David Esses

A trial of metoclopramide vs sumatriptan for the emergency department treatment of migraines

Objective: To compare the efficacy of 20 mg of IV metoclopramide, given up to four times over 2 hours as needed for persistent headache, with 6 mg of subcutaneous sumatriptan for the emergency department treatment of migraine headaches. Methods: This was a randomized, double-blind, clinical trial with two intervention arms. The primary endpoint was change in pain intensity as measured by an 11-point pain scale at 2 hours. Secondary endpoints included change in pain intensity at 24 hours and rates of pain-free headache relief at 2 and 24 hours. Results: Two hundred two patients were screened, and 78 of 91 eligible patients were randomized. The two groups had comparable pain scores at baseline. By 2 hours, the change in pain intensity for the metoclopramide group was 7.2 compared with 6.3 for the sumatriptan group (95% CI for difference: −0.2 to 2.2). When compared at 24 hours, the metoclopramide group had improved by 6.1 compared with baseline and the sumatriptan group had improved by 5.0 (95% CI for difference: −0.6 to 2.8). At 2 hours, pain-free rates were 59% in the metoclopramide arm and 35% in the sumatriptan arm (95% CI for difference of 24%: 2 to 46%). The most common side effects at both time points were weakness, dizziness, and drowsiness, which were distributed evenly between the two groups. There were no reports of chest pain within the first 2 hours. The incidence of restlessness, stiffness, and abnormal movements was distributed equally between the two groups. Conclusions: When compared at 2 and 24 hours, aggressive (20 mg dosed up to four times) IV metoclopramide and 6 mg of subcutaneous sumatriptan relieved migraine headache pain comparably. Some secondary endpoints suggest that metoclopramide may be the preferable therapy for migraines presenting to the emergency department.

Failure to Validate the San Francisco Syncope Rule in an Independent Emergency Department Population

STUDY OBJECTIVE We conduct a prospective independent validation of the San Francisco Syncope Rule to identify emergency department (ED) syncope patients with short-term serious outcomes. METHODS This was a prospective observational cohort study of adult patients presenting to a university hospital ED with acute syncope or near syncope. Patients meeting inclusion criteria as defined in the San Francisco Syncope Rule derivation were evaluated for 5 previously derived predictor variables: abnormal ECG result, shortness of breath, hematocrit level less than 30%, triage systolic blood pressure less than 90 mm Hg, and history of congestive heart failure. Hospital admission occurred at the discretion of the emergency physician, independent of the decision rule. Follow-up occurred through contact with the inpatient attending physician for admitted patients and by telephone contact with patients not hospitalized or those hospitalized and discharged before day 7. Predetermined outcome measures as defined by the San Francisco Syncope Rule were death, myocardial infarction, arrhythmia, pulmonary embolism, stroke, subarachnoid hemorrhage, significant hemorrhage, or any condition causing or likely to cause a return ED visit and hospitalization for a related event. RESULTS Complete predictor and follow-up data were available for 713 of 743 (96%) enrolled patients. Sixty-one of 713 (9%) patients met predetermined criteria for serious outcome. Sixteen of 61 (26%; 95% confidence interval [CI] 16% to 39%) patients with a serious outcome were not identified as high risk by the rule. Rule performance to predict serious outcomes was sensitivity 74% (95% CI 61% to 84%), specificity 57% (95% CI 53% to 61%); negative likelihood ratio 0.5 (95% CI 0.3 to 0.7) and positive likelihood ratio 1.7 (95% CI 1.4 to 2.0). CONCLUSION In this independent validation study, sensitivity and negative likelihood ratio of the San Francisco Syncope Rule were substantially lower than reported in the original studies and suggest that the rule has limited generalizability.

Randomized trial of IV valproate vs metoclopramide vs ketorolac for acute migraine

