Cardiac arrest during spinal anaesthesia in a patient with undiagnosed Brugada syndrome

Editor, We present a 49-year-old male patient with undiagnosed Brugada syndrome, who underwent emergency surgery for an incarcerated inguinal hernia. Brugada syndrome was first described in 1992 by the Brugada brothers as an inherited autosomal dominant sodium ion (Na+) channelopathy causing sudden cardiac death.1 Ventricular tachyarrhythmias can be triggered by many physiological and pharmacological factors, including the drugs regularly used in our daily clinical practice. To our knowledge, this is the first case report of cardiac arrest in a Brugada patient during spinal anaesthesia. Written informed consent was obtained from the patient. The patient had no medical history of syncope or arrhythmias. There was also no history of heart disease in his family. His pre-operative physiological examinations, laboratory analyses and the ECG were normal. In the operating room, routine monitoring of noninvasive blood pressure (BP), ECG and oxygen saturation (SpO2) were established. Heart rate (HR) was 75 bpm, BP was 123/71 mmHg and SpO2 was 99%. Subarachnoid block is the preferred option for inguinal herniorrhaphy in our clinic. With the patient in the sitting position, an atraumatic bloodless spinal was performed with a 25-gauge Quincke needle inserted in the L3/4 interspace. Following the free flow of clear cerebrospinal fluid, 0.5% hyperbaric bupivacaine (15 mg) was injected, after which the patient was placed in the supine position. At 15 min, HR was 65 bpm, BP was 112/68 mmHg and the sensory level was at T10 (blocked to pinprick). At 20 min, when surgery had not yet commenced, the patient's HR suddenly began to decrease (sensory block still at T10). A total dose of 1-mg atropine was given, but despite the atropine, the bradycardia was rapidly replaced by asystole and a flat-line ECG. Chest compressions were commenced immediately along with positive pressure mask ventilation with 100% O2. Fortunately, sinus rhythm was rapidly restored, and cardiopulmonary resuscitation (CPR) was terminated after a minute. The duration of the acute bradycardia and sinus arrest was approximately 3 min. Postresuscitation, the patient's HR was 85 bpm, BP 145/86 mmHg and spontaneous respiration returned. His SpO2 on 3 l min−1 O2 via a nasal cannula was 98%, Glasgow Coma Scale was 15/15, sensory level was still T10 and he described a mild headache. Post-CPR, the ECG showed a saddleback (type 2) pattern with ST elevations (Fig. 1). We decided to continue with surgery as it was an emergency procedure. The procedure was completed uneventfully. On postoperative follow-up, cardiac enzyme levels remained within normal limits. On the second postoperative day, with the suspicion of Brugada syndrome, an ajmaline challenge test was performed by cardiologists. An induced type 1 ECG was observed, confirming that the patient was positive for Brugada syndrome. Three days after the surgery, coronary angiography revealed normal coronary arteries. During this procedure, an implantable cardioverter-defibrillator was inserted. After a further 2 days of follow-up in the coronary care unit, the patient was discharged well from the hospital.Fig. 1: Postcardiopulmonary resuscitation 12-lead ECG showing a characteristic pattern of Brugada syndrome with saddleback (type 2) ST elevation in leads V2 and V3 (indicated by arrows).The prevalence of Brugada syndrome in the population is around 5/10 000, although there are ethnical and geographical differences.1 The syndrome is thought to be responsible for 20 to 50% of sudden cardiac deaths which occur without evidence of underlying structural heart disease. Arrhythmias are mostly observed at an average age of 40 years.1 The first mutation related to the syndrome was identified in the SCN5A gene. To date, more than 100 other different mutations associated with the syndrome have been found.2 Brugada syndrome has three types of specific ECG patterns with ST elevations on right precordial leads and right bundle branch block (RBBB).1 All three types of ECG patterns can be present in a single patient and may show intraday or daily fluctuations.3 Although all three patterns can be present in patients, only type 1 (coved type) ECG pattern is diagnostic for the disease. However, it is now well known that in a large percentage of individuals, the electrocardiographic hallmark, the ST segment elevation is not persistent, and a completely normal ECG may be present which makes the diagnosis more difficult.4 Many drugs have been reported to induce fatal ventricular tachyarrhythmias in Brugada syndrome: a list can be found in the review by Postema et al.5 Successful administration of both general and regional anaesthesia in Brugada patients are described in the literature.6 For general anaesthesia, propofol, midazolam, thiopental and fentanyl have all been used uneventfully, although some concerns remain for remifentanil. No problems have been reported