Emergency.

2017; 5 (1): e79

O RIGINAL R ESEARCH

Intranasal Lidocaine for Primary Headache Management

in Emergency Department; a Clinical Trial
Hassan Barzegari1 , Hassan Motamed1∗ , Behrad Ziapour1 , Majid Hajimohammadi1 , Mina Kadkhodazadeh1
1. Emergency Medicine Department, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Received: August 2017; Accepted: August 2017; Published online: 16 September 2017

Abstract: Introduction: Most of the headache cases only require pain management in emergency department (ED). The
present study aimed to evaluate the efficacy of intranasal lidocaine in this regard. Methods: In this clinical trial,
adult patients with primary headache were randomly treated with 7.5 mg intravenous (IV) chlorpromazine and
1 ml intranasal lidocaine 2% (treatment) or normal saline 0.9% (placebo), and were compared 5, 15, and 30
minutes later regarding success rate using SPSS 21. Results: 100 patients were assigned to either treatment or
placebo group. Number needed to treat of intranasal lidocaine at 5, 15, and 30 minutes were 4 (95% CI: 2.2 –
6.6), 3 (95% CI: 1.7 – 3.5), and 4 (95% CI: 2.3 – 15.9), respectively. These measures for absolute risk reduction
were 30 (95% CI: 15.2 – 44.8), 44 (95% CI: 28.7 – 59.3), and 26 percent (95% CI: 6.3 – 44.3), respectively. Pain
relapse occurred in 16% of treatment and 11% of control group within 1 hour of treatment (p = 0.402). Conclu-
sion: It seems that, intranasal lidocaine along with IV chlorpromazine could result in more successful and faster
management of primary headaches in ED.

Keywords: Pain management; tension-type Headache; administration, intranasal; lidocaine; migraine disorders
© Copyright (2017) Shahid Beheshti University of Medical Sciences

Cite this article as: Barzegari H, Motamed H, Ziapour B, Hajimohammadi M, Kadkhodazadeh M. Intranasal Lidocaine for Primary Headache
Management in Emergency Department; a Clinical Trial. Emergency. 2017; 5(1): e79.

1. Introduction as a an adjunctive medication in cluster headache control (8).

Studies have reported that nasal lidocaine decreased cluster
eadache is a common cause of emergency depart- and migraine headaches within several seconds to 2 minutes

H ment (ED) visits. Most of these patients only require

symptomatic treatment and referral to a neurolo-
gist or the patient’s family physician on an outpatient basis
(9, 10). However, Blanda and their colleagues didn’t find any
evidence that supports the mentioned issue (11).
There has been limited experiences regarding primary
(1). Migraine, tension, and cluster are three types of primary headache management through intranasal medication in
headaches with considerable clinical overlap, which suggests ED. Therefore, this study aimed to evaluate the efficacy of in-
the same pathophysiology (1). tranasal lidocaine in primary headache management in ED.
Common drugs used to treat these headaches are intra-
venous (IV) and oral opioids, ergot alkaloids, antiemetic, and 2. Methods
non-steroidal anti-inflammatory drugs (NSAIDS) (2, 3). In-
tranasal route of drug administration may be more effec-
2.1. Study design and setting
tive than other routes, with lower chance of emesis, and a This randomized, double blind placebo controlled trial was
quicker onset of action (3). Intranasal delivery of zolmitrip- done on patients presenting to emergency department of
tan, civamide, cocaine, and sumatriptan has been tried for Golestan Hospital, Ahwaz, Iran, from July 2012, to December
treatment of migraine and cluster headaches (4-7). 2014 with primary headache (migraine, cluster or tension).
Lawrence Robbins showed the safety of intranasal lidocaine The study design was approved by ethics committee of Ahvaz
Jundishapur University of Medical Sciences under the num-
ber U-91159 and registered on Iranian Registry of Clinical Tri-
∗ Corresponding Author: Hassan Motamed; Emergency Department, als under this number: IRCT201212289148N2. Written in-
Golestan Hospital, Golestan Avenue, Ahvaz, Khuzestan Province,
Iran. Postal code: 6135733118 Tel/Fax: +986133743099 Email:
formed consent was obtained from all patients. Researchers
hasan_motamed@yahoo.com adhered to declaration of Helsinki protocol and confidential-

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H. Barzegari et al. 2

were blinded to drugs given to each group.

