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Study Objective: Hydroxyzine is an antihistamine drug used for symptomatic relief of anxiety and tension. We hypothesized that managing the anxiety of patients with severe pain by adding hydroxyzine to a conventional intravenous morphine titration would relieve their pain more effectively., Methods: This was a randomized, double-blind, controlled group study of prehospital patients with acute pain scored greater than or equal to 6 on a 0-10 verbal numeric rating scale (NRS). Patients'anxiety was measured with the self-reported Face Anxiety Scale (FAS) ranking from 0 to 4. The percentage of patients with pain relief (NRS score ≤ 3) 15 min after the first injection was the primary outcome., Results: One hundred forty patients were enrolled. Fifty-one percent (95% CI 39% to 63%) of hydroxyzine patients versus 52% (95% CI 40% to 64%) of placebo patients reported a pain numeric rating scale score of 3 or lower at 15 min. Ninety-one percent (95% CI 83% to 98%) of patients receiving hydroxyzine reported no more severe anxiety versus 78% (95% CI 68% to 88%) of patients with placebo (p > 0.05). Adverse events were minor, with no difference between groups (6% in hydroxyzine patients and 14% in placebo patients)., Conclusion: Addition of hydroxyzine to morphine in the prehospital setting did not reduce pain or anxiety in patients with acute severe pain and therefore is not indicated based on our results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Managing severe acute nociceptive pain in buprenorphine-maintained individuals for opioid use disorder management is challenging owing to the high affinity and very slow dissociation of buprenorphine from μ-opioid receptors that hinders the use of full agonist opioid analgesics. In a translational approach, the aim of this study was to use an animal setting to investigate the effects of a chronic high dose of buprenorphine treatment on nociceptive thresholds before and after applying a severe acute nociceptive traumatic surgery stimulus and to screen postoperative pharmacological analgesic strategies. A chronic treatment of mice with a high dose of buprenorphine (BUP HD, 2 × 200 μg/kg/day; i.p.) revealed significant mechanical allodynia. One and two days after having discontinued buprenorphine administration and having induced a severe nociceptive acute pain by a closed tibial fracture, acute administration of morphine at a dose which has analgesic effects in absence of pretreatment (4.5 mg/kg; i.p.), was ineffective to reduce pain in the BUP HD group. However, mimicking multimodal analgesia strategy used in human postoperative context, the combination of morphine (administered at the same dose) with a NMDA receptor antagonist (ketamine) or an NSAID (ketoprofen) produced antinociceptive responses in these animals. The mouse model of closed tibial fracture could be useful to identify analgesic strategies of postoperative pain for patients with chronic exposure to opioids and suffering from hyperalgesia., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier B.V.)

Study Objectives: Morphine is the reference treatment for severe acute pain in an emergency department. The purpose of this study was to describe and analyse opioid-related ADRs (adverse drug reactions) in a large cohort of emergency department patients, and to identify predictive factors for those ADRs., Methods: In this prospective, observational, pharmaco-epidemiological international cohort study, all patients aged 18years or older who were treated with morphine were enrolled. The study was done in 23 emergency departments in the US and France. Baseline numerical rating scale score and initial and total doses of morphine titration were recorded. Logistic regression analysis was used to study the effects of demographic, clinical and medical history covariates on the occurrence of opioid-induced ADRs within 6h after treatment., Results: A total of 1128 patients were included over 10months. Median baseline initial pain scores were 8/10 (7-10) versus 3/10 (1-4) after morphine administration. Median titration duration was 10min (IQR, 1-30). The occurrence of opioid-induced ADRs was 25% and 2% were serious. Patients experienced mainly nausea and drowsiness. Medical history of travel sickness (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.01-2.86) and history of nausea or vomiting post morphine (OR, 3.86; 95% CI, 2.29-6.51) were independent predictors of morphine related ADRs., Conclusion: Serious morphine related ADRs are rare and unpredictable. Prophylactic antiemetic therapy could be proposed to patients with history of travel sickness and history of nausea or vomiting in a postoperative setting or after morphine administration., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: To assess the prescribing patterns in acute renal colic in emergency departments in US and France, by comparing physicians' intended prescription practices with actual prescription data in a sample of emergency practitioners., Methods: Pharmaco-epidemiological international study in two phases. First, we surveyed emergency physicians in US and France as to what analgesics they would use for simulated cases of renal colic. We then conducted a retrospective review of actual cases of emergency department patients with pain scores ≥6/10 with acute renal colic during a period of 6 months before the survey. We compared nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids used for pain treatment in the two groups, and the differences between the two countries., Results: One hundred six prescribers and 100 patients were included in the study. Comparison between simulated and real cases showed that NSAIDs and opioids were less frequently prescribed in real life (78% vs 99% and 51% vs 100% respectively). Morphine was the most prescribed opioid (96% of simulated cases and 34% of real ones). Acetaminophen use was increased in real life cases (58% vs 0%). Concerning the differences between countries, US physicians are more likely to administer morphine (64% vs 38%) and French physicians NSAIDs (88% vs 68%). The NSAIDs used are ketorolac in the United States (94% of simulated cases vs 64%) and ketoprofen in France (94% and 88% respectively)., Discussion: We showed clear differences between intended and real analgesic prescription practices for patients suffering from renal colic. Some differences exist for pain perceptions and treatments between US and France., (Copyright © 2016. Published by Elsevier Inc.)

