The Analgesic Efficacy and Safety of Intramuscular Hydromorphone versus Butorphanol for Acute Pain in the Emergency Department：A Randomized Trial

The Analgesic Efficacy and Safety of Intramuscular Hydromorphone versus Butorphanol for Acute Pain in the Emergency Department：A Randomized Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Analgesic Efficacy and Safety of Intramuscular Hydromorphone versus Butorphanol for Acute Pain in the Emergency Department：A Randomized Trial Yongping Huang, Xiaojing Peng, Bihua Zhang, Li Luo, Yufang Sun, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6831108/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Acute pain is a distressing encounter for most patients visiting the emergency department (ED), which severely affects their quality of life. Early analgesia is considered reasonable and necessary. However, the choice of analgesic drugs for acute pain still remains controversial. The aim of this study was to evaluate and compare the analgesic efficacy and safety of intramuscular hydromorphone and butorphanol in patients with acute pain in the ED. This randomized controlled clinical trial randomly divided 199 patients with moderate to severe acute pain into two groups in a 1:1 ratio, receiving intramuscular injections of 1 mg of hydromorphone and butorphanol, respectively. We compared the changes in pain intensity, as assessed by the Numerical Rating Scale (NRS), the requirement for supplemental analgesics, alterations in vital signs, incidence of adverse reactions, and the final destination of the patients in the two groups after the use of analgesic drugs. The results showed that, compared with the butorphanol group, the hydromorphone group showed more significant changes in NRS after administration, with higher pain relief rates at 1 h and 2 h, and a greater proportion of apparent relief at 2 h, especially in cases of severe pain ( P < 0.05). Additionally, we observed a significant difference in the requirement for supplemental analgesics between the two groups 2 h after analgesia (0.0% vs 6.1%, P < 0.05). There was no significant difference in the incidence of adverse reactions, the final destination of the patients, and the effects on heart rate, respiration, and oxygen saturation between the two groups ( P > 0.05). Common adverse reactions included dizziness or headache, nausea or vomiting, and injection pain, with one case of hypotension in the hydromorphone group. Our findings showed that both hydromorphone and butorphanol could effectively alleviate moderate to severe acute pain in the ED, and that the incidence of adverse reactions was similar. Notably, hydromorphone demonstrates superior analgesic efficacy compared to butorphanol, especially in patients with severe pain. This study has been registered in the Chinese Clinical Trial Registry (Registration Number: ChiCTR2400088376, Date: 2024-08-16, retrospectively registered) Hydromorphone Butorphanol Acute Pain Emergency Department Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Pain is recognized as the "fifth vital sign" [ 1 – 3 ], causing serious physical and psychological damage to patients, and is one of the major causes of disability [ 4 ]. Previous studies have confirmed that the administration of early analgesia does not hinder disease diagnosis; rather, it can effectively protect organ function, alleviate ischemic and hypoxic injury, and improve patient comfort and compliance with medical recommendations [ 3 , 5 ]. Currently, analgesic drugs include non-steroidal anti-inflammatory drugs, acetaminophen, and opioids. Among these, both domestic and international guidelines recommend opioids as the preferred treatment for moderate to severe pain (Numerical Rating Scale, NRS ≥ 4) [ 3 , 4 , 6 ]. Morphine, the most classic and widely used opioid analgesic, is increasingly associated with high rates of abuse and addiction, making the development of alternative drugs an urgent necessity [ 7 – 9 ]. Clinical studies have indicated that hydromorphone exhibits high bioavailability, with advantages of faster onset and longer duration of action compared to morphine [ 10 , 11 ]. Additionally, the incidence of adverse reactions is similar to or lower than morphine [ 10 – 14 ], making it a reasonable choice for the management of postoperative pain and cancer pain [ 10 , 15 – 17 ]. Statistically, more than 50.0% of emergency department (ED) visits are primarily for pain complaints, and 60.0–80.0% of ED patients experience pain [ 1 – 3 , 18 – 21 ]. Patients presenting to the ED with pain typically exhibit acute onset and severe intensity, often accompanied by ambiguous diagnosis. The selection of analgesic regimens for these patients differs significantly from chronic or postoperative pain. However, there remains a lack of evidence to support the safe, effective and timely selection of appropriate analgesic medications. Several clinical studies have shown that hydromorphone provides effective analgesia for acute pain in the ED [ 22 – 24 ]. Hydromorphone demonstrates an analgesic potency approximately 5–10 times greater than that of morphine when administered at equianalgesic doses [ 9 – 11 , 25 ]. Consequently, achieving comparable analgesic efficacy to hydromorphone necessitates a substantial dose escalation of morphine, which directly correlates with an increased risk of opioid-induced adverse effects. Butorphanol is a safe and effective analgesic medication [ 26 , 27 ], with an analgesic potency 3 to 8 times that of morphine [ 16 , 28 ], similar to that of hydromorphone. Therefore, this study aimed to evaluate and compare the analgesic efficacy and safety of hydromorphone and butorphanol in patients experiencing acute pain in the ED. Methods Study design and participants This was a prospective, randomized, parallel group, single-center trial conducted from September 2023 to January 2024 in the ED of the Third People's Hospital of Chengdu, Chengdu, China. Reporting was in accordance with the CONSORT statement. This study has been registered in the Chinese Clinical Trial Registry (Registration Number: ChiCTR2400088376). Trained emergency physicians conducted a rigorous screening of patients in accordance with the inclusion exclusion criteria established by the investigators. The inclusion criteria comprised: 1) patients experiencing acute moderate to severe pain (NRS ≥ 4) requiring opioid analgesic treatment; 2) adult patients (aged ≥ 18 years); 3) obtained informed consent from the patient. The exclusion criteria included: 1) pregnant or lactating women; 2) individuals with a known allergy to opioids, including hydromorphone or butorphanol; 3) chronic opioid users or those with a history of opioid addiction; 4) presence of medical conditions that may affect the metabolism of opioid analgesics (severe hepatic or renal insufficiency); 5) systolic blood pressure less than 90 mmHg, heart rate less than 50 beats per minute (bpm), or oxygen saturation less than 90% on room air; 6) intoxication by alcohol or other drugs; 7) presence of symptoms of respiratory depression, suffering from acute or severe bronchial asthma; 8) presence or risk of progression to gastrointestinal obstruction, especially paralytic intestinal obstruction; 9) loss of hearing or vision, or any other condition that may significantly hinder data collection for the study; 10) communication deficits (e.g. psychiatric or neurological disorders or sedation); 11) opioid use within the previous 24 hours; 12) concurrent use of medications that may interact the study medications; 13) concurrently participated in any clinical trial. Randomization Randomization was conducted using a computer-generated randomization table. Participants who met the inclusion and exclusion criteria and gave informed consent were randomly allocated to the hydromorphone or butorphanol groups by the researcher in a 1:1 ratio. The emergency physicians and the specialist nurse administering the injections were aware of the admission until after grouping. However, the patients and their legal representatives were blind to the grouping. Intervention All participants received treatment via a "1 + 1" titration method, as previous studies have indicated that 1 mg + 1 mg of hydromorphone yields an analgesic effect comparable to that of 2 mg, while potentially reducing the overall dosage of analgesic drugs [ 29 ]. The hydromorphone and butorphanol groups received intramuscular injections of 1 mg hydromorphone hydrochloride (pre-infused) (Yichang Human well Pharmaceutical Co., Ltd, Hubei, China) and 1 mg butorphanol tartrate (Jiangsu Hengrui Pharmaceutical Co., Ltd, Jiangsu, China), respectively. Two hours later, participants were queried regarding their need for additional analgesic medication. If the answer was yes, an additional 1 mg of the same medication was administered. Outcomes Pain intensity was measured by the NRS, which is represented by an integer from 0–10, with the side of 0 as no pain and 10 as the worst pain. The amount of NRS change was indicated as the pre-medication NRS (NRS 1 ) subtracted from the post-medication NRS (NRS 2 ), and the rate of NRS change relative to NRS 1 was indicated as the rate of pain relief [ 30 ]. Pain relief rate ≥ 50% was considered apparent relief [ 31 – 33 ]. Pain relief rate = (NRS 1 – NRS 2 )/NRS 1 * 100%. The primary outcome was the pain relief rate at 0.5 h, 1 h, and 2 h after administration and percentage of apparent relief. The secondary outcomes included whether additional analgesics were still needed after 2 h of medication; changes in participants' heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), and pulse oxygen saturation (SpO 2 ) at different times; and the occurrence of medication or injection related adverse effects such as nausea, vomiting, dizziness, respiratory depression, and needle-sickness, as well as the final destination of the participants. Statistics Based on the following parameters: two-sided alpha of 0.05, one-sided alpha of 0.10, SD of 2.8 units for the 0 to 10 NRS scale, and a minimum clinically significant difference of 1.3 units [ 22 , 23 ], we calculated that minimum of 196 subjects would be required for this study. To account for potential losses during follow-up, we ultimately included 200 subjects. Statistical analysis was performed using SPSS 25.0. Normally distributed data were expressed as mean ± standard deviation (x ± s), and group comparisons were made using two independent sample t-test. Non-normally distributed data were expressed as median [inter quartile range] and statistically analyzed using non-parametric tests. Categorical data were expressed as frequencies, component ratios, or percentages, and were subjected to chi-square tests. A P -value < 0.05 was considered to be statistically significant. Results Patient characteristics A total of 530 patients with acute pain were screened during the study period, 200 patients who fulfilled met the inclusion exclusion criteria were randomized. Following randomization, 100 patients were allocated to the hydromorphone group and 99 to the butorphanol group, with one participant lost to follow-up (Fig. 1 ). Baseline demographic and clinical characteristics were comparable between the two groups (Table 1 ). The cohort predominantly comprised male patients (63.3%), with the most frequently reported pain locations being abdominal (60.3%) and lumbar (30.6%) regions. Pain severity revealed that 28 patients (14.1%) experienced moderate pain (NRS 4–6) [ 3 ], whiles the majority, 171 patients (85.9%), presented with severe pain (NRS ≥ 7) [ 3 ] (Table 3 ). Table 1 Baseline characteristics Hydromorphone (n = 100) Butorphanol (n = 99) P -value Gender, n(%) 0.620 Male 65(65.0) 61(61.6) Female 35(35.0) 38(38.4) Age(years), mean ± SD 43.5 ± 15.5 44.7 ± 16.4 0.578 Weight(Kg), mean ± SD 65.9 ± 9.9 66.6 ± 10.5 0.644 NRS, median [IQR] 8[ 7 – 9 ] 8[ 7 – 8 ] 0.060 Pain location, n(%) 0.385 Abdomen 60(60.0) 60(60.6) Waist 33(33.0) 27(27.3) Others 7(7.0) 12(12.1) Pain intensity, n(%) 0.399 Moderate 12(12.0) 16(16.2) Severe 88(88.0) 83(83.8) Vital signs, mean ± SD HR (bpm) 79.6 ± 12.5 82.4 ± 15.8 0.170 MAP (mmHg) 102.3 ± 14.1 101.7 ± 14.4 0.772 RR (bpm) 19.8 ± 1.6 19.7 ± 1.4 0.807 SpO 2 (%) 98.4 ± 1.0 98.2 ± 1.3 0.230 NRS = numerical rating scale. HR = heart rate. RR = respiratory rate. MAP = mean arterial pressure. SpO 2 = pulse oxygen saturation. bpm = beats per minute. IQR = inter quartile range. SD = standard deviation Efficacy There was no significant difference in initial NRS between the two groups (8[ 7 – 9 ] vs 8[ 7 – 8 ], P > 0.05) (Table 1 ). The amount of change in NRS was significantly higher in the hydromorphone group than in the butorphanol group at 0.5 h, 1 h, and 2 h after medication ( P < 0.05) (Fig. 2 ), and the rate of pain relief in the hydromorphone group was also significantly higher than in the butorphanol group at 1 h and 2 h ( P < 0.05) (Table 2 ). Additionally, the percentage of apparent pain relief after 2 h of medication was higher in the hydromorphone group than in the butorphanol group (88.0% vs 69.7%, P < 0.01) (Table 2 ). Subsequently, we conducted a more in-depth stratified analysis to investigate the differences in analgesic effects between the two groups with different pain intensities (Table 3 and Fig. 3 ). There were no significant differences in pain relief rates, the amount of changes in NRS at 0.5 h, 1 h, and 2 h, and the percentage of apparent relief at 2 h between the two groups in patients with moderate pain ( P > 0.05). In contrast, among patients with severe pain, the amount of NRS change at 0.5h, 1h, and 2h, the rate of pain relief at 1h and 2h and, the percentage of apparent pain relief at 2 h after medication in the hydromorphone group were significantly higher than those in the butorphanol group ( P < 0.05). We further analyzed and compared the need for additional medication during the treatment process between the two groups. The results indicated that none of the patients in the hydromorphone group requested supplemental analgesic medication within the initial 2 h after treatment. In contrast, six patients (6.1%) in the butorphanol group with severe pain required an additional 1 mg of analgesic medication during the same time frame, demonstrating a statistically significant intergroup difference ( P < 0.05) (Table 2 , Table 3 ). Furthermore, an evaluation of patient final destination following treatment showed no significant differences between the two groups (Table 2 ). Table 2 Comparison of the changes in NRS, additional analgesics and patient destinations Hydromorphone (n = 100) Butorphanol (n = 99) P -value Pain relief rate, % 0.5h 38[22–50] 29[17–43] 0.081 1h 56[38–71] 44 [33–57] 0.013* 2h 67[56–78] 60 [43–71] 0.013* Apparent relief,n(%) 88(88.0) 69(69.7) 0.002** Additional analgesic, n(%) 0(0.0) 6(6.1) 0.014* Destination, n(%) 0.778 Return home 71(71.0) 67(67.7) Observed in emergency 19(19.0) 19(19.2) Admission 10(10.0) 13(13.1) NRS = numerical rating scale. * P < 0.05, ** P < 0.01 Table 3 Stratified analysis of the effects of hydromorphone and butorphanol with moderate and severe pain Moderate pain Severe pain Hydromorphone (n = 12) Butorphanol (n = 16) P -value Hydromorphone (n = 88) Butorphanol (n = 83) P -value Pain relief rate, % 0.5h 33[ 21 – 40 ] 33 [ 17 – 40 ] 0.887 38[22–50] 29[14–43] 0.071 1h 45[33–67] 45[33–50] 0.493 56[39–71] 44 [33–57] 0.020* 2h 60 [50–77] 60[50–67] 1.000 67[56–78] 57[43–71] 0.010* Apparent relief, n(%) 10(83.3) 13(81.3) 1.000 78(88.6) 56(67.5) 0.001** Adverse reaction, n(%) 0.791 0.835 Yes 2(16.7) 1(6.3) 17(19.3) 15(18.1) No 10(83.3) 15(93.8) 71(80.7) 68(81.9) Additional analgesics, n(%) 0 6(7.2) 0.031* NRS = numerical rating scale. * P < 0.05, ** P < 0.01 Safety The overall incidence of adverse reactions was 19.0% in the hydromorphone group and 16.2% in the butorphanol group, with moderate pain (16.7% vs. 6.3%) and severe pain (19.3% vs. 18.1%) (Table 3 and Table 4 ). However, statistical analysis revealed that these differences were not significant ( P > 0.05). Commonly reported adverse reactions in both groups included dizziness or headache (64.0% vs 55.0%), nausea or vomiting (20.0% vs 35.0%), injection site pain (12.0% vs 10.0%), and hypotension (4.0% vs 0.0%), with no instances of respiratory depression observed in either group (Table 4 ). Furthermore, no significant differences were detected between the two groups in terms of their effects on HR, RR, MAP, or SpO 2 (Fig. 4 ). Table 4 Incidence of adverse reactions Hydromorphone (n = 100) Butorphanol (n = 99) P -value Adverse reaction, n(%) 0.599 Yes 19(19.0) 16(16.2) No 81(81.0) 83(83.8) Types of adverse reactions, n(%) Dizziness or headaches 16(64.0) 11(55.0) Nausea or vomiting 5(20.0) 7(35.0) Injection site pain 3(12.0) 2(10.0) Hypotension 1(4.0) 0(0.0) Discussion This randomized controlled trial investigated the efficacy of emergency analgesia for acute pain management, comparing intramuscular administration of hydromorphone and butorphanol. Both agents demonstrated significant pain relief. However, hydromorphone exhibited a more rapid onset of action and superior analgesic potency relative to butorphanol, particularly in cases of severe pain. The safety profiles of both analgesics were comparable, with no significant differences in patient tolerance observed. Notably, hydromorphone administration was associated with a reduction in total opioid consumption. Previous studies have suggested that hydromorphone possesses favorable early analgesic properties [ 10 , 11 , 22 – 24 ], but others have reported no significant advantage in analgesic efficacy or safety when compared to alternative opioids (e.g. morphine, and oxycodone) [ 12 – 14 , 34 , 35 ]. Furthermore, a systematic review encompassing 24 studies concluded that hydromorphone does not exhibit superior analgesic efficacy or a reduced incidence of adverse effects relative to morphine [ 36 ]. Subsequent analysis revealed that these studies primarily focused on cancer-related pain and postoperative pain management. As the treatment of such conditions often requires sustained high plasma concentrations of analgesics to maintain prolonged pain relief, hydromorphone, as a short-acting opioid analgesic, may not fully demonstrate its potential advantages and therapeutic efficacy in these contexts. In other words, hydromorphone may not demonstrate significant superiority over other analgesics in the management of cancer-related and postoperative pain. In contrast, short-acting opioid analgesics are particularly advantageous for the treatment of acute pain, especially in the ED. However, when searching the data, we found a paucity of clinical studies examining the use of hydromorphone for acute pain management in the ED. This may be attributed to the challenges associated with the initial diagnosis of pain in ED, as the administration of analgesics prior to a definitive diagnosis, especially in patients with acute abdominal pain, is conventionally believed to potentially delay accurate diagnosis [ 37 , 38 ]. At the same time, the high rate of patient loss to follow-up further complicates clinical research in ED. Our study found that approximately 70.0% of patients were discharged home after emergency treatment, while only 10.0% required hospital admission for further treatment, with incomplete data often available for non-admitted patients. Multiple clinical trials investigating acute pain management in ED have demonstrated the superior analgesic efficacy of hydromorphone compared to acetaminophen, morphine, or lidocaine [ 10 , 22 – 24 ]. We also found that both hydromorphone and butorphanol significantly relieved patients' pain, with intramuscular injection of 1 mg hydromorphone achieving 66.7% pain relief within two hours, surpassing the 60.0% efficacy observed with butorphanol. Furthermore, 88.0% of patients in the hydromorphone group reported apparent pain relief, compared to 69.7% in the butorphanol group. However, stratified analysis revealed that this advantage was only in patients presenting with severe pain. Additionally, in the early stages of medication, the amount of changes in NRS was more favorable for hydromorphone than butorphanol, suggesting enhanced analgesic potency during the initial treatment period. Chang AK et al. [ 39 ] reported that 55.00% of patients achieved pain relief with only 1 mg of hydromorphone injections, while 45.0% required additional doses exceeding 1 mg. In contrast, our findings indicate that 88.0% of patients experienced significant pain relief following a single 1 mg hydromorphone injection without requiring supplemental analgesics. This difference may be attributed to methodological differences in assessment timing: Chang AK et al. [ 39 ] evaluated the need for additional analgesics at 30 min intervals, whereas our study employed a 2 h assessment. Because previous studies have found that intravenous hydromorphone reaches peak plasma concentrations at approximately 20 min, achieves maximal analgesic efficacy by 30 min, and maintains therapeutic effects for up to 2 h [ 40 ]. Therefore, we chose 2 h as the time point. Research has confirmed that excessive or repeated use of opioid or non-opioid analgesics can increase the risk of adverse drug reactions and potential addiction [ 9 , 29 , 39 , 41 ], potentially leading to analgesic shortages in critical clinical situations [ 9 , 29 , 39 , 41 ]. Furthermore, doctors or nurses tend to favor low-dose hydromorphone (1 mg) over higher-dose morphine (10 mg) when both options are available for pain management [ 42 ]. In clinical practice, the administration of opioid analgesics necessitates heightened vigilance regarding potential severe adverse effects, particularly respiratory depression, which poses a significant risk in critically ill patients and may increase mortality rates [ 27 ]. While previous some studies have reported that hydromorphone can cause significant reductions in SpO 2 , HR, or blood pressure [ 39 ], our research revealed that neither hydromorphone nor butorphanol significantly change in HR, RR, or SpO 2 , with the exception of a single case of hypotension attributed to hydromorphone. Additionally, the most frequently observed adverse reactions to both hydromorphone and butorphanol were dizziness or nausea, consistent with prior reports [ 11 , 24 , 39 ]. These results support the conclusion that hydromorphone is a safe option for emergency analgesia. Limitations Limitations of this study mainly include: First, the investigation was conducted as a single-center clinical trial within the ED of a single institution. Given that hydromorphone is not universally available across all healthcare facilities, with morphine or meperidine remaining the preferred analgesics in most settings, the generalizability of these findings to broader institutional or clinical contexts remains uncertain. Furthermore, the reliability and stability of the observed outcomes necessitate validation through additional research. To address this limitation, a multi-center clinical study is being conducted to further evaluate the clinical efficacy and safety of profile of hydromorphone. Second, the study was restricted to a 2 h follow-up period, during which over 25.0% of patients continued to experience moderate to severe pain. The persistence of the observed clinical benefits with prolonged medication duration remains unclear, potentially introducing bias into the interpretation of the results. Conclusion In the ED, the application of hydromorphone or butorphanol can significantly alleviate patients' acute moderate to severe pain, thus improving their healthcare experience. Both agents demonstrate comparable rates of adverse events. However, comparative