British Journal of Anaesthesia 85 (1): 80±90 (2000) Anaesthetic management of patients with diabetes mellitus G. R. McAnulty1, H. J. Robertshaw2 and G. M. Hall1* 1Department of Anaesthesia and Intensive Care Medicine, St George's Hospital Medical School, London SW17 0RE, UK. 2Department of Anaesthesia, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK Br J Anaesth 2000; 85: 80±90Keywords: complications, diabetes; blood, glucose; hormones, insulin; metabolism, The prevalence of diabetes mellitus in both adults and recommendations for new diagnostic criteria for diabetes children has been steadily rising throughout the world for mellitus.1 106 Both bodies advise a reduction in the threshold the past 20±30 yr.29 55 97 Recent changes in diagnostic limit for fasting plasma glucose concentrations and reaf®rm criteria,if widely adopted,will probably also lead to more a more aetiologically based nomenclature. The terms type 1 patients being classi®ed as having diabetes.16 Inevitably, (pancreatic B-cell destruction) and type 2 (defective insulin diabetic patients presenting for incidental surgery,or secretion and,usually,insulin resistance) diabetes are surgery related to their disease,will place an increasing recommended to replace completely the frequently mis- burden on anaesthetic services. Con¯ict will occur between leading terms `insulin-dependent' and `non-insulin-depend- an economic need to minimize hospital stay and traditional ent' diabetes. The ADA has speci®ed that the diagnosis of approaches to managing perioperative diabetic patients that diabetes mellitus should be made if a `casual' (random) rely on a period of inpatient preoperative `stabilization'.
plasma glucose value in an asymptomatic individual is Better glycaemic control in diabetic patients undergoing >11.1 mmol litre±1. If a fasting plasma glucose is >7.0 mmol major surgery has been shown to improve perioperative litre±1 (6.1 mmol litre±1 blood glucose) in an asymptomatic mortality and morbidity.44 90 Simple avoidance of hypogly- individual,the test should be repeated on a different day and caemia and gross hyperglycaemia are no longer adequate in a diagnosis made if the value remains above this limit. The the light of this knowledge. While there can be little ADA de®nes fasting plasma glucose concentrations be- argument about the management of diabetic patients tween 6.1 and 7.0 mmol litre±1 (5.6±6.1 mmol litre±1 blood undergoing major procedures,their management for minor glucose) as representing `impaired fasting glycaemia'. The surgery is an increasing dilemma. Under what circum- WHO also recommends that a diagnosis of diabetes mellitus stances are day-case anaesthesia and surgery appropriate? be made if a random plasma glucose concentration is >11.1 Does admission on the day of surgery add to the risk for the mmol litre±1 (venous whole blood >10.0 mmol litre±1). It diabetic patient? What investigations,if any,are needed to can also be diagnosed with a fasting plasma glucose assess the cardiovascular system of an asymptomatic concentration of >7.0 mmol litre±1 and a second similar diabetic who presents for major surgery? Unfortunately, test or an oral glucose tolerance test producing a result in the there are few data to provide answers to these questions. An diabetic range.
understanding of the pathophysiology of diabetes and of the The change in the fasting plasma glucose concentra- importance of recent research should improve the peri- tions used to de®ne diabetes and the role of a standard operative care of diabetic surgical patients. This review will oral glucose tolerance test may make it dif®cult to discuss some recent developments in the ®eld. It will not compare epidemiological studies using these new criteria provide `recipes' or algorithms for management. These can be found in any of the standard texts.
with those using previous ones. Inevitably,some indi- viduals will be diagnosed as having diabetes using criteria based solely on (lower) fasting plasma glucose concentrations who would not have been so diagnosed under the earlier de®nitions. There will be others who would have ful®lled the de®nition using an oral glucose Recently,both the American Diabetes Association (ADA) tolerance test but who will have acceptable fasting and the World Health Organization (WHO) published values. Thus it is likely that the new de®nitions will Ó The Board of Management and Trustees of the British Journal of Anaesthesia 2000 de®ne as diabetic a group of glucose intolerant individ- processes are inhibited by minimal levels of insulin secretion and are rare in type 2 diabetics unless there is an In addition to the two common types of diabetes,a additional stress such as sepsis or dehydration.122 number of causes of glucose intolerance can be de®ned Obviously,both groups are subject to the effects of according to a speci®c causal or pathological process. hyperglycaemia.
