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Intra-venous chlorpromazine with fluid treatment in status migrainosus
Clinical Neurology and Neurosurgery 119 (2014) 4–5
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Intra-venous chlorpromazine with fluid treatment in status migrainosus Uygar Utku ∗ , Mustafa Gokce, Elif Muruvvet Benli, Aytac¸ Dinc, Deniz Tuncel Department of Neurology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, 46050 Kahramanmaras, Turkey
a r t i c l e
i n f o
Article history: Received 5 December 2012 Received in revised form 21 July 2013 Accepted 2 January 2014 Available online 10 January 2014 Keywords: Acute headache treatment Intra-venous chlorpromazine Status migrainosus
a b s t r a c t Objective: To present the results of the intra-venous chlorpromazine with fluid treatment in patients with status migrainosus. Methods: Consecutive 21 patients with status migrainosus were received intra-venous chlorpromazine (maximum 25 mg) with fluid treatment and their results were documented. Results: Complete recovery of headache and nausea were seen in 20/21 and 17/21 of the patients respectively. 15/21 of patients were headache free following at 10 mg chlorpromazine infusion. Most patients went on sleep after 10 mg chlorpromazine infusion and when they wake already up headache free. Side effects such as tachycardia, palpitation, flushing and hypertension were seen only one of 21 patients following first dose 5 mg injection. Conclusions: This study showed that intra-venous chlorpromazine with fluid treatment for status migrainosus seems a good option. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Status migrainosus is defined by the International Headache Society criteria as an attack of migraine, the headache phase of which lasts more than 72 h, whether it is treated or not. The headache can be continuous throughout the attack or interrupted by headache-free intervals lasting less than 4 h. Relief during periods of sleep is disregarded [1]. The pathophysiology of migraine is still not well understood and various treatments are used in migraine attacks [2]. The treatment of status migrainosus is often a difficult for both the physician and the patient [2]. Although empirical treatments such as narcotic analgesics, metoclopramide, dihydroergotamine, oral and parenterally nonsteroidal anti-inflammatory agents, corticosteroids and triptans are used [3–5], there are no large series or double-blind treatment trials in status migrainosus. Although chlorpromazine treatment for migraine headache has been known since 1955 [6], however it has not been commonly used for the migraine headache treatment. Intra-venous chlorpromazine with fluid is relatively new treatment way for status migrainosus. Here, we presented the results of the
∗ Corresponding author at: Department of Neurology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, 46050 Kahramanmaras, Turkey. Tel.: +90 344 221 23 37x245; fax: +90 344 221 72 39; mobile: +90 505 572 59 32. E-mail addresses: [email protected], [email protected] (U. Utku). 0303-8467/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2014.01.002
intra-venous chlorpromazine with fluid treatment in patients with status migrainosus. 2. Materials and methods After good results had been observed in a few patients with status migrainosus with intravenous chlorpromazine with fluid treatment in our clinical practice, we decided to collect the data of patients with status migrainosus. After that time, 21 consecutive patients with status migrainosus received intra-venous chlorpromazine with fluid treatment. All patients applied to our emergency department. Diagnosis of status migrainosus was made according to the International Headache Society criteria by a neurologist [1]. Treatment was given to patients in the emergency department or in our neurology ward. General physical, neurological and fundoscopic examinations were performed to all patients including blood pressure and meningeal signs. Hemogram and routine biochemistry including liver and renal functions tests, sedimentation ratio were studied. Non-contrast brain computerized tomography performed to all patients in emergency department. All patients had been already received at least two or more oral and/or parenterally painkillers, antiemetic and triptans for their headaches before they came to our emergency department. The treatment protocol according to advice of the classic textbook is 500 cc fluids such as normal saline or 5% dextrose were used [7]. Initially 250 cc of saline was given and then 5 mg IV chlorpromazine was infused. Chlorpromazine 5 mg was given every 10 min until
U. Utku et al. / Clinical Neurology and Neurosurgery 119 (2014) 4–5 Table 1 Intra-venous chlorpromazine and fluid treatment protocol in status migrainosus. Step 1
Step 2 Step 3 Step 4 Step 5
Intra-venous access with 500 cc fluid (250 cc of 500 cc fluid was given immediately) and than 1 cc (5 mg) IV chlorpromazine 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 10 mg) 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 15 mg) 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 20 mg) 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 25 mg)
Waited 10 min after every step, if the headache persisted went to next step, if the pain healed or patient went into sleep the treatment was stopped. Maximum chlorpromazine dosage was 25 mg.
