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Anaesthesia for patients with impaired renal function
Anaesthesia for Patients with Impaired Renal Function
D. E. Holland and S. Old
End stage renal failure (ESRF), defined as a creatinine clearance < 10 ml min- 1(plasma creatinine >500 umol l-l), has an incidence of approximately 140/ million/year in the UK. About 60/million/year commence long term renal replacement therapy and with an annual mortality of 10% there are about 300/million patients with impaired renal function. In 1991, 1766 renal transplants were performed and 4000 await a suitable organ (UK Transplant Service, personal communication). Although most patients with ESRF will have elective surgery at their 'parent' renal unit hospital, many require emergency surgery in other hospitals. As minimal care dialysis facilities are disseminated away from large units, more patients with renal failure are likely to need surgery and anaesthesia in District General Hospitals. Isolated acute renal failure is uncommon and surgery in these patients can usually be deferred until they are stabilised on dialysis and they have the same problems as those with ESRF. The anaesthetic management of patients with acute renal failure associated with multiple organ failure, sepsis, trauma and surgery on the cardiovascular system is directed as much by the primary problem as the renal failure and this will not be addressed further. Safe anaesthesia for the patient with renal failure requires a knowledge of the etiology, pathophysiology, clinical manifestations and medical management of renal failure. Although the use of atracurium has revolutionised general anaesthesia in ESRF, a
working knowledge of the effects of renal failure on drug kinetics is essential.
Clinical pathophysiology Anaemia
Patients have a normochromic normocytic anaemia with a haemoglobin of 5-10g d1-1. The etiology of this is multifactorial. Uraemia depresses erythropoietin production and red cell release from the marrow, erythrocyte life span is reduced, aluminium toxicity decreases haemoglobin synthesis and there is repeated blood loss during haemodialysis when cells are also damaged in extracorporeal circuits. Untreated peptic ulcer disease leads to chronic blood and hence iron loss. Poor appetite and poor compliance with drug prescriptions often lead to reduced vitamin (B6, B12 and folate) and iron intake which exacerbates the problem. Hyperparathyroidism with marrow fibrosis will also impair erythrogenesis. Patients with polycystic renal disease tend to maintain a higher haemoglobin than those with other causes of ESRF and this is a powerful argument for resisting nephrectomy until the size of the kidney causes a significant space occupying problem or recurrent cyst infection occurs. Similarly, patients on continuous ambulatory peritoneal dialysis (CAPD) tend to maintain their haemoglobin better than those on haemodialysis (HD). Biosynthetic erythropoietin 1'2 now allows restoration of haemoglobin to normal levels but is expensive and not without adverse effects (hypertension, vascular thrombosis). It is generally reserved for those who
D. E. Holland, BMedSci, MB, MRCP, FRCAnaes, and S. Old, MA, MB, ChB, Department of Anaesthetics, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK Current Anaesthesia and Critical Care
© 1992LongmanGroupUK Ltd
(1992)3, 140-145 140
ANAESTHESIA FOR PATIENTS WITH IMPAIRED RENAL FUNCTION Table 1 - - Clinical features of chronic renal failure Cardiovascular
- hypertension - coronary artery disease - congestive cardiac failure pericarditis endocarditis - secondary valvular dysfunction - dyspnoea secondary to acidosis and anaemia infection - pulmonary fibrosis associated with other disease neutrophil sequestration with dialysis - normochromic normocytic anaemia increased bleeding time platelet dysfunction - myopathy - sensory neuropathy - occasional motor neuropathy - autonomic neuropathy - convulsions - anorexia - nausea and vomiting - delayed gastric emptying peptic ulceration - hyperkalaemia - hyperparathyroidism - glucose intolerance - hyperuricaemia altered lipid metabolism -
-
Respiratory
-
-
Haemopoietic
-
-
Nervous system
Gastrointestinal system
-
Metabolic
-
have symptoms, such as angina, associated with anaemia and interfering with activities of daily life or a haemoglobin < 8 g dl - t . The reduced oxygen transport effect of anaemia is c o m p e n s a t e d by an increase in cardiac output and increase in red cell 2,3-diphosphoglycerate which causes a right-ward shift of the oxyhaemoglobin dissociation curve. This favours oxygen unloading at the tissues. Whilst severe anaemia causes a reduction in the blood-gas partition coefficient for inhalation agents, with an increase in speed of onset and recovery, this is rarely a problem in clinical practice. The influence of blood transfusion on the i m m u n e system in E S R F continues to be a m o o t point. Although there is evidence that transfusion can induce immune tolerance it can also induce the formation of cytotoxic antibodies which m a k e kidney transplantation m o r e difficult. Our clinical practice is to transfuse pre-operatively only those with a haemoglobin less than 5g d1-1 or who have angina or dyspnoea which is known to improve with an increase in haemoglobin.
Bleeding diathesis The primary haemostatic defect in E S R F is thought to be an abnormality of platelet function. 3 Platelets show an increase in cytoplasmic free calcium and there are defects in the release and metabolism of arachidonic acid and exposure of fibrinogen receptors. Deficiencies in platelet aggregation are not correlated with the severity of renal failure but improve with dialysis. Bleeding time is prolonged but
141
transfusion or treatment with erythropoietin restore bleeding time towards normal. Although case reports of bleeding problems in E S R F abound, the true incidence is probably no greater than in patients without renal failure. Gastrointestinal h a e m o r r h a g e is c o m m o n but over 90% have a lesion detected at endoscopy. Excessive bleeding after haemodialysis should be treated with protamine according to laboratory studies of the coagulation cascade. Desamino-8-Darginine vasopressin (Desmopressin acetate, D D A V P ) 0.3mcg kg -1 has been used to reduce bleeding not associated with heparin.
