Clinical review: Strict or loose glycemic control in critically ill patients - implementing best available evidence from randomized controlled trials

Marcus J Schultz,Robin E Harmsen,Peter E Spronk

doi:10.1186/cc8966

Marcus J Schultz, Robin E Harmsen + Show 1 more

Open Access

https://doi.org/10.1186/cc8966

Copy DOI

Abstract

Glycemic control aiming at normoglycemia, frequently referred to as 'strict glycemic control' (SGC), decreased mortality and morbidity of adult critically ill patients in two randomized controlled trials (RCTs). Five successive RCTs, however, failed to show benefit of SGC with one trial even reporting an unexpected higher mortality. Consequently, enthusiasm for the implementation of SGC has declined, hampering translation of SGC into daily ICU practice. In this manuscript we attempt to explain the variances in outcomes of the RCTs of SGC, and point out other limitations of the current literature on glycemic control in ICU patients. There are several alternative explanations for why the five negative RCTs showed no beneficial effects of SGC, apart from the possibility that SGC may indeed not benefit ICU patients. These include, but are not restricted to, variability in the performance of SGC, differences among trial designs, changes in standard of care, differences in timing (that is, initiation) of SGC, and the convergence between the intervention groups and control groups with respect to achieved blood glucose levels in the successive RCTs. Additional factors that may hamper translation of SGC into daily ICU practice include the feared risk of severe hypoglycemia, additional labor associated with SGC, and uncertainties about who the primarily responsible caregiver should be for the implementation of SGC.

Highlights

Strict glycemic control (SGC) decreased mortality and morbidity of ICU patients in two randomized controlledAfter the publication of the first randomized controlled trials (RCTs) on SGC [1], the ICU community seemed divided on the best method of glycemic control
Many ICUs implemented some form of glycemic control, frequently the applied regimens tolerated higher blood glucose levels than those used in the SGC strategy as studied in the original trial [1]
Rather than concluding that SGC does not benefit critically ill patients based on the successive negative RCTs in other ICUs, we prefer first to search for differences between the designs of the positive and negative RCTs

Summary

Introduction

After the publication of the first RCT on SGC [1], the ICU community seemed divided on the best method of glycemic control. Many ICUs implemented some form of glycemic control, frequently the applied regimens tolerated higher blood glucose levels than those used in the SGC strategy as studied in the original trial [1]. After publication of the second RCT on SGC, which showed less strong though still significant benefits of SGC [2], the community continued to propagate glycemic control with insulin [9]. Since the publication of five successive negative RCTs [3,4,5,6,7], enthusiasm for implementation of SGC has declined, hampering the translation of SGC into daily ICU practice

Methods

Findings

Discussion

Conclusion