Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery: a prospective cohort study.

PURPOSE: Postoperative delirium is one of the most common complications after cardiovascular surgery in older adults. Benzodiazepines are a reported risk factor for delirium; however, there are no studies investigating remimazolam, a novel anesthetic agent. Therefore, we prospectively investigated the effect of remimazolam on postoperative delirium. METHODS: We included elective cardiovascular surgery patients aged ≥ 65 years at Hamamatsu University Hospital between August 2020 and February 2022. Patients who received general anesthesia with remimazolam were compared with those who received other anesthetics (control group). The primary outcome was delirium within 5 days after surgery. Secondary outcomes were delirium during intensive care unit stay and hospitalization, total duration of delirium, subsyndromal delirium, and differences in the Mini-Mental State Examination scores from preoperative to postoperative days 2 and 5. To adjust for differences in the groups' baseline covariates, we used stabilized inverse probability weighting as the primary analysis and propensity score matching as the sensitivity analysis. RESULTS: We enrolled 200 patients; 78 in the remimazolam group and 122 in the control group. After stabilized inverse probability weighting, 30.3% of the remimazolam group patients and 26.6% of the control group patients developed delirium within 5 days (risk difference, 3.8%; 95% confidence interval -11.5% to 19.1%; p = 0.63). The secondary outcomes did not differ significantly between the groups, and the sensitivity analysis results were similar to those for the primary analysis. CONCLUSION: Remimazolam was not significantly associated with postoperative delirium when compared with other anesthetic agents.

Obstetric admission to intensive care units in Japan: a cohort study using the Japanese Intensive care PAtient Database.

PURPOSE: This study aimed to describe the epidemiology and annual trends of obstetric patients using a multicenter intensive care database. METHODS: This multicenter, retrospective cohort study used the Japanese Intensive care PAtient Database (JIPAD). We included obstetric patients registered in the JIPAD between 2015 and 2020. We investigated the proportion of obstetric patients among all patients in the intensive care unit (ICU). We also described the characteristics, procedures, and outcomes of obstetric patients. In addition, the annual trends were examined by nonparametric tests for trends. RESULTS: Of the 184,705 patients enrolled in the JIPAD, 750 (0.41%) were obstetric patients from 61 facilities. The median age was 34 years, the number of post-emergency surgeries was 450 (60.0%), and the median APACHE III score was 36. Mechanical ventilation was the most common procedure performed in 247 (32.9%) patients. There were five (0.7%) in-hospital deaths. The proportion of obstetric patients in the ICU did not change between 2015 and 2020 (P for trend = 0.32). However, there was a trend for a significant decrease in the severity of illness and length of hospital stay on an annual basis between 2015 and 2020. Most patients were admitted to the ICU because of a pregnancy-related disorder postoperatively. CONCLUSION: The proportion of obstetric patients was 0.41% of all ICU admissions. The proportion of obstetric patients admitted to the ICU did not change from 2015 to 2020, but the patients' severity of illness and length of hospital stay significantly decreased over time.

