Bilateral upper extremity thrombophlebitis related to intravenous amiodarone: a case report.

Abstract: A 47-year-old male had bilateral upper extremity thrombophlebitis after use of intravenous amiodarone for sustained ventricular tachycardia complicating myocardial infarction. Intravenous amiodarone has been widely used since it was introduced 20 years ago for severe intractable arrhythmias. Superficial thrombophlebitis was frequently noted in the early case reports when high-dose intravenous amiodarone was used. Superficial thrombophlebitis could extend hospitalization and become a significant source of distress to our patients. Some authors recommend insertion of a central line to administer intravenous amiodarone especially with expected extended use of therapy. The treating physician should be vigilant and switch from intravenous therapy to oral therapy as soon as the patient's condition stabilizes and oral therapy can be started.

Key Words: amiodarone, side effect, superficial thrombophlebitis

**********

Intravenous amiodarone has been widely used since it was introduced 20 years ago for severe intractable arrhythmias and has been recently accepted as first line therapy in the advanced cardiac life support algorithms for pulseless ventricular tachycardia/ventricular fibrillation.

Although we are more familiar with this medicine nowadays, certain side effects are overlooked but potentially avoidable. Superficial thrombophlebitis was frequently noted in the early case reports when high-dose intravenous amiodarone was used.

Case Report

We report the case of a 47-year-old male patient with a medical history of essential hypertension, alcohol abuse, and manic-depressive disorder who was admitted for a major depressive episode to the psychiatry floor.

Around 3:00 AM the second day of admission, he woke up complaining of severe chest pain with nausea and vomiting. An immediate electrocardiogram showed inferior wall injury consistent with acute inferior myocardial infarction.

The patient was then transferred to the intensive care unit, and he was given a fibrinolytic agent and was started on anti-ischemic therapy. He continued to have chest pains with persistent electrocardiographic changes. The patient was taken for emergent angioplasty and a stent was placed in the right coronary artery. During the procedure, he had ventricular tachycardia requiring intravenous amiodarone.

He was transferred back to the intensive care unit, where intravenous amiodarone was continued. Amiodarone was mixed in D5W solution at a concentration of 2 mg/mL and given through a peripheral vein at a rate of 36 mg/h, which is within manufacturer accepted limits for intravenous administration of amiodarone. A transthoracic echocardiogram showed mild left ventricular hypertrophy, normal systolic function, mild pulmonary hypertension, and an enlarged right ventricle. Since the patient was clinically and hemodynamically stable, amiodarone was stopped, but his arrhythmias recurred with symptomatic ventricular tachycardia requiring reinstitution of intravenous amiodarone at another peripheral intravenous site in the right arm.

On day 5 of coronary care unit admission, the patient was noted to have some erythema and tenderness over the medial aspect of the right arm and forearm on the left side. The areas were warm and tender to palpation. No lymph nodes were palpable. His temperature was 101.4[degrees]F by tympanic thermometer. Chest roentgenogram, urinalysis, and blood cultures failed to show any source of extracutaneous infection. The patient was suspected to have bilateral upper extremity septic thrombophlebitis and was started empirically on dicloxacillin.

Intravenous therapy with amiodarone was discontinued, and the patient was started on sotalol. He became afebrile and the inflammation subsided. Venous Doppler ultrasound was performed and showed extensive thrombosis of the right basilic vein up to the axillary vein and the left basilic vein up to the antecubital fossa. This extension to the deep veins is why it is considered a severe case of thrombophlebitis. At that point, the diagnosis of superficial thrombophlebitis was confirmed. The patient was treated with hot compressors, analgesics, and arm elevation, which expedited the final resolution of symptoms and signs of thrombophlebitis.

Discussion

Superficial thrombophlebitis related to intravenous amiodarone is a potentially avoidable problem that was noted frequently in early literature. Aravanis et al (1) reported in 1982 the development of severe local reaction at the site of intravenous injection; this reaction was in the form of severe pain, swelling, and inflammation beyond the site of intravenous access. Two of the three reported cases occurred in the coronary care unit setting after myocardial infarction, after the development of intractable ventricular tachycardia. The third case occurred in a patient who had cardiomyopathy and supraventricular tachycardia. The dose given was reported as 7.5 to 10 mg/kg. In the first reported patient, changing the intravenous site created the same problem as in our patient. The author suggested the use of a central venous catheter to avoid this complication.

