At 3 a.m. you’re toned out to a single vehicle accident with one passenger who slid off the road and wrapped his car around a light pole. A 44-year-old male is alert, rates his pain a 13 on a 1—10 scale, and reports he has asthma. Vital signs include a heart rate of 70, blood pressure of 90/60, and a respiration rate of 25. Extrication will be at least 30 minutes and the patient has multiple fractures. What drug will you consider that can manage this patient’s pain, improve his cardiovascular state, and sedate him for extrication? Have you considered ketamine?
For 63 years ketamine has been administered across a spectrum of medical practices; from veterinary and human operating theaters to battlefield hospitals, EDs and now EMS. Its short-term usages that are of interest to EMS range from mild pain control and chemical restraint to complete sedation. From a prehospital standpoint, ketamine is easy to dose and administer, relatively safe, and has an onset time appropriate to field use. Because of the many mechanisms of action and broad range of uses, ketamine may be an excellent adjunct in the field.
Synthesized in 1962, ketamine is an American pharmaceutical created by scientist Calvin Stevens, PhD, to be an anesthetic for operating room use. Its primary mechanism of action is N-methyl-D-aspartate (NMDA) receptor blockade (antagonism) for anesthesia. However, ketamine dissociates (i.e., the drug molecule breaks apart and attaches to various receptors) and affects many different receptors such as opioid channels, L-type calcium channels, nicotinic acetyl-choline ion channels, and hyperpolarisation-activated cyclic nucleotide channels (HCN1).1—3
Pharmacology, Administration & Dosage
The primary mechanism of action that is of interest to EMS is the dissociative anesthesia, which consists of three parts: analgesia, amnesia and hypnosis.2 Ketamine may be used in both pediatrics and adults for pain control, psychiatric emergencies, and complete sedation with or without intubation. Because ketamine both enhances the sensitivity of opioid receptors through NMDA antagonism and binds to kappa and mu opioid receptors, it’s an effective adjunct for pain. It may be used alone or in combination with an opioid.2—4
Ketamine can be administered via IV, intramuscularly (IM), intraosseously (IO), orally, rectally or via intranasal spray.3 Dosage is weight-based and can be adjusted based on desired effect of the drug.3—6 (See Table 1, below.) The elimination half-life is approximately 180 minutes; however, sedation anesthesia begins to wear off in 10—15 minutes2,5,6 so it may have to be continuously infused via a drip or bolus as needed. Fast injection of ketamine can result in transient apnea, so the drug must be administered slowly over a minute. Ketamine and benzodiazepines must not be mixed in the same bag or syringe for a continuous infusion as precipitates can form.5,6
Airway, Sedation & Intubation
Ketamine doesn’t cause respiratory depression and may decrease bronchospasm.7,8 This property makes it possible to consider deep sedation without intubation, provided the airway is stable. Consider the patient involved in a trauma or mass casualty situation with multiple fractures who requires a prolonged extrication. Ketamine administration would allow for pain control, making extrication easier on both patient and provider, while preventing or delaying an intubation. Although the airway always requires monitoring, intubation isn’t necessarily required if the airway is stable–even under sedation. In an event where rapid sequence intubation or deep sedation is required, ketamine can be used as a single agent or in conjunction with a benzodiazepine when laryngeal reflex is still present.7,8
It should be noted that ketamine isn’t a paralytic. An asthmatic patient who’s refractory to standard treatments and who will require intubation may be more successfully intubated with ketamine because it’s not a paralytic agent and does have catecholamine-stimulating properties.7 Ketamine does have the potential to induce hypersalivation, which can be managed with suction or low-dose atropine.8,9
With increasing concerns over opioid addiction, ketamine is an alternative for pain management. It can be used alone or in conjunction with a smaller dose of opioid for more effective pain control.8,10
There are some injuries where pain is so severe opioids are ineffective or would have to be given in high enough doses to cause respiratory suppression. Burns, multiple fractures, abscess drainage, and mentally challenged patients of any age with overwrought responses to pain are considered excellent candidates for ketamine.8 It’s appropriate to attempt opioids first and then add ketamine for synergistic therapy or, depending on mechanism of pain, go directly to ketamine. Ketamine directly affects pain by its action on the mu and kappa receptors without causing respiratory depression.2,4 Narcan (naloxone) isn’t effective on ketamine.3,11—13
Cardiology, Neurology & Physiology
Catecholamines are stimulated and released by ketamine and elevate heart rate, blood pressure, and mean arterial pressure (MAP). This makes ketamine an appropriate consideration for patients in shock or experiencing profound hypotension. Further, the increased release of catecholamines may improve myocardial contractility.
