Effect of a Single Dose of Oral Opioid and Nonopioid Analgesics on Acute Extremity Pain in the Emergency Department: A Randomized Clinical Trial.
ABSTRACT: Importance:The choice of analgesic to treat acute pain in the emergency department (ED) lacks a clear evidence base. The combination of ibuprofen and acetaminophen (paracetamol) may represent a viable nonopioid alternative. Objectives:To compare the efficacy of 4 oral analgesics. Design, Settings, and Participants:Randomized clinical trial conducted at 2 urban EDs in the Bronx, New York, that included 416 patients aged 21 to 64 years with moderate to severe acute extremity pain enrolled from July 2015 to August 2016. Interventions:Participants (104 per each combination analgesic group) received 400 mg of ibuprofen and 1000 mg of acetaminophen; 5 mg of oxycodone and 325 mg of acetaminophen; 5 mg of hydrocodone and 300 mg of acetaminophen; or 30 mg of codeine and 300 mg of acetaminophen. Main Outcomes and Measures:The primary outcome was the between-group difference in decline in pain 2 hours after ingestion. Pain intensity was assessed using an 11-point numerical rating scale (NRS), in which 0 indicates no pain and 10 indicates the worst possible pain. The predefined minimum clinically important difference was 1.3 on the NRS. Analysis of variance was used to test the overall between-group difference at P?=?.05 and 99.2% CIs adjusted for multiple pairwise comparisons. Results:Of 416 patients randomized, 411 were analyzed (mean [SD] age, 37  years; 199 [48%] women; 247 [60%] Latino). The baseline mean NRS pain score was 8.7 (SD, 1.3). At 2 hours, the mean NRS pain score decreased by 4.3 (95% CI, 3.6 to 4.9) in the ibuprofen and acetaminophen group; by 4.4 (95% CI, 3.7 to 5.0) in the oxycodone and acetaminophen group; by 3.5 (95% CI, 2.9 to 4.2) in the hydrocodone and acetaminophen group; and by 3.9 (95% CI, 3.2 to 4.5) in the codeine and acetaminophen group (P?=?.053). The largest difference in decline in the NRS pain score from baseline to 2 hours was between the oxycodone and acetaminophen group and the hydrocodone and acetaminophen group (0.9; 99.2% CI, -0.1 to 1.8), which was less than the minimum clinically important difference in NRS pain score of 1.3. Adverse events were not assessed. Conclusions and Relevance:For patients presenting to the ED with acute extremity pain, there were no statistically significant or clinically important differences in pain reduction at 2 hours among single-dose treatment with ibuprofen and acetaminophen or with 3 different opioid and acetaminophen combination analgesics. Further research to assess adverse events and other dosing may be warranted. Trial Registration:clinicaltrials.gov Identifier: NCT02455518.
Project description:BACKGROUND:Opioids and acetaminophen are both widely used to relieve pain after non-operative treatment of limb fractures, but evidence for the superiority of opioids versus acetaminophen is lacking. In this study, we aim to determine whether acetaminophen is non-inferior to the acetaminophen/oxycodone combination for pain relief after non-operative fixation of an extremity limb fracture. We hypothesize that acetaminophen is non-inferior to the acetaminophen/oxycodone combination. METHODS:A double-blind randomized controlled trial will be conducted. Power analysis determined that 1226 participants will be needed (P <0.05, power 90%). Patients with acute limb fracture who receive non-operative treatment will be recruited and randomly allocated into two groups: the intervention group will receive oral oxycodone (10 mg) and acetaminophen (650 mg), and the control group will receive acetaminophen (650 mg) only. All participants will be instructed to take one pill of study medication on an as-needed basis and no more frequently than once every 8 h. The primary outcome measure will be scores on the 11-point Numeric Rating Scale (NRS-11) over 14 days. Secondary outcome measures are scores on the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), EuroQol five-dimension questionnaire (EQ-5D), self-rated satisfaction with the analgesia produced, self-reported nighttime sleep duration, number of intervention or control pills used, and total duration for taking intervention or control medication. Change of pain scores and the number of times that analgesic drugs were taken in the two groups will be statistically evaluated with Student t tests according to their fracture site. DISCUSSION:This study will be a randomized controlled trial that is adequately powered to test the hypothesis that acetaminophen is non-inferior to the combination of acetaminophen and oxycodone in relieving objectively measured pain after non-operative treatment of limb fractures in adults. It will hopefully provide a safe and effective analgesic plan for such patients. TRIAL REGISTRATION:ChiCTR registry: ChiCTR1800017015 . Registered on July 8, 2018.
