Analgesic Efficacy of Oral Aspirin/Ketamine Combination for Management of Acute Musculoskeletal Pain in the Emergency Department - A Proof of Concept Pilot Study.

BACKGROUND: Musculoskeletal pain (MSK) affects one out of three adults and is the most common source of significant long-term pain, physical disability, and under-treatment in the emergency department (ED). OBJECTIVE: We aimed to assess the analgesic efficacy of a combination of oral VTS-Aspirin® (Vitalis Analgesics, New York, NY) and ketamine in managing acute MSK pain in adult ED patients. METHODS: This was a prospective, proof-of-concept, single-arm, pilot study evaluating the analgesic efficacy of a single dose of oral combination of VTS-Aspirin and ketamine in adult ED patients with acute moderate-to-severe MSK pain. The primary outcome included the difference in pain scores on an 11-point numeric pain rating scale at 60 min. Secondary outcomes included the need for rescue analgesia, the occurrence of adverse events at 60 min, and a change in pain scores at 120 min. RESULTS: We enrolled 25 subjects in the study. The mean baseline pain score was 8.6 and the mean pain score at 60 min decreased to 4.8. The oral ketamine dose ranged from 24 mg to 50 mg, with a mean dose of 37.8 mg. No clinically concerning changes in vital signs were noted. No serious adverse events occurred in any of the subjects. Majority of adverse effects were transient and weak in intensity. CONCLUSION: We demonstrated that administration of an oral combination of VTS-Aspirin and ketamine to adult ED patients with acute MSK pain resulted in clinically significant pain relief in 80% of enrolled subjects.

Take-Pause: Efficacy of mindfulness-based virtual reality as an intervention in the pediatric emergency department.

BACKGROUND: Emergency department (ED) visits are known to be anxiety-ridden and stress-provoking experiences especially in the pediatric population. Distraction techniques have been used as a means to reduce anxiety and stress thereby facilitating care in the ED and making the visit less unpleasant. Our study aimed to evaluate the effectiveness of an active and immersive distraction technique, using a mindfulness-based virtual reality (VR) program (Take-Pause), to alleviate anxiety in pediatric ED patients. METHODS: A prospective, randomized, single-blinded study, evaluating ED patients aged 13-17 years with a chief complaint of acute pain was conducted. Patients were randomized either to the active distraction intervention (VR group), utilizing the VR headset for 5 min, or to the passive distraction intervention (iPad group), playing on an iPad for 5 min. The primary outcome was a difference in the change in anxiety scores on the Spielberger State-Trait Anxiety Inventory between the two groups. Secondary outcomes included a difference in pain scores, respiratory rate, and heart rate between the groups. RESULTS: A total of 110 subjects were enrolled. At 15 min, the mean anxiety score for the VR group improved by 10 points versus 6 points in the iPad group (p < 0.001; 95% confidence interval = 0.44 to 7.6). There was no statistical significance in the reduction of pain scores (p = 0.953) and respiratory rates (p = 0.776) between the groups. Patients enrolled in both groups did not experience any adverse effects. CONCLUSION: Take-Pause, offering an active and immersive distraction technique, is more effective than a passive distraction approach to lower anxiety levels in adolescent ED patients.

Comparison of Nebulized Ketamine at Three Different Dosing Regimens for Treating Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind Clinical Trial.

STUDY OBJECTIVE: We aimed to assess and compare the analgesic efficacies and adverse effects of ketamine administered through a breath-actuated nebulizer at 3 different dosing regimens for emergency department patients presenting with acute and chronic painful conditions. METHODS: This was a prospective, randomized, double-blinded trial comparing 3 doses of nebulized ketamine (0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg) administered through breath-actuated nebulizer in adult emergency department patients aged 18 years and older with moderate to severe acute and chronic pain. The primary outcome included the difference in pain scores on an 11-point numeric rating scale between all 3 groups at 30 minutes. Secondary outcomes included the need for rescue analgesia (additional doses of nebulized ketamine or intravenous morphine) and adverse events in each group at 30 and 60 minutes. RESULTS: We enrolled 120 subjects (40 per group). The difference in mean pain scores at 30 minutes between the 0.75 mg/kg and 1 mg/kg groups was 0.25 (95% confidence interval [CI] 1.28 to 1.78); between the 1 mg/kg and 1.5 mg/kg groups was -0.225 (95% CI -1.76 to 1.31); and between the 0.75 mg/kg and 1.5 mg/kg groups was 0.025 (95% CI -1.51 to 1.56). No clinically concerning changes in vital signs occurred. No serious adverse events occurred in any of the groups. CONCLUSION: We found no difference between all 3 doses of ketamine administered through breath-actuated nebulizer for short-term treatment of moderate to severe pain in the emergency department.

