Understanding prehospital ketamine: Dosing to drawbacks

In the right patient, with a solid understanding of the pharmacology and a plan to address potential side effects, ketamine can be an incredibly useful tool for EMS


We have a saying at work: “I don’t know what your question is, but the answer is probably ketamine!”

Obviously that statement cannot be taken at face value, but it does reflect the fact that ketamine use has increased significantly in my practice over the past few years, despite the fact that it has been around for a long time.

In the 1950s, the search for a safer anaesthetic agent resulted in the development of phencyclidine, a potent anaesthetic “without significant effect on the respiration, heart rate, blood pressure and body temperature” [1]. Human trials with phencyclidine, also known as PCP or by its current street name – angel dust – proved problematic because of severe agitation [2].

The dosing ranges for prehospital ketamine are straightforward; understanding ketamine’s unique pharmacology is a little more complicated. (Photo/Jon Lee)
The dosing ranges for prehospital ketamine are straightforward; understanding ketamine’s unique pharmacology is a little more complicated. (Photo/Jon Lee)

The search for a better anaesthetic led to a derivative of phencyclidine that had a much shorter action and significantly less stimulant effects compared to phencyclidine. It had a combination of profound analgesia, short acting anesthesia and psychic alterations that was coined “dissociative anaesthetic” [3]. Chemically, it was comprised of a ketone and an amine so it became known as ketamine [2].

One of the things that makes ketamine so useful in the out of hospital environment is that it can be given by a variety of different routes – intravenous (IV), intranasal (IN), intramuscular (IM), oral – and has a variety of different effects depending on the dosing range.

A solid understanding of ketamine can make it one of the most versatile drugs in your toolkit. The dosing ranges are straightforward and are listed in the table.

Understanding ketamine’s unique pharmacology is a little more complicated. My working knowledge is broken down into two broad categories: brain and body.

Table: Ketamine dosing ranges [7]

  IV administration IM administration
Sedation and analgesia 0.2-0.75mg/kg IV 2-4mg/kg IM
Induction of anesthesia 0.5-1.5mg/kg IV 4-10mg/kg IM

Ketamine and the brain

Functionally, ketamine blocks afferent signals from the white matter of the spinal cord [4]. Within the brain, it causes dissociation between the thalamo-neocortical system and the limbic system.

What does this mean? Ketamine interferes with incoming signals containing noxious stimulus (called nociception) from the spinal cord and depresses the emotional response that comes with pain perception [4]. Within the brain, ketamine allows impulses to reach the part of the brain that recognizes sensory inputs, but not the part of the brain that associates this with pain. It’s thought to be the reason for ketamine’s dissociative effects and it is what gives ketamine its analgesic properties, making it effective in the management of acute pain, and increasingly, explored for chronic and complex pain syndromes as well [5].

Chemically, ketamine is an NMDA receptor antagonist (glutamate is one of the body’s most prominent excitatory neurotransmitters, and NMDA is a glutamate receptor). Research has also linked ketamine to opioid receptors, cannabinoid receptors and neurotransmitters like GABA [4].

What does this mean? Blocking NDMA receptors is thought to give ketamine its unique anaesthetic properties, such as amnesia as well as its psychedelic effects. It’s what makes ketamine a useful drug for conscious sedation (for short painful procedures, like pacing or extrication) where pain needs to be controlled but the patient remains conscious, with the airway intact. At higher doses, in can be used to induce anaesthesia prior to intubation.

The hallucinations and psychedelic effects make ketamine a recreational drug of abuse, but also are responsible for ketamine’s well-known emergence reactions [5]. Occasionally, a patient can have a terrifying experience waking up from ketamine. Reducing stimulation as much as possible when the patient is waking up by keeping them in a dark, quiet room can help. Personal experience has proven midazolam or lorazepam helpful if the emergence reaction happens, but I usually find it best to try have the patient wake up in the hospital where it is more controlled and avoid the emergence reaction all together.

