Association between the red cell distribution width and mortality in elderly patients with non-traumatic coma: An observational cohort study.

Elevated red blood cell distribution width (RDW) can be associated with disease severity. However, studies on RDW for the prognosis of elderly patients with non-traumatic coma (NTC) are lacking. This study aims to examine the relationship between RDW and outcomes in elderly patients with NTC. This observational cohort study included elderly patients (aged ≥ 65 years) with NTC between January 2022 and December 2022. We measured RDW upon patient arrival at the emergency department (ED). We conducted a multivariable analysis using logistic regression of relevant covariates to predict in-hospital mortality. Survival curves based on 30-day mortality were designed using the Kaplan-Meier method. The primary outcome was in-hospital mortality, and the secondary outcome was 30-day mortality. A total of 689 patients were included in the study, and in-hospital mortality was 29.6% (n = 204). Our results found that the RDWs of non-survivors were significantly greater than those of survivors (14.6% vs 13.6%). Multivariable analysis showed that RDWs at ED arrival were independently associated with in-hospital mortality (odds ratio, 1.126; 95% confidence interval, 1.047-1.212; P < .001). The Kaplan-Meier curve indicated that the survival probability of patients with a low RDW was greater than those with a high RDW. Having a high RDW at ED arrival was associated with in-hospital mortality in elderly patients with NTC.

Impact of Blood Pressure Targets in Patients With Heart Failure Undergoing Postresuscitation Care: A Subgroup Analysis From a Randomized Controlled Trial.

BACKGROUND: To assess the effect of targeting higher or lower blood pressure during postresucitation intensive care among comatose patients with out-of-hospital cardiac arrest with a history of heart failure. METHODS: The BOX trial (Blood Pressure and Oxygenation Targets After Out-of-Hospital Cardiac Arrest) was a randomized, controlled, double-blinded, multicenter study comparing titration of vasopressors toward a mean arterial pressure (MAP) of 63 versus 77 mm Hg during postresuscitation intensive care. Patients with a history of heart failure were included in this substudy. Pulmonary artery catheters were inserted shortly after admission. History of heart failure was assessed through chart review of all included patients. The primary outcome was cardiac index during the first 72 hours. Secondary outcomes were left ventricular ejection fraction, heart rate, stroke volume, renal replacement therapy and all-cause mortality at 365 days. RESULTS: A total of 134 patients (17% of the BOX cohort) had a history of heart failure (patients with left ventricular ejection fraction, ≤40%: 103 [77%]) of which 71 (53%) were allocated to a MAP of 77 mm Hg. Cardiac index at intensive care unit arrival was 1.77±0.11 L/min·m-2 in the MAP63-group and 1.78±0.17 L/min·m-2 in the MAP77, P=0.92. During the next 72 hours, the mean difference was 0.15 (95% CI, -0.04 to 0.35) L/min·m-2; Pgroup=0.22. Left ventricular ejection fraction and stroke volume was similar between the groups. Patients allocated to MAP77 had significantly elevated heart rate (mean difference 6 [1-12] beats/min, Pgroup=0.03). Vasopressor usage was also significantly increased (P=0.006). At 365 days, 69 (51%) of the patients had died. The adjusted hazard ratio for 365 day mortality was 1.38 (0.84-2.27), P=0.20 and adjusted odds ratio for renal replacement therapy was 2.73 (0.84-8.89; P=0.09). CONCLUSIONS: In resuscitated patients with out-of-hospital cardiac arrest with a history of heart failure, allocation to a higher blood pressure target resulted in significantly increased heart rate in the higher blood pressure-target group. However, no certain differences was found for cardiac index, left ventricular ejection fraction or stroke volume. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03141099.

