Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury.

BACKGROUND: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear. METHODS: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months. RESULTS: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively. CONCLUSIONS: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.).

Brain Hypoxia Is Associated With Neuroglial Injury in Humans Post-Cardiac Arrest.

[Figure: see text].

High-normal versus low-normal mean arterial pressure thresholds in critically ill patients: a systematic review and meta-analysis of randomized trials.

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 vs low-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 vs a 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 vs low-normal MAP target. STUDY REGISTRATION: PROSPERO (CRD42022307601); registered 28 February 2022.

RéSUMé: OBJECTIF: Les seuils de pression artérielle ciblés demeurent incertains chez les patient·es gravement malades. Deux revues systématiques antérieures n'ont pas montré de différences dans la mortalité avec un seuil élevé de pression artérielle moyenne (PAM), mais de nouvelles études ont été publiées depuis. Pour cette raison, nous avons réalisé une revue systématique mise à jour et une méta-analyse d'études randomisées contrôlées (ERC) comparant l'effet d'une PAM normale élevée vs normale faible sur la mortalité, les devenirs neurologiques favorables, la nécessité d'un traitement substitutif de l'insuffisance rénale et les événements indésirables induits par les vasopresseurs chez les patient·es gravement malades. SOURCES: Nous avons effectué des recherches dans six bases de données depuis leur création jusqu'au 1er octobre 2022 pour trouver des ERC portant sur des patient·es gravement malades chez lesquel·les un seuil de PAM normale élevée ou normale faible a été ciblé pendant au moins 24 heures. Nous avons évalué la qualité des études à l'aide de l'outil de risque de biais 2 révisé de Cochrane, et le risque relatif (RR) a été utilisé comme mesure sommaire de l'association. Nous avons utilisé le système de notation GRADE (Grading of Recommendations Assessment, Development, and Evaluation) pour évaluer la certitude des données probantes. CONSTATATIONS PRINCIPALES: Nous avons inclus huit ERC portant sur 4561 personnes traitées. Quatre études ont été menées chez des patient·es à la suite d'un arrêt cardiaque hors de l'hôpital, deux chez des patient·es présentant un choc distributif nécessitant des vasopresseurs, une chez des patient·es présentant un choc septique et une chez des patient·es atteint·es d'un syndrome hépato-rénal. Les RR combinés pour la mortalité (huit ERC; 4439 personnes) et les devenirs neurologiques favorables (quatre ERC; 1065 personnes) étaient respectivement de 1,06 (intervalle de confiance [IC] à 95 %, 0,99 à 1,14; certitude modérée) et de 0,99 (IC 95 %, 0,90 à 1,08; certitude modérée). Le RR pour le besoin de traitement substitutif de l'insuffisance rénale (quatre ERC; 4071 patient·es) était de 0,97 (IC 95 %, 0,87 à 1,08; certitude modérée). Il n'y avait pas d'hétérogénéité statistique entre les études pour tous les critères d'évaluation. CONCLUSION: Ces revue systématique et méta-analyse mises à jour des ERC n'ont révélé aucune différence dans la mortalité, les devenirs neurologiques favorables ou la nécessité d'un traitement substitutif de l'insuffisance rénale entre les patient·es gravement malades assigné·es à une cible de PAM normale élevée vs normale faible. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42022307601); enregistrée le 28 février 2022.

The Use of Near-Infrared Spectroscopy and/or Transcranial Doppler as Non-Invasive Markers of Cerebral Perfusion in Adult Sepsis Patients With Delirium: A Systematic Review.

BACKGROUND: Several studies have previously reported the presence of altered cerebral perfusion during sepsis. However, the role of non-invasive neuromonitoring, and the impact of altered cerebral perfusion, in sepsis patients with delirium remains unclear. METHODS: We performed a systematic review of studies that used near-infrared spectroscopy (NIRS) and/or transcranial Doppler (TCD) to assess adults (≥18 years) with sepsis and delirium. From study inception to July 28, 2020, we searched the following databases: Ovid MedLine, Embase, Cochrane Library, and Web of Science. RESULTS: Of 1546 articles identified, 10 met our inclusion criteria. Although NIRS-derived regional cerebral oxygenation was consistently lower, this difference was only statistically significant in one study. TCD-derived cerebral blood flow velocity was inconsistent across studies. Importantly, both impaired cerebral autoregulation during sepsis and increased cerebrovascular resistance were associated with delirium during sepsis. However, the heterogeneity in NIRS and TCD devices, duration of recording (from 10 seconds to 72 hours), and delirium assessment methods (e.g., electronic medical records, confusion assessment method for the intensive care unit), precluded meta-analysis. CONCLUSION: The available literature demonstrates that cerebral perfusion disturbances may be associated with delirium in sepsis. However, future investigations will require consistent definitions of delirium, delirium assessment training, harmonized NIRS and TCD assessments (e.g., consistent measurement site and length of recording), as well as the quantification of secondary and tertiary variables (i.e., Cox, Mxa, MAPOPT), in order to fully assess the relationship between cerebral perfusion and delirium in patients with sepsis.

