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

[Figure: see text].

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.

Compassionate End-of-Life Care: Mixed-Methods Multisite Evaluation of the 3 Wishes Project.

Background: The 3 Wishes Project (3WP) is an end-of-life program that aims to honor the dignity of dying patients by creating meaningful patient- and family-centered memories while promoting humanistic interprofessional care. Objective: To determine whether this palliative intervention could be successfully implemented-defined as demonstrating value, transferability, affordability, and sustainability-beyond the intensive care unit in which it was created. Design: Mixed-methods formative program evaluation. (ClinicalTrials.gov: NCT04147169). Setting: 4 North American intensive care units. Participants: Dying patients, their families, clinicians, hospital managers, and administrators. Intervention: Wishes from dying patients, family members, and clinicians were elicited and implemented. Measurements: Patient characteristics and processes of care; the number, type, and cost of each wish; and semistructured interviews and focus groups with family members, clinicians, and managers. Results: A total of 730 patients were enrolled, and 3407 wishes were elicited. Qualitative data were gathered from 75 family members, 72 clinicians, and 20 managers or hospital administrators. Value included intentional comforting of families as they honored the lives and legacies of their loved ones while inspiring compassionate clinical care. Factors promoting transferability included family appreciation and a collaborative intensive care unit culture committed to dignity-conserving end-of-life care. Staff participation evolved from passive support to professional agency. Program initiation required minimal investment for reusable materials; thereafter, the mean cost was $5.19 (SD, $17.14) per wish. Sustainability was demonstrated by the continuation of 3WP at each site after study completion. Limitation: This descriptive formative evaluation describes tertiary care center-specific experiences rather than aiming for generalizability to all jurisdictions. Conclusion: The 3WP is a transferrable, affordable, and sustainable program that provides value to dying patients, their families, clinicians, and institutions. Primary Funding Source: Greenwall Foundation.

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.

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.

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.

Hypoglycemia and risk of death in critically ill patients.

BACKGROUND: Whether hypoglycemia leads to death in critically ill patients is unclear. METHODS: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates. RESULTS: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P<0.001) and 2.10 (95% CI, 1.59 to 2.77; P<0.001), respectively. The association with death was increased among patients who had moderate hypoglycemia on more than 1 day (>1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001). CONCLUSIONS: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).

Caractéristiques de départ et issues chez des patients atteints de COVID-19 hospitalisés dans des unités de soins intensifs à Vancouver (Canada) : série de cas.

CONTEXTE: 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. MÉTHODES: Nous avons procédé à l'étude rétrospective d'une série de cas graves d'infection au SRAS-CoV-2 confirmée en laboratoire hospitalisés dans l'une des 6 USI du Vancouver métropolitain, en Colombie-Britannique (Canada), entre le 21 février et le 14 avril 2020. Les données démographiques, les renseignements sur la prise en charge et les résultats ont été recueillis à partir des dossiers médicaux, électroniques ou non, des patients. RÉSULTATS: Entre le 21 février et le 14 avril 2020, 117 patients ont été admis dans une USI avec un diagnostic confirmé de COVID-19. L'âge médian était de 69 ans (écart interquartile [EI] 60­75 ans); et 38 (32,5 %) étaient des femmes. Au moins une comorbidité était présente chez 86 patients (73,5 %). La ventilation mécanique a été nécessaire chez 74 patients (63,2 %). La durée de la ventilation mécanique a été de 13,5 jours (EI 8­22 jours) dans l'ensemble et de 11 jours (II 6­16) chez les patients qui ont reçu leur congé de l'USI. Du tocilizumab a été administré à 4 patients et de l'hydroxychloroquine à 1 patient. En date du 5 mai 2020, 18 patients (15,4 %) étaient décédés, 12 (10,3 %) étaient toujours à l'USI, 16 (13,7 %) avaient obtenu leur congé de l'USI, mais restaient hospitalisés, et 71 (60,7 %) avaient pu retourner à la maison. INTERPRÉTATION: Dans cette étude, la mortalité chez les patients gravement malades de la COVID-19 hospitalisés dans une USI a été moins élevée que chez les patients d'études précédentes. Ces résultats donnent à penser que le pronostic des cas graves de COVID-19 pourrait ne pas être aussi sombre que ce qui avait d'abord été rapporté.

