Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial.

OBJECTIVE: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE. METHODS: We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug. RESULTS: A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061). CONCLUSION: The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT. TRIAL REGISTRATION NUMBER: jRCTs031190160.

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.

Intracranial pressure management and neurological outcome for patients with mild traumatic brain injury who required neurosurgical intervention: a Japanese database study.

Purpose: Among mild traumatic brain injuries (mTBI; a Glasgow Coma Scale score ≥13 on arrival), few result in severe neurological deficit, especially when they needed neurosurgical intervention. We investigated the association of intracranial pressure (ICP) control management with neurological outcome in patients with mTBI who needed neurosurgical intervention. Methods: From 1,092 records of the Japan Neurotrauma Data Bank during 2009-2011, we retrospectively identified 195 patients with neurosurgical intervention for mTBI. Using the Glasgow Outcome Scale, we grouped records into two: favorable and poor outcome. We analyzed neurological outcomes using a logistic regression analysis adjusted for ICP control managements. Results: Seventy patients had a poor outcome. Logistic regression analysis revealed that sedatives, hyperosmotic agents, and hyperventilation therapy were significantly associated with poor outcome (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.31-4.26; OR: 2.81, 95% CI: 1.17-6.75; OR: 9.36, 95% CI: 1.81-48.35). However, temperature management was significantly related with favorable outcome (OR: 0.26, 95% CI: 0.10-0.66). Conclusions: Our study, using a Japanese multicenter brain trauma registry, suggested that requirement of sedatives, hyperosmotic agents, and hyperventilation is associated with poor neurological outcome for patients with mTBI who underwent neurosurgical intervention, although temperature management was associated with favorable neurological outcome.

Feasibility and Safety of Intravascular Temperature Management for Severe Heat Stroke: A Prospective Multicenter Pilot Study.

OBJECTIVES: Heat stroke is a life-threatening condition with high mortality and morbidity. Although several cooling methods have been reported, the feasibility and safety of treating heat stroke using intravascular temperature management are unclear. This study evaluated the efficacies of conventional treatment with or without intravascular temperature management for severe heat stroke. DESIGN: Prospective multicenter study. SETTING: Critical care and emergency medical centers at 10 tertiary hospitals. PATIENTS: Patients with severe heat stroke hospitalized during two summers. INTERVENTIONS: Conventional cooling with or without intravascular temperature management. MEASUREMENTS AND MAIN RESULTS: Cooling efficacy, Sequential Organ Failure Assessment score, occurrence rate of serious adverse events, and prognosis based on the modified Rankin Scale and Cerebral Performance Category. Patient outcomes were compared between five centers that were prospectively assigned to perform conventional cooling (control group: eight patients) and five centers that were assigned to perform conventional cooling plus intravascular temperature management (intravascular temperature management group: 13 patients), based on equipment availability. Despite their higher initial temperatures, all patients in the intravascular temperature management group reached the target temperature of 37°C within 24 hours, although only 50% of the patients in the control group reached 37°C (p < 0.01). The intravascular temperature management group also had a significant decrease in the Sequential Organ Failure Assessment score during the first 24 hours after admission (4.0 vs 1.5; p = 0.04). Furthermore, the intravascular temperature management group experienced fewer serious adverse events during their hospitalization, compared with the control group. The percentages of favorable outcomes at discharge and 30 days after admission were not statistically significant. CONCLUSIONS: The combination of intravascular temperature management and conventional cooling was safe and feasible for treating severe heat stroke. The results indicate that better temperature management may help prevent organ failure. A large randomized controlled trial is needed to validate our findings.

Amiodarone Compared with Lidocaine for Out-Of-Hospital Cardiac Arrest with Refractory Ventricular Fibrillation on Hospital Arrival: a Nationwide Database Study.