2.5. Outcome
5, 15, and 30 minute success rates were considered as the
main outcome of the study.

2.6. Statistical Analysis

Considering 95% confidence interval (CI), 80% power, and
according to the Maizals et al. and Blanda et al. findings (11,
12), the minimum sample size for each study group was cal-
culated to be 50 cases. Data analysis (intention to treat anal-
ysis) was performed by the statistical package for social sci-
ences (SPSS) version 21. Findings were presented as mean ±
Figure 1: Pain severity at the baseline and 5, 15, and 30 minutes af-
standard deviation or frequency and percentage. Student t
ter treatment in lidocaine and placebo groups based on visual ana-
logue scale (VAS). test, ANOVA and chi square or Fisher’s exact tests were used
for comparisons. Success was defined as an at least 3 points
decrease of pain severity (based on VAS) 5, 15, or 30 minutes
ity of patients’ information. after treatment. P < 0.05 was considered as significant.

2.2. Participants
3. Results
The subjects were patients between 15 – 55 years old who
presented to the emergency department with complaints of 3.1. Baseline characteristics
primary headaches (migraine, cluster, or tension) according 100 patients were randomly assigned to either treatment (50
to the definition of International Headache Society and Ad cases) or control (50 cases) group (54.0% female). The mean
Hoc Committee on Classification of Headache. Patients with age of treatment and control groups were 32.96 ± 8.51 and
signs of secondary headaches such as fever, meningismus, 29.60 ± 8.64 years, respectively (p = 0.050). Table 1 shows the
trauma, unstable vital signs, and altered mental status were baseline characteristics of studied patients.
excluded. Lactating and pregnant women as well as who had
taken analgesic medications 2 hours before referring to ED 3.2. Pain control
were also excluded. Participants were randomly assigned to The mean pain severity of patients at the time of present-
either treatment or control group using simple random sam- ing to emergency department and 5, 15, and 30 minutes after
pling method. treatment are summarized in table 2 and figure 1.
2.3. Intervention The success rates of two groups at 5, 15, and 30 minutes are
compared in table 3. There was not any significant correla-
Patients in the treatment group received 1 mL intranasal li- tion between success rate and sex (p = 0.292), age (p = 0.380),
docaine 2% (20 mg lidocaine) and 7.5 mg intravenous (IV) and type of headache (p = 0.489).
chlorpromazine and those in control group received 1 mL in- Number needed to treat of intranasal lidocaine at 5, 15, and
tranasal normal saline 0.9% and 7.5 mg IV chlorpromazine. 30 minutes were 4 (95% CI: 2.2 – 6.6), 3 (95% CI: 1.7 – 3.5), and
The lidocaine and normal saline were sprayed with the same 4 (95% CI: 2.3 – 15.9), respectively. These measures for abso-
shape and color containers. lute risk reduction were 30 (95% CI: 15.2 – 44.8), 44 (95% CI:
28.7 – 59.3), and 26 percent (95% CI: 6.3 – 44.3), respectively.
2.4. Data gathering
The side effects related to treatment were not apparent in ei-
A checklist that consisted of baseline characteristics (sex, ther the treatment or the control group within 30 minutes af-
age), type of primary headache, pain severity, and possible ter treatment. Pain relapse occurred in 16% of the treatment
complications was filled for all patients by a senior emer- and 11% of the control group during 1 hour follow up (p =
gency medicine resident under supervision of an emergency 0.402).
medicine physician. Visual analog scale (VAS) was used to
rate the pain severity at the baseline as well as 5, 15, and
4. Discussion
30 minutes after drug administration. In addition, patients
were observed for an additional 30 minutes to assess whether Considering 30, 44, and 26 percent absolute risk reduction
they responded to the treatment or whether their pain re- at 5, 15, and 30 minutes after treatment, intranasal lidocaine
turned. Patients, in charge physicians, and data analyzer along with intravenous chlorpromazine could result in more

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3 Emergency. 2017; 5 (1): e79

Table 1: Baseline characteristics of the two studied groups

Group n (%)
Variable P value
Intranasal lidocaine Placebo
Sex
Male 22 (44.0) 24 (48.0)
0.688
Female 28(56.0) 26 (52.0)
Age (year)
20 – 29.9 20 (40.0) 31 (62.0)
30 – 39.9 10 (20.0) 10 (20.0) 0.038
≥ 40 20 (40.0) 9 (18.0)
Type of headache
Migraine 16 (32.0) 22 (44.0)
Tension 11 (22.0) 18 (36.0) 0.028
Cluster 23 (46.0) 10 (20.0)

Table 2: Pain severity of two studied groups based on visual analogue scale

Groups
Time (minute) P value
Intranasal lidocaine Placebo
Baseline 6.15 ± 1.19 5.87 ± 1.01 0.225
5 4.56 ± 1.54 5.30 ± 1.29 0.011
15 3.86 ± 1.57 4.76 ± 1.09 0.001
30 2.94 ± 1.63 3.94 ± 1.52 0.002

