Emergency (****); * (*): *-* This open-access article distributed under the terms of the Creative Commons Attribution Noncommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 99 Emergency (2015); 3 (3): 99-102 ORIGINAL RESEARCH Comparison of the Analgesic Effect of Intravenous Acetaminophen and Mor- phine Sulfate in Rib Fracture; a Randomized Double-Blind Clinical Trial Mehrdad Esmailian, Roshanak Moshiri*, Majid Zamani Department of Emergency Medicine, Al-Zahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran. *Corresponding Author: Roshanak Moshiri; Department of Emergency Medicine, Al-Zahra Hospital, Soffeh Blvd, Isfahan, Iran. Tel: +989136470851; Fax: +983117923445; Email: roshanak_moshiri86@yahoo.com Received: October 2014; Accepted: December 2014 Abstract Introduction: Rib fracture is one of the common causes of trauma disabilities in many events and the outcome of these patients are very extensive from temporary pain management to long-term significant disability. Control and management of the pain in such patients is one of the most important challenges in emergency departments. Thus, the aim of the present study was assessing the efficacy of IV acetaminophen in pain control of patients with rib fracture. Methods: In this double-blind clinical trial, 54 patients over 18 years of age, referred to two educational hospitals with rib fracture, were entered. Patients were randomly categorized in two groups of morphine sulfate (0.1 milligram per kilogram of body weight) and IV acetaminophen (1gram), as single-dose infused in 100 cc nor- mal saline. The pain severity was measured by numeric rating scale (NRS) on arrival and 30 minutes after drug administration. At least three scores reduction was reported as therapeutic success. Results: The mean and stand- ard deviation of patients’ age was 41.2 ± 14.1 years. There is no difference in gender (p=0.24) and age frequency (p=0.77) between groups. 30 minutes after drug administration the mean of pain severity were 5.5 ± 2.3 and 4.9 ± 1.7 in morphine and acetaminophen groups, respectively (p=0.23). Success rate in morphine and acetaminophen groups were 58.6% (95% Cl: 39.6-77.7) and 80% (95% Cl: 63.2-96.7), respectively, (p=0.09). Only 3 (5.6%) pa- tients had dizziness (p=0.44) and other effects were not seen in any of patients. Conclusion: The findings of the present study shows that intravenous acetaminophen and morphine have the same therapeutic value in relieving the pain of rib fracture. The success rate after 30 minutes drug administration were 80% and 58.6% in acetamino- phen and morphine groups, respectively. Presentation of side effects was similar in both groups. Key words: Acetaminophen; morphine; pain management; rib fractures Cite this article as: Esmailian M, Moshiri R, Zamani M. Comparison of the analgesic effect of intravenous acetaminophen and morphine sulfate in rib fracture; a randomized double-blind clinical trial. Emergency. 2015;3(3):99-102 Introduction: ib fracture is one of the common causes of trauma disabilities in many events such as traffic acci- dents, falling, occupational events, and inten- tional traumas (1-4). The outcome of these patients are very extensive from temporary pain management to long-term significant disability (1, 5, 6). Recent studies showed that prolonged pain in the chest wall of patients with rib fracture is more prevalent than previously thought, so that about 60% of them suffer from long- term pain and disability (1, 7). Patients with rib fracture have severe pain during breathing, speaking, coughing, and even body movements (3, 8). Thus, rapid pain con- trol has high priority to reduce the risk of pulmonary and systemic effects derived from the fracture such as decrease the respiratory effort which leads to hypoxia, atelectasis, and even pneumonia (9). The presence guidelines recommend using opioids for these patients, but tolerance, probability of breathing depression, and other side effects of these products limit their use. Con- sequently, the recent studies have searched to find alter- native or auxiliary treatments for decreasing such side effects. Intravenous (IV) acetaminophen, given the Food and Drug Administration confirmation in 2010 to man- agement of mild to moderate pains, is introduced as an auxiliary drug to treatment of moderate to severe pains. Although acetaminophen causes to relieve the pain sig- nificantly and improving opioid sparing effects, it does not reduce the adverse effects arise from opioids such as vomiting and nausea (10). However, recent researches have declared that with considering economical and clin- ical evidences, administration of IV