Aggressive intraoperative warming versus routine thermal management during non-cardiac surgery (PROTECT): a multicentre, parallel group, superiority trial.

BACKGROUND: Moderate intraoperative hypothermia promotes myocardial injury, surgical site infections, and blood loss. Whether aggressive warming to a truly normothermic temperature near 37°C improves outcomes remains unknown. We aimed to test the hypothesis that aggressive intraoperative warming reduces major perioperative complications. METHODS: In this multicentre, parallel group, superiority trial, patients at 12 sites in China and at the Cleveland Clinic in the USA were randomly assigned (1:1) to receive either aggressive warming to a target core temperature of 37°C (aggressively warmed group) or routine thermal management to a target of 35·5°C (routine thermal management group) during non-cardiac surgery. Randomisation was stratified by site, with computer-generated, randomly sized blocks. Eligible patients (aged ≥45 years) had at least one cardiovascular risk factor, were scheduled for inpatient non-cardiac surgery expected to last 2-6 h with general anaesthesia, and were expected to have at least half of the anterior skin surface available for warming. Patients requiring dialysis and those with a body-mass index exceeding 30 kg/m2 were excluded. The primary outcome was a composite of myocardial injury (troponin elevation, apparently of ischaemic origin), non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery, as assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03111875. FINDINGS: Between March 27, 2017, and March 16, 2021, 5056 participants were enrolled, of whom 5013 were included in the intention-to-treat population (2507 in the aggressively warmed group and 2506 in the routine thermal management group). Patients assigned to aggressive warming had a mean final intraoperative core temperature of 37·1°C (SD 0·3) whereas the routine thermal management group averaged 35·6°C (SD 0·3). At least one of the primary outcome components (myocardial injury after non-cardiac surgery, cardiac arrest, or mortality) occurred in 246 (9·9%) of 2497 patients in the aggressively warmed group and in 239 (9·6%) of 2490 patients in the routine thermal management group. The common effect relative risk of aggressive versus routine thermal management was an estimated 1·04 (95% CI 0·87-1·24, p=0·69). There were 39 adverse events in patients assigned to aggressive warming (17 of which were serious) and 54 in those assigned to routine thermal management (30 of which were serious). One serious adverse event, in an aggressively warmed patient, was deemed to be possibly related to thermal management. INTERPRETATION: The incidence of a 30-day composite of major cardiovascular outcomes did not differ significantly in patients randomised to 35·5°C and to 37°C. At least over a 1·5°C range from very mild hypothermia to full normothermia, there was no evidence that any substantive outcome varied. Keeping core temperature at least 35·5°C in surgical patients appears sufficient. FUNDING: 3M and the Health and Medical Research Fund, Food and Health Bureau, Hong Kong. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Sugammadex, neostigmine and postoperative pulmonary complications: an international randomised feasibility and pilot trial.

BACKGROUND: Sugammadex reduces residual neuromuscular blockade after anaesthesia, potentially preventing postoperative pulmonary complications. However, definitive evidence is lacking. We therefore conducted a feasibility and pilot trial for a large randomised controlled trial of sugammadex, neostigmine, and postoperative pulmonary complications. METHODS: Patients aged ≥40 years having elective or expedited abdominal or intrathoracic surgery were recruited in Australia and Hong Kong. Perioperative care was at the discretion of clinicians, except for the use of rocuronium and/or vecuronium for neuromuscular blockade and the randomised intervention (sugammadex or neostigmine) for reversal. Feasibility measurements included recruitment, crossover, acceptability, completeness, and workload. Trial coordinator feedback was systematically sought. Patient-reported quality of life was measured using the EQ-5D-5L score. The primary pilot outcome was the incidence of new pulmonary complications up to hospital discharge (or postoperative day 7 if still in hospital). RESULTS: Among 150 eligible patients, 120 consented to participate (recruitment rate 80%, 95% confidence interval [CI] 73 to 86%). The randomised intervention was administered without crossover to 115 of 117 patients who received reversal (98%, 95% CI 94 to 100%). The protocol was acceptable or highly acceptable to the anaesthetist in 108 of 116 cases (93%, 95% CI 87 to 97%; missing = 4). Four patients of the 120 patients were lost to follow-up at 3 months (3.3%, 95% CI 0.9 to 8.3%). Case report forms were complete at 3 months for all remaining patients. The median time to complete trial processes was 3.5 h (range 2.5-4.5 h). Trial coordinators reported no barriers to trial processes. Patients were aged 64 (standard deviation 11) years, 70 (58%) were male and 50 (42%) were female, and planned surgeries were thoracic (23 [19%]), upper abdominal (41 [34%]), and lower abdominal (56 [47%]). The primary outcome was observed in 5 (8.5%) of the 59 sugammadex patients and 5 (8.2%) of the 61 neostigmine patients (odds ratio 1.02, 95% CI 0.28 to 3.67). CONCLUSIONS: A large international randomised controlled trial of sugammadex, neostigmine and postoperative pulmonary complications in adult patients having abdominal and intrathoracic surgery, including collection of cost-effectiveness evidence for Health Technology Appraisal, is feasible. TRIAL REGISTRATION: Prospectively registered at the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001313921 ) on December 7, 2020. www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380645&isReview=true .

