Practical approach to thrombocytopenia in patients with sepsis: a narrative review.

Thrombocytopenia frequently occurs in patients with sepsis. Disseminated intravascular coagulation (DIC) may be a possible cause of thrombocytopenia owing to its high prevalence and association with poor outcomes; however, it is important to keep the presence of other diseases in mind in sepsis practice. Thrombotic microangiopathy (TMA), which is characterized by thrombotic thrombocytopenic purpura, Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (HUS), and complement-mediated HUS, is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ damage. TMA has become widely recognized in recent years because of the development of specific treatments. Previous studies have reported a remarkably lower prevalence of TMA than DIC; however, its epidemiology is not well defined, and there may be cases in which TMA is not correctly diagnosed, resulting in poor outcomes. Therefore, it is important to differentiate DIC from TMA. Nevertheless, differentiating between DIC and TMA remains a challenge as indicated by previous reports that most patients with TMA can be diagnosed as DIC using the universal coagulation scoring system. Several algorithms to differentiate sepsis-related DIC from TMA have been suggested, contributing to improving the care of septic patients with thrombocytopenia; however, it may be difficult to apply these algorithms to patients with coexisting DIC and TMA, which has recently been reported. This review describes the disease characteristics, including epidemiology, pathophysiology, and treatment, of DIC, TMA, and other diseases with thrombocytopenia and proposes a novel practical approach flow, which is characterized by the initiation of the diagnosis of TMA in parallel with the diagnosis of DIC. This practical flow also refers to the longitudinal diagnosis and treatment flow with TMA in mind and real clinical timeframes. In conclusion, we aim to widely disseminate the results of this review that emphasize the importance of incorporating consideration of TMA in the management of septic DIC. We anticipate that this practical new approach for the diagnostic and treatment flow will lead to the appropriate diagnosis and treatment of complex cases, improve patient outcomes, and generate new epidemiological evidence regarding TMA.

Exploring the Potential of CarbonCool® in Rapid Prehospital Cooling for Severe Heat Stroke.

OBJECTIVE: Heat stroke is a life-threatening condition that is characterized by body temperatures above 40 °C and central nervous system dysfunction. Immediate cooling is imperative to prevent irreversible cellular damage and improve patient outcomes. Here, we report two cases of heat stroke that highlight the use of a novel cooling suit (CarbonCool®) as a rapid cooling intervention administered in the prehospital setting, primarily focusing on patients with classic heat stroke. METHODS: This study was a retrospective review of two cases involving older patients with severe classic heat stroke, wherein CarbonCool® was used. The device was deployed at the scene of the incidents, throughout transport, and into the emergency department setting, allowing for continuous cooling and medical intervention as needed. The effectiveness of the cooling device was assessed based on the rate of temperature reduction and overall clinical outcomes of the patients. RESULTS: In both cases, CarbonCool® facilitated a rapid reduction in body temperature, aligning with the crucial requirement of immediate cooling for the management of heat stroke. The first case involved a comatose 90-year-old woman whose body temperature decreased from 42.0 to 35.8 °C within 60 min. The second case involved a comatose 70-year-old man who experienced a decrease in body temperature from 41.2 to 36.6 °C over 196 min. CarbonCool® allowed for the execution of concurrent resuscitative procedures and was compatible with various imaging modalities (including computed tomographic scan), allowing for continuous application from the scene to the intensive care unit. Moreover, both patients showed marked improvements in consciousness and were stabilized without the need for more invasive cooling procedures that are typically employed in hospital settings for such cases. Both patients were discharged without any disabilities. CONCLUSION: We present an innovative approach to prehospital care for patients with heat stroke through the use of CarbonCool®, highlighting its efficacy for rapid cooling and its potential impact on patient outcomes. However, further studies are warranted to fully confirm the efficacy of the system.

Neuromuscular blocking agents during targeted temperature management for out-of-hospital cardiac arrest patients.

BACKGROUND: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings. RESULTS: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes. CONCLUSIONS: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings.

Prediction of the neurological outcomes post-cardiac arrest: A prospective validation of the CAST and rCAST.

