Does intensive insulin therapy really reduce mortality in critically ill surgical patients? A reanalysis of meta-analytic data

Abstract

Two recent systematic reviews evaluating intensive insulin therapy (IIT) in critically ill patients grouped randomized controlled trials (RCTs) by type of intensive care unit (ICU). The more recent review found that IIT reduced mortality in patients admitted to a surgical ICU, but not in those admitted to medical ICUs or mixed medical-surgical ICUs, or in all patients combined. Our objective was to determine whether IIT saves lives in critically ill surgical patients regardless of the type of ICU. Pooling mortality data from surgical and medical subgroups in mixed-ICU RCTs (16 trials) with RCTs conducted exclusively in surgical ICUs (five trials) and in medical ICUs (five trials), respectively, showed no effect of IIT in the subgroups of surgical patients (risk ratio = 0.85, 95% confidence interval (CI) = 0.69 to 1.04, P = 0.11; I2 = 51%, 95% CI = 1 to 75%) or of medical patients (risk ratio = 1.02, 95% CI = 0.95 to 1.09, P = 0.61; I2 = 0%, 95% CI = 0 to 41%). There was no differential effect between subgroups (interaction P = 0.10). There was statistical heterogeneity in the surgical subgroup, with some trials demonstrating significant benefit and others demonstrating significant harm, but no surgical subgroup consistently benefited from IIT. Such a reanalysis suggests that IIT does not reduce mortality in critically ill surgical patients or medical patients. Further insights may come from individual patient data meta-analyses or from future large multicenter RCTs in more narrowly defined subgroups of surgical patients.

Figure 1

Effect of intensive insulin therapy on mortality in surgical and medical patients. A z test of interaction between the risk ratio (RR) for mortality in (A) all surgical patients and (B) all medical patients was not statistically significant (P = 0.10), indicating that treatment effects did not differ between these two groups. This was also the case if one compares medical and surgical patients only within the same - that is, mixed intensive care unit (ICU) - trials (P = 0.66). Of the 14 trials conducted in mixed ICUs [4,5,7-18], one enrolled only surgical patients [7] and one enrolled only medical patients [10]. Preiser and colleagues' article [11] is the full publication of the abstract included in the most recent review [2]. After accounting for readmissions, subgroup-specific outcomes data were available for 991 out of 1,078 patients randomized. Compared with data presented in the most recent systematic review [2], subgroup-specific outcomes data are complete for all other trials except for 1/535 patients with missing data in one trial [12]. CI, confidence interval; I², percentage of total variation across studies due to between-study heterogeneity rather than chance; IIT, intensive insulin therapy; n/N = number of deaths/number of patients randomized; SAH, subarachnoid hemorrhage; TBI, traumatic brain injury.