Skip to main content
Log in

The Expanding Role of Ketamine in the Emergency Department

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Patients frequently come to the emergency department for pain. For decades, ketamine has been used in the emergency department for procedural sedation but is now receiving attention as a potential alternative to opioids because of its unique analgesic effects. Additionally, ketamine’s dissociative properties have made it a popular choice for sedating profoundly agitated patients. In this narrative review, these new roles for ketamine in the emergency department are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Similar content being viewed by others

References

  1. Basic Principles of Pain Management in the Emergency Care Setting: Introduction, Recognition, and Assessment. University of Florida College of Medicine—Jacksonville, Department of Emergency Medicine. Pain Assessment and Management Initiative (PAMI): A Patient Safety Project [1/1/2017]. Retrieved from: http://pami.emergency.med.jax.ufl.edu/.

  2. Wang J, Goffer Y, Xu D, et al. A single subanesthetic dose of ketamine relieves depression-like behaviors induced by neuropathic pain in rats. Anesthesiology. 2011;115:812–21. https://doi.org/10.1097/ALN.0b013e31822f16ae.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Machado-Vieira R, Salvadore G, DiazGranados N, Zarate CA. Ketamine and the next generation of antidepressants with a rapid onset of action. Pharmacol Ther. 2009;123(2):143–50. https://doi.org/10.1016/j.pharmthera.2009.02.010.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017;35(7):1005–11. https://doi.org/10.1016/j.ajem.2017.02.002.

    Article  PubMed  Google Scholar 

  5. Riddell J, Tran A, Bengiamin R, Hendey GW, Armenian P. Ketamine as a first-line treatment for severely agitated emergency department patients. Am J Emerg Med. 2017;35(7):1000–4. https://doi.org/10.1016/j.ajem.2017.02.026.

    Article  PubMed  Google Scholar 

  6. Oye I, Paulsen O, Maurset A. Effects of ketamine on sensory perception: evidence for a role of N-methyl-d-aspartate receptors. J Pharmacol Exp Ther. 1992;260(3):1209 LP–1213. http://jpet.aspetjournals.org/content/260/3/1209.abstract.

  7. Pak DJ, Yong RJ, Kaye AD, et al. Chronification of pain: mechanisms, current understanding, and clinical implications. Curr Pain Headache Rep. 2018;22:9. https://doi.org/10.1007/s11916-018-0666-8.

    Article  PubMed  Google Scholar 

  8. Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-d-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991;44(3):293–9.

    Article  PubMed  CAS  Google Scholar 

  9. Weber A, Dwyer T, Mummery K. Morphine administration by paramedics: an application of the theory of planned behaviour. Injury. 2012;43(9):1393–6. https://doi.org/10.1016/j.injury.2010.12.006.

    Article  PubMed  Google Scholar 

  10. DuPen A, Shen D, Ersek M. Mechanisms of opioid-induced tolerance and hyperalgesia. Pain Manag Nurs. 2007;8(3):113–21. https://doi.org/10.1016/j.pmn.2007.02.004.

    Article  PubMed  Google Scholar 

  11. Hayes CJ, Painter JT. A comprehensive clinical review of opioid-induced allodynia: discussion of the current evidence and clinical implications. J Opioid Manag. 2017;13(2):95–103.

    Article  PubMed  Google Scholar 

  12. Zhang GF, Wang J, Han JF, Guo J, Xie ZM, Pan W, Yang JJ, Sun KJ. Acute single dose of ketamine relieves mechanical allodynia and consequent depression-like behaviors in a rat model. Neurosci Lett. 2016;19(631):7–12. https://doi.org/10.1016/j.neulet.2016.08.006.

    Article  CAS  Google Scholar 

  13. Kim K, Mishina M, Kokubo R, Nakajima T, Morimoto D, Isu T, et al. Ketamine for acute neuropathic pain in patients with spinal cord injury. J Clin Neurosci Off J Neurosurg Soc Australas. 2013;20(6):804–7.

    CAS  Google Scholar 

  14. Qi X, Evans AM, Wang J, Miners JO, Upton RN, Milne RW. Inhibition of morphine metabolism by ketamine. Drug Metab Dispos. 2010;38(5):728–31. https://doi.org/10.1124/dmd.109.030957.

