Proactive Temperature Management in CRS-HIPEC for Prevention of Delirium

Официальное название

Proactive Temperature Management and Delirium After Cytoreductive Surgery With HIPEC: A Randomized Controlled Trial

Обзор

This randomized controlled trial evaluates the efficacy of a proactive Goal-Directed Temperature Management (GDTM) protocol in reducing postoperative delirium among patients undergoing Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for pseudomyxoma peritonei. CRS-HIPEC presents a unique physiological challenge characterized by a biphasic thermal trajectory: potential hypothermia during extensive surgery followed by rapid iatrogenic hyperthermia during perfusion. This study compares a standardized GDTM strategy-which incorporates strict normothermia maintenance and anticipatory pre-cooling prior to perfusion-against standard reactive thermal management. The primary objective is to determine if optimized thermoregulation can attenuate thermal variability and improve early neurocognitive recovery.

Подробное описание

Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) imposes a formidable physiologic burden, involving extensive resections and a distinctive thermal paradox. Patients typically experience a prolonged cytoreductive phase prone to inadvertent hypothermia, followed by protocol-driven hyperthermia during the perfusion phase. This rapid thermal fluctuation may disrupt blood-brain barrier integrity and amplify neuroinflammation, potentially contributing to postoperative delirium (POD).

Despite these risks, perioperative thermoregulation often remains reactive, with interventions initiated only after temperature thresholds are violated. Evidence-based recommendations for managing the iatrogenic heat load inherent to HIPEC remain undefined.

This single-center, parallel-group, randomized controlled trial aims to address this gap. Eligible adult patients scheduled for elective CRS-HIPEC are randomized to receive either proactive Goal-Directed Temperature Management (GDTM) or Usual Care. The GDTM protocol utilizes a phase-based algorithm, including specific targets for normothermia during resection and a "thermal buffer" created by anticipatory cooling prior to the hyperthermic phase. The Usual Care group receives standard reactive management where interventions are triggered primarily by observed threshold violations.

The primary endpoint is the incidence of POD within the first 7 postoperative days. Secondary endpoints include delirium-free days, intraoperative thermal exposure metrics, delayed neurocognitive recovery, and 30-day major complications.

Вмешательства

• Процедура Proactive Goal-Directed Temperature Management
  The protocol consists of four phases: Cytoreductive Phase: Maintain core temperature 36.5-37.5°C. Pre-cooling Phase: Initiated \~30 min before HIPEC (e.g., during closure), targeting 36.0-36.3°C. HIPEC Phase: Proactive cooling to target 37.5-38.0°C; escalation triggered at 37.8°C. 4. Rewarming Phase: Restore 36.5-37.5°C prior to ICU transfer .
• Процедура Standard Reactive Temperature Management
  Hypothermia Management: Active warming initiated reactively only when core temperature falls below 36.0°C. Pre-cooling: No anticipatory pre-cooling is performed. 3. HIPEC Phase: Active cooling withheld unless core temperature exceeds standard safety thresholds (typically \>38.5°C) or for immediate safety indications .

Первичные конечные точки

• Incidence of Postoperative Delirium [Срок оценки: From ICU admission through postoperative day 7 (or hospital discharge, whichever occurs first)]

Вторичные конечные точки (10)

• Delirium- and Coma-Free Days (DCFDs) [Срок оценки: Within 7 days postoperatively]
• Intraoperative Thermal Exposure (AUC >38.5°C) [Срок оценки: From the initiation of HIPEC perfusion until the completion of perfusion, approximately 90 minutes.]
• 30-Day Major Complications Composite [Срок оценки: Within 30 days postoperatively]
• Delayed Neurocognitive Recovery (DNR) [Срок оценки: Discharge (or postoperative day 7) and 1 month postoperatively]
• Quality of Recovery (QoR-15 Score) [Срок оценки: Postoperative days 1, 3, and 7]
• Postoperative Pain Intensity (NRS Score) [Срок оценки: Postoperative days 1, 2, and 3]
• Length of Stay (ICU and Hospital) [Срок оценки: From date of surgery until date of hospital discharge, assessed up to 30 days.]
• Cumulative Opioid Consumption [Срок оценки: From the end of surgery up to 72 hours postoperatively.]
• Incidence of Severe Thermal Excursions [Срок оценки: From the start of anesthesia induction until the end of surgery, approximately 10 hours]
• Incidence of Thermal-Related Adverse Events [Срок оценки: From the end of surgery until hospital discharge, assessed up to 30 days.]

Критерии участия

Критерии включения

• Adult patients (aged 18-80 years).

American Society of Anesthesiologists (ASA) physical status of I to III.

Scheduled for elective Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Pseudomyxoma Peritonei (PMP).

Written informed consent obtained from the participant or legally authorized representative.

Критерии исключения

• Known diagnosis of dementia, major neurocognitive disorder, or severe psychiatric illness (e.g., schizophrenia) documented in the medical record.

Acute central nervous system pathology likely to confound delirium assessment (e.g., recent stroke, active seizure disorder, or traumatic brain injury).

Severe sensory or language barriers precluding valid cognitive screening (e.g., profound deafness or blindness, or language barriers not correctable with translation).

Preoperative coma, mechanical ventilation, or deep sedation precluding reliable baseline assessment.

Emergency surgery or repeat CRS-HIPEC during the same hospital admission.

History of alcohol or substance abuse likely to precipitate withdrawal symptoms.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Профилактика

Центры проведения

Китай · 1 центр

• Aerospace Center Hospital — Пекин

Идентификаторы

NCT: NCT07378371 · XYin-HIPEC-2026-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