analysis reveals that hydromorphone exhibits superior analgesic efficacy and a more rapid onset of action relative to butorphanol. Consequently, hydromorphone exhibits greater clinical utility in the management of acute pain in the ED, especially in patients with severe pain. Declarations Acknowledgements The authors would like to sincerely thank all the doctors and nurses in the Emergency Department of the Third People's Hospital of Chengdu for their valuable contributions. Author contributions Huang YP, Peng XJ and Zhang BH analyzed and summarized the data and drafted the manuscript. Luo L and Dai H contributed to the study conception and design. Data collection was completed by Sun YF, Zhang JM and Yin J. Xiang T and Xiong SQ revised the manuscript in detail. All authors have read and agreed to the published version of the manuscript. Date availability The datasets used or analyzed during the current study are available from the corresponding author on reasonable request. Conflict of interests The authors declare that they have no conflict of interest. Ethical approval All procedures and protocols were conducted in accordance with the Declaration of Helsinki and approved by the Ethics Review Committee of the Third People's Hospital of Chengdu (Ethical approval number: 2023-S-153). Informed consent Written informed consent was obtained from all participating subjects. References Rogers MP, Kuo PC (2020) Pain as the fifth vital sign. J Am Coll Surg 231(5):601–602. https://doi.org/10.1016/j.jamcollsurg.2020.07.508 Xu KT, Morris JE, Piel C (2021) The utility of pain scale to assess verifiable vs non-verifiable pain in united states emergency departments. West J Emerg Med 22(2):156–162. https://doi.org/10.5811/westjem.2020.11.49030 The Critical Care Working Group of the Emergency Branch of the Chinese Medical Doctor Association (2023) Expert consensus on the management of analgesia, sedation and delirium in adults with emergency care in China. Chin J Emerg Med 32:1594–1609. https://doi.org/10.3760/cma.j.issn.1671-0282.2023.12.004 Mankelow J, Ryan C, Taylor P, Atkinson G, Martin D (2022) A systematic review and meta-analysis of the effects of biopsychosocial pain education upon health care professional pain attitudes, knowledge, behavior and patient outcomes. J Pain 23(1):1–24. https://doi.org/10.1016/j.jpain.2021.06.010 Gavriilidis P, De'Angelis N, Tobias A (2019) To use or not to use opioid analgesia for acute abdominal pain before definitive surgical diagnosis? A systematic review and network meta-analysis. J Clin Med Res 11(2):121–126. https://doi.org/10.14740/jocmr3690 Hachimi-Idrissi S, Dobias V, Hautz WE, Leach R, Sauter TC, Sforzi I, Coffey F (2020) Approaching acute pain in emergency settings; European Society for Emergency Medicine (EUSEM) guidelines-part 2: management and recommendations. Intern Emerg Med 15(7):1141–1155. https://doi.org/10.1007/s11739-020-02411-2 Yang BK, Storr CL, Trinkoff AM, Sohn M, Idzik SK, Mckinnon M (2019) National opioid prescribing trends in emergency departments by provider type: 2005–2015. Am J Emerg Med 37(8):1439–1445. https://doi.org/10.1016/j.ajem.2018.10.041 Bruera E (2018) Parenteral opioid shortage - treating pain during the opioid-overdose epidemic. N Engl J Med 379(7):601–603. https://doi.org/10.1056/NEJMp1807117 Connors NJ, Mazer-Amirshahi M, Motov S, Kim HK (2021) Relative addictive potential of opioid analgesic agents. Pain Manag 11(2):201–215. https://doi.org/10.2217/pmt-2020-0048 Meissner K, Dahan A, Olofsen E, Göpfert C, Blood J, Wieditz J, Kharasch ED (2023) Morphine and hydromorphone effects, side effects, and variability: a crossover study in human volunteers. Anesthesiology 139(1):16–34. https://doi.org/10.1097/ALN.0000000000004567 Zeng X, Zhu J, Li J, Chen C, Sang L, Liu M, Song L, Liu H (2024) Patient controlled subcutaneous analgesia of hydromorphone versus morphine to treat moderate and severe cancer pain: a randomized double-blind controlled trial. J Pain Symptom Manage 67(1):50–58. https://doi.org/10.1016/j. jpainsymman.2023.09.018 Rodrigues S, Shin D, Conway M, Smulski S, Trenker E, Shanthanna H, Vanniyasingam T, Thabane L, Paul J (2021) Hydromorphone versus morphine: a historical cohort study to evaluate the quality of postoperative analgesia. Can J Anesth 68(2):226–234. https://doi.org/10.1007/s12630-020-01849-4 Wehrfritz A, Senger AS, Just P, Albart M, Munchsmeier M, Ihmsen H, Schuttler J, Jeleazcov C (2022) Patient-controlled analgesia after cardiac surgery with median sternotomy: no advantages of hydromorphone when compared to morphine. J Cardiothorac Vasc Anesth 36(9):3587–3595. https://doi.org/10.1053/j.jvca.2022.04.051 Hiratsuka Y, Tagami K, Inoue A, Sato M, Matsuda Y, Kosugi K, Kubo E, Natsume M, Ishiki H, Arakawa S, Shimizu M, Yokomichi N, Chiu S, Shimoda M, Hirayama H, Nishijima K, Ouchi K, Shimoi T, Shigeno T, Yamaguchi T, Miyashita M, Morita T, Satomi E (2023) Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study. Support Care Cancer 31(11). https://doi.org/10.1007/s00520-023-08099-2 Felden L, Walter C, Harder S, Treede RD, Kayser H, Drover D, Geisslinger G, Lotsch J (2011) Comparative clinical effects of hydromorphone and morphine: a meta-analysis. Br J Anaesth 107(3):319–328. https://doi.org/10.1093/bja/aer232 Dinges HC, Schubert AK, Rucker G, Otto S, Waldmann S, Wiesmann T, Wulf H, Eberhart L, Gehling M (2022) Equianalgesic potency ratios of opioids used in patient-controlled analgesia: A network meta-analysis. J Opioid Manag 18(6):567–586. https://doi.org/10.5055/jom.2022.0751 Ershoff BD, Grogan T, Hong JC, Chia PA, Gabel E, Cannesson M (2020) Hydromorphone unit dose affects intraoperative dosing. Anesthesiology 132(5):981–991. https://doi.org/10.1097/ALN. 0000000000003176 Zanza C, Romenskaya T, Zuliani M, Piccolella F, Bottinelli M, Caputo G, Rocca E, Maconi A, Savioli G, Longhitano Y (2023) Acute traumatic pain in the emergency department. Diseases 11(1):45. https://doi.org/10.3390/diseases11010045 Keefe FJ (2022) Managing acute pain with opioids in the emergency department: A teachable moment? Am J Public Health 112(S1). https://doi.org/10.2105/AJPH.2022.306748 . S9-S11 Krzyszycha R, Goniewicz M, Goniewicz K, Pawłowski W, Wańkowicz P (2016) Meta-analysis of pain and stress in emergency department patients. Zdrowie Publiczne 126(4):165–169. https://doi.org/10.1515/pjph-2016-0034 Yong RJ, Mullins PM, Bhattacharyya N (2022) Prevalence of chronic pain among adults in the United States. Pain 163(2):e328–e332. https://doi.org/10.1097/j.pain.0000000000002291 Kolli S, Friedman BW, Latev A, Chang AK, Naeem F, Feliciano C, Afrifa F, Walker C, Izzo A, Irizarry E (2022) A randomized study of intravenous hydromorphone versus intravenous acetaminophen for older adult patients with acute severe pain. Ann Emerg Med 80(5):432–439. https://doi.org/10.1016/j.annemergmed.2022.06.016 Barnaby DP, Chertoff AE, Restivo AJ, Campbell CM, Pearlman S, White D, Bijur PE, Gallagher EJ (2019) Randomized controlled trial of intravenous acetaminophen versus intravenous hydromorphone for the treatment of acute pain in the emergency department. Ann Emerg Med 73(2):133–140. https://doi.org/10.1016/j.annemergmed.2018.06.019 Chinn E, Friedman BW, Naeem F, Irizarry E, Afrifa F, Zias E, Jones MP, Pearlman S, Chertoff A, Wollowitz A, Gallagher EJ (2019) Randomized trial of intravenous lidocaine versus hydromorphone for acute abdominal pain in the emergency department. Ann Emerg Med 74(2):233–240. https://doi.org/10.1016/j.annemergmed.2019.01.021 Kim HK, Connors NJ, Mazer-Amirshahi ME (2019) The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs. Expert Opin Drug Saf 18(6):465–475. https://doi.org/10.1080/14740338.2019.1613372 Wang B, Wang N, Zhao Z, Huang S, Shen Q, Liu S, Zhou P, Lu L, Qian G (2024) Effectiveness of butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial. Sci Rep 14(1):6639. https://doi.org/10.1038/s41598-024-56876-8 Fu Y, Liu Q, Nie H (2023) Efficacy of opioids for traumatic pain in the emergency department: a systematic review and Bayesian network meta-analysis. Front Pharmacol 14. https://doi.org/10.3389/fphar.2023.1209131 Singh RR, Kiran A, Sinha AN (2015) Elucidation of analgesic effects of butorphanol compared with morphine: A prospective cohort study. J Biol Life Sci 6(2):130. https://doi.org/10.5296/jbls.v6i2.7524 Chang AKMM, Bijur PEP, Lupow JBM, Gallagher EJM (2013) Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the 1 + 1 hydromorphone ttration protocol in treatment of acute, severe pain in the first hour of emergency department presentation. Ann Emerg Med 62(4):304–310. https://doi.org/10.1016/j.annemergmed.2013.02.023 Takenori A, Ikuhiro M, Shogo U, Hiroe K, Junji S, Yasutaka T, Hiroya K, Miki N (2016) Immediate pain relief effect of low level laser therapy for sports injuries: Randomized, double-blind placebo clinical trial. J Sci Med Sport 19(12):980–983. https://doi.org/10.1016/j.jsams.2016.03.006 Fallon M, Dierberger K, Leng M, Hall PS, Allende S, Sabar R, Verastegui E, Gordon D, Grant L, Lee R, Mcwillams K, Murray GD, Norris L, Reid C, Sande TA, Caraceni A, Kaasa S, Laird BJA (2022) An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer. Ann Oncol 33(12):1296–1303. https://doi.org/10.1016/j.annonc.2022.08.083 Kopsky DJ, Szadek KM, Schober P, Vrancken AFJE, Steegers MAH (2022) Study design characteristics and endpoints for enriched enrollment randomized withdrawal trials for chronic pain patients: A systematic review. J Pain Res 15:479–496. https://doi.org/10.2147/JPR.S334840 Deer T, Gilligan C, Falowski S, Desai M, Pilitsis J, Jameson J, Moeschler S, Heros R, Tavel E, Christopher A, Patterson D, Wahezi S, Weisbein J, Antony A, Funk R, Ibrahim M, Lim C, Wilson D, Fishell M, Scarfo K, Dickerson D, Braun E, Buchanan P, Levy RM, Miller N, Duncan J, Xu J, Candido K, Kreiner S, Fahey ME, Yue J (2023) Treatment of refractory low back pain using passive recharge burst in patients without options for corrective surgery: findings and results from the DISTINCT Study, a prospective randomized multicenter controlled trial. Neuromodulation 26(7):1387–1399. https://doi.org/10.1016/j.neurom.2023.07.009 Li Y, Ma J, Lu G, Dou Z, Knaggs R, Xia J, Zhao S, Dong S, Yang L (2021) Hydromorphone for cancer pain. Cochrane Database Syst Rev 8(8):D11108. https://doi.org/10.1002/14651858.CD011108.pub3 Shanthanna H, Paul J, Lovrics P, Vanniyasingam T, Devereaux PJ, Bhandari M, Thabane L (2019) Satisfactory analgesia with minimal emesis in day surgeries: a randomised controlled trial of morphine versus hydromorphone. Br J Anaesth 122(6):e107–e113. https://doi.org/10.1016/j.bja.2019.03.036 Spénard S, Gélinas C, Trottier D, Tremblay-Racine E, Kleiber F N (2021) Morphine or hydromorphone: which should be preferred? A systematic review. Arch Dis Child 106(10):1002–1009. https://doi.org/10.1136/archdischild-2020-319059 Wolfe JM, Lein DY, Lenkoski K, Smithline HA (2000) Analgesic administration to patients with an acute abdomen: a survey of emergency medicine physicians. Am J Emerg Med 18(3):250–253. https://doi.org/10.1016/s0735-6757(00)90114-1 Bromberg R, Goldman RD (2007) Does analgesia mask diagnosis of appendicitis among children? Can Fam Physician 53(1):39–41 Chang AK, Bijur PE, Holden L, Gallagher EJ (2016) Efficacy of an acute pain titration protocol driven by patient response to a simple query: Do you want more pain medication? Ann Emerg Med 67(5):565–572. https://doi.org/10.1016/j.annemergmed.2015.04.035 Coda B, Tanaka A, Jacobson RC, Donaldson G, Chapman CR (1997) Hydromorphone analgesia after intravenous bolus administration. Pain 71(1):41–48. https://doi.org/10.1016/s0304-3959(97)03336-8 Curry CS, Craig WY, Richard JM, Ward DS (2021) Increasing intraoperative hydromorphone does not decrease postoperative pain: a retrospective observational study. Br J Anaesth: BJA 126(3):e95–e97. https://doi.org/10.1016/j.bja.2020.11.026 