CVVH continuous veno-venous hemofiltration

1. CVVHcontinuous veno-venous hemofiltration Mazen Kherallah, MD, FCCP King Faisal Specialist Hospital & Research Center Internal Medicine, Infectious Disease and Critical Care Medicine

2. History: Kramer 1979 (Germany) • Inadvertent cannulation of the femoral artery led to a spontaneous experiment with C-arterio-VH: • patient's cardiac function alone capable of driving the system • large volumes of ultrafiltrate were produced through the highly permeable hemofilter • 'continuous arterio-venous hemofiltration' system could provide complete renal replacement therapy in an anuric adult

3. History: pediatrics • Lieberman 1985 (USA): slow continuous ultrafiltration ('SCUF') to successfully support an anuric neonate with fluid overload • Ronco 1986 (Italy): CAVH in neonates • Leone 1986 (USA): CAVH in older kids • 1993: general acceptance of pump-driven CVVH as less problematic than CAVH

4. The Ideal Mode of Renal Replacement Therapy for Critically Ill Patients: • Remove excess fluid and treat fluid overload • Correct and control azotemia • Correct and control electrolyte imbalances • Assist in maintaining acid-base balance This goals must be accomplished without Precipitating additional hemodynamic instability

5. CVVH • 1. near-completecontrol of the rate of fluid removal (i.e. the ultrafiltration rate) • 2. precision and stability • 3. electrolytes or any formed element of the circulation, including platelets or red or white blood cells, be removed or added independently of changes in the volume of total body water.

6. CRRT: Indications • SCUF • Acute pulmonary edema • Severe edema in • Congestive heart failure with diuretic-unresponsive oliguria despite inotropic support • Hepatic failure • Oliguric or anuric patients with acute renal failure • Nephrotic syndrome • CVVHF • Drug intoxication • Septic shock • Rhabdomyolysis • Tumor-lysis syndrome • Hyperthermia • Severe lactic acidosis 

7. High Volume Hemofiltration and Therapeutic Plasma Exchange •  Thrombotic thrombocytopenic purpura • HUS • Hyperviscosity syndrome: macroglobulinemia, cryoglobulinemia, and multiple myeloma • Hyperbilirubinemia • Focal glomerulosclerosis • Rapid progressive glomerulonephritis • Mysthenia gravis • Lambert-Eaton syndrome • Guillan Barre Syndrome • Systemic vasculitis: SLE

8. CVVH: Advantages • Precise fluid control • Can be done in patients with low MAP • Less hemodynamic instability than IHD • Ease of initiation • Large volume of parenteral nutrition can be administered • No arterial cannulation • Better solute clearance than CAVH • Requires less technical support and equipment than IHF CVVH(D) is preferred mode of CRRT

9. CVVH: Disadvantages • Anticoagulation/bleeding • Hypotension • Hypothermia • Hyperglycemia • Air embolism • Access complication • Requires 1:1 nurse/patient ratio • Requires strict monitoring of fluid and electrolyte replacement to avoid deficits or overload

10. Hemodialysis allows the removal of water and solutes by diffusion across a concentration gradient. Blood is pumped along one side of a semi-permeable membrane; a crystalloid solution is pumped in the opposite direction on the other side of the membrane. Solutes of very small molecular weight diffuse across the membrane in an attempt to equilibrate their concentrations.

11. Ultrafiltration The pores in an ultrafiltration membrane are substantially larger than those in a dialysis membrane; ultrafiltration membranes allow passage of solutes up to 20,000 Daltons molecular weight. Filtration across the membrane is convective, similar to that found in the glomerulus of the kidney. Small (e.g., sodium, potassium, phosphate, bicarbonate) and medium-sized molecules (e.g., insulin, myoglobin, certain medications and toxins) cross freely.

12. diffusion and convection During any renal replacement therapy, there are two transport mechanisms that can be involved in the transfer of solutes across a semipermeable membrane: diffusion and convection. Diffusive transport is driven by the solute concentration gradients that exist between blood and dialysate. Solute molecules are transferred across the membrane in the direction of the lower solute concentration at a rate inversely proportional to molecular weight. Convective transport occurs when a solute molecule is swept through the membrane by a moving stream of ultrafiltrate, a process that is also called 'solvent drag.' Convective transport is independent of any solute concentration gradient that might be present across the membrane. Only the direction and force oftransmembrane fluid flux are important determinants of convective transport. During hemodialysis, solute movement across the dialysis membrane from blood to dialysate is primarily the result of diffusive transport. During hemofiltration since no dialysate is used, diffusive transport cannot occur, and solute transfer is entirely dependent on convective transport. Thus hemofiltration, which depends on convective transport, is relatively inefficient at solute removal from the blood

13. Diffusion • diffusion • solute molecules are transferred across the membrane in the direction of the lower solute concentration at a rate inversely proportional to molecular weight. • hemodialysis • during hemodialysis, solute movement across the dialysis membrane from blood to dialysate is primarily the result of diffusive transport.