    Article  PubMed  CAS  Google Scholar 

  15. Pacheco GS, Ferayorni A. Pediatric procedural sedation and analgesia. Emerg Med Clin North Am. 2013;31(3):831–52. https://doi.org/10.1016/j.emc.2013.04.002.

    Article  PubMed  Google Scholar 

  16. 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. Acad Emerg Med. 2017;24(6):676–85. https://doi.org/10.1111/acem.13172.

    Article  PubMed  Google Scholar 

  17. Loix S, De Kock M, Henin P. The anti-inflammatory effects of ketamine state of the art. Acta Anaesthesiol Belg. 2011;62(1):47–58.

    PubMed  CAS  Google Scholar 

  18. Rolan P, Lim S, Sunderland V, Liu Y, Molnar V. The absolute bioavailability of racemic ketamine from a novel sublingual formulation. Br J Clin Pharmacol. 2014;77(6):1011–6. https://doi.org/10.1111/bcp.12264.

    Article  PubMed  CAS  Google Scholar 

  19. Chong C, Schug SA, Page-Sharp M, Jenkins BIK. Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009;29(5):317–24. https://doi.org/10.2165/00044011-200929050-00004.

    Article  PubMed  CAS  Google Scholar 

  20. Yanagihara Y, Ohtani M, Kariya S, et al. Plasma concentration profiles of ketamine and norketamine after administration of various ketamine preparations to healthy Japanese volunteers. Biopharm Drug Dispos. 2003;24(1):37–43. https://doi.org/10.1002/bdd.336.

    Article  PubMed  CAS  Google Scholar 

  21. 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):601.e5–7. https://doi.org/10.1016/j.ajem.2014.09.029.

  22. Motov S, Mai M, Pushkar I, et al. A prospective randomized, double-dummy trial comparing intravenous push dose of low dose ketamine to short infusion of low dose ketamine for treatment of moderate to severe pain in the emergency department. Am J Emerg Med. 2017;35(8):1095–100. https://doi.org/10.1016/j.ajem.2017.03.004.

    Article  PubMed  Google Scholar 

  23. 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. 2014;33(3):402–8. https://doi.org/10.1016/j.ajem.2014.12.058.

    Article  Google Scholar 

  24. Ahern TL, Herring AA, Anderson ES, Madia VA, Fahimi J, Frazee BW. The first 500: initial experience with widespread use of low-dose ketamine for acute pain management in the ED. Am J Emerg Med. 2015;33:197–201. https://doi.org/10.1016/j.ajem.2014.11.010.

    Article  PubMed  Google Scholar 

  25. Ahern TL, Herring AA, Stone MB, Frazee BW. Effective analgesia with low-dose ketamine and reduced dose hydromorphone in ED patients with severe pain. Am J Emerg Med. 2013;31:847–51. https://doi.org/10.1016/j.ajem.2013.02.008.

    Article  PubMed  Google Scholar 

  26. Richards JR, Rockford RE. Low-dose ketamine analgesia: patient and physician experience in the ED. Am J Emerg Med. 2013;31:390–4. https://doi.org/10.1016/j.ajem.2012.07.027.

    Article  PubMed  Google Scholar 

  27. Ahern TL, Herring AA, Miller S, Frazee Md BW. Low-dose ketamine infusion for emergency department patients with severe pain. Pain Med. 2015;16:1402–9.

    Article  PubMed  Google Scholar 

  28. Motov S, Rockoff B, Cohen V, et al. Intravenous subdissociative-dose ketamine versus morphine for analgesia in the emergency department: a randomized controlled trial. Ann Emerg Med. 2015;66(3):222–229.e1. https://doi.org/10.1016/j.annemergmed.2015.03.004.

    Article  PubMed  Google Scholar 

  29. Losvik OK, Murad K, Skjerve E, Husum H. Ketamine for prehospital trauma analgesia in a low-resource rural trauma system: a retrospective comparative study of ketamine and opioid analgesia in a ten-year cohort in Iraq. Scand J Trauma Resusc Emerg. 2015;23(94):1–8. https://doi.org/10.1186/s13049-015-0176-1.

    Article  Google Scholar 

  30. Scheppke KA, Braghiroli J, Shalaby M, Chait R, Suchard J. Prehospital use of IM ketamine for sedation of violent and agitated patients. West J Emerg Med. 2014;15(7):736–41. https://doi.org/10.5811/westjem.2014.9.23229.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Langston WT, Wathen JE, Roback MG, Bajaj L. Effect of ondansetron on the incidence of vomiting associated with ketamine sedation in children: a double-blind, randomized, placebo-controlled trial. Ann Emerg Med. 2008. https://doi.org/10.1016/j.annemergmed.2008.01.326.