Effects of fentanyl administration in mechanically ventilated patients in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Fentanyl is selected to manage pain in critical care patients on mechanical ventilation in the intensive care unit (ICU). However, the usefulness of fentanyl compared with other opioids is unknown. This study examined the evidence for using fentanyl to improve the clinical outcomes of ICU patients, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. METHODS: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases in June 2021. Two independent assessors reviewed studies to identify randomized, controlled trials (RCTs) that compared the intravenous administration of fentanyl and other opioids in mechanically ventilated patients in the ICU. The study quality was assessed using the GRADE system and Cochrane methodology. The primary outcome was mortality. The secondary outcomes were the duration of mechanical ventilation, duration of the ICU stay, incidence of severe adverse events, and incidence of delirium. We integrated outcome data using a random-effects model and showed absolute values and certainty of evidence in the GRADE evidence profile. RESULTS: Seven RCTs met the study inclusion criteria with 534 patients (251 were treated with fentanyl and 283 with other opioids, including 242 with remifentanil and 41 with morphine). Among 191 participants from 2 RCTs, fentanyl was not associated with mortality (risk ratio [RR], 0.79; 95% confidence interval [CI], 0.24 to 2.60; low-quality evidence). Regarding the secondary outcomes, fentanyl did not shorten the duration of mechanical ventilation (mean difference, 0.49 h; 95% CI, - 0.90 to 1.88; moderate-quality evidence) or the duration of the ICU stay (mean difference, 7.04 h; 95% CI, - 3.27 to 17.35; moderate-quality evidence) compared with other opioids. Fentanyl did not increase the incidence of severe adverse events (RR, 0.98; 95% CI, 0.50 to 1.90; low-quality evidence) or delirium (RR, 1.27; 95% CI, 0.79 to 2.04; low-quality evidence). CONCLUSIONS: Although fentanyl is a frequently administered opioid in the ICU, patients' outcomes are not different between fentanyl use and use of other opioids. However, the GRADE evaluation provides little certainty to support the results of this systematic review. Therefore, further large RCTs are required to confirm our conclusions. TRIAL REGISTRATION: PROSPERO, CRD42019130648 ( https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130648 ).

Recall of extubation after remimazolam anesthesia with flumazenil antagonism during emergence: a retrospective clinical study.

PURPOSE: This study was performed to examine and compare the incidence of extubation recall in surgical patients who underwent remimazolam anesthesia with flumazenil antagonism during emergence and in those who underwent propofol anesthesia. METHODS: One hundred sixty-three patients who underwent surgery using general endotracheal or supraglottic airway anesthesia with propofol (n = 97) or remimazolam (n = 66) were retrospectively analyzed. Remimazolam was antagonized by flumazenil after discontinuation of remimazolam at the end of surgery. The endotracheal tube or supraglottic airway was removed after surgery was complete, and consciousness and adequate spontaneous breathing were confirmed. The incidence of extubation recall was compared between the remimazolam and propofol anesthesia groups using propensity score matching. RESULTS: Extubation recall was observed in 28 patients (17%). After propensity score matching, the incidence of extubation recall did not significantly differ between the remimazolam and propofol anesthesia groups (15.6% vs. 18.8%; p = 1.000). CONCLUSION: The incidence of extubation recall after remimazolam anesthesia with flumazenil antagonism during emergence did not significantly differ from that after propofol anesthesia.

Safety and efficacy of remimazolam in induction and maintenance of general anesthesia in high-risk surgical patients (ASA Class III): results of a multicenter, randomized, double-blind, parallel-group comparative trial.

PURPOSE: Remimazolam, an ultra-short-acting benzodiazepine sedative is equally effective as propofol in induction and maintenance of general anesthesia with improved hemodynamic stability in American Society of Anesthesiologists (ASA) Class I and II patients. This trial investigated remimazolam's efficacy and safety in vulnerable patients (ASA Class III) undergoing elective general surgery. METHODS: A multicenter, randomized, double-blind, parallel-group trial in 67 adult surgical patients undergoing general anesthesia with two remimazolam induction doses (6 mg kg-1 h-1-group A and 12 mg kg-1 h-1-group B) has been conducted in 6 trials sites in Japan. Remimazolam was infused up to 2 mg kg-1 h-1 for maintenance of anesthesia in both groups. RESULTS: The functional anesthetic capability of the investigated drug was 100% in both arms. The mean time to loss of consciousness (LoC) was significantly shorter in group B (81.7 s) compared to group A (97.2 s), p = 0.0139. The mean bispectral index (BIS) value during maintenance of anesthesia ranged from 46.0 to 68.0 and from 44.7 to 67.5 in group A and B, respectively. There was no statistically significant difference between the remimazolam arms concerning the incidence of blood pressure (BP) decrease (67.7% in group B vs. 54.8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs). CONCLUSION: Both induction regimens (6 and 12 mg kg-1 h-1) were equally efficacious and safe in surgical patients ASA Class III. A significantly shorter time to LoC was observed with the higher remimazolam dosage. Clinical trial registration This trial is registered with the Japan Pharmaceutical Information Center-Clinical Trials Information (JapicCTI). JapicCTI number: 121977.