Blood-Pressure Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: Evidence to support the choice of blood-pressure targets for the treatment of comatose survivors of out-of-hospital cardiac arrest who are receiving intensive care is limited. METHODS: In a double-blind, randomized trial with a 2-by-2 factorial design, we evaluated a mean arterial blood-pressure target of 63 mm Hg as compared with 77 mm Hg in comatose adults who had been resuscitated after an out-of-hospital cardiac arrest of presumed cardiac cause; patients were also assigned to one of two oxygen targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with a Cerebral Performance Category (CPC) of 3 or 4 within 90 days (range, 0 to 5, with higher categories indicating more severe disability; a category of 3 or 4 indicates severe disability or coma). Secondary outcomes included neuron-specific enolase levels at 48 hours, death from any cause, scores on the Montreal Cognitive Assessment (range, 0 to 30, with higher scores indicating better cognitive ability) and the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability) at 3 months, and the CPC at 3 months. RESULTS: A total of 789 patients were included in the analysis (393 in the high-target group and 396 in the low-target group). A primary-outcome event occurred in 133 patients (34%) in the high-target group and in 127 patients (32%) in the low-target group (hazard ratio, 1.08; 95% confidence interval [CI], 0.84 to 1.37; P = 0.56). At 90 days, 122 patients (31%) in the high-target group and 114 patients (29%) in the low-target group had died (hazard ratio, 1.13; 95% CI, 0.88 to 1.46). The median CPC was 1 (interquartile range, 1 to 5) in both the high-target group and the low-target group; the corresponding median modified Rankin scale scores were 1 (interquartile range, 0 to 6) and 1 (interquartile range, 0 to 6), and the corresponding median Montreal Cognitive Assessment scores were 27 (interquartile range, 24 to 29) and 26 (interquartile range, 24 to 29). The median neuron-specific enolase level at 48 hours was also similar in the two groups. The percentages of patients with adverse events did not differ significantly between the groups. CONCLUSIONS: Targeting a mean arterial blood pressure of 77 mm Hg or 63 mm Hg in patients who had been resuscitated from cardiac arrest did not result in significantly different percentages of patients dying or having severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

Oxygen Targets in Comatose Survivors of Cardiac Arrest.

BACKGROUND: The appropriate oxygenation target for mechanical ventilation in comatose survivors of out-of-hospital cardiac arrest is unknown. METHODS: In this randomized trial with a 2-by-2 factorial design, we randomly assigned comatose adults with out-of-hospital cardiac arrest in a 1:1 ratio to either a restrictive oxygen target of a partial pressure of arterial oxygen (Pao2) of 9 to 10 kPa (68 to 75 mm Hg) or a liberal oxygen target of a Pao2 of 13 to 14 kPa (98 to 105 mm Hg); patients were also assigned to one of two blood-pressure targets (reported separately). The primary outcome was a composite of death from any cause or hospital discharge with severe disability or coma (Cerebral Performance Category [CPC] of 3 or 4; categories range from 1 to 5, with higher values indicating more severe disability), whichever occurred first within 90 days after randomization. Secondary outcomes were neuron-specific enolase levels at 48 hours, death from any cause, the score on the Montreal Cognitive Assessment (ranging from 0 to 30, with higher scores indicating better cognitive ability), the score on the modified Rankin scale (ranging from 0 to 6, with higher scores indicating greater disability), and the CPC at 90 days. RESULTS: A total of 789 patients underwent randomization. A primary-outcome event occurred in 126 of 394 patients (32.0%) in the restrictive-target group and in 134 of 395 patients (33.9%) in the liberal-target group (hazard ratio, 0.95; 95% confidence interval, 0.75 to 1.21; P = 0.69). At 90 days, death had occurred in 113 patients (28.7%) in the restrictive-target group and in 123 (31.1%) in the liberal-target group. On the CPC, the median category was 1 in the two groups; on the modified Rankin scale, the median score was 2 in the restrictive-target group and 1 in the liberal-target group; and on the Montreal Cognitive Assessment, the median score was 27 in the two groups. At 48 hours, the median neuron-specific enolase level was 17 µg per liter in the restrictive-target group and 18 µg per liter in the liberal-target group. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Targeting of a restrictive or liberal oxygenation strategy in comatose patients after resuscitation for cardiac arrest resulted in a similar incidence of death or severe disability or coma. (Funded by the Novo Nordisk Foundation; BOX ClinicalTrials.gov number, NCT03141099.).

ICU delirium burden predicts functional neurologic outcomes.

BACKGROUND: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness. METHODS: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016. Altogether, patients were assessed daily for delirium 2941days using the Confusion Assessment Method for the ICU (CAM-ICU). Hospitalization delirium burden (DB) was quantified as number of hospital days with delirium divided by total days at risk. Survival status up to 2.5 years and neurologic outcomes using the Glasgow Outcome Scale were recorded at discharge 3, 6, and 12 months post-discharge. RESULTS: Of 178 patients, 19 (10.7%) were excluded from outcome analyses due to persistent coma. Among the remaining 159, 123 (77.4%) experienced delirium. DB was independently associated with >4-fold increased mortality at 2.5 years following ICU admission (adjusted hazard ratio [aHR], 4.77; 95% CI, 2.10-10.83; P < .001), and worse neurologic outcome at discharge (adjusted odds ratio [aOR], 0.02; 0.01-0.09; P < .001), 3 (aOR, 0.11; 0.04-0.31; P < .001), 6 (aOR, 0.10; 0.04-0.29; P < .001), and 12 months (aOR, 0.19; 0.07-0.52; P = .001). DB in the ICU alone was not associated with mortality (HR, 1.79; 0.93-3.44; P = .082) and predicted neurologic outcome less strongly than entire hospital stay DB. Similarly, the number of delirium days in the ICU and for whole hospitalization were not associated with mortality (HR, 1.00; 0.93-1.08; P = .917 and HR, 0.98; 0.94-1.03, P = .535) nor with neurological outcomes, except for the association between ICU delirium days and neurological outcome at discharge (OR, 0.90; 0.81-0.99, P = .038). CONCLUSIONS: Delirium burden throughout hospitalization independently predicts long term neurologic outcomes and death up to 2.5 years after critical illness, and is more predictive than delirium burden in the ICU alone and number of delirium days.

Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial.

Importance: Comatose survivors of out-of-hospital cardiac arrest experience high rates of death and severe neurologic injury. Current guidelines recommend targeted temperature management at 32 °C to 36 °C for 24 hours. However, small studies suggest a potential benefit of targeting lower body temperatures. Objective: To determine whether moderate hypothermia (31 °C), compared with mild hypothermia (34 °C), improves clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Design, Setting, and Participants: Single-center, double-blind, randomized, clinical superiority trial carried out in a tertiary cardiac care center in eastern Ontario, Canada. A total of 389 patients with out-of-hospital cardiac arrest were enrolled between August 4, 2013, and March 20, 2020, with final follow-up on October 15, 2020. Interventions: Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Main Outcomes and Measures: The primary outcome was all-cause mortality or poor neurologic outcome at 180 days. Neurologic outcome was assessed using the Disability Rating Scale, with poor neurologic outcome defined as a score greater than 5 (range, 0-29, with 29 being the worst outcome [vegetative state]). There were 19 secondary outcomes, including mortality at 180 days and length of stay in the intensive care unit. Results: Among 367 patients included in the primary analysis (mean age, 61 years; 69 women [19%]), 366 (99.7%) completed the trial. The primary outcome occurred in 89 of 184 patients (48.4%) in the 31 °C group and in 83 of 183 patients (45.4%) in the 34 °C group (risk difference, 3.0% [95% CI, 7.2%-13.2%]; relative risk, 1.07 [95% CI, 0.86-1.33]; P = .56). Of the 19 secondary outcomes, 18 were not statistically significant. Mortality at 180 days was 43.5% and 41.0% in patients treated with a target temperature of 31 °C and 34 °C, respectively (P = .63). The median length of stay in the intensive care unit was longer in the 31 °C group (10 vs 7 days; P = .004). Among adverse events in the 31 °C group vs the 34 °C group, deep vein thrombosis occurred in 11.4% vs 10.9% and thrombus in the inferior vena cava occurred in 3.8% and 7.7%, respectively. Conclusions and Relevance: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02011568.

Complementary roles of neural synchrony and complexity for indexing consciousness and chances of surviving in acute coma.

An open challenge in consciousness research is understanding how neural functions are altered by pathological loss of consciousness. To maintain consciousness, the brain needs synchronized communication of information across brain regions, and sufficient complexity in neural activity. Coordination of brain activity, typically indexed through measures of neural synchrony, has been shown to decrease when consciousness is lost and to reflect the clinical state of patients with disorders of consciousness. Moreover, when consciousness is lost, neural activity loses complexity, while the levels of neural noise, indexed by the slope of the electroencephalography (EEG) spectral exponent decrease. Although these properties have been well investigated in resting state activity, it remains unknown whether the sensory processing network, which has been shown to be preserved in coma, suffers from a loss of synchronization or information content. Here, we focused on acute coma and hypothesized that neural synchrony in response to auditory stimuli would reflect coma severity, while complexity, or neural noise, would reflect the presence or loss of consciousness. Results showed that neural synchrony of EEG signals was stronger for survivors than non-survivors and predictive of patients' outcome, but indistinguishable between survivors and healthy controls. Measures of neural complexity and neural noise were not informative of patients' outcome and had high or low values for patients compared to controls. Our results suggest different roles for neural synchrony and complexity in acute coma. Synchrony represents a precondition for consciousness, while complexity needs an equilibrium between high or low values to support conscious cognition.

