Alcohol Withdrawal Patho Basics

Introduction

Substance abuse-related complaints make up a significant number of emergency medicine encounters yearly, with roughly 5 percent of all 2021 visits involving alcohol in some way (HCAI). While a significant portion of these encounters involve only supportive care and discharge from the ED, it is important to maintain a high index of suspicion and be prepared for the potentially lethal complications of substance abuse. In this article, we will discuss the basic pathophysiology of alcohol, alcohol abuse, and necessary information for both the ER nurse and the EMS provider when encountering these patients.

The Basics - How Does Alcohol Work?

The brain uses a variety of neurotransmitters to send ‘messages’ and accomplish tasks. Almost everything we feel and do combines hormones, neurotransmitters, and our conscious beliefs influencing our actions.

The main inhibitory neurotransmitter is gamma-aminobutyric acid (GABA). GABA is responsible for helping the body relax, sleep, and reduce anxiety. It reduces neuron excitability and overall “dulls” the brain. Put simply, it helps carry out the parasympathetic nervous system. A plethora of mental health disorders including generalized anxiety disorder are associated with a deficiency of GABA. It is primarily opposed by glutamate, an excitatory neurotransmitter that promotes alertness, movement, and attention.

Alcohol is a GABA-agonist - that is, it increases the sensitivity of receptors in the brain to GABA. It raises the sensitivity of GABA receptors to GABA to make the effects of GABA more prominent. This causes disinhibition, lethargy, worsens muscle coordination, and is also responsible for the amnesia sometimes associated with heavy alcohol use. Alcohol also inhibits the action of glutamate to accomplish its effects. Excess GABA works as a sedative.

In addition, alcohol boosts the traditional “feel good” dopamine neurotransmitter, which in turn entices the user to drink more over time.

In response to the high GABA amounts from alcohol use, the body downregulates GABA production and GABA receptors; meaning that patients have less intrinsic GABA available in addition to a decreased sensitivity to it with prolonged use over time. This plays a role in patients developing tolerance - they need more and more alcohol to achieve the same effects each time. They also need alcohol on a more regular basis to make up for the GABA they are no longer producing in adequate amounts.

Alcohol Withdrawal Syndrome

Alcohol withdrawal syndrome is a potentially life-threatening complication of sudden alcohol cessation after long-term use. Unlike most other withdrawal syndromes, alcohol withdrawal has the potential to be fatal. Most other withdrawal syndromes cause extremely unpleasant and horrific body sensations, but alcohol can be lethal. Alcohol withdrawal requires supervised medical management to be done safely and often requires an inpatient stay of at least 2-3 days.

Alcohol withdrawal can onset at different times depending on the user’s usual timing and amount of alcohol intake. Someone who is used to drinking heavy amounts all day can have withdrawal onset within hours of their last drink, while a less heavy user may have withdrawal begin within days of ceasing use instead. Symptoms usually begin within 6-24 hours of the last drink and can peak at 36-72 hours (World Health Organization). The severity and length of withdrawal are often correlated with the length and severity of the patient’s alcohol use; a less heavy drinker will likely have more moderate symptoms compared to a heavier one, and vice versa.

Symptoms progress with time. Not every alcohol withdrawal patient will present the same, so make sure to maintain a high index of suspicion and be ready for the patient to decline while also not ruling out other medical complaints just because a patient has an alcoholism history. Remember: patients with alcohol abuse disorder also often have medical issues at the same time.

Typical symptoms include:
- Anxiety and restlessness

• Tachycardia and hypertension

• Diaphoresis

• Nausea and vomiting

• Weakness

• Agitation

• Fever or increased temperature

Isolated mild alcohol withdrawal often only ends with the above symptoms. However, more severe symptoms include:

• Hallucinations and abnormal sensations

  • Withdrawal patients often experience audiovisual hallucinations. They are typically fear-inducing. Classic examples include seeing bugs or creatures on the walls or hearing voices. Patients also often describe a crawling sensation on their skin, and may become panicked as a result.

• Tremors

  • Tremors associated with withdrawal can range from mild intention tremors to full body, uncontrollable jerking. It is important to manage this for patient comfort.

• Delirium, delirium tremens

  • Severe withdrawal can present with delirium and altered mental status, making history-taking and treatment in general difficult. These patients often become combative, have nonsensical speech with a loss of abstract thought patterns, and stop responding appropriately.

• Seizures

  • Seizures are the most immediate way that withdrawal can become lethal. Prolonged seizures can cause trauma as the patient flails in addition to hypoxia and aspiration. Treat these seizures like you would any other seizure - quick termination is key.

Managing Alcohol Withdrawal

Managing alcohol withdrawal involves a combination of supportive care and benzodiazepines/barbiturates. We will discuss the pathophysiology of the various medications commonly used in withdrawal management.