with volatile agents or muscle relaxants.6 It is suggested that cholinergic drugs (e.g. neostigmine) should be avoided for reversal of neuromuscular block, but, in some cases, neostigmine has been used without complications.6 Suggamadex is the recommended agent for reversal.7 Epidural anaesthesia has also been performed successfully in many patients. However, a Brugada-type ECG pattern (RBBB and ventricular tachyarrhythmia) has occurred after the epidural injection of bupivacaine or ropivacaine in three patients.6 No complications were observed with the use of intrathecal bupivacaine.6,8 There is one case report, which describes a more than 2 mm ST elevation and RBBB in the ECG after subarachnoid injection of prilocaine.9 In our patient, bradycardia and asystole occurred 20 min after the subarachnoid injection of hyperbaric bupivacaine. Common side effects of spinal anaesthesia are hypotension, bradycardia and vomiting: these are attributed to sympathetic blockade. The term Bezold–Jarisch reflex has now come to include reactions triggered by cardiac mechanoreceptor activation, and it has been used to describe peri-operative bradycardia with hypotension.10 The use of central depressant drugs in addition to regional anaesthesia along with upper thoracic levels of block from spinal anaesthesia (average of T4), and impaired venous return might have been responsible for cardiac arrest during regional anaesthesia.11 In the current case, central depressant drugs were not used and hydration was adequate. Spinal anaesthesia results in denervation of sympathetic, sensory and somatic motor fibres, and it is believed that the sympathetic block correlates best with cold discrimination testing.12 On average, the level of block to cold is about two spinal segments higher than the sensory (pinprick) level.12 With the patient's sensory block to pinprick at T10, when bradycardia/asystole occurred, a sympathetic block around T8 would be expected. However, in a study with healthy volunteers, it has been demonstrated that there was no significant change in HR, cardiac index and plasma catecholamine levels with spinal anaesthesia up to the T1 dermatome (median level T3), suggesting incomplete sympathetic block even in the presence of quite extensive neuraxial anaesthesia.13 Nevertheless, as Brugada patients are highly susceptible to vasovagal syncope,14 it is possible that the Bezold–Jarish reflex might have been triggered. The arrhythmias that have been recorded in the various studies include ventricular tachycardia or ventricular fibrillation. In this case, we did not observe ventricular tachycardia or ventricular fibrillation before or after the bradycardia and arrest period. But the Brugada type 2 ECG pattern was revealed. Large doses of bupivacaine are more likely to induce cardiovascular collapse or ventricular dysrhythmias.15 Toxic plasma concentrations of bupivacaine are reported to be 2 to 4 μg ml−1 which correspond to whole blood concentrations of 1 to 2 μg ml−1.16 Although the systemic absorption of subarachnoid bupivacaine is fast,17 with 65 to 85% of the maximum bupivacaine concentration detectable in the venous blood 10 min after the administration, the maximum blood concentrations at 20 min is only 0.22 μg ml−1.17 Such concentrations are 1/10th of the reported toxic doses in a person.18 Compared with a spinal, epidural analgesia results in much higher plasma levels. Thus, spinal anaesthesia is thought to be safer than epidural anaesthesia from the point of view of systemic local anaesthetic toxicity. But, as shown by Oliván et al.,9 although the very low, nontoxic systemic concentrations found with subarachnoid block are well tolerated for normal patients, they may be harmful for the sensitised hearts of Brugada patients. In this case, it is a problem for us to decide whether the reason for cardiac arrest is vagal activity or a direct bupivacaine effect. Most authors claim that spinal anaesthesia is safe in patients with Brugada syndrome. However, because of the small number of cases, a definite decision on this issue cannot be made. If the plan for anaesthesia is a regional block, the optimal choice of local anaesthetic for Brugada patients remains controversial, as the only literature is a few case reports. Accordingly, as all local anaesthetics are sodium channel blockers, the utmost attention to details to avoid systemic injection is recommended. Systemic absorption of the local anaesthetic is an important consideration in both central neuraxial blocks and peripheral nerve blocks. If a patient has been diagnosed with Brugada syndrome prior to surgery, general anaesthesia may be more beneficial to avoid the potential for cardiovascular complications caused by local anaesthetic drugs. All neuraxial techniques and drugs such as bupivacaine should be used with caution in Brugada patients. Acknowledgements relating to this article Assistance with the letter: none. Financial support and sponsorship: none. Conflicts of interest: none.