Targeted Temperature Management on Delayed Neurocognitive Recovery in Older Patients After Major Cancer Surgery

June 17, 2026 updated by: Dong-Xin Wang, Peking University First Hospital

Intraoperative Targeted Temperature Management on Delayed Neurocognitive Recovery in Older Patients After Major Cancer Surgery: a Multicenter Randomized Trial

With aging population, more older patients will receive major surgery for cancer. Older patients are at increased risk of postoperative neurocognitive complications including delayed neurocognitive recovery (dNCR), which is associated with prolonged hospital stay, raised complications, and impaired quality of life. Intraoperative hypothermia occurs in 57.1%-78.6% of patients undergoing major cancer surgery, especially in the elderly. Studies show that intraoperative hypothermia suppresses immunity, interferes with anesthetic metabolism, and delays anesthesia emergence. All these may be correlated with the occurrence of early postoperative dNCR. This study aims to verify whether intraoperative targeted temperature management (target core temperature: 36.8°C) compared with conventional temperature management (core temperature: 35.5°C) can reduce the incidence of dNCR in older patients undergoing major cancer surgery.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

With aging population, more older patients will undergo major surgery for cancer. Due to age-related cognitive decline, cancer-related frailty, as well as impacts from surgical trauma and anesthesia, older patients are at increased risk of postoperative neurocognitive complications including delayed neurocognitive recovery (dNCR), which refers to new-onset cognitive decline within 30 days after surgery. Studies reported that the incidence of dNCR within 7 days ranges from 23.2% to 41.4% in older patients after non-cardiac surgery. Patients with dNCR tend to have prolonged hospital stay, impaired quality of life, and even increased long-term cognitive disorders, and thus imposing a heavy burden on patients, their families, and the healthcare system.

The occurence of dNCR after surgery results from the combined effects of predisposing factors (e.g., advanced age, preoperative cognitive impairment, comorbidities, malnutrition) and precipitating factors (e.g., anesthetic management, surgical stress, residual drug effects, postoperative complications). Among modifiable precipitating factors, unintended intraoperative hypothermia (core temperature <36 °C) is a common yet long underappreciated clinical issue. Due to prolonged operative duration, extensive body cavity exposure, and massive intraoperative fluid and blood transfusion, patients undergoing major cancer surgery have an ncidence of intraoperative hypothermia between 57.1% and 78.6%.

Previous studies demonstrated that a core temperature below 35.5 °C is associated with multiple adverse events, including higher risks of intraoperative bleeding and blood transfusion and postoperative surgical site infections. The international multicenter randomized controlled PROTECT trial enrolled 5,056 patients over 45 years undergoing major non-cardiac surgery but found no significant differences in postoperative myocardial injury, surgical site infection, and blood loss between the routine management group (core temperature 35.5 °C) and the active warming group (core temperature 37 °C); these indicated that maintaining core temperature at 35.5 °C is safe wiith regard to these complications. However, neurocognitive function was not assessed in the PROTECT trial. Whether an intraoperative temperature of 35.5 °C is safe for the neurocognitive outcomes requires further investigation.

The pathogenesis of neurocognitive complications is complex, involving multiple pathological processes such as neuroinflammation, blood-brain barrier disruption, oxidative stress, and hippocampal neuronal injury. Perioperative hypothermia may trigger similar pathophysiological changes. Studies showed that hypothermia suppresses the immune function and promotes the release of peripheral pro-inflammatory cytokines including IL-6 and IL-1β, and thereby exacerbating central neuroinflammation, which is one of the core mechanisms underlying dNCR. Animal experiments demonstrated that hypothermia-induced cognitive dysfunction is associated with damage to hippocampal neurons and reduced expression of proteins related to synaptic plasticity. Furthermore, hypothermia impairs the metabolism of anesthetics and prolongs emergence time, which may contribute to the early manifestations of postoperative cognitive dysfunction.

There is still a lack of definitive evidence regarding whether intraoperative targeted temperature management can reduce dNCR in older patients undergoing major cancer surgery. Meanwhile, there remains debate over the hypothermia threshold and optimal target temperature range. We are currently conducting a multicenter randomized trial to verify whether intraoperative targeted temperature management (36.8 °C) reduces the incidence of delirium within 4 days in older paatients after major cancer surgery. Based on patients enrolled at our institution, this study aims to verify whether intraoperative targeted temperature management (target core temperature: 36.8°C) compared with conventional temperature management (core temperature: 35.5°C) can reduce the incidence of delayed neurocognitive recovery in older patients undergoing major cancer surgery.

