Contemporary surgical practice has developed in parallel with advances in the preoperative assessment and perioperative management of patients with increasingly complex underlying medical problems. In this chapter, we will consider some of these medical problems as well as briefly discussing current anaesthetic practice and postoperative care. Footnote 0

The assessment of the patient with coexisting medical disease is covered in detail elsewhere.

Clinical history includes determination of the presence of angina (either on exercise or at rest) and whether the patient has suffered known myocardial infarction in the past. Evaluation of exercise tolerance may be important in a patient with angina who is undergoing major surgery and who may be subjected to stress factors such as large fluid shifts or aortic cross clamping. The resting ECG is often normal in patients with ischaemic heart disease, but may show evidence of previous infarction (presence of Q waves, T wave inversion, or persistent ST segment elevation suggesting a ventricular aneurysm). This is significant, as the myocardial tissue will often be contracting either hypo- or akinetically, and the poor contractility be further depressed by the effects of most volatile anaesthetic agents (see below). Further tests to evaluate left ventricular function include either multiple gated acquisition (MUGA) or thallium scanning, and the predictive value of these in the preoperative assessment of the patient undergoing major vascular surgery is discussed elsewhere (Chapter 5.2). 3

In patients with known clinical or ECG evidence of previous myocardial infarction, the risk of reinfarction is increased by the combined effects of anaesthesia and surgery in the early post-infarct period. However, the risk falls to that seen in comparable patients not undergoing surgery by 6 months, and hence, elective surgery should be postponed for this period of time.

Care should be taken to maintain optimum drug therapy in the patient with ischaemic heart disease, who may be receiving &bgr;-adrenoceptor blocking drugs, calcium channel blockers, nitrates, or diuretics. Since abrupt cessation of therapy may worsen pre-existing angina, all medication should be continued up to the time that preoperative drugs are given. Patients with angina at rest may require additional perioperative medication, including transdermal or intravenously administered nitrates.

Postoperatively, the effects of abdominal surgery may decrease the gastrointestinal absorption of orally administered drugs, and medication must be provided by other routes, such as intravenous infusions, sublinguinal or intranasal calcium channel antagonists, and sustained release preparations of nitrates and &bgr;-adrenoceptor antagonists.

Laboratory testing must include assessment of plasma electrolytes and haemoglobin, the electrocardiogram, and chest radiograph. Other tests may be indicated by the presence of coexisting or predisposing factors, such as diabetes mellitus or hypertension.

A similar strategy is useful in the assessment of patients with hypertension, in whom adequacy of medication and the presence or absence of the end-organ manifestations of hypertension (hypertensive heart disease with left ventricular hypertrophy and myocardial ischaemia, hypertensive nephropathy and retinopathy, cerebrovascular disease manifest as strokes or transient ischaemic episodes) should be evaluated. Current drugs used in the treatment of hypertension include &bgr;-adrenoceptor and calcium channel blockers, angiotensin converting enzyme inhibitors and other vasodilators. As in the patient with myocardial ischaemia, abrupt cessation of treatment may lead to rebound of symptoms and severe hypertensive episodes; this is especially important in hypertensive patients treated with the &agr;&sub2;- agonist, clonidine. Drug treatment may be withheld if the patient exhibits preoperative orthostatic hypotension, if there is inadequate time available for optimization of drug therapy or there is an urgent need for the surgery to proceed.

The surgeon (and anaesthetist) is often faced with an untreated hypertensive patient presenting for elective surgery, and it is therefore important to have a strategy in deciding whether surgery is cancelled or allowed to proceed. Based on the WHO definition of hypertension (systolic pressure above 160 mmHg or diastolic pressure above 95 mmHg), we can recognize four groups of patients: those with diastolic pressure less than 110 mmHg but more than 95 mmHg on at least three occasions following admission; those with diastolic pressure above 110 mmHg but less than 120 mmHg on at least three occasions following admission; those with diastolic pressure over 120 mmHg on at least three occasions following admission and those in whom diastolic pressures are normal, but systolic pressures are elevated (often 200–250 mmHg).

There is little evidence of increased cardiovascular risk associated with anaesthesia in the first group of patients, and the anaesthetist is safe to proceed in the absence of end-organ damage. Other recent approaches to the management of mild hypertension include the prescribing of a single dose of a &bgr;-adrenoceptor blocking drug as part of premedication, or the administration of preoperative clonidine.

In patients with a diastolic blood pressure of 110 to 120 mmHg, but no evidence of end-organ disease, there is a need to balance the urgency of the surgery against the potential risks associated with anaesthesia. These patients should be carefully monitored before, during and after surgery, and active management of blood pressure should be undertaken. If end-organ disease is present the operation should be cancelled, and appropriate treatment instituted.

Anaesthetists and physicians agree that individuals with a diastolic pressure of over 120 mmHg should have their elective surgery postponed, while appropriate measures are taken to control the blood pressure. Although patients with a systolic arterial pressure of above 160 mmHg are defined as hypertensive, they are usually suffering not from hypertension but from arteriosclerosis. Whether any reduction in the perfusion pressure may lead to organ underperfusion, with resulting ischaemia and dysfunction of the heart, kidneys or brain, is debated.

When treatment prior to surgery is thought to be appropriate, the operation should be postponed for 4 to 6 weeks to allow optimization of therapy and resetting of the autoregulatory mechanisms of the body. Uncontrolled hypertension and tachycardia in the postoperative period require active and aggressive treatment: both increased blood pressure and tachycardia may cause an imbalance of coronary supply and demand, with the development of myocardial ischaemia.

General and regional anaesthesia are both contraindicated in the presence of acute heart failure. The combination of congestive cardiac failure with general anaesthesia will result in cardiac muscle depression and pronounced hypokinesia; regional techniques such as extradural and intrathecal blocks may lead to decreased systemic vascular resistance, with significant decreases in blood pressure because of venous pooling. The reduction in systemic vascular resistance may also lead to an increased cardiac output.

Whatever anaesthetic approach is used, intraoperative inotropic support with drugs such as dopamine, dobutamine or dopexamine may be required. Any significant increase in systemic vascular resistance caused by these agents may, however, lead to further reductions in stroke volume.

Clinical and radiological evidence of left ventricular failure in patients with ischaemic heart disease is linked with a poor clinical prognosis. Patients with congestive cardiac failure should undergo plasma urea and electrolyte monitoring before surgery. Patients receiving cardiac glycosides, and presenting with arrhythmias may have digitalis toxicity: digitalis levels should be checked.

The anaesthetist may be asked to provide sedation or analgesia for patients with chronic congestive cardiac failure undergoing endoscopic procedures such as cystoscopy and colonoscopy. Unfortunately, these procedures are frequently performed in areas with poor lighting, with reduced assistance for the anaesthetist and little monitoring equipment. If these procedures cannot be undertaken under light sedation with supplemental oxygen therapy, a full relaxant general anaesthetic with rapid sequence induction will need to be performed. Patients undergoing gastroscopy for acute indications often have significant quantities of blood in their stomachs, and are at risk of aspiration. Optimal monitoring should be available for these highly unstable patients.

The natural history of mitral valve disease is one of progressive impairment of myocardial function over a long period of time. Important factors in preoperative assessment are a history of, or the presence of left ventricular failure and atrial fibrillation, which carries the risk of systemic embolism to the brain or legs. With time, changes occur in left atrial function leading to increases in pulmonary vascular pressures, with reduced pulmonary compliance and increased work of respiration.

Anaesthetists should be aware of the importance of avoiding bradycardia, which, in the presence of relatively fixed stroke volume, will decrease cardiac output, and increase tachycardia; hence, decrease will diastolic filling time and further increase left atrial pressure, and hypovolaemia.

The natural history of aortic valve disease is shorter, in terms of symptomatology, than that of mitral valve disease. There is progressive hypertrophy of the left ventricular muscle, leading to left ventricular failure. The main symptoms are angina, syncope (Stokes–Adams attacks), and dyspnoea of effort; as left ventricular failure develops, orthopnoea, paroxysmal nocturnal dyspnoea, and congestive cardiac failure become apparent.

Anaesthesia in these patients should therefore avoid reductions in systemic vascular resistance. In aortic stenosis, this decreases coronary perfusion and may lead to falls in cardiac output. Conversely, any increase in systemic vascular resistance in patients with aortic regurgitation will further reduce forward blood flow. Bradycardia which, again, will lead to decreased cardiac output because of the relatively fixed stroke volume, should also be avoided, as should tachycardias, arrhythmias, and myocardial depression, which may occur with the use of volatile anaesthetic agents.

Patients with valvular heart disease present several important problems to the surgeon and the anaesthetist. Appropriate antibiotic prophylaxis against bacterial endocarditis should be provided. Drugs of choice include ampicillin or amoxycillin (or erythromycin in the penicillin-sensitive patient). These should be given prior to induction of anaesthesia, laryngoscopy and intubation to ensure peak drug concentrations at the time of any instrumentation of the oral cavity. Gentamicin should be added in patients scheduled for gastrointestinal or genitourinary surgery and instrumentation. The use of anticoagulants needs to be controlled in patients with prosthetic valves, and in those with atrial fibrillation and a history of systemic emboli (see later). The relatively fixed cardiac output means that techniques and procedures involving significant fluid shifts are especially hazardous.

A number of arrhythmias may be detected on ECG monitoring undertaken as part of the preoperative assessment of the elective general surgical patient.

If atrial fibrillation is present the ventricular rate should be controlled to about 100 beats/min or less, and there should be a ventriculo-radial deficit of less than 20 beats. Atrial flutter should be treated prior to surgery, with digoxin or amiodarone, or by cardioversion. Ventricular tachycardias and ventricular ectopics which are either multifocal or are occurring more frequently than 1 in 5 beats should be treated preoperatively. The anaesthetist and surgeon must consider the need for preoperative insertion of a temporary (or permanent) pacing wire in patients with any type of heart block. A permanent artificial cardiac pacemaker should be inserted when the patient has complete (third degree) heart block, the sick sinus syndrome or symptomatic bradycardia (rate less than 35 beats/min). Temporary pacing should be instituted for patients with any symptomatic heart block, Mobitz type II block, or right bundle branch block and left axis deviation on the ECG, indicative of bifascicular block involving the left anterior fascicle of the left bundle, and sick sinus syndrome.

All general anaesthetic agents are respiratory depressants, both in terms of the responses to hypoxia and to hypercapnia. In addition, anaesthetized patients who are breathing spontaneously show loss of the intercostal component of ventilation. During anaesthesia, both spontaneous ventilation and intermittent positive pressure ventilation result in a reduction in functional residual capacity of approximately 400 ml. This may be compounded by a similar reduction occurring on adopting the supine posture, as well as by the effects of obesity, upper abdominal surgery and crystalloid infusion. Thus, the functional residual capacity decreases towards the closing volume (that volume at which there is significant basal airway closure). The closing volume also increases markedly with age, obesity, smoking, and crystalloid infusion, with the result that airway closure occurs during anaesthesia and surgery, increasing the alveolar–arterial Po&sub2; difference.

Anaesthesia is also associated with a redistribution of ventilation away from dependent lung areas, while there is little change in perfusion. This mismatching of ventilation and perfusion results in a ‘true shunt’ developing. Matching of perfusion to ventilation requires an intact pulmonary vascular response to hypercarbia, acidosis and hypoxia (hypoxic pulmonary vasoconstriction). Most volatile anaesthetic agents inhibit the hypoxic pulmonary vasoconstriction reflex, while it is preserved with the intravenous agents. During general anaesthesia there is, therefore, a need to increase the inspired oxygen concentration to maintain a normal arterial Pao&sub2;.

Physiological dead space is also increased (by up to 50 per cent) during intermittent positive pressure ventilation as a result of ventilation of underperfused or non-perfused alveoli. Thus, this will increase the Paco&sub2; and so compound the effect of general anaesthetics as respiratory depressants.

These physiological changes which occur during anaesthesia and surgery also allow several groups of patients who are at risk of developing postoperative pulmonary complications to be identified. In cigarette smokers, hypersecretion of mucus and an increased closing volume will predispose to basal air trapping, leading to possible atelectasis and pneumonia. Obesity is associated with a decreased total pulmonary compliance, with an increased work of breathing, leading to early postoperative respiratory fatigue, in addition to changes in lung volume. This is particularly important in patients undergoing upper abdominal or thoracic surgery. Malnourished patients have a poor energy reserve, again predisposing to respiratory fatigue, while in the elderly lung volumes and altered sensitivity to anaesthetic agents and to opioids is increased. Patients with pre-existing lung disease are an obvious high-risk group. All of the above risk factors are further complicated by surgical problems which may influence postoperative lung function. These include surgery lasting more than 4 h; type of surgical incision; transverse incisions are associated with less disturbance of pulmonary function than midline incisions; and bowel distension, which decreases pulmonary function, particularly if an upper abdominal incision is used.

Symptoms which must be assessed include dyspnoea, cough, sputum production, haemoptysis, chest pain, and wheeze. Factors contributing to these symptoms include a history of smoking or occupational exposure to dust, and associated cardiovascular pathology (ischaemic heart disease, cardiac failure, hypertension, cor pulmonale).

Examination should concentrate on evidence of obstructive airway disease, evidence of poor respiratory expansion, including kyphoscoliosis and neuromuscular weakness due to myasthenia gravis or a myopathy, evidence of increased work of breathing manifested by increased respiratory and heart rates, tracheal tug, use of accessory muscles and intercostal indrawing, nature and quantity of sputum, evidence of an active chest infection, and evidence of respiratory failure or right heart failure with cor pulmonale, both of which are poor prognostic indicators in patients requiring elective general surgery.

Excessive mucus secretion is coupled with a variable degree of airway obstruction due to both bronchial oedema and retained secretions. In some patients, the disease progresses to hypoxia, hypercapnia and right ventricular failure. These patients show a loss of ventilatory sensitivity to CO&sub2;, and depend on their hypoxic ventilatory drive. Other patients develop emphysema associated with lung overdistension, alveolar parenchymal destruction, loss of elastic pulmonary compliance, and airway obstruction. These patients have an increased physiological dead space, and hyperventilate to maintain normocapnia.

For both groups, assessment should address normal exercise tolerance, previous response to surgery and response to bronchodilator therapy. Excessive sputum should be removed by physiotherapy and postural drainage, and infection should be treated with antibiotics.

The presence of a reversible element to the obstructive airways disease, which may be sensitive to bronchodilator drugs, should be assessed, and preoperative blood gases analysed in those patients who may require ventilatory support in the immediate postoperative period.

Preoperative investigations include spirometry and measurement of arterial blood gases (see Section 3.4). The ratio between the forced expiratory volume in 1 second (FEV&sub1;) and forced vital capacity (FVC) should be above 0.7; and the FEV&sub1; should be more than 1 litre. Patients with an FEV&sub1;/FVC of less than 0.5; and an FEV&sub1; less than 1 litre have an increased risk of postoperative morbidity. However, recent studies have shown that patients with FEV&sub1; values between 0.3 and 1 litre need have little extra morbidity. The best preoperative predictors of the need for postoperative ventilation are preoperative Pao&sub2; and presence of dyspnoea at rest.

Preoperative assessment should elicit the frequency and severity of asthma attacks, factors provoking attacks, drug history, and whether the patient has ever required ventilatory support. Elective surgery should not be undertaken unless the asthma is well controlled, with peak flow values above 250 to 300 1/min, and minimal or no diurnal ‘dips’ in peak flow. In patients with a marked seasonal fluctuation in symptoms, it is better not to undertake elective surgery during the poor season. For the severe asthmatic with intractable airway obstruction, especially those already on inhaled steroid therapy, a short course of systemic steroids (prednisolone 40–80 mg/day, reducing) may be useful. Where feasible, regional anaesthetic techniques should be employed. Where this is not possible general anaesthesia may be undertaken using a minimal intervention regimen or ‘balanced anaesthesia’. In the first approach spontaneous ventilation is supplemented, where appropriate, by regional anaesthetic techniques. Opioid analgesia and sedation are kept to a minimum. The aims are to avoid stimulating an irritable tracheobronchial tree and to minimize respiratory depression. Alternatively, asthmatics are managed using standard ‘balanced anaesthesia’ with a few modifications. The patient receives preoperative physiotherapy and inhaled salbutamol prior to going to theatre. The induction dose is higher than usual to avoid irritation of the trachea during intubation. Histamine releasing drugs such as d-tubocurarine, atracurium, and morphine are avoided.

Bronchiectasis is characterized by the overproduction of purulent sputum from disorganized and dilated bronchi. Causes in the older adult population include whooping cough, measles or tuberculosis. There may be some degree of airway obstruction, often poorly responsive to bronchodilator therapy. Patients should be admitted at least 3 days prior to surgery for postural drainage, physiotherapy, and treatment with antibiotics. Where appropriate regional anaesthesia is safest; if it is not possible patients should be intubated to allow for controlled ventilation and clearance of secretions. Endobronchial anaesthesia may prevent soiling of non-infected lung by the infected side. Postoperative care is important, and the recent introduction of the mini-tracheostomy tube has assisted the clearance of secretions in these patients where effective coughing is limited by pain from the operative site.

General anaesthesia is not contraindicated in younger children with cystic fibrosis, but care should be given to timing, such that surgery is undertaken at the optimum time of the child's well being. Early discharge prevents or reduces the risk of pulmonary colonization by hospital-acquired organisms.