Critical care capacity in Canada: results of a national cross-sectional study.

INTRODUCTION: Intensive Care Units (ICUs) provide life-supporting treatment; however, resources are limited, so demand may exceed supply in the event of pandemics, environmental disasters, or in the context of an aging population. We hypothesized that comprehensive national data on ICU resources would permit a better understanding of regional differences in system capacity. METHODS: After the 2009-2010 Influenza A (H1N1) pandemic, the Canadian Critical Care Trials Group surveyed all acute care hospitals in Canada to assess ICU capacity. Using a structured survey tool administered to physicians, respiratory therapists and nurses, we determined the number of ICU beds, ventilators, and the ability to provide specialized support for respiratory failure. RESULTS: We identified 286 hospitals with 3170 ICU beds and 4982 mechanical ventilators for critically ill patients. Twenty-two hospitals had an ICU that routinely cared for children; 15 had dedicated pediatric ICUs. Per 100,000 population, there was substantial variability in provincial capacity, with a mean of 0.9 hospitals with ICUs (provincial range 0.4-2.8), 10 ICU beds capable of providing mechanical ventilation (provincial range 6-19), and 15 invasive mechanical ventilators (provincial range 10-24). There was only moderate correlation between ventilation capacity and population size (coefficient of determination (R(2)) = 0.771). CONCLUSION: ICU resources vary widely across Canadian provinces, and during times of increased demand, may result in geographic differences in the ability to care for critically ill patients. These results highlight the need to evolve inter-jurisdictional resource sharing during periods of substantial increase in demand, and provide background data for the development of appropriate critical care capacity benchmarks.

The utility of exome sequencing for genetic diagnosis in a familial microcephaly epilepsy syndrome.

BACKGROUND: Despite remarkable advances in genetic testing, many adults with syndromic epilepsy remain without a molecular diagnosis. The challenge in providing genetic testing for this patient population lies in the extensive genetic heterogeneity associated with epilepsy. Even for the subset of epilepsy patients that present with a defining feature, such as microcephaly, the number of possible genes that would require interrogation by Sanger sequencing is extensive and often prohibitively expensive. CASE PRESENTATION: We report a family of French Canadian descent with four adult children affected with severe intellectual disability, epilepsy and microcephaly born to consanguineous parents and evaluated by the Genetics Service to provide informed genetic counseling to unaffected family members regarding possible recurrence risks. We used whole-exome sequencing (WES) of DNA from one affected sibling as a first-line diagnostic tool and compared the prioritization of variants using two strategies: 1) focusing on genes with homozygous variants; and, 2) focusing on genes associated with microcephaly. Both approaches prioritized the same homozygous novel frameshift mutation (p.Arg608Serfs*26) in WDR62, a gene known to cause autosomal recessive primary microcephaly. Sanger sequencing confirmed the presence of the homozygous mutation in the other three affected siblings. CONCLUSIONS: WES and subsequent filtering of the rare variants in a single affected family member led to the rapid and cost-effective identification of a novel homozygous frameshift mutation in WDR62, thereby explaining the severe neurodevelopmental disorder in this family and facilitating genetic counseling. Our findings support WES as an effective first-line diagnostic tool in families presenting with rare genetically heterogeneous neurological disorders.

Thromboprophylaxis patterns and determinants in critically ill patients: a multicenter audit.

