightly reduce the drug concentration, because elimination slows after this point.38 The risk of the residual anticoagulant activity and neuraxial hematoma needs to be weighed against the risk of VTE. However, the authors sug-gest that anticoagulation should be restarted after 8 h minus the time to reach maximum activity (Tmax), based on the their suggestion that it takes 8 h to establish a stable clot, and allowing time for the peak of anticoagulation to be reached.38 However, there may be considerable variability in the time needed to attain a dry vascular bed, especially after major orthopedic or oncologic surgery, and longer times may be needed because of the risk of bleeding compared to the risk of VTE.38 Recommendations for the use of the new anti-coagulants in the setting of neuraxial anesthesia have been proposed by Llau et al.39 based on existing guidelines and the pharmacokinetics of each drug (table 3).

A recent report evaluated bleeding rates from 7 days prior until 30 days following invasive procedures for patients receiving dabigatran.40 Based on 4,591 patients who had a first treatment interruption for an elective surgery or invasive procedure, 24.7% of patients were receiving dabigatran—110 mg, 25.4% were on dabigatran—150 mg, and 25.9% were on warfarin. The procedures included the

following: pacemaker/defibrillator insertion (10.3%), dental procedures (10.0%), diagnostic procedures (10.0%), cataract removal (9.3%), colonoscopy (8.6%), and joint replacement (6.2%). The last dose of dabigatran was given a mean of 49 (range: 35–85) h before the procedure, compared to a mean of 114 (range: 87–144) h for the last preprocedure dose of warfarin (P < 0.001). There was no significant difference in the rates of periprocedural major bleeding between patients receiving dabigatran, 110 mg (3.8%), or dabigatran, 150 mg (5.1%), or warfarin (4.6%). The relative risk for major bleeding with dabigatran-110 mg versus warfarin was 0.83 (95% CI, 0.59–1.17; P = 0.28), and with dabigatran-150 mg versus warfarin, it was 1.09 (95% CI, 0.80–1.49; P = 0.58). Among patients having urgent surgery, major bleeding occurred in 17.8% with dabigatran-110, 17.7% with dabigatran-150, and 21.6% with warfarin: dabigatran-110. There are no published data on perioperative outcomes in patients receiving rivaroxaban or apixaban who require elective or urgent surgery/procedures, although the same management principles should apply that incorporate procedure bleeding risk and drug elimination as with dabigatran-treated patients.

Reversal of the Novel Anticoagulants and Management of Acute BleedingImmediate reversal of anticoagulation is often needed in the bleeding patient or patient requiring emergency surgery. Current dosing and indications for these agents are listed in

Table 3. Recommendations for Novel Anticoagulants for Venous Thromboembolic Prophylaxis in the Setting of Peridural/Regional Anesthesia36

Dabigatran Rivaroxaban Apixaban

Time between epidural anesthetic technique and next anticoagulant dose 2–4 h 4–6 h 6 hTime before last anticoagulant dose and epidural catheter removal NR* 22–26 h 26–30 hTime between removal of epidural catheter and next anticoagulant dose 6 h 4–6 h 4–6 h

* Dabigatran in not recommended in patients undergoing anesthesia with postoperative indwelling catheters.NR = not recommended.

Table 4. Current Dosing Guidelines for New Oral Anticoagulation Agents

Dabigatran Rivaroxaban Apixiban*

Dosing for atrial fibrillation: normal renal function

150 mg BID 20 mg QD 5 mg BID

Dosing for atrial fibrillation: renal dysfunction

110 mg BID 15 mg QD with CrCl 15–50 ml/min 2.5 mg BIDUnited States: 75 mg BID with CrCl 15–30 ml/min

DVT prophylaxis 220 mg QD 10 mg QD† 2.5 mg BID

Renal dysfunction 150 mg QD Avoid with CrCl < 30 ml/min

Not approved in the United States for this indication

* For apixaban, no data available for use with CrCl < 15 ml/min or on dialysis. † For hip and knee surgery.BID = twice a day; CrCl = creatinine clearance; QD = daily.


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table 4. Although managing any anticoagulation agent in a bleeding patient is a challenge, it is important to note that warfarin and other vitamin K antagonist agents are not easily reversible with therapies available in the United States, such as vitamin K and/or fresh frozen plasma. Four-component prothrombin complex concentrates (PCCs) are currently preferred in Canada and most European countries and rec-ommended in recent guidelines.37,41,42 Stopping a NOAC and providing supportive care are the most important con-sideration and are often sufficient if the bleeding is not severe or if surgery can be delayed. However, when patients present with a major bleeding episode related to these agents and/or require emergency surgery, other measures must be taken.

For any significant bleeding event, initial measures should include volume resuscitation with fluids and/or packed red blood cells, identification of the bleeding source, and attempts at local hemostatic control. If an anticoagulant overdose is the suspected cause, activated charcoal may be effective in preventing additional drug absorption when administered within 1–2 h of ingestion. Activated charcoal has not been used in the clinical setting and is limited by its narrow win-dow of use and inability to use in a perioperative setting.

Hemodialysis or hemoperfusion is another potential option for the emergent removal of anticoagulants. Rivaroxaban and apixaban are too highly protein bound to be effectively removed by these methods, but dabigatran is an appropriate candidate for these therapies.10 In a study of six volunteers with end-stage renal disease who were given a 50-mg dose of dabigatran before routine hemodialysis, an average of 62% of the active dabigatran was removed after 2 h and 68% after 4 h.5 Unfortunately, attempting to perform either of these procedures in a bleeding patient in shock may not be possible.29 Therefore, the use of procoagulant agents should be considered for a life-threatening bleed. However, unlike when fresh frozen plasma or PCCs are used to replace depleted factors II, VII, IX, and X in warfarin-treated patients, the effectiveness of such clotting factor replacement therapies may be limited in NOAC-treated patients who do not harbor deficiencies of clotting factors but in whom there is an ongoing clotting factor inhibitory effect. It may be argued, therefore, that providing supraphysiologic levels of clotting factors may be ineffective in the setting of an ongoing NOAC-related inhibitory effect. On the contrary, such clotting factors may overwhelm such an ongoing inhibitory effect and, in cases of severe bleeding, may replace clotting factors that are depleted due to consumption.

