Remimazolam, an ultra-short-acting benzodiazepine rapidly metabolized by carboxylesterase-1, was developed as a promising alternative for ICU sedation. It was anticipated to overcome the unpredictable accumulation associated with midazolam and the hemodynamic/metabolic risks of propofol, offering superior hemodynamic stability and potential benefits in reducing postoperative delirium. Its ultra-short, predictable half-life positioned it as an ideal candidate for facile titration in critically ill patients. However, the trajectory of remimazolam's development for long-term ICU sedation faced a critical setback in Japan. Based on results from the ONO-2745-04 Phase II trial conducted on mechanically ventilated postoperative patients, the development program for the ICU indication was halted in 2013. The central safety concern was the unexpected pharmacokinetic failure observed in a subset of patients receiving continuous infusion for 24 h or longer. Specifically, this subgroup exhibited plasma concentrations of the parent drug far exceeding predicted levels, resulting in significantly delayed awakening and recover. This observation directly challenged the fundamental non-accumulating advantage of the drug. The mechanism is hypothesized to be compromised carboxylesterase-1 activity due to severe critical illness, systemic inflammation, or organ dysfunction—conditions that impair the very non-organ-dependent clearance pathway the drug relies upon. While international experience continues to validate the safe and effective use of remimazolam for short-to-medium-term ICU sedation, the Japanese experience serves as a critical clinical warning. It underscores that even drugs with inherently favorable pharmacokinetic profiles are susceptible to unpredictable parent drug accumulation in the highly heterogeneous and physiologically compromised ICU population during prolonged infusion. Therefore, extreme caution and individualized dosing strategies are warranted for remimazolam use in critically ill patients, especially those with severe systemic dysfunction.
There are few reports on the relationship between intraoperative hypotension and adverse events after off-pump coronary artery bypass (OPCAB). We examined whether hypotension during OPCAB was associated with postoperative adverse events. This single-center retrospective observational study included adult patients who underwent OPCAB and entered the ICU. Vital signs including intraoperative blood pressure were extracted every minute from the electronic anesthesia record. Data on adverse events including AKI, delirium and new-onset atrial fibrillation occurring during the ICU stay and up to the fourth postoperative day were collected. Sixty-three of 255 patients in the analysis developed postoperative adverse outcomes. Left ventricular ejection fraction (LVEF) was significantly lower in patients who experienced adverse events, and other patient background factors before surgery were not significantly different between the patients with and without postoperative adverse outcomes. Intraoperative data were comparable between the two groups. Univariate logistic regression analysis revealed that MAP < 55 mmHg for ≥ 6 min and MAP < 65 mmHg for ≥ 40 min were associated with postoperative adverse outcomes. However, the multivariate logistic regression analyses revealed that intraoperative MAP was not an independent explanatory factor for postoperative adverse events. LVEF < 50
BACKGROUND/AIM:Chemotherapy-induced nausea and vomiting (CINV) remain major challenges during concurrent chemoradiotherapy (CCRT) for cervical cancer. Mannitol and furosemide are agents widely used to prevent cisplatin-induced nephrotoxicity; however, the differences in their effect on CINV have not been characterized. This study aimed to evaluate the impact of concomitant diuretic administration (mannitol versus furosemide) on the incidence and timing of vomiting in patients with cervical cancer undergoing CCRT. PATIENTS AND METHODS:This multicenter, retrospective study evaluated the impact of concomitant diuretic administration on CINV in 485 patients receiving weekly, cisplatin-based CCRT between 2016 and 2024, including 206 who received mannitol and 279 who received furosemide. RESULTS:Vomiting occurred more frequently in the mannitol group than in the furosemide group (18.4% vs. 10.4%). Time-to-event analysis found that vomiting occurred earlier with mannitol during the entire CCRT course. CONCLUSION:These findings may reflect mannitol's osmotic properties and the increased, intestinal permeability associated with CCRT-related mucosal injury. To the best of our knowledge, this study is the largest investigation to date comparing diuretic agents in this setting. The results suggested that furosemide may be a more appropriate option for patients with a high risk of CINV.
We report a rare case of neuropsychiatric (NP) systemic lupus erythematosus (NPSLE) manifesting as brainstem encephalitis with generalized lymphadenopathy. A 32-year-old woman developed altered consciousness, fever, and pancytopenia, with diffusion-restricted brainstem lesions and elevated soluble interleukin-2 receptor (sIL-2R) levels in both serum and cerebrospinal fluid (CSF), accompanied by systemic lymphadenopathy and cytopenia, strongly mimicking malignant lymphoma. Histopathology excluded malignancy. The patient underwent immunosuppressive therapy with corticosteroids and cyclophosphamide, leading to marked neurological improvement. This case highlights the diagnostic challenge in differentiating NPSLE with brainstem involvement from lymphoproliferative disorders and underscores the importance of early biopsy and prompt immunosuppressive intervention to achieve favorable outcomes.
