Accident and Emergency Medicine, Ninewells Hospital, Dundee
basically two types of poisoning, non-intentional and intentional.
Non-intentional poisoning can be industrial, agricultural or domestic and
involves exposure to intrinsically harmful substances.
Domestic non-intentional poisoning is very common in young children under
the age of five, with the main culprits being household chemicals such as bleach
or organophosphates (weedkillers). Intentional
poisoning occurs after exposure to substances only harmful in excess.
The age groups most at risk are the 15 - 19 year olds coping with
adolescence. Although a patient can theoretically overdose on whatever is
at hand, and during my four weeks in A&E I saw Anadin Extra, Temazepam,
right through to Beta-blockers and Metformin, there are certain drugs that seem
to be favoured. Paracetamol, is by
far the leader, however the Compound Analgesics are catching up, after that
Tricyclic antidepressants, Ibuprofen, Opioids, Benzodiazepines and Barbiturates.
Alcohol should also always be considered as it is often taken to wash
down the overdose and can affect the management of a patient.
As I stated previously Paracetamol (Acetaminophen) is the most common
drug taken in overdose, and therefore is the topic of my essay.
is metabolised in the liver by Cytochromes P450, with a percentage metabolised
into toxic intermediates. Glutathione
then conjugates these into Mercapturic Acid.
If the dose is large enough, the glucuronidation pathways are disrupted
or if there is underlying liver damage Glutathione stores cannot cope and the
unconjugated toxic metabolites react with proteins causing hepatic cell damage
and death. Signs and symptoms are
In 1st 24 – 48 hrs patient
may appear well – however nausea and vomiting may occur, especially if taken
48 – 72 hrs: Anorexia
Nausea and vomiting
Right subcostal pain – indicator of hepatocellular
the majority of people make a complete recovery, even after substantial
overdoses, the liver healing with complete resolution, without fibrosis.
Conversely, hepatocellular damage can occur with as little as 20 – 30
tablets, about 150mg/kg. Those with chronic alcohol consumption have a lower toxic
threshold as they have increased levels of cytochromes P450 that metabolise the
toxic intermediates faster than glutathione stores can keep up with.
Concomitant drugs such as Isoniazid, Phenytoin and Zidovudine can also
lower the toxic dose threshold. Isoniazid
and Phenytoin increase the metabolism of paracetamol, and Zidovudine competes
for glucuronidation pathways. If
severe liver damage and failure occurs it does so usually within 3 days and is
ALT > 2000
occurs about 4 – 18 days later, usually from cerebral oedema and sepsis.
Management in A&E
Firstly, and most importantly:
majority of paracetamol overdose patients present early and are therefore
conscious and breathing normally.
the patient is unconscious the airway must be protected and tracheal intubation
may be required. There is a risk of
aspiration of stomach contents if the patient vomits.
all patients if a significant ingestion or suspicion of significant ingestion
has occurred, the following guidelines are used in A&E:
If within 1 hour of ingestion, gastric lavage can be carried out.
However this treatment is becoming increasingly unfashionable, as there
is no direct evidence that it improves the patient’s outcome and it carries
with it the risk of pulmonary aspiration of stomach contents.
If within 4 hours, patients can be given 50gm of activated charcoal.
This procedure is more efficient at preventing absorption of poisons
toxic in small amounts, eg Tricyclic Antidepressants.
Patients should be admitted to the short stay ward.
At 4 hours post ingestion, or on arrival to the department if greater
than 4 hours post ingestion, plasma paracetamol levels should be obtained.
At this time Paracetamol and Salicylate levels should be requested and
liver function tests should be done.
When the Paracetamol level is known, it should be plotted on an
individual nomogram for each patient.
below the treatment line, then no further action is required.
the patient is in a “High Risk” group i.e someone taking enzyme inducing
drugs such as Carbamazepine, Phenytoin, Phenobarbitone or Rifampicin, or if they
are malnourished such as chronic alcoholics, anorexics or known to be HIV
positive, then the threshold for treatment is the “High Risk” treatment
curve on the nomogram:
patient’s paracetamol level requires treatment they should
receive IV N Acetylcysteine (Parvolex) at the regime
stated below the
Acetylcysteine is a precursor of Glutathione, which increases Glutathione levels
in the liver, therefore increasing the rate of conjugation of the toxic
At 8 hours following ingestion a further paracetamol level and clotting
factor, in particular Prothrombin time, should be taken.
