18 Poisoning
Care of the unconscious patient
• All self-ventilated patients should be nursed in the left lateral position with the lower leg straight and the upper leg flexed; in this position the risk of aspiration is reduced. A clear passage for air should be ensured.
• Nursing care of the mouth and pressure areas should be instituted. Immediate catheterization of the bladder in unconscious patients is usually unnecessary, as it can be emptied by gentle suprapubic pressure.
• Insertion of a venous cannula is usual, but administration of IV fluids is unnecessary unless the patient has been unconscious for more than 12 hours or is hypotensive.
Ventilatory support
• If respiratory depression is present, as determined by pulse oximetry or preferably by arterial blood gas (ABG) analysis, an oro-pharyngeal airway should be inserted and oxygen should be administered.
• The gag reflex can be assessed by positioning the patient on one side and making him or her gag using a suction tube.
Cardiovascular support
• Although hypotension (systolic BP < 80 mmHg) is a recognized feature of acute poisoning, the classic features of shock — tachycardia and pale cold skin — are observed only rarely.
• In patients with marked hypotension, volume expansion with crystalloids should be used, guided by monitoring of central venous pressure (CVP).
Other problems
• Hypothermia: rectal temperature below 35°C. The patient should be covered with a ‘space blanket’ and, if necessary, given IV and fluids at normal body temperature. The administration of heated (37°C), humidified oxygen delivered by face mask is also useful.
• Skin blisters: may be found in poisoned patients who are, or have been, unconscious. Such lesions are not diagnostic of specific poisons, but are sufficiently common in poisoned patients (and sufficiently uncommon in patients unconscious from other causes) to be of diagnostic value.
• Rhabdomyolysis: can occur from pressure necrosis in drug-induced coma, or it may complicate, for example, ecstasy (MDMA) use in the absence of coma. Patients with rhabdomyolysis are at risk of developing:
• Convulsions: occur, for example, in poisoning due to tricyclic antidepressants, mefenamic acid or opioids. Usually the seizures are short-lived, but if they are prolonged, diazepam 10–20 mg IV or lorazepam 4 mg IV should be administered.
• Stress ulceration and bleeding: measures to prevent stress ulceration of the stomach should be started on admission in all patients who are unconscious and require intensive care. A proton pump inhibitor, e.g. omeprazole 40 mg, should be administered intravenously over 5 mins or as an infusion over 20–30 mins.
Reduction of poison absorption
• Poison absorption through the lungs is reduced by moving the person from the toxic atmosphere, without the rescuers themselves being put at risk.
• Contaminated clothing should be removed to reduce dermal absorption. In addition, contaminated skin should be washed thoroughly with soap and water.
• The efficacy of current methods for the removal of unabsorbed drugs from the gastrointestinal tract remains unproven. Efforts to remove small amounts of non-toxic drugs are not worthwhile or appropriate.
Gastric lavage
• Gastric lavage should not be used routinely. It is used if a patient has ingested a potentially life-threatening amount of a poison and the procedure is undertaken within 60 mins of ingestion. Even then, clinical benefit has not been confirmed in controlled studies.
Single-dose activated charcoal
• The effectiveness of activated charcoal decreases with time. (In volunteers the mean reduction in absorption was 40%, 16% and 21% at 1 hour, 2 hours and 3 hours.) Activated charcoal should therefore only be used in those who have ingested a potentially toxic amount of a poison (known to be adsorbed by charcoal) up to 1 hour previously. There are insufficient data to support or exclude its use after 1 hour.
Increasing poison elimination
Urine alkalinization
• Before commencing urine alkalinization, correct plasma volume depletion and hypokalaemia, as administration of sodium bicarbonate will exacerbate pre-existing hypokalaemia.
• Sodium bicarbonate, most conveniently administered as an 8.4% solution (1 mmol bicarbonate/mL), is infused intravenously to ensure that the pH of the urine, which is measured by narrow-range indicator paper or a pH meter, is > 7.5 and preferably close to 8.5. In most cases the administration of 225 mmol bicarbonate will be required to produce urine alkalinization initially.
Multiple-dose activated charcoal (MDAC)
• Multiple doses of activated charcoal aid the elimination of some drugs from the circulation by interrupting their entero-hepatic and enter-enteric circulations.
• MDAC should be used only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine or theophylline.
Haemodialysis, haemodiafiltration and haemofiltration (p. 358)
• Haemodialysis is of little value in patients who ingest poisons with large volumes of distribution, e.g. tricyclic antidepressants, because the plasma contains only a small proportion of the total amount of drug in the body.
• Haemodialysis is indicated in patients with severe features and high plasma concentrations of ethanol, ethylene glycol, isopropanol, lithium, methanol or salicylate.
• Although haemofiltration and haemodiafiltration are widely available and increase elimination of poisons such as ethylene glycol and methanol, haemofiltration is much less efficient than haemodialysis and therefore should not be used unless haemodialysis is unavailable. Haemodiafiltration is preferable to haemofiltration.