acetaminophen R This open-access article distributed under the terms of the Creative Commons Attribution Noncommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Esmailian et al 100 should not be replaced by rectal or oral form unless for the patient cannot take it through these ways. But, rapid pain relief in trauma patients is an indication for IV ad- ministration based on which new protocols have been presented to introduce it as the first-line therapy in pa- tients with rib fracture (9). Another indication of this drug is the patients who cannot tolerate non-opioid an- algesic or antipyretic drugs (11). Since the pain is a main obstacle to examination, diagnosis, and treatment, con- trol and management of the pain in trauma patients, es- pecially in those with rib fracture, is one of the most im- portant challenges in emergency departments (12, 13). In all studies, non-opioid analgesic drugs are presented as a therapeutic indication in trauma cases and their IV form such as acetaminophen is more considered by phy- sicians in critical conditions (9). Nevertheless, these findings have not yet been published to show their ther- apeutic value. Thus, the aim of the present study was as- sessing the efficacy of IV acetaminophen in pain control of patients with rib fracture. Methods: Study design and setting In this double-blind study, 54 patients over 18 years of age, referred to two educational hospitals with rib frac- ture, were entered and randomly categorized in two groups. The protocol of the study was confirmed by Eth- ical Committee of Esfahan University of Medical Sciences and consent form given from patients. During the study, all researchers observed the declaration of Helsinki. The study was registered in Iranian registry of clinical trial (IRCT number: IRCT2015042812072N2). Inclusion cri- teria were presence one or two rib fractures confirmed by chest radiography, normal level of consciousness (Glasgow Coma scale of 15), weight range between 60- 100 kg, and pain score>4 centimeters based on Numeric Rating Scale (14). Excluded criteria were dissatisfaction toward participation, background pulmonary problems, history of taking analgesic or opioid drugs, addiction, history of liver or kidney diseases, head trauma, preg- nancy, history of taking monoamine oxidase, hypnotic and sedative drugs, as well as phenobarbital and isonia- zid, respiratory arrest on arrival and repeated vomiting and nausea. Patients was sequentially entered to the study and randomization was done using computer gen- erated sets of random allocations by a physician who did not involve in data gathering. All emergency staff in- cluded physicians, nurses, and researches were blind to the study. To ensure from blindness status, drugs were prepared as clear solutions in dark packs and only the person prepared them was aware from their content. Drug packs were coded and delivered to the drug pre- scribers. For doing the study as double blind, prepara- tion and injection of solutions as well as record of results were separately performed by three physicians who did not in touch with each other during the study. Infor- mation regarding IV drugs was accessible to therapeutic staff only when side effects or other clinical changes hap- pened to the patient. Patients were randomly catego- rized in two groups of morphine sulfate (0.1 milligram per kilogram of body weight, single-dose, and infused in 100 cc normal saline) and IV acetaminophen (1gram, single-dose, and infused in 100 cc normal saline). If the pain was not relieved after the first 30 minutes, a rescue dose of morphine was injected by a trained physician, drugDemographic data of studied patients based on administered Table 1: Variables Morphine acetaminophen P Age (Mean ± SD) 41.3 ± 14.1 41.0 ± 14.3 0.77* Weight (Kilogram) 65.4 ± 2.9 64.9 ± 3.0 0.76* Gender Female 10 (34.5) 5 (20.0) Male 19 (65.5) 20 (80.0) 0.24 Reason of Fracture Road traffic injury 21 (72.4) 12 (48.0) 0.25# Falling <5 meters 5 (17.2) 8 (32.0) Falling >5 meters 0 (0.0) 1 (4.0) Direct trauma 3 (10.3) 4 (16.0) Fracture frequency One 20 (71.4) 15 (60.0) 0.38* Two 8 (28.6) 10 (40.0) Co-injury No 25 (89.3) 25 (100.0) 0.49# Pneumothorax 2 (7.1) 0 (0.0) Hemothorax 1 (3.6) 0 (0.0) Baseline pain severity (Mean ± SD) 8.6 ±1.6 9.2 ± 1.3 0.19 *, Based on Mann-Whitney U test; #, Based on Fisher's exact test; SD: Standard deviation; Pain severity measured by numeric rating scale. This open-access article distributed under the terms of the Creative Commons Attribution Noncommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com 101 Emergency (2015); 3 (3): 99-102 considered as a treatment