The use of ketamine in emergency and critical care medicine is a relatively new concept in the USA, despite the reality that ketamine has been used in hospitals throughout the world for several decades and remains throughout the decades on the World Health Organization Model List of Essential Medicines.
But there are still many myths and misconceptions surrounding Ketamine. To be clear, Ketamine is an excellent dissociative, analgesic, and sedative because it is highly effective and has a very wide therapeutic window. The goal of this discussion is to elaborate on some of the issues regarding the use of ketamine.
Ketamine was first synthesized in 1962 by Calvin Stevens at Parke-Davis Co (now Pfizer) as an alternative anesthetic to phencyclidine. It was first used in humans in 1965 by Corssen and Domino and was introduced into clinical practice by 1970. Ketamine is frequently described as a “unique drug” because it shows hypnotic (sleep-producing), analgesic (pain-relieving) and amnesic (short-term memory loss) effects; no other drug used in clinical practice produces these three important effects at the same time.
There is now plenty of evidence to support the use of Ketamine in the prehospital and hospital environment.
The benefits to ketamine include favorable effects on respiratory reflexes, mechanics and hemodynamics (Alternatives to Rapid Sequence Intubation: Contemporary Airway Management with Ketamine; Merelman; West J Emerg Med. 2019 May). Adjunctive continuous infusion ketamine promotes analgesic and sedative dose‐sparing effects in mechanically ventilated patients while improving time spent within goal sedation range; and Ketamine is the least cardio-depressant induction agent available (Morris et al, 2009; Gelissen et al, 1996). There is a wealth of evidence indicating the value of ketamine in the treatment of severe pain, including conditions such as trauma, fractures, abdominal and flank pain, low back pain, and extremity pain (Ketamine; Steven B. Rosenbaum, et Al.; StatPearls Publishing; 2020 Jan).
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 a medication of choice for patients with excited delirium, patients requiring disassociation, for rapid sequence airway management, for sedation and the maintenance of sedation. Ketamine also has a place in a number of other pathologies, including its newest area of research, use in depression.
In a patient with significant hemodynamic or respiratory instability, or potential instability, the use of any narcotic could potentially worsen their condition. Yet Ketamine will not result in detrimental effects.
With Ketamine, Upper airway reflexes remain intact and may be slightly exaggerated, suctioning of hypersalivation may be necessary but is uncommon. Blood pressure and pulse rate are not decreased and typically are mildly increased. Analgesia is typically substantial or complete, while total amnesia is typical.
Ketamine has been reported to cause apnea and respiratory depression with rapid IV push. Apnea has been reported for as long as 30 seconds with rapid IV push Ketamine. Apnea can be avoided through conscientious administration by slow IV push and by consideration of factors such as known airway anatomical issues or instability. Periods of apnea can be managed with basic airway techniques. IM and IN doses have not been reported to cause apnea in the literature.
Traumatic Brain Injury and Stroke have often been cited as a reason not to give Ketamine. However, most of the data that reported this information was anecdotal. There was a study in pediatric patients, that ketamine lowered intracranial pressure. There is also evidence to support that ketamine does not increase ICP in severe TBI patients that are sedated and ventilated, and in fact, may lower it in selected cases.
There currently exists Oxford level 2b, evidence to support that ketamine does not increase ICP in severe TBI patients that are sedated and ventilated, and in fact may lower it in selected cases.
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 and frequently associated with rapid IV push. 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. (Adjunctive atropine is unnecessary during ketamine sedation in children; 2008)
Laryngospasm is associated with poorly managed secretions entering the airway. This can be caused by Ketamine associated hypersalivation. This complication is rare. Prevention can be achieved with simple positioning or oral suctioning.
When viewed across a large range of studies, the typical dosing for disassociate and analgesic effect was 0.5-1mg/kg and 2mg/kg for sedation.
This article was last reviewed April 2018 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.
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.
- Q: Why are we having this conversation?
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A: Ketamine is one of the three medications recommended by the Committee on Tactical Combat Casualty Care (CoTCCC) for their triple option battlefield analgesia. The U.S. Army Institute of Surgical Research also included ketamine in their Analgesia and Sedation Management CPG. They both 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.
Saving lives on the battlefield: A Joint Trauma System review of pre-hospital trauma care in Combined Joint Operating Area-Afghanistan (CJOA-A). (2013)
A Triple-Option Analgesia Plan for Tactical Combat Casualty Care: TCCC Guidelines Change 13-04 (2014)
Prehospital Use of Ketamine in Battlefield Analgesia 2012-03 (2012)
Analgesia and Sedation Management During Prolonged Field Care (CPG ID: 61) (2017)
- Q: What are the indications for Ketamine use?
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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
Continuous intravenous infusion of Ketamine for maintenance sedation (2011)
Committee on Tactical Combat Casualty Care TCCC Guidelines for Medical Personnel 31 Jan 2017 (2017)
- Q: Why is Ketamine so great?