Although fresh frozen plasma is commonly administered for initial control of bleeding in anticoagulated patients, its use as a reversal agent for the NOACs has not been studied in humans.43 In a study of mice pretreated with dabigatran (4.5 mg/kg or 9.0 mg/kg) before induction of intracranial hemorrhage, fresh frozen plasma administration successfully limited hematoma expansion in the low-dose group but had no effect in the high-dose group and did not significantly

decrease mortality. There is insufficient evidence to recom-mend its use.43,44

Recombinant factor VIIa (rFVIIa) is increasingly used in an “off-label” manner as a universal hemostatic and rever-sal agent. However, it has not been studied in humans for reversal of NOACs, and the results of studies in animal mod-els are inconclusive. The benefit-to-risk balance for rFVIIa must be carefully weighed, as rFVIIa has been associated with an increased risk of arterial thrombosis among elderly patients.45,46 In several animal models, rFVIIa reversed bleed-ing time prolongation associated with dabigatran and rivar-oxaban, but it did not correct the underlying coagulopathy as suggested by other laboratory markers.44 In one study, rats received high-dose dabigatran before a standard tail incision, prolonging the bleeding time from 125 s in controls to 1455 s. A 0.5 mg/kg dose of rFVIIa decreased this bleeding time to 135 s. The partial thromboplastin time was 58 s after dabi-gatran exposure, versus 7 s in controls, and administration of rFVIIa reduced this to 27 s. In a similar study that exposed rats to supratherapeutic dabigatran levels, administration of rFVIIa rapidly corrected the bleeding time and preserved this effect for the entire 2-h study period.47 However, of the coagulation markers examined, only the prothrombin time was completely corrected. The partial thromboplastin time, the ecarin clotting time, and the thrombin time all failed to normalize.47

PCCs are available as three-factor (II, IX, X) and four-factor (II, VII, IX, X) varieties that are procoagulant and enhance thrombin generation.42 The four-factor PCCs have activated and nonactivated forms, and only three-factor PCCs are available in the United States.44 Small quantities of heparin, antithrombin, protein C, and protein S are added to the concentrates to reduce coagulation activation through endogenous pathways,48 but caution is required for off-label use as thrombotic events in 1–3% of treated patients have been reported with both formulations.49,50

Unlike the other procoagulant agents, four-factor PCCs have been studied as potential reversal agents in humans. In a small, randomized, double-blinded, placebo-controlled trial, 12 healthy men were given dabigatran 150 mg twice-daily or (supratherapeutic) rivaroxaban 20 mg twice-daily for 2.5 days, and subsequently received either a 50 IU/kg bolus of a four-factor PCC or saline.51 They were switched to the other anticoagulant following a wash-out period and the procedure was repeated. The addition of the PCC completely reversed both the prothrombin time prolongation and inhibition of endogenous thrombin potential associated with rivaroxaban, but only laboratory parameters were evaluated in this study, and no bleeding outcomes were measured in the volunteers. However, dabigatran-associated prolongations in the clotting assays and endogenous thrombin potential lag time were not corrected by the administration of the PCC. Recently, in an animal model, although both rFVIIa and PCC partially corrected laboratory assays (thromboelastography and thrombin generation assay), none of them reduced bleeding induced by rivaroxaban.52



Marlu et al.53 evaluated dabigatran and rivaroxaban rever-sal using thrombin generation tests evaluating 10 healthy volunteers randomized to receive rivaroxaban (20 mg) or dabigatran (150 mg) orally in a cross-over study, and blood was collected 2 h post-ingestion. Anticoagulation reversal was tested in vitro using PCC, rFVIIa, or factor eight inhibi-tory bypass activity at different concentrations.53 In rivar-oxaban-treated patients, PCC and factor eight inhibitory bypass activity corrected thrombin generation, but rFVIIa only modified the kinetic parameters. In dabigatran-treated patients, PCC increased thrombin generation as determined by area under the curve, but only rFVIIa and factor eight inhibitory bypass activity corrected the altered lag time.53

SummaryCommon principles of bleeding management as with any anticoagulant (including the known principles for warfa-rin) should be followed in patients receiving dabigatran. Hemodialysis is an additional, unique therapeutic option for urgently reducing exposure to dabigatran that has not been shown to be useful for other new oral anticoagulants.

Ongoing clinical studies are needed to determine the best method for reversal of the NOACs when bleeding occurs. Based on the available evidence, supportive care and interventions as discussed including dialysis for dabi-gatran should be considered in a bleeding patient and potential therapeutic approaches as listed in figure 2. For rivaroxaban-treated patients, studies in volunteers sug-gest the PCCs may be effective, but additional studies are needed. When possible, these drugs should be stopped preoperatively at times based on renal function and pro-cedure.54 Additional drug-specific antidotes are also under investigation.

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2010; 121:1523–32 2. Levy JH, Key NS, Azran MS: Novel oral anticoagulants:

