1 Department of Anaesthesia and Intensive Care Medicine, St Georges Hospital Medical School, London SW17 0RE, UK,
Corresponding author. E-mail: g.hall@sghms.ac.uk
The prevalence of diabetes mellitus has been increasing rapidly in recent years. In the USA it has been estimated that diabetes shortens life expectancy by up to 15 yr, and that the age-adjusted death rate for diabetes has increased by 30% since 1980.1 This is in marked contrast to other major multifactorial diseases, such as heart disease, stroke, and many cancers, for which the mortality rate has either declined or remained stable. Inevitably, diabetic patients present for surgery with the complications of the disease: cardiac, vascular, renal, ophthalmic, etc. The metabolic management of these patients in the perioperative period has become routine with agreement that all in-patients, except Type 2 diabetics presenting for minor surgery, should be treated with a glucoseinsulinpotassium infusion.2 Whether the choice of anaesthetic technique can make metabolic control easier to achieve has received little attention. In this issue of the Journal, Belhoula and colleagues have examined the effects of clonidine on glucose metabolism in Type 2 diabetics undergoing eye surgery.3
Several factors complicate the metabolic management of the diabetic patient in the perioperative period. These include starvation, before and after operation, the endocrine and consequent metabolic responses to surgery, and immobilization. Theoretically, any anaesthetic technique, which reduces the duration and severity of these factors should aid metabolic control.
Regional anaesthesia for ophthalmic surgery results in more rapid recovery with earlier mobilization, better pain relief, and less nausea and vomiting and so earlier oral intake, than general anaesthesia.4 For certain operative sites, including eye surgery, regional anaesthesia decreases and even abolishes the catabolic hormonal response to surgery with a resultant decrease in glucose mobilization.5 We have shown that regional anaesthesia for cataract extraction clamps the metabolic changes at the preoperative values in Type 2 diabetic patients.6 Further benefits of regional anaesthesia in diabetics include the avoidance of tracheal intubation in patients who may have the stiff-joint syndrome and gastroparesis. The well-recognized effects of regional anaesthesia in decreasing venous thromboembolism are particularly pertinent in diabetic patients who may have an increased tendency to clot (thrombophilia). Potential disadvantages of regional anaesthesia in diabetic patients include cardiovascular instability with extensive neuraxial block, increased risk of infection-epidural abscess and meningitis, and exacerbation of a peripheral neuropathy.2 Although regional anaesthesia appears to offer several benefits over general anaesthesia, there are no adequate trials to show that regional anaesthesia improves mortality and major morbidity in diabetic patients. It is preferable to use specific nerve blocks whenever possible to avoid the possible complications of central neuraxial block.
Drugs used in general anaesthesia may affect metabolism in diabetic patients either indirectly, by decreasing catabolic hormone secretion, or directly, by altering insulin secretion. The latter mechanism is relevant only in those patients with some residual insulin secretion (Type 2 diabetes).
Several drugs used as induction agents or premedicants decrease catabolic hormone secretion in non-diabetic patients. Etomidate, with its well-known inhibitory effect on adrenal steroidogenesis, has been found to decrease the glycaemic response to surgery in some, but not all, studies.7 8 Midazolam, at high doses, decreases ACTH/cortisol secretion and sympathoadrenal activity, but stimulates growth hormone (GH) secretion. The net effect is a decreased glycaemic response to surgery.9 The 2 adrenergic agonist, clonidine has similar effects in unstressed subjects; decreased sympathetic outflow from the hypothalamus, and inhibition of ACTH secretion with stimulation of GH release.1012 The effects of clonidine, either as a premedicant or co-induction agent, on the glucose response to surgery in non-diabetics are inconsistent.1315 This may reflect the dose and timing of administration of clonidine and the different surgical models studied. Nevertheless, in the present study by Belhoula and colleagues there was improved glycaemic control in Type 2 diabetic patients, with a significant decrease in the amount of insulin given.3 The improvement was associated with decreased circulating catecholamine values, no difference in cortisol concentrations, and enhanced GH secretion. The inference from the data is that glycaemic control improved as a result of decreased sympathoadrenal activity.
A notable feature of the data was the effect of clonidine in decreasing plasma C-peptide concentrations, indicating a reduction in endogenous insulin secretion. It is likely that this resulted from the peripheral 2 inhibitory effects of clonidine on insulin secretion.16 We have shown recently that dexmedetomidine, a highly selective and potent
2 agonist, also decreased insulin secretion after major surgery without exacerbating the glycaemic response, suggesting that the impairment of insulin secretion was balanced by reduced sympathetic activity.17 Other explanations for the lower C-peptide values in the diabetic ophthalmic patients include a decreased glycaemic stimulus, alterations in splanchnic blood flow, and improved insulin resistance consequent to sympathetic block.
It is important to note that Belhoula and colleagues3 used flunitrazepam 12 mg premedication in the control group of patients. High doses of benzodiazepines alter hypothalamicpituitary secretion (see above), but an effect of this low dose cannot be excluded. Isoflurane was used to supplement anaesthesia and there is considerable in vitro work to show that volatile agents inhibit glucose-stimulated insulin secretion in a dose-dependent manner.1820 Furthermore, there are clinical studies showing that glucose tolerance is impaired by volatile anaesthesia before and during surgery.21 22 Unfortunately, these studies used an unphysiological challenge of 25 g glucose i.v. Desborough and colleagues found a decrease in insulin response to a 5 g bolus of glucose during isoflurane anaesthesia before surgery, but the establishment of general anaesthesia was more important than the dose of isoflurane.23 At present, a direct effect of volatile agents in inhibiting residual insulin secretion in Type 2 diabetic patients has not been demonstrated. However, it would be prudent to measure accurately the amount of volatile agent used to control for a potentially confounding variable.
Is it possible to recommend an anaesthetic technique for the diabetic patient? Regional anaesthesia is an attractive option, particularly the use of specific nerve blocks.
For general anaesthesia, volatile supplementation should be used judiciously until the effects on insulin secretion have been clarified. If it becomes apparent that volatile agents are detrimental in Type 2 diabetics, then a total i.v. technique may be appropriate (TIVA). However, it is possible that the lipid load resulting from the propofol infusion may cause further impairment of metabolism in diabetic patients. It has been suggested that the use of 2 adrenergic agonists is inappropriate in diabetic patients because of their direct inhibitory effects on insulin secretion.24 It is evident from the current study, that with clonidine, this is more than compensated for by the sympatholytic properties of the drug.
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