Impact of Lactate Clearance on Clinical and Neurological Outcomes of Patients With Out-of-Hospital Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Secondary Data Analysis.

OBJECTIVES: Serial evaluations of lactate concentration may be more useful in predicting outcomes in patients with out-of-hospital cardiac arrest (OHCA) than a single measurement. This study aimed to evaluate the impact of lactate clearance (LC) on clinical and neurologic outcomes in patients with OHCA who underwent extracorporeal cardiopulmonary resuscitation (ECPR). DESIGN: Retrospective multicenter observational study. SETTING: Patients with OHCA receiving ECPR at 36 hospitals in Japan between January 1, 2013, and December 31, 2018. PATIENTS: This study evaluated 1227 patients, with lactate initial assessed upon emergency department admission and lactate second measured subsequently. To adjust for the disparity in the time between lactate measurements, the modified 6-hour LC was defined as follows: ([lactate initial -lactate second ]/lactate initial ) × 100 × (6/the duration between the initial and second measurements [hr]). The patients were divided into four groups according to the modified 6-hour LC with an equivalent number of patients among LC quartiles: Q1 (LC < 18.8), Q2 (18.8 < LC < 59.9), Q3 (60.0 < LC < 101.2), and Q4 (101.2 < LC). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 30-day survival rates increased as the 6-hour LC increased (Q1, 21.2%; Q2, 36.8%; Q3, 41.4%; Q4, 53.6%; p for trend < 0.001). In the multivariate analysis, the modified 6-hour LC was significantly associated with a 30-day survival rate (adjusted odds ratio [AOR], 1.003; 95% CI, 1.001-1.005; p < 0.001) and favorable neurologic outcome (AOR, 1.002; 95% CI, 1.000-1.004; p = 0.027). CONCLUSIONS: In patients with OHCA who underwent ECPR, an increase in the modified 6-hour LC was associated with favorable clinical and neurologic outcome. Thus, LC can be a criterion to assess whether ECPR should be continued.

Prognostic Significance of Signs of Life in Out-of-Hospital Cardiac Arrest Patients Undergoing Extracorporeal Cardiopulmonary Resuscitation.

OBJECTIVES: Signs of life (SOLs) during cardiac arrest (gasping, pupillary light reaction, or any form of body movement) are suggested to be associated with favorable neurologic outcomes in out-of-hospital cardiac arrest (OHCA). While data has demonstrated that extracorporeal cardiopulmonary resuscitation (ECPR) can improve outcomes in cases of refractory cardiac arrest, it is expected that other contributing factors lead to positive outcomes. This study aimed to investigate whether SOL on arrival is associated with neurologic outcomes in patients with OHCA who have undergone ECPR. DESIGN: Retrospective multicenter registry study. SETTING: Thirty-six facilities participating in the Study of Advanced life support for Ventricular fibrillation with Extracorporeal circulation in Japan II (SAVE-J II). PATIENTS: Consecutive patients older than 18 years old who were admitted to the Emergency Department with OHCA between January 1, 2013, and December 31, 2018, and received ECPR. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were classified into two groups according to the presence or absence of SOL on arrival. The primary outcome was a favorable neurologic outcome (Cerebral Performance Category 1 or 2) at discharge. Of the 2157 patients registered in the SAVE-J II database, 1395 met the inclusion criteria, and 250 (17.9%) had SOL upon arrival. Patients with SOL had more favorable neurologic outcomes than those without SOL (38.0% vs. 8.1%; p < 0.001). Multivariate analysis showed that SOL on arrival was independently associated with favorable neurologic outcomes (odds ratio, 5.65 [95% CI, 3.97-8.03]; p < 0.001). CONCLUSIONS: SOL on arrival was associated with favorable neurologic outcomes in patients with OHCA undergoing ECPR. In patients considered for ECPR, the presence of SOL on arrival can assist the decision to perform ECPR.

Sex differences in extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: nationwide multicenter retrospective study in Japan.

