Alcohol withdrawal syndrome

“Alcoholism is a well documented pathological reaction to unresolved grief.

”

— David Cook

Alcohol Withdrawal Syndrome: Pathophysiology, Assessment and Clinical Management

Alcohol Withdrawal Syndrome (AWS) remains one of the most frequently encountered yet potentially life-threatening presentations in acute and pre-hospital medicine. While it may initially present with tremor or anxiety, it exists on a spectrum that includes seizures and delirium tremens (DTs), both associated with significant morbidity and mortality.

Historically, alcohol withdrawal seizures were referred to as “Rum Fits”, a phenomenon recognised in both medical writing and literature for centuries. However, the causal relationship between alcohol cessation and seizures remained debated until the mid-20th century. A now ethically indefensible experiment conducted in the 1960s provided definitive evidence: ten incarcerated former morphine users were administered large quantities of alcohol over several months before abrupt cessation. All developed withdrawal symptoms, and several experienced tonic-clonic seizures, confirming both causation and a dose–response relationship between alcohol exposure and withdrawal severity [2].

Such a study could never be replicated today, but it cemented what clinicians now recognise daily — that withdrawal from alcohol is not benign.

Epidemiology

Alcohol misuse remains a significant public health issue in the UK. Approximately 11% of the population consume alcohol at high-risk levels, with around 1% meeting criteria for dependence [1]. Importantly, up to half of individuals who drink heavily may develop withdrawal symptoms during early abstinence [1,4].

Consequently, alcohol withdrawal is encountered frequently in acute care. It is estimated that up to 16% of hospital admissions involve or are complicated by AWS [1]. These figures alone underscore why clinicians across emergency, acute medicine, psychiatry, intensive care, and pre-hospital services must be competent in recognising and managing the syndrome.

Pathophysiology: Loss of Inhibitory Control

Understanding alcohol withdrawal requires revisiting the fundamental balance of the central nervous system (CNS).

Neuronal signalling relies upon a delicate equilibrium between inhibitory and excitatory neurotransmission. The principal inhibitory neurotransmitter is γ-aminobutyric acid (GABA), while the primary excitatory neurotransmitter is glutamate. Under normal physiological conditions, these systems maintain homeostasis through regulated ion channel activity and receptor modulation.

The Acute Effects of Alcohol

Alcohol is a central nervous system depressant. Its primary mechanisms are:

Enhancement of GABA-A receptor activity, increasing chloride influx and hyperpolarising neurons.
Inhibition of glutamatergic NMDA receptors, reducing excitatory transmission.

The combined effect is reduced neuronal firing. Clinically, this manifests as anxiolysis, sedation, impaired coordination, slowed reaction times, and at higher doses, respiratory depression and coma.

Chronic Adaptation

With prolonged exposure, the brain adapts in an attempt to restore equilibrium:

Down-regulation of GABA receptors
Up-regulation of NMDA (glutamate) receptors
Increased calcium channel expression, enhancing neuronal excitability

In essence, the CNS weakens its “brakes” and strengthens its “accelerator.” As long as alcohol remains present, this rebalanced system functions adequately. However, abrupt cessation removes the depressant effect, leaving unopposed excitatory activity.

Clinical Consequence

The result is widespread neuronal hyperexcitability, manifesting as:

Tremor
Anxiety
Agitation
Sweating
Tachycardia
Hypertension
Seizures
Delirium tremens

Importantly, the clinical issue is not the absence of alcohol per se — it is the unopposed excitatory drive within a sensitised CNS.

The Kindling Effect

Repeated cycles of intoxication and withdrawal produce cumulative neuronal stress. Each withdrawal episode increases glutamatergic activity and calcium influx, promoting long-term neuroadaptive changes. Over time, neurons become more easily triggered.

This phenomenon, known as the kindling effect, means:

Withdrawal symptoms occur earlier.
Severity increases with each episode.
Seizures and DTs may occur despite seemingly moderate consumption.

Patients with multiple prior withdrawals are therefore high risk, even if their current intake appears modest.

Clinical Spectrum and Assessment

AWS exists on a continuum from mild autonomic symptoms to life-threatening delirium tremens.

A Crucial Point

Alcohol withdrawal seizures in isolation do not automatically indicate delirium tremens or severe AWS [3]. Seizures may occur without significant autonomic disturbance. However, such patients require monitoring due to risk of progression.

