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The cerebral oxygen cascade includes three key stages: (a) convective oxygen delivery representing the bulk flow of oxygen to the cerebral vascular bed; (b) diffusion of oxygen from the blood into brain tissue; and (c) cellular utilisation of oxygen for aerobic metabolism. All three stages may become dysfunctional after resuscitation from cardiac arrest and contribute to hypoxic-ischaemic brain injury (HIBI). Improving convective cerebral oxygen delivery by optimising cerebral blood flow has been widely investigated as a strategy to mitigate HIBI. However, clinical trials aimed at optimising convective oxygen delivery have yielded neutral results. Advances in the understanding of HIBI pathophysiology suggest that impairments in the stages of the oxygen cascade pertaining to oxygen diffusion and cellular utilisation of oxygen should also be considered in identifying therapeutic strategies for the clinical management of HIBI patients. Culprit mechanisms for these impairments may include a widening of the diffusion barrier due to peri-vascular oedema and mitochondrial dysfunction. An integrated approach encompassing both intra-parenchymal and non-invasive neuromonitoring techniques may aid in detecting pathophysiologic changes in the oxygen cascade and enable patient-specific management aimed at reducing the severity of HIBI., Author(s): Ryan L. Hoiland [sup.1] [sup.2] [sup.3] [sup.4] [sup.5], Chiara Robba [sup.6] [sup.7], David K. Menon [sup.8], Giuseppe Citerio [sup.9], Claudio Sandroni [sup.10], Mypinder S. Sekhon [sup.1] [sup.4] [sup.5] [sup.11] [...]

Purpose Targeted temperature management (TTM) may improve survival and functional outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA), though the optimal target temperature remains unknown. We conducted a systematic review and network meta-analysis to investigate the efficacy and safety of deep hypothermia (31-32 °C), moderate hypothermia (33-34 °C), mild hypothermia (35-36 °C), and normothermia (37-37.8 °C) during TTM. Methods We searched six databases from inception to June 2021 for randomized controlled trials (RCTs) evaluating TTM in comatose OHCA survivors. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was survival with good functional outcome. We used GRADE to rate our certainty in estimates. Results We included 10 RCTs (4218 patients). Compared with normothermia, deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73-2.30), moderate hypothermia (OR 1.34, 95% CI 0.92-1.94) and mild hypothermia (OR 1.44, 95% CI 0.74-2.80) may have no effect on survival with good functional outcome (all low certainty). Deep hypothermia may not improve survival with good functional outcome, as compared to moderate hypothermia (OR 0.97, 95% CI 0.61-1.54, low certainty). Moderate hypothermia (OR 1.23, 95% CI 0.86-1.77) and deep hypothermia (OR 1.27, 95% CI 0.70-2.32) may have no effect on survival, as compared to normothermia. Finally, incidence of arrhythmia was higher with moderate hypothermia (OR 1.45, 95% CI 1.08-1.94) and deep hypothermia (OR 3.58, 95% CI 1.77-7.26), compared to normothermia (both high certainty). Conclusions Mild, moderate, or deep hypothermia may not improve survival or functional outcome after OHCA, as compared to normothermia. Moderate and deep hypothermia were associated with higher incidence of arrhythmia. Routine use of moderate or deep hypothermia in comatose survivors of OHCA may potentially be associated with more harm than benefit., Author(s): Shannon M. Fernando [sup.1] [sup.2], Pietro Di Santo [sup.3] [sup.4], Behnam Sadeghirad [sup.5] [sup.6], Jean-Baptiste Lascarrou [sup.7], Bram Rochwerg [sup.6] [sup.8], Rebecca Mathew [sup.1] [sup.3], Mypinder S. Sekhon [sup.9], [...]

Author(s): Ryan L. Hoiland [sup.1] [sup.2], Chiara Robba [sup.3], David K. Menon [sup.4], Mypinder S. Sekhon [sup.5] Author Affiliations: (1) grid.17091.3e, 0000 0001 2288 9830, Department of Anesthesiology, Pharmacology and [...]

Purpose Assess the relationship between optic nerve sheath diameter (ONSD) measured on bedside portable computed tomography (CT) scans and simultaneously measured intracranial pressure (ICP) in patients with severe traumatic brain injury. Methods Retrospective cohort study of 57 patients admitted between 2009 and 2013. Linear and logistic regression were used to model the correlation and discrimination between ONSD and ICP or intracranial hypertension, respectively. Results The cohort had a mean age of 40 years (SD 16) and a median admission Glasgow coma score of 7 (IQR 4-10). The between-rater agreement by intraclass coefficient was 0.89 (95 % CI 0.83-0.93, P < 0.001). The mean ONSD was 6.7 mm (SD 0.75) and the mean ICP during CT was 21.3 mmHg (SD 8.4). Using linear regression, there was a strong correlation between ICP and ONSD (r = 0.74, P < 0.001). ONSD had an area under the curve to discriminate elevated ICP ([greater than or equal to]20 mmHg vs. Conclusions Simultaneous measurement of ONSD on CT and ICP were strongly correlated and ONSD was discriminative for intracranial hypertension. ONSD was much more predictive of ICP than other CT features. There was excellent agreement between raters in measuring ONSD., Author(s): Mypinder S. Sekhon [sup.1] [sup.2], Donald E. Griesdale [sup.1] [sup.3] [sup.4], Chiara Robba [sup.2], Nick McGlashan [sup.2], Edward Needham [sup.2], Katherine Walland [sup.2], Alyssa C. Shook [sup.5], Peter Smielewski [...]

Author(s): Mypinder S. Sekhon [sup.1] [sup.2], Donald E. Griesdale [sup.1] [sup.3] [sup.4], Chiara Robba [sup.2], Nick McGlashan [sup.2], Edward Needham [sup.2], Katherine Walland [sup.2], Alyssa C. Shook [sup.5], Peter Smielewski [...]