Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury.
Massive cutaneous burn combined with smoke inhalation causes high mortality in fire victims. Cyclo-oxygenase (COX) and inducible nitric oxide (NO) synthase (iNOS) have been shown to be up-regulated in burn injury. Ketorolac, a non-steroidal, anti-inflammatory agent (NSAID), inhibits prostaglandin and thromboxane synthesis through inhibition of COX. NSAIDs have been shown to down-regulate iNOS. Thus we hypothesized that treatment with ketorolac would attenuate burn/smoke-related cardiopulmonary derangements. We conducted a fully controlled long-term laboratory investigation in an Intensive Care Unit setting. Eighteen female sheep were surgically prepared for chronic study. After a recovery period of 5 days, a tracheotomy was performed under ketamine/halothane anaesthesia. Sheep were given a 40% total body surface third-degree burn and insufflated with cotton smoke (48 breaths, <40 degrees C). Sheep were divided into three groups: sham (not injured and not treated; n =6), control (injured, but not treated; n =6) and treated (injured and administered ketorolac 60 mg/day; n =6). The sham group had stable cardiopulmonary and systemic haemodynamics. Control animals showed depressed cardiopulmonary function, decreased pulmonary gas exchange, increased pulmonary microvascular leakage and decreased left ventricle stroke work index with elevated left atrial pressure. Systemic vascular leak in control animals was evidenced by robust haemoconcentration (haematocrit and fluid net balance). Treatment with ketorolac prevented all of these morbidities. Post-treatment with ketorolac also resulted in significant inhibition of elevated plasma nitrite/nitrate levels in control animals. These results suggest that ketorolac may ameliorate cardiopulmonary morbidity, at least in part, by inhibiting excessive NO.
Enkhbaatar
Perenlei
P
Department of Anesthesiology, University Texas Medical Branch and Shriners Hospital for Children Burn Unit, Galveston, TX 77555-0833, USA.
Murakami
Kazunori
K
Shimoda
Katsumi
K
Salsbury
John
J
Cox
Robert
R
Hawkins
Hal
H
Traber
Lillian
L
Herndon
David
D
Traber
Daniel
D
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002056:Burns / Q000150:complications* / Q000276:immunology / Q000503:physiopathology; D005260:Female; D020910:Ketorolac / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000503:physiopathology; D023421:Models, Animal; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012128:Respiratory Distress Syndrome / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D012756:Sheep; D015208:Smoke Inhalation Injury / Q000150:complications* / Q000276:immunology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009566:Nitrates; D009573:Nitrites; D020910:Ketorolac