PURPOSE: The latest resuscitation guidelines recommend the use of amiodarone in adult patients with out-of-hospital cardiac arrest (OHCA) and refractory ventricular fibrillation (VF) to improve the rates of return of spontaneous circulation. However, there is limited evidence to suggest that amiodarone is superior to lidocaine with respect to survival at discharge. The purpose of the present study was to evaluate the hypothesis that amiodarone is superior to lidocaine with regard to the rate of survival to hospital discharge for OHCA patients with VF/pulseless VT (pVT) on hospital arrival. METHODS: Using the Japanese Diagnosis Procedure Combination inpatient database, we identified 3951 patients from 795 hospitals who experienced cardiogenic OHCA and had refractory ventricular fibrillation on hospital arrival between July 2007 and March 2013. The patients were categorized into amiodarone (n = 1743) and lidocaine (n = 2208) groups, from which 801 propensity score-matched pairs were generated. RESULTS: There was no significant difference in the rate of survival to hospital discharge between the amiodarone and lidocaine groups (15.2 % vs. 17.1 %; difference, -1.9 %; 95 % CI, -5.5 to 1.7) in propensity score-matched analyses. Cox regression analyses did not indicate significant in-hospital mortality differences between the amiodarone and lidocaine groups for the propensity score-matched groups (hazard ratio, 1.05; 95 % CI, 0.94 to 1.17). CONCLUSIONS: The present nationwide study suggested that there was no significant difference in the rate of survival to hospital discharge between cardiogenic OHCA patients with persistent ventricular fibrillation on hospital arrival treated with amiodarone or lidocaine.

Early antibiotics administration during targeted temperature management after out-of-hospital cardiac arrest: a nationwide database study.

BACKGROUND: Patients resuscitated after cardiac arrest are reportedly at high risk for infection and sepsis, especially those treated with targeted temperature management (TTM). There is, however, limited evidence suggesting that early antibiotic use improves patient outcomes. We examined the hypothesis that early treatment with antibiotics reduces mortality in patients with cardiac arrest receiving TTM. METHODS: We identified 2803 patients with cardiogenic out-of-hospital cardiac arrest (OHCA) that were treated with TTM and were admitted to 371 hospitals that contribute to the Japanese Diagnosis Procedure Combination inpatient database between July 2007 and March 2013. Of these, 1272 received antibiotics within the first 2 days (antibiotics) and 1531 did not (control). We generated 802 propensity score-matched pairs. RESULTS: There was no significant difference in 30-day mortality between the groups (control vs. antibiotics; 33.0 % vs. 29.9 %; difference, 3.1 %; 95 % confidence interval [CI], -1.4 to 7.7 %, p = 0.18). Analysis using the hospital antibiotics prescribing rate as an instrumental variable showed that antibiotic use was not significantly associated with a reduction in 30-day mortality (6.6 %, CI 95 %, -0.5 to 13.7 %, p = 0.28). A subgroup analysis of patients who required extracorporeal membrane oxygenation (ECMO) indicated a significant difference in 30-day mortality between the 2 groups (62.9 % vs. 43.5 %; difference 19.3 %, CI 95 %, 5.9 to 32.7 %, p = 0.005). In the instrumental variable model, the estimated reduction in 30-day mortality associated with antibiotics was 18.2 % (CI 95 %, 21.3 to 34.4 %, p = 0.03) in ECMO patients. CONCLUSIONS: Although there was no significant association between the use of antibiotics and mortality after overall cardiogenic OHCA treated with TTM, antibiotics may be beneficial in patients who require ECMO.

Optimal range of global end-diastolic volume for fluid management after aneurysmal subarachnoid hemorrhage: a multicenter prospective cohort study.

OBJECTIVES: Limited evidence supports the use of hemodynamic variables that correlate with delayed cerebral ischemia or pulmonary edema after aneurysmal subarachnoid hemorrhage. The aim of this study was to identify those hemodynamic variables that are associated with delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage. DESIGN: A multicenter prospective cohort study. SETTING: Nine university hospitals in Japan. PATIENTS: A total of 180 patients with aneurysmal subarachnoid hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively monitored using a transpulmonary thermodilution system in the 14 days following subarachnoid hemorrhage. Delayed cerebral ischemia was developed in 35 patients (19.4%) and severe pulmonary edema was developed in 47 patients (26.1%). Using the Cox proportional hazards model, the mean global end-diastolic volume index (normal range, 680-800 mL/m) was the independent factor associated with the occurrence of delayed cerebral ischemia (hazard ratio, 0.74; 95% CI, 0.60-0.93; p = 0.008). Significant differences in global end-diastolic volume index were detected between the delayed cerebral ischemia and non-delayed cerebral ischemia groups (783 ± 25 mL/m vs 870 ± 14 mL/m; p = 0.007). The global end-diastolic volume index threshold that best correlated with delayed cerebral ischemia was less than 822 mL/m, as determined by receiver operating characteristic curves. Analysis of the Cox proportional hazards model indicated that the mean global end-diastolic volume index was the independent factor that associated with the occurrence of pulmonary edema (hazard ratio, 1.31; 95% CI, 1.02-1.71; p = 0.03). Furthermore, a significant positive correlation was identified between global end-diastolic volume index and extravascular lung water (r = 0.46; p < 0.001). The global end-diastolic volume index threshold that best correlated with severe pulmonary edema was greater than 921 mL/m. CONCLUSIONS: Our findings suggest that global end-diastolic volume index impacts both delayed cerebral ischemia and pulmonary edema after subarachnoid hemorrhage. Maintaining global end-diastolic volume index slightly above normal levels has promise as a fluid management goal during the treatment of subarachnoid hemorrhage.