Nontraumatic coma in the pediatric intensive care unit: etiology, clinical characteristics and outcome

Background/aim: The purpose of this study was to evaluate the etiology, clinical characteristics, and outcome of nontraumatic coma (NTC) among children admitted to a pediatric intensive care unit (PICU). Materials and methods: A total of 159 children with NTC were included in the study. The modified Glasgow coma scale (GCS) was used to assess consciousness. Patients were classified with regard to etiology. For each patient, demographic and clinical characteristics, survival and degree of disability at PICU discharge were recorded. Results: Median age was 55 months (IQR: 17.0 - 109.0). The most common cause of NTC was neuroinfection (31.4%) followed by toxic- metabolic conditions (25.8%) and epileptic disorder (15.1%). There was no significant relationship between the level of encephalopathy at admission and NTC etiology. A total of 13 patients died (8.2%). Among the survivors, 61.6% were discharged without any neurologic deficit, 2.8% had severe neurologic disability, and 3.4% were in a vegetative state. Complete neurological recovery was significantly more common in patients with toxic metabolic disease, whereas neurological deficits were more frequent in patients with tuberculous meningo-encephalitis (P = 0.01 and P = 0.04, respectively). Higher pediatric risk of mortality III (PRISM III) score at PICU admission (Odds ratio: 1.51, 95% CI: 1.19 - 1.92; P < 0.001) was the only variable that was independently associated with mortality. The length of stay (LOS) at hospital (Odds ratio: 0.73, 95% CI: 0.58-0.91; P = 0.006) was associated with improved odds of survival. Conclusions: Although results obtained from this single-center study cannot be generalized to the pediatric population, the contribution to the literature in terms of the relationships between NTC etiology, and outcome can be crucial for clinical decision-making. We report neuroinfection as the most common cause of NTC, and the only factor that was closely associated with mortality was PRISM III score. Length of hospital stay was inversely correlated to patient mortality.

The time course of acute Percheron artery ischemic coma on imaging: A retrospective cohort study.

We were to investigate the time course of lesions for awakening in acute Percheron artery ischemic coma (PAIC), which was previously unknown. Patients who had newly identified acute PAIC events in 2012-2015 and had not received thrombolytic therapy were enrolled retrospectively. The time course of lesions in PAIC was investigated by diffusion-weighted imaging (DWI). Ninety-three patients met the inclusion criteria, of whom 63 and 30 had transient PAIC and persistent PAIC, respectively. The time course of awakening events in persistent PAIC decreased over time, with large lesions in the bilateral paramedian thalamus/ rostral midbrain on DWI almost in all patients who was either plus or minus a "top of basilar artery" strokes. Whereas awakening events in transient PAIC increased over time, with small or lacunar lesions in the unilateral or bilateral thalamus/rostral midbrain about in 30.2 % cases, and the rest in naturally recanalization of infarcts or TIA. Lesion volumes were larger for persistent PAIC than for transient PAIC (median, 2.4 cm3 vs. 0.03 cm3, P < 0.0001). In Cox hazards ratio (HR) analysis, a lower GCS score was associated with mortality (HR, 5.5; 95 % confidence interval [CI],1.427-21.45). Multivaliate analysis shown that the predictors of higher risk of persistent PAIC were only increased NIHSS scores (HR,1.3; 95 % CI,1.109-1.640) and large lesions in bilateral thalamus/rostral midbrain (HR,15.0; 95 % CI,1.440-58.13). The time course of acute PAIC included transient and persistent. Most persistent PAIC was associated with large lesions in bilateral paramedian thalamus/ rostral midbrain, and with high mortality.

Effect of acupuncture method of removing-stasisand resuscitating on the consciousness of patients with severe traumatic brain injury: A randomized clinical trial.

INTRODUCTION: With the development of social economy, transportation and various infrastructures have also developed, but it has objectively increased the number of patients with head injury. Although the current craniocerebral medicine technology continues to advance, long-term bed rest and other complications have led to an insignificant decrease in the mortality rate of coma patients. It is not uncommon for patients with disturbance of consciousness caused by head injury in major hospitals. METHODS/DESIGN: This will be a retrospective, single-blind clinical observational study. We will select 50 cases that meet the subject's selection criteria. According to whether they received acupuncture treatment or not, they will be randomly divided into 2 groups, namely treatment group and control group. The control group will be given conventional Western medicine treatment, and the treatment group will be given acupuncture method of removing-stasis and resuscitating treatment on the basis of the control group. DISCUSSION: Our purpose is to observe the role of acupuncture method of removing-stasis and resuscitating in promoting the recovery of patients with severe head injury. We aim to provide more evidence-based medical evidence for acupuncture treatment of this disease. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000034732, Registered on 19 July 2020.

Association of Initial Illness Severity and Outcomes After Cardiac Arrest With Targeted Temperature Management at 36 °C or 33 °C.

