IV Haloperidol vs. IV Metoclopramide for Migraines in the ED
IV Haloperidol vs. IV Metoclopramide for Migraines in the ED
Subject enrollment is detailed in Figure 1. A total of 138 patients presented during the enrollment time frame with a chief complaint of migraine headache. Potential candidates were identified by the triage nurse, primary nurse, or provider, and screened. A total of 64 patients were enrolled in the study, with 31 randomized to receive haloperidol and 33 receiving metoclopramide. The study protocol maintained an intention-to-treat analysis.
(Enlarge Image)
Figure 1.
Flow chart of subjects enrolled in the study.
The demographic characteristics of the subjects are found in Table 3 . Subjects in the two groups did not differ in age or sex.
VAS scales for pain, nausea, restlessness, and sedation were presented to the subjects at Time 0 ("Pre") and every 20 min until the last recorded measurement or the 80-min period ("Post"). When an individual subject's data collection was suspended prior to 80 min (usually for requesting discharge), the last recorded measurement of that variable was used for "Pre-Post" comparisons. Results are presented in Figure 2.
(Enlarge Image)
Figure 2.
Mean visual analog scale (VAS) in mm with 95% confidence intervals (CI).
The mean reduction in pain from baseline to the last recorded measure of pain on the 100-mm VAS scale was statistically and clinically significant for both haloperidol- and metoclopramide-treated groups: 57 mm for the haloperidol group and 49 mm for those treated with metoclopramide (p < 0.01 for each comparison). When compared to each other, the VAS pain scores for the haloperidol and metoclopramide groups did not differ at baseline, at the last recorded measurement, or in the magnitude of the pre-post treatment change (p > 0.05). The two regimens were also equivalent in the time to achieve maximum pain relief (defined as the average measurement interval in which the subjects lowest VAS score was first recorded): 55 min for metoclopramide, 56 min with haloperidol (p > 0.05; VAS - Figure 2)
Nausea. Overall, both agents were effective at treating nausea, when present, with mean VAS reductions of 27 mm for metoclopramide and 31 mm for haloperidol (p < 0.01 for both). There were no differences between the haloperidol and metoclopramide groups in reported nausea either prior to or after treatment (VAS - Figure 2).
Restlessness. Within groups, neither agent produced a statistically significant change in restlessness. There were no differences in restlessness between the groups prior to or after treatment (all p > 0.05).
Sedation. Subjects in both groups recorded a baseline level of sedation that did not change statistically within each group after treatment, and that did not differ at baseline or study completion between groups (all p > 0.05).
Eight of the 33 subjects in the metoclopramide group (24%) were given rescue medications, compared with only 1 of the 31 subjects (3%) receiving haloperidol (p < 0.02). In the metoclopramide group, 7 patients received intravenous ketorolac, and one patient received intravenous morphine. One patient in the haloperidol group received intravenous ketorolac and methylprednisolone as rescue medications. Only one patient required more diphenhydramine, and that patient was in the metoclopramide arm.
There was no difference in the number of subjects reporting adequate pain relief and requesting discharge prior to the 80 min point (35% in the haloperidol group and 21% in the metoclopramide group, p > 0.05).
When asked at the completion of their ED stay, 92% of 24 responding subjects in the haloperidol group (and 75% of 28 responding subjects in the metoclopramide group) would want the same medication again (p > 0.05, chi-squared).
Subjects were specifically queried regarding the presence of nausea, restlessness/anxiety, sleepiness, and chest discomfort at baseline and at the same 20-min intervals as the VAS scoring. Results are presented in Table 4 . The Table lists the proportions of subjects in the two groups who either responded affirmatively at baseline (prior to study-drug administration), or who reported the index symptom at least once beginning after intervention. The denominator was the number of subjects in each treatment group.
