If patients abruptly stop drinking alcohol after prolonged use, they may display symptoms of acute alcohol withdrawal.
Calculating Alcohol Units
One unit of alcohol is 8g or 10ml of pure alcohol. Alcoholic units can be calculated by:
Strength (ABV) x Volume (ml)/1000
The ABV is the alcohol by volume – a measure which is typically found on the labels of alcoholic drinks denoting the strength. An ABV of 8% means the volume of that drink contains 8% of pure alcohol.
If we say a glass of wine has an ABV of 13%, and you’re going to drink a 175ml glass;
13 x 175/1000 = 2275/1000 = 2.275 units of alcohol
As per NICE guidelines, patients (both male and female) are advised to drink a maximum of 14 units of alcohol a week, ideally spread out over at least 3 days. Additionally, women who are pregnant or trying to get pregnant are recommended to not drink alcohol.
Identifying Alcohol Dependence
This can be easily remembered by the mnemonic ‘CANT STOP’, which is as follow:
- Compulsion to drink alcohol
- Aware of physical harms but persist
- Neglect other activities
- Tolerant to alcohol
- Stopping leads to withdrawal
- Time preoccupied with alcohol is increased
- Out of control use
- Persistent wish to cut down
Pathophysiology
- When you start working in hospital, it’s always really important to take a social history – if a patient has been drinking excessive amounts of alcohol prior to admission, and they suddenly stop, they could go into alcohol withdrawal.
- There are two neurotransmitters and neuroreceptors you need to know about.
- GABA-A receptor: Binds GABA, a major inhibitory neurotransmitter
- NMDA receptor: Binds glutamate, an excitatory neurotransmitter
- Alcohol has two main effects at these receptors/with these neurotransmitters.
- It stimulates the GABA receptor (inhibitory mechanism)
- It inhibits the NMDA receptor (excitatory mechanism)
- As a compensatory mechanism, the CNS downregulates expression of GABA receptors and upregulates the expression of NMDA receptors, and produces additional glutamate to be able to bind to NMDA receptors.
- If alcohol is suddenly withdrawn, you suddenly have a lot of glutamate floating around without the alcohol around to bind to NMDA receptors, resulting in brain hyperexcitability.
- This manifests in the clinical features of alcohol withdrawal.
Clinical Features
- 6-12 hours since last drink
- Sweating
- Headache
- Anxiety
- Tremor
- Nausea/vomiting
- Palpitations
- 12-24 hours since last drink
- Alcoholic Hallucinosis: Hallucinations (auditory, visual, tactile), nightmares, and/or illusions but no delirium. The patient is aware their hallucinations are false perceptions.
- Withdrawal seizures: Usually tonic-clonic seizures
- 48 to 72 hours since last drink
- Delirium tremens: A triad of visual/auditory hallucinations, coarse tremor, and delirium (confusion)
- Tachycardia
- Hypertension
- Hyperthermia
Wernicke’s Encephalopathy
- Thiamine (vitamin B1) is required by the body, particularly in the Krebs cycle.
- Thiamine is not endogenously produced and is acquired via diet/supplements. It is absorbed in the duodenum.
- It is thought alcohol excess disrupts thiamine absorption from the duodenum. Additionally, patients who abuse alcohol may be malnourished, and thus do not acquire sufficient thiamine from diet.
- A lack of thiamine is problematic in multiple ways
- It’s involvement in the Krebs cycle results in reduced ATP production which can result in cell death
- It can also result in increased free radicals and oxidative stress
- All of this results in damage to the brain. Acutely, petechial haemorrhages can be seen of the mamillary bodies, and areas surrounding the third and fourth ventricles.
- Remember, it isn’t just alcohol that can cause WE – anything that might result in a thiamine deficiency can. Conditions such as the following can therefore cause it too:
- Hyperemesis gravidarum
- Hyperthyroidism: Due to increased thiamine metabolism
- Starvation
Clinical Features
- Wernicke’s encephalopathy in textbooks presents as a triad of confusion, ataxia and ophthalmoplegia.
