This refers to decreased glomerular filtration rate (GFR) due to reduced renal perfusion. There is no tubular damage. May be reversed by adequate fluid resuscitation and reperfusion of the kidney.

Decreased GFR is due to reduced perfusion, resulting in ischaemic renal tubular damage. There is no immediate reversal on restoration of perfusion, but it usually improves over time. This is the commonest pattern of ARF (requiring renal replacement therapy, e.g. haemofiltration) seen on ICU.

Total and irreversible loss of renal function results from severe prolonged ischaemia of kidneys. This is rare. It is seen occasionally in obstetric patients following placental abruption and haemorrhage where combination of a hypotension, hypercoagulable state and endothelial injury leads to thrombosis of renal vessels.

The main problems associated with acute renal failure (ARF) are inability to excrete fluid, impaired acid–base regulation, hyperkalaemia and accumulation of waste products.

Inability to excrete fluid may result in progressive fluid overload. This may be manifest as hypertension, tissue and pulmonary oedema.

Impaired acid–base balance results in progressive accumulation of hydrogen ions and metabolic acidosis. This may be exacerbated by the effects of excess chloride load (from use of 0.9% sodium chloride containing fluids) resulting in hyperchloraemic acidosis (see hyperchloraemic acidosis, p. 53).

Impaired excretion of potassium leads to hyperkalaemia. This can develop rapidly, particularly in critically ill patients, and is a medical emergency. Other problems of electrolyte disturbance include abnormalities of sodium, phosphate and calcium balance.

Accumulation of creatinine, urea and other molecules may produce clouding of conscious level, metabolic encephalopathy and myocardial depression. GIT side effects include gastric stasis and ileus. Coagulopathy may result from effects on platelet function.

The main concern in the acute phase is the development of ventricular dysrhythmias associated with hyperkalaemia. Potassium levels can rise quickly in the presence of severe sepsis and hypercatabolism. Patients with chronic renal failure (CRF) may tolerate hyperkalaemia much better than patients with ARF. A serum potassium greater than 6–6.5 mmol/L requires urgent treatment. Calcium, bicarbonate and dextrose/insulin buy time prior to dialysis but do not alter the underlying problem. (See Hyperkalaemia, p. 206.)

Typical indications for instituting renal replacement therapy in acute renal failure are shown in Box 7.2.

This is characterized by rising serum urea and creatinine despite adequate urine volumes. Urine biochemistry demonstrates a failure to concentrate urine. Indications for dialysis are as for oliguric renal failure but there are generally fewer problems with high potassium and fluid overload. Non-oliguric renal failure is said to have a better outcome than oliguric renal failure. It often accompanies the recovery phase of ATN.

The simplest form of continuous renal replacement is continuous venovenous haemofiltration (Fig. 7.1).

Fig. 7.1 Continuous venovenous haemofiltration. Replacement fluid may be delivered either (A) before the filter (pre-dilution) or (B) after the filter (post dilution). Pre-dilution may reduce clotting within the filter and prolong filter life.

Blood from the patient is passed through a filter, which allows plasma water, electrolytes and small molecular weight molecules to pass through down a pressure gradient. This filtrate is discarded and replaced by a balanced electrolyte solution. Typically 200–500 mL/h of filtrate are removed and replaced. Overall negative fluid balance can be achieved by replacing less fluid than is removed.

There has been a great deal of interest recently in the role of CVVHF in sepsis. Many of the proinflammatory molecules, toxins and cytokines, which are implicated in the pathogenesis of the systemic inflammatory response syndrome, are removed by haemofiltration. There is anecdotal evidence that some unstable patients have improved following the institution of CVVHF and many units now routinely haemofilter septic patients. There is some limited evidence that high volume haemofiltration, e.g. 2000 mL/h may stabilize the critically ill septic patient. (See Sepsis, p. 331.)

One problem with CVVHF is that clearance of small molecules and solutes is inefficient, and this can require large volumes of filtrate to be removed and replaced in order to achieve acceptable creatinine clearance.

In continuous haemodialysis (Fig. 7.2), dialysis fluid is passed over the filter membrane in a countercurrent manner. Fluids, electrolytes and small products can move in both directions across the filter, depending on hydrostatic pressure, ionic binding and osmotic gradients. Overall creatinine clearance is greatly improved compared with haemofiltration alone.

Fig. 7.2 Continuous venovenous haemodialysis (CVVHD). If dialysis machine is not set to remove any fluid, dialysis pumps A and B run at the same rate. If dialysis machine is set to remove fluid, dialysis pump B runs faster than pump A by the amount required to remove the fluid.

In CVVHD, provided the volume of dialysis fluid passing out from the system matches the volume of dialysis fluid passing in, there is no net gain or loss of fluid to the patient. By allowing more dialysate fluid to pass out of the filter than passes in, fluid can be effectively removed from the patient. Rates of fluid removal up to 200 mL/h can be achieved. In most CVVHD machines fluid removal is achieved by increasing the rate of the dialysis pump controlling the exit side of the filter by the amount of fluid to be removed (Fig. 7.2).