BACKGROUND: Previous studies examining sex differences in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) have indicated that women have favorable outcomes; however, detailed evidence remains lacking. We aimed to investigate sex differences in the backgrounds and outcomes of patients undergoing ECPR for OHCA. METHODS: This study was a secondary analysis of the registry from the SAVE-J II study, a retrospective multicenter study conducted in Japan from 2013 to 2018. Adult patients without external causes who underwent ECPR for OHCA were included. The primary outcome was a favorable neurological outcome (Cerebral Performance Status 1 or 2) at hospital discharge. We used multilevel logistic regression to evaluate the association of sex differences, adjusting for center-level (hospital) and individual-level variables (patient background, cardiac arrest situation, and in-hospital intervention factors). For sensitivity analyses, we performed three models of multilevel logistic regression when selecting confounders. RESULTS: Among the 1819 patients, 1523 (83.7%) were men, and 296 (16.3%) were women. The median age (61.0 vs. 58.0 years), presence of a witness (78.8% vs. 79.2%), and occurrence of bystander CPR (57.5% vs. 61.6%) were similar between groups. Women were more likely to present with an initial non-shockable rhythm (31.7% vs. 49.7%), as well as a non-shockable rhythm at hospital arrival (52.1% vs. 61.5%) and at ECMO initiation (48.1% vs. 57.1%). The proportion of favorable neurological outcomes was 12.3% in males and 15.9% in females (p = 0.10). Multilevel logistic regression analysis showed that the female sex was significantly associated with a favorable neurologic outcome at discharge (adjusted odds ratio: 1.60 [95% confidence interval: 1.05-2.43]; p = 0.03). This advantage in women was consistently observed in the sensitivity analyses. CONCLUSIONS: The female sex is significantly associated with favorable neurological outcomes at hospital discharge in patients who received ECPR for OHCA.

Prophylactic distal perfusion catheter and survival in patients with out-of-hospital cardiac arrest: Secondary analysis of the SAVE-J II study.

PURPOSE: The effect of a prophylactic distal perfusion catheter (DPC) after extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. Therefore, we aimed to clarify the association between prophylactic DPC and prognosis in patients with OHCA undergoing ECPR. MATERIALS AND METHODS: A secondary analysis of the Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J II) database was performed to compare groups of patients with and without prophylactic DPCs. A multivariate analysis of survival at discharge was performed using factors that were significant in the two-arm comparison. RESULTS: A total of 2044 patients were included in the analysis after excluding those who met the exclusion criteria. Survival at discharge was observed in 548 (26.9%) patients. In total, 100 (4.9%) patients developed limb ischemia, among whom 14 (0.7%) required therapeutic intervention. Multivariate analysis showed that prophylactic DPC did not result in a significant difference in survival at discharge (odds ratio: 0.898 [0.652-1.236], p = 0.509). CONCLUSIONS: The implementation of prophylactic DPC after ECPR for patients with OHCA may not contribute to survival at discharge.

Optimal chest compression for cardiac arrest until the establishment of ECPR: Secondary analysis of the SAVE-J II study.

INTRODUCTION: The widespread incorporation of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest requires the delivery of effective and high-quality chest compressions prior to the initiation of ECPR. The aim of this study was to evaluate and compare the effectiveness of mechanical and manual chest compressions until the initiation of ECPR. METHODS: This study was a secondary analysis of the Japanese retrospective multicenter registry "Study of Advanced Life Support for Ventricular Fibrillation by Extracorporeal Circulation II (SAVE-J II)". Patients were divided into two groups, one receiving mechanical chest compressions and the other receiving manual chest compressions. The primary outcome measure was mortality at hospital discharge, while the secondary outcome was the cerebral performance category (CPC) score at discharge. RESULTS: Of the 2157 patients enrolled in the SAVE-J II trial, 453 patients (329 in the manual compression group and 124 in the mechanical compression group) were included in the final analysis. Univariate analysis showed a significantly higher mortality rate at hospital discharge in the mechanical compression group compared to the manual compression group (odds ratio [95% CI] = 2.32 [1.34-4.02], p = 0.0026). Multivariate analysis showed that mechanical chest compressions were an independent factor associated with increased mortality at hospital discharge (adjusted odds ratio [95% CI] = 2.00 [1.11-3.58], p = 0.02). There was no statistically significant difference in CPC between the two groups. CONCLUSION: For patients with out-of-hospital cardiopulmonary arrest who require ECPR, extreme caution should be used when performing mechanical chest compressions.

Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

Survival benefits of interventional radiology and surgical teams collaboration during primary trauma surveys: a single-centre retrospective cohort study.

BACKGROUND: A team approach is essential for effective trauma management. Close collaboration between interventional radiologists and surgeons during the initial management of trauma patients is important for prompt and accurate trauma care. This study aimed to determine whether trauma patients benefit from close collaboration between interventional radiology (IR) and surgical teams during the primary trauma survey. METHODS: A retrospective observational study was conducted between 2014 and 2021 at a single institution. Patients were assigned to an embolization group (EG), a surgery group (SG), or a combination group (CG) according to their treatment. The primary and secondary outcomes were survival at hospital discharge compared with the probability of survival (Ps) and the time course of treatment. RESULTS: The analysis included 197 patients, consisting of 135 men and 62 women, with a median age of 56 [IQR, 38-72] years and an injury severity score of 20 [10-29]. The EG, SG, and CG included 114, 48, and 35 patients, respectively. Differences in organ injury patterns were observed between the three groups. In-hospital survival rates in all three groups were higher than the Ps. In particular, the survival rate in the CG was 15.5% higher than the Ps (95% CI: 7.5-23.6%; p < 0.001). In the CG, the median time for starting the initial procedure was 53 [37-79] min and the procedure times for IR and surgery were 48 [29-72] min and 63 [35-94] min, respectively. Those times were significantly shorter among three groups. CONCLUSION: Close collaboration between IR and surgical teams, including the primary survey, improves the survival of severe trauma patients who require both IR procedures and surgeries by improving appropriate treatment selection and reducing the time process.

Clinical Characteristics of Corynebacterium ulcerans Infection, Japan.

Corynebacterium ulcerans is a closely related bacterium to the diphtheria bacterium C. diphtheriae, and some C. ulcerans strains produce toxins that are similar to diphtheria toxin. C. ulcerans is widely distributed in the environment and is considered one of the most harmful pathogens to livestock and wildlife. Infection with C. ulcerans can cause respiratory or nonrespiratory symptoms in patients. Recently, the microorganism has been increasingly recognized as an emerging zoonotic agent of diphtheria-like illness in Japan. To clarify the overall clinical characteristics, treatment-related factors, and outcomes of C. ulcerans infection, we analyzed 34 cases of C. ulcerans that occurred in Japan during 2001-2020. During 2010-2020, the incidence rate of C. ulcerans infection increased markedly, and the overall mortality rate was 5.9%. It is recommended that adults be vaccinated with diphtheria toxoid vaccine to prevent the spread of this infection.

Prevalence, reasons, and timing of decisions to withhold/withdraw life-sustaining therapy for out-of-hospital cardiac arrest patients with extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is rapidly becoming a common treatment strategy for patients with refractory cardiac arrest. Despite its benefits, ECPR raises a variety of ethical concerns when the treatment is discontinued. There is little information about the decision to withhold/withdraw life-sustaining therapy (WLST) for out-of-hospital cardiac arrest (OHCA) patients after ECPR. METHODS: We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter study of ECPR in Japan. Adult patients who underwent ECPR for OHCA with medical causes were included. The prevalence, reasons, and timing of WLST decisions were recorded. Outcomes of patients with or without WLST decisions were compared. Further, factors associated with WLST decisions were examined. RESULTS: We included 1660 patients in the analysis; 510 (30.7%) had WLST decisions. The number of WLST decisions was the highest on the first day and WSLT decisions were made a median of two days after ICU admission. Reasons for WLST were perceived unfavorable neurological prognosis (300/510 [58.8%]), perceived unfavorable cardiac/pulmonary prognosis (105/510 [20.5%]), inability to maintain extracorporeal cardiopulmonary support (71/510 [13.9%]), complications (10/510 [1.9%]), exacerbation of comorbidity before cardiac arrest (7/510 [1.3%]), and others. Patients with WLST had lower 30-day survival (WLST vs. no-WLST: 36/506 [7.1%] vs. 386/1140 [33.8%], p < 0.001). Primary cerebral disorders as cause of cardiac arrest and higher severity of illness at intensive care unit admission were associated with WLST decisions. CONCLUSION: For approximately one-third of ECPR/OHCA patients, WLST was decided during admission, mainly because of perceived unfavorable neurological prognoses. Decisions and neurological assessments for ECPR/OHCA patients need further analysis.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Extracorporeal cardiopulmonary resuscitation in adult patients with out-of-hospital cardiac arrest: a retrospective large cohort multicenter study in Japan.

