The Effect of a Liberal Approach to Glucose Control in Critically Ill Patients with Type 2 Diabetes: A Multicenter, Parallel-Group, Open-Label Randomized Clinical Trial.

Rationale: Blood glucose concentrations affect outcomes in critically ill patients, but the optimal target blood glucose range in those with type 2 diabetes is unknown. Objectives: To evaluate the effects of a "liberal" approach to targeted blood glucose range during ICU admission. Methods: This mutlicenter, parallel-group, open-label randomized clinical trial included 419 adult patients with type 2 diabetes expected to be in the ICU on at least three consecutive days. In the intervention group intravenous insulin was commenced at a blood glucose >252 mg/dl and titrated to a target range of 180-252 mg/dl. In the comparator group insulin was commenced at a blood glucose >180 mg/dl and titrated to a target range of 108-180 mg/dl. The primary outcome was incident hypoglycemia (<72 mg/dl). Secondary outcomes included glucose metrics and clinical outcomes. Measurements and Main Results: By Day 28, at least one episode of hypoglycemia occurred in 10 of 210 (5%) patients assigned the intervention and 38 of 209 (18%) patients assigned the comparator (incident rate ratio, 0.21 [95% confidence interval (CI), 0.09 to 0.49]; P < 0.001). Those assigned the intervention had greater blood glucose concentrations (daily mean, minimum, maximum), less glucose variability, and less relative hypoglycemia (P < 0.001 for all comparisons). By Day 90, 62 of 210 (29.5%) in the intervention and 52 of 209 (24.9%) in the comparator group had died (absolute difference, 4.6 percentage points [95% CI, -3.9% to 13.2%]; P = 0.29). Conclusions: A liberal approach to blood glucose targets reduced incident hypoglycemia but did not improve patient-centered outcomes. Clinical trial registered with Australian New Zealand Clinical Trials Registry (ACTRN 12616001135404).

A multicenter randomized clinical trial of pharmacological vitamin B1 administration to critically ill patients who develop hypophosphatemia during enteral nutrition (The THIAMINE 4 HYPOPHOSPHATEMIA trial).

BACKGROUND: Hypophosphatemia may be a useful biomarker to identify thiamine deficiency in critically ill enterally-fed patients. The objective was to determine whether intravenous thiamine affects blood lactate, biochemical and clinical outcomes in this group. METHOD: This randomized clinical trial was conducted across 5 Intensive Care Units. Ninety critically ill adult patients with a serum phosphate ≤0.65 mmol/L within 72 h of commencing enteral nutrition were randomized to intravenous thiamine (200 mg every 12 h for up to 14 doses) or usual care (control). The primary outcome was blood lactate over time and data are median [IQR] unless specified. RESULTS: Baseline variables were well balanced (thiamine: lactate 1.2 [1.0, 1.6] mmol/L, phosphate 0.56 [0.44, 0.64] mmol/L vs. control: lactate 1.0 [0.8, 1.3], phosphate 0.54 [0.44, 0.61]). Patients randomized to the intervention received a median of 11 [7.5, 13.5] doses for a total of 2200 [1500, 2700] mg of thiamine. Blood lactate over the entire 7 days of treatment was similar between groups (mean difference = -0.1 (95 % CI -0.2 to 0.1) mmol/L; P = 0.55). The percentage change from lactate pre-randomization to T = 24 h was not statistically different (thiamine: -32 (-39, -26) vs. control: -24 (-31, -16) percent, P = 0.09). Clinical outcomes were not statistically different (days of vasopressor administration: thiamine 2 [1, 4] vs. control 2 [0, 5.5] days; P = 0.37, and deaths 9 (21 %) vs. 5 (11 %); P = 0.25). CONCLUSIONS: In critically ill enterally-fed patients who developed hypophosphatemia, intravenous thiamine did not cause measurable differences in blood lactate or clinical outcomes. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12619000121167).