Diabetes and Coronary Surgery : Metabolic and clinical studies on diabetic patients after coronary surgery with special reference to cardiac metabolism and high-dose GIK

Sammanfattning: Introduction An increasing proportion of the patients undergoing cardiac surgery have diabetes mellitus, in particular type II diabetes. In spite of this, diabetic patients have received limited attention in this setting. Although diabetes is a metabolic disease cardiac metabolism in association with surgery has previously not been explored in diabetics. This investigation was carried out to describe the metabolic state of the heart in diabetics after cardiac surgery and to study if it is accessible to metabolic intervention with high-dose GIK. Also, the potential hazards associated with such a regime in clinical practice were evaluated. Furthermore, a comparison of the outcome in diabetic and nondiabetic patients after coronary surgery was done.Methods Myocardial metabolism and how it was influenced by high-dose GIK was assessed with coronary sinus catheter technique in a prospective randomized study on 20 type II diabetic patients undergoing CABG (paper I, II). Safety issues concerning high-dose GIK were assessed in two retrospective studies. The potential role of metabolic interventions for neurological injury was assessed in a cohort of 775 consecutive patients undergoing CABG or combined CABG + valve surgery, in whom metabolic interventions gradually replaced traditional treatment for postoperative heart failure (paper III). A detailed analysis of blood glucose and electrolyte control was done in all cases (n=89) receiving high-dose GIK during one year (paper IV). The hemodynamic impact of highdose GIK was assessed with standard postoperative monitoring including Swan-Ganz catheters (paper II, IV). Outcome and prognosis after CABG in diabetic patients (n=540) were compared with nondiabetics (n=2239) with the aid of the institutional database comprising all isolated CABG procedures from 1995-1999 (paper V).Results The metabolism of the diabetic heart after CABG was characterized by predominant uptake of FFA and restricted uptake of carbohydrate substrates. A high extraction rate of beta-hydroxybutyric acid and glutamate was also found. Alanine was released from the heart (paper I). High-dose GIK induced a shift towards uptake of carbohydrates, in particular lactate, at the expense of FFA and betahydroxybutyric acid (paper II). A substantial systemic glucose uptake was found during high-dose GIK treatment but the uptake tended to be lower and blood glucose higher if adrenergic drugs were used or/and if the patient was a diabetic (paper IV). High-dose GIK was associated with beneficial effects on cardiac output both in the prospective and retrospective analyses (paper II, IV). No evidence for untoward neurological effects associated with GIK treatment was found. History of cerebrovascular disease was the most important risk factor for postoperative cerebral complications and in general markers for advanced atherosclerotic disease were found to be of importance (paper III). High-dose GIK in clinical practice was associated with acceptable blood glucose and electrolyte control and no serious adverse events were recorded (paper IV). Patients with diabetes undergoing CABG had an acceptable short-term mortality that did not differ significantly from non-diabetic patients. However, diabetic patients had a higher early postoperative morbidity particularly with regard to stroke, renal- and infectious complications. Also, long-term survival was markedly reduced in diabetic patients, particularly in insulin treated patients (paper V).Comments FFA were the main source of energy for the heart in type II diabetics after CABG whereas the uptake of carbohydrates was restricted. The high extraction rates of beta-hydroxybutyric acid and glutamate may represent an adaptation to the unfavorable metabolic situation of the post-ischemic diabetic heart. High-dose GIK can be used in type II diabetic patients after cardiac surgery to promote carbohydrate uptake at the expense of FFA and beta-hydroxybutyric acid. The magnitude of this shift was sufficient to account for the entire myocardial oxygen consumption assuming that the substrates extracted were oxidized. This could have implications for the treatment of the diabetic heart in association with surgery and ischemia. Provided careful monitoring high-dose GIK can be safely used in clinical practice and this treatment deserves further evaluation in the treatment of postoperative heart failure. High-dose GIK also provides a means for strict blood glucose control and as substantial amounts of glucose can be infused even in critically ill patients, it may prove useful for nutrition in critical care. Several of the risk factors for neurological injury identified constitute markers for advanced atherosclerotic disease, thus, also providing an explanation for the increased risk of neurological injury in diabetics after cardiac surgery. Short-term mortality was acceptable in diabetics after CABG. However, further efforts are warranted to address postoperative morbidity and late outcome. This represents a challenge as diabetic patients are accounting for an increasing proportion of the patients undergoing CABG.