In the past, one of the concerns about administration of ketamine was that it caused elevated intracranial pressure.7,8 Current research shows that in a head injury situation, maintaining cerebral blood flow and MAP is paramount in sustaining brain function, so the current recommendation suggests ketamine may be helpful and not harmful.2,7,8
Secondary Effects, Considerations & Contraindications
One of the effects of ketamine is hallucinations, and those occur within a certain dosage range. Surgical sedation dosage is 20 times higher than the dosage required to cause hallucinations, so as the drug is eliminated, patients may go through the hallucinogenic range.2 The dosage for pain control and hallucinations are very close together. This wearing off of ketamine is called an emergence reaction and may entail a variety of mood alteration, a floating sensation, hallucination, vivid dreams, and can be pleasant or unpleasant.
Not everyone experiences the emergence reaction, but it’s more common in patients over 16, women, people who dream, those who receive large doses or rapid administration.3,7 This isn’t usually an issue in the field, as the ketamine won’t have worn off, and hallucinations can be managed in the ED. However, if management is required, administration of a benzodiazepine, such as midazolam, is appropriate.
Ketamine may also cause increased intraocular pressure, so use with caution in patients with glaucoma or acute globe injury. Administration of ketamine can cause nystagmus or double vision. Once patients have been sedated, they may have an eyes wide open, glazed expression.
Due to the catecholamine-induced sympathetic activity, ketamine can increase myocardial oxygen demand. Continuous monitoring of the cardiac system is required. Elevations of blood pressure, heart rate, or cardiac output that become symptomatic can be treated supportively. Ethanol also inhibits NMDA function, so use with caution in an intoxicated patient.5,6,8,12
Ketamine doesn’t have a reversal agent.3,13 However, the effects that are most commonly seen in ketamine use can be managed supportively or end when the drug is eliminated from the system.2
There are no absolute contraindications to ketamine administration.5 It should be used with caution or only at the advice of medical control in severely hypertensive patients, schizophrenic patients or patients experiencing hallucinations or delusions, intoxicated patients, chronic alcoholics, or pregnant patients.6 Ketamine is pregnancy category C.5
Bedside counseling is very important when administering ketamine. Because of ketamine’s profound induction of a hypnotic and amnestic state, patients who were awake and talking suddenly because unresponsive and dazed, and this can be extremely scary, especially for parents who are with their children.
Always be sure to explain to patients, parents and children that ketamine may cause them to not respond and look and feel funny, but that they won’t feel pain or remember it.
Because it’s structurally similar to phencyclidine (PCP) and causes hallucinations, ketamine is a popular street drug referred to a “Special K,” “K,” “Kit Kat” or “Cat Valium,” among others. Users experience “K-holes” or “K-land” (i.e., subjective state of dissociation from the body commonly), or “baby food” (i.e., blissful, infantile inertia). It’s classified as a Schedule III controlled substance.14
If a patient has overdosed on ketamine, the signs and symptoms of OD may be sedation, hallucination, salivation, and increased heart rate, blood pressure, and decreased respirations. Treat supportively.
Wrapping it Up
Ketamine can be used in a variety of situations, possibly eliminating the need to carry multiple drugs where one would suffice. It can be used in conjunction with opioids or alone for pain control, as a single anesthetic with or without the need for intubation, and as a powerful chemical restraint in psychiatric emergencies.
Ketamine’s secondary benefits include support in shock situations, increasing cardiac contractility, and cerebral perfusion.
Research is currently underway studying the uses of ketamine for long-term management of severe refractory depression and chronic pain. Early evidence suggests positive outcomes.
It’s worth considering that patients who receive prehospital ketamine for sedation or pain control may experience long-term benefits that help manage pain during a prolonged healing process or depression that may accompany chronic pain.2—4,8
1. Domino EF. Taming the ketamine tiger. 1965. Anesthesiology. 2010;113(3):678—684.
2. Sleigh J, Harvey M, Voss L, et al. Ketamine–more mechanisms of action than just NMDA blockade. Trends in Anesthesia and Critical Care. 2014;4(2—3):76—81.