Efficacy and safety of remimazolam versus propofol for general anesthesia: a multicenter, single-blind, randomized, parallel-group, phase IIb/III trial.

PURPOSE: This trial was conducted to confirm the non-inferiority of remimazolam versus propofol in the induction and maintenance of general anesthesia in surgical patients. METHODS: Surgical patients (n = 375) were randomized to remimazolam started at 6 or 12 mg/kg/h by continuous intravenous (IV) infusion until the loss of consciousness (LoC), followed by 1 mg/kg/h to be adjusted as appropriate until the end of surgery or IV propofol administered as a slow bolus of 2.0-2.5 mg/kg until LoC followed by 4-10 mg/kg/h until the end of surgery. Efficacy was measured via the combined primary endpoint of no intraoperative awakening/recall, no need for rescue sedatives, and no body movements. Adverse events and adverse drug reactions (ADRs) were monitored for safety. RESULTS: Efficacy rates were 100% in all treatment groups, and the non-inferiority of remimazolam was demonstrated [95% confidence interval (- 0.0487; 0.0250)]. The time to LoC was longer in the remimazolam 6 (p < 0.0001) and 12 mg/kg/h (p = 0.0149) groups versus propofol. The time to extubation was longer in both remimazolam groups versus the propofol group (p ≤ 0.0001). The incidence of ADRs was similar in the remimazolam groups (39.3% and 42.7%, respectively) compared with the propofol group (61.3%). Decreased blood pressure occurred in 20.0% and 24.0% of patients treated with 6 and 12 mg/kg/h remimazolam, respectively, compared with 49.3% of patients receiving propofol. Injection site pain was reported in 18.7% of propofol patients but not in those receiving remimazolam. CONCLUSIONS: This trial demonstrated that remimazolam was well tolerated and non-inferior to propofol with regard to efficacy as a sedative hypnotics for general anesthesia. CLINICAL TRIAL REGISTRATION: This trial is registered with the Japan Pharmaceutical Information Center - Clinical Trials Information (JapicCTI). JapicCTI number: 121973.

1.2% Hydrogen gas inhalation protects the endothelial glycocalyx during hemorrhagic shock: a prospective laboratory study in rats.

PURPOSE: Hydrogen gas (H2) inhalation improved the survival rate of hemorrhagic shock. However, its mechanisms are unknown. We hypothesized that H2 protected the endothelial glycocalyx during hemorrhagic shock and prolonged survival time. METHODS: 83 Sprague-Dawley rats were anesthetized with isoflurane. The animals were randomly assigned to 5 groups: room air with no shock, 1.2% H2 with no shock, room air with shock (Control-S), 1.2% H2 with shock (H21.2%-S), and 3.0% H2 with shock (H23.0%-S). Shock groups were bled to a mean arterial pressure of 30-35 mmHg and held for 60 min, then resuscitated with normal saline at fourfold the amount of the shed blood volume. RESULTS: The syndecan-1 level was significantly lower in the H21.2%-S [8.3 ± 6.6 ng/ml; P = 0.01; 95% confidence interval (CI), 3.2-35.8] than in the Control-S (27.9 ± 17.0 ng/ml). The endothelial glycocalyx was significantly thicker in the H21.2%-S (0.15 ± 0.02 µm; P = 0.007; 95% CI, 0.02-0.2) than in the Control-S (0.06 ± 0.02 µm). The survival time was longer in the H21.2%-S (327 ± 67 min, P = 0.0160) than in the Control-S (246 ± 69 min). The hemoglobin level was significantly lower in the H21.2%-S (9.4 ± 0.5 g/dl; P = 0.0034; 95% CI, 0.6-2.9) than in the Control-S (11.1 ± 0.8 g/dl). However, the H23.0%-S was not significant. CONCLUSIONS: Inhalation of 1.2% H2 gas protected the endothelial glycocalyx and prolonged survival time during hemorrhagic shock. Therapeutic efficacy might vary depending on the concentration.

Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model.

PURPOSE: Heatstroke causes systemic inflammation, followed by vascular endothelial damage. The normal vascular endothelium is coated by endothelial glycocalyx (EGCX). Dexmedetomidine (DEX) has an anti-inflammatory effect, but there has been little investigation on the influence of heatstroke on EGCX and the effect of DEX on this condition. Therefore, we examined whether EGCX was disrupted in heatstroke and if DEX improved survival and preserves EGCX. METHODS: Anesthetized Wistar rats were randomly assigned to three groups: a DEX group treated with DEX (5 µg/kg/h) and 0.9% saline infused continuously at 10 ml/kg/h during heat exposure; a NSS group given 0.9% saline during heat exposure; and a SHAM group given 0.9% saline alone without heat exposure. Heatstroke was induced by exposure to an ambient temperature of 40 °C with relative humidity of 60%. The survival rate was assessed up to 2 h after the start of heat exposure. Plasma levels of syndecan-1 and the thickness of EGCX using electron microscopy were measured when the systolic blood pressure fell to less than 80 mmHg. RESULTS: The survival rate after 2 h of heat exposure was significantly higher in the DEX group compared to the NSS group (89% vs. 22%, P = 0.004). Plasma levels of syndecan-1 were 0.6 ± 1.3, 9.7 ± 5.9, and 2.1 ± 3.4 ng/ml in the SHAM, NSS and DEX groups, respectively (P = 0.013). The thickness of EGCX was significantly higher in the DEX group compared with the NSS group (P = 0.001). CONCLUSIONS: EGCX was disrupted in heatstroke, and DEX improved survival and preserved EGCX.

[Anesthetic Management of Massive Postpartum Haemorrhage in Which Uterine Compression Sutures Were Used].

BACKGROUND: Uteline compression sutures which preserve portion of placenta tends to cause disseminated intravascular coagulation (DIC). But there have been no reports of anesthetic management of massive postpartum haemorrhage in which uterine compression sutures were used. METHODS: We reviewed the anesthetic management of 9 cases of massive postpartum haemorrhage in which uterine compression sutures were used in our hospital from May 2010 until Sep 2012. RESULTS: Seven cases were complicated by DIC (or the possibility of DIC) and required early infusion of blood products. Six cases required the use of ventilators. All cases recovered and were ultimately discharged. CONCLUSIONS: In the cases of massive postpartum haemorrhage in which uterine compression sutures were used, serious blood loss occurred during the operation, leading to a high probability of the development of DIC. Thus, it is necessary to manage DIC immediately.

Treatment of acute exacerbation of idiopathic pulmonary fibrosis with direct hemoperfusion using a polymyxin B-immobilized fiber column improves survival.

BACKGROUND: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) has an extremely poor prognosis and there is currently no effective treatment for this condition. Direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) improves oxygenation, but it is unclear whether treatment of AE-IPF with PMX-DHP affects survival. This study elucidated the effectiveness and safety of PMX-DHP for the treatment of AE-IPF. METHODS: This study included 31 patients with 41 episodes of AE-IPF. All patients received steroids. Of 31, 14 patients (20 episodes) were treated with PMX-DHP. The laboratory and physiological test results after the start of therapy and survival were retrospectively compared between patients treated with and without PMX-DHP. RESULTS: Patients treated with PMX-DHP had a significantly greater change in PaO2/FiO2 ratio (mean ± SEM, 58.2 ± 22.5 vs. 0.7 ± 13.3, p = 0.034) and a smaller change in white blood cell count (-630 ± 959 /µL vs. 4500 ± 1190 /µL, p = 0.002) after 2 days of treatment than patients treated without PMX-DHP. The 12-month survival rate was significantly higher in patients treated with PMX-DHP (48.2% vs. 5.9%, p = 0.041). PMX-DHP was effective in patients with more severe underlying disease (GAP stages II or III; 12-month survival rate 57.1% with PMX-DHP vs. 0% without PMX-DHP, p = 0.021). Treatment with PMX-DHP was an independent predictor of better prognosis (hazard ratio 0.345, p = 0.037). Mild pulmonary thromboembolism occurred in one patient treated with PMX-DHP. CONCLUSIONS: Treatment of AE-IPF with PMX-DHP is tolerable and improves 12-month survival.

