A Successful Prevention of Reintubation Using the Mechanical Insufflation-Exsufflation in a Critically Ill Patient With Impaired Airway Mucus Expectoration: A Case Report.

We report a case of post-extubation respiratory failure due to insufficient airway mucus expectoration that was successfully treated using mechanical insufflation-exsufflation (MI-E). A 32-year-old woman with a long-term history of steroid therapy for Blau syndrome was admitted to our intensive care unit with refractory hypoxemia due to pneumonia associated with the novel coronavirus disease 2019. Mechanical ventilation with veno-venous extracorporeal membrane oxygenation (VV-ECMO) was required due to severe hypoxemia. She was weaned from VV-ECMO on the 10th day and extubated on the 13th day. A few hours after extubation, she presented respiratory distress due to massive pulmonary atelectasis caused by sputum accumulation as a result of the impaired cough reflex. MI-E was applied to facilitate coughing and sputum expectoration. MI-E dramatically improved the atelectasis and prevented reintubation. This case suggests that MI-E, which is primarily used to treat chronic neuromuscular diseases, may also be effective in treating acute respiratory failure.

Pre-hospital airway management and neurological status of patients with out-of-hospital cardiac arrest: A retrospective cohort study.

Purpose: Little is known about whether pre-hospital advanced airway management (AAM) under the presence of a physician could improve outcome of patients with cardiac arrest, compared with pre-hospital AAM under the absence of a physician. Methods: This retrospective multicentre-cohort study enrolled consecutive patients who were transported to participating hospitals after out-of-hospital cardiac arrest in Japan between 1 June 2014 and 31 December 2019. We included patients who underwent pre-hospital AAM and resuscitation after arrival at hospital, and who were ≥18 years of age, with medical aetiologies. The primary outcome was favourable neurological survival (Cerebral Performance Category score of 1 or 2) one month after cardiac arrest. The primary outcome was called one-month favourable neurological survival. The first confirmed cardiac rhythm was defined using 3-lead electrocardiogram monitor or an automated external defibrillator and by determining whether the carotid artery was pulsating. Previous research found that the presence of a pre-hospital physician was associated with improved patients' outcomes, after the type of first confirmed cardiac rhythm was considered. Therefore, the first confirmed cardiac rhythm in current study was subdivided into non-shockable or shockable groups. A multivariable logistic regression analysis was performed on propensity score-matched patients. Results: We analysed 16,703 patients. Among the 2,346 patients in the non-shockable group, 1.2% (N = 29) achieved the primary outcome. The adjusted odds ratio of pre-hospital AAM with or without a physician for the primary outcome in the results of the non-shockable group was 4.64 (95% confidence interval: 1.81-14.4). Among the 826 patients in the shockable group, 16.9% (N = 140) achieved the primary outcome and the adjusted odds ratio of pre-hospital AAM with or without a physician for the primary outcome in the results of the shockable group was 1.05 (95% confidence interval: 0.67-1.63). Conclusions: This retrospective multicentre-cohort study found that pre-hospital AAM under the presence of a physician was significantly associated with increased neurological outcome in specific patients with cardiac arrest, compared with pre-hospital AAM under the absence of a physician.

The current status of emergency departments in secondary emergency medical institutions in Japan: a questionnaire survey.

BACKGROUND: While emergency medicine (ER)-based emergency care is prevalent in many countries, in Japan, the "department-specific emergency care model" and the "emergency center model" are mainstream. We hypothesized that many secondary emergency medical institutions in Japan have inadequate systems. Using a questionnaire, we investigated the status of and problems in the emergency medical services system in secondary emergency medical institutions in Japan. Until date, there has not been an exhaustive survey of emergency facilities on a countrywide scale. The main objective of this study was to investigate problems in the Japanese emergency medical services system and thereby improve optimal care for emergency patients. RESULTS: A nationwide questionnaire survey involving 4063 facilities (all government-approved emergency medical facilities certified by prefectural governors) in Japan was conducted. Of the facilities that responded, all secondary emergency facilities were included in the analysis. Responses from 1289 facilities without a tertiary emergency medical care center were analyzed. Among them, 61% (792/1289) had ≤ 199 beds, and 8% were emergency department specialty training program core facilities. Moreover, 42% had an annual patient acceptance number of ≤ 500, 19% did not calculate the number of acceptances, 29% had an acceptance rate of ≥ 81%, and 25% had an acceptance rate of 61-80%. Pregnant women (63%) and children (56%) were the major types of patients that affected the acceptance rate. Factors affecting facilities with a response rate of 81% or higher were "hospitals designated for residency training" and "facilities making some efforts to improve the quality of emergency care and the emergency medical system" (logistic analysis, P < .001). CONCLUSION: Relevant authorities and core regional facilities should consider and implement specific measures for regions and hospitals with a shortage of emergency medicine specialists and physicians (e.g., development of ER-based emergency medicine and provision of education). This study may lead to further improvement in the optimal care of emergency patients through the nationwide establishment of the proposed measures as well as through grouping and integrating the structures and systems in emergency and other medical facilities.

