Poisoning - Paracetamol

Emergency Medicine

Clinicals - History

Fact Explanation
Patients may be brought to medical attention within few hours of ingestion with a history of paracetamol overdosing. Patients are usually asymptomatic in the initial 24 hours until manifestations of end organ damage appear. Upon presentation it is important to conduct a detailed assessment to establish the quantity and timing of paracetamol ingestion. It is important to differentiate whether the patient had being taking an overdose paracetamol over a long period of time or whether this is a single event. Patients may be brought to medical attention within few hours of ingestion with a history of paracetamol overdosing.
Patients are usually asymptomatic in the initial 24 hours until manifestations of end organ damage appear. Upon presentation it is important to conduct a detailed assessment to establish the quantity and timing of paracetamol ingestion. It is important to differentiate whether the patient had being taking an overdose paracetamol over a long period of time or whether this is a single event.
Nausea and vomiting/ abdominal pain The patient may experience minor gastrointestinal symptoms within the first 24 hours. Nausea and vomiting/ abdominal pain
The patient may experience minor gastrointestinal symptoms within the first 24 hours.
Confusion/ coma Patients may develop encephalopathy. Patients who have ingested massive amounts of paracetamol are prone to develop a coma. Confusion/ coma
Patients may develop encephalopathy. Patients who have ingested massive amounts of paracetamol are prone to develop a coma.
Right hypochondrial pain Due to hepatic necrosis in established liver damage. Right hypochondrial pain
Due to hepatic necrosis in established liver damage.
Presentation with features of liver failure: jaundice, impaired consciousness, fetor hepaticus, bleeding Paracetamol is mainly metabolized by the liver by conjugation to inactive metabolites. The reactive metabolite – N-acetyl-p-benzoquinoneimine (NAPQI) generated in this process is toxic to the liver. Liver injury will result if NAPQI is generated at an excess rate than its neutralization by glutathione. Presentation with features of liver failure: jaundice, impaired consciousness, fetor hepaticus, bleeding
Paracetamol is mainly metabolized by the liver by conjugation to inactive metabolites. The reactive metabolite – N-acetyl-p-benzoquinoneimine (NAPQI) generated in this process is toxic to the liver. Liver injury will result if NAPQI is generated at an excess rate than its neutralization by glutathione.
Low urine output Patients who ingest massive amounts of paracetamol are prone to develop renal failure secondary to hepatic dysfunction. The risk is exaggerated in patients with pre-existing renal disease and who are dehydrated. Low urine output
Patients who ingest massive amounts of paracetamol are prone to develop renal failure secondary to hepatic dysfunction. The risk is exaggerated in patients with pre-existing renal disease and who are dehydrated.
Syncope Patients with paracetamol poisoning are prone to develop hypoglycemia due to liver damage. Syncope
Patients with paracetamol poisoning are prone to develop hypoglycemia due to liver damage.

Clinicals - Examination

Fact Explanation
General examination – Conscious level The patient may present in an altered level of consciousness. This may range from a confused state to coma. Altered level of consciousness may be due to hypoglycemia, hepatic encephalopathy, shock etc. General examination – Conscious level
The patient may present in an altered level of consciousness. This may range from a confused state to coma. Altered level of consciousness may be due to hypoglycemia, hepatic encephalopathy, shock etc.
General examination – Features of liver failure The patient present with jaundice and bleeding manifestations. Features of hepatic encephalopathy include asterixis, constructional apraxia, hyper-reflexia and bilateral extensor plantar responses. Fetor hepaticus is a sweet musty odor to the breath which is associated with hepatic failure. General examination – Features of liver failure
The patient present with jaundice and bleeding manifestations. Features of hepatic encephalopathy include asterixis, constructional apraxia, hyper-reflexia and bilateral extensor plantar responses. Fetor hepaticus is a sweet musty odor to the breath which is associated with hepatic failure.
General examination – cachexia, malnourished Identification of malnourishment indicates a higher risk of developing hepatic injury due to depleted glutathione stores. General examination – cachexia, malnourished
Identification of malnourishment indicates a higher risk of developing hepatic injury due to depleted glutathione stores.
Abdominal examination Right upper quadrant tenderness may be elicited in the presence of hepatic damage. A tender hepatic edge may also be palpated. Abdominal examination
Right upper quadrant tenderness may be elicited in the presence of hepatic damage. A tender hepatic edge may also be palpated.
Cardiovascular system examination – Tachycardia and hypo tension Will indicate dehydration and fluid loss. Cardiovascular system examination – Tachycardia and hypo tension
Will indicate dehydration and fluid loss.

