Renal tolerance to delayed volume resuscitation following traumatic shock

Abstract

A potential resuscitative strategy for patients with severe traumatic shock is to maintain mean arterial pressure (MAP) at ~55mmHg when full resuscitation is temporarily unavailable. However, the renal tolerance to such prolonged hypotensive ischemia, especially beyond the golden hour (1h after injury), has not been determined. We hypothesized that resuscitation delayed for more than 1h after severe traumatic shock increases the incidence of acute kidney injury (AKI). Sprague Dawley rats (11-13 wks) were randomized into 3 groups: (time) control (no hemorrhage or resuscitation, n=4), 1-H (resuscitation after 1h of traumatic shock, n=5), and 2-H (resuscitation after 2h of traumatic shock, n=4). Rats were anesthetized (isoflurane with 30% oxygen) and extremity trauma was induced via clamping retrofemoral tissue groups, followed by closed fibula fracture. Five minutes after trauma, hemorrhage was performed via catheters with target MAP maintained at 55 mmHg for 1 or 2h. Hemorrhaged rats were then resuscitated with whole blood (from donor rats) until MAP spontaneously stabilized between 90-100 mmHg for 30 min. Rats were then allowed to regain consciousness and measurements of biomarkers and glomerular filtration rate (GFR, FITC-sinistrin) was immediately performed and repeated once daily for 3 days. The total blood volumes lost/resuscitated were similar between 1-H and 2-H groups (2.3±0.1 / 1.3±0.1 vs. 2.4±0.2 / 1.9±0.7 ml/100g). Compared to control group, traumatic shock increased creatinine (0.6±0.1 vs. 0.2±0.1mg/dl, p=0.02), BUN (26.5±0.5 vs. 19.3±0.3mg/dl, p=0.04), and lactate levels (6.3±0.8 vs. 1.7±0.3mM, p<0.01) in 1-H group. In the 2-H group, the increase in creatinine (1.0±0.1mg/dl), BUN (33.0±2.7mg/dl), and lactate (9.4±1.5mM) were more profound. Immediately after resuscitation, creatinine and BUN were not altered in 1-H and 2-H groups compared to pre-resuscitation levels. GFR and lactate were restored in 1-H group (1.1±0.2 vs. control 1.7±0.3ml/min/100g, p=0.1) with rapid correction in shock state (lactate level 0.2±0.2mM). In contrast, GFR in the 2-H group remained impaired with persistent hyperlactatemia (6.1±1.4mM) despite the normalized MAP. Mortality within 24h was 20% in 1-H and 75% in 2-H groups. In survivor rats, GFR, creatinine, BUN, and lactate levels remained within normal ranges for 3 days after resuscitation. These results suggest that resuscitation with blood administered 1h after injury preserves renal function, whereas further delay in resuscitation greatly increases incidence of AKI. DOD disclaimer: The views expressed in this abstract are those of the authors and do not reflect the official policy or position of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government.