Prochlorperazine in children with migraine: a look at its effectiveness and rate of akathisia
American Journal of Emergency Medicine (2012) 30, 456-463
Brief Report
Prochlorperazine in children with migraine: a look at its effectiveness and rate of akathisia
Evelyne D. Trottier MD a, Benoit Bailey MD a,b,?, Nathalie Lucas MD a, Anne Lortie MD c
aDivision of Emergency Medicine, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada H3T 1C5
bDivision of Clinical Pharmacology and Toxicology, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec,
Canada H3T 1C5
cDivision of Neurology, Department of Pediatrics, CHU Sainte-Justine, Montreal, Quebec, Canada H3T 1C5
Received 28 October 2010; revised 15 December 2010; accepted 15 December 2010
Abstract
Objective: The objective of this study is to evaluate the effectiveness of prochlorperazine and the rate of akathisia in children with severe migraine.
Methods: The study is a prospective cohort of a convenient sample of patients younger than 18 years old diagnosed with migraine and treated with intravenous prochlorperazine in adjunction with diphenhy- dramine in the emergency department. The evaluation of pain and akathisia was performed before the treatment and was repeated 60 minutes later and before discharge. A telephone follow-up was completed to assess relapse in pain and presence of akathisia. The effectiveness of prochlorperazine was determined using different outcomes: 50% reduction of pain, pain-free patients, treatment failure, and relapse of pain. Results: Of the 79 patients included in the study for 25 months, 64 (81%) either met the International Headache Society criteria or had a diagnosis of migraine confirmed by a neurologist at follow-up. Among these patients, 47 (100%) of 47 had a 50% reduction of pain, and 24 (50%) of 48 were pain free at discharge. Only 14 (22%) of 64 patients had a treatment failure. However, 43 (68%) of 63 patients had a relapse of their headache within the first week after discharge. Overall, among the 79 patients, 4 (5%) had a definitive diagnosis of akathisia, but 27 (34%) other patients presented symptoms suggesting a possible diagnosis of akathisia.
Conclusion: Prochlorperazine seems very effective to decrease pain on a short-term basis in children. However, more than two thirds of the patients, overall, had a relapse of their migraine at home in the first week. Despite the use of diphenhydramine, akathisia remains a concern.
(C) 2012
Introduction
Despite that up to 10% of children may suffer from migraine, very few studies have been conducted on the
* Corresponding author. Department of Pediatrics, CHU Ste-Justine, 3175 Chemin de la Cote-Ste-Catherine, Montreal, Quebec, Canada H3T 1C5. Tel.: +1 514 345 4931×6276; fax: +1 514 345 4823.
E-mail address: [email protected] (B. Bailey).
treatment of this condition, in particular, in the emergency department (ED) [1]. In fact, a recent meta-analysis demonstrated that only 1 randomized controlled trial (RCT) was performed in children who presented to an ED [2,3]. In that study, prochlorperazine was compared to ketorolac but only in short-term pain reduction (1 hour) [3]. Although the RCT seems to suggest prochlorperazine efficacy for this outcome, its effectiveness for other important outcomes relevant to the patient has only been evaluated retrospectively [4,5].
0735-6757/$ - see front matter (C) 2012 doi:10.1016/j.ajem.2010.12.020
Prochlorperazine is a dopamine receptor antagonist. It can precipitate extrapyramidal symptoms such as akathisia. In adult studies, as much as 36% to 44% of patients receiving prochlorperazine present akathisia [6-8]. We have no information on the rate of akathisia in children after its administration in the ED.
Therefore, the objectives of our study were to evaluate prospectively the effectiveness of prochlorperazine and the rate of akathisia after its administration.
Methods
Study design
This was a prospective cohort of a convenient sample of children diagnosed with migraine, as determined by pediatric emergency physicians, and treated with intravenous pro- chlorperazine in the ED because of severe migraine or “Status migrainosus.” The study was approved by our hospital institutional review board.