BACKGROUND: The prevalence of extracorporeal cardiopulmonary resuscitation (ECPR) in patients with out-of-hospital cardiac arrest (OHCA) has been increasing rapidly worldwide. However, guidelines or clinical studies do not provide sufficient data on ECPR practice. The aim of this study was to provide real-world data on ECPR for patients with OHCA, including details of complications. METHODS: We did a retrospective database analysis of observational multicenter cohort study in Japan. Adult patients with OHCA of presumed cardiac etiology who received ECPR between 2013 and 2018 were included. The primary outcome was favorable neurological outcome at hospital discharge, defined as a cerebral performance category of 1 or 2. RESULTS: A total of 1644 patients with OHCA were included in this study. The patient age was 18-93 years (median: 60 years). Shockable rhythm in the initial cardiac rhythm at the scene was 69.4%. The median estimated low flow time was 55 min (interquartile range: 45-66 min). Favorable neurological outcome at hospital discharge was observed in 14.1% of patients, and the rate of survival to hospital discharge was 27.2%. The proportions of favorable neurological outcome at hospital discharge in terms of shockable rhythm, pulseless electrical activity, and asystole were 16.7%, 9.2%, and 3.9%, respectively. Complications were observed during ECPR in 32.7% of patients, and the most common complication was bleeding, with the rates of cannulation site bleeding and other types of hemorrhage at 16.4% and 8.5%, respectively. CONCLUSIONS: In this large cohort, data on the ECPR of 1644 patients with OHCA show that the proportion of favorable neurological outcomes at hospital discharge was 14.1%, survival rate at hospital discharge was 27.2%, and complications were observed during ECPR in 32.7%.

Clinical characteristics and outcomes of critically ill COVID-19 patients in Tokyo: a single-center observational study from the first wave.

BACKGROUND: Many studies have been published about critically ill coronavirus disease 2019 (COVID-19) during the early phases of the pandemic but the characteristic or survival of critically ill Japanese patients have not yet been investigated. We sought to investigate the characteristics, inflammatory laboratory finding trends, and outcomes among critically ill Japanese patients who were admitted to the intensive care unit (ICU) with the first wave of COVID-19. METHODS: A retrospective observational study was performed in a single institution in the center of Tokyo. Laboratory-confirmed COVID-19 patients admitted to the ICU from March 19 to April 30, 2020 were included. Trends for significant inflammatory laboratory findings were analyzed. In-hospital death, days of mechanical ventilation or oxygen supplementation, days of ICU or hospital stay were followed until May 26, 2020. RESULTS: Twenty-four patients were included. Median age was 57.5 years, and 79% were male. The neutrophil-to-lymphocyte ratio was elevated to a median of 10.1 on admission and peaked on Day 10 of illness. Seventeen patients were intubated on Day 11 of illness and received mechanical ventilation. One patient underwent extracorporeal membrane oxygenation. The majority (88%) received systemic steroids, including 16 patients who received high dose methylprednisolone (500-1000 mg). Favipiravir was used in 38% of patients. Two patients, including 1 who refused intensive care, died. Eighteen patients were discharged. Median length of ICU and hospital stay for all patients was 6 and 22 days, respectively. Median length of ventilator dependency was 7 days. Four patients underwent a tracheostomy and received prolonged ventilation for more than 21 days. One patient receiving mechanical ventilation died. All survivors discontinued ventilator use. CONCLUSIONS: Mortality was remarkably low in our single institutional study. Three survivors received mechanical ventilation for more than 3 weeks. Trends of clinically significant laboratory markers reflected the clinical course of COVID-19.