Objective: We compared the efficacy of IV valproate with metoclopramide and with ketorolac in patients presenting to an emergency department (ED) with acute migraine. Methods: This was a double-blind comparative efficacy trial. Patients were randomized to 1,000 mg sodium valproate, 10 mg metoclopramide, or 30 mg ketorolac, each administered as an IV drip over 15 minutes. The primary outcome was improvement in headache by 1 hour, measured on a verbal 0 to 10 scale, at baseline and 60 minutes later. Important secondary outcomes included (1) need for rescue medication in the ED, and (2) sustained headache freedom. Results: Three hundred thirty patients were enrolled over 30 months beginning in October 2010. Baseline characteristics were comparable among the 3 arms. On the primary outcome, patients receiving IV valproate improved by a mean of 2.8 (95% confidence interval [CI]: 2.3, 3.3) on the 0 to 10 scale; those receiving IV metoclopramide improved by 4.7 (95% CI: 4.2, 5.2); and those receiving IV ketorolac improved by 3.9 (95% CI: 3.3, 4.5). On the secondary endpoints, 69% (95% CI: 60%, 78%) of patients receiving valproate required rescue medication, compared with 33% (95% CI: 24%, 42%) of metoclopramide patients and 52% (95% CI: 42%, 63%) of those assigned to ketorolac. Sustained headache freedom was achieved in 4% (95% CI: 0%, 7%) of those randomized to valproate, 11% (95% CI: 5%, 17%) of metoclopramide patients, and 16% (95% CI: 9%, 23%) receiving ketorolac. In the metoclopramide arm, 6% (95% CI: 3%, 12%) of patients reported feeling “very restless” after investigational medication administration. Conclusions: Valproate was less efficacious than either metoclopramide or ketorolac. Metoclopramide demonstrated superiority to ketorolac on several endpoints. Classification of evidence: This study provides Class I evidence that in ED patients with acute migraine, IV valproate is inferior to metoclopramide or ketorolac in improving headache outcomes.

Successful and Safe Implementation of a Trinary Interpretation and Reporting Strategy for V/Q Lung Scintigraphy

For the past 4 decades, ventilation–perfusion (V/Q) scan interpretation for pulmonary embolism (PE) was performed using probability-based assessments, which were neither well-received nor well-understood by many clinicians. Recently, we combined normal, very low probability, and low-probability interpretations in emergency department patients and found a false-negative (FN) rate of 1.2% on follow-up. Afterward, we transitioned to a new trinary interpretative strategy: no PE, PE present, and nondiagnostic. In this series, we compared the outcomes of the traditional and trinary interpretative strategies. Methods: We retrospectively identified all patients undergoing V/Q scans for the 1 year straddling the shift in interpretive strategy, with traditional interpretation being used between September 18, 2008, and March 17, 2009, and trinary interpretation being used between March 18, 2009, and September 17, 2009. A FN study was defined as development of deep vein thrombosis or PE within 3 months after a negative baseline evaluation. Results: The traditional interpretation group included 208 male patients (27%) and 570 female patients (73%), with a mean age (±SD) of 50.9 ± 18.4 years. These interpretations (n = 778) were high probability in 4.9% (38), intermediate probability in 5% (39), low probability in 59.5% (463), very low probability in 17.2% (134), and normal in 13.4% (104). The trinary interpretation group included 181 male patients (27%) and 483 female patients (73%), with a mean age of 50.0 ± 18.5 years. These interpretations (664) were positive in 8.4% (56), negative in 88.1% (585), and nondiagnostic in 3.5% (23). The FN rate was 1.14% (8/701; 7 deep vein thrombosis and 1 PE) for pooled normal, very low probability, and low probability in traditional interpretations versus 1.5% (9/585, 5 deep vein thrombosis and 4 PE) in trinary interpretations (P = 0.63). The individual FN rates for the normal, very low probability, and low-probability groups were 0.0%, 0.75%, and 1.51%, respectively (P = 0.36 for normal vs. low probability). Pediatric subgroup analysis showed 19 traditional interpretations: 5.3% high (1); 0 intermediate; and 94.7% (18) low probability, very low probability, and normal. 20 trinary interpretations were positive in 10% (2), nondiagnostic in 5% (1), and negative in 85% (17), with no FNs using either strategy. Conclusion: A simplified trinary interpretation strategy for V/Q lung scintigraphy provides outcomes similar to traditional probability assessments and facilitates clear communication.

Recurrence of Primary Headache Disorders After Emergency Department Discharge: Frequency and Predictors of Poor Pain and Functional Outcomes

