The efficacy of fentanyl for pain management in emergency department: a review.
Pain is the most prevalent complaint among patients referring to the emergency department. (1) The previous reports revealed pain is chief complaint among 75 % of patients and it is more weakening than cancer and heart diseases. (1-3) Untreated pain may elevate the level of plasma catecholamine, glucose, antidiuretic hormone, cortisol, and acute phase protein. (1, 3) To overcome these acute phase reactants, a diverse class of drugs and methods such as opioids, benzodiazepines, and local anesthesia are used to ameliorate the level of pain and distress. (4, 5) Opioids such as meperidine, morphine, hydromorphone, fentanyl, and methadone are the most common agents used for pain relief in the emergency department (ED). (6) Among these drugs, the most appropriate agent regarding BMI, age, and intensity of pain should be chosen as an analgesic or sedative. Fentanyl is a highly lipophilic, [mu]-opioid receptor agonist and diffuse across bloodbrain barrier rapidly. (7) Its equilibration t V is about six minutes and fentanyl is 100-fold more potent than morphine. (8) Fentanyl metabolized in the liver. (9, 11) and may induce some important and life-threatening adverse effects such as hypoventilation and respiratory depression, but, they are rare. In general, like as other opioids, nausea, vomiting, pruritus, and urinary retention are the commonest adverse effect of fentanyl. (12-13) The routes of administration of fentanyl include transdermal, intravenous, subcutaneous, oral transmucosal, sublingual, and neuraxial. Moreover, several formulations are accessible. (14) Previous practices have reported that fentanyl is well tolerated without any serious adverse effect. (15, 16) Moreover, it effectively decreases the level of pain as much as other analgesics with a lower serious side effect. (17) In this review, we evaluated the effectiveness and possible side effects of fentanyl for pain relief in adult patients referring to the emergency department with acute pain.
To data collecting for this review, we searched google, google scholar, Cochrane library, Medline, and PubMed and collected original articles, including randomized controlled trials, comparative studies, cohort, and case series related to fentanyl and its administration in the emergency department from 2010 to 2016. The following keywords were used: fentanyl; emergency department and pain management. The search was further limited by age group to adults, moreover, the duration of pain and the articles evaluating patients with chronic pain were excluded. Moreover, articles with duplicated records and irrelevant full text were excluded. Finally, 8 articles met the inclusion criteria and were enrolled to this review including one cohort and seven comparative studies including three double blinded placebo controlled trials.
In this review, 8 articles that were conducted between 2010 to 2016 were recruited and totally 44493 patients were evaluated. Four articles were retrospective and 4 articles were prospective. The later four articles were randomized placebo controlled and double blinded. Among all eight relevant articles, six of them compared the efficacy and adverse events of fentanyl with other opioids such as morphine and methoxyflurane and two of them compared the pain severity before and after fentanyl prescription. The route of administration of fentanyl in most of the experiences was intranasal but it was intravenous for morphine. The most of the articles demonstrated that fentanyl decreases pain score after administration and is more potent than morphine and methoxyflurane with lower side effects. The characteristics of the trial are summarized in table 1(Table 1). Moreover, Table 2 shows the number of the participants in each trials, the dose of administered drugs, the level of pain reduction etiology of pain and possible adverse effect of treatments (Table 2).
