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9. Intracranial Pressure-Derived Cerebrovascular Reactivity Indices and Their Critical Thresholds: A Canadian High Resolution-Traumatic Brain Injury Validation Study

Author

Stein, Kevin, Froese, Logan, Sekhon, Mypinder Singh, Griesdale, Donald E, Thelin, Eric Peter, Raj, Rahul, Tas, Jeanette, Aries, Marcel, Gallagher, Clare N, Bernard, Francis, Gomez, Alwyn, Kramer, Andreas H, Zeiler, Frederick A, Stein, Kevin, Froese, Logan, Sekhon, Mypinder Singh, Griesdale, Donald E, Thelin, Eric Peter, Raj, Rahul, Tas, Jeanette, Aries, Marcel, Gallagher, Clare N, Bernard, Francis, Gomez, Alwyn, Kramer, Andreas H, and Zeiler, Frederick A

Abstract

Current neurointensive care guidelines recommend intracranial pressure (ICP) and cerebral perfusion pressure (CPP) centered management for moderate-severe traumatic brain injury (TBI) due to their demonstrated associations with patient outcome. Cerebrovascular reactivity metrics, such as the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC index, have also demonstrated significant prognostic capabilities with regards to outcome. However, critical thresholds for cerebrovascular reactivity indices have only been identified in two studies conducted at the same center. In this study, we aim to determine the critical thresholds of these metrics by leveraging a unique multicenter database. The study included a total of 354 patients from the CAnadian High-Resolution TBI (CAHR-TBI) Research Collaborative. Based on 6-month Glasgow Outcome Scores, patients were dichotomized into Alive vs. Dead and Favorable vs. Unfavorable. Chi-square values were then computed for incrementally increasing values of each physiological parameter of interest against outcome. The values that generated the greatest chi-squares for each parameter were considered to be the thresholds with the greatest outcome discriminatory capacity. To confirm that the identified thresholds provide prognostic utility, univariate and multivariable logistic regression analyses were performed adjusting for the International Mission for Prognosis and Analysis of Clinical Trials (IMPACT) variables. Through the chi-square analysis, a lower limit CPP threshold of 60 mmHg and ICP thresholds of 18 mmHg and 22 mmHg were identified for both survival and favorable outcome predictions. For the cerebrovascular reactivity metrics, different thresholds were identified for the two outcome dichotomizations. For survival prediction, thresholds of 0.35, 0.25, and 0 were identified for PRx, PAx, and RAC, respectively. For favorable outcome prediction, thresholds of 0.325, 0.20, and 0.05 were found. Univariate logis

Published
2024

17. Near-Infrared Spectroscopy to Assess Cerebral Autoregulation and Optimal Mean Arterial Pressure in Patients With Hypoxic-Ischemic Brain Injury: A Prospective Multicenter Feasibility Study

Author

Griesdale, Donald. E. G., Sekhon, Mypinder S., Wood, Michael D., Cardim, Danilo, Brasher, Penelope M. A., McCredie, Victoria, Sirounis, Demetrious, Foster, Denise, Krasnogolova, Yulia, Smielewski, Peter, Scales, Damon C., Ainslie, Philip N., Menon, David K., Boyd, J. Gordon, Field, Thalia S., and Dorian, Paul

Published
2020
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18. The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019

Author

Stukas, Sophie, Hoiland, Ryan L., Cooper, Jennifer, Thiara, Sonny, Griesdale, Donald E., Thomas, Adam D., Orde, Matthew M., English, John C., Chen, Luke Y. C., Foster, Denise, Mitra, Anish R., Romano, Kali, Sweet, David D., Ronco, Juan J., Kanji, Hussein D., Chen, Yu-Wei R., Wong, Sophia L., Wellington, Cheryl L., and Sekhon, Mypinder S.

Published
2020
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27. Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution Traumatic Brain Injury (CAHR-TBI) Study

Author

Batson, Carleen, Froese, Logan, Sekhon, Mypinder Singh, Griesdale, Donald E, Gomez, Alwyn, Thelin, Eric Peter, Raj, Rahul, Aries, Marcel, Gallagher, Clare N, Bernard, Francis, Kramer, Andreas H, Zeiler, Frederick Adam, Batson, Carleen, Froese, Logan, Sekhon, Mypinder Singh, Griesdale, Donald E, Gomez, Alwyn, Thelin, Eric Peter, Raj, Rahul, Aries, Marcel, Gallagher, Clare N, Bernard, Francis, Kramer, Andreas H, and Zeiler, Frederick Adam

Abstract

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP)-based indices: 1) pressure reactivity index (PRx)-correlation between ICP and mean arterial pressure (MAP); 2) pulse amplitude index (PAx)-correlation between pulse amplitude of ICP (AMP) and MAP; and 3) RAC-correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60), and decades of age (< 30, 30-39, 40-49, 50-59, 60-69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC, and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect imp

Published
2023

32. Impact of Chronological Age and Biological Sex on Cerebrovascular Reactivity in Moderate/Severe Traumatic Brain Injury: A CAnadian High-Resolution TBI (CAHR-TBI) Study

Author

Batson, Carleen, Froese, Logan, Sekhon, Mypinder Singh, Griesdale, Donald E, Gomez, Alwyn, Thelin, Eric Peter, Raj, Rahul, Aries, Marcel, Gallagher, Clare N, Bernard, Francis, Kramer, Andreas H, Zeiler, Frederick Adam, Intensive Care, MUMC+: MA Medische Staf IC (9), and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience

Abstract

Impaired cerebrovascular reactivity has emerged as an important associate with poor long-term outcome after moderate/severe traumatic brain injury (TBI). However, our understanding of what drives or modulates the degree of impaired cerebrovascular function remains poor. Age and biological sex remain important modifiers of cerebrovascular function in health and disease, yet their impact on cerebrovascular reactivity after TBI remains unclear. The aim of this study was to explore subgroup responses based on age and biological sex on cerebral physiology. Data from 283 TBI patients from the CAnadian High Resolution TBI (CAHR-TBI) Research Collaborative were evaluated. Cerebrovascular reactivity was determined using high-frequency cerebral physiology for the derivation of three intracranial pressure (ICP) based indices: (1). PRx - correlation between ICP and mean arterial pressure (MAP), (2). PAx - correlation between pulse amplitude of ICP (AMP) and MAP and (3). RAC - correlation between AMP and cerebral perfusion pressure (CPP). Insult burden (% time above clinically defined thresholds) were calculated for these indices. These cerebral physiology indices were studied for their relationship with age via linear regression, age trichotomization (< 40, 40 - 60, > 60) and decades of age (< 30, 30 - 39, 40 - 49, 50 - 59, 60 - 69, > 69) schemes. Similarly, differences based on biological sex were assessed. A statistically significant positive linear correlation was found between PAx, RAC and age. In corollary, a statistically significant relationship was found between increasing age on trichotomized and decades of age analysis with PAx and RAC measures. PRx failed to demonstrate such relationships to advancing age. There was no clear difference in cerebrovascular reactivity profiles between biological sex categories. These findings suggest that AMP-based cerebrovascular reactivity indices may be better positioned to detect impairment in TBI patients with advancing age. Further investigation into the utility of PAx and RAC is required, as they may prove useful for certain subgroups of patients.

Published
2022

40. Therapeutic hypothermia attenuates physiologic, histologic, and metabolomic markers of injury in a porcine model of acute respiratory distress syndrome

Author

Angus, Sarah A., primary, Henderson, William R., additional, Banoei, Mohammad M., additional, Molgat‐Seon, Yannick, additional, Peters, Carli M., additional, Parmar, Hanna R., additional, Griesdale, Donald E. G., additional, Sekhon, Mypinder, additional, Sheel, Andrew William, additional, Winston, Brent W., additional, and Dominelli, Paolo B., additional

Published
2022
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41. Neurologic Prognostication After Cardiac Arrest Using Brain Biomarkers

Author

Hoiland, Ryan L., primary, Rikhraj, Kiran J. K., additional, Thiara, Sharanjit, additional, Fordyce, Christopher, additional, Kramer, Andreas H., additional, Skrifvars, Markus B., additional, Wellington, Cheryl L., additional, Griesdale, Donald E., additional, Fergusson, Nicholas A., additional, and Sekhon, Mypinder S., additional

Published
2022
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42. Optic nerve sheath diameter on computed tomography is correlated with simultaneously measured intracranial pressure in patients with severe traumatic brain injury

Author

Sekhon, Mypinder S., Griesdale, Donald E., Robba, Chiara, McGlashan, Nick, Needham, Edward, Walland, Katherine, and Shook, Alyssa C.

Subjects
Care and treatment, Measurement, Injuries, Intracranial pressure -- Measurement, Hypertension -- Care and treatment, Medical research -- Measurement, Brain injuries -- Care and treatment, CAT scans -- Measurement, Medicine, Experimental -- Measurement, Brain -- Injuries, CT imaging -- Measurement
Abstract

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 [...], 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.

Published
2014
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45. High–normal versuslow–normal mean arterial pressure thresholds in critically ill patients: a systematic review and meta-analysis of randomized trials

Author

Rikhraj, Kiran J. K., Ronsley, Claire, Sekhon, Mypinder S., Mitra, Anish R., and Griesdale, Donald E. G.

Abstract

Purpose: Targeted blood pressure thresholds remain unclear in critically ill patients. Two prior systematic reviews have not shown differences in mortality with a high mean arterial pressure (MAP) threshold, but there have been new studies published since. Thus, we conducted an updated systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the effect of a high–normal vslow–normal MAP on mortality, favourable neurologic outcome, need for renal replacement therapy, and adverse vasopressor-induced events in critically ill patients. Source: We searched six databases from inception until 1 October 2022 for RCTs of critically ill patients targeted to either a high–normal vsa low–normal MAP threshold for at least 24 hr. We assessed study quality using the revised Cochrane risk-of-bias 2 tool and the risk ratio (RR) was used as the summary measure of association. We used the Grading of Recommendations Assessment, Development, and Evaluation framework to assess the certainty of evidence. Principal findings: We included eight RCTs with 4,561 patients. Four trials were conducted in patients following out-of-hospital cardiac arrest, two in patients with distributive shock requiring vasopressors, one in patients with septic shock, and one in patients with hepatorenal syndrome. The pooled RRs for mortality (eight RCTs; 4,439 patients) and favourable neurologic outcome (four RCTs; 1,065 patients) were 1.06 (95% confidence interval [CI], 0.99 to 1.14; moderate certainty) and 0.99 (95% CI, 0.90 to 1.08; moderate certainty), respectively. The RR for the need for renal replacement therapy (four RCTs; 4,071 patients) was 0.97 (95% CI, 0.87 to 1.08; moderate certainty). There was no statistical between-study heterogeneity across all outcomes. Conclusion: This updated systematic review and meta-analysis of RCTs found no differences in mortality, favourable neurologic outcome, or the need for renal replacement therapy between critically ill patients assigned to a high–normal vslow–normal MAP target. Study registration: PROSPERO (CRD42022307601); registered 28 February 2022.

Published
2023
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