3. Annirudda P, Heining M. Ketamine. Contin Educ Anaesth Crit Care Pain. 2007;7(2): 59—63.
4. Craven R, Alkhafaji R. (June 10, 2006.) Ketamine in Anesthetic Practice. AnesthesiaUK. Retrieved Aug. 2, 2016, from www.frca.co.uk/article.aspx?articleid=100644.
5. Ketamine (RX). (n.d.) Medscape. Retrieved July 28, 2016, from http://reference.medscape.com/drug/formulary/ketalar-ketamine-343099#10.
6. Ketalar 10mg/ml Injection. (Aug. 17, 2016.) Electronic Medicine Compendium. Retrieved July 27, 2016, from www.medicines.org.uk/emc/medicine/12939/SPC.
7. Caro D. (May 11, 2016.) Induction agents for rapid sequence intubation in adults. UpToDate. Retrieved July 25, 2016, from www.uptodate.com/contents/induction-agents-for-rapid-sequence-intubation-in-adults.
8. Kurdi M, Theerth K, Deva R. Ketamine: Current applications in anesthesia, pain, and critical care. Anesth Essays Res. 2014;8(3):283—290.
9. Heinz P, Geelhoed G, Wee C, et al. Is atropine needed with ketamine sedation? A prospective, randomised, double blinded study. Emerg Med J. 2006;23(3):206—209.
10. Donnelly R. Physical compatibility and of ketamine-morphine in polypropylene syringes. Can J Hosp Pharm. 2009;62(1):28—33.
11. Mikkelsen S, Ilkjaer S, Brennum J, et al. The effect of naloxone on ketamine-induced effects on hyperalgesia and ketamine-induced side effects in humans. Anesthesiology. 1999:90(6):1539—1545.
12. Ron D, Wang J. Biology of the NMDA receptor. CRC Publishing: Boca Raton, pp. 59—70, 2009.
13. Crotty S. (2004.) Safe pediatric sedation. Ann & Robert Lurie Children’s Hospital. Retrieved Aug. 8, 2016, from www2.luriechildrens.org/ce/online/article.aspx?articleID=74.
14. Drug Enforcement Agency. (August 2013.) Ketamine (street names: special k, “k”, kit kat, cat valium). Drug Enforcement Agency Office of Diversion. Retrieved Aug. 8, 2016, from www.deadiversion.usdoj.gov/drug_chem_info/ketamine.pdf</
Quiz: Should you administer Ketamine?
At 0300 hrs you are toned out to a single vehicle accident with one passenger who slid off the road and wrapped his car around a light pole. The 44-year-old male is alert, rates his pain a 13 on a 1—10 scale, and reports that he has asthma. Vital signs are: heart rate 70, blood pressure 90/60 and respirations of 25. Extrication will be at least 30 minutes and the patient has multiple fractures. What drug will you consider that can manage this patient’s pain, improve his cardiovascular state and sedate him for extrication? Have you considered ketamine?
1) What makes this patient a candidate for Ketamine?
A) Multiple fractures
B) Prolonged extrication
D) History of asthma
E) All of the above
2) What is Ketamine’s mechanism of action?
A) NMDA antagonism
B) Sedation, hypnosis, analgesia
C) Opioid potentiation
E) All of the above
3) True or False: Ketamine may help prevent bronchospasm.
4) Which is NOT an appropriate way to administer Ketamine?
5) True or False: There is an antidote or reversal agent for Ketamine.
6) Ketamine increases which of the following:
B) Heart rate
C) Mean arterial pressure
D) All of the above
E) B & C
7) Which of the following is a caution to using ketamine?
C) Head injury
8) You decide the patient in the scenario is a candidate for sedation with ketamine. He tells you he weighs 160 lbs (~73kg). You cannot establish an IV while the patient is trapped in the vehicle, so you elect to give him IM ketamine. What dosage do you use?
B) 10 mg/kg
C) 10 mg bolus
9) While you are waiting for the onset of the ketamine you, want explain to your patient that he may experience which of the following:
B) A floating sensation
C) Vivid dreams
D) None of the above
E) All of the above
10) Upon sedation you note copious secretions from the patient’s oropharynx. How can you manage the secretions?
A) Emergent intubation
B) Low dose atropine
D) B & C only
E) All of the above