Abstract
Background:
Intraoperative hypothermia is common in patients undergoing laparoscopic radical resection for colorectal cancer. This study evaluated the effectiveness of maintaining 2 different intraoperative core temperature targets (36°C and 37°C) compared with routine thermal management in reducing postoperative myocardial injury in this patient population.
Methods:
In this randomized controlled trial, A total of 144 patients were randomly assigned to 1 of 3 groups: routine (target nasopharyngeal temperature ≥35°C), aggressive (≥36°C), or intensive (37°C) thermal management, utilizing a forced-air warming blanket and warm-water mattress. The primary outcome was postoperative myocardial injury, defined as a cardiac troponin I (cTnI) concentration of 0.04 ng/mL or greater. Secondary outcomes included severe arrhythmia, metabolic acidosis, shivering, and Quality of Recovery-15 (QoR-15) scores.
Results:
Postoperative cTnI levels were lower in the aggressive and intensive groups than in the routine group (P <.05). The incidence of myocardial injury was significantly lower in the intensive group than in the routine group (6.5% vs 25.0%; P <.05). The aggressive group had a lower incidence of metabolic acidosis than the routine group (P <.05). The incidence of shivering was lower in both the aggressive and intensive groups than in the routine group (P <.05) and was further reduced in the intensive group compared with that in the aggressive group (P <.05). On postoperative day 1, QoR-15 scores were higher in the aggressive and intensive groups than in the routine group (P <.05), with the intensive group demonstrating a higher score than the aggressive group (P <.05).
Conclusion:
In patients undergoing laparoscopic radical resection for colorectal cancer, targeting a core intraoperative temperature of 37°C significantly reduces the incidence of postoperative myocardial injury.
Keywords: cardiac troponin I, colorectal surgery, hypothermia, myocardial injury, postoperative
1. Introduction
Postoperative mortality within 30 days of surgery accounts for over 4.2 million deaths annually,[1,2] ranking as the third leading cause of death worldwide.[3] Cardiac events are the primary contributor to a substantial portion of these postoperative deaths.[1]
Myocardial injury after noncardiac surgery (MINS) occurs in approximately 20% of patients undergoing major surgery report.[4] The majority of these cases are asymptomatic perioperatively and are detected only through postoperative troponin surveillance.[4,5] MINS is independently and strongly associated with both short- and long-term postoperative mortality regardless of the presence of ischemia or progression to myocardial infarction.[6–8]
A potential contributor to MINS is intraoperative hypothermia, defined as a core body temperature below 36°C.[9] General and regional anesthesia impair normal thermoregulatory control and induce a redistribution of heat from the core to the periphery. These effects, combined with a cold operating room environment and the administration of large volumes of intravenous fluids and blood products, disrupt the balance between heat production and loss, leading to intraoperative hypothermia.[9] Previous studies have shown that most unwarmed surgical patients will develop inadvertent hypothermia. Nevertheless, access to active warming modalities and routine temperature monitoring remains limited for many patients, particularly in low- and middle-income countries.[10,11]
Patients with colorectal cancer are particularly vulnerable to intraoperative hypothermia. They are often of advanced age with compromised nutritional status. Furthermore, preoperative bowel preparation, extensive intraoperative irrigation, and prolonged surgical duration contribute to substantial heat loss, with core temperatures frequently decreasing to 34°C to 35°C. This increased susceptibility to hypothermia may place this population at a higher risk for developing MINS.[12]
Therefore, this study aimed to investigate the effect of different intraoperative core temperature targets on the incidence of postoperative myocardial injury in patients undergoing laparoscopic radical resection for colorectal cancer. We hypothesized that aggressive temperature management, maintaining a core temperature of 36°C or higher would reduce the incidence of MINS compared with conventional management. Furthermore, we hypothesized that intensive targeting a core temperature of 37°C would be even more effective in reducing MINS.
2. Methods
2.1. Study design and ethical approval
This prospective, randomized controlled trial was approved by the Ethics Committee of Xichang People’s Hospital (Ethics number: [2022] Ethical Approval No. 9) and registered with the Chinese Clinical Trials Registry (ChiCTR2300068382) prior to patient enrollment. This study was conducted in accordance with the Declaration of Helsinki, and the manuscript adheres to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Written informed consent was obtained from all participants before the initiation of study procedures.
2.2. Patient population
We enrolled patients older than 45 years with an American Society of Anesthesiologists physical status of I to III who were scheduled for elective laparoscopic radical resection of colorectal cancer at Xichang People’s Hospital between February 2023 and January 2024.
Exclusion criteria at screening were: a preoperative serum cardiac troponin I (cTnI) concentration of 0.04 ng/mL or greater; a body mass index >30 kg/m2; a preoperative core temperature >37.5°C or <36.0°C; and the presence of severe comorbidities, including major cardiovascular disease, renal failure, autoimmune disorders, a recent history of chemoradiotherapy, coagulopathy, or systemic infections. Patients were also excluded from the final analysis if they experienced any of the following: intraoperative blood loss of 800 mL or more, conversion to open laparotomy development of significant subcutaneous emphysema involving 2 or more regions (chest, neck, face, and limbs).
