Refractory cardiac arrest due to inadvertent intravenous injection of 0.25% bupivacaine used for local infiltration anesthesia.

The cardiotoxic effect of bupivacaine is a well-known fact that can lead to asystole, and most of the time it is refractory to resuscitative measures. We describe the case of a three-year-old child operated for anorectal malformation (ARM) by abdominal approach. Apart from congenital anomalies, preoperative evaluation was unremarkable. General anesthesia and controlled ventilation were instituted through endotracheal tube (ET). She had an uneventful intraoperative period. Immediately after surgery when local infiltration block was given using 0.25% of bupivacaine (6 ml volume) around the abdominal incision for postoperative analgesia, the patient went into cardiac asystole. Cardiopulmonary resuscitation (CPR) was continued for 60 minutes but the patient could not be revived. At that time we had neither lipid emulsion nor the facility for cardiopulmonary bypass in our hospital setup.

INTRODUCTION

Local anesthetics for regional blocks in children are usually administered under general anesthesia. Neurological signs of inadvertent intravascular administration of local anesthetics may be missing and sudden hemodynamic compromise may be the only first sign. Local anesthetic intoxication with circulatory collapse is a potential fatal complication and resuscitation may be challenging and prolonged.[1] In this report, we present a case of bupivacaine-induced cardiac arrest after local infiltration block for postoperative analgesia in a case of anorectal malformation (ARM) undergoing anorectoplasty, which was refractory to resuscitative measures.

CASE REPORT

A three-year-old female patient weighing 10 Kg was posted for anorectoplasty because of ARM. Associated with ARM, the patient was found to have some other congenital anomalies like malrotation of the gut, polydactyly, and high arched palate for which electrocardiogram (ECG), echocardiography, and chest X-ray with other relevant investigations were done to rule out any cardiovascular malformation. Echocardiography and ECG findings were normal. The pediatrician was consulted and he found no need for any active intervention before surgery. Preanesthetic checkup was unremarkable. The patient was premedicated with injection (inj) glycopyrrolate 0.1 mg intravenous (IV), inj ondansatron 1 mg, and inj fentanyl 20 mcg IV. After induction with inj propofol 20 mg IV and inj vecuronium 1 mg IV, the patient was intubated with a 4.5 mm ID uncuffed PVC endotracheal tube (ET) with the help of direct laryngoscopy. Monitoring of parameters like oxygen saturation (SpO2), end-tidal carbon dioxide (EtCO2), ECG, noninvasive blood pressure (NIBP), temperature, and esophageal stethoscope were used perioperatively. We used O2, N2O with Sevoflurane and intermittant inj. Vecuronium for maintenance of anaesthesia. All the vitals remained stable throughout the surgery. Total IV fluid was given according to the Holliday-Segar formula. Intraoperatively, 100 mL packed red cells were transfused and inj paracetamol 150 mg infusion was given. The surgery lasted two and a half hours. Initially, posterior sagittal anorectoplasty (PSARP) was attempted but due to difficulties, it was done through an abdominal incision. At the end of surgery, local infiltration block was applied by the surgeon using 6 ml 0.25% bupivacaine plain for postoperative analgesia. Just after the application of the complete volume, we noticed a fall in the heart rate on the multichannel and ECG monitors. Immediately, inj atropine 0.2 mg IV was given. For a while, the heart rate improved but again within 10 seconds, it fell abruptly and the patient went into cardiac asystole, which was detected by the person monitoring the patient using an esophageal stethoscope and was confirmed by ECG. Cardiopulmonary resuscitation (CPR) was started according to the pediatric advanced life support (PALS) guideline 2010. We continued CPR for 60 minutes. Adrenaline was given as soon as asystole was detected and it was repeated. Inj amiodarone was also given but the patient could not be revived despite all these efforts.

DISCUSSION

Bupivacaine-induced cardiotoxicity can result in sudden cardiac death; although rare, it has a high mortality rate. In the past years, studies on bupivacaine cardiotoxicity involved a variety of experimental models that included isolated animal hearts and unanesthetized mice, cats, and dogs. In 1978, Moore et al. found 15 systemic reactions in 11,080 nerve blocks (incidence 0.14%). All the 15 patients had symptoms of central nervous system (CNS) toxicity and recovered without sequel.[2] Cardiovascular collapse without prodromal CNS symptoms in six pregnant women following inadvertent intravenous injection of bupivacaine was reported by Albright et al. in 1979. Some of these cases were characterized by prolonged and difficult resuscitation.[3]

Local anesthetic agents produce their effect by blocking sodium channels. If it is absorbed intravenously, however, the same sodium channel blockade can occur in all tissues that include the brain and heart, producing similar dose-dependent attenuation of action potentials throughout these structures.[4] The decrease in cardiac contractility and maximum speed of depolarization of the action potential, produced by binding of bupivacaine to sodium channel receptors in a concentration-dependent manner has been ascribed to the mechanism of bupivacaine cardiotoxicity.[5] It acts as a fast-in and slow-out agent that slows the recovery from the block during diastole.[67] This predisposes to bradycardia, conduction delay through the myocardium, thereby allowing re-entrant arrhythmias, ventricular arrhythmias, and asystole.[48] This binding of amide local anesthetics, which are weak bases, to myocardium sodium channel receptors is enhanced by acidosis and tachycardia.[89] This acidosis and tachycardia occur frequently during cardiac arrest, causing an even greater binding of the local anaesthetic to the sodium channel receptor. This may account for the prolonged cardiac arrest despite effective advanced cardiac life support (ACLS) and all resuscitative equipments. Hence, the therapy for bupivacaine toxicity should be directed toward dissociating bupivacaine from the myocardium sodium channel.[4] This cardiotoxicity leading to cardiovascular collapse may occur without prodromal CNS symptoms. This fact can be explained by the electrophysiological difference between nerve and heart ion channels where nerves undergo very brief depolarization owing to rapid flux of sodium ions and neural blockade. In contrast, cardiac depolarization lasts 200-400 ms owing to an initial sodium flux followed by a long plateau phase which is calcium dependent; as a result, the blockade is produced by much lower drug concentrations as compared to those required for neural tissue.[4]

A 20% lipid emulsion has emerged as a potential treatment for such types of prolonged or refractory cardiac arrest.[10] According to Weinberg et al., the so-called “lipid sink effect” is suggested to be the basic mechanism of this therapeutic approach.[11] If available, cardiopulmonary bypass or extracorporeal membrane oxygenation (ECMO) should be considered that allows the patient to clear the drug from the circulatory system and regain normal cardiac function.[5]

The cause of death in this case can be attributed only to bupivacaine toxicity as according to the PALS guideline 2010, we had excluded all other possible and reversible causes, though the total dose given was 15 mg, which is well within safe limits for a 10 Kg patient. Neither was any associated cardiorespiratory malformation found preoperatively nor was any variation in vitals or events noticed intraoperatively. Moreover, the surgeon revealed that he did not aspirate before injection and had given it at a single site. Before presenting this case scenario, we bore in mind that there are some more informative studies on this same topic, although they are few in number. We have tried to explain the reason for prolonged and refractory CPR followed by bupivacaine toxicity, which is known to us, but not mentioned clearly or completely in previous articles and case reports. We have also re-emphasized the necessity for continuous ECG monitoring, rescue therapy like 20% lipid emulsion at the bedside even during infiltration at any nonvascular area, and the role of cardiopulmonary bypass or ECMO.