Acute Alcohol Withdrawal and Alcoholic Hepatitis

Acute alcohol withdrawal and alcoholic hepatitis are common scenarios presenting to the Emergency Department (ED) and the ward. Recognition, investigation and management principles are imperative to prevent serious complications.

Dr Liz Sweeney is a specialist hepatology registrar at the Royal Liverpool Hospital. In this episode, she talks to us about acute alcohol withdrawal and alcoholic hepatitis with key advice to junior doctors working in hospitals.

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Slide1

Ms KL is a 45 year old lady who is brought to the ED with sweating, shaking and vomiting following a 3 weeks of heavy alcohol intake. She has a background of type 2 diabetes and hypertension.

How would you manage this patient?

Any acutely unwell patient should be assessed with a structured A-E approach:

Airway

Breathing

Circulation

Disability

Exposure

Ms KL’s observations are:

  • HR 120
  • BP 125/80
  • Temperature 37 degrees
  • RR 22
  • SpO2 95% on room air

As you stabilise the patient by dealing with problems identified with the A-E approach, you can begin gathering more information through a history and more in-detail physical examination.

This is a classic presentation of Acute Alcohol Withdrawal and prompt management is vital to prevent serious complications as seizures and arrhythmias.

Acute alcohol withdrawal is caused by an abrupt cessation of alcohol consumption in patients with alcohol dependence or chronic alcoholism. Acute alcohol withdrawal should be viewed as a spectrum disorders rather than a single entity.

Screening questions should be used during you history taking for any patient. Any patient with significant alcohol use presenting for non-alcohol related reasons is at risk of withdrawal during their admission.

DSM IV diagnostic criteria1 for Acute Alcohol Withdrawal (AAW):

Definition of AAW:

  1. Cessation of (or reduction in) alcohol intake which has previously been prolonged/heavy

Two (or more) of the following, developing within several hours to a few days after criterion A:

  1. Autonomic hyperactivity (e.g. sweating/ HR >100)
  2. Increased hand tremor
  3. Insomnia
  4. Nausea or vomiting
  5. Transient visual, tactile, or auditory hallucinations or illusion
  6. Pyschomotor agitation
  7. Anxiety
  8. Grand mal seizures
  9. The symptoms in criterion B cause clinically significant distress or impairment in social, occupation or other important areas of functioning
  10. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder

Symptoms typically start to appear after 8 hours following a preciptous fall in serum ethanol levels which alters cerebral neuronal homeostasis. Levels fall significantly by day 2, resulting in maximum symptoms that should begin to resolve by day 4-5 with prompt management2.

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The spectrum of AAW can be divided into four parts:

  1. Acute withdrawal (6-12 hours after alcohol ingestion): minor symptoms of insomnia, tremor, headache, sweating, nausea and vomiting
  2. Alcoholic hallucinosis (12-24 hours post alcohol ingestion): visual, tactile and auditory hallucinations
  3. Withdrawal seizures (24-48 hours post alcohol ingestion): generalised tonic-clonic seizures often self resolving
  4. Delerium tremens (48-72 hours post alcohol ingestion): hyperadrenergic state with severe tachycardia, confusion and hallucinations

The Clinical Institute Withdrawal Assessment for Alcohol scale, revised version (CIWA-Ar)3 is helpful quantifying patient groups as mild (<8), moderate (8-15), and severe (>15). This assessment can aid diagnostic severity in ED, however does not alter the acute management principles. Studies have shown that use of the scale in management of alcohol withdrawal leads to decreased frequency of over-sedation with benzodiazepines in patients with milder alcohol withdrawal than would otherwise be detected without use of the scale, and decreased frequency of under-treatment in patients with greater severity of withdrawal than would otherwise be determined without the scale.4

The-CIWA-Ar

pathology alcohol

The underlying pathophysiology of Acute Alcohol Withdrawal is complex5

In brief:

Alcohol acts as a CNS depressant via its action on GABA receptors within the brain. Long term abuse of alcohol causes inhibitory GABA receptor down-regulation and excitatory NMDA up-regulation to achieve and maintain neurotransmitter homeostasis. When acute cessation in alcohol occurs there is over expression of excitatory neuronal activity (via NMDA receptors) and reduced inhibitory neuronal activity (via GABA receptors). This causes increased glutamatergic action with consequent hyper-excitability and development of acute alcohol withdrawal symptoms.