- In reality however, patients can present with various features including drowsiness, nystagmus, diplopia and more.
- The onset of WE is a medical emergency, and should be treated promptly with thiamine to prevent progression to Korsakoff syndrome.
Korsakoff Syndrome
Korsakoff Syndrome is a condition that occurs due to untreated Wernicke’s encephalopathy. It presents with the following features:
- Retrograde amnesia: Inability to remember previous events
- Anterograde amnesia: Inability to form new memories
- Confabulation: Patients will fill gaps in their own knowledge/memories by making things up – they are unaware that what they’re doing is not true and will genuinely believe in their own thoughts
Investigations
Bedside
- History and examination: Alcohol history
- ECG: You can get a prolonged QT syndrome in alcohol exces
Bloods
- LFT: Raised AST, ALT, gGT, or bilirubin may suggest history of alcohol excess
- Serum alcohol
- FBC: ?Macrocytic anaemia
- U&E: ?Hepatorenal syndrome from chronic alcohol abuse
- Clotting screen: ?Reduced synthetic function
Imaging
- CT Head: Particularly if the patient has new onset confusion/seizures to rule out a bleed or space occupying lesion
Management
- Clinical Institute Withdrawal Assessment for Alcohol (CIWA)
- The CIWA score is a scoring system to measure the withdrawal severity and helps guide management
- <10: Milder CIWA – will require lower doses of benzodiazepines e.g. 20mg PRN
- 11-15: Moderate CIWA - will require moderate doses of benzodiazepines e.g. 30mg PRN
- >15: High risk score - close monitoring and will need aggressive management - will require higher doses of benzodiazepines e.g. 40mg PRN
- Benzodiazepines
- GABA-A is the inhibitory neurotransmitter of the CNS, and its effects are lost secondary to alcohol.
- Benzodiazepines can act as GABA-A agonists to reinstate this inhibition on the CNS and help with the overexcitation of the brain that happens in alcohol withdrawal.
- In the UK, chlordiazepoxide, a long acting benzodiazepine, is the usual drug of choice. Other options include diazepam or lorazepam.
- This is given as either a reducing-dose regimen e.g. X mg QDS which reduces over a few days, alongside PRN top-up doses.
- It is important to watch out for over-sedation and respiratory depression in these patients as benzodiazepines can induce both of these things.
- Thiamine Replacement
- Patients will often have thiamine deficiencies due to poor nutritional intake.
- IV Pabrinex is a common choice for thiamine replacement in the UK.
- The main component is thiamine because it’s the thiamine administration that will help to prevent the development of Wernicke’s encephalopathy. IV Pabrinex carries a small risk of anaphylaxis. If this cannot be used, oral thiamine and vitamin B co-strong is usually given instead.
- Pabrinex contains various things including:
- Thiamine (Vitamin B1)
- Riboflavin (Vitamin B2)
- Nicotinamide (Vitamin B3)
- Pyridoxine Hydrochloride (Vitamin B6)
- Ascorbic Acid (Vitamin C)
- Drugs to Encourage Abstinence
- Acamprosate: Can help to reduce drinking frequency
- Naltrexone: Prevents relapses and reduces frequency of drinking
- Disulfiram: Reacts with alcohol to cause unpleasant effects to discourage drinking – it does not, however, reduce cravings
References
https://www.candi.nhs.uk/sites/default/files/Pabrinex%20Prescribing%20Protocol_PHA55_%20Mar%202020.pdf
Kumar and Clark’s
https://www.elsevier.com/__data/assets/pdf_file/0016/1010275/Alcohol-withdrawal_CO_140918.pdf
https://patient.info/doctor/acute-alcohol-withdrawal-and-delirium-tremens#nav-1
https://www.aafp.org/pubs/afp/issues/2004/0315/p1443.html
https://www.pathologyoutlines.com/topic/cnswernickekorsakoff.html
https://link.springer.com/article/10.1007/s11604-020-00989-3#Sec5
https://cks.nice.org.uk/topics/alcohol-problem-drinking/diagnosis/how-to-screen/#symptoms-of-alcohol-withdrawal