The normal response of the adrenal cortex to stress and trauma (including surgery and anaesthesia) is described elsewhere. In the patient receiving either steroid or adrenocorticotrophin therapy for the treatment of systemic diseases, failure to supplement the normal daily dose of enteral steroids may result in acute adrenocortical insufficiency. Preoperative stimulation tests will identify those patients unable to mount a response due to exogenous steroid suppression of native adrenocortical synthesis. In these individuals, maintenance therapy must be supplemented with additional doses of hydrocortisone. Regimens which have been advocated include 100 mg IV at induction of anaesthesia, followed by 100 mg every 6 hours for 3 days, and 25 mg IV hydrocortisone at induction, followed by 100 mg every 24 h. Alternatively, the normal daily steroid dose of all patients can be supplemented with hydrocortisone, the dose depending on the nature of the surgery. For minor procedures, a single dose of 100 mg IV hydrocortisone at induction is the sole supplement: an additional 100 mg 12 h later is advisable in those undergoing major surgery.

Serum urea and electrolytes levels and blood glucose should be monitored before surgery, and fluid balance should be carefully checked. Adrenal insufficiency in the postsurgical patient may be manifest as true collapse, or as malaise, lethargy, muscle weakness, and postural hypotension. Treatment should be by fluid infusion of colloid and crystalloid. These patients are often resistant to inotropes and large doses of steroids may be necessary.

Between 2 and 2.5 per cent of the population are known to be diabetic and there may be an equal number of undiagnosed diabetic patients. Diabetics affects about one in six patients over the age of 65 years, and one in four over the age of 85 years.

The perioperative mortality of diabetic patients varies between 4 and 13 per cent; most deaths result from the diseases associated with diabetes, including atherosclerosis, nephropathy, hypertension and ischaemic heart disease, and infection. In addition, a high proportion of patients suffer from autonomic and peripheral neuropathies, which may lead to postural hypotension or sudden cardiac arrest. Myopathy with muscle weakness may result in excessive increases in the plasma potassium concentration following the administration of suxamethonium. It has been estimated that 63 per cent of diabetic patients have symptoms or signs of cardiovascular disease, 44 per cent have peripheral vascular disease, and 24 per cent suffer from cerebrovascular disease.

Hyperglycaemia may result from a deficiency of insulin, insulin resistance and accelerated hepatic glucose production due to increased glucagon (non-insulin-dependent diabetes mellitus , type II), or from a lack of insulin (insulin-dependent diabetes mellitus,—type I). Ninety per cent of diabetic patients have type I disease: they are often obese and have normal or elevated plasma insulin levels. These patients are not prone to ketosis, but they may develop non-ketotic hyperosmolar coma. The insulin-dependent patient often has an abrupt onset of polyuria, polydipsia, weight loss, and fatigue.

The diagnosis of diabetes is made on the basis of a fasting venous blood glucose level above 140 mg/dl (7.8 mmol/1), and an abnormal glucose tolerance test: blood glucose concentration in excess of 200 mg/dl (11.0 mmol/1) 2 h after ingestion of 75 g of glucose.

Patients maintained by dietary treatment alone require no special medication before surgery, although some patients may need insulin therapy at least transiently during the postoperative period.

The oral hypoglycaemic agents in common usage are the sulphonylureas and biguanides. The former group (tolbutamide, chlorpropamide, glibenclamide, and glipizide) enhance insulin secretion by the pancreas, probably by increasing cyclic AMP levels in the &bgr;-cells. The pharmacological characteristics of these drugs are shown in Table 1 17. Because of the longer duration of action of chlorpropamide, the drug should ideally be stopped 24 to 36 h before surgery. The side effects of sulphonylurea therapy include hypoglycaemia, cholestatic jaundice, rashes, agranulocytosis, goitre, and inappropriate ADH secretion.

The mechanism of action of the biguanides, such as phenformin and metformin, is ill defined, but they appear to increase peripheral extrasplanchnic glucose utilization by a shift from oxidative to anaerobic metabolism. As such, they have been associated with the development of lactic acidosis.

Insulin has a number of different physiological effects. As well as its major effect of increasing peripheral uptake and utilization of glucose, and reducing glycogenolysis, it also decreases gluconeogenesis, increases formation of protein from amino acids, and increases synthesis of glycogen. Present day insulin preparations may be derived from bovine or porcine, or human sources; the former may be allergenic, leading to the development of tolerance. Insulin preparations vary in their times to onset, peak and duration of action; as well as in their origin. Short-acting preparations are soluble, while the longer acting insulins are formulated either as a zinc suspension, or as a suspension with protamine sulphate (isophanes) (Table 2) 18.

The signs and symptoms of diabetes should be assessed as should any associated pathology which may be present. Laboratory tests should include a full electrolyte, urea, and creatinine screen, blood count with white cell differential, chest radiograph, and ECG (Table 3) 19. Many patients will be receiving other coincidental therapy, which should be optimized before surgery (e.g. &bgr;-adrenoceptor blocking drugs, calcium channel inhibitors, angiotensin converting enzyme inhibitors, other antihypertensive agents, digitalis).

Plasma and whole body potassium levels may be decreased in patients with uncontrolled diabetes, and additional supplementation needs to be given before surgery. Diabetic autonomic neuropathy is manifest in its earliest stage as a lack of variation of the cardiac rate, with a tendency to higher than average resting heart rates. Other features include postural hypotension, and intraoperative episodes of bradycardia and hypotension occurring unexpectedly without apparent precipitating causes. A cardiac autonomic neuropathy is present in between 20 and 40 per cent of all diabetics and is associated with a poor prognosis.

Plasma glucose concentrations are generally unaffected by anaesthesia, but rise during surgery, the extent of the increase depending upon the applied surgical stimulus. Extradural anaesthesia reduces the glycaemic response. Ether is the only volatile anaesthetic agent which has a significant effect in increasing the plasma glucose concentration, although thiopentone may also have an effect on the plasma glucose concentration by action on hepatic phosphorylase. Hyperglycaemia is the result of a synergistic interaction between three hormones: adrenaline, glucagon, and insulin. Adrenaline increases plasma glucose concentration by inhibiting insulin secretion, stimulating hepatic glycogenolysis, and reducing tissue sensitivity to insulin. Glucagon acts primarily to increase glucose production, but also increases glucose utilization. Increased plasma cortisol enhances the duration of the additive effects of adrenaline and glucagon.

Although the major hazard in the diabetic patient is hypoglycaemia, it is now recognized that acute hyperglycaemia during surgery may result in altered host defence mechanisms, extracellular dehydration and electrolyte imbalance, intracellular dehydration, and impaired wound healing. The blood glucose level is best maintained in the range 4 to 8 mmol/1, with 6 mmol/1 being optimal. There is now much evidence linking chronic hyperglycaemia with the end-organ pathology responsible for the long-term complications of diabetes.

Most non-insulin-dependent diabetics secrete sufficient endogenous insulin to carry them through minor surgery (that not involving penetration of a body cavity or transection of a major limb bone) and do not need transient insulin therapy provided that glucose-containing solutions are withheld. When major surgery is undertaken exogenous insulin will usually be needed to prevent the development of ketosis. In all patients, oral hypoglycaemic agents should be discontinued before surgery and recommenced whenever possible the next day.

Various management regimens for the insulin-dependent patient have been suggested. These include a ‘laissez-faire’ minimal intervention approach, the ‘split-normal-dose’ regimen where the patient receives 25 to 50 per cent of the usual morning dose of insulin plus 5 per cent dextrose solution at a rate between 100 and 200 ml/h, regular administration of low-dose IV insulin or an infusion of insulin with the simultaneous infusion of 5 per cent dextrose (with adjustment of the rates of infusion of the insulin and/or glucose based on frequent blood glucose estimates), and an intensive glucose–insulin–potassium regimen. When monitoring these methods of diabetic control, blood glucose determinations are preferable to urine glucose analysis, since anaesthesia and surgery change the renal threshold to glucose excretion. An alternative approach is the administration of a long-acting insulin preparation the evening before surgery to achieve basal normoglycaemia, followed by IV insulin alone in doses (based on weight, height and blood glucose level) sufficient to maintain the peroperative plasma glucose level at between 4 and 8 mmol/1.

Fluid replacement should be given as normal saline solution (0.154M). Higher blood glucose levels (and therefore higher insulin requirements) are found in patients receiving either 5 per cent dextrose or Hartmann's solution (Ringer's lactate) the latter being an important gluconeogenic precursor, especially in starved or catabolic patients.

Various regimens of postoperative management have been described. Those based on sliding scales of urinary glucose level are no longer applicable because of the ready availability of blood glucose reflectance meters. Sliding scale doses of insulin given subcutaneously every 4 to 6 h based on plasma glucose concentrations, although preventing the extremes of hyper- and hypoglycaemia, often cause considerable fluctuations in diabetic control. Continuous infusion of insulin at a fixed rate (1–2 units/h) does not seem to improve glucose control over subcutaneous insulin administration, nor over the glucose—potassium—insulin regimen. A recently described bedside algorithm for postoperative diabetic care has been based on infusion of dextrose saline (100 ml/h) and potassium, and a separate infusion of insulin at a rate varying according to 2-hourly blood glucose estimations. This regimen aims to maintain the plasma glucose level between 6.7 and 10.0 mmol/1, with an insulin infusion rate varying between 0.5 and 5.0 U/h. There is, therefore, no standard procedure: each patient must be treated as an individual and the blood glucose titrated to the range 4.3 and 6.6 mmol/l during surgery and the postoperative period. There are few data to suggest that any of the above regimens for optimal intraoperative control is better than the others.

Renal function may be impaired as a result of parenchymous disease, or as a result of ageing. Patients with impaired renal function present a number of clinical problems of importance to the anaesthetist and surgeon.

Patients with chronic renal failure are unable to excrete acid metabolites. This results in metabolic acidosis, low plasma bicarbonate, hyponatraemia, hyperchloraemia, and hyperkalaemia. Hyperphosphataemia is associated with low serum calcium concentrations. Although the uraemic patient can tolerate mild to moderate degrees of hyperkalaemia, most authorities suggest that serum potassium levels of greater than 5.5 mmol/1 to 6.0 mmol/1 should be reduced prior to anaesthesia and surgery. This is of importance as a number of intraoperative factors may further increase the plasma potassium, including spontaneous ventilation, hypoventilation, repeated administration of suxamethonium, and the administration of stored blood. Methods of reducing high serum potassium concentrations include haemodialysis and haemofiltration, glucose–insulin therapy, administration of bicarbonate, hyperventilation, and calcium resonium enema (30–60 g).

Patients with chronic renal failure may present with a normochromic, normocytic anaemia of complex aetiology. Causes include decreased red cell production as a consequence of reduced erythropoietin synthesis and release, bone-marrow depression by uraemia, decreased red cell life-span, repeated blood losses during haemodialysis, and aluminium toxicity. Other factors include deficiency of iron, folate, and vitamins B&sub6; and B&sub1;&sub2;. These problems are now less prominent with the use of biosynthetic erythropoietin, which increases haemoglobin concentrations towards normal values.

These conditions affect 60 to 70 per cent of patients with chronic renal failure. Patients requiring treatment for hypertension (other than adequate haemodialysis) often show refractory hypertension, necessitating large doses of combination antihypertensive drugs (&bgr;-adrenoceptor blocking drugs, calcium channel antagonists, vasodilators, and angiotension converting enzyme inhibitors). Anaesthetic agents may interact with each of these, resulting in exaggerated hypotensive or bradycardic responses. In addition, these patients show exaggerated pressor responses to laryngoscopy and tracheal intubation, and to surgical stimulation. Medication must, therefore, be optimized before any elective surgery is undertaken. Patients with chronic renal failure (especially those on haemodialysis) are also liable to suffer from accelerated atherosclerosis, uraemic cardiomyopathy, and pericarditis.

Uraemic patients may present with bleeding problems, due to platelet dysfunction and thrombocytopenia, as well as decreased levels of platelet factor III which reduces platelet adhesiveness. Any preoperative abnormalities of coagulation (seen as a prolonged bleeding time, but unaltered prothrombin time or partial thromboplastin time) should be treated by platelet transfusion, cryoprecipitate or infusions of deamino- d-arginine vasopressin.

Uraemia initially manifests as malaise, fatigue, and reduced mental ability; patients may later progress to myoclonus and fitting, coma and death. Peripheral neuropathies are common in the lower limbs, and these may involve the autonomic nervous system, leading to postural hypotension.

Common gastrointestinal symptoms in patients with uraemia are anorexia, nausea and vomiting, gastrointestinal haemorrhage, diarrhoea, and hiccups. Chronic renal failure patients also show a delayed gastric emptying time, as well as increased volume and acidity of the gastric contents. Preoperative use of antacids and histamine H&sub2;-receptor antagonists is indicated.

All functioning shunts and fistulae must be protected during anaesthesia and surgery, with the sphygmomanometer cuff placed on the contralateral arm. Non-invasive blood pressure monitor cuffs must not be placed on the arm containing fistulae or shunts. The present generation of non-invasive blood pressure monitors has reduced the indications for intra-arterial blood pressure monitoring, but damage to future vascular access sites by arterial cannulation is unlikely with the new Teflon cannulae, especially for short-term intraoperative monitoring.

Venous access should be restricted (if at all possible) to distal sites on the dorsum of the hand, with preservation of all forearm and antecubital fossa veins. Central venous cannulation (useful as a guide to maintaining intraoperative normovolaemia) is best achieved via the subclavian or internal jugular routes.

Uraemic patients may show unusual drug responses due to intercurrent therapy, reduced plasma protein binding of intravenous drugs, and low plasma pseudocholinesterase activity. Electrolyte imbalance may affect the successful reversal of competitive neuromuscular blockade.

All intercurrent therapy should be continued up to the morning of surgery, and a history of peptic ulceration or discomfort, or symptoms of hiatus hernia or gastric reflux should be treated with antacids and/or H&sub2;-receptor antagonist drugs. Rapid sequence induction is more commonly used in patients with renal impairment because of the increased incidence of delayed gastric emptying shown by these patients. Care should be exercised with the use of central acting antiemetic drugs (phenothiazines, butyrophenones) as they can result in prolonged sedation and extrapyramidal side-effects in the patient with chronic renal failure. The introduction of routine preoperative haemofiltration or dialysis has improved greatly the medical status of surgical patients with chronic renal failure. Preoperative laboratory investigations should therefore include estimation of plasma electrolytes and creatinine, haemoglobin and haematocrit, platelets, and a clotting screen. In the diabetic patient with renal failure, preoperative monitoring of the blood glucose is imperative.

Premedication should be carefully chosen; the orally administered short-acting benzodiazepines (temazepam) offer suitable anxiolysis and mild sedation. Intramuscular opioid premedication is best avoided because of the propensity towards bleeding and the increased sensitivity of the uraemic patient to drugs of the morphine series.

Anaesthesia is best induced with either the combination hypnotic–opioid (using sleep doses of etomidate or thiopentone) or, in patients undergoing major abdominal or body-cavity surgery and in whom there is a history of recent myocardial infarction or poor left ventricular function, moderate to high doses of fentanyl or sufentanil followed by monitoring in the intensive care unit. Both regimens will attenuate the haemodynamic responses to induction, laryngoscopy and intubation, and surgical stress. Di-isopropylphenol (propofol) should be used with care in these patients because of the marked hypotension which can occur due to peripheral vasodilation.

Neuromuscular blockade is best achieved with incremental doses of agents which rely minimally on the kidney for their elimination (vecuronium, atracurium, or mivacurium), and with careful monitoring of the extent of neuromuscular blockade. Similarly, doses of analgesic drugs should be titrated against effect. Since active metabolites of pethidine and morphine accumulate in patients with chronic renal failure, the intraoperative use of drugs of the anilino-piperidine group (fentanyl, alfentanil, sufentanil) is preferred. Enflurane is generally avoided because of the tendency for fluoride ion to accumulate during longer cases, although the clinical significance of this is debated for routine surgery.

The four main functions of the liver are metabolism of glucose, amino acids, fatty acids, and cholesterol; production of bile, which is involved in absorption of drugs and fat from the intestines; detoxification of drugs and waste products; and synthesis of proteins (including albumin, clotting factors, and transport proteins). Each of these aspects may influence the safe conduct of anaesthesia.

The liver is the principal organ of drug metabolism, and changes in liver blood flow, hepatocellular function, and both the plasma protein concentration and the extent of drug binding will all affect drug pharmacokinetics. In addition, drugs administered during anaesthesia or in the perioperative period may affect hepatic function, either by alterating liver blood flow or through direct cellular effects. Halothane, for example, has been shown to exacerbate liver dysfunction, whereas isoflurane does not alter function in the cirrhotic liver. Patients with cirrhosis show a variable degree of alteration in drug metabolism; drugs undergoing phase 1 metabolism (oxidation, reduction, hydroxylation) have a greater impairment in clearance than drugs metabolized through conjugation reactions.

This should include evaluation of the patient's general condition, the presence of jaundice, the state of nutrition and hydration, the presence of encephalopathy, and evidence of clotting disorders. Liver disease may also affect cardiorespiratory and renal function. Grading of the severity of liver disease can help predict outcome.