Project description:INTRODUCTION:Inguinal and umbilical hernia repairs are among the most common surgical procedures performed in the US. Optimal perioperative pain control regimens remain challenging and opioid analgesics are commonly used. Preoperative nonsteroidal anti-inflammatory drug (NSAID) administration has been shown to reduce postoperative narcotic requirements. This study sought to evaluate the efficacy of perioperative intravenous (IV) ibuprofen on postoperative pain level and narcotic use in patients undergoing open or laparoscopic inguinal and/or umbilical hernia repair. METHODS:A single center, randomized, double-blind placebo-controlled trial involving patients ?18 years undergoing inguinal and/or umbilical hernia repair was performed. Patients were randomized to receive 800 mg of IV ibuprofen or placebo preoperatively. Outcomes assessed included postoperative pain medication required and visual analog scale (VAS) pain scores. RESULTS:Forty-eight adult male patients underwent inguinal and/or umbilical hernia repair. Patients receiving IV ibuprofen used more oxycodone/acetaminophen (32% vs 13%) and IV hydromorphone (12% vs 8.7%), and fewer combinations of pain medications (44% vs 65.2%) in the first two postoperative hours compared to placebo (p=0.556). The IV ibuprofen group had more patients pain free (28% vs 8.7%, p=0.087) and lower VAS scores (3.08±2.14 vs 3.95±1.54, p=0.134) at 2 hours postoperatively, compared to the placebo group, however, this was not statistically significant. Similar pain levels at 1, 3, and 7 days, postoperative and similar use of rescue medications in both groups were observed. CONCLUSION:Preoperative administration of IV ibuprofen did not significantly reduce postoperative pain among patients undergoing elective hernia repair. Considerable variability in postoperative narcotic analgesic requirement was noted, and larger scale studies are needed to better understand the narcotic analgesic requirements associated with IV ibuprofen in inguinal/umbilical hernia repair patients.
Project description: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.
Project description:OBJECTIVE:To evaluate the effect of oral gabapentin in conjunction with usual oral pain management regimens of lorazepam, ibuprofen, oxycodone, and acetaminophen for surgical abortion on pain 5 minutes postprocedure. METHODS:This was a randomized, double-blind, placebo-controlled trial of patients from 6 0/7-14 6/7 weeks of gestation scheduled to undergo surgical abortion at the Duke Family Planning Clinic. Participants were administered 600 mg of oral gabapentin compared with placebo with usual oral pain management. Pain score was assessed using a 100-mm visual analog scale, with the primary outcome being pain score 5 minutes after the procedure. The effect of gabapentin was assessed using a linear regression model controlling for baseline pain. We also measured pain perception 24 hours after the procedure. Secondary outcome measures included anxiety, side effects, and usage of opiate pain medication in the 24-hour postoperative period. RESULTS:Out of 113 women screened for this study; 96 women were recruited, enrolled, and randomized to study treatment arm from August 2016 to June 2018. Pain at 5 minutes after the procedure was similar between the gabapentin and placebo groups ((Equation is included in full-text article.)=3.40; 95% CI -8.20 to 15.0; P=.56). Gabapentin and placebo were well tolerated, with no statistically significant difference in side effects or anxiety levels. Although prescription of opioids after the procedure was not standardized among patients, 73% of women received a short-term prescription for oxycodone. A lower percentage of women in the gabapentin group self-reported taking opioids in the 24 hours postprocedure (18% vs 47%; odds ratio 0.26; 95% CI 0.09-0.75). CONCLUSION:The addition of gabapentin to usual oral pain management regimens with paracervical block did not reduce postoperative pain for patients undergoing outpatient surgical abortion. Although the addition of gabapentin was well tolerated and reduced oral opiate use 24 hours postprocedure, it did not affect the experience of pain during and immediately after the procedure. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT02725710.
Project description:BACKGROUND: Alternating ibuprofen and acetaminophen for the treatment of febrile children is a prevalent practice among physicians and parents, despite the lack of evidence on effectiveness or safety. This randomized, double-blind and placebo-controlled clinical trial aims at comparing the antipyretic effectiveness and safety of a single administration of alternating ibuprofen and acetaminophen doses to that of ibuprofen mono-therapy in febrile children. METHODS: Seventy febrile children were randomly allocated to receive either a single oral dose of 10 mg/kg ibuprofen and 15 mg/kg oral acetaminophen after 4 hours, or a similar dose of ibuprofen and placebo at 4 hours. Rectal temperature was measured at baseline, 4, 5, 6, 7 and 8 hours later. Endpoints included proportions of afebrile children at 6, 7 and 8 hours, maximum decline in temperature, time to recurrence of fever, and change in temperature from baseline at each time point. Intent-to-treat analysis was planned with statistical significance set at P < 0.05. RESULTS: A higher proportion of subjects in the intervention group (83.3%) became afebrile at 6 hours than in the control group (57.6%); P = 0.018. This difference was accentuated at 7 and 8 hours (P < 0.001) with a significantly longer time to recurrence of fever in the intervention group (mean +/- SD of 7.4 +/- 1.3 versus 5.7 +/- 2.2 hours), P < 0.001. Odds ratios (95%CI) for defervescence were 5.6 (1.3; 23.8), 19.5 (3.5; 108.9) and 15.3 (3.4; 68.3) at 6, 7 and 8 hours respectively. Two-way ANOVA with repeated measures over time revealed a significantly larger decline in temperature in the intervention group at times 7 (P = 0.026) and 8 (P = 0.002) hours. CONCLUSION: A single dose of alternating ibuprofen and acetaminophen appears to be a superior antipyretic regimen than ibuprofen mono-therapy. Further studies are needed to confirm these findings.
