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Analgesia

Date Last Search Run: Aug 01, 2024
Table last updated: Jun 22, 2024
Data last added: Oct 08, 2024

Recommendation RECOMMENDATION FOR INTERVENTION
STRENGTH OF EVIDENCE FOR INTERVENTION   SUPPORTIVE (Green) NEUTRAL (Yellow) AGAINST (Red) NOT YET GRADED (White)
1 (strong evidence exists)      
2 (fair evidence exists)    
3 (weak evidence exists)      


Interventions

Acetaminophen IV
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Decrease in pain Patient ED-MD Bektas F., Eken C., Karadeniz O., Goksu E., Cubuk M., Cete Y. Intravenous paracetamol or morphine for the treatment of renal colic: A randomized, placebo-controlled trial. Ann Emerg Med 2009; 54(4):568-74. Medline
I Supportive (Green) Pain score measured on a visual analogue scale Patient ED-MD Craig M., Jeavons R., Probert J., Benger J. Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department. Emerg Med J 2012; 29(1):37-9. Medline
I Neutral (Yellow) Pain reduction at 30 minutes Patient ED-MD Furyk J, Levas D, Close B, Laspina K, Fitzpatrick M, Robinson K, et al. Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting a prospective, double-blind, double-dummy, randomised controlled trial. EMJ 2018; 35(3) 179-84. Medline
II Neutral (Yellow) Safety Patient PH-Paramedic Strickmann B, Deicke M, Hoyer A, Kobiella A, Jansen G. Effectiveness and safety of prehospital analgesia including nalbuphine and paracetamol by paramedics: an observational study. Minerva Anestesiol 2023; 89(12):1105-14. Medline
III Supportive (Green) Pain relief (NRS or VAS) Patient PH-Paramedic Dijkstra BM., Berben SA., van Dongen RT., Schoonhoven L. Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands. Eur J Pain 2013; 18(1):3-19. Medline

Acetaminophen PO
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Pain reduction at 30 min. Patient ED-MD Furyk J, Levas D, Close B, Laspina K, Fitzpatrick M, Robinson K, et al. Intravenous versus oral paracetamol for acute pain in adults in the emergency department setting a prospective, double-blind, double-dummy, randomised controlled trial. EMJ 2018; 35(3) 179-84. Medline
III Supportive (Green) Pain relief (NRS or VAS) Patient PH-Paramedic Dijkstra BM., Berben SA., van Dongen RT., Schoonhoven L. Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands. Eur J Pain 2013; 18(1):3-19. Medline

Benzodiazepines
Level Direction Primary Outcome Patient/Process Setting Reference
II Opposes (Red) Analgesia Patient PH-Paramedic Auffret Y., Gouillou M., Jacob GR., et al. Does midazolam enhance pain control in prehospital management of traumatic severe pain? Am J Emerg Med 2014; 32(6):655-9. Medline

Fentanyl
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Pain scores at time zero and every 10 min until 30 min Patient ED-MD Borland M., Milsom S., Esson A. Equivalency of two concentrations of fentanyl administered by the intranasal route for acute analgesia in children in a paediatric emergency department: A randomized controlled trial. Emerg Med Australas 2011; 23(2):202-8. Medline
I Supportive (Green) VAS relief > 15 mm in pain Patient ED-MD 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; 33(6):791-5. Medline
I Supportive (Green) Reduction in pain Patient ED-MD Farahmand S., Shiralizadeh S., Talebian MT., et al. Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: A randomized clinical trial. Am J Emerg Med 2014; 32(9):1011-5. Medline
I Supportive (Green) Pain score Patient PH-Paramedic Friesgaard KD, Kirkegaard H, Rasmussen CH, Giebner M, Christensen EF, Nikolajsen L. Prehospital intravenous fentanyl administered by ambulance personnel: a cluster-randomised comparison of two treatment protocols. Scandinavian J of trauma, resuscitation and emergency medicine 2019; 27(1) 11. Medline
I Supportive (Green) Reduction in pain Patient ED-MD Furyk JS., Grabowski WJ., Black LH. Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: A randomized controlled trial. Emerg Med Australas 2009; 21(3):203-9. Medline
I Supportive (Green) Pain relief using the visual analog scale score Patient PH-Paramedic Galinski M., et al. A randomized double-blind study comparing morphine with fentanyl in prehospital analgesia. Am J Emerg Med 2005; 23:114-9. Medline
I Supportive (Green) Pain at 0, 10, 20 and 30 minutes. Patient ED-MD Miner JR., Kletti C., Herold M., Hubbard D., Biros MH. Randomized clinical trial of nebulized fentanyl citrate versus i.v. fentanyl citrate in children presenting to the emergency department with acute pain. Acad Emerg Med 2007; 14(10):895-8. Medline