[Anesthetic Management of a Patient Complicated with Marfan Syndrome and Suffering from Stanford Type A Aortic Dissection during Pregnancy].

We report a case of a 36-year-old woman at 34 weeks of gestation complicated with Marfan syndrome who underwent Bentall type aortic replacement surgery due to Stanford type A aortic dissection after undergoing caesarean section. Since this patient exhibited severe hypotension before coming to the operating room, it was very difficult to determine whether the cardiac surgery or caesarean section should be performed first. In this case, the caesarean section was performed first, followed by Bentall's surgery. Although intra-aortic balloon pumping and percutaneous cardiopulmonary support were required after weaning from the cardiopulmonary bypass, she was discharged on post-operative day (POD) 40 and the baby was discharged on POD 60, without signs of cerebral palsy. Unfortunately, this patient died on POD 57, due to heart failure. We discuss how to determine the priority of surgeries for patients who require emergency surgery for cardiovascular disease during pregnancy.

Impact of CYP3A5*3 on plasma exposure and urinary excretion of fentanyl and norfentanyl in the early postsurgical period.

BACKGROUND: The pharmacokinetic characteristics of intravenous fentanyl have not been fully clarified in the early postsurgical period. The aim of this study was to evaluate the plasma exposure and urinary excretion of fentanyl and norfentanyl according to cytochrome P450 (CYP) 3A5 genetic polymorphism. METHODS: Fifty-two adult Japanese postoperative patients receiving a continuous intravenous fentanyl infusion were enrolled. Plasma concentrations of fentanyl and norfentanyl were determined at 24 hours after the operation, and their urinary excretion from 12 to 36 hours was evaluated. RESULTS: Plasma concentrations of fentanyl normalized for infusion rate were significantly higher in the *3/*3 group than in the *1 carrier group. The plasma concentration ratio of norfentanyl to fentanyl was significantly lower in the *3/*3 group than in the *1 carrier group. Urinary excretion rates of fentanyl and norfentanyl were 4.4% and 71%, respectively, and no significant differences were observed between the CYP3A5 genotypes. Renal clearance ratios of fentanyl and norfentanyl to creatinine were 0.34 and 3.4, respectively. There were no significant differences in the renal clearance ratios between the genotypes. Free fractions of fentanyl and norfentanyl in human plasma were 4.9% and 95%, respectively. Total and nonrenal clearance of fentanyl were significantly lower in the *3/*3 group than in the *1 carrier group. CONCLUSIONS: CYP3A5*3 affected the plasma exposure of fentanyl but not urinary excretion in our postoperative patients. The renal clearance ratios of fentanyl and norfentanyl to creatinine were much higher than their free fractions in plasma. These findings suggest a slight contribution of renal tubular secretion of fentanyl and norfentanyl to their plasma exposures.

Safety and efficacy of dexmedetomidine for long-term sedation in critically ill patients.