Cardiovascular system Cardiovascular disease remains the leading cause of death in patients with E S R F and the second (to infection) most c o m m o n cause of death in those with a functioning transplant. 4 In patients of 2 5 - 4 5 years death from atherosclerosis is nearly four times greater than in the general population (47% versus 14%). Cardiovascular disease in E S R F is the product of hypertension, abnormal left ventricular function, pericardial disease and atherosclerotic coronary artery disease. 5 A b o u t 80% of patients will develop hypertension. This is related to an increase in systemic vascular resistance and salt and water loading. The effects of the associated left ventricular hypertrophy on myocardial oxygen supply and demand are well known (see ref. 5 pp 1-30). Although up to 65% of the hypertensive E S R F population have their blood pressure controlled by dialysis alone, many are taking antihypertensive drugs. First line treatment is often with calcium channel inhibitors or beta adrenoceptor blockers. These drugs tend to exacerbate the cardiovascular depression caused by the inhalational anaesthetic agents (additive effect) and spontanoeus ventilation techniques with inspired concentrations above 1 minimum alveolar concentration ( M A C ) should be avoided. Primary vasodilators (e.g. hydralazine, prazosin, minoxidil) are used less frequently now. The angiotensin converting enzyme inhibitors do not seem to cause significant problems with anaesthesia. All antihypertensives should normally be continued through the peri-operative period. 6 Hypertensive patients often show exaggerated changes in blood pressure and heart rate associated with induction of anaesthesia, laryngoscopy and intubation. M a r k e d increases and falls of blood pressure with tachy- or bradycardia can all lead to ST-T wave changes on the E C G normally associated with myocardial ischaemia. Whilst it seems prudent to try to adapt the anaesthetic technique to avoid these as much as possible (see below) there is no clear evidence that transient changes have a long term effect on postoperative morbidity or mortality.
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Overt pericardial disease is now uncommon with dialysis. Constrictive pericarditis with tamponade must be recognised and treated urgently. Tamponade is characterised by loss of the Y descent on the jugular venous pulse, which is elevated. There is pulsus paradoxus with loss of volume during inspiration. A pericardial effusion is usually seen on an echocardiogram. Tamponade is associated with severe restriction in cardiac output and great care is required at induction of anaesthesia for pericardectomy. There is a high incidence of abnormal lipoprotein metabolism in ESRF. Elevated cholesterol and decreased high density lipoprotein are associated with the development of coronary artery disease and peripheral vascular disease. Left sided, low output cardiac failure is present in 45% of patients and is predictive of an adverse effect on survival. In addition to ischaemic and hypertensive heart disease other mechanisms which may cause congestive failure are; intrinsic volume overload in aortic and mitral regurgitation, pressure overload in aortic stenosis; restricted diastolic function in mitral stenosis and pericardial disease with pulmonary venous hypertension and reduced cardiac output; extrinsic circulatory overload due to failure of sodium and water excretion. Further depression of cardiac output with anaesthetic drugs can induce a cycle of reduced blood pressure, impaired myocardial blood flow and diminishing cardiac output. Infective endocarditis occurs in 2.7% of patients on maintenance haemodialysis and in 9% of those who have an infection of a vascular access site. The mortality of endocarditis in this group is 45%. Antiseptic skin preparation before vascular access should be routine. Autonomic neuropathy is said to be common in ESRF. Impairment of sympathetic vasoconstriction and reflex increases in chronotropic and inotropic action on the heart can lead to marked falls in blood pressure in response to positive pressure ventilation (IPPV). The fall in blood pressure is exacerbated if patients are dehydrated, for example after dialysis.
Respiratory system Cardiovascular disease and the inability to excrete a fluid load make patients susceptible to pulmonary oedema. Dyspnoea is often exacerbated by acidosis and anaemia. Pulmonary lesions associated with the cause of the renal failure are not uncommon, for example pulmonary fibrosis associated with rheumatoid arthritis and amyloidosis. Modern 'biocompatible' (polysulfone, acetonitrile) dialysis membranes cause much less activation of inflammatory mediators than cuprophane membranes did. Complement activation with leucocyte sequestration in the lung occurs occasionally and can lead to low pressure pulmonary oedema (adult respiratory distress syndrome, ARDS).
The immunodepression of renal failure makes pulmonary infection common. The ideal of deferring surgery until the chest X-ray is clear and the patient well is not always a practical option.
Nervous system A peripheral, predominantly lower limb, sensory neuropathy is well recognised in ESRF and may progress to a motor neuropathy. Much of the weakness in uraemia is due to myopathy rather than neuropathy and these patients may show an exaggerated response to muscle relaxants. Twitches, cramps, 'restless' legs and pruritis are of uncertain etiology, cause much distress to the sufferer and may respond to quinine sulphate; they are of no consequence for the anaesthetist. The problems associated with autonomic neuropathy are mentioned above. Autonomic neuropathy is much commoner in diabetics. Grand mal fits and mental changes associated with the fluid and electrolyte shifts of over zealous haemodialysis should be a thing of the past. Occasionally cerebral oedema with impaired consciousness develops after regular dialysis is established: The anaesthetist may be asked to arrange ventilation to reduce arterial PaCO2; mannitol may be of some benefit. Ideally therapy should be directed by measurement of intracranial pressure.
Gastrointestinal system There is a high incidence of peptic ulcer disease in renal failure and many patients are already taking histamine H2 receptor antagonists. These should be continued through the peri-operative period as there is also delayed gastric emptying (and possibly increased gastric acid production) which predisposes to oesophageal reflux and aspiration.
Calcium and phosphate homoeostasis A fall in glomerular filtration rate (GFR) causes a rise in plasma phosphate with a fall in plasma calcium. Ionised calcium is preserved by the accompanying acidosis and tetany is rare. Defective hydroxylation of vitamin D in the diseased kidneys leads to defective mineralisation of bone and reduced absorption of calcium in the gut. Reduced plasma calcium stimulates production of parathyroid hormone (PTH) which raises calcium and lowers plasma phosphate. Hypocalcaemia combined with hypermagnesaemia (excessive consumption of antacids) potentiates nondepolarising muscle relaxants. Eventually the solubility product for calcium phosphate is exceeded and ectopic calcification occurs. In blood vessels this exacerbates the effects of atherosclerosis; calcification in the conducting system of the heart can lead to dysrhythmias and conduction abnormalities. Prolonged stimulation of the parathyroids leads to hyper-
ANAESTHESIA FOR PATIENTS WITH IMPAIRED RENAL FUNCTION 143
Table2 -- Influenceof renal failureon anaestheticdrugs Drug
Eliminationin ESRF
Thiopentone
? decreased
Ketamine Propofol Etomidate Fentanyl Alfentanil Phenoperidine Morphine Atracurium Neostigmine
Comments
Normal dose, slow administration ? Avoid: Hypertension 40% decrease Hypotensiona problem ? Decreased protein binding Little effecton CVS 25% decrease Cumulationonlya problem with high/ repeated doses 20% decrease Usefulto obtund response to intubation 50% decrease 50% unchangedin urine. Caution! ? unchanged Morphine-6-glucuronide accumulation unchanged Hoffman degradation 130% decrease Tailordose to residual neuromuscularblockade
1-1), calculated as the difference between plasma sodium and chloride + bicarbonate, is increased as sulphate and phosphate are retained. Acidosis is renowned for potentiating muscle relaxants with a quaternary ammonium group ('recurarisation'). There now seems little reason to use a relaxant other than atracurium. 7
Drugs in renal failure The influence of renal disease on pharmacokinetics and pharmacodynamics has been extensively investigated. The subject is reviewed in detail elsewhere. 8'9 The most important problems in anaesthesia for patients with ESRF relate to increased elimination half life (Table 2) and the effects of drugs on the cardiovascular system. Suxamethonium
plasia and autonomous production Parathyroidectomy is often required.
