Nobody Home
Want to know what medicine is derived from PCP? Why it’s medical use resulted in murder charges and convictions? Listen to find out!
This is the Pick Your Poison podcast. I’m your host Dr. JP and I’m here to share my passion for poisons in this interactive show. Will our patient survive this podcast? It’s up to you and the choices you make. Our episode today is called Nobody Home. Want to know what medicine is derived from PCP? Why it’s medical use resulted in murder charges and convictions? Stay tuned!
Happy New Year and welcome to Season 2. Thank you to everyone who listened to Season 1 making this possible!
Quick note - I was recently a guest on the Toxic History podcast and YouTube channel discussing the antibiotic that came to be called the elixir of death and how it started the modern FDA. Toxic History is less patient focused and more technical but still filled with fascinating facts. Check it out Toxic History! I love listening to the incredible stories of poisonings throughout history.
Today’s episode starts in the Emergency Department during a busy shift when you hear someone shout “Code Blue. Waiting room. Code Blue.” The staff scoops up the unconscious person and moves her into the critical care room.
What do you do first? Always the ABCs. Airway, breathing and circulation. The patient’s airway and breathing are intact. You put your fingers on her neck to check for a pulse and feel a steady thump.
Good news this is not a cardiac arrest. It is, however, an unconscious patient. You ask the nurse why the woman was in the waiting room. The triage note says the patient has had abdominal pain for one week, along with some bloody urine.
The patient’s vital signs were normal at the time of triage, six hours ago thanks to ED overcrowding. The nurse clicks through the rest of the electronic chart. Other than a few visits to primary care and OB/GYN for abdominal pain, there’s no other past history.
We’re on our own here.
The nurse checks her current temperature and reads off the rest of her vital signs from the monitor. Her temperature is 99.5, (37.5 C) blood pressure 150/90, heart rate 115 beats per minute. Oxygen saturation 100% on room air.
Abdominal pain and sudden onset altered mental status in an otherwise healthy person don’t often go together, except for one relatively common life-threatening emergency. An ectopic or tubal pregnancy. It’s a pregnancy in the fallopian tubes or elsewhere in the abdomen other than the uterus. A very emergent diagnosis and one at the top of my list in a woman with abdominal pain who passes out.
While you wait for the pregnancy test, you consider her vital signs. Mildly high blood pressure and fast heart rate. The blood pressure doesn’t fit. Ectopic pregnancies can rupture, causing hemorrhaging into the abdomen and death. If she were bleeding internally, we’d expect a low blood pressure. The pregnancy test is negative. A relief. We can move on with the workup.
She can’t give us any history, so it’s time for the physical exam. She's altered and confused, though maybe a little bit more awake than she was a few minutes ago. Her lungs are clear, her heartbeat is fast but regular. Her abdomen is tender suprapubically, over her bladder. The muscle exam is normal.
Her pupils are large. They’re also moving rhythmically, both back and forth as well as in a circular fashion. As you move the light to click it off, you notice something caked inside her nasal passages. White powder.
Two big clues.
Back and forth jerking of the eyes is called nystagmus. A number of diseases cause nystagmus, mostly neurological ones. Toxicologic causes of nystagmus include cerebellar poisons, including things we've discussed like alcohol, benzodiazepines, barbiturates, and GHB. Lithium, a treatment for bipolar disease classically causes nystagmus. Antiepileptics, seizure medicines, cause it. Also gabapentin, marijuana, amphetamines, and ecstasy.
In addition, she has a circular component, a subtype called rotary nystagmus. In toxicology, rotary nystagmus means two things: ketamine and pcp. Both of which can be powders. It could be either one. My guess: ketamine. Why? PCP is often smoked, while ketamine is often snorted. PCP typically causes agitation and ketamine causes k cramps or abdominal pain. More on this in a minute.
Question 1. Now that we suspect ketamine, we should administer the antidote.
A. True
B. False
Answer: B. False. There is no antidote for ketamine. The treatment is close observation on a cardiac monitor. Basically, watchful waiting. If she did lose her airway, we could intubate her and put her on a ventilator, though at this point doubtful she will need it.