INTRODUCTION: The neurologic prognosis of out-of-hospital cardiac arrest (OHCA) patients in whom return of spontaneous circulation (ROSC) is achieved remains poor. The aim of this study was to externally and prospectively validate two scoring systems developed by us: the CAST score, a scoring system to predict the neurological prognosis of OHCA patients undergoing targeted temperature management (TTM), and a simplified version of the same score developed for improved ease of use in clinical settings, the revised CAST (rCAST) score. METHODS: This study was a prospective, multicenter, observational study conducted using the SOS KANTO 2017 registry, an OHCA registry involving hospitals in the Kanto region (including Tokyo) of Japan. The primary outcome was favorable neurological outcome (defined as Cerebral Performance Category score of 1 or 2) at 30 days and the secondary outcomes were favorable neurological outcome at 90 days and survival at 30 and 90 days. The predictive accuracies of the original CAST (oCAST) and rCAST scores were evaluated by using area under the receiver operating characteristic curve (AUC). RESULTS: Of 9909 OHCA patients, 565 showed ROSC and received TTM. Of these, we analyzed the data of 259 patients in this study. The areas under the receiver operating characteristic curve (AUCs) of the oCAST and rCAST scores for predicting a favorable neurological outcome at 30 days were 0.86 and 0.87, respectively, and those for predicting a favorable neurological outcome at 90 days were 0.87 and 0.88, respectively. The rCAST showed a higher predictive accuracy for the neurological outcome as compared with the NULL-PLEASE score. The patients with a favorable neurological outcome who had been classified into the high severity group based on the rCAST tended to have hypothermia at hospital arrival and to not show any signs of loss of gray-white matter differentiation on brain CT. Neurological function at 90 days was correlated with the rCAST (r = 0.63, p < 0.001). CONCLUSIONS: rCAST showed high predictive accuracy for the neurological prognosis of OHCA patients managed by TTM, comparable to that of the oCAST score. The scores on the rCAST were strongly correlated with the neurological functions at 90 days, implying that the rCAST is a useful scale for assessing the severity of brain injury after cardiac arrest.

Association between institutional volume of out-of-hospital cardiac arrest cases and short term outcomes.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a serious condition. The volume-outcome relationship and various post-cardiac arrest care elements are believed to be associated with improved neurological outcomes. Although previous studies have investigated the volume-outcome relationship, adjusting for post-cardiac arrest care, intra-class correlation for each institution, and other covariates may have been insufficient. OBJECTIVE: To investigate the volume-outcome relationships and favorable neurological outcomes among OHCA cases in each institution. METHODS: We conducted a prospective observational study of adult patients with non-traumatic OHCA using the OHCA registry in Japan. The primary outcome was 30-day favorable neurological outcomes, and the secondary outcome was 30-day survival. We set the cutoff values to trisect the number of patients as equally as possible and classified institutions into high-, middle-, and low-volume. Generalized estimating equations (GEE) were performed to adjust for covariates and within-hospital clustering. RESULTS: Among the 9909 registry patients, 7857 were included. These patients were transported to either low- (2679), middle- (2657), or high- (2521) volume institutions. The median number of eligible patients per institution in 19 months of study periods was 82 (range, 1-207), 252 (range, 210-353), and 463 (range, 390-701), respectively. After multivariable GEE using the low-volume institution as a reference, no significant difference in odds ratios and 95% confidence intervals were noted for 30-day favorable neurological outcomes for middle volume [1.22 (0.69-2.17)] and high volume [0.80 (0.47-1.37)] institutions. Moreover, there was no significant difference for 30-day survival for middle volume [1.02 (0.51-2.02)] and high volume [1.09 (0.53-2.23)] institutions. CONCLUSION: The patient volume of each institution was not associated with 30-day favorable neurological outcomes. Although this result needs to be evaluated more comprehensively, there may be no need to set strict requirements for the type of institution when selecting a destination for OHCA cases.

Impact of the COVID-19 pandemic on prehospital and in-hospital treatment and outcomes of patients after out-of-hospital cardiac arrest: a Japanese multicenter cohort study.

BACKGROUND: In the chain of survival for Out-of-hospital cardiac arrest (OHCA), each component of care contributes to improve the prognosis of the patient with OHCA. The SARS-CoV-2 (COVID-19) pandemic potentially affected each part of care in the chain of survival. The aim of this study was to compare prehospital care, in-hospital treatment, and outcomes among OHCA patients before and after the COVID-19 pandemic. METHODS: We analyzed data from a multicenter prospective study in Kanto area, Japan, named SOS-KANTO 2017. We enrolled patients who registered during the pre-pandemic period (September 2019 to December 2019) and the post-pandemic period (June 2020 to March 2021). The main outcome measures were 30-day mortality and the proportion of favorable outcomes at 1 month, and secondary outcome measures were changes in prehospital and in-hospital treatments between the pre- and post-pandemic periods. RESULTS: There were 2015 patients in the pre-pandemic group, and 5023 in the post-pandemic group. The proportion of advanced airway management by emergency medical service (EMS) increased (p < 0.01), and EMS call-to-hospital time was prolonged (p < 0.01) in the post- versus pre-pandemic group. There were no differences between the groups in defibrillation, extracorporeal membrane oxygenation, or temperature control therapy (p = 0.43, p = 0.14, and p = 0.16, respectively). Survival rate at 1 month and favorable outcome rate at 1 month were lower (p = 0.01 and p < 0.01, respectively) in the post- versus pre-pandemic group. CONCLUSION: Survival rate and favorable outcome rate 1 month after return of spontaneous circulation of OHCA worsened, EMS response time was prolonged, and advanced airway management by EMS increased in the post- versus pre-pandemic group; however, most prehospital and in-hospital management did not change between pre- and post-COVID-19 pandemic.