2.3. Randomization and blinding
Eligible patients were randomly assigned in a 1:1:1 ratio to 1 of 3 thermal management groups: the routine group (target nasopharyngeal temperature ≥35°C), the aggressive group (target nasopharyngeal temperature ≥36°C), or intensive (target nasopharyngeal temperature ≥37°C). The allocation sequence was generated by a computer. Allocation concealment was ensured using sequentially numbered, sealed, opaque envelopes, which were opened after obtaining written informed consent. Due to the nature of the intervention, the attending anesthesiologists responsible for intraoperative care were not blinded to group allocation. However, the patients, data collectors, laboratory personnel, and outcome assessors remained blinded throughout the study.
2.4. Anesthesia and monitoring
Prior to anesthesia induction, all patients underwent cannulation of the radial artery for invasive blood monitoring and the internal jugular vein with a double-lumen catheter for central venous access. Standard intraoperative monitoring included continuous electrocardiogram, oximetry, invasive arterial blood pressure, and central venous pressure.
Anesthesia was induced with intravenous midazolam (0.05–0.1 mg·kg−1), sufentanil (0.5–0.8 μg·kg−1), vecuronium (0.1 mg·kg−1), and etomidate (0.2 mg·kg−1). Following tracheal intubation, anesthesia was maintained with a continuous intravenous infusion of remifentanil (0.1 μg·kg−1·min−1) and inhaled sevoflurane (1%–3%) to maintain a bispectral index value between 40 and 60. For postoperative analgesia, all patients received a patient-controlled intravenous analgesia pump for 48 hours. The patient-controlled intravenous analgesia device was programmed to deliver a sufentanil solution (1.5 µg/mL) with the following settings: a continuous basal infusion of 2 mL/h, a patient-administered bolus of 2 mL, and a lockout interval of 30 minutes.
Throughout the procedure, mechanical ventilation was adjusted to maintain an end-tidal carbon dioxide partial pressure between 35 and 45 mm Hg, using a tidal volume of 6 to 8 mL·kg−1, a respiratory rate of 10 to 15 breaths/min, and an inspiratory-to-expiratory ratio of 1:2. The fraction of inspired oxygen was maintained between 60% and 100%. Hemodynamic parameters were managed to keep blood pressure and heart rate within 20% of baseline values. Intraoperative fluid management aimed to maintain a urine output of at least 1 mL·kg−1·h−1 and a hematocrit of 30% or greater. Pneumoperitoneum pressure was maintained at or below 13 mm Hg. The ambient operating room temperature was maintained at 22°C with a relative humidity of 40% to 60%.
2.5. Temperature monitoring and thermal management protocol
Upon arrival in the operating room, tympanic membrane temperature was measured using a ThermoScan infrared thermometer (IRT 6520; Braun, Kronberg, Germany). Following tracheal intubation, a nasopharyngeal temperature probe (MR401B; Mindray, Shenzhen, China) was inserted to continuously monitor core body temperature, with measurements recorded every 15 minutes. All patients were placed on a warm-water mattress (Gaymar Blanket; Maquet, Rastatt, Germany) and covered with cotton sheets.
Patients in the aggressive and intensive groups also had a forced-air warming blanket (IBO-O11; Dacheng, Beijing, China) applied after being positioned in the lithotomy position. This blanket was specifically designed for this position, with 2 sections to individually wrap the lower extremities while leaving the surgical field exposed. The specific thermal management protocols for each group were as follows:
Routine Group: Patients received standard passive insulation. Active warming with the warm-water mattress was initiated only if the nasopharyngeal temperature fell below 35°C. Heating was continued until the temperature reached 35.2°C, at which point the device was deactivated.
Aggressive Group: The target nasopharyngeal temperature was maintained at or above 36°C. The forced-air warmer was set to 42°C. All intravenous fluids and blood products were warmed to 37°C using a fluid warmer. The warm-water mattress was used reactively if the core temperature fell below 36°C despite forced-air warming.
Intensive Group: The target nasopharyngeal temperature was maintained at or above 37°C. The warm-water mattress was pre-warmed to 42°C before the patient entered the operating room. After positioning, the forced-air warmer was set to 42°C, and all intravenous fluids and blood products were warmed to 37°C. The temperatures of both warming devices were adjusted as needed to maintain the target temperature.
3. Outcomes
3.1. Primary outcome
The primary outcome was the incidence of postoperative myocardial injury, which was defined as a peak serum cardiac troponin I (cTnI) concentration of 0.04 ng/mL or greater during the first 48 hours after surgery. This threshold is based on the 99th percentile upper reference limit for the assay used, consistent with the Fourth Universal Definition of Myocardial Infarction.[13] Serum cTnI concentrations were measured using a direct chemiluminescence immunoassay (cTnI kit, IM4407153; Macura, Riyadh, Saudi Arabia). Blood samples for cTnI measurement were collected at baseline (5 minutes after anesthesia induction) and at 6 to 12 hours, 24 hours, and 48 hours postoperatively.
cTnI is a regulatory protein with a high sensitivity and specifcity for myocardial injury, and it often increases in the early postoperative period.[14,15] As troponin screening within the first 2 days postoperatively captures 95% of MINS cases,[4] cTnI levels were assessed at several time points: 5 minutes after anesthesia induction (T0), as well as at 6 to 12 hours (T1), 24 hours (T2), and 48 hours (T3) postoperatively.
