title: Buprenorphine Analgesia Leads to Coagulopathy and Increased Plasma Fibrinogen in Healthy Rats: Implications For Small Animal Research.
abstract: Buprenorphine is the recommended analgesic for post-surgical pain and associated stress in small animal research. Our aim was to examine the effect of isoflurane anesthesia and buprenorphine analgesia on blood coagulation in the rat using rotational thromboelastometry.
  
  
  
  Adult male Sprague Dawley rats were randomly assigned to one of four groups (n = 6): baseline (Thiobarb anesthesia), 5% isoflurane anesthesia, isoflurane-buprenorphine (0.05-mg/kg s.c.), and buprenorphine alone. After 1 h, animals were anesthetized and blood was sampled.
  
  
  
  We report that isoflurane or buprenorphine had little or no effects on clotting times, clot formation, or clot lysis in EXTEM or INTEM. However, buprenorphine significantly increased FIBTEM alpha-angle, clot formation rates, and maximum clot formation velocities. Buprenorphine also increased EXTEM, FIBTEM, and INTEM A10 (clot strength), maximum clot firmness (clot quality), and maximum clot elasticity ( (clot elasticity). The combination of isoflurane and buprenorphine significantly increased clot amplitude but not to the same extent. The fibrinogen contribution to clot strength was 1.9-fold higher than baseline in the buprenorphine group, and 1.4-fold higher in the isoflurane-buprenorphine group. Plasma fibrinogen levels were 2.5-fold higher in both groups compared with the baseline value or isoflurane group (6.1 g/L vs. 2.4 g/L, P < 0.05).
  
  
  
  We conclude buprenorphine analgesia significantly increased clot strength without affecting fibrinolysis, and increased plasma fibrinogen, implying that the drug increased liver fibrinogen synthesis and release. Possible implications for small animal research are discussed.
authors.affiliation: Heart, Trauma and Sepsis Research Laboratory, Australian Institute of Tropical Health and Medicine, College of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
authors.forename: Maddison J
authors.initials: MJ
authors.lastname: Griffin
authors.forename: Hayley L
authors.initials: HL
authors.lastname: Letson
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Dobson
mesh_terms: D000698:Analgesia / Q000009:adverse effects*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D002047:Buprenorphine / Q000009:adverse effects*; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D007530:Isoflurane / Q000009:adverse effects; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002047:Buprenorphine; D005340:Fibrinogen; D007530:Isoflurane