Unexpected cholinergic crisis caused by distigmine bromide: A case report.

RATIONALE: Distigmine bromide is a cholinesterase (ChE) inhibitor used to treat dysuria due to a hypotonic bladder. We encountered a case of cholinergic crisis caused by distigmine bromide, which resulted in a rapid decrease in serum ChE levels, hypothermia, respiratory failure, and circulatory failure within a short period of time. PATIENT CONCERNS: A 51-year-old man was admitted to a psychiatric hospital to treat behavioral disorders due to irritability and violent behavior. The patient was referred to our hospital for septic shock secondary to urinary tract infection and respiratory failure. He had not defecated for 5 days before visiting our hospital. He had moderate intellectual disability. Immediately after admission, he developed hand tremors and drooling. The airway was obstructed by drooling due to vomiting of yellow clear gastric juice. DIAGNOSIS: The patient's high saliva volume, bradycardia, respiratory failure (54 breaths/min), constricted pupils (2.5/mm), poor oxygenation, and a history of oral medication were consistent with the diagnosis of cholinergic crisis due to distigmine bromide. INTERVENTIONS: On admission, the patient was immediately intubated. He was treated with noradrenaline (0.1 µg/kg/min) to increase his blood pressure. He was admitted to the intensive care unit (ICU). Since he had circulatory failure, vasopressin (approximately 1 U/h) was administered. Continuous intravenous atropine sulfate (0.6 mg/h) was also administered for high saliva volume. OUTCOMES: On the 8th ICU day, the patient's drooling and bradycardia improved. The patient was physically and mentally stable, and transferred to the referring hospital. LESSONS: ChE levels and symptoms before onset may not be useful for the early detection and prevention of adverse effects of cholinergic crisis caused by distigmine bromide. In addition to known risks such as renal impairment and older age, constipation should be recognized and communicated as a risk factor.

Optimal target blood pressure in elderly with septic shock (OPTPRESS) trial: study protocol for a randomized controlled trial.

BACKGROUND: Hemodynamic stabilization is a core component in the resuscitation of septic shock. However, the optimal target blood pressure remains debatable. Previous randomized controlled trials suggested that uniformly adopting a target mean arterial pressure (MAP) higher than 65 mmHg for all adult septic shock patients would not be beneficial; however, it has also been proposed that higher target MAP may be beneficial for elderly patients, especially those with arteriosclerosis. METHODS: A multicenter, pragmatic single-blind randomized controlled trial will be conducted to compare target MAP of 80-85 mmHg (high-target) and 65-70 mmHg (control) in the resuscitation of septic shock patients admitted to 28 hospitals in Japan. Patients with septic shock aged ≥65 years are randomly assigned to the high-target or control groups. The target MAP shall be maintained for 72 h after randomization or until vasopressors are no longer needed to improve patients' condition. To minimize the adverse effects related to catecholamines, if norepinephrine dose of ≥ 0.1 µg/kg/min is needed to maintain the target MAP, vasopressin will be initiated. Other therapeutic approaches, including fluid administration, hydrocortisone use, and antibiotic choice, will be determined by the physician in charge based on the latest clinical guidelines. The primary outcome is all-cause mortality at 90 days after randomization. DISCUSSION: The result of this trial will provide great insight on the resuscitation strategy for septic shock in the era of global aged society. Also, it will provide the better understanding on the importance of individualized treatment strategy in hemodynamic management in critically ill patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry; UMIN000041775. Registered 13 September 2020.