Specific poisons
Specific management for each poison is set out below alphabetically. Antidotes are available for only a small number of poisons (Table 18.1) and dosage recommendations are given under each poison.
| Poison | Antidote |
|---|---|
| Anticoagulants (oral) | Vitamin K1 |
| Arsenic | DMSA* Dimercaprol (BAL) |
| Benzodiazepines | Flumazenil |
| β-adrenoceptor-blocking drugs | Atropine Glucagon |
| Carbon monoxide | Oxygen |
| Copper | DMPS† |
| Cyanide | Oxygen Dicobalt edetate Hydroxocobalamin Sodium nitrite Sodium thiosulphate |
| Diethylene glycol | Fomepizole, ethanol |
| Digoxin | Digoxin-specific antibody fragments |
| Ethylene glycol | Fomepizole, ethanol |
| Iron salts | Desferrioxamine (deferoxamine) |
| Lead (inorganic) | Sodium calcium edetate DMSA* |
| Methaemoglobinaemia | Methylthioninium chloride (methylene blue) |
| Methanol | Fomepizole, ethanol |
| Mercury (inorganic) | DMPS† |
| Nerve agents | Atropine Pralidoxime, obidoxime |
| Opioids | Naloxone |
| Organophosphorus insecticides | Atropine Pralidoxime, obidoxime |
| Paracetamol | Acetylcysteine |
| Thallium | Berlin (Prussian) blue |
* Dimercaptosuccinic acid (succimer).
† 2,3-dimercaptopropanesulfonate (unithiol).
Acetone
Clinical features
• Acetone has an irritating effect on the mucous membranes of the eyes, nose and throat, causing burning and erythema. It also causes reversible corneal injury.
Treatment
• Give 50–100 g of activated charcoal in an adult who presents within 1 hour of a substantial ingestion, providing the airway is secure. In vitro studies suggest that acetone is adsorbed to activated charcoal.
• Monitor blood glucose 1–2-hourly in symptomatic patients and correct hyperglycaemia with insulin. Take blood for renal and liver function assessment and measurement of creatine kinase activity.
Amfetamines
The N-methylated derivative, metamfetamine, is now used widely; the crystalline form of this salt is known as ‘crystal meth’ or ‘ice’. Ecstasy (MDMA) is discussed on page 675.
Clinical features
• Euphoria, extrovert behaviour, a lack of desire to eat or sleep, tremor, dilated pupils, tachycardia and hypertension are seen.
• More severe intoxication is associated with agitation, paranoid delusions, hallucinations and violent behaviour.
Treatment
• Monitor electrolytes, renal function, liver function and creatine kinase (because of rhabdomyolysis) activity.
• Agitation may be controlled by diazepam 10–20 mg IV or haloperidol 2.5–5.0 mg IV or IM in an adult.
• The peripheral sympathomimetic actions of amfetamines (e.g. hypertension and arrhythmias) are antagonized by β-adrenoceptor blocking drugs (e.g. propranolol 40–80 mg orally or 1–5 mg IV slowly).
• Treat rhabdomyolysis conventionally with aggressive IV fluids to maintain high urine flow. There are theoretical reasons why urine alkalinization (p. 663) may be helpful in preventing or reducing the severity of rhabdomyolysis-induced kidney injury.
Anticonvulsants
See carbamazepine (p. 671), gabapentin (p. 677), lamotrigine (p. 679), phenytoin (p. 688) and sodium valproate (p. 691).
Antidepressants
See selective serotonin reuptake inhibitors (p. 690), mirtazapine (p. 681), monoamine oxidase inhibitors (p. 682), tricyclic antidepressants (p. 692) and venlafaxine (p. 693).
Batteries
Treatment
• Endoscopic removal is used for batteries lodged in the oesophagus or batteries that remain in the stomach more than 48 hours after ingestion, as they are at greater risk of leaking.
• If a small battery lies within the stomach on the first X-ray and patients are asymptomatic, they can be observed at home and return if any gastrointestinal symptoms develop. The stools should be inspected to confirm successful passage.
Beta2-adrenoceptor agonists
Clinical features
Treatment
• Severe hypokalaemia should be corrected as soon as possible, by administration of potassium 40–60 mmol/hour, diluted with 0.9% saline. As patients given potassium may develop significant hyperkalaemia during recovery, potassium concentrations should be monitored closely.
• A non-selective β-blocker, e.g. propranolol 1–5 mg, can be administered by slow IV injection to reverse hypokalaemia and sinus tachycardia but may exacerbate pre-existing obstructive pulmonary disease. Propranolol is more effective than atenolol in reversing the metabolic effects of salbutamol.
Beta-adrenoceptor-blocking drugs
Clinical features
• Widened QRS and ventricular dysrhythmias, first-degree heart block, intraventricular conduction defects, right and left bundle branch block, ST segment elevation, the Brugada syndrome, ventricular extrasystoles and absent P waves may also be seen on ECG.
Treatment
• IV glucagon 10 mg (150 mc/kg) in an adult is the treatment of choice for significant hypotension that persists despite volume replacement. This dose can be repeated every 3–5 mins but if there is no response it is unlikely that further boluses will be helpful. IV glucagon at this dose causes vomiting and should be given slowly. It can be diluted in 5% glucose and infused over 15 mins if necessary.
• Standard inotropes e.g. dobutamine may be added. Insulin and glucose therapy (hyperinsulinaemic euglycaemic therapy) is used experimentally in severe poisoning.
• If bradycardia is refractory to atropine 0.6–1.2 mg IV, repeated as necessary, and IV glucagon, transcutaneous or transvenous pacing may be necessary.
• If there is a favourable response in BP and/or pulse rate to glucagon, commence a glucagon infusion 5–10 mg/hour depending on response. Monitor blood glucose during glucagon therapy.
Benzodiazepines
Treatment
• If respiratory depression is present, flumazenil 0.5–1 mg IV should be administered in an adult and this dose may be repeated, if necessary.
• If the patient does not respond to flumazenil 1 mg it is likely that another respiratory depressant has been co-ingested.
Calcium channel blockers
Clinical features
• The ECG may progress from sinus bradycardia through first, then higher, degrees of block, to asystole.