Goal-Directed Care Using Invasive Neuromonitoring Versus Standard of Care After Cardiac Arrest: A Matched Cohort Study.

PURPOSE: Following return of spontaneous circulation after cardiac arrest, hypoxic ischemic brain injury is the primary cause of mortality and disability. Goal-directed care using invasive multimodal neuromonitoring has emerged as a possible resuscitation strategy. We evaluated whether goal-directed care was associated with improved neurologic outcome in hypoxic ischemic brain injury patients after cardiac arrest. DESIGN: Retrospective, single-center, matched observational cohort study. SETTING: Quaternary academic medical center. PATIENTS: Adult patients admitted to the ICU following return of spontaneous circulation postcardiac arrest with clinical evidence of hypoxic ischemic brain injury defined as greater than or equal to 10 minutes of cardiac arrest with an unconfounded postresuscitation Glasgow Coma Scale of less than or equal to 8. INTERVENTIONS: We compared patients who underwent goal-directed care using invasive neuromonitoring with those treated with standard of care (using both total and matched groups). MEASUREMENTS AND MAIN RESULTS: Goal-directed care patients were matched 1:1 to standard of care patients using propensity scores and exact matching. The primary outcome was a 6-month favorable neurologic outcome (Cerebral Performance Category of 1 or 2). We included 65 patients, of whom 21 received goal-directed care and 44 patients received standard of care. The median age was 50 (interquartile range, 35-61), 48 (74%) were male, and seven (11%) had shockable rhythms. Favorable neurologic outcome at 6 months was significantly greater in the goal-directed care group (n = 9/21 [43%]) compared with the matched (n = 2/21 [10%], p = 0.016) and total (n = 8/44 [18%], p = 0.034) standard of care groups. Goal-directed care group patients had higher mean arterial pressure (p < 0.001 vs total; p = 0.0060 vs matched) and lower temperature (p = 0.007 vs total; p = 0.041 vs matched). CONCLUSIONS: In this preliminary study of patients with hypoxic ischemic brain injury postcardiac arrest, goal-directed care guided by invasive neuromonitoring was associated with a 6-month favorable neurologic outcome (Cerebral Performance Category 1 or 2) versus standard of care. Significant work is required to confirm this finding in a prospectively designed study.

Transport Time and Mortality in Critically Ill Patients with Severe Traumatic Brain Injury.

PURPOSE: Severe traumatic brain injury (TBI) is a major cause of morbidity and mortality in critically ill patients. Pre-hospital care and transportation time may impact their outcomes. METHODS: Using the British Columbia Trauma Registry, we included 2,860 adult (≥18 years) patients with severe TBI (abbreviated injury scale head score ≥4), who were admitted to an intensive care unit (ICU) in a centre with neurosurgical services from January 1, 2000 to March 31, 2013. We evaluated the impact of transportation time (time of injury to time of arrival at a neurosurgical trauma centre) on in-hospital mortality and discharge disposition, adjusting for age, sex, year of injury, injury severity score (ISS), revised trauma score at the scene, location of injury, socio-economic status and direct versus indirect transfer. RESULTS: Patients had a median age of 43 years (interquartile range [IQR] 26-59) and 676 (23.6%) were female. They had a median ISS of 33 (IQR 26-43). Median transportation time was 80 minutes (IQR 40-315). ICU and hospital length of stay were 6 days (IQR 2-12) and 20 days (IQR 7-42), respectively. Six hundred and ninety-six (24.3%) patients died in hospital. After adjustment, there was no significant impact of transportation time on in-hospital mortality (odds ratio 0.98, 95% confidence interval 0.95-1.01). There was also no significant effect on discharge disposition. CONCLUSIONS: No association was found between pre-hospital transportation time and in-hospital mortality in critically ill patients with severe TBI.