ABCDE Approach

Assessment should always begin with structured ABCDE evaluation. While seizures are often self-terminating before arrival of emergency services, clinicians must avoid diagnostic anchoring. Patients with alcohol dependence are at increased risk of:

Electrolyte disturbances
Intracranial haemorrhage (A first time seizure typically warrants neuroimaging due to bleeding risk)
Infection
Hypoglycaemia
Gastrointestinal bleeding

History Taking

Key elements include:

Pattern of drinking (daily vs binge)
Duration (>3 months heavy daily use or ≥1 week sustained binge increases risk)
Time of last drink (symptoms may begin within hours; seizures peak 8–12 hours)
Previous withdrawal severity (predictive of future severity)
Reason for cessation (intentional detox vs intercurrent illness)
Compliance likelihood

Assessment Tools

CIWA-Ar

The Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) remains widely used. However:

Only 3 components are objective.
Most rely on patient reporting.
Inter-rater reliability may vary outside specialist settings.

Evidence suggests acceptable reliability in structured environments but less certainty in emergency contexts [1].

Take a Look at the CIWA-Ar Score

Inter-rater reliability and accuracy of a score is improved by clinician training. Check out this video on how to use the CIWA Score.

BAWS

The Brief Alcohol Withdrawal Scale (BAWS) was developed as a shorter, more objective alternative and has demonstrated favourable sensitivity and specificity compared with CIWA-Ar in early studies [1].

Whilst simple to use BAWS remains unfamiliar to many clinicians, limiting its usefulness as a communication tool.

Take a look at the BAW Score

Differential Diagnosis

Symptoms of AWS overlap with numerous conditions:

Benzodiazepine withdrawal
Thyrotoxicosis
Hypoglycaemia
Diabetic ketoacidosis
Stimulant intoxication
CNS infection
Status epilepticus
Intracranial haemorrhage
Hepatic encephalopathy
Psychosis

Hepatic Encephalopathy

Particularly relevant in chronic alcohol users, hepatic encephalopathy results from failure of hepatic detoxification. Elevated ammonia crosses the blood–brain barrier, causing astrocyte swelling and altered neurotransmission.

Key distinguishing features:

Asterixis (negative myoclonus)
Lethargy rather than agitation
Minimal autonomic hyperactivity

Recognition is critical, as management differs significantly.

Management Principles

Management directly reflects pathophysiology: restore inhibitory tone, prevent complications, and support physiological recovery.

Benzodiazepines: First-Line Therapy

NICE guidance recommends benzodiazepines as first-line therapy for AWS [5].

Benzodiazepines enhance GABA-A receptor activity, effectively substituting for alcohol’s inhibitory effects.

Chlordiazepoxide

Preferred in UK practice because it:

Has slower onset
Produces sustained effects
Reduces risk of oversedation
Helps mitigate kindling

Diazepam

Used when rapid onset or intravenous administration is required.

Lorazepam

Preferred in hepatic failure due to reduced reliance on oxidative metabolism.

There is no role for phenytoin in alcohol withdrawal seizures; the pathophysiology is global GABA deficiency rather than focal epileptogenesis [3].

Thiamine Replacement

Chronic alcohol use impairs thiamine absorption and storage. Deficiency risks Wernicke’s encephalopathy, characterised by:

Ophthalmoplegia
Ataxia
Confusion

Thiamine should be administered before glucose where possible [5].

Supportive Care

Patients often present with:

Dehydration
Hypokalaemia
Hypomagnesaemia
Risk of refeeding syndrome

Correction of electrolytes is essential, particularly magnesium, as deficiency may predispose to seizures.

Indications for Admission

NICE and RCEM guidance recommend admission for medically assisted withdrawal in patients who [6]:

Are at risk of DTs
Are at risk of seizures
Are frail or have significant comorbidities

Elective detoxification is not an indication for acute hospital admission; community pathways should be utilised.

Importantly, patients with mild AWS being discharged must never be advised to abruptly cease drinking, as this may precipitate severe withdrawal. Referral to structured outpatient services is recommended.

Pre-Hospital Considerations

The primary goal pre-hospital is prevention of severe AWS. Early benzodiazepine administration in high-risk patients reduces progression.

Key red flags:

Previous withdrawal seizures or DTs
Early symptom onset
Marked autonomic instability
Hallucinations or confusion

These patients require urgent escalation and close monitoring.

Conclusion

Alcohol Withdrawal Syndrome represents a predictable neurobiological consequence of chronic alcohol exposure. At its core lies a loss of inhibitory control (that foot on the brake pedal) within an overly sensitised CNS (from up regulation in glutamate receptors… a more powerful accelerator).

Given the prevalence of high-risk alcohol use in the UK and the frequency with which AWS complicates hospital admissions, competence in its assessment and management is not optional — it is fundamental clinical practice.

Remember, clinicians are responsible for their own practice. These podcasts are produced for informative purposes and should not be considered solely sufficient to adjust practice. We provide lots of learning resources, so don’t just take our word for it…navigate to these and reflect on this topic further. See "The Legal Bit" for more info.

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Emergency Care, Chronic ConditionsJoshua BarkerFebruary 22, 2026alcohol, withdrawal, fitting, seizures, addictionComment