Targeted Temperature Management at 35°C vs. 37°C for Heatstroke in ICU: A Pilot Randomized Controlled Trial.

OBJECTIVE: To evaluate the feasibility of conducting a trial comparing targeted temperature management (TTM) at 35°C-37°C in intubated heatstroke patients, while collecting preliminary data on safety and clinical outcomes. DESIGN: Pilot multicenter randomized clinical trial (June to December 2024). SETTING: Ten tertiary ICUs in China. PATIENTS: Thirty-five intubated adults (18 yr or older) with heatstroke meeting predefined diagnostic criteria. Key exclusions: nonenvironmental hyperthermia, expected death within 24 hours, or contraindications to temperature management. INTERVENTIONS: Patients were randomly assigned 1:1 to two TTM strategies. The therapeutic hypothermia group received protocolized rapid cooling using a combination of ice packs, precooled blankets, and ice-cold IV saline to achieve the target of 35.0°C within 2 hours, which was then maintained for 48 hours. The controlled normothermia group received conventional cooling measures (ice packs, 32°C blankets) only if body temperature exceeded 38.0°C, with the goal of maintaining core temperature between 36.5°C and 37.5°C. Shivering was managed according to a stepwise protocol, with a "lytic cocktail" (chlorpromazine, promethazine, and meperidine) available as rescue therapy for refractory shivering in both groups. MEASUREMENTS AND MAIN RESULTS: Recruitment rate was 83.7%, retention rate was 97.2%, and protocol adherence exceeded 88%. For clinical outcomes, no significant differences were observed in 28-day poor functional outcome (17.6% vs. 16.7%) or survival (82.4% vs. 83.3%). However, therapeutic hypothermia was associated with significantly higher rates of severe gastrointestinal injury (Acute Gastrointestinal Injury grade 3-4: 52.9% vs. 0%; p < 0.001) and arrhythmias (41.2% vs. 11.1%; p = 0.045). The lytic cocktail was required in 100% of hypothermia-group patients vs. 27.8% in the normothermia group (p < 0.001). CONCLUSIONS: This pilot study confirms the operational feasibility of a large-scale randomized clinical trial. However, therapeutic hypothermia was associated with significantly worse gastrointestinal injury and higher arrhythmia incidence, without evidence of neurologic or survival benefit. The universal requirement for pharmacological shivering control in the hypothermia group raises additional safety considerations. Based on current evidence, this strategy should not be routinely adopted in ICU heatstroke management.