PURPOSE: We evaluated the safety and efficacy of long-term administration of dexmedetomidine in patients in the intensive care unit (ICU). Primary endpoint was the incidence of hypotension, hypertension, and bradycardia. Secondary endpoints were withdrawal symptoms, rebound effects, the duration of sedation with Richmond Agitation-Sedation Scale (RASS) ≤ 0 relative to the total infusion time of dexmedetomidine, and the dose of additional sedatives or analgesics. METHODS: Dexmedetomidine 0.2-0.7 µg/kg/h was continuously infused for maintaining RASS ≤ 0 in patients requiring sedation in the ICU. Safety and efficacy of short-term (≤ 24 h) and long-term (>24 h) dexmedetomidine administration were compared. RESULTS: Seventy-five surgical and medical ICU patients were administered dexmedetomidine. The incidence of hypotension, hypertension, and bradycardia that occurred after 24 h (long-term) was not significantly different from that occurring within 24 h (short-term) (P = 0.546, 0.513, and 0.486, respectively). Regarding withdrawal symptoms, one event each of hypertension and headache occurred after the end of infusion, but both were mild in severity. Increases of mean arterial blood pressure and heart rate after terminating the infusion of dexmedetomidine were not associated with the increasing duration of its infusion. The ratio of duration with RASS ≤ 0 was ≥ 85 % until day 20, except day 9 (70 %) and day 10 (75 %). There was no increase in the dose of additional sedatives or analgesics after the first 24-h treatment period. CONCLUSIONS: Long-term safety of dexmedetomidine compared to its use for 24 h was confirmed. Dexmedetomidine was useful to maintain an adequate sedation level (RASS ≤ 0) during long-term infusion.

Comparison of postoperative nausea and vomiting between remimazolam and propofol: a propensity score-matched, retrospective, observational, single-center cohort study.

BACKGROUND: Remimazolam is a novel ultrashort-acting benzodiazepine that has recently become available for general anesthesia. However, the incidence of postoperative nausea and vomiting (PONV) associated with remimazolam remains unknown. In this propensity score-matched, retrospective, observational study, we compared the rates of PONV between remimazolam and propofol. METHODS: In this retrospective observational study, propensity score-matching was performed to minimize selection bias. Patients who received total intravenous anesthesia with remimazolam or propofol at the Hamamatsu University Hospital between August 2020 and July 2021 were enrolled in the study. Data on patient demographics, anesthetic agents, and PONV within the first 24 h were collected and analyzed. RESULTS: Of the 1,239 patients who met the study selection criteria, 585 received remimazolam and 684 received propofol. After propensity score matching, 333 matched pairs were further analyzed. Patient demographics and the anesthetic agents used were comparable between the matched cohorts. The incidence of PONV was significantly higher in the remimazolam group than in the propofol group (35% vs. 21%, P < 0.001). CONCLUSIONS: The incidence of PONV is higher with remimazolam anesthesia than with propofol anesthesia. The findings of this study require confirmation in larger prospective randomized controlled trials.

Postoperative norepinephrine versus dopamine in patients undergoing noncardiac surgery: a propensity-matched analysis using a nationwide intensive care database.

BACKGROUND: Choosing catecholamines, such as norepinephrine and dopamine, for perioperative blood pressure control is essential for anesthesiologists and intensivists. However, studies specific to noncardiac surgery are limited. Therefore, we aimed to evaluate the effects of postoperative norepinephrine and dopamine on clinical outcomes in adult noncardiac surgery patients by analyzing a nationwide intensive care patient database. METHODS: The Japanese Intensive care PAtient Database (JIPAD) was used for this multicenter retrospective study. Adult patients in the JIPAD who received norepinephrine or dopamine within 24 h after noncardiac surgery in 2018-2020 were included. We compared the norepinephrine and dopamine groups using a one-to-one propensity score matching analysis. The primary outcome was in-hospital mortality. Secondary outcomes were intensive care unit (ICU) mortality, hospital length of stay, and ICU length of stay. RESULTS: A total of 6,236 eligible patients from 69 ICUs were allocated to the norepinephrine (n = 4,652) or dopamine (n = 1,584) group. Propensity score matching was used to create a matched cohort of 1,230 pairs. No differences in the in-hospital mortality was found between the two propensity score matched groups (risk difference: 0.41%, 95% CI [-1.15, 1.96], P = 0.608). Among the secondary outcomes, only the ICU length of stay was significantly shorter in the norepinephrine group than in the dopamine group (median length: 3 vs. 4 days, respectively; P < 0.001). CONCLUSIONS: In adult patients after noncardiac surgery, norepinephrine was not associated with decreased mortality but was associated with a shorter ICU length of stay than dopamine.