Effect of triple-h prophylaxis on global end-diastolic volume and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Although prophylactic triple-H therapy has been used in a number of institutions globally to prevent delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH), limited evidence is available for the effectiveness of triple-H therapy on hemodynamic variables. Recent studies have suggested an association between low global end-diastolic volume index (GEDI), measured using a transpulmonary thermodilution method, and DCI onset. The current study aimed at assessing the effects of prophylactic triple-H therapy on GEDI. METHODS: This prospective multicenter study included aneurysmal SAH patients admitted to 9 hospitals in Japan. The decision to administer prophylactic triple-H therapy and the management protocols were left to the physician in charge (physician-directed therapy) of each participating institution. The primary endpoints were the changes in the hemodynamic variables as analyzed using a generalized linear mixed model. RESULTS: Of 178 patients, 62 (34.8 %) received prophylactic triple-H therapy and 116 (65.2 %) did not. DCI was observed in 35 patients (19.7 %), with no significant difference between the two groups [15 (24.2 %) vs. 20 (17.2 %), p = 0.27]. Although a greater amount of fluid (p < 0.001) and a higher mean arterial pressure (p = 0.005) were observed in the triple-H group, no significant difference was observed between the groups in GEDI (p = 0.81) or cardiac output (p = 0.62). CONCLUSIONS: Physician-directed prophylactic triple-H administration was not associated with improved clinical outcomes or quantitative hemodynamic indicators for intravascular volume. Further, GEDI-directed intervention studies are warranted to better define management algorithms for SAH patients with the aim of preventing DCI.

Changes Over 7 Years in Temperature Control Treatment and Outcomes After Out-of-Hospital Cardiac Arrest: A Japanese, Multicenter Cohort Study.

Temperature control is the only neuroprotective intervention suggested in current international guidelines for patients with return of spontaneous circulation after cardiac arrest, but the prevalence of temperature control therapy, temperature settings, and outcomes have not been clearly reported. We aimed to investigate changes over 7 years in provision of temperature control treatment among out-of-hospital cardiac arrest (OHCA) patients in Kanto region, Japan. Data of all adult OHCA patients who survived for more than 24 hours in the prospective cohort studies, SOS-KANTO 2012 (conducted from 2012 to 2013) and SOS-KANTO 2017 (conducted from 2019 to 2021), in Japan were included. We compared the prevalence of temperature control and the proportion of mild (≥35°C) and moderate (from 32°C to 34.9°C) hypothermia between the two study groups. We also performed a Cox regression analysis to evaluate 30-day mortality adjusted by temperature control therapy (none, moderate hypothermia, or mild hypothermia), age, sex, past medical history, witnessed status, bystander cardiopulmonary resuscitation, initial rhythm, location of arrest, and dataset (SOS-KANTO 2012 or 2017). We analyzed data from 2936 patients (n = 1710, SOS-KANTO 2012; n = 1226, SOS-KANTO 2017). Use of temperature control was lower (45.3% vs. 41.4%, p = 0.04), moderate hypothermia was lower (p < 0.01), and mild hypothermia was higher (p < 0.01) in SOS-KANTO 2017 compared with SOS-KANTO 2012. The survival rate was significantly higher for patients with mild (p < 0.01) and moderate (p < 0.01) hypothermia compared with those who did not receive temperature control therapy. Overall, the incidence of moderate hypothermia decreased and that of mild hypothermia increased and the use of temperature control decreased between the two studies conducted 7 years apart in the Kanto area, Japan. Temperature control management might improve survival of patients with OHCA.