Patients with cirrhosis may have reduced systemic vascular resistance, increased cardiac output, and both systemic and pulmonary shunting of blood. The last may result in hypoxia and may be associated with impaired hypoxic pulmonary vasoconstriction and hypoventilation. Analysis of arterial blood gases may show lowered tensions of O&sub2; and CO&sub2;. Hepatomegaly and ascites cause an increase in the pulmonary closing volume, leading to basal atelectasis. There may be associated pleural effusions.

There is a high incidence of postoperative renal failure in jaundiced patients undergoing abdominal surgery: one study reported an incidence of 17 per cent, with a mortality rate of 100 per cent. In addition, there is prognostic importance in the value of the preoperative creatinine; a value of 130 &mgr;mol/l is associated with a worse prognosis. Patients with cirrhosis are liable to develop the hepatorenal syndrome, the aetiology of which is complex. Measures to prevent its occurrence include maintenance of fluid and sodium balance, avoidance of nephrotoxins, and aggressive treatment of infection.

Decreased synthesis of clotting factors may lead to a haemorrhagic tendency during surgery and the postoperative period. Predisposing factors include a pre-existing coagulopathy, a dilutional coagulopathy due to rapid fluid replacement, an exaggerated fibrinolytic response, and the complicating metabolic problems of hypothermia, hypocalcaemia, and acidosis.

Patients with liver disease have reduced levels of clotting factors II VII, IX, and X, which may respond to the administration of vitamin K. Levels of factors V and XI are also often reduced, and this should be treated by the infusion of fresh frozen plasma. Similarly, platelet deficiency can be overcome by platelet infusions. Factor VIII levels often remain normal in severe liver disease, as it is synthesized by the reticuloendothelial system. A low level is usually indicative of disseminated intravascular coagulation.

Preoperative laboratory tests should include the thrombin time, activated partial thromboplastin time, prothrombin time, and platelet count. The history, clinical examination, and laboratory tests can together provide an indication of the degree of risk. Increased mortality is associated with serum albumin below 30g/l, presence of infection, white blood cell count above 10000/ml, treatment with more than two antibiotics, serum bilirubin above 50 &mgr;mol/l, presence of ascites, malnutrition, and the need for emergency surgery. The administration of preoperative oral bile salts has been shown to reduce the incidence of both endotoxaemia and postoperative renal impairment in patients with obstructive jaundice. Other protective measures include the intraoperative administration of mannitol and dopamine.

Intramuscular drugs should, in general, be avoided because of the pre-existing bleeding tendency, and even small doses of opiates may induce the development of acute liver failure. Hence most anaesthetists favour an oral short-acting benzodiazepine or no premedication. H&sub2;-receptor antagonists may be prescribed if there is a risk of gastric ulceration, as may vitamin K.

The anaesthetic sequence currently used by most units treating significant numbers of patients with liver disease is thiopentone, atracurium, and isoflurane for maintenance, with ventilation to normocapnia. Isoflurane maintains hepatic oxygen supply better than other agents, while atracurium depends on breakdown by Hoffman degradation rather than by hepatic metabolism. Occasional patients show resistance to atracurium due to increased binding by raised levels of globulin. Although plasma cholinesterase levels may be deficient in patients with liver failure, there is no contraindication to the administration of suxamethonium when clinically indicated; however the duration of its effect may be prolonged. Analgesia is usually provided by incremental doses of fentanyl or sufentanil. Many anaesthetists do not use nitrous oxide during prolonged surgery because of the development of bowel distension through diffusion of nitrous oxide into the gut. Intraoperative fluids (normal saline, blood, 5 per cent dextrose) should aim to maintain normovolaemia, a haemoglobin above 10 g/dl and normoglycaemia (4–7 mmol/l). Mannitol may be necessary to maintain a urinary output of about 1 ml/kg.

This may develop due to primary acute hepatocellular dysfunction or as a complication of cirrhosis, where it may be precipitated acutely by excessive alcohol ingestion. The encephalopathy may be due to decreased synthesis of essential cerebral metabolites (other than glucose) or to the accumulation of gut-derived substances affecting neurological function. The latter theory is favoured, with ammonia, mercaptans, fatty acids, and octopamine being implicated. The benzodiazepine antagonist, flumazenil, has recently been shown to improve encephalopathy clinically and electrophysiologically in about 80 per cent of subjects.

The normal range of haemoglobin concentration is 13.5 to 17.5 g/dl in men, and 11.5 to 15.5 g/dl in women. Anaemic patients may be asymptomatic, although lassitude and decreased exercise tolerance are common features. The patient may be pale. If anaemia is moderate or severe, physical examination may reveal cardiomegaly and functional heart murmurs. In the perioperative patient, tissue oxygenation is dependent upon arterial oxygen content, capillary blood flow, and the position of the oxyhaemoglobin dissociation curve.

This is determined from the partial pressure of oxygen and the percentage haemoglobin saturation according to the following equation: Equation 0

where Hb = haemoglobin content g/dl, Sao&sub2; = oxygen saturation, Pao&sub2; = partial pressure of oxygen, and 0.0225 = ml oxygen dissolved/100 ml blood/kPa oxygen tension.

In normal arterial blood, haemoglobin is almost fully saturated (96–98 per cent) in the patient breathing room air. In the patient with anaemia, the decreased oxygen content (due to the decreased amount of haemoglobin) can be partially offset by increasing the inspired oxygen concentration.

This varies with cardiac output, systemic vascular resistance and blood viscosity: although capillary blood flow increases because of reduced viscosity, this is offset by the reduction in oxygen content of the blood. Hence any factor causing a further fall in oxygen delivery, such as blood loss or myocardial depression, will cause tissue hypoxia.

At rest, basal oxygen consumption is about 250 ml/min. This is achieved through extraction by the tissues of about 5 ml oxygen per 100 ml blood. Mixed venous saturation is approximately 75 per cent and the mixed venous Po&sub2; about 5.3 kPa. The oxyhaemoglobin dissociation curve will be shifted to the left by hypothermia, reduced 2,3-diphosphoglycerate levels, or alkalosis. This leads to further reduction of Pvo&sub2; at 75 per cent saturation, and impaired tissue oxygenation. A right-shift of the oxyhaemoglobin dissociation curve will allow oxygen to be released to the tissues from haemoglobin, but only at higher Paco&sub2; levels.

Provided that cardiac output, and therefore tissue perfusion, remains unaltered, anaemia causes a reduction in both capillary and tissue Pao&sub2;. In patients with chronic anaemia two important physiological compensatory mechanisms come into play: levels of 2,3-diphosphoglycerate in red cells are increased, shifting the oxyhaemoglobin dissociation curve to the right, and cardiac output is increased due to reduced blood viscosity, so effectively reducing peripheral vascular resistance and capillary dilatation in response to the reduced oxygen content of the blood.

Although arterial oxygen content increases linearly as packed cell volume increases, there is also an accompanying increase in viscosity, which reduces capillary blood flow. As shown in Fig. 1 43, there is an optimal packed cell volume at which the balance between viscosity and arterial oxygen content results in the maximum volume of oxygen being transported to the tissues in a given time. This optimum packed cell volume is about 30 per cent, and the haemoglobin concentration, 8 to 9 g/dl.

There is no substantial evidence to show that normovolaemic anaemia increases the morbidity associated with surgery although risks are increased in the presence of other factors which may impair tissue oxygenation, such as pre-existing lung disease or hypovolaemia. Similarly, there are insufficient data to suggest that anaemia is associated with poorer wound healing, and it has been suggested that healing of colonic anastomoses is optimal if the haemoglobin level is maintained in the range 10 to 12 g/dl.

Since inhaled anaesthetic agents have a reduced solubility (15–25 per cent) in anaemic blood, the concentration of anaesthetic in the blood will increase more rapidly than normal. Although this increases the rates of onset of and recovery from anaesthesia, there is also the risk of overdosage or toxicity. The depressant effect which these drugs have on the cardiovascular system may be exaggerated in the anaemic patient.

Respiratory alkalosis (due to excessive mechanical ventilation) and hypothermia shift the oxyhaemoglobin dissociation curve to the left, reducing tissue oxygen release, while intraoperative hypovolaemia (secondary to blood loss) may decrease cardiac output and cause splanchnic vasoconstriction. Blood lost during surgery must therefore be replaced promptly. Pain and shivering in the postoperative period increase systemic vascular resistance and result in tissue hypoxia. Thus, oxygen should be administered to the anaemic patient in the immediate postoperative period, and subsequently if pulmonary function is impaired. Attention must be paid to cardiovascular function, avoiding hypovolaemia by appropriate administration of crystalloid, colloid, or blood, and treating arrhythmias or reduced cardiac output promptly.

These are caused by the inheritance of the sickle-cell gene, either alone or in combination with another haemoglobinopathy. The most common genotypes are homozygous sickle-cell disease (SS), sickle-cell trait (SA), sickle-cell haemoglobin C (SC), and sickle cell &bgr;-thalassaemia (S&bgr;thal). Under conditions of reduced oxygen tension, sickle haemoglobin undergoes gelation, altering the malleability of the erythocyte, which assumes an elongated sickle shape. These misshapen cells cause sludging of the blood in the capillaries leading to an increased blood viscosity, thromboembolic episodes and cell haemolysis. To reduce the risk of sickling during surgery, elective operations should be performed only when the patient is not having a crisis, and is free from infection. Safe and simple general anaesthesia in these patients requires adequate oxygenation, ventilation to normocapnia, maintenance of the circulating volume, and good postoperative care. The induction of hyponatraemia may reduce the risk of sickling, as may deliberate raising of pH. In patients with severe sickle-cell disease scheduled for major surgery, preoperative transfusion to decrease the absolute percentage of HbS to less than 40 per cent reduces the risk of vaso-occlusion, as well as suppressing the bone marrow, thereby resulting in decreased production of sickle cells.

Preoperative assessment should include the prescribing of adequate premedication, as anxiety may precipitate crises due to the associated vasoconstriction. The use of 50 per cent oxygen in nitrous oxide, supplemented by isoflurane, is the current technique of choice. Intraoperative monitoring should include oximetry and capnography (if available). The use of automated non-invasive blood pressure cuffs has been questioned because of a possible increase in problems due to stasis and sickling while a sphygmomanometer cuff is inflated. Postoperatively, arterial hypoxaemia is common, and this may be exacerbated by the depressant effects of postoperative analgesia. Oxygen should be given for 24 to 48 h after surgery. Local hypoxaemia and acidosis must be avoided, so tourniquets should not be applied for limb surgery, and major regional nerve blockade is contraindicated, as is intravenous regional anaesthesia.

Although sickle-cell trait (SA) patients are less at risk, adequate oxygenation is essential throughout the perioperative period.

Severe arrhythmias, including ventricular ectopic beats, may occur in the spontaneously breathing patient receiving volatile inhalational agents, especially halothane. The incidence appears greatest in patients undergoing oral surgery.

The intraoperative administration of vasopressor agents to patients receiving treatment with monoamine oxidase inhibitors may result in hypertensive crises. Monoamine oxidase inhibitors may also interact with opioids, resulting either in ‘excitatory’ signs (hypertension, hyperpyrexia, convulsions) or marked central nervous system depression (especially respiratory centre depression). After consultation with the patient's psychiatrist, monoamine oxidase inhibitors should, if possible, be discontinued at least 2 weeks prior to anaesthesia and surgery.

This treatment for manic depression may potentiate the effects of both depolarizing and non-depolarizing muscle relaxants, and the drug is therefore best discontinued prior to anaesthesia, following discussion with the psychiatrist concerned.

Surgery and anaesthesia may influence the disposition of these agents, resulting either in subtherapeutic drug concentrations, which increase the risk of seizures, or toxicity. Postoperatively, binding of phenytoin is reduced due to changes in the plasma concentrations of albumin, &agr;&sub1;-acid glycoprotein and free fatty acids. Drug binding and distribution may also be influenced by changes in acid–base status. Another important side-effect of chronic antiepileptic therapy (especially with phenobarbitone, phenytoin and carbamazepine) is hepatic microsomal enzyme induction: patients may require increased doses of both hypnotic and analgesic drugs for adequate anaesthesia and pain relief. Other enzyme-inducing agents include rifampicin, isoniazid, spironolactone, phenylbutazone, alcohol, cigarette smoking, and drugs such as the anabolic steroids.

Warfarin is best discontinued 3 to 4 days preoperatively and replaced with an infusion of heparin (24000 units per 24 h). Before induction anaesthesia, the International Normalized Ratio should be well below 1.5; any residual effect of warfarin should be reversed by vitamin K (phytomenadione) administration. Fresh frozen plasma or clotting factor concentrates may be administered to patients receiving warfarin who require emergency surgery.

Heparin treatment is usually discontinued just before surgery, the best time for stopping being at the time of oral premedication (the biological half life of the anticoagulant being dose-dependent, but ranging between 0.5 and 3 h). Postoperatively, when the patient is tolerating oral intake, warfarin treatment should be recommenced with an oral loading dose of 8 to 10 mg; the International Normalized Ratio should be checked at 48 h, and if it is greater than 2 to 2.5, heparin is discontinued.

For perioperative prophylaxis against deep venous thrombosis or pulmonary embolism, 5000 units of heparin should be given subcutaneously with premedication, and then continued 12-hourly for 3 days after surgery. The efficacy of this therapy is not usually monitored, but the risk of haemorrhagic episodes is increased in patients concurrently receiving antiplatelet therapy such as low-dose aspirin. Use of the new low molecular weight heparins is said to provide prophylaxis against thrombosis without the risk of haemorrhagic episodes. Additional prophylaxis may include elasticized or inflatable stockings and calf stimulators.

The combination of surgery and oral contraception increases the incidence of postoperative deep venous thrombosis, and intake of the oral contraceptive pill should be discontinued at least 4 to 6 weeks before surgery. If emergency surgery is required in a woman currently using oral contraception, prophylaxis against deep venous thrombosis may take the form of low-dose heparin, intraoperative infusion of dextran 70, and elasticated stockings. In theory, this increased risk of deep venous thrombosis should not exist in patients taking the progesterone-only pill.

As this is given in physiological (as opposed to pharmacological doses) there is no indication for this to be stopped prior to surgery.

Chronic smoking is associated with the increased likelihood of postoperative chest infections, and a reduction in the oxygen-carrying capacity of haemoglobin due to the presence of carboxyhaemoglobin. Hence, many surgeons and anaesthetists feel that smoking should be stopped at least 3 to 4 weeks prior to surgery.

Although the consumption of alcohol in moderate amounts presents no problems to the surgical patient, excessive quantities may be associated with enzyme induction or liver dysfunction. Alcoholics require increased doses of anaesthetic, opioid, and other drugs given during the perioperative period to achieve therapeutic effects. Abrupt withdrawal of alcohol over the perioperative period may precipitate symptoms, which may be treated by judicious doses of alcohol or chlormethiazole. In severe cases, seizures may occur which require intravenous diazepam and respiratory support before commencing chlormethiazole.

Other drugs of importance include marijuana, opioids, cocaine, and LSD. Again, withdrawal symptoms may occur perioperatively. The association of drug abuse with carriage of bloodborne infections such as hepatitis B or HIV should be considered, and appropriate precautions taken.

Deficiency of this enzyme, which is responsible for the metabolism of suxamethonium, procaine, 2-chloroprocaine, and tetracaine, may be either acquired or inherited. The latter may be expressed as both homozygous and heterozygous conditions, and causes variable degrees of prolongation of the duration of suxamethonium, causing apnoea, and the need for intermittent positive pressure ventilation. Delineation of the genotype in affected patients and if necessary, in their relatives, can be made by measuring the percentage enzyme inhibition caused by dibucaine (10&supminus;&sup5; M) and fluoride. A silent gene, lacking enzyme activity, and other genetic variants exist (e.g. C&sub5;).

This group of diseases is caused by inherited defects or acquired dysfunction of the enzymes responsible for haemopoiesis. Hepatic (acute intermittent) porphyria presents the most important problems to the anaesthetist and occurs about 1 in 100 000 live births in the United Kingdom, although higher rates occur in other countries (e.g. Sweden, southern Africa). The condition is due to a deficiency of uroporphyrinogen I synthase, which is diagnosed by an increased urinary concentration of aminolevulinic acid and porphyrobilinogen. Acute attacks may be precipitated by a number of anaesthetic-related drugs including barbiturates, flunitrazepam, the contraceptive pill, and prochlorperazine.

Preoperative examination of the patient should include careful assessment of the cardiovascular system for tachycardia and hypertension and of the central nervous system for neuritis, neuropathies (motor, sensory, and autonomic), and bulbar palsy. Regional anaesthesia is contraindicated as neurological complications may arise. Other forms of the disease which also have anaesthetic implications but which are less common include hereditary coproporphyria and porphyria cutanea tarda hereditaria. The same drugs may precipitate crises in these patients.

This defect of muscle calcium transport is inherited as an autosomal dominant characteristic located on chromosome 19. The disease is characterized by heat production (>1°C rise/h), muscle rigidity, excess lactate and CO&sub2; production, hypoxia, hyperkalaemia, respiratory and metabolic acidosis, and myoglobinuria. The incidence is about 1:200000 surgical patients in the United Kingdom.

