Intravenous Fluids Used for Resuscitation Alters the Adrenal Response to Traumatic Burn injury Depending on the Volume Given

Abstract

Severe thermal injury induces hypermetabolic stress which initiates a disruption in the hypothalamic‐pituitary‐adrenal (HPA) axis. While glucocorticoids contribute to maintaining blood pressure in healthy individuals, severely burned patients (i.e., >30% total body surface area; TBSA) have increased circulating cortisol levels that correspond to the extent of injury. However, little is known about adrenal damage following burn injury and the potential effects of common treatments such as intravenous (IV) fluid resuscitation. The objective of this study was to evaluate the effect of IV lactated Ringer's (LR) resuscitation on circulating cortisol, steroidogenic enzymes, and adrenal pathology following burn. Anesthetized Yorkshire swine sustained 40% TBSA burns from brass probes heated to 100 °C and placed on the skin for 30 s. Animals were recovered in metabolic cages to regain consciousness. Burned swine received IV fluid resuscitation with LR at two different volumes: 15 mL/kg body weight (BW)/day (Limited Volume; LV, n=6) or 2 mL/kg/%TBSA/day (Modified Brooke; MB, n=6). Non‐burned animals (Sham) were also Fluid Restricted (S‐FR, n=4) to induce some level of stress. Computerized tomography (CT) scans were performed before and 48 h post‐burn. Blood and urine was collected at baseline (BL), 6, 24, and 48 h following burn, with euthanasia at 48 h for adrenal gland collection. Adrenal histopathology was examined, as well as tissue cytokine levels. Heart and respiratory rate was similar in all animals, while temperature was elevated with burn. Urinary cortisol was elevated following surgery in all animals, however by 24 h S‐FR returned back to BL. Urinary cortisol levels at 48 h levels remained elevated in both MB (13,320±1,760 pg/mg creatinine; p=0.005) and LV (12,230±3,350 pg/mg creatinine; p=0.07) animals when compared with S‐FR (4,040±480 pg/mg creatinine). Similarly, while elevated at baseline, circulating cortisol was higher in the MB group (35449 ± 6878 pg/mL) but not the LR group (16511 ± 6077 pg/mL) compared to S‐FR (20549 ± 3078) at 48 hours. Gene expression of cleavage enzymes (3β‐HSD, CYP17, CYP11, and CYP21) along the cortisol synthesis pathway was not different between burned and S‐FR animals. No changes in CT‐angiography determined volume or Hounsfield units were found. Histologically, adrenal hemorrhaging was found in the cortex of burned animals. Intensity of TUNEL stain on adrenal sections was greatest in LV and MB groups within the cortex (p≤0.05) when compared to S‐FR. Protein levels of IL‐2, IL1ra, IL‐10, and IL‐12 were significantly elevated in LV, but not in MB when compared to S‐FR animals. This study demonstrates that at 48 h after a 40% burn in swine, cortisol remains elevated and adrenal gland integrity is compromised. Data from these studies can help shape resuscitative efforts of burn casualties for potentiating homeostasis of the HPA axis.Support or Funding InformationThis study was supported by Military Burn Research Program Award# W81XWH‐16‐2‐0041.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.