Neurology/original research
Intranasal Lidocaine in Acute Treatment of Migraine: A Randomized Controlled Trial

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Study objective

The study aims to evaluate the efficacy and safety of intranasal lidocaine administration for migraine treatment.

Methods

This single-center, double-blind, randomized, controlled trial was conducted in a tertiary care emergency department. Included patients met the migraine criteria of the International Headache Society. Patients were randomized to intranasal lidocaine or saline solution; all participants received 10 mg of intravenous metoclopramide. Patient pain intensity was assessed with an 11-point numeric rating scale score. The primary outcome measure was the change in pain scores at 15 minutes; secondary outcomes were changes in pain intensity after pain onset and need for rescue medication.

Results

Patients (n=162) were randomized into 2 groups with similar baseline migraine characteristics and numeric rating scale scores. The median reduction in numeric rating scale score at 15 minutes was 3 (interquartile range [IQR] 2 to 5) for the lidocaine group and 2 (IQR 1 to 4) for the saline solution group (median difference=1.0; 95% confidence interval 0.1 to 2.1). The reduction in pain score at 30 minutes was 4 (IQR 3 to 7) for the lidocaine group and 5 (IQR 2 to 7) for the saline solution group (median difference=1.0; 95% confidence interval 0.1 to 2.1). Need for rescue medication did not differ between the groups, and local irritation was the most common adverse event in the lidocaine group.

Conclusion

Although intranasal lidocaine was found no more efficacious than normal saline solution in our study, future studies should focus on patients who present earlier after headache onset.

Introduction

Headache is a frequent presentation to the emergency department (ED). The statistics on the prevalence and burden of headache disorders in the United States indicate that headache is the fourth leading cause of visits to the ED, accounting for 3.1% of all visits. In all ambulatory care settings, migraine accounts for 0.5% of all presentations.1

Editor’s Capsule Summary

What is already known on this topic

Intranasal lidocaine may reduce pain from migraine headache.

What question this study addressed

In migraine patients receiving protocol-based analgesic care, did intranasal lidocaine reduce pain?

What this study adds to our knowledge

In this randomized clinical trial of patients arriving between 5 and 7 hours after onset, intranasal lidocaine performed similarly to placebo in reducing pain while causing additional local irritation.

How this is relevant to clinical practice

Better treatments are needed for the emergency department management of headache. Clinical trials of intranasal lidocaine are conflicting, but the treatment has biologic promise.

Research we would like to see

A larger randomized clinical trial focused on patients arriving earlier after headache onset.

Current meta-analyses and systematic reviews reveal that abortive treatment of migraine consists of numerous medications, including triptans,2 nonsteroidal anti-inflammatory drugs,3, 4, 5 acetaminophen,6 aspirin,7 and antiemetics.8 These medications are widely used in the acute treatment of migraine, but uncertainty remains in regard to the comparative efficacy of presently available drugs. Intranasal administration is now viewed as effective in the treatment of acute migraine because of its rapid effectiveness, lack of need for an injection site, and rare adverse reactions.9

The entire pathophysiologic mechanism of migraine and its therapeutic pathways is not clearly understood. Activation of the trigeminovascular system and central brain sites is one of the suggested mechanisms involved in migraine pathogenesis.10 The sphenopalatine ganglion may have a pivotal role in the cranial parasympathetic outflow through the release of neuropeptides and may contribute to migraine pain by activating or sensitizing intracranial nociceptors.10, 11, 12 Reducing this parasympathetic outflow to brain sites by blocking the sphenopalatine ganglion was previously studied as a migraine treatment using different application methods.10, 11, 13 The sphenopalatine ganglion is located in an accessible region through both nostrils; thus, local anesthetics may affect the ganglion and prevent its signal transmission.11, 13

The parasympathetic outflow theory suggests that early interventions affecting the sphenopalatine ganglion might be more beneficial when delivered through an intranasal route in early-presenting migraineurs.14 In contrast, late presenters might not derive the same benefits if vasodilation and the effects on deep brain tissues involved in migraine attack have already occurred because peripheral nerve blocks might have no effect on pain control.

