I Dream of Pink Elephants

Delirium tremens (DTs), the final stage in the spectrum of alcohol withdrawal, was historically associated with hallucinations - the most common of which was seeing a pink elephant. This association is so common that the Huyghe brewery in Belgium named their award-winning ale the Delirium Tremens and its logo is that of a pink elephant. Prior to seeing these discolored large mammals, however, a patient undergoing alcohol withdrawal will pass through several other clinical stages.

Alcohol causes its euphoria and other intoxicating effects by inhibiting the flow of ions through the NMDA-glutamate receptors and enhancing the activity of GABA receptors - this leads to the release of Dopamine in the nucleus accumbens and prefrontal cortex. Chronic alcohol use leads to the down-regulation of GABA receptors due to their chronic excitatory state. After it has completed its reward pathway, alcohol is metabolized by the enzyme alcohol dehydrogenase into acetaldehyde and then finally into acetate and then acetyl CoA.

Once a patient has stopped consuming alcohol, the blood alcohol content begins to decrease - alcohol is metabolized at a rate of 15-30 mg/dL/hr. Patients can begin to experience the effects of withdrawal long before the alcohol is completely metabolized and can even experience effects several days after they have started withdrawal.

Initial symptoms of alcohol withdrawal include tremors, insomnia, nausea and vomiting, anxiety. Later symptoms include hallucinations (the pink elephants we will soon encounter) and seizure. Most of this pathology involves the now uninhibited but still down regulated GABA receptor. This makes sense then that a lot of the treatment of alcohol withdrawal revolves around GABA agonism. Treatment of alcohol withdrawal is guided by the Clinical Institute Withdrawal Assessment (CIWA) score - and treatment generally includes Benzodiazepine (GABAa agonist) therapy. Vitamin replacement is also commonly included in the treatment of alcohol withdrawal due to concern for chronic malnutrition in alcoholic patients. Seizures occur due to decreased seizure threshold from prolonged GABA receptor down-regulation - these are conveniently treated by Benzodiazepines as well.

Delirium tremens, the most severe phase of alcohol withdrawal, usually starts three to five days after their last drink, and can last up to 6 days. One case report even indicated that a patient underwent DTs for 28 days [1]. DTs are a clinical diagnosis, as no lab test or imaging study can identify this disorder. Patients who are in DTs require escalating doses of benzodiazepines and require admission to the ICU. Once they are no longer acutely delirious patients can be downgraded to the general medical floor, with medication management guided by repeat CIWA scores.

This information may make us rethink the scene in the original animated children’s movie Dumbo, which prominently features the young elephant drinking a little champagne and then hallucinating some pink and green friends.

As an aside - before pink elephants became the favorite association of delirium tremens, the most common saying was seeing “snakes in your boots," a line most famously said by Woody in Toy Story.

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6505229/