Frailty and Neurologic Outcomes of Patients Resuscitated From Nontraumatic Out-of-Hospital Cardiac Arrest: A Prospective Observational Study.

STUDY OBJECTIVE: To elucidate the clinical utility of the Clinical Frailty Scale score for predicting poor neurologic functions in patients resuscitated from out-of-hospital cardiac arrest (OHCA). METHODS: This was a prospective, multicenter, observational study conducted between 2019 and 2021. The study included adults with nontraumatic OHCA admitted to the intensive care unit after return of spontaneous circulation (ROSC). Pre-arrest high Clinical Frailty Scale score was defined as 5 or more. Favorable neurologic outcomes defined as a Cerebral Performance Category score of 2 or less at 30 days after admission were compared between patients with and without high Clinical Frailty Scale scores. Multivariable logistic regression analyses fitted with generalized estimating equations were performed to adjust for patient characteristics, out-of-hospital information, and resuscitation content and account for within-institution clustering. RESULTS: Of 9,909 patients with OHCA during the study period, 1,216 were included, and 317 had a pre-arrest high Clinical Frailty Scale score. Favorable neurologic outcomes were fewer among patients with high Clinical Frailty Scale scores. The high Clinical Frailty Scale score group showed a lower percentage of favorable neurologic outcomes after OHCA than the low Clinical Frailty Scale score group (6.1% vs 24.4%; adjusted odds ratio, 0.45 [95% confidence interval 0.22 to 0.93]). This relationship remained in subgroups with cardiogenic OHCA, with ROSC after hospital arrival, and without a high risk of dying (Clinical Frailty Scale score of 7 or less), whereas the neurologic outcomes were comparable regardless of pre-arrest frailty in those with noncardiogenic OHCA and with ROSC before hospital arrival. CONCLUSIONS: Pre-arrest high Clinical Frailty Scale score was associated with unfavorable neurologic functions among patients resuscitated from OHCA. The Clinical Frailty Scale score would help predict clinical consequences following intensive care after ROSC.

Associated organs and system with COVID-19 death with information of organ support: a multicenter observational study.

BACKGROUND: The organ dysfunction that is associated with death in COVID-19 patients has not been determined in multicenter epidemiologic studies. In this study, we evaluated the major association with death, concomitant organ dysfunction, and proportion of multiple organ failure in deaths in patients with COVID-19, along with information on organ support. METHODS: We performed an observational cohort study using the Japanese multicenter research of COVID-19 by assembling a real-world data (J-RECOVER) study database. This database consists of data on patients discharged between January 1 and September 31, 2020, with positive SARS-CoV-2 test results, regardless of intensive care unit admission status. These data were collected from the Diagnosis Procedure Combination and electronic medical records of 66 hospitals in Japan. The clinician identified and recorded the organ responsible for the death of COVID-19. RESULTS: During the research period, 4,700 patients with COVID-19 were discharged from 66 hospitals participating in the J-RECOVER study; of which, 272 patients (5.8%) from 47 institutions who died were included in this study. Respiratory system dysfunction (87.1%) was the leading association with death, followed by cardiovascular (4.8%), central nervous (2.9%), gastrointestinal (2.6%), and renal (1.1%) dysfunction. Most patients (96.7%) who died of COVID-19 had respiratory system damage, and about half (48.9%) had multi-organ damage. Of the patients whose main association with death was respiratory dysfunction, 120 (50.6%) received mechanical ventilation. CONCLUSION: This study showed that although respiratory dysfunction was the most common association with death in many cases, multi-organ dysfunction was associated with death due to COVID-19.

Characteristics and Outcomes of Traumatic Cardiac Arrests in the Pan-Asian Resuscitation Outcomes Study.