INTRODUCTION: Heparin is safe and prevents venous thromboembolism in critical illness. We aimed to determine the guideline concordance for thromboprophylaxis in critically ill patients and its predictors, and to analyze factors associated with the use of low molecular weight heparin (LMWH), as it may be associated with a lower risk of pulmonary embolism and heparin-induced thrombocytopenia without increasing the bleeding risk. METHODS: We performed a retrospective audit in 28 North American intensive care units (ICUs), including all consecutive medical-surgical patients admitted in November 2011. We documented ICU thromboprophylaxis and reasons for omission. Guideline concordance was determined by adding days in which patients without contraindications received thromboprophylaxis to days in which patients with contraindications did not receive it, divided by the total number of patient-days. We used multilevel logistic regression including time-varying, center and patient-level covariates to determine the predictors of guideline concordance and use of LMWH. RESULTS: We enrolled 1,935 patients (62.3 ± 16.7 years, Acute Physiology and Chronic Health Evaluation [APACHE] II score 19.1 ± 8.3). Patients received thromboprophylaxis with unfractionated heparin (UFH) (54.0%) or LMWH (27.6%). Guideline concordance occurred for 95.5% patient-days and was more likely in patients who were sicker (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.17, 1.75 per 10-point increase in APACHE II), heavier (OR 1.32, 95% CI 1.05, 1.65 per 10-m/kg2 increase in body mass index), had cancer (OR 3.22, 95% CI 1.81, 5.72), previous venous thromboembolism (OR 3.94, 95% CI 1.46,10.66), and received mechanical ventilation (OR 1.83, 95% CI 1.32,2.52). Reasons for not receiving thromboprophylaxis were high risk of bleeding (44.5%), current bleeding (16.3%), no reason (12.9%), recent or upcoming invasive procedure (10.2%), nighttime admission or discharge (9.7%), and life-support limitation (6.9%). LMWH was less often administered to sicker patients (OR 0.65, 95% CI 0.48, 0.89 per 10-point increase in APACHE II), surgical patients (OR 0.41, 95% CI 0.24, 0.72), those receiving vasoactive drugs (OR 0.47, 95% CI 0.35, 0.64) or renal replacement therapy (OR 0.10, 95% CI 0.05, 0.23). CONCLUSIONS: Guideline concordance for thromboprophylaxis was high, but LMWH was less commonly used, especially in patients who were sicker, had surgery, or received vasopressors or renal replacement therapy, representing a potential quality improvement target.

Intensive versus conventional glucose control in critically ill patients.

BACKGROUND: The optimal target range for blood glucose in critically ill patients remains unclear. METHODS: Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per deciliter (4.5 to 6.0 mmol per liter), or conventional glucose control, with a target of 180 mg or less per deciliter (10.0 mmol or less per liter). We defined the primary end point as death from any cause within 90 days after randomization. RESULTS: Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39). CONCLUSIONS: In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter. (ClinicalTrials.gov number, NCT00220987.)

The impact of an ED-only full-capacity protocol.

OBJECTIVE: The objective of this study was to assess the impact of an emergency department (ED)-only full-capacity protocol and diversion, controlling for patient volumes and other potential confounding factors. METHODS: This was a preintervention and postintervention cohort study using data 12 months before and 12 months after the implementation of the protocol. During the implementation period, attending physicians and charge nurses were educated with clear and simple figures on the criteria for the initiation of the new protocol. A multiple logistic regression model was used to compare ambulance diversion between the 2 periods. RESULTS: The proportion of days when the ED went on diversion at least once during a 24-hour period was 60.4% during the preimplementation period and 20% in the postimplementation periods (P < .001). In the multivariate logistic regression model, the use of the new protocol was significantly associated with decreased odds of diversion rate in the postimplementation period (odds ratio, 0.32; 95% confidence interval, 0.21-0.48). CONCLUSION: Our predivert/full-capacity protocol is a simple and generalizable strategy that can be implemented within the boundaries of the ED and is significantly associated with a decreased diversion rate.

Video-laryngoscopy versus direct laryngoscopy in critically ill patients: a pilot randomized trial.

