NCT06256354

Effects of Intraoperative Targeted Temperature Management on Incidence of Postoperative Delirium and Long-term Survival

Effects of Intraoperative Targeted Temperature Management on Incidence of Postoperative Delirium and Long-term Survival in Older Patients Having Major Cancer Surgery: A Multicenter Randomized Trial

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 3,992 (estimated)
• Sponsor: Peking University First Hospital · Academic / Other
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

Intraoperative hypothermia is common in patients having major surgery and the compliance with intraoperative temperature monitoring and management remains poor. Studies suggest that intraoperative hypothermia is an important risk factor of postoperative delirium, which is associated with worse early and long-term outcomes. Furthermore, perioperative hypothermia increases stress responses and provokes immune suppression, which might promote cancer recurrence and metastasis. In a recent trial, targeted temperature management reduced intraoperative hypothermia and emergence delirium. There was also a trend of reduced postoperative delirium, although not statistically significant. This trial is designed to test the hypothesis that intraoperative targeted temperature management may reduce postoperative delirium and improves progression-free survival in older patients recovering from major cancer surgery.

Detailed description

Perioperative hypothermia results from anesthetic-impaired thermoregulatory responses combined with cool operating rooms and exposed body cavities. Core temperatures \<35.5°C increases perioperative blood loss, delays post anesthetic recovery, and increases surgical wound infections. Despite guideline recommendations, compliance with intraoperative temperature monitoring and management remains poor. In a national survey published in 2017, intraoperative hypothermia (core temperature \<36.0°C) occurred in 44% of patients having elective surgery with general anesthesia. According to a survey of anesthesiologists in six Asia-Pacific countries (Singapore, Malaysia, Philippines, Thailand, India, and South Korea), only 67% of respondents measured temperature intraoperatively during general anesthesia, and only 44% report intraoperative active warming and warming was ineffective in more than half of their patients. Perioperative hypothermia thus remains common. The 5,056-patient PROTECT trial showed that myocardial injury, surgical site infections, and blood loss were similar in patients randomized to intraoperative core temperatures of 35.5 or 37°C. However, there are other important complications that may be caused by intraoperative hypothermia including delirium, cancer recurrence, shivering, and thermal discomfort. Perioperative neurocognitive disorders (NCDs), especially postoperative delirium and postoperative cognitive dysfunction (POCD), are significant challenges to older patients scheduled for surgery. Delirium is a syndrome of acutely occurring and fluctuating changes in attention, level of consciousness, and cognitive function. Postoperative cognitive dysfunction refers to cognitive decline (including the ability of study, memory, action, and judgement) detected from 30 days to 12 months after surgery. In patients aged 60 years or above, the incidence of postoperative delirium is about 12-24%. The incidence of POCD is about 7-12% at 3-month follow-up and is associated with delirium, although the relationship is probably not causal. Delirium and POCD are associated with worse perioperative outcomes including prolonged hospitalization, increased complications, and high mortality, and worse long-term outcomes including shortened overall survival, as well as increased dementia and lowered life quality. Postoperative delirium and POCD are multifactorial. Predisposing factors include advanced age, lower educational level, cognitive impairment, comorbidities (e.g., cerebrovascular disease, diabetes, and kidney disease), alcohol abuse, and malnutrition. Precipitating factors include deep anesthesia, opioid use, benzodiazepines, intraoperative blood loss/blood transfusion, and severe pain. Hypothermia may also increase the risk of delirium. Hypothermia provokes both autonomic and behavioral protective responses. The first autonomic response is arterio-venous shunt constriction. Thermoregulatory vasoconstriction occurs many times a day in a typical hospital environment. It is highly effective, but does not usually disturb people and is generally considered to be of little consequence. Shivering is the other primary autonomic thermoregulatory defense against cold and has a triggering threshold about 1°C below the core temperature that triggers vasoconstriction. Unlike vasoconstriction, shivering is uncomfortable for patients. Furthermore, it is accompanied by a tripling of catecholamine concentrations, hypertension, and tachycardia. Behavioral thermoregulatory defenses are mediated by thermal comfort, and provoke voluntary defensive measures such as putting on a sweater, open windows, etc. Behavioral defenses include air conditioning and building shelters and are thus far stronger than autonomic responses. Thermal comfort matters to patients and is thus worth evaluating. Despite advances in surgery and oncology, postoperative survival decreases about 10% per year, mainly due to cancer recurrence. The development of cancer recurrence mainly depends on the balance between the invasive ability of residual cancer cells and the anti-cancer immune function. Perioperative hypothermia increases stress responses and provokes immune suppression. The investigators therefore propose to determine whether intraoperative targeted temperature management decreases the incidence of delirium, improves thermal comfort, reduces postoperative shivering, and improves long-term survival in older patients recovering from major cancer surgery. Specifically, the investigators will test the primary short-term hypothesis that perioperative normothermia (core temperature near 36.8°C) reduces delirium over the initial 4 postoperative days. Secondary short-term hypotheses are that perioperative normothermia improves thermal comfort, reduces shivering, reduces incidence of emergence delirium, and reduces blood transfusion. The primary long-term hypothesis is that perioperative normothermia improves progression-free survival.

Conditions

• Cancer Surgery
• Hypothermia
• Delirium
• Long-term Survivors

Interventions

Type	Name	Description
OTHER	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 upper- or lower-body 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. The target nasopharyngeal temperature is 35.5°C.
OTHER	Target temperature management	Pre-warming is performed with a full-body forced-air cover and electrically heated blanket for about 30 minutes before induction of anesthesia. The warmer will initially be set to "high" which corresponds to about 43°C. It will be subsequently adjusted to make patients feel warm, but not uncomfortably so. Patients will be warmed during surgery using two forced-air covers or combining forced-air covers with electric heating blanket when clinically practical. All intravenous fluids will be warmed to body temperature. There is no need to control ambient temperature since ambient temperature has little effect on core temperature in patients warmed with forced air. The target nasopharyngeal temperature is 36.8℃.

Timeline

• Start date: 2024-05-29
• Primary completion: 2029-06-01
• Completion: 2032-06-01
• First posted: 2024-02-13
• Last updated: 2026-03-09

Locations

36 sites across 1 country: China