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CLINICAL GASTROENTEROLOGY AND HEPATOLOGY 2003;1:425–432

RIGINAL ARTICLES

ropofol Versus Midazolam/Fentanyl for Outpatientolonoscopy: Administration by Nurses Supervisedy Endoscopists

RIAN J. ULMER, JONATHAN J. HANSEN, CHRISTINE A. OVERLEY, MICHELLE R. SYMMS,IDYASREE CHADALAWADA, SUTHAT LIANGPUNSAKUL, ELOISE STRAHL, APRIL M. MENDEL,nd DOUGLAS K. REX

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ackground & Aims: Propofol is under evaluation as aedative for endoscopic procedures. We comparedurse-administered propofol to midazolam plus fentanylor outpatient colonoscopy. Methods: One hundred out-atients undergoing colonoscopy were randomized toeceive propofol or midazolam plus fentanyl, adminis-ered by a registered nurse and supervised only by anndoscopist. Endpoints were patient satisfaction, proce-ure and recovery times, neuropsychologic function, andomplications. Results: The mean dose of propofol ad-inistered was 277 mg; mean doses of midazolam and

entanyl were 7.2 mg and 117 �g, respectively. Meanime to sedation was faster with propofol (2.1 vs. 6.1

in; P < 0.0001), and depth of sedation was greaterP < 0.0001). Patients receiving propofol reached fullecovery sooner (16.5 vs. 27.5 min; P � 0.0001) andere discharged sooner (36.5 vs. 46.1 min; P � 0.01).fter recovery, the propofol group scored better on tests

eflective of learning, memory, working memory span,nd mental speed. Six minor complications occurred inhe propofol group: 4 episodes of hypotension, 1 epi-ode of bradycardia, and 1 rash. Five complicationsccurred with the use of midazolam and fentanyl: onepisode of oxygen desaturation requiring mask ventila-ion and 4 episodes of hypotension. Patients in theropofol vs. midazolam and fentanyl groups reportedimilar degrees of overall satisfaction using a 10-cmisual analog scale (9.3 vs. 9.4, P > 0.5). Conclusions:urse-administered propofol resulted in several advan-

ages for outpatient colonoscopy compared with mida-olam plus fentanyl, but did not improve patient satis-action.

he majority of patients in the United States prefer tobe sedated during colonoscopy.1 The most widely

sed form of sedation is the combination of a benzodi-zepine, which has amnesic, anxiolytic, and sedativeroperties, and an opioid, which provides analgesia, syn-

rgistic sedation with benzodiazepines, and additionalmnesia.2 Although the use of a benzodiazepine andpioid is used routinely for colonoscopy, the combinations associated with several undesirable effects, including aelay of several minutes from the time of injection beforehe drugs exert their effects,3 delay of discharge afterompletion of the procedure owing to lingering effects ofhe medications,4 and risk for respiratory depression.5

Propofol is being investigated as a sedative for endo-copic procedures.6–17 Propofol has a favorable pharma-okinetic profile that is superior to benzodiazepines andarcotics with regard to onset of action18 and recoveryime.6,7,10 Although concern about respiratory depressionesults in restriction of its use to anesthetists in somenstitutions, it has been our experience19 and the expe-ience of others20 that registered nurse–endoscopist ad-inistered propofol is safe when patients are selected and

ppropriate safety measures are taken. In a prospectivetudy of 80 patients, we showed that propofol was asso-iated with a faster time to sedation, faster recovery andischarge times, faster recovery of neuropsychologicunction, and higher overall patient satisfaction whenompared with midazolam and meperidine for outpatientolonoscopy.6 When used in combination with midazo-am, fentanyl has been associated with faster recoveryimes for upper21 and lower22 endoscopy compared witheperidine. Because the use of fentanyl as a substitute

or meperidine in endoscopic procedures is expanding,e performed a controlled, randomized study of propofols. midazolam and fentanyl as sedation for outpatientolonoscopy. Importantly, all medications were admin-

Abbreviations used in this paper: ASA, American Society of Anes-hesiology; P, propofol; M/F, midazolam and fentanyl.

© 2003 by the American Gastroenterological Association1542-3565/03/$30.00

PII: 10.1053/S1542-3565(03)00226-X

ivision of Gastroenterology and Hepatology, Department of Medicin
iana University Hospital, Indianapolis, Indiana e, Ind
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istered by registered nurses under the supervision of theendoscopists without an anesthesiologist or other physi-cian present.