I Supportive (Green) Pain relief Patient Niemi-Murola L., Unkuri J., Hamunen K. Parenteral opioids in emergency medicine - A systematic review of efficacy and safety. Scandinavian journal of pain 2017; 2(4):187-94. Medline
I Supportive (Green) Pain score reduction Patient ED-MD Shear ML., Adler JN., Shewakramani S., et al. Transbuccal fentanyl for rapid relief of orthopedic pain in the ED. Am J Emerg Med 2010; 28(8):847-852. Medline
II Supportive (Green) Pain relief Patient PH-Paramedic Bendall JC, Simpson PM, Middleton PM. Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients. Prehosp Emerg Care 2011; 15(2):158-65. Medline
II Supportive (Green) Change in pain score Patient Bronsky E.S., Koola C., Orlando A., Redmond D., D'Huyvetter C., Sieracki H., Tanner II A., Fowler R., Mains C., Bar-Or D., Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis, 2019; Prehospital Emergency Care, 23:1, 1-8, DOI: 10.1080/10903127.2018.1469704 Medline
II Supportive (Green) Efficacy Patient PH-Paramedic & MD Friesgaard KD, Vist GE, Hyldmo PK, Raatiniemi L, Kurola J, et al. Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review. Pain Ther 2022. Medline
II Supportive (Green) Pain relief Patient ED-MD 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. Medline
II Supportive (Green) Pain reduction using VNRS-11 Patient PH-Paramedic Middleton PM, Simpson PM, Sinclair G, Dobbins TA, Math B, Bendall JC. Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting. Prehosp Emerg Care 2010; 14(4):439-47. Medline
II Supportive (Green) Pain reduction Patient PH-Paramedic Samuel N., Steiner IP., Shavit I. Prehospital pain management of injured children: A systematic review of current evidence. Am J Emerg Med 2015; 33(3):451-4. Medline
III Supportive (Green) Decrease Pain Patient ED-MD Cole J., Shepherd M., Young P. Intranasal fentanyl in 1-3-year-olds: A prospective study of the effectiveness of intranasal fentanyl as acute analgesia. Emerg Med Australas 2009; 21(5):395-400. Medline
III Supportive (Green) Pain relief (NRS or VAS) Patient PH-Paramedic Dijkstra BM., Berben SA., van Dongen RT., Schoonhoven L. Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands. Eur J Pain 2013; 18(1):3-19. Medline
III Supportive (Green) Pain rating using NRS Patient Frakes MA., Lord WR., Kociszewski C., Wedel SK. Efficacy of fentanyl analgesia for trauma in critical care transport. Am J Emerg Med 2006; 24(3):286-9. Medline
III Supportive (Green) Pain relief Patient PH-Paramedic Kanowitz A., Dunn TM., Kanowitz EM., Dunn WW., Vanbuskirk K. Safety and effectiveness of fentanyl administration for prehospital pain management. Prehosp Emerg Care 2006; 10(1):1-7. Medline
III Supportive (Green) Pain Relief Patient PH-Paramedic Park CL., Roberts DE., Aldington DJ., Moore RA. Prehospital analgesia: systematic review of evidence. J R Army Med Corps 2010; 156(4 S1):295-300. Medline
III Supportive (Green) Pain relief Process Other Pietsch U, Fischer H, Rüst CA, Hossfeld B, Grünenfelder A, et al. Oral transmucosal fentanyl citrate analgesia in prehospital trauma care: an observational cohort study. Scand J Trauma Resusc Emerg Med 2023; 31(1):2. Medline
III Supportive (Green) Analgesia Patient PH-Paramedic Rickard C., et al. A RCT of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med 2007; 25:911-7. Medline
X Not Yet Graded (White) - Scharonow O, Vilcane S, Weilbach C, Scharonow M. Analgesic Therapy with the Opioids Fentanyl and Morphine by Ambulance Personnel in Rural Areas: An Observational Study Over 7 Years. J Pain Res January 2024; 17:345-355. Medline
X Not Yet Graded (White) - Patient Soriya GC., McVaney KE., Liao MM., et al. Safety of prehospital intravenous fentanyl for adult trauma patients. J Trauma Acute Care Surg 2012; 72(3):755-759. Medline

Ketamine
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Pain scale Patient ED-MD Abbasi S, Bidi N, Mahshidfar B, Hafezimoghadam P, Rezai M, Mofidi M, et al. Can low-dose of ketamine reduce the need for morphine in renal colic? A double-blind randomized clinical trial. Am J Emerg Med 2018; 36(3) 376-9. Medline
I Supportive (Green) Pain reduction Patient PH-Paramedic Andolfatto G., Innes K., Dick W., Jenneson S., Willman E., Stenstrom R., Zed P.J., Benoit G. Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults. Ann Emerg Med. 2019; [Epub ahead of print] Medline