Chang AK, Bijur PE, Meyer RH, Kenny MK, Solorzano C, Gallagher EJ (2006) Safety and efficacy of hydromorphone as an analgesic alternative to morphine in acute pain: a randomized clinical trial. Ann Emerg Med 48(2):164–172. https://doi.org/10.1016/j.annemergmed.2006.03.005 Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6831108","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471397818,"identity":"725c0ca5-8798-4e06-864d-5448b4039ded","order_by":0,"name":"Yongping Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYBACxgYIncDAwHzgwIcfpGlhSzw4s4cE24BaeIwPc7ARoZS5/ezBhz8q7uQZ3O75cJiBh0GeX+wAAYf15CUb85x5Vmxw5+yGwwUWDIYzZycQ0NKQYybN2HY4ccON3A2HZ/AwJBjcJqSl/435z5//QFpyHhzmYSNGy4wcMwbeBrAWBmK1vDGW5jl2OHHmnWMGwECWIOwXw/4cw48/ag4n9t1ufvzhww8beX5pQloaoAyFG2BKAr9yEJCHM2YQVjwKRsEoGAUjFAAAhE5P7n2l/oMAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-2394-1386","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yongping","middleName":"","lastName":"Huang","suffix":""},{"id":471397819,"identity":"f1aab2a4-bad6-4c2b-abf0-707cf76f53a2","order_by":1,"name":"Xiaojing Peng","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiaojing","middleName":"","lastName":"Peng","suffix":""},{"id":471397820,"identity":"b507059b-e25e-43d7-a676-94b0ed270019","order_by":2,"name":"Bihua Zhang","email":"","orcid":"","institution":"Shenzhen Hospital of Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Bihua","middleName":"","lastName":"Zhang","suffix":""},{"id":471397821,"identity":"33a57204-d4aa-4708-abd6-79c8c6a7e461","order_by":3,"name":"Li Luo","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Luo","suffix":""},{"id":471397822,"identity":"44cfc6d1-0fb8-4ef5-87b1-b4ee0c824f81","order_by":4,"name":"Yufang Sun","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yufang","middleName":"","lastName":"Sun","suffix":""},{"id":471397823,"identity":"a048c2aa-c38a-44f3-9f0a-3fc2901ee712","order_by":5,"name":"Hang Dai","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hang","middleName":"","lastName":"Dai","suffix":""},{"id":471397824,"identity":"cce705ae-b330-4979-99b9-a6622112c37b","order_by":6,"name":"Jimei Zhang","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jimei","middleName":"","lastName":"Zhang","suffix":""},{"id":471397825,"identity":"b030dfeb-5c37-4a34-903f-3af3bfe47153","order_by":7,"name":"Jia Yin","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jia","middleName":"","lastName":"Yin","suffix":""},{"id":471397826,"identity":"bfc73b4e-dd90-418d-9a80-056388f9d92b","order_by":8,"name":"Shiqiang Xiong","email":"","orcid":"","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shiqiang","middleName":"","lastName":"Xiong","suffix":""},{"id":471397827,"identity":"2e843d8b-9655-45bc-8381-91790d2d1d09","order_by":9,"name":"Tao Xiang","email":"","orcid":"https://orcid.org/0000-0002-5882-6521","institution":"Southwest Jiaotong University The Third Peoples Hospital of Chengdu: Chengdu Third People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Xiang","suffix":""}],"badges":[],"createdAt":"2025-06-05 16:54:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6831108/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6831108/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":85345154,"identity":"0c3bd100-b75e-4f30-bcdb-5bbaa0cc625a","added_by":"auto","created_at":"2025-06-25 01:57:06","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":73570,"visible":true,"origin":"","legend":"\u003cp\u003eConsolidated Standards of Reporting Trials diagram\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6831108/v1/8644b7b449267527bc3b4b72.jpg"},{"id":85345152,"identity":"112293f9-cc7c-460b-bbb2-06e9b1b2a090","added_by":"auto","created_at":"2025-06-25 01:57:06","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":32828,"visible":true,"origin":"","legend":"\u003cp\u003eThe amount of changes in NRS in the hydromorphone and butorphanol groups. NRS = numerical rating scale. \u003csup\u003e#\u003c/sup\u003e Pre-medication NRS subtracted from post-medication NRS at different times. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.05, \u003csup\u003e**\u003c/sup\u003e\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.01\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6831108/v1/b03b9aca44fe8ad5cbe3d71f.jpg"},{"id":85345736,"identity":"a87d1fb7-ee9b-4755-9712-148211457f61","added_by":"auto","created_at":"2025-06-25 02:05:06","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":57767,"visible":true,"origin":"","legend":"\u003cp\u003eA stratified analysis of changes in NRS was conducted between the hydromorphone and butorphanol groups at different pain intensity. Moderate pain (A), severe pain (B). NRS = numerical rating scale. \u003csup\u003e#\u003c/sup\u003e Pre-medication NRS subtracted from post-medication NRS at different times. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.05, \u003csup\u003e**\u003c/sup\u003e\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.01\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6831108/v1/5b66112f4f25f0908fa1c1e7.jpg"},{"id":85345168,"identity":"fe634377-36d9-474c-8f24-c24d27e35cd8","added_by":"auto","created_at":"2025-06-25 01:57:06","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":402122,"visible":true,"origin":"","legend":"\u003cp\u003eChanges in vital signs at different times in the hydromorphone and butorphanol groups (A-D). Heart rate (A), respiratory rate (B), mean arterial pressure (C), and pulse oxygen saturation (D). NRS = numerical rating scale. bpm = beats per minute.\u003csup\u003e*\u003c/sup\u003e\u003cem\u003eP \u003c/em\u003e\u0026lt; 0.05\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6831108/v1/3c14a541b70bd2bb243392c9.jpg"},{"id":87443534,"identity":"b6d14ece-dfda-44ea-b316-09fde84678d5","added_by":"auto","created_at":"2025-07-23 21:28:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1481426,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6831108/v1/77f1cbad-e91b-4440-b24f-fef31f89e4d8.pdf"}],"financialInterests":"","formattedTitle":"The Analgesic Efficacy and Safety of Intramuscular Hydromorphone versus Butorphanol for Acute Pain in the Emergency Department：A Randomized Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePain is recognized as the \"fifth vital sign\" [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], causing serious physical and psychological damage to patients, and is one of the major causes of disability [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Previous studies have confirmed that the administration of early analgesia does not hinder disease diagnosis; rather, it can effectively protect organ function, alleviate ischemic and hypoxic injury, and improve patient comfort and compliance with medical recommendations [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, analgesic drugs include non-steroidal anti-inflammatory drugs, acetaminophen, and opioids. Among these, both domestic and international guidelines recommend opioids as the preferred treatment for moderate to severe pain (Numerical Rating Scale, NRS\u0026thinsp;\u0026ge;\u0026thinsp;4) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Morphine, the most classic and widely used opioid analgesic, is increasingly associated with high rates of abuse and addiction, making the development of alternative drugs an urgent necessity [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Clinical studies have indicated that hydromorphone exhibits high bioavailability, with advantages of faster onset and longer duration of action compared to morphine [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, the incidence of adverse reactions is similar to or lower than morphine [\u003cspan additionalcitationids=\"CR11 CR12 CR13\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], making it a reasonable choice for the management of postoperative pain and cancer pain [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eStatistically, more than 50.0% of emergency department (ED) visits are primarily for pain complaints, and 60.0\u0026ndash;80.0% of ED patients experience pain [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Patients presenting to the ED with pain typically exhibit acute onset and severe intensity, often accompanied by ambiguous diagnosis. The selection of analgesic regimens for these patients differs significantly from chronic or postoperative pain. However, there remains a lack of evidence to support the safe, effective and timely selection of appropriate analgesic medications. Several clinical studies have shown that hydromorphone provides effective analgesia for acute pain in the ED [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Hydromorphone demonstrates an analgesic potency approximately 5\u0026ndash;10 times greater than that of morphine when administered at equianalgesic doses [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Consequently, achieving comparable analgesic efficacy to hydromorphone necessitates a substantial dose escalation of morphine, which directly correlates with an increased risk of opioid-induced adverse effects. Butorphanol is a safe and effective analgesic medication [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e], with an analgesic potency 3 to 8 times that of morphine [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], similar to that of hydromorphone. Therefore, this study aimed to evaluate and compare the analgesic efficacy and safety of hydromorphone and butorphanol in patients experiencing acute pain in the ED.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis was a prospective, randomized, parallel group, single-center trial conducted from September 2023 to January 2024 in the ED of the Third People's Hospital of Chengdu, Chengdu, China. Reporting was in accordance with the CONSORT statement. This study has been registered in the Chinese Clinical Trial Registry (Registration Number: ChiCTR2400088376).\u003c/p\u003e \u003cp\u003eTrained emergency physicians conducted a rigorous screening of patients in accordance with the inclusion exclusion criteria established by the investigators. The inclusion criteria comprised: 1) patients experiencing acute moderate to severe pain (NRS\u0026thinsp;\u0026ge;\u0026thinsp;4) requiring opioid analgesic treatment; 2) adult patients (aged\u0026thinsp;\u0026ge;\u0026thinsp;18 years); 3) obtained informed consent from the patient. The exclusion criteria included: 1) pregnant or lactating women; 2) individuals with a known allergy to opioids, including hydromorphone or butorphanol; 3) chronic opioid users or those with a history of opioid addiction; 4) presence of medical conditions that may affect the metabolism of opioid analgesics (severe hepatic or renal insufficiency); 5) systolic blood pressure less than 90 mmHg, heart rate less than 50 beats per minute (bpm), or oxygen saturation less than 90% on room air; 6) intoxication by alcohol or other drugs; 7) presence of symptoms of respiratory depression, suffering from acute or severe bronchial asthma; 8) presence or risk of progression to gastrointestinal obstruction, especially paralytic intestinal obstruction; 9) loss of hearing or vision, or any other condition that may significantly hinder data collection for the study; 10) communication deficits (e.g. psychiatric or neurological disorders or sedation); 11) opioid use within the previous 24 hours; 12) concurrent use of medications that may interact the study medications; 13) concurrently participated in any clinical trial.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRandomization\u003c/h3\u003e\n\u003cp\u003eRandomization was conducted using a computer-generated randomization table. Participants who met the inclusion and exclusion criteria and gave informed consent were randomly allocated to the hydromorphone or butorphanol groups by the researcher in a 1:1 ratio. The emergency physicians and the specialist nurse administering the injections were aware of the admission until after grouping. However, the patients and their legal representatives were blind to the grouping.