For the disease to be expressed, a genetically sensitive individual must be exposed to a trigger agent (inhalational agent, suxamethonium, and possibly nitrous oxide). A greater incidence of the condition is found among patients undergoing surgical correction of squints and hernia and minor orthopaedic procedures. Morbidity is high (24 per cent). Management of an attack involves intravenous administration of dantrolene, withdrawal of likely precipitating agents and supportive therapy, including control of hyperkalaemia and acidosis, surface and peritoneal cooling, and treatment of cardiac arrhythmias. Specific therapy with dantrolene sodium (1–10 mg/kg IV) has reduced the mortality, and the drug may also be used as prophylaxis in susceptible individuals. As the disease is genetically inherited, ‘at-risk’ individuals should be screened by the in-vitro examination of a muscle biopsy taken under local anaesthesia. Abnormal contracture following exposure to caffeine is the principal diagnostic test, combined with electron microscopy.

Preoperative laboratory testing of patients scheduled for elective surgery allows quantitation of an abnormality detected by history and physical examination, detection of significant abnormalities not revealed by history and examination, and offers medicolegal protection to medical staff.

There is general agreement that assessment of the severity of pre-existing disease is important. This allows the patient to be restored to optimum health before surgery, allows any support likely to be needed in the perioperative period to be predicted, and also assists in risk–benefit decisions. A detailed discussion of preoperative preparation of patients with the various commonly encountered diseases is outside the scope of this section.

‘Screening’ of asymptomatic patients in the belief that detection of abnormalities will improve perioperative course and outcome is of great significance. Until recently, minimal data have been available to support the assertions made. However, there has been increased evaluation of the benefits of preoperative laboratory testing of patients in the last decade. A retrospective study of patients undergoing inguinal herniorrhaphy or stripping of varicose veins, found only 63 abnormal results in 1972 tests, and in no instance was patient management influenced by these results. Similar results have been found by other workers and it is concluded that history and physical examination determine which tests are appropriate in all but a small minority of patients.

The use of a battery of tests to provide medicolegal protection has also been questioned. One review concluded that there was no benefit to patient management or cost–benefit from routine screening of asymptomatic patients. In addition, potential legal problems may be generated when false-positive results occur. Retrospective studies have shown that unexpected positive results in asymptomatic patients are generally ignored: for example, anaemia found on routine screening of children was ignored in 74 per cent of cases.

Agents used for premedication form part of the anaesthetic technique, with the provision of analgesia or supplementation to volatile agent-nitrous oxide or hypnotic infusion-nitrous oxide anaesthetics. The primary indications for preoperative medication are anxiolysis, sedation especially in paediatric patients, analgesia, amnesia, vagolysis to reduce salivary secretions, and prophylaxis against postoperative nausea and vomiting and hence aspiration pneumonitis.

Most patients experience some anxiety prior to surgery and this is best allayed by the combination of careful and sensitive discussion of the issues of concern to the patient and the use of anti-anxiety drugs, the most common agents being the benzodiazepines (diazepam, lorazepam, or temazepam) and some of the opioids (morphine, pethidine, and papaveretum).

This may also be achieved by administration of benzodiazepines or opioids. In children antihistamines such as trimeprazine (which can be given by the oral route) or rectal administration of ketamine or methohexitone can be used.

Many anaesthetists regard amnesia of the events leading up to anaesthesia and surgery as desirable, especially in the very young and in patients having repeated general anaesthetics. Amnesic drugs may also reduce the risk of awareness occurring during anaesthesia, allowing a lighter depth of anaesthesia to be maintained. The most effective amnesic agents are the benzodiazepines (especially lorazepam and midazolam). The anticholinergic agent, hyoscine, also exhibits amnestic properties.

The routine use of analgesic drugs as part of the premedication, except in patients experiencing severe acute or chronic preoperative pain has been criticized by some anaesthetists. However, the preoperative administration of analgesic drugs (both opioids and non-steroidal anti-inflammatory drugs) reduces the dose of induction agent and maintenance agents necessary for clinically adequate anaesthesia. In addition, the use of analgesia (either as part of the premedication, or intraoperatively) provides patient comfort in the initial postoperative period. The main disadvantages of all opioid drugs are their association with nausea and vomiting, and the risk of respiratory depression.

The response to many noxious stimuli is the development of a vagally medicated bradycardia. Intramuscularly administered anticholinergics have been shown to be ineffective in preventing these responses. Routine use of antisialogogues has major disadvantages: the patient suffers an unpleasant dry mouth during the preoperative period, and dry mucous membranes are sticky and easily damaged during laryngoscopy and intubation. Present use of these agents tends to be reserved for infants, and in those situations where a dry mouth is advantageous, (such as for intraoral surgery). Hyoscine is the most potent of the antisialogogues available and has the additional advantage of producing amnesia and sedation. In the elderly, however, there is a significant incidence of perioperative confusional states.

Drugs used for premedication may either reduce the emetic effects of the anaesthetic agents employed, or aid gastric emptying. The first group includes the antihistamines and butyrophenone drugs, as well as hyoscine; gastric emptying can be facilitated by administration of metoclopramide, and the gastrokinetic drug, cisapride. Additional effective medications include transdermal hyoscine, and the 5-hydroxytryptamine antagonist, ondansetron.

Agents to decrease gastric acidity are normally administered only to those patients either at risk of regurgitation of gastric contents into the pharynx with tracheal aspiration, such as the pregnant patient, those with a hiatus hernia or strong clinical history of gastric reflex, the obese, and those with clinical evidence of gastric stasis, or in those procedures associated with a high incidence of nausea and vomiting, such as laparoscopy. Such antacid therapy aims to reduce acid production, and to raise the gastric pH of residual contents to above 2.5. The first is achieved by administration of histamine H&sub2;-receptor antagonists (cimetidine, ranitidine, famotidine, or nizatidine) or the hydrogen-pump antagonist omeprazole given over several hours pre-surgery; the second is by alkalis such as sodium citrate or magnesium trisilicate given orally 15 to 30 min prior to induction.

Antihistamine drugs such as the phenothiazines promazine, chlorpromazine, and promethazine may also offer protection against the drug-mediated release of endogenous histamine and other autocoids in the atopic individual. Their protection is usually incomplete, and co-administration of sodium cromoglycate and hydrocortisone may be of benefit in the highly sensitized patient.

Although the most popular rates of administration are by the intramuscular (the traditional method) and oral routes, alternatives such as intravenous, rectal, and transdermal routes have specific indications.

Orally administered premedicants may be less effective than those administered parenterally. Gastric emptying and drug absorption will be influenced by pain, anxiety, opioids, and intra-abdominal pathology. However, the oral route is considered by many to be the route of choice for children, and it is the preferred route in patients with bleeding disorders (patients receiving anticoagulants, haemophiliacs, or those with other coagulation defects, and patients with liver and renal failure).

The timing of the premedication is of importance since maximum antisialogogue and antivagal effects need to be achieved before induction of anaesthesia: thus the majority of drugs are given 1 to 2 h preoperatively. For more rapid onset of anxiolysis, the short-acting benzodiazepine temazepam has been advocated, especially for use in day-care anaesthesia.

Safe general anaesthesia depends upon the administration and maintenance of an ‘adequate anaesthetic dose’ without the accompanying development of unwanted or adverse side-effects; the monitoring, where possible, of the depth of anaesthesia by clinical signs (such as heart rate, blood pressure or autonomic responses), or a derivate of brain activity, such as EEG or evoked potentials, relating, where possible, the presence of clinically adequate anaesthesia with a defined plasma drug concentration; and the prompt recovery of normal brain activity through the use of drugs that undergo rapid elimination and have no residual depressive effects on the central nervous system or other systems.

Unconsciousness may be induced by intravenous hypnotics alone or in combination with other agents (including opioids). Hypnotics (with the exception of ketamine) do not possess analgesic properties nor do they relax skeletal muscle. Although they are rarely used alone for the maintenance of anaesthesia, their use will reduce the requirement for other anaesthetic agents.

Thiopentone is still the archetypal hypnotic drug, providing a rapid, effective and safe onset of anaesthesia. Its non-hypnotic properties include cardiorespiratory depression, and, in large doses, prolonged recovery. Absolute contraindications are rare and include proven barbiturate allergy or a history of acute intermittent porphyria. Thiopentone should be used cautiously, with reduced dosage and careful titration of dose to effect in patients with respiratory obstruction or inadequate airway control before induction of anaesthesia, in severe cardiovascular collapse or shock, and in those with status asthmaticus, cardiovascular disease (ischaemic heart disease, hypertension, valvular heart disease), hypovolaemia, acute adrenocortical insufficiency, or uraemia.

Methohexitone and thiamylal have faster clearance rates than thiopentone, and both are broken down to inactive metabolites. The side-effects of methohexitone include pain on intravenous injection, a tendency to venous thrombophlebitis, and exaggerated involuntary movements, especially in the unpremedicated patient and patients with epilepsy.

Etomidate (a carboxylated imidazole) has the advantage of not inducing histamine release, and is therefore indicated for use in asthmatic and atopic patients. Induction of anaesthesia causes only minimal haemodynamic and respiratory changes. Pain on injection and myoclonic activity during induction have limited its use for routine surgery.

Ketamine is the only hypnotic agent possessing analgesic activities. In contrast to other agents, ketamine increases sympathetic autonomic activity, and is therefore useful for the rapid induction of anaesthesia in patients requiring high sympathetic activity for maintenance of cardiovascular function (e.g. in the presence of pericardial tamponade, and hypotension). Indications for the use of ketamine include: poor-risk surgical patients (e.g. those with poor myocardial function or hypovolaemia); debridement, application or removal of painful dressings and skin grafting in patients suffering from burns; short diagnostic or surgical procedures, including cardiac catheterization; and postoperative pain relief.

Propofol (di-isopropyl phenol) causes comparable cardiovascular and respiratory depression to thiopentone when used for induction of anaesthesia. Induction is often accompanied by pain on injection, especially when small veins are employed, with coughing and hiccoughing, and involuntary movements. It has a high clearance rate and can therefore be used for both induction and maintenance of anaesthesia, especially where prompt and complete recovery is important (e.g. day case surgery). The low incidence of nausea, vomiting, and headache is important for the ambulant patient. Because of its pharmacological effects, propofol should be used with care in patients with compromised cardiac function (ischaemic heart disease, hypertension) or hypovolaemia.

Midazolam, a water-soluble benzodiazepine, should be used to provide sedation, amnesia, and sleep—but not anaesthesia. It has a shorter duration of action than diazepam, but may cause unexpected ventilatory and cardiovascular depression, especially in patients with chronic obstructive pulmonary disease, hypotension associated with hypovolaemia, and in the elderly.

Anaesthesia may be maintained by infusions of hypnotic agents, volatile agents, or opioids, alone or in combination.

Use of intravenous infusions of anaesthetics has increased in popularity due to development of drugs with higher systemic clearance and metabolism to inactive metabolites, such as propofol or methohexitone. Some indications for the use of intravenous techniques include day-case anaesthesia, military or ‘field’ anaesthesia (where nitrous oxide is not available), and as a supplement to cardiopulmonary bypass or regional anaesthesia.

More commonly, volatile or inhalational agents provide the basis of general anaesthesia. The differing physicochemical properties of the different volatile agents will affect their pharmacological effects. Thus, agents with low blood/gas solubilities (e.g. nitrous oxide, desflurane, and sevoflurane) will cause rapid onset and recovery of central nervous system effects. The oil/gas solubility provides one index of potency, defined in terms of the minimum alveolar concentration (MAC), which is the alveolar concentration preventing a response to a surgical incision in 50 per cent of subjects (Table 5) 21.

Nitrous oxide is a weak anaesthetic agent (minimum alveolar concentration 105–110 per cent), which cannot alone suppress the somatic, autonomic, or haemodynamic responses to noxious stimuli during clinical use. However addition of nitrous oxide at inspired concentrations of 60 to 70 per cent significantly decreases the dose requirements of other more potent volatile agents (as well as those of the hypnotic and opioid drugs). Relative contraindications to the use of nitrous oxide include the need for high inspired oxygen concentrations (e.g. during bronchoscopy and upper airway surgery), and its high diffusibility into air-filled spaces so increasing their volume or pressure: this occurs in the presence of a pneumothorax, after pneumoencephalography, after tympanoplasty, in patients with grossly dilated bowel due to intestinal obstruction, and where air embolism may occur. Nitrous oxide should be avoided if possible during the first 4 weeks of pregnancy, because of its effects on organogenesis: the arguments concerning its effect on theatre pollution are covered in the section on medico-legal issues below.

Halothane, enflurane, and isoflurane are highly potent volatile agents, but have narrow margins of safety between their anaesthetic effects and cardiovascular depressive properties. They therefore have to be administered by calibrated vapourizers. All three separate components of the anaesthetic triad may be achieved with these agents; however the concentrations required to achieve appropriate anaesthetic depth may result in excessive hypotension through the combination of myocardial depression, vascular smooth muscle relaxation, and depression of the sympathetic nervous system. Thus, the inspired drug concentration tends to be regulated according to an adverse effect of the volatile agents—cardiovascular depression. This is most significant with enflurane, and may be exaggerated in the patients with hypovolaemia or congestive cardiac failure. Cardiovascular depression is less severe with halothane; other side-effects which may favour the choice of halothane as the volatile supplement include low pungency and laryngeal irritability, bronchodilation, and uterine muscular relaxation.

Isoflurane exhibits all of the favourable properties of the other two volatile agents, combined with a faster uptake and elimination, and minimal biotransformation, with its associated reduced risk of renal and hepatic toxicity. Although isoflurane produces vasodilation, this is accompanied by a reflex increase in sympathetic activity that either maintains or increases both heart rate and cardiac output. However hypotension may occur in patients with decreased sympathetic reserve, such as those receiving &bgr;-adrenoceptor blocking drugs.

In appropriate concentrations, all three agents are able to control the hyperdynamic responses to noxious stimulation during surgery. Dose requirements for volatile agents can be reduced by combination therapy with other centrally acting drugs (hypnotics, sedatives, and opioids), as well as achieving relaxation through use of myoneural blocking drugs. Other non-hypnotic effects of the volatile agents include possible alterations in myocardial blood flow distribution with development of ischaemia (the so-called coronary steal phenomenon) with isoflurane; increased cerebral blood flow and intracranial pressure (seen with both halothane and enflurane in clinical concentrations, but with isoflurane only at concentrations above 1.5 per cent); risk of seizures during enflurane anaesthesia, especially in presence of hypocarbia; hepatotoxicity (with halothane, enflurane, and possibly isoflurane); fluoride-induced nephrotoxicity due to enflurane biotransformation; malignant hyperpyrexia (may be triggered by all three agents), and impaired cellular-mediated immunity.

Opioid drugs may be given for premedication, introperative supplementation, or postoperative analgesia. As premedicants, or as supplements during anaesthesia, small doses of morphine (0.03–0.5 mg/kg) or pethidine (meperidine) (0.5–1.0 mg/kg) reduce the dosage requirements of the inhaled and other intravenous agents. Provided that ventilation is maintained, the side-effects of these doses are relatively minor and easily controlled. The newer synthetic opioids (fentanyl, sufentanil, and alfentanil) were developed to provide greater potency but with fewer side effects and greater margins of safety. Because of their minimal effects on the heart and circulation, opioids are sometimes used alone to maintain anaesthesia in high-risk patients. However, the major disadvantage of these agents when used alone is their limited anaesthetic efficacy (resulting in liability to awareness, recall, and sympathetic autonomic responses to noxious stimuli). In addition, large doses of opioids cause respiratory depression, necessitating postoperative respiratory support.

The safety of contemporary anaesthesia has been well documented; however, adverse effects may occur with all anaesthetic agents. Adverse effects of the volatile agents have been previously described. The adverse effects encountered with intravenous agents may be divided into non-hypnotic side-effects and anaphylactic or anaphylactoid responses.

Overdose may be absolute, due to acute excess administration, or to accumulation as a result of reduced elimination or metabolism, or relative, due to patient factors such as hypovolaemia, extremes of age, intercurrent disease (especially cardiac, renal, or hepatic impairment), and drug–drug interactions. Other problems may be due to bacterial contamination of the agent or the use of incompatible drug mixtures. For example, precipitation occurs if thiopentone and d-tubocurarine, or vecuronium are administered in the same syringe, or via the same intravenous cannula without flushing between drugs. Exaggerated pharmacological effects which may occur include excessive hypotension or bradycardia. These are seen following administration of large doses of the intravenous hypnotic agents and opioids, respectively. Idiosyncratic effects are not predictable from the pharmacology of the individual drug. Examples include porphyria, malignant hyperpyrexia, plasma pseudocholinesterase deficiency, glucose 6-phosphate dehydrogenase deficiency, and the genetic polymorphism of drug metabolism—fast and slow acetylators of hydralazine, slow and fast hydroxylators of desbrisoquin, or propranolol.

Most drugs administered during anaesthesia are of low molecular weight (less than 1000 Da). Alone they are not capable of initiating an immune response with the production of specific antibodies. However, many drugs are able to combine in vivo with a carrier protein (hapten) to form an antigenic moiety. The extent of basophil and mast cell degranulation induced depends on the amount of drug injected, the affinity of the drug for the antibodies, and the amount of cell-bound antibodies produced.

These depend upon classical antigen–antibody interactions that activate the complement cascade via the classical pathway. Complement activation results in mast cell disruption and the release of histamine and other autocoids which increase vascular permeability, and so allow the passage of phagocytes from extravascular sites to enter the bloodstream and break down the antigens.

