Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury

Perenlei Enkhbaatar, Kazunori Murakami, Katsumi Shimoda, John Salsbury, Robert Cox, Hal Hawkins, Lillian Traber, David Herndon, Daniel Traber

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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°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.

Original languageEnglish (US)
Pages (from-to)621-628
Number of pages8
JournalClinical Science
Volume105
Issue number5
DOIs
StatePublished - Nov 2003

Fingerprint

Smoke Inhalation Injury
Ketorolac
Sheep
Non-Steroidal Anti-Inflammatory Agents
Smoke
Nitric Oxide Synthase Type II
Prostaglandin-Endoperoxide Synthases
Pulmonary Gas Exchange
Morbidity
Tracheotomy
Atrial Pressure
Water-Electrolyte Balance
Thromboxanes
Ketamine
Halothane
Nitrites
Burns
Hematocrit
Nitric Oxide Synthase
Nitrates

Keywords

  • Acute respiratory distress syndrome (ARDS)
  • Burn
  • Cyclo-oxygenase (COX)
  • Ketorolac
  • Nitric oxide (NO)
  • Smoke

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury. / Enkhbaatar, Perenlei; Murakami, Kazunori; Shimoda, Katsumi; Salsbury, John; Cox, Robert; Hawkins, Hal; Traber, Lillian; Herndon, David; Traber, Daniel.

In: Clinical Science, Vol. 105, No. 5, 11.2003, p. 621-628.

Research output: Contribution to journalArticle

Enkhbaatar, P, Murakami, K, Shimoda, K, Salsbury, J, Cox, R, Hawkins, H, Traber, L, Herndon, D & Traber, D 2003, 'Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury', Clinical Science, vol. 105, no. 5, pp. 621-628. https://doi.org/10.1042/CS20030180
Enkhbaatar, Perenlei ; Murakami, Kazunori ; Shimoda, Katsumi ; Salsbury, John ; Cox, Robert ; Hawkins, Hal ; Traber, Lillian ; Herndon, David ; Traber, Daniel. / Ketorolac attenuates cardiopulmonary derangements in sheep with combined burn and smoke inhalation injury. In: Clinical Science. 2003 ; Vol. 105, No. 5. pp. 621-628.
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AU - Cox, Robert

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