Ketamine improves survival in burn followed by sepsis in rats

Objective

Ketamine was previously reported to decrease cytokine production and improve survival after E. coli-induced sepsis. The present studyexamined whether ketamine decreased cytokine production and improved survival after burn or after burn combined with sepsis.

Methods

In groups 1–4, rats sustained burn injury at time 0, and were given ketamine (10 mg/kg) or saline at 1 or 24 hours post burn. In groups 5–8 we created a 'two hit' model of burn followed by sepsis. Rats that sustained burn at time 0 were given E. coli (0.2 × 10⁹ CFU) at 24 h. The animals received ketamine or saline at 1 or 24 hours post burn. In all the above groups mortality was recorded for 7 days and IL-6 was measured in serum at 6 and 30 hours post burn.

Results

Ketamine given at 1 hour (but not 24 hours) after burn injury decreased serum IL-6 concentrations compared with saline (430.0 ± 36.71 vs 106.5 ± 3.403 pg/ml [mean ± SEM], P < 0.0001) without altering survival. After burn followed by sepsis, ketamine given at 1 hour tended to improve survival and decrease IL-6, and when given at 24 hours (i.e. immediately after E. coli inoculation) significantly improved survival (46.1% vs 13.3%, P = 0.008) and decreased IL-6 (72,640 ± 40,990 vs 332,300 ± 32,300 pg/ml, P = 0.0079).

Conclusion

We conclude that ketamine therapy improves survival in burn followed by sepsis. This beneficial effect probably is achieved by interfering with the inflammatory cascade, as evidenced by attenuation of cytokine concentrations.