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 Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department.

STUDY OBJECTIVE: We compare the efficacy and adverse effects of 5 oral analgesics in emergency department (ED) patients aged 21 to 64 years with acute musculoskeletal pain. METHODS: This was a randomized clinical trial conducted in 2 urban EDs. Patients received 400 mg ibuprofen/1,000 mg acetaminophen, 800 mg ibuprofen/1,000 mg acetaminophen, 30 mg codeine/300 mg acetaminophen, 5 mg hydrocodone/300 mg acetaminophen, or 5 mg oxycodone/325 mg acetaminophen. The primary outcome was change in pain before administration of medication (baseline) to 1 hour postbaseline. A numeric rating scale was used, varying from 0="no pain" to 10="worst imaginable pain." Secondary outcomes included receipt of rescue medication and adverse effects at 1 and 2 hours postbaseline. ANOVA was used to test differences in the primary outcome between treatment groups. RESULTS: Six hundred participants, predominantly men and Latino, were enrolled. Change in pain from baseline to 60 minutes did not differ by treatment (P=.69). The mean change in pain in numeric rating scale units was 400 mg ibuprofen/1,000 mg acetaminophen 3.0 (95% confidence interval [CI] 2.6 to 3.5); 800 mg ibuprofen/1,000 mg acetaminophen 3.0 (95% CI 2.5 to 3.5), 30 mg codeine/300 mg acetaminophen 3.4 (95% CI 2.9 to 3.9), 5 mg hydrocodone/300 mg acetaminophen 3.1 (95% CI 2.7 to 3.5), and 5 mg oxycodone/325 mg acetaminophen 3.3 (95% CI 2.8 to 3.7). Rescue medication was received before 1 hour had elapsed by 2 patients receiving 400 mg ibuprofen/1,000 mg acetaminophen (1.7%), 3 patients receiving 800 mg ibuprofen/1,000 mg acetaminophen (2.5%), zero patients receiving 30 mg codeine/300 mg acetaminophen (0.0%), 3 patients receiving 5 mg hydrocodone/300 mg acetaminophen (2.5%), and zero patients receiving 5 mg oxycodone/325 mg acetaminophen (0.0%) (P=.21). More patients who received opioids were nauseated or vomited compared with those who did not: 6.7% versus 1.7% (5.0% difference; 95% CI 1.7% to 8.2%). The findings at 2 hours were similar. CONCLUSION: No analgesic was more efficacious than others 1 or 2 hours after baseline. There was significantly more nausea and vomiting among patients treated with opioids.

Predicting the Transition to Chronic Pain 6 Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

BACKGROUND: Acute pain can transition to chronic pain, a potentially debilitating illness. OBJECTIVE: We determined how often acute pain transitions to chronic pain among patients in the emergency department (ED) and whether persistent pain 1 week after the ED visit was associated with chronic pain. METHODS: An observational cohort study conducted in two EDs. We included adults with acute pain (≤10 days) if an oral opioid was prescribed. Exclusion criteria were recent opioid use and use of any analgesics regularly prior to onset of the pain. Research associates interviewed patients during the ED visit and 1 week and 6 months later. The primary outcome, chronic pain, was defined as pain on > 50% of days since ED discharge. We constructed logistic regression models to evaluate the association between persistent pain 1 week after an ED visit and chronic pain, while adjusting for demographic and treatment variables. RESULTS: During a 9-month period, we approached 733 patients for participation and enrolled 484; 450 of 484 (93%) provided 1-week outcomes data and 410 of 484 (85%) provided 6-month outcomes data. One week after the ED visit, 348 of 453 (77%; 95% confidence interval [CI] 73-80%) patients reported pain in the affected area. New-onset chronic pain at 6 months was reported by 110 of 408 (27%; 95% CI 23-31%) patients. Presence of pain 1 week after ED visit was associated with chronic pain (odds ratio 3.6; 95% CI 1.6-8.5). CONCLUSIONS: About one-quarter of ED patients with acute pain transition to chronic pain within 6 months. Persistence of pain 1 week after the ED visit can identify patients at risk of transition.