Accidental hypothermia: Factors related to a prolonged hospital stay - A nationwide observational study in Japan.

BACKGROUND: The incidence of accidental hypothermia (AH) is low, and the length of hospital stay in patients with AH remains poorly understood. The present study explored which factors were related to prolonged hospitalization among patients with AH using Japan's nationwide registry data. METHODS: The data from the Hypothermia STUDY 2018, which included patients ≥18 years old with a body temperature ≤ 35 °C, were obtained from a multicenter registry for AH conducted at 89 institutions throughout Japan, collected from December 1, 2018, to February 28, 2019. The patients were divided into a "short-stay patients" group (within 7 days) and "long-stay patients" group (more than 7 days). A logistic regression analysis after multiple imputation was performed to obtain odds ratios (ORs) for prolonged hospitalization with age, frailty, location, causes underlying the hypothermia, temperature, pH, potassium level, and disseminated intravascular coagulation (DIC) score as independent variables. RESULTS: In total, 656 patients were included in the study, of which 362 were eligible for the analysis. The median length of hospital stay was 17 days. Of the 362 patients, 265 (73.2%) stayed in the hospital for more than 7 days. The factors associated with prolonged hospitalization were frailty (OR, 2.11; 95% confidence interval [CI], 1.09-4.10; p = 0.027), the occurrence of indoor (OR, 3.20; 95% CI, 1.58-6.46; p = 0.001), alcohol intoxication (OR, 0.17; 95% CI, 0.05-0.56; p = 0.004), pH (OR, 0.07; 95% CI, 0.01-0.76; p = 0.029), potassium level (OR, 1.36; 95% CI, 1.00-1.85; p = 0.048), and DIC score (OR, 1.54; 95% CI, 1.13-2.10; p = 0.006). CONCLUSIONS: Frailty, indoor situation, alcohol intoxication, pH value, potassium level, and DIC score were factors contributing to prolonged hospitalization in patients with AH. Preventing frailty may help reduce the length of hospital stay in patients with AH. In addition, measuring the pH value and potassium level by an arterial blood gas analysis at the ED is recommended for the early evaluation of AH.

The association between neuromuscular blockade use during target temperature management and neurological outcomes.

BACKGROUND: To date, no study has comprehensively analyzed the association between neuromuscular blockade (NMB) during target temperature management (TTM) and the neurological outcomes after out-of-hospital cardiac arrest (OHCA) using a multicenter dataset. We aimed to examine the association between NMB during TTM after cardiac arrest and neurological outcomes after OHCA. METHODS: This study was a secondary analysis of the Japanese Population-based Utstein-style study with defibrillation and basic/advanced Life Support Education and implementation-Hypothermia (J-PULSE-HYPO) study registry. The exposure of the current study was the use of NMB during TTM. The primary outcome was favorable neurological outcome, i.e., a cerebral performance category of 1-2, at hospital discharge. RESULTS: Of the 452 patients with OHCA enrolled in the J-PULSE-HYPO study, 431 were analyzed. NMB was used in 353 patients (81.9%). Multivariable logistic regression analysis revealed that NMB use was not independently associated with favorable outcomes [odds ratio (OR), 0.96; 95% confidence interval (CI), 0.42-2.18; p = .918)] or survival at discharge (OR, 0.83; 95% CI, 0.31-2.02; p = .688). After adjusting the covariates, the predicted probabilities did not reveal significant differences between NMB use and non-NMB use in the respective mean (95% CI) values for favorable neurological outcomes [53.6 (50.2-57.0) % vs. 58.0 (50.4-65.6) %, p = .304], and survival rates [77.1 (74.7-79.5) % vs. 75.8 (70.5-81.0) %, p = .647]. CONCLUSIONS: The NMB use during TTM was not associated with favorable neurological outcomes and survival rate in patients with OHCA.