Determining Optimal Mean Arterial Pressure After Cardiac Arrest: A Systematic Review.

The use of cerebral autoregulation monitoring to identify patient-specific optimal mean arterial pressure (MAPOPT) has emerged as a technique to augment cerebral oxygen delivery in post-cardiac arrest patients. Our systematic review aims to determine (a) the average MAPOPT in these patients, (b) the feasibility of identifying MAPOPT, (c) the brain tissue oxygenation levels when MAP is within proximity to the MAPOPT and (d) the relationship between neurological outcome and MAPOPT-targeted resuscitation strategies. We carried out this review in accordance with the PRISMA guidelines. We included all studies that used cerebral autoregulation to determine MAPOPT in adult patients (> 16 years old) who achieved return of spontaneous circulation (ROSC) following cardiac arrest. All studies had to include our primary outcome of MAPOPT. We excluded studies where the patients had any history of traumatic brain injury, ischemic stroke or intracranial hemorrhage. We identified six studies with 181 patients. There was wide variability in cerebral autoregulation monitoring methods, length of monitoring, calculation and reporting of MAPOPT. Amongst all studies, the median or mean MAPOPT was consistently above 65 mmHg (range 70-114 mmHg). Definitions of feasibility varied among studies and were difficult to summarize. Only one study noted that brain tissue oxygenation increased as patients' MAP approached MAPOPT. There was no consistent association between targeting MAPOPT and improved neurological outcome. There is considerable heterogeneity in MAPOPT due to differences in monitoring methods of autoregulation. Further research is needed to assess the clinical utility of MAPOPT-guided strategies on decreasing secondary injury and improving neurological outcomes after ROSC.

Brain Hypoxia Secondary to Diffusion Limitation in Hypoxic Ischemic Brain Injury Postcardiac Arrest.

OBJECTIVES: We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg). DESIGN: Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia. SETTING: Quaternary ICU. PATIENTS: Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest. INTERVENTIONS: Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively. MEASUREMENTS AND MAIN RESULTS: Both the normoxia and hypoxia groups consisted of seven patients. In the normoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen tension, and cerebral perfusion pressure were 29 mm Hg (SD, 9), 45 mm Hg (SD, 9), and 80 mm Hg (SD, 7), respectively. In the hypoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen to brain tissue oxygen tension gradient, and cerebral perfusion pressure were 14 mm Hg (SD, 4), 53 mm Hg (SD, 8), and 72 mm Hg (SD, 6), respectively. There were significant differences in the jugular venous bulb oxygen tension-brain oxygen tension gradient (16 mm Hg [sd, 6] vs 39 mm Hg SD, 11]; p < 0.001) and in the relationship of jugular venous bulb oxygen tension-brain oxygen tension gradient to cerebral perfusion pressure (p = 0.004) when comparing normoxia to hypoxia. Each 1 mm Hg increase in cerebral perfusion pressure led to a decrease in the jugular venous bulb oxygen tension-brain oxygen tension gradient by 0.36 mm Hg (95% CI, -0.54 to 0.18; p < 0.001) in the normoxia group, but no such relation was demonstrable in the hypoxia group. CONCLUSIONS: In hypoxic-ischemic brain injury patients with brain hypoxia, there is an elevation in the jugular venous bulb oxygen tension-brain oxygen tension gradient, which is not modulated by changes in cerebral perfusion pressure.

Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series.

BACKGROUND: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.

Medications to reduce emergence coughing after general anaesthesia with tracheal intubation: a systematic review and network meta-analysis.

BACKGROUND: Emergence coughing can harm the patient following completion of surgery, but it is unclear which medication is most effective at reducing this event. We conducted a systematic review and network meta-analysis of RCTs to determine the medications' relative efficacies on decreasing moderate to severe emergence coughing after general anaesthesia. Medications studied were lidocaine (i.v., intracuff, topical, or tracheal application), dexmedetomidine, remifentanil, and fentanyl. METHODS: We searched eight different medical literature databases, conference abstracts, and article references. After screening, included citations were evaluated for bias and had their data extracted. Pooled odds ratios and 95% confidence intervals for each treatment comparison were calculated. A surface under the cumulative ranking curve analysis (SUCRA) determined the relative rank of each intervention to decrease moderate to severe emergence coughing. Subgroup analyses included severe coughing only, extubation times, type of maintenance anaesthetic, and dosages. RESULTS: The network meta-analysis included 70 studies and 5286 patients. All study medications had favourable odds in reducing moderate and severe peri-extubation coughing compared with either no medication or placebo. No single medication was favoured over another. Dexmedetomidine had the highest SUCRA rank, followed in order by remifentanil, fentanyl, and lidocaine via intracuff, tracheal/topical, and i.v. routes. Remifentanil was ranked highest for decreasing severe coughing only. Intracuff lidocaine had higher odds of prolonging extubation times compared with placebo, dexmedetomidine, fentanyl, and remifentanil. CONCLUSION: All study medications were better than placebo or no medication in reducing moderate to severe emergence cough, with dexmedetomidine ranked the most effective. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42018102870.