These occur as a result of a direct pharmacological effect or some other non-immunological response by which the drug causes release of histamine. Some drugs, particularly those with basic properties (e.g. d-tubocurarine, suxamethonium, morphine, thiobarbiturates, and trimetaphan), cause direct competitive displacement of histamine (another basic molecule) from the mast cell. As will be discussed later, predisposing factors exist which may also play a role in the genesis of these anaphylactoid responses.

The main aetiologies of these anaphylactoid hypersensitivity reactions to drugs can be subdivided into activation of the alternative pathway of complement and direct pharmacological effects.

Unlike the classical pathway, preformed antibodies to a particular antigen are not necessary for alternative pathway activation. Hence prior exposure to the drug or endotoxin is not necessary.

Although adverse drug reactions may involve activation of one or other of the complement pathways, the majority are better described as anaphylactoid in nature, and occur as a result of a dose-related direct effect of the drug upon mast cells and basophils. Such reactions may be manifest as either local cutaneous signs, or as more severe systemic signs and symptoms of histamine release. With drugs such as thiopentone and some of the neuromuscular blocking agents, a flush and weal reaction is often seen following their intravenous injection. The systemic features of the reactions are usually mild (hypotension, tachycardia), and without the other stigmata of histamine release. Why some of these cases (for which no immunological basis will be found on subsequent testing) progress to more generalized systemic symptoms is uncertain.

Factors predisposing to the development of allergic reactions include patient factors, possible pharmacological factors, and potential at-risk patient groups.

Adverse reactions are rarer in children than in adults, but there is probably no sex difference in incidence. The apparently higher incidence in gynaecological patients may be related to pregnancy.

There is a high incidence of adverse reactions on first or subsequent exposure to certain IV anaesthetics in the pregnant patient, which may be due to the choice of drugs used for short gynaecological procedures. The immune status of these patients is also altered, and this may play a role.

Hypersensitivity reactions to IV anaesthetic drugs are more common in atopic individuals and asthmatics. The increased incidence of hypersensitivity reactions to first exposure in the atopic individual is small compared with the higher incidence of hypersensitivity reactions seen in patients receiving repeat administration of the same anaesthetic agent. The impression among some anaesthetists that adverse reactions are more common in nervous, anxious patients is not supported by any data. Apart from patients with a history of previous anaphylaxis or a proven sensitivity to one or more drugs, there are no other predictors of at-risk groups.

Many of the intravenous anaesthetic agents are poorly water soluble and hence glycols, macrogols, and non-ionic surfactants are added to increase their solubility. These solvents may trigger complement activation.

There is considerable variation in the severity and magnitude of the clinical features among different reactors. Factors that influence the severity of the symptoms include the amount of drug injected, the reactivity of basophils and mast cells; the responsiveness of the bronchial and vascular smooth muscle, and the activity of the autonomic nervous system. Control of peripheral autonomic nervous system activity is also regulated by higher centres. Thus, the increased emotional activity of the asthmatic patient prior to anaesthesia and surgery may both enhance any existing symptomatology, and exaggerate any adverse response to IV drug administration.

The various symptoms that may occur during adverse reactions are shown (Table 6) 22. The maximum intensity of the symptoms often occurs rapidly, usually within 30 min of IV drug administration. All of the clinical features can be attributed to mast cell and basophil degranulation, and this knowledge has been used in some of the methods used for preoperative prophylaxis in patients with a history of drug allergy. The usual order of the main clinical symptoms is skin changes, hypotension with tachycardia, and bronchospasm with resulting arterial hypoxia.

Skin changes are characterized by the classic triple response described by Lewis. Erythema is caused by dilatation of capillaries over the face, arms, and mantle; weal formation arises from increased vascular permeability causing fluid transudation, and flares are presumably due to an axon reflex response. Hypotension and tachycardia result from the transudation of fluid from the vascular to extravascular spaces. Histamine also causes vascular smooth muscle dilatation, and hence the venous pooling of blood may occur. The accompanying tachycardia is probably not a baroreflex response, but rather the chronotropic effect of increased circulating catecholamine levels following their release by histamine from the adrenal medulla. Bronchospasm is the most life-threatening of the symptoms, and treatment must primarily be aimed at preventing severe arterial hypoxia.

Following the successful treatment of an allergic reaction, the causative agent must be identified wherever possible. The laboratory diagnosis depends on the results of a number of routine haematology tests, including measurement of haematocrit. Changes in platelet and white cell numbers may be small, but of significance. Disappearance of basophils (expressed as a percentage of the total leucocyte count) is indicative of a type I response. Serial measurements should be made of the plasma concentrations of total IgE antibodies and complement proteins (C2, C4, and breakdown products C3a, C3b and C1 esterase inhibitor) during the 72 h after an adverse reaction. Metabolism of both C3 and C4 is indicative of an immune reaction which does not involve IgE antibodies, while C3 conversion alone is an indicator of a specific non-immune mechanism. In contrast to atopic patients who have increased levels of IgE, some individuals (10–20per cent) have very low levels of this immunoglobulin. Such people appear to be prone to non-immune mediated clinical reactions, and may produce positive intradermal tests to drugs which have a high potential for inducing histamine release.

Other in-vivo and in-vitro diagnostic tests which may be useful for later assessment to establish the identity of the drug responsible for the reaction include intradermal skin testing, the IgE inhibition test, leucocyte histamine release test, basophil degranulation test, radio-allergosorbent test, and delineation of specific antibodies.

The management of severe histamine release reactions has been comprehensively reviewed. The aims of treatment must be to correct hypoxia, inhibit further release of chemical mediators, and restore the vascular fluid volume (preferably with colloids). When the combination of adrenaline and adequate volume does not produce improvement, then noradrenaline may be lifesaving. Table 7 23 lists a management approach to allergic reactions.

There is considerable controversy as to whether steroids should be given routinely. Cortisol does not inhibit the allergen–antibody interaction, nor the release of vasoactive amine from mast cells and basophils. Thus, steroids are probably only indicated for the treatment of severe bronchospasm. Other stimulant drugs, such as isoprenaline, should only be given cautiously in the presence of cardiac arrhythmias or hypovolaemia. Vasoconstrictors should also be used with care, as they can provoke acute pulmonary oedema when coupled with rapid fluid infusion. Anticholinergic drugs, such as atropine, may attenuate the release of histamine by decreasing the intracellular concentrations of the second messenger, guanosine monophosphate. However, only limited data from which to draw conclusions are available. In cases of severe or intractable bronchospasm, there is need for drugs other than aminophylline. These include glucocorticoids, adrenaline, isoprenaline, salbutamol, and even general anaesthetic agents with bronchodilator properties (diethyl ether, halothane, ketamine, and isoflurane). Persistent vasodilatation can be reversed by dopamine, dobutamine, ephedrine, or adrenaline, given by repeat bolus doses or infusion. There is no evidence of any acute value in the administration of H&sub1; and H&sub2;-blocking drugs; however these drugs may have a role in prophylaxis.

Management of these patients after recovery should include counselling and an explanation of the significance of hypersensitivity, reassurance as to future anaesthesia, and registration of the patient with Medic Alert or similar organizations. In addition, a clear summary of the reaction should be placed in the patient's notes, and sent to the general practitioner.

Although the occurrence of a first exposure reaction of any drug is unpredictable, steps can be taken to prevent hypersensitivity reactions occurring on subsequent exposures. These include use of local rather than general anaesthesia where possible, although hypersensitivity to the ester type of local anaesthetics has been reported. When general anaesthesia is essential, the use of adequate preoperative anxiolysis and premedication may reduce stress. Preoperative prophylaxis should be aimed at both reducing histamine release, and at blocking its systemic effects. Sodium cromoglycate stabilizes mast cells, and so prevents degranulation and histamine release, salbutamol prevents bronchospasm, and hydrocortisone antihistamines (H&sub1;-receptor antagonists; e.g. chlorpheniramine or terfenadine and H&sub2;-receptor antagonists e.g. cimetidine or ranitidine) may also be administered. The last two groups of drugs inhibit histamine release, but also compete at the receptors to attenuate the decreases in systemic vascular resistance.

Repeat exposure to any drug that the patient has received intravenously in the recent past should be avoided and inhalational agents rather than IV agents should be used whenever possible, although caution should be taken to avoid repeat exposures to halothane. Plasma expanders such as Haemacel and Dextran should not be used.

These produce a transient and completely reversible blockade of nerve function, and hence an interruption of sensory perception. The first agent used in clinical practice was cocaine, described for ophthalmological surgery by Ko..hler in 1884. Procaine, the archetypal aminoester was synthesized in 1905, while the amide anaesthetic lignocaine (lidocaine) was introduced in 1943.

Local anaesthetics act by blocking sodium channels in the axon membrane and inhibiting sodium conductance, whilst having minimal effects on potassium currents. Other pharmacological actions relate to their interaction with calcium ions, perhaps by inhibiting the binding of calcium ions to phosphatidylserine.

The anaesthetics bind to a receptor site at the internal opening of the sodium channel, and some drugs such as benzocaine may actually penetrate the nerve membrane and cause conformational changes which lead to a decrease in the diameter of the sodium channel. Most of the local anaesthetic drugs have a pK&suba; value close to physiological pH, and will therefore exist in both ionized and unionized forms. Diffusion of drugs through the epineurium and nerve membrane can only occur in the unionized form, the fractions in the two forms being governed by the Henderson–Hasselbach relationship (pH = pK&suba; + log ionized/unionized). Blockade of the sodium channels is therefore dependent upon the presence of the ionized form of the local anaesthetic. Following blockade of these channels, there is a decrease in the rate and degree of the depolarization phase of the action potential, with failure to achieve the threshold potential and therefore no development of a propagated action potential.

Two types of drug can be recognised clinically—esters, such as cocaine, procaine, chloroprocaine, and tetracaine, and amides which include prilocaine, lignocaine, mepivacaine, and bupivacaine. The ester drugs are readily broken down by hydrolyase enzymes (e.g. plasma cholinesterase), and hence tend to be shorter acting. The amide drugs are broken down in the liver. One of the metabolites of the ester local anaesthetic drugs is para-amino benzoic acid, which is capable of inducing allergic reactions in some patients. The pharmacological properties of the different local anaesthetic agents are related to their lipid solubility, protein binding and pK&suba; values (Table 8) 24.

Lipid solubility is the primary determinant of anaesthetic potency, while protein binding influences the duration of anaesthetic activity. Procaine and chloroprocaine are agents with low potency and short duration, lignocaine, mepivacaine, and prilocaine have intermediate effects, and tetracaine and bupivicaine have long duration of effect with high potency.

The duration of effect of a local anaesthetic agent can be prolonged by addition of a vasoconstrictor such as adrenaline which decreases the rate of vascular absorption of drug from the site of administration. As well as producing conduction blockade, local anaesthetics have other important adverse effects on the cardiovascular and central nervous systems, and the neuromuscular junction.

Most local anaesthetic agents readily cross the blood–brain barrier, initially causing excitation and then, at higher doses, central nervous system depression. There is good correlation between the plasma concentration of lignocaine and associated central nervous system toxicity. At pharmacological concentrations, local anaesthetic agents exert effects on cardiac and peripheral vascular smooth muscle to cause arterial dilation and myocardial depression. At toxic concentrations, the combined effects of peripheral vasodilation, depressed myocardial contractility and depression of the heart rate and myocardial conducting pathways may result in circulatory collapse and cardiac arrest. Some of the local anaesthetic agents, such as procaine, have a quinidine-like effect on the heart, increasing the refractory period, raising the threshold for stimulation and prolonging the conduction time. Local anaesthetic agents also affect transmission at the neuromuscular junction, and may potentiate the effects of both depolarizing and non-depolarizing muscle relaxants.

In addition to these three main adverse effects, IV or topically administered local anaesthetic agents also have the ability to suppress the haemodynamic responses to laryngoscopy and endotracheal intubation, as well as decreasing the minimum alveolar concentration, and hence dose maintenance requirements, for volatile anaesthetic agents.

Accidental intravascular injection of an excessive amount of local anaesthetic into the epidural space can cause profound systemic effects. Toxicity is related to type of local anaesthetic agent and total dose administered, site of injection, rate of injection (intravascular injection), use of vasoconstrictors, and is increased in shock where relatively more of the cardiac output is directed to the heart and brain. Acidosis also increases toxicity.

 In general, the cardiovascular system is more resistant to the effects of local anaesthetic drugs than is the central nervous system, the dose ratio being of the order of 3.5 to 6.7:1. However, this ratio is low for bupivacaine, and this has resulted in cases of cardiovascular collapse following release of the tourniquet in patients given bupivacaine for intravenous regional analgesia, and following the use of 0.75 per cent bupivacaine in obstetric epidural practice. Cardiotoxicity appears to be related to the physicochemical characteristics of the local anaesthetic agents—namely high potency, high lipid solubility, and high plasma protein binding, and appears to be increased in the pregnant patient. The predisposition to ventricular arrhythmogenicity is due to the presence of butyl groups within the local anaesthetic side-chains (seen with bupivacaine but not with mepivacaine). Toxicity is influenced by acid–base status, hypercapnia, and acidosis reducing the threshold for convulsive activity and the threshold for cardiac depression. Other systemic effects, apart from the allergic reactions and those listed above, include development of methaemoglobinaemia, neurotoxicity, and initiation of episodes of malignant hyperpyrexia (see Table 10 26).

Systemic toxicity can be prevented by the establishment of venous access in all patients before the institution of regional anaesthesia, by the use of appropriate doses (Table 10) 26, by checking for accidental intravenous administration, and by using vasoconstrictors (to reduce systemic absorption) whenever possible.

If systemic toxicity does occur, oxygen should be administered, with careful monitoring of cardiovascular effects, and convulsive or CNS excitatory activity should be treated with diazepam or midazolam. Facilities for intubation and ventilation as well as drugs for support of the circulation should be available at all times.

Allergic responses to local anaesthetic agents in current use are rare (constituting probably less than 1 per cent of all reactions to drugs). In most patients, other causes of drug reactions are responsible, e.g. systemic toxicity, simple fainting, or reactions to added adrenaline. The recommended maximum dosage of these agents is shown in Table 10 26.

The ester group of local anaesthetics is more liable to provoke adverse reactions as these drugs contain both a p-aminobenzoic acid group, and methyl- or propyl-paraben as the added preservative. The systemic effects of adrenaline are undoubtedly the cause of some of the reported adverse reactions to the local anaesthetics. Use of 1/800 000 adrenaline in dental anaesthesia is frequently accompanied by tachycardia, palpitation, and chest tightness, although angina is rare.

The surgeon or anaesthetist may also be required to attend patients presenting with specific problems where an appreciation of the problems encountered by the anaesthetist are important.

Cerebral blood flow is maintained constant despite changes in perfusion pressure: this phenomenon is termed autoregulation and is also seen in the renal circulation. The normal cerebral blood flow is 44 ml/100 g tissue/min which equates to between 600 and 800 ml/min in an adult brain. Regional blood flow varies with grey matter receiving 80 ml/100 g/min and white matter 20 ml/100 g/min. Approximately 85 per cent of cerebral blood flow is supplied by the carotid circulation, and the remainder by the vertebral arteries. The cerebral oxygen consumption (measured as cerebral metabolic rate for oxygen, CMRO&sub2;) is of prime importance in anaesthesia for neurosurgical patients, since blood flow to the brain is frequently impaired due to raised intracranial pressure. The normal CMRO&sub2; is about 3 ml/100 g tissue/min. Beyond certain limits, autoregulation of cerebral blood flow is lost and perfusion pressure determines cerebral blood flow. Autoregulation is maintained within a range of perfusion pressures of 60 to 150 mmHg. The mechanism of autoregulation is not fully understood, and several theories have been advanced. These include a direct response to distension from perfusion pressure (myogenic theory or Bayliss effect), metabolic theory (local metabolic vasodilator products control arteriolar smooth muscle diameter directly), and a prominent role for innervation of cerebral blood vessels, although the role of autonomic factors in controlling autoregulation is not clear.

Factors influencing intracranial pressure include production of cerebrospinal fluid. This is produced by the choroid plexus at a rate of about 0.4 ml/min and is subsequently reabsorbed by the arachnoid villi. Other factors are cerebral blood flow, venous pressure—a raised venous pressure due to coughing or straining is reflected in a rise in intracranial pressure, and arterial CO&sub2;. An elevated Paco&sub2; causes marked vasodilation. The time course of this effect has been disputed but ranges of 20 s to 5 to 8 min have been quoted. Cerebrovascular disease reduces but does not abolish CO&sub2; responsiveness of vessels. Oxygen availability also has an effect on intracranial pressure, which increases in response to a lowered arterial Po&sub2; at levels below about 40 mmHg. The combination of hypoxia and hypercarbia has a synergistic effect on cerebral blood flow. High oxygen concentrations have a mild vasoconstrictor effect which is more marked under hyperbaric conditions. Brain bulk changes affect intracranial pressure, and the effect is determined by the extent and the rate of change. Compliance curves can be plotted for intracranial pressure against intracranial volume and these show that within physiological limits, compensatory mechanisms maintain a relatively constant intracranial pressure. However, when compensatory mechanisms are exhausted, further increases in intracranial volume (blood clot, etc) produce greater increases in intracranial pressure.

