Dexmedetomidine for refractory adrenergic crisis in familial dysautonomia

Abstract

Objective Adrenergic crises are a cardinal feature of familial dysautonomia (FD). Traditionally, adrenergic crisis have been treated with the sympatholytic agent clonidine or with benzodiazepines, which can cause excessive sedation and respiratory depression. Dexmedetomidine is an α2A-adrenergic agonist with greater selectivity and shorter half-life than clonidine. We aimed to evaluate the preliminary effectiveness and safety of intravenous dexmedetomidine in the treatment of refractory adrenergic crisis in patients with FD. Methods Retrospective chart review of patients with genetically confirmed FD who received intravenous dexmedetomidine for refractory adrenergic crises. The primary outcome was preliminary effectiveness of dexmedetomidine defined as change in blood pressure (BP) and heart rate (HR) 1-hour after the initiation of dexmedetomidine. Secondary outcomes included incidence of adverse events related to dexmedetomidine, hospital and intensive care unit (ICU) length of stay, and hemodynamic parameters 12-hours after dexmedetomidine cessation. Results Nine patients over 14 admissions were included in the final analysis. At 1-hour after the initiation of dexmedetomidine, systolic BP decreased from 160±7 to 122±7 mmHg (p=0.0005), diastolic BP decreased from 103±6 to 65±8 (p=0.0003), and HR decreased from 112±4 to 100±5 bpm (p=0.0047). The median total adverse events during dexmedetomidine infusion was 1 per admission. Median hospital length of stay was 9 days (IQR, 3 – 11 days) and median ICU length of stay was 7 days (IQR, 3 – 11 days). Conclusions Intravenous dexmedetomidine is safe in patients with FD and appears to be effective to treat refractory adrenergic crisis. Dexmedetomidine may be considered in FD patients who do not respond to conventional clonidine and benzodiazepine pharmacotherapy.

Afferent Baroreflex Dysfunction: Decreased or Excessive Signaling Results in Distinct Phenotypes

“…46 Acute episodes usually respond to intravenous dexmedetomidine, which has the advantage of rapid onset combined with a short half-life, allowing it to be tightly titrated. 47 Another approach to centrally inhibit sympathetic outflow is the α-2 adrenergic agonist, clonidine. 1 While effective, clonidine often causes extreme fatigue and/or rebound hypertension, making it a poor choice for patients in the long term.…”

Management of Paroxysmal Sympathetic Hyperactivity with Dexmedetomidine and Propranolol Following Traumatic Brain Injury in a Pediatric Patient

“…20 Additionally, two studies report the successful cessation of autonomic dysfunction with an associated decrease in blood pressure, heart rate, and improved symptom control utilizing dexmedetomidine as an infusion. 21,22 Furthermore, in a metaanalysis of adult critical care patients evaluating the overall efficacy and safety of dexmedetomidine showed dexmedetomidine was associated with a 48-hour reduction in ICU length of stay, mechanical ventilation duration, and delirium occurrence compared with lorazepam, midazolam, and propofol. Dexmedetomidine was also associated with an increase in bradycardia and hypotension.…”

“…Additionally, plasma norepinephrine levels on day 8 were 20% lower in the group who received propranolol and clonidine compared with placebo. 22 Diverse treatment options have been reported for aborting or decreasing the episodic frequency of PSH in pediatric patients with varying success. In our patient, traditional methods utilizing opiates and sedatives were not successful in mitigating episodes of PSH.…”

Intranasal dexmedetomidine for adrenergic crisis in familial dysautonomia

“…We had previously reported that the intravenous formulation of dexmedetomidine was safe and effective to treat adrenergic crises in these patients without causing respiratory depression [2]. …”

“…We have recently reported the successful use of intravenous dexmedetomidine, a centrally acting α 2 adrenergic agonist, to abort severe adrenergic crisis in patients with FD [2]. Dexmedetomidine has the advantage of having a rapid onset and very short half-life, but requires intravenous administration in the hospital setting.…”