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.

Randomized Clinical Trial of Intravenous (IV) Acetaminophen as an Adjunct to IV Hydromorphone for Acute Severe Pain in Emergency Department Patients.

BACKGROUND: A fundamental challenge for emergency department (ED) clinicians is to relieve severe, acute pain while simultaneously avoiding adverse events associated with opioid analgesics. Because there is evidence that intravenous (IV) acetaminophen is an effective adjuvant analgesic in postoperative settings, we examined whether it also has a role in the ED. METHODS: This was a two-arm, double-blind randomized clinical trial. All patients received 1 mg of IV hydromorphone. Patients were then randomized to receive 1 g of IV acetaminophen or placebo. The primary outcome was the between-group difference in change in pain from baseline (before treatment) to 60 minutes after administration of study drugs, measured on an 11-point numeric rating scale (NRS). RESULTS: Of 828 patients screened, 162 were enrolled and 159 had the primary outcome. Patients allocated to acetaminophen + hydromorphone had a mean decline in pain from baseline to 60 minutes of 6.2 NRS units; those receiving placebo + hydromorphone had a mean decline of 5.4, a difference of 0.8 NRS units (95% confidence interval [CI] = -0.01 to 1.8). Two patients in each group received additional analgesics in the first 60 minutes of the study. At 120 minutes the NRS pain difference was 0.6 (95% CI = -0.4 to 1.6). A total of 26.9% of patients who received acetaminophen wanted more analgesia versus 37.7% of those given placebo (difference = -10.8%, 95% CI = -24.3% to 4.4%). The incidence of adverse effects was similar in both groups. CONCLUSIONS: The addition of 1 g of IV acetaminophen to 1 mg of IV hydromorphone provided neither clinically meaningful nor statistically superior analgesia than hydromorphone alone.

Opioid Use During the Six Months After an Emergency Department Visit for Acute Pain: A Prospective Cohort Study.

STUDY OBJECTIVE: Despite the frequent use of opioids to treat acute pain, the long-term risks and analgesic benefits of an opioid prescription for an individual emergency department (ED) patient with acute pain are still poorly understood and inadequately quantified. Our objective was to determine the frequency of recurrent or persistent opioid use during the 6 months after the ED visit METHODS: This was a prospective, observational cohort study of opioid-naive patients presenting to 2 EDs for acute pain who were prescribed an opioid at discharge. Patients were followed by telephone 6 months after the ED visit. Additionally, we reviewed the statewide prescription monitoring program database. Outcomes included frequency of recurrent and persistent opioid use and frequency of persistent moderate or severe pain 6 months after the ED visit. Persistent opioid use was defined as filling greater than or equal to 6 prescriptions during the 6-month study period. RESULTS: During 9 months beginning in November 2017, 733 patients were approached for participation. Four hundred eighty-four met inclusion criteria and consented to participate. Four hundred ten patients (85%) provided 6-month telephone data. The prescription monitoring database was reviewed for all 484 patients (100%). Most patients (317/484, 66%; 95% confidence interval 61% to 70%) filled only the initial prescription they received in the ED. One in 5 patients (102/484, 21%; 95% confidence interval 18% to 25%) filled at least 2 prescriptions within the 6-month period. Five patients (1%; 95% confidence interval 0% to 2%) met criteria for persistent opioid use. Of these 5 patients, all but 1 reported moderate or severe pain in the affected body part 6 months later. CONCLUSION: Although 1 in 5 opioid-naive ED patients who received an opioid prescription for acute pain on ED discharge filled at least 2 opioid prescriptions in 6 months, only 1% had persistent opioid use. These patients with persistent opioid use were likely to report moderate or severe pain 6 months after the ED visit.

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.

Randomized Clinical Trial of Intravenous Acetaminophen as an Analgesic Adjunct for Older Adults With Acute Severe Pain.