14. Convection • convection • a solute molecule is swept through a membrane by a moving stream of ultrafiltrate, a process that is also called 'solvent drag.' • hemofiltration • during hemofiltration no dialysate is used, and diffusive transport cannot occur. Solute transfer is entirely dependent on convective transport, making hemofiltration relatively inefficient at solute removal.

15. Ultrafiltration • Filtration across an ultrafiltration membrane is convective, similar to that found in the glomerulus of the kidney.

17. Filtration Spectrum • Ultrafiltration membranes that are utilized in hemofilters allow the passage of molecules with a molecular weight of less than 20,000 Daltons. Thus ions and small chemicals present in plasma are filtered freely, including sodium, potassium, bicarbonate, glucose and ammonia. So are larger soluble endogenous substances such as myoglobin, insulin, and interleukins, and certain exogenous substances circulating in plasma, including medications (vancomycin, heparin) and toxins (endotoxin, pesticides). Molecules that are bound to plasma proteins would not be filtered effectively by an ultrafiltration membrane.

18. The hemofiltration membraneis a composite structure consisting of an inner thin layer adjacent to the blood path surrounded by a supporting superstructure that provides mechanical integrity without restricting the passage of water or any solutes small enough to pass through the pores of the inner layer Hemodialysis membranes contain long, tortuous inter-connecting channels that result in high resistance to fluid flow. The hemofiltration membrane consists of relatively straight channels of ever-increasing diameter that offer little resistance to fluid flow.

19. Sieving Coefficient • The ability of a solute to convectively cross a membrane • The ratio of the solute concentration in the ultrafiltrate to the concentration in the plasma: • SC= [UF]/[Plasma] • An SC of 1 means that the solute freely crosses the membrane and is removed in the same concentration as in the plasma • An SC of 0 means that there is no solute removal due to either large molecular size or to extensive protein binding

20. Several synthetic materials have been developed for use in hemofiltration membranes, including polysulfone, polyacrylonitrile, and polyamide, all of which are extremely biocompatible. Consequently, complement activation and leukopenia, both of which are common in hemodialysis, occur infrequently during hemofiltration. This high degree of biocompatibility is an essential feature of hemofiltration, because the membrane may remain in constant contact with the blood for many days

21. Biocompatibility • Various synthetic materials are used in hemofiltration membranes: • polysulfone • polyacrylonitrile • polyamide • all of which are extremely biocompatible. Consequently, complement activation and leukopenia, both of which are common in hemodialysis, occur infrequently during hemofiltration.

22. Hemofiltration Membrane Hemodialysis membranes contain long, tortuous inter-connecting channels that result in high resistance to fluid flow. The hemofiltration membrane consists of relatively straight channels of ever-increasing diameter that offer little resistance to fluid flow. phosphate bicarbonate interleukin-1 interleukin-6 endotoxin vancomycin heparin pesticides ammonia

23. Hemofiltration Membrane Hemofilters allow easy transfer of solutes of less than 100 daltons (e.g. urea, creatinine, uric acid, sodium, potassium, ionized calcium and almost all drugs not bound to plasma proteins). All CVVH hemofilters are impermeable to albumin and other solutes of greater than 50,000 daltons. phosphate bicarbonate ionized Ca++ interleukin-6 endotoxin vancomycin heparin pesticides ammonia  albumin   protein-bound medications   platelets 

24. Vascular access The most important circuit component is the vascular access catheter. Achieving adequate central venous access in infants and young children can be difficult. The use of double lumen hemodialysis catheters has simplified CVVH vascular access in our center. Double lumen catheters are designed to withdraw blood from a large vein through holes in the side of the catheter that enter the outside lumen (the arterial lumen). Blood is returned down the central “venous" lumen and delivered through a single hole in the tip of the catheter that extends a short distance further into the vessel beyond the "arterial" holes on the side of the catheter. This design is intended to reduce recirculation of hemofiltered blood as much as possible by withdrawing from a site that is more distal (to the heart) and returning to a more proximal location within the same large vein. When the catheter's overall diameter is too large and closely resembles the internal diameter of the vessel, poor arterial flow may result from collapse of the vein against the sideholes of the catheter. This problem may be resolved by reversing flow, withdrawing from the venous and returning through the arterial lumen. Although some recirculation is then unavoidable, the use of large filters with high clearance rates easily overcomes this problem.

