Insulin/glucose infusion successfully resuscitates bupivacaine-induced sudden-onset circulatory collapse in dogs

Abstract

Purpose In previous studies, insulin reversed the cardiac toxicity gradually induced by a continuous infusion of bupivacaine. In this randomized controlled study, we intended to simulate a more relevant clinical situation by injecting bupivacaine rapidly as a bolus to induce suddenonset circulatory collapse in dogs. We then evaluated the insulin effect.Methods Bupivacaine (10 mgÁkg -1 iv) was rapidly administered intravenously to 12 dogs. At the onset of circulatory collapse (defined as a mean arterial pressure [MAP] of 30 mmHg), external chest compression was initiated. Insulin (2 UÁkg -1 iv) was given to the insulinglucose (IG) group (n = 6) and the same volume of 0.9% saline was given to the control (C) group (n = 6). The primary outcome was successful resuscitation defined as both MAP C 60 mmHg and sinus rhythm on an electrocardiogram that lasted C 60 sec. Hemodynamic and blood variables were measured, including cardiac output and electrocardiogram intervals. Results All IG dogs were successfully resuscitated within 15 (3) min, whereas none of the control dogs were resuscitated (P = 0.002). After circulatory collapse, the average MAP was higher in group IG than in group C (P = 0.006). Conclusion Insulin effectively reversed the sudden-onset circulatory collapse in dogs caused by an intravenous bolus injection of bupivacaine. RésuméObjectif Dans des e´tudes pre´ce´demment publie´es, il a e´ted e´montre´que l'insuline neutralisait la toxicite´cardiaque progressivement induite par une perfusion continue de bupivacaı¨ne. Dans cette e´tude randomise´e contrôle´e, nous avons tente´de simuler une situation clinique plus pertinente en injectant rapidement de la bupivacaı¨ne en bolus afin d'induire un collapsus circulatoire subit chez les chiens. Nous avons ensuite e´value´l'effet de l'insuline. Méthode De la bupivacaı¨ne (10 mgÁkg -1 iv) intraveineuse a e´te´rapidement administre´e chez 12 chiens. Au de´but du collapsus circulatoire (de´fini tel qu'une tension arte´rielle moyenne [TAM] de 30 mmHg), un massage cardiaque a e´teÁ uthor contributions Mi-Hyun Kim, Kook-Hyun Lee, and ChongSoo Kim helped design the study.

Effects of insulin on the reversal of myocardial contractility after bupivacaine-induced cardiac asystole in vitro

“…Based on irreversible restoration of stimulated contractile responses by insulin under recirculation conditions in our results, Kim et al's in vivo findings highly suggest the importance of ongoing circulation accomplished with chest compressions to restore cardiac rhythm. Ongoing circulation by chest compression results in gradual redistribution of BPV by increasing blood flow to other organs [5] and possible enhancement of hepatic extraction of BPV [18] would lower BPV concentrations in the myocardium, which contributes to dissociation of BPV from the Na + channel to permit initiation of action potentials. However, a longer period of time was required to reverse impaired myocardial conduction [5].…”

“…Ongoing circulation by chest compression results in gradual redistribution of BPV by increasing blood flow to other organs [5] and possible enhancement of hepatic extraction of BPV [18] would lower BPV concentrations in the myocardium, which contributes to dissociation of BPV from the Na + channel to permit initiation of action potentials. However, a longer period of time was required to reverse impaired myocardial conduction [5]. Considering the redistribution of BPV by chest compression in whole animals or the clinical setting, our results in the recirculation and washout condition from an isolated rodent heart preparation have a limitation to extrapolate to whole animals or humans.…”

“…In an in vitro study using a Langendorff preparation in rats, Stehr et al [6] also found that insulin application reversed L-BPVinduced myocardial contractile depression, but did not improve impaired myocardial conduction induced by L-BPV. Insulin-glucose-potassium treatment in conjunction with chest compression effectively reversed mean arterial blood pressure in BPV-induced cardiovascular collapse in dogs, however, a longer period of time was also required to reverse impaired myocardial conduction [5].…”

“…An infusion of insulin will increase glucose uptake, and, through the glycolytic pathway, provide increased concentrations of pyruvate [3], resulting in replenishment of ATP and improvement in myocardial performance. In in vivo studies using dogs, insulin-glucosepotassium treatment effectively reversed severe BPV-induced myocardial depression [4] or cardiovascular collapse [5], whereas no control dogs were resuscitated. In an in vitro study using a Langendorff preparation in rats, Stehr et al [6] also found that insulin application reversed L-BPVinduced myocardial contractile depression, but did not improve impaired myocardial conduction induced by L-BPV.…”

Effects of insulin on the reversal of myocardial contractility after bupivacaine-induced cardiac asystole in vitro

“…In in vivo studies using dogs, insulin-glucose-potassium treatment effectively reversed severe BPVinduced myocardial depression [4] or cardiovascular collapse [5], whereas no control dogs were resuscitated. In an in vitro study using a Langendorff preparation in rats, Stehr et al [6] also found that insulin application reversed L-BPV-induced myocardial contractile depression, but did not improve impaired myocardial conduction induced by L-BPV.…”