Ketamine and the body

Ketamine is also known to stimulate the release of monoamines like serotonin, dopamine and norepinephrine. It also blocks the reuptake of catecholamines. This produces a sort of hyper-adrenergic state that has effects that extend outside of the brain to the whole body [6].

What does this mean? The hyper-adrenergic state gives ketamine one of its most useful properties. Typically, heart rate and blood pressure slightly increase versus the hypotension (sometimes significant) that can be seen with other agents like benzodiazepines or opiods. This makes ketamine an ideal drug for patients in shock states or who are at risk of hypotension [5].

Ketamine is also the induction agent of choice for asthmatics [5]. It has less pronounced effects on respiratory rate than other sedative drugs and the increased beta stimulation that comes from the hyper-adrenergic state may also provide the added benefit of bronchodilation.

Practical considerations for prehospital ketamine use

Ketamine has been incredibly useful for a wide range of patients. From low doses to provide analgesia to the hypotensive trauma patient, to higher doses to rapid sequence induction the septic shock patient. From moderate doses to sedate the asthmatic patient on BiPap, to high dose IM to chemically restrain the severely agitated patient with no IV access. Ketamine is generally very safe but there are still a few practical considerations to be aware of.

While ketamine is probably safer than other drugs when it comes to patients in shock states, that does not mean it is perfect. If a patient is profoundly catecholamine depleted, ketamine can cause hypotension, so it is reasonable to be more cautious in dosing and speed of administration with these patients. Alternatively, careful consideration should be given to patients who are morbidly hypertensive or tachycardic [7].

The same consideration should be given to patients with airway or respiratory compromise. Ketamine is relatively protective of the respiratory system, but care must be taken when ketamine is mixed with other drugs, either medical or recreational. Ketamine may also cause increased secretions or in extreme cases, laryngospasm [7].

Finally, ketamine has complex effects on brain chemistry that may even prove beneficial in certain psychological disorders, such as depression. However, these effects have led to concerns about is use in patients with schizophrenia [7].

Ketamine, just like every other drug, is neither good nor bad. What can be positive or negative is how it is used. With a solid understanding of the pharmacology, thoughtful patient selection and a plan for any of the unwanted side effects, ketamine can be an incredibly useful and flexible tool in the prehospital environment.

Read next: Ketamine administration comes under the spotlight

References

  1. Maddox, V. H., Godefroi, E. F., & Parcell, R. F. (1965). The Synthesis of Phencyclidine and Other 1-Arylcyclohexylamines. Journal of Medicinal Chemistry, 8(2), 230–235.doi:10.1021/jm00326a019
  2. Mion, G. (2017). History of anaesthesia: The ketamine story - past, present and future. European Journal of Anaesthesiology (Cambridge University Press)34(9), 571–575. https://doi.org/10.1097/EJA.0000000000000638
  3. Domino, E. F., Chodoff, P., & Corssen, G. (1965). Pharmacologic Effects of Ci-581, a New Dissociative Anesthetic, in Man. Clinical Pharmacology and Therapeutics6, 279–291.
  4. Mion, G., & Villevieille, T. (2013). Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS neuroscience & therapeutics, 19(6), 370–380. https://doi.org/10.1111/cns.12099
  5. Nowacka, A., & Borczyk, M. (2019). Ketamine applications beyond anesthesia - A literature review. European journal of pharmacology, 860, 172547. https://doi.org/10.1016/j.ejphar.2019.172547
  6. Lavender, E., Hirasawa-Fujita, M., & Domino, E. F. (2020). Ketamine's dose related multiple mechanisms of actions: Dissociative anesthetic to rapid antidepressant. Behavioural brain research, 390, 112631. https://doi.org/10.1016/j.bbr.2020.112631
  7. Kurdi, M. S., Theerth, K. A., & Deva, R. S. (2014). Ketamine: Current applications in anesthesia, pain, and critical care. Anesthesia, essays and researches8(3), 283–290. https://doi.org/10.4103/0259-1162.143110

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