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Ask ten different people their opinion on ketamine and you'll get ten different answers. It's a tribute to the drug's muddled popular conception as a horse tranquilizer, club drug, and cure for refractory depression. Regardless of modern placards, the World Health Organization lists ketamine as an "essential medicine," and among the safest and most efficacious ones known to science. Originally derived from PCP, ketamine possesses a versatility in the medical world like no other drug, and research on its many benefits is exploding. Navy Seal medics carry it in their pockets, as an ER doctor I routinely give it to toddlers, and if the above reasons don't make it planet Earth's most interesting pharmaceutical I'll go one step further and deem ketamine my favorite medicine of all time.
It starts with how the medicine works. Ketamine's predominant action in the human brain is to block the NMDA receptor, which normally activates neurons. When this receptor is blocked, the central nervous system begins to lose responsiveness. At lower doses, ketamine produces a mild state of hypnosis, pain relief, and alters the perception of sight and sound. Moderate doses begin to create illusions of separation from the environment or oneself and mild paralysis, commonly known as the "K-hole." At escalating doses, it will cause near-complete paralysis, amnesia, and sedation, with preservation of the respiratory reflexes.
This last part is pivotal to ketamine's ubiquity. Unlike all other general anesthetics ketamine will not cause a patient to stop breathing by suppressing the respiratory reflex. (However, a potentially fatal adverse reaction does exist when it's injected intravenously: laryngospasm, a condition where the vocal cords spasm and cause suffocation. It's sphincter-tightening for even the most seasoned physician to witness as it requires immediate and aggressive medical intervention to prevent cardiac arrest. Thankfully it only occurs in roughly 0.4 percent of cases, but this fact alone should strike fear in anyone considering using it without supervision from a medical professional.)
Ketamine isn't always perfect—in fact, it frequently isn't. The most common side effect I see, aside from elevation in heart rate and blood pressure, is nausea and vertigo. In the ER I always give anti-nausea medicine if I'm giving ketamine. It can also cause nightmares or vivid dreams, and can induce a schizophrenic-like state in healthy subjects. Further, mice given daily ketamine injections for six months were significantly worse at navigating a maze than both "sober" mice and mice injected regularly for three months. Analysis of their brains, specifically the area involved with learning, showed some key deficits. Although mouse studies are not a perfect stand-in for human studies, this does suggest evidence for an irreversible cognitive decline after chronic use.
Ketamine was initially synthesized (from PCP, from which it's only a few atoms away) in 1926, but gained popularity after its patent in 1963 as a veterinary anesthetic. The major attraction to ketamine was its minimal effect on respiratory function, which prompted its use in the remote jungles of the Vietnam War. Ketamine allowed lifesaving surgeries to be performed in remote locations without the need for cumbersome breathing machines, and crucially kept medevac patients stable during helicopter transport. This critical benefit brings us to the first and most utilitarian use of the drug.
It's an austere-environment anesthetic
Just like in the Vietnam War, ketamine is used in many developing-world operating rooms where breathing machines, an anesthesiologist, or even reliable electricity may not be available. The WHO describes ketamine as among " …the most efficacious, safe and cost–effective medicines for priority conditions" and recommends ready availability in every medical system.
Ketamine does not need to be refrigerated. It can be given in tablet form by mouth, easily injected into muscle, or given via IV. This portability and minimal need for airway monitoring allows countless surgeries, from lifesaving C-Sections to appendectomies, to be performed around the world.
It's a combat anesthetic
I trained at the Los Angeles County Medical Center, one of the nation's busiest trauma centers. The US Navy sends its Corpsmen and Navy Seal medics to train with us before deployment. The "Down-Range" or in-combat medics now carry syringes full of ketamine.
I asked a seasoned Navy Seal medic, who wished to remain anonymous, how they use it. "In severely injured soldiers, like a double or even quadruple amputee, we use a large dose of ketamine to not only subdue the wounded and often distraught soldier in the field of fire, but to provide amnesia and pain relief," he told me. "It also increases the soldier's heart rate and blood pressure, which helps with blood loss. A 'K-holed' soldier is much easier to load and transfer away from danger." In other words, it is the perfect combat anesthetic. I also reach for ketamine to sedate gunshot victims, severe car crashes, or any trauma victims with low blood pressure.
It puts kids in the K-hole
Many of my friends outside medicine are amused that I routinely put children into the K-hole, but it happens all the time. Kids frequently stick things in their ears, suffer big lacerations, and simply don't like holding still. Last week I had a toddler put a seashell deep into his ear. Due to his thrashing, it was impossible to remove when he was awake. After giving him ketamine, removing it could not have been easier for me—and most importantly, for him.
