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.

Saline versus Lactated Ringer's Solution: The Saline or Lactated Ringer's (SOLAR) Trial.

BACKGROUND: Both saline and lactated Ringer's solutions are commonly given to surgical patients. However, hyperchloremic acidosis consequent to saline administration may provoke complications. The authors therefore tested the primary hypothesis that a composite of in-hospital mortality and major postoperative complications is less common in patients given lactated Ringer's solution than normal saline. METHODS: The authors conducted an alternating cohort controlled trial in which adults having colorectal and orthopedic surgery were given either lactated Ringer's solution or normal saline in 2-week blocks between September 2015 and August 2018. The primary outcome was a composite of in-hospital mortality and major postoperative renal, respiratory, infectious, and hemorrhagic complications. The secondary outcome was postoperative acute kidney injury. RESULTS: Among 8,616 qualifying patients, 4,187 (49%) were assigned to lactated Ringer's solution, and 4,429 (51%) were assigned to saline. Each group received a median 1.9 l of fluid. The primary composite of major complications was observed in 5.8% of lactated Ringer's versus 6.1% of normal saline patients, with estimated average relative risk across the components of the composite of 1.16 (95% CI, 0.89 to 1.52; P = 0.261). The secondary outcome, postoperative acute kidney injury, Acute Kidney Injury Network stage I-III versus 0, occurred in 6.6% of lactated Ringer's patients versus 6.2% of normal saline patients, with an estimated relative risk of 1.18 (99.3% CI, 0.99 to 1.41; P = 0.009, significance criterion of 0.007). Absolute differences between the treatment groups for each outcome were less than 0.5%, an amount that is not clinically meaningful. CONCLUSIONS: In elective orthopedic and colorectal surgery patients, there was no clinically meaningful difference in postoperative complications with lactated Ringer's or saline volume replacement. Clinicians can reasonably use either solution intraoperatively.

Association of Neuraxial Anesthesia With Postoperative Venous Thromboembolism After Noncardiac Surgery: A Propensity-Matched Analysis of ACS-NSQIP Database.

BACKGROUND: Neuraxial anesthesia improves components of the Virchow's triad (hypercoagulability, venous stasis, and endothelial injury) which are key pathogenic contributors to venous thrombosis in surgical patients. However, whether neuraxial anesthesia reduces the incidence of venous thromboembolism (VTE) remain unclear. We therefore tested the primary hypothesis that neuraxial anesthesia reduces the incidence of 30-day VTE in adults recovering from orthopedic surgery. Secondarily, we tested the hypotheses that neuraxial anesthesia reduces 30-day readmission, 30-day mortality, and the duration of postoperative hospitalization. METHODS: Inpatient orthopedic surgeries from American College of Surgeons National Surgical Quality Improvement Program database (2011-2015) in adults lasting more than 1 hour with either neuraxial or general anesthesia were included. Groups were matched 1:1 by propensity score matching for appropriate confounders. Logistic regression model was used to assess the effect of neuraxial anesthesia on 30-day VTE, 30-day mortality, and readmission, while Cox proportional hazard regression model was used to assess its effect on length of stay. RESULTS: Neuraxial anesthesia decreased odds of 30-day VTE (odds ratio 0.85, 95% confidence interval, 0.78-0.95; P = .002) corresponding to number-needed-to-treat of 500. Although there was no difference in 30-day mortality, neuraxial anesthesia reduced 30-day readmission (odds ratio 0.90, 98.3% confidence interval, 0.85-0.95; P < .001) corresponding to number-needed-to-treat of 250 and had a shortened hospitalization (2.87 vs 3.11; P < .001). CONCLUSIONS: Neuraxial anesthesia appears to provide only weak VTE prophylaxis, but can be offered as an adjuvant to current thromboprophylaxis in high-risk patients.

Mild Perioperative Hypothermia and Myocardial Injury: A Retrospective Cohort Analysis.

BACKGROUND: We tested the primary hypothesis that final intraoperative esophageal temperature is associated with increased odds of a composite of in-hospital all-cause mortality and myocardial injury within 7 days after noncardiac surgery. Secondary exposures were time-weighted average intraoperative temperature and area <37°C threshold. METHODS: Myocardial injury was defined by postoperative fourth-generation troponin T ≥0.03 ng/mL apparently due to cardiac ischemia. Data were extracted for inpatients who had noncardiac surgery with general anesthesia at the Cleveland Clinic between 2012 and 2015. All had esophageal temperature monitoring and routine postoperative troponin monitoring. We estimated the confounder-adjusted association between final intraoperative esophageal temperature and the collapsed composite with multivariable logistic regression. We similarly estimated associations with time-weighted average intraoperative temperature and area <37°C. RESULTS: Two thousand two hundred ten patients were included. Nearly all final esophageal temperatures were 36°C-37°C. Ninety-seven patients (4.4%) had myocardial injury, and 7 (0.3%) died before discharge. Final intraoperative core temperature was not associated with the collapsed composite: odds ratio, 0.91 (95% confidence interval, 0.68-1.24) per 1°C decrease. Similarly, neither of the secondary exposures was associated with the composite outcome. CONCLUSIONS: We did not observe an association between mild perioperative hypothermia and mortality or myocardial injury in adults having noncardiac surgery. However, the range of final intraoperative temperatures was small and largely restricted to the normothermic range (36°C-37°C). Trials are needed to further assess the effect of temperature on myocardial injury.