Mypinder Sekhon - Academia.edu (original) (raw)

Papers by Mypinder Sekhon

Neurocritical Care

How continuous cerebral autoregulation (CCA) knowledge should be optimally gained and interpreted... more How continuous cerebral autoregulation (CCA) knowledge should be optimally gained and interpreted is still an active area of research and refinement. We now experience a unique situation of having indices clinically available before definitive evidence of benefit or practice guidelines, in a moment when high rates of institutional variability exist both in the application of monitoring as well as in monitoring-guided treatments. Responses from 47 international clinicians, experts in this field, were collected with polling and discussion of the results. The clinical use of CCA in critical illness was not universal among experts, with 34% not using it. Of those who use a CCA index in clinical practice, 64% use intracranial pressure-based Pressure Reactivity index (PRx). There seems to exist a considerable trust in the physiologic plausibility of CCA to guide individual arterial blood pressure and cerebral perfusion pressure therapy and provide benefit, regardless of the difficulty of proving this. A total of 59% feel the need for phase II and III prospective studies but would continue to use CCA information in their practice even if randomized controlled trials (RCTs) did not show clear clinical benefit. There was nearly universal interest to participate in an RCT, with agreement that the research community must together determine end points and interventions to reduce wasted effort and time, and that investigations should include the following: the most appropriate way of inclusion of CCA into the clinical workflow; whether CCA-guided interventions should be prophylactic, proactive; or reactive; and whether a CCAcentric (unimodal) or a multimodal monitoring-integrated tiered therapy approach should be adopted. Pediatric and neonatal populations were highlighted as having urgent need and even more plausibility than adults. On the whole, the initiative was enthusiastically embraced by the experts, with the general feeling that a strong push should be now made by the community to convert the plausible benefits of CCA monitoring, already implemented in some centers, into a more standardized and RCT-validated clinical reality.

Lancet Neurology, Jul 1, 2021

BACKGROUND The indications for intracranial pressure (ICP) monitoring in patients with acute brai... more BACKGROUND The indications for intracranial pressure (ICP) monitoring in patients with acute brain injury and the effects of ICP on patients' outcomes are uncertain. The aims of this study were to describe current ICP monitoring practises for patients with acute brain injury at centres around the world and to assess variations in indications for ICP monitoring and interventions, and their association with long-term patient outcomes. METHODS We did a prospective, observational cohort study at 146 intensive care units (ICUs) in 42 countries. We assessed for eligibility all patients aged 18 years or older who were admitted to the ICU with either acute brain injury due to primary haemorrhagic stroke (including intracranial haemorrhage or subarachnoid haemorrhage) or traumatic brain injury. We included patients with altered levels of consciousness at ICU admission or within the first 48 h after the brain injury, as defined by the Glasgow Coma Scale (GCS) eye response score of 1 (no eye opening) and a GCS motor response score of at least 5 (not obeying commands). Patients not admitted to the ICU or with other forms of acute brain injury were excluded from the study. Between-centre differences in use of ICP monitoring were quantified by using the median odds ratio (MOR). We used the therapy intensity level (TIL) to quantify practice variations in ICP interventions. Primary endpoints were 6 month mortality and 6 month Glasgow Outcome Scale Extended (GOSE) score. A propensity score method with inverse probability of treatment weighting was used to estimate the association between use of ICP monitoring and these 6 month outcomes, independently of measured baseline covariates. This study is registered with ClinicalTrial.gov, NCT03257904. FINDINGS Between March 15, 2018, and April 30, 2019, 4776 patients were assessed for eligibility and 2395 patients were included in the study, including 1287 (54%) with traumatic brain injury, 587 (25%) with intracranial haemorrhage, and 521 (22%) with subarachnoid haemorrhage. The median age of patients was 55 years (IQR 39-69) and 1567 (65%) patients were male. Considerable variability was recorded in the use of ICP monitoring across centres (MOR 4·5, 95% CI 3·8-4·9 between two randomly selected centres for patients with similar covariates). 6 month mortality was lower in patients who had ICP monitoring (441/1318 [34%]) than in those who were not monitored (517/1049 [49%]; p<0·0001). ICP monitoring was associated with significantly lower 6 month mortality in patients with at least one unreactive pupil (hazard ratio [HR] 0·35, 95% CI 0·26-0·47; p<0·0001), and better neurological outcome at 6 months (odds ratio 0·38, 95% CI 0·26-0·56; p=0·0025). Median TIL was higher in patients with ICP monitoring (9 [IQR 7-12]) than in those who were not monitored (5 [3-8]; p<0·0001) and an increment of one point in TIL was associated with a reduction in mortality (HR 0·94, 95% CI 0·91-0·98; p=0·0011). INTERPRETATION The use of ICP monitoring and ICP management varies greatly across centres and countries. The use of ICP monitoring might be associated with a more intensive therapeutic approach and with lower 6-month mortality in more severe cases. Intracranial hypertension treatment guided by monitoring might be considered in severe cases due to the potential associated improvement in long-term clinical results. FUNDING University of Milano-Bicocca and the European Society of Intensive Care Medicine.