Table 2 Dosage and response to treatment of patients (n: 21). Chlorpromazine dosage
Complete resolution of headache
Side effects
5 mg
None
10 mg 15 mg 20 mg 25 mg (max)
15/21 (71.4%) 3/21 (4.76%) 1/21 (14.3%) 1/21 (4.76%)
1/21; palpitation, flushing, elevated blood pressure and tachycardia None None None None
either five doses were given or the patient was completely/almost headache-free or went to the sleep prior to the next dose (Table 1). Maximum chlorpromazine dose was 25 mg in each patient. 3. Results There were 21 consecutive patients (20 women and 1 man) with status migrainosus. Most of patients (18 patients) were refereed from other territorial hospitals to our hospital and 3 patients primarily applied to our emergency department. Mean age was 37 years. Average duration of migraine disease of the patients was 9.9 years. The average lasting duration of migraine status of the patients was 5.3 days. Hemogram, routine biochemistry results and sedimentation ratio of all patients were in normal range. No abnormality was seen general physical, neurological and fundoscopic examination including blood pressure and meningeal sings. Non-contrast brain computerized topographies of all patients were normal. There were nausea in 17/21 patients, all of it disappeared with the treatment. Majority of the patients (15/21) were headache free following at 10 mg chlorpromazine infusion. 16 of the 21 patients went to the sleep within the treatment and all of them were headache free when they wake up. Eventually the headache in 20 of the 21 patients completely recovered with intra-venous chlorpromazine treatment (Table 2). After the treatment, headache relapse were not seen in any patients during 24 h. Side effects such as palpitation, flushing, elevated blood pressure and tachycardias were seen in only one patient after first 5 mg of chlorpromazine. Chlorpromazine infusion was ceased and then symptoms completely resolved within a short period. 4. Discussion Dehydration, tiredness due to lack of sleep and vomiting or electrolyte imbalance can occur in patients with status migrainosus.
5
Theoretically we can think that correction of these parameters is beneficial in these patients. Response to the treatment of status migrainosus has still main problem in the emergency department but good results about parenteral chlorpromazine treatment in migraine attack have been reported [8,9]. Chlorpromazine is a phenothiazine used mainly for the treatment of psychiatric disorders [10]. It is a powerful antagonist of the neurotransmitter action of dopamine in the basal ganglia and limbic system. Its neuroleptic actions appear to alter pain perception [10]. It is also a potent antiemetic through its action on the chemoreceptor trigger zone. Chlorpromazine very effectively blocks arousal produced by auditory and other types of peripheral stimulation [10]. Headache, nausea and associated symptoms in our patients were all resolved after intra-venous chlorpromazine with saline treatment. Drowsiness was frequently seen and 16 of the 21 patients went to the sleep within the treatment and all of them were headache free when they wake up. Chlorpromazine is also an adrenergic antagonist with some anticholinergic properties. The major blocking action of chlorpromazine can result in orthostatic hypotension [11]. Patients received prophylactic intravenous fluid prior to intra-venous chlorpromazine administration. Anyway there was no case of symptomatic orthostatic hypotension in our study. In addition, no dystonic reactions were seen. In an only one patient palpitation, flushing, elevated blood pressure and tachycardia were seen. Chlorpromazine infusion was ceased and then these symptoms completely resolved within a short period of time. We were not sure if this reaction had been directly related to chlorpromazine treatment in this patient. We know that intra-venous chlorpromazine treatment with fluid infusion in migraine status is suggested in a classical neurological textbook [7]. Headache free rate was 95.2% (20 of 21) in patients with status migrainosus in our patients. This study is not a case control study just only a case series presentation and demonstrates that intra-venous chlorpromazine with fluid is a safe medication that provides important relief from status migrainosus. References [1] Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia 2004;24:9–160. [2] Kelly AM, Bryant MG, Zebic S. The emergency department treatment of severe migraine. Emerg Med 1995;7:162–9. [3] Friedman BW, Greenwald P, Bania TC, Esses D, Hochberg M, Solorzano C. Randomized trial of IV dexamethasone for acute migraine in the emergency department. Neurology 2007;69:2038–44. [4] Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 1: Triptans, dihydroergotamine, and magnesium. Headache 2012;52:114–28. [5] Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache 2012;52:292–306. [6] Archibald HC. Chlorpromazine for headache. Am J Psychiatry 1955;112:390. [7] Boes CJ, Capobianco DJ, Cutrer, Dodick DW, Garza I, Swanson JW. Headache and other craniofacial pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, editors. Neurology in clinical practice. 5th ed. Boston: Elsevier-Academic Press; 2008. p. 2027–46. [8] Iserson KV. Parenteral chlorpromazine treatment of migraine. Ann Emerg Med 1983;12:756–8. [9] Bigal ME, Bordini CA, Speciali JG. Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial. J Emerg Med 2002;23:141–8. [10] Mosnaim AD, Ranade VV, Wolf ME, Puente J, Valenzuela MA. Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents. Am J Ther 2006;13:261–73. [11] Gilman AG, Rall TW, Nies AS, Taylor P. In: The pharmacological basis of therapeutics. 8th ed. London: Pergamon Press; 1991.
Contents lists available at ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Intra-venous chlorpromazine with fluid treatment in status migrainosus Uygar Utku ∗ , Mustafa Gokce, Elif Muruvvet Benli, Aytac¸ Dinc, Deniz Tuncel Department of Neurology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, 46050 Kahramanmaras, Turkey
a r t i c l e
i n f o
Article history: Received 5 December 2012 Received in revised form 21 July 2013 Accepted 2 January 2014 Available online 10 January 2014 Keywords: Acute headache treatment Intra-venous chlorpromazine Status migrainosus
a b s t r a c t Objective: To present the results of the intra-venous chlorpromazine with fluid treatment in patients with status migrainosus. Methods: Consecutive 21 patients with status migrainosus were received intra-venous chlorpromazine (maximum 25 mg) with fluid treatment and their results were documented. Results: Complete recovery of headache and nausea were seen in 20/21 and 17/21 of the patients respectively. 15/21 of patients were headache free following at 10 mg chlorpromazine infusion. Most patients went on sleep after 10 mg chlorpromazine infusion and when they wake already up headache free. Side effects such as tachycardia, palpitation, flushing and hypertension were seen only one of 21 patients following first dose 5 mg injection. Conclusions: This study showed that intra-venous chlorpromazine with fluid treatment for status migrainosus seems a good option. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Status migrainosus is defined by the International Headache Society criteria as an attack of migraine, the headache phase of which lasts more than 72 h, whether it is treated or not. The headache can be continuous throughout the attack or interrupted by headache-free intervals lasting less than 4 h. Relief during periods of sleep is disregarded [1]. The pathophysiology of migraine is still not well understood and various treatments are used in migraine attacks [2]. The treatment of status migrainosus is often a difficult for both the physician and the patient [2]. Although empirical treatments such as narcotic analgesics, metoclopramide, dihydroergotamine, oral and parenterally nonsteroidal anti-inflammatory agents, corticosteroids and triptans are used [3–5], there are no large series or double-blind treatment trials in status migrainosus. Although chlorpromazine treatment for migraine headache has been known since 1955 [6], however it has not been commonly used for the migraine headache treatment. Intra-venous chlorpromazine with fluid is relatively new treatment way for status migrainosus. Here, we presented the results of the
∗ Corresponding author at: Department of Neurology, Faculty of Medicine, Kahramanmaras Sutcu Imam University, 46050 Kahramanmaras, Turkey. Tel.: +90 344 221 23 37x245; fax: +90 344 221 72 39; mobile: +90 505 572 59 32. E-mail addresses: [email protected], [email protected] (U. Utku). 0303-8467/$ – see front matter © 2014 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2014.01.002
