Severe alcohol withdrawal in an adolescent male

Abstract

Ethanol remains one of the most frequently abused agents by adolescents, exceeding all others except for vaping nicotine, and use is rising. With increased ethanol use comes a greater risk for dependence and potential for alcohol withdrawal syndromes (AWS). Pediatric AWS is extremely rare and poorly characterized in the literature. Pediatric acute care practitioners may have limited exposure to AWS. We report the case of a 16-year-old male with a history of polysubstance abuse who presented with mild AWS and progressed rapidly to delirium tremens. His withdrawal was initially refractory to high dose benzodiazepine therapy but responded well to phenobarbital. This case highlights how rapidly and dangerously AWS can progress if not aggressively treated. Given the rise in adolescent alcohol use and potential for life threatening symptoms, practitioners, especially in acute care specialties such as emergency medicine, critical care, and hospital medicine, would benefit from additional familiarity with AWS diagnoses and management strategies.

Highlights

• •Pediatric ethanol use appears to be increasing.
• •Alcohol withdrawal syndrome (AWS) is associated with significant morbidity and mortality.
• •AWS is extremely rare in the pediatric population and management is not well-described.
• •This single case report delineates the presentation and management of severe pediatric AWS.

1. Introduction

Ethanol remains one of the most frequently used substances by adolescents. According to the National Institute on Drug Abuse (NIDA), in 2019 7.9 % of eighth graders, 18.4 % of tenth graders, and 29.3 % of twelfth-graders reported alcohol use within the previous 30 days, exceeding all other substances except for vaping nicotine.[1] Alcohol use among minors has increased during the COVID-19 pandemic, with the rate of daily drinking in the above groups rising from 0.2 % to 0.4 % for eighth graders, 0.6–1.0 % for tenth graders, and 1.7–2.7 % for twelfth graders between 2019 and 2020.[1], [2], [3] This can be problematic, as exposure to ethanol earlier in life is associated with future substance use and age of first consumption is inversely related to the risk of developing alcohol dependence.[4], [5].

With increasing adolescent ethanol use, alcohol withdrawal syndrome (AWS) rates may rise in this age group as well. Consequently, recognition and management of AWS is relevant to providers, especially in emergency medicine, hospital medicine, and intensive care, as serious morbidity and even mortality may result from delayed diagnosis and treatment.

Here, we report a 16-year-old male who rapidly progressed from mild to severe AWS including autonomic instability, discuss his diagnosis, and detail our management.

2. Case

A 16-year-old male weighing 64 kg with a history of polysubstance abuse presented to our pediatric referral center’s emergency department (ED) for agitation, hallucinations, and vomiting. He was admitted to a rehabilitation facility three days prior for polysubstance abuse. On the morning of ED presentation, he developed visual and auditory hallucinations, tremors, and vomiting, prompting the center to transfer him for evaluation.

He endorsed a history of drinking one unknown-sized bottle of liquor daily for the last three months, and endorsed frequent, lighter use since age twelve. His last drink was 48 h prior to rehabilitation center admission and 72 h prior to ED arrival. He also endorsed marijuana and fentanyl use the week prior and methamphetamine use five days prior. Nine months earlier, he had presented to our ED for ethanol intoxication with an initial serum ethanol concentration 164 mg/dL and was admitted for one day without developing withdrawal symptoms. At that time, he endorsed drinking two beers daily. He also had documented intermittent use of alprazolam five months prior but denied recent use.

The patient’s initial ED vital signs were normal. Physical examination was notable for diaphoresis and tremor. He was experiencing visual and auditory hallucinations but was oriented. A complete blood count, comprehensive metabolic panel, creatine kinase, ethanol, salicylate, and acetaminophen levels, and urine drug screening were obtained. Blood testing was unremarkable apart from a creatine kinase level of 1043 U/L (reference: 55–370 U/L). Acetaminophen, salicylate, and ethanol levels were undetectable. The urine drugs of abuse immunoassay (Ortho Clinical Diagnostics) was positive for tetrahydrocannabinol (THC) metabolites and negative for amphetamines as a class, barbiturates, benzodiazepines as a class, benzoylecgonine (cocaine metabolite), fentanyl, methadone, opiates, and phencyclidine. In the ED, he was administered a one-time dose of lorazepam 3 milligrams (mg) intravenously (IV) for agitation and one liter of normal saline IV bolus. He was subsequently admitted to an unmonitored general pediatric medical bed. Two milligrams of lorazepam IV was ordered on an as needed basis every two hours for agitation; this was changed to the intramuscular (IM) route after the patient removed his IV.

Over the next 10 h, the patient received a total of 8 mg of lorazepam (4 mg IV and 5 mg IM), 10 mg olanzapine IM, and an additional liter of normal saline. No validated assessment tool such as the revised Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) was used to document symptom severity or to guide medication administration.

The toxicology service was subsequently consulted for assistance in management. We evaluated the patient approximately 22 h after initial ED presentation. He was severely agitated requiring hard restraints, disoriented, and experiencing visual and auditory hallucinations. His heart rate was 151 beats per minute, blood pressure 155/87 mm Hg, respiratory rate of 24 breaths per minute, with an oral temperature of 99.1° F. We recommended larger doses of IV benzodiazepines and escalation of care to the intensive care unit for closer monitoring. We also recommended thiamine supplementation 500 mg three times daily for three days.

The patient had minimal response to escalating doses of lorazepam IV, starting at 2 mg IV, moving to 4 mg, then 8 mg. A total of 14 mg lorazepam IV was administered over 75 min. We then recommended administration of phenobarbital, 10 mg/kg IV divided in two doses over one hour. Within 45 min, the patient became sedate with normalization of his vital signs. Eleven hours after the second phenobarbital dose, during which time he required no additional medications or treatment, he remained somnolent but arousable to voice and was no longer disoriented, agitated, or hallucinating.