This term is best used for systems that intentionally combine both haemodialysis and haemofiltration. Dialysis fluid is passed across the filter to remove solutes by osmosis but at the same time ultrafiltrate is removed and replaced.

Venous access for venovenous renal replacement therapy is generally achieved using a large-bore double-lumen catheter (typically 11.5 Fr). These are sited using a Seldinger technique with the aid of a large, ‘stiff’ dilator. Care must be taken to avoid damage to the vessels and surrounding structures. Avoid siting in vessels with obvious tight corners, e.g. left internal jugular. Ideally, use right internal jugular or femoral veins. Ensure an appropriate length catheter is inserted to reach IVC or SVC/RA to give adequate flows and extended catheter life. (See Central venous access, p. 387.)

These large-bore catheters are prone to ‘clotting off’ when not in use. When the catheters are inserted, or when extracorporeal circuits are discontinued, catheters should be flushed with heparin (1000 units/mL) to the priming volume of the catheter, as printed on the hub.

In systems where blood passes through an extracorporeal circuit, anticoagulation is needed to prevent clotting, unless the patient has a severe underlying coagulopathy. Typical regimens are heparin 1000 units loading dose then 100–500 units/h or epoprostenol (prostacyclin) 5 ng kg⁻¹ min⁻¹. Infusions are run directly into the dialysis circuit. The effects of anticoagulation should be monitored regularly using activated clotting time (ACT) or activated partial thromboplastin time (APTT) and the anticoagulant regimen adjusted as necessary.

Excessive anticoagulation can result in bleeding problems. One approach to this has been the introduction of citrate as an anticoagulant for renal replacement therapy. As blood leaves the patient and enters the extracorporeal circuit, citrate is added. As the blood leaves the circuit, the calcium is added to reverse the effects of the citrate and prevent the patient becoming systemically anticoagulated.

The problems associated with renal replacement therapy are listed in Box 7.3.

It is common to see a fall in blood pressure and CO, and deterioration in oxygenation when blood enters any extracorporeal circuit. Factors which may contribute to this include fluid shifts, haemodilution and complement/cytokine activation from blood in the dialysis circuit. Hypotension generally responds to simple fluid loading, but may require vasopressor/inotrope infusion. Consider reducing the rate of fluid removal by the system if hypotension persists.

The so-called dialysis disequilibration syndrome may occur when biochemical abnormalities are corrected too quickly. The rapid removal of plasma solute renders the plasma hypotonic with respect to the brain and acute cerebral oedema develops. It is usually associated with conventional intermittent haemodialysis and is rare with modern practice.

For the purpose of prescribing, creatinine clearance during renal replacement therapy can be considered as being greatly reduced. (< 10 mL/min). Drug clearance is dependent on molecular size, charge, volume of distribution and water solubility. In general, non-ionized drugs with high fat solubility and large volume of distribution will not be cleared efficiently by dialysis (e.g. CNS-acting sedative and analgesic drugs).

The morphine metabolites (morphine-3-glucuronide and morphine-6-glucuronide) are both active and accumulate in renal failure. It is reasonable to give morphine derivatives as small intermittent intravenous injections but avoid infusing them over long periods of time. Pethidine is metabolized to norpethidine, which accumulates and may produce cerebral excitation and fits. Fentanyl, alfentanil and remifentanil accumulate less and may be used for continuous infusions.

The two most commonly used benzodiazepines in intensive care are midazolam and diazepam. Both are metabolized by the liver, but diazepam has an active metabolite that is excreted by the kidneys and may accumulate in renal failure.

Suxamethonium causes a transient elevation in serum potassium that is likely to be clinically relevant and potentially dangerous in patients with renal failure, particularly when this is associated with muscle damage. The use of suxamethonium should be carefully considered on balance of risks, as the risk of aspiration of gastric contents into the airway may be less than the risk of cardiac arrest due to hyperkalaemia (see Suxamethonium, p. 34).

Some non-depolarizing muscle relaxants may accumulate in renal failure. Atracurium and its isomer cis-atracurium undergo spontaneous (non-metabolic) degradation at body pH and temperature and are generally the most suitable for use in the critically ill (see Sedation and analgesia, p. 43).

The clearance of aminoglycosides is reduced in renal failure, and high levels are both nephrotoxic and cause deafness if maintained over time. Reduce the dosage/frequency and monitor levels (see Appendix 1, p. 449). Penicillins may accumulate and produce seizures at high concentrations. Dose and frequency should be reduced after loading doses have been given. Carbipenems, cephalosporins and other antibiotics may also need dose reduction. Seek advice.

Digoxin is unpredictable in renal failure. Levels may be substantially elevated compared with healthy patients. It is cleared to a variable extent by dialysis. Consider alternative agents, e.g. amiodarone.