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Background: Three trials of tight glucose control (TGC) found clinical benefit of normalization of blood glucose levels in the intensive care unit (ICU). Implementation of TGC was imperfect in subsequent trials, since attained blood glucose levels (BGLs) never reached the targets as in the original trials of TGC. We investigated whether implementation of the TGC guideline as used in the original trials of TGC is feasible and safe., Methods: In this study 3 ICUs adopted and implemented the TGC guideline as used in the original trials of TGC using a multifaceted practice change strategy; 3 ICUs that did not change their blood glucose control guideline served as controls. TGC was practiced by physicians and nurses during the first 12-month (period-2), thereafter exclusively by nurses (period-3). Blood glucose metrics 12-month before (period-1) and 24-month after implementation of the guideline were compared., Results: The analysis included 1321 in period-1, 1169 and 1006 patients in period-2, and -3, respectively, in the intervention ICUs, and 3110 patients in the control ICUs. After implementation of the new TGC guideline, patients in intervention ICUs had lower median BGLs (105 [IQR: 85-130] mg/dL vs. 119 [99-150] mg/dL in period-1, P<0.001; and vs. 113 [95-141] mg/dL in control ICUs, P<0.001). The incidence of severe hypoglycemia initially increased, but again decreased when exclusively nurses practiced TGC, and was not associated with increased mortality or morbidity., Conclusions: Implementation of the original TGC guideline is feasible and safe. Our study suggests a learning effect over time.

Introduction: Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear., Methods: Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint., Results: We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively., Conclusions: Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality.

Strict glycemic control (SGC) is reported to have a beneficial effect on critical illness polyneuropathy/myopathy (CINM) and the duration of mechanical ventilation. The methodology used to diagnose CINM differs substantially in studies on this topic. This may influence the reported treatment effect. We reviewed literature on the effect of SGC on CINM and duration of ventilation by conducting a OVID Medline systematic electronic search of literature describing effects of SGC on occurrence of CINM and the effect of SGC on the duration of mechanical ventilation. A beneficial effect of SGC on CINM, diagnosed by needle myography, was reported in three studies. One of these studies showed that the incidence of weakness or failure to wean did not decrease by SGC, as the number of electrophysiological studies (EMG) ordered for these problems remained the same. Another study reported no improvement of muscle strength due to SGC. SGC reduced the duration of mechanical ventilation in three studies while six other studies did not report this beneficial effect. SGC seems to have a beneficial effect on CINM, but the reported risk reduction is likely to be an overestimation of the treatment effect due to the diagnostic methods used. Duration of mechanical ventilation may not be a reliable surrogate marker for CINM and a beneficial effect of SGC on this parameter has not been proven. We propose to use the recently developed diagnostic criteria for ICU-acquired weakness and critical illness neuromyopathy in future studies.

Background: Hyperglycemia and glycemic variabilities are associated with adverse outcomes in critically ill patients. Blood glucose control with insulin mandates an adequate and precise assessment of blood glucose levels. Blood glucose levels, however, can change ex vivo after sampling. The aim of this study was to determine whether this phenomenon affects the practice of blood glucose control., Methods: We performed an observational study in a mixed medical-surgical intensive care unit (ICU). ICU nurses were the primary healthcare workers involved in the practice of blood glucose control, and they used an insulin-titration method and blood-sampling algorithm aimed at maintaining blood glucose levels between 5 to 8 mmol/L., Results: Blood glucose levels were measured directly after sampling, as well as after 30 and 60 minutes using the same samples. Blood glucose control algorithm recommendations were scored for each measurement. We collected 450 blood samples from 74 patients (median of 3 [2-8] samples per patient). The mean ex vivo changes in the blood glucose level were rather small (-0.1±1.6 mmol/L (range -1.4 to 0.7) and -0.2±1.6 mmol/L (range -1.3 to 0.5) at 30 and 60 minutes after sampling, respectively; P<0.05). An ex-vivo change in the blood glucose level hardly ever resulted in a change in algorithm recommendation (4% and 6% at 30 and 60 minutes after sampling, respectively). In most cases the algorithm advised a lower insulin infusion speed., Conclusion: Ex vivo changes in blood glucose levels, although statistically significant, seem clinically irrelevant.

Background: To study current clinical practice in blood glucose (BG) control in adult intensive care units (ICUs) in the Netherlands., Methods: We performed a national survey focusing on blood glucose targets, insulin administration, BG control guidelines, and opinions regarding BG control aiming for normoglycaemia (known as intensive insulin therapy, IIT)., Results: The completed questionnaire was returned by 88/113 (78%) of the participating centres. In 98% (86/88) of the ICUs some sort of BG control was being practised. Half of the ICUs (42/86, 48%) used tight BG targets as with IIT; 28/86 (33%) and 13/86 (15%) used more liberal targets of 4.4 to 7.0 mmol/l and 4.4 to 8.0 mmol/l, respectively. Eighty-two (93%) reported having a local guideline on BG control (or IIT). The BG threshold to start insulin was 7.0+/-1.3 mmol/l vs 7.8+/-1.3 mmol/l in ICUs that practised IIT vs ICUs that practised less tight BG control, respectively (p=0.005). In 28/86 (33%) measurement of the BG values was done according to a strict time schedule (i.e., BG values were measured on predefined time points). While respondents were fairly agreed on the benefits of IIT, opinions regarding ease of implementation and time needed to apply this strategy varied. In addition, severe hypoglycaemia was considered a serious side effect of IIT., Conclusion: Approximately half of the ICUs in the Netherlands reported having implemented IIT. However, the full guideline as used in the original studies on IIT was hardly ever implemented. Concerns about severe hypoglycaemia, at least in part, hampers implementation of IIT.

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.