In Pediatric Headache, Placebo Effect May Play a Role in Cervical Injection Response

An investigation into injected ropivacaine showed it is no better than injected saline for the treatment of headache in children, according to results from a  study published recently in Pediatrics.¹ Paracervical spinal injections were effective in about 30% of patients given ropivacaine compared with 28% given saline.

Approximately 10% to 51% of children in the United States experience headaches that are often treated in the emergency department (ED). Treatments such as nonopioid analgesics, ergotamines, dopamine receptor agonists, and intravenous (IV) fluids are all effective in many cases, but the onset of the effect is delayed. Studies by Mellick, et al^2,3 have demonstrated a more rapid response to intramuscular injections of a long-acting anesthetic into the lower cervical neck; however the placebo effect in pediatric headache studies is high, ranging from 38% to 53%, which can confound the results.⁴

For the double blind placebo controlled study, the investigators enrolled 150 children (78% white, 76% female) from the ED at the Children’s Hospital of Pittsburgh in Pennsylvania with a chief complaint of headache who were intended to be treated with IV therapy. Notably, a large number of patients (175) declined participation, largely due to reluctance about having 2 injections administered to the neck. Fifty children age 7 to 17 (median age 15.1) were randomly assigned to each of 3 arms: ropivacaine, normal saline, and natural history (control). Approximately 40% of participants had experienced more than 15 headache days in the previous month.

After 30 minutes, 16 (32%) patients receiving ropivacaine, 14 (28%) receiving saline, and 2 (4%) natural history patients (95% CI, 14%-21%) achieved sufficient therapeutic response to be discharged from the ED without further treatment. The investigators found the difference in response between the ropivicaine and saline groups to be insignificant, as the study was powered to detect a 30% difference between treatments. Likewise, there was no detectable difference between the treatments in rates of return to care, headache recurrence, neck pain, or the use of pain medications when the patients were followed up 72 hours after treatment.

The results were strongly indicative of a placebo response, according to the investigators, consistent with a meta-analysis of pooled results from 13 previous trials with 1324 patients, which reported 46% of complete pain responses and 21% of partial responses were associated with the placebo effect.⁴ “We favor a placebo response to explain all, or most of our results,” they wrote.

References

1. Yaeger SK, Perry MC, Caperell K, et al. Ropivacaine intramuscular paracervical injections for pediatric headache: a randomized placebo-controlled trial [published online April 28, 2017]. Ann Emerg Med.doi:10.1016/j.annemergmed.2017.03.011
2. Mellick LB, McIlrath ST, Mellick GA. Treatment of headaches in the ED with lower cervical intramuscular bupivacaine injections: a 1-year retrospective review of 417 patients. Headache. 2006;46:1441-1449.
3. Mellick LB, Pleasant MR. Do pediatric headaches respond to bilateral lower cervical paraspinous bupivacaine injections? Pediatr Emerg Care. 2010;26:192-196.
4. Fernandes R, Ferreira JJ, Sampaio C. The placebo response in studies of acute migraine. J Pediatr. 2008;152:527-533.