High early phase hemoglobin level is associated with favorable neurological outcome in patients with severe traumatic brain injury.

BACKGROUND: The appropriate hemoglobin (Hb) level threshold for the early phase (i.e. from Emergency Department to ICU admission) in patients with severe traumatic brain injury (TBI) is still unknown. Therefore, we aimed to examine the association between Hb levels during the early phase and neurological outcomes in patients with severe TBI using data from the Brain Hypothermia (B-HYPO) Study Group. METHODS: We performed a post-hoc analysis of the B-HYPO study (a prospective, multicenter, randomized controlled trial on patients with severe TBI who received either mild therapeutic hypothermia [MTH; 32.0 °C-34.0 °C] or fever control [35.5 °C-37.0 °C]). We calculated Hb levels during early phase by the formula: (admission Hb + Hb on day 1) / 2. The primary outcome was the association between during early phase Hb levels and 6-month neurological outcome after the TBI based on the Glasgow Outcome Scale scores (a measure of functional recovery defined as moderate disability or good recovery). RESULTS: We reviewed data from 130 patients and found favorable neurological outcomes in 48.5% of them. We found significant differences between the favorable and unfavorable neurological outcome groups in terms of their Hb levels on admission and on day 1. But, we found no Hb level differences after day 3 (including 1 day after rewarming). Our multivariable analysis showed that Hb levels during early phase were significantly associated with favorable neurological outcomes (odds ratio, 1.387; 95% confidence interval, 1.057-1.858; P = 0.018). CONCLUSIONS: High early phase Hb levels are associated with favorable neurological outcomes after severe TBI.

Association between frailty and mortality among patients with accidental hypothermia: a nationwide observational study in Japan.

BACKGROUND: Frailty has been associated with a risk of adverse outcomes, and mortality in patients with various conditions. However, there have been few studies on whether or not frailty is associated with mortality in patients with accidental hypothermia (AH). In this study, we aim to determine this association in patients with AH using Japan's nationwide registry data. METHODS: The data from the Hypothermia STUDY 2018&19, which included patients of ≥18 years of age with a body temperature of ≤35 °C, were obtained from a multicenter registry for AH conducted at 120 institutions throughout Japan, collected from December 2018 to February 2019 and December 2019 to February 2020. The clinical frailty scale (CFS) score was used to determine the presence and degree of frailty. The primary outcome was the comparison of mortality between the frail and non-frail patient groups. RESULTS: In total, 1363 patients were included in the study, of which 920 were eligible for the analysis. The 920 patients were divided into the frail patient group (N = 221) and non-frail patient group (N = 699). After 30-days of hospitalization, 32.6% of frail patients and 20.6% of non-frail patients had died (p < 0.001). Frail patients had a significantly higher risk of 90-day mortality (Hazard ratio [HR], 1.64; 95% confidence interval [CI], 1.25-2.17; p < 0.001). Based on the Cox proportional hazards analysis using multiple imputation, after adjustment for age, potassium level, lactate level, pH value, sex, CPK level, heart rate, platelet count, location of hypothermia incidence, and rate of tracheal intubation, the HR was 1.69 (95% CI, 1.25-2.29; p < 0.001). CONCLUSIONS: This study showed that frailty was associated with mortality in patients with AH. Preventive interventions for frailty may help to avoid death caused by AH.

Significance of body temperature in elderly patients with sepsis.