Materials and MethodsThe study was a randomized, blinded, prospective

study of 100 patients who presented for outpatient colonos-copy. The study was approved by the institutional reviewboard at Indiana University Purdue University Indianapolis(IUPUI)/Clarian Health Partners. Patients were invited toparticipate in the study during assessment before colonoscopy.Patients were recruited consecutively to the extent allowed bythe availability of a blinded person trained to make the neu-ropsychologic and other measurements required by the proto-col. Patients were eligible to enter the study if they were 18years of age or older, American Society of Anesthesiology(ASA) risk class I or II (unless they were class III on the basisof renal insufficiency only), and scheduled for colonoscopyonly. ASA class I is defined as no organic, physiologic, bio-chemical, or psychiatric disturbance. ASA class II is defined asa mild to moderate systemic disturbance caused either by thecondition being treated surgically or by other pathophysio-logic processes.

Exclusion criteria were: history of colonic or rectal resection,neurologic deficit, pregnancy, inability or unwillingness togive informed consent, inpatient status, known hypersensitiv-ity to any of the study medications or to either soy or eggproducts (listed as contraindications in the package insert ofpropofol [Diprivan; Astra Zeneca, Wilmington, DE]), obstruc-tive sleep apnea, acute gastrointestinal bleeding, anticoagula-tion, ASA class III (unless class III based only on renal insuf-ficiency) or higher, inability to open the mouth widely, shortthick neck, or desire to have colonoscopy without sedation.Sedation treatments were randomized before the start of thestudy by using a coin toss and blocks of 4, and the assignedsedation medications then were placed in sequentially num-bered opaque envelopes. The individual recruiting the patientswas unaware of the randomization scheme. The examiners whoperformed the neuropsychologic testing and assessed patientwakefulness, recovery room nurses, and the patients wereblinded to the type of sedation used. Endoscopists, nursesadministering the sedation, examiners recording intraproce-dure time points, and endoscopy technicians were not blindedto the sedation used.

Baseline neuropsychologic testing was assessed beforecolonoscopy using the Hopkins Verbal Learning Test Form 1,Stroop Color Word Test, Digit Span Test, and Trail MakingTests A and B. Details concerning these tests including theirpurposes have been reviewed by Lezak.23

In the procedure room, all patients were given supplementaloxygen (4 L/min) through a nasal cannula, and a 3-lead elec-trocardiogram, pulse oximetry, and blood pressure were mon-itored. Only registered nurses certified in advanced life supportand who completed a structured training program were per-mitted to administer propofol under the guidance of the

endoscopist. The nurse who administered the sedative medi-cations and physician were present for the entire period ofsedation and examination. The nurses attempted to achieve alevel of sedation that allowed the patient to tolerate theprocedure with minimal to mild pain while maintaining ad-equate cardiorespiratory function. In the propofol group, in-duction of sedation was begun with an initial 40-mg bolus(20–30-mg for elderly and smaller patients at the discretionof the endoscopist and nurse administering the medications)administered intravenously followed by titration with 10–20-mgboluses. The nurse evaluated the progress of the patient tosedation by observation of the following sequential series ofsigns: increased chatter, then vertical nystagmus, glassy-ap-pearing eyes, and/or yawning, and then muscular relaxation.Nurses also observed for a change in respiratory effort, respi-ratory rate, heart rate, and blood pressure. After an initial bolusinfusion of propofol, the patient was observed for 30–60seconds before deciding to administer the next bolus. Fentanylwas administered intravenously in 12.5- or 25-�g boluses andmidazolam as 0.5–1.0-mg boluses. Additional medication wastitrated at 1–3-minute intervals to achieve or maintain thedesired level of sedation. The nurse’s sole responsibility duringthe procedure was to sedate and monitor the patient. Anendoscopy technician was available to assist the colonoscopistwith technical maneuvers. This staffing pattern has been usedin our endoscopy suite for all sedated procedures for severalyears and was not changed for the study.