    Article  PubMed  Google Scholar 

  32. Lee JS, Jeon WC, Park EJ, et al. Does ondansetron have an effect on intramuscular ketamine-associated vomiting in children? A prospective, randomised, open, controlled study. J Paediatr Child Health. 2014. https://doi.org/10.1111/jpc.12515.

    Article  PubMed  Google Scholar 

  33. Green SM, Roback MG, Kennedy RM, Krauss B. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. Ann Emerg Med. 2011;57(5):450–61. https://doi.org/10.1016/j.annemergmed.2010.11.030.

    Article  Google Scholar 

  34. Gardner AE, Dannemiller FJDD. Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg. 1972;51(5):741–5.

    Article  PubMed  CAS  Google Scholar 

  35. Shaprio HM, Wyte SRHA. Ketamine anaesthesia in patients with intracranial pathology. Br J Anaesth. 1972;44(11):1200–4.

    Article  PubMed  CAS  Google Scholar 

  36. Green SM, Andolfatto G, Krauss BS. Ketamine and intracranial pressure: no contraindication except hydrocephalus. Ann Emerg Med. 2015;65(1):52–4. https://doi.org/10.1016/j.annemergmed.2014.08.025.

    Article  PubMed  Google Scholar 

  37. Sehdev RS, Riginal Esearch OR, Symmons DA, Kindl K. Ketamine for rapid sequence induction in patients with head injury in the emergency department. Emerg Med Australas. 2006;18(1):37–44. https://doi.org/10.1111/j.1742-6723.2006.00802.x.

    Article  PubMed  Google Scholar 

  38. Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NGW, Hohl CM. The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review. Ann Emerg Med. 2015;65(1):43–51. https://doi.org/10.1016/j.annemergmed.2014.06.018.

    Article  PubMed  Google Scholar 

  39. Albanèse J, Arnaud S, Rey M, Thomachot L, Alliez B, Martin C. Ketamine decreases intracranial pressure and electroencephalographic activity in TBI patients during propofol sedation. Anesthesiology. 1997;87(6):1328–34.

    Article  PubMed  Google Scholar 

  40. Schwedler M, Miletich DJ, Albrecht RF. cerebral blood flow and metabolism following ketamine administration. Can Anaesth Soc J. 1982;29(3):222–6. https://doi.org/10.1007/BF03007120.

    Article  PubMed  CAS  Google Scholar 

  41. Zeiler FA, Teitelbaum J, West M, Gillman LM. The ketamine effect on ICP in traumatic brain injury. Neurocrit Care. 2014;21(1):163–73. https://doi.org/10.1007/s12028-013-9950-y.

    Article  PubMed  CAS  Google Scholar 

  42. Pfenninger E, Griinert A, Bowdler I, Kilian J. The effect of ketamine on intracranial pressure during haemorrhagic shock under the conditions of both spontaneous breathing and controlled ventilation. Acta Neurochir (Wien). 1985;78(3–4):113–8.

    Article  CAS  Google Scholar 

  43. Upchurch CP, Russ S, et al. Comparison of etomidate and ketamine for induction during rapid sequence intubation of adult trauma patients. Ann Emerg Med. 2017;69(1):24–33.e2. https://doi.org/10.1016/j.annemergmed.2016.08.009.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Jabre P, Combes X, Lapostolle F, et al. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. Lancet. 2009;374(9686):293–300. https://doi.org/10.1016/S0140-6736(09)60949-1.

    Article  PubMed  CAS  Google Scholar 

  45. Weinbroum AA. Non-opioid IV adjuvants in the perioperative period: pharmacological and clinical aspects of ketamine and gabapentinoids. Pharmacol Res. 2012;65(4):411–29. https://doi.org/10.1016/j.phrs.2012.01.002.

    Article  PubMed  CAS  Google Scholar 

  46. 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. https://doi.org/10.1111/acem.12510.

    Article  PubMed  Google Scholar 

  47. Graudins A, Meek R, Egerton-Warburton D, Oakley E, Seith R. The PICHFORK (Pain in Children Fentanyl or Ketamine) Trial: a randomized controlled trial comparing intranasal ketamine and fentanyl for the relief of moderate to severe pain in children with limb injuries. Ann Emerg Med. 2015;65(3):248–254.e1. https://doi.org/10.1016/j.annemergmed.2014.09.024.

