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Ramon C. Mora M.D.

Ramon C. Mora M.D. Year Graduated : 1985 School : FEU-NRMF Institute of Medicine Residency : Veterans Memorial Medical Center (1987-1990) Fellowship : National Kidney & Transplant Institute (1990-1992) Affiliations: VMMC, FEU-NRMF MC, UDMC, NKTI. Measures to Optimize

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Ramon C. Mora M.D.

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  1. Ramon C. Mora M.D. • Year Graduated : 1985 • School : FEU-NRMF Institute of Medicine • Residency : Veterans Memorial Medical Center (1987-1990) • Fellowship : National Kidney & Transplant Institute (1990-1992) • Affiliations: VMMC, FEU-NRMF MC, UDMC, NKTI

  2. Measures to Optimize Anticoagulation in HD

  3. UFH UFH UFH CITRATE LMWH DTI UFH UFH CITRATE CITRATE

  4. Unfractionated Heparin Routine Heparin Tight Heparin

  5. Target Clotting Times During Dialysis Daugirdas, Handbook Dial, 3rd ed, p. 185

  6. CRRT Unfractionated Heparin Daugirdas, Handbook Dial, 3rd ed, p. 185

  7. Heparin protocol for continuous therapies Daugirdas, Handbook Dial, 3rd ed, p. 221

  8. CRRT Nomogram for Heparin Heparin solution is made by mixing 1 ml of 10,000 U/ml of heparin in 19 ml of normal saline for a heparin concentration of 500 U/ml. initial bolus is 25 U/kg followed by an infusion of 5 U/kg/hr. The goal of treatment is to maintain systemic prefilter aPTT between 45 and 55 seconds (1.5 times control). Seminars in Dialysis – Vol. 19, No. 4 (July – August) 2006

  9. Regional Heparin CRRT circuit showing infusion sites for heparin and protamine and collecting sites for patient and circuit aPTT samples Protamine Heparin Patient aPTT Circuit aPTT Arterial Line Venous Line

  10. Regional Heparin

  11. Regional Heparin Adjustments of Heparin and Protamine Infusion Rate According to aPTT Values J Nephrol 2003; 16: 566-571

  12. Regional Heparin • Potential problems • Complexity (balancing infusion rates) • Rebound anticoagulation/ dissociation of heparin-protamine complex • Side effects of protamine – flushing, bradycardia, hypotension, dyspnea, anaphylactic reaction among DM patients

  13. Low Molecular Weight Heparin

  14. Low Molecular Weight Heparin

  15. Conclusion • This meta-analysis identified no difference in bleeding events or thrombosis of extracorporeal circuit when LMWH was compared with UFH. • There was great deal of heterogeneity among studies, a variety of LMWH dosing regimens were used, and comparison between different preparations was not possible. • Inferences from these trials assessing anti-coagulation for patients who undergo hemodialysis will continue to be weak until larger, more rigorous randomized trials are conducted. Lim, et al J Am Soc Nephrol 2004

  16. Hemodialysis anticoagulation and adequacy • No clear differences in hemodialysis adequacy results have been demonstrated using UFH and LMWH. (Level II, limited data) • No differences in dialysis adequacy results are achieved using different LMWH. (Level II, limited data) • There is no clear difference in the risk of thrombosis or hemorrhage with LMWH compared with UFH, although the results of individual studies have been quite variable. (Level I) The CARI Guidelines – Caring for Australians with Renal Impairment, July 2005

  17. Conclusion • Standard oral regimen with an INR between 2 and 3 is insufficient to prevent clotting during hemodialysis. • Additional low-dose anticoagulation with a LMWH or heparin is necessary to facilitate treatment. Ziai, et al, KI 2005

  18. Regional Citrate

  19. Regional Citrate • Citrate Solution • D5W 1L + 40 gm trisodium citrate (40 mg/ml) • Initial infusion • 180 ml/hr • 90 ml/hr (liver failure/cirrhosis) • Goal: post filter ionized calcium between 0.25 – 0.35 mmol/L • Calcium Chloride Solution • 80 ml of 10% CaCl in 1000 ml of NS (0.056 mmol/L) via central venous catheter to maintain systemic ionized calcium of 1.0 – 1.35 mmol/L • Initial infusion: 40 ml/hr (2.2 mmol/hr) Seminars in Dialysis – Vol. 19, No. 4 (July – August) 2006

  20. CRRT Nomogram for Citrate Citrate solution is made by mixing trisodium citrate 40 g in 1000 ml D5W for a final concentration of 40 mg/ml. The infusion is started at 180 ml/hr. If the patient has suspected liver failure or cirrhosis, the infusion is started at 90 ml/hr. The goal of treatment is to maintain postfilter ionized calcium between 0.25 and 0.35 mmol/L. Seminars in Dialysis – Vol. 19, No. 4 (July – August) 2006