What is ketamine? It’s classified as a dissociative anesthetic. It was developed in 1962 by researchers looking for a drug like PCP without the side effects. PCP itself was developed as an anesthetic. It worked great except for the adverse drug effects as the patients awakened. In both animals and humans, it causes delirium and psychosis. We call this an emergence reaction when someone becomes agitated or delirious while waking up from anesthesia. Ketamine was synthesized with the goal of reducing these effects. It was first used in the Vietnam war to treat wounded soldiers on the front lines. While it’s much less likely to cause psychosis then PCP, emergence reactions are one of the main side effects of ketamine use. They're typically mild and short-lived, like bad dreams. They can be treated with a benzodiazepine if necessary.
Ketamine is a very important drug, on the United Nations list of Essential Medicines, and one I use frequently in the emergency department. How does it work? Like PCP, it blocks NMDA receptors. These receptors are incredibility important, yet our knowledge about them is still limited. Glutamate is the main excitatory neurotransmitter in the brain. Glutamate works by binding to NMDA receptors. Therefore, a drug blocking these receptors, blocks glutamate and causes sedation. Interesting detour, disorders in NMDA receptors contribute to diseases like Alzheimer’s, epilepsy, and rare form of encephalitis caused by benign ovarian tumors. Also, some of the cognitive effects of heavy metal poisoning may be via NMDA receptors.
As I mentioned, we use ketamine all the time in the ER for procedural sedation. It’s for procedures outside the operating room. The goal is to have the patient sedated, but still breathing on their own. If they require heavy sedation, then they require a ventilator, and an operating room. Procedural sedation is great for things like reducing, setting, a broken bone. Ketamine is great for painful procedures in pediatric patients.
We like it because, unlike most drugs used for sedation, it rarely stops the patient’s breathing. The other options we have include propofol and opioids, agents where respiratory arrest is a common side effect. Transient respiratory depression, mostly associated with rapid IV push, is reported. Anecdotally, I use ketamine all the time and I’ve never seen anyone stop breathing, so while possible, its rare. Another benefit is ketamine doesn’t lower the blood pressure like the others. In fact, you see high blood pressure and heart rate, though these are generally mild, as in the case of our patient.
I’m sure you already know ketamine isn’t just used by doctors, but is also a drug of abuse. Ketamine isn't as addictive as some drugs like opioids, but it does have abuse potential. Misuse was first noted in the West Coast in 1971. On the street, it’s often called special K, K or Ket. It's often associated with raves or dance parties. Historically, US sources were diverted from veterinary ketamine, but like many drugs is now manufactured and smuggled in from Mexico. It's used by vets as a sedative and is often in powdered form. Water is added, the mixture is dried into crystals, which are crushed then snorted. Use is increasing worldwide since the 1990s. According to some estimates as much as 11% of the world’s population has used ketamine, though numbers in the US are much lower.
What happens when you use ketamine? Well, depends on the dose. At low doses, typical “recreational” doses patients report feeling mellow and relaxed, feelings of euphoria, numbness and a dream-like state. It’s been called k-land, in stark contrast to a k-hole which most users hope to avoid. If you’re using ketamine outside the hospital and you experience a k-hole, you’ve taken too much. It’s the dissociative anesthetic effects, feeling like you can’t move, feelings of depression and some users even report near death experiences.
It’s been about twenty minutes since our patient was rushed back from the waiting room. She’s sitting up on the stretcher with her eyes open. Her eyes are roving around the room and she occasionally reaches out her arms to touch something that isn’t there. She doesn’t respond when spoken to or even look in the direction of the voice.
What’s happening? Has she developed a new problem?
No. This is the dissociative anesthetic effect. We call it “lights on, nobody home.” It’s what we’re aiming for with procedural sedation.
Before I give ketamine, I always warn family members ahead of time what to expect. Unlike other sedatives, the patient’s eyes will be open and moving. Sometimes they have purposeless movements, like reaching for things. They look like they’re awake. Again lights on, nobody home analogy. It’s strange for all involved because the patient looks awake, but they don’t notice and don’t pay any attention to the painful procedure like manipulating broken bones.