Analgesic efficacy of morphine sulfate immediate release vs. oxycodone/acetaminophen for acute pain in the emergency department.

OBJECTIVE: Previous research demonstrated that administration of Morphine Sulfate Immediate Release (MSIR) results in similar analgesic efficacy to Oxycodone but with significantly lesser degrees of euphoria and reward. The purpose of this study sit to investigate if MSIR combined with Acetaminophen can serve as an opioid analgesic alternative to Oxycodone combined with acetaminophen (Percocet) for acute pain in the Emergency Department (ED). METHODS: A prospective, randomized, double-blind trial of ED patients aged 18 to 64 years presenting with moderate to severe acute pain as defined by an 11-point numeric rating scale (NRS) with an initial score of ≥5 (0 = no pain and 10 = very severe pain). Patients were randomized to receive either 15 mg MSIR combined with 650 mg of Acetaminophen or 10 mg Oxycodone combined with 650 mg Acetaminophen. Patients were assessed at baseline, 30, 45 and 60 min. The primary outcome was reduction in pain at 60 min. Secondary outcomes include drug likeability and adverse events. RESULTS: 80 patients were enrolled in the study (40 per group). Demographic characteristics were similar between the groups (P > 0.05). Mean NRS pain scores at baseline were 8.44 for the MSIR group and 8.53 for the Percocet group (P = 0.788). Mean pain scores decreased over time but remained similar between the groups: 30 min (6.03 vs. 6.43; P = 0.453), 45 min (5.31 vs. 5.48; P = 0.779), and 60 min (4.22 vs. 4.87; P = 0.346). Reduction in mean NRS pain scores were statistically significant from baseline to 30, 45 and 60 min within each group (P < 0.0001 at each time point for both groups). The largest NRS mean difference was from baseline to 60 min: 4.2 (95% CI: 3.43 to 5.01) for MSIR group and 3.61 (95% CI: 2.79 to 4.43) for Percocet group. No clinically significant changes or any serious adverse events were observed in either group. CONCLUSION: MSIR provides similar analgesic efficacy as Percocet for short-term pain relief in the ED, similar rates of nausea/vomiting, and lower rates of likeability of the drug.

Comparison of Oral Ibuprofen and Acetaminophen with Either Analgesic Alone for Pediatric Emergency Department Patients with Acute Pain.

BACKGROUND: Ibuprofen (Motrin; Johnson & Johnson) and acetaminophen (APAP, paracetamol) are the most commonly used analgesics in the pediatric emergency department (ED) for managing a variety of acute traumatic and nontraumatic painful conditions. The multimodal pain management of using a combination of ibuprofen plus acetaminophen has the potential to result in greater analgesia. OBJECTIVE: We compared the analgesic efficacy of a combination of oral ibuprofen plus acetaminophen with either analgesic alone for pediatric ED patients with acute pain. METHODS: We performed a randomized, double-blind superiority trial assessing and comparing the analgesic efficacy of a combination of oral ibuprofen (10 mg/kg dose) plus acetaminophen (15 mg/kg per dose) to either analgesic alone for the treatment of acute traumatic and nontraumatic pain in the pediatric ED. Primary outcomes included a difference in pain scores among the three groups at 60 min. RESULTS: We enrolled 90 patients (30 per group). The difference in mean pain scores at 60 min between acetaminophen and combination groups was 0.30 (95% confidence interval [CI] -0.84 to 1.83); between ibuprofen and combination groups was -0.33 (95% CI -1.47 to 0.80); and between acetaminophen and ibuprofen groups was 0.63 (95% CI -0.54 to 1.81). Reductions in pain scores from baseline to 60 min were similar for all patients in each of the three groups. No adverse events occurred in any group. CONCLUSIONS: We found similar analgesic efficacy of oral ibuprofen and acetaminophen in comparison with each analgesic alone for short-term treatment of acute pain in the pediatric ED, but the trial was underpowered to demonstrate the analgesic superiority of the combination of oral ibuprofen plus acetaminophen in comparison with each analgesic alone.