All colonoscopies were performed by faculty-level endosco-pists using a standard technique with the patient initially onthe left side. A single colonoscopist (D.K.R.) performed 95 ofthe colonoscopies. No gastroenterology fellows participated inany part of any colonoscopy. The following time points wererecorded: initiation of sedation, full sedation (when the nurseand endoscopist mutually agreed the patient was sedated suf-ficiently to begin the procedure), colonoscope insertion, intu-bation of the cecum, and colonoscope removal from the anus.After the procedure, both the physician and the nurse com-pleted a questionnaire that assessed the patient’s level ofsedation, pain, and ability to cooperate. Any complications(decline in oxygen saturation to less than 85%, heart rate lessthan 50 beats per minute, blood pressure less than 90/50 mmHg, or need for mechanical ventilation) were recorded.

After completion of the procedure, patients were transferredto a separate recovery area when vital signs were judged to bestable by the nurse responsible for sedation. In the recoveryarea, patients were monitored with continuous electrocardiog-raphy, pulse oximetry, and blood pressure recordings. Anobserver was present with the patient at all times and recordedthe time of exit from the procedure room, ability to stand atthe bedside without assistance or instability, full recovery(heart rate and blood pressure within 20% of baseline, oxygensaturation greater than 90% on room air, and ability to standat the bedside without assistance), discharge from the recoveryroom (patients must have met criteria for full recovery inaddition to being able to drink liquids and being subjectivelystable as judged by a blinded recovery room nurse).

426 ULMER ET AL. CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol. 1, No. 6

After arriving in the recovery area, the patients were askedto repeat the Trail Making Test at fixed time intervals (TrailsA at 7.5, 22.5, 37.5, and 52.5 min; and Trails B at 15, 30, 45,and 60 min) until they met the criteria for full recovery. If thepatient felt that he/she was unable to perform the test, the testwas deferred until the next time interval. Degree of alertnesswas recorded every 7.5 minutes using the 5-point Observer’sAssessment of Alertness/Sedation scale.6

After recovery, all of the neuropsychologic tests were re-peated (Hopkins Verbal Learning Test-R [Form 2], Trails Aand B, Digit Span, and Stroop). The patient completed asatisfaction questionnaire by using a visual 10-cm analog scalefor “overall satisfaction with the colonoscopy procedure,” andquestions detailing pain, recollection of the procedure, andquality of sedation. Patients were contacted by phone within48 hours to repeat the satisfaction questionnaire that includeda rating of “overall satisfaction” on a verbal 10-point scale,subjective impairment from sedation, and details concerningpain and recollection of the procedure.

Mean values for patient characteristics with continuousmeasurements (age, weight, years of education, tobacco use,and ASA score) and procedure and recovery times were com-pared between groups by using 2-sample t tests. All categoricassessments were compared by using �2 tests. Vital signs,patient satisfaction scores, and neuropsychologic testing scoreswere compared with repeated-measures analysis of variance.

Sedation time, recovery time, discharge time, and patientsatisfaction were considered the primary outcomes, and Pvalues for those outcomes were adjusted for multiple hypoth-esis testing using a Bonferroni correction. No adjustments formultiple hypothesis testing were made for any of the remain-ing outcome measures.

ResultsBaseline characteristics of the 2 groups were sim-

ilar (Table 1). One patient, a 25-year-old woman withhistory of chronic narcotic use for pain control, wasunable to tolerate the procedure using midazolam andfentanyl and subsequently received propofol. Because itwas our intention to treat this patient with midazolamand fentanyl, she was included in the midazolam andfentanyl (M/F) group. The propofol (P) patients receiveda mean dose of 277 � 105 mg. The M/F patientsreceived mean doses of 7.2 � 2.6 mg and 117 � 30 �g,respectively. The mean time to reach the cecum wassimilar in the groups (P � 3.15 � 1.67 min, M/F �3.75 � 1.76 min; P � 0.08). The mean time to sedationwas shorter with propofol (P � 2.08 � 0.72 min, M/F �6.10 � 2.97 min, P � 0.0001) (Table 2).

Physicians and nurses responsible for sedation bothsubjectively rated the quality of sedation. The nursesreported an adequate level of sedation in 49 (98%)propofol patients and 34 (68%) M/F patients (P �0.00004) and judged one (2%) propofol patient and 11(22%) M/F patients as being difficult to sedate (P �0.002). On a 5-point scale, propofol patients were se-dated more deeply during the procedure (P � 4.9 � 0.2,M/F � 3.6 � 1.0, P � 0.00001). Fewer patients receiv-ing propofol required positional change during colonos-copy (P � 1, M/F � 12, P � 0.001). The patientreceiving propofol whose position was changed was re-ported as being unable to assist with maneuvering,whereas 7 of the 12 patients receiving M/F were able torespond to greater than 50% of commands. Abdominalcounterpressure was used in fewer patients in the propo-fol group, but the difference was not significant (P � 6,M/F � 12, P � 0.1).