Significant emergence reactions are reported in about 1% of pediatric patients and 10-20% of adult patients, though I have to say in my experience it’s been lower. If patients do become agitated or upset, you can give a short-acting benzodiazepine to calm them down until the drug fully wears off.
A benefit of ketamine both for patients and out of hospital users is its rapid onset and short duration of action. When given IV, it works within 1 to 2 minutes and lasts for 15 to 30 minutes. Users generally snort it, then onset takes about 10-15 minutes, and last for an hour or two.
We used to be concerned that ketamine worsened intracranial and intraocular pressure. As far as the ER is concerned, these have been mostly debunked. There’s only one category of patient in whom I wouldn’t use ketamine, schizophrenic patients. Ketamine could worsen their symptoms and it’s probably best avoided.
Is ketamine safe? This is a toxicology podcast, so you know by now nothing is completely safe. I mentioned ketamine is safer than many of the other drugs we use for sedation like propofol and opioids which both commonly cause respiratory arrest. Note this is in a highly monitored medcial setting. Anyone doing procedural sedation in the ER knows it usually takes longer to set up than it does to do the actual procedure. You need a dedicated nurse, a cardiac monitor, intubation equipment nearby, sometimes a respiratory therapist is required. You also need two practitioners, one to give the sedation and monitor, one to do the procedure. In most places, its like herding cats and takes forever. Strict hospital policies are in place to protect patients and I wouldn’t want to administer it any other way.
Ketamine isn’t like opioids, killing hundreds of thousands per year, we don’t see tons of ketamine overdoses in the ER like we do with fentanyl and heroin. That said, during use in an unmonitored setting, all bets are off.
The recent death of a celebrity tragically highlighted the danger of ketamine use.
Question 2. Which celebrity died of the acute effects of ketamine?
A. Matthew Perry
B. Jerry Springer
C. Sinead O’Connor
D. Lisa Marie Presley
Answer: A. Actor Matthew Perry drowned in his pool. A large dose of ketamine was in his system in autopsy, at a level compatible with doses used for surgical anesthesia. Pools and bathtubs are dangerous places for people who’ve used drugs and alcohol. Whitney Houston, her daughter Bobby Christina Brown, Jim Morrison, the pop star Aaron Carter all died in the bathtub. It doesn’t take a lot of sedation to drown in a small amount of water.
Driving under the influence of ketamine is also dangerous. A study from Hong Kong demonstrated 9% of fatal, single car traffic crashes involved ketamine. It’s also been used in drug facilitated sexual assault.
These are complications of acute ketamine exposure. Question #3. Chronic ketamine use effects which organ?
A. Lungs
B. Heart
C. Spinal Cord
D. Bladder
Answer D. Chronic use is associated with genitourinary problems. The mechanism of action isn’t well understood, but it effects the GU system from the kidneys, ureters, bladder and urethra. Ketamine cystitis is common, it’s like a urinary tract infection, but without the infection. No bacteria present, it’s irritation and inflammation instead. As such, it won’t improve with antibiotics. Patients report pain and bloody urine. It’s often referred to as k-cramps. The treatment - stopping ketamine.
Aside from its use in the OR and ER for sedation, ketamine is used to treat chronic pain and severe depression. Ketamine has analgesic properties and can treat acute pain. The data on it’s use in chronic pain is mixed as far as utility. On the other hand, it has promise in the treatment of refractory depression. After ketamine, patients report less depression and less suicidal thoughts. While I’m convinced about the data to support its use in depression, the toxicologist in me has concerns about side effects. In my opinion, ketamine for depression could become a lot like opioids for pain. There’s no doubt it works, but uncontrolled use may do more harm than good. The risk/benefit analysis isn’t well understood at this time, but studies are ongoing. Ketamine clinics give lower doses, avoiding k-holes and, theoretically, complications. Regulations for clinics and monitoring are variable. One source said private ketamine therapy clinics were like the “wild west.”
Leave it to the pharmaceutical companies to come up with a formulation no one knew we needed. There is now a ketamine-derived nasal spray. Yes, that’s right. It’s esketamine, under the brand name Spravato. Esketamine is an enantiomer of ketamine, basically the chemical structure is a mirror image of ketamine’s. The indications are treatment resistant depression or major depressive disorder with suicidal thoughts. Fortunately, it can only be administered in a medical office in what’s called a risk evaluation and mitigation strategy. Patients must be monitored for at least two hours and it can’t be dispensed for home use.