Screen Shot 2018-09-18 at 14.56.22

investigations

Key investigations:

Full Blood Count (FBC) – thrombocytponenia suggests potential cirrhosis due to splenic sequestration as a consequence of portal hypertension and also reduced liver production of thrombopoietin (TPO). A MACROcytosis occurs in chronic alcoholism. Raised White Cell Count (WCC) may suggest infection (but can occur due to other reasons)

Urea & Electrolytes/Renal profile (U&Es) – most importantly, patients with AAW can have dangerously derranged electrolytes. LOW Sodium, Potassium, Chloride, Magnesium and Calcium occur. Urea levels are frequently LOW (chronic malnutrition from reduced protein ingestion). ALWAYS request magnesium because patients can display a refeeding-like clinical picture and therefore replacement is essential.

Calcium profile – Calcium and phosphate levels will often coincide with other electrolytes and be low

Glucose – IMPORTANT! Chronic alcoholism leads to reduced glycogen stores and alcohol impairs glucogenesis. Hypoglycaemia is common!

Liver Function Tests (LFTs) – often in AAW there is an elevated GGT/alk phos. Most importantly assess the Bilirubin, with raised levels potentially indicating alcoholic hepatitis which caries a significantly worse mortality and requires prompt treatment.

Clotting profile – derranged clotting with prolonged prothrombin time and activated partial thromboplastin time (APTT) can indicate acute liver damage and impaired synthetic function of the liver.

**Handy mneumonic:

Liver synthetic function markers = ABC (albumin, bilirubin, clotting) J**

ECG – assess the QTc interval because deranged electrolytes predispose to life threatening arrhythmias. Remember: female patients QTc > 470 and male patients QTc >450 should be on continuous ECG monitoring or telemetry. Always discuss with your senior first

Ultrasound Liver: Up to date imaging of the liver should be sought e.g. USS liver/fibroscan to indicate whether cirrhotic changes are present.

CT head – this depends on the clinical presentation. If patients have described a fall or are acutely confused with no coherent history, an acute CT head may be required. Chronic alcoholism causes thrombocytopenia, prolonged prothrombin time and cerebral atrophy which all place patients at greater risk of bleeding from a low impact head trauma. Research has shown that chronic alcoholism is associated with greater increased risk of subdural haematomas after blunt head trauma6

beer management

Acute management relies on the principle of preventing serious complications e.g. seizures. Always admit patients with high risk features such as failed home detox, <18yrs, seizures, autonomic hyperactivity or concerns about home situations (always safer to admit rather than discharge patients). Those you do wish to discharge should be discussed with your seniors and the alcohol specialist nurse.

The mainstay of treatment is a reducing regime of benzodiazepines. Commonly used benzodiazapines include chlordiazapoxide (librium), diazepam or lorazepam. These are either given as a fixed reduxing regime or as per regular CIWA-AR assessments. Always ensure as required doses are prescribed should agitation develop prior to the next dose or overnight.

Screen Shot 2018-09-18 at 12.37.29

Screen Shot 2018-09-18 at 15.04.16

Intravenous thiamine in the form of Pabrinex as 2 pairs (I+II) three times a day (TDS) should be given to anyone with alcohol dependence. If they have a cannula, give them IV thiamine, even if they are on oral replacement. Chronic alcoholism leads to thiamine deficiency by three factors:

  1. Poor dietary intake
  2. Gastritis impairs absorption
  3. Thiamine consumed as a co-enzyme in alcohol metabolism

High dose Pabrinex is vital for prevention of serious complications including: Wernickes encephalopathy and Korsakoffs syndrome due to severe thiamine deficiency. Patients may require prolonged detox with 5 days of IV replacement.

Involvement of MDT members is vital and you should refer as able to alcohol specialist nurses and dieticians.

Delirium Tremens (DTs) is a severe form of alcohol withdrawal with a hyperadrenergic state representing a medical emergency. It often develops 24-72hrs after alcohol consumption with altered mental state and confusion, hallucinations/delusions and profound autonomic changes such as tachycardia and pyrexia. Acutely, you need to follow an A-E approach and use high dose benzodiazepines, sometimes patients may require enormous doses so do not be afraid of escalating quickly. IM sedation may be appropriate in severe cases with anti-psychotics such as haloperidol.

