Perioperative myocardial ischaemia and non-cardiac surgery

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1. Leake DW, Hii JLK. Giving bed nets "fair" tests in field trials against malaria. Southeast Asian J Trop Med Public Health 1989; 20: 379-84. 2. Graves PM, Brabin BJ, Charlwood JD, et al. Reduction in incidence and prevalence of Plasmodium falciparum in under 5-year-old children by permethrin impregnation of mosquito nets. Bull WHO 1987; 65: 869-77. 3. Snow RW, Rowan KM, Greenwood BM. A trial of permethrin-treated bed nets in the prevention of malaria in Gambian children. Trans R Soc Trop Med Hyg 1987; 81: 563-67. 4. Snow RW, Lindsay SW, Hayes RJ, Greenwood BM. Permethrin-treated bed nets (mosquito nets) prevent malaria in Gambian children. Trans R Soc Trop Med Hyg 1988; 82: 838-42. 5. Procacci PG, Lamizana L, Kumlien S, Habluetzel A, Rotigliano G. Permethrin-impregnated curtains in malaria control. Trans R Soc Trop Med Hyg 1991; 85: 181-85. 6. Sexton JD, Rueburgh TK, Brandling-Bennett AD, et al. Permethrinimpregnated curtains and bed nets prevent malaria in Western Kenya. Am J Trop Med Hyg 1990; 443: 11-18. 7. Sharma VP, Ansari MA, Mittal PK, Razdan RK. Insecticide impregnated ropes as mosquito repellent. Ind J Malariol 1989; 26: 179-85. 8. Chiang GL, Tay SL, Eng KL, Chan ST. Effectiveness of repellent/ insecticide bars against malaria and filariasis vectors in peninsular Malaysia. Southeast Asian J Trop Med Public Health 1990; 21: 412-17.

Perioperative myocardial ischaemia and non-cardiac surgery Heart attacks and their complications are the main cause of death after anaesthesia and surgery.1 The risk of surgery in the "general population", some of whom will of course have had an earlier myocardial infarction, will depend on what type of patients are studied. In a group of 1001 patients2 undergoing various major non-cardiac operations there were 19 perioperative cardiac deaths. Multifactorial analysis revealed several indpendent risk predictors, including a myocardial infarction in the previous 6 months, signs of heart failure, presence of any sustained cardiac arrhythmia, frequent ventricular extrasystoles, age over 70 years, vascular operations, aortic stenosis, and a generally poor medical condition. How risky is non-cardiac surgery in patients known have coronary disease? In a group of more than 30 000 patients who underwent surgery at the Mayo Clinic in 1967 and 1968, operations done in the

to

subgroup who had had a myocardial infarction in the preceding 3 months carried a 37% risk of reinfarction.3 In the 1970s it was reported that operations within 3 months of an infarction were associated with a 27% risk of reinfarction, whereas the risk was 11% for operations done after 3-6 months; operations done after more than 6 months carried a 4% risk of reinfarction, which seemed to remain constant.4 Findings such as these still have a profound effect on the attitude of surgeons and anaesthetists when they elective non-cardiac operations in are planning patients who have sustained a myocardial infarction, despite claims made in the 1980s that "aggressive invasive monitoring of hemodynamic status" can reduce the reinfarction rate to 5-7% even in the first 3 months after an infarction, and to 25% in the 3-6 month period.5 All these estimates may be pessimistic: patients included in the registry of the Coronary

