Alcohol Withdrawal and CIWA-Ar

1. Benzodiazepine Regimens

2. Agent Choice, Doses and Preparations

3. Thiamine

4. Delirium Tremens and Refractory Withdrawal

5. Relapse Prevention Pharmacotherapy

1. Why Withdrawal Happens, and Why It Worsens Each Time

Alcohol is a positive allosteric modulator at the GABA-A receptor and an antagonist at the NMDA glutamate receptor. Sustained exposure downregulates GABA-A receptors and shifts their subunit composition while upregulating NMDA receptors, so taking the alcohol away leaves the adapted brain with too little inhibition and too much excitation at the same time. That is why benzodiazepines work: they act at the receptor the alcohol was acting on, and nothing that does not act there can substitute for them. It is also why withdrawal kindles, each successive untreated episode more severe than the last, which makes a history of previous withdrawal the single most useful predictive question you can ask.

2. The Timeline Is the Most Useful Thing to Know

• A patient who becomes confused 12 hours after the last drink does not have delirium tremens. The diagnosis to pursue is hepatic encephalopathy, sepsis, hypoglycaemia or a subdural haematoma.
• A patient who is entirely well at 24 hours is not yet out of the window for delirium.

3. CIWA-Ar Measures What Is Happening, PAWSS Predicts What Will Happen

The two are routinely conflated and they answer different questions. CIWA-Ar is a severity instrument for a patient who is already withdrawing, and it drives dosing. PAWSS is scored on admission, before withdrawal has declared itself, and it drives placement and prophylaxis.

• The patient who most needs PAWSS is the one admitted for something else entirely, a fractured femur or a chest infection, who looks well on day one and convulses on day two.
• Ask every admitted patient the four questions that carry most of the predictive weight: have you had withdrawal before, have you ever had a fit when stopping, have you ever had the DTs, and when was your last drink.

4. Symptom-Triggered Dosing, and Where the Score Stops Working

Randomised comparisons have consistently shown that symptom-triggered dosing reduces cumulative benzodiazepine by roughly threefold to fourfold and shortens treatment duration, without an increase in seizures or delirium. That result depends entirely on the scoring being done properly and hourly by a nurse trained in the instrument.

• Where the score is copied forward from the previous shift, or performed once a day, symptom-triggered dosing becomes no dosing, and the patient who deteriorates does so unobserved.
• Indian context. Nursing ratios on general medical wards in most Indian teaching hospitals do not permit hourly scoring of every patient in withdrawal. That is a reason to be honest about which wards can support it and to use a fixed-dose taper on the others, not a reason to avoid the strategy.
• Six of the ten CIWA-Ar items require the patient to report a subjective symptom: nausea, anxiety, tactile, auditory and visual disturbances, and headache. A delirious patient cannot report these reliably, an intubated patient cannot report them at all, and a patient who does not share a language with the nurse scoring them will be scored low regardless of how unwell they are.
• Every item that cannot be obtained defaults to zero, so the score reassures falsely in exactly the patients who are sickest. Once delirium has set in, stop scoring CIWA-Ar and titrate against sedation level and autonomic signs.

5. Phenytoin Does Not Treat Alcohol Withdrawal Seizures

Withdrawal seizures arise from a transient receptor imbalance rather than from an epileptic focus, and randomised trials of phenytoin for their prevention and for the prevention of recurrence have been negative. Benzodiazepines are both the treatment and the prophylaxis, and intravenous lorazepam has been shown to reduce recurrence after a first withdrawal seizure.

• A patient already on phenytoin for established epilepsy continues it, and a first-ever seizure still needs proper evaluation.
• Focal onset, a prolonged postictal state, head injury, fever, or a seizure occurring outside the 6 to 48 hour window all argue against a simple withdrawal seizure and warrant imaging, glucose, sodium and consideration of meningitis. See the Seizure Pathway.

6. Thiamine, Magnesium and Glucose, in That Order

The classic triad of confusion, ataxia and ophthalmoplegia is present together in only about 10 to 16 per cent of Wernicke encephalopathy at presentation, and post-mortem series have consistently found the disease undiagnosed in life. Do not wait for it.