OBJECTIVES: Older adults are at risk for undertreatment of pain. We examined intravenous (IV) acetaminophen as an analgesic adjunct to IV opioids in the care of older emergency department (ED) patients with acute severe pain. METHODS: This was a randomized clinical trial conducted in two EDs in the Bronx, New York. Eligible adults aged 65 years and older with acute severe pain were randomized to 0.5 mg of IV hydromorphone and 1 g of IV acetaminophen or 0.5 mg of IV hydromorphone and 100 mL of normal saline placebo. The primary outcome was the between group difference in improvement of numerical rating scale (NRS) pain scores at 60 minutes. Secondary outcomes were the between-group differences in the proportion of patients who chose to forgo additional pain medications at 60 minutes; the proportion who developed side effects; the proportion who required rescue analgesia; and between-group differences in NRS pain scores at 5, 15, 30, and 45 minutes. RESULTS: Eighty-one patients were allocated to each arm. Eighty patients in the IV acetaminophen arm and 79 patients in the placebo arm had sufficient data for analysis. At 60 minutes, patients in the hydromorphone + IV acetaminophen group improved by 5.7 NRS units while those in the hydromorphone + placebo group improved by 5.2 NRS units, for a difference of 0.6 NRS units (95% confidence interval [CI] = -0.4 to 1.5). A total of 28.7% of patients in the hydromorphone + IV acetaminophen group wanted more analgesia at 60 minutes versus 29.1% in the hydromorphone + placebo group, for a difference of -0.4% (95% CI = -14.3% to 13.5%). These differences were neither clinically nor statistically significant. Safety profiles were similar in both groups. CONCLUSION: In this randomized clinical trial, the addition of IV acetaminophen to IV hydromorphone as an adjunctive analgesic for acute, severe, pain in older adults provided neither clinically nor statistically superior pain relief when compared to hydromorphone alone within the first hour of treatment.

Randomized Controlled Trial of Intravenous Acetaminophen Versus Intravenous Hydromorphone for the Treatment of Acute Pain in the Emergency Department.

STUDY OBJECTIVE: As clinicians look to nonnarcotic analgesics in the emergency department (ED), it is essential to understand the effectiveness and adverse effects of nonopioid medications in comparison with existing opioid treatments. Studies of intravenous acetaminophen for acute pain in the ED demonstrate mixed results and suffer from small sample sizes and methodological limitations. This study compares intravenous hydromorphone with intravenous acetaminophen in adult ED patients presenting with acute pain. METHODS: This was a prospective, randomized, clinical trial comparing 1 g intravenous acetaminophen with 1 mg intravenous hydromorphone for treatment of adults with severe, acute pain in the ED. The primary outcome was between-group difference in change in numeric rating scale from baseline to 60 minutes postadministration of study medication. Secondary outcomes included the difference in proportion of patients in each group who declined additional analgesia at 60 minutes, received additional medication before 60 minutes, and developed nausea, vomiting, or pruritus. RESULTS: Of 220 subjects randomized, 103 patients in each arm had sufficient data for analysis. At 60 minutes, the mean decrease in numeric rating scale pain score was 5.3 in the hydromorphone arm and 3.3 in the acetaminophen arm, a difference of 2.0 (95% confidence interval [CI] 1.2 to 2.7) favoring hydromorphone. A greater proportion of patients in the hydromorphone arm also declined additional analgesia at 60 minutes (65% versus 44%; difference 21%; (95% CI 8% to 35%). There was no difference in the proportion of patients receiving rescue analgesia before 60 minutes. Significantly more subjects in the hydromorphone group developed nausea (19% versus 3%; difference 16%; 95% CI 4% to 28%) and vomiting (14% versus 3%; difference 11%; 95% CI 0% to 23%). CONCLUSION: Although both 1 mg intravenous hydromorphone and 1 g intravenous acetaminophen provided clinically meaningful reductions in pain scores, treatment with hydromorphone provided both clinically and statistically greater analgesia than acetaminophen, at the cost of a higher incidence of nausea and vomiting.

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.