It is important to note that the mortality rate can be up to 35% if untreated but is less than 2% with early recognition and treatment7. Therefore, if you cannot get on top of the autonomic changes or agitation, the patient may require Critical Care for further management.

Escalate to your seniors and critical care early

Wernickes encephalopathy= often REVERSIBLE triad of confusion, ataxia and ophthalmoplegia. (n.b. <10% of patients present with all the triad features but useful to consider diagnosis with the presence of any single symptom listed)8

Korsakoffs syndrome= IRREVERSIBLE syndrome sequela of wernickes encephalopathy consisting of anterograde and retrograde amnesia, confabulation (fabricate imaginary experiences compensating for loss of memory).

alcoholic hepatitis

Alcoholic hepatitis accounts for 3.3 million deaths worldwide and reports show an average mortality of 6.7% with acute alcoholic hepatitis, rising significantly with increased severity9. It is characterised by acute inflammation of the liver due to excessive recent alcohol intake concomitant with COAGULOPATHY and JAUNDICE.

The approach to these patients for assessment and investigations follows the same format as for alcohol withdrawal and these patients may present with both together. Use a structured A-E approach for the acutely unwell patient and investigate based upon clinical picture with the investigations discussed previously.

Up to date imaging via ultrasound of the liver can assess the liver parenchyma to indicate early cirrhotic changes, evidence of ascites and portal vein flow (n.b. patency is important to exclude thrombosis).

Early referral to specialist Hepatologist is imperative in diagnosis and early management in these complex patients.

hep management

Always manage these patients with the same principles of AAW e.g. Pabrinex and reducing regime of chlordiazepoxide. Due to high mortality and immunosuppressive state, these patients are prone to infection and a full septic screen is important including: urine dip and culture, chest X-ray, blood cultures AND an ascitic tap with commencement of prophylactic broad spectrum antibiotics e.g. IV tazocin +/- antifungal e.g. fluconazole 100mg OD. The exact agents used will be guided by your local policies.

N-acetylcysteine (NAC) (100mg/kg in 1000ml 5% glucose, 16 hourly for 5 days) and IV Vitamin K (10mg) can be used when there is significant coagulopathy indicating acute liver damage. Early involvement of the dietician is imperative for maximizing patient care with regular ensures or nasogastric feeding which has been shown to reduce patient mortality and improve clinical outcomes10. Steroids e.g. 40mg Prednisolone can be given in severe cases where acute infection has been excluded- but ALWAYS discuss with a specialist prior to commencing any steroid.

Scoring systems are often used in alcoholic hepatitis to predict mortality and whether steroids would be beneficial. They use variables such as age, WCC, bilirubin level, PT level.

  1. Maddrey’s discriminant function (MDF) score of 32 or above can indicate severe disease and patient may benefit from steroids
  2. Glasgow score of alcoholic hepatitis– score of 9 or above indicates severe disease and patient may benefit from steroids

Severe alcoholic hepatitis (MDF score >32) is associated with a one month mortality of 30%11!! Infectious complications occur in approximately 50% of patients and are the MAIN cause of death in these patients11. Research has shown that cirrhosis-associated immune dysfunction (CAID) is responsible for the state of immunodeficiency and in conjunction with persistent activation of the immune system, places patients at increased risk of infections.

Whilst treatment regimes for alcoholic hepatitis still remains debated, corticosteroids are widely used with evidence showing a 14% reduction in 1-month mortality for severe cases11. Nevertheless, it is important to exclude concurrent infection in acute cases since initiating steroid regime will further potentiate immune dysregulation and place patients at increased risk of infections. Ultimately, you should also seek expert opinions prior from specialist Hepatologists prior to initiating steroids in this cohort of patients.

ascitic tap
Indications: any ACUTE ascites confirmed by clinical examination/USS.
Contraindications: relative contraindications are severe coagulopathy (INR >2) or thrombocytopenia <20. However the procedure can still be performed, with care taken to achieve haemostasis and should be performed by a senior clinician. If patients are acutely bleeding e.g. from Upper GI bleed/elsewhere it may be prudent to halt the procedure until FFP/Vit K/platelets are given.