• The Caine criteria are the practical bedside standard and are far more sensitive: two of dietary deficiency, oculomotor abnormality, cerebellar signs, and either altered mental state or mild memory impairment.
• Thiamine is inexpensive, essentially non-toxic, and the damage it prevents is irreversible once established. Any patient with alcohol dependence and any degree of confusion receives parenteral thiamine while the question is being settled, not after.
• Why glucose alone is dangerous. Thiamine pyrophosphate is the cofactor for transketolase, pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase. A glucose load in a thiamine-deplete patient drives these enzymes and can exhaust the remaining thiamine, which is how a well-intentioned dextrose infusion precipitates Wernicke encephalopathy.
• Why magnesium comes next. All three enzymes also require magnesium, so thiamine repletion can fail entirely while the serum magnesium is low, and hypomagnesaemia is close to universal in chronic alcohol use because of renal magnesium wasting.
• The sequence is thiamine, then magnesium, then glucose. The exception is the hypoglycaemic patient, in whom glucose goes in at once and thiamine immediately afterwards: hypoglycaemia will cause harm within minutes and the theoretical risk does not outrank it.

7. What Else Presents as Delirium Tremens

Delirium tremens is a diagnosis of exclusion in a population with an unusually high burden of the things it is confused with. The patient whose confusion does not improve with adequate benzodiazepine does not have delirium tremens, or does not have only delirium tremens.

• Hepatic encephalopathy, which shares the confusion and is worsened by the benzodiazepines that treat withdrawal. Asterixis and a search for precipitants are worth the two minutes they take.
• Subdural haematoma, common in patients who fall and who may be coagulopathic, and able to present days later with fluctuating confusion.
• Sepsis. Fever is not a feature of uncomplicated withdrawal, so a temperature above 100.4 F should send you looking for pneumonia or spontaneous bacterial peritonitis rather than being attributed to the withdrawal.
• Hypoglycaemia and hyponatraemia.
• Alcoholic ketoacidosis: heavy drinking, then stopping because of vomiting and abdominal pain, with a high anion gap metabolic acidosis, ketonuria and a glucose that is normal or low. It responds to thiamine followed by glucose-containing saline and does not require insulin.
• Methanol poisoning, the more urgent one in the Indian setting: a cluster of patients who drank country liquor or hooch, with visual disturbance, a severe high anion gap acidosis and an elevated osmolar gap. It needs fomepizole or ethanol and haemodialysis, and it is not withdrawal at all. The ABG Diagnostic Pathway will characterise the acidosis, but no module in this catalogue calculates the osmolar gap or holds antidote dosing.

8. Choosing the Benzodiazepine Is a Question About Metabolism

Chlordiazepoxide and diazepam undergo oxidative metabolism in the liver and generate long-lived active metabolites, principally desmethyldiazepam. That accumulation is exactly what gives them their smooth self-taper in a patient with normal hepatic function, and exactly what makes them dangerous in decompensated cirrhosis and in the elderly, where it produces prolonged sedation and can precipitate encephalopathy.

• Lorazepam, oxazepam and temazepam are conjugated directly by glucuronidation, a pathway comparatively preserved in liver disease, and have no active metabolites.
• The memory aid is the three agents whose names supply the letters L, O and T. In significant liver disease, in the elderly, and where respiratory reserve is limited, choose from those three and accept that you will need to dose more often.

9. Detoxification Without Relapse Prevention Is an Incomplete Admission

Most patients who are detoxified and discharged without pharmacotherapy relapse quickly, and the readmission is often more severe than the admission because of kindling. The decision belongs before discharge, not at a first follow-up visit that many patients never attend.

• Naltrexone has the best evidence for reducing heavy drinking, and can be started while the patient is still drinking.
• Acamprosate supports abstinence once it has been achieved, and is the choice in cirrhosis because it is cleared renally rather than hepatically.
• Disulfiram works by deterrence, so it works only when somebody else gives the tablet. Supervised disulfiram given by a family member has performed well in Indian pragmatic trials, for structural rather than pharmacological reasons. Where a spouse or parent is willing to give the tablet daily and the household is cooperative, the supervision the drug depends on is actually available. Use it deliberately rather than as an afterthought.

10. What This Pathway Does Not Decide

• Withdrawal in pregnancy, where untreated withdrawal is more dangerous to the pregnancy than benzodiazepine exposure but the decision belongs with an obstetrician.
• Patients below 18 years.
• Established Korsakoff syndrome and the rehabilitation that follows it.
• Psychiatric assessment of the comorbid depression, anxiety and suicide risk that accompany alcohol dependence at high frequency.
• The diagnosis itself. A patient who is confused and has been drinking is not necessarily in withdrawal, and section 7 lists what else to rule out before committing to that label.