Effect of pralidoxime on coronary perfusion pressure during cardiopulmonary resuscitation in a pig model

Abstract

ObjectivePralidoxime is widely used for the treatment of organophosphate poisoning. Multiple studies have reported its vasoconstrictive property, which may facilitate the restoration of spontaneous circulation (ROSC) after cardiac arrest by increasing the coronary perfusion pressure (CPP). 2,3-Butanedione monoxime, which belongs to the same oxime family, has been shown to facilitate ROSC by reducing left ventricular ischemic contracture. Because pralidoxime and 2,3-butanedione monoxime have several common mechanisms of action, both drugs may have similar effects on ischemic contracture. Thus, we investigated the effects of pralidoxime administration during cardiopulmonary resuscitation in a pig model with a focus on ischemic contracture and CPP.MethodsAfter 14 minutes of untreated ventricular fibrillation, followed by 8 minutes of basic life support, 16 pigs randomly received either 80 mg/kg of pralidoxime (pralidoxime group) or an equivalent volume of saline (control group) during advanced cardiovascular life support (ACLS).ResultsMixed-model analyses of left ventricular wall thickness and chamber area during ACLS revealed no significant group effects or group-time interactions, whereas a mixed-model analysis of the CPP during ACLS revealed a significant group effect (P=0.038) and group-time interaction (P<0.001). Post-hoc analyses revealed significant increases in CPP in the pralidoxime group, starting at 5 minutes after pralidoxime administration. No animal, except one in the pralidoxime group, achieved ROSC; thus, the rate of ROSC did not differ between the two groups.ConclusionIn a pig model of cardiac arrest, pralidoxime administered during cardiopulmonary resuscitation did not reduce ischemic contracture; however, it significantly improved CPP.

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

“…By contrast, the addition of pralidoxime increased CPP over the threshold level, which led to an improved ROSC rate in the pralidoxime group. This finding is consistent with that of a previous study in which the authors reported that pralidoxime potentiated the duration and intensity of the pressor response elicited by adrenaline in isolated rabbit aorta strips and reaffirms our earlier finding that pralidoxime administration during CPR improved CPP …”

“…This finding is consistent with that of a previous study in which the authors reported that pralidoxime potentiated the duration and intensity of the pressor response elicited by adrenaline in isolated rabbit aorta strips 4 and reaffirms our earlier finding that pralidoxime administration during CPR improved CPP. 10 The pressor effect of pralidoxime has long been reported in literature, [3][4][5][6][7] but none of them focused on the effect within the first few minutes after its administration. In the present study, arterial pressure increased shortly after the administration, and the highest pressure was observed within 1 minute, making this drug suitable for use during CPR.…”

“…An investigator opening the envelope prepared either a saline placebo or pralidoxime solution (80 mg/kg of pralidoxime chloride, JW Pharmaceutical) in equal volumes (20 mL). The same dose of pralidoxime (80 mg/kg) as that in our previous study was chosen in this sub‐study . All other investigators were blinded to the drug administered during experiments.…”

“…The primary outcomes of the sub‐study that was conducted in pigs were CPP and ROSC. The sample size of this sub‐study was calculated based on the CPP data from our previous study (group mean = 7.4 mm Hg in the control group, 10.3 mm Hg in the pralidoxime group; standard deviation σ within each group = 5.003) . We calculated that eight animals would be needed per group to reach α of 0.05 and a power of 90%.…”

“…The pressor effect of pralidoxime theoretically should increase coronary perfusion pressure (CPP), which is a major determinant of myocardial blood flow during cardiopulmonary resuscitation (CPR) . We recently compared the effects of pralidoxime administered during CPR with a placebo in 16 pigs subjected to 14 minutes of untreated ventricular fibrillation (VF) followed by 8 minutes of basic life support (BLS) . In this study, pralidoxime improved CPP significantly, but the CPP could not be brought to a threshold level that renders ROSC likely even in the animals that received pralidoxime.…”