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• based on use of a highly permeable membrane
  • polysulfone
  • polyamide
  • polyacrylonitrile
• large amounts of water lost by ultrafiltration and solutes by convection
• replaced with solutions containing the necessary amounts of electrolytes. Concentration of solutes in ultrafiltrate and remaining plasma are similar. Main change in concentrations results from replacement of ultrafiltrate with replacement solution
• determinants of ultrafiltration rate:

• hydraulic permeability of membrane
• surface area of membrane
• hydrostatic pressure gradient across membrane (transmembrane pressure)
• colloid osmotic pressure gradient across membrane (impedes filtration)
• haematocrit

• factors affecting clearance by convection:

• ultrafiltration rate
• pore size of membrane
• effective molecular diameter
• molecular charge (most dialysis membranes are negatively charged)

CVVH & CVVHDF

• Requires use of pump to pump blood around circuit. Blood flow rate 100-500 ml/hour
• Large volumes of fluids removed require extreme attention to fluid balance and intravascular pressures. Volumetric pumps used to control ultrafiltrate production at rate of up to 10 L/h
  • if filtration fraction (ultrafiltration rate/blood flow rate) >0.3 filter will clot
• Fluid replacement proceeds at a similar rate with allowances for other fluid
• CVVHDF slightly less logical than CAVHDF as raising the ultrafiltration rate by increasing blood pump speed (to increase transmembrane pressure) can achieve an identical increase in small molecule clearance with added benefit of higher middle molecule clearance. Unfortunately this leads to formation of a boundary layer of plasma proteins on the membrane surface which becomes thicker with increasing transmembrane pressure. Eventually interferes with membrane function so that any further increase in transmembrane pressure is not mirrored by an increase in ultrafiltration
• Advantages
  • suitable for haemodynamically unstable patients - slower rate of fluid removal
  • continuous therapy avoids periods of dehydration and hypotension which may delay recovery of renal function
  • less nurse training required
  • biocompatible membranes
• Disadvantages
  • more expensive than intermittent haemodialysis
  • low efficiency so that patient needs to be receive continuous therapy - interferes with other procedures
  • hypothermia
• ? better outcome than with intermittent haemodialysis

Replacement fluid

• Fluid for haemofiltration based systems is designed to normalize electrolyte and acid-base status
• Daily fluid replacement 10-50 l/day. As a result patient's serum soon has similar solute concentrations to replacement fluid
• Near-normal electrolyte balance can be achieved by alternating the following solutions:
  - 1l N/saline + 20ml 10% calcium gluconate ± KCl 3-4 mmol
  - 1L 1/2 normal saline + 50 mmol sodium bicarbonate ± KCl 3-4 mmol
  Mg and phosphate must be monitored closely as both are highly ultrafilterable.
  

• Bicarbonate passes into the ultrafiltrate and therefore if it is not replaced the patient rapidly becomes acidotic. Lactate and acetate are widely used as substitutes for bicarbonate as bicarbonate containing commercial replacement fluid has only recently become available. Problem is due to precipitation when combined with Ca or Mg. However in order to be effective replacements lactate and acetate must be fully metabolized by the liver.
• In patients with hepatic dysfunction lactate and acetate may not be metabolized adequately with resultant inadequate production of bicarbonate and high lactate/acetate concentrations. These may cause peripheral vasodilatation and myocardial depression as well as increased catabolism and impaired intracellular metabolism (lactate). Bicarbonate is lost in filtrate and thus metabolic acidosis may be exacerbated if it is not replaced by metabolism of lactate/acetate to bicarbonate. In patients who fail to metabolize lactate/acetate infusion of bicarbonate may be an appropriate alternative.
• In patients with chronic hyponatraemia replacement fluid needs to be adjusted to prevent an excessively rapid correction of hyponatraemia

Dialysate

• Standard PD solution can be used, usually at 1L/h
• Glucose rich PD fluid results in significant glucose transfer into patient.
• In some cases of metabolic acidosis lactate and acetate solutions may be inappropriate and a bicarbonate-based solution may be preferable

Anticoagulation

Generally administered into arterial limb of circuit

Unfractionated heparin

• Most widely used
• Loading dose of 1000 U followed by 400-1600 U/h aiming for APTT 2.5-3 times normal
• Ideally check ACT every 10 mins after start of treatment and then every 30 mins until stable dose of heparin established. Thereafter frequency can be gradually reduced t approximately 12 hourly

Regional heparinization

• Heparin infused into arterial limb (as usual) and protamine infused into venous limb
• Heparin 1000 U/h, protamine 10 mg/h
• Monitor 3 times per day with PT and APTT using arterial blood, post-heparin and post-protamine blood. Post-protamine neutralization of heparin should be incomplete to avoid clotting of venous limb of catheter
• Reasonable filter patency with decreased risk of bleeding
• Requires frequent monitoring and dosing modifications

Low molecular weight heparin

• Has theoretical advantage of dissociating antithrombotic activity from anticoagulant activity
• Role in anticoagulating extracorporeal circuits undefined
• Potential advantage: decreased risk of bleeding
• Disadvantages: prolonged half-life (>10 h), incomplete neutralization with protamine, limited availability of monitoring test (anti-factor Xa activity)

