Refractory bradycardia and hypotension in patients with autonomic dysfunction treated with pseudoephedrine

  1. Caleigh Curran 1,
  2. Farideh Davoudi 2,
  3. Gabriel Foster 3 and
  4. Patrick Gordan 2
  1. 1 Pharmacy, Salem Hospital, Salem, Massachusetts, USA
  2. 2 Internal Medicine, Salem Hospital, Salem, Massachusetts, USA
  3. 3 Cardiology, Salem Hospital, Salem, Massachusetts, USA
  1. Correspondence to Dr Patrick Gordan; PGORDAN@PARTNERS.ORG

Publication history

Accepted:05 Apr 2023
First published:26 Apr 2023
Online issue publication:26 Apr 2023

Case reports

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Abstract

We describe a man in his 40s with a history of chronic intranasal cocaine use and C5–C7 incomplete quadriplegia complicated by neurogenic orthostatic hypotension, admitted to the intensive care unit for worsening bradycardia and hypotension requiring initiation of dopamine and an increase of his home midodrine dose. The patient experienced refractory bradycardia and hypotension with weaning of dopamine, and therefore a recommendation was made to add pseudoephedrine to his current regimen. This case describes the addition of pseudoephedrine to facilitate weaning off intravenous vasopressors within 24 hours in a patient with refractory bradycardia and hypotension secondary to autonomic dysfunction.

Background

Hypotension related to autonomic dysfunction presents a particular challenge in patients on vasopressors who are refractory to conventional measures. Patients with autonomic dysfunction may continue to have complications related to bradycardia and hypotension despite resolution of their critical illness. Treatment with long-term use of intravenous vasopressors is not an optimal solution, and minimal guidance has been provided for transitioning patients with sustained hypotension to oral agents. Therefore, we describe a case with autonomic dysfunction where utilisation of oral pseudoephedrine resulted in increased blood pressure (BP) and heart rate (HR) and aided in discontinuation of intravenous vasopressors.

Case presentation

A man in his 40s (body mass index 14.8), with a history of chronic intranasal cocaine use and C5–C7 incomplete quadriplegia secondary to traumatic injury (gunshot wound in 1993) complicated by neurogenic orthostatic hypotension (on outpatient midodrine) and sinus bradycardia, chronic urinary retention, chronic obstructive pulmonary disease and anaemia, presented to the emergency room with worsening dysphagia secondary to severe oesophagitis in the setting of cocaine-induced vasoconstriction and ischaemia. The hospital course was complicated by worsening sinus bradycardia (HR ranging from 48 to 55 beats/min) associated with hypotension (BP 60/40 mm Hg), prompting transfer to the intensive care unit (ICU) for initiation of intravenous dopamine. The patient was started on dopamine at a rate of 7.5 µg/kg/min and his outpatient dose of midodrine was increased from 10 mg two times per day to 10 mg every 8 hours, resulting in sustained mean arterial pressures (MAPs) above 65 mm Hg with an HR ranging from 63 to 76 beats/min. In consultation with the cardiology team, the aetiology of his symptoms was deemed to be secondary to autonomic dysfunction. On day 2 of the patient’s ICU admission, dopamine infusion rate decreased to a rate of 5 µg/kg/min; however, this decrease resulted in recurrence of sinus bradycardia with HRs in the range of 50 beats per minute and hypotension with systolic BP in the range of 70 mm Hg. Midodrine dose was subsequently increased to 20 mg every 8 hours to help facilitate weaning off the dopamine infusion. Ultimately, given persistent bradycardia and hypotension, a recommendation was made to add oral pseudoephedrine 60 mg every 6 hours.

Treatment

  • Dopamine infusion.

  • Midodrine 20 mg every 8 hours.

  • Pseudoephedrine 60 mg every 6 hours.

Outcome and follow-up

After receiving the first two doses of pseudoephedrine, the patient could tolerate a dopamine infusion rate of 2 µg/kg/min, maintaining MAPs above 70 mm Hg and systolic BPs greater than 90 mm Hg. Less than 24 hours after initiation of pseudoephedrine, the patient was able to be fully weaned from dopamine. After 3 days of therapy with pseudoephedrine 60 mg every 6 hours, the dose was successfully titrated down to 30 mg every 6 hours with stable haemodynamics. On day 7 of the patient’s hospital admission, pseudoephedrine was discontinued, and the patient remained haemodynamically stable. On day 8, the patient was successfully discharged on midodrine 20 mg three times a day.

