Takotsubo cardiomyopathy is a stress-induced cardiomyopathy first described in Japan >20 years ago. Subsequently, several cases of anesthesia-related, perioperative takotsubo cardiomyopathy have been reported.1,2 Takotsubo cardiomyopathy has been described in patients undergoing liver transplantation.3–9 However, the anesthetic management of patients with a history of takotsubo cardiomyopathy remains unclear, especially in patients undergoing liver transplantation.
We describe the use of dexmedetomidine in the anesthetic management of a patient with a history of takotsubo cardiomyopathy who underwent living-donor liver transplantation. The use of perioperative dexmedetomidine may be a promising adjuvant to general anesthesia in these challenging patients.
We received approval from the institutional ethical committee and informed consent from the patient for publication of this report.
A 48-year-old male patient weighing 85 kg was scheduled to undergo living-donor liver transplantation. He did not have either diabetes or hypertension. The indication for transplantation was end-stage liver disease subsequent to hepatitis C-related cirrhosis. His preoperative workup included resting echocardiography and dobutamine stress echocardiography. Both of the studies revealed no regional wall motion abnormalities and a systolic function ejection fraction of 63%.
On arrival in the operating room, the patient stated that he was anxious about surgery. No premedication was given. General anesthesia was induced with 100 mg propofol, 10 mg cisatracurium, and 200 μg fentanyl. Anesthesia was maintained with 2% sevoflurane in oxygen (fraction of inspired oxygen, 0.6).
Ten minutes after the induction of anesthesia, before skin incision, the patient developed ventricular tachycardia at a rate of 180 beats/min. His arterial blood pressure decreased to 80/60 mm Hg. Electrocardioversion was administered twice, which restored normal sinus rhythm. Transesophageal echocardiography was performed and revealed severe left ventricular (LV) dysfunction. Norepinephrine infusion was started at 0.3 μg/kg/min. The patient was transferred to the surgical intensive care unit (ICU) on mechanical ventilation via an endotracheal tube. Twelve-lead electrocardiogram showed sinus tachycardia; heart rate 130 beat/min, prolonged QT interval, and inverted T wave but no ST segment elevation or depression. Transthoracic echocardiography confirmed the diagnosis of severe LV dysfunction with global akinesia of the entire LV except for the base, which functioned normally. His ejection fraction was 15% (Supplemental Digital Content 1, Video 1, http://links.lww.com/AACR/A30; Supplemental Digital Content 2, Video 2, http://links.lww.com/AACR/A31). Emergency cardiac catheterization demonstrated normal coronary arteries. Two days later, norepinephrine infusion was stopped, and the patient was discharged from the ICU on day 5. The diagnosis on discharge was takotsubo cardiomyopathy.
Forty days later, the patient was rescheduled for living-donor liver transplantation. Both resting and dobutamine stress echocardiography were performed, revealing normal cardiac function. On arrival in the preinduction room, transthoracic echocardiography was performed before the induction of anesthesia. The findings were normal. Dexmedetomidine infusion was started at a dose of 0.5 μg/kg/h without an initial loading dose. After 15 minutes of dexmedetomidine infusion, the patient’s Ramsay sedation scale score was 3 (responsive to commands only), heart rate 70 beats/min, and arterial blood pressure 110/60 mm Hg. Another transthoracic echocardiography was performed, and its findings were also normal (Supplemental Digital Content 3, Video 3, http://links.lww.com/AACR/A32).
General anesthesia was induced with 50 mg propofol, 10 mg cisatracurium, and 100 μg fentanyl. Anesthesia was maintained with 1% sevoflurane in oxygen (fraction of inspired oxygen, 0.6). A pulmonary artery catheter was inserted. His right atrial pressure was 10 mm Hg, pulmonary artery pressure 25/16 mm Hg, pulmonary capillary wedge pressure 10 mm Hg, cardiac output 11 L/min, and systemic vascular resistance 581/dyne-sec/cm5. Transesophageal echocardiography was performed after the induction of anesthesia and before skin incision demonstrated normal cardiac function. Dexmedetomidine infusion was maintained throughout the 3 stages of liver transplantation (the dissection, anhepatic, and reperfusion stages) at doses of 0.3–0.5 μg/kg/h guided by hemodynamic data. Twenty minutes after reperfusion, the patient’s arterial blood pressure decreased to 80/40 mm Hg. Transesophageal echocardiography was performed and revealed normal cardiac systolic function (Supplemental Digital Content 4, Video 4, http://links.lww.com/AACR/A33). Terlipressin (1 mg) was administered as an IV bolus followed by infusion at 2 μg/kg/h. This was supplemented with a low-dose norepinephrine infusion at 0.05 μg/kg/min to maintain mean arterial blood pressure at >70 mm Hg.
