Hangover
Want to know what disease is more common in the Emergency Department in the month of January? Has been called Jitterbug? Why Veterans hospitals used to have whisky on the formulary? 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 Hangover. Want to know what disease is more common in the Emergency Department in the month of January? Has been called Jitterbug? Why Veterans hospitals used to have whisky on the formulary? Listen to find out! This is the third part of our toxicology holiday miniseries.
Today's episode starts in a restaurant. You and your friends started this post-holiday tradition several years ago. Everyone who has to work during the holidays gathers to spend time together afterwards, rather than during. Around the table, everyone is laughing and enjoying themselves, while eating pizza and pasta. You're exchanging stories from the trenches about difficult cases, when you notice one friend become pale and sweaty. He’s a lawyer, so you immediately apologize for discussing a case that involved copious amounts of blood, forgetting ER stories aren’t always appropriate conversation while eating.
He brushes off your apology, saying he's not bothered by the conversation, but rather isn't feeling well. You ask what’s wrong, he says he’s been under the weather and might be coming down with the flu. A few minutes later, there's a huge bang. Your friend has fallen out of his chair. You jump up with a crash as your own chair falls backward. He starts convulsing, having a generalized tonic-clonic seizure.
Question #1. What do you do?
Put a spoon in his mouth
Hold his neck still
Roll him onto his side
Answer: C. Try to roll him on his side to prevent choking and aspirating. Don’t put anything into their mouth, it may cause harm. Don’t try to hold the person still as you may inadvertently cause injury.
Another friend calls 911. You ask if anyone knows if he has a history of a seizure disorder. Everyone shakes their head, no, including the person whose known him for ten years. After two or three minutes, the seizure stops. But he remains unconscious and tremulous.
Medics arrive and transport him to the hospital. Once again, of course, we wouldn't be his doctor, but this is a fictional case, so you need to figure out what's happening to your friend.
In the ED, his vital signs are as follows, temperature 98.5 Fahrenheit or 36.9 Celsius, heart rate 130 bpm, respiratory rate 22 breast per minute, oxygen saturation is 100% on room air, and his blood pressure is 190/70. The nurse removes his urine-soaked pants and gets him into a gown.
He has a contusion, a lump, on the back of his head, from the fall. He is opening his eyes, but not following commands or talking. His heart and lungs, other than the rapid heart rate and rapid breathing, are normal. He’s moving all of his extremities.
He is becoming more awake, but also agitated. He’s thrashing on the stretcher and trying to pull off the cardiac monitor leads. He clearly doesn’t recognize you or understand he’s in a hospital. You haven’t completed the physical exam, but stop because it’s increasing his agitation and becoming counterproductive. This isn’t unexpected behavior, and is most likely, a postictal phase due to the seizure. Patients can be unconscious, lethargic, confused, agitated, and aggressive afterwards. Instead, let’s start the workup, give him a few more minutes to recover, then come back for the rest of physical exam later.
What has happened to our friend? Could this be new onset epilepsy? Possible, but he’s 37, relatively old. If it's not epilepsy, was the seizure provoked by something else? By what?
The obvious answer here is trauma. Anytime you have serious head trauma, there’s a seizure risk, both from the trauma itself and if’s there’s a bleed, intracranial hemorrhage, that also can cause seizures. So maybe he seized because he fell out of the chair and hit his head. But why did he fall out of his chair? Accidents happen, but he’s not 90 and this seems like a lot for an otherwise healthy 30-year-old.
He did say he was under the weather, maybe with the flu. Can the flu cause seizures? Sure, any infection can cause seizures, including meningitis and encephalitis. That said he wasn't coughing, febrile, or really anything else. While, again, not impossible, a person well enough to go out to dinner is not the person with a random seizure from infection.
Did I hear you asking for a blood sugar? Great question. As we’ve previously discussed, high and low blood sugars can certainly cause seizures. The medics checked his blood sugar and it was normal.
He needs a HCT, labs, including electrolytes. I'd order an EKG to screen for risk factors for arrhythmias, which can be a seizure mimic. An infectious work up is indicated though likely low yield, but you send flu and Covid swabs, a chest x-ray, and a urine specimen.
Strokes and tumors also cause seizures, but this is a toxicology podcast so let's focus on toxins. The list of medicines causing them include antidepressants, bupropion especially. It was withdrawn from the market initially due to this side effect, though the FDA later reapproved it at a lower therapeutic dose. Tramadol, is an opioid that unlike most others causes seizures. Diphenhydramine, or Benadryl, but usually at high doses.
Alcohol is a culprit. There were several bottles of wine at the table, but he declined, saying he wasn't drinking. Sympathomimetics, like cocaine, methamphetamine, and amphetamine are definitely implicated. Is he using drugs? Always a possibility, but you'd like to think as a friend and a physician, you would've noticed other symptoms. Bottom line, the differential diagnosis list is long and I could go on, but nothing seems to fit exactly.
