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Alcohol Withdrawal Syndrome

Alcohol Withdrawal Syndrome (AWS): Pathophysiology & clinical findings
Authors: Rupali Manek Gurreet Bhandal Erika Russell Reviewers: Harjot Atwal Yvette Ysabel Yao Mao Ding Nureen Pirbhai* * MD at time of publication
Chronic alcohol use
↓Autonomic adrenergic systems
↓ Dopamine in the nucleus accumbens
↑ EtOH depressant effects on brain
↓ Glutamate- induced excitation
↑ GABA-induced inhibition
↑ Glutamate receptors in attempt to maintain normal arousal state
GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
Long-term physical dependence
Abrupt alcohol cessation àabrupt ↓ in blood EtOH concentration
Alcohol withdrawal Syndrome
Symptoms that occur when patients stop drinking or significantly decrease their alcohol intake after long-term dependence
↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use
Central nervous system overactivity
Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation
Fluid and electrolyte abnormalities
↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems)
↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating)
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation
↑ Dopamine in nucleus accumbens
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours
Alcohol withdrawal delirium (delirium tremens or DT):
Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days
Hypovolemia
(from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake)
Metabolic acidosis
(from hypoperfusion, infection, alcoholic ketoacidosis, or ↓
thiamine & other B vitamins)
↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↓ Phosphate
(from malnutrition)
Cardiac failure, rhabdomyolysis or muscle breakdown
↓ Phosphate available to make ATP
↓ ATP
↓ Magnesium (common in patients with DT)
Impaired Na-K ATPase function
Dysrhythmias
↑ Glutamate-activated depolarization in the brain
↑ Neuronal excitability
Seizures
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published Apr 15, 2017, updated Oct 18, 2023 on www.thecalgaryguide.com

Alcohol Withdrawal Syndrome (AWS): Pathophysiology & clinical findings
Authors: Rupali Manek Gurreet Bhandal Erika Russell Reviewers: Harjot Atwal Yvette Ysabel Yao Mao Ding Nureen Pirbhai* * MD at time of publication
Chronic alcohol use
↓Autonomic adrenergic systems
↓ Dopamine in the nucleus accumbens
↑ EtOH depressant effects on brain
↓ Glutamate- induced excitation
↑ GABA-induced inhibition
↑ Glutamate receptors in attempt to maintain normal arousal state
GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
Long-term physical dependence
Abrupt alcohol cessation àabrupt ↓ in blood EtOH concentration
Alcohol withdrawal Syndrome
Symptoms that occur when patients stop drinking or significantly decrease their alcohol intake after long-term dependence
↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use
Central nervous system overactivity
Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation
Fluid and electrolyte abnormalities
↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems)
↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating)
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation
↑ Dopamine in nucleus accumbens
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours
Alcohol withdrawal delirium (delirium tremens or DT):
Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days
Hypovolemia
(from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake)
Metabolic acidosis
(from hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins)
↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↓ Magnesium (common in patients with DT)
Dysrhythmias, seizures
↓ Phosphate
(from malnutrition)
↓ Phosphate available to make ATP
↓ ATP
Cardiac failure, rhabdomyolysis or muscle breakdown
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published April 28th, 2014 on www.thecalgaryguide.com

Alcohol Withdrawal: Pathophysiology & clinical findings
Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication
↓Autonomic adrenergic systems
↓ Glutamate-induced excitation
Chronic alcohol use
↑ EtOH depressant effects on brain
↓ Dopamine in the nucleus accumbens
↑ GABA-induced inhibition
↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems)
↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating)
Physical dependence due to chronic alcohol use
Abrupt alcohol cessation
Abrupt ↓ in blood EtOH concentration
Alcohol withdrawal
↓ GABA-induced inhibition &↑ glutamate-induced excitation relative to chronic alcohol use
Central nervous system overactivity
Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation
Fluid and electrolyte abnormalities
↑ Dopamine in nucleus accumbens
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals
12-24 hours after alcohol cessation, typically resolve within 24-48 hours
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation
Alcohol withdrawal delirium (delirium tremens or DT):
Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days
Hypovolemia (from diaphoresis, hyperthermia, vomiting,
↑RR & ↓oral intake)
Metabolic acidosis (from
hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins)
↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↓ Magnesium (common in patients with DT)
Dysrhythmias, seizures
↓ Phosphate (from malnutrition)
↓ Phosphate available to make ATP
↓ ATP
Cardiac failure, rhabdomyolysis or muscle breakdown
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published April 28th, 2014 on www.thecalgaryguide.com

Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: ↓Autonomic adrenergic systems ↓ Dopamine in the nucleus accumbens Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication
Alcohol Withdrawal: Pathophysiology & clinical findings Chronic alcohol use
↑ EtOH depressant effects on brain
↓ Glutamate-induced excitation ↑ GABA-induced inhibition
↑ Glutamate receptors in attempt to maintain normal arousal state GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems)
↑ Sympathetic activity: ↑ Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating)
Physical dependence due to chronic alcohol use
Abrupt alcohol cessation
Abrupt ↓ in blood EtOH concentration Alcohol withdrawal
↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use
Central nervous system overactivity
Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation
Fluid and electrolyte abnormalities
↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↑ Dopamine in nucleus accumbens
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals
12-24 hours after alcohol cessation, typically resolve within 24-48 hours
Alcohol withdrawal delirium (delirium tremens or DT):
Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation
Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake)
Metabolic acidosis (from
hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins)
↓ Magnesium (common in patients with DT)
Dysrhythmias, seizures
↓ Phosphate (from malnutrition) Cardiac failure, rhabdomyolysis
or muscle breakdown
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published April 28th, 2014 on www.thecalgaryguide.com

Alcohol Withdrawal: Pathophysiology & clinical findings Chronic alcohol use
↓ Dopamine in the nucleus accumbens ↓Autonomic adrenergic systems
Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal ↑ GABA-induced inhibition Nureen Pirbhai* * MD at time of publication
↑ EtOH depressant effects on brain
↓ Glutamate-induced excitation
↑ Glutamate receptors in attempt to maintain normal arousal state
GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
↑ Autonomic adrenergic systems (rebound over- activity of the brain and noradrenergic systems)
↑ Sympathetic activity: ↑Heart rate (HR), ↑respiratory rate (RR) ↑blood pressure (BP), tremor & diaphoresis (↑sweating)
Physical dependence due to chronic alcohol use
Abrupt alcohol cessation
Abrupt ↓ in blood EtOH concentration Alcohol withdrawal
↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use
Central nervous system overactivity
Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation
Fluid and electrolyte abnormalities
↑ Dopamine in nucleus accumbens
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals
12-24 hours after alcohol cessation, typically resolve within 24-48 hours
Alcohol withdrawal delirium (delirium tremens or DT):
Hallucinations (mostly visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations 6-12 hours after alcohol cessation
Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑RR & ↓oral intake)
Metabolic acidosis (from
hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins)
↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↓ Magnesium
(common in patients with DT)
Dysrhythmias, seizures
↓ Phosphate (from malnutrition)
Cardiac failure, rhabdomyolysis or muscle breakdown
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published April 28th, 2014 on www.thecalgaryguide.com

Alcohol Withdrawal: Pathophysiology & clinical findings
Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication
↑ EtOH depressant effects on brain
↓ Glutamate-induced excitation
↑ Glutamate receptors in attempt to maintain normal arousal state
Chronic alcohol use
↑ GABA-induced inhibition
GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
↓ Dopamine in the nucleus accumbens ↓Autonomic adrenergic systems
Abrupt alcohol cessation
Physical dependence due to chronic alcohol use
Alcohol withdrawal
↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use
Central nervous system overactivity
Withdrawal seizures: Generalized tonic-clonic convulsions 24-48 hours after alcohol cessation
↑ Autonomic adrenergic systems (rebound over-activity of the brain and noradrenergic systems)
↑ Sympathetic activity: ↑HR, ↑RR ↑BP, tremor & diaphoresis (↑sweating)
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations
6-12 hours after alcohol cessation
↑ Dopamine in nucleus accumbens
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals
12-24 hours after alcohol cessation, typically resolve within 24-48 hours
Alcohol withdrawal delirium (delirium tremens or DT):
Hallucinations (predominately visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis 48-96 hours after alcohol cessation and lasts 1-5 days
Fluid and electrolyte abnormalities
Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑ RR & ↓
oral intake)
Metabolic acidosis (from
hypoperfusion, infection, alcoholic ketoacidosis, or ↓ thiamine & other B vitamins)
↓ Potassium (K) (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↓ Magnesium
(common in patients with DT)
Dysrhythmias, seizures
↓ Phosphate (from malnutrition)
Cardiac failure, rhabdomyolysis or muscle breakdown
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published April 28th, 2014 on www.thecalgaryguide.com

