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Drugs

, Volume 78, Issue 7, pp 727–735 | Cite as

The Expanding Role of Ketamine in the Emergency Department

  • Sophia Sheikh
  • Phyllis Hendry
Review Article

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.

Notes

Acknowledgements

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

Compliance with Ethical Standards

Conflict of interest

SS and PH have no conflicts of interests to disclose.

Funding

SS and PH have no funding to disclose.

References

  1. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.Google Scholar
  13. 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.Google Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.CrossRefPubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.Google Scholar
  30. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 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.Google Scholar
  33. 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.Google Scholar
  34. 34.
    Gardner AE, Dannemiller FJDD. Intracranial cerebrospinal fluid pressure in man during ketamine anesthesia. Anesth Analg. 1972;51(5):741–5.CrossRefPubMedGoogle Scholar
  35. 35.
    Shaprio HM, Wyte SRHA. Ketamine anaesthesia in patients with intracranial pathology. Br J Anaesth. 1972;44(11):1200–4.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedGoogle Scholar
  38. 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.CrossRefPubMedGoogle Scholar
  39. 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.CrossRefPubMedGoogle Scholar
  40. 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.CrossRefPubMedGoogle Scholar
  41. 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.CrossRefPubMedGoogle Scholar
  42. 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.CrossRefGoogle Scholar
  43. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 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.CrossRefPubMedGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.Google Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefGoogle Scholar
  51. 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.CrossRefPubMedGoogle Scholar
  52. 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.CrossRefPubMedGoogle Scholar
  53. 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.CrossRefPubMedGoogle Scholar
  54. 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. 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.PubMedPubMedCentralGoogle Scholar
  56. 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.CrossRefPubMedGoogle Scholar
  57. 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.CrossRefPubMedGoogle Scholar
  58. 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.CrossRefPubMedGoogle Scholar
  59. 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.CrossRefGoogle Scholar
  60. 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.CrossRefPubMedGoogle Scholar
  61. 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.CrossRefPubMedGoogle Scholar
  62. 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.Google Scholar
  63. 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.CrossRefPubMedGoogle Scholar
  64. 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.CrossRefGoogle Scholar
  65. 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.CrossRefGoogle Scholar
  66. 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.CrossRefPubMedGoogle Scholar
  67. 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.CrossRefPubMedGoogle Scholar
  68. 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.CrossRefPubMedGoogle Scholar
  69. 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. 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.CrossRefGoogle Scholar
  71. 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.CrossRefPubMedGoogle Scholar
  72. 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.CrossRefGoogle Scholar
  73. 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.CrossRefPubMedGoogle Scholar
  74. 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.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Emergency MedicineUniversity of Florida College of Medicine-JacksonvilleJacksonvilleUSA

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