Alcohol Withdrawal in ED

Alcohol withdrawal is seen in those who stop or cut down their drinking abruptly. Symptoms  of withdrawal include tremors, nausea and vomiting, diaphoresis, hyperdynamic vitals, fever, agitation, craving, and anxiety, seizures, hallucinations, and delirium. Symptoms may begin within few hours after reduction in alcohol consumption. 

ED management

Ruling out the co-existing diagnosis and mimics (hyponatremia, hypoglycemia, hypomagnesemia, DKA, Wernicke’s encephalopathy, toxic ingestions, primary seizures, head injury, infection, sepsis)

Alcohol withdrawal seizures are tonic-clonic seizures that occur 6-48 hours after the decrease in intake or the last drink. Alcohol withdrawal seizures remains a diagnosis of exclusion. Focal seizures should prompt search for another diagnosis. Benzodiazepines are the drugs of choice for EtOH withdrawal fits. Phenytoin should not be used unless there is an underlying structural lesion. Lorazepam is typically started at 2mg IV and repeated as needed. 

Delirium tremens is characterised by fluctuating disturbances in consciousness, confusion, agitation, inattention and impairment in cognition and hallucinations. Patients are at risk of fluid and metabolic imbalances. High doses of sedatives are required to control agitation. Benzodiazepines are the initial treatment of choice and those who do not respond to BZDs need phenobarbital, propofol, or haloperidol. However, antipsychotics should be given only after adequate benzodiazepines are administered.

Treatment of concomitant illnesses and providing supportive care (hydration and electrolyte imbalance) is an important part of management. Patients may also need physical restraints until they are quiet and Pabrinex and Mg should be considered for all.

Goals of therapy

Our goal is to reduce autonomic hyperactivity and agitation. This is achieved mainly through BZDs.  

Lorazepam 1mg = Midazolam 2mg = Diazepam 5mg = Chlordiazepoxide 25mg

Lorazepam is well tolerated by patients with advanced liver disease. Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA) is a validated (not validated specifically for ED use), structured instrument for guiding continuing treatment once a diagnosis of alcohol withdrawal is established. A score <8 represents mild withdrawal; score of 9 to 15 moderate withdrawal, and score >15 severe withdrawal. 

Admission Criteria

• Concomitant other diagnosis 
• Suicidal or homicidal ideation 
• Advanced age
• Not responding well to ED treatment
• Prior history of delirium tremens 
• Alcohol withdrawal seizures

References:

1. Rathlev NK, Ulrich AS, Delanty N, D’Onofrio G: Alcohol-related seizures. J Emerg Med 31: 157, 2006.
2. Greenberg DM, Lee JW: Psychotic manifestations of alcoholism. Curr Psychiatry Rep 3: 314, 2001.
3. Kahan M, Borgundvaag B, Midmer D: Treatment variability and out come differences in emergency department management of alcohol withdrawal. Can J Emerg Med 7: 87, 2005.
4. Clinical Institute Withdrawal Assessment for Alcohol scale. CIWA-Ar available at: http://www.stvincentshospital.ie/documents/CIWA-Ar.pdf. Accessed February 22, 2010.
5. D’Onofrio G, Rathlev NK, Ulrich AS, et al: Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med 340: 915, 1999.
6. McCowan C, Marik P: Refractory delirium tremens treated with propofol: a case series. Crit Care Med 28: 1781, 2000.
7. Kang TM: Propofol infusion syndrome in critically ill patients. Ann Pharmacother 36(9): 1453, 2002.
8. Mayo-Smith MF, Beecher LH, Fischer TL, et al; for the Working Group on the Man- agement of Alcohol Withdrawal Delirium, Practice Guidelines Committee, American Society of Addiction Medicine: Management of alcohol withdrawal delirium: an evi- dence-based practice guideline. Arch Intern Med 164: 1405, 2004.
9. Kosten TR, O’Connor PG: Management of drug and alcohol withdrawal. N Engl J Med 348: 1786, 2003. 

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

EtOH intoxication

Ethanol is the one of the most commonly abused drug in the world. Mishaps generally happen due to secondary injuries after intoxication. We all see frequent attenders in ED who visit us almost every weekend and it is easy to miss underlying potentially life-threatening diseases if we fail to follow a systematic way to evaluate them.

