Metoclopramide versus Hydromorphone for the ED Treatment of Migraine Headaches

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Metoclopramide versus Hydromorphonefor the ED
Treatment of Migraine Headaches

• Justin Griffith, MD
• Mark Mycyk, MD
• Demetrios Kyriacou, MD, PhD
• ICEP Resident Research Forum
• NMH Division of Emergency Medicine
• April 29, 2004

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Background

• 28 million Americans with migraines
• 15 of migraineurs seek ED evaluation
• 5-17 billion in lost economic productivity

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Background

• Exact etiology of migraines remains unclear
• Complex phenomenon of select neurotransmitter
  interactions and cerebral vascular flow
• Opioid receptor not implicated in primary
  pathophysiology of migraines

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Background

• Multiple pharmaceutical options
• Prochlorperazine (Compazine) and Droperidol
  (Inapsine) previously identified as the most
  effective ED abortive migraine agents
  availability now limited

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Background

• Acetaminophen
• Dexamethasone
• Dihydroergotamine
• Diphenhydramine
• Fentanyl
• Hydromorphone
• Ketorolac
• Lidocaine
• Magnesium
• Meperidine

• Metoclopramide
• Morphine
• Naproxen
• Ondansetron
• Promethazine
• Prednisone
• Sumatriptan
• Tramadol
• Valproate
• Zolmitriptan

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Background (NMH)

• Metoclopramide(Reglan)
• Dopamine and serotonin receptor activity
• Previous studies support its effect on migraines

• Hydromorphone(Dilaudid)
• Opioid receptor activity
• Opioids are used more commonly than non-opioids
  for ED treatment of migraines

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Study Objective

• To evaluate the effectiveness of intravenous
  metoclopramide vs. hydromorphone as the initial
  abortive treatment of migraines in the Emergency
  Department.

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Methods

• Retrospective cohort study of patients with
  migraine headaches treated in NMH ED
• NMH ED Urban, academic, 75,000/year
• Complete ED chart review

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Methods

• Inclusion Criteria
• All ED patients with a discharge diagnosis of
  Migraine from October 2002 to March 2003
• Exclusion Criteria
• Non-migraine co-morbidities
• Incomplete charts
• Patients whose discharge diagnosis of migraine
  not consistent with patients ED evaluation
• Migraine patients who received no intervention

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Methods

• A validated, nursing administered numerical pain
  scale (0-10) was used to assess effectiveness of
  treatment interventions.
• Chi-squared analyses were performed to assess
  pain score changes.
• Cox proportion hazards multivariate regression
  analyses were performed to adjust for confounders.

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Results

• Study Population
• 183 subjects
• Ages 18-79 years (mean 40)
• 85.8 female

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Results

• Number of Subjects
• Metoclopramide 89
• Hydromorphone 48
• All Other Medications 46
• There were no significant age, gender, race, or
  initial pain score differences among the three
  groups

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Results

• Mean Pain Score Reductions
• Metoclopramide - 3.85
• Hydromorphone - 2.15
• All others combined - 2.61
• (ANOVA F statistic 7.42, P-value 0.0009)

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Results

• Metoclopramide vs. Hydromorphone
• For an effective pain reduction of 3 or more
• Crude RR 1.70 (95 CI, 1.15-2.53)
• P value 0.003
• Adjusted RR 1.87 (95 CI, 0.95-3.69)
• P value 0.072

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Results
Effective Pain Reduction
Metoclopramide
Yes
No
20
6
20
6
20/26 0.77
10 mg
28
18
28/46 0.61
28
18
20 mg
P value 0.165
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Results
Effective Pain Reduction
Yes
No
Hydromorphone
0.5 mg
4/14 0.29
4
10
1.0 mg
11
13
11/24 0.46
2.0 mg
5
0
0/5 0
4.0 mg
1
2
1/3 0.33
P value 0.241
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Conclusion

• Metoclopramide appears to be more effective than
  hydromorphone as an initial ED treatment of
  migraine headaches.
• Increasing doses of metoclopramide and
  hydromorphone demonstrated no significant pain
  reduction.

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Limitations

• Retrospective analysis
• Dosing and timing of interventions could not be
  controlled
• Unequal numbers in each treatment group

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Future Endeavors

• Prospective randomized trial
• Varied dosing regimens
• Sub-group analysis

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References

• Cameron JD, Lane PL, et al. Intravenous
  chlorpromazine vs. intravenous metoclopramide in
  acute migraine headache. Acad Emerg Med 1995
  2597-602.
• Coppola M, Yealy DM, et al. Randomized,
  placebo-controlled evaluation of prochlorperazine
  vs. metoclopramide for ED treatment of migraine
  headache. Ann Emerg Med 1995. 26529-30.
• Ellis GL, Delaney J, et al. The efficacy of
  metoclopramide in the treatment of migraine
  headache. Ann Emerg Med 1993 22191-5.
• Gralla R, Itri L, et al. Antiemetic efficacy of
  high-dose metoclopramide. New England Journal of
  Medicine. Oct 1981 305905-9.
• Miner J, Fish S., et al. Droperidol vs.
  Prochlorperazine for benign headaches in the ED.
  Acad Emerg Med 2001 8873-9.
• Tek DS, McClellan DS, et al. A prospective,
  double-blind study of metoclopramide for the
  control of migraine in the ED. Ann of Emerg Med
  1990 191083-7.
• Todd KH, Funk KG et al. Clinical significance of
  reported changes in pain severity. Ann of Emerg
  Med 199627485-9.
• Vinson DR, Hurtado TR, et al. Variations among
  EDs in the treatment of benign headache. Ann
  Emerg Med 2003 41190-97.

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With Gratitude

• Mark Mycyk, MD
• Demetrios Kyriacou, MD, PHD
• NMH
• ICEP