NAC Dosing Calculator for Paracetamol Poisoning
Compute weight-based intravenous N-acetylcysteine regimens for paracetamol poisoning: the traditional three-bag Prescott protocol and the modified two-bag protocol, with each bag's dose, diluent volume, and infusion rate. Use the calculator above, then read the guide below to interpret your result and its limitations.
This NAC dosing calculator gives the intravenous N-acetylcysteine regimen by weight. Enter the body weight and choose the traditional three-bag Prescott protocol (150 mg/kg over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours) or the modified two-bag protocol (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours), and you get each bag's dose in mg, the diluent volume, the infusion rate, and the total dose. Paracetamol overdose is the commonest cause of acute liver failure in the UK, and NAC is the treatment that prevents it, but only if the dose is right and the infusion actually runs. This is hospital treatment: the calculator supports the prescribing team, it does not replace toxicology guidance.
Calculate the IV NAC regimen
Why NAC saves livers
Paracetamol is safe at therapeutic doses because the liver clears it through harmless pathways: glucuronidation and sulfation. A small fraction, about 5 to 10 percent, goes through CYP2E1 to form NAPQI, a toxic metabolite that is instantly mopped up by glutathione. In overdose the safe pathways saturate, more drug is forced down the CYP2E1 route, glutathione is consumed faster than it regenerates, and free NAPQI binds to liver proteins and kills hepatocytes. That sequence, from glutathione depletion to centrilobular necrosis, is the entire story of paracetamol poisoning.
N-acetylcysteine works by restoring glutathione. It provides cysteine, the rate-limiting building block for glutathione synthesis, and may have additional protective effects on liver microcirculation. Given early, it prevents liver injury almost completely: patients treated within 8 hours of ingestion very rarely develop significant hepatotoxicity. Given late, after injury has begun, it still improves outcomes and is recommended even in established liver failure, where it supports the struggling liver through the critical days.
The decision to treat rests on the Rumack-Matthew nomogram, which plots the paracetamol concentration against the hours since ingestion on a semi-logarithmic chart. A level above the treatment line at 4 hours or later means NAC is indicated. Levels drawn before 4 hours cannot be interpreted on the nomogram because absorption is incomplete. For staggered overdoses, unknown timing, or modified-release preparations, the nomogram does not apply and toxicology guidance takes over: when in doubt, start NAC while advice is sought, because delay harms and unnecessary NAC, though unpleasant, is rarely dangerous.
The three-bag Prescott protocol
The traditional regimen, published by Prescott and colleagues, delivers 300 mg/kg over 21 hours in three bags: 150 mg/kg in 200 mL of 5 percent dextrose over 60 minutes, then 50 mg/kg in 500 mL over 4 hours, then 100 mg/kg in 1,000 mL over 16 hours. For a 70 kg adult that is 10,500 mg, then 3,500 mg, then 7,000 mg, totalling 21,000 mg. The diluent volumes quoted are for adults of 40 kg and above; children need fluid-restricted paediatric volumes from local guidance.
The logic of the three bags is pharmacological: a rapid initial load to replenish glutathione quickly, then a slower maintenance to keep it replenished while paracetamol clears. The first bag's speed is also its weakness, because rapid NAC infusion is what triggers most anaphylactoid reactions. This is not a reason to avoid the protocol, which has decades of evidence behind it, but it is the reason the two-bag modification was developed.
In practice the commonest failure is not the wrong protocol but the interrupted infusion. Bags get delayed between stages, pumps alarm unnoticed, or the infusion is stopped for a reaction and never restarted. Each gap is time the liver spends without glutathione cover. Prescribing the regimen is only half the job; the other half is making sure all three bags actually run to completion, which is a nursing and systems task as much as a medical one.
The two-bag modified protocol
The modified two-bag protocol gives the same 300 mg/kg total over 20 hours but restructures it: 200 mg/kg in 500 mL over 4 hours, then 100 mg/kg in 1,000 mL over 16 hours. For a 70 kg adult that is 14,000 mg then 7,000 mg. By removing the rapid 1-hour loading bag, it substantially reduces anaphylactoid reactions without compromising efficacy, and several centres have adopted it as their standard. Trials and observational studies support its effectiveness for the standard single acute ingestion.
The two-bag protocol is now recommended in several national guidelines as an acceptable, and in some settings preferred, alternative to the three-bag regimen. Its advantages are practical as well as pharmacological: fewer bag changes mean fewer opportunities for delay, and the slower start means fewer reactions interrupting treatment. The calculator offers both protocols so the team can follow whichever their hospital has standardised.
Neither protocol is the final word for every patient. Massive ingestions, staggered overdoses, modified-release paracetamol, and patients who present with established liver injury may need extended treatment beyond the standard bags: continued NAC until the paracetamol is undetectable and liver tests are improving, guided by the toxicologist. The protocols are starting frameworks, not ceilings.
Anaphylactoid reactions: expect them, manage them
NAC causes anaphylactoid reactions in a significant minority of patients, most often during the first bag: flushing, urticaria, itching, wheeze, and occasionally hypotension. These are not IgE-mediated allergies but direct histamine release, which has two practical consequences. First, they are rate-related, so slowing the infusion usually controls them. Second, a history of a previous reaction is not an absolute contraindication to future NAC: with a slower protocol and antihistamine cover, most patients complete treatment.
Management follows a standard sequence: pause or slow the infusion, give an antihistamine, add bronchodilators or adrenaline for wheeze or hypotension per local anaphylaxis guidance, and once the patient recovers, restart at a slower rate. The infusion should almost always be completed, because abandoning NAC for a manageable reaction leaves the liver unprotected. Patients with asthma are at higher risk and deserve closer observation during the first bag.