intra-venous chlorpromazine with fluid treatment in patients with status migrainosus. 2. Materials and methods After good results had been observed in a few patients with status migrainosus with intravenous chlorpromazine with fluid treatment in our clinical practice, we decided to collect the data of patients with status migrainosus. After that time, 21 consecutive patients with status migrainosus received intra-venous chlorpromazine with fluid treatment. All patients applied to our emergency department. Diagnosis of status migrainosus was made according to the International Headache Society criteria by a neurologist [1]. Treatment was given to patients in the emergency department or in our neurology ward. General physical, neurological and fundoscopic examinations were performed to all patients including blood pressure and meningeal signs. Hemogram and routine biochemistry including liver and renal functions tests, sedimentation ratio were studied. Non-contrast brain computerized tomography performed to all patients in emergency department. All patients had been already received at least two or more oral and/or parenterally painkillers, antiemetic and triptans for their headaches before they came to our emergency department. The treatment protocol according to advice of the classic textbook is 500 cc fluids such as normal saline or 5% dextrose were used [7]. Initially 250 cc of saline was given and then 5 mg IV chlorpromazine was infused. Chlorpromazine 5 mg was given every 10 min until
U. Utku et al. / Clinical Neurology and Neurosurgery 119 (2014) 4–5 Table 1 Intra-venous chlorpromazine and fluid treatment protocol in status migrainosus. Step 1
Step 2 Step 3 Step 4 Step 5
Intra-venous access with 500 cc fluid (250 cc of 500 cc fluid was given immediately) and than 1 cc (5 mg) IV chlorpromazine 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 10 mg) 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 15 mg) 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 20 mg) 1 cc (5 mg) IV chlorpromazine (total given chlorpromazine dosage 25 mg)
Waited 10 min after every step, if the headache persisted went to next step, if the pain healed or patient went into sleep the treatment was stopped. Maximum chlorpromazine dosage was 25 mg.
Table 2 Dosage and response to treatment of patients (n: 21). Chlorpromazine dosage
Complete resolution of headache
Side effects
5 mg
None
10 mg 15 mg 20 mg 25 mg (max)
15/21 (71.4%) 3/21 (4.76%) 1/21 (14.3%) 1/21 (4.76%)
1/21; palpitation, flushing, elevated blood pressure and tachycardia None None None None
either five doses were given or the patient was completely/almost headache-free or went to the sleep prior to the next dose (Table 1). Maximum chlorpromazine dose was 25 mg in each patient. 3. Results There were 21 consecutive patients (20 women and 1 man) with status migrainosus. Most of patients (18 patients) were refereed from other territorial hospitals to our hospital and 3 patients primarily applied to our emergency department. Mean age was 37 years. Average duration of migraine disease of the patients was 9.9 years. The average lasting duration of migraine status of the patients was 5.3 days. Hemogram, routine biochemistry results and sedimentation ratio of all patients were in normal range. No abnormality was seen general physical, neurological and fundoscopic examination including blood pressure and meningeal sings. Non-contrast brain computerized topographies of all patients were normal. There were nausea in 17/21 patients, all of it disappeared with the treatment. Majority of the patients (15/21) were headache free following at 10 mg chlorpromazine infusion. 16 of the 21 patients went to the sleep within the treatment and all of them were headache free when they wake up. Eventually the headache in 20 of the 21 patients completely recovered with intra-venous chlorpromazine treatment (Table 2). After the treatment, headache relapse were not seen in any patients during 24 h. Side effects such as palpitation, flushing, elevated blood pressure and tachycardias were seen in only one patient after first 5 mg of chlorpromazine. Chlorpromazine infusion was ceased and then symptoms completely resolved within a short period. 4. Discussion Dehydration, tiredness due to lack of sleep and vomiting or electrolyte imbalance can occur in patients with status migrainosus.