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Fig. 2. Management strategies for patients bleeding who have received the novel oral anticoagulation agents. In cases of mild bleeding, stopping or delaying the next dose should be considered. The new agents including dabigatran, rivaroxaban, and recently approved apixiban have relatively short half-lives, so stopping the drug in patients with normal renal function, the an-ticoagulant effect rapidly decreases compared to warfarin. In patients with moderate to severe bleeding, standard therapeutic approaches should be considered, including supportive care that includes volume resuscitation, hemodynamic support with vasoactive therapy, blood product transfusions as determined by testing, and identification of bleeding source that may require surgical or another intervention. If the agents were taken within ≈2 h of admission, administration of oral activated charcoal should be considered. For dabigatran,† hemodialysis can remove ≈60% of the drug after several hours of dialysis and should be considered in patients with impaired renal function who are bleeding and will have altered clearance. Apixaban and rivaroxaban are highly protein bound and will not be cleared by hemodialysis. However, emergency access for hemodialysis requires vascu-lar access with large bore catheters that may pose additional risk in the anticoagulated patient. For patients with life-threatening bleeding, hemodynamic and hemostatic resuscitation should be considered, with therapy similar to that for a trauma patient including the use of a massive transfusion protocol. Based on current data as discussed in the manuscript, the use of either three-factor or four-factor prothrombin complex concentrates (PCCs) depending on their availability should be considered as they have been shown to reverse or partially reverse the anticoagulation effect of the newer agents. ‡ In patients receiving dabigatran, the use of an activated PCC may be more effective. † However, there are no studies reporting the use of PCCs on actual bleeding in patients, and further studies including the development of specific reversal agents are underway currently. In hypotensive patients, hemodialysis is unlikely to be tolerated, and alternate methods for hemofiltration should be considered if needed. † The use of recombinant activated factor VIIa (rVIIa) decreases bleeding times in animal models, but there are no hu-man studies to determine if this is effective. † = for dabigatran. ‡ = for rivaroxaban and apixiban.


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original article

T h e n e w e ngl a nd j o u r na l o f m e dic i n e

n engl j med 369;5 nejm.org august 1, 2013428

A Trial of Intraoperative Low-Tidal-Volume Ventilation in Abdominal SurgeryEmmanuel Futier, M.D., Jean-Michel Constantin, M.D., Ph.D.,

Catherine Paugam-Burtz, M.D., Ph.D., Julien Pascal, M.D., Mathilde Eurin, M.D., Arthur Neuschwander, M.D., Emmanuel Marret, M.D.,

Marc Beaussier, M.D., Ph.D., Christophe Gutton, M.D., Jean-Yves Lefrant, M.D., Ph.D., Bernard Allaouchiche, M.D., Ph.D., Daniel Verzilli, M.D., Marc Leone, M.D., Ph.D.,

Audrey De Jong, M.D., Jean-Etienne Bazin, M.D., Ph.D., Bruno Pereira, Ph.D., and Samir Jaber, M.D., Ph.D., for the IMPROVE Study Group*

From the Département d’Anesthésie et Ré-animation, Hôpital Estaing (E.F., J.-M.C., J.P., J.-E.B.), Université de Clermont-Fer-rand, Retinoids, Reproduction, and Devel-opmental Diseases Unit, Équipe Accueil 7281 (E.F., J.-M.C.), and the Biostatistics Unit, Direction de la Recherche Clinique (B.P.), Centre Hospitalier Universitaire (CHU) de Clermont-Ferrand, Clermont-Ferrand; Assistance Publique–Hôpitaux de Paris (AP-HP), Département d’Anesthé-sie et Réanimation, Hôpital Beaujon, Hôpi-taux Universitaires Paris Nord Val de Seine and Université Paris Diderot, Sorbonne Paris Cité (C.P.-B., M.E., A.N.), Départe-ment d’Anes thé sie et Réanimation, Hôpi-tal Tenon (E.M.), and AP-HP, Départe-ment d’Anes thé sie et Réanimation, Hô pi tal Saint-Antoine (M.B., C.G.), Paris; CHU de Nîmes, Section d’Anesthésie and Dé partement d’Anesthésie et Réani-mation, Nîmes (J.-Y.L.); CHU de Lyon, Département d’Anesthésie et Réanima-tion, Hôpi tal Edouard Herriot, Lyon (B.A.); CHU de Montpellier, Département d’Anes-thésie et Réanimation B, Hôpital Saint-Eloi, and INSERM Unité 1046 and Univer-sité Montpellier 1, Montpellier (D.V., A.D.J., S.J.); and Assistance Publique–Hôpital de Marseille, Département d’Anesthésie et Réanimation, Hôpital Nord, Marseille (M.L.) — all in France. Address reprint re-quests to Dr. Jaber at the Département d’Anesthésie et Réanimation B (DAR B), 80 Ave. Augustin Fliche, 34295 Montpellier, France, or at [email protected].

* Additional investigators in the Intraop-erative Protective Ventilation (IMPROVE) Study Group are listed in the Supplemen-tary Appendix, available at NEJM.org.

N Engl J Med 2013;369:428-37. DOI: 10.1056/NEJMoa1301082Copyright © 2013 Massachusetts Medical Society.

A BS TR AC T

BACKGROUND

Lung-protective ventilation with the use of low tidal volumes and positive end-expiratory pressure is considered best practice in the care of many critically ill patients. However, its role in anesthetized patients undergoing major surgery is not known.

METHODS

In this multicenter, double-blind, parallel-group trial, we randomly assigned 400 adults at intermediate to high risk of pulmonary complications after major ab-dominal surgery to either nonprotective mechanical ventilation or a strategy of lung-protective ventilation. The primary outcome was a composite of major pul-monary and extrapulmonary complications occurring within the first 7 days after surgery.

RESULTS

The two intervention groups had similar characteristics at baseline. In the inten-tion-to-treat analysis, the primary outcome occurred in 21 of 200 patients (10.5%) assigned to lung-protective ventilation, as compared with 55 of 200 (27.5%) assigned to nonprotective ventilation (relative risk, 0.40; 95% confidence interval [CI], 0.24 to 0.68; P = 0.001). Over the 7-day postoperative period, 10 patients (5.0%) assigned to lung-protective ventilation required noninvasive ventilation or intubation for acute respiratory failure, as compared with 34 (17.0%) assigned to nonprotective ventilation (relative risk, 0.29; 95% CI, 0.14 to 0.61; P = 0.001). The length of the hospi-tal stay was shorter among patients receiving lung-protective ventilation than among those receiving nonprotective ventilation (mean difference, −2.45 days; 95% CI, −4.17 to −0.72; P = 0.006).

CONCLUSIONS

As compared with a practice of nonprotective mechanical ventilation, the use of a lung-protective ventilation strategy in intermediate-risk and high-risk patients undergoing major abdominal surgery was associated with improved clinical out-comes and reduced health care utilization. (IMPROVE ClinicalTrials.gov number, NCT01282996.)

