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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.)

Background: Studies have shown disparate results on the consequences of morphine use in ST-segment elevation myocardial infarction (STEMI). No study has evaluated alternative treatments that could be at least non-inferior to morphine without its potentially damaging consequences for myocardial function and platelet reactivity. The aim of this study was to evaluate whether nitrous oxide/oxygen plus intravenous acetaminophen (NOO-A) is non-inferior to morphine to control chest pain in STEMI patients., Methods: This multicenter, open-label, cluster-randomized, controlled, non-inferiority study compared NOO-A with morphine in 684 prehospital patients with ongoing suspected STEMI of < 12 h duration and a pain rating score ≥ 4. The primary endpoint was the proportion of patients achieving pain relief (numeric rating score ≤ 3) after 30 min. Secondary safety endpoints included serious adverse events and death at 30 days., Results: The median baseline pain score was 7.0 in both groups. The primary endpoint occurred in 51.7% of the NOO-A group and 73.6% of the morphine group (absolute risk difference - 21.7%; 95% confidence interval - 29.6 to - 13.8). At 30 days, the rate of serious adverse events was 16.0 and 18.8% in the NOO-A and morphine groups respectively (p = NS). The rate of death was 1.8% (NOO-A group) and 3.8% (morphine group) (p = NS)., Conclusion: Analgesia provided by NOO-A was inferior to morphine at 30 min in patients with acute STEMI in the prehospital setting. Rates of serious adverse events did not differ between groups., Trial Registration: ClinicalTrials.gov: NCT02198378.

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.)

Study Objective: We determine the best intravenous opioid titration protocol by comparing morphine and sufentanil for adult patients with severe traumatic acute pain in an out-of-hospital setting, with a physician providing care., Methods: In this double-blind randomized clinical trial, patients were eligible for inclusion if aged 18 years or older, with acute severe pain (defined as a numeric rating scale score ≥ 6/10) caused by trauma. They were assigned to receive either intravenous 0.15 μg/kg sufentanil, followed by 0.075 μg/kg every 3 minutes or intravenous 0.15 mg/kg morphine and then 0.075 mg/kg. The primary endpoint of the study was pain relief at 15 minutes, defined as a numeric rating scale less than or equal to 3 of 10. Secondary endpoints were time to analgesia, adverse events, and duration of analgesia during the first 6 hours., Results: A total of 108 patients were included, 54 in each group. At 15 minutes, 74% of the patients in the sufentanil group had a numeric rating scale score of 3 or lower versus 70% of those in the morphine group (Δ4%; 95% confidence interval -13% to 21%). At 9 minutes, 65% of the patients in the sufentanil group experienced pain relief versus 46% of those in the morphine group (Δ18%; 95% confidence interval 0.1% to 35%). The duration of analgesia was in favor of the morphine group. Nineteen percent of patients experienced an adverse event in both groups, all mild to moderate., Conclusion: Intravenous morphine titration using a loading dose of morphine followed by strictly administered lower doses at regular intervals remains the criterion standard. Moreover, this study supports the idea that the doses studied should be considered for routine administration in severe pain protocols., (Copyright © 2010 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Objective: To evaluate the efficacy and safety of inhaled morphine delivered in patients experiencing severe acute pain in an emergency setting., Patients and Methods: Patients were eligible for inclusion if they were aged 18 years or older, with a severe acute pain defined by a numerical rating scale (NRS) score of 60/100 or higher. The intervention involved administering a single dose of 0.2 mg/kg morphine nebulized using a Misty-Neb nebulizer system. NRSs were recorded and were repeated at 1, 3, 5, and 10 minute after the end of inhalation (T10). The protocol-defined primary outcome measure was pain relief (defined by an NRS score of 30/100 or lower) at T10. Secondary outcomes included differences between pain scores at baseline and at T10 and incidence of adverse events., Results: A total of 28 patients were included in this study. No patient experienced pain relief 10 minutes after the end of inhalation, and no adverse effects were recorded. Respective initial and final median NRS scores were 80 (70-90) and 70 (60-80), p < 0.0001. Despite achieving statistical significance, the value of this point estimate is less than the 14 NRS difference that was defined a priori as representing a minimum clinically significant difference in pain severity., Conclusion: 0.2 mg/kg nebulized morphine is not effective in managing acute pain in an emergency setting. In spite of the potential advantages of the pulmonary route of administration, opioids should be intravenous prescribed at short fixed intervals to control severe acute pain in an emergency setting.

Study Objective: We aimed to determine the best intravenous morphine titration protocol by comparing 2 protocols for prehospital treatment of patients with severe acute pain., Methods: Eligible patients with a numerical rating scale (NRS) score of 60/100 or higher were randomly allocated to receive either 0.05 mg/kg morphine then 0.025 mg/kg every 5 minutes (group A) or 0.1 mg/kg morphine then 0.05 mg/kg every 5 minutes (group B) intravenously. The protocol-defined primary outcome measure was the percentage of patients with pain relief (with a NRS score of 30/100 or lower) 30 minutes after the first injection., Results: A total of 106 consecutive patients were randomized. Thirty minutes after the injection, 66% of the patients in group A had an NRS of 30 or lower vs 76% of those in group B (P = .25). Ten minutes after the injection, 17% of the patients in group A had an NRS score of 30 or lower vs 40% of those in group B, (odds ratio, 3.4; 95% confidence interval, 1.3-8.8; P < .01). Patients in group B were significantly more satisfied with their analgesia. In addition, there were no serious complications in either group. However, patients in group B did experience almost twice the incidence of adverse effects overall and in particular 4 times the level of emesis, although neither of these observations were statistically significant. Using univariate and multivariate analysis, only an initial NRS score of 100 was an independent predictive factor for failure of analgesia (odds ratio, 0.125; 95% confidence interval, 0.02-0.68; P < .05)., Conclusion: The high-dose morphine regimen showed a similar analgesic response pattern to the low-dose one in severe acute pain in a prehospital setting. Patients in the high-dose group were more likely to experience pain relief 10 minutes after the injection. In the interests of achieving rapid pain relief, an initial dose of 0.05 mg/kg should no longer be recommended for treating severe acute pain in a prehospital setting. Another important message arising from our study is that a regimented dose of morphine, with an initial dose and strictly administered lower doses at regular intervals, is safe in the prehospital setting.