Pralidoxime administered during cardiopulmonary resuscitation facilitates successful resuscitation in a pig model of cardiac arrest

Abstract

Pralidoxime is a common antidote for organophosphate poisoning; however, studies have also reported pralidoxime's pressor effect, which may facilitate the restoration of spontaneous circulation (ROSC) after cardiac arrest by improving coronary perfusion pressure (CPP). We investigated the immediate cardiovascular effects of pralidoxime in anaesthetised normal rats and the effects of pralidoxime administration during cardiopulmonary resuscitation (CPR) in a pig model of cardiac arrest. To evaluate the immediate cardiovascular effects of pralidoxime, seven anaesthetised normal rats received saline or pralidoxime (20 mg/kg) in a randomised crossover design, and the responses were determined using the conductance catheter technique. To evaluate the effects of pralidoxime administration during CPR, 22 pigs randomly received either 80 mg/kg of pralidoxime or an equivalent volume of saline during CPR. In the rats, pralidoxime significantly increased arterial pressure than saline (P = .044). The peak effect on arterial pressure was observed in the first minute. In a pig model of cardiac arrest, CPP during CPR was higher in the pralidoxime group than in the control group (P = .002). ROSC was attained in three animals (27.3%) in the control group and nine animals (81.8%) in the pralidoxime group (P = .010). Three animals (27.3%) in the control group and eight animals (72.2%) in the pralidoxime group survived the 6‐hour period (P = .033). In conclusion, pralidoxime had a rapid onset of pressor effect. Pralidoxime administered during CPR led to significantly higher rates of ROSC and 6‐hour survival by improving CPP in a pig model.

Pralidoxime improves the hemodynamics and survival of rats with peritonitis-induced sepsis

“…There was a significant group effect for heart rate in both studies. This was consistent with our previous study where pralidoxime significantly decreased the heart rate compared with saline placebo in anesthetized normal rats [13]. In the present study, the increase in stroke volume after pralidoxime administration was not accompanied by an increase in the LV ejection fraction but rather by an increase in EDV and a decrease in heart rate (although this result was not statistically significant; see Fig 4).…”

“…However, MAP returned to baseline values within 60 minutes. In our previous study [13], an intravenous bolus administration of 20 mg/kg pralidoxime increased the MAP by approximately 5 mmHg in anesthetized normal rats. In this study, the increase in MAP after pralidoxime treatment in the hemodynamic study (4 [2.5-6.5] mmHg) was similar, suggesting that the action mechanism of pralidoxime, which remains to be determined but is non-adrenergic in nature, may not be impaired in septic shock.…”

“…Although several studies have reported its pressor effect [9][10][11], pralidoxime has never been used as a vasopressor agent in clinical practice. We previously reported that pralidoxime as an adjuvant to epinephrine increased aortic pressure during cardiopulmonary resuscitation in porcine models [12,13]. We recently investigated the effects of adrenergic antagonists on the pressor action of pralidoxime in anesthetized normal rats to determine the involvement of the sympathetic nervous system in the pressor action of pralidoxime [14].…”

Systematic review of swine models for ventricular fibrillation induction in evaluating cardiopulmonary resuscitation methods

“…First, we were unable to stratify the types of CPR interventions due to the heterogeneity of CPR interventions (including defibrillation, anti-arrhythmic drugs, adrenergic drugs, and mechanical CPR). Efforts were made to provide specific information in each article in Supplementary Material B [40–256] to identify the type of VF induction used in the experiment of interest. Second, the quality of the included studies was not assessed.…”

Clinical Analysis of Acute Organophosphorus Pesticide Poisoning and Successful Cardiopulmonary Resuscitation: A Case Series

“…However, for the detoxification of oxime to work, it need to be given within 48 h of poisoning. Animal studies have shown that pralidoxime can contribute to the successful resuscitation of cardiac arrest in organophosphate-induced pig models ( 23 ). The outlook for most patients is excellent, although cardiac arrest occurred in some severe cases ( 3 ).…”