Importance: It is uncertain what the optimal target temperature is for targeted temperature management (TTM) in patients who are comatose following cardiac arrest. Objective: To examine whether illness severity is associated with changes in the association between target temperature and patient outcome. Design, Setting, and Participants: This cohort study compared outcomes for 1319 patients who were comatose after cardiac arrest at a single center in Pittsburgh, Pennsylvania, from January 2010 to December 2018. Initial illness severity was based on coma and organ failure scores, presence of severe cerebral edema, and presence of highly malignant electroencephalogram (EEG) after resuscitation. Exposure: TTM at 36 °C or 33 °C. Main Outcomes and Measures: Primary outcome was survival to hospital discharge, and secondary outcomes were modified Rankin Scale and cerebral performance category. Results: Among 1319 patients, 728 (55.2%) had TTM at 33 °C (451 [62.0%] men; median [interquartile range] age, 61 [50-72] years) and 591 (44.8%) had TTM at 36 °C (353 [59.7%] men; median [interquartile range] age, 59 [48-69] years). Overall, 184 of 187 patients (98.4%) with severe cerebral edema died and 234 of 243 patients (96.3%) with highly malignant EEG died regardless of TTM strategy. Comparing TTM at 33 °C with TTM at 36 °C in 911 patients (69.1%) with neither severe cerebral edema nor highly malignant EEG, survival was lower in patients with mild to moderate coma and no shock (risk difference, -13.8%; 95% CI, -24.4% to -3.2%) but higher in patients with mild to moderate coma and cardiopulmonary failure (risk difference, 21.8%; 95% CI, 5.4% to 38.2%) or with severe coma (risk difference, 9.7%; 95% CI, 4.0% to 15.3%). Interactions were similar for functional outcomes. Most deaths (633 of 968 [65.4%]) resulted after withdrawal of life-sustaining therapies. Conclusions and Relevance: In this study, TTM at 33 °C was associated with better survival than TTM at 36 °C among patients with the most severe post-cardiac arrest illness but without severe cerebral edema or malignant EEG. However, TTM at 36 °C was associated with better survival among patients with mild- to moderate-severity illness.

Clinical characteristics and time trends of hospitalized methadone exposures in the United States based on the Toxicology Investigators Consortium (ToxIC) case registry: 2010-2017.

BACKGROUND: Methadone is well known for its long duration of action and propensity for mortality after an overdose. The present research was aimed at evaluating the clinical manifestations and time trends of methadone exposure in patients in US hospitals. METHODS: We queried the American College of Medical Toxicology's Toxicology Investigators Consortium case registry for all cases of methadone exposure between January 1, 2010, and December 31, 2017. The collected information included demographic features, clinical presentations, therapeutic interventions, poisoning type (acute, chronic, or acute on chronic), and the reason(s) for exposure. Descriptive data and relative frequencies were used to investigate the participants' characteristics. Our data analysis was performed using SPSS version 19 and Prism software. The trends and clinical manifestations of methadone poisoning over the time period of the study were specifically investigated. RESULTS: Nine hundred and seventy-three patients who met our inclusion criteria, with a mean age of 41.9 ± 16.6 years (range: 11 months-78 years) were analyzed. Five hundred eighty-two (60.2%) were male. The highest rate of methadone poisoning was observed in 2013. There was an increasing rate of methadone exposures in 2010-2013, followed by a decline in 2014-2017. The most common clinical manifestations in methadone-poisoned patients were coma (48.6%) and respiratory depression (33.6%). The in-hospital mortality rate of methadone poisoning was 1.4%. CONCLUSION: ToxIC Registry data showed that inpatient methadone exposures enhanced from 2010 to 2013, after which a reduction occurred in the years 2014 to 2017.

10 Years of Implementation of the "Glasgow 7" Quality Guarantee Program in the Mendoza Central Hospital: Epidemiology and Evolution of Neurocrytic Patients.

INTRODUCTION: In 2003, the Glasgow 7 Quality Guarantee Program was put into effect in Argentina with the objective of standardizing the donation and transplant process throughout the country, establishing the observation and registration of all neurocritical patients with a score on the Glasgow Coma Scale of 7 of 15 or less admitted to critical beds of selected establishments. MATERIALS AND METHODS: The following study is retrospective, observational, and cohort-based. It was developed in the Central Hospital of Mendoza, in the critical units, including guard, coronary, cardiovascular surgery recovery, and intensive care therapy. The inclusion criteria were admission to the institution with a score on the Glasgow Coma Scale of 7 or less with a structural cause of coma. Data collection was carried out in the national online database SINTRA. RESULTS: From January 1, 2008, to December 31, 2018, 1757 patients were enrolled at the Central Hospital of Mendoza, Argentina with Glasgow scores of 7 or less. The most frequent cause of coma was brain trauma (934 patients; 53%), followed by stroke (614 patients; 35%). Of those who scored 3 of 15 in the GCS upon admission, 65% progressed to brain death, whereas 72% of those who scored 7 were discharged. Of all these patients, 270 became donors, accounting for 43% of all brain deaths, whereas 187 had refused to become organ donors (30.6%). Of the total real donors, 55% were multiorganic (150 donors).