It carries a black box warning, with essentially the same things would be concerned about for ketamine, sedation, dissociation, respiratory depression, abuse and misuse, and suicidal thoughts and behaviors. Wait, a drug causing suicidal thoughts is used to treat suicidal thoughts? This gave me pause for a second too, but again it’s dose dependent. At low doses, hopefully the patient feels better. If they’re in a k-hole the dysphoria may make then feels worse.
I have to mention, during my research, I came across a study looking at the utility of ketamine mouthwash. If that gets approved what could possibly go wrong?
This brings us to a topic which has been recently both in the news and in the courts. Two paramedics in Colorado were convicted of murder after giving Elijah McClain ketamine. After administration, he suffered a cardiac arrest and died three days later. According to the court, he was given too large a dose for a person of his size and in addition, wasn’t monitored after it was given.
It raises the controversial issue of hyperactive delirium. In the emergency department, it’s common to see extremely agitated patients. We usually call it undifferentiated agitation because it can be caused by alcohol intoxication, substance use, mental illness, and medical illness just to name a few. A classic example of this is a person high on PCP, wildly agitated with seemingly superhuman strength who manages to flip over their stretcher. If they can’t be talked down, treatment is necessary given the danger of harming themselves and others. In the medical literature, there's always been a lot of discussion about how best to approach these patients, including which medicines are useful and which are best avoided.
In the past, the term excited delirium was used, it was coined in 1981 and taken from the psychiatric term acute exhaustive mania. Unfortunately, this term is associated with bias and has been used retroactively to justify the use of force by law enforcement. The American College of Emergency Physicians (ACEP) withdrew a 2009 white paper using this term. Similarly, in California, it’s not allowed as a diagnosis on autopsy. ACEP published a new paper in 2021 using the term hyperactive delirium.
We don’t understand very little about this topic because impossible to recreate these high stakes, adrenaline-fueled scenarios in a lab. What we do know is that hyperactive delirium with severe agitation is a life-threatening problem requiring emergent treatment. In fact, it was described as early as 1849. Bell’s mania described poor outcomes in severely agitated psychiatric patients before psychiatric medicines existed. Ketamine is one of the many drugs useful in treating this condition, though drug choice is based on a risk/benefit analysis for each patient as well local hospital protocols. Colorado passed a law restricting ketamine use by paramedics. Prior to use patients must be weighed and equipment to manage the airway and monitor vital signs must be present.
As with many controlled substances, synthetic ketamine derivatives exist, in an attempt to circumvent regulations. Often they’re sold legally online and may be labeled not for human consumption. Methoxetamine or Special M is a drug similar to ketamine with similar effects. It has a longer time of onset of 90 minutes and a longer duration of action. Taken orally it lasts 5 to 7 hours. Dissociative experiences are called mholes I don’t know about you, but a 5-7 hour k-hole doesn’t sound fun. Methoxetamine has been marketed as a “bladder friendly” alternative to ketamine, though this is probably not true since animal studies show the same effects on the urinary tract. As of 2002 methoxetamine is Schedule I drug in the US.
Back to our patient. An hour or two later, she’s back to baseline, awake and alert. She admits to frequent ketamine use, got bored in the waiting room, and insufflated or snorted a dose. Her CT scan shows findings consistent with ketamine cystitis. A small, shrunken bladder with a prominently thickened wall. She’d suspected this as the cause of her symptoms, but hadn’t revealed her ketamine use to other providers. You offer information for outpatient follow up and recovery services. This is a fictional case, as are all our cases, to protect the innocent. But it is based on real poisonings.
Last question in today’s podcast. Which celebrity says artwork in their home was inspired by a ketamine infusion?
A. Gweneth Paltrow
B. Jennifer Aniston
C. Chrissy Teigen
D. Cameron Diaz
Post your answers on our Twitter and Instagram feeds both @pickpoison1. Follow and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
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While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Thank you. Until next time, take care and stay safe.