Trial Outcomes & Findings for Perioperative Hypothermia and Myocardial Injury After Non-cardiac Surgery (NCT NCT03111875)

Last Updated: 2023-08-01

Results Overview

The primary outcome was a composite of myocardial injury after non-cardiac surgery, non-fatal cardiac arrest, and all-cause mortality within 30 days of surgery. Myocardial injury was diagnosed when available troponin concentrations exceeded generation-specific and type-specific thresholds and were apparently of ischaemic origin (ie, no other obvious cause for artifactual elevation). We used the following thresholds based on available literature at time of adjudication: 1) non-high-sensitivity (fourth-generation) troponin T ≥0.03 ng/ml2; 2) high-sensitivity troponin T ≥65 ng/L; or high-sensitivity troponin T 20-64 ng/L and an increase ≥5 ng/L from baseline3; 3) high-sensitivity troponin I (Abbott assay) is ≥75 ng/L4; 4) high-sensitivity troponin I (Siemens assay) is ≥60 ng/L5; or, 5) troponin I (other assays) greater than local 99th percentiles. Myocardial infarction diagnosis required both troponin elevation and at least one diagnostic symptom or sign.

Recruitment status

COMPLETED

Study phase

Target enrollment

5056 participants

Primary outcome timeframe

From the end of surgery to 30 days after surgery

Results posted on

2023-08-01

Participant Flow

4 more patients were enrolled due to potential withdrawal.

4 more patients than protocol were enrolled due to potential withdrawal. Thus we have a total of 5056 patients enrolled in the actual trial rather than 5052 specified in the protocol.

Participant milestones

Participant milestones
Measure	Routine Thermal Management Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Overall Study STARTED	2529	2527
Overall Study COMPLETED	2506	2507
Overall Study NOT COMPLETED	23	20

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Routine Thermal Management n=2506 Participants Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2507 Participants Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.	Total n=5013 Participants Total of all reporting groups
Age, Continuous	67.2 years STANDARD_DEVIATION 8 • n=2506 Participants	67.4 years STANDARD_DEVIATION 8 • n=2507 Participants	67.3 years STANDARD_DEVIATION 8 • n=5013 Participants
Sex: Female, Male Female	801 Participants n=2502 Participants • Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.	836 Participants n=2504 Participants • Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.	1637 Participants n=5006 Participants • Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.
Sex: Female, Male Male	1701 Participants n=2502 Participants • Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.	1668 Participants n=2504 Participants • Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.	3369 Participants n=5006 Participants • Baseline data were missing in three patients in the aggressive warming group and four patients in the routine thermal management group.
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Body mass index, kg/m^2	23.2 kg/m^2 STANDARD_DEVIATION 3 • n=2506 Participants	23.4 kg/m^2 STANDARD_DEVIATION 3 • n=2507 Participants	23.3 kg/m^2 STANDARD_DEVIATION 3 • n=5013 Participants
Type of surgery Orthopaedic	49 Participants n=2506 Participants	56 Participants n=2507 Participants	105 Participants n=5013 Participants
Type of surgery Laparoscopic	1301 Participants n=2506 Participants	1313 Participants n=2507 Participants	2614 Participants n=5013 Participants
Type of surgery Open abdominal	613 Participants n=2506 Participants	610 Participants n=2507 Participants	1223 Participants n=5013 Participants
Type of surgery Neurosurgical	89 Participants n=2506 Participants	126 Participants n=2507 Participants	215 Participants n=5013 Participants
Type of surgery Urological	138 Participants n=2506 Participants	138 Participants n=2507 Participants	276 Participants n=5013 Participants
Type of surgery Other	312 Participants n=2506 Participants	261 Participants n=2507 Participants	573 Participants n=5013 Participants
Type of surgery Unknown	4 Participants n=2506 Participants	3 Participants n=2507 Participants	7 Participants n=5013 Participants
Type of troponin Low-sensitivity T	199 Participants n=2506 Participants	200 Participants n=2507 Participants	399 Participants n=5013 Participants
Type of troponin High-sensitivity T	825 Participants n=2506 Participants	823 Participants n=2507 Participants	1648 Participants n=5013 Participants
Type of troponin Low-sensitivity I	1482 Participants n=2506 Participants	1484 Participants n=2507 Participants	2966 Participants n=5013 Participants
Timing of surgery Elective	2432 Participants n=2506 Participants	2440 Participants n=2507 Participants	4872 Participants n=5013 Participants
Timing of surgery Urgent or emergent	70 Participants n=2506 Participants	64 Participants n=2507 Participants	134 Participants n=5013 Participants
Timing of surgery Unknown	4 Participants n=2506 Participants	3 Participants n=2507 Participants	7 Participants n=5013 Participants
Risk of surgical site infection Any infection risk	1414 Participants n=2506 Participants	1421 Participants n=2507 Participants	2835 Participants n=5013 Participants
Risk of surgical site infection Colon resection	392 Participants n=2506 Participants	376 Participants n=2507 Participants	768 Participants n=5013 Participants
Risk of surgical site infection Rectal resection	344 Participants n=2506 Participants	378 Participants n=2507 Participants	722 Participants n=5013 Participants
Risk of surgical site infection Other abdominal surgeries	407 Participants n=2506 Participants	397 Participants n=2507 Participants	804 Participants n=5013 Participants
Risk of surgical site infection Contaminated or dirty-infected wound	438 Participants n=2506 Participants	429 Participants n=2507 Participants	867 Participants n=5013 Participants
Cardiac risk Any cardiac risk	1791 Participants n=2506 Participants	1755 Participants n=2507 Participants	3546 Participants n=5013 Participants
Cardiac risk Hypertension requiring treatment	1201 Participants n=2506 Participants	1234 Participants n=2507 Participants	2435 Participants n=5013 Participants
Cardiac risk Diabetes requiring medication (oral or insulin)	466 Participants n=2506 Participants	534 Participants n=2507 Participants	1000 Participants n=5013 Participants
Cardiac risk End-stage renal failure requiring dialysis	2 Participants n=2506 Participants	2 Participants n=2507 Participants	4 Participants n=5013 Participants
Cardiac risk Peripheral vascular disease	23 Participants n=2506 Participants	28 Participants n=2507 Participants	51 Participants n=5013 Participants
Cardiac risk Previous myocardial infarction	46 Participants n=2506 Participants	39 Participants n=2507 Participants	85 Participants n=5013 Participants
Cardiac risk Smoker	610 Participants n=2506 Participants	558 Participants n=2507 Participants	1168 Participants n=5013 Participants
Cardiac risk Congestive heart failure	18 Participants n=2506 Participants	14 Participants n=2507 Participants	32 Participants n=5013 Participants
Cardiac risk Chronic obstructive pulmonary disease	48 Participants n=2506 Participants	52 Participants n=2507 Participants	100 Participants n=5013 Participants
Medication use Any use of the following (beta blockers, Angiotension converting, Angiotension receptor, or Statin)	599 Participants n=2506 Participants	606 Participants n=2507 Participants	1205 Participants n=5013 Participants
Medication use Beta blockers	199 Participants n=2506 Participants	204 Participants n=2507 Participants	403 Participants n=5013 Participants
Medication use Angiotension converting enzyme inhibitors	128 Participants n=2506 Participants	143 Participants n=2507 Participants	271 Participants n=5013 Participants
Medication use Angiotension receptor blockers	197 Participants n=2506 Participants	211 Participants n=2507 Participants	408 Participants n=5013 Participants
Medication use Statin	313 Participants n=2506 Participants	294 Participants n=2507 Participants	607 Participants n=5013 Participants