Study Type

Interventional

Enrollment (Estimated)

1512

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100034
        • Peking University First Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Age ≥ 65 years.
  2. Planned potentially curative initial cancer surgery with an expected duration of 2 hours or longer under general anesthesia.

Exclusion Criteria:

  1. Preoperative fever (tympanic temperature ≥ 38℃).
  2. Known or suspected preoperative infection.
  3. Previous schizophrenia, epilepsy, Parkinson's disease, myasthenia gravis, or preexisting delirium.
  4. Inability to communicate due to coma, severe dementia, or hearing or speech impairment.
  5. Critically ill patients, defined as NYHA functional class > III or LVEF < 30%, Child-Pugh class C, preoperative dialysis dependence, ASA physical status > IV, or expected survival < 24 hours.
  6. Surgery for breast cancer, intracranial tumors, or rare cancers.
  7. Planned to undergo therapeutic hypothermia.
  8. Body mass index > 30 kg/m² (to facilitate temperature management).
  9. Previous enrollment in this study.
  10. Other conditions deemed unsuitable for study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Targeted Temperature Management Group

The operating room temperature will be maintained at approximately 22°C in accordance with routine clinical practice. Pre-warming with a full-body forced-air warming blanket and/or an electric heating mattress will be performed for 30 minutes before anesthesia induction (initial temperature set at 43°C, which may be adjusted by the investigator according to the patient's comfort or changes in body temperature).

During surgery, all intravenous fluids and blood products administered intraoperatively will be pre-warmed, and fluid/blood warming devices will be used as clinically indicated. Two forced-air warming blankets (or combined with an electric heating mattress) will be used to maintain core temperature. The goal is to maintain core temperature at 36.8°C.
Other: Targeted temperature management

The operating room temperature will be maintained at approximately 22°C in accordance with routine clinical practice. Pre-warming with a full-body forced-air warming blanket and/or an electric heating mattress will be performed for 30 minutes before anesthesia induction (initial temperature set at 43°C, which may be adjusted by the investigator according to the patient's comfort or changes in body temperature).

During surgery, all intravenous fluids and blood products administered intraoperatively will be pre-warmed, and fluid/blood warming devices will be used as clinically indicated. Two forced-air warming blankets (or combined with an electric heating mattress) will be used. The goal is to maintain the patient's core temperature at 36.8°C.
Other: Conventional Temperature Management Group

The operating room temperature will be maintained at approximately 22°C in accordance with routine clinical practice. No pre-warming will be applied to patients prior to anesthesia induction.

During surgery, only blood products will be pre-warmed before transfusion. One forced-air warming blanket will be placed over the patient's upper or lower body, but warming will only be initiated when the core temperature drops below 35.5°C to prevent further temperature reduction. The target core temperature is set at 35.5°C.
Other: Conventional temperature management

The operating room temperature will be maintained at approximately 22°C in accordance with routine clinical practice. No pre-warming will be applied to patients prior to anesthesia induction.

During surgery, only blood products will be pre-warmed before transfusion. One forced-air warming blanket will be placed over the patient's upper or lower body, but warming will only be initiated when the core temperature drops below 35.5°C to prevent further temperature reduction. The target core temperature is set at 35.5°C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of delayed neurocognitive recovery (dNCR)
Time Frame: At 5 days after surgery or before hospital discharge, whichever came first

Cognitive function will be assessed at baseline and at 5 days after surgery (or before hospital discharge) using the Montreal Cognitive Assessment (MoCA; scores range from 0 to 30, with higher scores indicating better cognitive function).