Physician's presence in pre-hospital setting improves one-month favorable neurological survival after out-of-hospital cardiac arrest: A propensity score matching analysis of the JAAM-OHCA Registry.

BACKGROUND: Using the out-of-hospital cardiac arrest (OHCA) registry in Japan, we evaluated the effectiveness of physicians' presence in pre-hospital settings after adjusting in-hospital treatments. METHODS: This was a multicenter cohort study. We registered all consecutive OHCA patients in Japan who, from 1 June 2014 through 31 December 2017, were transported to institutions participating in the Japanese Association for Acute Medicine OHCA registry. We included OHCA patients aged at least 18 years, with medical etiology, and who received resuscitation from emergency medical services (EMS) personnel and medical professionals in hospitals. The primary outcome was one-month favorable neurological survival. We estimated the propensity score by fitting a logistic regression model that was adjusted for several variables before the arrival of EMS personnel and/or pre-hospital physician. A multivariable logistic regression analysis in propensity score-matched patients was used to adjust confounders, including extracorporeal membrane oxygenation, percutaneous coronary intervention, intra-aortic balloon pumping, and targeted temperature management. RESULTS: We analyzed 19,247 patients. Among them, 5.4% (N = 1040) had a neurologically favorable outcome. The adjusted odds ratio (AOR) of the physicians' presence compared with their absence for primary outcome was 1.84 (95% confidence interval (CI): 1.43-2.37). Among first documented non-shockable cardiac rhythm, the AOR was 1.51 (95% CI: 1.04-2.22). Among first documented shockable cardiac rhythm, the AOR of the physicians' presence for primary outcome was 1.15 (95% CI: 0.83-1.59). CONCLUSION: The improved one-month favorable neurological survival was significantly associated with the physicians' presence in pre-hospital settings, compared with the physicians' absence.

Planned Versus On-Demand Relaparotomy Strategy in Initial Surgery for Non-occlusive Mesenteric Ischemia.

BACKGROUND: There has been insufficient evidence regarding a treatment strategy for patients with non-occlusive mesenteric ischemia (NOMI) due to the lack of large-scale studies. We aimed to evaluate the clinical benefit of strategic planned relaparotomy in patients with NOMI using detailed perioperative information. METHODS: We conducted a multicenter retrospective cohort study that included NOMI patients who underwent laparotomy. In-hospital mortality, 28-day mortality, incidence of total adverse events, ventilator-free days, and intensive care unit (ICU)-free days were compared between groups experiencing the planned and on-demand relaparotomy strategies. Analyses were performed using a multivariate mixed effects model and a propensity score matching model after adjusting for pre-operative, intra-operative, and hospital-related confounders. RESULTS: A total of 181 patients from 17 hospitals were included, of whom 107 (59.1%) were treated using the planned relaparotomy strategy. The multivariate mixed effects regression model indicated no significant differences for in-hospital mortality (61 patients [57.0%] in the planned relaparotomy group vs. 28 patients [37.8%] in the on-demand relaparotomy group; adjusted odds ratio [95% confidence interval] = 1.94 [0.78-4.80]), as well as in 28-day mortality, adverse events, and ICU-free days. Significant reduction in ventilator-free days was observed in the planned relaparotomy group. Propensity score matching analysis of 61 matched pairs with comparable patient severity did not show superiority of the planned relaparotomy strategy. CONCLUSIONS: The planned relaparotomy strategy, compared with on-demand relaparotomy strategy, did not show clinical benefits after the initial surgery of patients with NOMI. Further studies estimating potential subpopulations who may benefit from this strategy are required.

Human Soluble Recombinant Thrombomodulin, ART-123, Resolved Early Phase Coagulopathies, but Did Not Significantly Alter the 28 Day Outcome in the Treatment of DIC Associated with Infectious Systemic Inflammatory Response Syndromes.