3.2. Secondary outcomes
Secondary outcomes were assessed as follows:
Incidence of severe arrhythmia: This was defined as the occurrence of any of the following new-onset arrhythmias within the first 48 postoperative hours: atrial fibrillation, supraventricular tachycardia with a heart rate >120 beats/min, frequent premature ventricular contractions (≥6/min), second-degree Mobitz type II or third-degree atrioventricular block, complete left bundle branch block, or cardiac arrest. Arrhythmias were detected via continuous electrocardiographic monitoring in the post-anesthesia care unit and on the surgical ward.
Incidence of shivering: The occurrence of any shivering within the first 12 hours postoperatively was recorded based on patient self-report and documentation in nursing records.
Incidence of metabolic acidosis: Arterial blood gas analysis was performed at least twice within the first 12 postoperative hours. Metabolic acidosis was defined as a pH <7.35 and a serum bicarbonate concentration <22 mmol/L.
Quality of recovery: Postoperative quality of recovery was assessed using the Chinese-language version of the Quality of Recovery-15 (QoR-15) questionnaire. The QoR-15 was administered preoperatively (as a baseline) and on postoperative days 1 and 2. The questionnaire evaluates 5 domains of functional recovery: physical comfort, emotional state, physical independence, psychological support, and pain. Total scores range from 0 to 150, with higher scores indicating a better quality of recovery.
3.3. Statistical analysis
Statistical analyses were performed using SPSS Statistics, version 26.0 (IBM Corp., Armonk), and figures were created using GraphPad Prism, version 9.0 (GraphPad Software, La Jolla).
Data distribution was assessed for normality using the Shapiro–Wilk test. Normally distributed continuous data are presented as mean ± standard deviation and were compared among the 3 groups using one-way analysis of variance (ANOVA). Post-hoc pairwise comparisons were conducted using the least significant difference test or Tamhane T2 test, depending on the homogeneity of variances. Non-normally distributed continuous data, such as cTnI concentrations, are presented as median [interquartile range, IQR] and were compared using the Kruskal–Wallis test, followed by Dunn test with a Bonferroni correction for pairwise comparisons.
Categorical variables, including the incidence of myocardial injury, postoperative arrhythmia, metabolic acidosis, and shivering, are reported as counts and percentages. These were compared among the groups using the Pearson chi-squared test or Fisher exact test, as appropriate. A Bonferroni correction was applied for post-hoc pairwise comparisons of categorical data.
A 2-tailed P-value <.05 was considered statistically significant. For significant outcomes, relative risks with 95% confidence intervals were calculated for categorical data, and mean or median differences with 95% confidence intervals were calculated for continuous data.
3.4. Sample size calculation
The sample size calculation was based on the primary outcome, the incidence of postoperative myocardial injury. Previous studies have reported incidences of postoperative myocardial injury after colorectal surgery ranging from 4.4% to 7.2%.[16,17] Specifically, 1 study noted an incidence of 4.4% in patients maintained at a core temperature of 36°C to 37°C.[18] Based on these data and our own preliminary observations in 12 patients managed with routine thermal care (target temperature >35°C), where the incidence was 25% (3 of 12), we powered the study to detect a reduction in incidence from 25% in the routine group to 5% in the intensive group.
With a 2-sided significance level (α) of 0.05 and a statistical power (1-β) of 85%, a minimum of 43 patients per group was required, resulting in a total sample size of 129 patients. To account for a potential dropout rate of approximately 10%, we increased the target enrollment to 48 patients per group, for a total sample size of 144 participants. The calculation was performed using PASS 2021 (NCSS, LLC, Kaysville).
4. Results
4.1. Patient enrollment and characteristics
A total of 169 patients scheduled for elective laparoscopic radical resection for colorectal cancer were assessed for eligibility. Of these, 25 were excluded (16 did not meet inclusion criteria and 9 declined participation), leaving 144 patients who were enrolled and randomly assigned to 1 of the 3 thermal management groups (n = 48 per group).
Following randomization, a total of 8 patients were excluded from the final analysis: 4 from the routine group (2 due to conversion to open laparotomy and 2 due to excessive intraoperative blood loss), 2 from the aggressive group (1 due to conversion to laparotomy and 1 due to excessive blood loss), and 2 from the intensive group (1 due to conversion to laparotomy and 1 due to excessive blood loss). Consequently, the per-protocol analysis included 44 patients in the routine group, 46 in the aggressive group, and 46 in the intensive group (Fig. 1).
Figure 1.
Study flowchart outlining patient selection, randomization, and analysis. ASA = American Society of Anesthesiologists, BMI = body mass index, cTnI = cardiac troponin I.