How the high acuity unit changes mortality in the intensive care unit: a retrospective before-and-after study.

PURPOSE: High acuity units (HAU) are hospital units that provide patients with more acute care and closer monitoring than a general hospital ward but are not as resource intensive as an intensive care unit (ICU). Nevertheless, the impact of opening a HAU on ICU patient outcomes remains poorly defined. We investigated how the creation of a HAU impacted patient outcomes in the ICU. METHODS: This historical cohort study compared ICU patient in-hospital mortality, ICU length of stay (LOS), and hospital LOS before and after the creation of a HAU in a tertiary-care hospital with a medical/surgical ICU between 1 January 2013 and 31 December 2017. RESULTS: Data from 4,380 patients (984 in the pre-HAU group and 3,396 in the post-HAU group) were analyzed. In this cohort of ICU patients, 360 (37%) died in the pre-HAU group before the creation of a HAU, and 1,074 (32%) died in the post-HAU group after the creation of a HAU. The creation of a HAU was associated with lower relative risk of in-hospital mortality (adjusted risk ratio, 0.80; 95% confidence interval [CI], 0.72 to 0.89; P < 0.001). The creation of a HAU was also associated with reduced ICU and hospital LOS with a 12% increase in the rate of ICU discharge (adjusted sub-distribution hazard ratio [SHR], 1.12; 95% CI, 1.02 to 1.23; P = 0.02) and a 26% increase in the rate of hospital discharge (adjusted SHR, 1.26; 95% CI, 1.14 to 1.39; P < 0.001), when accounting for the competing risk of death. CONCLUSIONS: These data support the hypothesis that the creation of a HAU may be associated with reduced in-hospital mortality, ICU LOS, and hospital LOS for ICU patients.

RéSUMé: OBJECTIF: Les unités de soins intermédiaires sont des départements hospitaliers qui prodiguent des soins plus aigus et un monitorage plus serré aux patients qu'une unité générale, mais qui ne nécessitent pas autant de ressources qu'une unité de soins intensifs (USI). L'impact de l'ouverture d'une unité de soins intermédiaires sur les devenirs des patients à l'USI n'a pourtant été que peu décrit. Nous avons exploré la façon dont la création d'une unité de soins intermédiaires a eu un impact sur les devenirs des patients à l'USI. MéTHODE: Cette étude de cohorte historique a comparé la mortalité hospitalière, la durée de séjour à l'USI et la durée de séjour hospitalier des patients à l'USI avant et après la création d'une unité de soins intermédiaires dans un hôpital de soins tertiaires disposant d'une USI médicale/chirurgicale entre le 1er janvier 2013 et le 31 décembre 2017. RéSULTATS: Les données de 4380 patients (984 dans le groupe pré unité de soins intermédiaires et 3396 dans le groupe post unité de soins intermédiaires) ont été analysées. Dans cette cohorte de patients de l'USI, 360 (37 %) sont décédés avant la création de l'unité de soins intermédiaires, et 1074 (32 %) sont décédés après. La création d'une unité de soins intermédiaires a été associée à un risque relatif plus faible de mortalité hospitalière (risque relatif ajusté, 0,80; intervalle de confiance [IC] 95 %, 0,72 à 0,89; P < 0,001). La création d'une unité de soins intermédiaires a également été associée à une durée de séjour réduite à l'USI et à l'hôpital, avec une augmentation de 12 % du taux de congé de l'USI (rapport de risque ajusté [RRA], 1,12; IC 95 %, 1,02 à 1,23; P = 0,02) et une augmentation de 26 % du taux de congé de l'hôpital (RRA, 1,26; IC 95 %, 1,14 à 1,39; P < 0,001), en tenant compte du risque concurrent de décès. CONCLUSION: Ces données appuient l'hypothèse que la création d'une unité de soins intermédiaires pourrait être associée à une réduction de la mortalité hospitalière, de la durée de séjour à l'USI et de la durée de séjour à l'hôpital pour les patients de l'USI.