His trachea was extubated at the end of surgery while he was still receiving an dexmedetomidine infusion at a rate of 0.2 μg/kg/h, and he was transferred to the ICU. Two days later, the dexmedetomidine infusion was stopped, and the patient was discharged from the ICU on day 5.
Takotsubo cardiomyopathy was first described in Japan in 1990,10 but it was not reported in the perioperative period until 2006.11 Since then, many cases of perioperative takotsubo cardiomyopathy have been reported. However, it is not clear how these patients are best managed during anesthesia. Previous reports have described the perioperative management of patients with a history of takotsubo cardiomyopathy who underwent general12 and cardiac13,14 surgery. The in-hospital mortality rate of takotsubo cardiomyopathy is reportedly 1.1%–1.7%15 with a recurrence rate of 2%–10%.16,17 However, all available data were drawn from nonsurgical patients, and the true recurrence rate of perioperative takotsubo cardiomyopathy is unknown. There is no evidence to support any specific management strategy or drug to prevent the recurrence of perioperative takotsubo cardiomyopathy.
High perioperative doses of β-blockers are suggested to block excessive levels of endogenous catecholamines and prevent recurrence.18,19 This might benefit patients with liver cirrhosis because the current guidelines recommend the use of propranolol in these patients to reduce portal pressure and prevent variceal bleeding.20 Esmolol and labetalol have been used previously to prevent the recurrence of takotsubo cardiomyopathy during follow-up electric convulsive therapy treatments. However, in 1 report, 26% of patients with takotsubo cardiomyopathy were taking β-blockers at the time they presented with this syndrome.21
Although the pathophysiology of takotsubo cardiomyopathy remains unclear, there is increasing evidence that exaggerated sympathetic stimulation and high levels of endogenous catecholamines play a central role.22 Our patient developed LV failure and cardiogenic shock after electrocardioversion of ventricular tachycardia. Takotsubo cardiomyopathy has been reported consequent to various forms of electrical stimulation: electrical cardioversion23,24 and electroconvulsive therapy.25 However, it is not known whether electrical stimulation has a direct role in the development of the cardiomyopathy or whether the cardiomyopathy is merely the result of catecholamine overload.
We used dexmedetomidine to provide our patient with a deeper level of anxiolysis before the induction of anesthesia. Dexmedetomidine is a highly selective α2-adrenoceptor agonist. Stimulation of the α2-adrenoceptor in the central nervous system causes a 60%–80% reduction in sympathetic outflow and endogenous catecholamine levels.26 Thus, dexmedetomidine may have applications in preventing the recurrence of perioperative takotsubo cardiomyopathy.27 Dexmedetomidine is mainly metabolized in the liver. The elimination half-life of dexmedetomidine could increase in patients with Child–Pugh class C cirrhosis.28 In our case, we chose to omit the initial loading dose of dexmedetomidine and continued dexmedetomidine infusion at 0.3–0.5 μg/kg/h to minimize the accumulation of the drug and avoid undesirable hemodynamic effects.
Hemodynamic instability is a challenge in patients with a history of takotsubo cardiomyopathy. Intraoperative hypotension should be treated with a drug with predominantly α-adrenergic agonist activity. Drugs with inotropic properties should be used with caution, because they may precipitate development of the syndrome.29 In our case, we used terlipressin as the mainstay of intraoperative hypotension management. Terlipressin is a lysine vasopressin that exhibits greater selectivity for the V1 vasopressin receptor than arginine vasopressin.30 Stimulation of the V1 vasopressin receptor resulted in increased systemic vascular resistance and mean arterial blood pressure. Moreover, stimulation of V1 vasopressin receptors in the splanchnic area increases the effective arterial blood volume via splanchnic arteriolar vasoconstriction.31
In summary, we described a patient with a history of takotsubo cardiomyopathy in whom we used dexmedetomidine as an adjunct for general anesthesia during liver transplantation. We suggest this be considered for such patients and the results shared to confirm or refute the therapeutic use of dexmedetomidine in this setting.
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