Treatment
• Observe with cardiac and BP monitoring for at least 12 hours following overdose of a non-sustained-release preparation and at least 24 hours following overdose of a sustained-release preparation.
• Treat hypotension initially with IV crystalloid, 0.9% saline at a rate and volume appropriate to the age and co-morbidity of the patient. Expanding the intravascular volume in this way may be the only measure required in patients with hypotension secondary to peripheral vasodilatation who do not have evidence of impaired cardiac conduction.
• Correct metabolic acidosis that persists despite fluid resuscitation and adequate ventilation with 50–100 mmol of 8.4% sodium bicarbonate IV.
• Treat bradycardia with IV atropine 0.6–1.2 mg in an adult. This dose can be repeated as required. The response to atropine may be improved following parenteral calcium administration (see below).
• If there is evidence of cardiac conduction block, give 10% calcium chloride 5–10 mL IV (at 1–2 mL/min), or calcium gluconate solution, 10–20 mL to an adult. The initial dose can be repeated every 3–5 mins but if there is no response in BP or pulse rate after three such doses it is unlikely that further boluses will be helpful.
• If there is an initial response to calcium, give a continuous infusion; this may be given as 10% calcium chloride, 1–10 mL/hour. Serum calcium should be measured but note that modest hypercalcaemia is the aim of treatment.
• If significant hypotension persists despite volume replacement, give IV glucagon (see p. 668 for details).
• If there is a favourable response in BP to glucagon, commence a glucagon infusion 5–10 mg/hour depending on response. Monitor blood glucose during glucagon therapy.
• If hypotension persists despite the above measures administer a sympathomimetic amine intravenously. If hypotension is thought to be mainly due to reduced systemic vascular resistance, high-dose dopamine 10–30 mcg/kg/min is a reasonable choice. Alternatively, administer adrenaline (epinephrine) 0.1–1 mcg/kg/min.
• Insulin/glucose euglycaemia improves myocardial contractility and systemic perfusion and is used as an adjuvant to sympathomimetic amine therapy. Check serum potassium before commencing insulin/glucose and if it is < 3.0 mmol/L give 20 mmol K+ over 30 mins. If there is severe hypotension, give a loading bolus of IV 50 mL 50% glucose plus insulin 1.0 U/kg. An infusion of 10% glucose should be given, along with an infusion of insulin 0.5–1.0 U/kg/hour. Check blood sugar every 20 mins to determine the patient’s insulin and glucose requirements, then check hourly. Check serum potassium hourly and replace as necessary.
Cannabis (marijuana)
Clinical features
• Euphoria, distorted and heightened images, colours and sounds, altered tactile sensations, sinus tachycardia, hypotension and ataxia occur.
Carbamazepine
Carbon monoxide
• Carbon monoxide combines with haemoglobin to form carboxyhaemoglobin (COHb), thereby reducing the total oxygen-carrying capacity of the blood and increasing the affinity of the remaining haem groups for oxygen. This shifts the oxyhaemoglobin dissociation curve to the left, impairing liberation of oxygen to the cells. Tissue hypoxia results.
Clinical features
• Symptoms of mild to moderate exposure to carbon monoxide may be mistaken for a viral illness with headache, dizziness, nausea and vomiting.
• A peak COHb concentration of ≤ 10% is not normally associated with symptoms. Peak COHb concentrations of 10–30% may result only in headache and mild exertional dyspnoea.
Treatment
• In addition to removing the patient from carbon monoxide exposure, administer high-flow oxygen using a tight-fitting face mask.
• Measure ABGs. Metabolic acidosis (p. 382) with normal oxygen tension but reduced oxygen saturation is characteristic.
Chloroquine
Cocaine
Clinical features
Treatment
• Sedation with diazepam 10–20 mg IV, repeated as necessary, is effective in controlling agitation in adults.
• Hypertension and tachycardia usually respond to sedation and cooling. If hypertension persists, give IV nitrates such as glyceryl trinitrate starting at 1–2 mg/hour and gradually increase the dose (maximum 12 mg/hour) until BP is controlled. Calcium channel blockers such as nifedipine, verapamil or diltiazem are an alternative as second-line therapy. The use of β-blockers is controversial.
Copper
Clinical features
Corrosive ingestions
Clinical features
• Ingestion causes immediate pain, with pharyngeal oedema and burns. Drooling is common. Features of pharyngeal involvement include hoarseness, stridor, respiratory distress and laryngeal and/or epiglottic oedema. Perforation of the oesophagus or stomach may occur and can lead to chemical peritonitis.
Treatment
• The presence of laryngopharyngeal oedema requires expert assessment for the risk of airway compromise and need for intubation.
• Early endoscopy by an expert endoscopist is essential to grade the severity of injury. If drooling, severe pain or stridor is present, endoscopy should be undertaken immediately.
• Early surgical intervention may prevent life-threatening haemorrhage and perforation, and is the treatment of choice in those with severe oesophageal or gastric burns.
Cyanide
Cyanide reversibly inhibits cytochrome oxidase a3 so that cellular respiration ceases.
Clinical features
Treatment
• Oxygen should be administered, as it prevents inhibition of cytochrome oxidase a3 and accelerates its reactivation.
• Dicobalt edetate or hydroxocobalamin should then be given; hydroxocobalamin is much more expensive than dicobalt edetate.
• Dicobalt edetate solutions contain free cobalt, which complexes six times more cyanide than dicobalt edetate itself. Cobalt is toxic, however, and the use of this formulation in the absence of cyanide poisoning may cause cobalt toxicity. Dicobalt edetate 300 mg IV should therefore be administered only when the diagnosis is certain; the dose may be repeated in severe cases.