Adding vitamin C to hydrocortisone lacks benefit in septic shock: a historical cohort study.

PURPOSE: Sepsis has high incidence and mortality rates, particularly in the intensive care unit (ICU). Corticosteroids may improve outcomes, and vitamin C may add benefit. We aimed to assess whether vitamin C and corticosteroids improved outcomes compared with corticosteroids alone. METHODS: This historical cohort study (11 December 2016 to 21 February 2018) was conducted in the ICU of a quaternary referral hospital. Patients with an ICU admission diagnosis of sepsis or septic shock who received vitamin C and hydrocortisone within 72 hr were compared with those who received only hydrocortisone. All patients received standard sepsis care including source control, antibiotics, and fluid resuscitation. Most patients received thiamine as standard ICU care. The primary outcome was hospital mortality. Secondary outcomes included ICU mortality, ventilator-free days, vasopressor-free days, dialysis use, and duration of ICU admission. RESULTS: One hundred and forty-four patients were included in the study. The mean (standard deviation [SD]) age was 64 (15) yr; 39% were female; and the mean (SD) Acute Physiology And Chronic Health Evaluation IV score was 89 (30). Eighty-eight patients did not receive vitamin C and 52 received vitamin C. There was no observed difference in hospital mortality between the non-vitamin C (36%) and vitamin C (39%) groups (adjusted odds ratio for hospital death, 0.52; 95% confidence interval, 0.20 to 1.34; P = 0.18). There were no statistically significant differences in any secondary outcomes. CONCLUSION: In this small observational study of ICU patients with septic shock, the addition of vitamin C to hydrocortisone therapy did significantly affect hospital mortality or other measures of mortality or organ dysfunction.

RéSUMé: OBJECTIF: Le sepsis comporte une incidence et des taux de mortalité élevés, particulièrement à l'unité de soins intensifs (USI). Les corticostéroïdes pourraient améliorer les pronostics, et la vitamine C pourrait être bénéfique. Notre objectif était d'évaluer si la vitamine C et les corticostéroïdes amélioraient les devenirs par rapport à un traitement de corticostéroïdes seulement. MéTHODE: Cette étude de cohorte historique (réalisée entre le 11 décembre 2016 et le 21 février 2018) a été réalisée à l'USI d'un hôpital quaternaire. Les patients ayant un diagnostic de sepsis ou de choc septique lors de leur admission à l'USI et ayant reçu de la vitamine C et de l'hydrocortisone dans les premières 72 heures ont été comparés à ceux n'ayant reçu que de l'hydrocortisone. Tous les patients ont reçu des soins standard pour le sepsis, soit un contrôle de la source de l'infection, un traitement antibiotique et une réanimation liquidienne. La plupart des patients ont reçu de la thiamine, un traitement standard à l'USI. Le critère d'évaluation principal était la mortalité hospitalière. Les critères d'évaluation secondaires comprenaient la mortalité à l'USI, les jours sans respirateur, les jours sans vasopresseurs, le recours à la dialyse et la durée de séjour à l'USI. RéSULTATS: Cent quarante-quatre patients ont été inclus dans notre étude. L'âge moyen (écart type [ÉT]) était de 64 (15) ans; 39 % étaient de sexe féminin; et le score APACHE IV moyen (ÉT) de 89 (30). Quatre-vingt-huit patients n'ont pas reçu de vitamine C et 52 en ont reçu. Aucune différence n'a été observée en matière de mortalité hospitalière entre les groupes sans vitamine C (36 %) ou avec vitamine C (39 %) (rapport de cotes ajusté pour la mortalité hospitalière, 0,52; intervalle de confiance 95 %, 0,20 à 1,34; P = 0,18). Il n'y a eu aucune différence statistiquement significative en ce qui touchait aux critères d'évaluation secondaires. CONCLUSION: Dans cette petite étude observationnelle portant sur des patients de l'USI en choc septique, l'ajout de vitamine C à un traitement d'hydrocortisone n'a pas eu d'impact significatif sur la mortalité hospitalière ou les autres mesures de mortalité ou d'atteintes organiques.

Association of intensive care unit occupancy during admission and inpatient mortality: a retrospective cohort study.

