Chronic critical illness after hypothermia in trauma patients

Abstract

ObjectivesChronic critical illness (CCI) is a phenotype that occurs frequently in patients with severe injury. Previous work has suggested that inflammatory changes leading to CCI occur early following injury. However, the modifiable factors associated with CCI are unknown. We hypothesized that hypothermia, an early modifiable factor, is associated with CCI.MethodsTo determine the association of hypothermia and CCI, a secondary analysis of the Inflammation and Host Response to Injury database was performed, and subsequently validated on a similar cohort of patients from a single level 1 trauma center from January 2015 to December 2019. Hypothermia was defined as initial body temperature ≤34.5°C. CCI was defined as death or sustained multiorgan failure ≥14 days after injury. Data were analyzed using univariable analyses with Student’s t-test and Pearson’s χ2 test, and logistic regression. An arrayed genomic analysis of the transcriptome of circulating immune cells was performed in these patients.ResultsOf the initial 1675 patients, 254 had hypothermia and 1421 did not. On univariable analysis, 120/254 (47.2%) of patients with hypothermia had CCI, compared with 520/1421 (36.6%) without hypothermia who had CCI, p<0.001. On multivariable logistic regression, hypothermia was independently associated with CCI, OR 1.61 (95% CI 1.17 to 2.21) but not mortality. Subsequent validation in 1264 patients of which 172 (13.6%) were hypothermic, verified that hypothermia was independently associated with CCI on multivariable logistic regression, OR 1.84 (95% CI 1.21 to 2.41). Transcriptomic analysis in hypothermic and non-hypothermic patients revealed unique cellular-specific genomic changes to only circulating monocytes, without any distinct effect on neutrophils or lymphocytes.ConclusionsHypothermia is associated with the development of CCI in severely injured patients. There are transcriptomic changes which indicate that the changes induced by hypothermia may be associated with persistent CCI. Thus, early reversal of hypothermia following injury may prevent the CCI.Level of evidenceIII.

The injured monocyte: The link to chronic critical illness and mortality following injury

“…Monocytes have been implicated as key contributors to organ failure development and CCI following injury. 8,9,19 Furthermore, monocytes have been demonstrated to have unique phenotypic alterations in several different inflammatory diseases such as severe COVID-19 infections and sepsis, especially in those that develop long-term complications. 8,19,[31][32][33] In the current study, we explore the dynamic alterations in monocyte subset frequencies following severe traumatic injury associated with hemorrhagic shock.…”

“…Compartmentalization of the inflammatory response is a well-known phenomenon and could restrict the generalizability to the immune findings, despite previous data highlighting the importance of monocytes. 9,48 Over the past 50 years, trauma care has witnessed continuous improvement in prehospital, operative, and postoperative care. However, patients who survive their initial trauma are at risk of long-term physiologic changes and disability that is unfortunately associated with a significant risk of late mortality.…”

“…24,29 Unfortunately, despite substantial resources applied, the 1-year mortality rate for injured patients developing CCI is excessively high, similar to previous data in trauma and sepsis. 9,24,29,30 As a result, it is essential that the biology resulting in CCI be unraveled to improve the outcome following severe traumatic injury. The current study specifically aims to evaluate a part but important component of the inflammatory response following injury, the peripheral blood monocyte.…”

“…6,7 Despite varied definitions of CCI, it is recognized as a distinct clinical entity, spurring research on its prediction, diagnosis, and management. [8][9][10] Traumatic injury triggers pro-inflammatory systemic and anti-inflammatory response, linked to CCI. 6,11 This immune dysregulation is similar to that seen in conditions like sepsis and COVID-19.…”

Accidental hypothermia and related risk factors among trauma patients in prehospital setting

“…The mortality rate in trauma patients is significantly increased by hypothermia combined with acidosis and coagulopathy [7]. Additionally, prolonged intensive care unit (ICU) stays and increased incidences of cardiovascular, neurological, renal, and coagulation issues are linked to hypothermia in injured patients [5,8]. The factors that cause hypothermia in trauma patients have been researched, and some have been identified.…”