The patient’s course was complicated by a rising creatine kinase that peaked at 22,162 U/L on hospital day three. His renal function remained normal until discharge. He received no other medications during his hospitalization. He never experienced seizures, nor recurrent agitation or delirium. He was discharged to a rehabilitation facility on hospital day 5 without medication. The patient required no additional medications at the facility.

3. Discussion

Alcohol use disorder (AUD) is defined as recurrent ethanol consumption with physiologic dependence, risky use, loss of control, and impaired social functioning.[6] Adolescent AUD is common. A 2018 national survey reported 5 % of adolescents met AUD criteria.[7] As noted previously, adolescent ethanol use is rising, prompting concern for increased adolescent AUD and the potential for subsequent withdrawal, which has not been studied in pediatric populations.

Ethanol is a central nervous system depressant that interacts with various receptors, including as a gamma aminobutyric acid (GABA)-A receptor agonist and as a postsynaptic N-methyl-D-aspartate (NMDA) glutamate receptor antagonist.[8] Chronic use alters GABA-A and NMDA receptor function and expression, leading to tolerance and imbalanced inhibitory and excitatory neurotransmission. This imbalance is thought to result in AWS following ethanol reduction or abstinence.[9] Mild AWS presents with anxiety, tremulousness, tachycardia, tachypnea, hypertension, and insomnia. Moderate AWS includes diaphoresis, vomiting, and hallucinations.[10] Severe AWS, historically referred to interchangeably with delirium tremens (DT), may present with delirium, agitation, hyperthermia, tachycardia and varying degrees of hypertension. Seizures can occur at any time but may herald more serious AWS.[10], [11].

In contrast to more moderate disease, severe AWS is characterized by disturbances in consciousness and cognition. It is generally seen 3–5 days after ethanol cessation and sometimes develops after an admission for AWS in otherwise lucid patients.[11] Severe AWS has been described in up to 5–10 % of adult patients hospitalized for ethanol withdrawal and often does not resolve for multiple days in this population.[12], [13] No published data exists that we are aware of on adolescent severe AWS or treatment of AWS in this population.

Benzodiazepines, which are GABA-A agonists, have well-demonstrated efficacy for both preventing and treating the entire spectrum of AWS.[14], [15], [16] When compared with other treatment options such as dopamine antagonists, benzodiazepines were demonstrated to decrease mortality.[17], [18] Benzodiazepines remain the most widely accepted first-line therapy for all forms of AWS, and practitioners have become comfortable with their administration even at higher doses.[14], [15] Various AWS scoring systems such as CIWA-Ar have been developed in adults to assist in recognition and management, often paired with benzodiazepine administration under symptom-triggered protocols. Studies have shown that symptom-triggered strategies reduce cumulative benzodiazepine doses compared with fixed-schedule dosing.[19], [20] We are not aware of any strategies developed specifically for pediatric patients. Certain adult patients may require extremely large benzodiazepine doses to effectively manage withdrawal, exceeding comfort levels for many practitioners. One study in adults with severe AWS described a median cumulative diazepam dose to achieve symptom control of 562 mg.[20] Given that ethanol interacts with multiple receptors, and that benzodiazepines exclusively agonize GABA-A, it is unsurprising that certain patients with severe AWS are refractory to benzodiazepine therapy.[21] We opted to utilize phenobarbital in this case.

Phenobarbital has emerged as a popular choice in many adult EDs, both for benzodiazepine-refractory AWS and as a monotherapy AWS treatment.[22] Phenobarbital has multiple properties that make it appealing for use in AWS. Unlike benzodiazepines, phenobarbital has both GABA-A receptor agonism and NMDA receptor antagonism. It has predictable and well-described IV pharmacokinetics and pharmacodynamics, namely a rapid onset and predictable peak central nervous system depression (approximately thirty minutes), and a comparatively long half-life (3–4 days). Multiple studies show an equivalent safety and efficacy profile as benzodiazepines for AWS, with some even demonstrating decreased ICU length of stay and decreased need for mechanical ventilation compared with benzodiazepines. The long half-life of phenobarbital is particularly appealing as it can reduce additional doses in the inpatient setting and avoid the need for discharge medication.[21], [24], [25]. Various dosing protocols for phenobarbital exist but an optimal regimen remains to be established. Unfamiliarity with phenobarbital and its dosing for AWS has been recognized as a challenge in adoption.[25] Physicians are often concerned about the CNS depressant properties, respiratory depression, and need for airway control, although this complication is uncommon even in patients receiving high cumulative doses of the drug for treatment of severe AWS.[26] Part of this concern may derive from confusion with pentobarbital, which at therapeutic dosing does cause much more CNS sedation.[23], [27].

Of note, we could not rule out coincident withdrawal from benzodiazepines in our patient, although the history of him denying recent or frequent benzodiazepine use renders this complication unlikely. The urine drug screen utilized at our hospital captures most of the benzodiazepine class and would trigger a positive with frequent or recent alprazolam use.

In summary, this adolescent presented with AWS that became rapidly life threatening. While AWS is common in adults, this is the first published report that we are aware of in an adolescent in AWS progressing to severe AWS; the only other documented pediatric case is of a 9-year-old from 1975.[28] It is also the first to detail the utilization of phenobarbital for AWS in this population.

With rising adolescent alcohol use and abuse rates, cases like this may become more common. Pediatric providers should become familiar with AWS and management strategies, as the necessary doses of benzodiazepines and barbiturates are much larger than typical for pediatric patients.

Funding

No funding was secured for this report.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Handling Editor: Dr. L.H. Lash

Data Availability

No data was used for the research described in the article.