\u003c/p\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003eAll participants received treatment via a \"1\u0026thinsp;+\u0026thinsp;1\" titration method, as previous studies have indicated that 1 mg\u0026thinsp;+\u0026thinsp;1 mg of hydromorphone yields an analgesic effect comparable to that of 2 mg, while potentially reducing the overall dosage of analgesic drugs [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The hydromorphone and butorphanol groups received intramuscular injections of 1 mg hydromorphone hydrochloride (pre-infused) (Yichang Human well Pharmaceutical Co., Ltd, Hubei, China) and 1 mg butorphanol tartrate (Jiangsu Hengrui Pharmaceutical Co., Ltd, Jiangsu, China), respectively. Two hours later, participants were queried regarding their need for additional analgesic medication. If the answer was yes, an additional 1 mg of the same medication was administered.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003ePain intensity was measured by the NRS, which is represented by an integer from 0\u0026ndash;10, with the side of 0 as no pain and 10 as the worst pain. The amount of NRS change was indicated as the pre-medication NRS (NRS\u003csub\u003e1\u003c/sub\u003e) subtracted from the post-medication NRS (NRS\u003csub\u003e2\u003c/sub\u003e), and the rate of NRS change relative to NRS\u003csub\u003e1\u003c/sub\u003e was indicated as the rate of pain relief [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Pain relief rate\u0026thinsp;\u0026ge;\u0026thinsp;50% was considered apparent relief [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePain relief rate = (NRS\u003csub\u003e1\u003c/sub\u003e\u0026ndash; NRS\u003csub\u003e2\u003c/sub\u003e)/NRS\u003csub\u003e1\u003c/sub\u003e * 100%.\u003c/p\u003e \u003cp\u003eThe primary outcome was the pain relief rate at 0.5 h, 1 h, and 2 h after administration and percentage of apparent relief. The secondary outcomes included whether additional analgesics were still needed after 2 h of medication; changes in participants' heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), and pulse oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e) at different times; and the occurrence of medication or injection related adverse effects such as nausea, vomiting, dizziness, respiratory depression, and needle-sickness, as well as the final destination of the participants.\u003c/p\u003e\n\u003ch3\u003eStatistics\u003c/h3\u003e\n\u003cp\u003eBased on the following parameters: two-sided alpha of 0.05, one-sided alpha of 0.10, SD of 2.8 units for the 0 to 10 NRS scale, and a minimum clinically significant difference of 1.3 units [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], we calculated that minimum of 196 subjects would be required for this study. To account for potential losses during follow-up, we ultimately included 200 subjects.\u003c/p\u003e \u003cp\u003eStatistical analysis was performed using SPSS 25.0. Normally distributed data were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), and group comparisons were made using two independent sample t-test. Non-normally distributed data were expressed as median [inter quartile range] and statistically analyzed using non-parametric tests. Categorical data were expressed as frequencies, component ratios, or percentages, and were subjected to chi-square tests. A \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered to be statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 530 patients with acute pain were screened during the study period, 200 patients who fulfilled met the inclusion exclusion criteria were randomized. Following randomization, 100 patients were allocated to the hydromorphone group and 99 to the butorphanol group, with one participant lost to follow-up (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Baseline demographic and clinical characteristics were comparable between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The cohort predominantly comprised male patients (63.3%), with the most frequently reported pain locations being abdominal (60.3%) and lumbar (30.6%) regions. Pain severity revealed that 28 patients (14.1%) experienced moderate pain (NRS 4\u0026ndash;6) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], whiles the majority, 171 patients (85.9%), presented with severe pain (NRS\u0026thinsp;\u0026ge;\u0026thinsp;7) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydromorphone (n\u0026thinsp;=\u0026thinsp;100)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eButorphanol (n\u0026thinsp;=\u0026thinsp;99)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGender, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65(65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61(61.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35(35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38(38.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge(years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43.5\u0026thinsp;\u0026plusmn;\u0026thinsp;15.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44.7\u0026thinsp;\u0026plusmn;\u0026thinsp;16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.578\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eWeight(Kg), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65.9\u0026thinsp;\u0026plusmn;\u0026thinsp;9.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.644\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eNRS, median [IQR]\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.060\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePain location, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.385\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAbdomen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60(60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60(60.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWaist\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33(33.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27(27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOthers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7(7.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12(12.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePain intensity, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.399\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12(12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88(88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83(83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVital signs, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.4\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e102.3\u0026thinsp;\u0026plusmn;\u0026thinsp;14.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e101.7\u0026thinsp;\u0026plusmn;\u0026thinsp;14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.807\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e98.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eNRS\u0026thinsp;=\u0026thinsp;numerical rating scale. HR\u0026thinsp;=\u0026thinsp;heart rate. RR\u0026thinsp;=\u0026thinsp;respiratory rate. MAP\u0026thinsp;=\u0026thinsp;mean arterial pressure. SpO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;pulse oxygen saturation. bpm\u0026thinsp;=\u0026thinsp;beats per minute. IQR\u0026thinsp;=\u0026thinsp;inter quartile range. SD\u0026thinsp;=\u0026thinsp;standard deviation\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEfficacy\u003c/h3\u003e\n\u003cp\u003eThere was no significant difference in initial NRS between the two groups (8[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] vs 8[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The amount of change in NRS was significantly higher in the hydromorphone group than in the butorphanol group at 0.5 h, 1 h, and 2 h after medication (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and the rate of pain relief in the hydromorphone group was also significantly higher than in the butorphanol group at 1 h and 2 h (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Additionally, the percentage of apparent pain relief after 2 h of medication was higher in the hydromorphone group than in the butorphanol group (88.0% vs 69.7%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSubsequently, we conducted a more in-depth stratified analysis to investigate the differences in analgesic effects between the two groups with different pain intensities (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). There were no significant differences in pain relief rates, the amount of changes in NRS at 0.5 h, 1 h, and 2 h, and the percentage of apparent relief at 2 h between the two groups in patients with moderate pain (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In contrast, among patients with severe pain, the amount of NRS change at 0.5h, 1h, and 2h, the rate of pain relief at 1h and 2h and, the percentage of apparent pain relief at 2 h after medication in the hydromorphone group were significantly higher than those in the butorphanol group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eWe further analyzed and compared the need for additional medication during the treatment process between the two groups. The results indicated that none of the patients in the hydromorphone group requested supplemental analgesic medication within the initial 2 h after treatment. In contrast, six patients (6.1%) in the butorphanol group with severe pain required an additional 1 mg of analgesic medication during the same time frame, demonstrating a statistically significant intergroup difference (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Furthermore, an evaluation of patient final destination following treatment showed no significant differences between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of the changes in NRS, additional analgesics and patient destinations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydromorphone (n\u0026thinsp;=\u0026thinsp;100)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eButorphanol (n\u0026thinsp;=\u0026thinsp;99)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain relief rate, %\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.5h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38[22\u0026ndash;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29[17\u0026ndash;43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56[38\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44 [33\u0026ndash;57]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67[56\u0026ndash;78]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60 [43\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eApparent relief,n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88(88.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e69(69.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdditional analgesic, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6(6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.014*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDestination, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReturn home\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71(71.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67(67.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObserved in emergency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19(19.