Near-infrared Spectroscopy-derived Cerebral Autoregulation Indices Independently Predict Clinical Outcome in Acutely Ill Comatose Patients.

OBJECTIVE: Outcome prediction in comatose patients with acute brain injury remains challenging. Regional cerebral oxygenation (rSO2) derived from near-infrared spectroscopy (NIRS) is a surrogate for cerebral blood flow and can be used to calculate cerebral autoregulation (CA) continuously at the bedside from the derived cerebral oximetry index (COx). We hypothesized that COx derived thresholds for CA are associated with outcomes in patients with acute coma from neurological injury. METHODS: A prospective cohort study was conducted in 88 acutely comatose adults with heterogenous brain injury diagnoses who were continuously monitored with COx for up to 3 consecutive days. Multivariable logistic regression was performed to investigate association between averaged COx and short (in-hospital and 3 mo) and long-term (6 mo) outcomes. RESULTS: Six month mortality rate was 62%. Median COx in nonsurvivors at hospital discharge was 0.082 [interquartile range, IQR: 0.045 to 0.160] compared with 0.042 [IQR: -0.005 to 0.110] in survivors (P=0.012). At 6 months, median COx was 0.075 [IQR: 0.27 to 0.158] in nonsurvivors compared with 0.029 [IQR: -0.015 to 0.077] in survivors (P=0.02). In the multivariable logistic regression model adjusted for confounders, average COx ≥0.05 was associated with both in-hospital mortality (adjusted odds ratio [OR]=2.9, 95% confidence interval [CI]=1.15-7.33, P=0.02), mortality at 6 months (adjusted OR=4.4, 95% CI=1.41-13.7, P=0.01), and severe disability (modified Rankin Score ≥4) at 6 months (adjusted OR=4.4, 95% CI=1.07-17.8, P=0.04). Area under the receiver operating characteristic curve for predicting mortality and severe disability at 6 months were 0.783 and 0.825, respectively. CONCLUSIONS: Averaged COx ≥0.05 is independently associated with short and long-term mortality and long-term severe disability in acutely comatose adults with neurological injury. We propose that COx ≥0.05 represents an accurate threshold to predict long-term functional outcome in acutely comatose adults.

Targeted Temperature Management at 33 Versus 36 Degrees: A Retrospective Cohort Study.

OBJECTIVES: To determine the association between targeted temperature management goal temperature of 33°C versus 36°C and neurologic outcome after out-of-hospital cardiac arrest. DESIGN: This was a retrospective, before-and-after, cohort study. SETTING: Urban, academic, level 1 trauma center from 2010 to 2017. PATIENTS: Adults with nontraumatic out-of-hospital cardiac arrest who received targeted temperature management. INTERVENTIONS: Our primary exposure was targeted temperature management goal temperature, which was changed from 33°C to 36°C in April of 2014 at the study hospital. Primary outcome was neurologically intact survival to discharge. Secondary outcomes included hospital mortality and care processes. MEASUREMENTS AND MAIN RESULTS: Of 782 out-of-hospital cardiac arrest patients transported to the study hospital, 453 (58%) received targeted temperature management. Of these, 258 (57%) were treated during the 33°C period (targeted temperature management 33°C) and 195 (43%) were treated during the 36°C period (targeted temperature management 36°C). Patients treated during targeted temperature management 33°C were older (57 vs 52 yr; p < 0.05) and had more arrests of cardiac etiology (45% vs 35%; p < 0.05), but otherwise had similar baseline characteristics, including initial cardiac rhythm. A total of 40% of patients treated during targeted temperature management 33°C survived with favorable neurologic outcome, compared with 30% in the targeted temperature management 36°C group (p < 0.05). After adjustment for demographic and cardiac arrest characteristics, targeted temperature management 33°C was associated with increased odds of neurologically intact survival to discharge (odds ratio, 1.79; 95% CI, 1.09-2.94). Targeted temperature management 33°C was not associated with significantly improved hospital mortality. Targeted temperature management was implemented faster (1.9 vs 3.5 hr from 911 call; p < 0.001) and more frequently in the emergency department during the targeted temperature management 33°C period (87% vs 55%; p < 0.001). CONCLUSIONS: Comatose, adult out-of-hospital cardiac arrest patients treated during the targeted temperature management 33°C period had higher odds of neurologically intact survival to hospital discharge compared with those treated during the targeted temperature management 36°C period. There was no significant difference in hospital mortality.

