Ketamine Improves Survival in Burn Injury Followed by Sepsis in Rats

• Published in: Anesthesia and analgesia Vol. 103; no. 2; pp. 396 - 402
• Main Authors: Gurfinkel, Reuven, Czeiger, David, Douvdevani, Amos, Shapira, Yoram, Artru, Alan A, Sufaro, Yuval, Mazar, Julia, Shaked, Gad
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.08.2006; Lippincott
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Burns - drug therapy; Burns - immunology; Dose-Response Relationship, Drug; Interleukin-6 - blood; Ketamine - therapeutic use; Male; Medical sciences; Rats; Rats, Sprague-Dawley; Sepsis - drug therapy; Survival Rate; Time Factors; Rat; Rodentia; Glutamate receptor; Survival; Burn; Infection; Sepsis syndrome; Vertebrata; Mammalia; Ketamine; General anesthetic; Animal; Anesthesia; Antagonist; NMDA receptor
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1213/01.ane.0000226140.84281.3e

Ketamine was reported to decrease cytokine production and improve survival after Escherichia coli-induced sepsis. We examined whether ketamine decreased interleukin (IL)-6 production and improved survival after 1) burn injury or 2) burn injury combined with sepsis (E. coli) at 24 h. Ketamine (10 mg/kg) or saline was given at 1 h after burn injury (G 1, 2, 5, 6), 24 h after burn injury (G 3, 4), or at E. coli inoculation (G 7, 8). Mortality was recorded for 7 days and IL-6 was measured in serum at 6 h after burn (G 1–2), 30 h after burn (G 3–4), or 6 h after sepsis (30 h after burn) (G 5–8). Burn injury onlyKetamine given immediately (1 h) after burn injury but not 24 h after, decreased the burn-induced increase of IL-6 but did not improve survival. Burn injury + sepsisKetamine given immediately after burn injury did not significantly decrease the sepsis-induced increase of IL-6 or improve survival. In contrast, ketamine given immediately after sepsis significantly improved survival (46.1% versus 13.3%, P = 0.008) and decreased IL-6 production (72,640 ± 40,990 vs 332,300 ± 32,300 pg/mL, P = 0.008). We conclude that ketamine therapy improves survival in burn injury followed by sepsis. This beneficial effect is probably achieved through interference with the inflammatory cascade, as evidenced by attenuation of the proinflammatory marker IL-6.