After completion of colonoscopy, patients in thepropofol group left the procedure room sooner than the

Table 1. Patient Characteristics (SD or Percent)

Propofol Midazolam and fentanyl

Age (yr) 55.6 (11.2) 55.3 (11.8)Weight (lb) 182.6 (34.0) 180.2 (46.4)Gender

Male 29 (58%) 25 (50%)Female 21 (42%) 25 (50%)

HandednessRight 45 (90%) 42 (84%)Left 5 (10%) 8 (16%)

RaceWhite 44 (88%) 44 (88%)Black 6 (12%) 4 (8%)Asian 0 (0%) 1 (2%)Hispanic 0 (0%) 1 (2%)

Educational degreeNo degree 0 (0%) 2 (4%)High school 16 (32%) 10 (20%)Technical 13 (26%) 13 (26%)College 9 (18%) 10 (20%)Graduate degree 12 (24%) 15 (30%)

Years of education 15.0 (2.7) 15.3 (2.9)Prior colonoscopy

Yes 22 (44%) 22 (44%)No 28 (56%) 28 (56%)

Alcohol consumption�1 drink/day 42 (84%) 38 (76%)1–3 drinks/day 7 (14%) 12 (24%)3–6 drinks/day 1 (2%) 0 (0%)�6 drinks/day 0 (0%) 0 (0%)

Tobacco use (pk/day) 0.1 (0.3) 0.1 (0.4)ASA score 1.36 (0.45) 1.31 (0.60)

Table 2. Endoscopic and Recovery Room Times

Mean (SD) time to Propofol M/F P

Sedate 2.1 (0.7) 6.1 (3.0) �0.0001Cecum 3.2 (1.7) 3.8 (1.7) 0.08Recovery room 6.8 (3.5) 8.2 (5.2) 0.15Full recovery 16.5 (8.5) 27.5 (16.2) 0.0001Discharge 36.5 (11.9) 46.1 (21.4) 0.01

NOTE. Data are given in minutes (standard deviation).

November 2003 PROPOFOL VERSUS MIDAZOLAM/FENTANYL 427

midazolam/fentanyl group, although this difference wasnot significant (P � 6.8 � 3.5 min, M/F � 8.2 � 5.2min, P � 0.15). Once in the recovery area, patients whoreceived propofol required less time to reach full recovery(P � 16.5 � 8.6 min, M/F � 27.5 � 16.2 min, P �0.0001) and were discharged by the recovery room nursesooner (P � 36.5 � 11.6, M/F � 46.1 � 21.4 min, P �0.01). After arriving in the recovery area, only 8 patientsin the propofol group required greater than 30 minutesto reach full recovery compared with 22 patients in themidazolam/fentanyl group (P � 0.001). Three patientsin the propofol group required observation in the recov-ery area greater than 1 hour vs. 16 patients in themidazolam/fentanyl group (P � 0.001). One patient whoreceived midazolam/fentanyl required over 2 hours ofobservation postcolonoscopy. When the total proceduretime and recovery times are added together, patients whoreceived propofol progressed through the endoscopy suiteover 15 minutes faster than those who received midazo-lam/fentanyl (P � 60.0 � 13.7 min, M/F � 75.5 �22.5 min, P � 0.0004).

Patients in the propofol group recovered sooner usingthe Observer’s Assessment of Alertness/Sedation Scale.By 15 minutes after arrival to the recovery area, 98% ofpatients who received propofol were judged to be fullyrecovered (score of 5) compared with 68% of those whoreceived midazolam/fentanyl (P � 0.001).