Gestational diabetes is glucose intolerance which has its Diabetics are at increased risk of myocardial ischaemia, onset in,or is ®rst diagnosed during,pregnancy. The cerebrovascular infarction and renal ischaemia because of severity varies and the de®nition applies whether or not their increased incidence of coronary artery disease,94 insulin is administered in treatment. Women with diabetes arterial atheroma51 and renal parenchymal disease.14 diagnosed before pregnancy are de®ned as having `diabetes Increased mortality is found in all diabetics undergoing mellitus and pregnancy',not gestational diabetes.1 The surgery44 90 and type 1 diabetics are particularly at risk of neonatal outcome of type 1 diabetic women who become post-operative complications.111 Increased wound compli- pregnant is poor. Their infants are approximately ®ve times cations are associated with diabetes24 64 72 126 and more likely to be stillborn and 10 times more likely to have anastomotic healing is severely impaired when glycaemic congenital malformations than those born to non-diabetic control is poor.118 mothers.10 Management in a specialist centre may improve The `stress response' to surgery is associated with the incidence of perinatal mortality.34 Abnormally in- hyperglycaemia in non-diabetic patients as a result of creased membrane transport of glucose,even in mothers increased secretion of catabolic hormones in the presence of whose diabetes is well controlled,may explain the continu- a relative insulin de®ciency. This de®ciency arises from a ing high rates of congenital malformations (particularly combination of reduced insulin secretion41 and insulin macrosomia) despite improved treatment.48 Increasing the resistance.109 Insulin resistance may result,in part,from the frequency of insulin administration from two to four times increase in secretion of catecholamines,cortisol and growth daily during pregnancy can lead to better maternal hormone42 and involves an alteration of post-receptor glycaemic control with a lower incidence of neonatal binding of insulin and subsequent reduction of trans- hypoglycaemia and hyperbilirubinaemia without increasing membrane glucose transport.79 Some,at least,of the metabolic effects of the suppression of insulin secretion There is a number of rare genetic causes of glucose are reversed by intraoperative insulin infusion37 and both intolerance. Among these are defects of B-cell function oral and i.v. perioperative administration of glucose (formerly called maturity-onset diabetes of the young,or enhance postoperative glucose utilization rates.56 62 80 MODY) and defects in insulin action (formerly called type A insulin resistance). Diffuse diseases of the exocrine pancreas (such as pancreatitis),speci®c viral infections which destroy pancreatic B cells (rubella,Coxsackie B, Adverse effects of hyperglycaemia cytomegalovirus,mumps and others) and immune-mediated The consequences of a reduction in,or complete lack of, processes (insulin autoantibodies or insulin receptor anti- insulin-mediated metabolic processes can be classi®ed bodies) can also lead to a `diabetic state'.1 Endocrinopathies according to chronicity and to histopathological effects.
associated with excess secretion of counter-regulatory Acute consequences of untreated,or inadequately treated, hormones (such as growth hormone,cortisol,glucagon diabetes mellitus include dehydration (resulting from the and epinephrine) can lead to hyperglycaemia.
osmotic diuretic effect of glycosuria),acidaemia (because A number of drugs can induce glucose intolerance either of accumulation of lactic and/or ketoacids),fatigue,weight by inhibiting the secretion of insulin or by interfering with loss and muscle wasting (because of lipolysis and the peripheral action of insulin.1 In anaesthesia,glucocorti- proteolysis in absolute insulin de®ciency). Ketoacidosis is coids and adrenergic agonists are most frequently impli- rare in type 2 diabetics but is frequently a presenting cated. The new oral corticosteroid,de¯azacort,may be less symptom of type 1 disease. It is a medical emergency that `diabetogenic' than prednisolone or betamethasone.2 still carries a considerable mortality rate of up to 15%.4 49 `Metabolic syndrome' (also called syndrome X or insulin The mortality of hyperosmolar non-ketotic hyperglycaemic resistance syndrome) is a non-causally linked cluster of coma in type 2 diabetics may be even greater,63 probably symptoms which carry a high risk of macrovascular disease. re¯ecting a more elderly population with a higher incidence The cluster includes impaired glucose tolerance or diabetes, of co-existing disease.