    Article  PubMed  Google Scholar 

  48. Johansson P, Kongstad P, Johansson A. The effect of combined treatment with morphine sulphate and low-dose ketamine in a prehospital setting. Scand J Trauma Resusc Emerg Med. 2009;17(61):1–5. https://doi.org/10.1186/1757-7241-17-61.

    Article  Google Scholar 

  49. Galinski M, Dolveck F, Combes X, et al. Management of severe acute pain in emergency settings: ketamine reduces morphine consumption. Am J Emerg Med. 2007;25(4):385–90. https://doi.org/10.1016/j.ajem.2006.11.016.

    Article  PubMed  Google Scholar 

  50. Jouguelet-Lacoste J, La Colla L, Schilling D, Chelly J. The use of intravenous infusion or single of low-dose ketamine for postoperative analgesia: a review of the current literature. Pain Med (United States). 2014;16:383–403. https://doi.org/10.1111/pme.12266.

    Article  Google Scholar 

  51. Subramaniam K, Subramaniam B, Steinbrook RA. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. Anesth Analg. 2004;99:482–95. https://doi.org/10.1213/01.ANE.0000118109.12855.07.

    Article  PubMed  CAS  Google Scholar 

  52. Gharaei B, Jafari A, Aghamohammadi H, et al. Opioid-sparing effect of preemptive bolus low-dose ketamine for moderate sedation in opioid abusers undergoing extracorporeal shock wave lithotripsy: a randomized clinical trial. Anesth Analg. 2013;116(1):75–80. https://doi.org/10.1213/ANE.0b013e31826f0622.

    Article  PubMed  CAS  Google Scholar 

  53. Herring A, Ahern T, Stone M, Frazee B. Emerging applications of low-dose ketamine for pain management in the ED. Am J Emerg Med. 2013;31(2):416–9. https://doi.org/10.1016/j.ajem.2012.08.027.

    Article  PubMed  Google Scholar 

  54. Majidinejad S, Esmailian M, Emadi M. Comparison of intravenous ketamine with morphine in pain relief of long bones fractures: a double blind randomized clinical trial. Emerg (Tehran). 2014;2(2):77–80.

    Google Scholar 

  55. Ahmadi O, Isfahani MN, Feizi A. Comparing low-dose intravenous ketamine-midazolam with intravenous morphine with respect to pain control in patients with closed limb fracture. J Res Med Sci. 2014;19(6):502–8.

    PubMed  PubMed Central  CAS  Google Scholar 

  56. Kennedy RM, Porter FL, Miller JP, Jaffe DM. Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic emergencies. Pediatrics. 1998;102(4 Pt 1):956–63. https://doi.org/10.1542/peds.102.4.956.

    Article  PubMed  CAS  Google Scholar 

  57. Andolfatto G, Willman E, Joo D, et al. Intranasal ketamine for analgesia in the emergency department: a prospective observational series. Acad Emerg Med. 2013;20(10):1050–4. https://doi.org/10.1111/acem.12229.

    Article  PubMed  Google Scholar 

  58. Yeaman F, Oakley E, Meek R, Graudins A. Sub-dissociative dose intranasal ketamine for limb injury pain in children in the emergency department: a pilot study. Emerg Med Australas. 2013;25:161–7. https://doi.org/10.1111/1742-6723.12059.

    Article  PubMed  Google Scholar 

  59. Shrestha R, Pant S, Shrestha A, et al. Intranasal ketamine for the treatment of patients with acute pain in the emergency department. World J Emerg Med. 2016;77(11):19–24. https://doi.org/10.5847/wjem.j.1920-8642.2016.01.003.

    Article  Google Scholar 

  60. Farnia MR, Jalali A, Vahidi E, Momeni M, Seyedhosseini J, Saeedi M. Comparison of intranasal ketamine versus IV morphine in reducing pain in patients with renal colic. Am J Emerg Med. 2016;35(3):434–7. https://doi.org/10.1016/j.ajem.2016.11.043.

    Article  PubMed  Google Scholar 

  61. Yeaman F, Meek R, Egerton-Warburton D, Rosengarten P, Graudins A. Sub-dissociative-dose intranasal ketamine for moderate to severe pain in adult emergency department patients. Emerg Med Australas. 2014;26:237–42. https://doi.org/10.1111/1742-6723.12173.