Sleepiness and nausea were most commonly reported. Even prior to study drug administration, both nausea and sleepiness were acknowledged by two-thirds of all subjects. After the study drug was administered, an additional 22% of patients reported new sleepiness. Only one subject developed nausea after treatment. Sleepiness was statistically more common in the group that was to receive haloperidol. There were no other differences between the groups in any of the other side-effect questions asked. In addition to the four specific questions, caregivers were encouraged to report separately any observed adverse events. There were recorded events for four subjects in the haloperidol group ("restless"/"loopy"; "restless legs"; "nausea – given ondansetron"; "difficult to wake"). Two metoclopramide-treated subjects had recorded observations: "jittery, momentarily short of breath during i.v. push"; "symptoms relieved at 40 min but returned."
Subjects were to remain on cardiac monitors throughout their ED stay. QTc intervals were obtained from the printed ECGs. All subjects had unremarkable pretreatment ECGs. Posttreatment cardiograms were performed on 45% of the subjects. Their pre- and posttreatment QTc intervals are presented in Table 5. Mean QTcs were equal and normal in the two groups and did not change after treatment for either group.
No dysrhythmias were reported. The four subjects reporting chest pain were re-evaluated and received repeat ECGs, and subsequently, they were not felt to require further cardiac evaluation. No subject complained of palpitations, had clinically relevant dysrhythmias, or had any cardiac adverse event during treatment.
Of the 64 enrolled subjects, 43 were reached for a follow-up phone interview. Overall, 90% answered affirmatively when asked if they were happy with the medication they received in the ED. Sixty percent of metoclopramide-treated subjects and 48% of haloperidol-treated subjects reported return of headache symptoms after discharge. Three subjects, all in the metoclopramide group, returned to the ED. In response to questions about other symptoms since ED discharge, sleepiness was the most commonly reported, affecting 40% and 52% of the metoclopramide and haloperidol groups, respectively. The only statistically significant difference in side effects between treatment groups was in reported restlessness, reported in 43% of the haloperidol group, but in only 10% of those receiving metoclopramide. Agitation and nausea were infrequently reported and no subject contacted had vomiting or chest pain (See Table 6).
Results
Characteristics of Study Subjects
Subject enrollment is detailed in Figure 1. A total of 138 patients presented during the enrollment time frame with a chief complaint of migraine headache. Potential candidates were identified by the triage nurse, primary nurse, or provider, and screened. A total of 64 patients were enrolled in the study, with 31 randomized to receive haloperidol and 33 receiving metoclopramide. The study protocol maintained an intention-to-treat analysis.
(Enlarge Image)
Figure 1.
Flow chart of subjects enrolled in the study.
The demographic characteristics of the subjects are found in Table 3 . Subjects in the two groups did not differ in age or sex.
Main Results
VAS scales for pain, nausea, restlessness, and sedation were presented to the subjects at Time 0 ("Pre") and every 20 min until the last recorded measurement or the 80-min period ("Post"). When an individual subject's data collection was suspended prior to 80 min (usually for requesting discharge), the last recorded measurement of that variable was used for "Pre-Post" comparisons. Results are presented in Figure 2.
(Enlarge Image)
Figure 2.
Mean visual analog scale (VAS) in mm with 95% confidence intervals (CI).
Primary Outcome
The mean reduction in pain from baseline to the last recorded measure of pain on the 100-mm VAS scale was statistically and clinically significant for both haloperidol- and metoclopramide-treated groups: 57 mm for the haloperidol group and 49 mm for those treated with metoclopramide (p < 0.01 for each comparison). When compared to each other, the VAS pain scores for the haloperidol and metoclopramide groups did not differ at baseline, at the last recorded measurement, or in the magnitude of the pre-post treatment change (p > 0.05). The two regimens were also equivalent in the time to achieve maximum pain relief (defined as the average measurement interval in which the subjects lowest VAS score was first recorded): 55 min for metoclopramide, 56 min with haloperidol (p > 0.05; VAS - Figure 2)
Secondary Outcomes
Nausea. Overall, both agents were effective at treating nausea, when present, with mean VAS reductions of 27 mm for metoclopramide and 31 mm for haloperidol (p < 0.01 for both). There were no differences between the haloperidol and metoclopramide groups in reported nausea either prior to or after treatment (VAS - Figure 2).