insulin resistance,raised arterial pressure,raised plasma Ketoacidosis is treated by rehydration and insulin triglycerides,central obesity and microalbuminuria.1 infusion with frequent measurements of serum electrolytes and acid±base status. Sequential estimations of blood b-hydroxybutyrate concentrations and concomitant con- tinuation of intensive insulin therapy may expedite treat- Type 1 diabetics completely lack insulin secretion,making ment.124 Non-ketotic hyperglycaemic coma is frequently them prone to lipolysis,proteolysis and ketogenesis. These precipitated by infection and is commonly associated with multi-organ system dysfunction. Blood glucose concentra- may be frequently too short to avoid periods of hypoinsu- linaemia and subsequent risk of lipolysis and proteolysis in Chronic effects of diabetes can be divided into micro- patients with no endogenous insulin secretion.
vascular (including proliferative retinopathy and diabetic Insulin is synthesized in the pancreas as part of a longer- nephropathy),neuropathic (autonomic and peripheral chain protein called proinsulin. This is cleaved by mem- neuropathies) and macrovascular complications (athero- brane-bound proteases producing the polypeptides insulin sclerotic disease). The incidence of microvascular and and C-peptide. These two polypeptides are secreted into the neuropathic complications in types 1 and 2 diabetics is circulation in equimolar amounts. C-peptide is useful similar when adjusted for duration of disease and quality of experimentally in determining native insulin production in glycaemic control. The cumulative lifetime incidence of type 2 diabetic subjects receiving insulin. It was once proliferative retinopathy,proteinuria and distal neuropathy thought that C-peptide had no physiological role other than is roughly 50% for both type 1 and type 2 diabetics. This facilitating the folding of the proinsulin molecule. However, implies that the primary cause of these complications is more recent studies point to a possible role for C-peptide in hyperglycaemia itself,as the underlying metabolic path- glucose transport in skeletal muscle,renal tubular function ology is different for type 1 and type 2 disease.31 and in the prevention of autonomic neuropathy.119 Macrovascular complications (as measured by rates of coronary artery,cerebrovascular and peripheral vascular disease) are also similar for type 1 and 2 diabetics Hypoglycaemic therapy (cardiovascular mortality is 30±54% for type 1 and 38± Type 1 diabetics require insulin. Type 2 diabetics may 41% for type 2 diabetes).31 In type 2 patients,at least, require insulin but,in many cases,maintain reasonable abnormally high concentrations of plasminogen activator glycaemic control with an appropriate diet and often the use inhibitor-1 (PAI-1) and,therefore,impaired ®brinolysis, of oral hypoglycaemic drugs.
have been implicated in the accelerated rates of develop- Therapeutic insulin may be extracted from beef (now rarely used) or pork pancreas,or synthesized using Improved glycaemic control has a bene®cial effect on recombinant DNA technology from Escherichia coli.6 The microvascular and neuropathic complications in type 2 amino acid sequences of insulin differ somewhat between diabetes.114 Although there is probably no adverse effect,83 species; however,modifying porcine insulin can produce improvement in glycaemic control alone appears not to human-sequence insulin. It was hoped that the replacement improve the incidence of macrovascular disease in these of animal- by human-sequence insulins would reduce the patients.114 However,tight control of blood pressure (with induction of antibodies and therefore insulin resistance,but an angiotensin-converting enzyme inhibitor or a b-blocker) clinical trials have been disappointing.66 in patients with type 2 diabetes and hypertension reduces the The three types of insulin preparation are classi®ed risk of diabetes-related death,including that secondary to according to their length of action. Soluble insulins have a macrovascular complications,as well as the risk of other rapid onset and short duration of action (depending upon the diabetes-related complications and eye disease.115 116 route of administration). When injected subcutaneously the duration of action is from 30 min up to 8 h with a peak at 2±4 h. Human-sequence soluble insulin has a slightly shorter onset time and duration of action. Insulin lispro,a recently introduced recombinant human insulin analogue, has an even shorter duration of action. Soluble insulin Insulin is secreted into the bloodstream from pancreatic injected i.v. has a half-life of approximately 5 min.6 B cells via the portal system so that there is normally a Longer-acting insulin preparations are made with sus- portal±peripheral insulin concentration gradient which can- pensions of insulin with either protamine (`isophane insu- not be mimicked by subcutaneous or i.v. insulin adminis- lin') or zinc (`crystalline insulin') salts or both together.