Alcohol Metabolism

Ethanol is a CNS depressant that enhances the inhibitory neurotransmitter GABA receptors and blockade of excitatory NMDA receptors. Because of the phenomenon of tolerance, blood ethanol levels correlate poorly with degree of intoxication.  At low concentrations, ethanol metabolism follows first-order kinetics, but as concentrations rise, metabolism switches to zero-order kinetics i.e. a fixed amount is metabolised per unit of time. Rates of elimination from the blood vary between 20-30 milligrams/dL/h.

The legal limit to drive a vehicle varies in different countries. UK, Canada and the United States state 80 mg/dL as the legal definition of intoxication for the purposes of driving motor vehicles whereas in India, the limit is 30mg/dL. 

 Clinical Presentation

Lethargy, Drowsiness, Disinhibition, Euphoria, Agitation and Combativeness are classical clinical features. However, severe intoxication may present with slurred speech, nystagmus, ataxia, and decreased motor coordination and this can be hard to differentiate from Wernicke’s. Treat them with fluids if they are tachycardic (reflex tachycardia due to peripheral vasodilatation). Fever should prompt workup for sepsis and possible Delirium Tremens. Ethanol ingestion may also cause hypoglycemia, due to poor glycogen reserve, poor oral intake and reduced gluconeogenesis.

Potential Mimics and co-existing conditions

• Encephalopathy (Hepatic, Uremic, Septic)
• Hypoglycaemia
• Traumatic Brain Injury (Subdural)
• Stroke
• Seizure
• Wernickes
• Concomittant drug ingestions
• Dyselectrolytemia (HypoNa, HyperNa, HyperCa)
• Alcoholic Ketoacidosis
• Hypothermia
• DKA
• Myxoedema
• Psychosis
• Alcoholic Hepatitis and Pancreatitis

ED Management

Performing a detailed physical examination is paramount (Speech, Cranial Nerves, Gait, Nystagmus, GCS, Cerebellum, Evidence of trauma, Abdomen exam) to avoid missing co-existing conditions. Fill the gaps in your history via paramedics, by standers. Usually, uncomplicated intoxication improves within a few hours but if they don’t get sober or worsen then begin evaluation for other causes of altered mental status.

If history and exam are benign then investigations are of limited benefit. At least, obtain a bedside glucose level or a venous blood gas. Acute intoxication may be associated with mild metabolic acidosis, but a significant HAGMA suggests the presence of lactic acidosis, ketoacidosis, or methanol or ethylene glycol toxicity. Ethanol blood levels are not required unless there is a diagnostic dilemma but many prefer to do it anyways to ensure documentation. 

Most physicians agree that observation is the way to go until they are sober. Manage symptoms and beware of hypoglycemia. The classical teaching of Wernicke’s encephalopathy being precipitated by prolonged sustained administration of IV carbohydrate does not hold true and currently there is no evidence that a single dose of IV glucose can cause Wernicke’s.  Otherwise, majority of them do NOT need Pabrinex but administer if you suspect Wernicke’s. Additionally, bolus IV fluids do not help to attain sobriety any earlier. Metadoxine is used in some countries to enhance the metabolism of ethanol and accelerate recovery.

Take Home:

Simple ethanol intoxication needs ED observation until sober. Admit if they are suicidal, homicidal or psychotic. Always try and arrange appropriate transport for them and discharge in the care of a responsible companion.

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

Alcohol Related Ketoacidosis (AKA)

Alcoholic ketoacidosis is often associated with acute cessation of alcohol consumption after long term consumption. Few cases have been described in binge drinkers as well. It shows up as a high anion gap metabolic acidosis (HAGMA) on blood gas and is typically associated with nausea, vomiting, and GI complaints. Metabolism of alcohol combined with poor glycogen reserves results in elevated ketoacid levels. Death can occur from excessive ketonemia and thus treatment is focused on fluid and electrolytes management. βHB is the pre- dominant ketone product formed in AKA. 

