Daily Anesthesiology Research Analysis

IMPORTANCE: Whether the use of inhaled or intravenous sedation affects outcomes differentially in mechanically ventilated adults with acute respiratory distress syndrome (ARDS) is unknown. OBJECTIVE: To determine the efficacy and safety of inhaled sevoflurane compared with intravenous propofol for sedation in patients with ARDS. DESIGN, SETTING, AND PARTICIPANTS: Phase 3 randomized, open-label, assessor-blinded clinical trial conducted from May 2020 to October 2023 with 90-day follow-up. Adults with early moderate to severe ARDS (defined by a ratio of Pao2 to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure of ≥8 cm H2O) were enrolled in 37 French intensive care units. INTERVENTIONS: Patients were randomized to a strategy of inhaled sedation with sevoflurane (intervention group) or to a strategy of intravenous sedation with propofol (control group) for up to 7 days. MAIN OUTCOMES AND MEASURES: The primary end point was the number of ventilator-free days at 28 days; the key secondary end point was 90-day survival. RESULTS: Of 687 patients enrolled (mean [SD] age, 65 [12] years; 30% female), 346 were randomized to sevoflurane and 341 to propofol. The median total duration of sedation was 7 days (IQR, 4 to 7) in both groups. The number of ventilator-free days through day 28 was 0.0 days (IQR, 0.0 to 11.9) in the sevoflurane group and 0.0 days (IQR, 0.0 to 18.7) in the propofol group (median difference, -2.1 [95% CI, -3.6 to -0.7]; standardized hazard ratio, 0.76 [95% CI, 0.50 to 0.97]). The 90-day survival rates were 47.1% and 55.7% in the sevoflurane and propofol groups, respectively (hazard ratio, 1.31 [95% CI, 1.05 to 1.62]). Among 4 secondary outcomes, sevoflurane was associated with higher 7-day mortality (19.4% vs 13.5%, respectively; relative risk, 1.44 [95% CI, 1.02 to 2.03]) and fewer intensive care unit-free days through day 28 (median, 0.0 [IQR, 0.0 to 6.0] vs 0.0 [IQR, 0.0 to 15.0]; median difference, -2.5 [95% CI, -3.7 to -1.4]) compared with propofol. CONCLUSIONS AND RELEVANCE: Among patients with moderate to severe ARDS, inhaled sedation with sevoflurane resulted in fewer ventilator-free days at day 28 and lower 90-day survival than sedation with propofol. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04235608.

IMPORTANCE: Norepinephrine is the first-line vasopressor for patients with septic shock. When and whether a second agent, such as vasopressin, should be added is unknown. OBJECTIVE: To derive and validate a reinforcement learning model to determine the optimal initiation rule for vasopressin in adult, critically ill patients receiving norepinephrine for septic shock. DESIGN, SETTING, AND PARTICIPANTS: Reinforcement learning was used to generate the optimal rule for vasopressin initiation to improve short-term and hospital outcomes, using electronic health record data from 3608 patients who met the Sepsis-3 shock criteria at 5 California hospitals from 2012 to 2023. The rule was evaluated in 628 patients from the California dataset and 3 external datasets comprising 10 217 patients from 227 US hospitals, using weighted importance sampling and pooled logistic regression with inverse probability weighting. EXPOSURES: Clinical, laboratory, and treatment variables grouped hourly for 120 hours in the electronic health record. MAIN OUTCOME AND MEASURE: The primary outcome was in-hospital mortality. RESULTS: The derivation cohort (n = 3608) included 2075 men (57%) and had a median (IQR) age of 63 (56-70) years and Sequential Organ Failure Assessment (SOFA) score at shock onset of 5 (3-7 [range, 0-24, with higher scores associated with greater mortality]). The validation cohorts (n = 10 217) were 56% male (n = 5743) with a median (IQR) age of 67 (57-75) years and a SOFA score of 6 (4-9). In validation data, the model suggested vasopressin initiation in more patients (87% vs 31%), earlier relative to shock onset (median [IQR], 4 [1-8] vs 5 [1-14] hours), and at lower norepinephrine doses (median [IQR], 0.20 [0.08-0.45] vs 0.37 [0.17-0.69] µg/kg/min) compared with clinicians' actions. The rule was associated with a larger expected reward in validation data compared with clinician actions (weighted importance sampling difference, 31 [95% CI, 15-52]). The adjusted odds of hospital mortality were lower if vasopressin initiation was similar to the rule compared with different (odds ratio, 0.81 [95% CI, 0.73-0.91]), a finding consistent across external validation sets. CONCLUSIONS AND RELEVANCE: In adult patients with septic shock receiving norepinephrine, the use of vasopressin was variable. A reinforcement learning model developed and validated in several observational datasets recommended more frequent and earlier use of vasopressin than average care patterns and was associated with reduced mortality.

BACKGROUND: Ropivacaine is commonly used in abdominal wall blocks due to its safety profile, and the addition of epinephrine is hypothesized to prolong analgesic duration and reduce systemic absorption. However, previous studies have been limited by non-weight-adjusted dosing and potential pharmacokinetic interactions, and inadequate investigation of the free form of ropivacaine. OBJECTIVE: To characterize and compare the pharmacokinetics of total and free ropivacaine administered at a weight-adjusted dose of 1 mg/kg in Transversus Abdominis Plane (TAP) blocks, with and without epinephrine (1:200 000; 5 µg/mL). METHODS: In this randomized controlled trial, 40 patients undergoing laparoscopic colectomy received bilateral TAP blocks with ropivacaine alone (TAP/E-) or ropivacaine with epinephrine (TAP/E+). Pharmacokinetic parameters, including maximum plasma concentration (Cmax), time to Cmax (Tmax), and area under the concentration-time curve, were assessed over 240 min. Secondary outcomes included α₁-acid glycoprotein (AGP), analgesia, safety, and mean plasma concentration (Cmean). RESULTS: The mean Cmax in the TAP/E+ group (0.531±0.245 µg/mL) was not significantly different from that in the TAP/E- group (0.746±0.428 µg/mL). Epinephrine significantly prolonged Tmax (165 vs 55.9 min in TAP/E-, p<0.001) and reduced Cmean (p=0.005). No serious adverse events occurred, though QT interval prolongation was observed in both groups. CONCLUSION: This study demonstrates that adding epinephrine did not alter the Cmax of ropivacaine in TAP blocks, but did prolong the time to reach Cmax. These findings support the routine inclusion of epinephrine in TAP blocks and provide a basis for multimodal analgesia strategies. TRIAL REGISTRATION NUMBER: NCT04959123.