PURPOSE: There is conflicting evidence regarding the influence of intensive care unit (ICU) occupancy at the time of admission on important patient outcomes such as mortality. The objective of this analysis was to characterize the association between ICU occupancy at the time of ICU admission and subsequent mortality. METHODS: This single-centre, retrospective cohort study included all patients admitted to the ICU at the Vancouver General Hospital between 4 January 2010 and 8 October 2017. Intensive care unit occupancy was defined as the number of ICU bed hours utilized in a day divided by the total amount of ICU bed hours available for that day. We constructed mixed-effects logistic regression models controlling for relevant covariates to assess the impact of admission occupancy quintiles on total inpatient (ICU and ward) and early (72-hr) ICU mortality. RESULTS: This analysis included 10,365 ICU admissions by 8,562 unique patients. Compared with ICU admissions in the median occupancy quintile, admissions in the highest and second highest occupancy quintile were associated with a significant increase in the odds of inpatient mortality (highest: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.12 to 1.59; P value < 0.001; second highest: OR, 1.21; 95% CI, 1.02 to 1.44; P value < 0.03). No association between admission occupancy and 72-hr ICU mortality was observed. CONCLUSIONS: Admission to the ICU on days of high occupancy was associated with increased inpatient mortality, but not with increased 72-hr ICU mortality. Capacity strain on the ICU may result in significant negative consequences for patients, but further research is needed to fully characterize the complex effects of capacity strain.

Association between intensive care unit occupancy at discharge, afterhours discharges, and clinical outcomes: a historical cohort study.

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 (per 10% increase: adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.03 to 1.20; P = 0.005). Discharge occupancy was not associated with 72-hr readmission (per 10% increase: aOR, 0.97; 95% CI, 0.87 to 1.09; P = 0.62) or 30-day mortality (per 10% increase: aOR, 1.05; 95% CI, 0.95 to 1.16; P = 0.32). Afterhours discharge was not associated with 72-hr readmission (aOR, 1.15; 95% CI, 0.86 to 1.54; P = 0.34) or 30-day mortality (aOR, 1.05; 95% CI, 0.82 to 1.36; P = 0.69). CONCLUSIONS: Greater ICU discharge occupancy was associated with a significant increase in afterhours discharges. Nevertheless, neither discharge occupancy nor afterhours discharge were associated with 72-hr readmission or 30-day mortality.

RéSUMé: OBJECTIF: Il n'existe que peu de données probantes évaluant si le taux d'occupation de l'unité de soins intensifs (USI) au moment du congé est associé aux devenirs cliniques. Nous ne savons pas si un taux d'occupation plus élevé au moment du congé entraîne davantage de congés pendant la nuit et si cette situation a des conséquences. Nous avons exploré l'association entre le taux d'occupation de l'USI au moment du congé et les congés donnés pendant la nuit, la réadmission dans les premières 72 h, et la mortalité à 30 jours. MéTHODE: Cette étude de cohorte historique et monocentrique a englobé tous les patients ayant reçu leur congé de l'USI de l'Hôpital général de Vancouver entre le 5 avril 2010 et le 13 septembre 2017. Les données ont été tirées de la Base de données des soins intensifs de Colombie-Britannique (British Columbia Critical Care Database). Le taux d'occupation était défini comme le nombre d'heures d'occupation de lit de l'USI utilisées divisé par le nombre d'heures d'occupation de lit disponibles pour ladite journée. Tout congé reçu entre 22 h et 6 h 59 était considéré comme survenant pendant la nuit. Des modèles de régression logistique ont été élaborés afin de tenir compte des covariables importantes. RéSULTATS: Nous avons inclus 8862 congés de l'USI, représentant 7288 patients individuels. Au total, il y a eu 1180 (13,3 %) congés donnés pendant la nuit, 408 (4,6 %) réadmissions dans les 72 h suivantes, et 574 (6,5 %) décès à 30 jours après le congé. Un taux d'occupation plus élevé au moment du congé était associé à des congés pendant la nuit (par augmentation de 10 % : rapport de cotes ajusté [RCA], 1,12; intervalle de confiance [IC] 95 %, 1,03 à 1,20; P = 0,005). Le taux d'occupation lors du congé n'a pas été associé à une réadmission dans les premières 72 h (par augmentation de 10 % : RCA, 0,97; IC 95 %, 0,87 à 1,09; P = 0,62) ou à une mortalité à 30 jours (par augmentation de 10 % : RCA, 1,05; IC 95 %, 0,95 à 1,16; P = 0,32). Les congés pendant la nuit n'ont pas été associés à une réadmission dans les 72 h suivantes (RCA, 1,15; IC 95 %, 0,86 à 1,54; P = 0,34) ou à une mortalité à 30 jours (RCA, 1,05; IC 95 %, 0,82 à 1,36; P = 0,69). CONCLUSION: Un taux d'occupation de l'USI plus élevé au moment du congé était associé à une augmentation significative des congés donnés pendant la nuit. Cependant, ni le taux d'occupation lors du congé, ni le congé donné pendant la nuit, n'étaient associés à une réadmission à 72 h ou une mortalité à 30 jours.