Efficacy, safety, and pharmacokinetics of MR13A11A, a generic of remifentanil, for pain management of Japanese patients in the intensive care unit: a double-blinded, fentanyl-controlled, randomized, non-inferiority phase 3 study.

BACKGROUND: The aims of this study were to evaluate the efficacy, safety, and pharmacokinetics (PK) of continuous intravenous administration of remifentanil in mechanically ventilated patients in the intensive care unit (ICU). METHODS: This was a multicenter, randomized, double-blinded, fentanyl-controlled, non-inferiority phase 3 study. Patients aged ≥ 20 years requiring 6 h to 10 days mechanical ventilation in an ICU and requiring pain relief were randomly assigned in a 1:1 ratio to receive either remifentanil (n = 98) or fentanyl (n = 98). Dose was titrated from an infusion rate of 1 mL/h (remifentanil: 0.025 µg/kg/min, fentanyl: 0.1 µg/kg/h) until the target level of analgesia (behavioral pain scale [BPS] ≤ 5 or numerical rating score [NRS] ≤ 3) was achieved by escalating the dose in 1 mL/h increasing. Administration was then adjusted to maintain the target level of analgesia until weaning from the ventilator. The primary endpoint was the proportion of patients who did not require rescue fentanyl. Safety was assessed according to standard procedures. PK of remifentanil in the arterial blood was assessed in 24 patients. RESULTS: The proportion of patients achieving the primary endpoint in the remifentanil and fentanyl groups was 100% (92/92) and 97.8% (88/90), respectively. The difference between the groups was 2.2% (95% confidence interval, - 0.8-5.3) and non-inferiority of remifentanil to fentanyl was verified (p < 0.0001). The incidences of any adverse events in the remifentanil and fentanyl groups was 34 of 92 patients (37.0%) and 34 of 90 patients (37.8%), respectively. Adverse drug reactions was 12 in 92 patients (13.0%) and 15 in 90 patients (16.7%), respectively. In the PK analysis, blood remifentanil concentration decreased within 10 min to almost 50% of the end of administration, suggesting rapid offset of action following discontinuation of remifentanil. CONCLUSIONS: Remifentanil can be used safely for pain management in mechanically ventilated Japanese patients in the ICU. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT2080224954. Registered 20 November 2019, https://jrct.niph.go.jp/latest-detail/jRCT2080224954 .

Effect of remimazolam versus sevoflurane on intraoperative hemodynamics in noncardiac surgery: a retrospective observational study using propensity score matching.

BACKGROUND: This study compared the effects of remimazolam and sevoflurane on intraoperative hemodynamics including intraoperative hypotension (IOH). RESULTS: This study involved adult patients undergoing noncardiac surgery using remimazolam (Group R) or sevoflurane (Group S) for maintenance anesthesia, and invasive arterial pressure measurements, from September 2020 to March 2023 at our hospital. IOH was defined as a mean blood pressure < 65 mmHg occurring for a cumulative duration of at least 10 min. A 1:1 propensity score-matching method was used. The primary endpoint was the occurrence of IOH, and the secondary endpoints were the cumulative hypotensive time, incidence of vasopressor use, and dose of vasopressor used (ephedrine, phenylephrine, dopamine, and noradrenaline). Group R comprised 169 patients, Group S comprised 393 patients, and a matched cohort of 141 patients was created by propensity score matching. There was no significant difference in the incidence of IOH between the two groups (85.1% in Group R vs. 91.5% in Group S, p = 0.138). Patients in Group R had a significantly lower cumulative hypotension duration (55 [18-119] vs. 83 [39-144] min, p = 0.005), vasopressor use (81.6% vs. 91.5%, p = 0.023), and dose of ephedrine (4 [0-8] vs. 12 [4-20] mg, p < 0.001) than those in Group S. There were no significant differences in the doses of other vasopressors between groups. CONCLUSIONS: Compared with sevoflurane, the maintenance of anesthesia with remimazolam was not associated with a decreased incidence of IOH; however, it reduced the cumulative hypotension time, incidence of vasopressor use, and dose of ephedrine.

