Proactive Temperature Management in CRS-HIPEC for Prevention of Delirium

N/ANot Yet RecruitingNCT07378371

Aerospace Center Hospital174 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Interventions

Proactive Goal-Directed Temperature ManagementPROCEDURE

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 .

Standard Reactive Temperature ManagementPROCEDURE

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 .

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

Incidence of Postoperative Delirium

Delirium is assessed twice daily (08:00-10:00 and 18:00-20:00) using the Confusion Assessment Method for the ICU (CAM-ICU) for mechanically ventilated or ICU patients, and the standard CAM for ward patients. Postoperative delirium is defined as at least one positive CAM-ICU or CAM assessment during the assessment window .

Time frame: From ICU admission through postoperative day 7 (or hospital discharge, whichever occurs first)

Secondary Outcomes

Delirium- and Coma-Free Days (DCFDs)

Calculated as the number of days alive and free of both delirium and coma. A day is scored as "free" only if the patient is alive, not comatose, and delirium-negative on all assessments .

Time frame: Within 7 days postoperatively

Intraoperative Thermal Exposure (AUC >38.5°C)

Calculated as the Area Under the Curve (AUC) for core temperature \>38.5°C during the HIPEC phase to quantify physiologic thermal load.

Time frame: From the initiation of HIPEC perfusion until the completion of perfusion, approximately 90 minutes.

30-Day Major Complications Composite

A composite of Clavien-Dindo grade III-V complications (including mortality).

Time frame: Within 30 days postoperatively

Delayed Neurocognitive Recovery (DNR)

Assessed using the Montreal Cognitive Assessment (MoCA). DNR is defined as a decline in MoCA score of ≥1 SD from the preoperative baseline mean, adjusted for age and education .

Time frame: Discharge (or postoperative day 7) and 1 month postoperatively

Quality of Recovery (QoR-15 Score)

Evaluated using the QoR-15 questionnaire, a 15-item patient-reported outcome measure. Scores range from 0 to 150, with higher scores indicating better quality of recovery.

Time frame: Postoperative days 1, 3, and 7

Postoperative Pain Intensity (NRS Score)

Assessed using an 11-point Numeric Rating Scale (NRS), where 0 indicates no pain and 10 indicates the worst pain imaginable.

Time frame: Postoperative days 1, 2, and 3

Length of Stay (ICU and Hospital)

Duration of stay in the Intensive Care Unit (ICU) and total hospital length of stay from surgery to discharge

Time frame: From date of surgery until date of hospital discharge, assessed up to 30 days.

Cumulative Opioid Consumption

Total postoperative opioid consumption converted to morphine milligram equivalents (MME).

Time frame: From the end of surgery up to 72 hours postoperatively.

Incidence of Severe Thermal Excursions

Defined as core temperature \<35.0°C (severe hypothermia) or \>39.0°C (severe hyperthermia)

Time frame: From the start of anesthesia induction until the end of surgery, approximately 10 hours

Incidence of Thermal-Related Adverse Events

Includes postoperative shivering requiring pharmacologic treatment and device-related skin injury (e.g., thermal burns, cold injury, pressure ulcers).

Time frame: From the end of surgery until hospital discharge, assessed up to 30 days.