Neurocritical Care, Apr 20, 2023

Alzheimers & Dementia, Dec 1, 2022

Intensive Care Medicine Experimental

Background Brain tissue oxygen tension (PbtO2) and cerebrovascular pressure reactivity monitoring... more Background Brain tissue oxygen tension (PbtO2) and cerebrovascular pressure reactivity monitoring have emerged as potential modalities to individualize care in moderate and severe traumatic brain injury (TBI). The relationship between these modalities has had limited exploration. The aim of this study was to examine the relationship between PbtO2 and cerebral perfusion pressure (CPP) and how this relationship is modified by the state of cerebrovascular pressure reactivity. Methods A retrospective multi-institution cohort study utilizing prospectively collected high-resolution physiologic data from the CAnadian High Resolution-TBI (CAHR-TBI) Research Collaborative database collected between 2011 and 2021 was performed. Included in the study were critically ill TBI patients with intracranial pressure (ICP), arterial blood pressure (ABP), and PbtO2 monitoring treated in any one of three CAHR-TBI affiliated adult intensive care units (ICU). The outcome of interest was how PbtO2 and CPP ...

Journal of Neurotrauma

People interested in the research are advised to contact the author for the final version of the ... more People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal. If the publication is distributed under the terms of Article 25fa of the Dutch Copyright Act, indicated by the "Taverne" license above, please follow below link for the End User Agreement:

The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack... more The COVID-19 pandemic continues to challenge the capacities of hospital ICUs which currently lack the ability to identify prospectively those patients who may require extended management. In this study of 90 ICU COVID-19 patients, we evaluated serum levels of four cytokines (IL-1β, IL-6, IL-10 and TNFα) as well as standard clinical and laboratory measurements. On 42 of these patients (binned into Initial and Replication Cohorts), we further performed CyTOF-based deep immunophenotyping of peripheral blood mononuclear cells with a panel of 38 antibodies. All measurements and patient samples were taken at time of ICU admission and retrospectively linked to patient clinical outcomes through statistical approaches. These analyses resulted in the definition of a new measure of patient clinical outcome: patients who will recover after short ICU stays (< 6 days) and those who will subsequently die or recover after long ICU stays (> 6 days). Based on these clinical outcome categories, ...

Medical Microbiology and Immunology, 2022

Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that caus... more Mechanisms underlying the SARS-CoV-2-triggered hyperacute thrombo-inflammatory response that causes multi-organ damage in coronavirus disease 2019 (COVID-19) are poorly understood. Several lines of evidence implicate overactivation of complement. To delineate the involvement of complement in COVID-19, we prospectively studied 25 ICU-hospitalized patients for up to 21 days. Complement biomarkers in patient sera and healthy controls were quantified by enzyme-linked immunosorbent assays. Correlations with respiratory function and mortality were analyzed. Activation of complement via the classical/lectin pathways was variably increased. Strikingly, all patients had increased activation of the alternative pathway (AP) with elevated levels of activation fragments, Ba and Bb. This was associated with a reduction of the AP negative regulator, factor (F) H. Correspondingly, terminal pathway biomarkers of complement activation, C5a and sC5b-9, were significantly elevated in all COVID-19 patient sera. C5a and AP constituents Ba and Bb, were significantly associated with hypoxemia. Ba and FD at the time of ICU admission were strong independent predictors of mortality in the following 30 days. Levels of all complement activation markers were sustained throughout the patients' ICU stays, contrasting with the varying serum levels of IL-6, C-reactive protein, and ferritin. Severely ill COVID-19 patients have increased and persistent activation of complement, mediated strongly via the AP. Complement activation biomarkers may be valuable measures of severity of lung disease and the risk of mortality. Large-scale studies will reveal the relevance of these findings to thromboinflammation in acute and post-acute COVID-19.

