Antimicrobial stewardship and automated pharmacy technology improve antibiotic appropriateness for community-acquired pneumonia.

BACKGROUND: The Centers for Medicare and Medicaid Services' (CMS's) Hospital Inpatient Quality Reporting program includes the initial selection of antibiotics for adult community-acquired pneumonia (CAP) patients as a performance measure. A multidisciplinary team defined opportunities for improving performance in appropriate antibiotic use among CAP patients. The team consisted of personnel from the emergency department (ED), the antimicrobial stewardship program (infectious disease, pharmacy), and performance improvement. DESIGN: Quasi-experimental before-after study. SETTING: A large, urban, multicampus academic medical center. Interventions. Interventions included an algorithm for ED providers identifying appropriate antibiotic selections, development of a CAP kit consisting of appropriate antibiotics and dosing regimens bundled with the treatment algorithm, and preloading an automated ED medication dispensing and management system. A quality improvement methodology ("plan, do, check, act") was used to pilot stewardship interventions at one ED campus and later at a second ED campus. RESULTS: In the pilot ED, appropriate antibiotic selection for CAP improved from 54.9% before the intervention in 2008 to 93.4% after the intervention in 2011 (P = .001). Subsequently, in the second ED appropriate antibiotic regimens for CAP improved from 64.6% before the intervention in 2008 to 91.3% after the intervention in 2011 (P = .004)). The rates of another CMS measure, antibiotic administration within 6 hours, were not statistically different before and after the interventions. In an interrupted time series logistic regression analysis, the intervention was found to be significantly associated with the improved prescribing ([Formula: see text]). DISCUSSION: The combination of interdisciplinary teamwork, antibiotic stewardship, education, and information technology is associated with replicable and sustained prescribing improvements.

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.

A randomized trial of diphenhydramine as prophylaxis against metoclopramide-induced akathisia in nauseated emergency department patients.

STUDY OBJECTIVE: Akathisia, 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. METHODS: This 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. RESULTS: Two 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%). CONCLUSION: Routine 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.

A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine.

STUDY OBJECTIVE: We compare prochlorperazine 10 mg intravenously versus metoclopramide 20 mg intravenously for the emergency department (ED) treatment of acute migraine. METHODS: This was a randomized, double-blind, clinical trial comparing 2 parenteral dopamine antagonists. Both drugs were administered during 15 minutes with 25 mg intravenous diphenhydramine. Pain scores on a numeric rating scale were assessed at baseline, every 30 minutes for 2 hours, and by telephone 24 hours after discharge. The primary endpoint was the between-group difference in change in numeric rating scale from baseline to 1 hour postbaseline. Secondary endpoints included mean differences in change in numeric rating scale at 2 and 24 hours, headache relief, adverse effects, and desire to receive the same treatment for future migraines. RESULTS: Of 152 patients screened, 97 were eligible and 77 were randomized. The mean change in numeric rating scale scores at 1 hour was 5.5 and 5.2 in subjects receiving prochlorperazine and metoclopramide, respectively (difference=0.3; 95% confidence interval [CI] -1.0 to 1.6). Findings were similar at 2 hours and 24 hours. Forty-six percent (18/39) of prochlorperazine and 32% (12/38) of metoclopramide subjects reported adverse events (difference=15%; 95% CI -6% to 36%). Seventy-seven percent (26/34) of prochlorperazine and 73% (27/37) of metoclopramide subjects wanted to receive the same medication in future ED visits (difference=4%; 95% CI -16% to 24%). CONCLUSION: Either prochlorperazine 10 mg intravenously or metoclopramide 20 mg intravenously, combined with diphenhydramine 25 mg intravenously, is an efficacious treatment for ED patients with acute migraine. Three quarters of subjects in both arms would want the same medication for their next migraine.

Parenteral corticosteroids for Emergency Department patients with non-radicular low back pain.

Although not recommended for low back pain, the efficacy of systemic corticosteroids has never been evaluated in a general low back pain population. To test the efficacy of systemic corticosteroids for Emergency Department (ED) patients with low back pain, a randomized, double-blind, placebo-controlled trial of long-acting methylprednisolone was conducted with follow-up assessment 1 month after ED discharge. Patients with non-traumatic low back pain were included if their straight leg raise test was negative. The primary outcome was a comparison of the change in a numerical rating scale (NRS) 1 month after discharge. Of 87 subjects randomized, 86 were successfully followed to the 1-month endpoint. The change in NRS between discharge and 1 month differed between the two groups by 0.6 (95% confidence interval -1.0 to 2.2), a clinically and statistically insignificant difference. Disability, medication use, and healthcare resources utilized were comparable in both groups. Corticosteroids do not seem to benefit patients with acute non-radicular low back pain.

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. OBJECTIVE: To test the hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH, would have a larger reduction in their pain scores than patients given SQ sumatriptan. METHODS: This was an ED-based, randomized, double-blind, "double-dummy" clinical trial comparing 2 parenteral treatments for acute migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores, disability scores, associated symptoms, and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration. The primary outcome was the between-group difference in reduction of pain intensity as measured by a validated numerical rating scale 2 hours after medication administration. This study was designed to detect superiority of TMB/DPH; therefore, a 1-tailed t-test was used. An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached. RESULTS: The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan. Baseline pain scores were comparable between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB (95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was comparable between the groups. No serious or frequent adverse effects were noted in either group. CONCLUSIONS: SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours. However, TMB/DPH was well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24 hours. TMB/DPH might have a role in select populations in which sumatriptan is contraindicated or likely to be ineffective.