One precaution in children is that it can cause an emergence phenomenon, or a bad trip. This is almost always avoided by walking the child through their most pleasant memories prior to administration. If they sink into the K-hole happy, they will rise happy.
It works for severe asthma
Asthma is a disease caused by hyperactive small airways clamping down and decreasing airflow through the lungs. Ketamine has an interesting side effect, in which it dilates, or opens, these small airways. It is only given in severe life-threatening asthma, so don't ask for ketamine to replace your regular inhalers. In small doses it can also calm a patient who otherwise is breathing too fast.
It's good for acute pain
The emergency department is filled with broken bones and painful injuries, but one of the most painful injuries I have ever treated occurred when a young man was run over by a semi-truck. It tore all the skin from his groin down to his left knee completely off, and left several of his thigh muscles completely shredded. He was in severe pain, so severe that multiple doses of morphine and the traditional opioid pain relievers were not working for him. I had two options: Put him in a medically induced coma and on a breathing machine, or try ketamine. I switched to mild doses of ketamine and it worked beautifully. His pain subsided, and he was even able to converse with his family when they arrived.
Surgeons are also using ketamine to control post-operative pain. Studies show that when ketamine is given prior to or during surgery, it reduces morphine consumption and decreased pain scores.
It's also useful for chronic pain
Chronic pain of any form is a debilitating disease that can be difficult to treat. Neuropathic pain, a common type of chronic pain, is the result of damage to nerves or neurons in the peripheral nervous system. These peripheral nerves also contain the NMDA receptors that ketamine blocks. Traditional medicines such as opioids are highly addictive, and other first-choice agents, including antidepressants, have success rates of only 30 to 40 percent.
Pain specialists are investigating the use of low-dose ketamine for a number of neuropathic pain syndromes, including chronic migraines, fibromyalgia, phantom limb pain and spinal cord injuries. They are finding pain relief of up to three months if patients are given a low-dose ketamine drip for 100 continuous hours, or if given four hours a day for two weeks.
There have been more than 50 clinical trials in the US alone studying ketamine and depression. Ketamine has remarkably fast antidepressant effects and has been used for treatment-resistant depression, especially in those patients with active and severe suicidal ideations. Ketamine has shown reduction in depression in as little as 40 minutes.
But about its use as Special K...
Ketamine continues to gain popularity as a recreational drug, especially in Southern China, UK, and even Kenya. Snorted or ingested when used for party purposes, taken via IV for the more seasoned user, the desired effects of ketamine include derealization—a feeling that one's surroundings are not real—visual hallucinations, increased awareness of sound and color, and euphoria. The dose to achieve these effects has some variability from person to person. In the ER, I know exactly how much ketamine I've given to a patient, but as an illicit drug, due to unknown purity and cutting practices, it's impossible to know how much you're getting.
Without knowing how much ketamine they're taking, many times recreational users will over-ingest and bypass the desired or derealization effects and move on to a K-hole experience. Getting higher still will cause sedation and complete amnesia. Whether the drug is snorted, ingested, or injected, any effects will last no more than two hours.
In recreational use, ketamine is often cut with other drugs such as cough syrup, methamphetamine, and MDMA. In my own anecdotal experience, the deaths resulting from ketamine are usually the result of co-ingestion of other drugs, many times unknowingly.
Chronic ketamine abuse does not create any physical withdrawal symptoms, like the torture of heroin or fatal seizures of alcohol, but it does create a psychological dependence that is very difficult to kick. Chronic abusers often inject ketamine intravenously, and besides their risking suffocation via Laryngospasm, it will eventually cause liver failure, bladder dysfunction leading to kidney failure, and even death.
The ketamine controversy
China produces most of the world's ketamine and its recreational use there and in surrounding South East Asian countries is skyrocketing. Despite its prolific medical benefits, China has proposed an international classification change of ketamine from a Schedule III drug to a Schedule I drug, or drugs without any medical benefit and high potential for abuse. Schedule I drugs undergo international monitoring, not just national control, and would put ketamine into the same class as LSD, peyote, MDMA, mescaline, and paradoxically, marijuana.
A change to a Schedule I designation would result in tighter regulations of ketamine worldwide and a drastic decrease in production that could mean an end to regular medical and veterinary availability in even the United States, much less developing countries. Both international humanitarian agencies like the WHO and veterinarian agencies like the American Veterinary Medical Association staunchly oppose the classification change, citing the fact that the benefits of ketamine greatly outweigh its abuse potential. The debate continues, but so far China has not succeeded.
Ketamine has so many uses and has saved so many of my own patients from pain and even death, I couldn't imagine working in an ER without it. The medicine is so versatile that if I am ever stranded on a deserted island—or just going somewhere far away to escape Trumpocalypse—it's the drug I'd be sure to bring along.
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