of
PTH.
Potassium
Potassium is normally filtered at the glomerulus and almost completely reabsorbed at the proximal tubule and loop of Henle. As GFR declines, potassium balance is maintained by increasing secretion in the distal tubule and decreasing reabsorption. Faecal loss of potassium increases up to four fold. Acidosis causes a shift of potassium from the intracellular to extracellular space. In ESRF plasma potassium levels are elevated and there is inability to cope with the normal dietary load of potassium. Care must be taken to ensure that potassium containing intravenous fluids (e.g. Hartmann's solution) are only given if the potassium is known to be abnormally low. Abnormal plasma potassium concentrations are well known to promote cardiac dysrhythmias and should be corrected before surgery. The electrocardiographic changes of hyperkalaemia (high peaked T waves, decreased R wave amplitude, wide QRS complex, low amplitude P wave and ultimately 'sine wave' ECG) are well known. Hyperkalaemia is treated with intravenous calcium gluconate 10% 5-10ml, sodium bicarbonate 50mmol, 50% glucose 100ml with 20-25 units actrapid insulin or calcium resonium 30g orally (or 30-60g rectally) depending on the plasma potassium and ECG changes. Acid-base balance
With declining GFR there is inability to excrete non-volatile 'fixed' acid metabolites. The metabolic acidosis is compensated for by hyperventilation with a fall in PaCO2, bicarbonate, buffering by alkaline bone salts with increased urinary calcium to buffer hydrogen ions and increasing production of ammonia in the kidney. The anion gap (normal 10-16 mmol
Suxamethonium causes a rise in plasma potassium of about 0.5 mmol 1-1 in patients with and without ESRF.m It should be used only when plasma potassium is low-normal. The reduction in plasma cholinesterase activity which occurs in ESRF is not associated with a clinically significant prolongation of action of suxamethonium.
Type of surgery Patients with ESRF may present for surgery unrelated to the renal disease, but frequently need vascular and peritoneal dialysis access procedures, nephrectomy, parathyroidectomy, revascularisation operations, limb amputation and eye surgery. Table 3 summarises some of the problems with these operations. Anaesthesia for renal transplantation is considered in more detail elsewhere. 9'14
Pre-operative assessment Cardiovascular and respiratory systems 11
A history of new or excessive dyspnoea, orthopnoea, syncope and angina should be sought. A full examination of the cardiovascular system should be made. It is important to detect aortic stenosis and other valvular lesions and make some assessment of their haemodynamic significance. Carotid bruits merit Doppler ultrasound assessment before anaesthesia. Antihypertensive medication should be reviewed and continued through the peri-operative period. A recent ECG and chest X-ray should be inspected to evaluate ventricular hypertrophy and exclude incipient pulmonary oedema. Left ventricular ejection fraction is an independent predictor of the outcome of patients with cardiac disease and can be determined with echocardiography, lz
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CURRENT ANAESTHESIA AND CRITICAL CARE
The site of arterio-venous fistulas should be noted. Arterio-venous fistulas can cause a factitious unilateral elevation of the jugular venous pulse. Assessment of the respiratory system is well described in standard anaesthetic texts. Renal failure per se does not cause specific problems with the respiratory system. Fluid and electrolyte status Patients should be asked how much urine they normally pass and the dose of diuretic required to stimulate this. Fluid balance is considerably easier to manage if over generous intraoperative fluid administration can be corrected with a diuretic. The patients 'target' and/or 'dry' weights should be noted and compared with the actual preoperative weight. This gives the best indication of fluid balance. Patients are often dialysed before surgery and relative dehydration can lead to marked falls in blood pressure at induction of anaesthesia. Rehydration and fluid loading at renal transplantation is best monitored with a central venous pressure (CVP) line. Plasma potassium concentration should have been measured
Table 3 - - C o m m o n operations in patients with end stage renal failure (ESRF)
Operation Vascular access - arterio-venous fistula - arterio-venous Impra graft Peritoneal dialysis - catheter insertion
- catheter removal Nephrectomy - polycystic kidney
- transplanted kidney
Parathyroidectomy
Vascular surgery - limb revascularisation
- operations on aorta Limb amputation
Eye surgery - cataract extraction - vitrectomy
Problems Fistula patency - keep warm and well hydrated Graft patency. A n a s t o m o s i s leak - watch for subcutaneous h a e m a t o m a Mini-laparotomy but often brief operation; m a y proceed to resection of omentum
Large abdominal mass: Respiratory impairment. Vascular pedicle difficult to reach; risk of h a e m o r r h a g e from renal vessels Fibrosis around graft: risk of h a e m o r r h a g e with mobilisation Potential for air embolism. Obstruction of endotracheal tube. ? Oximeter dysfunction with methylene blue. May need sternotomy. Liable to fractures High incidence of ischaemic heart disease. Epidural improves graft patency but not with impaired coagulation Renal blood supply threatened Patients often diabetic. High incidence of ischaemic heart disease High risk eye in diabetics
within the 48h prior to surgery and abnormalities corrected. Premedication Most patients with ESRF are well acclimatised to the hospital environment. Specific concerns about anaesthesia and surgery are best allayed by reassurance and discussion with the anaesthetist or surgeon. Sedative drugs often prolong recovery after relatively short operations such as insertion of a peritoneal dialysis catheter and should be prescribed sparingly. Opiate analgesics can be given intravenously during surgery and anticholinergics are rarely required.