Relationship Between Duration of Targeted Temperature Management, Ischemic Interval, and Good Functional Outcome From Out-of-Hospital Cardiac Arrest.

OBJECTIVES: Tailoring hypothermia duration to ischemia duration may improve outcome from out-of-hospital cardiac arrest. We investigated the association between the hypothermia/ischemia ratio and functional outcome in a secondary analysis of data from the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, or Placebo Study trial. DESIGN: Cohort study of out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study. SETTING: Multicenter study across North America. PATIENTS: Adult, nontraumatic, out-of-hospital cardiac arrest patients screened for Resuscitation Outcomes Consortium-Amiodarone, Lidocaine, or Placebo Study who survived to hospital admission and received targeted temperature management between May 2012 and October 2015. INTERVENTIONS: Targeted temperature management in comatose survivors of out-of-hospital cardiac arrest. We defined hypothermia/ischemia ratio as total targeted temperature management time (initiation through rewarming) divided by calculated total ischemia time (approximate time of arrest [9-1-1 call or emergency medical services-witnessed] to return of spontaneous circulation). MEASUREMENTS AND MAIN RESULTS: The primary outcome was hospital survival with good functional status (modified Rankin Score, 0-3) at hospital discharge. We fitted logistic regression models to estimate the association between hypothermia/ischemia ratio and the primary outcome, adjusting for demographics, arrest characteristics, and Resuscitation Outcomes Consortium enrolling site. A total of 3,429 patients were eligible for inclusion, of whom 36.2% were discharged with good functional outcome. Patients had a mean age of 62.0 years (SD, 15.8), with 69.7% male, and 58.0% receiving lay-rescuer cardiopulmonary resuscitation. Median time to return of spontaneous circulation was 21.1 minutes (interquartile range, 16.1-26.9), and median duration of targeted temperature management was 32.9 hours (interquartile range, 23.7-37.8). A total of 2,579 had complete data and were included in adjusted regression analyses. After adjustment for patient characteristics and Resuscitation Outcomes Consortium site, a greater hypothermia/ischemia ratio was associated with increased survival with good functional outcome (odds ratio, 2.01; 95% CI, 1.82-2.23). This relationship, however, appears to be primarily driven by time to return of spontaneous circulation in this patient cohort. CONCLUSIONS: Although a larger hypothermia/ischemia ratio was associated with good functional outcome after out-of-hospital cardiac arrest in this cohort, this association is primarily driven by duration of time to return of spontaneous circulation. Tailoring duration of targeted temperature management based on duration of time to return of spontaneous circulation or patient characteristics requires prospective study.

Association of Japan Coma Scale score on hospital arrival with in-hospital mortality among trauma patients.

BACKGROUND: The Japan Coma Scale (JCS) score has been widely used to assess patients' consciousness level in Japan. JCS scores are divided into four main categories: alert (0) and one-, two-, and three-digit codes based on an eye response test, each of which has three subcategories. The purpose of this study was to investigate the utility of the JCS score on hospital arrival in predicting outcomes among adult trauma patients. METHODS: Using the Japan Trauma Data Bank, we conducted a nationwide registry-based retrospective cohort study. Patients 16 years old or older directly transported from the trauma scene between January 2004 and December 2017 were included. Our primary outcome was in-hospital mortality. We examined outcome prediction accuracy based on area under the receiver operating characteristic curve (AUROC) and multiple logistic regression analysis with multiple imputation. RESULTS: A total of 222,540 subjects were included; their in-hospital mortality rate was 7.1% (n = 15,860). The 10-point scale JCS and the total sum of Glasgow Coma Scale (GCS) scores demonstrated similar performance, in which the AUROC (95% CIs) showed 0.874 (0.871-0.878) and 0.878 (0.874-0.881), respectively. Multiple logistic regression analysis revealed that the higher the JCS score, the higher the predictability of in-hospital death. When we focused on the simple four-point scale JCS score, the adjusted odds ratio (95% confidence intervals [CIs]) were 2.31 (2.12-2.45), 4.81 (4.42-5.24), and 27.88 (25.74-30.20) in the groups with one-digit, two-digit, and three-digit scores, respectively, with JCS of 0 as a reference category. CONCLUSIONS: JCS score on hospital arrival after trauma would be useful for predicting in-hospital mortality, similar to the GCS score.

Association between the Japan Coma Scale scores at the scene of injury and in-hospital outcomes in trauma patients: an analysis from the nationwide trauma database in Japan.