tration. Additionally,even the most sophisticated arti®cial They are often administered in combination with soluble insulin delivery systems cannot hope to replicate the insulin to obtain rapid onset together with a long duration of complex local interaction between the B cells and A,D action.6 They are not suitable for i.v. use. Long-acting and PP cells of the islets of Langerhans (which secrete insulins may act for up to 36 h for animal-91 and 24 h for glucagon,somatostatin and pancreatic polypeptide,respect- human-sequence preparations.47 ively) and the effects of the extrapancreatic neurohormonal There are four groups of oral hypoglycaemic agents: the system. Insulin secretion in response to varying states of sulphonylureas,the biguanides,the (recently developed) feeding or starvation changes by 20- to 50-fold and thiazolidinediones and modi®ers of glucose absorption from maintains a basal insulin secretion during the fasting state. the gut. In the main,sulphonylureas enhance the secretion of Insulin administered subcutaneously,even if timed opti- insulin in response to glucose and increase sensitivity to its mally,will inevitably have inadequate peak concentrations peripheral actions. Biguanides (metformin is the only for expected postprandial periods,and its duration of action compound in this group available in the UK) promote glucose utilization and reduce hepatic glucose production. solutions with a concentration of insulin of >400 ng ml±1 Thiazolidinediones,which are still under clinical evaluation (~10 U litre±1) the effect is minimal.8 However,signi®cant (and currently under a cloud because of reported hepato- amounts of insulin may be adsorbed on to giving sets, toxicity),enhance insulin action in the periphery and inhibit particularly if they have a relatively high surface area, hepatic gluconeogenesis,perhaps via a speci®c receptor thereby reducing initial rates of insulin delivery if a high- mechanism. The a-glucosidase inhibitor,acarbose,sup- volume,low-insulin concentration regimen is used.69 More presses the breakdown of complex carbohydrates in the gut consistent delivery can be achieved with more concentrated and therefore delays the rise in postprandial blood glucose solutions of lower volume administered from a syringe.92 When normal oral nutrition is not possible,parenteral Intensive,effective glycaemic control of type 2 diabetes administration of carbohydrate is required to safeguard results in a reduction of microvascular,but probably not against inadvertent hypoglycaemia and excessive catabo- macrovascular,complications of the disease.31 114 Where lism. Safety is always a concern when insulin infusions are adequate control can be achieved (haemoglobin A1c administered. Glucose±insulin±potassium (GIK) systems, concentration 7±8%31) there is no clear advantage for any such as the Alberti regimen,are inherently safe because they therapeutic agent; oral hypoglycaemics and insulin have provide insulin and glucose in the same solution.107 With similar effects.76 Metformin may be a better choice in obese separate glucose and insulin infusions one may be stopped type 2 diabetics. It was associated with a lower incidence of inadvertently with potentially disastrous consequences.
mortality and diabetes-related morbidity when used as a However,separate infusions were preferred by nursing ®rst-line treatment compared with either sulphonylureas or staff and resulted in marginally improved perioperative insulin in the recently-reported UK Prospective Diabetes glycaemic control when compared with a GIK system in one Study (UKPDS).113 However,addition of metformin to randomized controlled trial of 58 surgical patients.101 Fifty patients receiving sulphonylureas in the UKPDS was per cent glucose solutions containing 0.25 or 0.5 U insulin associated with a worrying increase in mortality. Despite ml±1 can provide amounts of glucose and insulin equivalent concerns about rare but potentially lethal lactic acidosis, to the more conventional systems using 10% glucose and which may be more likely in the elderly,100 in association with renal failure25 and hepatic failure and after surgery,71 avoid the administration of large volumes of free water.68 metformin is well tolerated and less likely to cause However,the hypertonic 50% solution needs to be infused hypoglycaemia than sulphonylureas or insulin.28 113 Interest in the potassium channel-blocking effect of sulphonylureas and,hence,interference with myocardial ischaemic preconditioning,has increased recently.5 The metabolic challenge of surgery for the Glimepiride may not block potassium channels,58 but diabetic patient angioplasty patients receiving sulphonylureas have greater mortality and morbidity than those given insulin.30 The The immediate perioperative problems facing the diabetic general implications of this observation are not clear but, patient are: (i) surgical induction of the stress response with until data from well-conducted studies are available,it catabolic hormone secretion; (ii) interruption of food intake, would seem prudent to convert patients taking sulphonyl- which may be prolonged following gastrointestinal proced- ureas to insulin several days before cardiac or other major ures; (iii) altered consciousness,which masks the symptoms surgery or procedures where myocardial perfusion may be of hypoglycaemia and necessitates frequent blood glucose estimations; and (iv) circulatory disturbances associated with anaesthesia and surgery,which may alter the absorp- Surgery evokes the `stress response',that is,the secretion Type 2 diabetics not receiving insulin and undergoing minor of catecholamines,cortisol,growth hormone and,in some surgery usually can be managed satisfactorily without cases,glucagon. These hormones oppose glucose homeo- insulin.108 However,diabetic patients scheduled for major stasis,as they have `anti-insulin' and hyperglycaemic surgery,who are receiving hypoglycaemic medication or effects. Gluconeogenesis is stimulated and peripheral glu- who have poor glycaemic control,should be established on cose uptake decreased. Although diabetics need increased insulin therapy preoperatively. Continuous i.v. infusion of insulin during the perioperative period,requirements for insulin is a better option than intermittent s.c. bolus glucose and insulin in this period are unpredictable and regimens11 and,at least in perioperative cardiac surgical close monitoring is essential,especially in the unconscious patients,may be associated with improved outcome.27 or sedated patient.
