Polly E. Bijur

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.

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.

Safety and Efficacy of Rapid Titration Using 1mg Doses of Intravenous Hydromorphone in Emergency Department Patients With Acute Severe Pain: The “1+1” Protocol

STUDY OBJECTIVEnWe evaluate the safety and efficacy of a pain protocol using 1 mg intravenous (IV) hydromorphone followed by an optional dose of 1 mg IV hydromorphone 15 minutes later.nnnMETHODSnProspective interventional study at an urban academic emergency department (ED). One milligram of IV hydromorphone was administered to adults 21 to 64 years of age who had acute severe pain. Fifteen minutes later, patients were asked whether they wanted more pain medication. If they answered yes, they received another 1 mg of IV hydromorphone and were again asked 15 minutes later whether they wanted more pain medication. The primary efficacy outcome was the proportion of patients who had adequate analgesia, defined as declining additional hydromorphone within 1 hour of entering the protocol. The primary safety outcome was incidence of oxygen desaturation less than 95%. Secondary outcomes included numeric rating scale pain scores and adverse events.nnnRESULTSnOf the 223 patients with complete data, 1 mg IV hydromorphone provided adequate analgesia for 77% (95% confidence interval 71% to 82%) within 15 minutes and 96% (95% confidence interval 92% to 98%) within 1 hour of entering the protocol. Eighty-six percent of patients reported pain scores that decreased by 2 or more numeric rating scale units. Five percent experienced transient oxygen desaturation below 95%, which was corrected promptly with oxygen.nnnCONCLUSIONnA rapid titration protocol using IV hydromorphone (1 mg hydromorphone followed by an optional 1 mg 15 minutes later) is efficacious in nonelderly ED patients with acute severe pain. There were no serious adverse events.

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.

Randomized Clinical Trial Comparing a Patient-Driven Titration Protocol of Intravenous Hydromorphone With Traditional Physician-Driven Management of Emergency Department Patients With Acute Severe Pain

STUDY OBJECTIVEnWe test the null hypothesis that the 1+1 hydromorphone patient-driven protocol is clinically and statistically equivalent in safety and efficacy to that of traditional physician-driven administration of opioids for emergency department (ED) treatment of acute severe pain.nnnMETHODSnThis was a prospective randomized clinical trial of nonelderly adults presenting to an urban academic ED with acute pain of sufficient severity to warrant intravenous (IV) opioids in the judgment of the attending physician. Patients randomized to the 1+1 hydromorphone patient-driven protocol received 1 mg IV hydromorphone followed by a second 1-mg dose 15 minutes later if the patient responded affirmatively to the question, Do you want more pain medication? Patients in the physician-driven group received any IV opioid in the dose chosen by the ED attending physician, with any additional analgesia provided at the discretion of that physician. The primary outcome was the difference in improvement in pain between the 2 groups at 60 minutes, as measured by a validated and reproducible numeric rating scale. Secondary outcomes included incidence of oxygen desaturation, hypoventilation, hypotension, bradycardia, nausea, vomiting, pruritus, and use of naloxone.nnnRESULTSnThe mean decrease in numeric rating scale pain scores for the 1+1 hydromorphone patient-driven group was 5.6 versus 4.5 in the physician-driven group. The difference of 1.1 numeric rating scale units (95% confidence interval 0.3 to 1.9) was statistically significant but fell 0.2 numeric rating scale units short of the 1.3 numeric rating scale unit threshold required to attain clinically significant efficacy. Safety profiles were similarly satisfactory in both groups. Ninety-four percent of the 1+1 hydromorphone patient-driven group achieved adequate analgesia (as defined by the patient) within 60 minutes of protocol initiation.nnnCONCLUSIONnThe 1+1 hydromorphone patient-driven protocol is statistically superior and at least as clinically efficacious and safe as traditional physician-driven treatment of ED patients with acute severe pain. More than 9 of 10 patients randomized to the study protocol achieved satisfactory pain control, as defined by the patient, within an hour or less.

Dosing and titration of intravenous opioid analgesics administered to ED patients in acute severe pain

OBJECTIVESnThe objectives were to describe the dose of opioids and incidence of titration for management of acute pain in emergency department patients and, secondarily, to assess the association between change in pain and dose.nnnMETHODSnData from control groups of 2 randomized clinical trials were analyzed. Patients 21 to 64 years with acute pain judged to warrant intravenous (i.v.) opioids were eligible. We calculated the mean weight-based dose of i.v. opioids, distribution of dose, proportion of patients receiving additional i.v. opioids, and 95% confidence intervals. We compared these statistics to 3 recommendations: 0.1 mg/kg morphine, 10 mg morphine, and titration to analgesic effect. We used multiple linear regression to assess the association between change in pain measured on a numerical rating scale and dose.nnnRESULTSnThere were 281 patients with an initial median pain score of 10 (interquartile range: 8, 10). Mean weight-based dose of i.v. opioids was 0.08 mg/kg (0.07, 0.08 mg/kg). A total of 268 patients (95.4% [92.2%, 97.5%]) received less than 10 mg i.v. morphine equivalents; 7 patients (2.5% [1.0%, 5.0%]) received additional opioids. There was a weak association between change in pain in the 15, 30, and 60 minutes after the initial bolus and dose: b = 0.22 (0.07, 0.37), b = 0.17 (0.02, 0.32), and b = 0.12 (-0.03, 0.28), respectively, after adjustment for baseline pain.nnnCONCLUSIONnAnalgesic practice did not conform to recommended doses or regimens. There was only a weak association between change of pain and dose in the range of doses given. These findings suggest that oligoanalgesia continues to be a problem despite improvements over the past 20 years.

