Randomized Study of Metoclopramide Plus Diphenhydramine for Acute Posttraumatic Headache.

OBJECTIVE: To determine whether IV metoclopramide 20 mg + diphenhydramine 25 mg (M + D) was more efficacious than IV placebo for acute moderate or severe posttraumatic headache in the emergency room. METHODS: We conducted this randomized, double-blind, placebo-controlled, parallel-group study in 2 urban emergency departments (EDs). Participants who experienced head trauma and presented to our EDs within 10 days with a headache fulfilling criteria for acute posttraumatic headache were included. We randomized participants in a 1:1 ratio to M + D or placebo. Participants, caregivers, and outcome assessors were blinded to assignment. The primary outcome was improvement in pain on a scale of 0 to 10 between baseline and 1 hour after treatment. RESULTS: This study was completed between August 2017 and March 2020. We screened 414 patients for participation and randomized 160: 81 to M + D and 79 to placebo. Baseline characteristics were comparable between the groups. All enrolled participants provided primary outcome data. Patients receiving placebo reported mean improvement of 3.8 (SD 2.6), while those receiving M + D improved by 5.2 (SD 2.3), for a difference favoring metoclopramide of 1.4 (95% confidence interval [CI] 0.7-2.2, p < 0.01). Adverse events were reported by 35 of 81 (43%) patients who received metoclopramide and 22 of 79 (28%) of patients who received placebo (95% CI 1-30 for difference of 15%, p = 0.04). CONCLUSION: M + D was more efficacious than placebo with regard to relief of posttraumatic headache in the ED. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT03220958. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with acute moderate or severe posttraumatic headache, IV M + D significantly improved pain compared to placebo.

A Randomized, Double-Dummy, Emergency Department-Based Study of Greater Occipital Nerve Block With Bupivacaine vs Intravenous Metoclopramide for Treatment of Migraine.

BACKGROUND: Greater occipital nerve blocks (GONB) are used increasingly to treat acute migraine. OBJECTIVE: We conducted a randomized controlled trial to determine whether GONB was as effective as intravenous metoclopramide for migraine. METHODS: This was a double-dummy, double-blind, parallel-arm, non-inferiority study conducted in 2 emergency departments (EDs). Patients with migraine of moderate or severe intensity were randomized to receive bilateral GONB with each side administered 3 mL of bupivacaine 0.5% or metoclopramide 10 mg IV, the putative standard of care. The primary outcome was improvement in pain on a 0-10 scale between time 0 and 1 hour later. To reject the null hypothesis that metoclopramide would be more efficacious in relieving pain, we required that the lower limit of the 95% CI for the difference in pain improvement between those randomized to GONB vs those randomized to metoclopramide be >-1.3, a validated minimum clinically important difference. Secondary outcomes included sustained headache relief, defined as achieving and maintaining for 48 hours a headache level of mild or none without the use of additional analgesic medication, and the use of rescue medication in the ED. RESULTS: Over a 2.5-year study period, 1358 patients were screened for participation and 99 were randomized, 51 to GONB and 48 to metoclopramide. All of these patients were included in the primary analysis. Patients who received the GONB reported mean improvement of 5.0 (95% CI: 4.1, 5.8) while those who received metoclopramide reported a larger mean improvement of 6.1 (95% CI: 5.2, 6.9). The 95% CI for the between group difference of -1.1 was -2.3, 0.1. Sustained headache relief was reported by 11/51 (22%) GONB and 18/47 (38%) metoclopramide patients (95% CI for rounded difference of 17%: -1, 35%). Of the 51 GONB patients, 17 (33%) required rescue medication in the ED vs 8/48 (17%) metoclopramide patients (95% CI for rounded difference of 17%: 0, 33%). An adverse event was reported by 16/51 (31%) GONB patients and 18/48 (38%) metoclopramide patients (95% CI for (rounded) difference of 6%: -13, 25%). CONCLUSION: GONB with bupivacaine was not as efficacious as IV metoclopramide for the first-line treatment of migraine in the ED.

Ibuprofen Plus Acetaminophen Versus Ibuprofen Alone for Acute Low Back Pain: An Emergency Department-based Randomized Study.