Disseminated intravascular coagulation (DIC) is a catastrophic systemic disorder of coagulation, resulting in uncontrollable bleeding, multiple organ failure, and death. Sepsis is one of the common causes of DIC. Despite many attempts to correct these coagulation pathologies, no adjunctive treatments have been shown to improve the mortality of DIC associated with sepsis. Although some clinical studies showed a recently developed human recombinant thrombomodulin, ART-123, might be effective in the treatment of DIC, few randomized, placebo-controlled studies have been conducted. In this study, we treated 60 DIC patients associated with systemic inflammatory response syndrome (SIRS) using ART-123 (n = 29) or saline as a placebo (n = 31). The basal clinical characteristics were similar in both groups. We compared clinical severity scores and DIC score in acute phase, and 28 day mortality between the two groups. Our study demonstrated the DIC score improved a few days earlier in the ART-123 group than the placebo group, and there were no major life-threatening adverse events in both groups. The overall survival rate at day 28 was not significantly altered. In conclusion, ART-123 can be used safely in DIC associated with infectious SIRS patients; however, its true efficacy in the treatment of DIC needs to be further investigated.

Public access defibrillation and outcomes after pediatric out-of-hospital cardiac arrest.

BACKGROUND: Use of automated external defibrillators (AEDs) has been recommended for pediatric out-of-hospital cardiac arrest (OHCA). However, there are no conclusive studies that elucidated the effectiveness of public-access defibrillation (PAD) in children. METHODS: This was a nationwide, population-based, propensity score-matched study of pediatric OHCA in Japan from 2011 to 2012, based on data from the All-Japan Utstein Registry. We included pediatric OHCA patients (aged 1-17 years) who received bystander cardiopulmonary resuscitation. The primary outcome was a favorable neurological state 1 month after OHCA (defined as a CPC score of 1-2). RESULTS: A total of 1193 patients were included in the final cohort; 57 received PAD and 1136 did not. Among 1193 patients, 188 (15.8%) survived with a favorable neurological status 1 month after OHCA. The odds of neurologically favorable survival were significantly higher for patients receiving PAD after adjusting for potential confounders: propensity score matching, OR 3.17 (95% CI 1.40-7.17), and multivariable logistic regression modeling, ORadjusted 5.10 (95% CI 2.01-13.70). Similar findings were observed for the secondary outcomes (i.e., neurologically favorable survival with a CPC score of 1, one-month survival, and prehospital return of spontaneous circulation). In subgroup analyses, there were no significant differences in neurologically favorable survival between the PAD group and non-PAD group in the unwitnessed cohort (ORadjusted 7.76 [0.75-81.90]) or the non-cardiac etiology cohort (ORadjusted 6.65 [0.64-66.24]). CONCLUSIONS: PAD was associated with an increased chance of neurologically favorable survival in pediatric OHCA (aged 1-17 years) who received bystander CPR, except for in cases of unwitnessed or non-cardiac etiology.

Effect of rescue breathing by lay rescuers for out-of-hospital cardiac arrest caused by respiratory disease: a nationwide, population-based, propensity score-matched study.

The importance of respiratory care in cardiopulmonary resuscitation may vary depending on the cause of cardiac arrest. No previous study has investigated the effects of rescue breathing performed by a lay rescuer on the outcomes of patients with out-of-hospital cardiac arrest (OHCA) caused by intrinsic respiratory diseases. The aim of this study was to investigate whether rescue breathing performed by a lay rescuer is associated with outcomes after respiratory disease-related OHCA. In a nationwide, population-based, propensity score-matched study in Japan, among adult patients with OHCA caused by respiratory disease who received bystander cardiopulmonary resuscitation from January 1, 2005 to December 31, 2010, we compared patients with rescue breathing to those without rescue breathing. The primary outcome was neurologically favorable survival 1 month after OHCA. Of the eligible 14,781 patients, 4970 received rescue breathing from a lay rescuer and 9811 did not receive rescue breathing. In a propensity score-matched cohort (4897 vs. 4897 patients), the neurologically favorable survival rate was similar between patients with and without rescue breathing from a lay rescuer [0.9 vs. 0.7 %; OR 1.23 (95 % CI 0.79-1.93)]. Additionally, in subgroup analyses, rescue breathing was not associated with neurological outcome regardless of the type of rescuer [family member: adjusted OR 0.83 (95 % CI 0.39-1.70); or non-family member: adjusted OR 1.91 (95 % CI 0.79-5.35)]. Even among patients with OHCA caused by respiratory disease, rescue breathing performed by a lay rescuer was not associated with neurological outcomes, regardless of the type of lay rescuer.