Evaluation of clinical response to empirical antimicrobial therapy on day 7 and mortality in the intensive care unit: sub-analysis of the DIANA study Japanese data.

It is not clear whether evaluating the clinical response to antibiotic use at day 7 among critically ill patients accurately predicts outcomes. We aimed to evaluate the relationship between clinical response to the initial empiric therapy on day 7 and mortality. Methods: The determinants of antimicrobial use and de-escalation in critical care (DIANA) study was an international, multicenter, observational study on antibiotic use in the intensive care unit (ICU). ICU patients ages over 18 years in whom an empiric antimicrobial regimen in Japan was initiated were included. We compared patients who were evaluated as cured or improved ("effective") 7 days after starting antibiotic treatment with patients who were evaluated as deteriorated ("failure"). Results: Overall, 217 (83%) patients were in the effective group, and 45 (17%) were in the failure group. Both the infection-related mortality rate in the ICU and the in-hospital infection-related mortality rate in the effective group were lower than those in the failure group (0% versus 24.4%; P < 0.01 and 0.5% versus 28.9%; P < 0.01, respectively). Conclusion: Assessment of efficacy of empiric antimicrobial treatment on day 7 may predict a favorable outcome among patients suffering from infection in the ICU.

Comparison of the effectiveness of pericardiocentesis and surgical pericardiotomy in the prognosis of patients with blunt traumatic cardiac tamponade: a multicenter study using the Japan Trauma Data Bank.

Aim: To compare the prognostic impact of pericardiocentesis (PCC) and surgical pericardiotomy (SP) in blunt traumatic pericardial tamponade. Methods: Among 361,706 trauma patients registered in the Japan Trauma Data Bank from January 2004 to December 2018, we included those with blunt traumatic cardiac tamponade who underwent PCC and/or SP. We excluded patients with penetrating trauma, age younger than 15 years, Injury Severity Score (ISS) equal to 75, blood pressure 0 mmHg at the time of admission, head Abbreviated Injury Scale (AIS) score 5 or more, and those with missing data for outcomes. To examine the effect of SP, patients were divided into a PCC group and an SP-only group. Missing values of age, sex, systolic blood pressure, respiratory rate, pulse rate, time from emergency call to hospital arrival, head AIS, chest AIS, abdomen/pelvis AIS, Glasgow Coma Scale score, and ISS were estimated using multiple imputation. In-hospital mortality was analyzed using multivariable analysis, and we undertook a survival analysis. Results: We analyzed 305 patients, 150 (49.2%) in the PCC group and 155 (50.8%) in the SP-only group. The in-hospital mortality rate was 40.7% in the PCC group and 76.8% in the SP-only group. Multivariable analysis after multiple imputation showed an odds ratio of SP for in-hospital mortality 5.34 (95% confidence interval, 2.80-10.18; P < 0.01) compared with PCC. Using the Kaplan-Meier method, SP showed a significant risk of mortality (hazard ratio 2.16; 95% confidence interval, 1.58-2.95; P < 0.01). Conclusions: In patients with blunt traumatic cardiac tamponade, SP was associated with poor prognosis.

Utility of a Compatibility Chart for Continuous Infusions in the Intensive Care Unit.

BACKGROUND: In the intensive care unit (ICU), multiple intravenous drugs are often administered through the same catheter line, greatly increasing the risk of drug incompatibility. We previously developed a compatibility chart including 27 drugs and have used it to avoid drug incompatibilities in the ICU. This retrospective study evaluated the utility of this chart by analyzing prescriptions and incidents of incompatibilities in an ICU. METHODS: We analyzed 257 ICU prescriptions of two or more continuous infusions on the same day during the period between March 2016 and February 2017 and investigated the rate of compliance with the compatibility chart. Drug combinations were classified as "compatible," "tolerable compatible," "incompatible," and "no data." For all combinations, the compliance rate was defined as the ratio of compatible and tolerable compatible combinations. Additionally, using our hospital incident report database, we analyzed 27,117 injections administered in the ICU between March 2016 and February 2017 and investigated incidents related to incompatibility. RESULTS: Three hundred infusion combinations were identified in the prescriptions. The compliance rate was 97% (n = 293). Of the 113 combinations judged to be tolerable compatible, 98% (n = 111) consisted of three or more continuous medications injected through the same intravenous line. Of the two incidents related to incompatibility in the incident report database, the combination "nicardipine and furosemide" was defined as incompatible in the compatibility chart. CONCLUSIONS: The high rate of compliance with the compatibility chart suggested it was useful in preventing drug incompatibility.

