Proactive Temperature Management in CRS-HIPEC for Prevention of Delirium

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Pseudomyxoma Peritonei; Postoperative Delirium (POD)
• Intervention / Treatment: Procedure: Proactive Goal-Directed Temperature Management; Procedure: Standard Reactive Temperature Management

Detailed Description

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
• Enrollment (Estimated): 174
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Xinrui Yin; Phone Number: +86-13029315156; Email: ahywvn@pku.org.cn

Study Locations

• China
  • Beijing, China
    • Aerospace Center Hospital
    • Contact: Xinrui Yin; Phone Number: +86-13029315156; Email: ahywvn@pku.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GDTM Group; Participants assigned to this group receive a protocolized, phase-based temperature management algorithm. This includes strict normothermia maintenance during cytoreduction, anticipatory pre-cooling prior to HIPEC perfusion, and proactive cooling during the hyperthermic phase to attenuate thermal variability .	Procedure: 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 .
Active Comparator: Usual Care Group; Participants receive standard institutional thermal management characterized by a reactive approach. Therapeutic interventions (warming or cooling) are determined by the attending anesthesiologist based on observed threshold violations (e.g., core temperature <36.0°C or >38.5°C) rather than a prespecified goal-directed algorithm .	Procedure: 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 .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 .	From ICU admission through postoperative day 7 (or hospital discharge, whichever occurs first)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 .	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.	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).	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 .	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.	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.	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	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).	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)	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).	From the end of surgery until hospital discharge, assessed up to 30 days.

Collaborators and Investigators

• Sponsor: Aerospace Center Hospital
• Investigators: Study Chair: Xiangli Zheng, Aerospace Center Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): March 20, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: January 18, 2026
• First Submitted That Met QC Criteria: January 27, 2026
• First Posted (Actual): January 30, 2026

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: HIPEC; Hyperthermic Intraperitoneal Chemotherapy; Cytoreductive Surgery; Temperature Management; Goal-Directed Therapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Postoperative Complications; Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neoplasms, Cystic, Mucinous, and Serous; Delirium; Adenocarcinoma, Mucinous; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Emergence Delirium; Pseudomyxoma Peritonei
• Other Study ID Numbers: XYin-HIPEC-2026-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No