Study setting
All patients were treated in the ED of a tertiary care pediatric hospital with 60 000 visits annually. Members of the ED have been using a standardized protocol for the treatment of migraine and status migrainosus for the last 10 years. This protocol suggests treatment with prochlorper- azine (0.15 mg/kg intravenously [IV] administered in 2-3 minutes; maximal dose, 10 mg) in addition to diphenhydra- mine (0.5 mg/kg IV; maximal dose, 25 mg) for patients older than 8 years presenting with severe migraine or status migrainosus. No intravenous fluid treatment is proposed. No specific instrument is suggested in the protocol to evaluate the presence of akathisia. It does not recommend any particular Rescue therapy if the primary treatment is not effective or if the patient presents adverse effects such as akathisia. In addition, the length of stay in the ED after intravenous treatment with prochlorperazine is determined by the Clinical response of the patient and the absence of adverse effect, which is evaluated by the staff physician. On discharge, the protocol suggests using naproxen for 7 days.
Participants
Patients younger than 18 years who presented to the ED between July 2007 and July 2009 with severe migraine or status migrainosus requiring prochlorperazine treatment were approached by a research assistant or a member of the research team to participate in the study when they were available. At inclusion in the study, patients did not necessarily meet the International Headache Society (IHS) criteria [9]. These criteria being restrictive compared to expert clinical diagnosis, we decided to use the clinical
diagnosis of the ED physician as inclusion criteria [10]. However, the diagnosis was further ascertained during the ED stay by a standardized questionnaire reviewing the IHS criteria and later by neurologists at a follow-up visit. Patients with developmental delay were excluded because ability to answer the questionnaire was required. Written informed consent and assent were obtained from a parent and the patient, respectively. Patients and parents were not told of the risk of akathisia specifically but they were aware that we were studying the adverse effect of prochlorperazine.
Study protocol
Once consents were obtained and before prochlorperazine and diphenhydramine were administered, patients were asked to rate the intensity of the migraine on a Visual analog scale from 0 to 100 mm and using the verbal numeric scale (VNS) from 0 to 10. On the same questionnaire, the patients had to answer 3 questions about akathisia symptoms according to the long instrument for the diagnosis and grading of acute drug-induced akathisia suggested by Vinson (Appendix A) [11]. At the same time, the nurse in charge of the patient evaluated the objective signs of akathisia using the same scale [11]. The subjective component of this scale consists of 3 questions graded on a 4-point severity scale (Appendix A). The objective component consists of 2 questions graded on a 5-point severity scale (Appendix A). Evaluation of pain and akathisia was repeated 60 minutes after prochlorperazine administration or as soon as possible if the patient was asleep at that time. This assessment was also performed just before discharge. A telephone follow-up was completed by a research nurse 48 hours and 1 week after the treatment in the ED to assess the relapse of pain and the presence of akathisia. Patients were asked if they had relapse of headache since their discharge from the ED. If so, they were asked to rate their worst pain since discharge using the VNS from 0 to 10. The use of medication at home was noted. The presence of akathisia was assessed during this follow-up using the subjective component of the long instrument for the diagnosis and grading of acute drug-induced akathisia (Appendix A) [11].
During the ED stay, parents were asked to help their child list their migraine symptoms using a standardized question- naire to have a better understanding of their symptoms and to determine if their migraine fitted the IHS criteria [5].
The medical charts of the patients were reviewed to evaluate the need for further medication in the ED after the Initial administration of prochlorperazine. We also noted if a treatment was prescribed at discharge. In addition, we evaluated if the patient required hospitaliza- tion or if he or she returned to the ED within 7 days after treatment because of headache or adverse effects. Finally, we reviewed the medical charts to document any adverse effects associated with the prochlorperazine treatment and if the adverse effects were treated when diagnosed by the ED physician. We specifically looked for akathisia by
reading all physicians and nurses’ notes looking for any behavior suggesting akathisia.
A follow-up by a pediatric neurologist was arranged within 3 months of the ED visit. At that time, the neurologist determined if the patient did have migraine.
Outcome
The effectiveness of prochlorperazine was determined using outcomes relevant to the patients [5]: (1) the number of patients with a 50% reduction in pain as measured with the VAS 1 to 2 hours after its administration and at time of discharge from the ED; (2) the number of patients who were pain free (VAS 0/100 mm) 1 to 2 hours after its administration and at time of discharge from the ED; (3) the number of patients who required rescue therapy (rescue therapies were defined as oral doses of opiates or triptans or any other parenteral medications, including a second dose of prochlorperazine; the following medications were consid- ered as a beginning of Prophylactic treatment or minor analgesic and were therefore not considered as rescue therapy: acetaminophen, nonsteroidal anti-inflammatory drugs (NSAID), or amitryptilline); (4) the number of hospitalization at the initial visit; (5) the number of patients who returned to the ED within 7 days of the index visit for headache or akathisia; (6) the number of treatment failure defined as the use of rescue therapy after its administration, hospitalization at the initial visit, or the return visit to the ED within 7 days; and (7) the relapse of pain within the first week after discharge evaluated by telephone follow-up at 48 hours and 1 week.