Background: Acute and chronic pains are reported to be highly prevalent in patients under opioid maintenance treatment (OMT). Lack of knowledge concerning the complex relationship between pain, opioid use, and their impact on OMT efficacy can account for the barriers encountered for pain management., Objectives: To assess the impact of acute pain exposure on long-term OMT retention in a cohort of patients under buprenorphine or methadone followed up during 12 months., Study Design: Prospective, multi-center observational cohort clinical study., Setting: Emergency departments, surgery departments, and specialized addiction care centers in an outpatient setting in south-western France (Midi-Pyrenees area), from April 2008 to January 2010., Methods: Patients aged 18 or more under OMT for at least 3 months, and followed up by a physician were recruited. Acute pain was assessed using the Visual Analog Scale (VAS) or the Verbal Rating Scale (VRS). Exposed patients were those with a pain score greater than 0 at the time of admission on any of the rating scales. The OMT rate after 12 months was compared among exposed and unexposed patients. OMT retention was also investigated after 3 and 6 months follow-up., Results: A total of 151 patients, 81 exposed and 70 unexposed, were recruited; among them, respectively, 26 (32%) and 34 (49%) completed 12-months follow-up. Acute pain exposure appeared to be significantly and negatively associated with retention in treatment (crude OR: 0.44; 95% CI [0.22 - 0.87]; adjusted OR: 0.46; 95% CI [0.23 - 0.93]). Compared to methadone users, patients under buprenorphine were less likely to have their OMT maintained after 12 months (OR 0.37; 95% CI [0.18 - 0.75]; adjusted OR 0.38; 95% CI [0.18 - 0.80])., Limitations: Follow-up rate was 40% (60/151)., Conclusion: This study demonstrates the strong negative impact of acute pain on OMT in a population mainly composed of patients under buprenorphine, as well as differential response depending on the OMT medication. The findings highlight the need to consider the characteristics of pain in the population under OMT and to develop evidence-based guidelines for pain management., Trial Registration: The study was registered at www.clinical.trials.gov with the study identifier: NCT00738036. Ethics Committee approval was received on February 11, 2008. Participants' written consent was not required.

Objectives: Although 50% nitrous oxide (N(2) O) and oxygen is a widely used treatment, its efficacy had never been evaluated in the prehospital setting. The objective of this study was to demonstrate the efficacy of premixed N(2) O and oxygen in patients with out-of-hospital moderate traumatic acute pain., Methods: This prospective, randomized, multicenter, double-blind trial enrolled patients with acute moderate pain (numeric rating scale [NRS] score between 4 and 6 out of 10) caused by trauma. Patients were assigned to receive either 50/50 N(2) O and oxygen 9 L/min (N(2) O group) or medical air (MA) 9 L/min (MA group), in ambulances from two nurse-staffed fire department centers. After the first 15 minutes, every patient received N(2) O and oxygen. The primary endpoint was pain relief at 15 minutes (T15), defined as a NRS ≤ 3 of 10. The NRS was measured every 5 minutes. Secondary endpoints were treatment safety and adverse events, time to analgesia, and patient and investigator satisfaction with analgesia., Results: Sixty patients were included with no differences between groups in age (median = 34 years, interquartile range [IQR] = 23 to 53 years), sex (37 males, 66%), and initial median NRS of 6 (IQR = 5 to 6). At T15, 67% of the patients in the N(2) O group had an NRS score of 3 or lower versus 27% of those in the MA group (delta = 40%, 95% confidence interval [CI] = 17% to 63%; p < 0.001). The median pain scores were lower in the N(2) O group at T15, 2 (IQR = 1 to 4) versus 5 (IQR = 3 to 6). There was a difference at 5 minutes that persisted at all subsequent time points. Four patients (one in the N(2) O group) experienced adverse events (nausea) during the protocol., Conclusions: This study demonstrates the efficacy of N(2) O for the treatment of pain from acute trauma in adults in the prehospital setting., (© 2013 by the Society for Academic Emergency Medicine.)