Steps:

  1. Gain consent from patient for procedure
  2. Mark area of dullness (either LIF or RIF) depending on evidence of hepato vs splenomegaly and area of greatest clinical ascites
  3. Wash hands, apply sterile gloves and clean area with chlorhexidine sponge in a circular motion inside->out
  4. Insert green needle (21G) perpendicular to skin edge at area marked aspirating every time the needle is advanced
  5. Keep aspirating then advancing needle until ascitic fluid is aspirated and aspirate 10-20mls of fluid
  6. Withdraw needle, apply dressing to area and thank the patient
  7. Send fluid for MC&S, inoculate blood culture bottles (anaerobic and aerobic) and also send for: bilirubin, protein, glucose, cytology.

Screen Shot 2018-09-18 at 15.22.29

Analysis

WCC >250 and >50% polymophs are indicative of sponateous bacterial peritonitis (SBP) and IV antibiotics e.g. Tazocin should be commenced immediately (often commenced empirically after the ascitic tap whilst awaiting for the results)

Serum-ascites albumin gradient: helps to determine whether ascitic fluid is transudate or exudate >11=transudate, <11=exudate

*transudative causes: cirrhosis, hepatic failure, cardiac failure, liver metastasis, alcoholic hepatitis.

*exudative causes: malignancy, infection, pancreatitis, nephrotic syndrome, bowel infarction, bile leakage.

As ever, please take a look at some of the evidence for yourself and discuss with those around you if considering a change to your practice rather than taking our word for it.

Please see comprehensive reviews and learning tools for additional reading: acute alcohol withdrawal5,alcoholic hepatitis12 and a guide for junior doctors13

take home points

Acute Alcohol Withdrawal is relatively common and ranges from mild to severe including Delerium Tremens which carries a high mortality. It is managed by following an A-E approach with benzodiazapines and thiamine supplementation as the mainstay of therapy. These patients need prudent investigations screening for complications guided by the clinical picture.

Alcoholic hepatitis can carry a high mortality and needs careful managment, often with the same treatment as acute withdrawal. Complications such as spontaneous bacterial peritonitis need excluding as soon as possible because these patients are extremely high risk for infection. Referral to specialist gastroenterology or hepatology services is essential in managment.

Any patient presenting with features suggestive of alcohol misus or chronic dependence should be referred to alcohol specailist services. Taking a complete alcohol history in every patient can identify these patients before the begin withdrawing.

Speak soon,

Ollie Wright

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References

  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5thArlington: American Psychiatric Association; 2013.
  2. Dillard R, Welch T, Abdul-Hamed S, et al. Ethanol infusion for alcohol withdrawal prophylaxis does not cause intoxication. SWRCCC 2016; 4(16): 11-18.
  3. Sullivan JT, Sykora K, Schneiderman J et al, Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar)”. British Journal of Addiction. 1989; 84 (11): 1353–7.
  4. Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 278 (2): 144–51.
  5. Mirijello A, D’Angelo C, Ferrulli A, et al. Identification and management of alcohol withdrawal syndrome. 2015; 75 (4): 353-365.
  6. Sim YW, Min KS, Lee MS, et al; Recent changes in risk factors of chronic subdural hematoma. J Korean Neurosurg Soc. 2012 Sep52(3):234-9.
  7. Ignjatovic-Ristic D, Rancid N, Novokmet S, et al; Risk factors for lethal outcome in patients with delirium tremens – psychiatrist’s perspective: a nested case-control study. Ann Gen Psychiatry. 2013 Dec 212(1):39.
  8. Donnino MW, Vega J, Miller J, et al. Myths and misconceptions of Wernicke’s encephalopathy: what every emergency physician should know. Ann Emerg Med. 2007; 50(6): 715-21.
  9. Liangpunsakul S. Clinical characteristics and mortality of hospitalized alcoholic hepatitis patients in the United States. J Clin Gastroenterol. 2011;45(8):714–719.
  10. Griffith CM, S Schenker. The role of nutrional therapy in alcoholic liver disease. Alcohol Research, 2006. 29(4) 296-306.
  11. Karakike E, Moreno C, Gustot T. Infections in severe alcoholic hepatitis. Ann Gastroenterol. 2016; 30(2) 152-160.
  12. Parker R and McCune CA. Diagnosis and treatment of alcoholic hepatitis. Gastroenterology 2013; 0: 1-7.
  13. Smith PJ and Sweeney E. Gastroenterology Handbook: A guide for Junior Doctors based on the ward. BSG guidance 2015.p1-32.

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