Vital signs were not different between the 2 groupsbefore sedation (Table 3). After colonoscopy, the heartrate, systolic blood pressure, and diastolic blood pressuredeclined in the propofol group, whereas only the systolicblood pressure was significantly lower compared withbaseline in the midazolam/fentanyl group. Both systolicand diastolic blood pressures were significantly lower inthe propofol group vs. the midazolam/fentanyl groupimmediately after the procedure. At arrival to the recov-ery area, the systolic and diastolic blood pressures were

lower compared with baseline in the propofol group. Inthe midazolam/fentanyl group, the systolic blood pres-sure and oxygen saturation were lower than baseline, andthe oxygen saturation in the midazolam/fentanyl groupwas significantly lower than the propofol group. At thetime of discharge, vital signs were similar betweengroups, and only the heart rate in the propofol group wassignificantly declined from baseline. In the recovery area,patients in the midazolam/fentanyl group experienced alower nadir oxygen saturation (P � 96.2% � 2.1%,M/F � 93.6% � 4.0%, P � 0.001) compared with thepropofol group.

Both at the time of discharge and 48 hours aftercolonoscopy, patients in the propofol and midazolam/fentanyl groups reported similar degrees of satisfactionwith the procedure (Table 4). Forty-nine patients in thepropofol group stated that level of sedation was justright, with one patient reporting that less sedation wasrequired; however, 3 patients in the midazolam/fentanylgroup felt that less sedation was needed, and 2 patientsdesired a higher level of sedation. Two of the 4 patientsin the propofol group who rated the sedation less thanexcellent reported that they experienced no pain duringthe procedure, and 2 patients reported mild pain. Theone patient in the propofol group who rated satisfactionwith the procedure as poor at 48 hours developed apruritic rash the day after the procedure. Of the 10patients in the midazolam/fentanyl group who reportedthe sedation less than excellent, 3 patients stated thatthey experienced mild pain, and 7 reported no pain.Forty-eight hours after the procedure, 5 patients in themidazolam/fentanyl group reported feeling moderatelyor severely impaired in the 24 hours after colonoscopy,whereas none of the propofol patients experienced morethan mild impairment. Patients who received midazo-lam/fentanyl spent a significantly longer time sleeping inthe 24 hours after colonoscopy than those who received

Table 3. Vital Sign Summary

Baseline Post procedure Recovery room Discharge

PropofolHeart rate 76.3 (13.2) 73.4 (12.1) 72.7 (10.3) 69.4 (11.4)Systolic BP 138.3 (22.8) 111.8 (19.6)a 121.1 (25.4) 136.0 (22.7)Diastolic BP 75.3 (11.3) 65.3 (13.2)a 66.7 (15.2) 75.7 (14.4)O2 Sat 97.9 (2.1) 99.0 (1.5) 97.3 (2.4)a 98.0 (2.0)

M/FHeart rate 73.6 (13.0) 71.0 (10.8) 71.1 (12.5) 69.4 (10.3)Systolic BP 133.2 (17.2) 123.9 (22.1)a 122.2 (23.2) 130.3 (19.3)Diastolic BP 73.7 (13.7) 71.5 (15.9)a 72.5 (18.7) 76.0 (16.5)O2 Sat 98.2 (1.8) 98.9 (1.8) 94.8 (5.0)a 97.6 (2.4)

NOTE. Data are given as mean (SD).BP, blood pressure; M/F, midazolam/fentanyl.aP � 0.05 between 2 groups at same time.


propofol (P � 7.6 � 1.4 h, M/F � 9.9 � 1.7 h, P �0.04).

A total of 11 minor complications occurred. Fourpatients in the propofol group experienced episodes ofhypotension (systolic blood pressure � 90 mm Hg). All4 cases improved without specific treatment. One patientwho received propofol experienced an episode of brady-cardia (heart rate � 50 per minute) that responded toatropine, and one patient in the propofol group devel-oped a rash. In the midazolam/fentanyl group, 4 patientsexperienced hypotension, and each resolved without spe-cific treatment. One patient who received midazolam/fentanyl, a 70-year-old woman, had oxygen desaturationto 73% that resolved with mask ventilation for about 30seconds.

To assess verbal learning and memory, the HopkinsVerbal Learning Test-R Form 1 was administered beforecolonoscopy, and Form 2 was administered after recovery(Figure 1). The preprocedure test scores were not differ-ent between the 2 groups in any category (Trials 1–3,

delayed recall, discrimination). After recovery, thepropofol patients had higher verbal recall than the mi-dazolam/fentanyl patients in all categories (P � 0.0001).After each successive listing of the words, the propofol

Figure 1. Postrecovery performance on Hopkins Verbal Learning Test(Form 2). After recovery, the propofol group had significantly higherscores than the midazolam/fentanyl group in all areas of measure-ment (P � 0.0001).