Elective Endovascular Stent-Graft Implantation for External Iliac Artery Injury after Blunt Pelvic Trauma.

External iliac artery (EIA) injuries caused by blunt trauma are rare. Here, we describe a blunt EIA injury after a motorbike accident suffered by a 16-year-old male. Despite conservative treatment, intermittent claudication persisted. He was successfully treated by elective endovascular stent-graft implantation on day 59 after the injury. Ankle-brachial index (ABI) improved, as did his symptoms. A contrast-enhanced computed tomography scan on postoperative day 90 showed no residual stenosis and favorable peripheral blood flow. This report suggests that elective endovascular stent-graft implantation might be a viable treatment option for blunt EIA injuries.

Effect of angioembolization for isolated complex pelvic injury: A post-hoc analysis of a nationwide multicenter trauma database in Japan.

BACKGROUND AND IMPORTANCE: Complex pelvic injuries are among the types of trauma with the highest mortality. Treatment strategies should be based on the hemodynamic status, the anatomical type of fracture, and the associated injuries. Combination therapies, including preperitoneal pelvic packing, temporary mechanical stabilization, resuscitative endovascular balloon occlusion of the aorta, and angioembolization, are recommended for pelvic injuries. OBJECTIVE: To investigate the effect of urgent angioembolization alone on severe pelvic injury-associated mortality. DESIGN, SETTINGS, AND PARTICIPANTS: We used the Japan Trauma Data Bank database, a multicenter observational study, to retrospectively identify adult patients with isolated blunt pelvic injuries (Abbreviated Injury Scale [AIS] score: 3-5) from 2004 to 2018. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure was in-hospital mortality. We subdivided patients into two groups, those who underwent urgent angioembolization and non-urgent angioembolization, and compared their mortality rates. We performed multiple imputation and multivariable analyzes to compare the mortality rates between groups after adjusting for known potential confounding factors (age, sex, Glasgow Coma Scale score, systolic blood pressure on hospital arrival, Injury Severity Score, pelvic AIS score, laparotomy, resuscitative endovascular balloon occlusion of the aorta, and external fixation) and for within-hospital clustering using the generalized estimating equation. MAIN RESULTS: We analyzed 4207 of 345,932 trauma patients, of whom 799 underwent urgent angioembolization. The in-hospital mortality rate was significantly higher in the urgent embolization group than in the non-urgent embolization group (7.4 vs. 4.0%; p < 0.01). However, logistic regression analysis revealed that the mortality rates of patients with urgent angioembolization significantly decreased after adjusting for factors independently associated with mortality (odds ratio: 0.60; 95% confidence interval: 0.37-0.96; p = 0.03). CONCLUSION: Urgent angioembolization may be an effective treatment for severe pelvic injury regardless of the pelvic AIS score and the systolic blood pressure on hospital arrival.

Neurointensive Care of Traumatic Brain Injury Patients Based on Coagulation and Fibrinolytic Parameter Monitoring.

Coagulopathy, a common complication of traumatic brain injury (TBI), is characterized by a hypercoagulable state developing immediately after injury, with hyperfibrinolysis and bleeding tendency peaking 3 h after injury, followed by fibrinolysis shutdown. Reflecting this timeframe, the coagulation factor fibrinogen is first consumed and then degraded after TBI, its concentration rapidly decreasing by 3 h post-TBI. The fibrinolytic marker D-dimer reaches its maximum concentration at the same time. Hyperfibrinolysis in the acute phase of TBI is associated with poor prognosis via hematoma expansion. In the acute phase, the coagulation and fibrinolysis parameters must be monitored to determine the treatment strategy. The combination of D-dimer plasma level at admission and the level of consciousness upon arrival at the hospital can be used to predict the patients who will "talk and deteriorate." Fibrinogen and D-dimer levels should determine case selection and the amount of fresh frozen plasma required for transfusion. Surgery around 3 h after injury, when fibrinolysis and bleeding diathesis peak, should be avoided if possible. In recent years, attempts have been made to estimate the time of injury from the time course of coagulation and fibrinolysis parameter levels, which has been particularly useful in some cases of pediatric abusive head trauma patients.

