A placebo-controlled randomized clinical trial of amantadine hydrochloride for evaluating the functional improvement of patients following severe acute traumatic brain injury.

BACKGROUND: Considering the known derangements in the dopaminergic neurotransmitter systems following traumatic brain injury (TBI), dopamine agonists are used as a pharmacologic option. In this study, we evaluate the effects of amantadine hydrochloride on the functional improvement of severe TBI patients. METHODS: Within a triple-blinded (patients, intervention administrators, and outcome assessors) placebo-controlled randomized clinical trial, we evaluated the effects of amantadine (100 mg BD (twice a day) for 14 days, then 150 mg BD for another 7 days, and 200 mg BD for another 21 days) on outcome measurements of weekly mean Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS), through six weeks of trial for 57 patients (29 amantadine, 28 placeboes) with severe TBI admitted in our hospital. RESULTS: Although both groups had improvement in their DRS, the change from baseline was significantly better in the amantadine group (10.88±5.24 for amantadine vs. 8.04±4.07 for placebo, P=0.015). No significant difference was observed between groups for GOS (1.04±0.55 for amantadine vs. 1.12±1.05 for placebo, P=0.966). CONCLUSIONS: Based on our findings, amantadine hydrochloride might improve the speed of functional ability improvement in severe TBI patients, evaluated by DRS, and is also well tolerated by patients. Although, there were some limitations in this study, including small sample size, short time interval, not providing a wash-off period and invalidity of GOS for measuring recovery rates in short-term periods.

Predisposing Factors for Hypoglycemia and Its Relation With Mortality in Critically Ill Patients Undergoing Insulin Therapy in an Intensive Care Unit.

BACKGROUND: Hypoglycemia is a common and the most important complication of intensive insulin therapy in critically ill patients. Because of hypoglycemia's impact on the cardinal organs as a fuel, if untreated it could results in permanent brain damage and increased mortality. OBJECTIVES: In this study, we aim to evaluate the incidence of hypoglycemia, its risk factors, and its relationship with mortality in critically ill patients. PATIENTS AND METHODS: Five hundred adult patients who admitted to an intensive care unit (ICU) were enrolled in this study. A program of glycemic control with a target of 100 - 140 mg/dL was instituted. We used the threshold of 150 mg/dL for septic patients, which were monitored by point of care devices for capillary blood measurement. We detected hypoglycemia with a blood sugar of less than 50 mg/dL and with the detection of each episode of hypoglycemia, blood glucose measurement was performed every 30 minutes. RESULTS: Five hundred patients experienced at least one episode of hypoglycemia, almost always on the third day. Of 15 expired patients who had one hypoglycemia episode, the most common causes were multiple trauma and sepsis. Increases in the sequential organ failure assessment (SOFA) number augmented the hypoglycemia risk to 52% (P < 0.001). Moreover, in patients with acute kidney injury (AKI), the risk of hypoglycemia is 10 times greater than in those without AKI (RR: 10.3, CI: 3.16 - 33.6, P < 0.001). ICU admission blood sugar has a significant relationship with mortality (RR: 1.01, CI: 1.004 - 1.02, P < 0.006). Hypoglycemia increased the mortality rate twofold, but it was not significant (RR: 1.2, CI: 0.927 - 1.58, P = 0.221). CONCLUSIONS: Our results showed that the SOFA score, AKI, and hemoglobin A1c are the independent risk factors for the development of hypoglycemia and demonstrated that ICU admission blood glucose, Hba1c, and hypoglycemia increased the risk of death, but only ICU admission blood glucose is significantly related to increased mortality.