Although intermittent i.v. bolus regimens are still used,87 Diabetic patients established on longer-acting insulin are this approach is dif®cult to recommend.38 45 at risk of hypoglycaemia if regular food intake is inter- Adsorption of insulin on to the surface of syringes,i.v. rupted,and of lipolysis and proteolysis if insulin therapy is ¯uid bags and i.v. giving sets is an unavoidable problem. In delayed. Postoperative wound healing and infection may be in¯uenced by the adequacy of perioperative glycaemic Glycosylated haemoglobin (HbAc1) measurement has no value in the perioperative period but is a valuable guide to long-term glycaemic control.31 If HbAc1 values have been consistently >8% it is probable that microvascular compli- Options for the perioperative management of cations of diabetes are present.
diabetesThe main concern for the anaesthetist in the perioperative management of diabetic patients has been the avoidance of Anaesthetic technique and the diabetic harmful hypoglycaemia; mild hyperglycaemia has tended to patient be seen as acceptable. This has been attributed to the Anaesthetic techniques,particularly the use of spinal, dif®culties of measuring blood glucose when the reduced epidural,splanchnic or other regional blockade,may level of consciousness perioperatively masks signs and modulate the secretion of the catabolic hormones and any symptoms of hypoglycaemia. However,in the past decade residual insulin secretion. The perioperative increase in the availability of more accurate and easy-to-use glucose circulating glucose,epinephrine and cortisol concentrations monitors,with evidence that good glycaemic control found in non-diabetic patients exposed to surgical stress improves short-term outcome,makes the practice of under general anaesthesia is blocked by epidural anaesthe- `permissive hyperglycaemia' unacceptable.
sia.39 125 The perioperative infusion of phentolamine,a One survey of anaesthetic practice in the Oxford region of competitive a-adrenergic receptor blocking drug,decreases the UK suggests that anaesthetists are likely to manage the glycaemic response to surgery by partially reversing the hyperglycaemia in perioperative diabetic patients more suppression of insulin secretion.75 Interestingly,a small aggressively now than they did in 1985.22 However,of the study of non-diabetic patients showed preservation of the 172 respondents in this survey,22% still preferred to insulin response to a bolus of glucose after the use of low, maintain blood glucose at >10 mmol litre±1 in diabetic but not high,spinal anaesthesia.40 This implies that basal patients and 2% preferred a value of >13 mmol litre±1. The islet cell secretion is maintained by b-adrenergic stimula- vast majority of respondents maintained glycaemic control tion. Whether extensive spinal blockade is detrimental in for type 1 diabetic patients undergoing major surgery with type 2 diabetics is not known. Cataract surgery in type 2 glucose and insulin infusions,either separately or com- patients using local analgesia,when compared with general bined. Nearly 90% of respondents did not consider it anaesthesia,was associated with much less disruption of necessary,in type 2 diabetics undergoing minor surgery,for glucose metabolism: blood glucose,lactate,b-hydroxybu- there to be any greater intervention than omitting the usual tyrate,serum cortisol,insulin and plasma non-esteri®ed hypoglycaemic therapy and avoidance of glucose-contain- fatty acid concentrations were measured perioperatively.3 ing i.v. solutions. Surprisingly,17% of senior anaesthetists Diabetic patients undergoing surgery with neural block- had the same approach to type 2 diabetics undergoing major ade will usually resume oral intake earlier than after general surgery. Cost and inconvenience may in¯uence decisions anaesthesia. It is now common practice in cataract surgery about the intensity of blood glucose management and,until to allow normal oral intake and hypoglycaemic therapy recently,there has been little evidence to support strategies throughout the perioperative period. In a series of 12 000 aimed at tightening glycaemic control.35 Between the two cataract extractions under local anaesthesia,in which extremes of a diet-controlled stable type 2 diabetic patients were not starved,eight patients showed evidence presenting for minor surgery and the `brittle' type 1 patient of brain stem anaesthesia,and one developed cerebral undergoing major abdominal surgery,about whom there is spread of local anaesthetic solution. In only one patient was little argument,there remains considerable disagreement surgery postponed because of persistent nausea.43 However, about the ideal regimen for managing blood glucose.