I Supportive (Green) Pain relief Patient ED-MD Arroyo-Novoa CM., Figueroa-Ramos MI., Miaskowski C., et al. Efficacy of small doses of ketamine with morphine to decrease procedural pain responses during open wound care. Clin J Pain 2011; 27(7):561-6. Medline
I Supportive (Green) pain score Patient ED-MD Balzer N, McLeod SL, Walsh C, Grewal K. Low-dose Ketamine For Acute Pain Control in the Emergency Department: A Systematic Review and Meta-analysis. Acad Emerg Med 2021; 28(4):444-54. Medline
I Supportive (Green) Pain relief Patient ED-MD Beaudoin FL., Lin C., Guan W., Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: Results of a randomized, double-blind, clinical trial. Acad Emerg Med 2014; 21(11):1193-202. Medline
I Supportive (Green) Improvement in pain at 30 min Patient ED-MD Benish T, Villalobos D, Love S, Casmaer M, Hunter CJ, Summers SM, et al. The THINK (Treatment of Headache with Intranasal Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine with Intravenous Metoclopramide. J Emerg Med 2019; 56(3) 248-57. Medline
I Supportive (Green) Pain reduction using NRS Patient ED-MD Kampan S, Thong-On K, Sri-On J. A non-inferiority randomized controlled trial comparing nebulized ketamine to intravenous morphine for older adults in the emergency department with acute musculoskeletal pain. Age Ageing January 2024; 53(1). Medline
I Supportive (Green) Change in VAS or NRS Patient ED-MD Karlow N, Schlaepfer CH, Stoll CRT, Doering M, Carpenter CR, Colditz GA, et al. A Systematic Review and Meta-analysis of Ketamine as an Alternative to Opioids for Acute Pain in the Emergency Department. Academic emergency medicine 2018; 25(10) 1086-97. Medline
I Supportive (Green) Analgesia Patient ED-MD Lovett S, Reed T, Riggs R, Lew G, Koch E, Durazo-Aruizu RA, et al. A randomized, noninferiority, controlled trial of two doses of intravenous subdissociative ketamine for analgesia in the emergency department. Acad Emerg Med 2021; 28(6):647–54. Medline
I Supportive (Green) Adverse events Patient ED-MD Motov S, Mai M, Pushkar I, Likourezos A, Drapkin J, Yasavolian M, et al. A prospective randomized, double-dummy trial comparing IV push low dose ketamine to short infusion of low dose ketamine for treatment of pain in the ED. Am J Emerg Med 2017; 35(8) 1095-100. Medline
I Supportive (Green) Reduction of pain using NRS Patient ED-MD Motov S, Mann S, Drapkin J, Butt M, Likourezos A, Yetter E, et al. Intravenous subdissociative-dose ketamine versus morphine for acute geriatric pain in the Emergency Department A randomized controlled trial. Am J Emerg Med 2019; 37(2) 220-7. Medline
I Supportive (Green) Tolerance to procedure Patient ED-MD Qureshi FA., Mellis PT., McFadden MA. Efficacy of oral ketamine for providing sedation and analgesia to children requiring laceration repair. Pediatr Emerg Care 1995; 11(2):93-7. Medline
I Supportive (Green) Pain score at 15 minutes post-intervention Patient ED-MD Sin B, Tatunchak T, Paryavi M, Olivo M, Mian U, Ruiz J, et al. The Use of Ketamine for Acute Treatment of Pain: A Randomized, Double-Blind, Placebo-Controlled Trial. J Emerg Med 2017; 52(5) 601-8. Medline
I Neutral (Yellow) Adverse events Patient ED-MD Cevik E., Bilgic S., Kilic E., Cinar O., Hasman H., Acar AY., et al. Comparison of ketamine-low-dose midozolam with midazolam-fentanyl for orthopedic emergencies: a double-blind randomized trial. Am J Emerg Med 2013; 31(1):108-13. Medline
I Neutral (Yellow) Pain reduction at 30 minutes Patient ED-MD & CCP Lee EN, Lee JH. The Effects of Low-Dose Ketamine on Acute Pain in an Emergency Setting: A Systematic Review and Meta-Analysis. PloS one 2016; 11(10) e0165461. Medline
I Neutral (Yellow) Pain relief Patient ED-MD Miller JP., Schauer SG., Ganem VJ., Bebarta VS. Low-dose ketamine vs morphine for acute pain in the ED: A randomized controlled trial. Am J Emerg Med 2015; 33(3):402-8. Medline
II Supportive (Green) Pain control Patient ED-MD Bowers KJ, McAllister KB, Ray M, Heitz C. Ketamine as an Adjunct to Opioids for Acute Pain in the Emergency Department A Randomized Controlled Trial. Academic emergency medicine 2017; 24(6) 676-85. Medline
II Supportive (Green) Change in pain score Patient Bronsky E.S., Koola C., Orlando A., Redmond D., D'Huyvetter C., Sieracki H., Tanner II A., Fowler R., Mains C., Bar-Or D., Intravenous Low-Dose Ketamine Provides Greater Pain Control Compared to Fentanyl in a Civilian Prehospital Trauma System: A Propensity Matched Analysis, 2019; Prehospital Emergency Care, 23:1, 1-8, DOI: 10.1080/10903127.2018.1469704 Medline
