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3 reasons to use ketamine for prehospital analgesia

With the increased use of ketamine by the military medics and emergency departments is it time for more widespread use of ketamine by civilian EMS?

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Spc. Dameon Williams, human resource specialist, 2nd Battalion, 25th Aviation Regiment, 25th Combat Aviation Brigade, evaluates a casualty by initially checking her consciousness during the 25th CAB’s CLS training and qualification field training exercise at Wheeler Army Air Field, Nov. 18.

By Major Andrew D. Fisher, MPAS, APA, PA-C
75th Ranger Regiment, Fort Benning

Recently, ketamine has made resurgence in the areas of emergency and pre-hospital medicine, and for good reasons.

Ketamine was first developed in 1962 and is on the WHO Model List of Essential Medications.[1,2] It is commonly used for pediatric sedation in emergency or operating room settings prior to painful procedures.[3]

The safety profile and effectiveness of ketamine make it an ideal medication in the pre-hospital setting. The use of ketamine in EMS has been somewhat limited to sedation for psychosis, other behavioral health issues, and intubation.[4-7]

In 2011, the Committee on Tactical Combat Casualty Care (CoTCCC) added it to the Tactical Combat Casualty Care (TCCC) guidelines and soon after the Defense Health Board authorized it for battlefield/pre-hospital analgesia.[8,9]

Ketamine acts as an N-methyl-D-aspartate (NMDA) receptor antagonist, but also binds to the mu and kappa opioid receptors.[10]

It can be given intravenously (IV), intramuscular (IM), intranasally (IN) and by mouth (PO). Ketamine is a dissociative anesthetic with a recommended dose of 1.0-2.0 mg/kg IV. Onset is typically within 1 minute, with effective dissociation in 5-10 minutes.[3] When given IM, dose range from 3-4 mg/kg with onset between 5-20 minutes.[2,3] Above 1.5 mg/kg IV dose, there does not appear to be any deeper sedation, only longer duration.3 Ketamine also offers analgesia in sub-anesthetic doses, depending on the literature; doses may range from 0.2 mg/kg-1.0 mg/kg IV.[2,3,10,11]

The U.S. Military has successfully been using ketamine on the battlefields of Irag and Afghanistan for the past several years.

The CoTCCC recommends 20 mg IV or 50 mg IM/IN for the initial dose with multiple anecdotal reports discussing great effects.[8,12] The 75th Ranger Regiment has used ketamine since 2009 and has noted good effects and safety in a small case series with larger doses; their current protocol uses ketamine at 75 mg IV and 250-500 mg IM.[13]

With the increased use of ketamine by the military and emergency departments, is it time for more wide spread use of ketamine by civilian EMS systems? If so, should it be used instead of opioids for analgesia in the pre-hospital setting?

1. Ketamine is safe for patients in shock

Opioids often cause undesired effects in patients, especially those who are in shock.[8]

Commonly used narcotics: morphine, fentanyl, and dilaudid, can cause hypotension, bradycardia, and respiratory depression.

When in shock there is decreased blood flow to the musculoskeletal system which can negatively effect the bioavailability of medications delivered intramuscularly.[14]

Ketamine offers instead multiple positive effects, one of which is the release of catecholamines.[10] This allows the EMS provider to treat pain without the worry of hypotension or worsening shock due to medication administration.

In addition, ketamine increases heart rate, stroke volume, and is a bronchodilator.[10] A recent study by Shackelford and colleagues, compared blood pressures in patients who received opioids versus ketamine. Initially, the morphine group had higher blood pressures but after medication administration, the ketamine group showed an increase in blood pressure, compared to morphine, which caused a drop.[15]

Ketamine’s positive effects on the cardiovascular system make it superior to opioids in the acutely injured patient.

2. Ketamine, chronic pain and PTSD

Pain is often seen as a symptom of injury, but maybe we should view it as a disease state of the central nervous system.[16] Clifford et al. noted that neurons are not the only cells responsible for pain; glial cells can release pro-inflammatory cytokines, nitric oxide, prostaglandins, and excitatory amino acids, which can decrease the efficacy of morphine.[17]

EMT-Ps should move past thinking of pain as just a symptom of trauma and injury, and should start to consider the long-term outcomes of the patients. What are the long-term outcomes of poorly treated pain? Untreated pain can manifest itself as chronic pain, anxiety, anger, sensitivity to external stimuli, and withdrawal from interpersonal contact.[16] By treating pain early, EMT-Ps can help decrease the morbidity associated with poorly treated pain.

There is ample data that supports early pain management in an effort to reduce the incidence of PTSD symptoms.[16-21] The properties of ketamine are thought to play a role in the reduction of PTSD by blocking glutamate via NMDA receptor blockade.[16-22] As discussed above, acutely injured patients often present in shock making opioids possibly not the best medication choice. The early administration of ketamine can control pain and possibly help decrease the incidence of PTSD.

3. Ketamine’s safety profile

Unlike opioids, ketamine has a wider safety profile. Even with accidental overdoses of ketamine in pediatric patients, there were no adverse outcomes in this population.[23] There were many concerns about ketamine’s effect on intraocular pressure (IOP) and intracranial pressure (ICP). However, these were most likely overestimated, in fact, one study demonstrated a 30 percent decrease in ICP in children undergoing procedures.[3,24,25]

Conclusion: Ketamine is a safe and effective analgesia

Opioids for pain management have dominated medical practice since the Civil War. Opioids are effective in many situations, but at the same time they may not be the best choice in the pre-hospital/EMS environment. As an alternative, ketamine is a safe and effective form of analgesia at doses that range from 0.2-1.0 mg/kg.

EMS protocols give a tremendous amount of responsibility to the EMT-P, as they provide critical care to severely injured patients. Ketamine is an option and maybe a better option for pain management for EMT-Ps in the pre-hospital environment.