  21. CRRT Nomogram for Calcium Chloride Calcium chloride solution is made by mixing 80 ml of 10% calcium chloride in 1000 ml of normal saline for a concentration of 0.056 mmol/L. Systemic calcium homeostasis is maintained by infusion for a targeted systemic ionized calcium of 1.00-1.35 mmol/L. The infusion is initiated at 40 ml/hr (2.2 mmol/hr). Seminars in Dialysis – Vol. 19, No. 4 (July – August) 2006

  22. Regional Citrate • Potential Complications • Hypernatremia • Metabolic alkalosis • Hypocalcemia • Hypercalcemia

  23. Continuous renal replacement therapies: anticoagulation in the critically ill at high risk of bleeding Morabito et al, J Nephrol 2003

  24. Continuous renal replacement therapies… • Methods • 59 patients underwent CRRT for ARF following cardiac surgery • Non-anticoag CRRT: spontaneous bleeding, aPTT >45 seconds, thrombocytopenia, recent surgery (<48 h) • Results • 22 (37.3%) non-anticoagulation • 12 patients continued (38.3 h filter life) • 10 patients switched to regional heparin (38 h filter life) Morabito et al, J Nephrol 2003

  25. Continuous renal replacement therapies… Regional Coagulation Morabito et al, J Nephrol 2003

  26. Continuous renal replacement therapies… Probabilities of circuit remaining free from clotting Filter life Morabito et al, J Nephrol 2003

  27. Continuous renal replacement therapies… • Conclusion • Non-anticoagulaiton CRRT allowed an adequate filter life in most patients with a high risk of bleeding for prolonged aPTT and/or thrombocytopenia. Despite concerns regarding the need for careful monitoring, regional anticoagulation with heparin and protamine can be considered as a safe and valid alternative when non-anticoagulation is unsuitable because of early filter failure. Morabito et al, J Nephrol 2003

  28. CANBERRA HOSPITAL NURSING SERVICE • ANTICOAGULATION FREE DIALYSIS • Rapid blood flow rate desirable to reduce clotting (>300 ml/min). Where disequilibrium is an issue, use a smaller filter and co-current dialysate flow. • Routine flushes using NaCl 0.9%. Make sure NS flushes are added to UF volume. • Change whole circuit after 1.5 to 2 hours of hemodialysis. • Avoid giving blood transfusion and high UFR. • Decrease dialysis length time where possible but ensure patient does extra time for the next dialysis. • Watch out for signs and symptoms of clotting in the circuit.

  29. EUROPEAN BEST PRACTICE GUIDELINES

  30. EUROPEAN BEST PRACTICE GUIDELINES

  31. EUROPEAN BEST PRACTICE GUIDELINES

  32. EUROPEAN BEST PRACTICE GUIDELINES

  33. Heparin-Induced Thrombocytopenia • Type I • Transient reduction of platelet count occurring after 5 days. • Type II • Antibody mediated complex of heparin and platelet factor 4 • >20,000 platelet count, severe bleeding is rare • Prevalence 1-3% • Main clinical complication: arterial thrombosis • Specific tests for type II HIT: Serotonin release assay, heparin-induced platelet aggregation assay, solid phase immunoassays • Treatment: avoidance

  34. Direct Thrombin Inhibitors • Bivaluridin, Lepirudin, Argatroban • DOSE: 3 dose regimens for Argatroban • 250 ug/kg bolus, with an additional 250 ug/kg if the ACT at 2 hours was less than 140% of baseline • 250 ug/kg bolus followed by 2 ug/kg/min continuous infusion • Steady state infusion of 2 ug/kg/min initiated 4 hours prior to session • Other recommended doses • 15-25 mg/hr or 0.1-0.2 mg/kg/hr • 0.5 ug/kg/min (hepatic impairment) • Target aPTT values 1.5-3.0 times baseline

  35. Prostacyclin • Inhibits interaction between platelets and artificial membranes • Dose: 0.4 – 0.5 ng/kg/min • Intensive Care Medicine, 2002 • Safety and efficacy of Epoprostenol • 7.8% (4/51): major bleeding • 15.5%: hypotension requiring vassopressors • Median life of filter = 15.0 hrs • Blood Purification, 2005 • Citrate anticoagulation has longer filter survival during continuous hemofiltration compared to the combination of PGI2 and heparin

  36. Prostacyclin • Adverse Effects • Increased intracranial pressure • Decreased systemic and pulmonary vascular resistance and MAP • Increased pulmonary ventilation/perfusion mismatch resulting in decreased tissue oxygen delivery and uptake worsening acidosis and lactate production • High cost

  37. Nafamostat • Synthetic serine protease inhibitor, mainly used in Japan • Safer than anticoagulation with regional or low dose heparin • Adsorbed by negatively charged membranes, cannot be used with PAN

  38. Danaparoid • Mixture of dermatan sulfate and heparan sulfate. • Has anti-factor Xa activity • Disadvantages: • Need to determine anti-Xa activity • Long half-life (25+ 100 h) in renal failure • Absence of reversing agent • High cost

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