PURPOSE: Endotracheal intubation in critically ill patients is associated with a high risk of complications that tend to increase with multiple attempts at laryngoscopy. In this pilot study, we compared direct laryngoscopy (DL) with video-laryngoscopy (VL) with regard to the number of attempts and other clinical parameters during endotracheal intubation of critically ill patients performed by novice providers. METHODS: Patients were randomized to either VL or DL for endotracheal intubation. Exclusion criteria for the study included: requirement for immediate endotracheal intubation, cervical spine precautions, anticipated difficult intubation, oxygen saturation < 90%, or systolic blood pressure < 80 mmHg despite resuscitation. The providers, predominantly non-anesthesiology residents in their first three years of postgraduate training, received a one-hour teaching and mannequin session prior to performing the procedures. RESULTS: Forty patients, mean age 65 (standard deviation, 16) yr were randomized to VL (n = 20) or DL (n = 20). Sixty percent of the patients received endotracheal intubation for respiratory failure, and all patients received a neuromuscular blocker. Multiple attempts were required in 25/40 (63%) patients, and this did not differ with technique (P = 1.0) Video-laryngoscopy resulted in improved glottic visualization with 85% of patients having a Cormack-Lehane grade 1 view compared with 30% of patients in the DL group (P < 0.001). Total time-to-intubation for VL was 221 sec (interquartile range [IQR 103-291]) vs 156 sec [IQR 67-220] for DL (P = 0.15). Video-laryngoscopy resulted in a lower median SaO(2) (86%) during endotracheal intubation [IQR 75-93] compared with a median SaO(2) of 95% in the DL group [IQR 85-99] (P = 0.04). CONCLUSIONS: Video-laryngoscopy resulted in improved glottic visualization compared with DL; however, this did not translate into improved clinical outcomes. The trial was registered on ClinicalTrials.gov number, NCT00911755.

Lack of agreement between optimal mean arterial pressure determination using pressure reactivity index versus cerebral oximetry index in hypoxic ischemic brain injury after cardiac arrest.

INTRODUCTION: Invasive monitoring of cerebral autoregulation using the pressure reactivity index (PRx) allows for the determination of optimal mean arterial pressure (MAPOPT) in hypoxic ischemic brain injury (HIBI) patients following cardiac arrest. However, the utility of non-invasive surrogates to determine MAPOPT has not been addressed. We aimed to determine the agreement between PRx-derived MAPOPT versus MAPOPT determined by the near-infrared spectroscopy (NIRS) based cerebral oximetry index (COx). METHODS: Ten HIBI patients were enrolled. PRx-derived MAPOPT, lower (LLA) and upper limits of autoregulation (ULA) were compared against COx-derived MAPOPT, LLA and ULA. Multimodal neuromonitoring included mean arterial pressure, intracranial pressure, brain tissue oxygenation, jugular venous oxygen saturation, and NIRS-derived regional cerebral oxygen saturation. RESULTS: Repeated measures Bland-Altman plots demonstrated limited agreement between MAPOPT derived from COx and PRx (mean bias: 1.4 mmHg; upper limit of agreement: 25.9 mmHg; lower limit of agreement: -23.0 mmHg). Similarly, there was limited agreement between the absolute values of PRx and COx. Mean bias was 0.26 and the upper and lower limits of agreement were 1.05 and -0.53, respectively. Systematic bias was apparent, whereby at low PRx values COx overestimated PRx and at high PRx values, COx underestimated PRx. COx was limited in its ability to determine impaired autoregulation defined by PRx (receiver operator characteristic area under the curve was 0.488). CONCLUSION: Collectively, we demonstrate that COx-based determination of MAPOPT lacks agreement with MAPOPT derived from PRx. Further research must be done to evaluate the physiologic and clinical efficacy of PRx derived MAPOPT in HIBI.

