Download - A New Perspective on Vascular Access
A New Perspective on A New Perspective on Vascular Access Vascular Access
by Steve Chenby Steve Chen
Director of Nephrology, Hsin-Chu Branch of Taipei Veterans General Hospital
Together Everyone Achieves More
Highlights in vascular accessHighlights in vascular access
First hemodialysis: 1924 by George Haas First vascular access: 1943 Quinton-Scribner shunt: 1960 Brescia-Cimino fistula: 1966 Synthetic polytetrafluoroethylene (PTFE) AVG:
1970s Permanent tunneled cuffed indwelling HD
catheter: 1980s Synthetic polyurethane AVG (Vectra): 1990s
Catheter
AVFAVG
Shunt
Access use at initiation of dialysisAccess use at initiation of dialysis
Access at initiation of HD for Access at initiation of HD for early referral early referral
Burdens in vascular access Burdens in vascular access Ivan D. Maya et al: AJKD 2008 (University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008 (University of Alabama at Birmingham)
>20% of dialysis patients hospitalizations: access related
Adjusted mortality: 40 ~ 70% greater for catheter > AV shunt
Fistula prevalence: USA < Europe/Japan75% of US patients initiate dialysis with a
catheter
Choices in vascular accessChoices in vascular accessIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
Feature Fistula Graft Catheter
Primary failure rate % 20 ~ 50 10 ~ 20 <5
Time to 1st use (W) 4 ~ 12 2 ~ 3 Immediate
Need to intervene VL Mod H
Qb Excel Excel Mod
Thrombosis rate VL Mod H
Infection rate VL Mod VH
Longevity ~ 5Y ~ 2Y <1Y
Vascular access monitoringVascular access monitoringIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
PE: absent thrill, abnormal bruit, distal edema, pulsating swelling aneurysm (F) or pseudo-aneurysm (G)
Dialysis abnormality: difficult puncture, aspiration of clots, prolonged bleeding from needle site
Unexplained decrease in Kt/V
Vascular access surveillanceVascular access surveillanceIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
Static dialysis venous pressure (DVP): Ratio of DVP to systolic BP > 0.5: inaccurate predictor
Access blood flow: < 600mL/min(G) or <400-500 mL/min(F)
A decrease in Qa > 33% from baseline Doppler ultrasound: peak systolic velocity (PSV)
ratio > 2/1 Dynamic DVP and recirculation: less useful Flow and change in flow(Qa and DVP) early in a
dialysis session by monthly flow surveillance: inaccurate predictor Sunanda et al: ALKD 52: 930-938, 2008 (N=176)
WD paulson et al: KI 81: 132-142, 2010
AVF
What is a successful fistula? What is a successful fistula?
Allon et al, KI 62: 1109-24, 2002Allon et al, KI 62: 1109-24, 2002Caliber large enoughBlood flow rate: access Qb > dialysis Qb by at least 100
ml/min to avoid vein collapse and re-circulation
mean dialysis Qb: 400 ml/M (USA) 300 ml/M(Europe) 200 ml/M(Japan)
Vein wall hypertrophy enough Superficial enough
How is a successful fistula? How is a successful fistula?
