Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.     

Optimization of infusional calcium gluconate for prevention of hypocalcemic reactions during therapeutic plasma exchange

We sought to optimize direct intravenous infusion of calcium gluconate (CaGlu) for maintaining plasma ionized calcium concentration ([Ca²⁺]) and preventing hypocalcemic reactions during 34 consecutive 1-volume therapeutic plasma exchanges (TPEs) in eight patients. CaGlu, 2 g in 50 mL of 0.9% NaCl, was prepared by our hospital pharmacy and infused at either 1.0 or 1.6 g/h during alternate TPE. Plasma [Ca²⁺] was monitored at intervals of 20 to 30 minutes. At 1 g/h of CaGlu, plasma [Ca²⁺] fell by 8.35% after 40 to 50 minutes and then plateaued. At 1.6 g/h of CaGlu, plasma [Ca²⁺] fell by 6% after 20 to 30 minutes and then plateaued. The difference at 40 to 50 minutes was significant (P = .015). Hypocalcemic reactions were noted in three patients during 5 of 17 TPE at 1.0 g/h (all after 40 to 60 minutes) but 0 of 17 TPE at 1.6 g/h (P = .044). CaGlu at 1.6 g/h stabilized plasma [Ca²⁺] and appears to prevent hypocalcemic reactions during TPE.     

Dermal elastolysis in the setting of combination immunotherapy

Multiple cutaneous side effects have been reported with the use of immunotherapies including programmed cell death protein 1 inhibitors. We report 2 patients who presented with papillary dermal elastolysis presenting as multiple, skin‐colored, wrinkled papules and atrophic macules following an inflammatory eruption in the setting of combination chemotherapy with nivolumab and cabiralizumab. These two cases highlight a novel finding, elastolysis in the setting of chemotherapy with nivolumab and cabiralizumab.     

Body surface area and medication dosing in patients with heart failure with reduced ejection fraction

Multiple medications are proven to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), but data regarding personalized approaches to optimize medication dosing remain limited. Current treatment guidelines recommend up-titration to target or maximally tolerated doses of these medications, yet use and dosing remain suboptimal in clinical practice. Body surface area (BSA) is a readily available clinical metric, used for dosing many medications, closely associated with blood pressure, renal function, and vascular congestion, and may influence efficacy, safety, and tolerability of HFrEF medications. In this review, we examine the rationale, strengths/weaknesses, and potential utility of BSA as a means of optimizing HFrEF medication use and dosing.