Table 1 Characteristics of the children enrolled in the cohort study
Akathisia was evaluated with the long instrument for the diagnosis and grading of acute drug-induced akathisia [11]. This required an increase of at least 2 points in the subjective component and of at least 1 point in the objective component 1 to 2 hours after prochlorperazine administration or at dis- charge compared to the premedication assessment [11]. These patients were classified as having a definitive diagnosis of akathisia. Patients who had a 2-point increase in the sub- jective component only or those who had a 1-point increase in the objective component only 1 to 2 hours after prochlorpera- zine, at discharge, or at the telephone follow-up compared to the initial questionnaire were reported as possible akathi- sia. The number of patients who received a treatment for akathisia in the ED and those suspected of having akathisia based on notes in the chart were reported separately.
Data analysis
All data were entered in an Excel database (Microsoft, Redmond, WA). Statistical analysis was performed using SPSS v16.0 (Rainbow technologies Chicago, IL).
All effectiveness outcomes were reported according to the way migraine was diagnosed: (1) according to the IHS criteria or according to the neurologist assessment (con-
firmed migraine) and (2) according to the pediatric emergency physician (Probable migraine). The intensity of the migraine relapse at telephone follow-up was reported as a percentage of the intensity of the initial headache using the VNS.
A posteriori, we compared the incidence of relapse in those taking either an NSAID or, more specifically, naproxen, as per our protocol, using ?2. We also compared the intensity of the pain at discharge in those with and without relapse using a Mann-Whitney U test. The difference between the proportions or the median and its 95% confidence interval (CI) were reported. The level of significance was set at P b .05.
Results
From July 2007 to July 2009, 79 patients with a diagnosis of migraine made by the pediatric emergency physicians were treated with prochlorperazine and agreed to take part in the study (Table 1). One patient was 5 years old and did not
|
Patients (n = 79) |
|
Age (y) (mean +- SD) 13.6 +- 2.3
Boys (%) 42 (53) History of migraine 36 (46) Initial pain intensity on the 100 mm 72 (58-80) VAS (median [IQR]) Duration of the migraine in h 72 (32-168) (median [IQR]) Medications used at home before 56 (71) the ED visit (%) a Ibuprofen 33 Acetaminophen 25 Naproxen 4 Dimenhydrinate 2 acetylsalicylic acid + caffeine 1 Amitryptilline 1 Codeine 1 Fiorinal 1 Rizatriptan 1 Medications prescribed on discharge 71 (90) from the ED a Naproxen 35 Ibuprofen 13 Acetaminophen 13 Amitryptilline 8 Codeine 3 Fiorinal 1 Pyridoxine 1 Dimenhydrinate 1 |
|
a Patients may have taken more than one medication. |
complete the VAS to rate the intensity of the migraine. Seven other patients were approached but refused 220 to participate in the study. Several patients (71%) had received medica- tions at home before their ED visit in an unsuccessful attempt to treat their symptoms.
Of the 79 patients included in the study, 28 (35%) met the IHS criteria (27 of them also had their diagnosis confirmed by a neurologist-the other was not seen at the neurology clinic), and 36 (46%) had a diagnosis of migraine confirmed exclusively by a neurologist at follow-up without necessarily meeting the IHS criteria on our questionnaire in the ED. The 15 patients (19%) left had a diagnosis of migraine solely made by the pediatric emergency physician at the time of the ED consultation. Of those, we know that 3 had another diagnosis proposed at follow-up: 1 patient hospitalized was discharge with a diagnosis of viral meningiti, 1 patient had a diagnosis of nonspecific headache made by the neurologist at follow-up, and 1 had a diagnosis of Posttraumatic headache also made by the neurologist at follow-up. We have no reason to suspect other diagnosis in the remaining 12 patients. They were not seen at the neurology clinic, and they never returned to the ED with an alternative diagnosis.
