Critical Care Bulletin - May 2022

Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial

 

by Drewry, Anne M.; Mohr, Nicholas M.; Ablordeppey, Enyo A.; Dalton, Catherine M.; Doctor, Rebecca J.; Fuller, Brian M.; Kollef, Marin H.; Hotchkiss, Richard S. 

 

Critical Care Medicine: June 2022 - Volume 50 - Issue 6 - p 924-934

 

OBJECTIVES: 

To test the hypothesis that forced-air warming of critically ill afebrile sepsis patients improves immune function compared to standard temperature management.

DESIGN: 

Single-center, prospective, open-label, randomized controlled trial.

SETTING: 

One thousand two hundred-bed academic medical center.

PATIENTS: 

Eligible patients were mechanically ventilated septic adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) anticipated need for mechanical ventilation of greater than 48 hours; and 3) a maximum temperature less than 38.3°C within the 24 hours prior to enrollment. Primary exclusion criteria included: immunologic diseases, immune-suppressing medications, and any existing condition sensitive to therapeutic hyperthermia (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma (IFN-γ) production, mortality, and 28-day hospital-free days.

INTERVENTIONS: 

External warming using a forced-air warming blanket for 48 hours, with a goal temperature 1.5°C above the lowest temperature documented in the previous 24 hours.

MEASUREMENTS AND MAIN RESULTS: 

We enrolled 56 participants in the study. No differences were observed between the groups in HLA-DR expression (692 vs 2,002; p = 0.396) or IFN-γ production (31 vs 69; p = 0.678). Participants allocated to external warming had lower 28-day mortality (18% vs 43%; absolute risk reduction, 25%; 95% CI, 2–48%) and more 28-day hospital-free days (difference, 2.6 d; 95% CI, 0–11.6).

CONCLUSIONS: 

Participants randomized to external forced-air warming did not have a difference in HLA-DR expression or IFN-γ production. In this pilot study, however, 28-day mortality was lower in the intervention group. Future research should seek to better elucidate the impact of temperature modulation on immune and nonimmune organ failure pathways in sepsis.