Ketamine Basics
Ketamine is a small molecule used as medication in both humans and animals. It effects many targets throughout the body, but most notably the NMDA receptors on our nerve cells. At different doses, ketamine has different effects. High doses can be used to put people to sleep for surgery. At lower doses, ketamine represents an effective way of treating pain, minimizing the use of more harmful medications like opiates. Low dose ketamine is also very useful in the treatment of multiple mental health problems, such as severe depression.
Ketamine wears a lot of hats from a clinical perspective. This versatility makes it an ideal medication in resource limited environments, like outer space. On top of this, its proven safety profile with intermittent and appropriate use as well as the fact that it does not impair breathing makes ketamine even more desirable. Clinicians in every setting of care can and often should be using ketamine in their practice.
The biggest downfall of ketamine is its potential for addiction. As it so effectively treats pain and mental health conditions, it can be habit forming. On top of this, its dissociative and hallucinogenic properties are also sought after by recreational drug users. While providers should be aware of these things, they should not discourage the use of ketamine in the clinical environment.
Ketamine has been described as a panacea, or cure all. Panacea was the daughter of Asclepius, the God of Medicine and son of Apollo in Greek mythology. While important, no pharmaceutical drug, including ketamine, should be described in this way. The only panacea’s currently available in 2020 are lifestyle changes, namely regular exercise and a healthy diet!
Space – The Final Frontier
Outer Space is the final frontier. It calls us. Private rocket companies like SpaceX are redefining what is possible and inspiring a new generation. Even government space agencies like NASA and the Air Force’s Space Force seem newly energized. This is such an exciting time in human space exploration and we are seeing more rocket launches then ever in 2020. In the next few years human colonies on the moon and Mars may become a reality. However, space remains a very dangerous place for humans to be.
The Harms of Space and the Discipline of Space Medicine
Microgravity, ionizing radiation, extreme temperatures, space junk traveling at thousands of miles an hour, and the absence of pressure make outer space a very dangerous environment! Without sealed protective barriers and fine-tuned environmental controls, humans would not stand a chance. Object surface temperatures in space can be so hot and so cold that astronauts can injure themselves through space suit gloves. Imagine a place that is 250F in the sun and negative 150F in the shade!
Space medicine is a medical specialty focused on keeping people safe and healthy during spaceflight operations as well as prolonged periods of time living in space. This specialty was born out of aviation medicine, a field focused on keeping pilots safe who operate aircraft within earth’s atmosphere. Both fields are near and dear to me. I am very excited to join the field of aviation medicine this fall and start offering medical certificates for civil airman/pilots as an aviation medical examiner!
The field of space medicine was born out of the inherent dangers present in space and the need to protect human space travelers. However, even with the best resources, training, and research, the ability to provide medical care in space will always be limited. Space is a low resource environment. Getting things to and from space is expensive. Until SpaceX entered the industry, it costs almost 20,000$ to launch a kilogram (2.2lbs) into space. Now the price is coming down, perhaps as low as 2,500$/kg. But cargo space remains severely limited, particularly on long voyages.
Prioritizing Medication and Medical Supplies in Outer Space
As a result of this, every piece of equipment brought into space must be highly scrutinized. Pack light space voyagers! Even medical kits and medical supplies are limited. As a result, specialists in Space Medicine think long and hard about what medications, medical supplies, and diagnostics will be most useful and most likely to be needed. I am sure that any available epidemiological data regarding space injuries and illnesses, mathematical models, and any planned medical research likely plays a driving role. On top of this, any medications or supplies which can serve multiple purposes will be particularly useful.
To this end, the NMDA receptor antagonist Ketamine, must surely make the list!
Ketamine’s Potential Roles in Space Medicine – Talk about a Utility Player!
1. Depression and Anxiety
At low, sub-dissociative doses, ketamine works wonders for depression and anxiety. Traveling to Mars with today’s technology takes 4 to 6 months. This will be a lonely and isolating time. Ketamine’s ability to pull people out of mental slumps may prove particularly relevant on long and lonely space voyages.
2. Suicidal Ideation
Ketamine is the only medication I am aware of that has been shown to rapidly and effectively ameliorate (reverse or improve) suicidal ideation. On long isolated tours in space, I would anticipate that even some otherwise healthy people may experience suicidal thoughts and impulses. Especially in light of the unavoidable failures and catastrophe’s that will be a part of early human expansion into space.
3. Acute and Chronic Pain
Ketamine’s ability to treat both acute and chronic pain is legendary. It is safer than opiate medications and can be titrated easily to desired effect.
4. Acute Sedation for Reckless Behavior
Space can and surely will drive many people insane. Even levelheaded people could potentially lose their cool under hypoxic, or low oxygen, atmospheric conditions. A crazy person on a spaceship would represents an absolute disaster. Such individuals will need to be sedated immediately. At higher dissociative doses, ketamine will do the trick. It will stop crazy people who are potentially a danger to themselves and others. Ketamine can be used intramuscularly for this purpose and will generally not affect breathing, even at high doses.
5. Surgical Procedures
Ketamine has the ability to put people fully to sleep, while minimizing pain, and preserving breathing. This makes it the perfect candidate for surgery and emergency procedures, when airway management is not available. Whether you are doing a cesarean section in a remote jungle in Peru or on Mars, ketamine will be your anesthetic of choice.
Additional Key Points Regarding Ketamine
- Ketamine is a derivative of phencyclidine (PCP) and because it causes much less agitation, aggressive behavior, and sympathomimetic symptoms, it has enjoyed wide-spread and sustained clinical use.
- Ketamine primarily acts as an inhibitor of the NMDA receptor. However, it has effects at a number of other targets including multiple opioid receptors. Ketamine also inhibits the reuptake of multiple neurotransmitters including serotonin, norepinephrine, and dopamine.
- Ketamine can be used at lower doses for mental health conditions like depression, anxiety, OCD, and suicidal ideation.
- NMDA receptors modulate neuronal development, plasticity, and connectivity. I hypothesize that acute plasticity afforded by ketamine allows individuals with mental health issues a unique opportunity to leave negative thought patterns and view themselves from a different level of consciousness.
- Its effectiveness in treating both acute and chronic pain makes it very desirable.
- At higher doses, ketamine causes sedation with preserved respiratory function. This makes it ideal for resource limited settings.
- Ketamine can cause a number of side effects. Most notably an emergence reaction some people experience when waking up from dissociative or sedative doses of ketamine.
- This emergence reaction can be effectively treated by limiting sensory stimulation and administration of benzodiazepines like lorazepam. Alpha antagonists like clonidine and antihistamines like hydroxyzine may also be helpful. Avoiding antipsychotics in this setting is recommended by some due to the risks of dystonic reactions.
- Ketamine can also cause bladder and urinary tract dysfunction. Particularly with frequent illicit use.
- Memory impairment and depressive symptoms also can occur with frequent use.
- Fatalities from ketamine toxicity are almost unheard of. The LD50 in mice was 600 mg/kg. However, accidents can certainly occur and be fatal in recreational use.
- There is a lot of controversy regarding ketamine’s clinical effects. For instance, is ketamine neuroprotective in trauma? What is its effect on seizures at lower doses? Ketamine can cause hypotension, hypertension, tachycardia, and bradycardia. Its action at multiple receptors, dose dependent effects, and the heterogeneity of human subjects likely explains a lot of this controversy.
- Ketamine’s proven safety record, low cost, unique clinical properties, multiple uses, as well as its ability to provide full anesthesia without significant respiratory depression, make it an absolute must have, in resource poor settings.
Conclusion
Ketamine is a medication useful in a number of different conditions. It is likely to be just as valuable in an expedition medical kit on the way to Mars as it is in today’s hospitals and clinics. For more information on Ketamine, check out Episode 19: Ketamine part 1, available at FullScope.org.
References
- Olson KR et al. Poisoning and drug Overdose, 6th ed. Arminian P. Phencyclidine and Ketamin. 2012. McGraw Hill. 325-327
- Nelson LS et al. GoldFrank’s Toxicological Emergencies, 11th ed. Olmedo RE. Phencyclidine and Ketamin, chapter 83. 2019. McGraw Hill. 1210-1221. (NMDA receptor information from other chapters as well)
- George D, Galvez V, Martin D, Kumar D, Leyden J, Pavlovic DH, Harper
Brodaty H, D.Sc, Glue P, Taylor R, Mitchell P, Loo CK. Pilot randomized controlled trial of titrated subcutaneous ketamine in older patients with treatment-resistant depression. Am J Geriatr Pscychiatry.2017; 25(11): 1199-1209.
- Murrough JW, Losifescu DV, Chang LC, Jurdi RKA, Green CM, Perez AM, Iqbal S, Pillemer S, Foulkes A, Shah A, Charney DS, Mathew SJ. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013; 170(100): 1134-1142.
- Rodriguez CI, Kegeles LS, Levinson A, Feng T, Marcus SM, Vermes D, Flood P, Simpson HB. Randomized controlled crossover trial of ketamine in obsessive-compulsive disorder: proof-of-concept. Neuropsychopharmacology. 2013; 38:2475-2483.
- Michelet D, Brasher C, Horlin AL, Bellon M, Marsollier FJ, Vacher T, Pontone S, Dahmani S. Ketamine for chronic non-cancer pain: A meta-analysis and trial sequential analysis of randomized control trials. Eur J Pain. 2018; 22:632-646.
- Price RB, Losifescu DV, Murrough JW, Chang LC, Jurdi RKA, Iqbal SZ, Soleimani L, Charney DS, Foulkes AL, Matthew SJ. Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety. 2014; 31(4): 335-343.
- Lapidus KAB, Levitch CF, Perez AM, Brallier JW, Parides MK, Soleimani L, Feder A, Losifescu DV, Charney DS, Murrough JW. A randomized controlled trial of intrasal ketamine in major depressive disorder. Biol Pscyhiatry. 2014; 76(12): 970-976.
- Zanos P, Gould TD. Mechanisms of Ketamine Action as an Antidepressant. Mol Psychiatry. 2018; 23(4): 801-811.
Olmedo R. Phencyclidine and Ketamine. 2011. In: Goldfrank LR, ed.
- Orhurhu VJ et al. Ketamine Toxicity. StatPearls. 2020. Available at: https://www.ncbi.nlm.nih.gov/books/NBK541087/
- Wikipedia – Ketamine, Enantiomers, NMDA, etc.