Clinical Presentation

Classically presents with history of heavy drinking followed by vomiting and an acute decrease in alcohol consumption. Common symptoms are nausea, vomiting, and nonspecific abdominal pain. AKA can present with concomitant gastritis or pancreatitis, hypoglycemia, alcohol-withdrawal seizures, GI Bleed, Hepatitis, Sepsis or unrecognized head injury. 


Diagnosis (AKA is a diagnosis of exclusion)

• Low, normal, or slightly elevated serum glucose 
• Binge drinking ending in nausea, vomiting, and decreased intake 
• High anion gap metabolic acidosis
• Positive serum ketones
• Wide anion gap metabolic acidosis without alternate explanation

BHB Ketosis

Normally, the ratio of  Beta HB (beta hydroxybutyric acid) to acetoacetate to 1:1 but in alcoholic ketoacidosis, the ratio can go up to 7:1. Ketone production can be further stimulated in malnourished, vomiting patients. The nitroprusside reagent used to measure urine and serum ketones measures acetoacetate, acetone is only weakly reactive and βHB is not detected at all. Therefore, initial ketone levels may be low or negative in AKA. Mild lactic acidosis may be present due to a shift to pyruvate metabolism toward lactate

In AKA, the average ratio of beta hydroxybutyric acid to acetoacetic acid (5:1) tends to be higher than that which occurs in diabetic ketoacidosis (3:1). With initial therapy, ketone formation shifts toward the production of acetoacetic acid. Thus measured ketone levels rise with initial treatment, although β-OH levels decrease.

   

Differential Diagnosis

• Lactic Acidosis
• Toxic Alcohol Ingestion
• Sepsis
• DKA
• Renal Failure 
• Alcohol Withdrawal 

Treatment

• Dextrose Normal Saline is the initial fluid of choice (to correct hypoglycaemia and acidosis)
• Supplement Electrolytes (Mg, K
• Supplement Multivitamins  (Pabrinex)

• Acidosis usually settles with fluids and bicarbonate use is recommended if pH remains <7.0 despite fluid resuscitation 

Indications for admission

• Persisting Acidosis despite fluid resuscitation
• Unable to tolerate orally
• Other concerning concomitant diagnosis (GI Bleed, Sepsis, Pancreatitis etc)

Take Home

• AKA is diagnosis of exclusion. Rule out other causes of HAGMA (MUDPILES)
• Treatment is focused on Fluid and electrolyte management 

  
References:

1. McGuire, LC, Cruickshank AM, Munro PT: Alcoholic ketoacidosis. Emerg Med J 23: 417, 2006.
   
2. Wrenn KD, Slovis CM, Minion GE, Rutkowski R: The syndrome of alcoholic ketoaci- dosis. Am J Med 91: 119, 1991.
3. Iten PX, Meier M: Beta-hydroxybutyric acid: An indicator for an alcoholic ketoacidosis as cause of death in deceased alcohol abusers. J Forens Sci 45: 624, 2000.
   
   
   Posted by:
   
   
   
   

   

                 

        Lakshay Chanana

        

        Speciality Doctor

        Northwick Park Hospital

        Department of Emergency Medicine

        England

   
   

        @EMDidactic

   
   

Wernicke's Encephalopathy

Wernicke’s encephalopathy (WE) is a neuropsychiatric disorder which arises as a result of thiamine deficiency. In 80% of cases, the diagnosis is not made clinically prior to autopsy and inadequate treatment can leave the patient with permanent neurological sequelae and can possibly lead to Korsakoff syndrome. Therefore over-dignosis is preferred over under-diagnosis. Just like several other disease entities, Wernicke’s encephalopathy can be precipitated by other clinical diseases such as sepsis. 

Many physicians consider this only restricted to alcoholics which is not the case. Especially among non-alcoholics, the diagnosis is missed. 

WE is a result of thiamine deficiency, which can occur in ANY nutritionally deficient state. 

Classic Triad

The classic clinical triad of Wernicke’s encephalopathy consists of mental status changes, ophthalmoplegia, and gait ataxia. Complete triad is present only in about 10% cases. Other signs of disease such as hypothermia, vestibular dysfunction, and other ocular abnormalities can be present. Out of the eye signs, nystagmus is the most common ocular abnormality, not complete ophthalmoplegia. 