Conduct of anaesthesia Vascular access Venous cannulation should be in the dorsum of the dominant hand, unless this arm has a fistula, so that veins in the non-dominant arm and forearm are preserved for fistula formation. Similarly, arterial cannulation should be avoided unless absolutely essential. Long term central venous dialysis lines should not be used during anaesthesia to reduce the risk of them becoming infected. Arterio-venous fistulas should be protected from mechanical trauma and kept warm, by wrapping lightly in gamgee or cotton wool, to encourage flow and discourage thrombosis. Monitoring Non-invasive blood pressure, ECG, peripheral oxygen saturation, airway pressure (ventilator disconnect), inspired oxygen and expired carbon dioxide should be monitored from induction of anaesthesia. 13 Blood pressure and saturation monitoring should be continued in the recovery room until the patient is fully awake and haemodynamically stable. CVP and pulmonary capillary wedge pressure should be monitored when clinically indicated by the pre-operative assessment of the cardiovascular system. Adequate hydration at the time of release of vascular clamps during renal transplantation has been shown to correlate with improved graft survival and we now monitor CVP routinely. Induction of anaesthesia Patients with ESRF have a reduced rate of gastric emptying. Those with a clear history of gastro-oesophageal reflux should have a rapid sequence induction with suxamethonium, having established a low normal plasma potassium before surgery. All patients should be given a histamine H2 receptor antagonist on the night before and morning of surgery. Some anaesthetists advocate supplementing this with
ANAESTHESIA FOR PATIENTS WITH IMPAIRED RENAL FUNCTION
sodium citrate 30ml 0.3 molar by mouth in the anaesthetic room and adopting a modified rapid sequence induction, giving a non-depolarising relaxant before the induction agent. Continuous intravenous access must be guaranteed if this is to be done as there is a risk of paralysing the patient before sleep is induced. The relative disadvantages of suxamethonium are discussed above. Pre-oxygenation of all patients with ESRF seems sensible. The cardiovascular effects of the commonly used induction agents are well known and cautious administration of any is compatible with safe anaesthesia. Topical lignocaine to the tongue, pharynx and larynx before intubation reduces the hypertensive response to laryngoscopy.
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Post operative fluid replacement is best based on previous hours output (urine plus drainage) plus 0.5ml kg -1 h -1 for insensible loss.
Postoperative management An inspired FiO2 of 0.4 or more should be maintained for at least 24h after surgery. It is traditional to avoid intramuscular injections because of the haemostatic defect but there is no objective evidence that this is a significant problem. Intravenous analgesia should be titrated against effect and in many hospitals this will mean care on a high dependency or intensive care unit. Non-steroidal analgesics reduce renal function by altering renal prostaglandin synthesis and are contraindicated.
Maintenance of anaesthesia We advocate intubation and ventilation in all but the relatively fit, younger patient having a short operation (e.g. removal of a peritoneal dialysis catheter). In the presence of anaemia, IPPV with 50% inspired oxygen (FiO2) avoids hypoxia associated with hypoventilation during spontaneous ventilation of inhalation agents. Care must be taken to ensure adequate supplementation to avoid awareness but avoiding cardiovascular depression by interaction with antihypertensive drugs. Maintenance of normocapnia avoids the left shift of the oxyhaemoglobin dissociation curve associated with hyperventilation. Atracurium is the muscle relaxant of choice and should be reversed with an anticholinergic - anticolinesterase depending on the degre of residual paralysis. Regional anaesthetic techniques (spinal, epidural) offer many advantages but there is some concern about causing an epidural haematoma when coagulation is impaired. The risks and potential benefits must be considered for each patient.
Intravenous fluids Fluid deficits from pre-operative starvation and intraoperative losses should be replaced as in normal patients except that blood loss should be replaced by blood transfusion rather than large amounts of crystalloid, which tends to precipitate pulmonary oedema in the anuric patient. For renal transplantation a mixture of equal amounts of colloid and crystalloid should be given to raise the CVP to 7-10mm Hg at the time of graft revascularisation.
References 1. Erslev AJ. Erythropoietin. New Engl J Med 1991; 324: 133%1344 2. Macdougall IC, Hutton RD, Cavill I, Coles GA, Williams JD. Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm. Br Med J 1990; 300:655~59 3. George JN, Shanil SJ. The clinical importance of acquired abnormalities of platelet function. New Engl J Med 1991; 324:27-39 4. Forst DH, O'Rourke RA. Cardiovascular complications of chronic renal failure. In: Brenner BM, Stein JH, eds. Contemporary issues in nephrology Vol. 7: Chronic renal failure. New York: Churchill Livingstone, 1981; 84-115 5. O'Rourke RA, Brenner BM, Stein JH, eds. Contemporary issues in nephrology Vol. 13: The heart and renal disease. New York: Churchill Livingstone, 1984 6. Prys-Roberts C. Anaesthesia and hypertension. Br J Anaesth 1984; 56:711-724 7. Pollard BJ. Neuromuscular blocking drugs and renal failure. Br J Anaes 1992; 68:545-546 8. Muther RS, Bennett WM. Drug metabolism in renal failure. In: Brenner BM, Stein JH, eds. Contemporary issue in nephrology Vol. 7: Chronic renal failure. New York: Churchill Livingstone, 1981; 287-323 9. Sear JW, Holland DE. Anaesthesia for patients with renal dysfunction. In: Nimmo WS, Smith G, eds. Anaesthesia. Oxford: Blackwell Scientific, 1989; 912-932 10. Way WL, Miller RD, Hamilton WK, Layzer RB. Succinylcholine induced hyperkalemia in patients with renal failure? Anesthesiology 1972; 36:138-141 11. Masey SA, Burton GW. Anaesthesia for patients with cardiac disease: Preoperative management. Br J Hosp Med 1987; 37:386-396 12. Goldman L. Cardiac risk assessment in patients with arteriosclerotic vascular disease. In: Kaplan JA, ed. Vascular anesthesia. New York: Churchill Livingstone, 1991; 1-20 13. Ballard P. Anaesthesia for patients with cardiac disease: Intraoperative management. Br J Hosp Med 1987; 37: 398410. 14. Cottam S, Eason J. Anaesthesia for renal transplantation. In: Kaufman L, ed. Anaesthesia review 8. Edinburgh: Churchill Livingstone, 1992; 15%178
D. E. Holland and S. Old
End stage renal failure (ESRF), defined as a creatinine clearance < 10 ml min- 1(plasma creatinine >500 umol l-l), has an incidence of approximately 140/ million/year in the UK. About 60/million/year commence long term renal replacement therapy and with an annual mortality of 10% there are about 300/million patients with impaired renal function. In 1991, 1766 renal transplants were performed and 4000 await a suitable organ (UK Transplant Service, personal communication). Although most patients with ESRF will have elective surgery at their 'parent' renal unit hospital, many require emergency surgery in other hospitals. As minimal care dialysis facilities are disseminated away from large units, more patients with renal failure are likely to need surgery and anaesthesia in District General Hospitals. Isolated acute renal failure is uncommon and surgery in these patients can usually be deferred until they are stabilised on dialysis and they have the same problems as those with ESRF. The anaesthetic management of patients with acute renal failure associated with multiple organ failure, sepsis, trauma and surgery on the cardiovascular system is directed as much by the primary problem as the renal failure and this will not be addressed further. Safe anaesthesia for the patient with renal failure requires a knowledge of the etiology, pathophysiology, clinical manifestations and medical management of renal failure. Although the use of atracurium has revolutionised general anaesthesia in ESRF, a
working knowledge of the effects of renal failure on drug kinetics is essential.