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eNRS\u0026thinsp;=\u0026thinsp;numerical rating scale. *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eStratified analysis of the effects of hydromorphone and butorphanol with moderate and severe pain\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eModerate pain\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eSevere pain\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydromorphone (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eButorphanol (n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eHydromorphone (n\u0026thinsp;=\u0026thinsp;88)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eButorphanol (n\u0026thinsp;=\u0026thinsp;83)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain relief rate, %\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0.5h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e33[\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33 [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26 CR27 CR28 CR29 CR30 CR31 CR32 CR33 CR34 CR35 CR36 CR37 CR38 CR39\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.887\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e38[22\u0026ndash;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29[14\u0026ndash;43]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45[33\u0026ndash;67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45[33\u0026ndash;50]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.493\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56[39\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44 [33\u0026ndash;57]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.020*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60 [50\u0026ndash;77]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e60[50\u0026ndash;67]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e67[56\u0026ndash;78]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e57[43\u0026ndash;71]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.010*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eApparent relief, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(81.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e78(88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56(67.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.001**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdverse reaction, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.791\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.835\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2(16.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1(6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17(19.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e15(18.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10(83.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(93.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e71(80.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e68(81.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdditional analgesics, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6(7.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.031*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"8\"\u003eNRS\u0026thinsp;=\u0026thinsp;numerical rating scale. *\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, **\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eSafety\u003c/h2\u003e \u003cp\u003eThe overall incidence of adverse reactions was 19.0% in the hydromorphone group and 16.2% in the butorphanol group, with moderate pain (16.7% vs. 6.3%) and severe pain (19.3% vs. 18.1%) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). However, statistical analysis revealed that these differences were not significant (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Commonly reported adverse reactions in both groups included dizziness or headache (64.0% vs 55.0%), nausea or vomiting (20.0% vs 35.0%), injection site pain (12.0% vs 10.0%), and hypotension (4.0% vs 0.0%), with no instances of respiratory depression observed in either group (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Furthermore, no significant differences were detected between the two groups in terms of their effects on HR, RR, MAP, or SpO\u003csub\u003e2\u003c/sub\u003e (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIncidence of adverse reactions\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHydromorphone (n\u0026thinsp;=\u0026thinsp;100)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eButorphanol (n\u0026thinsp;=\u0026thinsp;99)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdverse reaction, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19(19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16(16.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e81(81.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e83(83.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTypes of adverse reactions, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDizziness or headaches\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16(64.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11(55.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNausea or vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5(20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7(35.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjection site pain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3(12.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2(10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1(4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0(0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis randomized controlled trial investigated the efficacy of emergency analgesia for acute pain management, comparing intramuscular administration of hydromorphone and butorphanol. Both agents demonstrated significant pain relief. However, hydromorphone exhibited a more rapid onset of action and superior analgesic potency relative to butorphanol, particularly in cases of severe pain. The safety profiles of both analgesics were comparable, with no significant differences in patient tolerance observed. Notably, hydromorphone administration was associated with a reduction in total opioid consumption.\u003c/p\u003e \u003cp\u003ePrevious studies have suggested that hydromorphone possesses favorable early analgesic properties [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], but others have reported no significant advantage in analgesic efficacy or safety when compared to alternative opioids (e.g. morphine, and oxycodone) [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Furthermore, a systematic review encompassing 24 studies concluded that hydromorphone does not exhibit superior analgesic efficacy or a reduced incidence of adverse effects relative to morphine [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. Subsequent analysis revealed that these studies primarily focused on cancer-related pain and postoperative pain management. As the treatment of such conditions often requires sustained high plasma concentrations of analgesics to maintain prolonged pain relief, hydromorphone, as a short-acting opioid analgesic, may not fully demonstrate its potential advantages and therapeutic efficacy in these contexts. In other words, hydromorphone may not demonstrate significant superiority over other analgesics in the management of cancer-related and postoperative pain. In contrast, short-acting opioid analgesics are particularly advantageous for the treatment of acute pain, especially in the ED. However, when searching the data, we found a paucity of clinical studies examining the use of hydromorphone for acute pain management in the ED. This may be attributed to the challenges associated with the initial diagnosis of pain in ED, as the administration of analgesics prior to a definitive diagnosis, especially in patients with acute abdominal pain, is conventionally believed to potentially delay accurate diagnosis [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e, \u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. At the same time, the high rate of patient loss to follow-up further complicates clinical research in ED. Our study found that approximately 70.0% of patients were discharged home after emergency treatment, while only 10.0% required hospital admission for further treatment, with incomplete data often available for non-admitted patients.\u003c/p\u003e \u003cp\u003eMultiple clinical trials investigating acute pain management in ED have demonstrated the superior analgesic efficacy of hydromorphone compared to acetaminophen, morphine, or lidocaine [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. We also found that both hydromorphone and butorphanol significantly relieved patients' pain, with intramuscular injection of 1 mg hydromorphone achieving 66.7% pain relief within two hours, surpassing the 60.0% efficacy observed with butorphanol. Furthermore, 88.0% of patients in the hydromorphone group reported apparent pain relief, compared to 69.7% in the butorphanol group. However, stratified analysis revealed that this advantage was only in patients presenting with severe pain. Additionally, in the early stages of medication, the amount of changes in NRS was more favorable for hydromorphone than butorphanol, suggesting enhanced analgesic potency during the initial treatment period.\u003c/p\u003e \u003cp\u003eChang AK et al. [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] reported that 55.00% of patients achieved pain relief with only 1 mg of hydromorphone injections, while 45.0% required additional doses exceeding 1 mg. In contrast, our findings indicate that 88.0% of patients experienced significant pain relief following a single 1 mg hydromorphone injection without requiring supplemental analgesics. This difference may be attributed to methodological differences in assessment timing: Chang AK et al. [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] evaluated the need for additional analgesics at 30 min intervals, whereas our study employed a 2 h assessment. Because previous studies have found that intravenous hydromorphone reaches peak plasma concentrations at approximately 20 min, achieves maximal analgesic efficacy by 30 min, and maintains therapeutic effects for up to 2 h [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Therefore, we chose 2 h as the time point. Research has confirmed that excessive or repeated use of opioid or non-opioid analgesics can increase the risk of adverse drug reactions and potential addiction [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e], potentially leading to analgesic shortages in critical clinical situations [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Furthermore, doctors or nurses tend to favor low-dose hydromorphone (1 mg) over higher-dose morphine (10 mg) when both options are available for pain management [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn clinical practice, the administration of opioid analgesics necessitates heightened vigilance regarding potential severe adverse effects, particularly respiratory depression, which poses a significant risk in critically ill patients and may increase mortality rates [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. While previous some studies have reported that hydromorphone can cause significant reductions in SpO\u003csub\u003e2\u003c/sub\u003e, HR, or blood pressure [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e], our research revealed that neither hydromorphone nor butorphanol significantly change in HR, RR, or SpO\u003csub\u003e2\u003c/sub\u003e, with the exception of a single case of hypotension attributed to hydromorphone. Additionally, the most frequently observed adverse reactions to both hydromorphone and butorphanol were dizziness or nausea, consistent with prior reports [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. These results support the conclusion that hydromorphone is a safe option for emergency analgesia.