Pain reduction
Among the patients with a diagnosis of migraine confirmed either by the IHS criteria or by a neurologist, 43 (94%) of 46 had a 50% reduction in the intensity of their migraine at the time of the first evaluation after prochlor- perazine administration and 47 (100%) of 47, at discharge
Table 2 Effectiveness of prochlorperazine in children treated in the ED because of migraine or status migrainosus
Diagnosis of migraine ascertained by
IHS criteria a Neurologist a Only by ED physician a All patients
Outcome n = 28 (%) n = 36 (%) n = 15 (%) n = 79 (%)
(Table 2). Pain-free status was reached in 16 (33%) of 48 patients with a diagnosis of migraine confirmed either by the IHS criteria or by a neurologist at the time of the first evaluation after prochlorperazine administration and in 24 (50%) of 48 of them at discharge (Table 2).
Treatment failure
The use of a rescue therapy in the ED after prochlorper- azine administration was required in 6 (9%) of 64 patients with a diagnosis of migraine confirmed either by the IHS criteria or by a neurologist (Table 2). A decision to admit the patient because of persisting symptoms after treatment in the ED was made for 6 (9%) of 64 patients in the confirmed diagnosis group (Table 2). Among the successfully treated patients at discharge, 8 (12%) of 64 patients with a diagnosis of migraine confirmed returned to the ED within 7 days after prochlorperazine treatment. Therefore, in total, 14 (22%) of the 64 patients with a confirmed diagnosis of migraine either by the IHS criteria or by a neurologist had a treatment failure after prochlorperazine administration (Table 2).
Relapse of symptoms at telephone follow-up
The telephone follow-up revealed that 43 (68%) of 63 patients with a confirmed diagnosis of migraine had a relapse of their headache within the first week after discharge (Table 2). Of those 43, 29 (67%) patients were taking an NSAID after discharge, including 22 patients taking naproxen as
suggested in the protocol for migraine treatment in our ED. Of the patients without relapse and a diagnosis of migraine confirmed, 16 (80%) of 20 were taking an NSAID, including 12 patients taking naproxen as per the ED protocol. The difference in use of an NSAID or naproxen among the patients with a diagnosis of migraine confirmed either by the IHS criteria or by a neurologist with or without relapse was not significant: D -13% (95% CI, -33-13) and D -8% (95% CI, -29-15), respectively. Overall, the intensity of those relapses was more than two thirds of the initial migraine attack in each group and occurred at a median of 24 hours after discharge from the ED (Table 2). There was no difference in the median intensity of pain at the time of discharge between patients with or without relapse among those with a confirmed diagnosis: 0 (interquantile range [IQR], 0-16) and 1 (0-10), respectively, on the 0 to 100 mm
VAS scale, a difference of 0, (95% CI, -2-4).
Akathisia
Definitive diagnosis: positive subjective and objective components
Using the long instrument as a diagnosis tool, 2 patients (3%) presented with akathisia on the first evaluation performed at a median of 115 minutes (IQR, 78-189) after prochlorperazine administration, and 3 patients (6%) pre- sented with akathisia at the evaluation performed at discharge at a median of 230 minutes (IQR, 185-345) after
Table 3 Akathisia after prochlorperazine administration in children treated in the ED because of migraine or status migrainosus
prochlorperazine administration (Table 3). This represents a total of 4 patients (5%) (2 mild and 2 moderate). Within this group, 2 patients were successfully treated with an additional dose of diphenhydramine in the ED. The other 2 patients identified by the long instrument were not treated but the symptoms of akathisia were described in the charts.
Possible diagnosis: positive subjective component and positive objective component but at different time One patient probably also had akathisia according to the long instrument, but missing data prevent us from being certain. The objective component was positive 1 hour after treatment, but the patient did not complete the sub- jective part. However, the subjective component was posi-
tive at discharge.
Possible diagnosis: positive subjective component only
A total of 22 patients (28%) presented a positive subjective component without an elevation in the objective component: 5 in the ED and 17 on the telephone follow-up. Those patients might also have been affected by akathisia.