Allon et al, KI 62: 1109-24, 2002Allon et al, KI 62: 1109-24, 2002 Experience ( >12 procedures) of the surgeon Site of fistula:
primary failure rate: 66% in forearm; 41% upper arm
Pre-operative sonographic vascular mapping: age, DM, race, BMI
Hand exercise ? Anti-platelet agents for 3 ~ 6 W
Kaufman et a, Semin dial 13: 40-46, 2000
Pre-operative vascular mapping Pre-operative vascular mapping
Allon et al, KI 62: 1109-24, 2002Allon et al, KI 62: 1109-24, 2002 Mapping with ultrasonography or venography
Criteria for placement of a shunt: Minimum vein diameter: 0.25cm (AVF) Minimum vein diameter: 0.40cm (AVG) Minimum artery diameter: 0.20cm Draining vein or central vein: lack of stenosis, sclerosis, or
thrombosis A change of planned surgical procedure: 31% Order of preference of vascular access to be
placed: Distal F > Proximal F > Proximal transposed brachio-basilic F > Upper extremity G> Thigh G> Unusual G (Necklace, chest wall)
Assessment of fistula maturationAssessment of fistula maturation
Allon et al, KI 62: 1109-24, 2002Allon et al, KI 62: 1109-24, 2002Post-operative sonographic measurement at
2M: A: minimum vein diameter: >0.4cm
B: Access Qb> 500ml/min A or B: 70% A+B: 95% neither: 33%
Time interval for dialysis use: 2 ~ 4M
AF fistulas: primary failureAF fistulas: primary failureIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
High primary failure rate: 20 ~ 50% Steal syndrome: 1 ~ 4%
Post-operative ultrasound to evaluate maturation: 4 ~ 8 W after surgery
Ultrasound criteria for maturity: Fistula diameter 0.4cm ≧ Access flow 500mL/min ≧ Distance from skin 0.5cm≦
Primary failure rate : early thrombosis or failure to mature adequately (Juxta-anastomotic
stenosis/Large accessory veins/Excessively deep fistula)Primary survival ( intervention-free): time from
access placement to initial intervention Cumulative survival ( assisted ) : time from
access placement to permanent failurePrimary or cumulative survival at 1 year:
Oliver et al, KI 60: 1532-39, 2001 F > G: if primary failure excluded F = G: if primary failure included
Primary failure
Effect of clopidogrel on early Effect of clopidogrel on early failure of AVFs for HDfailure of AVFs for HD
Multicenter randomized controlled trial: N= 877 Clopidogrel: 300mg loading dose/75mg/D for 6 weeks
Inclusion criteria: upper extremity AVF/start HD within 6 M Primary outcome: unassisted AVF patency at 6W Secondary outcome: AVF dialysis suitability ( Use of AVF with 2
needles at Q-b >300 ml/min for 8 sessions this began 120 days after ≧ ≧AVF creation)
Clopidogrel group: 37% lower risk of thrombosis(RR 0.46 p=0.018); Forearm(RR 0.53); upper arm(RR 0.89)
A surprising high primary failure in both groups(61%/59%) →more than reducing early fistula thrombosis in required Dember LM et al: JAMA 299: 2164-71, 2008
Anti-platelet agents for fistula Anti-platelet agents for fistula
Study N Intervention/Duration Thrombosis (%) Intervention Control
Andrassy et al 92 Aspirin 500mg/D x 4W 4 23 1974
Grontoft et al 36 Ticlopidine 250mg/D x 4W 11 47 1985
Grontoft et al 260 Ticlopidine 250mg/D x 4W 12 19 1998
Dember et al 877 Clopidegrel 300mg/D(L) 12 19 2008 75mg/D x 6W
DOPPS: N= 2815: aspirin to reduce significantly lower risk of final AVF failure
AV fistulas: late failureAV fistulas: late failureIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
Late fistula failure by stenosis 60% at venous outlet 25% at arterial anastomosis 5% at central vessels A large aneurysm, rarely
Thrombosed fistula requires thrombectomy with 48 Hr
Primary patency rate after: 27 ~ 81% at 6M; 18 ~ 70% at 12M
AVG: go faster!
AV grafts: graft failureAV grafts: graft failureIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
Graft failure: ~ 80% thrombosis ~ 20% infection A large pseudo-aneurysm, rarely
Underlying stenosis in most thrombosed grafts: ~ 60% Venous anastomosis 15% venous outlet 10% central veins 10% intragraft 5% arterial anastomosis
AV grafts: graft failureAV grafts: graft failureIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
Intervention-free patency after elective angioplasty: 70 ~ 85% at 3M; 20 ~ 40% at 12M
Intervention-free patency after thrombectomy: 33 ~ 63% at 3M; 10 ~ 39% at 6M
Stents may prolong patency in selected grafts: elastic lesion
No clear advantage of bovine or cadaveric human vein grafts over PTFE grafts
Polyurethane grafts (Vectra): can be cannulated within 24 Hr
Vascular access stenosis: VNHVascular access stenosis: VNHIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
VNH: venous neo-intimal hyperplasia (NIH) Hemo-dynamic turbulence: an shear forces Dialysis needle injury Surgical vascular damage PTFE Uremia Vascular damage from angioplasty Expression of genes for cytokines Local anti-proliferative drug delivery system:
Human study in progress
Myofibroblasts: an ideal target to prevent AVF failure ?