Conventional Versus Compression-Only Versus No-Bystander Cardiopulmonary Resuscitation for Pediatric Out-of-Hospital Cardiac Arrest.

BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) (chest compression and rescue breathing) has been recommended for pediatric out-of-hospital cardiac arrest (OHCA) because of the asphyxial nature of the majority of pediatric cardiac arrest events. However, the clinical effectiveness of additional rescue breathing (conventional CPR) compared with compression-only CPR in children is uncertain. METHODS: This nationwide population-based study of pediatric OHCA patients was based on data from the All-Japan Utstein Registry. We included all pediatric patients who experienced OHCA in Japan from January 1, 2011, to December 31, 2012. The primary outcome was a favorable neurological state 1 month after OHCA defined as a Glasgow-Pittsburgh Cerebral Performance Category score of 1 to 2 (corresponding to a Pediatric Cerebral Performance Category score of 1-3). Outcomes were compared with logistic regression with uni- and multivariable modeling in the overall cohort and for a propensity-matched subset of patients. RESULTS: A total of 2157 patients were included; 417 received conventional CPR, 733 received compression-only CPR, and 1007 did not receive any bystander CPR. Among these patients, 213 (9.9%) survived with a favorable neurological status 1 month after OHCA, including 108/417 (25.9%) for conventional, 68/733 (9.3%) for compression-only, and 37/1007 (3.7%) for no-bystander CPR. In unadjusted analyses, conventional CPR was superior to compression-only CPR in neurologically favorable survival (odds ratio [OR] 3.42, 95% confidence interval [CI] 2.45-4.76; P<0.0001), with a trend favoring conventional CPR that was no longer statistically significant after multivariable adjustment (ORadjusted 1.52, 95% CI 0.93-2.49), and with further attenuation of the difference in a propensity-matched subset (OR 1.20, 95% CI 0.81-1.77). Both conventional and compression-only CPR were associated with higher odds for neurologically favorable survival compared with no-bystander CPR (ORadjusted 5.01, 95% CI 2.98-8.57, and ORadjusted 3.29, 95% CI 1.93-5.71), respectively. CONCLUSIONS: In this population-based study of pediatric OHCA in Japan, both conventional and compression-only CPR were associated with superior outcomes compared with no-bystander CPR. Unadjusted outcomes with conventional CPR were superior to compression-only CPR, with the magnitude of difference attenuated and no longer statistically significant after statistical adjustments. These findings support randomized clinical trials comparing conventional versus compression-only CPR in children, with conventional CPR preferred until such controlled comparative data are available, and either method preferred over no-bystander CPR.

Epidemiology, Risk Factors, and Outcomes of Out-of-Hospital Cardiac Arrest Caused by Stroke: A Population-Based Study.

Limited information is available regarding stroke-related out-of-hospital cardiac arrest (OHCA). We aimed to assess the clinical characteristics of stroke-related OHCA and to identify the factors associated with patient outcomes.We conducted a nationwide population-based study of adult OHCA patients in Japan from January 1, 2006 to December 31, 2009. We examined the epidemiology, risk factors, and outcomes of stroke-related OHCA compared with cardiogenic OHCA. The primary outcome was neurologically favorable survival.Of the 243,140 eligible patients, 18,682 (7.7%) were diagnosed with stroke-related OHCA. Compared to OHCA with a presumed cardiac etiology, stroke-related OHCA patients had a greater chance of prehospital return of spontaneous circulation (ROSC) (9.9% vs 5.9%, P < 0.0001) but a reduced chance of 1-month survival (3.6% vs 4.9%, P < 0.0001) or favorable neurological outcomes (1.2% vs 2.6%, P < 0.0001). After adjusting for a variety of confounding factors, the prehospital ROSC rates were higher (adjusted OR 2.47, 95% confidence interval [CI] 2.34-2.62), but the neurologically favorable survival rates were lower (adjusted OR 0.66, 95%CI 0.57-0.76), among the stroke-related OHCA patients. In stroke-related OHCA cases, having a younger age, witness, and shockable 1st documented rhythm were associated with improved outcomes. Men had more favorable neurological outcomes. Seasonal or circadian factors had no critical impact on favorable neurological outcomes. Prehospital advanced life support techniques (i.e., epinephrine administration or advanced airway management) were not associated with favorable neurological outcomes.Although stroke-related OHCA had lower 1-month survival rates and poorer neurological outcomes than cardiogenic OHCA, the rates were not considered to be medically futile. Characteristically, sex differences might impact neurologically favorable survival.