Table 4. Patient Satisfaction Survey

Discharge 48 hours after procedure

Propofol M/F Propofol M/F

Patient satisfaction 9.3 (1.4) 9.4 (0.9) 9.6 (0.7) 9.6 (1.0)Quality of sedation

Excellent 46 (92%) 40 (80%) 23 (82%) 30 (91%)Good 4 (8%) 9 (18%) 4 (14%) 3 (9%)Fair 0 (0%) 1 (2%) 0 (0%) 0 (0%)Poor 0 (0%) 0 (0%) 1 (4%) 0 (0%)

Adjustment in sedationMore sedation 0 (0%) 2 (4%) 0 (0%) 0 (0%)Just right 49 (98%) 44 (88%) 27 (96%) 32 (97%)Less sedation 1 (2%) 3 (6%) 1 (4%) 1 (3%)

PainNone 46 (92%) 44 (88%) 28 (100%) 33 (100%)Mild 4 (8%) 6 (12%) 0 (0%) 0 (0%)Moderate 0 (0%) 0 (0%) 0 (0%) 0 (0%)Severe 0 (0%) 0 (0%) 0 (0%) 0 (0%)

Patient recallInsertion of colonoscope

Yes 2 (4%) 6 (12%) 0 (0%) 1 (3%)No 48 (96%) 44 (88%) 28 (100%) 32 (97%)

During procedureYes 2 (4%)a 10 (20%)a 0 (0%) 3 (9%)No 48 (96%)a 40 (80%)a 28 (100%) 30 (91%)

Removal of colonoscopeYes 4 (8%) 8 (16%) 0 (0%) 0 (0%)No 46 (92%) 41 (82%) 28 (100%) 33 (100%)

Leaving procedure roomYes 27 (54%) 21 (42%) 1 (4%)a 7 (21%)a

No 22 (44%) 29 (58%) 27 (96%)a 26 (79%)a

Subjective impairmentNone 16 (57%) 21 (64%)Mild 12 (43%) 7 (21%)Moderate 0 (0%) 4 (12%)Severe 0 (0%) 1 (3%)

Hours of sleep 7.6 (1.4)a 9.9 (1.7)a

M/F, midazolam/fentanyl.aP � 0.05.


group was able to recall a significantly greater number ofwords. The delayed recall (recall 20 minutes after theword has been read) was worse in the midazolam/fentanylgroup (P � 5.4 � 3.5 words, M/F � 1.1 � 2.2 words,P � 0.0001). Patients who had received propofol wereable to discriminate between a greater number of wordsthat had been read to them (true positives) and those thathad not been read (false positives), as reflected by thediscrimination scores (P � 9.0 � 1.9 words, M/F �6.0 � 2.6 words, P � 0.0001).

Auditory working memory and attention were mea-sured with Digit Span. There was no difference betweengroups before sedation. After recovery, the ability torecall numbers both forward and backward was lower inthe midazolam/fentanyl group (P � 0.003, 0.008, re-spectively).

The ability to perform tasks of visual-motor coordi-nation, to numerically sequence, and to perform cogni-tive functions were tested with the Trails test (Figure 2).Before sedation, there was no difference between thegroups. After recovery, patients who had received propo-fol performed significantly better on both the Trails Aand Trails B tests than those who received midazolam/fentanyl (P � 0.02, 0.007, respectively).

There was no baseline difference between groups forthe Stroop Word test, a measure of divided attention andresponse inhibition. After recovery, the score for thepropofol group was better than that for the midazolam/fentanyl group (P � 39.6 � 11.4, M/F � 31.3 � 10.7,P � 0.001) (Figure 3).

DiscussionThis report describes a randomized, controlled,

clinical trial comparing propofol with midazolam andfentanyl for outpatient colonoscopy in average-risk pa-tients with intact colons. All medications were admin-istered by a registered nurse who was supervised only by

the endoscopist performing the procedure. Propofol re-sulted in shorter sedation and recovery times and betterpostprocedure neuropsychologic function than the com-bination of midazolam and fentanyl. There was no dif-ference between the 2 groups with regard to overallpatient satisfaction with the procedure. Propofol resultedin a deeper level of sedation.