OBJECTIVE: Little is known about survival outcomes after traumatic cardiac arrest in Asia, or the association of Utstein factors with survival after traumatic cardiac arrests. This study aimed to describe the epidemiology and outcomes of traumatic cardiac arrests in Asia, and analyze Utstein factors associated with survival. METHODS: Traumatic cardiac arrest patients from 13 countries in the Pan-Asian Resuscitation Outcomes Study registry from 2009 to 2018 were analyzed. Multilevel logistic regression was performed to identify factors associated with the primary outcomes of survival to hospital discharge and favorable neurological outcome (Cerebral Performance Category (CPC) 1-2), and the secondary outcome of return of spontaneous circulation (ROSC). RESULTS: There were 207,455 out-of-hospital cardiac arrest cases, of which 13,631 (6.6%) were trauma patients aged 18 years and above with resuscitation attempted and who had survival outcomes reported. The median age was 57 years (interquartile range 39-73), 23.0% received bystander cardiopulmonary resuscitation (CPR), 1750 (12.8%) had ROSC, 461 (3.4%) survived to discharge, and 131 (1.0%) had CPC 1-2. Factors associated with higher rates of survival to discharge and favorable neurological outcome were arrests witnessed by emergency medical services or private ambulances (survival to discharge adjusted odds ratio (aOR) = 2.95, 95% confidence interval (CI) = 1.99-4.38; CPC 1-2 aOR = 2.57, 95% CI = 1.25-5.27), bystander CPR (survival to discharge aOR = 2.16; 95% CI 1.71-2.72; CPC 1-2 aOR = 4.98, 95% CI = 3.27-7.57), and initial shockable rhythm (survival to discharge aOR = 12.00; 95% CI = 6.80-21.17; CPC 1-2 aOR = 33.28, 95% CI = 11.39-97.23) or initial pulseless electrical activity (survival to discharge aOR = 3.98; 95% CI = 2.99-5.30; CPC 1-2 aOR = 5.67, 95% CI = 3.05-10.53) relative to asystole. CONCLUSIONS: In traumatic cardiac arrest, early aggressive resuscitation may not be futile and bystander CPR may improve outcomes.

Rapidly progressive cerebral atrophy following a posterior cranial fossa stroke: Assessment with semiautomatic CT volumetry.

BACKGROUND: The effect of posterior cranial fossa stroke on changes in cerebral volume is not known. We assessed cerebral volume changes in patients with acute posterior fossa stroke using CT scans, and looked for risk factors for cerebral atrophy. METHODS: Patients with cerebellar or brainstem hemorrhage/infarction admitted to the ICU, and who underwent at least two subsequent inpatient head CT scans during hospitalization were included (n = 60). The cerebral volume was estimated using an automatic segmentation method. Patients with cerebral volume reduction > 0% from the first to the last scan were defined as the "cerebral atrophy group (n = 47)," and those with ≤ 0% were defined as the "no cerebral atrophy group (n = 13)." RESULTS: The cerebral atrophy group showed a significant decrease in cerebral volume (first CT scan: 0.974 ± 0.109 L vs. last CT scan: 0.927 ± 0.104 L, P < 0.001). The mean percentage change in cerebral volume between CT scans in the cerebral atrophy group was -4.7%, equivalent to a cerebral volume of 46.8 cm3, over a median of 17 days. The proportions of cases with a history of hypertension, diabetes mellitus, and median time on mechanical ventilation were significantly higher in the cerebral atrophy group than in the no cerebral atrophy group. CONCLUSIONS: Many ICU patients with posterior cranial fossa stroke showed signs of cerebral atrophy. Those with rapidly progressive cerebral atrophy were more likely to have a history of hypertension or diabetes mellitus and required prolonged ventilation.

Prehospital ABC (Age, Bystander and Cardiogram) scoring system to predict neurological outcomes of cardiopulmonary arrest on arrival: post hoc analysis of a multicentre prospective observational study.

BACKGROUND: There is currently limited evidence to guide prehospital identification of patients with cardiopulmonary arrest on arrival (CPAOA) to hospital who have potentially favourable neurological function. This study aimed to develop a simple scoring system that can be determined at the contact point with emergency medical services to predict neurological outcomes. METHODS: We analysed data from patients with CPAOA using a regional Japanese database (SOS-KANTO), from January 2012 to March 2013. Patients were randomly assigned into derivation and validation cohorts. Favourable neurological outcomes were defined as cerebral performance category 1 or 2. We developed a new scoring system using logistic regression analysis with the following predictors: age, no-flow time, initial cardiac rhythm and arrest place. The model was internally validated by assessing discrimination and calibration. RESULTS: Among 4907 patients in the derivation cohort and 4908 patients in the validation cohort, the probabilities of favourable outcome were 0.9% and 0.8%, respectively. In the derivation cohort, age ≤70 years (OR 5.11; 95% CI 2.35 to 11.14), no-flow time ≤5 min (OR 4.06; 95% CI 2.06 to 8.01) and ventricular tachycardia or fibrillation as initial cardiac rhythm (OR 6.66; 95% CI 3.45 to 12.88) were identified as predictors of favourable outcome. The ABC score consisting of Age, information from Bystander and Cardiogram was created. The areas under the receiver operating characteristic curves of this score were 0.863 in the derivation and 0.885 in the validation cohorts. Positive likelihood ratios were 6.15 and 6.39 in patients with scores >2 points and were 11.06 and 17.75 in those with 3 points. CONCLUSION: The ABC score showed good accuracy for predicting favourable neurological outcomes in patients with CPAOA. This simple scoring system could potentially be used to select patients for extracorporeal cardiopulmonary resuscitation and minimise low-flow time.