the possibility of having to convert a regional technique to general anaesthesia may militate against this practice in other forms of surgery. At present,there is no evidence that regional anaesthesia alone,or in combination with general The advent of semi-automated devices has improved the anaesthesia,confers any bene®t in the diabetic surgical accuracy of measurement of blood and capillary glucose patient,in terms of mortality and major complications.
concentrations in both the community and hospital.7 For Regional anaesthesia may carry greater risks in the these machines to be effective they must be calibrated diabetic patient with autonomic neuropathy. Profound regularly and people using them must be trained.
hypotension may occur with deleterious consequences in a Recent work has suggested that measurement of circu- patient with co-existing coronary artery,cerebrovascular or lating b-hydroxybutyrate concentrations may be helpful in renovascular disease. The risks of infection and vascular treating acutely unstable diabetes70 124 and the development damage may be increased with the use of regional of a bedside device will enable the usefulness of sequential techniques in diabetic patients; epidural abscesses occur estimations of ketonaemia to be assessed.70 more commonly following spinal and epidural anaesthe- sia.54 77 Conversely,a diabetic peripheral neuropathy with dif®cult laryngoscopy and intubation. Stiffness of the presenting after epidural anaesthesia may be confused fourth and ®fth interphalangeal joints is a common feature with an anaesthetic complication of regional blockade.50 and the resulting alteration in palm print may be a good predictor of dif®cult intubation.74 However,in one retro- spective review of the anaesthetic records of 725 patients who underwent renal and/or pancreatic transplantation (of Induction agents may affect glucose homeostasis periopera- whom 209 were diabetic),none were reported as having tively. Etomidate blocks adrenal steroidogenesis and hence `moderate to extreme dif®culty' of laryngoscopy. A total of cortisol synthesis,by its action on 11b-hydroxylase and 4.8% of the diabetics presented `minimal to moderate' cholesterol cleavage enzymes,and consequently decreases dif®culty for intubation compared with 1.0% of the non- the hyperglycaemic response to surgery by approximately 1 diabetics. All were intubated successfully although one was mmol litre±1 in non-diabetic subjects.26 The effects on intubated electively with the aid of a ®bre-optic ¯exible diabetic patients have not been established.
Benzodiazepines decrease the secretion of ACTH,and so the production of cortisol,when used in high doses during surgery.18 They reduce sympathetic stimulation but,para- Coronary heart disease doxically,stimulate growth hormone secretion and result in Diabetic men are more than four times as likely,and women a decrease in the glycaemic response to surgery. These ®ve times as likely,to have coronary heart disease (CHD) effects are minimal when midazolam is given in usual than non-diabetics.15 The annual cardiac event rate for sedative doses,but may be relevant if the drug is given by untreated patients is 2.5% and even treated patients have continuous i.v. infusion to patients in intensive care.