• If these two preferred antidotes are not available, sodium nitrite 30 mg IV and sodium thiosulphate 12.5 mg IV should be administered (preferred treatment in the USA). Sodium nitrite produces methaemoglobinaemia; methaemoglobin combines with cyanide to form cyanmethaemoglobin. As the effect of sodium nitrite is relatively rapid and methaemoglobin formation slower, the benefit of sodium nitrite may also be from its vasodilator action and the consequent improved tissue perfusion. Sodium thiosulphate enhances endogenous cyanide detoxification mechanisms.
Digoxin
Toxicity occurring during chronic administration is common; acute poisoning is infrequent.
Clinical features
• These include nausea, vomiting, dizziness, anorexia and drowsiness. Rarely, confusion, visual disturbances and hallucinations occur. Sinus bradycardia is often marked and may be followed by supraventricular arrhythmias with or without heart block, ventricular premature beats and ventricular tachycardia.
Treatment
• Sinus bradycardia, atrioventricular block and sinoatrial standstill are often reduced or abolished by atropine 1.2–2.4 mg IV.
• The indications for digoxin-specific antibody therapy are significant hyperkalaemia and marked arrhythmias, usually severe bradycardia compromising cardiac output and, more rarely, ventricular arrhythmias and asystole.
• In patients not prescribed digoxin, serum digoxin concentrations do not equate to the total body burden, as tissue distribution will not have occurred. Calculations using serum concentrations are therefore likely to result in too much antibody being administered. It is recommended that half the calculated dose (based on serum concentration or ingested dose) should be administered and the impact on clinical features observed.
• In patients who are prescribed digoxin and develop poisoning, the serum digoxin concentration will reflect the total body load. However, since such patients are receiving digoxin for therapeutic purposes, full neutralization is again not indicated. Half the calculated dose, based on serum concentration, should be administered.
• To calculate the total body burden of digoxin, multiply serum concentration in mcg/L (nmol/L × 1.28) × weight (kg) × volume of distribution (adults 8 L/kg, children 2–10 years 13 L/kg, infants 2–24 months 16 L/kg, neonates 10 L/kg). As one 40 mg vial of digoxin-specific antibody binds 0.6 mg of digoxin, the total calculated number of 40 mg vials required = total body burden/0.6. This number is then halved.
Ecstasy (3,4-methylenedioxymethamfetamine; MDMA)
Clinical features
• Mild cases are characterized by agitation, tachycardia, hypertension, widely dilated pupils, trismus and sweating.
• Hyperthermia, hyponatraemia, cerebral oedema, seizures, disseminated intravascular coagulation, rhabdomyolysis, severe hepatic damage including fulminant hepatic failure (experimentally, hyperthermia potentiates ecstasy-induced hepatotoxicity), and acute kidney injury predominate in more severe cases.
Ethanol
Clinical features
Treatment
• Supportive measures are all that is required for most patients with acute ethanol intoxication, even if the blood ethanol concentration is very high. Particular care should be taken to protect the airway.
• Lactic acidosis requires correction of hypoglycaemia, hypovolaemia and circulatory insufficiency, if present. An infusion of sodium bicarbonate 50–100 mmol will be necessary in those patients in whom a lactic acidosis persists.
• Blood sugar should be determined hourly and the rate of IV glucose adjusted accordingly. If blood sugar concentrations fall despite an infusion of 5–10% glucose, a 20% glucose solution 50 mL IV should be given; hypoglycaemia is usually unresponsive to glucagon.
Ethylene and diethylene glycols
Clinical features
• The features observed are due to the metabolites predominantly, not the parent chemical. Ethylene glycol is oxidized by alcohol dehydrogenase to glycoaldehyde. Aldehyde dehydrogenase rapidly converts glycoaldehyde to glycolate. The conversion of glycolate to glyoxylate is slow. A small proportion of glyoxylate is metabolized to oxalate. Calcium ions chelate oxalate to form insoluble calcium oxalate monohydrate crystals. Diethylene glycol is metabolized by alcohol dehydrogenase to 2-hydroxyethoxyacetaldehyde and by aldehyde dehydrogenase to 2-hydroxyethoxyacetate (2-HEAA).
• Initially, the features of ethylene glycol (in antifreeze and windscreen de-icer) poisoning are similar to ethanol intoxication (though there is no ethanol on the breath). Coma and convulsions follow and a variety of neurological abnormalities, including nystagmus and ophthalmoplegias, may be observed. Severe metabolic acidosis, hypocalcaemia and the presence of calcium oxalate crystalluria are well-recognised complications.
Treatment
• Supportive measures to combat cardiorespiratory depression should be employed and metabolic acidosis, hypocalcaemia and acute kidney injury should be treated conventionally.
• If the patient presents early after ingestion, the priority is to inhibit metabolism of ethylene or diethylene glycol using either IV fomepizole or ethanol (if fomepizole is not available). Do not wait for confirmatory blood concentrations before starting treatment.
• Fomepizole 15 mg/kg should be administered over 30 mins, followed by four 12-hourly doses of 10 mg/kg and then by 15 mg/kg 12-hourly until the glycol concentration is not detectable. If haemodialysis or haemodiafiltration is used, the frequency of dosing should be increased to 4-hourly, as fomepizole is dialysable.
