buprenorphine and Shock--Septic

Sepsis research relies on animal models. The models that most closely resemble clinical disease, such as cecal ligation and puncture, require surgery. After surgery, analgesics may not be included in experimental protocols because of concern over effects on inflammatory responses. This often generates animal welfare controversies within institutions; however, there are no scientific studies directly addressing the effects of analgesics on surgical models of sepsis. The purpose of this study was to characterize the effects of opioids on key parameters used in sepsis research.Female ICR mice were divided into four treatment groups (Ringer's lactate solution, high- or low-dose tramadol,buprenorphine) for 3-week mortality studies (n = 12 per treatment). Experimental groups were then repeated, and mice were killed at 12, 24, and 48 h postsurgery for cell counts, differentials, and cytokine levels in blood, peritoneum, and airways. Mortality studies demonstrated no significant differences between controls and any treatment group. However,significant differences were noted between buprenorphine and high-dose tramadol, revealing more and later deaths with tramadol. For comparison of immune parameters, Mann-Whitney U or Student t test was performed, emphasizing comparisons between treatment and control. Although several results were significant, comparisons between control and any treatment group yielded no differences that remained consistently apparent during the observation period. Again,differences were observed between the treatments. The results suggest that judicious and limited use of some analgesics may not dramatically affect the outcome of similarly conducted cecal ligation and puncture studies when compared with those not using analgesics. However, when different analgesics are used, comparisons between studies may be complicated.

Topics: Animal Welfare; Animals; Ascitic Fluid; Bronchoalveolar Lavage Fluid; Buprenorphine; Cecum; Cell Count; Cytokines; Female; Intestinal Perforation; Leukocyte Count; Ligation; Macrophages; Mice; Mice, Inbred ICR; Models, Animal; Narcotics; Pain; Pain Perception; Peritonitis; Shock, Septic; Tramadol

Endotoxic shock is presented with a complex pathophysiology and is associated with high mortality. Recently, it has been reported that endogenous opioids play an important role in endotoxic shock. Pressor effect of naloxone in shock may be mediated through antagonism of endogenous opioid inhibition of the sympatho-adrenal catecholaminergic system. In endotoxemic animal, circulating catecholamine levels were not elevated by naloxone. It is possible that naloxone acts upon opiate receptors to enhance catecholamine actions at the receptor level or post-receptor level. We investigated endotoxic shock using a rat model. The animals anesthetized with phenobarbital were infused with E. coli LPS for 30 minutes. They were divided into 5 groups. After an endotoxin i.v. infusion of 15 mg/kg (LD 60), a significant fall in mean arterial pressure (MAP), heart rate and pH occurred in all groups. Treatment with naloxone or buprenorphine or naloxone + epinephrine resulted in significant improvement in MAP, pH and base excess. Treatment with morphine resulted in a decrease in MAP and an increase in heart rate. The pressor response to epinephrine 10, 30, 60 microgram/kg i.v. caused an increase of 62%, 48% and 17% of control values respectively in endotoxic treated rats. The duration of the pressor response to epinephrine was significantly increased by naloxone, although no significant effects on survival were seen at 4 hours after the start of treatment. These findings suggest that the buprenorphine may prove to be an alternative to naloxone, the co-administration of naloxone and epinephrine may be of benefit in the management of septic shock.

Topics: Animals; Blood Pressure; Buprenorphine; Epinephrine; Heart Rate; Male; Morphine; Naloxone; Rats; Rats, Sprague-Dawley; Shock, Septic

The cardiovascular and metabolic responses to treatment with naloxone or buprenorphine (a partial opiate agonist) were investigated in a porcine model of septicaemia. Animals anaesthetised with alpha-chloralose were infused with live E. coli over two hours. They were then divided into three groups and received either naloxone (2 mg kg-1 + 1.5 mg kg-1 hr-1) or buprenorphine (0.3 mg kg-1) or an equivalent volume of normal saline. Treatment was started one hour after commencing the infusion, by which time a significant fall in cardiac index (CI), stroke index (SI), mean arterial pressure (MAP), and pH had occurred in all groups, together with a significant rise in mixed venous blood lactate and packed cell volume. Treatment with both naloxone and buprenorphine resulted in significant improvements in CI, pH, and base excess and in a fall in mixed venous lactate and packed cell volume. Although no significant effect on survival was seen at three hours after the start of treatment, buprenorphine may prove to be a suitable alternative to naloxone in the management of septic shock.

Topics: Animals; Blood Pressure; Buprenorphine; Cardiac Output; Disease Models, Animal; Erythrocyte Indices; Escherichia coli Infections; Female; Lactates; Naloxone; Shock, Septic; Swine