Association of Obstructive Sleep Apnea With Difficult Intubation: Prospective Multicenter Observational Cohort Study.

BACKGROUND: Obstructive sleep apnea (OSA) has been found to be associated with difficult airway, although there is a paucity of prospective studies investigating thresholds of OSA severity with difficult airway outcomes. The aim of this study was to examine the association between OSA and difficult intubation or difficult mask ventilation. We also explored the utility of the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender (STOP-Bang) score for difficult airway prediction. METHODS: The Postoperative Vascular Complications in Unrecognized Obstructive Sleep Apnea (POSA) trial was an international prospective cohort study of surgical patients 45 years or older with one or more cardiac risk factor presenting for noncardiac surgery, with planned secondary analyses of difficult airway outcomes. Multivariable logistic regression analyses tested associations between OSA severity and predictors of difficult airway with difficult intubation or difficult mask ventilation. Overall, 869 patients without prior diagnosis of OSA were screened for OSA risk with the STOP-Bang tool, underwent preoperative sleep study, and had routine perioperative care, including general anesthesia with tracheal intubation. The primary outcome analyzed was difficult intubation, and the secondary outcome was difficult mask ventilation. RESULTS: Based on the sleep studies, 287 (33%), 324 (37%), 169 (20%), and 89 (10%) of the 869 patients had no, mild, moderate, and severe OSA, respectively. One hundred and seventy-two (20%) had a STOP-Bang score of 0-2 (low risk), 483 (55%) had a STOP-Bang score of 3-4 (intermediate risk), and 214 (25%) had a STOP-Bang score 5-8 (high risk). The incidence of difficult intubation was 6.7% (58 of 869), and difficult mask ventilation was 3.7% (32 of 869). Multivariable logistic regression demonstrated that moderate OSA (odds ratio [OR] = 3.26 [95% confidence interval {CI}, 1.37-8.38], adjusted P = .010) and severe OSA (OR = 4.05 [95% CI, 1.51-11.36], adjusted P = .006) but not mild OSA were independently associated with difficult intubation compared to patients without OSA. Relative to scores of 0-2, STOP-Bang scores of 3-4 and 5-8 were associated with increased odds of difficult intubation (OR = 3.01 [95% CI, 1.13-10.40, adjusted P = .046] and 4.38 [95% CI, 1.46-16.36, adjusted P = .014]), respectively. OSA was not associated with difficult mask ventilation, and only increasing neck circumference was found to be associated (adjusted P = .002). CONCLUSIONS: Moderate and severe OSA were associated with difficult intubation, and increasing neck circumference was associated with difficult mask ventilation. A higher STOP-Bang score of 3 or more may be associated with difficult intubation versus STOP-Bang score of 0-2. Anesthesiologists should be vigilant for difficult intubation when managing patients suspected or diagnosed with OSA.

Diagnostic performance of the STOP-Bang questionnaire as a screening tool for obstructive sleep apnea in different ethnic groups.

STUDY OBJECTIVES: The STOP-Bang questionnaire is a concise and easy screening tool for obstructive sleep apnea (OSA). Using modified body mass index (BMI), we assessed the diagnostic performance of the STOP-Bang questionnaire in predicting OSA in ethnically different groups of patients undergoing surgery. METHODS: This was a multicenter prospective cohort study involving patients with cardiovascular risk factors who were undergoing major noncardiac surgery. Patients underwent home sleep apnea testing. All patients completed the STOP-Bang questionnaire. The predictive parameters of STOP-Bang scores were calculated against the apnea-hypopnea index. RESULTS: From 4 ethnic groups 1,205 patients (666 Chinese, 161 Indian, 195 Malay, and 183 Caucasian) were included in the study. The mean BMI ranged from 25 ± 4 to 30 ± 6 kg/m² and mean age ranged from 64 ± 8 to 71 ± 10 years. For the Chinese and Indian patients, diagnostic parameters are presented using BMI threshold of 27.5 kg/m² with the area under curve to predict moderate-to-severe OSA being 0.709 (0.665-0.753) and 0.722 (0.635-0.808), respectively. For the Malay and Caucasian, diagnostic parameters are presented using BMI threshold of 35 kg/m² with the area under curve for predicting moderate-to-severe OSA being 0.645 (0.572-0.720) and 0.657 (0.578-0.736), respectively. Balancing the sensitivity and specificity, the optimal STOP-Bang thresholds for the Chinese, Indian, Malay, and Caucasian groups were determined to be 4 or greater. CONCLUSIONS: For predicting moderate-to-severe OSA, we recommend BMI threshold of 27.5 kg/m² for Chinese and Indian patients and 35 kg/m² for Malay and Caucasian patients. The optimal STOP-Bang threshold for the Chinese, Indian, Malay and Caucasian groups is 4 or greater. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Postoperative Vascular Events in Unrecognized Obstructive Sleep Apnea; URL: https://clinicaltrials.gov/ct2/show/study/NCT01494181; Identifier: NCT01494181.

