Effects of hypertonic sodium chloride solution on the electrophysiologic alterations caused by bupivacaine in the dog heart

Abstract

The effects of various hypertonic solutions on the intraventricular conduction, ventricular repolarization and the arrhythmias caused by the intravenous (iv) injection of bupivacaine (6.5 mg/kg) were studied in sodium pentobarbital-anesthetized mongrel dogs. Hypertonic solutions, given iv 5 min before bupivacaine, were 7.5% (w/v) NaCl, 5.4% (w/v) LiCl, 50% (w/v) glucose (2,400 mOsm/l, 5 ml/kg), or 20% (w/v) mannitol (1,200 mOsm/l, 10 ml/kg). Bupivacaine induced severe arrhythmias and ventricular conduction and repolarization disturbances, as reflected by significant increases in QRS complex duration, HV interval, IV interval and monophasic action potential duration, as well as severe hemodynamic impairment. Significant prevention against ventricular electrophysiologic and hemodynamic disturbances and ventricular arrhythmias was observed with 7.5% NaCl (percent increase in QRS complex duration: 164.4 ± 21.8% in the non-pretreated group vs 74.7 ± 14.1% in the pretreated group, P<0.05; percent increase in HV interval: 131.4 ± 16.1% in the non-pretreated group vs 58.2 ± 7.5% in the pretreated group, P<0.05; percent increase in monophasic action potential duration: 22.7 ± 6.8% in the non-pretreated group vs 9.8 ± 6.3% in the pretreated group, P<0.05; percent decrease in cardiac index: -46 ± 6% in the non-pretreated group vs -28 ± 5% in the pretreated group, P<0.05). The other three hypertonic solutions were ineffective. These findings suggest an involvement of sodium ions in the mechanism of hypertonic protection.

Effect of hypertonic saline on electrocardiography QRS duration in rabbit model of bupivacaine toxicity resuscitated by intravenous lipid

“…..................................................................................................................................................................................................................... Ó 2010 The Authors blockers at their binding sites [10][11][12]. Previous investigators exploring hypertonic saline solutions in bupivacaine cardiotoxicity have demonstrated that 7.5% sodium chloride prevents the detrimental effects of bupivacaine on cardiac stimulus conduction and ventricular repolarisation in whole dogs, independent of hypertonicity alone [13]. This work proposes reversal, at least in part, of the bupivacaine-induced sodium channel blockade as the principal beneficial mechanism of action of hypertonic saline.…”

“…High-dose insulin dextrose euglycaemia has been shown to exert a positive inotropic action in bupivacaineinduced myocardial depression, perhaps via an antagonistic influence of insulin on sodium channel inhibition, transient outward potassium current, calcium-dependent adenosine triphosphatase, or even improved myocardial glucose utilisation [9]. Hypertonic saline solutions have been shown to reverse the cardiodepressant and arrhythmogenic effects of bupivacaine intoxication both in vitro [10] and in vivo [11][12][13]. Given the differing mechanisms of action between these unique therapies and lipid emulsion, largely pharmacodynamic in the case of the former and pharmacokinetic in the latter, potential exists at least theoretically for any combined effect to be cumulative.…”