Restlessness. Within groups, neither agent produced a statistically significant change in restlessness. There were no differences in restlessness between the groups prior to or after treatment (all p > 0.05).
Sedation. Subjects in both groups recorded a baseline level of sedation that did not change statistically within each group after treatment, and that did not differ at baseline or study completion between groups (all p > 0.05).
Rescue Medications
Eight of the 33 subjects in the metoclopramide group (24%) were given rescue medications, compared with only 1 of the 31 subjects (3%) receiving haloperidol (p < 0.02). In the metoclopramide group, 7 patients received intravenous ketorolac, and one patient received intravenous morphine. One patient in the haloperidol group received intravenous ketorolac and methylprednisolone as rescue medications. Only one patient required more diphenhydramine, and that patient was in the metoclopramide arm.
Early Discharge
There was no difference in the number of subjects reporting adequate pain relief and requesting discharge prior to the 80 min point (35% in the haloperidol group and 21% in the metoclopramide group, p > 0.05).
Patient Satisfaction
When asked at the completion of their ED stay, 92% of 24 responding subjects in the haloperidol group (and 75% of 28 responding subjects in the metoclopramide group) would want the same medication again (p > 0.05, chi-squared).
Side Effects/Adverse Events
Subjects were specifically queried regarding the presence of nausea, restlessness/anxiety, sleepiness, and chest discomfort at baseline and at the same 20-min intervals as the VAS scoring. Results are presented in Table 4 . The Table lists the proportions of subjects in the two groups who either responded affirmatively at baseline (prior to study-drug administration), or who reported the index symptom at least once beginning after intervention. The denominator was the number of subjects in each treatment group.
Sleepiness and nausea were most commonly reported. Even prior to study drug administration, both nausea and sleepiness were acknowledged by two-thirds of all subjects. After the study drug was administered, an additional 22% of patients reported new sleepiness. Only one subject developed nausea after treatment. Sleepiness was statistically more common in the group that was to receive haloperidol. There were no other differences between the groups in any of the other side-effect questions asked. In addition to the four specific questions, caregivers were encouraged to report separately any observed adverse events. There were recorded events for four subjects in the haloperidol group ("restless"/"loopy"; "restless legs"; "nausea – given ondansetron"; "difficult to wake"). Two metoclopramide-treated subjects had recorded observations: "jittery, momentarily short of breath during i.v. push"; "symptoms relieved at 40 min but returned."
ECG and QTc Intervals
Subjects were to remain on cardiac monitors throughout their ED stay. QTc intervals were obtained from the printed ECGs. All subjects had unremarkable pretreatment ECGs. Posttreatment cardiograms were performed on 45% of the subjects. Their pre- and posttreatment QTc intervals are presented in Table 5. Mean QTcs were equal and normal in the two groups and did not change after treatment for either group.
No dysrhythmias were reported. The four subjects reporting chest pain were re-evaluated and received repeat ECGs, and subsequently, they were not felt to require further cardiac evaluation. No subject complained of palpitations, had clinically relevant dysrhythmias, or had any cardiac adverse event during treatment.
Follow-Up
Of the 64 enrolled subjects, 43 were reached for a follow-up phone interview. Overall, 90% answered affirmatively when asked if they were happy with the medication they received in the ED. Sixty percent of metoclopramide-treated subjects and 48% of haloperidol-treated subjects reported return of headache symptoms after discharge. Three subjects, all in the metoclopramide group, returned to the ED. In response to questions about other symptoms since ED discharge, sleepiness was the most commonly reported, affecting 40% and 52% of the metoclopramide and haloperidol groups, respectively. The only statistically significant difference in side effects between treatment groups was in reported restlessness, reported in 43% of the haloperidol group, but in only 10% of those receiving metoclopramide. Agitation and nausea were infrequently reported and no subject contacted had vomiting or chest pain (See Table 6).
