Anesth Pain Med 2014; 9: 205-208 ￭Case Report￭

Cardiac arrest following reversal of muscle relaxation by -A case report-

Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, *Hallym University College of Medicine, Seoul, Korea

Jun Young Jo, Jung Min Yi, Yoon Kyung Lee*, Seung Woo Ku, and Pyung Hwan Park

The anticholinesterase pyridostigmine is usually used as a reversal agent of non-depolarizing muscle relaxants in general anesthesia. Most adverse muscarinic effects of anticholinesterases are controll- CASE REPORT ed by ; however, there is still a potential for fatal cardiac complications. We report a case of cardiac arrest associa- A 61-year-old male patient suffering from obstructive sleep ted with coronary vasospasm that developed during emergence apnea syndrome underwent uvulopalatopharyngoplasty. He from general anesthesia in a 61-year-old male patient undergoing smoked 30 packs of cigarettes per year. His height was 168 uvulopalatopharyngoplasty with preoperatively undiagnosed corona- ry vasospastic angina. Anticholinesterases should be administered cm, his weight was 81 kg, and his body mass index was 28.7 2 with caution for neuromuscular blockade reversal, especially in kg/m . He was healthy but on for hypertension. All patients with coronary vasospastic angina. (Anesth Pain Med 2014; preoperative examinations, including laboratory tests, 12-lead 9: 205-208) ECG, and plain chest radiography were normal. Transthoracic Key Words: Cardiac arrest, Coronary spasm, Pyridostigmine, echocardiography showed borderline concentric left ventricular Reversal of neuromuscular block. hypertrophy and normal left ventricular function with ejection fraction of 60%. The vital signs of the patient prior to general anesthesia Anticholinesterases are used as reversal agents of were stable; his blood pressure (BP: systole/diastole) was non-depolarizing muscle relaxants during emergence from 132/72 mmHg and his heart rate (HR) was 81 beats/min. general anesthesia. Some of the less serious adverse effects of Routine hemodynamic monitoring was performed, including anticholinesterases are well known and these can be controlled 3-lead ECG, noninvasive BP monitoring, and pulse oximetry. by the co-administration of anticholinergics. However, fatal Anesthesia was induced and maintained with sevoflurane, complications, such as QT interval prolongation or ST segment nitrous oxide, and 50% oxygen, and 50 mg rocuronium was elevation on electrocardiography (ECG) and cardiac arrest, can administered for endotracheal intubation. No particular event still occur [1-4]. We report a transient ST segment elevation was observed and his vital signs remained stable throughout followed by cardiac arrest during emergence from general the operation. After the surgical procedure was completed, anesthesia in a patient with coronary vasospastic angina that respiratory movement was recovered spontaneously and 15 mg was possibly linked to pyridostigmine. pyridostigmine and 0.4 mg glycopyrrolate were administered intravenously to reverse muscle relaxation. Several minutes later, a ST segment elevation with a Mobitz type II Received: February 3, 2014. Revised: February 25, 2014. atrioventricular block appeared in the lead II ECG and the Accepted: March 21, 2014. patient’s HR dropped to 38 beats/min. At this time, the Corresponding author: Seung Woo Ku, M.D., Department of patient’s BP was 111/78 mmHg and 0.5 mg atropine was Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul injected immediately. However, there was no response to 138-736, Korea. Tel: 82-2-3010-3868, Fax: 82-2-3010-6790, E-mail: atropine and the ECG changed to complete atrioventricular [email protected] block, followed by asystole. Manual chest compression was

205 206 Anesth Pain Med Vol. 9, No. 3, 2014 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Fig. 1. The coronary angiography was normal prior to provocation with ergo- novine maleate. (A) Left anterior descen- ding artery and left circumflex artery. (B) Right coronary artery.