His results come back, all normal, including his head CT. You return to his room. He’s awake and now cooperative, allowing you to finish his exam. You ask him to open his mouth, noting abrasions on his tongue, secondary to biting it during the seizure. You also see sinuous movements along the sides of his tongue. His neurological exam is unremarkable except for ongoing shaking and tremulousness.
He starts talking, not to you but to someone else. Except there's no one else in the room. When you ask him, he points to the chair next to his bed. The empty chair. Meaning he’s now awake, but hallucinating. He continues to have a rapid heart rate and high blood pressure. Putting this together, Hallucinations plus tremor gives us the diagnosis.
Question number two. Time to pick your poison. What is the diagnosis?
A. Cocaine use
B. Alcohol intoxication
C. Methamphetamine use
D. Alcohol withdrawal.
The answer is D. Unfortunately for our friend, this is a classic case of alcohol withdrawal, and more importantly it’s very dangerous complication, delirium tremens or DTs. Unlike opioid withdrawal, this is a true medical emergency. This really isn’t a diagnosis we want to make in a friend, so is there a test we can send to confirm? No. It's based on the clinical exam in conjunction with the history. Currently the history is lacking, as is often the case in emergency medicine, but the symptoms fit and I wouldn't hesitate to treat before it gets worse.
Question number three. What is the treatment for alcohol withdrawal?
A. Alcohol.
B. Benzodiazepines like diazepam or lorazepam (ie Valium and Ativan)
C. Barbiturates like phenobarbital
D. All of the above.
The answer is. D. All the above are useful to treatment alcohol withdrawal.
Patients with alcohol use disorders routinely of course use alcohol to stave off withdrawal, like a morning eye opener. In fact, liquid alcohol was on the VA hospital formulary at the VA hospital as late as 2006, including beer, wine and whiskey. In most hospitals, we use benzodiazepines and barbiturates for DTs. More on this a bit but first, let's start treatment.
Both oral and IV routes are acceptable, since our patient is in frank DTs and has already had a seizure, I would move right ahead with IV treatment. There are different protocols regarding choice of drug, frequency, etc and pluses and minuses are routinely debated by toxicologists. Drug shortages further confound the issue. Bottom line, treat early with high doses. I’d use IV diazepam if available because it's time to onset is fast, but lorazepam or any other benzodiazepine will work just fine.
Atypically in medicine, this is no time to start with a tiny dose. These patients have high tolerances to alcohol, obviously. Cross reactivity means also a high tolerance to benzodiazepines and barbiturates. For example, I often start with 20mg of diazepam or Valium and double the dose every 20 minutes until the symptoms are under control.
What is symptom control? There are different scores for grading the severity of withdrawal, but in the ED, my main goal is normalization of the vital signs and resolution of tremulousness and tongue fasciculations.
Patients with serious alcohol used disorders and severe withdrawal may require thousands of milligrams of benzos. You heard me right. Even as much as 2,000mg. If high doses aren't working, I'd switch to barbiturates. You order 20mg of diazepam IV for your friend. While we wait to see how this works, let's take a step back first and talk about alcohol withdrawal, what happens in the brain, and then how treatment works.
The syndrome of alcohol withdrawal was recognized as far back as the first century BCE with Pliny the Elder writing about trembling hands, haunted sleep, and unrestful nights. According to records from New York City, between 1902 to 1935 an estimated 2.5 - 5 admissions per thousand New York City residents for acute alcoholic delirium or alcohol withdrawal. It was a huge problem with a mortality rate of 50%, due in part to treatment with supportive care, bedrest, cold baths, and opium. Slang for DTs included colorful terms like pink elephants, the rats, jitterbug and bottle ache.
Debate about the cause of withdrawal, was it alcohol use itself, withdrawal, or underlying psychiatric disease, continued in the 1950s when the question was definitively answered during a research study. Brace yourself, I'm about to discuss some of the dark corners of medicine. Incarcerated men were exposed to alcohol for 6 to 12 weeks, followed by a two-week period of forced abstinence. 2/3 of the men developed elevated heart rate, sweatiness, and hallucinations, consistent with DTs. Several had seizures. The prisoners were apparently volunteers, all were "former morphine addicts". Obviously, this type of study is completely unethical.
Let’s take one more step back to discuss changes in the brain due to chronic alcohol exposure. Alcohol works by stimulating GABA receptors, a major inhibitory neurotransmitter. The reason you become sleepy and eventually unconscious with heavy drinking. Chronic exposure results in down regulation of GABA receptors. Essentially, trying to stay awake, the body reduces the total number of receptors, reflected in tolerance. Patients can drink large amounts before exhibiting usual side effects. Alcohol also causes changes, increasing effects of glutamate and excitatory NMDA receptors. Withdrawal, therefore, causes overexcitation due to an imbalance of not enough GABA and too much glutamate, resulting in the classic symptoms of high blood pressure, fast heart rate, agitation, shakiness, seizures, and delirium.