Alcohol Withdrawal: Pathophysiology & clinical findings
Authors: Erika Russell Rupali Manek Gurreet Bhandal Reviewers: Yvette Ysabel Yao Harjot Atwal Nureen Pirbhai* * MD at time of publication
↓ GABA-induced inhibition &↑ Glutamate-induced excitation relative to chronic alcohol use
CNS overactivity
Alcohol withdrawal delirium (delirium tremens or DT): Hallucinations (predominately visual), disorientation, tachycardia, hypertension, hyperthermia, agitation, and diaphoresis
48-96 hours after alcohol cessation and lasts 1-5 days
Alcohol cessation ↓ Dopamine
Alcohol withdrawal
Chronic alcohol use
↑ EtOH depressant effects on brain
in the NAc
↓Autonomic adrenergic systems
↑ Dopamine in nucleus accumbens
(NAc) relative to chronic alcohol use
Alcoholic hallucinosis: Usually visual (but can be auditory or tactile), normal vitals 12-24 hours after alcohol cessation, typically resolve within 24-48 hours
↑ Autonomic adrenergic systems relative to chronic alcohol use
↑ Sympathetic activity: ↑HR, ↑RR ↑BP, tremor & diaphoresis (↑sweating)
↓ Glutamate- induced excitation
↑ Glutamate receptors in attempt to maintain normal arousal state
↑ GABA-induced inhibition
GABA insensitivity (↑ GABA needed to maintain a constant inhibitory tone)
Early symptoms: Insomnia, tremulousness, anxiety, digestive upset, anorexia, headache, sweating, palpitations
6-12 hours after alcohol cessation
Withdrawal seizures: Generalized tonic- clonic convulsions 24-48 hours after alcohol cessation
Fluid and electrolyte abnormalities
Abbreviations:
CNS – Central nervous system K – Potassium
DT – Delirium tremens
Mg – Magnesium
NAc – Nucleus accumbens NMDA – N-methyl-D-aspartate EtOH – Alcohol
NT – Neurotransmitter
Hypovolemia (from diaphoresis, hyperthermia, vomiting, ↑ RR & ↓
oral intake)
Metabolic acidosis (from hypoperfusion, infection, alcoholic ketoacidosis, or ↓
thiamine & other B vitamins)
↓ K (renal & extrarenal K losses, alterations in aldosterone concentrations, and changes in K distribution across the cell membrane)
↓ Mg (common in patients with DT)
Dysrhythmias, seizures
↓ Phosphate (from malnutrition)
Cardiac failure, rhabdomyolysis or muscle breakdown
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
Published April 28th, 2014 on www.thecalgaryguide.com

Alcohol Withdrawal: Clinical Findings and Complications
Authors: Erika Russell Reviewers: Harjot Atwal Nureen Pirbhai* * MD at time of publication
Note: *The onset of alcohol withdrawal generally begins 6-24 hours after the last drink with symptoms peaking between 24-36 hours after and gradually lessening.
Symptoms typically progress from early symptoms and increased sympathetic activityà hallucinationsàseizures àpotentially Delirium Tremens.
Alcohol withdrawal is mild-moderate in severity for 90% of patients. Those who progressively worsen however can enter Delirium Tremens (DT) which has a mortality rate of up to 20%. More likely to have DT if had DT before, age >30 years, concurrent illness, >2 days after EtOH cessation before seeking help, and history of sustained drinking.
Long term, heavy alcohol use that leads to physical dependence
Abrupt ↓ in blood EtOH concentration
Negative physiological reactions to ↓ alcohol intake
Adaptive suppression of GABA activity from chronic alcohol enhancement
Alcohol Withdrawal*
Withdrawal symptoms alleviated by ingesting alcohol
Alcohol taken to relieve withdrawal AND/OR
Social and internal relapse cues trigger urge to use alcohol
Blood EtOH levels >600 mg% can lead to lethal respiratory depression by suppressing the respiratory centers in the brainstem
Upregulated autonomic adrenergic systems from chronic alcohol inhibition
Discontinuation of alcohol leads to rebound over-
activity of the brain and noradrenergic systems
Increased Sympathetic Activity Tachycardia, hypertension, tremor and diaphoresis
Generalized Tonic-Clonic Seizures
Usually begin within 8-24 hours of alcohol cessation and peak after 24 hours. Risk of having seizures ↑ with repeated withdrawals. 1/3 of people can progress to DT if seizures left untreated.
Discontinuation of alcohol causes a sudden relative
deficiency in inhibitory GABA activity
Reduction in dopamine in the nucleus accumbens
(NAc) from chronic alcohol exposure
Discontinuation of alcohol causes a increase in dopamine levels in NAc
Hallucinations
Commonly visual (but can be auditory or tactile), develop 12-24 hours after alcohol cessation.
Early Symptoms
Anxiety, insomnia, vivid dreams, anorexia, nausea, headache and psychomotor agitation
Delirium Tremens (DT)
Life-threatening state of greatly exaggerated withdrawal symptoms (severe tachycardia, diaphoresis etc.) with confusion/disorientation and hallucinations that generally appears 72-96 hours after the last drink and lasts 2-3 days.
Legend:
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Pathophysiology
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