Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation

Abstract

Background/purpose: Infants requiring extracorporeal membrane oxygenation (ECMO) have the highest rates of protein catabolism ever reported. Recent investigations have found that such extreme protein breakdown is refractory to conventional nutritional management. In this pilot study, the authors sought to use the anabolic hormone insulin to reduce the profound protein degradation in this cohort.

Methods: Four parenterally fed infants on ECMO were enrolled in a prospective, randomized, crossover trial. Subjects were administered an insulin infusion using a 4-hour hyperinsulinemic euglycemic clamp followed by a control saline infusion on consecutive days in random order. Whole-body protein flux and breakdown were quantified using a primed continuous infusion of the stable isotope L-[1-13C]leucine. Statistical analyses were performed using paired t tests.

Results: Serum insulin levels were increased 15-fold during the insulin clamp compared with the saline control (407 +/- 103 v 26 +/- 12 microU/mL; P <.05). During the insulin infusion, infants had decreased rates of total leucine flux (214 +/- 25 v 298 +/- 38 micromol/kg/h; P <.05) and leucine flux derived from protein breakdown (156 +/- 40 v 227 +/- 54 micromol/kg/h; P <.05) when compared with saline control. Overall, insulin administration produced a 32% reduction in protein breakdown (P <.05).

Conclusions: In this pilot study, the anabolic hormone insulin markedly reduced protein breakdown in critically ill infants on ECMO. Because elevated protein breakdown correlates with mortality and morbidity, the administration of intravenous insulin may ultimately have broad applicability to the metabolic management of critically ill infants.

Fig 1

The hyperinsulinemic euglycemic clamp increased the serum concentration of insulin by 15-fold when compared with the control saline infusion. (*P < .05).

Fig 2

As measured by mass spectrometry, a steady state was achieved using 1-[¹³C] α-KICA during the last hour of the stable isotope infusion protocol.

Fig 3

The hyperinsulinemic euglycemic clamp reduced the total leucine flux and the endogenous leucine flux (a marker of the leucine derived from protein breakdown) by an average of 32%, equivalent to 3.1 g/kg/d of protein (*P < .05). In the figues, “Insulin” and “Saline” correspond to the intravenous insulin infusion and the control saline infusion, respectively.