Possible diagnosis: positive objective component only
Three patients had an isolated positive objective component without significant change in the subjective
|
After discharge |
||||||
|
First evaluation a |
Discharge b |
2 d |
7 d |
|||
|
n = 79 c |
n = 79 c |
n = 79 c |
n = 79 c |
|
Positive long instrument d
|
2/60 (3) |
3/52 (6) |
ND |
ND |
|
Mild |
1 |
2 |
||
|
Moderate |
1 |
1 |
||
|
Severe |
0 |
0 |
||
|
Positive subjective component e |
8/65 (12) |
9/64 (14) |
15/74 (20) |
6/69 (9) |
|
Mild |
6 |
6 |
9 |
6 |
|
Moderate |
2 |
2 |
2 |
0 |
|
Severe |
0 |
1 |
4 |
0 |
|
Positive objective component f |
6/60 (10) |
5/60 (8) |
ND |
ND |
|
Mild |
5 |
5 |
||
|
Moderate |
1 |
0 |
||
|
Severe |
0 |
0 |
||
|
ND indicates not done. a Performed at a median of 115 minutes (IQR, 78-189). b Performed at a median of 230 minutes (IQR 185-345). c The change in denominator results from missing data. d The long instrument is based on the combined point increase in subjective and objective components from the preinfusion to the postinfusion assessment: mild, 3 to 7 points; moderate, 8 to 12; severe, 13 to 17. e Point increase in subjective component: mild, 2 to 3; moderate, 4 to 6; severe, 7 to 9. f Point increase in objective component: mild, 1 to 2; moderate, 3 to 5; severe, 6 to 8. |
||||
component of the long instrument; one of them had symptoms of akathisia recorded in the medical chart. Finally, another patient did not have any positive component, but the physician reported signs of akathisia in his medical notes. Those 4 patients might also have signs consistent with akathisia.
Thus, in addition to the 4 patients (5%) with a definitive diagnosis of akathisia according to the long instrument, 27 patients (34%) presented features suggest- ing a possible diagnosis of akathisia after prochlorper- azine administration.
Discussion
This is the first prospective study that evaluated the effectiveness of prochlorperazine used for the treatment of severe migraine and status migrainosus in children that studied different outcomes important to the patient [5]. We not only demonstrated that prochlorperazine was effective to decrease pain by 50% in all patients and to produce pain-free status in almost half of the patients during the ED stay but also that a minimal number of patients required other rescue therapy in the ED, hospitalization, or a return visit to the ED in the first 7 days after its administration. However, our study also demonstrated that more than two thirds of all the patients treated successfully with prochlorperazine in the ED had a relapse of their headache at home in the first week even if most of them were prescribed an NSAID at discharge. In addition, we found that akathisia still occurred after prochlorperazine administration in children despite the use of diphenhydramine to prevent it.
As other studies performed in children have demons- trated, prochlorperazine is very effective in decreasing pain intensity within a short period. In an RCT by Brousseau et al [3], a reduction in at least 50% of the pain intensity 1 hour after prochlorperazine administration was reported in 28 (85%) of 33 patients compared to 16 (55%) of 29 after ketorolac administration, a difference of 30% (95% CI, 8-52). These results were confirmed by a cohort study of children with status migrainosus followed up in a headache center; 15 (75%) of 20 patients had a pain reduction of at least 50% at 1 hour and 19 (95%) of 20 at 3 hour after prochlorperazine administration [12]. In our study, 93% of the patients with a confirmed diagnosis of migraine had their symptoms reduced by 1 hour, with 33% being pain free. The treatment seems even more successful at discharge, with 100% of patients reaching 50% reduction of pain and with 50% being pain free.
The analysis of other important aspects of the effective- ness of the treatment such as the need of second rescue therapy, hospitalization, or a return visit to the ED within
7 days reveals that prochlorperazine treatment failure occurred in 22% in the confirmed migraine group in our study. This is a similar rate to a retrospective study reviewing similar treatment failure outcomes [4]. In that study, 13
(14%) of 92 patients had a treatment failure using the same criteria retrospectively.
The need of rescue therapy after prochlorperazine has been reported in 2 prospective studies and in 1 retrospective study. In the RCT, 4 (12%) of 33 of those initially treated with prochlorperazine needed a rescue therapy (ketorolac) compared to 12 (41%) of 29 of those treated with ketorolac, a difference of -29% (95% CI, -49 to -7) [3]. In the prospective cohort study, 1 (5%) of 20 patients received a rescue therapy after prochlorperazine administration [12]. In the retrospective study, 8 (9%) of 92 needed a Rescue medication [4]. In our study, 6 (9%) of 64 of the confirmed migraine patients received a rescue medication after pro- chlorperazine administration.
