Paracetamol Overdose: Dangers and Treatment

paracetamol overdose

Prelude

Repeatedly taking marginally too much paracetamol (acetaminophen, Panadol) over time can cause a dangerous overdose that is hard to detect and can lead to death, because patients usually don’t report an overdose when they visit the hospital, rather that they feel unwell. Clinicians need to be able to detect these cases rapidly so that they can provide prompt and effective treatment, as these patients are in greater danger compared with those who have taken a single overdose.

Dr Simpson and colleagues at the University of Edinburgh and the Scottish Liver Transplantation Unit in Scotland, evaluated data from 663 patients admitted to the Royal Infirmary of Edinburgh between 1992 and 2008 with paracetamol-induced liver injury. They reported that 161 patients had taken a staggered overdose, typically to ease various common pains like headache, toothache, abdominal or muscular pains.

Signs and symptoms

Most patients who overdose on acetaminophen will initially be asymptomatic, as clinical symptoms of end-organ toxicity do not manifest until 24-48 hours after an acute ingestion. Therefore, to identify a patient who may be at risk of hepatoxicity, the clinician should determine the time(s) of ingestion, the quantity, and the formulation of acetaminophen ingested.

Minimum toxic doses of acetaminophen for a single ingestion, posing significant risk of severe hepatotoxicity, are as follows:

  • Adults: 7.5-10 g
  • Children: 150 mg/kg; 200 mg/kg in healthy children aged 1-6 years

The clinical course of acetaminophen toxicity generally is divided into four phases. Physical findings may vary, depending on the degree of hepatotoxicity.

Phase 1

  • 0.5-24 hours after ingestion
  • Patients may be asymptomatic or report anorexia, nausea or vomiting, and malaise
  • Physical examination may reveal pallor, diaphoresis, malaise, and fatigue

Phase 2

  • 18-72 h after ingestion
  • Patients develop right upper quadrant abdominal pain, anorexia, nausea, and vomiting
  • Right upper quadrant tenderness may be present
  • Tachycardia and hypotension may indicate volume losses
  • Some patients may report decreased urinary output (oliguria)

Phase 3: Hepatic phase

  • 72-96 h after ingestion
  • Patients have continued nausea and vomiting, abdominal pain, and a tender hepatic edge
  • Hepatic necrosis and dysfunction may manifest as jaundice, coagulopathy, hypoglycemia, and hepatic encephalopathy
  • Acute renal failure develops in some critically ill patients
  • Death from multi-organ failure may occur

Phase 4: Recovery phase

  • 4 d to 3 wk after ingestion
  • Patients who survive critical illness in phase 3 have complete resolution of symptoms and complete resolution of organ failure

How is paracetamol toxicity assessed in hospital?

The healthcare professional will make a full assessment and will also ask about:

  • The number of tablets taken.
  • What time the overdose was taken.
  • Whether the medicine was in tablet, caplet, liquid or soluble form.
  • Whether any other tablets were taken at the same time.
  • Whether any alcohol was taken at the same time.
  • Any suicide risk, such as whether a note was written.

They will also undertake a full examination which early on may not find anything. Once liver damage sets in there may be jaundice, a tender liver and presence of brain involvement (called encephalopathy).

What investigations are needed?

This mainly consists of blood tests and includes:

  • Paracetamol levels:
    • If the tablets were all taken in one go: the paracetamol level needs to be checked four hours after the time of the overdose. If the time is unknown or more than four hours have passed then a sample will be taken immediately.
    • If the tablets have been taken over several hours or days: this is called a ‘staggered overdose’ and a paracetamol level will be taken immediately and treatment started before the level is back. The level here only tells us that paracetamol has been taken.
  • Liver function tests: these are a group of blood tests that reveal how the liver is functioning. Early on, they may be normal. When they go high this tells us that liver cells have died and liver failure is possible. A blood clotting test (called prothrombin time) is an earlier and better indicator of liver damage.
  • Prothrombin time: as part of the blood clotting tests that will be requested, this gives an idea of how ‘thin’ the blood is. The liver makes important factors for blood clotting. When the liver becomes damaged, the prothrombin time rises. The higher the level, the more severe the liver involvement. It will be checked several times.
  • Renal function tests: these are blood tests looking at the function of the kidney. They will show if there is any kidney damage or kidney failure.
  • Blood sugar levels: low levels (called hypoglycaemia) can occur when the liver is failing. A fingertip test will need to be done hourly.
  • Arterial blood gas: this involves an arterial blood sample being taken (usually at the wrist where the pulse is taken) and reveals levels of acid in the blood. Acid levels are very tightly controlled by the body and in paracetamol overdose acid levels can rise early. These patients are probably going to be sicker and some will develop liver failure.

Other tests that are requested will depend on each individual case and the patient’s course. For example, if other medications were taken then their levels may need to be checked.

Rumack-Matthew nomogram

  • Used to interpret plasma acetaminophen values to assess hepatotoxicity risk after a single, acute ingestion
  • Nomogram tracking begins 4 hours after ingestion (time when acetaminophen absorption is likely to be complete) and ends 24 hours after ingestion
  • About 60% of patients with values above the “probable” line develop hepatotoxicity

Treatment

Immediate management will require resuscitation and stabilization. If the patient is unstable – such as having low blood pressure – or there is overwhelming liver failure, they will need to be treated on an intensive care unit.

Gastrointestinal decontamination agents can be used in the emergency setting during the immediate post-ingestion time frame. Administer activated charcoal (AC) if the patient is alert and presents, ideally, within 1 hour post ingestion. This time frame can be extended if the patient has ingested an acetaminophen-based sustained-release medication or if the ingestion includes agents that are known to slow gastric emptying. Patients with acetaminophen concentrations below the “possible” line for hepatotoxicity on the Rumack-Matthew nomogram may be discharged home after they are medically cleared.

Admit patients with acetaminophen concentration above the “possible” line on the Rumack-Matthew nomogram for treatment with N -acetylcysteine (NAC). NAC is nearly 100% hepatoprotective when it is given within 8 hours after an acute acetaminophen ingestion, but can be beneficial in patients who present more than 24 hours after ingestion. NAC is approved for both oral and IV administration.

The FDA-approved regimen for oral administration of NAC (Mucomyst) is as follows:

  • Loading dose of 140 mg/kg
  • 17 doses of 70 mg/kg given every 4 hours
  • Total treatment duration of 72 hours

The IV formulation of NAC (Acetadote) is commonly used in many institutions for the treatment of acetaminophen ingestion. Use of the IV formulation of NAC is preferred in the following situations:

  • Altered mental status
  • GI bleeding and/or obstruction
  • A history of caustic ingestion
  • Potential toxicity in a pregnant woman
  • Inability to tolerate oral NAC because of emesis refractory to proper use of antiemetics

Surgical evaluation for possible liver transplantation is indicated for patients who have severe hepatotoxicity and potential to progress to hepatic failure. Criteria for liver transplantation include the following:

  • Metabolic acidosis, persistent after fluid resuscitation
  • Renal failure
  • Coagulopathy
  • Encephalopathy
 Credits:
www.patient.info
www.medscape.com
www.medicalnewstoday.com
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