BACKGROUND: Elderly patients have a blunted host response, which may influence vital signs and clinical outcomes of sepsis. This study was aimed to investigate whether the associations between the vital signs and mortality are different in elderly and non-elderly patients with sepsis. METHODS: This was a retrospective observational study. A Japanese multicenter sepsis cohort (FORECAST, n = 1148) was used for the discovery analyses. Significant discovery results were tested for replication using two validation cohorts of sepsis (JAAMSR, Japan, n = 624; SPH, Canada, n = 1004). Patients were categorized into elderly and non-elderly groups (age ≥ 75 or < 75 years). We tested for association between vital signs (body temperature [BT], heart rate, mean arterial pressure, systolic blood pressure, and respiratory rate) and 90-day in-hospital mortality (primary outcome). RESULTS: In the discovery cohort, non-elderly patients with BT < 36.0 °C had significantly increased 90-day mortality (P = 0.025, adjusted hazard ratio 1.70, 95% CI 1.07-2.71). In the validation cohorts, non-elderly patients with BT < 36.0 °C had significantly increased mortality (JAAMSR, P = 0.0024, adjusted hazard ratio 2.05, 95% CI 1.29-3.26; SPH, P = 0.029, adjusted hazard ratio 1.36, 95% CI 1.03-1.80). These differences were not observed in elderly patients in the three cohorts. Associations between the other four vital signs and mortality were not different in elderly and non-elderly patients. The interaction of age and hypothermia/fever was significant (P < 0.05). CONCLUSIONS: In septic patients, we found mortality in non-elderly sepsis patients was increased with hypothermia and decreased with fever. However, mortality in elderly patients was not associated with BT. These results illuminate the difference in the inflammatory response of the elderly compared to non-elderly sepsis patients.

Neuroleptic malignant syndrome in patients with COVID-19.

We report the first two cases of Coronavirus Disease 2019 (COVID-19) who were receiving intensive care including favipiravir, and were clinically diagnosed with neuroleptic malignant syndrome (NMS) to focus attention on NMS in COVID-19 management. Case 1: A 46-year-old-man with acute respiratory distress syndrome (ARDS) caused by COVID-19 infection was being administered favipiravir. Fentanyl, propofol, and rocuronium were also given. On day 3, midazolam administration was initiated for deep sedation. On day 5, his high body temperature increased to 41.2 °C, creatine kinase level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS was suspected, and supportive therapy was initiated. High-grade fever persisted for 4 days and subsided on day 9. Case 2: A 44-year-old-man with ARDS caused by COVID-19 infection was being treated with favipiravir. On day 5, risperidone was started for delirium. On day 7, his body temperature suddenly increased to 40.8 °C, his CK level elevated, and he developed tachycardia, tachypnea, altered consciousness, and diaphoresis. NMS diagnosis was confirmed, and both, favipiravir and risperidone were discontinued on day 8. On the same day, his CK levels decreased, and his body temperature normalized on day 9. Patients with COVID-19 infection frequently require deep sedation and develop delirium; therefore, more attention should be paid to the development of NMS in patients who are being administered such causative agents. The mechanism underlying the occurrence of NMS in COVID-19 patients treated with favipiravir remains unknown. Therefore, careful consideration of NMS development is necessary in the management of COVID-19 patients.

Characteristics and outcomes of frail patients with suspected infection in intensive care units: a descriptive analysis from a multicenter cohort study.

BACKGROUND: Frailty is associated with morbidity and mortality in patients admitted to intensive care units (ICUs). However, the characteristics of frail patients with suspected infection remain unclear. We aimed to investigate the characteristics and outcomes of frail patients with suspected infection in ICUs. METHODS: This is a secondary analysis of a multicenter cohort study, including 22 ICUs in Japan. Adult patients (aged ≥16 years) with newly suspected infection from December 2017 to May 2018 were included. We compared baseline patient characteristics and outcomes among three frailty groups based on the Clinical Frailty Scale (CFS) score: fit (score, 1-3), vulnerable (score, 4), and frail (score, 5-9). We conducted subgroup analysis of patients with sepsis defined as per Sepsis-3 criteria. We also produced Kaplan-Meier survival curves for 90-day survival. RESULTS: We enrolled 650 patients with suspected infection, including 599 (92.2%) patients with sepsis. Patients with a median CFS score of 3 (interquartile range [IQR] 3-5) were included: 337 (51.8%) were fit, 109 (16.8%) were vulnerable, and 204 (31.4%) were frail. The median patient age was 72 years (IQR 60-81). The Sequential Organ Failure Assessment scores for fit, vulnerable, and frail patients were 7 (IQR 4-10), 8 (IQR 5-11), and 7 (IQR 5-10), respectively (p = 0.59). The median body temperatures of fit, vulnerable, and frail patients were 37.5 °C (IQR 36.5 °C-38.5 °C), 37.5 °C (IQR 36.4 °C-38.6 °C), and 37.0 °C (IQR 36.3 °C-38.1 °C), respectively (p < 0.01). The median C-reactive protein levels of fit, vulnerable, and frail patients were 13.6 (IQR 4.6-24.5), 12.1 (IQR 3.9-24.9), 10.5 (IQR 3.0-21.0) mg/dL, respectively (p < 0.01). In-hospital mortality did not statistically differ among the patients according to frailty (p = 0.19). Kaplan-Meier survival curves showed little difference in the mortality rate during short-term follow-up. However, more vulnerable and frail patients died after 30-day than fit patients; this difference was not statistically significant (p = 0.25). Compared with the fit and vulnerable groups, the rate of home discharge was lower in the frail group. CONCLUSION: Frail and vulnerable patients with suspected infection tend to have poor disease outcomes. However, they did not show a statistically significant increase in the 90-day mortality risk.