The relapse of symptoms after treatment is another important outcome to report especially when studying the effectiveness of a medication for the treatment of migraine [5]. Brousseau et al [3] reported a relapse of symptoms within 48 hours in 7 (27%) of 26 patients treated with prochlorperazine without significant difference compared to the patients treated with ketorolac (4 [31%]/13; difference of -4% [95% CI, -34-27]). The cohort study by Kabbouche et al [12] showed that 2 (10%) of 20 patients were not pain free at a 24-hour follow-up. In our study, as much as 68% of the confirmed migraine group had a relapse of symptoms at telephone follow-up (and 73% of all patients) mainly 24 hours after the treatment. Moreover, the intensity of the relapse was 73% (IQR, 48-103) of the intensity of the initial migraine in the confirmed migraine group. Overall, although prochlorperazine appears to be very effective in decreasing the intensity of pain in the ED for all the outcomes we studied (50% decrease in pain, pain-free status, need for rescue therapy, and Need for hospitalization), the high rate of symptoms relapse at follow-up emphasizes the need for additional prophylactic treatment at discharge after a severe migraine episode. Most of our patients had an NSAID prescribed (information from their file or at telephone follow-up). However, we have no information about compliance with this medication or about the possible improvement of symptoms when the medication was used and thus cannot specifically conclude on its effectiveness. In an adult study, NSAID was demonstrated to be as effective as sumatriptan when used to treat recurrent headache at home after IV treatment of migraine in the ED (improvement of
4.3 vs 4.2 on a 0-10 VNS; a difference of 0.1 [95% CI, -1.3- 1.5]) [13]. Interestingly, of the 73% of patients who had presented recurrent headache at their 48-hour telephone follow-up after the ED consultation, only 51% had decided to take the investigational medication [13]. In addition, to our knowledge, no study on the efficacy of dexamethasone administered at discharge for the prevention of those relapse has been performed in children, although some evidence do exist in adults [14]. In addition, the evidence on the role of triptans or preventive medications such as amitryptilline is still poor. Considering its initial efficacy in the ED, the use of oral prochlorperazine at home after discharge could also be
studied in the future to assess its efficacy in preventing these recurrences.
Another important outcome is the need to return to the ED despite the treatment with prochlorperazine. In the retrospective study, 3 (3%) of 92 patients returned to the ED in the 48 hours after prochlorperazine treatment because of symptoms relapse [4]. The RCT and the cohort study did not report this specific outcome [3,12]. In the present study, 8 (12%) of 64 patients of the confirmed migraine group returned in the ED in the following 7 days after the prochlorperazine administration because of migraine relapse. Considering the high number of relapse we had on telephone follow-up, we do not know why some patients did return to the ED and why other did not. We can speculate that this is the same reason why half of the patients did not take the investigational medication in the adult study mentioned earlier [13].
Akathisia, an extrapyramidal symptom, has been reported after prochlorperazine treatment. In adult studies, 36% to 44% of patients present akathisia after prochlorperazine alone and in 14% of patients when diphenhydramine is added in adjunction [6-8]. In children, the RCT reported 2 patients with possible extrapyramidal symptoms after prochlorperazine administration based on the symptoms mentioned in the article, although akathisia was not clearly diagnosed; one of them have been successfully treated with diphenhydramine [3]. The other patient had his symptoms resolved spontaneously [3]. No side effect was reported in the cohort study [12]. In the retrospective study, 1 patient was treated with diphenhydramine because of akathisia and 5 others patients had suspected akathisia symptoms based on medical and nurse’s notes in the charts [4]. Another retrospective study only presented as an abstract reported 6 (12%) of 51 patients with a positive subjective component of the long instrument for the diagnosis and grading of acute drug-induced akathisia at a 24-hour telephone follow-up after migraine treatment in the ED with prochlorperazine and diphenhydramine [15]. In our study, 4 patients had a definitive diagnosis of akathisia using the long instrument, and 1 other patient probably also had akathisia but was not detected by the long instrument because of missing data. Two of them were successfully treated with an additional dose of diphenhydramine, and the other 3 were not treated. Surprisingly, 22 other patients (28%) had a positive subjective component at some point. Those patients may also have presented akathisia that was underdiagnosed by the medical team. The 2-minute observation of the seated patient proposed by Vinson to look for extrapyramidal symptoms might not have always been respected while filling up the objective questionnaire [11]. However, none of the patients returned to the ED because of akathisia. The impact of akathisia is important for the patient. First, the troublesome symptoms may persist for 24 to 48 hours. In addition, in our experience, after a patient has experienced this adverse effect, he or she is likely to request that prochlorperazine is not used in future episode especially if it was left untreated.