Investigations - Diagnosis

Fact Explanation
Serum paracetamol level A history of paracetamol ingestion and determination of paracetamol level is important for diagnosis and management of patients. Whether to commence antidote treatment (N-acetylcysteine) is based on blood paracetamol levels. For accurate estimation of paracetamol levels blood should be collected 4 hours after ingestion. The measurement is less reliable after 15 hours. Serum paracetamol level
A history of paracetamol ingestion and determination of paracetamol level is important for diagnosis and management of patients. Whether to commence antidote treatment (N-acetylcysteine) is based on blood paracetamol levels. For accurate estimation of paracetamol levels blood should be collected 4 hours after ingestion. The measurement is less reliable after 15 hours.

Investigations - Management

Fact Explanation
Liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin, alkaline phosphatase Evidence for hepatic injury is monitored for by regular liver function tests usually performed 12 hourly. Biochemical evidence of severe liver damage as indicated by Alt > 1000 IU/L may develop 48-96 hours after ingestion. Liver function tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum bilirubin, alkaline phosphatase
Evidence for hepatic injury is monitored for by regular liver function tests usually performed 12 hourly. Biochemical evidence of severe liver damage as indicated by Alt > 1000 IU/L may develop 48-96 hours after ingestion.
Prothrombin time with INR To check for bleeding tendency associated with hepatic failure. Prothrombin time with INR
To check for bleeding tendency associated with hepatic failure.
Capillary blood glucose Blood glucose levels are monitored regularly due to the risk of hypoglycemia. Capillary blood glucose
Blood glucose levels are monitored regularly due to the risk of hypoglycemia.
Arterial blood gas assessment Patients with paracetamol poisoning may develop lactic acidosis. The development of lactic acidosis is described in two pathways - Due to hepatic failure leading to reduced clearance of lactate & in shocked patients due to peripheral anaerobic respiration. The arterial blood gas assessment will reveal a metabolic acidosis with an increased anion gap. Arterial blood gas assessment
Patients with paracetamol poisoning may develop lactic acidosis. The development of lactic acidosis is described in two pathways - Due to hepatic failure leading to reduced clearance of lactate & in shocked patients due to peripheral anaerobic respiration. The arterial blood gas assessment will reveal a metabolic acidosis with an increased anion gap.
Serum creatinine level/ Serum electrolytes To monitor renal functions. Serum creatinine level/ Serum electrolytes
To monitor renal functions.

Management - Supportive

Fact Explanation
Regular monitoring of the patient Monitor the patients' vital parameters, urine output and conscious level. Observations should be made to detect features of hepatic dysfunction. Biochemical investigations such as liver function tests, serum creatinine, prothrombin time test & blood glucose levels are also used for monitoring the patient. Regular monitoring of the patient
Monitor the patients' vital parameters, urine output and conscious level. Observations should be made to detect features of hepatic dysfunction. Biochemical investigations such as liver function tests, serum creatinine, prothrombin time test & blood glucose levels are also used for monitoring the patient.
Patient counseling and psychiatric referral Following acute phase management, a detailed history should be evaluated with regards to finding the etiology for paracetamol overdose. Patients who have ingested paracetamol with the intention of deliberate self harm or suicide need a risk assessment for future recurrence of similar acts. Patients with a low risk of recurrence need counseling with regards to coping strategies and stress management. High risk patients need psychiatric referral. Patient counseling and psychiatric referral
Following acute phase management, a detailed history should be evaluated with regards to finding the etiology for paracetamol overdose. Patients who have ingested paracetamol with the intention of deliberate self harm or suicide need a risk assessment for future recurrence of similar acts. Patients with a low risk of recurrence need counseling with regards to coping strategies and stress management. High risk patients need psychiatric referral.