The management of pain is a wide field and several hypotheses about the pain relief and agents that can decrease the pain are presented, but most of these guidelines and recommendations are insufficient. For instance, several opioid agonist-antagonists such as buprenorphine, butorphanol, nalbuphine, and pentazocine have been used for decades to reduce pain in patients with acute pain in the emergency department, in the ambulance or in the hospital with some useful effect but with serious complications such as dysphoria. (18) In this review, we gathered the articles that were performed to evaluate the efficacy of fentanyl on pain relief in patients in the emergency department. Four studies have compared the efficacy and adverse events of fentanyl with morphine, two of these were double blinded randomized trials including; A study by Deaton et al. in 2015 that compared the effect of nebulized fentanyl (NF) (2 [micro]g/ kg) with intravenous morphine (IVM) (0.1 mg/kg) in patients with acute abdominal pain presenting to emergency departments. They revealed that the pain reduction occurred sooner in the NF group and more sustained. Moreover, the authors showed that the satisfaction of patients and doctors in fentanyl group was more than morphine group. (18)
Another study by Farahmand in 2014 also compared the effectiveness of nebulized fentanyl (4 [micro]g/kg) (47 patients) with intravenous (IV) morphine (0.1 mg/ kg) (43 patients) and showed no difference regarding pain reduction and patients' satisfaction between two groups after 10 minutes, however, after 15 the pain relief in fentanyl group was significantly more than morphine (19). Moreover, one non-blinded study by Wenderoth et al.in 2013 compared the analgesic response and safety of intravenous morphine with fentanyl on adult trauma patients who referred to the emergency department (ED). The pain score reduction in two groups did not differ significantly, although the pain reduction in fentanyl occurred sooner than morphine group. The difference between two groups regarding side effects was not significant (20). Another non-blinded study by Fleischman in 2010 was conducted on 168 patients who were assigned in fentanyl (N=84) and morphine (N=84) groups. The severity of injury in fentanyl was more than morphine group. Five patients in two groups regularly used opioids before admission.
They found that morphine and fentanyl provide the comparative analgesic effect, however, the opioids consumption in fentanyl groups was higher than patients receiving morphine. On the other hand, the adverse events in morphine group was more than fentanyl group (21). Among the comparative surveys, one non-blinded study by Johnston et al. compared the pain relief effect of intranasal fentanyl with methoxyflurane and proved that fentanyl was more effective than methoxyflurane (22). Only one study among surveys evaluated in this review by Middleton compared two analgesics including morphine and methoxyflurane with fentanyl and demonstrated that IV morphine and intranasal fentanyl was more effective than methoxyflurane regarding the pain relief among the out patients. Moreover, in comparison between fentanyl and morphine, they proved that morphine was more effective than fentanyl. While IN fentanyl was more accessible and useable (23). Only one of the study was double-blinded controlled trial and compared the efficacy of fentanyl with controls conducted by Taylor et al. that confirmed fentanyl pectin nasal spray (FPNS) was an effective agent in pain relief. Additionally, they indicated that FPNS is well tolerated and leads to more patients' satisfaction (24). Three of practices were conducted by the authors as cohort study and compared the pain score before and after fentanyl administration. Wedmore et al. in 2012 studied the effectiveness and safety of 286 out hospital patients that were treated with oral transmucosal fentanyl citrate (OTFC) and revealed a significant difference between pain score before and 15, 30 minutes after treatment. Moreover, they emphasized that fentanyl is safe, however, in high dose administration, nausea, hypoventilation and O2 saturation less than 90% may occur (25).
Of the 8 studies included in this review, only three studies were randomized and double-blinded, which emphasizes the fact that further high quality double-blinded randomized controlled trials are required to validate results reported in these articles. Moreover, we did not enroll studies on children and all recruited practices were conducted in patients more than 16 years of age. Studies in children may lead to different results. Additionally, we could not confirm that whether fentanyl is a useful agent in the patients with chronic pain such as patients with cancers other painful chronic diseases.
In summary, the studies proved that fentanyl significantly decreases the acute pain intensity and well tolerated by the patients. The adverse effects related to fentanyl were not serious and were transient. Pain reduction is related to function improvement in patients and increased the level of patients' satisfaction. A review by Downey et al. indicated that pain reduction increases satisfaction and function of patients, moreover they emphasized that pain relief improves patients doctor communication (26). The most of the experiences reviewed in this article used fentanyl as an intranasal spray and showed this is an alternative to the traditional routes of administration such as oral administration and intravenous injection. Finally, we concluded that fentanyl significantly decreases the pain intensity in patients referring with acute pain to the emergency department. Moreover, it is more effective than morphine and methoxyflurane in the most of the patients.
Conflict of interest: No funding was used for the preparation of this review.