Normally, cerebral blood flow matches tissue perfusion needs; however areas of brain with localized damage, such as may occur near tumours, trauma, or infarcts, may receive blood flow in excess of their metabolic needs. This has been termed ‘luxury perfusion syndrome’ and is due to a localized loss of autoregulation. If carbon dioxide levels are raised, nearby intact autoregulated vessels will dilate causing a reduced blood flow through the areas of adjacent damaged non-autoregulating vessels, the ‘intracerebral steal effect’. If, however, carbon dioxide levels are lowered, normal vessels vasoconstrict and hence blood flow increases to the damaged areas (inverse steal or Robin Hood syndrome).

Trauma produces a large increase in brain bulk due to clot formation, localized oedema from damaged cells and cellular disruption. Gunshot wounds produce the greatest rise in intracranial pressure because of the effects of the velocity of the projectile. Intracerebral aneurysms in themselves rarely produce a large increase in intracranial pressure. However, an episode of bleeding is followed by a marked rise in pressure due to the clot formation and cerebral oedema associated with damage to neurones. Cerebral arteriovenous malformations may be functional space-occupying lesions even in the absence of haemorrhage. Tumours, abscesses, and hydrocephalus also affect intracranial pressure.

The ability of compensatory mechanisms to act is dependent on the rate of rise of intracranial pressure as well as the integrity of the responses and the region involved. A slow growing meningioma in the posterior fossa may reach substantial size before causing problems due to raised intracranial pressure, whereas a rapidly expanding intracerebral haematoma may cause pressure related symptoms quickly.

Osmotic diuretics produce a transient reduction in total body water, including that in the cerebrum. Mannitol is the principal agent currently employed, a dose of 1 to 1.5 g/kg being given IV over about 20 min. Mannitol may cause a rise in blood pressure if administered rapidly, and in the presence of blood–brain barrier damage it may leak out and cause fluid retention in these regions. For this reason, many anaesthetists prefer frusemide in doses of 20–40 mg IV, which produces a rapid diuresis without these potential adverse effects.

Hypoxia and hypercarbia have a synergistic effect, increasing cerebral vasodilation and hence intracerebral blood flow. Arterial oxygen tension should be maintained above 100 mmHg and Paco&sub2; should not exceed 40 mmHg (5.3 kPa). During anaesthesia, Paco&sub2; should be maintained in the range 25 to 30 mmHg (3.3–4 kPa). The elderly are less tolerant of prolonged hypocardia which has been shown to lead to postoperative memory impairment.

Cortisone, dexamethasone, and hydrocortisone have also been used to control intracranial pressure. The maximal effect is exerted on the oedema surrounding cerebral tumours. If steroids have been administered for a prolonged period of time, the risk of adrenal suppression becomes significant and gradual tapering off rather than abrupt cessation of therapy should occur.

Hypothermia is effective in reducing cerebral metabolic needs and hence provides protection against cerebral hypoxia. Technically it is very difficult to achieve: surface cooling methods are generally slow and cumbersome and the possibility of overshoot to below a core temperature of about 32°C leads to an increasing risk of ventricular irritability and difficult-to-treat ventricular arrhythmias occur. Cardiopulmonary bypass has been used intraoperatively but problems of haemostasis and technical difficulty have limited its adoption.

Lumbar drainage of cerebrospinal fluid may be used to increase exposure to the pituitary gland and to aneurysms which have not bled. Its use in patients with raised intracranial pressure is potentially hazardous due to the likelihood of herniation of the cerebellar tonsils through the foramen magnum, or ‘coning’. In certain cases neurosurgeons may use an intraoperative ventricular tap to drain cerebrospinal fluid and thus assist exposure.

Anaesthetic drugs affect intracranial pressure through their effects on cerebral vasodilatation and on the cerebral metabolic rate for oxygen. Some agents, such as methohexitone and enflurane, also have an effect on the seizure threshold. Postoperative somnolence or respiratory depression may cause significant problems following infusions of opiates and barbiturate. Anaesthetic doses of thiopentone reduce cerebral blood flow and CMRO&sub2;. For this reason, thiopentone has been widely used in neuroanaesthesia. However, its infusion is associated with delayed recovery because of its partial metabolism to an active, more slowly cleared metabolite (pentobarbitone) and to a saturation of the hepatic metabolic pathways. Ketamine causes a dose-dependent rise in cerebral blood flow of 61 per cent; if 67 to 70 per cent nitrous oxide is administered as well, there are further increases in CMRO&sub2; (by up to 16 to 20 per cent). For these reasons, it is not used in neuroanaesthesia.

Of the volatile anaesthetic agents, halothane is a potent cerebral vasodilator and causes an increase in cerebral blood flow of about 13 per cent. Enflurane also increases cerebral blood flow, but of greater significance is its production of EEG abnormalities. For these reasons neither agent is used in neuroanaesthesia. Isoflurane at doses below 1 per cent has been shown to produce minimal change in cerebral blood flow or CMRO&sub2; and for these reasons it is widely used in neuroanaesthesia. In concentrations above 1 per cent, isoflurane increases the intracranial pressure in hydrocephalic patients, and then its use is not recommended until the brain has been surgically decompressed.

The assessment of these patients may be very difficult due to the lack of co-operation accompanying confusion associated with raised intracranial pressure. The level of consciousness and whether this is stable or fluctuates should be noted. A history of early morning headaches, vomiting, or photophopia is indicative of raised intracranial pressure. If there is a significant impairment of conscious state, a history should be obtained from relatives, because of difficulties in eliciting drug allergies, medications, and previous anaesthetic problems from people with impaired levels of consciousness. Adequate physical examination is frequently difficult in patients who have significantly raised intracranial pressure because of lack of co-operation. A full neurological examination need not normally be performed by the anaesthetist.

Trauma patients should have a thorough examination to exclude possible sites of concealed blood loss or active bleeding: these may be very difficult to diagnose or treat once a craniotomy is proceeding. Assessment should also include likelihood of cervical spine damage, pneumothorax, or lung trauma, as these will have a marked bearing on intraoperative and postoperative management. The combination of significant head and chest injuries is usually an indication for postoperative respiratory support because of the importance of maintaining optimal oxygenation postoperatively and the difficulties of performing adequate chest physiotherapy in people with impaired consciousness. Patients with profound rises in intracranial pressure may manifest pulmonary oedema. The aetiology is uncertain but is believed to be mediated centrally via catecholamine release. Hypertension also frequently accompanies severe raised intracranial pressure.

Laboratory investigations should include serum urea and electrolytes, haemoglobin, and clotting studies. Patients over 40 years should also have chest radiographs and ECG performed.

A detailed account of the anaesthetic considerations in all neurosurgical conditions is not appropriate. However aspects relating to the more frequently encountered problems will be mentioned.

Management of trauma patients is influenced by the need to protect the patient's airway because of faciomaxillary damage and impaired conscious state, the need for respiratory support because of impaired respiratory drive or thoracic problems, management of acute blood loss from other sites, and the possibility of coexisting cervical spine injury.

Anaesthesia is usually induced on the operating table with monitoring equipment attached to the patient. All trauma patients should be assumed to have a full stomach and thus a rapid sequence induction technique is used. Cervical spine damage should usually be assumed unless it is actually excluded by imaging or, more rarely, by a good history of the injury sustained. Monitoring will be determined mainly by the other injuries sustained, but would normally include ECG, blood pressure, oximetry, and inspired oxygen content. A urinary catheter should be in situ. Maintenance of anaesthesia will vary with anaesthetist's preference and patient's condition; however use of agents causing cerebral vasodilation or increased cerebral metabolic rate, such as ketamine, halothane, or enflurane, are usually avoided.

Patients with severe multiple injuries or significant combined head and chest injuries usually require respiratory support in the intensive care unit. No hard and fast rules can be given regarding postoperative management, but the maintenance of optimal respiratory function is of paramount importance. The Pao&sub2; should be maintained above 100 mmHg (13.3 kPa) and the Paco&sub2; should be below 40mmHg (5.3 kPa). Antiepileptic medication is routinely given intraoperatively because of the risk of seizures.

Outpatient anaesthesia has progressed in both the United States and Europe from the performance of simple procedures under local anaesthesia to the total anaesthetic care of patients with complex medical problems. This allows costs per patient per operation and disruption of the patient's personal life to be reduced and also decreases the risk of exposure to hospital-acquired infections.

Patients scheduled for outpatient surgery must be willing and able to comply with both preoperative and postoperative instructions. Although initial experiences in most day surgery units were limited to ASA group I and II patients (American Society of Anesthesiologists classification of stress), some units are now accepting medically stable ASA group III patients. The imposition of a rigid age range is illogical as there appears to be no age-related increase in recovery time or incidence of postoperative anaesthetic complications.

Careful selection of patients is of prime importance to the efficient running of a day surgical unit. A full history and physical examination are required before surgery and this can be conducted either by the surgeon in the outpatient clinic or by the anaesthetist. The latter may see patients either in a special pre-anaesthetic assessment clinic, or by prior arrangement in the day-care unit. Details of the patient's past medical and drug histories can be obtained readily by a simple questionnaire completed at the out-patient clinic. In many centres, this questionnaire alone is used as the major screening tool in deciding the suitability of the patient for day case anaesthesia and surgery.

Preoperative assessment should also include the facility for performing simple laboratory tests, depending on the patient's age, state of health and concurrent drug history. For young healthy outpatients undergoing body surface surgery, there is no evidence of the value of any routine laboratory tests for male patients, and only a haemoglobin estimation is worthwhile for females. Patients with controlled chronic diseases (hypertension, diabetes mellitus) will require additional laboratory screening (electrolytes, urea or creatinine, blood sugar) as appropriate.

There is considerable disagreement between the United States and Great Britain over the length of surgery that can be performed on an outpatient basis. In the United Kingdom, much surgery is limited to less than 30 min duration, while in the United States, operations lasting 2 to 3 h are successfully conducted in many outpatient facilities. Studies have shown no correlation between anaesthetic time and recovery (or discharge) time.

One of the major causes of ‘surgical’ readmissions following out-patient surgery is inadequate pain relief; hence the adequate provision of pain relief is of paramount importance. Although injection of long-acting local anaesthetic drugs (bupivacaine, mepivacaine) at the site of incision may help to decrease postoperative analgesic requirements, pain can be controlled in many patients with conventional oral analgesic drugs such as codeine, paracetamol, mefenamic acid, and dextropropoxyphene. The recent introduction of the non-steroidal anti-inflammatory agents diclofenac and ketorolac, with their ‘morphine sparing effects’ has led to a major reconsideration of the methods of providing analgesia for the outpatient.

The use of premedication in the outpatient setting has been the subject of much debate and interest: although it has been stated (without supporting data) that premedication prolongs the recovery period, appropriate premedication (e.g. rapid and short-acting analgesic drugs) may decrease recovery times as a result of their ability to reduce anaesthetic requirements. Furthermore, premedication with analgesic or sedative drugs does not appear to increase the percentage of outpatients at risk of developing aspiration pneumonitis. However, excess administration of centrally acting sedative and analgesic drugs has been shown to impair motor co-ordination and psychomotor performance for up to 5 to 12 h.

Because outpatients may have a greater residual gastric volume than inpatients at the time of induction of anaesthesia, many authorities have recommended the routine administration of oral antacids, with or without gastrokinetic agents, before outpatient surgery. Unfortunately, colloid antacid suspensions can produce serious pulmonary sequelae if aspirated, and the reliability and efficacy of a single dose (30 ml) of sodium citrate has been questioned. Moreover, the use of oral antacids will per se increase the residual gastric volume. Histamine H&sub2;-receptor antagonists and the gastrokinetic agents metoclopramide and cisapride are of greater efficacy.

Since prolonged fasting does not guarantee complete gastric emptying, there is further controversy over the length of the period of fasting before outpatient surgery, especially as there is good evidence that preoperative hunger and thirst contribute significantly to preoperative anxiety. Furthermore, prolonged fasting may result in the patient arriving in the anaesthetic room with a plasma glucose concentration of less than 4 mmol/l. Ingestion of 150 ml of water as late as 2 h prior to surgery has been reported to decrease significantly the severity of thirst without increasing the gastric volume in fasted outpatients.

Postoperative nausea and vomiting is a common problem after general anaesthesia, and can delay discharge as well as leading to unexpected hospital admissions from outpatient facilities. Factors alleged to increase the incidence of nausea and vomiting include body habitus, type of surgery (laparoscopy, orchidopexy, strabismus surgery, therapeutic terminations of pregnancy), assisted ventilation using a face mask (with the resultant passage of air into the stomach) and poor choice of anaesthetic agents (e.g. combinations involving all or some of fentanyl, etomidate, nitrous oxide, isoflurane). Droperidol (5–75 &mgr;g/kg IV) has been found to be an effective prophylactic antiemetic in both children and adults undergoing treatment as outpatients. Other authors favour the combination of low dose droperidol (0.5–1.0 mg IV) and metoclopramide. Other promising treatments include transdermal hyoscine, and the newer drugs domperidone and ondansetron.

The ideal outpatient anaesthetic agent should provide rapid and smooth onset of hypnosis, intraoperative amnesia and analgesia, good surgical conditions, and a short recovery period with minimal or no complications. There are no good criteria for excluding endotracheal intubation as part of any outpatient anaesthetic technique, although the introduction of the largyneal mask has reduced the need for endotracheal intubations where neuromuscular relaxation is not required. Of greatest importance to the efficient and safe conduct of outpatient anaesthesia and surgery is the seniority of the operators. The outpatient facility is not the remit of either junior anaesthetists or surgeons in training; cases should be managed by senior personnel experienced in the types of anaesthesia and surgery best suited to the patients.

There is an increased awareness of deficiencies in the traditional management of peroperative pain. In recent years there has been rapid expansion of knowledge of both the mechanisms of pain and alternative approaches to pain control. One of the major problems in pain management has always been the objective assessment of pain and the problems related to observer bias by medical and nursing staff. By defining pain as ‘what the patient says hurts’, we can remove this bias. The inadequacy of the traditional intramuscular opioid regimen is generally acknowledged and the incidence of inadequate pain relief by this method varies between 25 and 70 per cent.

A patient's analgesic requirements may be affected by surgical factors such as site of surgery and type of incision, anaesthetic factors, including type of anaesthesia and incidence of vomiting, patient factors, including age and sex, concurrent drug therapy, and psychological factors, such as cultural background, past experience, the understanding of pain, fear, and anxiety, and the ability of the patient to cope. Past bad experiences can affect later treatment of pain.

Pain and its inadequate control may affect many body systems, resulting in morbidity. Decreased O&sub2; and increased CO&sub2; due to diaphragmatic splinting and impaired intercostal muscle function will cause a decreased tidal volume and decreased functional residual volume. This may lead to sputum retention, atelectasis, decreased cough and infection. Sympathetic stimulation causes tachycardia and hypertension which can lead to myocardial ischaemia, increased peripheral resistance, and increased O&sub2; consumption. Reduced mobility because of pain may increase the incidence of deep vein and pulmonary thromboembolism. Increased gastric statis and reduced intestinal motility increase the incidence of postoperative vomiting. Other problems include urinary retention, restlessness, anxiety, increased postoperative confusion and impaired sleeping, and endocrine effects including increases in cortisol, catecholamines, aldosterones, and ADH. This results in sodium and water retention, and the anti-insulin effects of those hormones worsen diabetic control.

Opioid receptors were first identified in 1973, and the endogenous opioids were isolated in 1975. The enkephalins, endorphins, and other endogenous peptides are released in response to pain. Five receptor sub-types have been identified: mu, delta, kappa, sigma, and epsilon (Table 11) 27.

Side-effects of opioids are generally dose-dependent. Respiratory effects include respiratory depression, impaired CO&sub2; response, and suppressed cough reflex.

Effects on the central nervous system include sedation, euphoria, miosis, nausea and vomiting, and muscle rigidity after high doses of opiates.

Other side effects include myocardial depression (dose-dependent), reduced myocardial oxygen consumption, vasodilation due to direct histamine release, bradycardia, delayed gastric emptying and gastrointestinal motility, and some opiates may cause spasm of the spincter of Oddi. Retention of urine and itching may also occur. Potency varies between opiates, but the maximal effect is similar.

The so-called multimodal approach to pain relief employs combinations of different agents and techniques to control postoperative pain. The pre-emptive use of analgesics allows doses of opioids to be reduced: once pain is established, pain relief requires higher total doses, with the associated increase in incidence of undesirable effects such as sedation and respiratory depression. Combining opioids with local anaesthetic agents and prostaglandin synthetase inhibitors (non-steroidal anti-inflammatory drugs) further reduces total opioid dosage and increases the safety margin. The role of anxiety in postoperative pain and the importance of reducing anxiety by explanation and reassurance should be appreciated and incorporated in overall pain management.

With this regimen, a fixed, prescribed dose of opioid is given as required. There are many problems with this system. Failure may occur because of pharmacokinetic factors, such as variability in absorption, distribution, metabolism, and excretion. Plasma concentrations of morphine are a poor reflection of the drug concentration in the central nervous system. Pharmacodynamic factors may also result in failure of pain relief: the ‘minimum effective analgesic concentration’ shows a four- to five-fold variability in surgical patients undergoing the same operation. Administration factors also play a role. The delay between the patient perceiving pain and nursing staff being able to administer opiate means that there is frequently a significant painful period between doses. The interpatient variability in dose requirement is not appreciated and patients with higher dose requirements are inadequately treated.

