The effect of insulin on whole body protein and glucose metabolism after cardiac surgery using stable isotope kinetics: a pilot study

High doses of insulin are required to prevent the hyperglycemic response to open heart surgery. Insulin has been shown to produce hypoaminoacidemia during coronary artery bypass graft (CABG) surgery. The present study investigated the effect of high-dose insulin therapy on whole body protein and glucose metabolism in patients undergoing CABG surgery using stable isotope tracers [6,6-2H2]glucose and L-[1-13C]-leucine. Hyperinsulinemic-normoglycemic clamp was used to deliver high-dose insulin. The primary objective was to establish a protocol and to assess the feasibility of using stable isotope tracers after cardiac surgery while continuously infusing high-dose insulin. The effect of high-dose insulin on protein breakdown, synthesis and oxidation and glucose turnover was evaluated.Fifteen patients were recruited to the study, seven in the control group receiving standard glycemic control and eight in the insulin group receiving the hyperinsulinemic-normoglycemic clamp. Isotopic plateaus of L-[1-13C]leucine, [6,6-2H2]glucose and expired 13CO2 were attained in all patients in both groups with a coefficient of variance <5%. Protein breakdown and synthesis both decreased in patients who received high-dose insulin, while protein oxidation remained the same, resulting in a negative protein balance regardless of treatment group. Endogenous glucose production was almost completely suppressed by the administration of high-dose insulin and 20% dextrose solution. The hyperinsulinemic-normoglycemic clamp is a metabolic intervention that when used in the perioperative setting of cardiac surgery, has significant effects on whole body protein breakdown.Lors de chirurgies pour pontage aorto-coronarien, l'utilisation de hautes doses d'insuline est habituellement nécessaire pour prévenir l'augmentation de la glycémie en réponse au stress chirurgical. Il a été démontré que l'administration d'insuline induit une hypoaminoacidémie chez ces patients. La présente étude a pour but d'évaluer les effets de l'administration de hautes doses d'insuline sur le métabolisme des protéines et du glucose par l'usage d'isotopes stables pour ce type d'intervention chirurgicale. Les isotopes utilisés étaient le [6,6-2H2]glucose et la L-[1-13C]leucine. L'objectif principal était de vérifier s'il est possible de faire le suivi postopératoire de ces marqueurs isotopiques en présence de hautes doses d'insuline, et ce afin d'établir un protocole. Les effets de ces hautes doses d'insuline sur la lyse, la synthèse et l'oxydation protéique ainsi que les effets sur le métabolisme du glucose ont été évalués. Quinze sujets ont été recrutés, soit sept dans le groupe témoin recevant le traitement habituel de contrôle de glycémie, et les huit autres dans le groupe d'étude soumis à des hautes doses d'insuline. Les plateaux du [6,6-2H2]glucose, de la L-[1-13C]leucine et du 13CO2 ont été obtenus pour tous les candidats des deux groupes, avec un coefficient de variance < 5%. La lyse et la synthèse protéiques des patients recevant de hautes concentrations d'insuline ont toutes deux diminuées alors que l'oxydation, quant à elle, est restée la même. Un bilan de protéines négatif a été obtenu quelque soit le groupe de traitement. La production endogène de glucose a pratiquement été abolie par l'administration de grande quantité d'insuline et de dextrose 20%. Cette intervention métabolique, lorsqu'utilisée dans le contexte de chirurgies cardiaques, a des effets significatifs sur le métabolisme global des protéines et du glucose des patients

Perioperative fluid management in kidney transplantation: a black box

Abstract The incidence of delayed graft function in patients undergoing kidney transplantation remains significant. Optimal fluid therapy has been shown to decrease delayed graft function after renal transplantation. Traditionally, the perioperative volume infusion regimen in this patient population has been guided by central venous pressure as an estimation of the patient’s volume status and mean arterial pressure, but this is based on sparse evidence from mostly retrospective observational studies. Excessive volume infusion to the point of no further fluid responsiveness can damage the endothelial glycocalyx and is no longer considered to be the best approach. However, achievement of adequate flow to maintain sufficient tissue perfusion without maximization of cardiac filling remains a challenge. Novel minimally invasive technologies seem to reliably assess volume responsiveness, heart function and perfusion adequacy. Prospective comparative clinical studies are required to better understand the use of dynamic analyses of flow parameters for adequate fluid management in kidney transplant recipients. We review perioperative fluid assessment techniques and discuss conventional and novel monitoring strategies in the kidney transplant recipient

Intraoperative Maintenance of Normoglycemia with Insulin and Glucose Preserves Verbal Learning after Cardiac Surgery

ObjectiveThe hyperglycemic response to surgery may be a risk factor for cognitive dysfunction. We hypothesize that strict maintenance of normoglycemia during cardiac surgery preserves postoperative cognitive function.MethodsAs part of a larger randomized, single-blind, interventional efficacy study on the effects of hyperinsulinemic glucose control in cardiac surgery (NCT00524472), consenting patients were randomly assigned to receive combined administration of insulin and glucose, titrated to preserve normoglycemia (3.5–6.1 mmol L−1; experimental group), or standard metabolic care (blood glucose 3.5–10 mmol L−1; control group), during open heart surgery. The patients’ cognitive function was assessed during three home visits, approximately two weeks before the operation, and two months and seven months after surgery. The following tests were performed: Rey Auditory Verbal Learning Task (RAVLT for verbal learning and memory), Digit Span Task (working memory), Trail Making A & B (visuomotor tracking and attention), and the Word Pair Task (implicit memory). Questionnaires measuring specific traits known to affect cognitive performance, such as self-esteem, depression, chronic stress and social support, were also administered. The primary outcome was to assess the effect of hyperinsulinemic-normoglycemic clamp therapy versus standard therapy on specific cognitive parameters in patients receiving normoglycemic clamp, or standard metabolic care.ResultsTwenty-six patients completed the study with 14 patients in the normoglycemia and 12 patients in the control group. Multiple analysis of covariance (MANCOVA) for the RAVLT showed a significant effect for the interaction of group by visit (F = 4.07, p = 0.035), and group by visit by recall (F = 2.21, p = 0.04). The differences occurred at the second and third visit. MANCOVA for the digit span task, trail making and word pair association test showed no significant effect.ConclusionsPreserving intraoperative normoglycemia by intravenous insulin and glucose may prevent the impairment of memory function, both short and long-term, after cardiac surgery.publishe

Raw scores and differences between groups for digit span, trail making and word-pair association tests over the three visits.

2<p>GIN = Glucose and insulin administration while maintaining normoglycemia</p

Characteristics of patients.

1<p>GIN = Glucose and insulin administration while maintaining normoglycemia.</p

Performance of the subjects in the two groups over the course of the experiment.

<p>GIN: Experimental group with variable insulin infusion; Control: Best practice treatment; Pre-surgery: Neuropsychological assessment before surgery; Post surgery 1: Neuropsychological assessment approximately two months after surgery; Post surgery 2: Neuropsychological assessment approximately seven months after surgery; x-axis legend 1–1 to 3–7: days and iteration of verbal learning task.</p

Perioperative data.

2<p>GIN = Glucose and insulin administration while maintaining normoglycemia.</p>3<p>CABG = Coronary artery bypass grafting.</p>4<p>CPB = Cardiopulmonary bypass.</p>5<p>ICU = Intensive care unit.</p