Project description:BACKGROUND:Total hip replacement (THR) is often accompanied by severe postoperative pain. We aimed to study whether oxycodone can be an effective alternative for fentanyl in the management of early postoperative pain after total hip replacement. METHODS:We conducted a randomized controlled trial on 46 patients scheduled to undergo THR. We followed a standard general anesthetic technique, with endotracheal intubation. Twenty minutes before the end of surgery, single bolus injection of fentanyl, 50??g (fentanyl group [group F], n?=?23) or oxycodone, 4?mg (oxycodone group [group O], n?=?23) was administered intravenously. Numeric rating scale (NRS) was used to assess pain in the post-anesthesia care unit (PACU). All patients had intravenous patient-controlled analgesia (PCA) with 10??g/kg of fentanyl for 48?hours. Intravenous boluses of 50??g were administered for breakthrough pain. The cumulative opioid dose administered at 6, 12, 24, and 48?h after surgery were recorded. A P value of less than .05 was considered statistically significant. RESULTS:The NRS of group O in the PACU was significantly lower (P?<.05); fewer patients in group O required additional fentanyl boluses in the PACU (P?<.05). The cumulative opioid requirement was significantly less in group O at 6, 12, 24, and 48?hours after surgery. (P?<.05) CONCLUSIONS:: A single bolus injection of oxycodone is more effective than that of fentanyl in the acute phase of postoperative pain after THR. It may be used as an alternative drug for fentanyl in pain control after orthopedic surgery.
Project description:Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC).Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ?3/10 at rest or ?5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen.At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration.In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.
Project description:Optimal postoperative pain management is important to ensure patient comfort and early mobilization.In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ?18 years of age who had pain at rest ?5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1-3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1-3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated.The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1-3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1-3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively.Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption.NCT00820027.
Project description:The objective of the study was to compare nitrous oxide with oxygen (N2O/O2) to oral hydrocodone/acetaminophen and lorazepam for analgesia during first-trimester surgical abortion.This double-blind randomized trial assigned women undergoing first-trimester surgical abortion at<11 weeks' gestation to inhaled N2O/O2 vs. oral sedation for pain management. The N2O/O2 group received up to 70:30 ratio during the procedure and placebo pills preprocedure; the oral group received inhaled oxygen during the procedure and oral hydrocodone/acetaminophen 5 mg/325 mg and lorazepam 1 mg preprocedure. The primary outcome was maximum procedural pain, assessed on a 100-mm visual analog scale (VAS; anchors 0=no pain and 100=worst pain) at 2 min postprocedure. A difference of 13 mm on the VAS was considered clinically significant. Satisfaction with pain management was measured on a 100-mm VAS (anchors 0=very unsatisfied, 100=very satisfied).We randomized 140 women, 70 per study arm. Mean age of participants was 26±6.6 years; mean gestational age was 7.3±1.5 weeks. Mean maximum procedure pain scores were 52.5±26.7 and 60.8±24.4 for N2O/O2 and oral groups, respectively (p=.09). Satisfaction with pain management was 69.3±28.4 and 61.5±30.4 for N2O/O2 and oral groups. respectively (p=.15).We found no difference in mean procedural pain scores between women assigned to N2O/O2 vs. those assigned to oral sedation for first-trimester surgical abortion. Satisfaction with both options was high.Women undergoing early surgical abortion experienced no differences in pain and satisfaction between those who used inhaled nitrous oxide and oral sedation. Nitrous oxide, with side effects limited to the duration of inhalation and no need for a ride home, is a viable alternative to oral sedation for first-trimester abortion pain management.
Project description:Controlled-release oxycodone/naloxone (OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone (OX-CR) for the control of cancer-related pain in Korean patients.In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20 years or older with moderate to severe cancer-related pain [numeric rating scale (NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat (ITT) population were randomized (1:1) to OXN-CR or OX-CR groups. OXN-CR was administered starting at 20 mg/10 mg per day and up-titrated to a maximum of 80 mg/40 mg per day for 4 weeks, and OX-CR was administered starting at 20 mg/day and up-titrated to a maximum of 80 mg/day for 4 weeks. The primary efficacy endpoint was the change in NRS pain score from baseline to week 4, with non-inferiority margin of -1.5. Secondary endpoints included analgesic rescue medication intake, patient-reported change in bowel habits, laxative intake, quality of life (QoL), and safety assessments.Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group (n = 58) and the OX-CR group (n = 59) (-1.586 vs. -1.559, P = 0.948). The lower limit of the one-sided 95% confidence interval (-0.776 to 0.830) for the difference exceeded the non-inferiority margin (P < 0.001). The OXN-CR and OX-CR groups did not differ significantly in terms of analgesic rescue medication intake, change in bowel habits, laxative intake, QoL, and safety assessments.OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4 weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation. Trial registration ClinicalTrials.gov NCT01313780, registered March 8, 2011.