Documentation matters: record the reaction, its timing, its severity, and how it was managed, so future teams know this patient needs the slower protocol from the start. And counsel the patient that the reaction was to the infusion rate, not a permanent drug allergy, to avoid NAC being wrongly withheld in a future overdose.
Children, pregnancy, and special situations
Children are dosed by the same mg/kg protocols, but the diluent volumes must come from paediatric guidance, not by scaling adult bags. A small child given adult fluid volumes risks fluid overload and, with hypotonic diluents, hyponatraemia and cerebral oedema. Most paediatric protocols restrict total fluid and use weight-based diluent volumes. The calculator flags weights under 40 kg explicitly and withholds adult volumes rather than guessing.
In pregnancy, paracetamol overdose threatens two patients, and NAC is the treatment for both. It crosses the placenta and protects the foetal liver too. The threshold for treatment should be low and toxicology input sought early, but NAC must not be withheld from a pregnant patient who meets criteria: the risks of untreated poisoning far exceed the risks of treatment. Breastfeeding can continue with appropriate advice.
Patients who present late, beyond 24 hours, or with established liver injury need NAC regardless of the nomogram, which no longer applies. The King's College criteria help identify those who need transplant assessment, but NAC continues during the evaluation. Acetylcysteine has also shown benefit in non-paracetamol acute liver failure in some studies, though that use follows specialist direction rather than the poisoning protocols.
Monitoring during and after treatment
During the infusion, monitor for reactions, especially in the first bag, and confirm each bag completes on schedule. Paracetamol levels, liver function tests, INR, creatinine, and venous blood gas with lactate track the poisoning's course. A falling paracetamol level with stable liver tests is reassuring; a rising INR, climbing transaminases into the thousands, or worsening acidosis means the liver is failing despite treatment and senior toxicology and transplant input are needed.
At the end of the protocol, the decision is not automatic. If the paracetamol is undetectable, liver tests are normal or clearly improving, and the patient is well, treatment can stop. If paracetamol remains detectable, transaminases are still rising, or there is any sign of liver dysfunction, the infusion continues, usually with the final bag's rate, until toxicology advises stopping. The protocol's end is a decision point, not a finish line.
Do not forget the patient behind the poisoning. Most paracetamol overdoses are deliberate self-harm, and the medical treatment is only half the care. Psychiatric assessment before discharge, safeguarding where relevant, and follow-up arrangements are as much a part of the management as the NAC bags. The calculator handles the arithmetic; the team handles the person.
Sources
- Prescott LF, et al. Intravenous N-acetylcysteine: the treatment of choice for paracetamol poisoning. British Medical Journal. 1979;2(6198):1097-1100. doi:10.1136/bmj.2.6198.1097
- Bateman DN, et al. Effect of the UK's revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs. British Journal of Clinical Pharmacology. 2014;77(6):1042-1050. doi:10.1111/bcp.12362
Key takeaways
- NAC replenishes glutathione and prevents liver failure in paracetamol poisoning; it works best within 8 hours but helps late presenters too.
- The three-bag Prescott protocol gives 150, then 50, then 100 mg/kg over 21 hours; the two-bag modification gives 200 then 100 mg/kg over 20 hours with fewer reactions.
- Start NAC on the Rumack-Matthew nomogram for single acute ingestions; for staggered or unknown timing, seek toxicology advice and do not delay treatment.
- Anaphylactoid reactions are rate-related and managed by slowing the infusion, not abandoning it; children need paediatric fluid volumes, not scaled adult bags.
Frequently asked questions
What is the NAC protocol for paracetamol poisoning?
The traditional three-bag Prescott protocol gives 150 mg/kg IV over 1 hour, then 50 mg/kg over 4 hours, then 100 mg/kg over 16 hours (300 mg/kg total over 21 hours). The modified two-bag protocol gives 200 mg/kg over 4 hours then 100 mg/kg over 16 hours (300 mg/kg over 20 hours), with fewer infusion reactions. Both use 5 percent dextrose as the diluent in adults.
How do I know if NAC is needed?
For a single acute ingestion, plot the paracetamol level taken at least 4 hours after ingestion on the Rumack-Matthew nomogram: a level above the treatment line means NAC is indicated. For staggered ingestions, unknown timing, or modified-release preparations the nomogram does not apply, so seek toxicology advice urgently and consider starting NAC while waiting.
What should I do if the patient reacts to the NAC infusion?
Pause or slow the infusion, treat symptoms (antihistamine for flushing or hives; bronchodilators or adrenaline for wheeze or hypotension per local guidance), and restart at a slower rate once recovered. Most patients complete treatment. The reaction is rate-related histamine release, not true allergy, so it rarely justifies abandoning NAC.
Can NAC be given late after the overdose?
Yes. Benefit is greatest within 8 hours, but NAC is recommended for late presenters and even in established paracetamol-induced liver failure, where it improves outcomes. Do not withhold it because time has passed; instead seek toxicology input on extended treatment.
How is NAC dosed in children?
Children receive the same mg/kg doses, but diluent volumes must follow paediatric guidance with restricted fluids: adult bag volumes scaled down can cause fluid overload and hyponatraemia. Use your hospital's paediatric paracetamol poisoning protocol for the fluid prescription.
Is NAC safe in pregnancy?
Yes, and it should not be withheld. Paracetamol poisoning threatens both mother and foetus, and NAC crosses the placenta to protect the foetal liver. Treat on the same criteria with a low threshold, involve toxicology and obstetrics early, and continue breastfeeding advice per local guidance.
Clinical sources: Prescott LF et al. Br Med J. 1979;2(6198):1097-1100; Bateman DN et al. Br J Clin Pharmacol. 2014;77(6):1042-1050.