This situation leaves the ED physician with Alternative therapies that may be less effective than prochlorperazine.
Limitations
There are some limitations to this study. First, this was a convenient sample of patients with severe migraine or status migrainosus treated with prochlorperazine. Because it was not a placebo RCT study, we had no control group to evaluate the placebo effect. The placebo effect is important in the treatment of migraine in children [16]. Our study demonstrated that prochlorperazine is effective in decreasing pain in the ED but that many patients had a relapse of their symptoms within the next week. In addition, we do not know the difference between the patients treated in the ED with prochlorperazine and those not treated.
We tried to standardize the evaluation of akathisia with a questionnaire using the long instrument proposed by Vinson [11]. Unfortunately, some data concerning the subjective part of the scale were missing. Some patients were sleeping at the 1- to 2-hour evaluation post prochlorperazine, whereas others did not fill up their questionnaire before leaving the ED. This is also true for the evaluation of pain. For the objective part of the scale, nurses were supposed to observe patients for 2 minutes before grading the akathisia. We have no way of knowing if this recommendation was followed in the setting of a busy ED. However, we believe that the way the tool was used represent the real practice in the ED.
In the ED, the grading of pain before and after prochlorperazine was recorded prospectively. Unfortunately, some patients forgot to fill up some part of the pain questionnaire. As an example, some patients were sleeping 1 to 2 hours after treatment and wake up only at discharge therefore filling up only the discharge questionnaire. After discharge, all patients had a telephone follow-up to assess their symptoms (headache and adverse effects). However, the evaluation of the relapse of the migraine symptoms as well as akathisia by telephone 48 hours and 1 week later might have been done a day or later after the symptoms, and thus, a recall bias may have occurred. At least 1 patient could not recall the severity at the time of follow-up.
Although this study suggests the limitations of NSAID to prevent relapse of migraine after discharge from the ED, it was not designed to evaluate this aspect of the treatment. This will need to be studied specifically in the future to help improve the care of children with severe migraine or status migrainosus.
In conclusion, our study demonstrated that prochlorper- azine was effective to decrease pain on a short-term basis with few treatment failures in the ED. However, more than two thirds of the patients had a relapse of their headache at home in the first week, including most in the first or second day, emphasizing the need for adequate maintenance therapy. Moreover, despite the use of diphenhydramine, akathisia remains a concern after prochlorperazine adminis- tration in children.
Appendix A
|
Subjective component |
Reported |
severity |
||||
|
Questions answered by patients |
No |
Mild |
Moderate |
Major |
||
|
Do you feel a restless urge to move, especially in your legs? |
0 |
1 |
2 |
3 |
||
|
Are you unable to keep your legs still? |
0 |
1 |
2 |
3 |
||
|
Are you unable to remain still, either standing or sitting? |
0 |
1 |
2 |
3 |
||
|
Objective component Observed frequency |
||||||
|
Absent |
Infrequent |
Some |
Frequent |
Constant |
||
|
2-minute observation of seated patient |
0%-5% |
5%-25% |
25%-50% |
50%-90% |
N90% |
|
|
Inability to remain seated. Frequency of torso shifting |
0 |
1 |
2 |
3 |
4 |
|
|
Frequency of semipurposeful or purposeless leg movements |
0 |
1 |
2 |
3 |
4 |
|
References
Appendix Table 1 Long instrument for the diagnosis and grading of acute drug-induced akathisia [11]
- Winner P, Martinez W, Mate L, Bello L. Classification of pediatric migraine: proposed revisions to the IHS criteria. Headache 1995;35: 407-10.
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- Brousseau DC, Duffy SJ, Anderson AC, Linakis JG. Treatment of pediatric migraine headaches: a randomized, double-blind trial of prochlorperazine versus ketorolac. Ann Emerg Med 2004;43:256-62.
- Trottier ED, Bailey B, Dauphin-Pierre S, Gravel J. Clinical outcomes of children treated with intravenous prochlorperazine for migraine in a pediatric emergency department. J Emerg Med 2010;39:166-73.
- International Headache Society Clinical Trials Subcommittee. Guide- lines for controlled trials of drugs in migraine second edition. Cephalalgia 2000;20:765-86.
- Drotts DL, Vinson DR. Prochlorperazine induces akathisia in emergency patients. Ann Emerg Med 1999;34:469-75.
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