3 reasons to use ketamine for prehospital analgesia

3 reasons to use ketamine for prehospital analgesia

Dr. Ramon Reyes, MD

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

May 11, 2015

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. It 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 post traumatic stress disorder (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).

This article was last reviewed in June of 2017 and is based on research available at that time. We will attempt to update this page as new evidence and best practice becomes available.

For many PAs and Doctors, the use of ketamine in battlefield medicine is a relatively new and unknown concept. Although ketamine has been used in hospitals throughout the world for several decades, there are still many myths and misconceptions surrounding it. Ketamine is an excellent analgesic because it is highly effective and has a very wide therapeutic window. The goal of this page is to give the medic a resource for engaging with their battalion PA or Surgeon regarding the use of ketamine.

Step 1: Read the Literature

Decisions in medicine are made, in large part, based on the evidence presented in well-researched literature. The best way to provide your battalion medical providers with the information they need is to know it yourself. Take the time to find and read through the articles below.

Frequently Asked Questions

Q: Why are we having this conversation?

A: Ketamine is one of the three medications recommended by the Committee on Tactical Combat Casualty Care (CoTCCC) for their triple option battlefield analgesia. They have found that ketamine is very effective at controlling pain and has a great safety profile. There is now plenty of evidence to support the use of Ketamine by the well-trained medic. In 2013 the ratio of use between Ketamine and Morphine, which has ample evidence against its use, among U.S. forces was 1:25. The poor outcomes associated with Morphine use on the battlefield are well documented. We can do better.

1. Saving lives on the battlefield: A Joint Trauma System review of pre-hospital trauma care in Combined Joint Operating Area-Afghanistan (CJOA-A). (2013)
2. A Triple-Option Analgesia Plan for Tactical Combat Casualty Care: TCCC Guidelines Change 13-04 (2014)
3. Prehospital Use of Ketamine in Battlefield Analgesia 2012-03 (2012)

Q: What are the indications for Ketamine use?

A: Ketamine is the medication of choice for traumatically injured patients with moderate to severe pain and whose vital signs are potentially unstable. Ketamine is also indicated for patients with excited delirium, for rapid sequence airway management, and for the maintenance of sedation.

TCCC Guidelines for Combat Medics

For Moderate to Severe Pain and casualty is in hemorrhagic shock or respiratory distress:

• Administer Ketamine 50mg IM or IN repeating q30min prn

OR

• Administer Ketamine 20mg Slow IV or IO repeating q20min prn

Endpoint control of pain or development of nystagmus

Consider Ondansetron 4mg ODT/IV/IO/IM q8hours prn for nausea and vomiting

1. Continuous intravenous infusion of Ketamine for maintenance sedation (2011)
2. Committee on Tactical Combat Casualty Care TCCC Guidelines for Medical Personnel 31 Jan 2017 (2017)

Q: Why is Ketamine so great?

A: Maintenance of airway reflexes: Upper airway reflexes remain intact and may be slightly exaggerated. Intubation is unnecessary, but occasional repositioning of the head may be necessary for optimal airway patency. Suctioning of hypersalivation may be necessary but is uncommon.

Cardiovascular stability: Blood pressure and pulse rate are not decreased and typically are mildly increased.

Analgesia & Amnesia: Analgesia is typically substantial or complete. Total amnesia is typical.

1. Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial (2015)

Q: Does Ketamine cause apnea?

A: Ketamine can cause short-term apnea if pushed too quickly through an IV. Apnea has been reported for as long as 30 seconds. Apnea can be avoided through conscientious administration by slow IV push. Periods of apnea can be managed with basic airway techniques. IM and IN doses have not been reported to cause apnea.

Q: Does Ketamine increase intraocular pressure (IOP)?

A: Data on this are inconclusive. In the healthy patient, increases on IOP are not concerning. Doses high enough to cause dissociative sedation may have risk in patients with penetrating eye injury or underlying glaucoma, but evidence supporting this is weak. There was a study that demonstrated an IOP decrease with ketamine administration. More data are needed to determine whether Ketamine is safe for patients with penetrating eye injuries.

1. Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. (2012)
2. Ketamine and intraocular pressure in children. (2014)

Q: Is Ketamine safe for TBI patients?

A: This has often been cited as an absolute contraindication. However, most of the data that reported this information was anecdotal. There was a study in pediatric patients, that ketamine lowered intracranial pressure.

1. Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. (2009)

Q: How often does Ketamine cause sialorrhea?

A: Excessive salivation or drooling is uncommon and airway complications from it are rare. Airway complication from hypersalivation is often cited as a serious issue but it is very rare.

Treatment with anticholinergic medication is shown to be unnecessary in most cases. However, providers may order either Glycopyrrolate 0.1–0.2mg by SC/IM/IV/IO every 4 hours or Atropine 0.01mg/kg by IV/IO push once 30 minutes prior to Ketamine administration.