4.2. Baseline characteristics and intraoperative core temperature
There were no statistically significant differences among the 3 groups with respect to patient demographics, preoperative clinical characteristics, or key intraoperative variables, including duration of surgery and intraoperative fluid balance (Table 1).
Table 1.
Baseline characteristics and intraoperative management.
| Routine group (n = 44) | Aggressive group (n = 46) | Intensive group (n = 46) | P-value | |
|---|---|---|---|---|
| Age, years (SD) | 65.0 (7.4) | 62.9 (6.3) | 62.4 (7.5) | .195 |
| Sex | ||||
| Male | 22 (50.0%) | 27 (58.7%) | 28 (60.9%) | .626 |
| Female | 22 (50.0%) | 19 (41.3%) | 18 (39.1%) | |
| Ethnic | ||||
| Han ethnic group | 31 (70.5%) | 27 (58.7%) | 32 (69.6%) | .364 |
| Yi ethnic group | 10 (22.7%) | 18 (39.1%) | 11 (23.9%) | |
| Others | 3 (6.8%) | 1 (2.2%) | 3 (6.5%) | |
| BMI, kg/m2 (SD) | 23.8 (2.7) | 24.8 (2.6) | 23.7 (2.9) | .132 |
| History of cardiovascular risk factors | ||||
| Smoking | 12 (27.3%) | 8 (17.4%) | 14 (30.4%) | .338 |
| Hypertension | 17 (38.6%) | 14 (30.4%) | 15 (32.4%) | .725 |
| Diabetes | 4 (9.1%) | 2 (4.3%) | 6 (13%) | .335 |
| Stroke | 3 (6.8%) | 1 (2.2%) | 1 (2.2%) | .448 |
| Heart disease history | 4 (9.1%) | 7 (15.2%) | 4 (10.9%) | .619 |
| ASA physical status | ||||
| Ⅰ | 2 (4.5%) | 2 (4.3%) | 5 (10.9%) | .647 |
| Ⅱ | 18 (40.9%) | 23 (50.0%) | 19 (40.3%) | |
| Ⅲ | 24 (54.5%) | 21 (45.7%) | 22 (47.8%) | |
| Type of disease | ||||
| Colon cancer | 31 (70.5%) | 35 (76.1%) | 36 (78.3%) | .726 |
| Rectal cancer | 13 (29.5%) | 11 (23.9%) | 10 (21.7%) | |
| MAP, mm Hg (SD) | 93.7 (9.5) | 90.1 (6.5) | 91.3 (9.17) | .123 |
| HR, bpm (SD) | 75.8 (11.6) | 78.4 (11.7) | 75.3 (10.8) | .383 |
| SpO2, % (IQR) | 98 (3) | 98 (3) | 98 (2) | .746 |
| CVP, mm Hg (SD) | 5.9 (1.8) | 6.5 (1.8) | 6.1 (1.9) | .311 |
| Final core temperature, °C (SD) | 35.01 (0.15) | 36.06 (0.15)* | 37.10 (0.16)*,** | <.001 |
| TWA core temperature, °C (SD) | 35.51 (0.15) | 36.15 (0.10)* | 36.84 (0.14)*,** | <.001 |
| Operative duration, min (SD) | 245 (42) | 239 (38) | 229 (32) | .128 |
| Blood loss, mL (IQR) | 50 (60) | 50 (30) | 50 (30) | .872 |
| Urine volume, mL (SD) | 618 (159) | 697 (238) | 709 (224) | .09 |
| Transfusion, mL (SD) | 2568 (518) | 2507 (481) | 2535 (469) | .837 |
ASA = American Society of Anesthesiologists, BMI = body mass index, CVP = central venous pressure, HR = heart rate, IQR = interquartile range, MAP = mean arterial pressure, SD = standard deviation, SpO2, percutaneous arterial oxygen saturation, TWA = time-weighted average.
Values are n (%), mean (SD), or median (IQR).
P <.05, compared with the routine group.
P <.05, compared with the aggressive group. The P-values are corrected using the Bonferroni test for post-hoc pairwise comparison.
The thermal management protocols successfully achieved and maintained a clear separation in intraoperative core temperatures among the groups throughout the procedure (Fig. 2). The mean time-weighted average core temperatures were significantly different among the routine (35.51°C ± 0.15°C), aggressive (36.15°C ± 0.10°C), and intensive (36.84°C ± 0.14°C) groups (P <.001). Similarly, the mean final core temperature measured as patients were leaving the operating room differed significantly: 35.01°C ± 0.15°C in the routine group, 36.06°C ± 0.15°C in the aggressive group, and 37.10°C ± 0.16°C in the intensive group (P <.001) (Table 1).
Figure 2.
Average core temperature over time after anesthesia induction in the routine, aggressive, and intensive groups. The temperature is not shown after 5.5 h, as the surgery continued in <10% of patients. Data are presented as means ± SDs. SDs = standard deviations.