A Randomized Trial of Diphenhydramine as Prophylaxis Against Metoclopramide-Induced Akathisia in Nauseated Emergency Department Patients

STUDY OBJECTIVEnAkathisia, an adverse effect observed at times after administration of parenteral metoclopramide, is an unpleasant symptom complex characterized by restlessness and agitation. Some try to limit the development of akathisia by coadministering diphenhydramine when using parenteral metoclopramide. The goal of this investigation is to determine whether concomitant administration of diphenhydramine 25 mg decreased the rate of development of akathisia after administration of 10 mg or 20 mg of intravenous metoclopramide.nnnMETHODSnThis was a randomized, double-blind, factorial design trial. Patients who presented to our emergency department with a primary or secondary chief complaint of nausea were randomized to one of the following 4 groups: (1) metoclopramide 10 mg+diphenhydramine 25 mg; (2) metoclopramide 10 mg+placebo; (3) metoclopramide 20 mg+diphenhydramine 25 mg; (4) metoclopramide 20 mg+placebo. The medications were inserted into a 50-mL bag of normal saline solution and administered as an intravenous drip during 15 minutes. Primary outcome was development of akathisia within 60 minutes of medication administration, as measured by blinded assessors using a short akathisia instrument, or use of rescue medication for treatment of akathisia by blinded clinical staff. Patients were also asked at baseline and 30 minutes later whether they felt restless.nnnRESULTSnTwo hundred eighty-nine patients were randomized and 286 patients were included in the final analysis. Within 1 hour of medication administration, 17 of 143 patients randomized to diphenhydramine (12%; 95% confidence interval [CI] 8% to 18%) and 17 of 143 (12%; 95% CI 8% to 18%) randomized to placebo developed akathisia (95% CI for difference of 0%: -8% to 8%). Thirteen of 143 patients randomized to metoclopramide 10 mg (9%; 95% CI 5% to 15%) and 21 of 143 randomized to metoclopramide 20 mg (15%; 95% CI 10% to 22%) developed akathisia (95% CI for difference of 6%: -2% to 14%). In those administered prophylactic diphenhydramine, odds of akathisia relative to placebo were 1.0 (95% CI 0.5 to 2.0). Odds of akathisia in those administered 20 mg of metoclopramide relative to the 10-mg dose were 1.7 (95% CI 0.8 to 3.6). Among patients who received 20 mg of metoclopramide, subjective restlessness was reported by 7 of 72 (9.7%) patients who received diphenhydramine and 14 of 71 (19.7%) patients who received placebo (95% CI for difference of 10%: -2% to 22%).nnnCONCLUSIONnRoutine prophylaxis with diphenhydramine to prevent akathisia is unwarranted when intravenous metoclopramide is administered over 15 minutes. For patients administered 20 mg of metoclopramide, prophylactic diphenhydramine may decrease subjective restlessness.

Efficacy of patient-controlled analgesia for patients with acute abdominal pain in the emergency department: a randomized trial.

OBJECTIVESnThe objective was to assess the efficacy of patient-controlled analgesia (PCA) in the emergency department (ED) and to compare two PCA dosing regimens.nnnMETHODSnA randomized controlled trial with three treatment arms was performed in an urban ED. A convenience sample of ED patients ages 18 to 65 years with abdominal pain of 7 days or less duration requiring intravenous (IV) opioid analgesia was enrolled between April 2009 and June 2010. All patients received an initial dose of 0.1 mg/kg IV morphine followed by physician-managed analgesia as needed. Patients in the PCA arms also received IV morphine with on-demand doses of 1 or 1.5 mg, with a 6-minute lockout between doses. Pain intensity was rated by patients on an 11-point numeric rating scale (NRS). Satisfaction with pain treatment, desire for the same treatment in the future, and need for additional analgesia were assessed at study end. Adverse events (O(2) sat < 92%, respiratory rate [RR] < 10/min, systolic blood pressure [sBP] < 90 mm Hg, and naloxone use) were counted. One-way analysis of variance was used to test the difference among groups in short-term pain relief, as assessed by mean change in NRS pain intensity from baseline to 30 minutes and pain over the entire 2-hour study period measured by area under the curve (AUC) of NRS pain ratings. A post hoc hierarchical linear model was used to test the observed difference in NRS between the groups between 30 and 120 minutes.nnnRESULTSnA total of 211 patients were enrolled. A sharp, nearly identical decline in mean NRS scores occurred from baseline to 30 minutes in the three groups (p = 0.82). Between 30 and 120 minutes, there was little further decline in the non-PCA NRS scores, while both PCA groups continued to decline (p = 0.004). The net treatment effect over the entire 2 hours was smallest in the non-PCA group and largest in the group receiving 1.5 mg of morphine (p = 0.06). The mean decline in pain from baseline to 120 minutes postbaseline in both PCA groups was 1.4 NRS units (95% confidence interval [CI] = 0.3 to 2.4) greater than the decline in patients treated without PCA. More patients in the PCA arms reported satisfaction, wanting the same pain management in the future, and not wanting further analgesics at 120 minutes than patients who did not receive PCA. There were no clinically or statistically significant differences in any outcomes between the two PCA groups. One PCA patient had a transient oxygen saturation of 88% after the initial bolus only, and one non-PCA patient had a brief drop in sBP to 87 mm Hg.nnnCONCLUSIONSnThis study provides support for efficacy of PCA when applied to the ED setting. Future studies designed to assess implementation of this modality in the context of conditions of actual ED staffing and competing patient demands are warranted.