Diagnostic Reliability of Headset-Type Continuous Video EEG Monitoring for Detection of ICU Patterns and NCSE in Patients with Altered Mental Status with Unknown Etiology.

BACKGROUND/OBJECTIVE: Simplified continuous electroencephalogram (cEEG) monitoring has shown improvement in detecting seizures; however, it is insufficient in detecting abnormal EEG patterns, such as periodic discharges (PDs), rhythmic delta activity (RDA), spikes and waves (SW), and continuous slow wave (CS), as well as nonconvulsive status epilepticus (NCSE). Headset-type continuous video EEG monitoring (HS-cv EEG monitoring; AE-120A EEG Headset™, Nihon Kohden, Tokyo, Japan) is a recently developed easy-to-use technology with eight channels. However, its ability to detect abnormal EEG patterns with raw EEG data has not been comprehensively evaluated. We aimed to examine the diagnostic accuracy of HS-cv EEG monitoring in detecting abnormal EEG patterns and NCSE in patients with altered mental status (AMS) with unknown etiology. We also evaluated the time required to initiate HS-cv EEG monitoring in these patients. METHODS: We prospectively observed and retrospectively examined patients who were admitted with AMS between January and December 2017 at the neurointensive care unit at Asakadai Central General Hospital, Saitama, Japan. We excluded patients whose data were missing for various reasons, such as difficulties in recording, and those whose consciousness had recovered between HS-cv EEG and conventional cEEG (C-cEEG) monitoring. For the included patients, we performed HS-cv EEG monitoring followed by C-cEEG monitoring. Definitive diagnosis was confirmed by C-cEEG monitoring with the international 10-20 system. As the primary outcome, we verified the sensitivity and specificity of HS-cv EEG monitoring in detecting abnormal EEG patterns including PDs, RDA, SW, and CS, in detecting the presence of PDs, and in detecting NCSE. As the secondary outcome, we calculated the time to initiate HS-cv EEG monitoring after making the decision. RESULTS: Fifty patients (76.9%) were included in the final analyses. The median age was 72 years, and 66% of the patients were male. The sensitivity and specificity of HS-cv EEG monitoring for detecting abnormal EEG patterns were 0.974 (0.865-0.999) and 0.909 (0.587-0.998), respectively, and for detecting PDs were 0.824 (0.566-0.926) and 0.970 (0.842-0.999), respectively. We diagnosed 13 (26%) patients with NCSE using HS-cv EEG monitoring and could detect NCSE with a sensitivity and specificity of 0.706 (0.440-0.897) and 0.970 (0.842-0.999), respectively. The median time needed to initiate HS-cv EEG was 57 min (5-142). CONCLUSIONS: HS-cv EEG monitoring is highly reliable in detecting abnormal EEG patterns, with moderate reliability for PDs and NCSE, and rapidly initiates cEEG monitoring in patients with AMS with unknown etiology.