who present late to the department (8 – 24 hours) with significant ingestion
i.e greater than 150mg/kg or when ingestion time is staggered should be
commenced on Parvolex immediately and blood investigations taken appropriately.
patients presenting more than 24 hours after ingestion can also be given
parvolex particularly if their investigations are abnormal and they are
who stay over night in the short stay ward are assessed the next morning in the
ward round.The patient will also be seen by a
psychiatric nurse who will arrange appropriate counselling and help.
Case study – Miss X
Miss X is a 17year old female
who presented to A&E having taken 16 Paracetamol and 32 Ibuprofen.
This worked out to be 8g of Paracetamol.
She was asymptomatic on presentation, having been brought in about an
hour after ingestion after her father realised she had ingested a large amount
of tablets. On examination there
was evidence of deliberate self-harm. She
had a history of overdose with a previous attempt at 14 years old, and was on
Fluoxetine, however her GP was in the process of changing her prescription and
she had been without medication for about three days.
At 4 hours post ingestion her plasma Paracetamol and Salicylate levels
were measured and found to be:
Paracetamol – 0.61 mmol/l
Salicylate – none detected
This was plotted on her
individual nomogram and found to be below the treatment line and required no
treatment with Parvolex. Miss VM
was admitted to the short stay ward overnight for observation.
In the morning she was assessed by the psychiatric nurse and I sat in on
Compound Analgesic Poisoning
Compound Analgesic preparations
contain a simple analgesic (usually Paracetamol) with an opioid component.
Therefore an overdose carries the added complications of opiate
poisoning. Examples of such
preparations (of which there are many) include Co-proxamol, which contains 325mg
of Paracetamol and 32.5mg of Dextropropoxyphene hydrochloride per tablet, and
Solpadeine, which contains 500mg of Paracetamol, 8mg of Codeine phosphate and
30mg of caffeine per tablet. Along
with the signs and symptoms of paracetamol poisoning, the patient will also show
signs of opiate poisoning:
Management in A&E
well as the management for Paracetamol poisoning discussed above, Naloxone may
have to be administered if respiratory depression is severe.
This is a short acting Opioid antagonist that is administered IV and may
be repeated several times without ill-effects.
This is sometimes the case as Naloxone has a shorter half-life than the
Case Study – Mr Y
is a 58year old male who presented to A&E having taken approximately 30 –
40 tablets of Solpadeine about 10 hours previously. He had been drinking alcohol prior to the overdose.
On examination he was found to have a tender epigastrium and pin-point
pupils. His plasma Paracetamol and
Salicylate levels were measured immediately and found to be:
– None detected
this was below the treatment curve, Mr GC had been drinking heavily for a period
of time before his overdose and was therefore assessed using the “High
Risk”curve, which he was above, and therefore was given Parvolex.
He had managed to survive respiratory depression overnight without the
need for Naloxone.
Fulminant Hepatic Failure (FHF)
hepatic failure is the rapid development of hepatocellular dysfunction and
encephalopathy in a previously normal liver.
One of the most common causes is Paracetamol toxicity, where it usually
develops in less than 1 week. As
little as 4g of Paracetamol in high-risk patients can cause FHF.
The clinical presentation is:
Nausea, vomiting, fatigue and malaise
Jaundice – due to impaired bilirubin
Coagulopathy – due to decreased
synthesis of factors I, II, V, VII, IX & X.
Hypoglycaemia – due to decreased
Metabolic acidosis – due to decreased
lactate uptake and anaerobic glycolysis producing lactate.
Encephalopathy – 4 stages:
Insomnia, poor concentration
Drowsiness, confusion, disorientation
Cerebral oedema – may be as a result of
a disruption in the blood brain barrier by gut derived neurotoxins that escaped
hepatic clearance, causing vasogenic oedema.
Infection – 33% are fungal
Multiple Organ Failure
In patients with paracetamol
poisoning, any one of the following features is serious:
1. Prothrombin Time > 6.5
Arterial pH < 7.3
Serum Creatinine > 3.4 mg/dL
Management in A&E
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