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Background Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. Methods This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. Results A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. Conclusions In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Regional anesthesia and analgesia reduce the stress response to surgery and decrease the need for volatile anesthesia and opioids, thereby preserving cancer-specific immune defenses. This study therefore tested the primary hypothesis that combining epidural anesthesia–analgesia with general anesthesia improves recurrence-free survival after lung cancer surgery. Methods Adults scheduled for video-assisted thoracoscopic lung cancer resections were randomized 1:1 to general anesthesia and intravenous opioid analgesia or combined epidural–general anesthesia and epidural analgesia. The primary outcome was recurrence-free survival (time from surgery to the earliest date of recurrence/metastasis or all-cause death). Secondary outcomes included overall survival (time from surgery to all-cause death) and cancer-specific survival (time from surgery to cancer-specific death). Long-term outcome assessors were blinded to treatment. Results Between May 2015 and November 2017, 400 patients were enrolled and randomized to general anesthesia alone (n = 200) or combined epidural–general anesthesia (n = 200). All were included in the analysis. The median follow-up duration was 32 months (interquartile range, 24 to 48). Recurrence-free survival was similar in each group, with 54 events (27%) with general anesthesia alone versus 48 events (24%) with combined epidural–general anesthesia (adjusted hazard ratio, 0.90; 95% CI, 0.60 to 1.35; P = 0.608). Overall survival was also similar with 25 events (13%) versus 31 (16%; adjusted hazard ratio, 1.12; 95% CI, 0.64 to 1.96; P = 0.697). There was also no significant difference in cancer-specific survival with 24 events (12%) versus 29 (15%; adjusted hazard ratio, 1.08; 95% CI, 0.61 to 1.91; P = 0.802). Patients assigned to combined epidural–general had more intraoperative hypotension: 94 patients (47%) versus 121 (61%; relative risk, 1.29; 95% CI, 1.07 to 1.55; P = 0.007). Conclusions Epidural anesthesia–analgesia for major lung cancer surgery did not improve recurrence-free, overall, or cancer-specific survival compared with general anesthesia alone, although the CI included both substantial benefit and harm. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Experimental and observational research suggests that combined epidural–general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural–general anesthesia improves long-term survival in elderly patients. Methods This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. Results Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural–general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural–general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural–general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural–general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. Conclusions In elderly patients having major thoracic and abdominal surgery, combined epidural–general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation–guided intraoperative care reduces postoperative nausea and vomiting. Methods This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation–guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality. Results Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation–guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P < 0.001; forearm, 53 vs. 245% · min, P < 0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation–guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study. Conclusions In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation–guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background Delirium is a common and serious postoperative complication, especially in the elderly. Epidural anesthesia may reduce delirium by improving analgesia, reducing opioid consumption, and blunting stress response to surgery. This trial therefore tested the hypothesis that combined epidural–general anesthesia reduces the incidence of postoperative delirium in elderly patients recovering from major noncardiac surgery. Methods Patients aged 60 to 90 yr scheduled for major noncardiac thoracic or abdominal surgeries expected to last 2 h or more were enrolled. Participants were randomized 1:1 to either combined epidural–general anesthesia with postoperative epidural analgesia or general anesthesia with postoperative intravenous analgesia. The primary outcome was the incidence of delirium, which was assessed with the Confusion Assessment Method for the Intensive Care Unit twice daily during the initial 7 postoperative days. Results Between November 2011 and May 2015, 1,802 patients were randomized to combined epidural–general anesthesia (n = 901) or general anesthesia alone (n = 901). Among these, 1,720 patients (mean age, 70 yr; 35% women) completed the study and were included in the intention-to-treat analysis. Delirium was significantly less common in the combined epidural–general anesthesia group (15 [1.8%] of 857 patients) than in the general anesthesia group (43 [5.0%] of 863 patients; relative risk, 0.351; 95% CI, 0.197 to 0.627; P < 0.001; number needed to treat 31). Intraoperative hypotension (systolic blood pressure less than 80 mmHg) was more common in patients assigned to epidural anesthesia (421 [49%] vs. 288 [33%]; relative risk, 1.47, 95% CI, 1.31 to 1.65; P < 0.001), and more epidural patients were given vasopressors (495 [58%] vs. 387 [45%]; relative risk, 1.29; 95% CI, 1.17 to 1.41; P < 0.001). Conclusions Older patients randomized to combined epidural-general anesthesia for major thoracic and abdominal surgeries had one third as much delirium but 50% more hypotension. Clinicians should consider combining epidural and general anesthesia in patients at risk of postoperative delirium, and avoiding the combination in patients at risk of hypotension. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Suboptimal tissue perfusion and oxygenation during surgery may be responsible for postoperative nausea and vomiting in some patients. This trial tested the hypothesis that muscular tissue oxygen saturation-guided intraoperative care reduces postoperative nausea and vomiting.This multicenter, pragmatic, patient- and assessor-blinded randomized controlled (1:1 ratio) trial was conducted from September 2018 to June 2019 at six teaching hospitals in four different cities in China. Nonsmoking women, 18 to 65 yr old, and having elective laparoscopic surgery involving hysterectomy (n = 800) were randomly assigned to receive either intraoperative muscular tissue oxygen saturation-guided care or usual care. The goal was to maintain muscular tissue oxygen saturation, measured at flank and on forearm, greater than baseline or 70%, whichever was higher. The primary outcome was 24-h postoperative nausea and vomiting. Secondary outcomes included nausea severity, quality of recovery, and 30-day morbidity and mortality.Of the 800 randomized patients (median age, 50 yr [range, 27 to 65]), 799 were assessed for the primary outcome. The below-goal muscular tissue oxygen saturation area under the curve was significantly smaller in patients receiving muscular tissue oxygen saturation-guided care (n = 400) than in those receiving usual care (n = 399; flank, 50 vs. 140% · min, P0.001; forearm, 53 vs. 245% · min, P0.001). The incidences of 24-h postoperative nausea and vomiting were 32% (127 of 400) in the muscular tissue oxygen saturation-guided care group and 36% (142 of 399) in the usual care group, which were not significantly different (risk ratio, 0.89; 95% CI, 0.73 to 1.08; P = 0.251). There were no significant between-group differences for secondary outcomes. No harm was observed throughout the study.In a relatively young and healthy female patient population, personalized, goal-directed, muscular tissue oxygen saturation-guided intraoperative care is effective in treating decreased muscular tissue oxygen saturation but does not reduce the incidence of 24-h posthysterectomy nausea and vomiting.

Background Patients admitted to the intensive care unit (ICU) after surgery often develop sleep disturbances. The authors tested the hypothesis that low-dose dexmedetomidine infusion could improve sleep architecture in nonmechanically ventilated elderly patients in the ICU after surgery. Methods This was a pilot, randomized controlled trial. Seventy-six patients age 65 yr or older who were admitted to the ICU after noncardiac surgery and did not require mechanical ventilation were randomized to receive dexmedetomidine (continuous infusion at a rate of 0.1 μg kg−1 h−1; n = 38) or placebo (n = 38) for 15 h, i.e., from 5:00 pm on the day of surgery until 8:00 am on the first day after surgery. Polysomnogram was monitored during the period of study-drug infusion. The primary endpoint was the percentage of stage 2 non–rapid eye movement (stage N2) sleep. Results Complete polysomnogram recordings were obtained in 61 patients (30 in the placebo group and 31 in the dexmedetomidine group). Dexmedetomidine infusion increased the percentage of stage N2 sleep from median 15.8% (interquartile range, 1.3 to 62.8) with placebo to 43.5% (16.6 to 80.2) with dexmedetomidine (difference, 14.7%; 95% CI, 0.0 to 31.9; P = 0.048); it also prolonged the total sleep time, decreased the percentage of stage N1 sleep, increased the sleep efficiency, and improved the subjective sleep quality. Dexmedetomidine increased the incidence of hypotension without significant intervention. Conclusions In nonmechanically ventilated elderly patients who were admitted to the ICU after noncardiac surgery, the prophylactic low-dose dexmedetomidine infusion may improve overall sleep quality.

Patients admitted to the intensive care unit (ICU) after surgery often develop sleep disturbances. The authors tested the hypothesis that low-dose dexmedetomidine infusion could improve sleep architecture in nonmechanically ventilated elderly patients in the ICU after surgery.This was a pilot, randomized controlled trial. Seventy-six patients age 65 yr or older who were admitted to the ICU after noncardiac surgery and did not require mechanical ventilation were randomized to receive dexmedetomidine (continuous infusion at a rate of 0.1 μg kg h; n = 38) or placebo (n = 38) for 15 h, i.e., from 5:00 PM on the day of surgery until 8:00 AM on the first day after surgery. Polysomnogram was monitored during the period of study-drug infusion. The primary endpoint was the percentage of stage 2 non-rapid eye movement (stage N2) sleep.Complete polysomnogram recordings were obtained in 61 patients (30 in the placebo group and 31 in the dexmedetomidine group). Dexmedetomidine infusion increased the percentage of stage N2 sleep from median 15.8% (interquartile range, 1.3 to 62.8) with placebo to 43.5% (16.6 to 80.2) with dexmedetomidine (difference, 14.7%; 95% CI, 0.0 to 31.9; P = 0.048); it also prolonged the total sleep time, decreased the percentage of stage N1 sleep, increased the sleep efficiency, and improved the subjective sleep quality. Dexmedetomidine increased the incidence of hypotension without significant intervention.In nonmechanically ventilated elderly patients who were admitted to the ICU after noncardiac surgery, the prophylactic low-dose dexmedetomidine infusion may improve overall sleep quality.