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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 3,992
- 试验地点
- 50
- 主要终点
- Incidence of delirium within 4 days after surgery
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥65 years.
- •Planned potentially curative initial cancer surgery with an expected duration of 2 hours or longer under general anesthesia.
排除标准
- •Preoperative fever (tympanic temperature ≥38℃).
- •Known or suspected preoperative infection.
- •Previous history of schizophrenia, epilepsy, Parkinson disease, myasthenia gravis, or delirium.
- •Unable to communicate due to severe dementia, language barrier, or coma.
- •Critically ill (Left ventricular ejection fraction <30%, Child-Pugh grades C, requirement of renal replacement therapy, American Society of Anesthesiologists physical status>IV, or expected survival <24 hours).
- •Scheduled surgery for breast cancer, intracranial tumors, or rare cancers.
- •Planned to undergo therapeutic hypothermia.
- •Body mass index >30 kg/m2 (to facilitate thermal management).
- •Have participated in this study previously.
- •Any other conditions that are considered unsuitable for study participation.
研究组 & 干预措施
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.
干预措施: Routine thermal management (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°C.
干预措施: Target temperature management (Other)
结局指标
主要结局
Incidence of delirium within 4 days after surgery
时间窗: During the first four days after surgery.
Occurrence of delirium during the first four postoperative days is assessed with the 3D-Confusion Assessment Method (3D-CAM) or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU; for intubated patients) twice daily (8-10 am and 6-8 pm). Any positive CAM evaluation will be considered evidence of delirium. Immediately before assessing delirium, sedation or agitation is assessed with the Richmond Agitation-Sedation Scale (RASS; scores range from -5 \[unarousable\] to +4 \[combative\] and 0 indicates alert and calm). Deeply sedated or unarousable patients (RASS -4 or -5) is recorded as comatose and not assessed for delirium.
Progression-free survival after surgery [long-term]
时间窗: Up to 3 years after surgery of the last enrolled patient.
Time interval from index surgery to cancer recurrence/metastasis/progression or all-cause death, whichever comes first.
Incidence of delirium within 4 days after surgery
时间窗: During the first four days after surgery.
Occurrence of delirium during the first four postoperative days is assessed with the 3D-Confusion Assessment Method (3D-CAM) or Confusion Assessment Method for the Intensive Care Unit (CAM-ICU; for intubated patients) twice daily (8-10 am and 6-8 pm). Any positive CAM evaluation will be considered evidence of delirium. Immediately before assessing delirium, sedation or agitation is assessed with the Richmond Agitation-Sedation Scale (RASS; scores range from -5 \[unarousable\] to +4 \[combative\] and 0 indicates alert and calm). Deeply sedated or unarousable patients (RASS -4 or -5) is recorded as comatose and not assessed for delirium.
Progression-free survival after surgery [long-term]
时间窗: Up to 3 years after surgery of the last enrolled patient.
Time interval from index surgery to cancer recurrence/metastasis/progression or all-cause death, whichever comes first.
次要结局
- Postoperative thermal comfort(Up to 30 minutes after arriving PACU/ICU or after extubation.)
- Postoperative shivering intensity(Up to 30 minutes after arriving PACU/ICU or after extubation.)
- Postoperative thermal comfort(Up to 30 minutes after arriving PACU/ICU or after extubation.)
- Postoperative shivering intensity(Up to 30 minutes after arriving PACU/ICU or after extubation.)
- Incidence of emergence delirium(Up to 30 minutes after arriving PACU/ICU or after extubation.)
- Units of blood transfused during and within 4 days of surgery(Up to 4 days after surgery.)
- Incidence of postoperative neurocognitive disorders at 6 months after surgery [long-term](At 6 months after surgery.)
- Cancer-specific survival after surgery [long-term](Up to 3 years after surgery of the last enrolled patient.)
研究者
Dong-Xin Wang
Professor and Chairman, Department of Anesthesiology
Peking University First Hospital