The venous cells that can transform into myofibroblasts are (1) adventitial fibroblasts (2) pericytes (3) endothelial cells (EMT) (4) smooth muscle cells
Preventive strategy for VNHPreventive strategy for VNHStrategy Mechanism of action Used in AVF model
Mechanical design Tapered graft and pre-cuffed graft geometry at anastomosis Y Deculluarized xenograft elastic mismatch between graft/vessel Y
Biological reagents Antisense ODNs inhibit DNA transcription N Decoy(E2F) inhibit cell cycle progression Y Gene transfer VEGF promote endothelialization N C-type natriuretic peptide inhibit proliferation via cGMP Y Cell based therapy Endothelial progenitor cells promote endothelialization of graft surface Y Endothelial cell implant promote endothelial function Y
Small molecule drugs Rapamycin inhibit protein translation Y Paclitaxel inhibit mitosis by stabilizing microtubules Y Dypiridamole inhibit phosphodiesterase activity Y Imatinib inhibit PDGF receptor activity N
Irradiation induce DNA damage Y
ODN: antisense oligonucleotide Li Li Christi et al: KI 74 1247-61, 2008(University of Utah, USA)
Catheter: fastest!
28
So think twice…
Catheter-related bacteremia Catheter-related bacteremia (CRB) (CRB)
N Per 1000 catheter-days
GPC
Kairaitis
Bethard
Saad
Cuevas
105
387
101
189
6.5
3.4
5.5
1.54
100%
84.5%
67.4%
84%
Definition of CRBDefinition of CRB Public Health Agency of CanadaDefinite CRB diagnosis:
1> blood cultures from both catheter lumen and a peripheral vein grow the same organism 2>Colony count in catheter (C) ≧ 5~ 10X colony count in vein (V) or C V, ≧ 2 Hours earlier
False positive diagnosis: colonization if from only one lumen
Diagnosis of CRBDiagnosis of CRB
Probable CRB diagnosis: 2 positive blood ≧culture ( blood culture/catheter tip:+/- or -/+ ) + no evidence of a source of infection other than catheter
Possible CRB diagnosis: negative or single blood culture + no evidence of a source of infection other than catheter , but fever ↓after catheter removal
Catheter culture( positive ): CRB 63%
Catheter-related bacteremia (CRB)Catheter-related bacteremia (CRB)
Similar rates but different average timetunneled: 1/1000 catheter-days
non-tunneled: 1.54/1000 catheter-days (p=0.98) Cuevas et al, JASN 1999
tunneled: 66.2 days non-tunneled: 20.6 days
35% of patients within 3 months48% of patients within 6 months
Risk factors for CRBRisk factors for CRB
Femoral route Duration of catheter use ( FVC: 5D; JVC: 3 ~ 4W) Nasal/skin colonization with S.A. Poor personal hygiene:
Povidone-iodine/Mupirocin over exit site of catheter
Use of occlusive transparent dressing DM Immuno-suppression Low albumin; high ferritin
Complications of bacteremiaComplications of bacteremia
Mortality: 8 ~ 25% Recurrence: 14.5 ~ 44% Endocarditis: mortality 30% Epidural abscess Purulent pericarditis Septic arthritis or osteomyelitis Septic pulmonary emboli Liver abscess Endopthalmitis
Use rate of HD permanent catheter < 10% NKF-K/DOQI guidelines
CQI process to reduce catheter rates in CQI process to reduce catheter rates in incident patients: a call to action incident patients: a call to action
1. Discuss with referral sources about criteria for referral: GFR≦ 30 ml/min2. Refer patients and family to educational classes about treatment options that should include PD, transplantation, etc: GFR ≦ 20 ml/min3.Explicitly discuss with patients and family the need for a permanent access at a GFR ≦ 20 ml/min4.Track success of surgical outcomes by surgeon Refer back to surgeon in 6-8 weeks if fistula is not maturing 5.Provide full disclosure of catheter related risks to patients and family who refuse surgery for permanent access6.Weaning of a medi-alert bracelet to protect one arm from veni-puncture 7.Classify requests to hospitals for access placement as urgent