PRIMARY outcome

Timeframe: From the end of surgery to 30 days after surgery

Population: 16 patients were missing in Routine thermal management and 10 patients were missing in aggressive thermal management group.

Outcome measures

Outcome measures
Measure	Routine Thermal Management n=2490 Participants Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2497 Participants Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Number of Participants With a Composite Outcome Consisted of Myocardial Injury After Non-cardiac Surgery (MINS), Non-fatal Cardiac Arrest, and All-cause Mortality	239 Participants	246 Participants

SECONDARY outcome

Timeframe: From the end of surgery to 30 days after surgery

Population: 20 patients were missing on this outcome in aggressive thermal management group and 27 patients were missing in routine thermal management group

Surgical site infection is defined by US Centers for Disease Control and Prevention criteria. It is consisted of superficial infection, deep infection, and organ-space infection. Superficial infection: Infection involves only skin or subcutaneous tissue of the incision. Deep infection: Infection appears to be related to the operation and infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision. Organ-space infection: Infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation.

Outcome measures

Outcome measures
Measure	Routine Thermal Management n=2479 Participants Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2487 Participants Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Deep or Organ-space Surgical Site Infection	157 Participants	178 Participants

SECONDARY outcome

Timeframe: From surgery start to surgery end

Population: 13 patients missing on this outcome from treatment group and 20 patients missing on this outcome from control group

intraoperative transfusion will be yes if this patient received more than 0 unit of red blood cells.

