A New Perspective on Vascular Access


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A New Perspective on Vascular Access

  1. 1. A New Perspective on Vascular Access by Steve Chen Director of Nephrology, Shin-Chu Branch of Taipei Veterans General Hospital
  2. 2. Highlights 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
  3. 3. ShuntAVG AVF Catheter
  4. 4. Access use at initiation of dialysis
  5. 5. Access at initiation of HD for early referral
  6. 6. Burdens in vascular access 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/Japan 75% of US patients initiate dialysis with a catheter
  7. 7. Choices in vascular access Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham)Feature Fistula Graft CatheterPrimary failure rate % 20 ~ 50 10 ~ 20 <5Time to 1st use (W) 4 ~ 12 2~ 3ImmediateNeed to intervene VL Mod HQb Excel Excel ModThrombosis rate VL Mod HInfection rate VL Mod VHLongevity ~ 5Y ~ 2Y <1Y
  8. 8. Vascular access monitoring 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
  9. 9. Vascular access surveillance 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 WD paulson et al: KI 81: 132-142, 2010 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)
  10. 10. AVF
  11. 11. What is a successful fistula? Allon et al, KI 62: 1109-24, 2002 Caliber large enough Blood 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
  12. 12. How is a successful fistula? Allon 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
  13. 13. Pre-operative vascular mapping Allon 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)
  14. 14. Assessment of fistula maturation Allon et al, KI 62: 1109-24, 2002 Post-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
  15. 15. AF fistulas: primary failure 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
  16. 16. Primary failure 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 failure Primary 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
  17. 17. Effect of clopidogrel on early failure 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
  18. 18. Anti-platelet agents for fistulaStudy N Intervention/Duration Thrombosis (%) Intervention ControlAndrassy et al 92 Aspirin 500mg/D x 4W 4 231974Grontoft et al 36 Ticlopidine 250mg/D x 4W 11 471985Grontoft et al 260 Ticlopidine 250mg/D x 4W 12 191998Dember et al 877 Clopidegrel 300mg/D(L) 12 192008 75mg/D x 6WDOPPS: N= 2815: aspirin to reduce significantly lower risk of final AVF failure
  19. 19. AV fistulas: late failure 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
  20. 20. AVG: go faster!
  21. 21. AV grafts: graft failure 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
  22. 22. AV grafts: graft failure 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
  23. 23. Vascular access stenosis: VNH Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham) VNH: venous neo-intimal hyperplasia (SMC + micro-F + microvessels) 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
  24. 24. Preventive strategy for VNHStrategy Mechanism of action Used in AVFmodelMechanical design Tapered graft and pre-cuffed graft geometry at anastomosis Y Deculluarized xenograft elastic mismatch between graft/vessel YBiological 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 YSmall molecule drugs Rapamycin inhibit protein translation Y Paclitaxel inhibit mitosis by stabilizing microtubules Y Dypiridamole inhibit phosphodiesterase activity Y Imatinib inhibit PDGF receptor activity NIrradiation induce DNA damage YODN: antisense oligonucleotide Li Li Christi et al: KI 74 1247-61, 2008(University of Utah, USA)
  25. 25. Catheter: fastest!
  26. 26. So think twice… 26
  27. 27. Catheter-related bacteremia (CRB) N Per 1000 GPC catheter-daysKairaitis 105 6.5 100%Bethard 387 3.4 84.5%Saad 101 5.5 67.4%Cuevas 189 1.54 84%
  28. 28. Definition of CRB Public Health Agency of Canada Definite 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
  29. 29. Diagnosis 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%
  30. 30. Catheter-related bacteremia (CRB) Similar rates but different average time tunneled: 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 months 48% of patients within 6 months
  31. 31. Risk 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
  32. 32. Complications 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
  33. 33. Use rate of HD permanent catheter < 10% NKF-K/DOQI guidelines
  34. 34. CQI process to reduce catheter rates in incident patients: a call to action1. Discuss with referral sources aboutcriteria 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 permanentaccess 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 maturing5.Provide full disclosure of catheter related risks to patients and familywho refuse surgery for permanent access6.Weaning of a medi-alert bracelet to protect one arm from veni-puncture7.Classify requests to hospitals for access placement as urgent RM Hakim et al: K 76: 1040-1048, 2009
  35. 35. Prophylaxis 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
  36. 36. Vancomycin 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%
  37. 37. Clinical approach to (tunneled) CRB Ivan D. Maya et al: AJKD 2008(University of Alabama at Birmingham) Vancomycin/Ceftazidime or GM /Antibiotic lockNegative culture Positive culture Positive culture X 5D Fever resolve in 2-3D Fever persists Catheter(-) CNS GNB CPS Candida ECHO Stop Metastatic Catheter(+) Workup: bone Keep lock Catheter(-) Catheter(-) Anti Duration Anti: 3W Anti: 3W Fluconazole 6-8W Guidewire Consider 2W exchange ECHO/bone scan
  38. 38. Catheter removal ? Non-cuffed CuffedExit site infection Yes NoTunnel infection Yes YesCatheter-related Yes S.A.: Yesbacteremia(CRB) CNS: No ? Enterococcus: Yes
  39. 39. Antibiotic dosing in HD patients Systemic antibioticsVancomycin 20mg/Kg loading during last one hour ; 500 mg TIWGentamicin 1mg/Kg (maximum <100mg) TIWCeftazidime 1G TIWCefazolin 20mg/Kg TIWDaptomycin 6mg/Kg TIW Antibiotic lock: volume of solution(ml)Vancomycin/Ceftazidime /Heparin: 1.0 /0.5/0.5Vancomycin/Heparin: 1.0/1.0Ceftazidime/Heparin: 1.0/1.0Cefazolin/Heparin: 1.0/1.0
  40. 40. 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
  41. 41. Careful observation needed for tunnel infection !
  42. 42. Exit 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
  43. 43. Watch out the signs of AVGinfection!
  44. 44. AVG 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
  45. 45. AVG infection: S/S Local pain, irritation, tenderness Redness, warmth Diffuse or local swelling Skin breakdown Serous or purulent discharge Leukocytosis, fever
  46. 46. Sub-clavian vein obstruction CVC placed for > 2 ~ 3 weeks: 40 ~ 50% If infected: 75% PTA+/- stent Veno-venous bypass surgery Access ligantion
  47. 47. Antibiotic-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
  48. 48. Antibiotic lock: indications Catheterretained during an episode of catheter-related bacteremia O’Grady et al, MMWR Morb Mortal Wkly Rep 51: 1-29, 2002 Historyof multiple catheter-related bacterremias despite optimal aseptic technique Mernet et al, Clinical Infect Dis 32: 1249-72, 2001
  49. 49. Antibiotic lock: pathogen Allon et al, NDT 200490%80%70%60%50% Positive surv cx40% Persistent fever30% Success20%10% 0% GNB CNS SA
  50. 50. 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
  51. 51. Potential antimicrobial lock solutions Michael Allon: AJKD 44: 2004 1st 2nd 3rd 4th 殺菌 低阻 質合安全GM 40mg/dl /Citrate OK No OK OK30% Citrate OK OK OK OK70% Isopropyl alcohol OK OK OK NoTaurolidine OK OK OK No
  52. 52. CRB prevalence: per 1000 days4.5 43.5 32.5 Heparin lock 2 Antimicrobial lock1.5 10.5 0 Dogra Mcintyre Kim Nori Saxena
  53. 53. CRB prevalence: per 1000 days 4.5 4 3.5 3 2.5 Taurolidine 2 30% Citrate 1.5 1 0.5 0 Betjes Weijmer
  54. 54. Antibiotic 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