Quantification of Neurological Blood-Based Biomarkers in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: To provide an objective characterization of acute neurologic injury in critically ill patients with coronavirus disease 2019. DESIGN: Prospective observational study. Demographics, comorbidities, and daily clinical physiologic and laboratory data were collected. Plasma levels of neurofilament-light chain, total tau, ubiquitin carboxy-terminal hydrolase L1, and glial fibrillary acidic protein were measured. The primary neurologic outcome was delirium defined by the Intensive Care Delirium Screening Checklist (scale 1-8). Associations among plasma biomarkers, respiratory failure, and inflammation were analyzed. SETTING: Multicenter study in ICUs. PATIENTS: Critically ill patients with respiratory failure, with coronavirus disease 2019, or without (ICU control). MEASUREMENTS AND MAIN RESULTS: A total of 27 patients with coronavirus disease 2019 and 19 ICU controls were enrolled. Compared with ICU controls with pneumonia of other etiology, patients with coronavirus disease 2019 had significantly higher glial fibrillary acidic protein (272 pg/mL [150-555 pg/mL] vs 118 pg/mL [78.5-168 pg/mL]; p = 0.0009). In coronavirus disease 2019 patients, glial fibrillary acidic protein (rho = 0.5115, p = 0.0064), ubiquitin carboxy-terminal hydrolase L1 (rho = 0.4056, p = 0.0358), and neurofilament-light chain (rho = 0.6223, p = 0.0005) positively correlated with Intensive Care Delirium Screening Checklist score and were increased in patients with delirium (Intensive Care Delirium Screening Checklist ≥ 4) in the coronavirus disease 2019 group but not in ICU controls. There were no associations between the measures of respiratory function or cytokines with glial fibrillary acidic protein, total tau, ubiquitin carboxy-terminal hydrolase L1, or neurofilament-light chain levels in patients with coronavirus disease 2019. CONCLUSIONS: Plasma glial fibrillary acidic protein is two-fold higher in critically ill patients with coronavirus disease 2019 compared with ICU controls. Higher levels of glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and neurofilament-light chain associate with delirium in patients with coronavirus disease 2019. Elevated plasma glial fibrillary acidic protein, ubiquitin carboxy-terminal hydrolase L1, and neurofilament-light chain are independent of respiratory function and peripheral cytokines.

Family and Clinician Experiences of Sympathy Cards in the 3 Wishes Project.

BACKGROUND: A recent randomized trial of bereaved family members of patients who died in an intensive care unit identified symptoms of depression and posttraumatic stress in recipients of semistructured condolence letters. OBJECTIVES: To explore family member and clinician experiences with receiving or sending handwritten sympathy cards upon the death of patients involved in a personalized end-of-life intervention, the 3 Wishes Project. METHODS: Interviews and focus groups were held with 171 family members and 222 clinicians at 4 centers to discuss their experiences with the 3 Wishes Project. Interview transcripts were searched to identify participants who discussed sympathy cards. Data related to sympathy cards were independently coded by 2 investigators through conventional content analysis. RESULTS: Sympathy cards were discussed during 32 interviews (by 25 family members of 21 patients and by 11 clinicians) and 2 focus groups (8 other clinicians). Family members reported that personalized sympathy cards were a welcome surprise; they experienced them as a heartfelt act of compassion. Clinicians viewed cards as an opportunity to express shared humanity with families, reminding them that they and their loved one were not forgotten. Signing cards allowed clinicians to reminisce individually and collectively with colleagues. Family members and clinicians experienced sympathy cards as a meaningful continuation of care after a patient's death. CONCLUSIONS: Inviting clinicians who cared for deceased patients to offer personalized, handwritten condolences to bereaved family members may cultivate sincere and individualized expressions of sympathy that bereaved families appreciate after the death of patients involved in the 3 Wishes Project.