Patients receiving propofol for colonoscopy requiredfewer positional changes during the procedure comparedwith those receiving midazolam and fentanyl. This indi-cates that the colonoscopists performing the procedurewere more willing to push through loops, likely becausethe patients receiving propofol tolerated loop formationwithout pain. This may be of concern to colonoscopistswho believe that the perception of pain is a warning signof impending perforation. The senior endoscopist in thisstudy (D.K.R.) believes that it is much more importantnever to push against fixed resistance, regardless ofwhether the patient is in pain, to prevent mechanicalperforation of the colon. It is our concern that less-experienced colonoscopists may be more willing to pushagainst fixed resistance if the patient does not express asensation of pain. In a review of our initial 2357 colonos-copies using propofol at our institutions, all performedby experienced colonoscopists, there were no perfora-tions.24

Controversy exists over the administration of propofolwithout the presence of a specialist in anesthesia, mainlyowing to concern of respiratory depression. To ensurepatient safety, our institution uses a strict protocol re-quiring structured training of nurses and physicians inthe administration of the drug, advanced life supportcertification for both the nurses and endoscopists, andsupplemental administration of oxygen to all patients. Ina review of the first 2000 endoscopic cases using propofol

Figure 2. Performance on Trails tests. There was no difference be-tween the groups at baseline. Following recovery, the propofol groupperformed better on both the Trails A (P � 0.02) and Trails B (P �0.007) tests.

Figure 3. Stroop Color Word Test performance. There was no differ-ence between the groups at baseline. After recovery, mental flexibilityand speed scores in the propofol group improved while the scores inthe midazolam/fentanyl group declined (P � 0.001).


administered by registered nurses in our group, we re-ported 5 episodes of oxygen desaturation to less than85%, with no cases requiring endotracheal intubation.19

We have now given the drug to more than 6000 patients(unpublished observations), without a single instancerequiring endotracheal intubation, hospitalization, or re-sulting in sequelae. Although we believe that propofolcan be administered safely by a registered nurse whensupervised by the endoscopist, appropriate caution mustbe undertaken when using the drug. Modalities such ascontinuous measurement of expiratory carbon dioxide15

deserve further investigation as tools for monitoringrespiratory function. It should be noted that in our study,the nurse administering propofol had no other responsi-bilities. A second assistant was present to assist with thetechnical aspects of the procedure. Also, our patientpopulation was relatively young. As with other hypnot-ics, lower initial doses and bolus increments and cautioustitration are essential to safety in the elderly.

Our hospital pharmacy paid $7.69 for a 200-mg vialof propofol (Diprivan) and charged patients $22.10. Thepharmacy paid $0.24 per 100-mcg of fentanyl, for whichpatients were charged $4.20. Midazolam (Versed; RochePharmaceuticals, Nutley, NJ) cost the pharmacy $1.15per 5-mg vial, for which patients were charged $6.40.The time from onset of sedation to discharge from therecovery room was on average 15 minutes shorter withpropofol than with midazolam and fentanyl, and thiscould result in savings that offset the cost of propofol.Also, although we did not use it, propofol is available asa generic formulation.

In a previous study,6 we found nurse-administeredpropofol to result in better patient satisfaction whencompared with meperidine plus midazolam. However, inthe current study no difference in satisfaction was ob-served between propofol and fentanyl/midazolam. Webelieve that the higher level of patient satisfaction ob-served with fentanyl/midazolam may be owing to thefaster recovery21,22 and lower incidence of adverse effects(i.e., nausea, headache) of fentanyl compared with me-peridine. This observation may be of particular interestto those colonoscopists still using meperidine.

In conclusion, nurse-administered propofol sedationoffered several advantages over midazolam plus fentanylfor outpatient colonoscopy. Given that a substantial andacceptable safety experience with nurse-administeredpropofol has accumulated,19,20 it appears appropriate tocontinue evaluation of nurse administered propofol seda-tion as a new paradigm for colonoscopy performed byskilled endoscopists and appropriately trained nurses andphysicians.

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Address requests for reprints to: Douglas K. Rex, M.D., IndianaUniversity Hospital, #4100, 550 University Boulevard, Indianapolis,Indiana 46202. e-mail: [email protected]; fax: (317) 274-5449.


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