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eLimitations of this study mainly include: First, the investigation was conducted as a single-center clinical trial within the ED of a single institution. Given that hydromorphone is not universally available across all healthcare facilities, with morphine or meperidine remaining the preferred analgesics in most settings, the generalizability of these findings to broader institutional or clinical contexts remains uncertain. Furthermore, the reliability and stability of the observed outcomes necessitate validation through additional research. To address this limitation, a multi-center clinical study is being conducted to further evaluate the clinical efficacy and safety of profile of hydromorphone. Second, the study was restricted to a 2 h follow-up period, during which over 25.0% of patients continued to experience moderate to severe pain. The persistence of the observed clinical benefits with prolonged medication duration remains unclear, potentially introducing bias into the interpretation of the results.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the ED, the application of hydromorphone or butorphanol can significantly alleviate patients' acute moderate to severe pain, thus improving their healthcare experience. Both agents demonstrate comparable rates of adverse events. However, comparative analysis reveals that hydromorphone exhibits superior analgesic efficacy and a more rapid onset of action relative to butorphanol. Consequently, hydromorphone exhibits greater clinical utility in the management of acute pain in the ED, especially in patients with severe pain.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003eThe authors would like to sincerely thank all the doctors and nurses in the Emergency Department of the Third People\u0026apos;s Hospital of Chengdu for their valuable contributions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003eHuang YP, Peng XJ and Zhang BH analyzed and summarized the data and drafted the manuscript. Luo L and Dai H contributed to the study conception and design.\u0026nbsp;Data collection was completed by Sun YF, Zhang JM and Yin J. Xiang T and Xiong SQ revised the manuscript in detail. All authors have read and agreed to the published version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDate availability\u0026nbsp;\u003c/strong\u003eThe datasets used or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interests\u0026nbsp;\u003c/strong\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u0026nbsp;\u003c/strong\u003eAll procedures and protocols were conducted in accordance with the Declaration of Helsinki and approved by the Ethics Review Committee of the Third People\u0026apos;s Hospital of Chengdu (Ethical approval number: 2023-S-153).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from all participating subjects.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRogers MP, Kuo PC (2020) Pain as the fifth vital sign. J Am Coll Surg 231(5):601\u0026ndash;602. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jamcollsurg.2020.07.508\u003c/span\u003e\u003cspan address=\"10.1016/j.jamcollsurg.2020.07.508\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu KT, Morris JE, Piel C (2021) The utility of pain scale to assess verifiable vs non-verifiable pain in united states emergency departments. West J Emerg Med 22(2):156\u0026ndash;162. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5811/westjem.2020.11.49030\u003c/span\u003e\u003cspan address=\"10.5811/westjem.2020.11.49030\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThe Critical Care Working Group of the Emergency Branch of the Chinese Medical Doctor Association (2023) Expert consensus on the management of analgesia, sedation and delirium in adults with emergency care in China. Chin J Emerg Med 32:1594\u0026ndash;1609. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3760/cma.j.issn.1671-0282.2023.12.004\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.issn.1671-0282.2023.12.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMankelow J, Ryan C, Taylor P, Atkinson G, Martin D (2022) A systematic review and meta-analysis of the effects of biopsychosocial pain education upon health care professional pain attitudes, knowledge, behavior and patient outcomes. J Pain 23(1):1\u0026ndash;24. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jpain.2021.06.010\u003c/span\u003e\u003cspan address=\"10.1016/j.jpain.2021.06.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGavriilidis P, De'Angelis N, Tobias A (2019) To use or not to use opioid analgesia for acute abdominal pain before definitive surgical diagnosis? A systematic review and network meta-analysis. J Clin Med Res 11(2):121\u0026ndash;126. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.14740/jocmr3690\u003c/span\u003e\u003cspan address=\"10.14740/jocmr3690\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHachimi-Idrissi S, Dobias V, Hautz WE, Leach R, Sauter TC, Sforzi I, Coffey F (2020) Approaching acute pain in emergency settings; European Society for Emergency Medicine (EUSEM) guidelines-part 2: management and recommendations. Intern Emerg Med 15(7):1141\u0026ndash;1155. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11739-020-02411-2\u003c/span\u003e\u003cspan address=\"10.1007/s11739-020-02411-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang BK, Storr CL, Trinkoff AM, Sohn M, Idzik SK, Mckinnon M (2019) National opioid prescribing trends in emergency departments by provider type: 2005\u0026ndash;2015. Am J Emerg Med 37(8):1439\u0026ndash;1445. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajem.2018.10.041\u003c/span\u003e\u003cspan address=\"10.1016/j.ajem.2018.10.041\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBruera E (2018) Parenteral opioid shortage - treating pain during the opioid-overdose epidemic. N Engl J Med 379(7):601\u0026ndash;603. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMp1807117\u003c/span\u003e\u003cspan address=\"10.1056/NEJMp1807117\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConnors NJ, Mazer-Amirshahi M, Motov S, Kim HK (2021) Relative addictive potential of opioid analgesic agents. Pain Manag 11(2):201\u0026ndash;215. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2217/pmt-2020-0048\u003c/span\u003e\u003cspan address=\"10.2217/pmt-2020-0048\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeissner K, Dahan A, Olofsen E, G\u0026ouml;pfert C, Blood J, Wieditz J, Kharasch ED (2023) Morphine and hydromorphone effects, side effects, and variability: a crossover study in human volunteers. Anesthesiology 139(1):16\u0026ndash;34. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ALN.0000000000004567\u003c/span\u003e\u003cspan address=\"10.1097/ALN.0000000000004567\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng X, Zhu J, Li J, Chen C, Sang L, Liu M, Song L, Liu H (2024) Patient controlled subcutaneous analgesia of hydromorphone versus morphine to treat moderate and severe cancer pain: a randomized double-blind controlled trial. J Pain Symptom Manage 67(1):50\u0026ndash;58. https://doi.org/10.1016/j. jpainsymman.2023.09.018\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodrigues S, Shin D, Conway M, Smulski S, Trenker E, Shanthanna H, Vanniyasingam T, Thabane L, Paul J (2021) Hydromorphone versus morphine: a historical cohort study to evaluate the quality of postoperative analgesia. Can J Anesth 68(2):226\u0026ndash;234. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s12630-020-01849-4\u003c/span\u003e\u003cspan address=\"10.1007/s12630-020-01849-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWehrfritz A, Senger AS, Just P, Albart M, Munchsmeier M, Ihmsen H, Schuttler J, Jeleazcov C (2022) Patient-controlled analgesia after cardiac surgery with median sternotomy: no advantages of hydromorphone when compared to morphine. J Cardiothorac Vasc Anesth 36(9):3587\u0026ndash;3595. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/j.jvca.2022.04.051\u003c/span\u003e\u003cspan address=\"10.1053/j.jvca.2022.04.051\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHiratsuka Y, Tagami K, Inoue A, Sato M, Matsuda Y, Kosugi K, Kubo E, Natsume M, Ishiki H, Arakawa S, Shimizu M, Yokomichi N, Chiu S, Shimoda M, Hirayama H, Nishijima K, Ouchi K, Shimoi T, Shigeno T, Yamaguchi T, Miyashita M, Morita T, Satomi E (2023) Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study. Support Care Cancer 31(11). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00520-023-08099-2\u003c/span\u003e\u003cspan address=\"10.1007/s00520-023-08099-2\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFelden L, Walter C, Harder S, Treede RD, Kayser H, Drover D, Geisslinger G, Lotsch J (2011) Comparative clinical effects of hydromorphone and morphine: a meta-analysis. Br J Anaesth 107(3):319\u0026ndash;328. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1093/bja/aer232\u003c/span\u003e\u003cspan address=\"10.1093/bja/aer232\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDinges HC, Schubert AK, Rucker G, Otto S, Waldmann S, Wiesmann T, Wulf H, Eberhart L, Gehling M (2022) Equianalgesic potency ratios of opioids used in patient-controlled analgesia: A network meta-analysis. J Opioid Manag 18(6):567\u0026ndash;586. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5055/jom.2022.0751\u003c/span\u003e\u003cspan address=\"10.5055/jom.2022.0751\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eErshoff BD, Grogan T, Hong JC, Chia PA, Gabel E, Cannesson M (2020) Hydromorphone unit dose affects intraoperative dosing. Anesthesiology 132(5):981\u0026ndash;991. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/ALN. 0000000000003176\u003c/span\u003e\u003cspan address=\"10.1097/ALN. 0000000000003176\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZanza C, Romenskaya T, Zuliani M, Piccolella F, Bottinelli M, Caputo G, Rocca E, Maconi A, Savioli G, Longhitano Y (2023) Acute traumatic pain in the emergency department. Diseases 11(1):45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/diseases11010045\u003c/span\u003e\u003cspan address=\"10.3390/diseases11010045\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeefe FJ (2022) Managing acute pain with opioids in the emergency department: A teachable moment? Am J Public Health 112(S1). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2105/AJPH.2022.306748\u003c/span\u003e\u003cspan address=\"10.2105/AJPH.2022.306748\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. S9-S11\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrzyszycha R, Goniewicz M, Goniewicz K, Pawłowski W, Wańkowicz P (2016) Meta-analysis of pain and stress in emergency department patients. Zdrowie Publiczne 126(4):165\u0026ndash;169. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1515/pjph-2016-0034\u003c/span\u003e\u003cspan address=\"10.1515/pjph-2016-0034\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYong RJ, Mullins PM, Bhattacharyya N (2022) Prevalence of chronic pain among adults in the United States. Pain 163(2):e328\u0026ndash;e332. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/j.pain.0000000000002291\u003c/span\u003e\u003cspan address=\"10.1097/j.pain.0000000000002291\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKolli S, Friedman BW, Latev A, Chang AK, Naeem F, Feliciano C, Afrifa F, Walker C, Izzo A, Irizarry E (2022) A randomized study of intravenous hydromorphone versus intravenous acetaminophen for older adult patients with acute severe pain. Ann Emerg Med 80(5):432\u0026ndash;439. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annemergmed.2022.06.016\u003c/span\u003e\u003cspan address=\"10.1016/j.annemergmed.2022.06.