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A: In a casualty with hemodynamic or respiratory instability, or potential instability, “the use of any narcotic, even fentanyl could potentially worsen their condition.”2 The ideal agent in such a casualty is ketamine.
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.
Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial (2015)
Battlefield Analgesia in Tactical Combat Casualty Care (2017)
- Q: Does Ketamine cause apnea?
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A: There have been reports of apneic periods following Ketamine administration. Ketamine can cause apnea and respiratory depression with rapid IV push. Apnea is commonly defined as a pause in breathing lasting greater than 20 seconds and has been reported for as long as 30 seconds with rapid IV push Ketamine. Apnea can be avoided through conscientious administration by slow IV push and by consideration of factors such as known airway anatomical issues or instability. Periods of apnea can be managed with basic airway techniques. IM and IN doses have not been reported to cause apnea.
Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update (2011)
- Q: Does Ketamine increase intraocular pressure (IOP)?
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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.
Ketamine sedation is not associated with clinically meaningful elevation of intraocular pressure. (2012)
Ketamine and intraocular pressure in children. (2014)
- Q: Is Ketamine safe for TBI patients?
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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. There is also evidence to support that ketamine does not increase ICP in severe TBI patients that are sedated and ventilated, and in fact, may lower it in selected cases. Studies regarding the potential neuroprotective attributes of Ketamine are promising and ongoing.
Effectiveness of ketamine in decreasing intracranial pressure in children with intracranial hypertension. (2009)
The Ketamine Effect on ICP in Traumatic Brain Injury. (2014)
- Q: How often does Ketamine cause sialorrhea?
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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.
Adjunctive atropine is unnecessary during ketamine sedation in children. (2008)
- Q: Does Ketamine cause laryngospasm?
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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?
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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.
Inadvertent ketamine overdose in children: clinical manifestations and outcome (1999)
- Q: What is an emergence phenomenon?
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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 0.01 mg/kg or 0.5-1 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?
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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?
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A: Ketamine can be given by slow IV or IO push, as an IM injection, or through an IN atomizer. Some agencies have elected to give the intended dose through an IV infusion of 100mL 0.9% Saline over 10 minutes.
- Q: How much Ketamine should I give?
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A: Ketamine has two therapeutic ranges split by a “recreational” range. Low dose Ketamine is excellent for pain control, especially in conjunction with other agents. High dose Ketamine is great for procedural sedation and induction. The chart below illustrates how Ketamine can be integrated into a pain control algorithm.
Pain Control Algorithm
TCCC and PFC Pain control algorithm. (courtesy of Andrew Fisher)
- Q: What are the side effects of Ketamine?
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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)
At high doses or in susceptible patients Ketamine can cause direct dose-dependent negative inotropic effect, decreasing cardiac muscle contractility. This is especially true in patients who are hemodynamically unstable or in other “low flow” low cardiac output states.
Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. (2011)
Ketamine depresses myocardial contractility as evaluated by the preload recruitable stroke work relationship in chronically instrumented dogs with autonomic nervous system blockade. (1992)
Effects of ketamine on the contractility of failing and nonfailing human heart muscles in vitro. (1998)
- Q: Who should not get Ketamine?
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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 is used and emergence managed with an amnesic such as Midazolam.
Consider the “start low, go slow” approach in patients with hemodynamic instability (signs of shock) or who may be in a catecholamine-depleted state (sleep deprived, or having done a tremendous amount of work). Any medicine administered tends to have a delayed onset, a higher peak concentration, and a delayed elimination in this patient population.
Clinical practice guideline for emergency department ketamine dissociative sedation: 2011 update. (2011)
The Case of the Dying Soldiers: Practical Applications of Pharmacology Concepts in Critical Care (2018)
- Q: Can Ketamine be given with other medications?
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A: Opioids. Administering low-dose Ketamine along with or before administration of opioids has sparing effect where a lower dose of opioid is required for a similar relief of pain.
Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery (2013)
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.
Ketamine Use in the ER Expanded; Ketamine Plus Propofol May Be Better Than Propofol Alone (2011)
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.
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.
Etomidate versus ketamine for rapid sequence intubation in acutely ill patients: a multicentre randomised controlled trial. (2009)
Pro-Con Debate: Etomidate or Ketamine for Rapid Sequence Intubation in Pediatric Patients (2012)
Rapid-sequence intubation: a review of the process and considerations when choosing medications. (2014)
- Q: Isn’t Ketamine a horse tranquilizer?
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A: When ketamine was first synthesized in the early 1960’s, it demonstrated therapeutic value in both animal and human test subjects. Many animals, including working dogs and pack animals, require more narcotic to achieve pain relief while still succumbing to respiratory depression and hypotension. Ketamine is an ideal drug for both human and veterinary patients.