Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

A case of plastic bronchitis with a remarkable response to steroids.

Plastic bronchitis can cause fatal airway obstruction. An 85-year-old woman with no medical history presented to the emergency department of our hospital with progressing respiratory failure and hemoptysis. Bronchoscopy revealed a fibrin-type cast thrombus in the trachea, and plastic bronchitis was diagnosed. Initial treatment involved airway thrombus removal, and the patient survived. However, bleeding persisted for 6 days, and respiratory status showed slight improvement despite ventilatory management. Steroids were administered for concomitant acute respiratory distress syndrome, and there was marked improvement in both airway hemorrhage and respiratory failure. The patient was extubated, the steroid dose was reduced, and no rebleeding was observed. The patient was discharged from the hospital 1 month after the onset of symptoms. Blood tests were positive for the myeloperoxidase-anti-neutrophil cytoplasmic antibody; however, no biopsy was performed, and no specific symptoms were observed. A definitive diagnosis was therefore not reached. The causes of plastic bronchitis are numerous, and there are no standardized diagnostic criteria or treatment guidelines for this condition. The present case suggests that steroids may be effective in some patients with plastic bronchitis.

Delayed neurologic improvement and long-term survival of patients with poor neurologic status after out-of-hospital cardiac arrest: A retrospective cohort study in Japan.

AIM: To assess survival duration and frequency of delayed neurologic improvement in patients with poor neurologic status at discharge from emergency hospitals after out-of-hospital cardiac arrest (OHCA). METHODS: This retrospective cohort study included OHCA patients admitted to two tertiary emergency hospitals in Japan between January 2014 and December 2020. Pre-hospital, tertiary emergency hospital, and post-acute care hospital data, were retrospectively collected by reviewing medical records. Neurologic improvements were defined as an improvement of Cerebral Performance Category (CPC) scores from 3 or 4 at hospital discharge to 1 or 2. The primary outcome was neurologic improvement after discharge, while the secondary outcome was survival time after cardiac arrest. RESULTS: Of all patients (n = 1,012) admitted to tertiary emergency hospitals after OHCA during the observation period, 239 with CPC 3 or 4 at discharge were included, and all were Japanese. Median age was 75 years, 64% were male, and 31% had initially shockable rhythms. Neurologic improvements were observed in nine patients (3.6%), higher in CPC 3 (31%) than CPC 4 (1.3%) patients, but not after 6 months from cardiac arrest. The median survival time after cardiac arrest was 386 days (95% confidence interval: 303-469). CONCLUSION: Survival probability in patients with CPC 3 or 4 was 50% at 1-year and 20% at 3-year. Neurologic improvements were observed in 3.6% patients, higher in CPC 3 than in CPC 4 patients. During the first 6 months after OHCA, the neurologic status may improve in patients with CPC 3 or 4.

Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis.

BACKGROUND: A shortage of donor organs amid high demand for transplantable organs is a worldwide problem, and an increase in organ donation would be welcomed by the global healthcare system. Patients with brain death (BD) are potential organ donors, and early prediction of patients with BD may facilitate the process of organ procurement. Therefore, we developed a model for the early prediction of BD in patients who survived the initial phase of out-of-hospital cardiac arrest (OHCA). METHODS: We retrospectively analyzed data of patients aged < 80 years who experienced OHCA with a return of spontaneous circulation (ROSC) and were admitted to our hospital between 2006 and 2018. We categorized patients into either a non-BD or BD group. Demographic and laboratory data on ED admission were used for stepwise logistic regression analysis. Prediction scores of BD after OHCA were based on ß-coefficients of prognostic factors identified in the multivariable logistic model. RESULTS: Overall, 419 OHCA patients with ROSC were admitted to our hospital during the study period. Seventy-seven patients showed BD (18.3%). Age and etiology of OHCA were significantly different between the groups. Logistic regression analysis confirmed that age, low-flow time, pH, and etiology were independent predictors of BD. The area under the receiver operating characteristic curve for this model was 0.831 (95% confidence interval, 0.786-0.876). CONCLUSIONS: We developed and internally validated a new prediction model for BD after OHCA, which could aid in the early identification of potential organ donors for early donor organ procurement.

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.

Epidemiological features after emergency declaration in Hokkaido and report of 15 cases of COVID-19 including 3 cases requiring mechanical ventilation.