more aggressive coronary disease and experience worse High-dose opiate anaesthetic techniques produce not only outcomes at any stage of the disease.96 Some patients may haemodynamic,but also hormonal and metabolic stability. have signi®cant CHD causing myocardial ischaemia and These techniques effectively block the entire sympathetic even suffer myocardial infarction without typical symp- nervous system and the hypothalamic±pituitary axis,prob- toms. This may result from autonomic neuropathy,67 but ably by a direct effect on the hypothalamus and higher such `silent ischaemia' is unlikely to occur without the co- centres.36 Abolition of the catabolic hormonal response to existence of multiple risk factors. However,even selective surgery will,therefore,abolish the hyperglycaemia seen in screening targeted at patients with speci®c multiple risk normal patients and may be of bene®t in the diabetic factors has been discouraged because there is no evidence to support intervention (in the form of angioplasty or surgery) Halothane,en¯urane and iso¯urane,in vitro,inhibit the for asymptomatic diabetic patients.99 What is the anaes- insulin response to glucose in a reversible and dose- thetist to do when presented with an asymptomatic diabetic dependent manner.19 32 The effect of propofol on insulin patient who has some or all of the other risk factors such as secretion is not known. Diabetic patients show a reduced advanced age,smoking,hyperlipidaemia and hypertension? ability to clear lipids from the circulation.123 Although this Perioperative management of such a patient may be altered is unlikely to be relevant during short anaesthetics when if it is known that there is a likelihood of myocardial propofol is used for maintenance or as an induction agent ischaemia even if intervention by coronary artery bypass only,it may have implications for patients receiving grafting or angioplasty (although perhaps not coronary propofol for prolonged sedation in the intensive care unit.
stenting) carries an unacceptable risk:bene®t ratio.81 Asymptomatic type 1 diabetics with severe nephropathy scheduled for renal transplantation have been shown to bene®t from preoperative screening and appropriate coron- Microvascular,neuropathic and macrovascular complica- ary revascularization.65 A similar strategy may well be tions of diabetes mellitus are of special concern for the appropriate for high-risk diabetics,particularly those with anaesthetist. Of particular importance are coronary heart `metabolic syndrome',about to undergo major,elective disease,diabetic nephropathy and autonomic neuropathy non-cardiac surgery.
because these may have a direct effect on the development Diabetic patients have a worse outcome after coronary of perioperative complications. In addition,young patients artery bypass surgery96 and tend to stay in hospital longer.60 with long-standing type 1 diabetes and poor glycaemic They are more likely to develop postoperative renal control were found to have signi®cantly decreased lung failure13 and suffer delayed stroke.46 Deep sternal wound volume,lung diffusing capacity and cardiac stroke index infection rates are also higher than in the non-diabetic during exercise when compared with patients treated with population,126 but the incidence may be reduced by improving diabetic control with continuous insulin infu- Because of glycosylation of collagen in the cervical sions.27 Mortality following coronary artery bypass surgery joints,part of a generalized phenomenon called `stiff joint in diabetics is generally reported as signi®cantly greater syndrome',98 diabetic patients are more likely to present than that in non-diabetics.110 pathy,there is loss of HRV. The severe impairment of HRV In most countries,the leading causes of end-stage renal in patients with end-stage diabetic nephropathy probably failure are hypertension and diabetes mellitus. In the USA, results from autonomic neuropathy and partly from co- 30±40% of patients with type 1 diabetes will develop existing heart disease.57 The loss of HRV may be a diabetic nephropathy and end-stage renal failure.93 There is contributory risk factor for ventricular arrhythmias and now substantial evidence that angiotensin-converting en- sudden death in these patients.57 The presence of autonomic zyme (ACE) inhibitors have a renal protective effect in dysfunction in diabetics undergoing coronary artery surgery patients with type 1 diabetes.61 This may also be the case in is not,however,automatically associated with haemody- type 2 diabetes,but the evidence is less convincing. No namic instability during induction and the cardiovascular agent has been shown to be renoprotective in the responses in non-diabetic and diabetic patients were very perioperative period and some of the traditional drugs similar.53 used for this purpose may be harmful.17 105 Ensuring Diabetic gastroparesis is characterized by a delay in adequate renal perfusion by expanding the extracellular gastric emptying without any gastric outlet obstruction.117 space (salt loading) or,more speci®cally,the intravascular The increased amount of gastric contents enhances the risk space