The New England Journal of Medicine Downloaded from nejm.org at MERCY HOSP ST LOUIS on August 12, 2013. For personal use only. No other uses without permission.

Copyright © 2013 Massachusetts Medical Society. All rights reserved.

Intr aoper ative Low-Tidal-Volume Ventilation

n engl j med 369;5 nejm.org august 1, 2013 429

Worldwide, more than 230 million patients undergoing major surgery each year require general anesthesia and

mechanical ventilation.1 Postoperative pulmo-nary complications adversely affect clinical out-comes and health care utilization,2 so preven-tion of these complications has become a measure of the quality of hospital care.3 Previ-ous, large cohort studies have shown that 20 to 30% of patients undergoing surgery with gen-eral anesthesia are at intermediate to high risk for postoperative pulmonary complications.4,5

Mechanical ventilation with the use of high tidal volumes (10 to 15 ml per kilogram of pre-dicted body weight) has traditionally been rec-ommended to prevent hypoxemia and atelecta-sis in anesthetized patients.6 There is, however, considerable evidence from experimental and observational studies that mechanical ventila-tion — in particular, high tidal volumes that cause alveolar overstretching — can initiate ventilator-associated lung injury7 and contrib-ute to extrapulmonary organ dysfunction through systemic release of inflammatory me-diators.8,9

Lung-protective ventilation, which refers to the use of low tidal volumes and positive end-expiratory pressure (PEEP), and which may also include the use of recruitment maneuvers (peri-odic hyperinflation of the lungs),10 has been shown to reduce mortality among patients with the acute respiratory distress syndrome11 and is now considered best practice in the care of many critically ill patients.12 Although this ap-proach may be beneficial in a broader popula-tion,13,14 some physicians have questioned the benefits of using lung-protective ventilation in the surgical setting,15-18 especially since the use of high tidal volumes and no PEEP is still com-monplace and less than 20% of patients receive protective ventilation in routine anesthetic practice.19,20

We conducted the Intraoperative Protective Ventilation (IMPROVE) trial to determine wheth-er a multifaceted strategy of prophylactic lung-protective ventilation that combined low tidal volumes, PEEP, and recruitment maneuvers could improve outcomes after abdominal sur-gery, as compared with the standard practice of nonprotective mechanical ventilation.

ME THODS

TRIAL DESIGN AND OVERSIGHT

The IMPROVE trial was an investigator-initiated, multicenter, double-blind, stratified, parallel-group, clinical trial. Randomization was performed with the use of a computer-generated assignment se-quence and a centralized telephone system. The study protocol and statistical analysis plan were approved for all centers by a central ethics commit-tee (Comité de Protection des Personnes Sud-Est I, Saint-Etienne, France) according to French law. The protocol, including the statistical analysis plan, is available with the full text of this article at NEJM.org. An independent data and safety moni-toring committee oversaw the study conduct and reviewed blinded safety data. The members of the steering committee (see the Supplementary Appendix, available at NEJM.org) vouch for the accuracy and completeness of the data and analy-ses and the fidelity of the study to the protocol. There was no industry support or involvement in the trial.

Patients were screened and underwent random-ization between January 31, 2011, and August 10, 2012, at seven French university teaching hospitals. Written informed consent was obtained before randomization from each patient, on the day be-fore surgery. Randomization was stratified accord-ing to study site and the planned use or nonuse of postoperative epidural analgesia, which is a factor that may influence outcomes.21 Treatment assign-ments were concealed from patients, research staff, the statistician, and the data and safety monitor-ing committee. Although the staff members who collected data during surgery were aware of the group assignments, outcome assessors were un-aware of these assignments throughout the study.

PATIENTS

Patients were eligible for participation in the study if they were older than 40 years of age, were scheduled to undergo laparoscopic or non-laparoscopic elective major abdominal surgery1 with an expected duration of at least 2 hours, and had a preoperative risk index for pulmonary complications5 of more than 2. The risk index uses risk classes that range from 1 to 5, with higher risk classes indicating a higher risk of postoperative pulmonary complications (see the





Supplementary Appendix). Patients were ineligible if they had received mechanical ventilation within the 2 weeks preceding surgery, had a body-mass index (the weight in kilograms divided by the square of the height in meters) of 35 or higher, had a history of respiratory failure or sepsis with-in the 2 weeks preceding surgery, had a require-ment for intrathoracic or emergency surgery, or had a progressive neuromuscular illness.

INTERVENTIONS

Patients were assigned to receive volume-con-trolled mechanical ventilation according to one of two strategies: nonprotective ventilation with a tidal volume of 10 to 12 ml per kilogram of predicted body weight, with no PEEP and no re-cruitment maneuvers, as previously described20 (the nonprotective-ventilation group), or lung-protective ventilation with a tidal volume of 6 to 8 ml per kilogram of predicted body weight, a PEEP of 6 to 8 cm of water, and recruitment ma-neuvers repeated every 30 minutes after tracheal intubation (the protective-ventilation group). Each recruitment maneuver consisted of applying a continuous positive airway pressure of 30 cm of water for 30 seconds. During anesthesia, a plateau pressure of no more than 30 cm of water was targeted in each group. All other ventilation pro-cedures were identical in the two study groups (see the Supplementary Appendix).

The predicted body weight was calculated for each patient with the use of previously defined formulas.11 For episodes of arterial desaturation (defined as a peripheral oxygen saturation of ≤92%), a transient increase in the fraction of in-spired oxygen (Fio2) to 100% was permitted, and in patients assigned to nonprotective ventilation, the use of PEEP, recruitment maneuvers, or both was allowed, if required. Decisions about all other aspects of patient care during the intraop-erative and postoperative periods, including gen-eral anesthesia, administration of fluids, use of prophylactic antibiotic agents, and postoperative pain management, were made by the attending physician according to the expertise of the staff at each center and routine clinical practice.