The ongoing spread of coronavirus disease (COVID-19) is a worldwide crisis. Hokkaido Prefecture in Japan promptly declared a state of emergency following the rapid increase of COVID-19 cases, and the policy became an example to mitigate the spread of COVID-19. We herein report 15 cases of COVID-19 including 3 cases requiring mechanical ventilation. Based on review of our cases, among patients over 50 years of age with underlying diseases such as hypertension and diabetes mellitus, and those who required oxygen administration tended to deteriorate. These cases highlight the importance of understanding the background and clinical course of severe cases to predict prognosis.

Disseminated intravascular coagulation with increased fibrinolysis during the early phase of isolated traumatic brain injury.

BACKGROUND: There is evidence to demonstrate that the coagulopathy which occurs in patients with traumatic brain injury coincides with disseminated intravascular coagulation (DIC). We hypothesized that DIC with increased fibrinolysis during the early stage of isolated traumatic brain injury (iTBI) affects the outcome of the patients and that hypoperfusion contributes to hyperfibrinolysis in the DIC. METHODS: This retrospective study included 92 patients with iTBI who were divided into DIC and non-DIC groups according to the Japanese Association Acute Medicine DIC scoring system. The DIC patients were subdivided into those with and without hyperfibrinolysis. The platelet counts and global markers of coagulation and fibrinolysis were measured. Systemic inflammatory response syndrome (SIRS), organ dysfunction (assessed by the Sequential Organ Failure Assessment score), tissue hypoperfusion (assessed by the lactate levels) and the transfusion volume were also evaluated. The outcome measure was all-cause hospital mortality. RESULTS: DIC patients showed consumption coagulopathy, lower antithrombin levels and higher fibrin/fibrinogen degradation products (FDP) and D-dimer levels than non-DIC patients. All of the DIC patients developed SIRS accompanied by organ dysfunction and required higher blood transfusion volumes, leading to a worse outcome than non-DIC patients. These changes were more prominent in DIC with hyperfibrinolysis. A higher FDP/D-dimer ratio suggests that DIC belongs to the fibrinolytic phenotype and involves fibrin(ogen)olysis. The mean blood pressures of the patients with and without DIC on arrival were identical. Hypoperfusion and the lactate levels were not identified as independent predictors of hyperfibrinolysis. CONCLUSIONS: DIC, especially DIC with hyperfibrinolysis, affects the outcome of patients with iTBI. Low blood pressure-induced tissue hypoperfusion does not contribute to hyperfibrinolysis in this type of DIC.

Fibrin/fibrinogen degradation products (FDP) at hospital admission predict neurological outcomes in out-of-hospital cardiac arrest patients.

OBJECTIVE: This study aimed to test the hypothesis that coagulation, fibrinolytic markers and disseminated intravascular coagulation (DIC) score (International Society on Thrombosis and Haemostasis) at hospital admission of out-of-hospital cardiac arrest (OHCA) patients can predict neurological outcomes 1 month after cardiac arrest. METHODS: In this retrospective, observational analysis, data were collected from the Sapporo Utstein Registry and medical records at Hokkaido University Hospital. We included patients who experienced OHCA with successful return of spontaneous circulation (ROSC) between 2006 and 2012 and were transferred to Hokkaido University Hospital. From medical records, we collected information about the following coagulation and fibrinolytic factors at hospital admission: platelet count; prothrombin time; activated partial thromboplastin time; plasma levels of fibrinogen, D-dimer, fibrin/fibrinogen degradation products (FDP), and antithrombin; and calculated DIC score. Favorable neurological outcomes were defined as a cerebral performance category 1-2. RESULTS: We analyzed data for 315 patients. Except for fibrinogen level, all coagulation variables, fibrinolytic variables, and DIC score were associated with favorable neurological outcomes. In the receiver operating characteristic curve analysis, FDP level had the largest area under the curve (AUC; 0.795). In addition, the AUC of FDP level was larger than that of lactate level. CONCLUSIONS: All of the coagulation and fibrinolytic markers, except for fibrinogen level, and DIC score at hospital admission, were associated with favorable neurological outcomes. Of all of the variables, FDP level was most closely associated with favorable neurological outcomes in OHCA patients who successfully achieved ROSC.