Administration of Nebulized Ketamine for Managing Acute Pain in the Emergency Department: A Case Series.

Ketamine administration in sub-dissociative doses in the emergency department (ED) results in effective pain relief in patients with acute traumatic and non-traumatic pain, chronic pain, and opioid-tolerant pain. This case series describes five adult ED patients who received nebulized ketamine for predominantly acute traumatic pain. Three patients received nebulized ketamine at 1.5 milligrams per kilogram (mg/kg) dose, one patient at 0.75 mg/kg, and one patient at 1 mg/kg. All five patients experienced a decrease in pain from the baseline up to 120 minutes. The inhalation route of ketamine delivery via breath-actuated nebulizer may have utility for managing pain in the ED.

Comparison of intravenous lidocaine/ketorolac combination to either analgesic alone for suspected renal colic pain in the ED.

STUDY OBJECTIVE: To compare analgesic efficacy and safety of intravenous lidocaine and ketorolac combination to each analgesic alone for ED patients with suspected renal colic. METHODS: We conducted a randomized, double-blind trial comparing analgesic efficacy of a combination of intravenous lidocaine (1.5 mg/kg) and ketorolac (30 mg), to ketorolac (30 mg), and to lidocaine (1.5 mg/kg) in patients aged 18-64 presenting to the ED with suspected renal colic. Primary outcome included difference in pain scores between the groups at 30 min. Secondary outcomes included a comparative reduction in pain scores in each group from baseline to 30 and 60 min as well as rates of adverse events and need for rescue analgesia at 30 and 60 min. RESULTS: We enrolled 150 subjects (50 per group). The difference in mean pain scores at 30 min between Lidocaine and Lidocaine/Ketorolac groups was -2.89 (95% CI: -4.39 to -1.39); between Ketorolac and Lidocaine/Ketorolac group was -0.92 (95% CI: -2.44 to 0.61); and between Ketorolac and Lidocaine was -1.98 (95% CI: -3.69 to -0.27). A comparative percentage of subjects in each group required rescue analgesia at 30 and 60 min. No clinically concerning changes in vital signs were observed. No serious adverse events occurred in either group. Commonly reported adverse effects were dizziness, nausea, and headache. CONCLUSION: The administration of intravenous lidocaine/ketorolac combination to ED patients with suspected renal colic results in better analgesia in comparison to lidocaine alone but provides no analgesic advantages over ketorolac alone. Clinicaltrials.gov Registration: NCT02902770.

Comparison of Oral Ibuprofen at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial.

STUDY OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used extensively for the management of acute pain, with ibuprofen being one of the most frequently used oral analgesics in the emergency department (ED). We compare the analgesic efficacy of oral ibuprofen at 3 different doses for adult ED patients with acute pain. METHODS: This was a randomized, double-blind trial comparing analgesic efficacy of 3 doses of oral ibuprofen (400, 600, and 800 mg) in adult ED patients with acute painful conditions. Primary outcome included difference in pain scores between the 3 groups at 60 minutes. RESULTS: We enrolled 225 subjects (75 per group). The difference in mean pain scores at 60 minutes between the 400- and 600-mg groups was -0.14 (95% confidence interval [CI] -0.67 to 0.39); between the 400- and 800-mg groups, 0.14 (95% CI -0.65 to 0.37); and between the 600- and 800-mg groups, 0.00 (95% CI -0.47 to 0.47). Reductions in pain scores from baseline to 60 minutes were similar for all subjects in each of the 3 groups. No adverse events occurred in any group. CONCLUSION: Oral ibuprofen administered at doses of 400, 600, and 800 mg has similar analgesic efficacy for short-term pain relief in adult patients presenting to the ED with acute pain.

Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department: A randomized controlled trial.