The Burden of Brain Hypoxia and Optimal Mean Arterial Pressure in Patients With Hypoxic Ischemic Brain Injury After Cardiac Arrest.

OBJECTIVES: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation. DESIGN: Prospective interventional study. SETTING: Quaternary ICU. PATIENTS: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest. INTERVENTIONS: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software. MEASUREMENTS AND MAIN RESULTS: Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure. CONCLUSIONS: Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest.

Effect of Cerebral Perfusion Pressure on Acute Respiratory Distress Syndrome.

BACKGROUND: Increased cerebral perfusion pressure (CPP)>70 mmHg has been associated with acute respiratory distress syndrome (ARDS) after traumatic brain injury (TBI). Since this reported association, significant changes in ventilation strategies and fluid management have been accepted as routine critical care. Recently, individualized perfusion targets using autoregulation monitoring suggest CPP titration>70 mmHg. Given these clinical advances, the association between ARDS and increased CPP requires further delineation. OBJECTIVE: To determine the association between ARDS and increased CPP after TBI. METHODS: We conducted a single-center historical cohort study investigating the association of increased CPP and ARDS after TBI. We collected demographic data and physiologic data for CPP, intracranial pressure, mechanical ventilation, cumulative fluid balance and delta/driving pressure (ΔP). We collected outcomes measures pertaining to duration of ventilation, intensive care unit admission length, hospitalization length and 6-month neurological outcome. RESULTS: In total, 113 patients with severe TBI and multimodal neuromonitoring were included. In total, 16 patients (14%) developed ARDS according to the Berlin definition. There was no difference in the mean CPP during the first 7 days of admission between patients who developed ARDS (74 mmHg SD 18 vs. 73 mmHg SD 18, p=0.86) versus those who did not. Patients who developed ARDS had a higher ΔP (15 mmHg [5] vs. 12 mmHg [4], p=0.016) and lower lung compliance (35 ml/cmH2O [10] vs. 49 ml/cmH2O [18], p=0.024) versus those who did not. CONCLUSION: We did not observe an association between increased CPP and ARDS. Patients with ARDS had higher ΔP and lower lung compliance.

A Systematic Review of the Risks and Benefits of Venous Thromboembolism Prophylaxis in Traumatic Brain Injury.

BACKGROUND: Patients suffering from traumatic brain injury (TBI) are at increased risk of venous thromboembolism (VTE). However, initiation of pharmacological venous thromboprophylaxis (VTEp) may cause further intracranial hemorrhage. We reviewed the literature to determine the postinjury time interval at which VTEp can be administered without risk of TBI evolution and hematoma expansion. METHODS: MEDLINE and EMBASE databases were searched. Inclusion criteria were studies investigating timing and safety of VTEp in TBI patients not previously on oral anticoagulation. Two investigators extracted data and graded the papers' levels of evidence. Randomized controlled trials were assessed for bias according to the Cochrane Collaboration Tool and Cohort studies were evaluated for bias using the Newcastle-Ottawa Scale. We performed univariate meta-regression analysis in an attempt to identify a relationship between VTEp timing and hemorrhagic progression and assess study heterogeneity using an I 2 statistic. RESULTS: Twenty-one studies were included in the systematic review. Eighteen total studies demonstrated that VTEp postinjury in patients with stable head computed tomography scan does not lead to TBI progression. Fourteen studies demonstrated that VTEp administration 24 to 72 hours postinjury is safe in patients with stable injury. Four studies suggested that administering VTEp within 24 hours of injury in patients with stable TBI does not lead to progressive intracranial hemorrhage. Overall, meta-regression analysis demonstrated that there was no relationship between rate of hemorrhagic progression and VTEp timing. CONCLUSIONS: Literature suggests that administering VTEp 24 to 48 hours postinjury may be safe for patients with low-hemorrhagic-risk TBIs and stable injury on repeat imaging.

Feasibility of continuous sedation monitoring in critically ill intensive care unit patients using the NeuroSENSE WAVCNS index.