Low-Flow Duration and Outcomes of Extracorporeal Cardiopulmonary Resuscitation in Adults With In-Hospital Cardiac Arrest: A Nationwide Inpatient Database Study.

OBJECTIVES: Although existing guidelines recommend commencing cannulation for extracorporeal cardiopulmonary resuscitation (ECPR) within 10-20 minutes of failed conventional resuscitation efforts for cardiac arrest, there is little supportive evidence. The present study aimed to determine the association of low-flow duration with survival-to-discharge rate in in-hospital cardiac arrest patients who received ECPR. DESIGN: A nationwide retrospective cohort study analyzed a nationwide inpatient database in Japan. Low-flow duration was defined as the time interval from initiation of chest compression to termination of chest compression. We assessed the association between low-flow duration and survival-to-discharge rate by predicting estimates with covariate adjustment stratified by categories of low-flow duration. SETTING: More than 1,600 acute-care hospitals in Japan. PATIENTS: All in-hospital cardiac arrest patients greater than or equal to 18 years old who received ECPR during hospitalization from July 2010 to March 2018. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 303,319 in-hospital cardiac arrest patients, 9,844 (3.2%) received ECPR in 697 hospitals during the study period and 9,433 were eligible in the study. The overall survival-to-discharge rate was 20.5% (1,932/9,433). The median low-flow duration was 26.0 minutes (interquartile range, 12.0-46.0 min) in the overall cohort. The highest and lowest estimated survival-to-discharge rates were 35.1% in the group with low-flow duration 0-5 minutes and 7.9% in the group with low-flow duration greater than 90 minutes. The estimated survival-to-discharge rate dropped sharply by about 20% during the first 35 minutes of low-flow duration (decreasing by about 3% every 5 min), followed by small decreases after the first 35 minutes. CONCLUSIONS: The estimated survival-to-discharge rate was markedly decreased by approximately 20% during the first 35 minutes of low-flow duration. Whether we should wait for the first 10-20 minutes of cardiac arrest without preparing for ECPR is questionable.

Diagnostic value of transpulmonary thermodilution measurements for acute respiratory distress syndrome in a pig model of septic shock.

BACKGROUND: No direct approach assessing pulmonary vascular permeability exists in the current therapeutic strategy for patients with acute respiratory distress syndrome (ARDS). Transpulmonary thermodilution measures hemodynamic parameters such as pulmonary vascular permeability index and extravascular lung water, enabling clinicians to assess ARDS severity. The aim of this study is to explore a precise transpulmonary thermodilution-based criteria for quantifying the severity of lung injury using a clinically relevant septic-ARDS pig model. METHODS: Thirteen female pigs (weight: 31 ± 2 kg) were intubated, mechanically ventilated under anesthesia, and either assigned to septic shock-induced ARDS or control group. To confirm the development of ARDS, we performed computed tomography (CT) imaging in randomly selected animals. The pulmonary vascular permeability index, extravascular lung water, and other hemodynamic parameters were consecutively measured during the development of septic lung injury. Lung status was categorized as normal (partial pressure of oxygen/fraction of inspired oxygen ≥ 400), or injured at different degrees: pre-ARDS (300-400), mild-to-moderate ARDS (100-300), or severe ARDS (< 100). We also measured serum inflammatory cytokines and high mobility group box 1 levels during the experiment to explore the relationship of the pulmonary vascular permeability index with these inflammatory markers. RESULTS: Using CT image, we verified that animals subjected to ARDS presented an extent of consolidation in bilateral gravitationally dependent gradient that expands over time, with diffuse ground-glass opacification. Further, the post-mortem histopathological analysis for lung tissue identified the key features of diffuse alveolar damage in all animals subjected to ARDS. Both pulmonary vascular permeability index and extravascular lung water increased significantly, according to disease severity. Receiver operating characteristic analysis demonstrated that a cut-off value of 3.9 for the permeability index provided optimal sensitivity and specificity for predicting severe ARDS (area under the curve: 0.99, 95% confidence interval, 0.98-1.00; sensitivity = 100%, and specificity = 92.5%). The pulmonary vascular permeability index was superior in its diagnostic value than extravascular lung water. Furthermore, the pulmonary vascular permeability index was significantly associated with multiple parameters reflecting clinicopathological changes in animals with ARDS. CONCLUSION: The pulmonary vascular permeability index is an effective indicator to measure septic ARDS severity.