STUDY OBJECTIVE: We compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine (SDK) versus morphine in geriatric Emergency Department (ED) patients. METHODS: This was a prospective, randomized, double-blind trial evaluating ED patients aged 65 and older experiencing moderate to severe acute abdominal, flank, musculoskeletal, or malignant pain. Patients were randomized to receive SDK at 0.3 mg/kg or morphine at 0.1 mg/kg by short intravenous infusion over 15 min. Evaluations occurred at 15, 30, 60, 90, and 120 min. Primary outcome was reduction in pain at 30 min. Secondary outcomes included overall rates of adverse effects and incidence of rescue analgesia. RESULTS: Thirty patients per group were enrolled in the study. The primary change in mean pain scores was not significantly different in the ketamine and morphine groups: 9.0 versus 8.4 at baseline (mean difference 0.6; 95% CI -0.30 to 1.43) and 4.2 versus 4.4 at 30 min (mean difference -0.2; 95% CI -1.93 to1.46). Patients in the SDK group reported higher rates of psychoperceptual adverse effects at 15, 30, and 60 min post drug administration. Two patients in the ketamine group and one in the morphine group experienced brief desaturation episodes. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. CONCLUSION: SDK administered at 0.3 mg/kg over 15 min provides analgesic efficacy comparable to morphine for short-term treatment of acute pain in the geriatric ED patients but results in higher rates of psychoperceptual adverse effects. ClinicalTrials.gov Registration #: NCT02673372.

Analgesic Administration for Patients with Renal Colic in the Emergency Department Before and After Implementation of an Opioid Reduction Initiative.

INTRODUCTION: We aimed to evaluate the patterns of analgesic prescribing for emergency department (ED) patients suffering from pain of renal colic before, during, and after implementation of an opioid reduction initiative. We hypothesized that this initiative based on the concept of channels/enzymes/receptors-targeted analgesia would result in overall decrease in opioid utilization in the ED and at discharge. METHODS: We performed a retrospective analysis of ED electronic medical record of patients presenting with renal colic who received analgesics in the ED and at discharge over a five-year period. Patients were divided into three groups based on the following periods: 2012-2014 (pre-implementation phase); 2014-2015 (implementation phase); and 2015-2017 (post-implementation). RESULTS: A total of 4,490 patients presented to the ED with renal colic over a five-year study period. Analgesics were administered to 3,793 ED patients of whom 1,704 received opioids and 2,675 received non-opioid analgesics. A total of 3,533 ED patients received a prescription for analgesic(s) upon discharge from the ED: 2,692 patients received opioids, and 2,228 received non-opioids. We observed a 12.7% overall decrease from the pre-implementation to post-implementation time period in opioid prescribing in the ED and a 25.5% decrease in opioid prescribing at discharge, which translated into 432 and 768 fewer patients receiving opioids, respectively. CONCLUSION: Implementation of an opioid-reduction initiative based on patient-specific, pain syndrome-targeted opioid alternative protocols resulted in a reduction in opioid administration in the ED by 12.7% and at prescriptions at discharge by 25.5%. Adoption of similar ED initiatives nationwide has the potential to foster effective non-opioid analgesic practices for ED patients presenting with renal colic and to reduce physicians' reliance on administering and prescribing opioids.

Pain management of renal colic in the emergency department with intravenous lidocaine.

OBJECTIVE: To describe our experience with intravenous lidocaine (IVL) to manage pain of renal colic origin in the emergency department (ED). METHODS: A retrospective analysis of all patients presenting with pain of renal colic origin from the periods of 2014 to 2017 by using the ED electronic medical record database (Allscripts™). RESULTS: Forty-four patients received IVL for renal colic over a three-year period. The average dose of IVL as a primary analgesic was 117.2 mg, and as a rescue was 108 mg. Administration of IVL resulted in a decrease in overall pain score by 6.3 points (numerical rating scale), by 7.4 points when IVL was used as a primary analgesic, and by 5.2 points when IVL was given as a rescue. There were no documented adverse effects. CONCLUSION: Intravenous lidocaine has a potential of being used for patients presenting to the ED with a pain of renal colic origin as a primary analgesic or as a rescue. Although promising, this therapy will need to be studied in prospective randomized fashion and larger patients' population with underlying cardiac disease before it can be recommended for broad use in the ED.