Helpful Only When Elevated: Initial Serum Lactate in Stable Emergency Department Patients with Sepsis Is Specific, but Not Sensitive for Future Deterioration.

BACKGROUND: Early emergency department (ED) identification of septic patients at risk of deterioration is critical. Lactate is associated with 28-day mortality in admitted patients, but little evidence exists on its use in predicting short-term deterioration. OBJECTIVE: Our aim was to determine the role of initial serum lactate for prediction of short-term deterioration in stable ED patients with suspected sepsis. METHODS: We conducted a prospective cohort study of adult ED sepsis patients. Venous lactate was obtained within 2 h of ED arrival. Main outcome was subsequent deterioration (defined as any of the following: death, intensive care admission > 24 h, intubation, vasoactive medications for > 1 h, or noninvasive positive pressure ventilation for > 1 h) within 72 h. Patients meeting any endpoint within 1 h of arrival were excluded. RESULTS: Nine hundred and eighty-five patients were enrolled, of whom 84 (8.5%) met the primary outcome of deterioration. Initial lactate ≥ 4.0 mmol/L had a specificity of 97% (95% confidence interval [CI] 94-100%), but a sensitivity of 27% (95% CI 18-37%) for predicting deterioration, with positive and negative likelihood ratios of 10.7 (95% CI 6.3-18.3) and 0.8 (95% CI 0.7-0.9), respectively. A lower threshold of lactate (≥2.0 mmol/L) had a sensitivity of 67% (95% CI 55-76%) and specificity of 66% (95% CI 63-69%), with corresponding positive and negative likelihood ratios of 2.0 (95% CI 1.7-2.3) and 0.5 (95% CI 0.4-0.7). CONCLUSIONS: High ED lactate is predictive of subsequent deterioration from sepsis within 72 h, and may be useful in determining disposition, but low lactate is not effective in screening stable patients at risk of deterioration.

Use of the low-frequency/high-frequency ratio of heart rate variability to predict short-term deterioration in emergency department patients with sepsis.

OBJECTIVE: To examine the ability of the low-frequency/high-frequency (LF/HF) ratio of heart rate variability (HRV) analysis to identify patients with sepsis at risk of early deterioration. METHODS: This is a prospective observational cohort study of patients with sepsis presenting to the Montefiore Medical Center ED from December 2014 through September 2015. On presentation, a single ECG Holter recording was obtained and analysed to obtain the LF/HF ratio of HRV. Initial Sequential Organ Failure Assessment (SOFA) scores were computed. Patients were followed for 72 hours to identify those with early deterioration. RESULTS: 466 patients presenting to the ED with sepsis were analysed. Thirty-two (7%) reached at least one endpoint within 72 hours. An LF/HF ratio <1 had a sensitivity and specificity of 34% (95% CI (19% to 53%)) and 82% (95% CI (78% to 85%)), respectively, with positive and negative likelihood ratios of 1.9 (95% CI (1.1 to 3.2)) and 0.8 (95% CI (0.6 to 1.0)). An initial SOFA score ≥3 had a sensitivity and specificity of 38% (95% CI (22% to 56%)) and 92% (95% CI (89% to 95%)), with positive and negative likelihood ratios of 4.9 (95% CI (2.8 to 8.6)) and 0.7 (95% CI (0.5 to 0.9)). The composite measure of HRV+SOFA had improved sensitivity (56%, 95% CI (38% to 73%)) but at the expense of specificity (77%, 95% CI (72% to 80%)), with positive and negative likelihood ratios of 2.4 (95% CI (1.7 to 3.4)) and 0.6 (95% CI (0.4 to 0.9)). Receiver operating characteristic analysis did not identify a superior alternate threshold for the LF/HF ratio. Kaplan-Meier survival functions differed significantly (p=0.02) between low (<1) and high (≥1) LF/HF groups. CONCLUSIONS: While we found a statistically significant relationship between HRV, SOFA and HRV+SOFA, and early deterioration, none reliably functioned as a clinical predictive tool. More complex multivariable models will likely be required to construct models with clinical utility.