Clinical pathophysiology Anaemia
Patients have a normochromic normocytic anaemia with a haemoglobin of 5-10g d1-1. The etiology of this is multifactorial. Uraemia depresses erythropoietin production and red cell release from the marrow, erythrocyte life span is reduced, aluminium toxicity decreases haemoglobin synthesis and there is repeated blood loss during haemodialysis when cells are also damaged in extracorporeal circuits. Untreated peptic ulcer disease leads to chronic blood and hence iron loss. Poor appetite and poor compliance with drug prescriptions often lead to reduced vitamin (B6, B12 and folate) and iron intake which exacerbates the problem. Hyperparathyroidism with marrow fibrosis will also impair erythrogenesis. Patients with polycystic renal disease tend to maintain a higher haemoglobin than those with other causes of ESRF and this is a powerful argument for resisting nephrectomy until the size of the kidney causes a significant space occupying problem or recurrent cyst infection occurs. Similarly, patients on continuous ambulatory peritoneal dialysis (CAPD) tend to maintain their haemoglobin better than those on haemodialysis (HD). Biosynthetic erythropoietin 1'2 now allows restoration of haemoglobin to normal levels but is expensive and not without adverse effects (hypertension, vascular thrombosis). It is generally reserved for those who
D. E. Holland, BMedSci, MB, MRCP, FRCAnaes, and S. Old, MA, MB, ChB, Department of Anaesthetics, Southmead Hospital, Westbury on Trym, Bristol BS10 5NB, UK Current Anaesthesia and Critical Care
© 1992LongmanGroupUK Ltd
(1992)3, 140-145 140
ANAESTHESIA FOR PATIENTS WITH IMPAIRED RENAL FUNCTION Table 1 - - Clinical features of chronic renal failure Cardiovascular
- hypertension - coronary artery disease - congestive cardiac failure pericarditis endocarditis - secondary valvular dysfunction - dyspnoea secondary to acidosis and anaemia infection - pulmonary fibrosis associated with other disease neutrophil sequestration with dialysis - normochromic normocytic anaemia increased bleeding time platelet dysfunction - myopathy - sensory neuropathy - occasional motor neuropathy - autonomic neuropathy - convulsions - anorexia - nausea and vomiting - delayed gastric emptying peptic ulceration - hyperkalaemia - hyperparathyroidism - glucose intolerance - hyperuricaemia altered lipid metabolism -
-
Respiratory
-
-
Haemopoietic
-
-
Nervous system
Gastrointestinal system
-
Metabolic
-
have symptoms, such as angina, associated with anaemia and interfering with activities of daily life or a haemoglobin < 8 g dl - t . The reduced oxygen transport effect of anaemia is c o m p e n s a t e d by an increase in cardiac output and increase in red cell 2,3-diphosphoglycerate which causes a right-ward shift of the oxyhaemoglobin dissociation curve. This favours oxygen unloading at the tissues. Whilst severe anaemia causes a reduction in the blood-gas partition coefficient for inhalation agents, with an increase in speed of onset and recovery, this is rarely a problem in clinical practice. The influence of blood transfusion on the i m m u n e system in E S R F continues to be a m o o t point. Although there is evidence that transfusion can induce immune tolerance it can also induce the formation of cytotoxic antibodies which m a k e kidney transplantation m o r e difficult. Our clinical practice is to transfuse pre-operatively only those with a haemoglobin less than 5g d1-1 or who have angina or dyspnoea which is known to improve with an increase in haemoglobin.
Bleeding diathesis The primary haemostatic defect in E S R F is thought to be an abnormality of platelet function. 3 Platelets show an increase in cytoplasmic free calcium and there are defects in the release and metabolism of arachidonic acid and exposure of fibrinogen receptors. Deficiencies in platelet aggregation are not correlated with the severity of renal failure but improve with dialysis. Bleeding time is prolonged but
141
transfusion or treatment with erythropoietin restore bleeding time towards normal. Although case reports of bleeding problems in E S R F abound, the true incidence is probably no greater than in patients without renal failure. Gastrointestinal h a e m o r r h a g e is c o m m o n but over 90% have a lesion detected at endoscopy. Excessive bleeding after haemodialysis should be treated with protamine according to laboratory studies of the coagulation cascade. Desamino-8-Darginine vasopressin (Desmopressin acetate, D D A V P ) 0.3mcg kg -1 has been used to reduce bleeding not associated with heparin.