[Monitoring of brain function].

Despite being the most important of organs, the brain is disproportionately unmonitored compared to other systems such as cardiorespiratory in anesthesia settings. In order to optimize level of anesthesia, it is important to quantify the brain activity suppressed by anesthetic agents. Adverse cerebral outcomes remain a continued problem in patients undergoing various surgical procedures. By providing information on a range of physiologic parameters, brain monitoring may contribute to improve perioperative outcomes. This article addresses the various brain monitoring equipments including bispectral index (BIS), auditory evoked potentials (AEP), near-infrared spectroscopy (NIRS), transcranial Doppler ultrasonography (TCD) and oxygen saturation of the jugular vein (Sjv(O2)).

Association Between the Presence of Pulmonary Hypertension Before Cardiovascular Surgery and the Nephroprotective Effect of Carperitide: A Retrospective Cohort Study.

Introduction We hypothesized that the nephroprotective and diuretic effects of carperitide are effective in patients with pulmonary hypertension. We examined the presence of preoperative pulmonary hypertension and the effects of carperitide. Methods In this retrospective cohort study, we included patients aged 20 years or older who received carperitide during cardiovascular surgery and were admitted to the postoperative intensive care unit. We used hospital data from March 2019 to September 2021. The outcomes were the incidence of acute kidney injury, the number of patients using renal replacement therapy in the intensive care unit, urine volume in the first 24 hours after surgery, and the difference in serum creatinine concentrations between before and after surgery. After adjusting for confounding factors by multivariate analysis, we compared the difference in outcomes with and without preoperative pulmonary hypertension (systolic pulmonary artery pressure ≥36 mmHg). Results The study included 244 patients, with 72 (29.5%) in the pulmonary hypertension group and 172 (70.5%) in the control group. Acute kidney injury occurred in eight (11.1%) patients in the pulmonary hypertension group and in 18 (10.5%) patients in the control group, with no significant difference by logistic regression analysis (odds ratio 1.40, 95% confidence interval 0.54-3.62, p=0.49). Additionally, the use of renal replacement therapy, urine volume at 24 hours postoperatively, and the difference in serum creatinine concentrations were not different between the two groups. Conclusions Our results suggest that the effect of carperitide during cardiovascular surgery is not affected by the presence or absence of pulmonary hypertension.

General anesthesia with remimazolam in a patient with mitochondrial encephalomyopathy: a case report.

BACKGROUND: Systemic anesthetic management of patients with mitochondrial disease requires careful preoperative preparation to administer adequate anesthesia and address potential disease-related complications. The appropriate general anesthetic agents to use in these patients remain controversial. CASE PRESENTATION: A 54-year-old woman (height, 145 cm; weight, 43 kg) diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes underwent elective cochlear implantation. Infusions of intravenous remimazolam and remifentanil guided by patient state index monitoring were used for anesthesia induction and maintenance. Neither lactic acidosis nor prolonged muscle relaxation occurred in the perioperative period. At the end of surgery, flumazenil was administered to antagonize sedation, which rapidly resulted in consciousness. CONCLUSIONS: Remimazolam administration and reversal with flumazenil were successfully used for general anesthesia in a patient with mitochondrial disease.