• Alternatively, a loading dose of IV ethanol 50 g for an adult (50 mL of absolute ethanol in 1 L 5% glucose, i.e. a 5% ethanol solution) should be given, followed by an IV infusion of ethanol 10–12 g/hour (most easily given as 1 L 5% ethanol solution over 4–5 hours), to achieve a blood ethanol concentration of ~1000 mg/L. Administration of ethanol should be continued until the glycol is undetectable in the blood. If dialysis is used, greater amounts of ethanol (17–22 g/hour) must be given, because ethanol is readily dialysable. Ideally, glycol and ethanol concentrations should be measured frequently until recovery.
• Haemodialysis and haemodiafiltration remove glycol, glycolaldehyde and glycolate, but not oxalate, and will also correct acid–base disturbances; haemodialysis is 2–3 times more efficient than peritoneal dialysis. Haemodialysis or haemodiafiltration should be employed, particularly if presentation is late and marked metabolic acidosis is present. Dialysis should be continued until the glycol and glycolate are no longer detectable in the blood.
Gamma-hydroxybutyrate (GHB)
Clinical features
• Low doses cause mild agitation, excitement, nausea and vomiting with euphoria and possibly hallucinations at higher doses progressing to coma, bradycardia and respiratory depression in the most severely poisoned.
• The most unique aspect of GHB intoxication is its brief duration. Patients may progress from deep coma requiring intubation to self-extubation and full alertness over only a few hours.
Household products
• If the ingestion of these products is accidental and in children ≤ 5 years old, features very rarely occur, except in the case of petroleum distillates (p. 687).
Iron
Clinical features
• The initial features are nausea, vomiting (the vomit may be grey or black in colour), abdominal pain and diarrhoea.
Treatment
• The serum iron concentration should be measured some 4 hours after ingestion. If the concentration exceeds 5 mg/L (90 µmol/L), free iron is circulating and treatment with desferrioxamine 15 mg/kg/hour IV is used (total amount of infusion not usually to exceed 80 mg/kg in 24 hours).
• If a patient develops coma or shock, desferrioxamine (deferoxamine) should be given without delay.
Isopropanol
This is more toxic than ethanol and is the base for many hand washes.
Treatment
• Activated charcoal does not bind isopropanol. Gastric lavage is unlikely to be of value, as its absorption is rapid.
• Isopropanol has a small volume of distribution (0.6–0.7 L/kg) and is responsible (together with its metabolite, acetone, p. 358) for toxicity. Haemodialysis or haemodiafiltration may therefore be helpful in severely poisoned patients in whom the plasma isopropanol concentrations are high. Acetone is also removed effectively by haemodialysis or haemodiafiltration.
Lead
Clinical features
Treatment
• Identification of the source of lead exposure and prevention of further exposure are the priorities.
• The decision to use chelation therapy is based not only on the blood lead concentration but also on the presence of symptoms.
• Give either IV sodium calcium edetate 75 mg/kg/day or oral dimercaptosuccinic acid (DMSA) 30 mg/kg/day. These antidotes are of similar efficacy and the choice is usually determined by availability and whether an oral agent is feasible.
• Chelation therapy should be continued for 5 days, or until the 24-hour urine lead excretion is no longer substantially greater than pre-chelation urine lead excretion.
• During chelation, measure plasma electrolyte and creatinine concentrations daily, particularly with sodium calcium edetate, since transiently impaired renal function is a potential adverse effect of this agent.
Lithium
Clinical features
Mercury
Clinical features
• Acute mercury vapour inhalation causes headache, conjunctivitis, cough, nausea and vomiting, dyspnoea and chest pain. Chemical pneumonitis occurs and, in severe cases, renal and/or liver failure may occur.
• Repeated exposure to low mercury vapour concentrations presents typically with characteristic neurological features such as fine tremor, lethargy, memory loss, insomnia, personality changes and ataxia. Other features include stomatitis, gingivitis, hypersalivation and renal tubular damage. Mixed motor and sensory peripheral neuropathy may develop.
Treatment
• Perform an X-ray if elemental mercury has been injected or ingested, as elemental mercury is radiopaque.
• Respiratory features following acute mercury vapour inhalation require only symptomatic and supportive measures.
• Soft-tissue deposits of elemental mercury usually require surgical excision, preferably under X-ray control.
• If there is analytical evidence of a substantial body burden of mercury and symptoms of mercury poisoning, chelation therapy with IV DMPS 30 mg/kg/day (typically for 5 days) is used. Where extracorporeal renal support is required for the management of acute kidney injury, there is some evidence that continuous venous–venous haemofiltration is more effective than haemodialysis at removing DMPS–mercury complexes.
Methanol
This is found in windscreen washer fluid, antifreeze and duplicator fluid.
Clinical features
• Patients often present after a delay of several hours, with nausea, vomiting, abdominal pain, tachypnoea, inebriation and drowsiness; after a latent period coma supervenes.
• Blurred vision and diminished visual acuity occur. The presence of dilated pupils that are unreactive to light suggests that permanent blindness is likely to occur.
• A severe metabolic acidosis may develop and be accompanied by hyperglycaemia and a raised serum amylase activity.
Mirtazapine
This is a 5HT2 and 5HT3 receptor agonist and a potent α2-adrenergic blocker.
Monoamine oxidase inhibitors
Clinical features
Neuroleptics and atypical neuroleptics
Clinical features
• These include impaired consciousness, hypotension, respiratory depression, hypothermia or hyperthermia, antimuscarinic effects such as tachycardia, dry mouth and blurred vision, occasionally seizures, rhabdomyolysis, cardiac arrhythmias (both atrial and ventricular) and ARDS.
Treatment
• Correct metabolic acidosis that persists despite fluid resuscitation and adequate ventilation with 50–100 mmol of sodium bicarbonate (50–100 mL of 8.4% sodium bicarbonate). IV administration of 8.4% sodium bicarbonate must be through a wide-bore cannula that has been tested for patency since it will cause tissue necrosis if extravasation occurs. Alternatively, administer sodium bicarbonate through a central venous line.