OBJECTIVES: Patients with low back pain (LBP) are often treated with nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs are modestly effective for LBP, but many patients with LBP continue to suffer despite treatment with these medications. We compared pain and functional outcomes 1 week after emergency department (ED) discharge among patients randomized to a 1-week course of ibuprofen plus acetaminophen versus ibuprofen plus placebo. METHODS: This was a randomized, double-blind study conducted in two urban EDs. Patients presenting with acute, nontraumatic, nonradicular LBP of no more than 2 weeks' duration were eligible for enrollment immediately prior to discharge from an ED if they had a score > 5 on the Roland Morris Disability Questionnaire (RMDQ), a 24-item validated instrument, indicating more than minimal functional impairment. All patients were given a standardized 10-minute LBP educational session prior to discharge. The primary outcome was improvement on the RMDQ between ED discharge and 1 week later. One secondary outcome was pain intensity, as measured on a 4-point descriptive scale (severe, moderate, mild, none) at 1 week. RESULTS: Enrollment began in October 2018. A total of 120 patients met selection criteria and were randomized. Baseline demographic characteristics were comparable between the two groups. By 1 week after the ED visit, patients randomized to ibuprofen plus placebo reported a mean (±SD) improvement in the RMDQ of 11.9 (±9.7), while those randomized to ibuprofen plus acetaminophen reported a mean (±SD) improvement of 11.1 (±10.7). The 95% CI for the between-group difference of 0.8 was -3.0 to 4.7. At 1 week, moderate or severe pain was reported by 15 of 53 (28%) patients in the ibuprofen plus placebo group and 16 of 57 (28%) patients in the ibuprofen plus acetaminophen group (95% CI for between-group difference of 0% = -17% to 17%). CONCLUSION: Among ED patients with acute, nontraumatic, nonradicular LBP, adding acetaminophen to ibuprofen does not improve outcomes within 1 week.

A Randomized, Placebo-Controlled Trial of Ibuprofen Plus Metaxalone, Tizanidine, or Baclofen for Acute Low Back Pain.

STUDY OBJECTIVE: Patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and skeletal muscle relaxants. We compare functional outcomes and pain among patients with acute low back pain who were randomized to a 1-week course of ibuprofen plus placebo versus ibuprofen plus 1 of 3 skeletal muscle relaxants: baclofen, metaxalone, and tizanidine. METHODS: This was a randomized, double-blind, parallel-group, 4-arm study conducted in 2 urban emergency departments (EDs). Patients with nonradicular low back pain for less than or equal to 2 weeks were eligible if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a 24-item inventory of functional impairment caused by low back pain. All participants received 21 tablets of ibuprofen 600 mg, to be taken 3 times a day as needed. Additionally, they were randomized to baclofen 10 mg, metaxalone 400 mg, tizanidine 2 mg, or placebo. Participants were instructed to take 1 or 2 of these capsules 3 times a day as needed. All participants received a 10-minute educational session. The primary outcome was improvement on the Roland-Morris Disability Questionnaire between ED discharge and 1week later. Secondary outcomes included pain intensity 1 week after ED discharge (severe, moderate, mild, or none). RESULTS: Three hundred twenty patients were randomized. One week later, the mean Roland-Morris Disability Questionnaire score of patients randomized to placebo improved by 11.1 points (95% confidence interval [CI] 9.0 to 13.3), baclofen by 10.6 points (95% CI 8.6 to 12.7), metaxalone by 10.1 points (95% CI 8.0 to 12.3), and tizanidine by 11.2 points (95% CI 9.2 to 13.2). At 1-week follow-up, 30% of placebo patients (95% CI 21% to 41%) reported moderate to severe low back pain versus 33% of baclofen patients (95% CI 24% to 44%), 37% of metaxalone patients (95% CI 27% to 48%), and 33% of tizanidine patients (95% CI 23% to 44%). CONCLUSION: Adding baclofen, metaxalone, or tizanidine to ibuprofen does not appear to improve functioning or pain any more than placebo plus ibuprofen by 1 week after an ED visit for acute low back pain.

Randomized Trial of Intravenous Lidocaine Versus Hydromorphone for Acute Abdominal Pain in the Emergency Department.