Heart Rate and Mortality After Resuscitation in Patients With Out-of-Hospital Cardiac Arrest　- Insights From the SOS-KANTO Registry.

BACKGROUND: Heart rate (HR) predicts outcomes in patients with acute coronary syndrome (ACS), whereas the impact of HR on outcomes after out-of-hospital cardiac arrest (OHCA) remains unclear. This study aimed to investigate the impact of HR after resuscitation on outcomes after OHCA and whether the impact differs with OHCA etiology.Methods and Results: Of 16,452 patients suffering from OHCA, this study analyzed 741 adults for whom HR after resuscitation was recorded by 12-lead electrocardiogram upon hospital arrival. Etiology of OHCA was categorized into 3 groups: ACS, non-ACS, and non-cardiac. Patients in each etiology group were further divided into tachycardia (>100 beats/min) and non-tachycardia (≤100 beats/min). The impact of HR on outcomes was evaluated in each group. Among the 741 patients, the mean age was 67.6 years and 497 (67.1%) patients were male. The primary outcome - 3-month all-cause mortality - was observed in 55.8% of patients. Tachycardia after resuscitation in patients with ACS was significantly associated with higher all-cause mortality at 3 months (P=0.002), but there was no significant association between tachycardia and mortality in non-ACS and non-cardiac etiology patients. In a multivariate analysis model, the incidence of tachycardia after resuscitation independently predicted higher 3-month all-cause mortality in OHCA patients with ACS (hazard ratio: 2.17 [95% confidence interval: 1.05-4.48], P=0.04). CONCLUSIONS: Increased HR after resuscitation was associated with higher mortality only in patients with ACS.

Extravascular lung water levels are associated with mortality: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of extravascular lung water (EVLW) measured by transpulmonary thermodilution (TPTD) in critically ill patients is debated. We performed a systematic review and meta-analysis of studies assessing the effects of TPTD-estimated EVLW on mortality in critically ill patients. METHODS: Cohort studies published in English from Embase, MEDLINE, and the Cochrane Database of Systematic Reviews from 1960 to 1 June 2021 were systematically searched. From eligible studies, the values of the odds ratio (OR) of EVLW as a risk factor for mortality, and the value of EVLW in survivors and non-survivors were extracted. Pooled OR were calculated from available studies. Mean differences and standard deviation of the EVLW between survivors and non-survivors were calculated. A random effects model was computed on the weighted mean differences across the two groups to estimate the pooled size effect. Subgroup analyses were performed to explore the possible sources of heterogeneity. RESULTS: Of the 18 studies included (1296 patients), OR could be extracted from 11 studies including 905 patients (464 survivors vs. 441 non-survivors), and 17 studies reported EVLW values of survivors and non-survivors, including 1246 patients (680 survivors vs. 566 non-survivors). The pooled OR of EVLW for mortality from eleven studies was 1.69 (95% confidence interval (CI) [1.22; 2.34], p < 0.0015). EVLW was significantly lower in survivors than non-survivors, with a mean difference of -4.97 mL/kg (95% CI [-6.54; -3.41], p < 0.001). The results regarding OR and mean differences were consistent in subgroup analyses. CONCLUSIONS: The value of EVLW measured by TPTD is associated with mortality in critically ill patients and is significantly higher in non-survivors than in survivors. This finding may also be interpreted as an indirect confirmation of the reliability of TPTD for estimating EVLW at the bedside. Nevertheless, our results should be considered cautiously due to the high risk of bias of many studies included in the meta-analysis and the low rating of certainty of evidence. Trial registration the study protocol was prospectively registered on PROSPERO: CRD42019126985.

Early intubation and decreased in-hospital mortality in patients with coronavirus disease 2019.