OUTCOMES

The primary outcome was a composite of major pulmonary and extrapulmonary complications occurring by day 7 after surgery. Major pulmo-nary complications were defined as pneumonia

(defined according to standard criteria; see the Supplementary Appendix) or the need for invasive or noninvasive ventilation for acute respiratory fail-ure. Major extrapulmonary complications were de-fined as sepsis, severe sepsis and septic shock (de-fined according to consensus criteria),22 or death.

Secondary outcomes within the 30-day fol-low-up period were the incidence of pulmonary complications due to any cause, graded on a scale from 0 (no pulmonary complications) to 4 (the most severe complications)23 (see the Supplemen-tary Appendix); ventilation-related adverse events during surgery; postoperative gas exchange; un-expected need for admission to the intensive care unit (ICU); extrapulmonary complications; durations of ICU and hospital stays; and the rate of death from any cause 30 days after surgery. Pulmonary complications were analyzed sepa-rately; in particular, the need for invasive or noninvasive ventilation because of acute respira-tory failure, the development of postoperative atelectasis, pneumonia, acute lung injury, and the acute respiratory distress syndrome, defined ac-cording to standard criteria (see the Supplementary Appendix). Extrapulmonary complications in cluded the systemic inflammatory response syndrome (SIRS); sepsis; severe sepsis and septic shock; and surgical complications, including intraabdomi-nal abscess, anastomotic leakage, and unplanned reoperation (all defined according to consensus criteria22,24).

STATISTICAL ANALYSIS

We calculated that a sample of 400 patients would provide 80% power to detect a relative dif-ference of 50% in the primary outcome, at a two-sided alpha level of 0.05, assuming a 20% rate of postoperative complications in the nonprotective-ventilation group.25 For safety reasons, an interim analysis was conducted after the enrollment of the first 200 patients, according to the a priori statistical analysis plan. The data and safety mon-itoring committee did not recommend discontin-uation of the trial on the basis of that analysis, and 400 patients were therefore included. A total of 3 patients were excluded after randomization; surgery was stopped prematurely in 2 of the 3 pa-tients because of extensive illness (duration of sur-gery, <2 hours), and 1 had undergone random-ization in error (violation of exclusion criteria). An additional 3 patients were thus randomly as-signed to a study group to obtain the full sample.





All analyses were conducted on data from the modified intention-to-treat population, which in-cluded all patients who underwent randomization except the three who were excluded (Fig. 1). An un-adjusted chi-square test was used for the primary outcome analysis. Multiple logistic-regression anal-ysis was used to identify relevant baseline covariates associated with the primary outcome, in addition to the stratification variables (use or nonuse of epidural analgesia and study center). Variables tested in the model were selected if the P value was less than 0.10 and if they were clinically rel-evant. Adjusted analyses were performed with the

use of robust Poisson generalized-linear-model re-gression26 and are presented as relative risks with 95% confidence intervals. A chi-square test (or Fisher’s exact test, as appropriate) was used for secondary binary outcomes. The Hochberg pro-cedure was used to adjust for multiple testing of components of the composite primary outcome.27 Adjusted analyses were performed with the use of the same adjustment variables that were used in the robust Poisson regression analysis. Con-tinuous variables were compared with the use of an unpaired t-test or the Mann–Whitney U test. Adjusted analyses were performed with the use

601 Underwent screening

1803 Patients were scheduled to undergoelective abdominal surgery

1202 Were ineligible47 Were ≤40 yr of age

102 Had expected duration of surgery of <2 hr1053 Had preoperative risk index for pulmonary

complications of <2

198 Were excluded49 Declined to participate

149 Met exclusion criteria

400 Underwent randomization

3 Were excluded after randomization2 Had extensive illness (surgery <2 hr)1 Had violation of exclusion criteria (age ≤40 yr)

An additional 3 underwent randomization

200 Were assigned to receive nonprotective mechanical ventilation

200 Were assigned to receive lung-protective mechanical ventilation

200 (100%) Were included in 30-day analysis 200 (100%) Were included in 30-day analysis

Figure 1. Assessment, Randomization, and Follow-up of Patients.

A total of 1803 patients awaiting abdominal surgery were assessed preoperatively for trial eligibility by the research staff. A total of 400 patients were included in the modified intention-to-treat analysis and were followed for 30 days after surgery. After randomization, 3 patients were excluded; 2 patients were excluded because surgery was stopped prematurely (duration, <2 hours), owing to extensive illness, and 1 had undergone randomization in error. An addi-tional 3 patients were then enrolled in the study.





of the same adjustment variables that were used in the linear-regression model. The time-to-event curves were calculated with the Kaplan–Meier method. Details regarding the handling of missing data are provided in the Supplementary Appendix.

All analyses were conducted with the use of Stata software, version 12 (StataCorp). A two-sided P value of less than 0.05 was considered to indicate statistical significance.

R ESULT S

STUDY POPULATION

From January 2011 through August 2012, a total of 1803 patients awaiting abdominal surgery were assessed for trial eligibility. A total of 400 pa-tients were included in the modified intention-to-treat analysis and were followed for 30 days after surgery (Fig. 1). One patient in the nonpro-tective-ventilation group received lung-protective ventilation but was included in the analysis for the group to which he was assigned. Data on the primary outcome were available for all patients. Baseline characteristics were similar between the two groups (Table 1). Open laparotomy, mainly for cancer resection, was performed in 156 patients (78.0%) in the nonprotective-ventilation group and in 159 (79.5%) in the protective-ventilation group (P = 0.80).

