Daily Anesthesiology Research Analysis

BACKGROUND: Tonsillectomy is one of the most frequently performed pediatric surgeries; however, little evidence guides the choice of intraoperative opioids in a population at an elevated risk for perioperative respiratory complications. This study tested the hypothesis that fewer children who received hydromorphone during tonsillectomy would require postoperative "rescue" opioids compared to children who received fentanyl. METHODS: We conducted a triple-blind, randomized, controlled trial to compare intravenous hydromorphone versus fentanyl in pediatric patients undergoing tonsillectomy. Children aged 2-15 years undergoing bilateral tonsillectomy or adenotonsillectomy were assigned (1:1) to receive hydromorphone (10 mcg/kg) or fentanyl (1 mcg/kg) intraoperatively. The primary endpoint was the number of patients who required rescue intravenous opioid analgesia following endotracheal extubation. Secondary endpoints included pain scores, pulse oximetry saturations, postoperative nausea, time in the recovery room, morphine milligram equivalents in the post-anesthesia care unit, and adverse events. RESULTS: A total of 188 children underwent randomization, and 180 were analyzed (90 in each group). The median age was 5 years (interquartile range: 3-7 years). Rescue intravenous opioid was administered to 48 (53%) children who received intraoperative hydromorphone and 66 (73%) children who received intraoperative fentanyl (difference, 20.0 percentage points; 95% confidence interval, 6.2-33.8) (p = 0.005). Children who received hydromorphone also had lower mean pain scores for the first 15 min postoperatively and lower median morphine milligram equivalents. The incidence of adverse events was similar between the two groups. CONCLUSIONS: This study in children undergoing tonsillectomy found that intraoperative hydromorphone resulted in improved analgesia in the recovery room compared to fentanyl. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04230681.

Cardiac complications after major hepatic surgery are frequent, yet how hepatic ischemia-reperfusion injury (HIRI) damages the remote heart is unknown. In 382 hepatectomy patients, the incidence of myocardial injury after noncardiac surgery (MINS) rose from 20.5% to 50% with increasing postoperative liver damage severity (P < 0.0001). In a murine HIRI model, cardiac dysfunction lagged behind hepatic injury; circulating ATP surged within one hour of reperfusion from the ischemic liver and was both sufficient and necessary to drive remote cardiac damage. Extracellular ATP activated the P2X7 receptor on cardiac macrophages, triggering NLRP3 inflammasome assembly and gasdermin D (GSDMD)-dependent cardiomyocyte pyroptosis; siRNA-based dominant-gating co-culture identified macrophage P2X7 as the upstream gating step, with cardiomyocyte-side P2X7 knockdown failing to abrogate downstream pyroptosis. Single-cell profiling traced this program to monocyte-derived macrophages differentiating into inflammatory macrophages, and macrophages amplified hepatocyte-derived ATP into IL-1β-driven cardiomyocyte pyroptosis in vitro. Clodronate-mediated macrophage depletion preserved cardiac function. The selective P2X7 antagonist JNJ-47965567 polarized cardiac macrophages toward an anti-inflammatory phenotype and suppressed NLRP3-GSDMD pyroptosis when administered up to approximately 3hours after reperfusion onset, defining a clinically relevant therapeutic window. Adenosine activated the A2A receptor and attenuated cardiac injury dose-dependently, reversed by SCH-58261, and conferred greater cardiac protection than dexamethasone or N-acetylcysteine. These findings establish cardiac macrophages as amplifiers of liver-derived danger signals and identify the ATP-P2X7/adenosine-A2A purinergic axis as a potential pharmacological target for perioperative cardioprotection.

BACKGROUND: Although widely performed, video-assisted thoracoscopic surgery (VATS) is associated with significant postoperative pain. Thoracic paravertebral block (TPVB) is a guideline-favored regional technique, while intrathecal morphine (ITM) is a technically less demanding and more widely applicable neuraxial alternative. We hypothesized that ITM would provide analgesic efficacy non-inferior to TPVB in terms of 24-hour intravenous morphine milligram equivalents (IV-MME). METHODS: This was a prospective, randomized, controlled, observer-blinded non-inferiority trial. Adults undergoing elective VATS were randomized 1:1 to TPVB (0.25% bupivacaine, 0.4 mL/kg+epinephrine 1:400,000) or ITM (5 mcg/kg based on ideal body weight). The primary endpoint was 24-hour IV-MME (intraoperative opioids excluded). Secondary endpoints included 12-hour IV-MME, pain (Numeric Rating Scale at rest/activity), rescue analgesia, time to first opioid demand, 15-item Quality of Recovery, safety (postoperative nausea/vomiting, pruritus, respiratory depression), and 30-day complications. The prespecified non-inferiority margin was 5.05 mg. Analyses followed intention-to-treat with per-protocol sensitivity. RESULTS: Of 82 screened, 72 were randomized (ITM n=36; TPVB n=36); 2 TPVB conversions to thoracotomy were excluded from the per-protocol set (n=70). For the primary endpoint, the median difference (ITM-TPVB) in 24-hour IV-MME was 6.5 mg (95% CI 1 to 17; p=0.009) in intention-to-treat and 9.0 mg (95% CI 2 to 18; p=0.002) in per-protocol; in both analyses, the upper CI bound exceeded 5.05 mg, and non-inferiority was not met. Individual 24-hour and 12-hour IV-MME favored TPVB; rescue analgesia was more frequent with ITM (21/36 vs 12/36; p=0.033). Pain outcomes, quality of recovery scores, and time to first opioid demand were similar, with no respiratory depression. Although mild 30-day Clavien-Dindo grade I events differed between groups, no apparent clinically meaningful safety signal was observed. CONCLUSIONS: ITM did not demonstrate non-inferiority to TPVB for 24-hour IV-MME; TPVB was associated with lower systemic opioid use, while pain outcomes were similar. TRIAL REGISTRATION NUMBER: NCT07126483.