(1.) Tanabe P Buschmann M. A prospective study of ED pain management practices and the patients prospective. J Emerg Nurs. 1999;25:171-7. [PubMed]
(2.) Garbez RO, Chan GK, Neighbor M, Puntillo K. Pain after discharge: A pilot study of factors associated with pain management and functional status. J Emerg Nurs. 2006;32(4):288-93. [PubMed]
(3.) Dillard J, Knapp S. Complementary and Alternative Pain Therapy in the Emergency Department. Emerg Med Clin North Am. 2005;23:529-49. [PubMed]
(4.) Sephton VC, Shaw A, Cowan CM, Thomas K, Wood S, Barclav PM, et al. Sedation and analgesia for transvaginal oocyte retrieval: an audit resulting in a change of clinical practice. Human Fertil(Camb). 2001 ;4(2): 94-98. [PubMed]
(5.) Jones, N, LongL, Zeitz, K. The role of the nurse sedationist. Collegian.2011;18(3):115-123. [PubMed]
(6.) Gutstein HB, Akil H. Opioid analgesics. In: Hardman JG, Limbrid LE, Gilman AG, eds. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 10th edition. New York, NY: McGraw-Hill; 2001:569-619.
(7.) Scott JC, Ponganis KV, Stanski DR. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 1985;62(3):234-241. [PubMed]
(8.) Grape S, Schug SA, Lauer S, Schug BS. Formulations of fentanyl for the management of pain. Drugs. 2010;70(1):57-72. [PubMed]
(9.) Cephalon. FENTORA[R] (fentanyl buccal tablet) [package insert]. Salt Lake City: Cephalon, Inc.; 2011. 23. Browne B, Linter S. Monoamine oxidase inhibitors and narcotic analgesics. A critical review of the implications for treatment. Br J Psychiatry. 1987;151:210-212.
(10.) Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ. Cardiac surgery in a patient taking monoamine oxidase inhibitors: an adverse fentanyl reaction. Anesth Analg. 1994;78(3):593-597. [PubMed]
(11.) Food and Drug Administration. FDA warns of potential serious side effects with breakthrough cancer pain drug [press release]. Silver Spring (MD): FDA; September 26, 2007. Available from: http://www. fda.gov/ NewsEvents/ Newsroom/ PressAnnouncements/ 2007/ ucm108994.htm. Accessed June 1, 2011.
(12.) Knill R, Cosgrove JF, Olley PM, Levison H. Components of respiratory depression after narcotic premedication in adolescents. Can Anaesth Soc J. 1976;23(5):449-458. [PubMed]
(13.) Rigg JR, Goldsmith CH. Recovery of ventilatory response to carbon dioxide after thiopentone, morphine and fentanyl in man. Can Anaesth Soc J. 1976;23:370-382.
(14.) Cephalon. ACTIQ[R] (oral transmucosal fentanyl citrate) [package insert]. Salt Lake City: Cephalon, Inc.; 2011.
(15.) Hansen MS, Dahl JB.Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review. Dan Med J 2013;60(1):A4563. [PubMed]
(16.) Borland M, Milsom S, Esson A. Equivalency of two concentrationsof fentanyl administered by the intranasal route for acute analgesia inchildren in a paediatric emergency department: a randomizedcontrolled trial. Emerg Med Australas. 2011;23(2):202208. doi: 10.1111/j.17426723.2011.01391.x[PubMed]
(17.) Holdgate A, Cao A, Lo KM. The implementation of intranasal fentanyl for children in a mixed adult and pediatric emergency department reduces time to analgesic administration. Acad Emerg Med.2010;17(2):214217. doi: 10.1111/j.15532712.2009.00636.x[PubMed]
(18.) Ziegler DK."Opioids in headache treatment: is there a role?"Neurologic Clinics, vol. 15, no. 1, pp. 199-207, 1997.