RM Hakim et al: K 76: 1040-1048, 2009
Prophylaxis of CRBProphylaxis of CRB
Nasal mupirocin or 5-D course of oral RIF/3M: S.A. carrier (50% in HD )who have a previous catheter-related bacteremia caused by S.A. and continue to need HD catheter ongoing by IDSA: Infectious Diseases Society of America
Prophylaxis of exit site colonization by mupirocin or polysporin( Bacitracin+gramicidin+polymyxin B) ointment at exit site
Lock therapy: GM/Citrate; Taurolidine/Citrate
Vancomycin plus Gentamicin in febrile HDVancomycin plus Gentamicin in febrile HD Life-threatening infection by β-lactam resistant
GPC or MRSA GPC infection+ serious allergy to β-lactam
antibiotics Antibiotic-associated colitis unresponsive to
Metronidazole or that is life-threatening Prophylaxis of endocarditis in high-risk Patients:
Presence of central venous dialysis catheter Alternative: Vancomycin plus 3rd cephalosporin Rationale: mixed bacteremia 9.8 ~ 12.2%
Clinical approach to (tunneled) CRBClinical approach to (tunneled) CRBIvan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)
Vancomycin/Ceftazidime or GM/Antibiotic lock
Negative cultureX 5D
Positive cultureFever resolve in 2-3D
Positive cultureFever persists
Stop
CNS GNB CPS CandidaCatheter(-)
ECHOMetastatic
Workup: bone Anti Duration
6-8W
Catheter(+)Keep lockAnti: 3W
Guidewire exchange
Catheter(-)Anti: 3WConsider
ECHO/bone scan
Catheter(-)Fluconazole
2W
Catheter removal ?Catheter removal ?
Non-cuffed Cuffed
Exit site infection Yes No
Tunnel infection Yes Yes
Catheter-related bacteremia(CRB)
Yes S.A.: Yes
CNS: No ?
Enterococcus: Yes
Antibiotic dosing in HD patients Antibiotic dosing in HD patients
Systemic antibiotics
Vancomycin 20mg/Kg loading during last one hour ; 500 mg TIW Gentamicin 1mg/Kg (maximum <100mg) TIWCeftazidime 1G TIWCefazolin 20mg/Kg TIWDaptomycin 6mg/Kg TIW
Antibiotic lock: volume of solution(ml)
Vancomycin/Ceftazidime /Heparin: 1.0 /0.5/0.5 Vancomycin/Heparin: 1.0/1.0Ceftazidime/Heparin: 1.0/1.0Cefazolin/Heparin: 1.0/1.0
Tunnel infection Tunnel infection CDC guideline:
Erythema, tenderness, and induration in tissues overlying the catheter + > 2cm from the exit site
Public Health Agency of Canada: Definite: 1> Purulent discharge from tunnel 2> Erythema, tenderness, induration(2/3) at tunnel with a positive culture from serous discharge Probable: Erythema, tenderness, induration(2/3) at tunnel with serous discharge, but negative culture /no discharge, but lack of alternative Possible: Erythema, tenderness, induration(2/3) at tunnel , but alternative cause cannot be ruled out
Careful observation needed for tunnel infection !
Exit site infectionExit site infection CDC guideline:
Erythema, tenderness, and induration or purulence in tissues overlying the catheter within 2cm from the exit site
Public Health Agency of Canada: Definite: 1> Purulent discharge at exit site 2> Erythema, tenderness, induration(2/3) at exit site with a positive culture from serous discharge Probable: Erythema, tenderness, induration(2/3) at exit site with serous discharge, but negative culture /no discharge, but lack of alternative Possible: Erythema, tenderness, induration(2/3) at exit site , but alternative cause cannot be ruled out
Watch out the signs of AVG infection!
