Key result
Pralidoxime significantly improved the 24-hour survival rate to 68.1% compared to 27.2% with saline placebo and 22.7% with norepinephrine in rats with peritonitis-induced sepsis.
Why the study?
Sympathetic overstimulation exerts deleterious effects in septic shock, but pralidoxime may provide non-sympathetic pressor effects buffered by sympathoinhibition.
Does pralidoxime improve hemodynamics and survival in rats with peritonitis-induced sepsis?
RCT (n=110)
Blinded
Randomized
No
Does pralidoxime improve hemodynamics and survival in rats with peritonitis-induced sepsis?
In a rat model of peritonitis-induced sepsis, pralidoxime significantly improved hemodynamics and 24-hour survival compared to norepinephrine or placebo.
Answers are grounded in this paper and cite their sources.
Pralidoxime improved hemodynamics and survival versus norepinephrine in septic rats; leaves open translation to human septic shock.
Several studies have suggested that sympathetic overstimulation causes deleterious effects in septic shock. A previous study suggested that pralidoxime exerted a pressor effect through a mechanism unrelated to the sympathetic nervous system; this effect was buffered by the vasodepressor action of pralidoxime mediated through sympathoinhibition. In this study, we explored the effects of pralidoxime on hemodynamics and survival in rats with peritonitis-induced sepsis. This study consisted of two sub-studies: survival and hemodynamic studies. In the survival study, 66 rats, which survived for 10 hours after cecal ligation and puncture (CLP), randomly received saline placebo, pralidoxime, or norepinephrine treatment and were monitored for up to 24 hours. In the hemodynamic study, 44 rats were randomly assigned to sham, CLP-saline placebo, CLP-pralidoxime, or CLP-norepinephrine groups, and hemodynamic measurements were performed using a conductance catheter placed in the left ventricle. In the survival study, 6 (27.2%), 15 (68.1%), and 5 (22.7%) animals survived the entire 24-hour monitoring period in the saline, pralidoxime, and norepinephrine groups, respectively (log-rank test P = 0.006). In the hemodynamic study, pralidoxime but not norepinephrine increased end-diastolic volume (P <0.001), stroke volume (P = 0.002), cardiac output (P = 0.003), mean arterial pressure (P = 0.041), and stroke work (P <0.001). The pressor effect of norepinephrine was short-lived, such that by 60 minutes after the initiation of norepinephrine infusion, it no longer had any significant effect on mean arterial pressure. In addition, norepinephrine significantly increased heart rate (P <0.001) and the ratio of arterial elastance to ventricular end-systolic elastance (P = 0.010), but pralidoxime did not. In conclusion, pralidoxime improved the hemodynamics and 24-hour survival rate in rats with peritonitis-induced sepsis, but norepinephrine did not.
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Mamadjonov et al. (2021) conducted an RCT in Peritonitis-induced sepsis (n=110). Pralidoxime vs. Saline placebo and norepinephrine was evaluated on Survival to 24 hours (p=0.006). Pralidoxime significantly improved the 24-hour survival rate to 68.1% compared to 27.2% with saline placebo and 22.7% with norepinephrine in rats with peritonitis-induced sepsis.
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