Management - Specific

Fact Explanation
Treatment with N-acetylcysteine (NAC) The first line treatment for paracetamol poisoning is NAC. The mechanism of action is yet to be fully understood but involves neutralization of N-acetyl-p-benzoquinoneimine and improved synthesis of glutathione. The standard infusion regime of NAC is administered in 3 stages with a total dose of 300 mg/kg:
1. 150 mg/kg over the first hour
2. 50 mg/kg over the next 4 hours
3. 100mg/kg over the next 16 hours
NAC infusion is continued at a rate of 150mg/kg/24h in 5% dextrose/ 0.9% saline if features of liver damage manifest. This is continued until liver damage is seen to recover.
Treatment with N-acetylcysteine (NAC)
The first line treatment for paracetamol poisoning is NAC. The mechanism of action is yet to be fully understood but involves neutralization of N-acetyl-p-benzoquinoneimine and improved synthesis of glutathione. The standard infusion regime of NAC is administered in 3 stages with a total dose of 300 mg/kg:
1. 150 mg/kg over the first hour
2. 50 mg/kg over the next 4 hours
3. 100mg/kg over the next 16 hours
NAC infusion is continued at a rate of 150mg/kg/24h in 5% dextrose/ 0.9% saline if features of liver damage manifest. This is continued until liver damage is seen to recover.
Decision on when to administer NAC Treat all patients with a single overdose of more than 10g or 200mg/kg body weight and when the time of ingestion is not reliable. In all other patients treatment is based on the timing of ingestion and plasma paracetamol level. Rumack-Matthew normogram is used to plot plasma paracetamol levels against the timing of ingestion and decide on the need to initiate NAC treatment. Some charts include a separate curve for high risk patients (Patients who are heavy alcoholics, on enzyme inducing drugs, malnourished etc) where the treatment threshold is lower than for a normal healthy individual. Decision on when to administer NAC
Treat all patients with a single overdose of more than 10g or 200mg/kg body weight and when the time of ingestion is not reliable. In all other patients treatment is based on the timing of ingestion and plasma paracetamol level. Rumack-Matthew normogram is used to plot plasma paracetamol levels against the timing of ingestion and decide on the need to initiate NAC treatment. Some charts include a separate curve for high risk patients (Patients who are heavy alcoholics, on enzyme inducing drugs, malnourished etc) where the treatment threshold is lower than for a normal healthy individual.
Gastrointestinal decontamination Gastrointestinal decontamination can be used in patients presenting within 2 hours of ingestion. Gastric lavage followed by administering activated charcoal limit absorption of paracetamol via the stomach. Gastrointestinal decontamination is effective for a longer duration if the paracetamol product ingested is a slow release product. Gastrointestinal decontamination
Gastrointestinal decontamination can be used in patients presenting within 2 hours of ingestion. Gastric lavage followed by administering activated charcoal limit absorption of paracetamol via the stomach. Gastrointestinal decontamination is effective for a longer duration if the paracetamol product ingested is a slow release product.
Treatment of patients presenting within 8 hours of ingestion Blood sample is collected for measurement of plasma paracetamol level at 4 hours after ingestion or later and the value obtained is plotted in the normogram. The NAC treatment regime is initiated if the paracetamol level is above the treatment line. Continue monitoring the patient during treatment. Patients with paracetamol level below the treatment threshold could be discharged after arranging appropriate follow-up. Treatment of patients presenting within 8 hours of ingestion
Blood sample is collected for measurement of plasma paracetamol level at 4 hours after ingestion or later and the value obtained is plotted in the normogram. The NAC treatment regime is initiated if the paracetamol level is above the treatment line. Continue monitoring the patient during treatment. Patients with paracetamol level below the treatment threshold could be discharged after arranging appropriate follow-up.
Treatment of patients presenting within 8- 24 hours of ingestion Initiate treatment with NAC pending plasma paracetamol level. The value is plotted in the graph and the NAC infusion is continued if the value is above the treatment threshold. Treatment with NAC is discontinued if the plasma level is below the treatment line. Treatment of patients presenting within 8- 24 hours of ingestion
Initiate treatment with NAC pending plasma paracetamol level. The value is plotted in the graph and the NAC infusion is continued if the value is above the treatment threshold. Treatment with NAC is discontinued if the plasma level is below the treatment line.
Treatment of patients presenting after 24 hours of ingestion Assessment of paracetamol level is less reliable at this stage. Examine the patient for evidence for hepatotoxicity and if present NAC is administered. Following the initial dose of 300mg/kg, NAC is continued at a dose of 150mg/kg/24h until features of liver damage show improvement. Treatment of patients presenting after 24 hours of ingestion
Assessment of paracetamol level is less reliable at this stage. Examine the patient for evidence for hepatotoxicity and if present NAC is administered. Following the initial dose of 300mg/kg, NAC is continued at a dose of 150mg/kg/24h until features of liver damage show improvement.
Management of complications Observe the patient to detect development of acute renal failure, hypoglycaemia, acute liver failure & lactic acidosis and manage accordingly. Management of complications
Observe the patient to detect development of acute renal failure, hypoglycaemia, acute liver failure & lactic acidosis and manage accordingly.
Allergic reaction to NAC Inquire about previous allergic reactions to NAC. NAC can be administered with the cover of hydrocortisone and chlorpheniramine in such situations. Allergic reaction to NAC
Inquire about previous allergic reactions to NAC. NAC can be administered with the cover of hydrocortisone and chlorpheniramine in such situations.
Methionine as an alternative to NAC Methionine is effective if given within 8 hours of ingestion. It is administered at a dose of 2.5g orally every 4 hours. Methionine as an alternative to NAC
Methionine is effective if given within 8 hours of ingestion. It is administered at a dose of 2.5g orally every 4 hours.

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