4.3. Primary outcome: postoperative myocardial injury
Baseline serum cTnI concentrations, measured after anesthesia induction, were low and did not differ significantly among the 3 groups (P >.05). Postoperatively, median cTnI concentrations increased in all groups but were significantly lower in both the aggressive and intensive groups compared with the routine group at all measured time points (6–12, 24, and 48 hours; P <.05 for all comparisons). While the median cTnI concentration at 6 to 12 hours was significantly lower in the intensive group than in the aggressive group (P <.05), no significant differences were observed between these 2 groups at 24 and 48 hours (P >.05) (Fig. 3).
Figure 3.
The distribution of the serum cTnI levels in the routine, aggressive, and intensive groups at T0, T1, T2, and T3. cTnI level above the cutoff value of 0.04 ng/mL is considered myocardial injury. The values are presented as medians and IQR of the 3 groups and compared. *P <.05. The P-values were corrected using the Bonferroni test for post hoc pairwise comparison. T0, 5 min after anesthesia induction; T1, postoperative 6 to 12 h; T2, postoperative 24 h; T3, postoperative 48 h. IQR = interquartile range.
The incidence of postoperative myocardial injury (defined as a peak serum cTnI concentration ≥0.04 ng/mL) was 25.0% in the routine group (11 of 44 patients), 10.9% in the aggressive group (5 of 46 patients), and 6.5% in the intensive group (3 of 46 patients).
The primary outcome analysis revealed that the incidence of myocardial injury was significantly lower in the intensive group compared with the routine group (relative risk, 0.26; 95% CI, 0.08–0.83; P = .02). There was no statistically significant difference in the incidence of myocardial injury between the aggressive group and the routine group (relative risk, 0.44; 95% CI, 0.16–1.15; P = .09) or between the intensive group and the aggressive group (relative risk, 0.60; 95% CI, 0.15–2.36; P = .45) (Tables 2 and 3).
Table 2.
Comparison of myocardial injury and postoperative complications.
| Routine group (n = 44) | Aggressive group (n = 46) | Intensive group (n = 46) | P-value | |
|---|---|---|---|---|
| Primary endpoint | ||||
| Myocardial injury | 11 (25.0%) | 5 (10.9%) | 3 (6.5%)* | .031 |
| Secondary endpoint | ||||
| Severe arrhythmia | 6 (13.6%) | 2 (4.3%) | 2 (4.3%) | .176 |
| Supraventricular | 3 | 1 | 1 | |
| Ventricular | 3 | 1 | 1 | |
| Conduction block | 1 | 1 | 0 | |
| Cardiac arrest | 0 | 0 | 0 | |
| metabolic acidosis | 17 (38.6%) | 7 (15.2%)* | 10 (21.7%) | .046 |
| Shivering | 15 (34.1%) | 4 (8.7%)* | 0 (0%)* | <.001 |
| QoR-15 scale | ||||
| Preoperative | ||||
| Physical comfort (SD) | 42.9 (4.2) | 44.0 (3.8) | 42.3 (4.0) | .12 |
| Physical independence (IQR) | 20 (0) | 20 (0) | 20 (0) | .97 |
| Psychological support (IQR) | 20 (0) | 20 (0) | 20 (1) | .544 |
| Pain (IQR) | 20 (0) | 20 (0) | 20 (0) | .481 |
| Emotional status (SD) | 33.7 (3.3) | 33.4 (3.2) | 34.4 (3.4) | .373 |
| Total QoR-15 (SD) | 135.7 (6.0) | 136.8 (4.8) | 135.7 (6.7) | .635 |
| postoperative day 1 | ||||
| Physical comfort (SD) | 31.4 (5.5) | 32.7 (5.3) | 35.4 (4.3)*,** | .001 |
| Physical independence (IQR) | 2 (3) | 3 (3) | 3 (4) | .094 |
| Psychological support (IQR) | 18 (4) | 19 (3) | 19 (3) | .277 |
| Pain (SD) | 12.9 (3.9) | 14.5 (3.0)* | 14.8 (3.0)* | .013 |
| Emotional status (SD) | 30.4 (4.6) | 33.5 (3.6)* | 34.5 (3.3)* | <.001 |
| Total QoR-15 (SD) | 95.5 (9.1) | 103.1 (7.8)* | 107.0 (6.6)*,** | <.001 |
| postoperative day 2 | ||||
| Physical comfort (SD) | 35.1 (5.1) | 36.0 (4.5) | 38.1 (4.2)*,** | .006 |
| Physical independence (IQR) | 5.5 (3.8) | 6 (5) | 7 (5) | .329 |
| Psychological support (IQR) | 18.5 (3.5) | 18 (3) | 19 (1.3) | .365 |
| Pain (SD) | 15.1 (2.7) | 16.5 (2.1)* | 16.3 (2.3)* | .009 |
| Emotional status (SD) | 32.9 (2.5) | 34.7 (2.3)* | 34.3 (2.9)* | .003 |
| Total QoR-15 (SD) | 106.8 (8.9) | 111.4 (7.1)* | 114.1 (6.1)* | <.001 |
Values are n (%), mean (SD), or median (IQR).
IQR = interquartile range, SD = standard deviation.
P <.05, compared with the routine group.
