Hypothermia: Pathophysiology and the propensity for infection - 10/02/25

Doi : 10.1016/j.ajem.2024.11.029

Lacie M. Werner, PhD ^{^⁎,}^{^{1
These authors contributed equally to the manuscript.}} , Richard T. Kevorkian, PhD ^{^{1
These authors contributed equally to the manuscript.}}, Derese Getnet, PhD, Kariana E. Rios, PhD, Dawn M. Hull, DVM PhD, Paul M. Robben, MD, Robert J. Cybulski, PhD, Alexander G. Bobrov, MD, PhD ^{^⁎}
Walter Reed Army Institute of Research, 503 Robert Grant Ave. Silver Spring, MD, 20910, USA

^⁎Corresponding authors.

Abstract

Hypothermia in combination with infection presents a complex challenge in clinical and battlefield medicine. Multifaceted physiological and immunological consequences of hypothermia drastically change the risk, progression, and treatment of a concomitant infection. Managing hypothermia and infection in extreme cold settings is particularly relevant in an era with increased risk of military operations in Polar climates. Here, we discuss the elevated instance of infection during accidental and therapeutic hypothermia and speculate how a compromised immune system may contribute. We focus on skin and soft tissue infections and sepsis, which are among the serious infectious complications of hypothermia and battlefield injuries. We also present the challenges associated with treating infections under hypothermic conditions. Finally, we advocate for a renewed focus on identifying causal relationships between hypothermia and infection risk and assessing established infection treatment regiments in hypothermic patients to enhance trauma management and survival outcomes in hypothermia-related injuries.

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Highlights

•	Military advancement into the Arctic is expected increase prevalence of hypothermia.
•	Hypothermia causes changes in cytokines and immune cell responses consistent with immunosuppression.
•	Accidental hypothermia during clean-contaminated procedures is associated with surgical site infections.
•	In septic patients, hypothermia correlates with higher rates of mortality compared to normothermia or hyperthermia.
•	Prophylactic antibiotics, immunomodulators, and rewarming may reduce risk of infection in hypothermic individuals.