Prostacyclin

• Usually reserved for patients with bleeding that is thought to be exacerbated by heparin
• Reduce heparin infusion rate to 100-400 U/h. Start prostacyclin at 150 ng/kg/h for first 30 mins. Can be increased to 300 ng/kg/h if it is not causing unacceptable adverse effects (eg hypotension, headache, flushing, nausea and abdominal cramps)
• Can be used alone (450 ng/kg/h) but incidence of side effects is high
• Does not affect any of the routine laboratory coagulation tests and monitoring requires platelet aggregation studies
• Anti-platelet acitivity still present 2 h after cessation of infusion. No means of rapid reversal
• Excellent filter patency

Citrate

• Use in conjunction with calcium-free replacement fluid. Calcium can be replaced separately
• Provides regional anticoagulation of circuit without systemic anticoagulation
• Risks include metabolic alkalosis and hypocalcaemia. Monitor ABG and ionized calcium

Non-anticoagulated techniques

• Use short tubing and predilution
• Thrombocytopaenia (with plts<100) increases filter patency. Prolonged PT may or may not help

Complications and problems

Poor vascular access

• Reduced blood flow through circuit. Causes clotting and decreased ultrafiltration. In CAVH/D these may be only signs
• In CVVH/D problems with arterial lumen of cannula results in collapse of arterial limb of circuit due to negative pressure generated by blood pump. Also produces foam in arterial limb and activation of arterial pressure alarm. Poor flow may result in fall in venous pressure and activation of low venous pressure alarm causing pump to stop
• Problems with venous lumen (CVVH/D) activates venous high pressure alarmand should stop pump
• If flow is poor:
  - turn down pump speed
  - clamp filtrate line
  - check no clamps on blood lines
  - check blood lines not otherwise occluded
  - treat hypotension (AV circuits)
  - alter position of patient
  - manipulate catheter (eg pull back slightly)
  - reverse polarity (VV circuits)
  - consider flushing catheter with thrombolytic
  - replace catheter
  If problem has not been rectified within 5 mins blood lines should be disconnected from vascular access and joined end to end so that blood can be recirculated continously to prevent clotting

Complications due to catheter

eg arterial puncture, pneumothorax, infection

Clotting

• Results in patient losing approx. 200 ml of blood. Costly in terms of time and resources
• Earliest sign is darkening of colour of extracorporeal blood. Blood lines in AV circuits feel cool and when lines have clotted completely plasma separates from red cells. In VV circuit venous pressure gradually rises
• If clotting suspected turn down speed of pump, clamp venous line and give bolus of 10-50 ml normal saline into arterial line. This dilutes blood sufficiently to reveal any clots. Then unclamp venous line. If clots are well formed as much extracorporeal blood as possible should be washed back (clots will be retained in bubble trap). If there are just "stringy bits" an increase in dose of heparin should be sufficient
• Heparin resistance is usually due to acquired deficiency of antithrombin III. Can be treated with antithrombin III concentrate or FFP

Bleeding

• Carries very poor prognosis
• Control bleeding locally if possible
• Other options:
  - stop anticoagulation. Circuit less likely to clot if patient is thrombocytopaenic, if predilution used and if blood pump speed is high
  - regional anticoagulation with citrate
  - use prostacyclin. Although widely used large series have not demonstrated benefit
  - change to HD or PD

Poor solute clearance

Can be improved by:

• increasing transmembrane pressure. However this method is self-limiting due to deposition of plasma proteins on membrane (see above)
• using kidney with higher membrane surface area
• changing from HF to HDF
• supplementary intermittent HD

Air in extracorporeal circuit

• Usually results from operator error
• Immediate action is to clamp venous limb. Air and foam detector on blood pump monitors should ensure this happens automatically
• Treat air embolism along conventional lines

Other complications

• hypothermia
• hyponatraemia (usually due to lower Na concentration in enteral or parenteral feed than in ultrafiltrate that is being removed to make room for feed)
• increased lactate concentration due to use of lactate buffered replacement fluid in patients with sepsis or hepatic dysfunction

Drug dosage

Haemofiltration

• drug extraction depends on its sieving coefficient (ie concentration in ultrafiltrate divided by mean of concentrations in pre and post filter blood)
• clearance = sieving coefficient x ultrafiltration rate
• for most drugs sieving concentration for unbound drug is close to 1. Thus if published figures not available and estimate of sieving coefficient can be derived from degree of protein binding

Simplified method of drug dosing

• filters similar in sieving to functioning glomerulus
• consider day's total filtrate as equivalent to GFR
• adjust drug dosing according to GFR-based recommendations

Recommended antibiotic doses

SCUF-D

• Slow continuous ultrafiltration with dialysis
• Uses high dialysate flows (eg 2L/h), minimal controlled ultrafiltration (100-200 ml/h) and no requirement for fluid replacement.
• Provides excellent removal of small molecules but fails to significantly remove larger molecules (>500 daltons). As a result less suitable than CVVH/CVVHD for septic patients

©Charles Gomersall, May, 2013 unless otherwise stated. The author, editor and The Chinese University of Hong Kong take no responsibility for any adverse event resulting from the use of this webpage.
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