Critical Care Explorations, 2021

Objectives: We aimed to characterize the cerebrovascular physiology of cerebral fat embolism usin... more Objectives: We aimed to characterize the cerebrovascular physiology of cerebral fat embolism using invasive multimodal neuromonitoring. Data Sources: ICU, Vancouver General Hospital, Vancouver, BC, Canada. Study Selection: Case report. Data Extraction: Patient monitoring software (ICM+, Cambridge, United Kingdom), clinical records, and surgical records. Data Synthesis: None. Conclusions: Our integrated assessment of the cerebrovascular physiology of fat embolism syndrome provides a physiologic basis to investigate the importance of augmenting mean arterial pressure to optimize cerebral oxygen delivery for the mitigation of long-term neurologic ischemic sequelae of cerebral fat embolism.

Journal of Neurotrauma, 2021

Following acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarac... more Following acute traumatic spinal cord injury (SCI), the spinal cord can swell to fill the subarachnoid space and become compressed by the surrounding dura. In a porcine model of SCI, we performed a duraplasty to expand the subarachnoid space around the injured spinal cord and evaluated how this influenced acute intraparenchymal hemodynamic and metabolic responses, in addition to histological and behavioral recovery. Female Yucatan pigs were subjected to a T10 SCI, with or without duraplasty. Using micro-sensors implanted into the spinal cord parenchyma, changes in blood flow (ΔSCBF), oxygenation (ΔPO2), and spinal cord pressure (ΔSCP) during and after SCI were monitored, alongside metabolic responses. Behavioral recovery was tested weekly using the Porcine Injury Behavior Scale (PTIBS). Thereafter, spinal cords were harvested for histological analyses. In both duraplasty and non-duraplasty animals, the ΔSCP increased ~5 mmHg in the first 6 hours post-injury. After this, the SCP appeared to be slightly reduced in the duraplasty animals, although the group differences were not statistically significant after controlling for injury severity in terms of impact force. During the first 7 days post-SCI, the ΔSCBF or ΔPO2 values were not different between the duraplasty and control animals. Over 12 weeks, there was no improvement in hindlimb locomotion as assessed by PTIBS scores and no reduction in tissue damage at the injury site in the duraplasty animals. In our porcine model of SCI, duraplasty did not provide any clear evidence of long-term behavioral or histological benefit after SCI.

The Lancet Respiratory Medicine, 2021

Canadian Journal of Anesthesia/Journal canadien d'anesthésie, 2020

Purpose There is a paucity of evidence evaluating whether intensive care unit (ICU) discharge occ... more Purpose There is a paucity of evidence evaluating whether intensive care unit (ICU) discharge occupancy is associated with clinical outcomes. It is unknown whether increased discharge occupancy leads to greater afterhours discharges and downstream consequences. We explore the association between ICU discharge occupancy and afterhours discharges, 72-hr readmission, and 30-day mortality. Methods This single-centre, historical cohort study included all patients discharged from the Vancouver General Hospital ICU between 5 April 2010 and 13 September 2017. Data were obtained from the British Columbia Critical Care Database. Occupancy was defined as the number of ICU bed hours utilized divided by the available bed hours for that day. Any discharge between 22:00 and 6:59 was considered afterhours. Logistic regression models adjusting for important covariates were constructed. Results We included 8,862 ICU discharges representing 7,288 individual patients. There were 1,180 (13.3%) afterhours discharges, 408 (4.6%) 72-hr readmissions, and 574 (6.5%) 30-day post-discharge deaths. Greater discharge occupancy was associated with afterhours discharges

Journal of Applied Physiology, 2021

The acute effects of passive whole-body hyperthermia on the integrity of the neurovascular unit (... more The acute effects of passive whole-body hyperthermia on the integrity of the neurovascular unit (NVU) in humans have remained unclear. We demonstrate that passive heating for ∼1 h until an increase of +2°C esophageal temperature in healthy men does not increase the cerebral release of neuronal parenchymal stress biomarkers, suggesting the NVU integrity is maintained. This preliminary study indicates passive heating is safe for the brain, at least in young healthy men.

Canadian Medical Association Journal, 2020

La pandémie de maladie à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est asso... more La pandémie de maladie à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est associée à une mortalité élevée dans les unités de soins intensifs (USI). Nous avons voulu décrire les caractéristiques cliniques et les issues des patients gravement atteints de la maladie à coronavirus 2019 (COVID-19) en contexte canadien.