P <.05, compared with the aggressive group. The P-values are corrected using the Bonferroni test for post-hoc pairwise comparison.
Table 3.
Estimated effect sizes of core temperature and outcomes for intergroup comparisons.
| Routine group (n = 44) | Aggressive group (n = 46) | Intensive group (n = 46) | Effect size (95% CI) | ||||
|---|---|---|---|---|---|---|---|
| Measures | Aggressive/routine | Intensive/routine | Intensive/aggressive | ||||
| Final core temperature, °C (SD) | 35.01 (0.15) | 36.06 (0.15) | 37.10 (0.16) | Mean difference | 0.64 (0.57–0.71) | 1.33 (1.26–1.40) | 0.69 (0.63–0.75) |
| TWA core temperature, °C (SD) | 35.51 (0.15) | 36.15 (0.10) | 36.84 (0.14) | Mean difference | 1.05 (0.98–1.13) | 2.10 (2.01–2.17) | 1.04 (0.96–1.12) |
| cTnI level | |||||||
| 5 min after induction of anesthesia (IQR) | 0.009 (0.006) | 0.008 (0.005) | 0.009 (0.006) | Median difference | 0.001 (−0.001 to 0.003) | −0.001 (−0.003 to 0.001) | 0.001 (−0.001 to 0.003) |
| Postoperative 6–12 h (IQR) | 0.029 (0.019) | 0.018 (0.013) | 0.013 (0.012) | Median difference | −0.005 (−0.009 to −0.001) | −0.013 (−0.018 to −0.008) | −0.005 (−0.009 to −0.001) |
| Postoperative 24 h (IQR) | 0.029 (0.020) | 0.019 (0.018) | 0.018 (0.016) | Median difference | −0.001 (−0.006 to 0.003) | −0.009 (−0.016 to −0.003) | −0.001 (−0.006 to 0.003) |
| Postoperative 48 h (IQR) | 0.023 (0.016) | 0.015 (0.013) | 0.014 (0.009) | Median difference | −0.001 (−0.004 to 0.002) | −0.008 (−0.012 to −0.003) | −0.001 (−0.004 to 0.002) |
| Myocardial injury | 11 (23.9%) | 5 (10.9%) | 3 (6.5%) | Relative risk | 0.44 (0.16–1.15) | 0.27 (0.08–0.91) | 0.60 (0.15–2.37) |
| Severe arrhythmia | 6 (13.0%) | 2 (4.3%) | 2 (4.3%) | Relative risk | 0.32 (0.07–1.50) | 0.32 (0.07–1.50) | 1.00 (0.15–6.80) |
| Metabolic | 17 (37.0%) | 7(15.2%) | 10 (21.7%) | Relative risk | 0.39 (0.18–0.86) | 0.56 (0.29–1.09) | 1.43 (0.60–3.43) |
| Shiver | 15 (32.6%) | 4 (8.7%) | 0 (0%) | Relative risk | 0.26 (0.09–0.71) | – | – |
| QoR-15 scale | |||||||
| Preoperatively (SD) | 135.7 (5.8) | 136.8 (4.8) | 135.7 (6.7) | Mean difference | 1.01 (−1.44 to 13.47) | −0.01 (−2.46 to 2.44) | −1.02 (−3.45 to 1.40) |
| Postoperative day 1 (SD) | 95.5 (9.1) | 103.1 (7.8) | 107.0 (6.6) | Mean difference | 7.59(4.23–10.87) | 11.46 (8.17–14.74) | 3.87 (0.62–7.12) |
| Postoperative day 2 (SD) | 107.0 (8.8) | 111.4 (7.1) | 114.1 (6.1) | Mean difference | 4.64 (0.50–8.78) | 7.31 (3.39–11.24) | 2.67 (−0.68 to 6.03) |
Values are n (%), mean (SD), or median (IQR). The P-values are corrected using the Bonferroni test for post hoc pairwise comparison.
CI = confidence interval, IQR = interquartile range, SD = standard deviation.
4.4. Secondary outcomes
The incidences of postoperative complications and patient recovery scores are summarized in Table 2.
Arrhythmias, Acidosis, and Shivering
The incidence of severe arrhythmia did not differ significantly among the 3 groups (13.6% in the routine group vs 4.3% in the aggressive group and 4.3% in the intensive group; P >.05).
The incidence of postoperative metabolic acidosis was significantly lower in the aggressive group (15.2%) compared with the routine group (38.6%; P = .02). However, there was no statistically significant difference between the intensive group (21.7%) and the routine group (P = .11), nor between the intensive and aggressive groups (P = .45).
The incidence of shivering was significantly reduced in both the aggressive group (8.7%) and the intensive group (0%) compared with the routine group (34.1%; P <.01 for both comparisons). Furthermore, the incidence of shivering was significantly lower in the intensive group than in the aggressive group (P = .04).
4.5. Quality of recovery (QoR-15)
There were no significant differences in preoperative baseline QoR-15 scores among the 3 groups (P >.05). Postoperatively, total QoR-15 scores were significantly higher in both the aggressive and intensive groups compared with the routine group on postoperative days 1 and 2 (P <.05 for all comparisons). When comparing the 2 active warming groups, the intensive group had a significantly higher total QoR-15 score on postoperative day 1 than the aggressive group (P <.05), but this difference was no longer significant by postoperative day 2 (P >.05).