1. Adjunctive atropine is unnecessary during ketamine sedation in children. (2008)

Q: Does Ketamine cause laryngospasm?

A: Laryngospasm is associated with poorly managed secretions entering the airway. This can be caused by Ketamine associated hypersalivation. As discussed above, this complication is rare. Prevention can be achieved with simple positioning or oral suctioning.

Q: Is there a reversal agent for Ketamine overdose?

A: There is no reversal agent for Ketamine. The patient must metabolize and clear the drug naturally. Thanks to Ketamine’s airway protective effects and hemodynamic stability, this hasn’t been shown to be a problem even in the presence of overdose. The most pronounced effect of Ketamine overdose is prolonged sedation. There are case reports of patients receiving much greater doses than intended dose, being disassociated for several hours, and recovering without any ill effects.

1. Inadvertent ketamine overdose in children: clinical manifestations and outcome(1999)

Q: What is an emergence phenomenon?

A: Ketamine has three dose ranges: a low analgesic dose, a medium recreational dose, and a high anesthetic dose. As a dissociated patient metabolizes the Ketamine, they must “descend” or “emerge” through the recreational dose range. During this emergence, around 10-30% of adults will experience hallucinations of an unpleasant nature, delirium, excitation, and combativeness. This is most effectively managed with amnesic medication such as Versed (midazolam 0.03 mg/kg or 1-2 mg IV). There is a small amount of evidence that coaching patients into and out of the “K-hole” will help the emergence. Reduction of noxious stimuli such as noise and light may also help.

Q: Does ketamine cause nausea and vomiting?

A: Nausea and vomiting are relatively common, it is recommended to treat prophylactically with 4 mg ondansetron (Zofran) IV.

Q: How can Ketamine be given?

A: Ketamine can be given by slow IV or IO push, as an IM injection, or through an IN atomizer.

Q: What are the side effects of Ketamine?

A: Ketamine does not depress breathing reflexes or blood pressure, as opioids such as morphine do. Below is a list of side effects. Percentage estimates are for children; corresponding adult estimates are not yet reliable enough to report.

• Airway misalignment requiring repositioning of head (occasional)
• Transient laryngospasm (0.3%)
• Transient apnea or respiratory depression (0.8%)
• Hypersalivation (rare)
• Emesis, usually well into recovery (8.4%)
• Recovery agitation (mild in 6.3%, clinically important in 1.4%)
• Muscular hypertonicity and random, purposeless movements (common)
• Clonus, hiccupping, or short-lived nonallergic rash of face and neck (rash incidence increased with atropine administration)

1. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. (2011)

Q: Who should not get Ketamine?

A: Use with caution with procedures which may stimulate the larynx, with children ages 3-12 months, in those with cardiac disease, asthma, and URIs. There appear to be only two types of patients that have absolute contraindications for ketamine:

• Infants; and
• Schizophrenics*.  It is recommended that the full dissociative dose be used and emergence managed with an amnesic.

1. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. (2011)

Q: Can Ketamine be given with other medications? 

A: Opioids. Administering low-dose Ketamine along with or before administration of opioids has sparing effect where less opioids are required for a similar relief of pain.

1. Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery (2013)
2. Opioid-Sparing Effect of Preemptive Bolus Low-Dose Ketamine for Moderate Sedation in Opioid Abusers (2013)

Propofol. Known in ER slang as “Ketafol”, the combination of Ketamine and Propofol has been shown to decrease the amount of medication required for sedation while reducing the respiratory depression and blood pressure decrease often seen with Propofol.

1. Ketamine Use in the ER Expanded; Ketamine Plus Propofol May Be Better Than Propofol Alone (2011)
2. Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. (2011)

Benzodiazepines. The combination of Versed (midazolam) and ketamine provides effective procedural sedation and analgesia in adult patients and appears to be safe. Emergence reactions can be effectively managed with midazolam.

1. A combination of midazolam and ketamine for procedural sedation and analgesia in adult emergency department patients. (2000)

Paralytics. While the use of paralytics for airway management and maintenance of a sedated patient falls within the skillset of an advanced provider, it is good for the medic to have an understanding of the science behind it. The use of Ketamine and a paralytic such as Rocuronium (called “RocKet” in ED parlance) is a safe and valuable alternative to the time-honored combination of etomidate and succinylcholine for endotracheal intubation in critically ill patients, especially those with unstable vitals.

1. Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. (2009)
2. Pro-Con Debate: Etomidate or Ketamine for Rapid Sequence Intubation in Pediatric Patients (2012)
3. Rapid-sequence intubation: a review of the process and considerations when choosing medications. (2014)

Additional Resources for Gettin’ Smart

EMCrit – Procedural Sedation Part I

A National Trauma Care System: Integrating Military and Civilian Trauma Systems to Achieve Zero Preventable Deaths After Injury (2016)

Tactical Medicine Collective ; Pharmacology  Ketamine

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