Dobutamine-Induced Myoclonus in a Patient With Advanced Heart Failure and Chronic Kidney Disease

Abstract

Dobutamine is a positive inotropic agent often used in treatment of cardiogenic shock. Although there are well-documented adverse effects, dobutamine-induced myoclonus is a rarely reported phenomenon. Our case offers a direct and temporally related description of myoclonus, with onset observed within hours of dobutamine initiation and complete resolution within minutes of discontinuation.

Graphical abstract

History of Presentation

A 51-year-old woman with known systolic heart failure presented with dyspnea on exertion, lightheadedness, orthopnea, and hypotension. In the weeks before presentation, the patient had developed symptomatic hypotension for which sacubitril/valsartan and carvedilol were discontinued by her primary cardiologist. Medications on admission included aspirin 81 mg daily, atorvastatin 20 mg daily, bupropion 300 mg daily, hydroxyzine 50 mg 3 times daily as needed for anxiety, sertraline 50 mg daily, and trazodone 50 mg nightly as needed for insomnia.

Learning Objectives

• •To recognize myoclonus as a rare yet debilitating side effect of continuous dobutamine infusion.
• •To recognize that dobutamine-induced myoclonus can have prompt symptom resolution once clinicians substitute inotropic agents.

On examination, her heart rate was 65 beats/min and blood pressure 91/62 mm Hg. The jugular venous pressure was 4 cm of water, lungs were clear to auscultation, there were regular heart rate and rhythm with no murmurs, and extremities were without edema. Laboratory tests showed sodium 137 mmol/L, potassium 4.0 mEq/L, creatinine 1.57 mg/dL, and estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration 2021 equation of 40 mL/min/1.73 m².

Given the patient’s persistent, symptomatic hypotension despite cessation of goal-directed medical therapy, a pulmonary artery catheter was placed. This showed a cardiac index by thermodilution of 1.95 L/min/m².

Dobutamine 3 μg/kg/min was initiated. Approximately 12 hours later, the patient exhibited sudden onset of involuntary jerking movements in her neck, torso, and arms bilaterally. These episodes increased in frequency throughout the night, occurring at rest, and worsened with voluntary movement. By the afternoon of hospitalization day 3, the episodes were occurring every few seconds. On physical examination, the patient had normal mental status and an otherwise unremarkable neurologic examination, including normal tone, coordination, strength, sensation, and deep tendon reflexes in the extremities. There was no stimulus-induced myoclonus or resting, action, or postural tremor noted.

Past Medical History

The patient had a history significant for nonischemic cardiomyopathy diagnosed in 2014, stage 3a chronic kidney disease (CKD), biventricular automatic implantable cardioverter-defibrillator, and treated hypothyroidism.

Differential Diagnosis

The initial differential diagnosis included focal seizure without impaired awareness, electrolyte imbalances, serotonin syndrome due to the presence of multiple serotonergic medications including trazodone, sertraline, and bupropion, and drug-induced myoclonus.

Investigations

There were no metabolic abnormalities; specifically, potassium, sodium, magnesium, blood urea nitrogen, and phosphorus were all within normal limits.

Neurologic consultation was obtained. Given that the patient remained afebrile, hemodynamically stable, showed no signs of muscle rigidity, was without rhythmic jerking motions, and had no alterations in her home medications either preceding or during admission, it was believed that serotonin syndrome and focal seizure were unlikely. Thus, electroencephalogram was not performed.

Management

The clinical suspicion of dobutamine-induced myoclonus led to a therapeutic trial of dobutamine discontinuation. Dopamine at 3 μg/min/min was initiated when dobutamine was stopped. Remarkably, within 30 minutes of dobutamine cessation, the patient had rapid, complete resolution of her symptoms with no further recurrence of myoclonus.

Discussion

We present a unique case of rapid-onset dobutamine-induced myoclonus. Our case provides the most direct and temporally related description of this phenomenon reported in the literature thus far, with myoclonus onset within hours of initiation and complete resolution within minutes of discontinuation.

A literature review revealed only 3 previous reports documenting this phenomenon.1, 2, 3 All previous reports describe onset of myoclonus following dobutamine infusion within 2 days to 3 weeks. In 1 report, a patient on peritoneal dialysis exhibited myoclonus after receiving 3 days of dobutamine 3 μg/kg/min². In another patient on peritoneal dialysis and dobutamine 5 μg/kg/min, myoclonus occurred 3 weeks after initiation.³ There are also reports in patients not on dialysis exhibiting myoclonus after dobutamine infusions up to 3 days later.¹

Drug-induced myoclonus can be a diagnostic challenge, especially in the setting of medical comorbidities and polypharmacy. Medications such as selective serotonin reuptake inhibitors, antibiotics including cefepime and levofloxacin, and antiepileptic drugs including lamotrigine and phenytoin have been associated with myoclonus.⁴ However, dobutamine has only rarely been associated with myoclonus with very few documented cases in the literature, all of which are in patients with advanced CKD or on dialysis. Importantly, pharmacologic references including Micromedex, Drug Facts and Comparisons, and American Society of Health-Systems Pharmacists Drug Information do not list myoclonus as a dobutamine adverse effect.

The mechanism underlying dobutamine-induced myoclonus remains unclear but may be linked to kidney failure and neurotoxicity. P-glycoprotein inhibition is suggested to decrease biotransformation and enhance dobutamine penetration into the central nervous system. Severe kidney failure and uremia could further alter O-methylation of dobutamine, prolonging its half-life.¹

The observed association between dobutamine and myoclonus could be strengthened with further investigation in future reports. Serum dobutamine levels paired with symptom severity would provide valuable quantitative data and evidence towards a dose-dependent relationship between myoclonus severity and drug levels. Although clinically implausible, a demonstration of symptom recurrence with re-initiation of dobutamine would strengthen the association, allowing for a definite association on the Naranjo scale.⁵

Follow-up

The patient was re-admitted for orthotopic heart transplantation 1 month after discharge from our service (Figure 1). She did not have recurrence of myoclonus in the interim. Fortunately, the operation was successful.

Figure 1.

Clinical Timeline

Temporal overview of myoclonus onset and resolution in relation to dobutamine initiation and discontinuation.

Conclusions

This case contributes to the limited but growing body of literature shedding light on myoclonus as a rare side effect of dobutamine. Furthermore, we emphasize the importance of clinician awareness of the potential adverse event of myoclonus when initiating dobutamine in patients with cardiogenic shock, especially with concomitant CKD. Multidisciplinary collaboration among cardiologists, nephrologists, and neurologists is essential in the diagnostic evaluation and management of dobutamine-induced myoclonus.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.