Reliance on the presence of the clinical triad as the sole criterion for disease is often inadequate and may lead to under diagnosis.

Risk Factors for WE:

• Alcohol Abuse (inadequate dietary intake, reduced GI absorption, and decreased hepatic storage)
• AIDS
• Malignancy
• Hyperemesis Gravidarum
• Post Surgical Patients
• Post Gastric Bypass

Thiamine Deficiency Syndromes

Why thiamine is so important?

Thiamine is a cofactor for several essential enzymes. Because thiamine-dependent enzymes play an important role in cerebral energy use, deficiency may initiate tissue injury by inhibiting metabolism in brain regions with high metabolic requirements. A decrease in their activity may lead to increased buildup of toxic intermediates. Lactate accumulation occurs both in the brain and serum because pyruvate cannot enter the Krebs cycle. 

Malnutrition + elevated lactate - Think thiamine deficiency

CNS lesions

The lesions of Wernicke’s encephalopathy occur in a symmetrical distribution in structures surrounding the third ventricle, aqueduct, and fourth ventricle. MRI is the imaging of choice. The mammillary bodies are involved in up to 80% of cases; atrophy of these structures is specific for Wernicke’s encephalopathy. However, empiric treatment is a norm in ED. 

Korsakoff Syndrome
Korsakoff syndrome refers to a persistent state of mental dysfunction characterized by memory impairment associated with confabulation. 

Differential Diagnosis

• Intracranial Hemmorhage
• Stroke
• Cerebral Venous Thrombosis
• Delirium Tremens
• Hepatic Encephalopathy
• Intracranial Space Occupying Lesions
• Cerebellar Disease
• Meningitis
• Marchiafava-Bignami disease (demyelination of the corpus callous due to nutritional deficiencies)

Treatment

Low suspicion of disease - a minimum of 100 mg IV
Highly suspected disease - 500 mg IV

Administration of thiamine improves disease to some degree in almost all cases; however, persistent neurologic dysfunction is common. 

All patients presumed to have Wernicke’s Encephalopathy or at risk of developing Wernicke’s Encephalopathy should receive two pairs* of vials of Pabrinex in 100 ml of crystalloid i.v. over 30 minutes initially in A&E.

*(1 pair = ampoule 1 + ampoule 2). Pabrinex is available as 5ml or 10ml pairs of ampoules. 

IV thrice daily dosing is generally continued for 3-5 days for an established diagnosis and then oral Thiamine 100mg OD is continued for a month. On extremely rare occasions, Thiamine may cause allergic reactions and anaphylaxis. 

Glucose before thiamine Myth!

Iatrogenic exacerbation of Wernicke’s encephalopathy can occur with prolonged glucose or carbohydrate loading in the absence of adequate thiamine. A single acute administration of glucose does not appear to cause this effect. Urgent administration of glucose should not be withheld pending thiamine administration. 


IV Fluids to sober them up?
There is no evidence that intravenous fluids expedite sobriety in patients with acute alcohol intoxication. Read more on REBELEM and St.Emlyn's. 


References:

1. Reuler JB, Girard DE, Cooney TG. Current concepts. Wernicke’s encephalopathy. N Engl J Med. 1985;312:1035-1039.
2. Watson AJ, Walker JF, Tomkin GH, et al. Acute Wernicke’s encephalopathy precipitated by glucose loading. Ir J Med Sci. 1981;150:301-303.
3. Zimitat C, Nixon PF. Glucose loading precipitates acute encephalopathy in thiamin-deficient rats. Metab Brain Dis. 1999; 14:1-20.
4. Zimitat C, Nixon PF. Glucose induced IEG expression in the thiamin-deficient rat brain. Brain Res. 2001;892:218-227. 59. Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA. 1998;279:583-584. 
5. https://www.medicines.org.uk/emc/medicine/6571
6. Donnino MW, Vega J, Miller J, Walsh M. Myths and misconceptions of Wernicke’s encephalopathy: what every emergency physician should know. Annals of emergency medicine. 2007 Dec 31;50(6):715-21.

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic