Updated: Apr 3, 2021
Ketamine in Clinical Care
Ketamine, the comparatively safe but potentially addictive hallucinogenic dissociative is also a rapid acting, albeit transient, antidepressant. (1) Ketamine has been shown to significantly reduce suicide rates for up to three days after administration.(2)
A schedule III drug in the United States, Ketamine causes glutamate flooding in the brain. It was widely used as a field anesthetic during the Vietnam war and is still a go-to fast-acting anesthetic utilized emergently in the theatre of war to this very day. Ketamine’s efficacy has earned it a place on the World Health Organization's List of Essential Medicines
“Ketamine is a non-competitive NMDA-receptor agonist, binding to the “PCP site” on the N-methyl-D-aspartate glutamate receptor and preventing neuro-transmission. Glutamate is a central neurotransmitter involved in memory learning, thinking, perception, and other cognitive functions of the hippocampus, temporal, and frontal lobes.” Dale Pendall (3)
Compared to other available anesthetics, Ketamine does not tend to depress the cardio-pulmonary systems. There is little to no significant reduction in breathing or heart rate as a direct result of induction with Ketamine.(4)
There are lingering questions surrounding Ketamine and how neuro-protective against neuro excito-toxicity it is. These questions will only be answered through clinical studies. Some doctors believe that this glutamate flooded mind state is identical to that experienced during a near-death experience (NDE). Coincidentally Glutamate flooding is also initiated when a patient goes hyper-carbic (excessive carbon dioxide build up in the body),hypoxic, ischemic, hypoglycemic, or epileptic specifically in the temporal lobe. When this pathology occurs the neurons in the cortex will continue to receive ions until the cell ruptures from too much energy input. This scenario is referred to as excito-toxicity. With this said the consensus among care providers is that Ketamine is safe for use in the patient population considered severely injured.(5)
“Dr. Karl Jansen believes that IV injections of Ketamine create an experience indistinguishable from an NDE. Once the Ketamine experience results from a Glutimate flood, and NDEs (if one may generalize about them in any way) might be associated with a Glutimate flood, there could potentially be an as yet undiscovered brain chemical that plays the role of Ketamine by binding to the NMDA-receptor and protecting it from cell-death by excito-toxicity…A Ketamine brain scan actually shows most of the cortex shut down, but the Hippopcampus…stays lit up…this may explain why so many traumatic memories can be re-lived on Ketamine--- and how difficult memories that can’t be classified and archived get stuck in the Hippocampus (Quincy,2005). Ketamine brings them back into the experience.”(6)
Ketamine has a Broncho-dilating effect and can be used with patients who have a history of asthma, severe reactive airway disorder, bronchospasm, chronic obstructive airway disease. Ketamine preserves protective airway functions.(7)
From threshold range to higher sub-anesthetic doses, Ketamine’s psychiatric effects are prominent. Feelings of discombobulation, floating, disembodiment as well as visual distortions are described by the majority of patients.
Approximately 8% of those injected with Ketamine find that the drowsy confusing euphoria makes it pleasantly difficult to concentrate or speak. This induced psychosis may involve hallucinations where one experiences feelings described as melting but not unpleasant, or being pulled into a visually present vorticial hole in the space immediately near you (called a K-hole). Sometimes patient’s report feeling as if they have disappeared or are disappearing. Non-Psychiatric adverse side effects affecting greater than 10% of the patient population include nausea, hypertension, fluctuating body temperature, blurred vision, dry mouth. These effects are immediately noticed upon injection and are greatly diminished within 40 minutes as the Ketamine metabolizes within the patient’s body. The effects of the Ketamine injection reduce to zero within 4 hours of injection.(8)
Here is an anecdotal Ketamine experience as related, second-hand, by the father of an 8yo M who received an anesthetic dose of Ketamine prior to induction for a standard tonsillectomy. After the surgery the child relayed his experience prior to induction. He hugged Mom and Dad and then was wheeled in his patient bed back to one of the OR’s by two nice and comforting nurses. He expressed being very comfortable with everything that was happening. As an aside, we do not have a record of which, if any, Benzodiazepines he may have been given in pre-surgery when the anesthesiologist was putting in lines and IVs. Benzodiazepines may act in synergy with Ketamine. Once in the Operating room the OR staff gathered around the child and gave him o2 for about five minutes. After 5-minutes the anesthesiologist asked the child to count backwards from 10 and by the time the patient got to 7 he went unconscious and was intubated and anesthesia was maintained via Ketamine and Propofol at approximately (.75 MAC). The very interesting part comes from the child’s perspective: "I was looking up at 5 doctors and they were all looking down at me in my bed and they were wearing green masks and holding my wrist and looking in my eyes while I breathed in air from the breather (an oxygen mask) and then they told me to count backwards from ten. Just then the room shook, the ceiling turned into a giant black and white checkerboard, then all the doctors turned into ducks and all the ducks were looking down at me (apparently the nurse’ and surgeon’s face mask turned into duck bill’s) and then the entire checker-board ceiling started to swirl above the doctor-ducks (clock-wise) and out of the center of the ceiling came a tornado tail that dropped down from the ceiling and went into my forehead…….. And then I woke up and my throat was sore.” This child hallucinated just prior to disappearing into a K-Hole, but described never being afraid during the entire experience that he was in care of the anesthesia team and surgical team.
There is a tendency for ketamine to be abused in the manner of other insufflated or injected recreational drugs. When Ketamine is abused and therefore when large amounts of the drug are used in a non-medical and unsupervised manner, urinary toxicity and liver dysfunction are common occurrences with extreme cases leading to complete kidney failure.(9)
Poorly controlled psychosis.
Severe liver disease such as cirrhosis.
Active substance abuse (for serial ketamine injections).
Age less than 3 months.(11)
Sanacora G, Frye MA, McDonald W, Mathew SJ, Turner MS, Schatzberg AF, et al. (April 2017). "A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders". JAMA Psychiatry. 74 (4): 399–405. doi:10.1001/jamapsychiatry.2017.0080. PMID 28249076. S2CID 28320520.
Witt K, Potts J, Hubers A, Grunebaum MF, Murrough JW, Loo C, Cipriani A, Hawton K (January 2020). "Ketamine for suicidal ideation in adults with psychiatric disorders: A systematic review and meta-analysis of treatment trials". Aust N Z J Psychiatry. 54 (1): 29–45. doi:10.1177/0004867419883341. PMID 31729893. S2CID 208035394.
Dale Pendall 2005, Pharmako Gnosis page 276
Heshmati F, Zeinali MB, Noroozinia H, Abbacivash R, Mahoori A (December 2003). "Use of ketamine in severe status asthmaticus in intensive care unit". Iranian Journal of Allergy, Asthma, and Immunology. 2 (4): 175–80. PMID 17301376. Archived from the original on 6 October 2014.
Cohen L, Athaide V, Wickham ME, Doyle-Waters MM, Rose NG, Hohl CM (January 2015). "The effect of ketamine on intracranial and cerebral perfusion pressure and health outcomes: a systematic review". Annals of Emergency Medicine. 65 (1): 43–51.e2. doi:10.1016/j.annemergmed.2014.06.018. PMID 25064742.
Dale Pendall 2005, Pharmako Gnosis page 277
Kurdi MS, Theerth KA, Deva RS (September 2014). "Ketamine: Current applications in anesthesia, pain, and critical care". Anesthesia: Essays and Researches. 8 (3): 283–90. doi:10.4103/0259-1162.143110. PMC 4258981. PMID 25886322.
Acevedo-Diaz EE, Cavanaugh GW, Greenstein D, Kraus C, Kadriu B, Zarate CA, Park LT (February 2020). "Comprehensive assessment of side effects associated with a single dose of ketamine in treatment-resistant depression". J Affect Disord. 263: 568–575. doi:10.1016/j.jad.2019.11.028. PMID 31791675.
Castellani D, Pirola GM, Gubbiotti M, Rubilotta E, Gudaru K, Gregori A, Dellabella M (April 2020). "What urologists need to know about ketamine-induced uropathy: A systematic review". Neurourol Urodyn. 39 (4): 1049–1062. doi:10.1002/nau.24341. PMID 32212278. S2CID 214643776.
Schwenk ES, Viscusi ER, Buvanendran A, Hurley RW, Wasan AD, Narouze S, Bhatia A, Davis FN, Hooten WM, Cohen SP (July 2018). "Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Acute Pain Management From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists". Reg Anesth Pain Med. 43 (5): 456–466. doi:10.1097/AAP.0000000000000806. PMC 6023582. PMID 29870457.
Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, Weatherall A, Paal P (June 2013). "Ketamine: use in anesthesia". CNS Neurosci Ther. 19 (6): 381–9. doi:10.1111/cns.12072. PMC 6493613. PMID 23521979.