BACKGROUND: Some academic organizations recommended that physicians intubate patients with COVID-19 with a relatively lower threshold of oxygen usage particularly in the early phase of pandemic. We aimed to elucidate whether early intubation is associated with decreased in-hospital mortality among patients with novel coronavirus disease 2019 (COVID-19) who required intubation. METHODS: A multicenter, retrospective, observational study was conducted at 66 hospitals in Japan where patients with moderate-to-severe COVID-19 were treated between January and September 2020. Patients who were diagnosed as COVID-19 with a positive reverse-transcription polymerase chain reaction test and intubated during admission were included. Early intubation was defined as intubation conducted in the setting of ≤ 6 L/min of oxygen usage. In-hospital mortality was compared between patients with early and non-early intubation. Inverse probability weighting analyses with propensity scores were performed to adjust patient demographics, comorbidities, hemodynamic status on admission and time at intubation, medications before intubation, severity of COVID-19, and institution characteristics. Subgroup analyses were conducted on the basis of age, severity of hypoxemia at intubation, and days from admission to intubation. RESULTS: Among 412 patients eligible for the study, 110 underwent early intubation. In-hospital mortality was lower in patients with early intubation than those with non-early intubation (18 [16.4%] vs. 88 [29.1%]; odds ratio, 0.48 [95% confidence interval 0.27-0.84]; p = 0.009, and adjusted odds ratio, 0.28 [95% confidence interval 0.19-0.42]; p < 0.001). The beneficial effects of early intubation were observed regardless of age and severity of hypoxemia at time of intubation; however, early intubation was associated with lower in-hospital mortality only among patients who were intubated later than 2 days after admission. CONCLUSIONS: Early intubation in the setting of ≤ 6 L/min of oxygen usage was associated with decreased in-hospital mortality among patients with COVID-19 who required intubation. Trial Registration None.

External validation of simplified out-of-hospital cardiac arrest and cardiac arrest hospital prognosis scores in a Japanese population: a multicentre retrospective cohort study.

BACKGROUND: The novel simplified out-of-hospital cardiac arrest (sOHCA) and simplified cardiac arrest hospital prognosis (sCAHP) scores used for prognostication of hospitalised patients have not been externally validated. Therefore, this study aimed to externally validate the sOHCA and sCAHP scores in a Japanese population. METHODS: We retrospectively analysed data from a prospectively maintained Japanese database (January 2012 to March 2013). We identified adult patients who had been resuscitated and hospitalised after intrinsic out-of-hospital cardiac arrest (OHCA) (n=2428, age ≥18 years). We validated the sOHCA and sCAHP scores with reference to the original scores in predicting 1-month unfavourable neurological outcomes (cerebral performance categories 3-5) based on the discrimination and calibration measures of area under the receiver operating characteristic curves (AUCs) and a Hosmer-Lemeshow goodness-of-fit test with a calibration plot, respectively. RESULTS: In total, 1985/2484 (82%) patients had a 1-month unfavourable neurological outcome. The original OHCA, sOHCA, original cardiac arrest hospital prognosis (CAHP) and sCAHP scores were available for 855/2428 (35%), 1359/2428 (56%), 1130/2428 (47%) and 1834/2428 (76%) patients, respectively. The AUCs of simplified scores did not differ significantly from those of the original scores, whereas the AUC of the sCAHP score was significantly higher than that of the sOHCA score (0.88 vs 0.81, p<0.001). The goodness of fit was poor in the sOHCA score (ν=8, χ2=19.1 and Hosmer-Lemeshow test: p=0.014) but not in the sCAHP score (ν=8, χ2=13.5 and Hosmer-Lemeshow test: p=0.10). CONCLUSION: The performances of the original and simplified OHCA and CAHP scores in predicting neurological outcomes in successfully resuscitated OHCA patients were acceptable. With the highest availability, similar discrimination and good calibration, the sCAHP score has promising potential for clinical implementation, although further validation studies to evaluate its clinical acceptance are necessary.

Rapidly progressive brain atrophy in septic ICU patients: a retrospective descriptive study using semiautomatic CT volumetry.

BACKGROUND: Sepsis is often associated with multiple organ failure; however, changes in brain volume with sepsis are not well understood. We assessed brain atrophy in the acute phase of sepsis using brain computed tomography (CT) scans, and their findings' relationship to risk factors and outcomes. METHODS: Patients with sepsis admitted to an intensive care unit (ICU) and who underwent at least two head CT scans during hospitalization were included (n = 48). The first brain CT scan was routinely performed on admission, and the second and further brain CT scans were obtained whenever prolonged disturbance of consciousness or abnormal neurological findings were observed. Brain volume was estimated using an automatic segmentation method and any changes in brain volume between the two scans were recorded. Patients with a brain volume change < 0% from the first CT scan to the second CT scan were defined as the "brain atrophy group (n = 42)", and those with ≥ 0% were defined as the "no brain atrophy group (n = 6)." Use and duration of mechanical ventilation, length of ICU stay, length of hospital stay, and mortality were compared between the groups. RESULTS: Analysis of all 42 cases in the brain atrophy group showed a significant decrease in brain volume (first CT scan: 1.041 ± 0.123 L vs. second CT scan: 1.002 ± 0.121 L, t (41) = 9.436, p < 0.001). The mean percentage change in brain volume between CT scans in the brain atrophy group was -3.7% over a median of 31 days, which is equivalent to a brain volume of 38.5 cm3. The proportion of cases on mechanical ventilation (95.2% vs. 66.7%; p = 0.02) and median time on mechanical ventilation (28 [IQR 15-57] days vs. 15 [IQR 0-25] days, p = 0.04) were significantly higher in the brain atrophy group than in the no brain atrophy group. CONCLUSIONS: Many ICU patients with severe sepsis who developed prolonged mental status changes and neurological sequelae showed signs of brain atrophy. Patients with rapidly progressive brain atrophy were more likely to have required mechanical ventilation.