with appropriate haemodynamic monitoring may of acid aspiration during the induction of anaesthesia.82 reduce the risk of postoperative renal dysfunction. These patients are often asymptomatic and unpredictable Hydration with 0.45% sodium chloride solution alone dif®culties in tracheal intubation increase even further the provides better protection against radiocontrast medium- risk of aspiration.88 Studies have shown little effect of pro- induced renal failure in at-risk subjects than saline with the kinetic agents,such as cisapride,in reducing the volume of Postoperative respiratory arrest seems to be more com- mon in diabetic patients. Acute,unexpected respiratory problems in the recovery room are more common in men,in those aged >60 years,and in obese or diabetic patients.95 Diabetic patients frequently develop neuropathy,most commonly a distal symmetrical sensory or sensorimotor polyneuropathy with a variable degree of autonomic Wound healing and infection involvement.12 Autonomic dysfunction,which is of par- It has long been recognized that wound healing is impaired ticular importance to the anaesthetist,is detectable in up to in diabetic patients.9 44 This observation has been repeated 40% of type 121 and 17% of type 2 diabetic patients.23 Only in animal models where it has been shown that pre- and a small proportion of these patients are symptomatic,with postoperative glycaemic control with insulin,not post- signs and symptoms such as gastroparesis,postural operative alone,can restore normal anastomotic healing.118 hypotension,gustatory sweating,diabetic diarrhoea and Recent work suggests that better glycaemic control with bladder paresis.121 Many pathogenic mechanisms have been insulin infusions may reduce the incidence of deep sternal suggested for diabetic autonomic neuropathy,including wound infections in diabetic patients who have undergone local ischaemia,112 tissue accumulation of sorbitol,20 altered cardiac surgery.27 This observation is supported by a study function of neuronal Na+/K+-ATPase pump activity103 and demonstrating better preservation of neutrophil function with `aggressive' glycaemic control using an insulin The cardiovascular effects of insulin are paradoxical in infusion,compared with intermittent therapy,in diabetic autonomic neuropathy patients. In normal subjects,i.v. or cardiac surgical patients.86 Interestingly,high-dose insulin s.c. insulin administration activates the sympathetic nervous and glucose infusions,aimed at maintaining supranormal system,causing an increase in circulating norepinephrine, plasma insulin concentrations and euglycaemia in non- supine arterial pressure and peripheral vascular resistance.85 diabetic burns patients,signi®cantly decreased donor-site At the supraphysiological concentrations often used in the healing time after skin grafting.84 treatment of diabetes,vasodilation occurs with decreased peripheral vascular resistance and increased ¯ow.85 These observations suggest that insulin has dual effects,namely a Conclusion vasoconstrictor effect mediated by the sympathetic nervous It is well known that diabetic patients are at greater risk of system at low insulin concentrations,and a vasodilator perioperative mortality and morbidity after major surgery effect,perhaps mediated by nitric oxide release at higher and have a higher incidence of co-existing disease. Over concentrations. In patients with autonomic neuropathy, recent years evidence has accumulated that improving insulin causes a decrease in supine arterial pressure and glycaemic control in both the short and long term improves outcome. Attention to detail in the day-to-day management Detection of autonomic neuropathy in patients without of the disease itself and associated conditions,such as symptoms has relied on methods such as assessment of heart hypertension,reduces the devastating consequences of rate variability (HRV).104 In diabetic autonomic neuro- microvascular and macrovascular complications. In add- ition,a more aggressive approach to glycaemic control in Reanalysis of European epidemiological data. Br Med J 1998; 317: the perioperative period results in better wound healing, lower morbidity and shorter hospital stays. Gone are the 17 Denton MD, Chertow, GM, Brady HR. `Renal-dose' dopamine days when anaesthetists could tolerate `permissive hyper- for the treatment of acute renal failure: Scienti®c rationale, glycaemia' with the idea that this approach was in the experimental studies and clinical trials. Kidney Int 1996; 49: 4±14 18 Desborough JP, Hall GM, Hart GR, Burrin JP. Midazolam patient's best interest. Tight metabolic control in the modi®es pancreatic and anterior pituitary secretion during perioperative period is imperative and is a goal which is upper abdominal surgery. Br J Anaesth 1991; 67: 390±96 19 Desborough JP, Jones PM, Persaud SJ, Landon MJ, Howell SL.
Iso¯urane inhibits insulin secretion in isolated rat pancreatic islets of Langerhans. Br J Anaesth 1993; 71: 873±6 20 Dyck P, Zimmerman B, Vilen T. Nerve glucose, fructose, sorbitol 1 Alberti KGMM, Zimmet PZ for the WHO Consultation.
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