    Article  PubMed  Google Scholar 

  62. Gurnani A, Sharma PK, Rautela RS, Bhattacharya A. Analgesia for acute musculoskeletal trauma: low-dose subcutaneous infusion of ketamine. Anesth Intensive Care. 1996;24(1):32–6.

    CAS  Google Scholar 

  63. 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.

    Article  PubMed  CAS  Google Scholar 

  64. Bredmose PP, Grier G, Davies GE, Lockey DJ. Pre-hospital use of ketamine in paediatric trauma. Acta Anaesthesiol Scand. 2009;53(4):534–45. https://doi.org/10.1111/j.1399-6576.2008.01852.x.

    Article  CAS  Google Scholar 

  65. Wiel E, Zitouni D, Assez N, et al. Prehospital emergency care continuous infusion of ketamine for out-of-hospital isolated orthopedic injuries secondary to trauma: a randomized controlled trial. Prehospital Emerg Care. 2015;19(1):10–6. https://doi.org/10.3109/10903127.2014.923076.

    Article  Google Scholar 

  66. Hopper AB, Vilke GM, Castillo EM, Campillo A, Davie T, Wilson MP. Ketamine use for acute agitation in the emergency department. J Emerg Med. 2015;48(6):712–9. https://doi.org/10.1016/j.jemermed.2015.02.019.

    Article  PubMed  Google Scholar 

  67. Kowalski JM, Kopec KT, Lavelle J, Osterhoudt K. A novel agent for management of agitated delirium a case series of ketamine utilization in the pediatric emergency department. Pediatr Emerg Care. 2017;33(9):e58–62.

    Article  PubMed  Google Scholar 

  68. Isbister GK, Calver LA, Downes MA, Page CB. Ketamine as rescue treatment for difficult-to-sedate severe acute behavioral disturbance in the emergency department. Ann Emerg Med. 2016;67(5):581–7. https://doi.org/10.1016/j.annemergmed.2015.11.028.

    Article  PubMed  Google Scholar 

  69. ACEP Excited Delirium Task Force. White paper report on excited delirium syndrome. (Downloaded 08/10/2017); 2009. https://www.acep.org/uploadedFiles/ACEP/Practice_Resources/disater_and_EMS/EMS_resources/ACEP%20Excited%20Delirium%20White%20Paper%20final%20form.pdf.

  70. Olives TD, Nystrom PC, Cole JB, Dodd KW, Ho JD. Intubation of profoundly agitated patients treated with prehospital ketamine. Prehosp Disaster Med. 2017;31(6):593–601. https://doi.org/10.1017/S1049023X16000819.

    Article  Google Scholar 

  71. Lahti A. Subanesthetic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology. 1995;13(1):9–19. https://doi.org/10.1016/0893-133X(94)00131-I.

    Article  PubMed  CAS  Google Scholar 

  72. Cole JB, Moore JC, Nystrom PC, et al. A prospective study of ketamine versus haloperidol for severe prehospital agitation. Clin Toxicol. 2016;54(7):556–62. https://doi.org/10.1080/15563650.2016.1177652.

    Article  CAS  Google Scholar 

  73. Burnett AM, Peterson BK, Stellpflug SJ, et al. The association between ketamine given for prehospital chemical restraint with intubation and hospital admission. Am J Emerg Med. 2015;33(1):76–9. https://doi.org/10.1016/j.ajem.2014.10.016.

    Article  PubMed  Google Scholar 

  74. Le Cong M, Humble I. A ketamine protocol and intubation rates for psychiatric air medical retrieval. Air Med J. 2015;34(6):357–9. https://doi.org/10.1016/j.amj.2015.07.007.

    Article  Google Scholar 

Download references

Acknowledgements

The study authors would like to thank Taylor Miller, BS and Caroline Dodd, BS for their help in the preparation of this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sophia Sheikh.

Ethics declarations

Conflict of interest

SS and PH have no conflicts of interests to disclose.

Funding

SS and PH have no funding to disclose.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sheikh, S., Hendry, P. The Expanding Role of Ketamine in the Emergency Department. Drugs 78, 727–735 (2018). https://doi.org/10.1007/s40265-018-0904-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-0904-8

Navigation