Prediction protocol for neurological outcome for survivors of out-of-hospital cardiac arrest treated with targeted temperature management.

AIM: To identify patients who can obtain the full benefit from targeted temperature management (TTM) after out-of-hospital cardiac arrest. METHODS: We performed a retrospective observational study of comatose patients treated with TTM after an out-of-hospital cardiac arrest from January 2006 to February 2011. Neurological outcome was evaluated with the Glasgow-Pittsburgh Cerebral Performance category (CPC) at discharge and predictors were determined. RESULTS: Of 66 patients studied, 40 (60.6%) survived to neurologically intact discharge (CPC 1 or 2). According to multivariate analysis, predictors of good neurological outcome included arrest-to-first cardiopulmonary resuscitation attempt interval ≤5 min, ventricular fibrillation or ventricular tachycardia in the first monitored rhythm, absence of re-arrest before leaving the emergency department, arrest-to-return of spontaneous circulation interval ≤30 min and recovery of pupillary light reflex, which were identifiable in the emergency department. Based on this analysis, we developed a seven-point score (5-R score). If the score was ≥5, it predicted good neurological outcome with a sensitivity of 82.5% (95% confidence interval [CI], 67.2-92.7%) and specificity of 92.3% (95% CI, 74.9-99.1%). The negative predictive value of a score ≥4 was 100% (95% CI, 81.5-100%). Our prediction model was validated internally by a bootstrapping technique. CONCLUSIONS: The prediction protocol using the 5-R score was associated with good neurological outcome of patients treated with TTM. Therefore, it could be helpful in clinical decision making on whether to initiate cooling.

Wilms' tumour 1 gene expression is increased in hepatocellular carcinoma and associated with poor prognosis.

BACKGROUND/AIMS: Wilms' tumour 1 gene (WT1) was originally isolated as a tumour-suppressor gene. We investigated the expression of WT1 in hepatocellular carcinoma (HCC; T) and in non-cancerous hepatic tissues (non-tumour: NT) from patients with chronic liver diseases, and then examined the role of WT1 in the carcinogenesis or prognosis of HCC. METHODS: The expression of WT1 in T and NT from 50 patients with HCC was investigated using Western blotting, immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined whether WT1 expression was related to clinicopathological factors in individual patients in addition to prognostic factors in 50 patients with HCC and in 26 without HCC. RESULTS: Western blotting and immunohistochemical staining showed that WT1 was overexpressed in T compared with NT (P<0.001) and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) showed that WT1 mRNA expression was similarly increased. Overexpressed WT1 in HCC was significantly associated with T factors at the TNM stage, and short doubling time of HCC. Univariate and multivariate analyses revealed that WT1 overexpression was an independent prognostic factor for HCC. The disease-free survival period in patients with overexpressed WT1 in NT tissues was significantly reduced. CONCLUSION: The expression of WT1 is increased more in HCC than in non-tumour tissues. Moreover, overexpressed WT1 was associated with tumour growth, and resulted in a worsening prognosis of HCC. Our findings from NT tissues revealed that WT1 overexpression might contribute to oncogenic potential.

Anti-HBs-positive liver failure due to hepatitis B virus reactivation induced by rituximab.

A 59-year-old man developed acute hepatitis with reactivated hepatitis B virus (HBV) following administration of rituximab (anti-CD20 monoclonal antibody). The patient was diagnosed with malignant lymphoma in 1998, and virus marker testing indicated HBV surface antigen (HBsAg)-negative and anti-HBs antibody (anti-HBs)-positive results when chemotherapy including rituximab was started. Levels of aminotransferases were elevated, and HBsAg results turned positive. Despite therapy for late-onset hepatic failure, the patient died. Rituximab appears likely to have induced HBV reactivation in this case. Anti-viral agents should be administered for both HBsAg-positive and anti-HBs-positive patients who are scheduled to receive rituximab.