Cerebral metabolic effects of strict versus conventional glycaemic targets following severe traumatic brain injury.

Optimal glycaemic targets for patients with severe traumatic brain injury remain unclear. The primary objective of this microdialysis study was to compare cerebral metabolism between strict and conventional glycaemic control. Methods We performed a prospective single-centre randomised controlled within-subject crossover study in 20 adult patients admitted to an academic neurointensive care unit with severe traumatic brain injury. Patients underwent randomised, consecutive 24-hour periods of strict (4 - 7 mmol/L; 72 - 126 mg/dL) and conventional (<10 mmol/L; 180 mg/dL) glycaemic control with microdialysis measurements performed hourly. The first 12 hours of each study period was designated as ‘wash-out’ with the subsequent 12 hours being the period of interest. Results Cerebral glucose was lower during strict glycaemia compared to conventional control (1.05 (0.58, 1.51) mmol/L versus 1.28 (0.81, 1.74) mmol/L; P = 0.03) as was lactate (3.07 (2.44, 3.70) versus 3.56 (2.81, 4.30); P <0.001). There were no significant differences in pyruvate or the lactate/pyruvate ratio between treatment phases. Strict glycaemia increased the frequency of low cerebral glucose (<0.8 mmol/L), OR 1.91, 95% CI 1.01 – 3.65; P <0.05, however, there were no differences in the frequency of critically low glucose (<0.2 mmol/L) or critically elevated lactate/pyruvate ratio between phases. Conclusions Compared with conventional glycaemic targets, strict blood glucose control was associated with lower mean levels of cerebral glucose and an increased frequency of abnormally low glucose levels. These data support conventional glycaemic targets following TBI

Impact of nasogastric tubes on swallowing physiology in older, healthy subjects: a randomized controlled crossover trial

Background & aims: The presence of a nasogastric tube (NGT) affects swallowing physiology but not function in healthy young adults. The swallowing mechanism changes with increasing age, therefore the impact of a NGT on swallowing in elderly individuals is likely to be different but is not yet known. The aims of this study were to determine the effects of NGTs of different diameter on (1) airway penetration-aspiration, (2) pharyngeal residue, and (3) pharyngeal transit, in older healthy subjects

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Demographic data by study group.

<p>Demographic data by study group.</p

CONSORT style flowchart of patients included in analysis.

<p>SIH, stress induced hyperglycemia.</p

Sub-hazard ratios for the risk of type 2 diabetes by glycemic category and age group.

<p>Control group = blue bars; stress induced hyperglycemia = red bars. Age is grouped approximately into deciles with normoglycemia and age 18–29 years as the base reference; Data are sub-hazard ratios ± 95% confidence intervals.</p

Cumulative incidence for type 2 diabetes for the control group (blue line) versus stress induced hyperglycemia (red line).

<p>Cumulative incidence for type 2 diabetes for the control group (blue line) versus stress induced hyperglycemia (red line).</p