Background: There is a paucity of contemporary, patient-level data evaluating the association bet... more Background: There is a paucity of contemporary, patient-level data evaluating the association between discharge occupancy in the intensive care unit (ICU) and clinical outcomes such as readmission and mortality. Additionally, it is unknown whether increased occupancy at discharge may modify the timing of discharge (i.e. increased afterhours discharge) and further provoke negative clinical consequences. The objective of this single-center historical cohort study was to explore the association between ICU occupancy on the day of discharge and afterhours discharges, 72-hour readmission and 30-day mortality. Methods: This was a historical cohort study of a single large quaternary ICU in Canada. Discharge occupancy was defined as the number of hours of patient care delivered on the day of discharge divided by the total amount of hours of care available for that day (number of funded beds x 24 hours). Afterhours discharge was defined as a discharge between 22:00 and 6:59. Logistic regress...

Somatization may contribute to persistent symptoms after mild traumatic brain injury (mTBI). In t... more Somatization may contribute to persistent symptoms after mild traumatic brain injury (mTBI). In two independently-recruited study samples, we characterized the extent to which symptoms atypical of mTBI but typical for somatoform disorders (e.g., gastrointestinal upset, joint pain) were present in adult patients with prolonged recovery following mTBI. The first sample was cross-sectional and consisted of mTBI patients recruited from the community who reported ongoing symptoms attributable to a previous mTBI (n = 16) along with a healthy control group (n = 15). The second sample consisted of patients with mTBI prospectively recruited from a Level 1 trauma center who had either good recovery (GOSE = 8; n = 33) or poor recovery (GOSE < 8; n = 29). In all participants, we evaluated atypical somatic symptoms using the Patient Health Questionnaire-15 and typical post-concussion symptoms with the Rivermead Post-Concussion Symptom Questionnaire. Participants with poor recovery from mTBI h...

Intensive care medicine experimental, 2016

Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high ris... more Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high risk for developing nutritional deficiencies and undernutrition is known to be a risk factor for morbidity and mortality. Malnutrition represents a continuous spectrum ranging from marginal nutrient status to severe metabolic and functional alterations and this in turn, affects clinical outcome. Objectives: The aim of the study was to assess nutritional status of critically ill children admitted to the PICU and its association to clinical outcomes. Methods: Critically ill children age 6 months to 18 years were prospectively enrolled on PICU admission. Nutritional status was assessed by weight for age (WFA: underweight), weight for height (WFH: wasting), height for age (HFA: stunting) z-scores and mid upper arm circumference (MUAC: wasting) according to the WHO. (1,2) Malnutrition was defined as mild, moderate, and severe if z-scores were > −1, > − 2, and > −3, respectively. Hospital and PICU length of stay (LOS), duration of mechanical ventilation (MV), and risk of mortality (ROM) by the Pediatric Index of Mortality 2 (PIM2) were obtained. Sensitivity and specificity of the MUAC to identify children with wasting (WFH) were calculated. Results: Two hundred and fifty children (136 males), aged 81 months (23-167; median (25-75 th IQR)), were prospectively included in the study. The hospital LOS was 8 (4-16) days; PICU LOS: 2 (1-4) days; duration of MV, 0 (0-1.5) days;

This practical new resource uses a highly visual approach to summarise and simplify neurocritical... more This practical new resource uses a highly visual approach to summarise and simplify neurocritical care topics which can often seem daunting in their complexity. Diagrams, flowcharts, figures and tables highlight the main principles of disease pathophysiology, diagnosis and management, giving an easy-to-understand insight into this new and exciting field of medicine. Numerous high-quality radiographic images demonstrate the neuroimaging of neurological and neurosurgical diseases, and overviews of major clinical trials and studies provide an evidence-based perspective. Incorporating a full grounding in the fundamentals of neuroanatomy, neurophysiology and examination, and summaries of key points and suggested reading for each chapter, this book is a concise yet thorough reference for all those working in neurocritical care. Ideal for both trainees and specialists in neurology, neurosurgery, intensive care, anaesthesiology, emergency medicine and internal medicine.

Neurocritical Care Essentials

By Charles. mcKendree, a.b., m.D. Philadelphia and uol',llS-W. B. Saunders Company. 1928. Pp. 280... more By Charles. mcKendree, a.b., m.D. Philadelphia and uol',llS-W. B. Saunders Company. 1928. Pp. 280. I" trated.