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

We provide preliminary multicenter data to suggest that recruitment and collection of physiologic data necessary to quantify cerebral autoregulation and individualized blood pressure targets are feasible in postcardiac arrest patients. We evaluated the feasibility of a multicenter protocol to enroll patients across centers, as well as collect continuous recording (≥ 80% of monitoring time) of regional cerebral oxygenation and mean arterial pressure, which is required to quantify cerebral autoregulation, using the cerebral oximetry index, and individualized optimal mean arterial pressure thresholds. Additionally, we conducted an exploratory analysis to assess if an increased percentage of monitoring time where mean arterial pressure was greater than or equal to 5 mm Hg below optimal mean arterial pressure, percentage of monitoring time with dysfunctional cerebral autoregulation (i.e., cerebral oximetry index ≥ 0.3), and time to return of spontaneous circulation were associated with an unfavorable neurologic outcome (i.e., 6-mo Cerebral Performance Category score ≥ 3). DESIGN SETTING AND PATIENTS: A prospective multicenter cohort study was conducted in ICUs in three teaching hospitals across Canada. Patients (≥ 16 yr old) were included if their cardiac arrest occurred within the previous 36 hours, they had greater than or equal to 20 consecutive minutes of spontaneous circulation following resuscitation, and they had a post-resuscitation Glasgow Coma Scale of less than or equal to 8. MEASUREMENTS AND MAIN RESULTS: Recruitment rates were calculated across sites, and patients underwent continuous regional cerebral oxygenation monitoring using near-infrared spectroscopy, as well as invasive blood pressure monitoring. Exploratory multivariable logistic regression was performed. Although it was feasible to recruit patients across multiple centers, there was variability in the recruitment rates. Physiologic data were captured in 86.2% of the total monitoring time and the median monitoring time was 47.5 hours (interquartile interval, 29.4-65.0 hr) across 59 patients. Specifically, 88% of mean arterial pressure and 96% of bilateral frontal regional cerebral oxygenation data were acquired, and 90% of cerebral oximetry index and 70% of optimal mean arterial pressure values were quantified. However, there was substantial variation in the amount of data captured among individuals. Time to return of spontaneous circulation was associated with an increased odds of an unfavorable neurologic outcome. CONCLUSIONS AND RELEVANCE: We demonstrated feasibility to recruit and collect high frequency physiologic data in patients after cardiac arrest. Future investigations will need to systematically document the reasons for data attrition, as well as how these methodological complications were resolved. Due to underpowered analyses and the inability to control for potential confounds, further studies are needed to explore the association between cerebral autoregulatory capacity and individualized mean arterial pressure thresholds with neurologic outcomes.

The association of ABO blood group with indices of disease severity and multiorgan dysfunction in COVID-19.

Studies on severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) suggest a protective effect of anti-A antibodies against viral cell entry that may hold relevance for SARS-CoV-2 infection. Therefore, we aimed to determine whether ABO blood groups are associated with different severities of COVID-19. We conducted a multicenter retrospective analysis and nested prospective observational substudy of critically ill patients with COVID-19. We collected data pertaining to age, sex, comorbidities, dates of symptom onset, hospital admission, intensive care unit (ICU) admission, mechanical ventilation, continuous renal replacement therapy (CRRT), standard laboratory parameters, and serum inflammatory cytokines. National (N = 398 671; P = .38) and provincial (n = 62 246; P = .60) ABO blood group distributions did not differ from our cohort (n = 95). A higher proportion of COVID-19 patients with blood group A or AB required mechanical ventilation (P = .02) and CRRT (P = .004) and had a longer ICU stay (P = .03) compared with patients with blood group O or B. Blood group A or AB also had an increased probability of requiring mechanical ventilation and CRRT after adjusting for age, sex, and presence of ≥1 comorbidity. Inflammatory cytokines did not differ between patients with blood group A or AB (n = 11) vs O or B (n = 14; P > .10 for all cytokines). Collectively, our data indicate that critically ill COVID-19 patients with blood group A or AB are at increased risk for requiring mechanical ventilation, CRRT, and prolonged ICU admission compared with patients with blood group O or B. Further work is needed to understand the underlying mechanisms.