Ultra-Early Induction of General Anesthesia for Reducing Rebleeding Rates in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Rebleeding of aneurysmal subarachnoid hemorrhage (aSAH) is one of the significant risk factors for poor clinical outcome. The rebleeding risk is the highest during the acute phase with an approximate rebleeding rate of 9-17% within the first 24 h. Theoretically, general anesthesia can stabilize a patient's vital signs; however, its effectiveness as initial management for preventing post-aSAH rebleeding remains unclear. The purpose of this study was to determine the feasibility and safety of ultra-early general anesthesia induction for reducing the rebleeding rates among patients with aSAH. MATERIALS AND METHODS: We retrospectively evaluated patients with aSAH who were admitted to our department between January 2013 and December 2019. All the patients underwent ultra-early general anesthesia induction as initial management regardless of their severity. We evaluated the rebleeding rate before definitive treatment, factors influencing rebleeding, and general anesthesia complications. RESULTS: We included 191 patients with two-third of them having a poor clinical grade (World Federation of Neurological Society [WFNS] grade IV or V). The median duration from admission to general anesthesia induction was 22 min. Rebleeding before definitive treatment occurred in nine patients (4.7%). There were significant differences in the Glasgow Coma Scale score (p = 0.047), WFNS grade (p = 0.02), and dissecting aneurysm (p <0.001) between the rebleeding and non-rebleeding patients. There were no cases of unsuccessful tracheal intubation or rebleeding during general anesthesia induction. CONCLUSION: Ultra-early general anesthesia induction could be performed safely in patients with aSAH, regardless of the WFNS grade; moreover, it resulted in lower rebleeding rate than that reported in previous epidemiological reports.

Heart rate n-variability (HRnV) and its application to risk stratification of chest pain patients in the emergency department.

BACKGROUND: Chest pain is one of the most common complaints among patients presenting to the emergency department (ED). Causes of chest pain can be benign or life threatening, making accurate risk stratification a critical issue in the ED. In addition to the use of established clinical scores, prior studies have attempted to create predictive models with heart rate variability (HRV). In this study, we proposed heart rate n-variability (HRnV), an alternative representation of beat-to-beat variation in electrocardiogram (ECG), and investigated its association with major adverse cardiac events (MACE) in ED patients with chest pain. METHODS: We conducted a retrospective analysis of data collected from the ED of a tertiary hospital in Singapore between September 2010 and July 2015. Patients > 20 years old who presented to the ED with chief complaint of chest pain were conveniently recruited. Five to six-minute single-lead ECGs, demographics, medical history, troponin, and other required variables were collected. We developed the HRnV-Calc software to calculate HRnV parameters. The primary outcome was 30-day MACE, which included all-cause death, acute myocardial infarction, and revascularization. Univariable and multivariable logistic regression analyses were conducted to investigate the association between individual risk factors and the outcome. Receiver operating characteristic (ROC) analysis was performed to compare the HRnV model (based on leave-one-out cross-validation) against other clinical scores in predicting 30-day MACE. RESULTS: A total of 795 patients were included in the analysis, of which 247 (31%) had MACE within 30 days. The MACE group was older, with a higher proportion being male patients. Twenty-one conventional HRV and 115 HRnV parameters were calculated. In univariable analysis, eleven HRV and 48 HRnV parameters were significantly associated with 30-day MACE. The multivariable stepwise logistic regression identified 16 predictors that were strongly associated with MACE outcome; these predictors consisted of one HRV, seven HRnV parameters, troponin, ST segment changes, and several other factors. The HRnV model outperformed several clinical scores in the ROC analysis. CONCLUSIONS: The novel HRnV representation demonstrated its value of augmenting HRV and traditional risk factors in designing a robust risk stratification tool for patients with chest pain in the ED.