Cardiovascular system Cardiovascular disease remains the leading cause of death in patients with E S R F and the second (to infection) most c o m m o n cause of death in those with a functioning transplant. 4 In patients of 2 5 - 4 5 years death from atherosclerosis is nearly four times greater than in the general population (47% versus 14%). Cardiovascular disease in E S R F is the product of hypertension, abnormal left ventricular function, pericardial disease and atherosclerotic coronary artery disease. 5 A b o u t 80% of patients will develop hypertension. This is related to an increase in systemic vascular resistance and salt and water loading. The effects of the associated left ventricular hypertrophy on myocardial oxygen supply and demand are well known (see ref. 5 pp 1-30). Although up to 65% of the hypertensive E S R F population have their blood pressure controlled by dialysis alone, many are taking antihypertensive drugs. First line treatment is often with calcium channel inhibitors or beta adrenoceptor blockers. These drugs tend to exacerbate the cardiovascular depression caused by the inhalational anaesthetic agents (additive effect) and spontanoeus ventilation techniques with inspired concentrations above 1 minimum alveolar concentration ( M A C ) should be avoided. Primary vasodilators (e.g. hydralazine, prazosin, minoxidil) are used less frequently now. The angiotensin converting enzyme inhibitors do not seem to cause significant problems with anaesthesia. All antihypertensives should normally be continued through the peri-operative period. 6 Hypertensive patients often show exaggerated changes in blood pressure and heart rate associated with induction of anaesthesia, laryngoscopy and intubation. M a r k e d increases and falls of blood pressure with tachy- or bradycardia can all lead to ST-T wave changes on the E C G normally associated with myocardial ischaemia. Whilst it seems prudent to try to adapt the anaesthetic technique to avoid these as much as possible (see below) there is no clear evidence that transient changes have a long term effect on postoperative morbidity or mortality.
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C U R R E N T A N A E S T H E S I A A N D CRITICAL C A R E
Overt pericardial disease is now uncommon with dialysis. Constrictive pericarditis with tamponade must be recognised and treated urgently. Tamponade is characterised by loss of the Y descent on the jugular venous pulse, which is elevated. There is pulsus paradoxus with loss of volume during inspiration. A pericardial effusion is usually seen on an echocardiogram. Tamponade is associated with severe restriction in cardiac output and great care is required at induction of anaesthesia for pericardectomy. There is a high incidence of abnormal lipoprotein metabolism in ESRF. Elevated cholesterol and decreased high density lipoprotein are associated with the development of coronary artery disease and peripheral vascular disease. Left sided, low output cardiac failure is present in 45% of patients and is predictive of an adverse effect on survival. In addition to ischaemic and hypertensive heart disease other mechanisms which may cause congestive failure are; intrinsic volume overload in aortic and mitral regurgitation, pressure overload in aortic stenosis; restricted diastolic function in mitral stenosis and pericardial disease with pulmonary venous hypertension and reduced cardiac output; extrinsic circulatory overload due to failure of sodium and water excretion. Further depression of cardiac output with anaesthetic drugs can induce a cycle of reduced blood pressure, impaired myocardial blood flow and diminishing cardiac output. Infective endocarditis occurs in 2.7% of patients on maintenance haemodialysis and in 9% of those who have an infection of a vascular access site. The mortality of endocarditis in this group is 45%. Antiseptic skin preparation before vascular access should be routine. Autonomic neuropathy is said to be common in ESRF. Impairment of sympathetic vasoconstriction and reflex increases in chronotropic and inotropic action on the heart can lead to marked falls in blood pressure in response to positive pressure ventilation (IPPV). The fall in blood pressure is exacerbated if patients are dehydrated, for example after dialysis.
Respiratory system Cardiovascular disease and the inability to excrete a fluid load make patients susceptible to pulmonary oedema. Dyspnoea is often exacerbated by acidosis and anaemia. Pulmonary lesions associated with the cause of the renal failure are not uncommon, for example pulmonary fibrosis associated with rheumatoid arthritis and amyloidosis. Modern 'biocompatible' (polysulfone, acetonitrile) dialysis membranes cause much less activation of inflammatory mediators than cuprophane membranes did. Complement activation with leucocyte sequestration in the lung occurs occasionally and can lead to low pressure pulmonary oedema (adult respiratory distress syndrome, ARDS).
The immunodepression of renal failure makes pulmonary infection common. The ideal of deferring surgery until the chest X-ray is clear and the patient well is not always a practical option.
Nervous system A peripheral, predominantly lower limb, sensory neuropathy is well recognised in ESRF and may progress to a motor neuropathy. Much of the weakness in uraemia is due to myopathy rather than neuropathy and these patients may show an exaggerated response to muscle relaxants. Twitches, cramps, 'restless' legs and pruritis are of uncertain etiology, cause much distress to the sufferer and may respond to quinine sulphate; they are of no consequence for the anaesthetist. The problems associated with autonomic neuropathy are mentioned above. Autonomic neuropathy is much commoner in diabetics. Grand mal fits and mental changes associated with the fluid and electrolyte shifts of over zealous haemodialysis should be a thing of the past. Occasionally cerebral oedema with impaired consciousness develops after regular dialysis is established: The anaesthetist may be asked to arrange ventilation to reduce arterial PaCO2; mannitol may be of some benefit. Ideally therapy should be directed by measurement of intracranial pressure.
Gastrointestinal system There is a high incidence of peptic ulcer disease in renal failure and many patients are already taking histamine H2 receptor antagonists. These should be continued through the peri-operative period as there is also delayed gastric emptying (and possibly increased gastric acid production) which predisposes to oesophageal reflux and aspiration.
Calcium and phosphate homoeostasis A fall in glomerular filtration rate (GFR) causes a rise in plasma phosphate with a fall in plasma calcium. Ionised calcium is preserved by the accompanying acidosis and tetany is rare. Defective hydroxylation of vitamin D in the diseased kidneys leads to defective mineralisation of bone and reduced absorption of calcium in the gut. Reduced plasma calcium stimulates production of parathyroid hormone (PTH) which raises calcium and lowers plasma phosphate. Hypocalcaemia combined with hypermagnesaemia (excessive consumption of antacids) potentiates nondepolarising muscle relaxants. Eventually the solubility product for calcium phosphate is exceeded and ectopic calcification occurs. In blood vessels this exacerbates the effects of atherosclerosis; calcification in the conducting system of the heart can lead to dysrhythmias and conduction abnormalities. Prolonged stimulation of the parathyroids leads to hyper-
ANAESTHESIA FOR PATIENTS WITH IMPAIRED RENAL FUNCTION 143
Table2 -- Influenceof renal failureon anaestheticdrugs Drug
Eliminationin ESRF
Thiopentone
? decreased
Ketamine Propofol Etomidate Fentanyl Alfentanil Phenoperidine Morphine Atracurium Neostigmine
Comments
Normal dose, slow administration ? Avoid: Hypertension 40% decrease Hypotensiona problem ? Decreased protein binding Little effecton CVS 25% decrease Cumulationonlya problem with high/ repeated doses 20% decrease Usefulto obtund response to intubation 50% decrease 50% unchangedin urine. Caution! ? unchanged Morphine-6-glucuronide accumulation unchanged Hoffman degradation 130% decrease Tailordose to residual neuromuscularblockade
1-1), calculated as the difference between plasma sodium and chloride + bicarbonate, is increased as sulphate and phosphate are retained. Acidosis is renowned for potentiating muscle relaxants with a quaternary ammonium group ('recurarisation'). There now seems little reason to use a relaxant other than atracurium. 7
Drugs in renal failure The influence of renal disease on pharmacokinetics and pharmacodynamics has been extensively investigated. The subject is reviewed in detail elsewhere. 8'9 The most important problems in anaesthesia for patients with ESRF relate to increased elimination half life (Table 2) and the effects of drugs on the cardiovascular system. Suxamethonium
plasia and autonomous production Parathyroidectomy is often required.