OBJECTIVE: Japan Coma Scale (JCS) is a grading system used to evaluate disturbed consciousness in prehospital care settings. We aimed to identify the association between the JCS levels at the scene with in-hospital mortality, as well as the discrimination ability for the outcomes. DESIGN: A retrospective cohort study based on the nationwide trauma database in Japan. SETTING: Multicentre cohort study using data from the Japan Trauma Data Bank, which is a nationwide, prospective, observational trauma registry derived from 235 hospitals. PARTICIPANTS: Adult trauma victims transferred directly from the scene of injury to the hospital from January 2004 to December 2017 were eligible for inclusion. PRIMARY AND SECONDARY OUTCOMES: Primary outcome was the association between the JCS levels at the scene with in-hospital mortality. We conducted a multivariate logistic regression analysis to calculate the adjusted ORs of JCS levels with 95% CIs for in-hospital mortality. We also calculated the c-statistics for in-hospital mortality. RESULTS: 164 723 patients were included in the analysis. In a multivariate logistic regression analysis, the corresponding adjusted ORs of JCS levels 2 and 3 referred to level 1 for in-hospital mortality were 4.1 (95% CI 3.8 to 4.4) and 26.0 (95% CI 24.8 to 27.2). The c-statistics of the JCS level for in-hospital mortality was 0.845 (95% CI 0.842 to 0.849). CONCLUSIONS: Data from large multicentre prospective registry revealed strong associations of the JCS level at the scene of injury with in-hospital mortality as well as the good discriminatory performance for this outcome.

Differences in 90-day mortality of delirium subtypes in the intensive care unit: A retrospective cohort study.

INTRODUCTION: Many intensive care unit (ICU) patients suffer from delirium which is associated with deleterious short-term and long-term effects, including mortality. We determined the association between different delirium subtypes and 90-day mortality. MATERIALS AND METHODS: Retrospective cohort study in ICU patients admitted in 2015-2017. Delirium, including its subtypes, was determined using the confusion assessment method-ICU (CAM-ICU) and Richmond agitation sedation scale (RASS). Exclusion criteria were insufficient assessments and persistent coma. Cox-regression analysis was used to determine associations of delirium subtypes with 90-day mortality, including relevant covariates (APACHE-IV, length of ICU stay and mechanical ventilation). RESULTS: 7362 ICU patients were eligible of whom 6323 (86%) were included. Delirium occurred in 1600 (25%) patients (stratified for delirium subtype: N = 571-36% mixed, N = 485-30% rapidly reversible, N = 433-27% hypoactive, N = 111-7% hyperactive). The crude hazard ratio (HR) for overall prevalent delirium with 90-day mortality was 2.84 (95%CI: 2.32-3.49), and the adjusted HR 1.29 (95%CI: 1.01-1.65). The adjusted HR for 90-day mortality was 1.57 (95%CI: 1.51-2.14) for the mixed subtype, 1.40 (95%CI: 0.71-2.73) for hyperactive, 1.31 (95%CI: 0.93-1.84) for hypoactive and 0.95 (95%CI: 0.64-1.42) for rapidly reversible delirium. CONCLUSION: After adjusting for covariates, including competing risk factors, only the mixed delirium subtype was significantly associated with 90-day mortality.

Death after awakening from post-anoxic coma: the "Best CPC" project.

BACKGROUND: In patients who recover consciousness after cardiac arrest (CA), a subsequent death from non-neurological causes may confound the assessment of long-term neurological outcome. We investigated the prevalence and causes of death after awakening (DAA) in a multicenter cohort of CA patients. METHODS: Observational multicenter cohort study on patients resuscitated from CA in eight European intensive care units (ICUs) from January 2007 to December 2014. DAA during the hospital stay was extracted retrospectively from patient medical records. Demographics, comorbidities, initial CA characteristics, concomitant therapies, prognostic tests (clinical examination, electroencephalography (EEG), somatosensory evoked potentials (SSEPs)), and cause of death were identified. RESULTS: From a total 4646 CA patients, 2478 (53%) died in-hospital, of whom 196 (4.2%; ranges 0.6-13.0%) had DAA. DAA was less frequent among out-of-hospital than in-hospital CA (82/2997 [2.7%] vs. 114/1649 [6.9%]; p < 0.001). Median times from CA to awakening and from awakening to death were 2 [1-5] and 9 [3-18] days, respectively. The main causes of DAA were multiple organ failure (n = 61), cardiogenic shock (n = 61), and re-arrest (n = 26). At day 3 from admission, results from EEG (n = 56) and SSEPs (n = 60) did not indicate poor outcome. CONCLUSIONS: In this large multicenter cohort, DAA was observed in 4.2% of non-survivors. Information on DAA is crucial since it may influence epidemiology and the design of future CA studies evaluating neuroprognostication and neuroprotection.