Ketorolac and enoxaparin affect arterial thrombosis and bleeding in the rabbit.
BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with hemostasis during the perioperative period, and the combination of NSAID and enoxaparin could increase this effect. The aim of this prospective, blinded experimental study was to assess these effects using a model of arterial thrombosis and bleeding in the rabbit.


METHODS
After anesthesia was induced and monitors placed, the common carotid arteries were exposed, and 60% stenosis of the right common carotid artery was produced. Twenty minutes later, a compression injury of the artery was produced that triggered a series of cyclic episodes of thrombosis and clot lysis. This was manifested as cyclic flow reductions (CFR; measured with an electromagnetic flow meter). After the first flow reduction was noted, the rabbits were immediately and randomly assigned to one of four groups (n = 10 each) that received intravenous infusions: control, ketorolac (2 mg/kg), enoxaparin (0.5 mg/kg), and ketorolac plus enoxaparin (2 mg/kg and 0.5 mg/kg, respectively). The number of CFRs that occurred in the subsequent 20-min period was used as a measure of treatment effect. The contralateral common carotid artery was exposed, and both stenosis and injury were produced. The ability of the administered drug to prevent thrombosis was assessed as the number of CFRs that occurred during the first 20-min period after vessel injury. In addition, both before and after group assignment and drug injection, bleeding times were noted and a platelet aggregation test was performed. Laparotomy was followed by a spleen section, and the extent of the wound and the amount of splenic bleeding were measured.


RESULTS
The treatment effect was indicated by the median number of CFRs, which was 5.5 in the control group, 1 in the ketorolac group, 2 in the enoxaparin group, and 0 in the ketorolac + enoxaparin group. The prevention effect was indicated by the median number of CFRs, which was 4 in the control group, 0 in the ketorolac group, 2 in the enoxaparin group, and 0.5 in the ketorolac + enoxaparin group. Bleeding time was significantly lengthened in the enoxaparin and in the ketorolac + enoxaparin groups. Splenic and wound bleeding was greater in the ketorolac group. Platelet aggregation was completely inhibited in the ketorolac and the ketorolac + enoxaparin groups.


CONCLUSIONS
Ketorolac had an important antithrombotic activity. The association of enoxaparin with ketorolac seemed to lengthen the bleeding time observed with ketorolac.
Delaporte-Cerceau
S
S
Department of Anesthesiology, Hôpital Pitié-Salpêtrière, Paris, France.
Samama
C M
CM
Riou
B
B
Bonnin
P
P
Guillosson
J J
JJ
Coriat
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects*; D002341:Carotid Artery Thrombosis / Q000188:drug therapy / Q000503:physiopathology*; D004347:Drug Interactions; D017984:Enoxaparin / Q000494:pharmacology*; D020910:Ketorolac; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D014046:Tolmetin / Q000031:analogs & derivatives* / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D017984:Enoxaparin; D010975:Platelet Aggregation Inhibitors; D014046:Tolmetin; D020910:Ketorolac