Fig. 2. After injection of 200 g ergo- novine maleate, the coronary angiogra- phy showed subtotal occlusion of the left anterior descending artery (A) and diffuse spasm of whole coronary arteries, accompanied by chest pain and ST segment elevation on the anterior chest lead (A, B). performed immediately and a single bolus injection of 1 mg and self-respiration. Serial cardiac markers, including troponin-I epinephrine was administered. Despite this cardiopulmonary and creatine kinase MB, were checked. The troponin-I resuscitation, ventricular fibrillation was detected and a 200-J concentration was within the normal range but creatine kinase shock was given. After the defibrillation, a normal sinus MB concentration was elevated to 5.7 ng/ml about 14 hours rhythm was recovered, but the ST segment was still elevated after the initial ST segment elevation. On postoperative day 3, by more than 2 mm and the patient’s BP was 67/47 mmHg. the endotracheal tube was extubated, and the patient underwent Continuous infusion of 4 g/kg/min isosorbide dinitrate and 20 coronary angiography and a provocation test with 200 g g/kg/min dobutamine was started. A 20-gauge catheter was ergonovine maleate. The angiography was normal prior to the inserted into his femoral artery to monitor his arterial BP injection of ergonovine maleate (Fig. 1). However, following continuously and a 16-gauge catheter was inserted into his this injection, it showed diffuse spasm in coronary arteries femoral vein. At this time, the patient’s BP was 118/92 overall and subtotal occlusion of the left anterior descending mmHg and his HR was 53 beats/min, but ventricular coronary artery (Fig. 2), in association with ST segment tachycardia was detected. 200-J cardioversion was applied elevation in V2 -4 leads and chest pain. After 500 g again, after which the patient’s heart rhythm normalized. His nitroglycerin was injected directly into the coronary artery, the BP and HR recovered to 95/55 mmHg and 42 beats/min, patient’s pain was subsided and the coronary angiography respectively, and his ST segment was normal. The patient was returned to normal (Fig. 3). The patient was finally diagnosed transferred to the intensive care unit, with continuous infusion with coronary vasospastic angina and started medication. He of 10 g/kg/min dobutamine and 1 g/kg/min isosorbide was discharged without any complications on postoperative day dinitrate without extubation. 7. On postoperative day 1, the patient regained consciousness Jun Young Jo, et al：Pyridostigmine and coronary vasospasm 207 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Fig. 3. Intracoronary nitroglycerine injec- tion relieved the spasm and the coronary angiography recovered. (A) Left coronary circulation (B) Right coronary artery.