• Procyclidine 5–10 mg IV or IM in an adult is occasionally required for the treatment of dyskinesia and oculogyric crisis.
• Single brief convulsions do not require treatment. If frequent or prolonged, control with IV diazepam 10–20 mg in an adult.
Opiates and opioids
Treatment
• Naloxone 1.2 mg IV in an adult (5–10 mcg body weight in a child) will reverse severe respiratory depression and coma, at least partially.
Organophosphorus insecticides
These insecticides inhibit acetylcholinesterase, allowing accumulation of acetylcholine.
Clinical features
• Poisoning is characterized by anxiety, restlessness, headache, and muscarinic features such as nausea, vomiting, abdominal colic, diarrhoea, sweating, hypersalivation and chest tightness.
• Nicotinic effects include muscle fasciculation and flaccid paresis of limb muscles, respiratory and, occasionally, extra-ocular muscles.
Paracetamol (acetaminophen)
Clinical features
• Following the ingestion of an overdose of paracetamol, patients usually remain asymptomatic or may have nausea and vomiting and abdominal pain.
• Liver damage is not usually detectable by routine LFTs until at least 18 hours after ingestion of the drug.
Treatment
• The treatment protocol is dependent on the time of presentation (Fig. 18.1) and this is summarized in Box 18.1. IV acetylcysteine is an effective protective agent, provided that it is administered within 8–10 hours of ingestion of the overdose.
• Some 10% of patients treated with IV acetylcysteine (20.25-hour regimen) develop rash, angio-oedema, hypotension and bronchospasm.
• These reactions, which are related to the initial bolus, are seldom serious and temporarily discontinuing the infusion is usually all that is required.
• If liver or renal failure ensues, this should be treated conventionally, though there is evidence that a continuing infusion of acetylcysteine (continue 16-hour infusion until recovery) will improve the morbidity and mortality.
• Liver transplantation has been performed successfully in patients with paracetamol-induced fulminant hepatic failure using established criteria (p. 187).
Fig. 18.1 Nomogram of paracetamol. For definition of ‘high risk’, see text.
(British National Formulary 2009, with permission.)
Box 18.1 Management of patients with paracetamol poisoning
≤ 8 hours after ingestion
• Take blood for urgent estimation of the plasma paracetamol concentration as soon as 4 hours or more have elapsed since ingestion. Check INR, plasma creatinine and ALT activity
• Assess whether the patient is at increased risk of liver damage. Patients with pre-existing liver disease, those with a high alcohol intake and poor nutrition, those receiving enzyme-inducing drugs, and those suffering from anorexia nervosa and other eating disorders (including those who have starved for 2–3 days during an intercurrent illness) or HIV infection should be considered to be at greater risk and given treatment at plasma paracetamol concentrations lower than those normally used for interpretation, i.e. according to the ‘high-risk line’ (Fig. 18.1)
• If needed, give acetylcysteine 150 mg/kg over 15 min, then 50 mg/kg over the next 4 hours and then 100 mg/kg over the ensuing 16 hours (total dose 300 mg/kg over 20.25 hours)
8–15 hours after ingestion
• Urgent action is required because the efficacy of treatment declines progressively from 8 hours after overdose. If > 150 mg/kg paracetamol has been ingested, start treatment immediately
• Take blood for urgent estimation of the plasma paracetamol concentration, INR, plasma creatinine and ALT activity
• In patients already receiving treatment, only discontinue if the plasma paracetamol concentration is below the relevant treatment line (Fig. 18.1), there is no abnormality of the INR, plasma creatinine or ALT activity, and the patient is asymptomatic. Do not discontinue the infusion if there is any doubt as to the timing of the overdose
15–36 hours after ingestion
• Urgent action is required because the efficacy of treatment is limited more than 15 hours after overdose. Start treatment immediately if > 150 mg/kg paracetamol has been ingested
• In all patients, take blood for urgent estimation of the plasma paracetamol concentration, INR, plasma creatinine and ALT activity
Paraquat
Clinical features
• Mild poisoning follows the ingestion of < 20 mg of paraquat ion/kg body weight. Patients are asymptomatic or develop vomiting and diarrhoea. Full recovery occurs but there may be a transient fall in the gas transfer factor and vital capacity.
• Moderate to severe poisoning follows the ingestion of 20–40 mg of paraquat ion/kg body weight. Vomiting and diarrhoea occur and pulmonary fibrosis develops in all cases. In addition, kidney injury and, sometimes, hepatic dysfunction may supervene. Death occurs in the majority of cases but can be delayed for 2 or 3 weeks.
• Acute fulminant poisoning follows the ingestion of more than (usually considerably in excess of) 40 mg of paraquat ion/kg body weight. In addition to nausea and vomiting, there is marked ulceration of the oropharynx with multiple organ (cardiac, respiratory, hepatic, renal, adrenal, pancreatic, neurological) failure. The mortality is 100%. Death commonly occurs within 24 hours of ingestion and is never delayed for more than 1 week.
Petroleum distillates
Clinical features
• After ingestion, nausea and vomiting are likely but systemic toxicity is not expected unless aspiration has occurred since absorption of petroleum distillates from the gastrointestinal tract is poor.
• Aspiration causes chemical pneumonitis. Signs and symptoms progress over 24–48 hours with wheeze, breathlessness, dyspnoea, tachypnoea, bronchospasm, hypoxia, cyanosis, fever and leucocytosis.