Impact of Locally Adopted Simulation-Based Crew Resource Management Training on Patient Safety Culture: Comparison Between Operating Room Personnel and General Health Care Populations Pre and Post Course.

Crew resource management (CRM) was introduced to enhance patient safety and reduce medical errors through multidisciplinary learning experience. This study investigates the impact of locally adopted simulation-based CRM training on participants' perceptions and knowledge. A 32-item web-based questionnaire was administered pre course, 1 month, and 1 year post course to assess changes in perceptions and knowledge. Another 12-item paper-based questionnaire was administered immediately post course to assess reactions. Among 712 participants analyzed, 165 were operating room staff. The majority agreed that the training is useful and relevant in daily practice. All participants showed significant improvements in perception and knowledge 1 month post course; however, these improvements declined 1 year post course. The CRM course is associated with satisfactory reaction (Kirkpatrick level 1) and improvement in attitude and knowledge (level 2) toward patient safety. However, the effect may be short-lived and regular refresher courses should be mandatory to sustain momentum of ongoing change.

Association of Unrecognized Obstructive Sleep Apnea With Postoperative Cardiovascular Events in Patients Undergoing Major Noncardiac Surgery.

Importance: Unrecognized obstructive sleep apnea increases cardiovascular risks in the general population, but whether obstructive sleep apnea poses a similar risk in the perioperative period remains uncertain. Objectives: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery. Design, Setting, and Participants: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations. Exposures: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring. Main Outcomes and Measures: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications. Results: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P < .001). No significant interaction effects on perioperative outcomes were observed with type of anesthesia, use of postoperative opioids, and supplemental oxygen therapy. Conclusions and Relevance: Among at-risk adults undergoing major noncardiac surgery, unrecognized severe obstructive sleep apnea was significantly associated with increased risk of 30-day postoperative cardiovascular complications. Further research would be needed to assess whether interventions can modify this risk.

Targeted Genotyping Identifies Susceptibility Locus in Brain-derived Neurotrophic Factor Gene for Chronic Postsurgical Pain.

BACKGROUND: The purpose of this study was to evaluate the association between single-nucleotide polymorphisms and chronic postsurgical pain. METHODS: Using GoldenGate genotyping assays, we genotyped 638 polymorphisms within 54 pain-related genes in 1,152 surgical patients who were enrolled in our Persistent Pain after Surgery Study. Patients were contacted by phone to determine whether they had chronic postsurgical pain at 12 months. Polymorphisms identified were validated in a matched cohort of 103 patients with chronic postsurgical pain and 103 patients who were pain free. The functions of targeted polymorphisms were tested in an experimental plantar incisional nociception model using knock-in mice. RESULTS: At 12 months after surgery, 246 (21.4%) patients reported chronic postsurgical pain. Forty-two polymorphisms were found to be associated with chronic postsurgical pain, 19 decreased the risk of pain, and 23 increased the risk of pain. Patients carrying allele A of rs6265 polymorphism in brain-derived neurotrophic factor (BDNF) had a lower risk of chronic postsurgical pain in the discovery and validation cohorts, with an adjusted odds ratio (95% CI) of 0.62 (0.43 to 0.90) and 0.57 (0.39 to 0.85), respectively. Age less than 65 yr, male sex, and prior history of pain syndrome were associated with an increased risk of pain. Genetic polymorphisms had higher population attributable risk (7.36 to 11.7%) compared with clinical risk factors (2.90 to 5.93%). Importantly, rs6265 is a substitution of valine by methionine at amino acid residue 66 (Val66Met) and was associated with less mechanical allodynia in BDNF mice compared with BDNF group after plantar incision. CONCLUSIONS: This study demonstrated that genetic variant of BDNF rs6265G>A is associated with decreased risk of chronic postsurgical pain.