II Supportive (Green) Change in pain score Patient ED-MD Cohen B, Talmy T, Gelikas S, Radomislensky I, Kontorovich-Chen D, Benov A, Avital G. Opioid Sparing Effect of Ketamine in Military Pre-Hospital Pain Management - A Retrospective Study. J Trauma Acute Care Surg 2022. Medline
II Supportive (Green) Pain Control (<3) Patient PH-Paramedic & CCT Dubecq C, Montagnon R, Morand G, et al. Combat Casualties Treated With Intranasal Ketamine for Prehospital Analgesia: A Case Series. J Spec Oper Med 2023. Medline
II Supportive (Green) Analgesia Patient PH-Paramedic Frawley J, Goyal A, Gappy R, et al. A Comparison of Prehospital Pediatric Analgesic Use of Ketamine and Opioids. Prehosp Emerg Care March 2023 :1-5. Medline
II Supportive (Green) Effective Analgesia Patient ED-MD Ghate G, Clark E, Vaillancourt C. Systematic review of the use of low-dose ketamine for analgesia in the emergency department. CJEM 2018; 20(1) 36-45. Medline
II Supportive (Green) PTSD diagnosis within 1 year Patient PH-Paramedic Melcer T, Walker GJ, Dye JL, Walrath B, MacGregor AJ, Perez K, Galarneau MR. Is Prehospital Ketamine Associated With a Change in the Prognosis of PTSD? Mil Med 2022. Medline
II Supportive (Green) Analgesia Patient ED-MD Motov S, Rosenbaum S, Vilke GM, Nakajima Y. Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an Adjunct to Opioids or as a Single Agent for Acute Pain Management in the Emergency Department? J Emerg Med 2016; 51(6) 752-7. Medline
II Supportive (Green) Pre-Hospital Ketamine use does not increase length of stay when compared to Morphine and Fentanyl Patient PH-Paramedic Robinson EJ, Watanabe BL, Brown LH. Ketamine for Prehospital Pain Management Does Not Prolong Emerg Department Length of Stay. PEC 2020:1-8. Medline
II Supportive (Green) ED Length Of Stay Patient PH-Paramedic Robinson EJ, Watanabe BL, Brown LH. Ketamine for Prehospital Pain Management Does Not Prolong Emerg Department Length of Stay. PEC 2020:1-8. Medline
II Supportive (Green) Pain reduction Patient PH-Paramedic Samuel N., Steiner IP., Shavit I. Prehospital pain management of injured children: A systematic review of current evidence. Am J Emerg Med 2015; 33(3):451-4. Medline
II Supportive (Green) Use of sublingual ketamine for pain management Patient Other Tohira H, Brink D, Davids L, et al. Use of ketamine wafer for pain management by volunteer emergency medical technicians in rural Western Australia. Emerg Med Australas 2023. Medline
II Supportive (Green) Pain management Patient Other Tohira H, Brink D, Davids L, et al. Use of ketamine wafer for pain management by volunteer emergency medical technicians in rural Western Australia. Emerg Med Australas 2023. Medline
II Neutral (Yellow) Chronic Pain Patient PH-Paramedic Jennings PA., Cameron P., Bernard S., et al. Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial. Emerg Med J 2014; 31(10):840-3. Medline
III Supportive (Green) Reduction in pain Patient ED-MD Goltser A., Soleyman-Zomalan E., Kresch F., Motov S. Short (low-dose) ketamine infusion for managing acute pain in the ED: Case-report series. Am J Emerg Med 2015; 33(4):e5-7. Medline
III Supportive (Green) Analgesia Patient PH-Paramedic Goyal A, Frawley J, Gappy R, Sandoval S, Chen NW, Crowe R, Swor R. Prehospital Ketamine Use in Pediatrics. Prehosp Emerg Care 2022; 1–11 Medline
III Supportive (Green) Analgesia Process PH-Paramedic & MD Häske D, Dorau W, Heinemann N, Eppler F, Schopp T, Schempf B. Efficacy and safety in ketamine-guided prehospital analgesia for abdominal pain. Intern Emerg Med 2022; 17(8):2291–7. Medline
III Supportive (Green) Pain Relief Patient PH-Paramedic Jennings PA., Cameron P., Bernard S. Ketamine as an analgesic in the pre-hospital setting: a systematic review. Acta Anaesthesiol Scand 2011; 55(6):638-43. Medline
III Supportive (Green) Pain reduction Patient PH-Paramedic Patrick C, Smith M, Rafique Z, Rogers Keene K, De La Rosa X. Nebulized Ketamine for Analgesia in the Prehospital Setting: A Case Series. Prehosp Emerg Care 2022:1–8. Medline
III Supportive (Green) Pain relief Patient PH-Paramedic Quinn E, Dhanraj S, Liu J, Motov S, Friedman M, Eng D. Nebulized Ketamine Used for Managing Ankle Fracture in the Prehospital Emergency Setting: A Case Report. Clin Pr Cases Emerg Med 2023; 7(1):43-6. Medline