reported. , which can be used to treat urinary DISCUSSION retention and myasthenia gravis, can cause coronary vasospasm [2,4]. Moreover, in general anesthesia, neostigmine reportedly There are various causes of cardiac arrest during the causes QT interval prolongation followed by cardiac arrest [3]. perioperative period. In the present case, the patient Although the exact mechanism underlying coronary experienced cardiac arrest after a reversal agent of muscle vasoconstriction needs to be elucidated, in patients with relaxation was used during emergence from general anesthesia, coronary vasospastic angina, the sensitivity of coronary arteries and he was later diagnosed with variant angina. to is increased and acetylcholine may causes Variant angina, which is also referred to as Prinzmetal’s vasoconstriction [10]. angina and coronary vasospastic angina, is a clinical entity In the present case, ST segment elevation on an ECG characterized by episodes of chest pain without exertion at rest strongly suggested acute coronary spasm. The atrioventricular or between midnight and early morning in association with ST block might have resulted from decreased perfusion of the segment elevation on an ECG [5]. The pathogenesis of this atrioventricular nodal branch that arose from the spastic artery. disorder is coronary vasospasm, which is also related to other The provocation test with ergonovine maleate showed a ischemic heart diseases [6]. Hence, angina caused by coronary positive result and there were no other triggering factors for vasospasm is usually called coronary vasospastic angina, rather vasospasm prior to administration of the reversal agents than variant angina [6]. Several factors may precipitate (pyridostigmine and glycopyrrolate). Therefore, we suspect that coronary vasospasm. Cold exposure, the Valsalva maneuver, the cardiac arrest following the ECG change was associated hypomagnesemia and hyperventilation may cause coronary with pyridostigmine, which could induce coronary vasospasm spasm [7-9]. Various drugs also trigger coronary vasospasm, in this patient with coronary vasospastic angina. Moreover, including; parasympathomimetic agents (acetylcholine, metha- several previous reports showed a relationship between , pilocarpine, etc.), anticholinesterase agents, ergonovine, neostigmine and coronary vasospasm, which supports the catecholamine, histamine, and beta blockers [10]. Furthermore, hypothesis that coronary spasm can be associated with alpha-adrenergic stimulation can cause coronary vasospasm pyridostigmine [1,2,4]. The creatine kinase MB concentration [11], and there is a case report of coronary artery spasm was elevated slightly, but the fraction of creatine kinase MB during general anesthesia in which phenylephrine may have in total creatine kinase was not raised sufficiently to explain played an important role [12]. Among these factors, anticho- the myocardial damage, and the troponin-I concentration was linesterase agents and ergonovine are generally used to within the normal range (Table 1). This implies that sponta- diagnose coronary vasospastic angina [13]. neous circulation was restored fast enough to avoid serious In general anesthesia, anticholinesterases are usually used to damage to myocardial tissue. reverse the residual effects of non-depolarizing muscle In this case, an increase in acetylcholine concentration in relaxants. Besides their anticipated muscarinic effects, several sensitive coronary arteries induced by an anticholinesterase fatal cardiac complications of anticholinesterase have been agent caused coronary vasospasm. Therefore, in patients with 208 Anesth Pain Med Vol. 9, No. 3, 2014 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Table 1. Serial Measurements of Creatine Kinase (CK), CK- MB, 4. Yamabe H, Yasue H, Okumura K, Ogawa H, Obata K, Oshima Troponin-I (TnI) and the Fraction of CK-MB in Total CK S. Coronary spastic angina precipitated by the administration of an anticholinesterase drug (distigmine bromide). Am Heart J 1990; Amount of time 120: 211-3. after the initial CK CK-MB Fraction TnI 5. Prinzmetal M, Kennamer R, Merliss R, Wada T, Bor N. Angina ST segment (IU/L) (ng/ml) (%) (ng/ml) pectoris I. A variant form of angina pectoris: Preliminary report. elevation Am J Med 1959; 27: 375-88. 30 min 50 1.6 3.2 0.006 6. Yasue H, Kugiyama K. Coronary spasm: clinical features and 4 hr 138 4.1 2.97 pathogenesis. Intern Med 1997; 36: 760-5. 8 hr 240 3.9 1.63 0.162 7. Miyagi H, Yasue H, Okumura K, Ogawa H, Goto K, Oshima S. 14 hr 357 5.7 1.6 Effect of magnesium on anginal attack induced by hyperventilation in patients with variant angina. Circulation 1989; 79: 597-602. 8. Nakao M, Ohgushi M, Yoshimura M, Morooka M, Okumura M, Ogawa M, et al. Hyperventilation as a specific test for diagnosis coronary vasospastic angina, the effects of the muscle relaxant of coronary artery spasm. Am J Cardiol 1997; 80: 545-9. should be reversed using a method that does not increase the 9. Raizner AE, Chahine RA, Ishimori T, Verani MS, Zacca N, Jamal acetylcholine concentration. Sugammadex may be a good N, et al. Provocation of coronary artery spasm by the cold pressor alternative because it selectively blocks rocuronium without test. Hemodynamic, arteriographic and quantitative angiographic relying on anticholinesterase activity, and it is also an effective observations. Circulation 1980; 62: 925-32. 10. Yasue H, Nakagawa H, Itoh T, Harada E, Mizuno Y. Coronary reversal agent of vecuronium [14]. artery spasm—clinical features, diagnosis, pathogenesis, and In conclusion, we report a patient who was resuscitated treatment. J Cardiol 2008; 51: 2-17. from cardiovascular collapse that was probably due to coronary 11. Yasue H, Touyama M, Kato H, Tanaka S, Akiyama F. vasospasm following pyridostigmine administration. Anesthe- Prinzmetal's variant form of angina as a manifestation of siologists should use anticholinesterases with caution in patients alpha-adrenergic receptor-mediated coronary artery spasm: with coronary vasospastic angina. documentation by coronary arteriography. Am Heart J 1976; 91: 148-55. 12. Kim YL, Kim EJ, Seo DM, Lee JH, Lee SG, Ban JS. Coronary REFERENCES artery spasm following intravenous phenylephrine on a patient under general anesthesia with previously undiagnosed variant 1. Kido K, Mizuta K, Mizuta F, Yasuda M, Igari T, Takahashi M. angina and successful treatment by nitroglycerin−A case report−. Coronary vasospasm during the reversal of neuromuscular block Anesth Pain Med 2013; 8: 99-103. using neostigmine. Acta Anaesthesiol Scand 2005; 49: 1395-6. 13. Sueda S, Kohno H, Fukuda H, Ochi N, Kawada H, Hayashi Y, 2. Suzuki M, Yoshii T, Ohtsuka T, Sasaki O, Hara Y, Okura T, et et al. Induction of coronary artery spasm by two pharmacological al. Coronary spastic angina induced by anticholinesterase agents: comparison between intracoronary injection of acetylcho- medication for myasthenia gravis a case report. Angiology 2000; line and ergonovine. Coron Artery Dis 2003; 14: 451-7. 51: 1031-4. 14. Suy K, Morias K, Cammu G, Hans P, van Duijnhoven WG, 3. Tüfek A, Yildirim B, Tokgöz O, Karaman H, Çelik F, Aycan IÖ. Heeringa M, et al. Effective reversal of moderate rocuronium-or Immediate cardiac arrest after neostigmine administration. J Pak vecuronium-induced neuromuscular block with sugammadex, a Med Assoc 2012; 62: 609. selective relaxant binding agent. Anesthesiology 2007; 106: 283-8.