Blood concentration of levetiracetam after bolus administration in patients with status epilepticus.

PURPOSE: We aimed to evaluate the blood concentration of levetiracetam (LEV), as a second-line drug, in patients with status epilepticus (SE) in an emergency clinical setting. METHODS: We prospectively evaluated 20 consecutive patients with SE admitted to our department between July 2017 and July 2019. LEV (2500 mg) was administered via bolus infusion after diazepam infusion, followed by 500 mg every 12 h for 48 h and then 500 mg orally. The primary outcomes were LEV blood concentration 15 min, 12 h, 48 h, and 96 h after administration and the proportion of patients showing trough LEV concentration within the therapeutic range. The secondary outcomes were the discontinuation of apparent convulsive seizure, epileptic wave on electroencephalogram, tracheal intubation, adverse events related to blood parameters, and abnormal findings in vital signs examination. RESULTS: Median blood LEV (2500 mg) concentration at 15 min after administration was 81.6 µg/mL. The median trough concentration after 12, 48, and 96 h was 28.8, 10.5, and 9.1 µg/mL, respectively. Moreover, 95% of patients had trough concentration above the lower limit of the therapeutic blood concentration (>12 µg/mL) after 12 h. Regarding secondary outcomes, endotracheal intubation, seizure suppression, and abnormal electroencephalogram findings were observed in approximately 40%, 90%-95%, and 41% of patients, respectively. No abnormal findings were noted in blood tests and vital sign examination, although the AST/ALT levels increased in 10% of the patients. CONCLUSION: After bolus administration of 2500 mg, the blood LEV concentration reached the therapeutic window in patients with early-stage SE.

Endovascular treatment of acute basilar artery occlusion: Outcomes, influencing factors and imaging characteristics from the Tama-REgistry of acute thrombectomy (TREAT) study.

OBJECTIVE: The effectiveness of mechanical thrombectomy (MT) for acute basilar artery occlusion (ABAO) remains unknown. We evaluated the feasibility, safety, and efficacy of endovascular treatment for ABAO. METHODS: We retrospectively investigated patients with ABAO who underwent MT using modern stent retrievers and an aspiration device between January 2015 and March 2019 at 12 comprehensive stroke centers. Functional outcomes and 90-day mortality rates were analyzed as primary outcomes. Factors influencing outcomes were analyzed as secondary outcomes. Relationships between outcome and affected area of infarction on arrival were also analyzed. RESULTS: Seventy-three patients were included. Good outcome (modified Rankin Scale (mRS) score 0-2) was achieved in 25/73 patients (34.2%) and the all-cause 90-day mortality rate was 23.3% (17/73). Successful recanalization (modified Thrombolysis In Cerebral Infarction grade 2b and 3) was achieved in 70/73 patients (95.9%). In univariate analyses, age, National Institutes of Health Stroke Scale score, and posterior circulation Alberta Stroke Program Early CT Score (pc-ASPECTS) differed significantly between good and poor functional outcome groups. Age and pc-ASPECTS were significantly associated with functional outcomes in the logistic regression model. Positive findings for the midbrain on diffusion-weighted imaging on pc-ASPECTS and brainstem score were significantly associated with poor outcomes. CONCLUSION: MT with modern devices for ABAO resulted in highly successful recanalization and good outcomes. A positive finding for the midbrain on initial imaging might predict poor outcomes. Further studies are required to confirm our results.

Head positioning in suspected patients with acute stroke from prehospital to emergency department settings: a systematic review and meta-analysis.