Ketorolac (Toradol)
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Pain reduction at 30 mins Patient ED-MD Motov S, Yasavolian M, Likourezos A, Pushkar I, Hossain R, Drapkin J, et al. Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department A Randomized Controlled Trial. Ann Emerg Med 2017; 70(2) 177-84. Medline
I Supportive (Green) Pain relief Patient ED-MD Neighbor ML., Puntillo KA. Intramuscular ketorolac vs oral ibuprofen in emergency department patients with acute pain. Acad Emerg Med 1998; 5(2):118-22. Medline
I Supportive (Green) Change in VAS pain score after 60 minutes. Patient ED-MD Turner NJ, Long DA, Bongiomo JR, Katoski TP, Jin LM, Horsch JP, et al. Comparing two doses of intramuscular ketorolac for treatment of acute musculoskeletal pain in a military emergency department. Am J Emerg Med 2021; 50:142–7. Medline
II Supportive (Green) Pain level Patient ED-MD Buccelletti F., Marsiliani D., Zuccala G., et al. Paracetamol-codeine compared to ketorolac for pain control in the emergency department. Eur Rev Med Pharmacol Sci 2014; 18(20):3139-43. Medline
II Supportive (Green) Pain relief Patient ED-MD Pollack CV, Diercks DB, Thomas SH, Shapiro NI, Fanikos J, Mace SE, et al. Patient-reported Outcomes from A National, Prospective, Observational Study of Emergency Department Acute Pain Management With an Intranasal Nonsteroidal Anti-inflammatory Drug, Opioids, or Both. Academic emergency medicine 2016; 23(3) 331-41. Medline

Methoxyflurane (Penthrox)
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Analgesia Patient ED-MD Brichko L, Gaddam R, Roman C, O'Reilly G, Luckhoff C, Jennings P, et al. Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED) Study: A Randomized Controlled Trial of Methoxyflurane Versus Standard Care. Acad Emerg Med 2021; 28(2):164-71. Medline
I Supportive (Green) Change in pain intensity (using VAS) Patient Other Coffey F, Dissmann P, Mirza K, Lomax M. Methoxyflurane Analgesia in Adult Patients in the Emergency Department: A Subgroup Analysis of a Randomized, Double-blind, Placebo-controlled Study (STOP!). Adv Ther 2016; 33(11):2012-31. Medline
I Supportive (Green) Change in pain (VAS) Patient ED-MD Coffey F, Wright J, Hartshorn S, Hunt P, Locker T, Mirza K, et al. STOP!: a randomised, double-blind, placebo-controlled study of the efficacy and safety of methoxyflurane for the treatment of acute pain. Emerg Med J 2014; 31(8):613-8. Medline
I Supportive (Green) Change in pain (VAS) Patient ED-MD Mercadante S, Voza A, Serra S, Ruggiano G, Carpinteri G, Gangitano G, et al. Analgesic Efficacy, Practicality and Safety of Inhaled Methoxyflurane Versus Standard Analgesic Treatment for Acute Trauma Pain in the Emergency Setting: A Randomised, Open-Label, Active-Controlled, Multicentre Trial in Italy (MEDITA). Adv Ther 2019; 36(11):3030-46. Medline
I Supportive (Green) Duration and intensity of pain Patient Other Zaki H, Türkmen S, Azad A, et al. Clinical assessment and risk stratification for prehospital use of methoxyflurane versus standard analgesia in adult patients with trauma pain. Turk J Emerg Med April 2023; 23(2):65-74. Medline
II Supportive (Green) Safety and efficacy Patient PH-Paramedic & CCT Babl FE, Jamison SR, Spicer M, Bernard S. Inhaled methoxyflurane as a prehospital analgesic in children. Emerg Med Australas 2006; 18(4):404-10. Medline
II Supportive (Green) Pain relief Patient PH-Paramedic Bendall JC, Simpson PM, Middleton PM. Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients. Prehosp Emerg Care 2011; 15(2):158-65. Medline
II Supportive (Green) Change in pain (VAS) Patient PH-Paramedic 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. Medline
II Supportive (Green) Change in VAS pain score Patient PH-Paramedic Lord BA, Parsell B. Measurement of pain in the prehospital setting using a visual analogue scale. Prehosp Disaster Med 2003; 18(4):353-8. Medline
II Supportive (Green) Hepatic and renal events at 12 weeks after index date Patient Other Qizilbash N, Kataria H, Jarman H, et al. Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study. BMC Emerg Med August 2023; 23(1):100. Medline
II Supportive (Green) Sufficient Analgesia Patient PH-Paramedic & MD Trimmel H, Egger A, Doppler R, Pimiskern M, Voelckel WG. Usability and effectiveness of inhaled methoxyflurane for prehospital analgesia - a prospective, observational study. BMC Emerg Med 2022; 22(1):8. Medline