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarnaby DP, Chertoff AE, Restivo AJ, Campbell CM, Pearlman S, White D, Bijur PE, Gallagher EJ (2019) Randomized controlled trial of intravenous acetaminophen versus intravenous hydromorphone for the treatment of acute pain in the emergency department. Ann Emerg Med 73(2):133\u0026ndash;140. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annemergmed.2018.06.019\u003c/span\u003e\u003cspan address=\"10.1016/j.annemergmed.2018.06.019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChinn E, Friedman BW, Naeem F, Irizarry E, Afrifa F, Zias E, Jones MP, Pearlman S, Chertoff A, Wollowitz A, Gallagher EJ (2019) Randomized trial of intravenous lidocaine versus hydromorphone for acute abdominal pain in the emergency department. Ann Emerg Med 74(2):233\u0026ndash;240. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annemergmed.2019.01.021\u003c/span\u003e\u003cspan address=\"10.1016/j.annemergmed.2019.01.021\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim HK, Connors NJ, Mazer-Amirshahi ME (2019) The role of take-home naloxone in the epidemic of opioid overdose involving illicitly manufactured fentanyl and its analogs. Expert Opin Drug Saf 18(6):465\u0026ndash;475. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/14740338.2019.1613372\u003c/span\u003e\u003cspan address=\"10.1080/14740338.2019.1613372\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang B, Wang N, Zhao Z, Huang S, Shen Q, Liu S, Zhou P, Lu L, Qian G (2024) Effectiveness of butorphanol in alleviating intra- and post-operative visceral pain following microwave ablation for hepatic tumor: a dual-central, randomized, controlled trial. Sci Rep 14(1):6639. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-024-56876-8\u003c/span\u003e\u003cspan address=\"10.1038/s41598-024-56876-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFu Y, Liu Q, Nie H (2023) Efficacy of opioids for traumatic pain in the emergency department: a systematic review and Bayesian network meta-analysis. Front Pharmacol 14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fphar.2023.1209131\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2023.1209131\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSingh RR, Kiran A, Sinha AN (2015) Elucidation of analgesic effects of butorphanol compared with morphine: A prospective cohort study. J Biol Life Sci 6(2):130. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.5296/jbls.v6i2.7524\u003c/span\u003e\u003cspan address=\"10.5296/jbls.v6i2.7524\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang AKMM, Bijur PEP, Lupow JBM, Gallagher EJM (2013) Randomized clinical trial of the 2 mg hydromorphone bolus protocol versus the 1\u0026thinsp;+\u0026thinsp;1 hydromorphone ttration protocol in treatment of acute, severe pain in the first hour of emergency department presentation. Ann Emerg Med 62(4):304\u0026ndash;310. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annemergmed.2013.02.023\u003c/span\u003e\u003cspan address=\"10.1016/j.annemergmed.2013.02.023\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakenori A, Ikuhiro M, Shogo U, Hiroe K, Junji S, Yasutaka T, Hiroya K, Miki N (2016) Immediate pain relief effect of low level laser therapy for sports injuries: Randomized, double-blind placebo clinical trial. J Sci Med Sport 19(12):980\u0026ndash;983. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jsams.2016.03.006\u003c/span\u003e\u003cspan address=\"10.1016/j.jsams.2016.03.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFallon M, Dierberger K, Leng M, Hall PS, Allende S, Sabar R, Verastegui E, Gordon D, Grant L, Lee R, Mcwillams K, Murray GD, Norris L, Reid C, Sande TA, Caraceni A, Kaasa S, Laird BJA (2022) An international, open-label, randomised trial comparing a two-step approach versus the standard three-step approach of the WHO analgesic ladder in patients with cancer. Ann Oncol 33(12):1296\u0026ndash;1303. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annonc.2022.08.083\u003c/span\u003e\u003cspan address=\"10.1016/j.annonc.2022.08.083\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKopsky DJ, Szadek KM, Schober P, Vrancken AFJE, Steegers MAH (2022) Study design characteristics and endpoints for enriched enrollment randomized withdrawal trials for chronic pain patients: A systematic review. J Pain Res 15:479\u0026ndash;496. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2147/JPR.S334840\u003c/span\u003e\u003cspan address=\"10.2147/JPR.S334840\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDeer T, Gilligan C, Falowski S, Desai M, Pilitsis J, Jameson J, Moeschler S, Heros R, Tavel E, Christopher A, Patterson D, Wahezi S, Weisbein J, Antony A, Funk R, Ibrahim M, Lim C, Wilson D, Fishell M, Scarfo K, Dickerson D, Braun E, Buchanan P, Levy RM, Miller N, Duncan J, Xu J, Candido K, Kreiner S, Fahey ME, Yue J (2023) Treatment of refractory low back pain using passive recharge burst in patients without options for corrective surgery: findings and results from the DISTINCT Study, a prospective randomized multicenter controlled trial. Neuromodulation 26(7):1387\u0026ndash;1399. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.neurom.2023.07.009\u003c/span\u003e\u003cspan address=\"10.1016/j.neurom.2023.07.009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Ma J, Lu G, Dou Z, Knaggs R, Xia J, Zhao S, Dong S, Yang L (2021) Hydromorphone for cancer pain. Cochrane Database Syst Rev 8(8):D11108. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/14651858.CD011108.pub3\u003c/span\u003e\u003cspan address=\"10.1002/14651858.CD011108.pub3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShanthanna H, Paul J, Lovrics P, Vanniyasingam T, Devereaux PJ, Bhandari M, Thabane L (2019) Satisfactory analgesia with minimal emesis in day surgeries: a randomised controlled trial of morphine versus hydromorphone. Br J Anaesth 122(6):e107\u0026ndash;e113. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bja.2019.03.036\u003c/span\u003e\u003cspan address=\"10.1016/j.bja.2019.03.036\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSp\u0026eacute;nard S, G\u0026eacute;linas C, Trottier D, Tremblay-Racine E, Kleiber F N (2021) Morphine or hydromorphone: which should be preferred? A systematic review. Arch Dis Child 106(10):1002\u0026ndash;1009. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/archdischild-2020-319059\u003c/span\u003e\u003cspan address=\"10.1136/archdischild-2020-319059\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWolfe JM, Lein DY, Lenkoski K, Smithline HA (2000) Analgesic administration to patients with an acute abdomen: a survey of emergency medicine physicians. Am J Emerg Med 18(3):250\u0026ndash;253. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0735-6757(00)90114-1\u003c/span\u003e\u003cspan address=\"10.1016/s0735-6757(00)90114-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBromberg R, Goldman RD (2007) Does analgesia mask diagnosis of appendicitis among children? Can Fam Physician 53(1):39\u0026ndash;41\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang AK, Bijur PE, Holden L, Gallagher EJ (2016) Efficacy of an acute pain titration protocol driven by patient response to a simple query: Do you want more pain medication? Ann Emerg Med 67(5):565\u0026ndash;572. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annemergmed.2015.04.035\u003c/span\u003e\u003cspan address=\"10.1016/j.annemergmed.2015.04.035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoda B, Tanaka A, Jacobson RC, Donaldson G, Chapman CR (1997) Hydromorphone analgesia after intravenous bolus administration. Pain 71(1):41\u0026ndash;48. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s0304-3959(97)03336-8\u003c/span\u003e\u003cspan address=\"10.1016/s0304-3959(97)03336-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCurry CS, Craig WY, Richard JM, Ward DS (2021) Increasing intraoperative hydromorphone does not decrease postoperative pain: a retrospective observational study. Br J Anaesth: BJA 126(3):e95\u0026ndash;e97. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.bja.2020.11.026\u003c/span\u003e\u003cspan address=\"10.1016/j.bja.2020.11.026\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChang AK, Bijur PE, Meyer RH, Kenny MK, Solorzano C, Gallagher EJ (2006) Safety and efficacy of hydromorphone as an analgesic alternative to morphine in acute pain: a randomized clinical trial. Ann Emerg Med 48(2):164\u0026ndash;172. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.annemergmed.2006.03.005\u003c/span\u003e\u003cspan address=\"10.1016/j.annemergmed.2006.03.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Hydromorphone, Butorphanol, Acute Pain, Emergency Department","lastPublishedDoi":"10.21203/rs.3.rs-6831108/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6831108/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAcute pain is a distressing encounter for most patients visiting the emergency department (ED), which severely affects their quality of life. Early analgesia is considered reasonable and necessary. However, the choice of analgesic drugs for acute pain still remains controversial. The aim of this study was to evaluate and compare the analgesic efficacy and safety of intramuscular hydromorphone and butorphanol in patients with acute pain in the ED. This randomized controlled clinical trial randomly divided 199 patients with moderate to severe acute pain into two groups in a 1:1 ratio, receiving intramuscular injections of 1 mg of hydromorphone and butorphanol, respectively. We compared the changes in pain intensity, as assessed by the Numerical Rating Scale (NRS), the requirement for supplemental analgesics, alterations in vital signs, incidence of adverse reactions, and the final destination of the patients in the two groups after the use of analgesic drugs. The results showed that, compared with the butorphanol group, the hydromorphone group showed more significant changes in NRS after administration, with higher pain relief rates at 1 h and 2 h, and a greater proportion of apparent relief at 2 h, especially in cases of severe pain (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, we observed a significant difference in the requirement for supplemental analgesics between the two groups 2 h after analgesia (0.0% vs 6.1%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There was no significant difference in the incidence of adverse reactions, the final destination of the patients, and the effects on heart rate, respiration, and oxygen saturation between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Common adverse reactions included dizziness or headache, nausea or vomiting, and injection pain, with one case of hypotension in the hydromorphone group. Our findings showed that both hydromorphone and butorphanol could effectively alleviate moderate to severe acute pain in the ED, and that the incidence of adverse reactions was similar. Notably, hydromorphone demonstrates superior analgesic efficacy compared to butorphanol, especially in patients with severe pain.\u003c/p\u003e \u003cp\u003eThis study has been registered in the Chinese Clinical Trial Registry (Registration Number: ChiCTR2400088376, Date: 2024-08-16, retrospectively registered)\u003c/p\u003e","manuscriptTitle":"The Analgesic Efficacy and Safety of Intramuscular Hydromorphone versus Butorphanol for Acute Pain in the Emergency Department：A Randomized Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-25 01:57:01","doi":"10.21203/rs.3.rs-6831108/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3bd218f9-c16f-44c8-ba17-b9ff13f35b78","owner":[],"postedDate":"June 25th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-07-23T21:20:40+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-25 01:57:01","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6831108","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6831108","identity":"rs-6831108","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}