AIM: This study aimed to clarify whether the lying-flat position from prehospital to emergency department settings more effectively improves neurological outcomes of patients suspected with acute stroke over the sitting-up position. METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi for published randomized controlled trials until September 2019. The study population included patients suspected with acute stroke from prehospital to emergency department settings. We compared outcomes between the lying-flat position and sitting-up position groups. The critical outcome was the modified Rankin Scale score at 90 days, and important composite outcomes were 90-day mortality, pneumonia recurrence, and recurrent ischemic stroke. The certainty of evidence of the outcome level was compared using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: In total, 881 studies were identified from the databases, and two randomized controlled trials were included in the analysis. The pooled risk ratio of 90-day modified Rankin Scale score was not statistically significant (risk ratio 0.86; 95% confidence interval [CI] 0.56-1.32) between the lying-flat position and sitting-up position groups. When comparing the 90-day mortality, pneumonia occurrence, and recurrent ischemic stroke, no significant differences were observed between the two groups. Risk ratio was 1.00 (95% CI 0.87-1.14), 0.90 (95% CI 0.74-1.11), and 0.81 (95% CI 0.14-4.64) for 90-day mortality, pneumonia occurrence, and recurrent ischemic stroke, respectively. CONCLUSION: This study suggests that the lying-flat position is not more effective than the sitting-up position in terms of 90-day modified Rankin Scale score in patients suspected with acute stroke.

Validation of sepsis-induced coagulopathy score in critically ill patients with septic shock: post hoc analysis of a nationwide multicenter observational study in Japan.

Coagulation disorder is a major cause of death in sepsis patients. Recently, sepsis-induced coagulopathy (SIC) scoring was developed as a new criterion for coagulopathy-associated sepsis. We aimed to evaluate the accuracy of the SIC score for predicting the prognosis of septic shock. We analyzed data from a multicenter observational study conducted from 2011 to 2013. We grouped the participants into those who did and did not use vasopressors, and compared the in-hospital mortality rates of SIC and non-SIC patients. Patients who needed vasopressors were considered to have septic shock. We performed survival analysis adjusted by factors independently associated with mortality. SIC developed in 66.4% of patients who used vasopressors and 42.2% of patients who did not. The in-hospital mortality difference between the SIC and non-SIC groups was statistically significant in those who needed vasopressors (35.8% vs 27.9%, p < 0.01). Cox regression analysis indicated that SIC was significantly correlated with mortality risk in patients who used vasopressors (hazard ratio [HR] 1.39; 95% confidence interval [CI] 1.13-1.70; p < 0.01), but not in those who did not (HR 1.38; 95% CI 0.81-2.34; p = 0.23). In conclusion, the SIC score might be a good diagnostic indicator of fatal coagulopathy among sepsis patients who need vasopressors.

Association between mortality and age among mechanically ventilated COVID-19 patients: a Japanese nationwide COVID-19 database study.

BACKGROUND: Only a few studies have reported the association between age and mortality in COVID-19 patients who require invasive mechanical ventilation (IMV). We aimed to evaluate the effect of age on COVID-19-related mortality among patients undergoing IMV therapy. METHODS: This cohort study was conducted using the COVID-19 Registry Japan database, a nationwide multi-centre study of hospitalized patients with laboratory-confirmed COVID-19. Of all 33,808 cases registered between 1 January 2020 to 28 February 2021, we analysed 1555 patients who had undergone IMV. We evaluated mortality rates between age groups using multivariable regression analysis after adjusting for known potential components, such as within-hospital clustering, comorbidities, steroid use, medication for COVID-19, and vital signs on admission, using generalized estimation equation. RESULTS: By age group, the mortality rates in the IMV group were 8.6%, 20.7%, 34.9%, 49.7% and 83.3% for patients in their 50s, 60s, 70s, 80s, and 90s, respectively. Multivariable analysis showed that compared with those for patients aged < 60 years, the odds ratios (95% confidence interval) of death were 2.6 (1.6-4.1), 6.9 (4.2-11.3), 13.2 (7.2-24.1), 92.6 (16.7-515.0) for patients in their 60s, 70s, 80s, and 90s, respectively. CONCLUSIONS: In this cohort study, age had a great effect on mortality in COVID-19 patients undergoing IMV, after adjusting for variables independently associated with mortality. This study suggested that age was associated with higher mortality and that preventing progression to severe COVID-19 in elderly patients may be a great public health issue.