INTRAOPERATIVE PROCEDURES

Table 2 shows the distribution of the main intra-operative procedures. Mean (±SD) tidal volumes were 11.1±1.1 ml per kilogram in the nonprotec-tive-ventilation group, as compared with 6.4±0.8 ml per kilogram in the protective-ventilation group (P<0.001), and values remained within tar-get ranges throughout the intraoperative period. In the protective-ventilation group, the median PEEP was 6 cm of water (interquartile range, 6 to 8), and the median number of recruitment maneu-vers was 9 (interquartile range, 6 to 12); in the nonprotective-ventilation group, the value for each of these measures was 0 (interquartile range, 0 to 0) (Table 2). There were no significant between-group differences in type and duration of sur-gery, use or nonuse of epidural analgesia, blood loss, volume of fluids administered, and need for vasopressor administration. Five patients in the nonprotective-ventilation group required at least one intraoperative rescue therapy for arterial de-

Table 1. Baseline Characteristics of the Patients.*

Characteristic

Nonprotective Ventilation (N = 200)

Lung-Protective Ventilation (N = 200)

Age — yr 63.4±10.0 61.6±11.0

Male sex — no. (%) 121 (60.5) 116 (58.0)

Height — cm 169.5±9.0 169.1±8.8

Body weight — kg

Actual 71.3±13.9 71.4±14.2

Predicted† 63.8±9.9 63.3±9.7

Body-mass index‡

Mean 24.7±3.8 24.8±3.8

25–35 — no. (%) 88 (44.0) 99 (49.5)

Preoperative risk index — no. (%)§

Risk class 2 100 (50.0) 101 (50.5)

Risk class 3 94 (47.0) 93 (46.5)

Risk class 4 or 5 6 (3.0) 6 (3.0)

Coexisting condition — no. (%)¶

Current smoking 50 (25.0) 51 (25.5)

Any alcohol intake 10 (5.0) 21 (10.5)

Not fully independent in activities of daily living

8 (4.0) 8 (4.0)

Chronic obstructive pulmonary disease

20 (10.0) 20 (10.0)

Loss of >10% of body weight in previous 6 mo

44 (22.0) 40 (20.0)

Long-term glucocorticoid use 4 (2.0) 7 (3.5)

Laparoscopic surgery — no. (%) 44 (22.0) 41 (20.5)

Type of surgery — no. (%)

Pancreaticoduodenectomy 80 (40.0) 84 (42.0)

Liver resection 52 (26.0) 44 (22.0)

Gastrectomy 17 (8.5) 15 (7.5)

Colorectal resection 40 (20.0) 47 (23.5)

Other procedure 11 (5.5) 10 (5.0)

Diagnosis — no. (%)

Cancer 164 (82.0) 155 (77.5)

Diagnosis other than cancer 36 (18.0) 45 (22.5)

* Plus–minus values are means ±SD. There were no significant differences between the two groups (P>0.05).

† The predicted body weight was calculated as follows: for men, 50+0.91(height in centimeters − 152.4); and for women, 45.5 + 0.91(height in centimeters − 152.4).11

‡ The body-mass index is the weight in kilograms divided by the square of the height in meters.

§ The preoperative risk index for pulmonary complications5 uses risk classes that range from 1 to 5, with higher risk classes indicating a higher risk of postoperative complications. Patients with a risk class of 2 or more were eligi-ble for participation in the study.

¶ All factors listed as coexisting conditions were included in the preoperative risk index as predictors of postoperative pulmonary complications.





Table 2. Intraoperative Procedures.*

Variable

NonprotectiveVentilation(N = 200)

Lung-Protective Ventilation(N = 200) P Value

Tidal volume — ml 719.0±127.8 406.7±75.6 <0.001

Tidal volume — ml/kg of predicted body weight 11.1±1.1 6.4±0.8 <0.001

PEEP — cm of water

Baseline <0.001

Median 0 6

Interquartile range 0–0 6–8

End of surgery <0.001

Median 0 6


No. of recruitment maneuvers <0.001

Median 0 9


Peak pressure — cm of water

Baseline 20.1±4.9 18.9±3.6 0.04

End of surgery 20.6±4.4 20.0±4.0 0.15

Plateau pressure — cm of water

Baseline 16.1±4.3 15.2±3.0 0.02

End of surgery 16.6±3.5 15.2±2.6 <0.001

Respiratory system compliance — ml/cm of water

Baseline 48.4±17.8 55.2±26.6 0.06

End of surgery 45.1±12.9 55.2±26.7 <0.001

Fio2 — % 47.2±7.6 46.4±7.3 0.27

Volume of fluids administered — liters

Crystalloid 0.47

Median 2.0 1.5

Interquartile range 1.5–3.5 2.0–3.0

Colloid 0.97

Median 0.5 0.5

Interquartile range 0.25–1.0 0.50–1.0

Duration of surgery — no./total no. (%)† 0.95

2–4 hr 76/192 (39.6) 75/195 (38.5)

>4–6 hr 75/192 (39.1) 76/195 (39.0)

>6 hr 41/192 (21.4) 44/195 (22.6)

Duration of mechanical ventilation — min 344±127.9 319±139.4 0.84

Epidural analgesia — no. (%) 77 (38.5) 83 (41.5) 0.61

* Plus–minus values are means ±SD. Detailed data on intraoperative procedures are given in Table S2 in the Supplementary Appendix. Fio2 denotes inspired oxygen fraction, and PEEP positive end-expiratory pressure.

† The duration of surgery was calculated as the time between skin incision and closure of the incision.





saturation (PEEP in one patient, recruitment ma-neuvers in two, and both in two), as compared with no patients in the protective-ventilation group (P = 0.06).

OUTCOMES

Primary OutcomeMajor pulmonary and extrapulmonary complica-tions occurred within the first 7 days after sur-gery in 21 patients (10.5%) in the protective-ven-tilation group, as compared with 55 (27.5%) in the nonprotective-ventilation group (adjusted relative risk, 0.40; 95% confidence interval [CI], 0.24 to 0.68; P = 0.001) (Table 3). The results of associated univariate and multivariate analyses are provided in Table S1 in the Supplementary Appendix.

Secondary OutcomesOne or more pulmonary complications developed within the first 7 days after surgery in 35 patients (17.5%) in the protective-ventilation group, as com-pared with 72 (36.0%) in the nonprotective-ventila-tion group (adjusted relative risk, 0.49; 95% CI, 0.32 to 0.74; P<0.001). More patients in the non-protective-ventilation group than in the protec-tive-ventilation group had major (grade ≥3) pul-monary complications (Table 3, and Tables S3 and S4 in the Supplementary Appendix) and major pulmonary and extrapulmonary complications dur-ing the 30 days after surgery (P<0.001 by the log-rank test) (Fig. 2). There were no relevant between-group differences in gas exchange after extubation and on day 1 after surgery (Table S5 in the Supple-mentary Appendix).

