Overdose : מינון יתר

4.9   Overdose

In overdose, symptoms corresponding to heavy smoking may be seen, however the toxicity of nicotine cannot be directly compared with that of smoking, because tobacco smoke contains additional toxic substances (eg. Carbon monoxide and tar).

Overdose with Nicotinell gum may only occur if many pieces are chewed simultaneously. Nicotine toxicity after ingestion will most likely be minimized as a result of early nausea and vomiting that occur following excessive nicotine exposure. Risk of poisoning by swallowing the gum is small. Since the release of nicotine from the gum is slow, very little nicotine is absorbed from the stomach and intestine, and if any is, it will be inactivated in the liver.

Chronic smokers can tolerate doses of nicotine that, in a non-smoker, would be more toxic, because of the development of tolerance.

The acute lethal dose of nicotine in a non-tolerant man has been estimated to be 0.5 0.75 mg per kg bodyweight,corresponding in an adult to 40-60mg.
Even small quantities of nicotine are dangerous in children, and may result in severe symptoms of poisoning which may prove fatal. If poisoning is suspected in a child, a doctor must be consulted immediately.

Symptoms
Symptoms of acute nicotine poisoning include nausea, vomiting, salivation, throat burn, abdominal pain, diarrhoea, perspiration, headache, dizziness, hearing and visual disturbances and marked weakness. In extreme cases, these symptoms may be followed by hypotension, tachycardia, cardiac arrhythmia, dyspnoea, prostration, circulatory collapse, coma and terminal convulsions.

Treatment of overdose
Treatment of overdose should be immediate as symptoms may develop rapidly (particularly in children). All nicotine intake should stop immediately. Emesis is usually spontaneous. Artificial respiration with oxygen should be instituted if necessary. Consider activated charcoal, provided airway can be protected in those presenting within 1 hour of ingestion of more than 0.2mg/kg of nicotine.
Monitor vital signs and treat symptomatically.

Toxicity
Nicotine is highly toxic by ingestion, inhalation and skin contact. The fatal dose has been estimated to be as little as 40 mg of nicotine in an adult and just a few milligrams of nicotine have caused severe symptoms. It can be very rapidly absorbed with CNS, neuromuscular and autonomic features. The half-life of nicotine ranges from 24 minutes to 2 hours but symptoms may persist for up to 72 hours in severe cases of poisoning.
• All patients who have taken a deliberate overdose should be referred for assessment.
• Children and adults who have ingested 0.2 mg/kg or more nicotine, or those who are symptomatic, should be referred for medical assessment.
•Children or adults who have accidentally ingested less than 0.2 mg/kg nicotine and who have no new symptoms since the time of ingestion do not need to be referred for medical assessment. Patients should be advised to seek medical attention if symptoms develop.
• All symptomatic children and adults following accidental transdermal patch application should be referred for medical assessment.

Features

• Early features of ingestion include burning in the mouth and throat, nausea, vomiting, confusion, dizziness, weakness, hypersalivation, sweating and increased bronchial secretions. There may be sympathetic features including tachycardia, tachypnoea, hypertension and agitation followed by bradycardia, systemic hypotension and respiratory depression.
• More severe poisoning leads to arrhythmias including atrial fibrillation, coma, convulsions and respiratory and cardiac arrest. Recovery is likely if survival exceeds 2-3 hours.
• Skin contact may lead to irritation followed by variable absorption depending on the length of exposure and concentration. Systemic features may follow.
• Eye contact with liquid may lead to irritation and lacrimation.

Management

General measures

• Maintain a clear airway/ensure adequate ventilation. Monitor pulse and BP. Perform 12 lead ECG and measure QRS duration and QT interval and repeat especially if the patient is symptomatic or has taken slow release preparations.
• Good neurological outcome after cardiac arrest (due to nicotine poisoning) may occur after prolonged resuscitation. Cardiac arrest in hospital or witnessed out of hospital, with bystander CPR, should be continued for at least 1 hour (discuss with local poisons centre).
• The benefits of gastric decontamination are uncertain. Consider activated charcoal (50g adults: 1g/kg children) provided airway can be protected in those presenting within 1 hour of ingestion of more than 0.2mg/kg of nicotine.
• Asymptomatic patients who have ingested more than 0.2mg/kg of nicotine should be observed for at least 4 hours. However, if other cardiac/cardiotoxic agents have been taken monitor for the longest period recommended for these.
• In symptomatic patients check U&Es, creatinine kinase and arterial blood gases.
• Contact the local poisons information centre for specific advice.

Bradycardia
• If symptomatic give IV atropine
• If associated with hypotension, dobutamine or isoprenaline may be considered
• Temporary pacemaker or external pacing may be required 
Agitation
• Agitated adults can be sedated (IV diazepam: if ineffective oral or parenteral haloperidol)
• Agitated children are better managed without sedation. Exclude other causes (eg hypoxia: infection: hypoglycaemia: raised ICP). Seek expert paediatric advice.

Hypertension
• Adults: in agitated patient hypertension may settle with sedation. If hypertension persists give IV nitrates until blood pressure controlled. Calcium antagonists are an alternative as second line therapy.
Phentolamine or sodium nitroprusside are options if there is hypertension without evidence of cardiac ischaemia (but may cause a rapid fall in blood pressure) or alternatively IV labetalol.
• Children (under 5 years): Seek expert paediatric advice.

Convulsions
• Give oxygen, check blood sugar, U&Es and arterial blood gases. Correct acidbase balance and metabolic disturbances as necessary.
• A single brief convulsion does not require treatment. Otherwise control with IV diazepam or lorazepam. If unresponsive seek advice from NPIS/NPIC or appropriate specialist.

Other points to note
• A high percentage of urine screens will be positive for nicotine in both smokers and non-smokers.
• Quantitative blood concentrations are not readily available. Appropriate history and recognition of clinical finding are important.
• Other treatments/measures indicated by patient's clinical condition.
• On discharge patients should be advised to seek medical attention if symptoms develop.

Skin exposure
• Remove soiled clothes, nicotine patches or contaminating fluid.
• Wash skin with soap and water.
• Treat symptoms of systemic toxicity as above.