These can be given as solutions or tablets, or as sustained-release suppositories (e.g. morphine sulphate, sustained release tablets, MST)). However, the vomiting and delayed gastric emptying which follows some surgery means that drugs are poorly absorbed and have variable efficacy. In addition, some opioids undergo extensive first pass or presystemic metabolism in the walls of the intestine and the liver before entering the circulation; this reduces their bioavailability. The effective dose is less than the administered dose.

One of the disadvantages of intramuscular or intravenous bolus dosing is the constantly changing plasma drug concentration, causing either toxic effects or subtherapeutic ineffective concentrations over a period of time.

A drug infused at a constant rate takes five half-lives to reach steady state. For morphine, which has a T&subhalf; of 1.5 to 4 h, 20 h may be needed to reach a stable analgesic level. A loading dose is needed, yet this is often forgotten when altering infusion rates. Problems arise when a plateau is established which is too high or low compared with the therapeutic window. Drug or metabolites may accumulate, particularly when rates are not reduced with reducing requirements. Requirements reduce markedly after 24 to 48 h and at night during sleep, allowing for reduction of infusion rates.

Respiratory depression and hypoxia are a significant complication with all opioid administration techniques, but these are especially seen with constant rate intravenous infusions, and hence careful respiratory monitoring is mandatory. Because the rate of increase of the plasma opioid concentration is slow, the infusion allowed may not provide total analgesia, so necessitating ‘intravenous bolus top-up doses’.

This modification of intravenous infusion techniques uses a computerized syringe pump to deliver bolus doses whenever the patient presses a button. A lockout period ensures that the full effect of the dose is achieved before patient can deliver more drug. Advantages include reduction in swings in blood concentration and reduced side-effects, removal of observer bias or judgement of analgesic requirements and tailoring drug requirements to changing analgesic needs. Some studies have also suggested a reduced total requirement.

The most commonly used local anaesthetic agents are lignocaine, prilocaine, and bupivacaine. The duration of effect varies, but most blocks will provide 2 to 4 h of analgesia; occasionally the effect will last for 8 to 12 h. The advantages of this technique are that profound analgesia can be produced without opioid side-effects and without respiratory depression. However, although local blocks can block wound pain, tissue-related pain is not relieved. In addition, toxic side-effects of local anaesthetics limit the volume of agent which can be used and there is a risk of damage to adjacent structures or tissues, including intravenous or intra-arterial injection, pneumothorax, haemorrhage, infection, and permanent nerve damage.

Techniques for the administration of local anaesthetic blocks include wound infiltration, nerve blocks, epidural blocks, paravertebral blockade, and intrapleural blockade. The role of the last is still to be evaluated. The advantage of the last two techniques is that, unlike epidural blockade, there is no effect on limb or bladder innervation, and no sympathetic blockade.

These may be classified into the peripheral acting, non-steroidal anti-inflammatory drugs and centrally acting drugs such as paracetamol and nefopam. Paracetamol (acetaminophen) has analgesic and antipyretic effects, but no anti-inflammatory activity. High doses can cause hepato- and nephrotoxicity. Non-steroidal anti-inflammatory drugs all act by inhibition of prostaglandin synthase. However, their potency as inhibitors of this enzyme does not parallel their therapeutic efficacy; other factors are involved. Since they are weak acids, they accumulate in the parietal cells of the stomach and inhibit local prostaglandins that are responsible for a protective role in the mucosa. This action is possibly responsible for the high incidence of gastric irritation, although newer drugs have a lesser effect on the stomach.

Newer drugs which may have a role in postoperative pain relief are diclofenac, piroxicam, and ketoralac. They have several important properties: when used as adjuvants to conventional therapy; they have been shown to exhibit a ‘morphine-sparing’ effect; in conjunction with opioids, they may lessen the incidence of opioid-induced side-effects; and they can be given orally, rectally or intramuscularly. These drugs are the current first-line treatment for mild to moderate pain, and especially for bone pain. First choice drugs are the propionic acid derivatives (ibuprofen and ketoprofen, or naproxen); other drugs include salicyclates (where the adverse effects may be reduced by taking the drug with food) or benoylate; while third choice are drugs such as indomethacin, sulindac, and folmetin.

These have been advocated as suitable analgesic agents for postoperative pain relief without the side-effects of pure opioid agonists. The archetypal mixed agonist–antagonist was nalorphine, which acts as an antagonist at low doses. In higher doses, it has mild agonist properties. The partial agonists act at the &kgr; and &dgr; receptors as well as the &mgr; receptors. Examples include buprenorphine and butorphanol.

The epidural space is bounded by the ligamentatum flavum and dura. By placing a catheter in this space, continuous administration of epidural opiates is possible. More lipid soluble opiates tend to remain at the dermatome segments of administration, whereas morphine (water soluble) may spread via the cerebrospinal fluid to the brain-stem. Delayed respiratory depression, including apnoea, has been documented up to 18 to 24 h after morphine administration. This is less of a problem with lipid soluble drugs.

Advantages of the epidural route over conventional intravenous techniques include superior analgesia, improved lung function, less sedation, and improved mobility, as well as earlier hospital discharge. Disadvantages include pruritus, nausea, vomiting, and urinary retention with opiates.

Local anaesthetics such as bupivacaine cause sympathetic blockade which may lead to hypotension, and reduced concentrations are used to minimize this complication. Combinations of local anaesthetic and narcotic are synergistic at the spinal cord level and are being used increasingly. Other complications include epidural haematoma, neurological sequelae at time of catheter insertion or removal and, rarely, infection.

Many authors believe that spinal opioids are highly effective, and that they may produce superior analgesia to parenterally administered drugs. Compared with local anaesthetic agents given extradurally or intrathecally, opioids do not cause hypotension. However, the advantages are not seen in all patients. There may be incomplete analgesia (unblocked segments), and there is patient variability in dose–response relationships. In addition, techniques are time-consuming, technically demanding and must be carried out with full aseptic precautions, and there is a high incidence of nausea and vomiting, pruritus, and urinary retention. Respiratory depression may occur, and this may be delayed for several hours after drug administration, especially with morphine.

The body's fluid balance can be considered in terms of the quantity of fluid—the circulating blood volume and its distribution, and the quality of that fluid, as characterized by plasma or serum osmolality, sodium and potassium concentrations and pH (Table 13) 29.

The distribution of the circulating blood volume will not be covered here, except to emphasize its important role in the maintenance of normal cardiac output.

Abnormalities of fluid balance during surgery and the perioperative period

The homeostatic control of reabsorption and excretion of water and salts by the kidney is achieved through a number of different hormones and mechanisms, several of which are influenced by the stress responses to anaesthesia and surgery.

Water excretion is impaired during the perioperative period, as a result of increased secretion of ADH or AVP. Sodium excretion is also reduced, while excretion of potassium and nitrogen is increased, as a result of the increased levels of corticosteroids (glucocorticoids and mineralocorticoids) that are present in the body during this period. The increased release of ADH, which may persist for up to 72 h postoperatively, is due both to osmotic and non-osmotic factors. The latter pathways include stimulation of arterial baroreceptors through hypotension, stimulation of left atrial receptors by intermittent positive pressure ventilation, pain, the emotion or anxiety associated with surgery, hypoglycaemia, and &bgr;-adrenoceptor stimulation. Although morphine was generally believed to stimulate ADH release, this has subsequently been shown to be incorrect. In fact, opioids alone inhibit ADH release by increasing the osmoregulatory threshold to secretion. However, significant increases do occur due to surgical stimulation.

Sodium retention occurs as a result of stress factors accompanying anaesthesia and surgery. There is an increase in plasma aldosterone release from the adrenal glomerular cells, as well as an alteration in renal haemodynamics with redistribution of renal blood flow away from the tubular regions. The third factor is the so-called ‘third space effect’—secretion of fluid in spaces such as the bowel in patients undergoing prolonged abdominal surgery, pleural fluid, and peritoneal fluid (ascites).

All of the volatile anaesthetic agents so far investigated, including ether, cyclopropane, isoflurane, enflurane, and halothane, cause a decrease in urinary volume and an associated increase in urinary osmolality. The decrease in urinary volume is brought about by a decrease in renal blood flow and a secondary decrease in glomerular filtration rate. This reduction in urinary volume influences the quantity of perioperative fluid required by the patient.

Most of the factors so far described promote salt and water retention. For over 30 years, there has been conjecture over the presence of a ‘natriuretic factor’. This has now been isolated from cardiac atrial tissue and is a peptide that induces a diuresis, natriuresis, and moderate kaliuresis (atrial natriuretic factor, or atriopeptin). The peptide is synthesized as a 151 amino-acid sequence (pre-pro-atrial natriuretic factor), is stored within atrial myocytes as a 126 amino-acid pro-hormone (pro-atrial natriuretic factor or atriopeptigen), and is then cleaved to provide an active 28 amino-acid peptide. It has a short circulating half-life (about 3 min), and is metabolized in the kidney, as well as at other sites. Physiologically increased concentrations of atrial natriuretic factor are found after intravascular volume expansion which leads to atrial stretching, and after high sodium diets. Levels are also increased in cardiac disease, and in volume overloaded patients with chronic renal failure.

Atrial natriuretic factor increases the glomerular filtration rate without altering total renal blood flow. It causes vasoconstriction of the efferent glomerular vessels, inhibits angiotensin II, antagonizes the effects of noradrenaline, and blocks renin release, and hence aldosterone secretion. Data are conflicting on the effects of anaesthesia and surgery on atrial natriuretic factor levels in man. Fentanyl-isoflurane anaesthesia was associated with no increase in atrial natriuretic factor in patients undergoing infrarenal aortic clamping or carotid artery surgery, but there were increases following thoracic aortic clamping. Levels of atrial natriuretic factor seen during cardiac surgery for coronary artery grafting or valve replacement were higher than were seen in healthy controls. This increase in atrial natriuretic factor during bypass may act as the stimulus to promote the postsurgical diuresis that occurs despite the high circulating levels of ADH, glucocorticoids, and mineralocorticoids.

Other hormones which promote intrarenal vasodilatation and salt excretion include the prostaglandins (PGD&sub2;, PGE&sub2;, and PGI&sub2;), and the kinins (bradykinin and kallidin) which enhance the effects of the prostaglandins, and modulate the renin–angiotensin system.

Other perioperative hormonal changes influencing fluid balance include increases in levels of growth hormone and prolactin in response to the stress and trauma of surgery. Both of these hormones may lead to salt and water retention. There are conflicting data on the effects of surgery on oestrogen levels in the perioperative period, but increased oestrogen levels would lead to salt and water retention.

Perioperative fluid requirements depend on the length and complexity of the surgery. Requirements for routine surgical practice in the United Kingdom and the rest of Europe would be approximately 7 ml/kg of normal saline or 5 ml/kg of an isotonic solution containing sodium and potassium, such as Hartmann's solution (Ringer's sodium lactate). The anaesthetist should be aware of the risk of fluid overload, particularly in patients with cardiac or renal disease.

About 30 ml/kg of water is required over the first 24 h after surgery to achieve a fluid balance comparable with preoperative conditions. Sodium (1–2 mmol/kg) and potassium (1 mmol/kg) are also required. Measured extra losses, such as those due to blood loss or third-space effects, must also be replaced.

The hypovolaemic patient presents postoperatively with low blood pressure, low central venous pressure, low cardiac output and, probably, low pulmonary capillary wedge pressure. A number of therapeutic manoeuvres are available for the management of these low-perfusion conditions.

Since 1980, numerous studies have been published concerning critical incidents during anaesthesia. A critical incident is defined as some event which either contributed directly to an adverse outcome or which, if not rectified, would have caused an adverse outcome. Critical incident analysis was developed during the Second World War during the training of aircrew and has been widely adopted in anaesthesia in the various quality assurance programmes run at local and national levels. Resulting from this analysis, priority areas in education can be established to improve patient outcome from anaesthesia. Unfortunately, problems relating to the adequacy of checking of equipment before use continue to cause significant problems.

This is a major cause of anaesthetic morbidity. The traditional fasting period prior to surgery has become increasingly questioned in recent years. It may be harmful to deprive children of fluids for this amount of time, and more recent recommendations involve feeding with clear fluid to within 2 h of surgery. If emergency surgery is required waiting 4 h does not guarantee that gastric emptying will occur: following trauma, gastric emptying effectively ceases and hence delay of the surgery does not decrease the risks of aspiration. Most anaesthetists would now elect to induce anaesthesia as early as practicable and then use Sellick's manoeuvre (cricoid pressure) combined with a rapid sequence induction to reduce the incidence of aspiration. If aspiration occurs, prompt airway suctioning and the maintenance of adequate oxygenation are the cornerstones of therapy. Cricoid pressure should be applied to reduce the chance of further aspiration. The patient may need to be placed in the lateral position and oxygen saturation should be monitored. The urgency of surgery and the extent of inhalation should be considered when deciding whether to proceed or to defer surgery. If saturation remains satisfactory postoperatively in the recovery room, no further treatment is necessary. Inadequate or falling saturation is an indication for monitoring in a high dependency area. The role of steroids is debated and the use of prophylactic antibiotics is no longer encouraged.

Problems with the delivery of anaesthetic gases may rapidly lead to hypoxic brain damage unless prompt diagnosis and correction are instituted. The routine use of oxygen analysers and capnography with appropriately set alarms allows the early detection and correction of the majority of these faults before physiological changes ensue. Oximetry is a relatively late and non-specific detector of failure of gas delivery. There are numerous potential causes of a failure of gas delivery and removal, and these are outlined in Table 14 30. It should be noted that all of these problems have been reported.

Absorption of irrigation fluid following transurethral resection of the prostate may lead to neurological and cardiovascular changes. The incidence of this complication has been estimated to be as high as 3.9 per cent. Water has been replaced by glycine as an irrigant because of problems due to water toxicity. Glycine, however, may also be absorbed into the circulation, causing dilutional hyponatraemia, hyperammonaemia, and fluid overload. This causes neurological and circulatory changes. Neurological symptoms include apprehension, disorientation, nausea and vomiting, visual disturbances, and coma or seizures. Symptoms occur between 15 min after surgery has commenced up to several hours after surgery has ended. Cardiovascular changes include bradycardia, raised central venous pressure, hypertension, angina, and ECG changes.

Several factors affect the onset of the TURP syndrome including hydrostatic pressure of the irrigant, the experience of the surgeon (which affects the number of venous sinuses opened), duration of surgery, peripheral venous pressure, and the type of fluid used for irrigation. The clinical effects of hyponatraemia relate to both the speed of onset and the extent of the fall in serum sodium. A gradual fall is better tolerated neurologically than is an abrupt fall. As glycine is metabolized to other amino acids, ammonia is produced, and this contributes to the development of neurological sequelae, in combination with hyponatremia (Table 15) 31. In addition, elevated serum glycine levels (above 4000 &mgr;mol/l) have been associated with visual disturbances.

Diagnosis is generally made clinically, and hence spinal anaesthesia has become the most popular technique for this operation. This allows assessment of the patient's mental state to be made throughout the operation. In addition, co-existing respiratory disease is common in this group and spinal anaesthesia is well tolerated by such patients. Following clinical diagnosis, the surgeon should be informed whilst electrolytes and osmolarity are checked.

The osmolal gap (the difference between measured and calculated osmolalities) is increased in the TURP syndrome, due to the presence of an osmotically active particle (glycine) which contributes to measured osmolality but which is not included in the equation for estimation of osmolality. Equation 1

Mildly symptomatic patients experience nausea, vomiting, confusion, and visual disturbances and have a serum sodium above 120 mmol/l. Treatment involves cessation of surgery, reassurance, administration of a diuretic, and ophthalmic consultation if visual disturbances occur. In severe cases, involving loss of consciousness, other causes of loss of consciousness should be excluded (Table 16) 32.

Management involves assessment and support of the airway and ventilation in those with impaired conscious state. The degree of hyponatremia should be assessed: a serum sodium level below 120 mmol/l is life-threatening. The optimal rate of correction of hyponatraemia is controversial. While it is claimed that rapid correction of chronic hyponatraemia may lead to demyelination, the significance of this in acute hyponatraemia is uncertain. Hypertonic saline should be administered slowly until the serum sodium exceeds 120 mmol/l. Many use frusemide in addition to reduce fluid overload. Patients with renal failure may need dialysis to correct abnormalities.

The anaesthetized patient has lost his normal protective reflexes and is therefore vulnerable to a variety of traumatic problems including slips or falls during patient transfer or if sides are absent, pressure sores, corneal ulcers, diathermy burns, electrocution, and peripheral nerve palsies. Urinary bladder distension causes increased sympathetic drive and pain, tachycardia, or occasional arrhythmias in the recovery room.

This may occur when veins at a level above the heart are held distended by bone rather than collapsing due to atmospheric pressure. Situations predisposing to this include neurosurgical procedures performed in the sitting position and prone laminectomies, and it may also occur during total hip replacement during reaming of the femur. Rarely, gases may be injected into the circulation directly, for example during laparoscopy (carbon dioxide embolism). The features of air embolism depend on several factors, including volume of gas involved, speed of gas entrainment and presence of a patent foramen ovale where gas may reach the left side of the heart, causing symptoms in coronary and cerebral circulations.