STUDY OBJECTIVE We determine the frequency of moderate or severe headache during the first 24 hours after an emergency department (ED) visit for a primary headache disorder (such as migraine or tension-type headache), determine the burden of headache during the 3 months after the ED visit, and identify predictors of poor pain and functional outcomes after ED discharge for each of these periods. METHODS In this prospective cohort study, we enrolled headache patients during their initial ED visit, interviewed them by using a standardized questionnaire, and followed them by telephone 24 hours and 3 months after ED discharge. Two emergency physicians classified all headaches according to criteria established by the International Headache Society, using a valid questionnaire and a reproducible technique. RESULTS During an 18-month period, we enrolled 309 primary headache disorder patients in the cohort. The most common primary headache diagnoses assigned to patients were migraine, tension-type headache, and unclassifiable recurrent headache disorder. We successfully obtained follow-up in 94% of patients 24 hours after ED discharge and in 94% 3 months after ED discharge. Moderate or severe headache was present within 24 hours of ED discharge in 31% (95% confidence interval [CI] 25% to 38%) of migraine patients, 19% (95% CI 9% to 36%) of tension-type headache patients, and 27% (95% CI 18% to 38%) of the unclassifiable headache patients. Multiple functionally impairing headaches occurred during the 3 months after ED discharge in 37% of migraine patients (95% CI 30% to 44%), 38% of tension-type headache patients (95% CI 23% to 54%), and 26% of the unclassifiable headache patients (95% CI 17% to 37). After multivariate adjustment, independent predictors of poor 24-hour outcomes were severe baseline pain, baseline nausea, screening positive for depression, and longer duration of headache; the independent predictor of poor 3-month outcomes was Medicaid insurance. CONCLUSION Regardless of type of primary headache disorder, ED headache patients frequently experience pain and functional impairment during the hours and months after discharge.

Response to morphine in male and female patients: Analgesia and adverse events

BackgroundThere is little agreement about a differential response of men and women to opioid analgesics. Some experimental and clinical studies have shown that women have a better response to opioids, others have found no difference, and still others have found opioids to be more effective analgesics for men than women. ObjectivesTo assess sex differences in analgesic response to morphine and incidence of adverse events in patients receiving a dose of 0.1 mg intravenous morphine/kg. MethodsSecondary analysis of the control arms of 6 randomized clinical trials that compared 0.1 mg/kg intravenous morphine with other opioids or other doses of morphine in patients aged 21 to 65 with acute pain. The setting was an academic medical center Emergency Department serving primarily Latino and African-American patients. Change in self-reported pain intensity from baseline to 30 minutes postbaseline on a validated and reproducible 11-point numerical rating scale and count of adverse events were the primary outcomes. ResultsThe sample consisted of 211 women and 144 men. The mean change in pain from baseline to 30 minutes postbaseline was 3.7 in women, 3.6 men (difference=0.04; 95% confidence interval: −0.52, 0.60). In women without nausea before administration of morphine, the incidence of adverse events was 18.3% versus 10.7% in men without initial nausea (difference=7.6%; 95% confidence interval: −2.0, 17.2). DiscussionMen and women presenting to the Emergency Department did not have a differential response to a single weight-based dose of morphine for alleviation of acute pain. Women without baseline nausea had more adverse events than men.

A randomized placebo-controlled trial of single-dose IM corticosteroid for radicular low back pain.

Study Design. A randomized, double-blind, placebo-controlled trial of patients with radicular low back pain who present to an emergency department (ED) within 1 week of pain onset. Objective. We hypothesized that a single intramuscular 160 mg dose of methylprednisolone acetate would improve pain and functional outcomes 1 month after ED discharge if the corticosteroid were administered early in disease symptomotology. Summary of Background Data. Parenteral corticosteroids are not recommended for acute, radicular low back pain, though their role in this disease process is ill-defined. To date, this medication class has only been studied in a highly selected group of patients requiring hospitalization. Methods. Adults between the ages of 21 and 50 who presented to an ED with low back pain and a positive straight leg raise test were enrolled. The primary outcome was change in pain intensity on an 11 point numerical rating scale 1 month after ED visit. Secondary outcomes 1 month after ED discharge included analgesic use, functional disability, and adverse medication effects. Results. Six hundred thirty-seven patients were approached for participation, 133 were eligible, and 82 were randomized. Baseline characteristics were comparable between the groups. The primary outcome, a comparison of the mean improvement in pain intensity, favored methylprednisolone by 1.3 (P = 0.10). Some secondary outcomes favored methylprednisolone, such as use of analgesic medication within the previous 24 hours (22% vs. 43%, 95% CI for difference of 20%: 0%–40%) and functional disability (19% vs. 49%, 95% CI for difference of 29%: 9%–49%). Adverse medication effects 1 week after ED discharge were reported by 32% of methylprednisolone and 24% of placebo patients (95% CI for difference of 9%: −12% to 30%). Conclusion. This study was a negative study, though there was a suggestion of benefit of methylprednisolone acetate in a population of young adults with acute radicular low back pain. Further work with a larger sample of patients is needed.