AVG infectionAVG infection
30-day infection rate: 6% Risk factors:
femoral route poor hygiene repetitive cannulations perigraft hematoma formation prolonged postdialysis bleeding from graft repeat surgical revisions HIV status(30%), DM, low albumin, high ferritin transient bacteremia from distal site or CRB
AVG infection: S/SAVG infection: S/S
Local pain, irritation, tendernessRedness, warmthDiffuse or local swelling Skin breakdownSerous or purulent discharge Leukocytosis, fever
Sub-clavian vein obstructionSub-clavian vein obstruction
CVC placed for > 2 ~ 3 weeks:
40 ~ 50% If infected:
75% PTA+/- stentVeno-venous bypass surgeryAccess ligantion
Antibiotic-heparin lock therapyAntibiotic-heparin lock therapy
If Vancomycin: 2.0 mg/ml; Ceftazidime: 2.0 mg/ml plus heparin 5000IU/ml, each concentration > 100µg/ml will persist > 21 days.
Cefazolin, Vancomycin: 10mg/ml; Ceftazidime, Ciprofloxacin: 10mg/ml; Gentamycin: 5mg/ml
No benefit to UK instillation as an adjunct to antibiotic lock
Antibiotic lock: indications Antibiotic lock: indications
Catheter retained during an episode of catheter-related bacteremia O’Grady et al, MMWR Morb Mortal Wkly Rep 51: 1-29, 2002
History of multiple catheter-related bacterremias despite optimal aseptic technique Mernet et al, Clinical Infect Dis 32: 1249-72, 2001
Antibiotic lock: pathogenAntibiotic lock: pathogenAllon et al, NDT 2004Allon et al, NDT 2004
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
GNB CNS SA
Positive surv cx
Persistent fever
Success
Ideal lock solution for prophylaxis Ideal lock solution for prophylaxis
Prophylaxis of bio-film formation → CRB↓1> Cidal activity against a broad spectrum of
GPC/GNB/Fungi 2> Low likelihood of promoting antibiotic resistant bacteria 3> Compatible with catheter material and anticoagulant agent 4> Safe if inadvertently instilled systemically
Potential antimicrobial lock solutionsPotential antimicrobial lock solutionsMichael Allon: AJKD 44: 2004Michael Allon: AJKD 44: 2004
1st 2nd 3rd 4th
殺菌 低阻 質合 安全GM 40mg/dl /Citrate OK No OK OK
30% Citrate OK OK OK OK
70% Isopropyl alcohol OK OK OK No
Taurolidine OK OK OK No
CRB prevalence: per 1000 daysCRB prevalence: per 1000 days
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Dogra Mcintyre Kim Nori Saxena
Heparin lock
Antimicrobial lock
CRB prevalence: per 1000 daysCRB prevalence: per 1000 days
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Betjes Weijmer
Taurolidine
30% Citrate
Antibiotic lock: barriersAntibiotic lock: barriers
All randomized trials: F-U for < 6M Selection of antibiotic resistant infection if longer use
Systemic toxicity from leaks into circulation 10-fold lower concentration of GM: 4 ~ 5 mg/mL
Economic FDA not approved
Anatomic variation of the internal jugular vein relative to the common carotid artery Right-sided, axial section (viewed from above)
1. lateral (0–84%) and far lateral (0–4%), both with no overlap 2. 18% of internal jugular veins are not visible or are thrombosed
Anatomic variation of the common femoral vein relative to the common femoral artery Right-sided, axial section (viewed from above)
1. Over 25% overlap between the common femoral vein and common femoral artery occurs in 8% of patients 2. 65% of patients have some degree of overlap
1. Given that the complications of NTHC insertion are frequent and can be fatal, it is important that nephrologists and trainees practice techniques that limit these risks and are evidence based.
2. In addition to using real-time US guidance for all NTHC insertions at the IJ site, US guidance should also be used for NTHC insertions at the femoral site.
3. Infection-control ‘bundles’ of specific evidence-based practices to reduce the risk of exit-site infections should be implemented in all settings in which NTHCs are inserted and used.
4. This should include the use of detailed checklists for the insertion of catheters, as well as for a daily assessment of whether or not a NTHC is still required or should be removed.
5. Citrate (4%) catheter locks should be used for NTHCs rather than heparin.
6. There is currently insufficient evidence to support the routine use of specialized catheters with antimicrobial properties.
7. If possible, the subclavian site should be avoided due to the long-term risk of central venous stenosis.
8. RCT evidence now suggests that the femoral site may not be associated with a higher risk of infection and is possibly even preferable in patients who are critically ill and bed-bound with a BMI less than 24.