Analysis of the QoR-15 subscales revealed that on both postoperative days 1 and 2, patients in the aggressive and intensive groups reported significantly higher scores for the physical comfort, pain, and emotional state domains compared with the routine group (P <.05 for all). The intensive group also demonstrated significantly higher physical comfort scores than the aggressive group on both days (P <.05). In contrast, no significant intergroup differences were found for the physical independence or psychological support domains (P >.05).
5. Discussion
This study examined the efficacy of maintaining intraoperative temperatures at 36°C and 37°C compared to traditional intraoperative temperature management in reducing postoperative myocardial injury. Our findings revealed that both aggressive (36°C) and intensive (37°C) temperature management strategies can effectively reduce cTnI levels following laparoscopic radical resection of colorectal cancer. Moreover, the incidence of postoperative myocardial injury was further reduced with intensive intraoperative body temperature management. These findings highlight the importance of intraoperative temperature management and suggest the significance of selecting an appropriate target temperature for managing patients undergoing laparoscopic radical resection for colorectal cancer. By contrast, a retrospective cohort analysis by Schacham et al[18] reported no association between mild perioperative hypothermia and MINS in adults. However, it is worth noting that their study was confined to the final postoperative temperature range of 36°C to 37°C. In addition, in a previous large multicenter trial conducted by Sessler et al,[19] 5056 patients were randomized into different body temperature management groups targeting 35.6°C or 37.1°C, and the MINS incidence determined using cardiac troponin T (cTnT) levels did not differ significantly (9.0% vs 9.4%, P >.05). Thus, under the corresponding temperatures, the incidence of MINS in Sessler study was consistent with that reported in our study (10.9% and 6.5%, respectively). The negative outcome in these studies may be attributed to the temperature range (above 35.5°C) in the aforementioned studies. However, the intraoperative temperature of patients undergoing colorectal surgery may routinely be ≤35°C. Indeed, a 2015 cohort study reported a mean lowest intraoperative body temperature of 34.3°C,[12] and a previous study reported a mean final intraoperative body temperature of 34.7°C, both in patients undergoing radical resection for colorectal cancer.[20] In a prospective randomized controlled study of patients undergoing laparoscopic radical resection for esophageal cancer, Zhang et al[21] defined MINS using cTnI and high-sensitivity cTnT levels. The study revealed that, compared with hypothermia at 35°C, maintaining the intraoperative body temperature above 36°C could reduce the incidence of MINS (31.4% vs 8.6%, P <.05), which is consistent with our findings. A notable finding was that although targeting a core temperature of 36°C significantly lowered postoperative cTnI concentrations compared with routine care, this did not translate into a statistically significant reduction in the incidence of myocardial injury. This phenomenon likely reflects the statistical limitations inherent in dichotomizing a continuous biomarker. While many patients in the aggressive group experienced a reduction in their peak cTnI, the magnitude of this reduction was insufficient to move a statistically significant number of them below the predefined diagnostic threshold of 0.04 ng/mL. It is possible that our study was underpowered to detect a more modest difference in incidence for this comparison, and a larger trial might have found this difference to be statistically significant. However, the clinical importance of reducing the magnitude of cTnI elevation should not be overlooked. There is substantial evidence that the degree of troponin elevation postoperatively exists on a continuum of risk, where any increase – even that which remains below the threshold for myocardial injury – is independently associated with an increased risk of 30-day and long-term mortality.[22] Therefore, the reduction in peak cTnI concentrations observed in the aggressive group, while not meeting the primary endpoint for incidence, may still represent a clinically meaningful, cardioprotective benefit.
The likely mechanism linking hypothermia to postoperative myocardial injury is a profound physiologic stress response. Hypothermia is a potent trigger for sympathetic nervous system activation and catecholamine release, leading to tachycardia, peripheral vasoconstriction, and an increase in systemic vascular resistance. This cascade increases cardiac workload and myocardial oxygen consumption, which, in the setting of fixed coronary stenoses or perioperative anemia, can precipitate a critical imbalance between myocardial oxygen supply and demand.[23,24] Previous research has confirmed the association between perioperative hypothermia and postoperative arrhythmias,[25] A study by Fank et al[26] encompassing 300 patients, confirmed that perioperative hypothermia is associated with postoperative arrhythmia. Moreover, a meta-analysis suggested that perioperative active warming reduces the risk of postoperative arrhythmia.[27] Consistent with these data, we observed a clinically meaningful, albeit not statistically significant, reduction in the incidence of severe arrhythmia in our active warming groups compared with the routine group (4.3% vs 13.0%).. The lack of statistical significance for this secondary outcome may be attributable to 2 key limitations. First, our arrhythmia surveillance relied on standard telemetry and nursing documentation rather than continuous Holter monitoring, which may have underestimated the true event rate across all groups. Second, and more importantly, our study was powered to detect a difference in the primary outcome of myocardial injury, a more frequent event. Consequently, the trial was likely underpowered to detect a true, but smaller, difference in the incidence of severe arrhythmia.