Alcohol withdrawal isn’t just DTs. It’s a very large spectrum. A few hours after stopping drinking, some patients might feel anxious, jittery and unwell. This can be called alcoholic tremulousness. Some patients develop alcoholic hallucinosis, hallucinations alone, think pink elephants. This is different than DTs because they aren’t delirious and don’t have vital sign disturbances. About 10% of patients have withdrawal seizures, called rum fits in the past. Untreated withdrawal can progress all the way up to delirium tremens, typically 48 to 96 hours after cessation of drinking.
This isn’t just a historical problem. Current data suggests 20% of ICU admissions are due to alcohol related complications. The presence of an alcohol use disorder or withdrawal was associated with a twofold increase in mortality amongst ICU patients in organ failure. Vigilance is required in patients admitted to the hospital for other reasons. Some studies report withdrawal occurring in 31% of trauma patients and 16% of postop patients. Development of withdrawal is associated with a threefold increase in mortality, even while in the hospital.
So how do benzos work to treat this problem? Just like alcohol, by increasing GABA. The goal is then to gradually taper the benzos down, allowing the brain to reset, hopefully back to normal. Some protocols use phenobarbital as a first line agent rather than benzos. Why? Barbiturates act directly on the GABA channel, while benzos act indirectly, so some suggest it’s a better first line agent.
Benzos and barbiturates are the mainstays of treatment for DTs. Side note, this means they themselves cause withdrawal. It looks the same as alcohol withdrawal, acts the same, and is similarly life-threatening. The treatment is restarting the medicine, then tapering off slowly.
We also use other adjunctive agents to help. Gabapentin and clonidine are two common drugs. Both are sedating and clonidine slows the heart rate and lowers the blood pressure. They shouldn’t be used with a benzo or barb for seizures or DTs. Interestingly, new data suggests semaglutide, Ozempic, reduces alcohol cravings.
Several pitfalls to watch out for. First, never use regular antiepileptics for withdrawal seizures. They won’t work. Also, do not diagnose alcohol withdrawal and stop there. Frequently patients with alcohol use disorders become too sick to drink and not the other way around. In addition to DTs, a patient may also have intracranial hemorrhage, gastrointestinal bleeding, meningitis and other serious infections, liver failure, and electrolyte disturbances just to name a few. Thanks to alcohol’s chronic effects on the immune system, for example you may not see a fever or other expected signs.
Question #4. A patient can have withdrawal with an elevated blood alcohol level.
True
False
The answer is true. Thanks to habitual exposure, users have a high tolerance, you don’t need a level of zero to have withdrawal or DTs. In the US the legal blood alcohol limit for driving is 0.8, or 80 mg/dL. I’ve had patients in DTs with an alcohol level of 400 mg/dL.
Back to our patient. You’ve been dragging your feet at your computer and checking in on the other patients. Time to stop avoiding a difficult conversation with your friend. His reaction might range from outright denial, anger, to shame to anything in between. First, you assess his mental status. He’s calm and no longer hallucinating. His vital signs are almost back to normal with a heart rate of 110 and a blood pressure of 135/65. The tremor is gone. You’ve given him a total of 160 mg of diazepam. This is pretty good symptom control, I’d be satisfied with the dose for now.
You ask him how things are going. He says terrible, but isn’t otherwise forthcoming. Finally, after many questions on your part and few answers on his, he says he’ll confide in you if you promise not to write anything in his chart.
He’s been having a difficult time at work, drank excessively at the holiday party and insulted his boss and most of his colleagues. He’s expecting to be fired and in the hopes of saving his job, he stopped drinking two days ago. He admits to drinking a bottle of vodka daily for the past six months due to pressures at work. He’s wanted to seek help, but is terrified of being disbarred, or facing other legal repercussions. You admit him to the ICU for ongoing benzodiazepines, treatment and monitoring. You also call the substance use psychiatrist for help with both treatment as well as help minimizing repercussions. She says your state has a Lawyer Assistance Program to help address these issues.
You and your friends have another get together in six months, this time at a spa, to celebrate his sobriety. This is a fictional case as are all our cases to protect the innocent. We do see a lot of alcohol withdrawal in the Emergency department, especially after the holidays. If you are suffering with an alcohol use problem and want help, don’t try to do it on your own. Talk to a medical professional or call the SAMHSA National helpline at 1-800-662-HELP for assistance.
The Last question in today’s podcast. What author may have died from DTs?
Ernest Hemingway
Truman Capote
Edgar Allen Poe
Dylan Thomas
Follow the Twitter and Instagram feeds both @pickpoison1 and you’ll see the answer when I post it. Remember, never try anything on this podcast at home or anywhere else.
Thanks so much for your attention. It helps if you subscribe, leave reviews and/or tell your friends. Transcripts are available on the website at pickpoison.com.
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.