of
PTH.
Potassium
Potassium is normally filtered at the glomerulus and almost completely reabsorbed at the proximal tubule and loop of Henle. As GFR declines, potassium balance is maintained by increasing secretion in the distal tubule and decreasing reabsorption. Faecal loss of potassium increases up to four fold. Acidosis causes a shift of potassium from the intracellular to extracellular space. In ESRF plasma potassium levels are elevated and there is inability to cope with the normal dietary load of potassium. Care must be taken to ensure that potassium containing intravenous fluids (e.g. Hartmann's solution) are only given if the potassium is known to be abnormally low. Abnormal plasma potassium concentrations are well known to promote cardiac dysrhythmias and should be corrected before surgery. The electrocardiographic changes of hyperkalaemia (high peaked T waves, decreased R wave amplitude, wide QRS complex, low amplitude P wave and ultimately 'sine wave' ECG) are well known. Hyperkalaemia is treated with intravenous calcium gluconate 10% 5-10ml, sodium bicarbonate 50mmol, 50% glucose 100ml with 20-25 units actrapid insulin or calcium resonium 30g orally (or 30-60g rectally) depending on the plasma potassium and ECG changes. Acid-base balance
With declining GFR there is inability to excrete non-volatile 'fixed' acid metabolites. The metabolic acidosis is compensated for by hyperventilation with a fall in PaCO2, bicarbonate, buffering by alkaline bone salts with increased urinary calcium to buffer hydrogen ions and increasing production of ammonia in the kidney. The anion gap (normal 10-16 mmol
Suxamethonium causes a rise in plasma potassium of about 0.5 mmol 1-1 in patients with and without ESRF.m It should be used only when plasma potassium is low-normal. The reduction in plasma cholinesterase activity which occurs in ESRF is not associated with a clinically significant prolongation of action of suxamethonium.
Type of surgery Patients with ESRF may present for surgery unrelated to the renal disease, but frequently need vascular and peritoneal dialysis access procedures, nephrectomy, parathyroidectomy, revascularisation operations, limb amputation and eye surgery. Table 3 summarises some of the problems with these operations. Anaesthesia for renal transplantation is considered in more detail elsewhere. 9'14
Pre-operative assessment Cardiovascular and respiratory systems 11
A history of new or excessive dyspnoea, orthopnoea, syncope and angina should be sought. A full examination of the cardiovascular system should be made. It is important to detect aortic stenosis and other valvular lesions and make some assessment of their haemodynamic significance. Carotid bruits merit Doppler ultrasound assessment before anaesthesia. Antihypertensive medication should be reviewed and continued through the peri-operative period. A recent ECG and chest X-ray should be inspected to evaluate ventricular hypertrophy and exclude incipient pulmonary oedema. Left ventricular ejection fraction is an independent predictor of the outcome of patients with cardiac disease and can be determined with echocardiography, lz
144
CURRENT ANAESTHESIA AND CRITICAL CARE
The site of arterio-venous fistulas should be noted. Arterio-venous fistulas can cause a factitious unilateral elevation of the jugular venous pulse. Assessment of the respiratory system is well described in standard anaesthetic texts. Renal failure per se does not cause specific problems with the respiratory system. Fluid and electrolyte status Patients should be asked how much urine they normally pass and the dose of diuretic required to stimulate this. Fluid balance is considerably easier to manage if over generous intraoperative fluid administration can be corrected with a diuretic. The patients 'target' and/or 'dry' weights should be noted and compared with the actual preoperative weight. This gives the best indication of fluid balance. Patients are often dialysed before surgery and relative dehydration can lead to marked falls in blood pressure at induction of anaesthesia. Rehydration and fluid loading at renal transplantation is best monitored with a central venous pressure (CVP) line. Plasma potassium concentration should have been measured
Table 3 - - C o m m o n operations in patients with end stage renal failure (ESRF)
Operation Vascular access - arterio-venous fistula - arterio-venous Impra graft Peritoneal dialysis - catheter insertion
- catheter removal Nephrectomy - polycystic kidney
- transplanted kidney
Parathyroidectomy
Vascular surgery - limb revascularisation
- operations on aorta Limb amputation
Eye surgery - cataract extraction - vitrectomy
Problems Fistula patency - keep warm and well hydrated Graft patency. A n a s t o m o s i s leak - watch for subcutaneous h a e m a t o m a Mini-laparotomy but often brief operation; m a y proceed to resection of omentum
Large abdominal mass: Respiratory impairment. Vascular pedicle difficult to reach; risk of h a e m o r r h a g e from renal vessels Fibrosis around graft: risk of h a e m o r r h a g e with mobilisation Potential for air embolism. Obstruction of endotracheal tube. ? Oximeter dysfunction with methylene blue. May need sternotomy. Liable to fractures High incidence of ischaemic heart disease. Epidural improves graft patency but not with impaired coagulation Renal blood supply threatened Patients often diabetic. High incidence of ischaemic heart disease High risk eye in diabetics
within the 48h prior to surgery and abnormalities corrected. Premedication Most patients with ESRF are well acclimatised to the hospital environment. Specific concerns about anaesthesia and surgery are best allayed by reassurance and discussion with the anaesthetist or surgeon. Sedative drugs often prolong recovery after relatively short operations such as insertion of a peritoneal dialysis catheter and should be prescribed sparingly. Opiate analgesics can be given intravenously during surgery and anticholinergics are rarely required.