Outcome measures

Outcome measures
Measure	Routine Thermal Management n=2486 Participants Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2494 Participants Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Number of Patients Requiring Intraoperative Transfusion	236 Participants	254 Participants

SECONDARY outcome

Timeframe: From the day of surgery to the day of discharge, or 30 days after surgery if the patients is still hospitalized

Population: 35 patients were missing on this outcome from treatment group and 41 patients were missing on this outcome from control group

The length of hospital stay in days, censored at 30 days

Outcome measures

Outcome measures
Measure	Routine Thermal Management n=2465 Participants Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2472 Participants Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Duration of Hospitalization	8 days Interval 6.0 to 12.0	8 days Interval 6.0 to 12.0

SECONDARY outcome

Timeframe: From the end of surgery to 30 days after surgery

Population: 59 patients were missing on this outcome from control group and 45 patients were missing on this outcome from treatment group

Readmission to a hospital within a month of surgery

Outcome measures

Outcome measures
Measure	Routine Thermal Management n=2447 Participants Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2462 Participants Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Readmission	135 Participants	161 Participants

Adverse Events

Routine Thermal Management

Serious events: 30 serious events

Other events: 24 other events

Deaths: 24 deaths

Aggressive Thermal Management

Serious events: 17 serious events

Other events: 22 other events

Deaths: 18 deaths

Serious adverse events

Serious adverse events
Measure	Routine Thermal Management n=2506 participants at risk Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2507 participants at risk Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Infections and infestations infection	0.04% 1/2506 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.04% 1/2507 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Renal and urinary disorders Acute kidney injury	0.16% 4/2506 • Number of events 4 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.04% 1/2507 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Blood and lymphatic system disorders blood transfusion issue	0.04% 1/2506 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.00% 0/2507 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Cardiac disorders hypotension	0.24% 6/2506 • Number of events 6 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.16% 4/2507 • Number of events 4 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Gastrointestinal disorders diarrhea or ilues	0.08% 2/2506 • Number of events 2 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.00% 0/2507 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Hepatobiliary disorders Intraoperative liver rupture, abdominal bleeding	0.04% 1/2506 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.00% 0/2507 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Injury, poisoning and procedural complications Injury	0.40% 10/2506 • Number of events 10 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.28% 7/2507 • Number of events 7 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Respiratory, thoracic and mediastinal disorders respiratory disorder	0.20% 5/2506 • Number of events 5 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.08% 2/2507 • Number of events 2 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Vascular disorders vascular disorder	0.00% 0/2506 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.08% 2/2507 • Number of events 2 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.

Other adverse events

Other adverse events
Measure	Routine Thermal Management n=2506 participants at risk Patients assigned to routine thermal management will not be pre-warmed and ambient intraoperative temperature will be maintained near 20°C per routine. Only transfused blood will be warmed. An Multi-Position Upper Body Warming Blanket forced-air cover will be positioned over an appropriate non-operative site, but will not initially be activated. Should core temperature decrease to 35.5°C, the warmer will be activated as necessary to prevent core temperature from decreasing further. routine thermal management: A forced-air cover will be positioned but will not initially be activated. The warmer will be activated when core temperature decrease to 35.5°C.	Aggressive Thermal Management n=2507 participants at risk Patients assigned to aggressive warming will be pre-warmed with a full-body Bair Hugger or Bair Paws cover for ≈30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to ≈43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C, using an Multi-Position Upper Body and Full Access Underbody Warming Blankets forced-air covers when clinically practical. All intravenous fluids will be warmed to body temperature. aggressive warming: Patients will be pre-warming 30 minutes before induction of anesthesia and aggressively warmed during surgery to a target intraoperative core temperature between 37 and 37.5°C.
Cardiac disorders Cardiac disorders	0.20% 5/2506 • Number of events 5 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.20% 5/2507 • Number of events 5 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Gastrointestinal disorders Gastrointestinal disorders	0.08% 2/2506 • Number of events 2 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.00% 0/2507 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
General disorders General disorders	0.04% 1/2506 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.12% 3/2507 • Number of events 3 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Infections and infestations Infections and infestations	0.04% 1/2506 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.08% 2/2507 • Number of events 2 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications	0.40% 10/2506 • Number of events 10 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.32% 8/2507 • Number of events 8 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Nervous system disorders Nervous system disorders	0.00% 0/2506 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.04% 1/2507 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Renal and urinary disorders Renal and urinary disorders	0.00% 0/2506 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.04% 1/2507 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	0.16% 4/2506 • Number of events 4 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.08% 2/2507 • Number of events 2 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.
Vascular disorders Vascular disorders	0.04% 1/2506 • Number of events 1 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.	0.00% 0/2507 • from end of surgery to postoperative 30 days Adverse events were tabulated as a measure of safety. We considered unexpected safety events that were not predefined outcomes to be adverse events. Events were designated serious when they prolonged hospitalisation or were life threatening. Events were reported by site investigators to the central coordination site at the Cleveland Clinic. Each was independently designated as serious or not by two investigators (EYA, MCC, FA-C, and SML) who were blinded to treatment allocation.

Additional Information

Daniel I. Sessler, MD

Cleveland Clinic

Phone: 216-444-4900

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place