Table 3: Success rate of the two studied groups 5, 15, and 30 minutes after treatment

Group n (%)
Time (minute) P value
Intranasal lidocaine Placebo
5 18 (36) 3 (6) < 0.0001
15 25 (50) 3 (6) < 0.0001
30 30 (60) 17 (34) 0.009

successful pain management of primary headaches in ED. Although the experience of drug delivery through nasal mu-
This study showed that patients who received intranasal li- cosa goes back to many years ago, based on a review in 2013
docaine along with IV chlorpromazine significantly experi- the present method for delivering the drug to the posterior-
enced higher success rate in pain control at 5, 15, and 30 min- superior part of the nose is not that effective and this could
utes after treatment. affect the success rate of this method to a great extent (13).
Although the two studied groups had different baseline char- It seems that using a new method that can be applied by the
acteristics, the analysis of data didn’t show any relationship patients themselves without the need for visiting the hospi-
between age, sex, and type of primary headache with treat- tal should be considered more seriously. This is of great im-
ment success rate. portance, especially for cases such as primary headaches that
Maizels and Geiger evaluated the efficacy of intranasal li- are usually recurrent and distractive. Of course, there is still
docaine in a double-blind controlled trial with open-label a long way to go in making the use of these drugs public and
follow-up. They found that headache was relieved within 15 revising traditional methods.
min in 35.8% of patients in the treatment group, with a 20.6%
relapse rate (12). Mohammadkarimi and colleagues using in- 5. Limitation
tranasal lidocaine in 90 patients with primary and secondary
headaches found significant pain relief after 1 minute, and In the current study, we administered intranasal 2% lidocaine
showed that the level of patients’ pain did not significantly for different types of headache and not just for migraine. We
change over the course of the study. They did not assess the followed patients in both the treatment and control groups
relapse rates or side effects related to treatment (9). In con- for only a short time. We did not perform follow-up assess-
trast, Blanda and colleagues found that the intranasal lido- ments. In addition, because our treatment group received
caine did not relieve pain after 5 or 30 minutes (11). lidocaine and chlorpromazine together, our study is limited

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H. Barzegari et al. 4

in its assessment of pure lidocaine’s ability in pain manage- headache Randomized placebo-controlled double-blind
ment. study. Neurology. 2003;60(4):630-3.
5. Cittadini E, May A, Straube A, Evers S, Bussone G,
6. Conclusion Goadsby PJ. Effectiveness of intranasal zolmitriptan
in acute cluster headache: a randomized, placebo-
Considering 30, 44, and 26 percent absolute risk reduction
controlled, double-blind crossover study. Archives of
at 5, 15, and 30 minutes after treatment, intranasal lidocaine
neurology. 2006;63(11):1537-42.
along with IV chlorpromazine could result in more successful
6. Diamond S, Freitag F, Phillips S, Bernstein J, Saper J. In-
and faster management of primary headaches in ED.
tranasal Civamide for the Acute Treatment of Migraine
Headache. Cephalalgia. 2000;20(6):597-602.
7. Appendix 7. Costa A, Pucci E, Antonaci F, Sances G, Granella F, Broich
7.1. Acknowledgements G, et al. The effect of intranasal cocaine and lidocaine
on nitroglycerin-induced attacks in cluster headache.
The cooperation of Golestan Hospital, Ahvaz, staff members
Cephalalgia. 2000;20(2):85-91.
is appreciated.
8. Robbins L. Intranasal Lidocaine for Cluster Headache.
7.2. Author contribution Headache: The Journal of Head and Face Pain.
1995;35(2):83-4.
All the authors meet the standard criteria of authorship based
9. Mohammadkarimi N, Jafari M, Mellat A, Kazemi E, Shi-
on the recommendations of the international committee of
rali A. Evaluation of efficacy of intra-nasal lidocaine for
medical journal editors.
headache relief in patients refer to emergency depart-
7.3. Funding/Support ment. Journal of research in medical sciences: the of-
ficial journal of Isfahan University of Medical Sciences.
None.
2014;19(4):331.
7.4. Conflict of interest 10. Generali J, Cada DJ. Intranasal lidocaine: Migraine
headaches. Hospital Pharmacy. 2001;36(2):192-223.
None.
11. Blanda M, Rench T, Gerson LW, Weigand JV. Intranasal
lidocaine for the treatment of migraine headache:
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