The efficacy of intranasal lidocaine versus placebo was evaluated in 3 randomized trials of migraine headache.10, 11, 15 However, drug administration methods and outcome measures were different in each study and the results were conflicting.

The aim of the present trial was to investigate the efficacy and safety of an intranasal 10% lidocaine treatment compared with placebo for patients presenting to the ED with migraine headache and receiving intravenous metoclopramide as part of standard care. Also, we aimed to evaluate the relationship between pain onset and the efficacy of lidocaine.

Section snippets

Study Design and Setting

This single-center, prospective, double-blind, placebo-controlled, randomized trial was carried out with patients with acute migraine attack. Results are reported according to the Consolidated Standards of Reporting Trials guideline. The study was conducted from January to October 2014 in an academic ED with an annual census of approximately 45,000 patients per year. The efficacy and safety of intranasal lidocaine were compared with those of intranasal normal saline solution in the acute

Results

During the study period, 1,383 patients were screened for migraine headache. A total of 193 patients were assessed for eligibility according to the International Headache Society criteria for migraine, and 31 patients were excluded from the study (Figure 2). Ultimately, 162 patients were included in the randomization (81 for each treatment arm). Of these, 3 subjects in the lidocaine group and 4 in the normal saline solution group discontinued after baseline measurement. Also, 6 subjects in the

Limitations

The present study has several limitations: First, intranasal lidocaine is more irritating than intranasal saline solution; thus, the lidocaine group experienced this discomfort, which may have interfered with blinding of the participants in the lidocaine arm. However, this is an inevitable problem in studies involving local anesthetics because they produced a burning sensation in mucosal tissues.

Second, the comparisons for median numeric rating scale changes between the lidocaine and saline

Discussion

Acute migraine is common in the ED, and treatment by means of the intranasal route has gained popularity because of its rapid application and relatively few adverse effects. Our study suggests that intranasal 10% lidocaine is no more effective than normal saline solution at the intervals studied; this lack of effect holds true when the time between pain onset and presentation is taken into account. In our study, no statistically significant difference was observed between the groups in regard

References (21)

There are more references available in the full text version of this article.

Cited by (19)

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    Five studies used lidocaine (10 to 80 mg) and 6 studies used bupivacaine (3 to 80 mg) as the choice of anesthetic when performing the peripheral nerve block. We classified 10 trials as placebo-controlled, where normal saline solution was used in place of local anesthetic.12,15,33,34,36,38-41 Two trials used standard headache treatment (eg, dopamine antagonist) in the control arm.35,37

  • Comparison of greater occipital nerve and supra orbital nerve blocks methods in the treatment of acute migraine attack: A randomized double-blind controlled trial

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    Citation Excerpt :

    However, the main limitations of treatment methods are the inadequacy of current treatments, tolerance and addiction development to opioids and undesirable side effects such as peptic ulcer, renal disease developing due to NSAIDs [5–8,18]. These factors contribute to treatment failure in acute migraine attacks and the necessity to discuss different treatment alternatives [5,10,11,15,19–21]. The safe nature, ease of application and effectiveness of nerve block treatments make them considered as an alternative to non-invasive treatments in acute migraine attacks as both first line treatment and salvage treatment.

  • Migraine in the Emergency Department

    2019, Neurologic Clinics
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Please see page 744 for the Editor’s Capsule Summary of this article.

Supervising editor: William J. Meurer, MD, MS

Author contributions: NA and NOD conceived the study and designed the trial. NA, CA, and LEA supervised the conduct of the trial and data collection. NOD and MP provided statistical advice on study design and analyzed the data. NOD, EY, and SY drafted the article, and all authors contributed substantially to its revision. NOD takes responsibility for the paper as a whole.

All authors attest to meeting the four ICMJE.org authorship criteria: (1) Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; AND (2) Drafting the work or revising it critically for important intellectual content; AND (3) Final approval of the version to be published; AND (4) Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist.

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