5
Theoretically we can think that correction of these parameters is beneficial in these patients. Response to the treatment of status migrainosus has still main problem in the emergency department but good results about parenteral chlorpromazine treatment in migraine attack have been reported [8,9]. Chlorpromazine is a phenothiazine used mainly for the treatment of psychiatric disorders [10]. It is a powerful antagonist of the neurotransmitter action of dopamine in the basal ganglia and limbic system. Its neuroleptic actions appear to alter pain perception [10]. It is also a potent antiemetic through its action on the chemoreceptor trigger zone. Chlorpromazine very effectively blocks arousal produced by auditory and other types of peripheral stimulation [10]. Headache, nausea and associated symptoms in our patients were all resolved after intra-venous chlorpromazine with saline treatment. Drowsiness was frequently seen and 16 of the 21 patients went to the sleep within the treatment and all of them were headache free when they wake up. Chlorpromazine is also an adrenergic antagonist with some anticholinergic properties. The major blocking action of chlorpromazine can result in orthostatic hypotension [11]. Patients received prophylactic intravenous fluid prior to intra-venous chlorpromazine administration. Anyway there was no case of symptomatic orthostatic hypotension in our study. In addition, no dystonic reactions were seen. In an only one patient palpitation, flushing, elevated blood pressure and tachycardia were seen. Chlorpromazine infusion was ceased and then these symptoms completely resolved within a short period of time. We were not sure if this reaction had been directly related to chlorpromazine treatment in this patient. We know that intra-venous chlorpromazine treatment with fluid infusion in migraine status is suggested in a classical neurological textbook [7]. Headache free rate was 95.2% (20 of 21) in patients with status migrainosus in our patients. This study is not a case control study just only a case series presentation and demonstrates that intra-venous chlorpromazine with fluid is a safe medication that provides important relief from status migrainosus. References [1] Headache Classification Subcommittee of the International Headache Society. The international classification of headache disorders: 2nd edition. Cephalalgia 2004;24:9–160. [2] Kelly AM, Bryant MG, Zebic S. The emergency department treatment of severe migraine. Emerg Med 1995;7:162–9. [3] Friedman BW, Greenwald P, Bania TC, Esses D, Hochberg M, Solorzano C. Randomized trial of IV dexamethasone for acute migraine in the emergency department. Neurology 2007;69:2038–44. [4] Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 1: Triptans, dihydroergotamine, and magnesium. Headache 2012;52:114–28. [5] Kelley NE, Tepper DE. Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others. Headache 2012;52:292–306. [6] Archibald HC. Chlorpromazine for headache. Am J Psychiatry 1955;112:390. [7] Boes CJ, Capobianco DJ, Cutrer, Dodick DW, Garza I, Swanson JW. Headache and other craniofacial pain. In: Bradley WG, Daroff RB, Fenichel GM, Marsden CD, editors. Neurology in clinical practice. 5th ed. Boston: Elsevier-Academic Press; 2008. p. 2027–46. [8] Iserson KV. Parenteral chlorpromazine treatment of migraine. Ann Emerg Med 1983;12:756–8. [9] Bigal ME, Bordini CA, Speciali JG. Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial. J Emerg Med 2002;23:141–8. [10] Mosnaim AD, Ranade VV, Wolf ME, Puente J, Valenzuela MA. Phenothiazine molecule provides the basic chemical structure for various classes of pharmacotherapeutic agents. Am J Ther 2006;13:261–73. [11] Gilman AG, Rall TW, Nies AS, Taylor P. In: The pharmacological basis of therapeutics. 8th ed. London: Pergamon Press; 1991.