II Neutral (Yellow) Pain reduction using VNRS-11 Patient PH-Paramedic Middleton PM, Simpson PM, Sinclair G, Dobbins TA, Math B, Bendall JC. Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting. Prehosp Emerg Care 2010; 14(4):439-47. Medline
III Supportive (Green) Analgesia Patient Other Alexander E, Tobias H, Stefan H, Jakob F, Josef B, Helmut T, et al. Efficacy and safety of methoxyflurane for treatment of acute traumatic pain by EMTs during alpine rescue operations: The “PainDrop” Trial. Prehosp Emerg Care 2022; 1–12. Medline
III Supportive (Green) Pain reduction Patient PH-Paramedic Buntine P, Thom O, Babl F, Bailey M, Bernard S. Prehospital analgesia in adults using inhaled methoxyflurane. Emerg Med Australas 2007; 19(6):509-14. Medline
III Supportive (Green) Perceived pain Patient Other Johansson A, Svensson A, Wihlborg J. Pain management with methoxyflurane (Penthrox®) in Swedish ambulance care - An observational pilot study. Int Emerg Nurs 2021; 59:101076. Medline
III Neutral (Yellow) Analgesia Patient PH-Paramedic Rickard C., et al. A RCT of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med 2007; 25:911-7. Medline
III Neutral (Yellow) Efficacy Patient PH-Paramedic Simpson PM, Bendall JC, Tiedemann A, Lord SR, Close JC. Provision of out-of-hospital analgesia to older fallers with suspected fractures: above par, but opportunities for improvement exist. Acad Emerg Med 2013; 20(8):761-8. Medline
X Not Yet Graded (White) - Brichko L, Gaddam R, Roman C, O'Reilly G, Luckhoff C, Jennings P, et al. Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED) Study: A Randomized Controlled Trial of Methoxyflurane Versus Standard Care. Acad Emerg Med 2021; 28(2):164-71. Medline

Morphine
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Pain relief Patient ED-MD Arroyo-Novoa CM., Figueroa-Ramos MI., Miaskowski C., et al. Efficacy of small doses of ketamine with morphine to decrease procedural pain responses during open wound care. Clin J Pain 2011; 27(7):561-6. Medline
I Supportive (Green) Pain relief Patient ED-MD Beaudoin FL., Lin C., Guan W., Merchant RC. Low-dose ketamine improves pain relief in patients receiving intravenous opioids for acute pain in the emergency department: Results of a randomized, double-blind, clinical trial. Acad Emerg Med 2014; 21(11):1193-202. Medline
I Supportive (Green) Decrease in pain Patient ED-MD Bektas F., Eken C., Karadeniz O., Goksu E., Cubuk M., Cete Y. Intravenous paracetamol or morphine for the treatment of renal colic: A randomized, placebo-controlled trial. Ann Emerg Med 2009; 54(4):568-74. Medline
I Supportive (Green) Pain Scale Patient ED-MD Birnbaum A., Esses D., Bijur PE., Holden L., Gallagher EJ. Randomized double-blind placebo-controlled trial of two intravenous morphine dosages (0.10 mg/kg and 0.15 mg/kg) in emergency department patients with moderate to severe acute pain. Ann Emerg Med 2007; 49(4):445-53. Medline
I Supportive (Green) Analgesia Patient PH-Paramedic Bounes V., Charpentier S., Houze-Cerfon CH., Bellard C., Ducassé JL. Is there an ideal morphine dose for prehospital treatment of severe acute pain? A randomized, double-blind comparison of 2 doses. Am J Emerg Med 2008; 26(2):148-54. Medline
I Supportive (Green) Pain score measured on a Visual Analogue Scale Patient ED-MD Craig M., Jeavons R., Probert J., Benger J. Randomised comparison of intravenous paracetamol and intravenous morphine for acute traumatic limb pain in the emergency department. Emerg Med J 2012; 29(1):37-9. Medline
I Supportive (Green) Reduction in pain Patient ED-MD Farahmand S., Shiralizadeh S., Talebian MT., et al. Nebulized fentanyl vs intravenous morphine for ED patients with acute limb pain: A randomized clinical trial. Am J Emerg Med 2014; 32(9):1011-5. Medline
I Supportive (Green) Reduction in pain Patient ED-MD Furyk JS., Grabowski WJ., Black LH. Nebulized fentanyl versus intravenous morphine in children with suspected limb fractures in the emergency department: A randomized controlled trial. Emerg Med Australas 2009; 21(3):203-9. Medline
I Supportive (Green) Pain relief using the visual analog scale score Patient PH-Paramedic Galinski M., et al. A randomized double-blind study comparing morphine with fentanyl in prehospital analgesia. Am J Emerg Med 2005; 23:114-9. Medline
I Supportive (Green) Pain management Patient ED-MD Kampan S, Thong-On K, Sri-On J. A non-inferiority randomized controlled trial comparing nebulized ketamine to intravenous morphine for older adults in the emergency department with acute musculoskeletal pain. Age Ageing January 2024; 53(1). Medline