A Randomized, Double-Blind, Placebo-Controlled Trial of Naproxen With or Without Orphenadrine or Methocarbamol for Acute Low Back Pain.

STUDY OBJECTIVE: In US emergency departments (EDs), patients with low back pain are often treated with nonsteroidal anti-inflammatory drugs and muscle relaxants. We compare functional outcomes among patients randomized to a 1-week course of naproxen+placebo versus naproxen+orphenadrine or naproxen+methocarbamol. METHODS: This was a randomized, double-blind, comparative effectiveness trial conducted in 2 urban EDs. Patients presenting with acute, nontraumatic, nonradicular low back pain were enrolled. The primary outcome was improvement on the Roland-Morris Disability Questionnaire (RMDQ) between ED discharge and 1 week later. All patients were given 14 tablets of naproxen 500 mg, to be used twice a day, as needed for low back pain. Additionally, patients were randomized to receive a 1-week supply of orphenadrine 100 mg, to be used twice a day as needed, methocarbamol 750 mg, to be used as 1 or 2 tablets 3 times per day as needed, or placebo. All patients received a standardized 10-minute low back pain educational session before discharge. RESULTS: Two hundred forty patients were randomized. Baseline demographic characteristics were comparable. The mean RMDQ score of patients randomized to naproxen+placebo improved by 10.9 points (95% confidence interval [CI] 8.9 to 12.9). The mean RMDQ score of patients randomized to naproxen+orphenadrine improved by 9.4 points (95% CI 7.4 to 11.5). The mean RMDQ score of patients randomized to naproxen+methocarbamol improved by 8.1 points (95% CI 6.1 to 10.1). None of the between-group differences surpassed our threshold for clinical significance. Adverse events were reported by 17% (95% CI 10% to 28%) of placebo patients, 9% (95% CI 4% to 19%) of orphenadrine patients, and 19% (95% CI 11% to 29%) of methocarbamol patients. CONCLUSION: Among ED patients with acute, nontraumatic, nonradicular low back pain, combining naproxen with either orphenadrine or methocarbamol did not improve functional outcomes compared with naproxen+placebo.

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.

Comparative Effectiveness of Patient-Controlled Analgesia for Treating Acute Pain in the Emergency Department.

STUDY OBJECTIVE: We assess the effectiveness of patient-controlled analgesia in the emergency department (ED). We hypothesized that decline in pain intensity from 30 to 120 minutes after initial intravenous opioid administration is greater in patients receiving morphine by patient-controlled analgesia compared with usual care and would differ by a clinically significant amount. METHOD: This was a pragmatic randomized controlled trial of patient-controlled analgesia and usual care (opioid and dose at physician's discretion) in 4 EDs. Entry criteria included age 18 to 65 years and acute pain requiring intravenous opioids. The primary outcome was decline in numeric rating scale pain score 30 to 120 minutes postbaseline. Secondary outcomes included satisfaction, time to analgesia, adverse events, and patient-controlled analgesia pump-related problems. We used a mixed-effects linear model to compare rate of decline in pain (slope) between groups. A clinically significant difference between groups was defined as a difference in slopes equivalent to 1.3 numeric rating scale units. RESULTS: Six hundred thirty-six patients were enrolled. The rate of decline in pain from 30 to 120 minutes was greater for patients receiving patient-controlled analgesia than usual care (difference=1.0 numeric rating scale unit; 95% confidence interval [CI] 0.6 to 1.5; P<.001) but did not reach the threshold for clinical significance. More patients receiving patient-controlled analgesia were satisfied with pain management (difference=9.3%; 95% CI 3.3% to 15.1%). Median time to initial analgesia was 15 minutes longer for patient-controlled analgesia than usual care (95% CI 11.4 to 18.6 minutes). There were 7 adverse events in the patient-controlled analgesia group and 1 in the usual care group (difference=2.0%; 95% CI 0.04% to 3.9%), and 11 pump-programming errors. CONCLUSION: The findings of this study do not favor patient-controlled analgesia over usual ED care for acute pain management.