Sedation in the intensive care unit (ICU) is challenging, as both over- and under-sedation are detrimental. Current methods of assessment, such as the Richmond Agitation Sedation Scale (RASS), are measured intermittently and rely on patients' behavioral response to stimulation, which may interrupt sleep/rest. A non-stimulating method for continuous sedation monitoring may be beneficial and allow more frequent assessment. Processed electroencephalography (EEG) monitors have not been routinely adopted in the ICU. The aim of this observational study was to assess the feasibility of using the NeuroSENSE™ monitor for EEG-based continuous sedation assessment. With ethical approval, ICU patients on continuous propofol sedation were recruited. Depth-of-hypnosis index (WAVCNS) values were obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE, performed regular RASS assessments and maintained the sedation regimen as per standard of care. Participants were monitored throughout the duration of their propofol infusion, up to 24 h. Fifteen patients, with median [interquartile range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7-20.1] h. Valid WAVCNS values were obtained for 89% [66-99] of monitoring time and were widely distributed within and between individuals, with 6% [1-31] spent < 40 (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89 (40%) assessments. The WAVCNS variability, and incidence of EEG suppression, highlight the limitations of using RASS as a standalone sedation measure, and suggests potential benefit of adjunct continuous brain monitoring.

Exercise-induced quadriceps muscle fatigue in men and women: effects of arterial oxygen content and respiratory muscle work.

KEY POINTS: High work of breathing and exercise-induced arterial hypoxaemia (EIAH) can decrease O2 delivery and exacerbate exercise-induced quadriceps fatigue in healthy men. Women have a higher work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles and develop EIAH. Despite a greater reduction in men's work of breathing, the attenuation of quadriceps fatigue was similar between the sexes. The degree of EIAH was similar between sexes, and regardless of sex, those who developed the greatest hypoxaemia during exercise demonstrated the most attenuation of quadriceps fatigue. Based on our previous finding that women have a greater relative oxygen cost of breathing, women appear to be especially susceptible to work of breathing-related changes in quadriceps muscle fatigue. ABSTRACT: Reducing the work of breathing or eliminating exercise-induced arterial hypoxaemia (EIAH) during exercise decreases the severity of quadriceps fatigue in men. Women have a greater work of breathing during exercise, dedicate a greater fraction of whole-body V̇O2 towards their respiratory muscles, and demonstrate EIAH, suggesting women may be especially susceptible to quadriceps fatigue. Healthy subjects (8 male, 8 female) completed three constant load exercise tests over 4 days. During the first (control) test, subjects exercised at ∼85% of maximum while arterial blood gases and work of breathing were assessed. Subsequent constant load exercise tests were iso-time and iso-work rate, but with EIAH prevented by inspiring hyperoxic gas or work of breathing reduced via a proportional assist ventilator (PAV). Quadriceps fatigue was assessed by measuring force in response to femoral nerve stimulation. For both sexes, quadriceps force was equally reduced after the control trial (-27 ± 2% baseline) and was attenuated with hyperoxia and PAV (-18 ± 1 and -17 ± 2% baseline, P < 0.01, respectively), with no sex difference. EIAH was similar between the sexes, and regardless of sex, subjects with the lowest oxyhaemoglobin saturation during the control test had the greatest quadriceps fatigue attenuation with hyperoxia (r2  = 0.79, P < 0.0001). For the PAV trial, despite reducing the work of breathing to a greater degree in men (men: 60 ± 5, women: 75 ± 6% control, P < 0.05), the attenuation of quadriceps fatigue was similar between the sexes (36 ± 4 vs. 37 ± 7%). Owing to a greater relative V̇O2 of the respiratory muscles in women, less of a change in work of breathing is needed to reduce quadriceps fatigue.

Individualized perfusion targets in hypoxic ischemic brain injury after cardiac arrest.

Secondary injury is a major determinant of outcome in hypoxic ischemic brain injury (HIBI) after cardiac arrest and may be mitigated by optimizing cerebral oxygen delivery (CDO2). CDO2 is determined by cerebral blood flow (CBF), which is dependent upon mean arterial pressure (MAP). In health, CBF remains constant over the MAP range through cerebral autoregulation. In HIBI, the zone of intact cerebral autoregulation is narrowed and varies for each patient. Maintaining MAP within the intact autoregulation zone may mitigate ischemia, hyperemia and secondary injury. The optimal MAP in individual patients can be determined using real time autoregulation monitoring techniques.