Treatment
• Patients with significant respiratory compromise need urgent supportive measures (oxygen, bronchodilators).
• All patients with a definite history of ingestion should have a CXR since radiological abnormalities may be present even in asymptomatic patients. However, the X-ray should be delayed until at least 6 hours post ingestion in those who have no or only minimal symptoms at presentation.
Plant toxins
Yellow oleander (Thevetia peruviana)
• Treatment
• Sinus bradycardia, atrioventricular block and sinoatrial standstill are often reduced or abolished by atropine 1.2–2.4 mg IV.
• The administration of IV digoxin-specific antibody fragments (see digoxin poisoning, p. 675) has been shown in an RCT to reverse yellow oleander-induced arrhythmias rapidly, restore sinus rhythm, and reverse bradycardia and hyperkalaemia rapidly.
Gloriosa superba
• Clinical features Severe abdominal pain, vomiting, diarrhoea (sometimes bloody), electrolyte imbalance, hypovolaemia and shock occur.
Quinine
Salicylates
Clinical features
Treatment
• Severe metabolic acidosis requires at least partial correction with the administration of sodium bicarbonate 50–100 mmol intravenously (p. 382).
• Mild cases of salicylate poisoning may be managed with parenteral fluid and electrolyte replacement only.
Selective serotonin reuptake inhibitors (SSRIs)
Snake bites
Clinical features
• Viperidae (Viperinae and Crotalinae) Russell’s viper causes most of the snake-bite mortality in India, Pakistan and Myanmar.
• Evidence of systemic involvement (envenomation) occurs within 30 mins, including vomiting, evidence of shock and hypotension.
• Elapidae There is usually no swelling at the site of the bite, except with Asian cobras and African spitting cobras — here the bite is painful and is followed by local tissue necrosis.
Treatment
• A firm pressure bandage should be placed over the bite and the limb immobilized, which may delay the spread of the venom. Arterial tourniquets should not be used, and incision or excision of the bite area should not be performed.
• In about 50% of cases no venom has been injected by the bite. Nevertheless, careful observation for 12–24 hours is necessary in case envenomation develops.
• General supportive measures include IV fluids with volume expanders for hypotension and diazepam 5–10 mg for anxiety.
• Some forms of neurotoxicity, such as those induced by the death adder, have responded to therapy with neostigmine and atropine.
• Antivenoms are not generally indicated unless envenomation is present, as they can cause severe allergic reactions. They can rapidly neutralize venom, but only if an amount in excess of the amount of venom is given. Large quantities may be required. As antivenoms cannot reverse the effects of the venom, they must be given early to minimize some of the local effects and may prevent necrosis at the site of the bite. Antivenoms should be administered intravenously by slow infusion, the same dose being given to children and adults. Side-effects: allergic reactions are frequent, and adrenaline (epinephrine) 1 in 1000 solution should be available. In severe cases, the antivenom infusion should be continued, even if an allergic reaction occurs, with SC injections of adrenaline being given as necessary.
Sodium valproate
Clinical features
Treatment
• Early IV supplementation with carnitine (100 mg/kg, followed by 15 mg/kg every 4 hours) to reduce formation of hepatotoxic metabolites and ammonaemia, may improve survival in severe valproate-induced hepatotoxicity, although clinical benefit in terms of liver protection or hastening of recovery from unconsciousness has not been clearly established.
Theophylline
Clinical features
Treatment
• However, protracted theophylline-induced vomiting may mitigate the benefit of this therapy. Vomiting may be suppressed by, for example, ondansetron 8 mg IV in an adult.
Tricyclic antidepressants (TCAs)
Clinical features
• Features of poisoning usually begin within 60 mins of ingestion and reach maximum intensity in 6–12 hours.
• Drowsiness, sinus tachycardia, dry mouth, dilated pupils, urinary retention, increased reflexes and extensor plantar responses are the most common features of mild poisoning.
• Severe intoxication leads to coma, often with divergent strabismus and convulsions. Plantar, oculo-cephalic and oculo-vestibular reflexes may be abolished temporarily.
Treatment
• The majority of patients recover with supportive therapy alone (ingestion of < 20 mg/kg). Overdose of 35 mg/kg is a median lethal dose; > 50 mg/kg is likely to be fatal.
• Priority should be given to the correction of hypoxia, hypotension, electrolyte abnormalities and acidosis.
• Patients may deteriorate rapidly in the first few hours of poisoning and close cardiorespiratory monitoring is essential during this time.
• Establish IV access and give a crystalloid bolus, e.g. 0.9% saline 500–1000 mL to an adult, if hypotension is present.
• Correct metabolic acidosis that persists despite fluid resuscitation and adequate ventilation with IV 50–100 mmol of sodium bicarbonate (e.g. 50–100 mL of 8.4% sodium bicarbonate).
• Alkalinization (IV 1–2 mmol of sodium bicarbonate/kg) to a systemic pH of 7.45–7.55 may reverse TCA-induced cardiotoxicity even in the absence of acidosis.
• Avoid conventional anti-arrhythmic agents, particularly class Ia (e.g. procainamide) and class Ic (e.g. flecainide), as these will exacerbate TCA-induced cardiotoxicity.
• There may be an occasional role for class Ib (lidocaine) or class II (β-blockers) agents (or magnesium) in refractory ventricular arrhythmias.
• Treat sustained convulsions with IV diazepam 10–20 mg. Phenytoin is best avoided in TCA overdose because, in common with TCAs, it blocks sodium channels and may increase the risk of cardiac arrhythmias.
Venlafaxine
This antidepressant is a serotonin–noradrenaline (norepinephrine) reuptake inhibitor (SNRI).