I Supportive (Green) Pain relief Patient ED-MD Miller JP., Schauer SG., Ganem VJ., Bebarta VS. Low-dose ketamine vs morphine for acute pain in the ED: A randomized controlled trial. Am J Emerg Med 2015; 33(3):402-8. Medline
I Supportive (Green) VAS scores Patient ED-MD Miner JR., Moore J., Gray RO., Skinner L., Biros MH. Oral versus intravenous opioid dosing for the initial treatment of acute musculoskeletal pain in the emergency department. Acad Emerg Med 2008; 15(12):1234-40. Medline
I Supportive (Green) Pain relief Patient Niemi-Murola L., Unkuri J., Hamunen K. Parenteral opioids in emergency medicine - A systematic review of efficacy and safety. Scandinavian journal of pain 2017; 2(4):187-94. Medline
I Supportive (Green) Pain intensity on VAS Patient ED-MD Sin B, Jeffrey I, Halpern Z, Adebayo A, Wing T, Lee AS, et al. Intranasal Sufentanil Versus Intravenous Morphine for Acute Pain in the Emergency Department A Randomized Pilot Trial. J Emerg Med 2019; 56(3) 301-7. Medline
I Supportive (Green) Efficacy Patient PH-Paramedic Vergnion M., Degesves S., Garcet L., Magotteaux V. Tramadol, an alternative to morphine for treating posttraumatic pain in the prehospital situation. Anesth Analg 2001; 92(6):1543-1546. Medline
I Neutral (Yellow) Decrease in pain from baseline to 30 minutes Patient ED-MD Chang AK., Bijur PE., Baccelieri A., Gallagher EJ. Efficacy and safety profile of a single dose of hydromorphone compared with morphine in older adults with acute, severe pain: A prospective, randomized, double-blind clinical trial. Am J Geriatr Pharmacother 2009; 7(1):1-10. Medline
I Neutral (Yellow) VAS relief > 15 mm in pain Patient ED-MD 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; 33(6):791-5. Medline
II Supportive (Green) Pain relief Patient PH-Paramedic Bendall JC, Simpson PM, Middleton PM. Effectiveness of prehospital morphine, fentanyl, and methoxyflurane in pediatric patients. Prehosp Emerg Care 2011; 15(2):158-65. Medline
II Supportive (Green) Pain reduction using VNRS-11 Patient PH-Paramedic Middleton PM, Simpson PM, Sinclair G, Dobbins TA, Math B, Bendall JC. Effectiveness of morphine, fentanyl, and methoxyflurane in the prehospital setting. Prehosp Emerg Care 2010; 14(4):439-47. Medline
II Supportive (Green) Analgesia Patient PH-Paramedic Ricard-Hibon A., et al. Compliance with a morphine protocol and effect on pain relief in out-of-hospital patients. J Emerg Med 2008; 34:305-10. Medline
II Supportive (Green) Pain reduction Patient PH-Paramedic Samuel N., Steiner IP., Shavit I. Prehospital pain management of injured children: A systematic review of current evidence. Am J Emerg Med 2015; 33(3):451-4. Medline
II Supportive (Green) Analgesia Patient PH-Paramedic Scharonow O, Vilcane S, Weilbach C, Scharonow M. Analgesic Therapy with the Opioids Fentanyl and Morphine by Ambulance Personnel in Rural Areas: An Observational Study Over 7 Years. J Pain Res January 2024; 17:345-355. Medline
II Neutral (Yellow) Chronic Pain Patient PH-Paramedic Jennings PA., Cameron P., Bernard S., et al. Long-term pain prevalence and health-related quality of life outcomes for patients enrolled in a ketamine versus morphine for prehospital traumatic pain randomised controlled trial. Emerg Med J 2014; 31(10):840-3. Medline
II Neutral (Yellow) Likelihood of receiving analgesic Patient PH-Paramedic Michael GE., Sporer KA., Youngblood GM. Women are less likely than men to receive prehospital analgesia for isolated extremity injuries. Am J Emerg Med 2007; 25:901-6. Medline
III Supportive (Green) Pain relief (NRS or VAS) Patient PH-Paramedic Dijkstra BM., Berben SA., van Dongen RT., Schoonhoven L. Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands. Eur J Pain 2013; 18(1):3-19. Medline
III Supportive (Green) Time to morphine administration Process PH-Paramedic Fullerton-Gleason L., Crandall C., Sklar D. Prehospital Administration of Morphine for Isolated Extremity Injuries: A Change in Protocol Reduces Time to Medication. Prehospital Emergency Care 2002; 6(4):411-6. Medline
III Supportive (Green) Pain Relief Patient PH-Paramedic Park CL., Roberts DE., Aldington DJ., Moore RA. Prehospital analgesia: systematic review of evidence. J R Army Med Corps 2010; 156(4 S1):295-300. Medline