failure. The patient was con- tinuously monitored and vital signs (body temperature, blood pressure, respiratory rate, and pulse rate), level of arterial oxygen saturation, and drug side effects were recorded. The pain severity was measured by Numeric Rating Scale on arrival and 30 minutes after drug admin- istration. In addition, adverse effects of drugs including vomiting and nausea, respiratory depression (respira- tory rate less than 10 times per minute) and dizziness were evaluated. The primary outcome was defined as de- creasing the pain severity that at least three scores re- duction was reported as therapeutic success. Presenta- tion of side effects was also considered as secondary out- come. With considering 95% confidence interval (α=0.05), 80% power (β=0.2), and 1.65 standard devia- tion, with 1.3 centimeters reduction in pain severity be- cause of drug efficacy (d=1.3), the sample volume was calculated 25 subjects in each group (15). Statistical analysis Data was analyzed using SPSS 11.0 version. Pain severity was showed as mean and standard deviation as well as successful rate as frequency and percentage. Mann- Whitney U test was applied for assessing the difference of quantitative and rating factors, while Chi-square and Fisher’s exact tests for qualitative and numerical ones. P<0.05 was statistically significant. Results: 54 patients were entered, 29 cases in morphine group and 25 ones in acetaminophen, 39 (72.2%) cases was male. The mean and standard deviation of patients’ age was 41.2 ± 14.1 years. There is no difference in gender (p=0.24) and age frequency (p=0.77) between groups. Table 1 shows demographic data of the studied patients. Figure 1: The success rate of morphine and acetaminophen in reducing the pain of fractures. Data is shown as percentage with 95% confidence interval. The mean of pain severity on arrival were 8.6 ± 1.6 and 9.2 ± 1.3 in morphine and acetaminophen groups (p=0.19), respectively. 30 minutes after drug admin- istration this mean were 5.5 ± 2.3 and 4.9 ± 1.7 in mor- phine and acetaminophen groups, respectively (p=0.23). Success rate in morphine and acetaminophen groups were 58.6% (95% Cl: 39.6-77.7) and 80% (95% Cl: 63.2- 96.7), respectively, (p=0.09) (Figure 1). Only 3 (5.6%) patients had dizziness, 1 (3.5%) case in morphine group and 2 (8%) ones in acetaminophen (p=0.44). Other ef- fects were not seen in any of patients. Discussion: The findings of the present study showed that IV aceta- minophen and morphine have the same therapeutic value in relieving the pain of rib fracture. The pain of rib fracture may lead to exacerbate the lung injuries in chest trauma. Thus, administration of an analgesic and seda- tive drug has priority for these patients to improving the breathing, cough reflex, and respiratory physiotherapy (16). A review article in 2003 showed that presentation of a safe and effected method as a standard tool to de- crease the pain of rib fracture is complicated. Therefore, having enough knowledge regarding strong and weak points of each drug is essential for physician to choose the appropriate medication according to clinical condi- tions and patient’s status (17). Only one protocol in 2014 was published that considered the role of IV acetamino- phen in pain management of rib fracture (fracture in three ribs or more). This protocol, which was written based on the experiences of a therapeutic center, showed that IV acetaminophen is the first-line therapy in such patients (9). Similar to this guideline, the present study declared that using IV acetaminophen as single- dose can be an appropriate medication for patients with rib fracture. The success rate reported for this drug in this study was 80% that although did not have signifi- cant difference with morphine (58.6%), it had more im- provement rate, clinically. Even with supposing the same rate of success between the two drugs, using IV aceta- minophen because of clinical (lesser side effects and con- traindications) and economical (being cheaper) aspects are more rational. Also, in Tsang et al. study, it was de- clared that administration of IV acetaminophen with morphine causes to decrease the dose of morphine sig- nificantly, while both treatment protocols (acetamino- phen with morphine and morphine alone) have the same efficacy in reducing the pain (18). Moreover, Zare et al. showed that administration of IV acetaminophen and oral oxycodone have more efficacy than morphine in pain management, but they have more side effects in compare to morphine (19). Finally, no difference was seen between side effects of drugs in two groups, repre- sentative the safety of acetaminophen