Australian Regenerative Medicine Institute

Glucose-Insulin and Potassium Infusions in Septic Shock: Discussion

We have described two cases of neutropenic septic shock in which the administration of a high-dose GIK infusion was temporally associated with an improvement in hemodynamic profile, permitting cessation of inotropic support. Septic shock and the systemic inflammatory response is characterized by reversible myocardial depression, which can prove resistant to catecholamine and fluid administration. Circulating “myocardial depressant factor”—probably representing the synergistic effects of tumor necrosis factor (TNF)-a, interleukin (IL)-1p, other cytokines, and nitric oxide—is implicated in pathogenesis. Macrovascular myocardial ischemia and hypoperfusion are unlikely contributors.
GIK infusions were first proposed as a metabolic treatment for acute myocardial ischemia in the 1960s, with recent renewed interest in its use in the context of acute myocardial infarction and cardiac surgery. Acute myocardial ischemia results in an increased collateral blood flow and elevates circulating catecholamine levels as a result of physiologic stress. Depletion of carbohydrate reserves occurs in parallel with a switch to the use of less efficient energy substrates such as free fatty acids (FFAs), lactic acid, amino acids, and ketone bodies. These provide lower adenosine triphosphate yield per metabolized oxygen molecule. “Forcing” the ischemic myocardium to use glucose (through GIK administration) may thus improve the metabolic state of the myocardium when oxygen and fuel delivery is limited.

Such metabolic support may also limit reperfusion injury. Indeed, GIK improves myocardial perfusion and left ventricular function in diabetic patients, improves systolic function in patients with stable coronary artery disease, and ischemically preconditions the myocar-dium. Meta-analysis suggest GIK use to be associated with reduced in-hospital mortality after acute myocardial infarction, a conclusion supported by one large randomized control study. Further randomized control studies, however, have shown no significant benefit in salvaging myocardium or improving mortality following primary angioplasty. In a randomized controlled trial in patients treated for myocardial infarction, high-dose GIK had neutral effects on mortality, cardiac arrest, and cardiogenic shock. Meanwhile, GIK seems associated with dramatic increases in cardiac index with reduced inotropic support in the context of coronary artery bypass sur-gery.
Few studies have, however, addressed the role of GIK in septic myocardial depression. Mauritz et al showed that GIK (70%; 1 g/kg body weight; insulin, 1.5 units/kg; potassium, 10 mmol/L) improved MAP and cardiac and stroke work indexes in 15 patients with hypodynamic septic shock secondary to peritonitis. Similarly, Bronsveld et al showed a 20-min GIK infusion (glucose, 50%; 1 g/kg body weight; insulin, 1.5 ^/kg; potassium, 10 mmol/L) to significantly improve left ventricular stroke work indexes in 6 patients with fluid- and pressor-resistant hypodynamic septic shock. There were similar nonsignificant improvements in nine hyperdynamic patients. Our reports are thus consistent with those previously described.

Category: Septic Shock

Tags: antiinflammatory, glucose-insulin and potassium, insulin, myocardium, sepsis, shock