Buprenorphine Analgesia Reduces Survival with ALM Resuscitation in a Rat Model of Uncontrolled Hemorrhage: Concerns for Trauma-Related Research.

The effect of analgesia on physiological systems has received little attention in trauma research. Our aim was to examine the effect of two different analgesics, buprenorphine and carprofen, on adenosine, lidocaine, and magnesium (ALM) resuscitation in a rat model of laparotomy and non-compressible hemorrhage. Male Sprague-Dawley rats were randomly assigned to Saline Carprieve®, ALM Carprieve®, Saline Buprenorphine, or ALM Buprenorphine (all n = 10). Anesthetized animals underwent surgical placement of chronic catheters and laparotomy, then hemorrhage was induced by liver resection (60% left lateral lobe). After 15 min, animals received 0.7 ml/kg 3% NaCl ± ALM bolus, and after 60 min, 4hr 0.5 ml/kg/hr 0.9% NaCl±ALM drip with 72hr monitoring. Carprieve® groups received 5 mg/kg s.c. every 24hr and Buprenorphine groups received 0.05 mg/kg Temgesic™ every 6-12hr. Survival, hemodynamics, blood chemistry and hematology were measured. ALM Carprieve® led to 100% survival compared to 40% survival in ALM Buprenorphine group (p = 0.004). In Saline-treated rats, buprenorphine reduced median survival time by 91% (22hr to 2hr). Recovery of mean arterial pressure (MAP) at 60 min was lower in the buprenorphine vs Carprieve® groups (83% vs 101% for ALM and 62% vs 95% for Saline groups). Buprenorphine was also associated with higher blood lactates and potassium. No analgesic-related differences were found in total white cells, lymphocytes, platelet count, hyperthermia, weight loss or pica. We conclude that reduced survival and MAP recovery appears to a buprenorphine effect on cardiovascular function. Until the underlying mechanisms can be elucidated, buprenorphine should be used with caution in small and possibly large models of trauma and shock.