The proportion of patients who required post-operative ventilatory assistance (noninvasive ven-tilation or intubation) for acute respiratory failure was lower in the protective-ventilation group than in the nonprotective-ventilation group during the first 7 days after surgery (10 of 200 patients [5.0%], vs. 34 of 200 [17.0%]; adjusted relative risk, 0.29; 95% CI, 0.14 to 0.61; P = 0.001), and the proportion was also lower with protective ventilation during the first 13 days after surgery (6.5% vs. 18.5%; adjusted relative risk, 0.36; 95% CI, 0.19 to 0.70; P = 0.003) (Table 3). In addition, the cumulative 30-day probability of an event requiring intuba-tion or noninvasive ventilation for postoperative acute respiratory failure was lower among pa-tients who received lung-protective ventilation than among those who received nonprotective

ventilation (P<0.001 by the log-rank test) (Fig. S1 in the Supplementary Appendix).

There was no significant difference between the protective-ventilation group and the nonpro-tective-ventilation group with respect to the pro-portion of patients who were unexpectedly ad-mitted to the ICU during the 30-day period after surgery (11.0 and 12.5%, respectively; adjusted rela-tive risk with protective ventilation, 0.88; 95% CI, 0.49 to 1.59; P = 0.67), nor was there a significant between-group difference in the rate of adverse events (Table S3 in the Supplementary Appendix). Mortality at 30 days in the protective-ventilation group was similar to that in the nonprotective-ventilation group (3.0% and 3.5%, respectively; adjusted relative risk with protective ventilation, 1.13; 95% CI, 0.36 to 3.61; P = 0.83). However, the median hospital stay was shorter in the protec-tive-ventilation group than in the nonprotective-ventilation group (Table 3).

DISCUSSION

In this trial, intraoperative lung-protective me-chanical ventilation, as compared with non-protective ventilation, led to improved clinical outcomes and reduced health care utilization after abdominal surgery. The observed rate of postoperative complications in our study was slightly higher than predicted.25 This was due, in part, to the exclusion of patients with a low risk of complications, as well as the large pro-portion of patients who underwent major ab-dominal procedures, which are associated with increased morbidity rates. Of the 400 patients en rolled, 19 had postoperative pneumonia and 47 had respiratory failure requiring intubation or noninvasive ventilation. These rates are con-sistent with previously reported rates of pulmo-nary complications25,28 and mortality.29 Our lung-protective ventilation strategy resulted in a 69% reduction in the number of patients requiring ventilatory support within the first 7 days after surgery.

Several hypotheses could explain some of the differences between the results of the pres-ent study and findings in other trials of lung-protective ventilation during high-risk surgery. Previous trials have included small numbers of patients, have focused on different (and not necessarily clinically relevant) outcomes,17 and





have used either very low levels of PEEP or no PEEP.15,16,18 One strength of the present trial is our use of a robust composite outcome that is highly pertinent to this high-risk surgical population.5

Mechanical ventilation itself can induce an in-flammatory response30 and can synergize with the response induced by major surgery at both local and systemic levels. This amplification of

Table 3. Results of Unadjusted and Adjusted Outcome Analyses.*

Variable

NonprotectiveVentilation(N = 200)

Lung-Protective Ventilation(N = 200)

UnadjustedRelative Risk or Between-Group

Difference(95% CI) P Value†

AdjustedRelative Risk or Between-Group

Difference(95% CI)‡ P Value

Primary composite outcome — no. (%)

Within 7 days§ 55 (27.5) 21 (10.5) 0.38 (0.24–0.61) <0.001 0.40 (0.24–0.68) 0.001

Within 30 days 58 (29.0) 25 (12.5) 0.43 (0.28–0.66) <0.001 0.45 (0.28–0.73) <0.001

Secondary outcomes — no. (%)

Pulmonary complication within 7 days¶

Grade 1 or 2 30 (15.0) 25 (12.5) 0.69 (0.42–1.13) 0.14 0.67 (0.39–1.16) 0.16

Grade ≥3 42 (21.0) 10 (5.0) 0.24 (0.12–0.46) <0.001 0.23 (0.11–0.49) <0.001

Atelectasis within 7 days‖ 34 (17.0) 13 (6.5) 0.38 (0.21–0.70) 0.001 0.37 (0.19–0.73) 0.004

Pneumonia within 7 days 16 (8.0) 3 (1.5) 0.19 (0.05–0.63) 0.01 0.19 (0.05–0.66) 0.009

Acute lung injury or ARDS within 7 days 6 (3.0) 1 (0.5) 0.17 (0.02–1.37) 0.12 0.21 (0.02–1.71) 0.14

Need for ventilation within 7 days

Invasive 7 (3.5) 2 (1.0) 0.29 (0.06–1.36) 0.51 0.40 (0.08–1.97) 0.26

Noninvasive 29 (14.5) 9 (4.5) 0.31 (0.15–0.64) 0.006 0.29 (0.13–0.65) 0.002

Extrapulmonary complication within 7 days

SIRS 100 (50.0) 86 (43.0) 0.86 (0.70–1.06) 0.16 0.87 (0.65–1.17) 0.37

Sepsis 29 (14.5) 13 (6.5) 0.45 (0.24–0.84) 0.04 0.48 (0.25–0.93) 0.03

Severe sepsis or septic shock 9 (4.5) 8 (4.0) 0.89 (0.35–2.26) 0.80 1.48 (0.51–4.32) 0.47

Death within 30 days 7 (3.5) 6 (3.0) 0.86 (0.29–2.51) 0.80 1.13 (0.36–3.61) 0.83

Duration of stay in hospital and ICU — days

Hospital 0.02 0.006

Median 13 11 −2.25 (−4.04 to −0.47) −2.45 (−4.17 to −0.72)


ICU 0.58 0.69

Median 7 6 −1.48 (−6.87 to 3.91) −1.21 (−4.98 to 7.40)


* All postoperative complications were defined according to consensus criteria (see the Supplementary Appendix). For additional data on postoperative outcomes, see Tables S3 and S4 in the Supplementary Appendix. ARDS denotes acute respiratory distress syndrome, CI confi-dence interval, ICU intensive care unit, and SIRS systemic inflammatory response syndrome. Relative risks are shown for outcome variables, and differences between groups are shown for the duration of stays in the hospital and ICU.