25. Blood Flow Rate In theory, pump speed should be sufficient to provide a filter blood flow rate (Qb) that yields an adequate ultrafiltration rate (UFR) without severely dehydrating the blood. Qb is determined by pump speed, vascular access catheter length, lumen diameters and patency, blood viscosity, and patency of the hemofilter's blood pathway (i.e. how many of the hemofilter's hollow fibers have clotted or are obstructed by entrapment of air). It should be remembered that as blood flows down each of the tiny hollow fibers in the hemofilter, fluid is removed, so that by the "venous" end of the hemofilter, each hollow fiber contains blood that is more concentrated. Hematocrit rises and the number of activated platelets increases, along with the concentrations of other clotting factors. When the blood is too dehydrated, the risk of clotting increases.

26. Blood Flow Rate

27. Filtration Fraction • The degree of blood dehydration can be estimated by determining the filtration fraction (FF), which is the fraction of plasma water removed by ultrafiltration: • FF(%) = (UFR x 100) / QP • where QP is the filter plasma flow rate in ml/min. • QP = BFR* x (1-Hct) • *BFR: blood flow rate

28. Ultrafiltrate Rate • FF(%) = (UFR x 100) / QP • QP = BFR* x (1-Hct) • For example, when BFR = 100 ml/min and Hct = 0.30 (i.e. 30%), QP = 70 ml/min. A filtration fraction > 30% promotes filter clotting. In the example above, when the maximum allowable FF is set at 30%, a BFR of 100 ml/min yields a UFR = 21 ml/min. • QP: the filter plasma flow rate in ml/min.

29. Rate of Solute Clearance • Solute Clearance= SC X UFR

30. Urea Clearance • In CVVH, ultrafiltrate urea concentration and BUN are the same, canceling out of the equation, which becomes: • Curea = UFR • Curea:(ml/min/1.73 m2 BSA)

31. urea clearance • Curea = UFR x 1.73 • pt’s BSA • Thus, in a child with body surface area = 1.0 m2, a Curea of about 15 ml/min/1.73 m2 is obtained when UFR = 8.7 ml/min or 520 ml/hr. • This same clearance can be achieved in the 1.73 m2 adolescent with a UFR = 900 ml/hr. • Curea:(ml/min/1.73 m2 BSA)

32. urea clearance • When target urea clearance (Curea) is set at 15 ml/min/1.73 m2, the equation can be solved for UFR: • 15 = UFR x 1.73 / pt’s BSA • UFR = 15 / 1.73 = 8.7 ml/min • Curea:(ml/min/1.73 m2 BSA)

33. Sluggishness • A filtration rate of more than 25 - 30% greatly increases blood viscosity within the circuit, risking clot and malfunction. Oncotic pressure increases as Protein-free plasma is filtered, at one point the oncotic pressure will equalize the hydrostatic pressure and filtration will cease.

34. Replacement • Ultrafiltrate is concurrently replaced with a combination of: • custom physiologic solutions • ringer’s lactate • total parenteral nutrition solutions • In patients with fluid overload, a portion of the ultrafiltrate volume is simply not replaced, resulting in predictable and controllable negative fluid balance.

35. Pre-dilution • Sludging problems are reduced, but the efficiency of ultrafiltration is compromised, as the ultrafiltrate now contains a portion of the replacement fluid. Pre-dilution will reduce clearance of solutes

36. Replacement fluid: potassium • Potassium is usually excluded from the initial FRF formula in patients with renal failure. Eventually, most patients need some potassium (and phosphate) supplementation. • a physiologic concentration of potassium must be added to each of the four FRF bags • if instead 16 mEq of KCl were added to a single bag, serious hyperkalemia could develop quickly

37. Replacement Fluid: Ringer’s • Many adults are successfully treated with CVVH using Lactated Ringer's solution as the FRF. Ringer’s is: • convenient • cheaper • eliminates risk of pharmacy error in formulation of the Michigan bags • Michigan FRF may be preferable in critically ill children, especially infants, but we have not compared the two solutions systematically.