Benzodiazepines - Benzodiazepines essentially work by replenishing the deficient GABA in the patient’s body. During withdrawal, the body has deficient GABA because it was previously being provided by alcohol intake. Glutamate and other stimulatory neurotransmitters become dominant and spike, prompting sympathetic symptoms like diaphoresis and seizures. Benzodiazepine administration is titrated to the severity of alcohol withdrawal symptoms and is usually dosed every several hours until symptoms subside. Common benzo examples include lorazepam (ativan), midazolam (versed), and diazepam in both oral and IV units.

Barbituates - Barbituates are also GABA agonists and work by increasing circulating GABA. They work similar to benzodiazepines and can be added on top of benzodiazepines or used as a monotherapy. Examples of barbituates include phenobarbital, often in IV or IV drip form.

Magnesium - Alcohol is a natural diuretic that can deplete magnesium over time. Liver damage also causes magnesium depletion. In addition, alcohol use and withdrawal can induce vomiting which in turn will expel all electrolytes in the process. Patients who are chronic alcohol users will often need PO or IV magnesium repletion during their hospital stay.

CIWA Scores

Clinical Withdrawal Assessment scores are a standardized way to gauge the severity of withdrawal symptoms and help steer treatment methods for the patient. A higher CIWA score correlates with worse symptom severity and a higher risk of adverse events. Patients with higher CIWA scores will receive higher doses of benzodiazepines/barbiturates in addition to other treatments. We titrate the dosing to the CIWA score. The ultimate goal is to wean a patient off needing benzodiazepines and achieve a low CIWA score.

Altered Mental Status & Liver Disease

There are a variety of ways that alcohol use, acute or chronic, can induce altered mental status. Beyond classic intoxication, liver disease associated with chronic abuse can cause altered mental status.

Wernicke encephalopathy is a severe depletion of vitamin B1 (thiamine), which is necessary for normal motor functions and cognition. WE is characterized by neuro deficits such as nystagmus, ataxia, poor gait, and neuropathy. It is treated with thiamine replacement, typically via IV or PO forms. These are the classic “banana bags” that used to be more common in EDs.

“Banana bags” are IV fluid solutions with various electrolytes including magnesium, thiamine, and folic acid. They have become common for outpatient elective IV infusion clinics.

Hepatic encephalopathy is a severe accumulation of ammonia due to a deficiency of the liver’s ability to expel it (Ali & Nagalli, 2023). Ammonia is a natural toxic byproduct of metabolic processes in the body and is ordinarily excreted without issue by the liver. However, patients with liver disease do a poor job of excreting ammonia in addition to other byproducts. If allowed to accumulate, ammonia can become neurotoxic and manifest with neuro deficits. Common neuro deficits include general fatigue and poor responsiveness, ataxia, asterixis, and confusion (Ali & Nagalli, 2023).

Clinical Pearls

• Patients experiencing alcohol withdrawal are often anxious and extremely paranoid. This is a severe state of mental and physical stress. Take your time when assessing and communicating with these patients. Reorient them as necessary, even if they are not orientable in their current state.

• Patients experiencing withdrawal often experience varying electrolyte disturbances. Perform a full assessment of these patients and be prepared to handle any associated dysrhythmias. These patients may also need fluid resuscitation as they become profoundly dehydrated.

• Obtain blood glucose early and often with these patients. As we discussed in our article on hypoglycemia, patients with underlying liver disease are prone to glucose derangement. It is also a rule-out cause for AMS.

  • Lipase elevation is pertinent for assessing for concomitant pancreatitis (University of Rochester Medical Center, n.d.).
    

Conclusion

In this article, we discussed the basics of alcohol withdrawal syndrome and the most common symptoms that EMS/ER providers will see. In addition, we discussed the main treatment for withdrawal and the CIWA scoring system. Approaching patients in alcohol withdrawal requires tact, compassion, and a high index of suspicion for complications. Do not undertreat or disregard these patients - they are often amongst the the most ill patients that we encounter.

References

Alcohol Use Disorder (AUD) in the United States: Age groups and demographic characteristics | National Institute on Alcohol Abuse and Alcoholism (NIAAA). (n.d.). https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-use-disorder-aud-united-states-age-groups-and-demographic-characteristics

Ali, R., & Nagalli, S. (2023, April 7). Hyperammonemia. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK557504/#:~:text=Hyperammonemia%20is%20a%20metabolic%20condition,depending%20on%20the%20underlying%20abnormality.

Lipase - Health Encyclopedia - University of Rochester Medical Center. (n.d.). https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=167&contentid=lipase#:~:text=Higher%20than%20normal%20levels%20of,cirrhosis%2C%20or%20a%20bowel%20problem.

Sellers, E. (n.d.). CIWA-AR for alcohol withdrawal. MDCalc. https://www.mdcalc.com/calc/1736/ciwa-ar-alcohol-withdrawal

Vasan, S., & Kumar, A. (2023, August 14). Wernicke encephalopathy. StatPearls - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK470344/

World Health Organization. (2009). Withdrawal management. Clinical Guidelines for Withdrawal Management and Treatment of Drug Dependence in Closed Settings - NCBI Bookshelf. https://www.ncbi.nlm.nih.gov/books/NBK310652/