in relieving the pain of rib fracture. Paydar and colleagues also stated that during one year using IV acetaminophen in patients 58.6 80.0 0 20 40 60 80 100 120 Morphine Acetaminophen S u c c e s s r a te ( % ) Treatment This open-access article distributed under the terms of the Creative Commons Attribution Noncommercial 3.0 License (CC BY-NC 3.0). Copyright © 2015 Shahid Beheshti University of Medical Sciences. All rights reserved. Downloaded from: www.jemerg.com Esmailian et al 102 with rib fracture, no cases of hypotension, respiratory depression, loss of consciousness, and etc. was observed (9). Small sample size was the limitation of this study; if the number of patients was more, maybe the difference between success rate of acetaminophen and morphine would be significant in pain relieving of rib fracture. In addition, lacking of placebo was considered as another limitation of the present project, which because of ethi- cal issues there was no possible to cancel the medication. Conclusion: The findings of the present study shows that IV aceta- minophen and morphine have the same therapeutic value in relieving the pain of rib fracture. The success rate after 30 minutes drug administration were 80% and 58.6% in acetaminophen and morphine groups, respec- tively. Presentation of side effects was similar in both groups. Acknowledgments: The authors appreciate the insightful cooperation of staffs of the Emergency Department of Al-Zahra Hospi- tals, Isfahan, Iran. Conflict of interest: None Funding support: None Authors’ contributions: All authors met four criteria for authorship contribution based on recommendations of the International Com- mittee of Medical Journal Editors. References: 1. Fabricant L, Ham B, Mullins R, Mayberry J. Prolonged pain and disability are common after rib fractures. Am J Surg. 2013;205(5):511-6. 2. Brasel KJ, Guse CE, Layde P, Weigelt JA. Rib fractures: Relationship with pneumonia and mortality. Crit Care Med. 2006;34(6):1642-6. 3. Gordy S, Fabricant L, Ham B, Mullins R, Mayberry J. The contribution of rib fractures to chronic pain and disability. Am J Surg. 2014;207(5):659-63. 4. Alimohammadi H, Baratloo A, Abdalvand A, Rouhipour A, Safari S. Effects of Pain Relief on Arterial Blood O2 Saturation. Trauma monthly. 2014;19(1). 5. Lotfipour S, Kaku SK, Vaca FE, et al. Factors associated with complications in older adults with isolated blunt chest trauma. West J Emerg Med. 2009;10(2):79-84. 6. Safari S, Baratloo A, Negida AS, Taheri MS, Hashemi B, Selkisari SH. Comparing the Interpretation of Traumatic Chest X-Ray by Emergency Medicine Specialists and Radiologists. Archives of trauma research. 2014;3(4). 7. Forouzanfar MM, Safari S, Niazazari M, et al. Clinical decision rule to prevent unnecessary chest X-ray in patients with blunt multiple traumas. Emergency Medicine Australasia. 2014;26(6):561-6. 8. Marasco S, Lee G, Summerhayes R, Fitzgerald M, Bailey M. Quality of life after major trauma with multiple rib fractures. Injury. 2014;46(1):61-5. 9. Paydar S, Farhadi P, Ghaffarpasand F, et al. Acute Trauma Pain Control Algorithm. Bull Emerg Trauma. 2014;2(4):170-1. 10. Pasero C, Stannard D. The role of intravenous acetaminophen in acute pain management: a case-illustrated review. Pain Manag Nurs. 2012;13(2):107-24. 11. Yeh YC, Reddy P. Clinical and economic evidence for intravenous acetaminophen. Pharmacotherapy. 2012;32(6):559-79. 12. Wattana MK, Nelson LS, Todd KH. Prescription Opioid Guidelines and the Emergency Department. J Pain Palliat Care Pharmacother. 2013;27(2):155-62. 13. Khan MS, Shuaib W, Evans DD, et al. Evidence-Based Practice: Best Imaging Practice in Musculoskeletal Disorders. J Trauma Nurs. 2014;21(4):170-9. 14. Farrar JT, Young Jr JP, LaMoreaux L, Werth JL, Poole RM. Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149-58. 15. Todd KH, Funk KG, Funk JP, Bonacci R. Clinical significance of reported changes in pain severity. Ann Emerg Med. 1996;27(4):485-9. 16. Merritt CK, Salinas OJ, Kaye AD. Pain Control in Acute Trauma. Anesthesia for Trauma: Springer; 2014. p. 107-30. 17. Karmakar MK, Ho AM-H. Acute pain management of patients with multiple fractured ribs. J Trauma. 2003;54(3):615-25. 18. Tsang KS, Page J, Mackenney P. Can intravenous paracetamol reduce opioid use in preoperative hip fracture patients? Orthopedics. 2013;36(2 Suppl):20-4. 19. Zare MA, Ghalyaie AH, Fathi M, Farsi D, Abbasi S, Hafezimoghadam P. Oral oxycodone plus intravenous acetaminophen versus intravenous morphine sulfate in acute bone fracture pain control: a double-blind placebo-controlled randomized clinical trial. Eur J Orthop Surg Traumatol. 2014;24(7):1305-9.