Artery Surgery Study (CASS) who had

coronary

documented at angiography had a perioperative infarction rate of 1.1% associated with non-cardiac surgery. Nevertheless, few of these patients had sustained a myocardial infarction in the months preceding their operation. Perioperative myocardial infarction can be difficult to diagnose: patients will have postoperative pain and will be given analgesics, so cardiac pain may not be noticed. Tachycardia, hypotension, and fever may be ascribed to blood loss, pulmonary emboli, or infection rather than to a myocardial infarction. When attempts have been made to detect myocardial ischaemia associated with non-cardiac surgery, it has been found to be very common. Mangano et aF used continuous electrocardiographic (ECG) monitoring to detect ischaemic ST segment changes following non-cardiac surgery in 243 men with known coronary disease and in 231 who were thought to be at high risk of having it. 83 of these patients (18%) had postoperative events attributable to cardiac ischaemia, and there was a nine-fold increase in the risk of an ischaemic event among those shown to have ischaemia by ECG monitoring. When a similar monitoring technique was used to compare episodes of ischaemia before, during, and after elective surgery8,9 it was found that, among 100 men with or at risk from coronary disease, 28 patients had 105 episodes of ischaemia in the 2 days before surgery. During anaesthesia itself, 27 patients had 39 episodes of ischaemia. In the 2 days following surgery, 42 patients had 187 ischaemic episodes detected on their ECG; in the postoperative period the duration of ischaemia and the degree of ST segment depression were greater than in the period leading up to the operation. The excess of postoperative ischaemia appeared to be related to an increased heart disease

rate.

Perhaps the most striking finding in these detailed studies of perioperative cardiac ischaemia8,9 was that almost all the episodes were "silent": the characteristic ECG changes of ischaemia were not accompanied by cardiac pain. These silent ECG changes are known to be due to cardiac ischaemia,10 although why they are not associated with pain is unclear. 11,12 The prognostic importance of silent, as opposed to symptomatic, ischaemia is likewise uncertain. If silent ischaemia and perioperative cardiac events are related,8 it could be argued that ECG monitoring for ST segment changes is necessary before, during, and for a few days after non-cardiac surgery. This policy would be extremely expensive and is unlikely to be cost effective. Such monitoring should not become standard practice until its value has been compared with simple tests (eg, an ECG recorded at rest or under stress). Preoperative exercise testing adds little to a routine ECG in the prediction of cardiac events during or after surgery, and in a study of 200 patients a cardiac event occurred in 23% of those with an abnormal preoperative ECG compared with 2% of those whose ECG was normal.13

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It seems prudent to defer elective non-cardiac surgery for at least 3, and possibly 6, months after a myocardial infarction. It may be sensible to record a

preoperative ECG on any patient undergoing major surgery if he or she seems to have an increased risk of having coronary disease-though of course that could include any man or woman in middle age or beyond. However, in the absence of evidence that recording of a preoperative ECG affects outcome, failure to do so cannot be considered negligent. 1.

Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990; 72:

153-84. 2. Goldman L, Caldera DL, Nussbaum SR, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 1977; 297: 845-50. 3. Tarhan S, Moffitt EA, Taylor WF, et al. Myocardial infarction after general anesthesia. JAMA 1972; 230: 1451-54. 4. Steen PA, Tinker JH, Tarhan S. Myocardia reinfarction after anesthesia and surgery. JAMA 1978; 239: 2566-70. 5. Rao TLK, Jacobs KH, El-Etr AA. Reinfarction following anesthesia in patients with myocardial infarction. Anesthesiology 1983; 59: 499-505. 6. Foster ED, David KB, Carpenter JA, Abele S, Fray D. Risk of noncardiac operation in patients with defined coronary disease: the Coronary Artery Surgery Study (CASS) registry experience. Ann Thorac Surg 1986; 41: 42-50. 7. Mangano DT, Browner WS, Hollenberg M, et al. Association of perioperative myocardial ischemia with cardiac morbidity and mortality in men undergoing noncardiac surgery. N Engl J Med 1990;

323: 1781-88.

Mangano DT, Hollenberg M, Fegert G, et al. Perioperative myocardial ischemia in patients undergoing noncardiac surgery—I: incidence and severity during the 4 day perioperative period. J ACC 1991; 17: 843-50. 9. Mangano DT, Wong MG, London MJ, et al. Perioperative myocardial ischemia in patients undergoing noncardiac surgery—II: incidence and severity during the 1st week after surgery. JACC 1991; 17: 851-57. 10. Deanfield JE, Maseri A, Selwyn AP, et al. Myocardial ischaemia during daily life in patients with stable angina: its relation to symptoms and heart rate changes. Lancet 1983; ii: 753-58. 11. Cecchi AC, Dovellini EV, Marchi F, et al. Silent myocardial ischemia during ambulatory electrocardiographic monitoring in patients with effort angina. JACC 1983; 1: 934-39. 12. Cohn PF. Silent myocardial ischemia. Ann Intern Med 1988; 109: 312-17. 13. Carliner NH, Fisher ML, Plotnick GD, et al. Routine preoperative exercise testing in patients undergoing major noncardiac surgery. Am J Cardiol 1985; 56: 51-58. 8.