38. Replacement Fluid: Commercial

39. Fluid Balance • Precise fluid balance is one of the most useful features of CVVH. Each hour, the volume of filtration replacement fluid (FRF) is adjusted to yield the desired fluid balance.

40. physiologic replacement fluid university of michigan formula

41. Replacement Fluid: final conc. university of michigan formula

42. Drug Clearance & Dosing • Drug therapy should be adjusted using frequent blood level determinations, or by using tables that provide dosage adjustments in patients with reduced renal function: • Bennett's tables require an approximation of patient's GFR • the CVVH 'GFR' is approximated by the ultrafiltrate rate (UFR), plus any residual renal clearance • using Bennett's tables, in most CVVH patients, drug dosing can be adjusted for a 'GFR' in the range of 10 to 50 ml/min.

43. DRUG LOADING DOSE MAINTENANCE DOSE Acyclovir --- 5 mg/kg Q12H Amikacin 7.5 mg/kg 7.5 mg/kg Q24H Aztreonam 2 g 1 g Q12H Cefepime 2 g 1 g Q12H Cefoperazone 2 g 1 g Q12H Ceftazidime 2 g 1 g Q12H Cimetidine --- 300 mg Q8H 900 mg/24H in TPN Ciprofloxacin --- 400 mg Q24H Co-trimoxazole (SMX/TMP) (IV) --- 2.5 mg/kg TMP Q8H Fluconazole 400 mg 200 mg Q24H Gent/Tobra 2 mg/kg 1.5 – 2 mg/kg Q24H Ganciclovir --- 2 mg/kg Q24H Imipenem --- 500 mg Q8H Metronidazole 1 g 500 mg Q8H Piperacillin --- 3 g Q8H Procainamide (IV) 1-2 g 1 mg/min Ranitidine (IV) --- 150 mg/24H in TPN or 50 mg Q8-12H Vancomycin 15 mg/kg 10 mg/kg Q24H

44. Anti-coagulation • To prevent clotting within and shutdown of the CVVH circuit, active anti-coagulation is often needed. • - heparin - citrate • - ‘local’ vs. systemic

45. Anti-coagulation • Patients with coagulopathies may not need any heparin. • if patient's ACT is > 200 seconds before treatment, we do not use heparin • coagulopathies spontaneously improve, often signaled by filter clotting…

46. Anti-coagulation: heparin • Patients with coagulopathies may not need any heparin. • when the ACT is <200 seconds, a loading dose of heparin @ 5-20 units/kg is given • heparin as a continuous infusion (initial rate 5 units/kg/hr) into ‘prefilter’ limb of circuit • adjust heparin rate to keep ACT from the venous limb (‘postfilter’) 160 to 200 seconds

47. Anti-coagulation: citrate • Citrate regional anticoagulation of the CVVH circuit may be employed when systemic (i.e., patient) anticoagulation is contraindicated for any reason (usually, when a severe coagulopathy pre-exists). • CVVH-D mode has countercurrent dialysis across the filter cartridge • CVVH-D helps prevent inducing hypernatremia with the trisodium citrate solution

48. Anti-coagulation: citrate • Citrate regional anticoagulation of the CVVH circuit : • 4% trisodium citrate ‘prefilter’ • citrate infusion rate = filtration rate (ml/min) x 60 min. x 0.03 • replacement fluid: normal saline • calcium infusion: 8% CaCl in NS through a distal site • dialysate: Na 117 . glucose 100-200 . K 4 . HCO3 22 . Cl 100 . Mg 1.5 • Ionized calcium in the circuit will drop to < 0.3, while the systemic calcium concentration is maintained by the infusion. • Sramek et al:Intensive Care Med. 1998; 24(3): 262-264.

49. PRISMA: Flow Rates • Blood Flow: 10-180 ml/min • Replacement solution flow: • 0-4500 ml/hr with CVVH • 0-2000 ml/hr with other modes • Dialysate flow: 50-2500 ml/hr • Fluid removal flow: • 10-2000 ml/hr with SCUF • 0-1000 ml/hr other modes • Effluent flow (dialysate plus ultrafiltrate): max 5500 ml/h

50. PRISMA: Pressure Monitoring ranges: • Access line pressure: +50 to –250 • Return line pressure: -50 to +350 • Prefilter pressure: -50 to +500 • Effluent line: -350 to +50