Clinical features
Treatment
• Gastric lavage or the administration of oral activated charcoal 50–100 g to an adult is used if the patient presents within the first hour, although no clinical trials have confirmed the efficacy of either procedure.
• Correct metabolic acidosis that persists despite fluid resuscitation and adequate ventilation with IV 50–100 mmol of sodium bicarbonate (e.g. 50–100 mL of 8.4% sodium bicarbonate).
Warfarin (p. 245)
Clinical features
Treatment
• Routine measurement of the INR (p. 246) is unnecessary in young children, as they invariably ingest only very small amounts of warfarin.
• If active bleeding occurs, prothrombin complex concentrate (which contains factors II, VII, IX and X) 50 U/kg or fresh frozen plasma 15 mL/kg (if no concentrate is available) and phytomenadione 10 mg IV (100 mcg/kg body weight for a child) should be given, see p. 250 and Table 7.3.
• If there is no active bleeding and the INR is ≤ 4.0, treatment with phytomenadione is not required.
• If the INR is ≥4.0, phytomenadione 10 mg by slow intravenous injection (100 µg/kg body weight for a child) should be administered, unless the patient is anticoagulated for therapeutic reasons.
• If the patient is prescribed anticoagulants and the INR is ≥ 8.0, but there is no active bleeding or only minor bleeding, stop warfarin (restart when the INR ≤ 5.0), give phytomenadione 0.5 mg by slow intravenous injection and repeat the dose if the INR is ≥ 8.0 24 hours later.
Bailey B. Glucagon in β-blocker and calcium channel blocker overdoses: a systematic review. J Toxicol Clin Toxicol. 2003;41:595-602.
Barceloux D, McGuigan M, Hartigan-Go K, et al. Position paper: cathartics. J Toxicol Clin Toxicol. 2004;42:243-253.
Bateman DN. Digoxin-specific antibody fragments: how much and when? Toxicol Rev. 2004;23:135-143.
Bateman DN. Tricyclic antidepressant poisoning: central nervous system effects and management. Toxicol Rev. 2005;24:181-186.
Borron SW, Baud FJ, Barriot P, et al. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007;49:794-801.
Bradberry S, Sheehan T, Vale A. Use of oral dimercaptosuccinic acid (succimer; DMSA) in adult patients with inorganic lead poisoning. QJM. 2009;102:721-732.
Bradberry SM, Sheehan TMT, Barraclough CR, Vale JA. DMPS can reverse the features of severe mercury vapor-induced neurological damage. Clin Toxicol. 2009;47:894-898.
Bradberry SM, Thanacoody HKR, Watt BE, et al. Management of the cardiovascular complications of tricyclic antidepressant poisoning: role of sodium bicarbonate. Toxicol Rev. 2005;24:195-204.
Brent J. Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009;360:2216-2223.
British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary 58. London: BMJ Group and RPS Publishing; 2009.
Buckley NA, Isbister GK, Stokes B, Juurlink DN. Hyperbaric oxygen for carbon monoxide poisoning: a systematic review and critical analysis of the evidence. Toxicol Rev. 2005;24:75-92.
Chyka PA, Seger D, Krenzelok EP, et al. Position paper: single-dose activated charcoal. Clin Toxicol. 2005;43:61-87.
DeWitt CR, Waksman JC. Pharmacology, pathophysiology and management of calcium channel blocker and beta-blocker toxicity. Toxicol Rev. 2004;23:223-238.
Flamminger A, Maibach H. Sulfuric acid burns (corrosion and acute irritation): evidence-based overview of management. Cutan Ocul Toxicol. 2006;25:55-61.
Hall AP, Henry JA. Acute toxic effects of ‘ecstasy’ (MDMA) and related compounds: overview of pathophysiology and clinical management. Br J Anaesth. 2006;96:678-685.
Hoffman RS. Cocaine and β-blockers: should the controversy continue? Ann Emerg Med. 2008;51:127-129.
Krenzelok EP, McGuigan M, Lheureux P, et al. Position paper: ipecac syrup. J Toxicol Clin Toxicol. 2004;42:133-143.
Kulig K, Vale JA. Position paper: gastric lavage. J Toxicol Clin Toxicol. 2004;42:933-943.
Lheureux PE, Zahir S, Gris M, et al. Bench-to-bedside review: hyperinsulinaemia/euglycaemia therapy in the management of overdose of calcium-channel blockers. Crit Care. 2006;10:212.
Lheureux PER, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol. 2009;47:101-111.
Morgan M, Hackett LP, Isbister GK. Olanzepine overdose: a series of analytically confirmed cases. Int Clin Psychopharmacol. 2007;22:183-186.
Proudfoot AT, Krenzelok EP, Brent J, Vale JA. Does urine alkalinization increase salicylate elimination? If so, why? Toxicol Rev. 2003;22:129-136.
Proudfoot AT, Krenzelok EP, Vale JA. Position paper on urine alkalinization. J Toxicol Clin Toxicol. 2004;42:1-26.
Tenenbein M, Lheureux P. Position paper: whole bowel irrigation. J Toxicol Clin Toxicol. 2004;42:843-854.
Vale JA, Krenzelok EP, Barceloux DG, et al. Position statement and practice guidelines on the use of multi-dose activated charcoal in the treatment of acute poisoning. J Toxicol Clin Toxicol. 1999;37:731-751.
Waring WS, Good AM, Bateman DN. Lack of significant toxicity after mirtazapine overdose: a five-year review of cases admitted to a regional toxicology unit. Clin Toxicol. 2007;45:45-50.
