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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: Published MONTH, DAY, YEAR on www.thecalgaryguide.com Pathophysiology Mechanism Sign/Symptom/Lab Finding Complications