Delayed neurocognitive decline (dNCR) is defined as: a |Z| value of decline in MoCA score ≥1.96. Z value = [(change from baseline in MoCA score in a surgical patient - mean change from baseline in MoCA score in the non-surgical group)] / (standard deviation of change from baseline in MoCA score in the non-surgical group).
At 5 days after surgery or before hospital discharge, whichever came first

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of postoperative delirium
Time Frame: Up to 4 days after surgery
Delirium will be assessed twice daily (8-10 am and 6-8 pm) using the 3-Dimensional Confusion Assessment Method (3D-CAM) for patients without intubation or the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for patients with intubation.
Up to 4 days after surgery
Incidence of postoperative neurocognitive disorder
Time Frame: At 30 days after surgery

Cognitive function will be assessed at baseline using MoCA (MoCA-22; scores range from 0 to 22, with higher scores indicating better cognitive function) and at 30 days after surgery using MoCA via telephone (T-MoCA; scores range from 0 to 22, with higher scores indicating better cognitive function).

Postoperative neurocognitive disorder (pNCD) is defined as: a |Z| value of decline in MoCA score ≥1.96. Z value = [(change from baseline in MoCA score in a surgical patient - mean change from baseline in MoCA score in the nonsurgical group)] / (standard deviation of change from baseline in MoCA score in the non-surgical group).
At 30 days after surgery

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause 30-day mortality
Time Frame: Up to 30 days after surgery
All-cause 30-day mortality
Up to 30 days after surgery
Postoperative thermal discomfort
Time Frame: Up to 30 minutes after arriving PACU/ICU or after extubation

Postoperative thermal comfort will be evaluated with the Numerical Rating Scale (NRS; an 11-point scale where 0=intense cold, 5=thermal comfort, and 10=intense warm).

For patients who are extubated in the operation room, evaluation is conducted at 5 and 30 minutes after arriving post-anesthesia care unit (PACU)/intensive care unit (ICU). For patients who are admitted to PACU/ICU with endotracheal intubation, evaluation is conducted at 5 and 30 minutes after extubation. If patients remain intubated 2 hours after surgery, no further thermal comfort assessments will be conducted.
Up to 30 minutes after arriving PACU/ICU or after extubation
Postoperative shivering intensity
Time Frame: Up to 30 minutes after arriving PACU/ICU or after extubation

Postoperative shivering intensity is evaluated with a four-point scale (0=no shivering, 1=intermittent, mild shivering, 2=moderate shivering, and 3=persistent, intense shivering).

For patients who are extubated in the operation room, evaluation is conducted at 5 and 30 minutes after arriving post-anesthesia care unit (PACU)/intensive care unit (ICU). For patients who are admitted to PACU/ICU with endotracheal intubation, evaluation is conducted at 5 and 30 minutes after extubation. If patients remain intubated 2 hours after surgery, no further shivering assessments will be conducted.
Up to 30 minutes after arriving PACU/ICU or after extubation
Quality of recovery on postoperative day 1
Time Frame: At 24 hours after surgery
Quality of recovery will be assessed at 24 hours after surgery, using the 15-item quality of recovery scale (QoR-15; scores range from 0 to 150 points, with higher scores indicating better recovery).
At 24 hours after surgery
Units of blood transfused during and within 4 days of surgery
Time Frame: Up to 4 days after surgery
Units of blood transfused during surgery and the first 4 days after surgery.
Up to 4 days after surgery
Length of stay in post-anesthesia care unit (PACU)
Time Frame: Up to 24 hours after surgery
Length of stay in post-anesthesia care unit (PACU)
Up to 24 hours after surgery
Length of hospital stay after suregry
Time Frame: Up to 30 days after surgery
Length of hospital stay after surgery
Up to 30 days after surgery
Incidence of surgical site infections
Time Frame: Up to 30 days after surgery
Surgical site infections will include deep and organ-space infections, anastomotic leaks, wound dehiscence, abscess, and sepsis. The definitions were modified from "Guideline for prevention of surgical site infection, 1999" (https://stacks.cdc.gov/view/cdc/7160).
Up to 30 days after surgery
Incidence of other major complications
Time Frame: Up to 30 days after surgery
Other major complications are defined as new-onset condition that are deemed harmful and required therateutic intervention, i.e., class II or higher on the Clavien-Dindo classification.
Up to 30 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peking University First Hospital

Collaborators

Peking University Shenzhen Hospital

Investigators

  • Principal Investigator: Dong-Xin U Wang, Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 1, 2026

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

June 13, 2026

First Submitted That Met QC Criteria

June 17, 2026

First Posted (Actual)

June 18, 2026

Study Record Updates

Last Update Posted (Actual)

June 18, 2026

Last Update Submitted That Met QC Criteria

June 17, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026R0324

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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