Many factors have been shown to affect vigilance levels of anaesthetic personnel. The ergonomics of the anaesthetic machine have been increasingly examined in recent years. The original Boyle's machine has evolved into a complex piece of equipment with numerous modifications that comply with increased demand for safety features. On newer machines dials and controls have been regrouped into a tidier and more easily visualized unit. There has also been the need to produce a machine which is easy to clean following the increased number of ‘dirty cases’ currently being undertaken. The placement of monitors on the anaesthetic machine and the machine's placement with respect to the patient affect the ease and frequency of observations made by the anaesthetist.

When complications occur in the recovery room or in the perioperative period the importance of consultation with the anaesthetist who gave the anaesthetic cannot be over-emphasized. The anaesthetist may be able to suggest other causes for the problem, and may wish to see the patient to discuss these problems further.

Postoperative respiratory depression is most commonly due to opiates used for pain relief. However, other causes may include over-sedation, recurarization, or the development of pulmonary oedema. Consultation with the anaesthetist is important. When respiratory depression is severe, immediate respiratory support is necessary, using an Ambu bag or similar device.

Atelectasis may occur when inadequately treated pain limits chest movement, and pre-existing disease may increase the severity. Optimal analgesia and intensive physiotherapy are needed. Occasionally, bronchoscopy may be required to remove sputum.

Cardiac failure occurs when reduced myocardial contractility is unable to cope with the additional stress of fluid shifts and drug-induced depression of myocardial contractility. Clinical manifestations range from dyspnoea, which may mimic asthma in mild cases to frank pulmonary oedema with frothy sputum. Management involves optimization of oxygenation, posture, and diuretics and in severe cases intermittent positive pressure ventilation may be required. The ECG should be reviewed as ischaemia or arrhythmias will worsen cardiac output.

Postoperative hypertension may be due to pain, or to the withdrawal of preoperative antihypertensive medication. Optimal pain relief should be ensured before further antihypertensive medication is given. Initially, drugs should be given intravenously to reduce delays and to ensure that reliable blood levels are achieved.

Hypotension is most commonly due to inadequate fluid replacement. Drain tubes should be checked for correct function and concealed blood loss should be excluded. Following spinal or epidural anaesthesia, especially in patients whose operations were performed in the lithotomy position, fluid shifts can occur because of the loss of sympathetic tone. In the absence of demonstrable fluid problems, ischaemia, arrhythmia, and drug-induced myocardial depression should be excluded. Uncommon causes of postoperative hypotension include relative cortisol deficiency in steroid-dependent patients and subclinical hypothyroidism.

Atrial fibrillation is the most common arrhythmia arising postoperatively. Patients previously maintained on digitalis may suffer arrhythmias following cessation of therapy or due to poor absorption in the presence of abdominal conditions. Following ECG confirmation of the arrhythmia, specific therapy should be commenced. Rapid atrial fibrillation with haemodynamic instability may require intravenous verapamil or in very severe cases, DC countershock. Pre-existing disease, pain, poorly controlled hypotension, intraoperative events, and suboptimal oxygenation, especially in combination with hypertension or tachycardia, may lead to ischaemic events in the perioperative period.

Confusion is common in the perioperative period, especially in the elderly. Diagnosis is frequently difficult and management is often suboptimal. Diagnosis is frequently made by exclusion of possible causes and in many cases no obvious cause for the acute brain syndrome is ever discovered (Table 17) 33.

Relatively inexperienced house staff often have to manage patients with acute postoperative confusional states. Hypoxia must be excluded, either by oximetry or blood gas estimation. Review of the anaesthetic chart or recovery room notes will often reveal a likely cause; however, in the majority of cases no cause is ever ascertained. Management involves reassurance of the patient and staff, combined with measures to prevent damage to suture lines, intravenous equipment and wound drains. Sedation should be used cautiously if at all.

The anaesthetized patient is vulnerable to nerve injury because of the loss of protective reflexes. Nerves especially vulnerable are the ulnar nerve at the elbow, the lateral popliteal nerve during lithotomy, the brachial plexus (lower nerves during abduction, and upper plexus in the Trendelenburg postion) and the supraorbital nerve.

If nerve damage following surgery is suspected, early anaesthetic consultation is recommended, followed by neurological referral.

This is a frequent complaint especially in patients confined to bed following surgery. Inability to pass urine may be related to fluid deficiency, pain, or difficulties managing bottles and bedpans, especially in noisy or crowded wards.

Catheter-related problems, and postoperative urinary tract infections, although not relevant to the anaesthetic management, need careful follow-up.

The development of incontinence following spinal or epidural anaesthesia needs immediate follow-up by the anaesthetist in consultation with a neurologist.

Postoperative jaundice is an uncommon problem. Full clinical and biochemical assessment is important. Halothane hepatitis is a rare postoperative event and its diagnosis is generally made by exclusion. Many cases of ‘halothane hepatitis’ have turned out to be infection with cytomegalovirus or other viruses. Jaundice may also rarely occur following enflurane anaesthesia. Up to 1987 six cases had been reported; thus the incidence of jaundice is significantly lower than that following halothane anaesthesia and the mortality in established cases is also lower. Death occurred in 21 per cent of enflurane hepatitis cases compared with 50 per cent of halothane cases.

Management in the operating theatre should be supportive until other metabolic pathways eliminate the suxamethonium. Sedation should be administered to reduce unpleasant recollections of awakening whilst paralysed.

This is one of the most common and distressing postoperative complications. The incidence of vomiting ranges from 10 to 50 per cent depending on the type of surgery. Many factors contribute to the incidence of vomiting, including use of opiates, type of surgery (gynaecological surgery has a very high incidence), gastrointestinal distension (due to ileus), and early ambulation.

The anaesthetist should be notified immediately, to allow early dental consultation. Crowned, capped, and carious teeth are especially vulnerable to damage during anaesthesia and surgery. Damage may be caused at intubation, by oral airways, or during suctioning of the patient.

Skin rashes may be caused by reaction to anaesthetic agents, antibiotics, adhesive dressings, or skin prep solution. Management is generally conservative, but well demarcated lesions related to areas of adhesive or skin preparation require follow-up to prevent recurrence in future operations.

The incidence of sore throat following endotracheal intubation varies between 2 and 70 per cent of cases. Predisposing factors are the use of red-rubber endotracheal tubes, cigarette smoking, difficult or traumatic intubation, prolonged intubation, and prior laryngeal pathology. Conflicting results have been found with ‘high volume-low pressure’ cuff designs used for short-term intubation. The management of postintubation sore throat is conservative; reassurance is usually all that is required.

The development of muscle pains is common in fit, ambulant, muscular young subjects given suxamethonium to facilitate endotracheal intubation. The pain may be quite severe and resembles that caused by unaccustomed exercise. Management involves notification of the anaesthetist concerned, reassurance of the patient, and non-opioid analgesics.

During the 1970s and 1980s there was substantial interest in the possible deleterious effects of chronic exposure of operating room personnel to trace concentrations of volatile anaesthetic agents. Possible problems included increased abortion rate amongst female staff, decreased fertility rates, and effects on concentration and performance, as well as possible immunological effects. As a result of this concern, scavenging of anaesthetic agents has become widespread practice throughout the world.

Over the last decade, there has been debate over the real implications of these observations as a survey of practising hospital female doctors aged less than 40 years has failed to support these findings. The results to date reveal no significant correlation between miscarriage rates or incidence of congenital anomalies and hours spent in operating suites or the doctor's medical specialty. However, during the 1980s scavenging has been almost universally adopted in an attempt to alleviate any problems; in many countries it is mandatory. The belief that adoption of such scavenging measures has eliminated the problem has been disputed by recent evidence suggesting exposure levels are frequently quite high. Reasons include faulty scavenging, high gas flow techniques with frequent periods when the mask is not applied to the face, and the practice of leaving the gas flow running between cases.

Further legislation in the United Kingdom has been enacted as the Control of Substances Hazardous to Health (COSHH) regulations. These were adopted in 1990, and require assessments of the level of pollution in theatre environment to be made.

This may be active, when applied suction extracts the gases vented from the anaesthetic machine, or passive when the gases pass along large diameter tubing and are released into the atmosphere. Problems have occurred with both types of system. The application of suction directly to the lungs causing failure of ventilation of the patient can occur, or obstruction of tubing can lead to barotrauma. Currently, only active scavenging may be installed in new anaesthetic installations in the United Kingdom.

These may be employed in place of the traditional ‘T-piece’ apparatus used in the United Kingdom. They lead to a reduction in fresh gas flows of at least 50 per cent, so resulting in lower volumes of waste gases for removal as well as reduced volatile agent costs.

These can be used to reduce flows further, but they require higher levels of monitoring and have not achieved widespread acceptance.

This eliminates pollution but currently available agents are expensive, and the techniques are not suited to all cases (see earlier).

Improvements in practice such as turning flows off between cases, or not moving masks from the face during cases, further reduce pollution.

Improvements to theatre ventilation, including non-recycling of theatre air, lead to lower pollutant levels but are very costly.

The wider issue of environmental pollution by anaesthetic agents is less clear. However, it has been stated that the contribution by anaesthetic agents to ozone layer depletion is minimal, that the effects of nitrous oxide on the greenhouse effect are complex, and that the overall effect of anaesthetic agents on global pollution is minimal.

The risks of fires and explosions have declined since the decline in use of explosive volatile anaesthetic agents. Whilst these older agents had great merits, the proliferation of electrical devices in the operating suite has greatly increased the risks involved with their use.

This hazard continues to occur and has been commented on detrimentally by the various Colleges and Defence Unions.

This is of especial concern when surgery involves the upper airway and oesophagus. A variety of ingenious devices have appeared in an attempt to minimize the risk of ignition of the endotracheal tube (for example some anaesthetists have wrapped foil or foil-tape around conventional PVC or rubber endotracheal tubes). Cases have been reported in which the foil has unwrapped and ignition has nonetheless still occurred. A variety of purpose-built endotracheal tubes have appeared including those where aluminium powder is deposited on the surface to dissipate the generated heat, and those with saline filled cuffs and metal spirals embedded in the wall of the tube. In all cases the goal is to reduce the chance of ignition from a casual contact with the laser beam. Recently a fire occurring with one of these tubes has been reported. The ultimate problem relates to the enhanced flammability of plastics in the presence of high concentrations of oxygen or nitrous oxide. Interest and research have therefore centred on the use of total intravenous anaesthetic techniques (employing infusions of propofol or methohexitone), low inspired oxygen concentrations, and avoiding the use of nitrous oxide.

All faulty mains voltage equipment must be discarded or sent for repair. Problems have occurred with surgical headlights, heating blankets, and junction boxes.

These include diathermy into gas-containing viscera (during bowel surgery) or diathermy in a nitrous oxide inflated abdomen during laparoscopy; anaesthetic machine mishaps due to oil and grease contamination of pipelines resulting in explosions when exposed to high oxygen concentrations; and trailing ends of fibreoptic light sources left on paper drapes.

There are 25 to 100 carriers of HIV for each person with the clinical picture of AIDS. A recent estimate suggested that, on average, each anaesthetist is likely to encounter three HIV carriers in a year of clinical practice. Infection with HIV leads to inevitable damage to the immune system followed by the development of tumours or opportunistic infections. It is now generally accepted that most carriers will develop AIDS within 8 years of exposure and that death will usually occur within a year.

The HIV virus contains RNA and the enzyme ‘reverse transcriptase’ which generates DNA from RNA. The virally generated DNA becomes incorporated into the host's DNA, and subsequently codes for the production and release of virus particles which infect other host cells. It is this combination with host DNA which makes effective treatment and vaccination difficult at the present time.

Prevention remains the only therapeutic ‘option’ available. The public have been exposed to an extensive advertising campaign which has produced only a small change in social behaviour. Estimates on seroconversion following a single needlestick injury vary widely, but a figure of 1 per cent has been quoted. The delay between inoculation and seroconversion can be long, and the risks of seroconversion following mucous membrane contact (such as produced by the ‘aerosol’ of blood and bone fragments produced during orthopaedic surgery) have not been estimated. There are clear implications for anaesthetic and surgical practice regarding the precautions to be taken for all patients (irrespective of their HIV status) as well as presently unanswered questions regarding staff testing for HIV, routine patient testing for HIV status, and the exposure of trainees to patients known to have AIDS.

There is general agreement that, in the United Kingdom, the attitude of the public is considerably less legalistic than in North America. However, for consent to be legally valid, the doctor should provide sufficient details and information about proposals for treatment to enable the patient to form a proper decision as to his or her choices.

It is not necessary under English law to explain every possible complication of the proposed procedure, and the degree of explanation may well vary between individuals, having regard to factors such as education, cultural background, pre-existing anxiety, and urgency of surgery, as well as physical status. The term ‘informed consent’ has different meanings in different indexs. Similarly, the use of ‘blanket’ consent forms affords very little protection. Although legally consent does not require written documentation, it is to be recommended as the long intervals existing between incident and litigation may leave both parties unable accurately to recall what was said. A record that the consent was given after an adequate discussion of the potential risks and benefits is of greater value. Clinical judgement is required regarding the provision of an adequate explanation on the one hand, and needless discouragement of a patient from undergoing necessary surgery on the other. In emergency situations, the opportunity for detailed discussion is curtailed, and it is recommended that associated non-urgent procedures be deferred until the patient can give adequate consent.

It has been estimated that 0.5 per cent of patients undergoing balanced anaesthesia involving relaxants may recall intraoperative events. Of these, 10 per cent may experience pain or remember paralysis. In many cases the anaesthetist is not notified of this complication and the opportunity to discuss the circumstances leading to the awareness was lost. Of those patients pursuing litigation, in many cases the lack of a sympathetic acceptance of the legitimacy of the complaint and explanation of why it may have occurred has contributed to the seeking of legal redress.

When awareness has occurred the anaesthetist should be informed at the earliest opportunity so as to allow discussion whilst the patient is still in hospital. Advice from the Medical Defence Union recommends that the patient should be reassured that their experience was genuine, and that in the absence of faulty equipment or anaesthetic technique, their experience was a sequel to the use of balanced anaesthetic techniques where the volatile agent concentration is minimized to avoid potentially toxic effects.

Dreams may occur either during anaesthesia or at any time in the perioperative period. They do not usually involve the operation but may be very distressing. Awareness can usually be prevented by careful checking of the anaesthetic machine to detect for disconnections or faulty apparatus, and by intraoperative vigilance. However, awareness may be difficult to avoid under some circumstances (e.g. in the patient undergoing caesarian section, or the critically ill patient receiving general anaesthesia under life-threatening circumstances), and this highlights the importance of meticulous record keeping. Whether patients should be told before the operation of the risk of awareness has not been resolved; however, most would currently argue against this as routine practice.

Ever since the first cases of death associated with anaesthesia, both surgeons and anaesthetists have either formally or informally audited their complications. At present in the United Kingdom, it is the responsibility of the anaesthetist to report to the coroner (or his equivalent in Scotland and Northern Ireland) cases where either death has occurred within 24 h of surgery, or where it has occurred later but the patient has failed to recover complete consciousness after the operation. Similar mechanisms exist for reporting perioperative mortality in the United States and many other countries in the Western world. However, until recently, there were few data available to allow determination of the incidence of perioperative mortality in different patient groups.

In 1982, Lunn and Mushin published the results of their study on deaths occurring within 6 days of anaesthesia. This was a voluntary study encompassing five regions in the United Kingdom. Their conclusions were that 0.6 per cent of patients die within 6 days of surgery and that in only 1 in 10 000 cases was anaesthesia solely responsible for death.

In 1987, the Confidential Enquiry into Perioperative Deaths (CEPOD) was published. This study spanned 30 days after surgery and involved three regions in the United Kingdom; it excluded certain patient groups (e.g. cardiac surgery patients, children and neonates, obstetrics patients). The last group is audited in the United Kingdom by the Triennial Confidential Enquiry into Maternal Mortality. Only three deaths were judged solely due to anaesthesia, giving a rate of 1 in 185 000. The main conclusions made were: the need for the availability of proper recovery facilities; the provision and utilization of essential monitoring; and the adequate supervision of trainees. Of particular importance is the consultation between surgeon and anaesthetist regarding emergency cases, and those patients suffering from intercurrent illness. Too frequently, there is inadequate notification to allow optimization in management of those patients suffering from multisystem illness.

The toxicity of volatile anaesthetic agents has been known since the introduction of diethyl ether and chloroform. Concern over modern agents led to the National Halothane Survey in the United States by Bunker in 1969. It was found that the incidence of hepatic toxicity following halothane was no greater than that after the earlier agents. Further studies highlighted the problem of ‘unexplained hepatitis following halothane’.

The quoted incidence for ‘halothane-associated hepatitis’ varies between 1:2500 and 1:36 000 exposures, and is substantially lower in children at between 1:82 000 to 1:200 000. Halothane does not function as a classical liver toxin; there is no dose-dependent degree of liver damage, nor a recognized mechanism of action, nor are its effects consistent in different species. Investigations have centred on the various metabolic pathways halothane may follow under different circumstances. Halothane may undergo reductive or oxidative metabolism with production of trifluoroacetic acid, and inorganic chloride, bromide, and fluoride. The diagnosis of halothane hepatitis is one of exclusion, as there is no pathognomonic test available. The recommended interval between halothane anaesthetics recommended by the Committee on Safety of Medicines is 3 months (although the logic of this may be questioned in the light of an assumed immune aetiology in at least some cases). It is also recommended that halothane is contraindicated if undefined fever and jaundice have developed after halothane anaesthesia. Cirrhosis, chronic hepatitis, and liver tumours were not seen as contraindications.