Intravenous dihydroergotamine treatment of refractory pediatric headache

Nelson, Gary R., MD; Bale, James F., MD; Kerr, Lynne M., MD, PhD.  Outcome and cost of inpatient hospitalization for intravenous dihydroergotamine treatment of refractory pediatric headache.  Pediatric Neurology.  Article in press.

Abstract

Objective

To determine the cost and efficacy of admitting patients for intravenous dihydroergotamine (IV DHE) treatment and to identify factors that are associated with a higher likelihood of response to treatment.

Methods

We performed a retrospective review of all pediatric hospitalizations from 2001-2010 for IV DHE therapy for headache. Data were collected using the REDcap database and consisted of multiple variables, including pre-admission demographics, headache duration, use of prophylactic medications, inpatient therapies including DHE dosing, procedures and consultations, total hospital cost, and headache severity at discharge and follow-up.

Results

Seventy-four percent of the 145 hospitalizations were female patients. Mean age was 14.9 years. Headache was described as chronic or daily in almost all patients and 28 (19%) had status migrainosus. Sixty-six percent had a first-degree relative with migraine. The average length of stay was 3.7 days, and the average cost was $7,569/hospitalization. Patients received an average of 8 doses of DHE. On discharge, 63% of patients reported improvement. Follow up was available for 68% of the cohort at a median of 42 days after discharge, and 21/99 (21%) had sustained relief of headache. Response to DHE was correlated with a lower rate of comorbid diagnoses, lumbar puncture, and outpatient neuroimaging. Response also correlated to less expensive hospitalizations with an average cost of $5379 per hospitalization versus $7105 per hospitalization without positive response. Response was also correlated with a patient receiving more doses of IV DHE.

Conclusions

Although intravenous DHE is an effective abortive medication for intractable migraine, DHE may provide only short-term headache relief in many pediatric patients. Hospitalization is relatively costly with only modest long-term benefit, especially in patients with chronic migraine or chronic daily headache.

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From the article

 Many options exist for the treatment of intractable headaches. Some children and adolescents require hospitalization to break the headache cycle. Therapy during hospitalization often involves intravenous dihydroergotamine (IV DHE) and additional medical consultations and treatments. Ergot derivatives were historically used to treat migraine, but the formulation of dihydroergotamine created a better-tolerated compound equipotent to previous ergot derivatives. Intravenous DHE has been shown to be effective in treating intractable headaches in children, including chronic migraine and status migrainosus , but no studies have identified the factors associated with improvement with DHE or evaluated the cost of hospitalization for this therapy. Data on the long-term outcomes of hospitalizations for IV DHE treatment are also limited…

All patients are managed using a treatment protocol which consists of insertion of a percutaneous catheter for IV DHE administration. This was based on institutional experience prior to the initiation of the protocol that peripheral IV (PIV) administration of DHE led to repeated IV placements and considerable difficulty obtaining IV access after initiation of IV DHE due to the systemic vasoconstriction…

DHE is administered with a test dose of 0.1 mg IV and incremental increases to a maximum of 0.5-1 mg per dose based on age.  Patients are pre-medicated 30 minutes prior to each dose with appropriate weight-based dosing of metoclopramide, promethazine or ondansetron to decrease nausea or vomiting…

Ninety-two of 145 hospitalizations (63%) showed response to IV DHE. Table 2 summarizes the characteristics of responders and non-responders. Complete resolution of headache occurred in 31 hospitalizations (21%) when considering all hospitalizations, but occurred in 50% of hospitalizations where the headache met criteria for status migrainosus…

Responders received more doses of IV DHE, an average of 8.3 doses +/- 2.8 doses, while non-responders received an average of 7.2 doses +/- 3.4 doses (p=0.002). For each additional IV DHE dose during hospitalization, the likelihood of a favorable response was increased by 27%...

Despite an initial response rate of 63% during hospitalization, only 29% of responders and 9% of non-responders reported improved headache frequency or intensity at follow-up.