Conduct of anaesthesia Vascular access Venous cannulation should be in the dorsum of the dominant hand, unless this arm has a fistula, so that veins in the non-dominant arm and forearm are preserved for fistula formation. Similarly, arterial cannulation should be avoided unless absolutely essential. Long term central venous dialysis lines should not be used during anaesthesia to reduce the risk of them becoming infected. Arterio-venous fistulas should be protected from mechanical trauma and kept warm, by wrapping lightly in gamgee or cotton wool, to encourage flow and discourage thrombosis. Monitoring Non-invasive blood pressure, ECG, peripheral oxygen saturation, airway pressure (ventilator disconnect), inspired oxygen and expired carbon dioxide should be monitored from induction of anaesthesia. 13 Blood pressure and saturation monitoring should be continued in the recovery room until the patient is fully awake and haemodynamically stable. CVP and pulmonary capillary wedge pressure should be monitored when clinically indicated by the pre-operative assessment of the cardiovascular system. Adequate hydration at the time of release of vascular clamps during renal transplantation has been shown to correlate with improved graft survival and we now monitor CVP routinely. Induction of anaesthesia Patients with ESRF have a reduced rate of gastric emptying. Those with a clear history of gastro-oesophageal reflux should have a rapid sequence induction with suxamethonium, having established a low normal plasma potassium before surgery. All patients should be given a histamine H2 receptor antagonist on the night before and morning of surgery. Some anaesthetists advocate supplementing this with
ANAESTHESIA FOR PATIENTS WITH IMPAIRED RENAL FUNCTION
sodium citrate 30ml 0.3 molar by mouth in the anaesthetic room and adopting a modified rapid sequence induction, giving a non-depolarising relaxant before the induction agent. Continuous intravenous access must be guaranteed if this is to be done as there is a risk of paralysing the patient before sleep is induced. The relative disadvantages of suxamethonium are discussed above. Pre-oxygenation of all patients with ESRF seems sensible. The cardiovascular effects of the commonly used induction agents are well known and cautious administration of any is compatible with safe anaesthesia. Topical lignocaine to the tongue, pharynx and larynx before intubation reduces the hypertensive response to laryngoscopy.
145
Post operative fluid replacement is best based on previous hours output (urine plus drainage) plus 0.5ml kg -1 h -1 for insensible loss.
Postoperative management An inspired FiO2 of 0.4 or more should be maintained for at least 24h after surgery. It is traditional to avoid intramuscular injections because of the haemostatic defect but there is no objective evidence that this is a significant problem. Intravenous analgesia should be titrated against effect and in many hospitals this will mean care on a high dependency or intensive care unit. Non-steroidal analgesics reduce renal function by altering renal prostaglandin synthesis and are contraindicated.
Maintenance of anaesthesia We advocate intubation and ventilation in all but the relatively fit, younger patient having a short operation (e.g. removal of a peritoneal dialysis catheter). In the presence of anaemia, IPPV with 50% inspired oxygen (FiO2) avoids hypoxia associated with hypoventilation during spontaneous ventilation of inhalation agents. Care must be taken to ensure adequate supplementation to avoid awareness but avoiding cardiovascular depression by interaction with antihypertensive drugs. Maintenance of normocapnia avoids the left shift of the oxyhaemoglobin dissociation curve associated with hyperventilation. Atracurium is the muscle relaxant of choice and should be reversed with an anticholinergic - anticolinesterase depending on the degre of residual paralysis. Regional anaesthetic techniques (spinal, epidural) offer many advantages but there is some concern about causing an epidural haematoma when coagulation is impaired. The risks and potential benefits must be considered for each patient.
Intravenous fluids Fluid deficits from pre-operative starvation and intraoperative losses should be replaced as in normal patients except that blood loss should be replaced by blood transfusion rather than large amounts of crystalloid, which tends to precipitate pulmonary oedema in the anuric patient. For renal transplantation a mixture of equal amounts of colloid and crystalloid should be given to raise the CVP to 7-10mm Hg at the time of graft revascularisation.
References 1. Erslev AJ. Erythropoietin. New Engl J Med 1991; 324: 133%1344 2. Macdougall IC, Hutton RD, Cavill I, Coles GA, Williams JD. Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm. Br Med J 1990; 300:655~59 3. George JN, Shanil SJ. The clinical importance of acquired abnormalities of platelet function. New Engl J Med 1991; 324:27-39 4. Forst DH, O'Rourke RA. Cardiovascular complications of chronic renal failure. In: Brenner BM, Stein JH, eds. Contemporary issues in nephrology Vol. 7: Chronic renal failure. New York: Churchill Livingstone, 1981; 84-115 5. O'Rourke RA, Brenner BM, Stein JH, eds. Contemporary issues in nephrology Vol. 13: The heart and renal disease. New York: Churchill Livingstone, 1984 6. Prys-Roberts C. Anaesthesia and hypertension. Br J Anaesth 1984; 56:711-724 7. Pollard BJ. Neuromuscular blocking drugs and renal failure. Br J Anaes 1992; 68:545-546 8. Muther RS, Bennett WM. Drug metabolism in renal failure. In: Brenner BM, Stein JH, eds. Contemporary issue in nephrology Vol. 7: Chronic renal failure. New York: Churchill Livingstone, 1981; 287-323 9. Sear JW, Holland DE. Anaesthesia for patients with renal dysfunction. In: Nimmo WS, Smith G, eds. Anaesthesia. Oxford: Blackwell Scientific, 1989; 912-932 10. Way WL, Miller RD, Hamilton WK, Layzer RB. Succinylcholine induced hyperkalemia in patients with renal failure? Anesthesiology 1972; 36:138-141 11. Masey SA, Burton GW. Anaesthesia for patients with cardiac disease: Preoperative management. Br J Hosp Med 1987; 37:386-396 12. Goldman L. Cardiac risk assessment in patients with arteriosclerotic vascular disease. In: Kaplan JA, ed. Vascular anesthesia. New York: Churchill Livingstone, 1991; 1-20 13. Ballard P. Anaesthesia for patients with cardiac disease: Intraoperative management. Br J Hosp Med 1987; 37: 398410. 14. Cottam S, Eason J. Anaesthesia for renal transplantation. In: Kaufman L, ed. Anaesthesia review 8. Edinburgh: Churchill Livingstone, 1992; 15%178