Case Study: Cardiomyopathy From Epinephrine in Anesthesia

"Medical Journeys" is a set of clinical resources reviewed by doctors, meant for physicians and other healthcare professionals as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. "Medical Journeys" chart a path each step of the way for physicians and patients and provide continual resources and support, as the caregiver team navigates the course of a disease.

This month: A noteworthy case study.

Presentation for Endoscopic Sinus Surgery

A 78-year-old woman with mycosis in the maxillary sinus presented to a hospital for scheduled endoscopic sinus surgery. She had a history of high blood pressure and hyperlipidemia. Physical and laboratory examinations were all normal, including chest x-ray, electrocardiography (ECG), and spirometry.

The anesthesiologist administered propofol and remifentanil, inducing anesthesia without any complications. Just prior to the incision, the patient received a submucosal injection of 3 mL of local anesthetics (lidocaine 0.5%; epinephrine 1:200,000). At that point, clinicians noted a sharp increase in the patient's blood pressure to 254/185 mmHg and onset of ventricular tachycardia (135 bpm).

In response, the team administered 50 mg of intravenous lidocaine, which restored a normal sinus rhythm, without cardioversion. The ECG revealed slight ST-segment elevation in the limb lead II, but hemodynamic stability was restored. At that point, arterial blood gas analysis showed no evidence of lactic acidosis, and clinicians proceeded with the surgery as planned.

Post-Surgery Exams, Tests

Following the surgery, clinicians conducted a detailed examination of the patient, including chest x-ray and review of the time changes of the 12-lead ECG. Compared with the preoperative findings, the chest x-ray performed post-surgery showed slight cardiac dilatation. At 1 hour after surgery, the 12-lead ECG revealed slight ST-segment elevation in the precordial lead V2 and slight depression in leads V3 to V6. Additionally, an echocardiogram showed apical akinesis -- findings associated with acute coronary syndrome or Takotsubo cardiomyopathy (TCM).

As a result, clinicians performed a coronary arteriography the same day, which showed no evidence of significant stenosis of the coronary artery. However, a left ventricular angiography demonstrated akinesis from the area of the apex to the left ventricle anterior wall.

Postoperative blood tests were performed, and 1 hour after the surgery, the patient's creatine kinase and creatine kinase isozyme-MB levels had returned to normal, with a slight elevation in the troponin-I level.

Diagnosis of Takotsubo Cardiomyopathy

Based on these findings, clinicians diagnosed the patient with TCM.

Six hours after surgery, the patient's creatine kinase and troponin-I levels rose to peak levels, and then decreased gradually. To prevent intraventricular thrombosis, clinicians administered 5,000 units/day of heparin. On day 1 following surgery, a 12-lead ECG continued to show an abnormal pattern; however, an echocardiogram showed that the left ventricular wall motion had improved, leading clinicians to discontinue the heparin.

On the second day after surgery, the 12-lead ECG revealed a giant negative T wave; this finally improved 4 months after surgery. On postoperative day 8, ¹²³I-metaiodobenzylguanidine myocardial scintigraphy was performed, which showed decreased accumulation in the septum and increased accumulation in the base, reflecting a diagnosis of TCM. On day 9 post-surgery, the patient was discharged from the hospital.

Warning Signs

Clinicians reporting this case of a patient who develops intraoperative TCM after receiving a local anesthetic containing a very low dose of epinephrine noted that even as little as 0.015 mg of epinephrine can induce TCM. They cautioned healthcare team members to consider the possibility of asymptomatic TCM in patients who develop hemodynamic changes and ST segment abnormalities of the ST segment after receiving epinephrine.

Characteristic features of TCM include reversible left ventricular dysfunction, with distinctive regional wall motion abnormalities. Because TCM can be induced by emotional or physical stress, it has also been called "stress-induced cardiomyopathy." Usual triggers include "a major emotional stressor or a serious medical illness; sometimes, even the stress from surgery can trigger TCM," the case authors noted.

Intraoperative TCM is not uncommon, and may be triggered not by stress but by the use of epinephrine during surgery: Epinephrine-induced (Ei)-TCM emerges immediately after epinephrine administration, the authors explained, urging caution when administering the drug, especially in the nasal mucosa, vaginal mucosa, and uterus.

TCM Triggers

TCM is thought to be triggered when epinephrine induces "a switch in signal trafficking through the pleiotropic β2-adrenergic receptor between the canonical stimulatory G-protein-activated cardiostimulant and inhibitory G-protein-activated cardiodepressant pathways," the case authors explained. During onset, TCM is associated with a mean left ventricular ejection fraction of about 40%, and although the prognosis is generally good, with cardiac function restored within days or weeks, common complications include cardiogenic shock, lung edema, and severe arrhythmia.

The observations in this case, including the time of onset, the data of the detailed postoperative examination, and the postoperative course, were consistent with Ei-TCM, the case authors said. Likewise, the patient's symptom onset-transient increase in blood pressure, ventricular tachycardia, followed by slight ST elevation all reflect Ei-TCM.

When the patient's sinus rhythm normalized and hemodynamic stability was restored, the decision was made to proceed with surgery as planned, and followed up with a postoperative 12-lead ECG.

The case authors noted that epinephrine is used at the time of surgery to prevent allergic reactions like anaphylaxis and asthma, as well as bleeding from the surgical site. And while about 40 cases of Ei-TCM have been reported, most have occurred when epinephrine has been administered for anaphylaxis or when high doses have been administered by mistake. Rare instances of Ei-TCM have also occurred when epinephrine has been administered to the nasal mucosa to achieve surface anesthesia or used as irrigation fluid for arthroscopy, with fatal consequences.

The typical dose of epinephrine is 0.3 mg to 1 mg, and levels above that have been significantly linked to risk of complications such as heart failure, cardiogenic shock, and pulmonary edema, the case authors said.

The dose of 0.015 mg used in this patient "is the smallest among previously reported cases," the authors said, highlighting that even very low doses can induce TCM. Thus, the group advised caution in even local use of epinephrine-containing anesthetics, and careful monitoring of patients' vital signs.

"In particular, the local administration of epinephrine via the nasal mucosa, vaginal mucosa, and uterus, where the blood flow is relatively abundant, has been identified in many TCM cases," the authors noted. While the drug "is extremely effective and useful for the hemostasis of these tissues, administration of such a drug via these tissues [requires caution] because it is highly prone to misinjection into the vessel."

Read previous installments in this series:

Part 1: Cardiomyopathy: What are the Signs, What are the Symptoms?

Part 2: Diagnosing Cardiomyopathy: History, Examination, and Testing

Part 3: Cardiomyopathy: Epidemiology, Etiology, and Pathophysiology