Metoclopramide for Acute Migraine: A Dose-Finding Randomized Clinical Trial

STUDY OBJECTIVE Intravenous metoclopramide is effective as primary therapy for acute migraine, but the optimal dose of this medication is not yet known. The objective of this study is to compare the efficacy and safety of 3 different doses of intravenous metoclopramide for the treatment of acute migraine. METHODS This was a randomized, double-blind, dose-finding study conducted on patients who presented to our emergency department (ED) meeting International Classification of Headache Disorders criteria for migraine without aura. We randomized patients to 10, 20, or 40 mg of intravenous metoclopramide. We coadministered diphenhydramine to all patients to prevent extrapyramidal adverse effects. The primary outcome was improvement in pain on an 11-point numeric rating scale at 1 hour. Secondary outcomes included sustained pain freedom at 48 hours and adverse effects. RESULTS In this study, 356 patients were randomized. Baseline demographics and headache features were comparable among the groups. At 1 hour, those who received 10 mg of intravenous metoclopramide improved by a mean of 4.7 numeric rating scale points (95% confidence interval [CI] 4.2 to 5.2 points); those who received 20 mg improved by 4.9 points (95% CI 4.4 to 5.4 points), and those who received 40 mg improved by 5.3 points (95% CI 4.8 to 5.9 points). Rates of 48-hour sustained pain freedom in the 10-, 20-, and 40-mg groups were 16% (95% CI 10% to 24%), 20% (95% CI 14% to 28%), and 21% (95% CI 15% to 29%), respectively. The most commonly occurring adverse event was drowsiness, which impaired function in 17% (95% CI 13% to 21%) of the overall study population. Akathisia developed in 33 patients. Both drowsiness and akathisia were evenly distributed across the 3 arms of the study. One month later, no patient had developed tardive dyskinesia. CONCLUSION Twenty milligrams or 40 mg of metoclopramide is no better for acute migraine than 10 mg of metoclopramide.

Treating Headache Recurrence After Emergency Department Discharge: A Randomized Controlled Trial of Naproxen Versus Sumatriptan

STUDY OBJECTIVE Multiple parenteral medications are used to treat migraine and other acute primary headaches in the emergency department (ED). Regardless of specific headache diagnosis, no medication eliminates the frequent recurrence of primary headache after ED discharge. It is uncertain which medication primary headache patients should be given on discharge from an ED. The aim of this study is to compare the efficacy of oral sumatriptan with naproxen for treatment of post-ED recurrent primary headache. METHODS This was a randomized, double-blind efficacy trial. We randomized patients to either naproxen 500 mg or sumatriptan 100 mg for headache recurrence after ED discharge. Patients were eligible if they received parenteral therapy for an acute exacerbation of a primary headache in the ED. Patients who met established criteria for migraine without aura were designated a priori as a homogenous subgroup of interest. We followed all patients by telephone 48 hours after ED discharge. The primary endpoint was the between-group difference in change in pain intensity during the 2-hour period after ingestion of either 500 mg naproxen or 100 mg sumatriptan. This difference was measured on a validated 11-point (0 to 10) verbal numeric rating scale (NRS). Satisfaction with the medication and adverse effects were also assessed. Patients who met criteria for migraine without aura were analyzed twice according to a priori design: once as a homogenous subgroup and then again combined with all other primary headaches. RESULTS Of 410 patients randomized, 383 (93%) had outcome data available for analysis. Two hundred eighty (73%; 95% confidence interval [CI] 68% to 77%) reported headache post-ED discharge and 196 (51%; 95% CI 44% to 58%), including 88 with migraine, took the investigational medication provided to them. The naproxen group improved by a mean of 4.3 NRS points, whereas the sumatriptan group improved by 4.1 points (95% CI for difference of 0.2 points: -0.7 to 1.1 points). Findings were virtually identical among the migraine subset (4.3 versus 4.2 NRS points; 95% CI for difference of 0.1 points: -1.3 to 1.5 points). Seventy-one percent (95% CI 62% to 80%) of naproxen patients and 75% (95% CI 66% to 84%) of sumatriptan patients would want to take the same medication the next time. Adverse effect profiles were also comparable. CONCLUSION In this trial, nearly three quarters of patients reported headache recurrence within 48 hours of ED discharge. Naproxen 500 mg and sumatriptan 100 mg taken orally relieve post-ED recurrent primary headache and migraine comparably. Clinicians should be guided by medication costs, contraindications, and a patients previous experience with the medication.

A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for acute migraines.

Background.—Although various classes of medication are used to treat acute migraine in the emergency department (ED), no treatment offers complete pain relief without side effects or recurrence of headache. Consequently, even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine, there remains a need for more effective parenteral therapies. Open‐label studies suggest that the combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide effective relief in a high proportion of migraineurs.