III Supportive (Green) Analgesia Patient PH-Paramedic Rickard C., et al. A RCT of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting. Am J Emerg Med 2007; 25:911-7. Medline
III Neutral (Yellow) Decrease in pain Patient ED-MD Bijur PE., Kenny MK., Gallagher EJ. Intravenous Morphine at 0.1mg/kg is not effective for controlling severe acute pain in the majority of patients. Annals of Emergency Medicine 2005; 46(4):362-7. Medline
III Neutral (Yellow) Appropriate administration, complications Process PH-Paramedic Bruns BM., Dieckmann R., Shagoury C., et al. Safety of prehospital therapy with morphine sulfate. Am J Emerg Med 1992; 10(1):53-7. Medline
III Neutral (Yellow) Rate of missed appendicitis Process ED-MD Green R., Bulloch B., Kabani A., Hancock BJ., Tenenbein M. Early analgesia for children with acute abdominal pain. Pediatrics 2005; 116(4):978-83. Medline
III Neutral (Yellow) Administration of analgesics Patient PH-Paramedic White LJ., Cooper JD., Chambers RM., Gradisek RE. Prehospital use of analgesia for suspected extremity fractures. PEC 2000; 4:205-08. Medline

Nitrous Oxide
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Pain at 15 minutes Patient PH-Paramedic Ducasse JL., Siksik G., Durand-Bechu M., Couarraze S., Valle B., Lecoules N., et al. Nitrous oxide for early analgesia in the emergency setting: a randomized, double-blind multicenter prehospital trial. Acad Emerg Med 2013; 20(2):178-84. Medline
I Supportive (Green) Pain score (VAS or NRS) Patient ED-Paramedic & MD Xing Y, Zhou L, Yu J, Wang Z, Ding Z, Xie C, et al. Analgesic efficacy of nitrous oxide in adults in the emergency department: A meta-analysis of randomized controlled trials. Am J Emerg Med 2022; 56:92–9. Medline
II Supportive (Green) Analgesia Patient PH-Paramedic McKinnon KDL. Prehospital analgesia with nitrous oxide/oxygen. CMA Journal 1981; 125:836-40. Medline
III Supportive (Green) Pain relief Patient PH-Paramedic Amey BD., Ballinger JA., Harrison EE. Prehospital Administration of Nitrous Oxide for Control of Pain. Ann Emerg Med 1981; 10(5):247-51. Medline
III Supportive (Green) Pain scale Patient PH-Paramedic Buntine P., et al. Prehospital analgesia in adults using inhaled methoxyflurane. Emerg Med Aus 2007; 19(6):509-14. Medline
III Supportive (Green) Pain behaviour Patient ED-MD Gamis AS., Knapp JF., Glenski JA. Nitrous oxide analgesia in a pediatric emergency department. Ann Emerg Med 1989; 18(2):177-81. Medline
III Supportive (Green) Pain and anxiety Patient Hoeffe J., Doyon TE., Bailey B., et al. Intranasal fentanyl and inhaled nitrous oxide for fracture reduction: The FAN observational study. Am J Emerg Med 2017; 35(5):710-5. Medline
III Supportive (Green) Patient satisfaction Patient PH-Paramedic Johnson JC., Atherton Gl. Effectiveness of Nitrous Oxide in a rural EMS System. The Journal of Emergency Medicine 1991; 9:45-53. Medline
III Supportive (Green) Analgesia Patient PH-Paramedic Peterson TD., Kerns DE. Prehospital Pain Control: Nitrous Oxide Inhalation. Iowa Medicine 1989; 15-7. Medline

NSAIDs
Level Direction Primary Outcome Patient/Process Setting Reference
I Supportive (Green) Analgesia Patient ED-MD Bijur PE, Friedman BW, Irizarry E, Chang AK, Gallagher EJ. A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department. Ann Emerg Med 2021; 77(3):345-56. Medline
I Supportive (Green) Pain reduction of at least 15mm on a 100mm visual analog scale Patient ED-MD Khwaja SM., Minnerop M., Singer AJ. Comparison of ibuprofen, cyclobenzaprine or both in patients with acute cervical strain: A randomized controlled trial. CJEM 2010; 12(1):39-44. Medline
I Supportive (Green) Change in Faces Pain Scale over time Patient ED-MD Koller DM., Myers AB., Lorenz D., Godambe SA. Effectiveness of oxycodone, ibuprofen, or the combination in the initial management of orthopedic injury-related pain in children. Pediatr Emerg Care 2007; 23(9):627-33. Medline
I Neutral (Yellow) Prediction of severe sepsis Process PH-Paramedic Neighbor ML., Puntillo KA. Intramuscular ketorolac vs oral ibuprofen in emergency department patients with acute pain. Acad Emerg Med 1998; 5(2):118-22. Medline
III Neutral (Yellow) Pain relief (NRS or VAS) Patient PH-Paramedic Dijkstra BM., Berben SA., van Dongen RT., Schoonhoven L. Review on pharmacological pain management in trauma patients in (pre-hospital) emergency medicine in the Netherlands. Eur J Pain 2013; 18(1):3-19. Medline


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