STUDY OBJECTIVE: We compare the efficacy and safety of intravenous lidocaine with that of hydromorphone for the treatment of acute abdominal pain in the emergency department (ED). METHODS: This was a randomized, double-blind, clinical trial conducted in 2 EDs in the Bronx, NY. Adults weighing 60 to 120 kg were randomized to receive 120 mg of intravenous lidocaine or 1 mg of intravenous hydromorphone. Thirty minutes after administration of the first dose of the study drug, participants were asked whether they needed a second dose of the investigational medication to which they were randomized. Patients were also stratified according to clinical suspicion of nephrolithiasis. The primary outcome was improvement in pain scores of 0 to 10 between baseline and 90 minutes. An important secondary outcome was need for "off-protocol" parenteral analgesics, including opioids and nonsteroidal anti-inflammatory drugs. RESULTS: We enrolled 154 patients, of whom 77 received lidocaine and 77 received hydromorphone. By 90 minutes, patients randomized to lidocaine improved by a mean of 3.8 points on the 0-to-10 scale, whereas those randomized to hydromorphone improved by a mean of 5.0 points (mean difference 1.2; 95% confidence interval 0.3 to 2.2). Need for off-protocol "rescue" analgesics occurred for 39 of 77 lidocaine patients (51%) and 20 of 77 hydromorphone patients (26%) (difference 25%; 95% confidence interval 10% to 40%). Adverse events were comparable between groups. Among the subset of 22 patients with nephrolithiasis, lidocaine patients reported a mean improvement of 3.4 points on the pain scale, whereas hydromorphone patients reported a mean improvement of 6.4 points (mean difference 3.0; 95% confidence interval 0.5 to 5.5). CONCLUSION: Intravenous hydromorphone was superior to intravenous lidocaine both for general abdominal pain and a subset of patients with nephrolithiasis. A majority of patients randomly allocated to lidocaine required additional analgesics.

A Randomized Trial of a Long-Acting Depot Corticosteroid Versus Dexamethasone to Prevent Headache Recurrence Among Patients With Acute Migraine Who Are Discharged From an Emergency Department.

STUDY OBJECTIVE: Migraine patients continue to report headache during the days and weeks after emergency department (ED) discharge. Dexamethasone is an evidence-based treatment of acute migraine that decreases the frequency of moderate or severe headache within 72 hours of ED discharge. We hypothesize that intramuscular methylprednisolone acetate, a long-acting steroid that remains biologically active for 14 days, will decrease the number of days with headache during the week after ED discharge by at least 1 day compared with intramuscular dexamethasone. METHODS: We conducted a randomized, blinded clinical trial comparing intravenous metoclopramide at 10 mg+intramuscular dexamethasone at 10 mg with intravenous metoclopramide at 10 mg+intramuscular methylprednisolone acetate at a dose of 160 mg for patients presenting to 2 different EDs with moderate or severe migraine. Outcomes were assessed by telephone with a standardized instrument. The primary outcome was number of days with headache during the week after ED discharge. Secondary outcomes were complete freedom from headache, without the necessity of additional headache medication for the entire week after ED discharge, and medication preference, as determined by asking the patient whether he or she would want to receive the same medication again. RESULTS: One hundred nine patients received dexamethasone and 111 received methylprednisolone acetate. We obtained primary outcome data from 101 dexamethasone patients and 106 methylprednisolone acetate patients. Dexamethasone patients reported 3.0 headache days and methylprednisolone acetate 3.3 headache days (95% confidence interval for rounded mean difference of 0.4 days: -0.4 to 1.1). Of 107 dexamethasone patients with analyzable data, 10 (9%) reported complete freedom from headache at 1 week versus 6 of 110 (5%) methylprednisolone acetate patients (95% confidence interval for difference of 4%: -3% to 11%). In the dexamethasone group, 76 of 101 (75%) patients would want the same medication again versus 75 of 106 (71%) of methylprednisolone acetate patients (95% confidence interval for difference of 4%: -8% to 17%). Other than injection site reactions, which were more common in the methylprednisolone acetate group, there were no substantial differences in frequency of adverse events. CONCLUSION: Methylprednisolone acetate does not decrease the frequency of post-ED discharge headache days compared with dexamethasone. Most migraine patients are likely to continue to experience headache during the week after ED discharge.

Randomized study of IV prochlorperazine plus diphenhydramine vs IV hydromorphone for migraine.