About the author
MAJ Fisher is the current Regimental Physician Assistant for the 75th Ranger Regiment, Fort Benning, Georgia. He has deployed seven times in support of Operation Enduring Freedom and Operation Iraqi Freedom. He is the recipient of the Purple Heart and four Bronze Star Medals, one with Valor Device. Prior to becoming a physician assistant, he worked as a paramedic for a hospital based 911 service in Indianapolis.

I would like to thank COL Shawn Kane, MD for his valuable comments and review of the manuscript.

References

1. Schauer S, Fisher AD, Mabry RL. Battle Tested: Ketamine Proves its Worth on the Front Lines. Emergency Physicians Monthly. 2015. http://www.epmonthly.com/www.epmonthly.com/features/current-features/battle-tested-ketamine-proves-its-worth-on-the-front-lines/. Accessed May 5, 2015.
2. Best W, Bodenschatz C, Beran D. Ketamine. World Health Organization: Expert Committee on Drug Dependance; 2014; Geneva, Switzerland.
3. Green SM, Roback MG, Kennedy RM, Baruch K. Clinical Practice Guideline for Emergency Department Ketamine Dissociative Sedation: 2011 Update. Annals of Emergency Medicine. 2011;57(5):449-461.
4. Burnett AM SJ, Griffith KR, Kroeger B, Frascone RJ. The Emergency Department Experience with Prehospital Ketamine: A Case Series of 13 Patients. Prehospital Emergency Care. 2012;16(4):553-559.
5. Le Cong M, Gynther B, Hunter E, Schuller P. Ketamine sedation for patients with acute agitation and psychiatric illness requiring aeromedical retrieval. Emerg Med J. 2012;29(4):335-337.
6. Ho JD, Smith SW, Nystrom PC, et al. Successful management of excited delirium syndrome with prehospital ketamine: two case examples. Prehosp Emerg Care. 2013;17(2):274-279.
7. Sibley A, Mackenzie M, Bawden J, Anstett D, Villa-Roel C, Rowe BH. A prospective review of the use of ketamine to facilitate endotracheal intubation in the helicopter emergency medical services (HEMS) setting. Emerg Med J. 2011;28(6):521-526.
8. Butler FK, Kotwal RS, Buckenmaier III CC, et al. A Triple-Option Analgesia Plan for Tactical Combat Casualty Care: TCCC Guidelines Change 13-04. Journal of Special Operations Medicine. 2014;14(1).
9. Defense Health Board. Prehospital Use of Ketamine in Battlefield Analgesia 2012-03. In: Department of Defense; 2012.
10. Craven R. Ketamine. Anaesthesia. 2007;62:S48-S53.
11. Svenson JE, Abernathy MK. Ketamine for prehospital use: new look at an old drug. Am J Emerg Med. 2007;25(8):977-980.
12. Schauer S, Robinson JB, Mabry RL, Howard JT. Battlefield analgesia: TCCC Guidelines Are Not Being Followed. J Spec Oper Med. 2015;15(1):63-67.
13. Fisher AD, Rippee B, Shehan JH, Conklin CC, Mabry RL. Prehospital Analgesia With Ketamine for Combat Wounds: A Case Series. J Spec Oper Med. 2014;14(4):11-17.
14. Eastridge BJ, Salinas J, Wade CE, Blackbourne LH. Hypotension is 100 mm Hg on the battlefield. Am J Surg. 2011;202(4):404-408.
15. Shackelford SA, Fowler M, Schultz K, et al. Prehospital pain medication use by U.S. Forces in Afghanistan. Mil Med. 2015;180(3):304-309.
16. Buckenmaier III CC, Griffith S. Military Pain Management in 21st Century War. Military Medicine. 2010;175(7):7-12.
17. Clifford JL, Fowler M, Hansen JJ, et al. State of the science review: Advances in pain management in wounded service members over a decade at war. J Trauma Acute Care Surg. 2014;77(3 Suppl 2):S228-236.
18. Feder A, Parides MK, Murrough JW, et al. Efficacy of Intravenous Ketamine for Treatment of Chronic Post-traumatic Stress Disorder. JAMA Psychiatry. 2014:E1-E8.
19. Grieger TA, Cozza SJ, Ursano RJ, et al. Posttraumatic Stress Disorder and Depression in Battle-Injured Soldiers. American Journal of Psychiatry. 2006;163:1777-1783.
20. Holbrook TL, Galarneau MR, Dye JL, Quinn K, Dougherty AL. Morphine Use after Combat Injury in Iraq and Post-Traumatic Stress Disorder. The new england journal of medicine. 2010;362(2):110-117.
21. McGhee LL, Maani CV, Garza TH, Gaylord KM, Black IH. The correlation between ketamine and posttraumatic stress disorder in burned service members. The Journal of TRAUMA Injury, Infection, and Critical Care. 2008;64:S195-S198.
22. Rothbaum BO, Kearns MC, Price M, et al. Early intervention may prevent the development of posttraumatic stress disorder: a randomized pilot civilian study with modified prolonged exposure. Biol Psychiatry. 2012;72(11):957-963.
23. Green SM, Clark R, Hostetler MA, Cohen M, Carlson D, Rothrock SG. Inadvertent Ketamine Overdose in Children: Clinical Manifestations and Outcomes. Annals of Emergency Medicine. 1999;34(4):492-497.
24. Bar-Joseph G, Guilburd Y, Tamir A, Guilburd JN. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. The Journal of Neurosurgery: Pediatrics. 2009;4:40-46.
25. Drayna P, Estrada CW, Saville BR, Arnold D. Ketamine is not associated with elevation of intraocular pressure during procedural sedation. American Journal of Emergency Medicine. 2012;30(7).

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