Yoshitaka Aoki

Background: Perioperative cardiac arrest is rare but often catastrophic. The use of extracorporeal cardiopulmonary resuscitation (ECPR) with veno-arterial extracorporeal membrane oxygenation in perioperative settings remains limited. This study evaluated the characteristics and outcomes of patients who underwent ECPR for perioperative cardiac arrest. Methods: This retrospective cohort study used data from the Japanese Intensive Care PAtient Database, a nationwide registry of 129 intensive care units (ICUs), covering fiscal years 2015 to 2023. Adults undergoing noncardiac surgery who experienced cardiac arrest before ICU admission were included. Patients were classified as ECPR if veno-arterial extracorporeal membrane oxygenation was documented. The primary outcome was in-hospital mortality. Secondary outcomes were discharge to home, transfer to another facility, ICU mortality, length of hospital stay, and length of ICU stay. Multivariable logistic regression, adjusted for potential confounders, was used to assess the association between ECPR and in-hospital mortality. Results: Among 518 patients with perioperative cardiac arrest, 44 (8.5%) received ECPR. The mean age was 66 yr and 62% were male. Patients who received ECPR had higher severity scores, higher lactate levels, and more frequent use of mechanical ventilation and catecholamines than those without ECPR. Unadjusted in-hospital mortality was significantly higher in the ECPR group (61.4 vs. 34.0%; P = 0.001). In the multivariable logistic regression analysis, no statistically significant association was observed between ECPR and in-hospital mortality (odds ratio, 0.85; 95% CI, 0.37 to 1.97). Conclusions: In this nationwide cohort, ECPR was used in 8.5% of patients with perioperative cardiac arrest in noncardiac surgery. Its effect on in-hospital mortality in the studied population remains inconclusive due to the limited sample size. Further data accumulation is warranted to clarify the clinical role of ECPR in this setting.

Background: The pharmacokinetics of prolonged remimazolam infusion in patients undergoing long-term mechanical ventilation remain unclear. This study aimed to evaluate the pharmacokinetics of remimazolam administered continuously for 24 h. Methods: This open-label pharmacokinetic analysis enrolled patients requiring mechanical ventilation into two groups: the surgical group, which received remimazolam during and after surgery, and the medical ICU group, which received remimazolam in the intensive care unit (ICU). Remimazolam was administered at a fixed rate of 0.1 mg/kg/h for ≥ 24 h, and blood samples were collected at regular intervals. Plasma remimazolam concentrations were measured by tandem mass spectrometry. Results: Twenty patients (10 in each group) completed the study. The median duration of remimazolam infusion was 24.0 h in the surgical group and 102.0 h in the medical ICU group. The steady-state plasma concentrations in both the surgical and medical ICU groups exhibited modest intrasubject variability (4.46–32.73%) and moderate intersubject variability (16.45–31.71%), with all values falling within clinically acceptable intermediate ranges. The plasma remimazolam concentration at the end of infusion was 130.7 ng/mL (95% confidence interval [CI] 115.2–146.1) in the surgical group and 134.3 ng/mL (95% CI 98.7–170.0) in the medical ICU group. Noncompartmental analysis showed that the clearance was 54.3 L/h (95% CI 47.6–61.8) and 55.6 L/h (95% CI 42.8–72.1) ( P = 0.856), while the volume of distribution at steady state was 284 L (95% CI 215–376) and 316 L (95% CI 142–707) ( P = 0.780), with no statistically significant differences between the groups. Conclusions: In this preliminary study, both the surgical ICU group (approximately 24 h) and the medical ICU group (beyond 24 h) showed no evidence of time-dependent accumulation of plasma remimazolam, indicating a generally stable pharmacokinetic profile under the examined conditions. Trial registration : In compliance with the Japanese Clinical Trials Act, the study was classified as a Specified Clinical Trial owing to the use of unapproved pharmaceuticals, which were reviewed by a certified review board (CRB) and registered in the Japan Registry of Clinical Trials (jRCTs041200076) on December 15, 2020.

Objectives: Sepsis and septic shock require prompt intervention to improve outcomes. A rapid response team (RRT) system facilitates early recognition and management, including transfer to the ICU, but its impact on clinical outcomes remains unclear. This study assessed the association between RRT activation and clinical outcomes in septic patients initially managed in general wards, in a cohort of predominantly tertiary care hospitals in Japan. Design: Secondary analysis of prospectively collected data from the Japanese Intensive Care PAtient Database (JIPAD) for the fiscal years 2017–2022. Setting: A multicenter study using the JIPAD, which includes 324,037 patients across 95 ICUs in Japan. Patients: We identified 3883 adult patients admitted to the ICU with sepsis or septic shock after initial management in a general ward. Interventions: The patients were divided into those in whom the RRT was activated before ICU admission (the RRT group) and those in whom it was not (the control group). Measurements and Main Results: The primary outcome was in-hospital mortality. Secondary outcomes included rate of discharge to home, ICU mortality, length of hospital stay, and length of ICU stay. All outcome analyses were performed after stabilized inverse probability of treatment weighting using generalized estimating equations to account for clustering at the hospital level. There was no statistically significant difference in-hospital mortality between the RRT group ( n = 850) and the control group ( n = 3033; 38.6% vs. 37.1%; risk difference, 1.4%; 95% CI, –2.8% to 5.6%; p = 0.51). No significant differences were observed in secondary outcomes. Conclusions: In this nationwide study of septic patients requiring ICU admission, RRT activation was not associated with improvement of in-hospital mortality or other clinical outcomes. Despite the widespread implementation of RRTs, their impact on outcomes of sepsis in well-resourced healthcare systems such as Japan remains uncertain.

Purpose The association between postoperative body temperature and in-hospital mortality remains unclear. We sought to evaluate this association across all surgical patients and assessed whether it is affected by the indication for surgery (i.e., surgical source control of infection vs other indications). Methods In a nationwide cohort study, we included critically ill adult patients registered in the Japanese Intensive Care Patient Database who underwent surgery between 2015 and 2021. We evaluated whether the body temperature was associated with in-hospital mortality, and if a differential effect was observed in patients who underwent surgery for source control of infection vs other indications (control group). We categorized the highest body temperatures recorded in the 24 hr after admission following surgery in 0.5-°C intervals and evaluated them using multivariable regression. We conducted a subgroup analysis of patients who underwent surgery for infection control vs other indications. We report the summary estimates using adjusted odds ratios (ORs) and 95% confidence intervals (CIs). We examined the association between body temperature category and in-hospital mortality using cubic spline models to assess nonlinear associations. Results Among 157,028 patients, the overall in-hospital mortality was 2.9%. We observed a U-shaped association of temperature and mortality, with increased mortality at body temperatures < 36.0 °C (OR, 2.15; 95% CI, 1.62 to 2.86) and > 40.0 °C (OR, 1.41; 95% CI, 1.02 to 1.96). We observed the lowest mortality at 37.5–37.9 °C (OR, 0.62; 95% CI, 0.55 to 0.70). Low body temperatures were associated with increased mortality regardless of the presence or absence of infection, while high body temperatures were not associated with increased mortality in patients undergoing surgery for source control of infection. Conclusions In this large nationwide cohort of critically ill surgical patients in Japan, we observed that low and high postoperative body temperatures were associated with increased in-hospital mortality. Nevertheless, we did not observe the association with high body temperature and increased mortality in the subgroup of patients having undergone surgery for infection control.