Discussion

First-line agents for treatment of shock include vasopressors, which can be either pure vasoconstrictors (phenylephrine, vasopressin) or inoconstrictors (dopamine, norepinephrine and epinephrine).1 Such agents are typically administered intravenously, which is not an optimal solution for those who require long-term therapy. Limited options for oral agents are available, primarily restricted to midodrine, an α1-receptor agonist, which augments BP in those with persistent hypotension from chronic conditions. Pseudoephedrine is another peripheral α1-adrenergic receptor agonist, which also directly stimulates β-adrenergic receptors in the postsynaptic nerve terminals.2 Downstream effects of such receptor activation include vasoconstriction, bronchodilation, increased HR and contractility. In a meta-analysis of 12 studies including 1285 patients, pseudoephedrine was found to cause a notable increase in systolic BP and HR, especially when using the immediate release formulation. Authors also described a dose–response relationship between systolic BP and the immediate release formulation, where more substantial elevations in systolic BP were found with higher doses of pseudoephedrine (>60 mg). A limitation of this meta-analysis lies in the fact that it only evaluated the outcome of BP and HR, excluding any additional adverse effects that pseudoephedrine may pose.3 Limited evidence otherwise exists regarding the use of oral pseudoephedrine as an adjunctive treatment for refractory neurogenic sinus bradycardia and hypotension.4 5 After thorough review of the literature, this is the first case report describing the use of oral pseudoephedrine for patients with acute-on-chronic bradycardia and hypotension secondary to autonomic dysfunction related to a traumatic spinal cord injury, to help facilitate discontinuation of intravenous vasopressors. There is a single case report detailing pseudoephedrine use to wean off vasopressor support in a patient with underlying paraplegia; however, this was in the setting of septic shock.5

In individuals with autonomic dysfunction, compensatory mechanisms for regulating BP such as parasympathetic inhibition and increased sympathetic outflow are decreased.6 Primary causes of neurogenic orthostatic hypotension include disease states such as Parkinson’s disease, Lewy body dementia, multiple system atrophy and familial dysautonomia. Secondary causes can involve those that target the spinal cord including traumatic tetraplegia, subacute combined degeneration or syringomyelia. In addition to hypotension, bradycardia has also been reported in patients with autonomic dysfunction such as patients with diabetes mellitus, Guillain-Barré syndrome and autoimmune autonomic neuropathy.7 Given our patient’s history of chronic hypotension and bradycardia secondary to spinal cord injury and incomplete quadriplegia, pseudoephedrine was successfully added to his current regimen of midodrine to facilitate discontinuation of intravenous dopamine. Pseudoephedrine has a rapid onset of action within 30 min, and peak effect around 1–4 hours after absorption from the gastrointestinal tract.2 In this case, pseudoephedrine was able to augment discontinuation of intravenous vasopressors within 24 hours of initiation of therapy.

In summary, short-term use of pseudoephedrine in addition to midodrine facilitated discontinuation of intravenous dopamine in a case with acute-on-chronic bradycardia and hypotension secondary to autonomic dysfunction and chronic cocaine use. While firm conclusions are not possible in the context of clinical outcomes in a single case, the potential utility of pseudoephedrine in patients with autonomic dysfunction requires large-scale long-term research.

Learning points

  • Medication options for management of hypotension in the setting of autonomic dysfunction are limited, and there is minimal guidance for transitioning from intravenous vasopressor to oral medical therapy in the acute setting.

  • Pseudoephedrine exhibits both α and β adrenergic effect, leading to vasoconstriction, increased contractility, increased heart rate and bronchodilation.

  • In this case report, we report the use of pseudoephedrine as adjunctive therapy to midodrine in the management of hypotension related to autonomic dysfunction.

Ethics statements

Patient consent for publication

Footnotes

  • Twitter @caleigh123xo

  • Contributors CC wrote the first draft of the manuscript and edited all subsequent versions. FD, GF and PG provided intellectual guidance, edited subsequent versions and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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