(19.) Deaton T, Auten JD, Darracq MA.Nebulized fentanyl vs intravenous morphine for ED patients with acute abdominal pain: a randomized double-blinded, placebo-controlled clinical trial. Am J Emerg Med. 2015 Jun;33(6):791-5. doi: 10.1016/j. ajem.2015.03.046. Epub 2015 Mar 25. [PubMed]
(20.) Farahmand S, Shiralizadeh S, Talebian MT, Bagheri-Hariri S, Arbab M, Basirghafouri H, et al. Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: a randomized clinical trial. Am J Emerg Med. 2014 Sep;32(9):1011-5. doi: 10.1016/j.ajem.2014.05.051. Epub 2014 Jun 12. [PubMed]
(21.) Wenderoth BR, Kaneda E , Amini A, Amini R, Patanwala AE.Morphine versus fentanyl for pain due to traumatic injury in the emergency department. J Trauma Nurs. 2013 Jan-Mar;20(1):10-5. doi: 10.1097/ JTN.0b013e31828660b5. [PubMed]
(22.) Fleischman RJ, Frazer DG, Daya M, Jui J, Newgard CD.Effectiveness and Safety of Fentanyl Compared with Morphine for Out-of-Hospital An algesia. 2010; 14(2):167-175 doi: 10.3109/10903120903572301 [Pub Med][Free full text]
(23.) Johnston S, Wilkes GJ, Thompson JA, Ziman M, brightwell R. Inhaled methoxyflurane and intranasal fentanyl for prehospital management of visceral pain in an Australian ambulance service. Emerg Med J. 2011;28(1):57-63. doi: 10.1136/ emj.2009.078717 [PubMed]
(24.) Middleton PM, Simpson PM, Sinclair G, Dobbins T, Math B, Bendal JC. Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting. Prehosp Emerg Care. 2010;14:439-47. doi: 10.3109/10903127.2010.497896. [PubMed]
(25.) Taylor D, Galan V, Weinstein SM, Reyes E, Pupo-Araya AR, Rauck R. Fentanyl Pectin Nasal Spray in Breakthrough Cancer Pain .J Support Oncol 2010;8(4):184-190. [PubMed]
(26.) Wedmore IS, Kotwal RS, McManus JG, Pennardt A, Talbot TS, Fowler M, et al. Safety and efficacy of oral transmucosal fentanyl citrate for prehospital pain control on the battlefield. J Trauma Acute Care Surg. 2012 Dec;73(6 Suppl 5):S490-5. doi: 10.1097/ TA.0b013e3182754674. [PubMed]
(27.) DowneyLA, Zun LS.Pain management in the emergency department and its relationship to patient satisfaction J Emerg Trauma Shock. 2010 Oct-Dec;3(4): 326-330. doi: 10.4103/0974-2700.70749. [PubMed][Free full text]
* Assistant Professor of Emergency Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences, Kermanshah, (Iran)
Correspondence: Sara Payami
Department of Emergency Medicine, Imam Reza Hospital, Kermanshah University of Medical Science, Kermanshah, Iran; Phone: 00989121466649, 00988334276326; E-mail: email@example.com
Received: 4 Mar 2018
Reviewed: 22 May 2018
Corrected: 30 May 2018
Accepted: 2 Jun 2018
Table 1: Characteristics of the trials Authors Year Setting Route of Type of study administration Middleton 2010 No blinding, IN fentanyl vs Retrospective, et al. no IV morphine vs comparative, randomization methoxyflurane observational (N=42, 844) Taylor 2010 Randomized, Fentanyl Prospective et al. placebo- pectin nasal randomized controlled, spray (FPNS) double-blind (n=114) Fleischman 2010 No blinding no IV Fentanyl vs Retrospective, randomization Morphine comparative (n=718) Johnston 2011 No blinding no IN fentanyl vs Retrospective, et al. randomization methoxyflurane comparative, (n=1024) observational Wedmore 2012 No control, no Oral Prospective et al. randomization, transmucosal Cohort no blinding fentanyl (N=197) citrate (OTFC) Fentanyl (different doses) Wenderoth 2013 No control, no IV Fentanyl vs Retrospective et al. randomization, morphine comparative no blinding (N=168) Farahmand 2014 Placebo- Nebulized Controlled controlled, fentanyl vs trial double-blind, intravenous randomized, morphine clinical trial. (N=90) Deaton 2015 Randomized, Nebulized Controlled double- fentanyl vs trial blinded, intravenous double- morphine placebo- controlled trial (N=40) Table 2: The number of the participants, dose, level and etiology of pain and possible adverse effects Author (Year) Number of Patients Dose of analgesic Middleton 42844 patients; Morphine Morphine 0.5 mg/ et al. (12955), Fentanyl (3778), kg, IN fentanyl (2010) Methoxyflurane (19235), 90 [micro]g Combination (morphine, fentanyl, or methoxyflurane) (6876). Taylor et al. 114 (FPNS and placebo) BTCP: 7 episodes (2010) for case and 3 for placebo Fleischman 718 (355 morphine, 363 Morphine IV 2--5 (2010) fentanyl) mg, maximum 20 mg. Fentanyl 50-[micro]g IV dose, maximum 200 [micro]g. Johnston 1024;MTX (465), INF(393), INF (15-180 [micro]g et al. both (162) first, 15-60 [micro]g (2011) second dose), MTX (3 ml at a concentration of 0.2%-0.4%) Wedmore 197(156 received OTFC) OTFC (962.4 et al. (452.7) [micro]g (2010) Wenderoth 168 (84 in fentanyl and morphine 4 mg IV, et al. 84 in morphine group) fentanyl 50 [micro]g IV. (2013) Farahmand 90 patients (47 nebulized nebulized fentanyl (4 et al. fentanyl, 43 morphine) [micro]g/kg) and IV (2014) normal saline as placebo. IV morphine (0.1 mg/kg) and nebulized normal saline as placebo Deaton, 40 (20 NF, 20 IVM) IVM = 0.1 mg/kg et al. 5, NF= 2 [micro]g/kg (2015) Author (Year) Pain score * Etiology of pain at admission [right arrow] after treatment Middleton 8.4-3.9 Pain in abdomen, back, et al. respiratory, chest, (2010) obstetrics Taylor et al. Two point discretion in cancer (2010) pain intensity Fleischman morphine (8.3 [right Extremity and hip pain, (2010) arrow] 5.4), fentanyl burns Atraumatic (8.1 [right arrow] 5) abdominal and pelvic pain, ischemic chest pain, Back pain, Other chest pain, Head and neck pain Johnston MTX (8 [right arrow] visceral pain(abdominal, et al. 5.5), INF (7.6 [right cardiac, renal) (2011) arrow] 4.4), both (8.8 [right arrow] 5.4) Wedmore 8 [right arrow] 3.2 Gun shot, orthopedic et al. injuries, laceration (2010) Wenderoth fentanyl = 10 [right All types of trauma et al. arrow] 8, morphine = 8 (2013) [right arrow] 6 Farahmand fentanyl (8.7 [right Wound and soft tissue et al. arrow] 3.5), morphine injuries Fractures (2014) (8.4 [right arrow] 3.8) Sprains and strains Deaton, IVM =7.5, [right arrow] undifferentiated et al. 5.9 NF= 6.6 [right arrow] abdominal pain (2015) 2.8 Author (Year) Side effects Middleton Not reported et al. (2010) Taylor et al. Patients with adverse (2010) events were excluded Fleischman Nausea, Hypotension (2010) Johnston Not report et al. (2011) Wedmore nausea, pruritus, et al. drowsiness, dizziness (2010) Wenderoth In fentanyl: hypotension, et al. respiratory depression, (2013) oxygen desaturation Farahmand Nausea, vomiting et al. Lightheaded-ness, loss (2014) of consciousness Deaton, Not reported et al. (2015) Legend: IN = intranasal, IVM = intravenous morphine, NF = nebulized fentanyl, OTFC = oral transmucosal fentanyl citrate, MTX) = Methoxyflurane, INF: intranasal Fentanyl, Fentanyl pectin nasal spray (FPNS), breakthrough cancer pain = BTCP * NRS (1-10)
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|Publication:||Anaesthesia, Pain & Intensive Care|
|Date:||Apr 1, 2018|
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