OBJECTIVE: To determine outcomes among patients with migraine in the emergency department (ED) who receive IV hydromorphone vs IV prochlorperazine + diphenhydramine. METHODS: This study was conducted in 2 EDs in New York City. Patients who met international criteria for migraine were eligible for participation if they had not used an opioid within the previous month. Clinicians, participants, investigators, and research personnel were blinded to treatment. Patients were randomized in blocks of 4. Participants received hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg. Diphenhydramine was administered to prevent akathisia, a common side effect of IV prochlorperazine. The primary outcome was sustained headache relief, defined as achieving a headache level of mild or none within 2 hours of medication administration and maintaining that level for 48 hours without the requirement of rescue medication. A planned interim analysis was conducted once 48-hour data were available for 120 patients. RESULTS: The trial was halted by the data monitoring committee after 127 patients had been enrolled. The primary outcome was achieved in the prochlorperazine arm by 37 of 62 (60%) participants and in the hydromorphone arm by 20 of 64 (31%) participants (difference 28%, 95% confidence interval 12-45, number needed to treat 4, 95% confidence interval 2-9). CONCLUSIONS: IV hydromorphone is substantially less effective than IV prochlorperazine for the treatment of acute migraine in the ED and should not be used as first-line therapy. CLINICALTRIALSGOV IDENTIFIER: NCT02389829. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients in the ED with migraine, IV prochlorperazine + diphenhydramine is superior to IV hydromorphone.

Diazepam Is No Better Than Placebo When Added to Naproxen for Acute Low Back Pain.

STUDY OBJECTIVE: Low back pain causes more than 2.5 million visits to US emergency departments (EDs) annually. Low back pain patients are often treated with nonsteroidal anti-inflammatory drugs and benzodiazepines. The former is an evidence-based intervention, whereas the efficacy of the latter has not been established. We compare pain and functional outcomes 1 week and 3 months after ED discharge among patients randomized to a 1-week course of naproxen+diazepam versus naproxen+placebo. METHODS: This was a randomized, double-blind, comparative efficacy clinical trial conducted in an urban health care system. Patients presenting with acute, nontraumatic, nonradicular low back pain of no more than a duration of 2 weeks were eligible for enrollment immediately before discharge from an ED if they had a score greater than 5 on the Roland-Morris Disability Questionnaire, a validated 24-item inventory of functional impairment caused by low back pain. Higher scores on the questionnaire indicate greater functional disability. The primary outcome in the trial was improvement in the score between ED discharge and 1 week later. Secondary outcomes included pain intensity 1 week and 3 months after ED discharge, as measured on a 4-point descriptive scale (severe, moderate, mild, and none). All patients were given 20 tablets of naproxen 500 mg, to be taken twice a day as needed for low back pain. Additionally, patients were randomized to receive either 28 tablets of diazepam 5 mg or identical placebo, to be received as 1 or 2 tablets every 12 hours as needed for low back pain. All patients received a standardized 10-minute low back pain educational session before discharge. Using a between-group mean difference of 5 Roland-Morris Disability Questionnaire points, a previously validated threshold for clinical significance, we calculated the need for at least 100 patients with primary outcome data. RESULTS: Enrollment began in June 2015 and continued for 9 months. Five hundred forty-five patients were screened for eligibility. One hundred fourteen patients met selection criteria and were randomized. Baseline demographic characteristics were not substantially different between the 2 groups. One hundred twelve patients (98%) provided 1-week outcome data. The mean Roland-Morris Disability Questionnaire score of patients randomized to naproxen+diazepam improved by 11 (95% confidence interval [CI] 9 to 13), as did the mean score of patients randomized to naproxen+placebo (11; 95% CI 8 to 13). At 1-week follow-up, 18 of 57 diazepam patients (32%; 95% CI 21% to 45%) reported moderate or severe low back pain versus 12 of 55 placebo patients (22%; 95% CI 13% to 35%). At 3-month follow-up, 6 of 50 diazepam patients (12%; 95% CI 5% to 24%) reported moderate or severe low back pain versus 5 of 53 placebo patients (9%; 95% CI 4% to 21%). Adverse events were reported by 12 of 57 diazepam patients (21%; 95% CI 12% to 33%) and 8 of 55 placebo patients (15%; 95% CI 7% to 26%). CONCLUSION: Among ED patients with acute, nontraumatic, nonradicular low back pain, naproxen+diazepam did not improve functional outcomes or pain compared with naproxen+placebo 1 week and 3 months after ED discharge.