GLUTS and diabetes Glucose

cell membranes in mammals by kidney and intestine, the co-transporters are active-transport

crosses

two processes. In the

Na+-glucose

systems in the epithelial membranes; they concentrate glucose from the lumen of the intestine or proximal nephron against a concentration gradient.1 By contrast, the facilitative glucose transporters are a family of structurally related proteins which accelerate glucose movement down a concentration gradient (in or out of cells) by energy-independent means; these transporters probably reside on the surface of all cell Facilitative glucose types throughout the body.2>3 transporters have lately been the focus of intense interest because of their possible role in the pathogenesis of diabetes mellitus.44 Glucose transporters have been classified and named either according to the order in which they were first identified3 (GLUT 1,2, &c), or according to the tissues in which they are especially abundant.5 The GLUT 1, erythrocyte, or HepG2 (after a human

hepatoma cell line) transporter is very widely distributed and probably provides for the basal glucose needs of all cells. Expression of GLUT 1 is increased, for example, by low ambient glucose concentrations and by cellular growth and division. The GLUT 2 or liver transporter is especially evident in liver, kidney, intestine, and pancreatic islet B cells. It is unusual in having a high Km,6 which ensures that glucose transport rises in proportion to glucose levels in organs where glucose is delivered from the cell to the blood. The GLUT 4 or muscle/fat transporter is the main species in insulin-sensitive tissues, mostly skeletal muscle and adipose tissue cells. Insulin causes a 15-fold to 20-fold increase in glucose uptake in fat cells by translocation of microvesicles containing GLUT 4 from an intracellular pool to the plasma membrane of the cell.7,8Exercise likewise stimulates GLUT 4 translocation and glucose uptake in muscle cells, although the intracellular pool of transporters is probably different from that affected by insulin.9 The functions of GLUT 3 and GLUT 5 are less well defined. How might glucose transporters be involved in diabetes? In non-insulin-dependent diabetes mellitus (NIDDM), hyperglycaemia is caused both by resistance to the action of insulin at its target cells, with increased hepatic glucose output and diminished peripheral glucose uptake, and by diminished insulin secretion from the islet B cells in response to glucose.1o Glucose sensing by the islet requires uptake and metabolism by B-cells.11 The GLUT 2 transporter, structurally identical to liver GLUT 2, is present in high amounts in B cells12 and may be closely associated with the enzyme glucokinase, perhaps via electrostatic

binding, thereby forming a glucose-sensing complex.13 The high Km of GLUT 2 allows for uptake into the B cell over the range of glucose concentrations that stimulate insulin secretion (about 5-15 mmol/1). In insulinoma cells, which do not respond to glucose stimulation, GLUT 2 is replaced by GLUT 1.14 Thus a defect in glucose transport into islet B cells may contribute to the impaired insulin secretion of NIDDM. In two animal models of human NIDDM-Zucker diabetic fatty rats and neonatal streptozotocin-treated rats-GLUT 2 expression and messenger RNA are strikingly reduced and these reductions are matched by loss of glucose-induced insulin secretion. 15-17 Furthermore, the changes in GLUT 2 expression do not seem to be secondary to raised glucose concentrations since chronic hyperglycaemia, if anything, increases GLUT 2 mRNA and immunostaining in islet B cells.16 Evidence for a defect in the GLUT 2 gene in NIDDM is conflicting.18,19 The change in glucose transporters that correlates with peripheral insulin resistance is reduced transporter (GLUT 4) in adipocytes from NIDDM patients20 and from streptozotocin-treated diabetic rats,21 which are known to display insulin resistance. Nevertheless, GLUT 4 expression in muscle