† Adjustment was performed for stratification variables (use or nonuse of epidural analgesia and study center), preoperative risk index for postoperative pulmonary complications, sex, duration of surgery, and need for blood transfusion (yes or no).

‡ The Hochberg procedure was used to adjust for multiple testing of components of the composite primary outcome.27

§ The primary outcome was a composite of major pulmonary complications (defined as pneumonia or need for invasive or noninvasive ventilation for acute respiratory failure) and extrapulmonary complications (defined as sepsis, septic shock, or death) within the first 7 days after surgery.

¶ Postoperative pulmonary complications were scored with the use of a graded scale23 from 0 (no pulmonary complications) to 4 (the most severe complications) (see the Supplementary Appendix).

‖ Atelectasis was defined as opacification of the lung with shift of the mediastinum, hilum, or hemidiaphragm toward the affected area and compensatory overinflation in the adjacent, nonatelectatic lung.





the inflammation cascade contributes to the subsequent development of lung injury31 and sys-temic organ failure.8,32

The use of very low levels of PEEP in previous trials may have promoted the repeated opening and closing of small airways, leading to atelec-tasis, which can precipitate the development of pulmonary complications.6,33 We used a multi-faceted strategy of lung-protective ventilation that combined low tidal volumes, recruitment maneuvers to open collapsed alveoli, and moder-ate levels of PEEP to prevent further collapse.34 Other strengths of the present trial include the methods used to minimize bias (blinded and centralized randomization, complete follow-up, and intention-to-treat analyses); the pragmatic nature of the trial protocol, with routine practice being maintained; and the enrollment of pa-tients with characteristics similar to those of patients enrolled in other studies analyzing out-comes after major surgery.29

Our findings are consistent with the observa-tion of transient arterial hypotension during re-cruitment maneuvers.35 Consequently, recruit-

ment maneuvers, in which hemodynamic effects are potentially influenced by the applied level of alveolar pressure,36 should be used with caution in patients with hemodynamic instability.

There are several limitations to our study. The trial design did not include standardization of the administration of fluids. However, this limi-tation is unlikely to have affected our results, since the volume of fluids administered was similar in the two groups. The definition of nonprotective ventilation was arbitrary but is supported in the literature.19,20 The trial protocol did not include standardization of requirements for noninvasive ventilation; however, it was rec-ommended that the study centers follow clinical-practice guidelines,37,38 and postoperative care was conducted by health care workers who were unaware of the study assignments. The utiliza-tion of noninvasive ventilation in our trial is close to that reported in earlier studies.37 We therefore consider it unlikely that any imbalance in interventions affected our results.

In conclusion, our study provides evidence that a multifaceted strategy of prophylactic lung-pro-tective ventilation during surgery, as compared with a practice of nonprotective mechanical ven-tilation, results in fewer postoperative complica-tions and reduced health care utilization.

Dr. Futier reports receiving consulting fees from General Electric Medical Systems, lecture fees from Fresenius Kabi, and reimbursement of travel expenses from Fisher and Paykel Healthcare. Dr Constantin reports receiving consulting fees from Baxter, Fresenius Kabi, Dräger, and General Electric Medi-cal Systems, payment for expert testimony from Baxter, Dräger, and Fresenius Kabi, lecture fees from General Electric Medical Systems, Dräger, Fresenius Kabi, Baxter, Hospal, Merck Sharp & Dohme, and LFB Biomedicaments, payment for the development of educational presentations from Dräger, General Electric Medical Systems, Baxter, and Fresenius Kabi, and reimburse-ment of travel expenses from Bird, Astute Medical, Astellas, Fresenius Kabi, Baxter, and Hospal. Dr. Paugam-Burtz reports receiving consulting fees from Fresenius Kabi, lecture fees and reimbursement of travel expenses from Astellas, and payment for the development of educational presentations from LFB Bio-medicaments and Merck Sharp & Dohme. Dr. Allaouchiche re-ports receiving consulting fees from Fresenius Kabi and lecture fees from Novartis and Astellas. Dr. Leone reports receiving consulting fees from LFB Biomedicaments and lecture fees from Fresenius Kabi and Novartis. Dr. Jaber reports receiving consult-ing fees from Dräger France and Maquet France, lecture fees from Fisher and Paykel Healthcare, Abbott, and Philips, and re-imbursement of travel expenses from Pfizer. No other potential conflict of interest relevant to this article was reported.

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank all the patients who participated in the study; the clinical and research staff at all the trial sites, without whose as-sistance the study would never have been completed; and Mervyn Singer for valuable advice during the preparation of the manuscript.

Prob

abili

ty o

f Eve

nt0.50

0.30

0.40

0.20

0.10

0.001 3 7 3015

Days since Randomization

No. at RiskNonprotective

ventilationLung-protective

ventilation

200

200

182

192

163

184

145

179

142

176

142

175

Lung-protective ventilation

Nonprotective ventilation

Figure 2. Kaplan–Meier Estimates of the Probability of the Composite Primary Outcome.

Data for the Kaplan–Meier estimates of the probability of the composite primary outcome of major pulmonary or extrapulmonary complications were censored at 30 days after surgery. Major pulmonary complications included pneumonia or the need for invasive or noninvasive ventilation for acute respiratory failure. Major extrapulmonary complications were sepsis, severe sepsis, septic shock, and death. P<0.001 by the log-rank test for the between-group difference in the probability of the primary outcome.





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