In their letter to the editor, Drs. Antonelli and Barzilay (2) reported superficial thrombophlebitis secondary to amiodarone at a lower dose (2 to 4 mg/kg). Amiodarone was given intravenously in 36 patients for intractable ventricular arrhythmias or supraventricular arrhythmias. In 33 patients, amiodarone was given through a peripheral vein; in the rest it was given through the subclavian vein. In 24 of the 33 patients (73%), signs of inflammation were present at the site of the infusion few hours after the beginning of the treatment, whereas no signs of inflammation were noticed in those who received amiodarone through the subclavian vein. One thousand units of heparin and 10 mg of hydrocortisone were added separately to the 5% glucose solution containing amiodarone, but these measures were ineffective.

In one study (3) that tested the effectiveness and safety of intravenous amiodarone in recent-onset atrial fibrillation, 1,200 mg of intravenous amiodarone was given in 24 hours followed up by oral amiodarone. The frequency of thrombophlebitis was 25% of cases during hospitalization. In another study (4) conducted on patients with atrial fibrillation, amiodarone was given at a dose of 5 mg/kg intravenously over 30 minutes, then 400 mg orally every 8 hours for 6 doses; 1 of 38 patients who received amiodarone had development of thrombophlebitis.

Intravenous amiodarone was also used in postcardiothoracic surgeries to prevent atrial fibrillation. In one study, (5) amiodarone was given intravenously as 1 g/d for 48 hours and then 400 mg/d orally. One in 50 patients given intravenous amiodarone had development of thrombophlebitis.

Conclusions

Intravenous amiodarone has been extensively used to treat various arrhythmias. It is associated with severe local reaction at the intravenous site, especially with high-dose therapy given through a peripheral line for an extended period of time. This side effect is encountered less frequently nowadays with the current recommended dosage.

Superficial thrombophlebitis could extend hospitalization and become a significant source of distress to our patients. Some authors recommended insertion of a central line to administer intravenous amiodarone, especially with expected extended use of therapy. Drs. Antonelli and Barzilay (2) tried adding local intravenous heparin and hydrocortisone to prevent this complication, without significant benefit.

On the other hand, oral amiodarone has excellent bioavailability, is significantly less expensive than intravenous preparations, and can be safely used in stable arrhythmias. The treating physician should be vigilant to switch from intravenous therapy to oral therapy as soon as the patient's condition stabilizes and oral therapy can be started.

References

1. Aravanis C, Papasteriades E, Steriotis J. Acute thrombophlebitis due to IV use of amiodarone. Chest 1982;82:515-516.

2. Antonelli D, Barzilay J. Acute thrombophlebitis following IV amiodarone administration. Chest 1983;84:120.

3. Kreiss Y, Sidi Y, Gur H. Efficacy and safety of intravenous amiodarone in recent-onset atrial fibrillation: experience in patients admitted to a general internal medicine department. Postgrad Med J 1999;75:278-281.

4. Joseph AP, Ward MR. A prospective, randomized controlled trial comparing the efficacy and safety of sotalol, amiodarone, and digoxin for the reversion of new-onset atrial fibrillation. Ann Emerg Med 2000;36:1-9.

5. Solomon AJ, Greenberg MD, Kilborn MJ, et al. Amiodarone versus a B-blocker to prevent atrial fibrillation after cardiovascular surgery. Am Heart J 2001;142:811-815.

Reading maketh a full man, conference a ready man, and writing an exact
man.
--Sir Francis Bacon

Omar Aljitawi, MD, Baha Shabaneh, MD, and Jack Whitaker, MD

From the Division of Cardiology and Department of Internal Medicine, James H. Quillen College of Medicine, East Tennessee State University, and James H. Quillen VA Medical Center, Johnson City, TN.

Reprint requests to Dr. Omar Aljitawi, 4916 W. 08th Terrace, #723, Leawood KS 66211. Email: [e-mail]

Accepted December 16, 2004.

RELATED ARTICLE: Key Points

* Intravenous amiodarone has been extensively used to treat various arrhythmias. It is associated with severe local reaction at the intravenous site, especially with high-dose therapy given through a peripheral line for an extended period of time.

* Superficial thrombophlebitis could extend hospitalization and become a significant source of distress to our patients.

* To avoid thrombophlebitis related to intravenous amiodarone, some authors recommend insertion of a central line to administer intravenous amiodarone, especially with expected extended use of therapy.

* Oral amiodarone has excellent bioavailability, is significantly less expensive than intravenous preparations, and could be safely used in stable arrhythmias.