title: Rapid rewarming after mild hypothermia accentuates the inflammatory response after acute volume controlled haemorrhage in spontaneously breathing rats.
abstract: Accidental hypothermia is a common companion of trauma/haemorrhage, and several clinical studies have identified reduced body temperature as an independent risk predisposing to increased morbidity and mortality. Accordingly, the majority of trauma care guidelines prescribe early and aggressive rewarming of hypothermic patients. Enzyme reactions are generally downregulated at temperatures below 37 degrees C, including most of those responsible for the inflammatory response. The rationale for adhering to these recommendations uncritically may therefore be questioned. In a rat model of mild hypothermia and haemorrhagic shock we wanted to compare the influence of rapid rewarming with persistently reduced temperature on the synthesis of early inflammatory mediators and organ function. Thirty-four male albino Sprague-Dawley rats were studied. Withdrawal of 2.5 ml blood/100 g body weight was performed over 10 min, with simultaneous reduction of body temperature to 32.5-33.5 degrees C. Seventy-five minutes after initiation of bleeding, two-thirds of the shed blood was retransfused. One group (n=17) was rewarmed to normothermia, the other (n=17) was kept hypothermic. The study was terminated after an observation period of 2 h. At the end of the study the rewarmed animals had a significantly lower mean arterial pressure, higher heart rate, higher synthesis of reactive oxygen species from peritoneal phagocytes, increased circulating levels of nitric oxide, and higher values of the organ markers aspartate aminotransferase and urea. The pro-inflammatory cytokines TNF-alpha and IL-6, the anti-inflammatory cytokine IL-10, the organ markers alanine aminotransferase, alpha-glutathione S-transferase and creatinine, as well as organ injury scores were equal in both groups. Three rewarmed rats died prematurely, versus one hypothermic animal. In conclusion, the results suggest that during the early stages after haemorrhagic shock, rapid rewarming from mild hypothermia may have unfavourable effects both on basic haemodynamic variables, and on the internal inflammatory environment of cells and tissues.
authors.affiliation: Norwegian Defence Research Establishment, Division of Protection and Material, N-2027 Kjeller, Norway. per.vaagenes@ffi.no
authors.forename: Per
authors.initials: P
authors.lastname: Vaagenes
authors.forename: Yngvar
authors.initials: Y
authors.lastname: Gundersen
authors.forename: Per Kristian
authors.initials: PK
authors.lastname: Opstad
mesh_terms: D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D007035:Hypothermia / Q000150:complications / Q000628:therapy*; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D008163:Luminescent Measurements; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017694:Rewarming / Q000009:adverse effects*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000503:physiopathology*