Our findings also demonstrate that active thermal management is effective in reducing the incidence of postoperative shivering and metabolic acidosis. These complications are not benign; they are markers of significant physiological stress. Shivering, a common consequence of rewarming after hypothermia, imposes a substantial metabolic cost, capable of increasing total body oxygen consumption by up to 40%. These complications are not benign; they are markers of significant physiological stress.[24] Shivering, a common consequence of rewarming after hypothermia, imposes a substantial metabolic cost, capable of increasing total body oxygen consumption by up to 40%.[9,24] Simultaneously, hypothermia impairs tissue oxygen delivery through peripheral vasoconstriction, increased blood viscosity, and a leftward shift of the oxyhemoglobin dissociation curve, predisposing patients to tissue hypoxia and metabolic acidosis. The combination of a massive increase in myocardial oxygen demand (driven by shivering) and a compromised systemic oxygen supply (driven by the direct effects of hypothermia) creates a classic supply-demand mismatch that can precipitate or exacerbate postoperative myocardial injury. Therefore, by mitigating both shivering and metabolic acidosis, effective thermal management likely confers its cardioprotective benefit through multiple synergistic pathways.[28,29]
The improvements in physiological outcomes were mirrored by improvements in patient-reported recovery. We found that both active warming strategies were associated with significantly higher postoperative Quality of Recovery-15 (QoR-15) scores, a validated measure of a patient’s functional and subjective well-being.[30] This finding is not surprising, as the benefits of maintaining normothermia extend beyond cardioprotection. By preventing hypothermia, active warming mitigates a cascade of well-established adverse effects – including thermal discomfort, wound infection, coagulopathy, and delayed drug metabolism – all of which are known to hinder recovery and prolong hospitalization. A patient who is spared these complications will logically report a better overall quality of recovery.[9,31]
6. Limitations
This study has several limitations. First, the single-center design may limit the external validity of our findings, and the results may not be generalizable to institutions with different patient populations or perioperative protocols. Second, while the study was adequately powered for the primary outcome, it was likely underpowered to detect smaller differences in some secondary outcomes, such as severe arrhythmia. Therefore, the nonsignificant findings for these outcomes should be interpreted with caution. Finally, our results are specific to patients undergoing relatively prolonged laparoscopic colorectal surgery, and their applicability to shorter procedures or other types of surgery remains to be determined.
7. Conclusion
In conclusion, among patients undergoing laparoscopic radical resection for colorectal cancer, targeting an intraoperative core temperature of 37°C significantly reduces the incidence of postoperative myocardial injury. This simple, physiology-based intervention represents an important strategy to enhance perioperative cardiac safety in this high-risk population. Large, multicenter randomized trials are warranted to confirm these findings and to evaluate the impact of this intensive thermal management strategy on longer-term cardiovascular outcomes.
Acknowledgments
The authors express their sincere gratitude to all the participants and study personnel involved in this research for their invaluable contributions.
Author contributions
Conceptualization: Wen Wu, Jinqiao Qian.
Data curation: Qiqin Lan, Xi Yuan, Wenmei Xu.
Formal analysis: Wen Wu, Wenmei Xu, Huaqiu Chen.
Funding acquisition: Wen Wu.
Investigation: Qiqin Lan.
Methodology: Wen Wu, Jinqiao Qian.
Supervision: Wen Wu, Xi Yuan, Hao Yin.
Writing – original draft: Wen Wu, Hao Yin.
Writing – review & editing: Wen Wu, Qiqin Lan, Xi Yuan, Hao Yin, Wenmei Xu, Jinqiao Qian.
Abbreviations:
- ANOVA
- single-factor analysis of variance
- cTnI
- cardiac troponin I
- MINS
- myocardial injury after noncardiac surgery
- QoR-15
- quality of recovery-15
- SD
- standard deviation
This work was supported by the Key R&D Project of Science and Technology in Liangshan Yi Autonomous Prefecture (22ZDYF0072 and 23ZDYF0210) and the Science and Technology Project of Xichang City (ZDXM-2023-03).
This trial was approved by the Ethics Committee of the Xichang People’s Hospital (Ethics number: [2022] Ethical Approval No. 9) and registered in the Chinese Clinical Trials Registry (ChiCTR2300068382). This study was conducted in accordance with the principles of the Declaration of Helsinki.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Wu W, Lan Q, Yuan X, Yin H, Xu W, Chen H, Qian J. Effects of temperature management on postoperative myocardial injury in patients undergoing laparoscopic radical resection for colorectal cancer: A randomized controlled trial. Medicine 2026;105:17(e48486).
Contributor Information
Wen Wu, Email: wuwen009@126.com.
Qiqin Lan, Email: lan77abc@163.com.
Xi Yuan, Email: xiyuan111@126.com.
Hao Yin, Email: yinhao032@163.com.
Wenmei Xu, Email: 17781085082@163.com.
Huaqiu Chen, Email: 18181305772@163.com.
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