Stephen Haydock
Synopsis
Deliberate overdose with drugs is a common clinical problem. Poisoning may also occur as a result of accidental ingestion, occupational exposure and in the context of recreational substance use. The effective management of poisoning is based upon the use of general supportive measures, reduction of drug absorption or increase in elimination and the use of specific pharmacological agents (‘antidotes’). This chapter will examine:
• Background.
• Initial assessment.
• Resuscitation.
• Supportive treatment.
• Prevention of further absorption of the poison.
• Acceleration of elimination of the poison.
• Specific antidotes.
• Psychiatric and social assessment.
• Poisoning by non-drug chemicals: heavy metals, cyanide, methanol, ethylene glycol, hydrocarbons, volatile solvents, heavy metals, herbicides and pesticides.
• Poisoning by biological substances.
Introduction
The UK has one of the highest rates of deliberate self-harm in Europe. Deliberate self-harm involves intentional self-poisoning or self-injury irrespective of the intended purpose of that act. Self-poisoning is the commonest form of deliberate self-harm after self-mutilation. Poisoning, usually by medicines taken in overdose, is currently responsible for over 150 000 hospital attendances per annum in England and Wales (population 54 million). Prescribed drugs are involved in more than 75% of episodes, but teenagers tend to favour non-prescribed analgesics available by direct sale. In particular, over half of these involve ingestion of paracetamol, with the associated risk of serious toxicity. In order to address this problem the pack size of paracetamol was reduced to 8 g for non-prescription purchase and 16 g for prescription in the UK in 1998. Evidence suggests that this has not so far been effective in reducing paracetamol-related deaths but the mortality rate of self-poisoning overall is very low (less than 1% of acute hospital admissions with poisoning). The total number of deaths related to drug poisoning in England and Wales increased each year from 1993 to a peak in 1999, and then began to decline.
Most patients who die from deliberate ingestion of drugs do so before reaching medical assistance; overall only 11–28% of those who die following the deliberate ingestion of drugs reach hospital alive. The drugs most frequently implicated in hospital deaths of such individuals in the UK are paracetamol, tricyclic antidepressants and benzodiazepines. In India, deliberate self harm is seen with similar prescribed agents, together with frequent deliberate self harm with the antimalarial chloroquine and accidental or deliberate injury from pesticides such as the organophosphates or aluminium phosphide. In Sri Lanka deliberate pesticide ingestion is also a serious public health issue.
Accidental self-poisoning, causing admission to hospital, occurs predominantly among children under 5 years of age, usually from medicines left within their reach or with commonly available domestic chemicals, e.g. bleach, detergents.
Most patients who die from deliberate ingestion of drugs do so before reaching medical assistance. For those reaching hospital, the overall mortality is very low.
Initial assessment
It is important to obtain information on the poison that has been taken. The key pieces of information are:
• The identity of the substance(s) taken.
• The dose(s).
• The time that has elapsed since ingestion.
• Whether alcohol was also taken.
• Whether the subject has vomited since ingestion.
Adults may be sufficiently conscious to give some indication of the poison or may have referred to it in a suicide note, or there may be other circumstantial evidence e.g. knowledge of the prescribed drugs that the patient had access to, empty drug containers in pocket or at the scene. The ambulance crew attending to the patient at home may have very valuable information and should be questioned for any clues to the ingested drug. Any family or friends attending with the patient should be similarly questioned.
The response to a specific antidote may provide a diagnosis, e.g. dilatation of constricted pupils and increased respiratory rate after intravenous naloxone (opioid poisoning) or arousal from unconsciousness in response to intravenous flumazenil (benzodiazepine poisoning).
Many substances used in accidental or self-poisoning produce recognisable symptoms and signs. Some arise from dysfunction of the central or autonomic nervous systems; other agents produce individual effects. They can be useful diagnostically and provide characteristic toxic syndromes or ‘toxidromes’ (Table 10.1).
Table 10.1 Characteristic drug ‘toxidromes’
|
Toxidrome |
Clinical features |
Causative agents |
|
Antimuscarinic |
Tachycardia |
Antipsychotics |
|
Muscarinic |
Salivation |
Anticholinesterases |
|
Sympathomimetic |
Tachycardia |
In addition, sedatives, opioids and ethanol cause signs that may include respiratory depression, miosis, hyporeflexia, coma, hypotension and hypothermia. Other drugs and non-drug chemicals that produce characteristic effects include: salicylates, methanol and ethylene glycol, iron, selective serotonin reuptake inhibitors. Effects of overdose (and treatment) with other individual drugs or drug groups appear in the relevant accounts throughout the book.
Resuscitation
In concert with attempts to define the nature of the overdose it is essential to carry out standard resuscitation methods. Maintenance of an adequate oxygen supply is the first priority and the airway must be sucked clear of oropharyngeal secretions or regurgitated matter. Shock in acute poisoning is usually due to expansion of the venous capacitance bed and placing the patient in the head-down position to encourage venous return to the heart, or a colloid plasma expander administered intravenously restores blood pressure. External cardiac compression may be necessary and should be continued until the cardiac output is self-sustaining, which may be a long time when the patient is hypothermic or poisoned with a cardiodepressant drug, e.g. tricyclic antidepressant, β-adrenoceptor blocker.
External cardiac compression may be required for prolonged periods of cardiac arrest, up to several hours. In young patients the heart is anatomically and physiologically normal and will recover when the poison has been eliminated from the body.
Investigations may include arterial blood gas analysis and examination of plasma for specific substances that would require treatment with an antidote, e.g. with paracetamol, iron and digoxin.
Plasma concentration measurement is also used to quantify the risk. Particular treatments such as haemodialysis or urine alkalinisation may be indicated for overdose with salicylate, lithium and some sedative drugs, e.g. trichloroethanol derivatives, phenobarbital.
Rapid biochemical ‘screens’ of urine are widely available in hospital emergency departments and will detect a range of drugs (Table 10.2).
Table 10.2 Drugs that can be readily tested for and detected in urine in the emergency department
|
Drugs detectable on rapid urine testing |
|
• Amfetamine |
|
• Methamfetamine |
|
• Cannabis |
|
• Methadone |
|
• Benzodiazepines |
|
• Barbiturates |
|
• Phencyclidine (angel dust) |
|
• Opiates |
Supportive treatment
The majority of patients admitted to hospital will require only observation combined with medical and nursing supportive measures while they metabolise and eliminate the poison. Some will require specific measures to reduce absorption or to increase elimination. A few will require administration of a specific antidote. A very few will need intensive care facilities. In the event of serious overdose, always obtain the latest advice on management.
In the UK, regional medicines information centres provide specialist advice and information over the telephone throughout the day and night (0870 600 6266).
TOXBASE, the primary clinical toxicology database of the UK National Poisons Information Service, is available on the internet to registered users at: http://www.toxbase.org
The most efficient eliminating mechanisms are the patient's own physiological processes, which, given time, will inactivate and eliminate all the poison. Most patients recover from acute poisonings provided they are adequately oxygenated, hydrated and perfused.
Special problems introduced by poisoning are as follows:
• Airway maintenance is essential; some patients require a cuffed endotracheal tube but seldom for more than 24 h.
• Ventilation: a mixed respiratory and metabolic acidosis is common; the inspired air is supplemented with oxygen to correct the hypoxia. Mechanical ventilation is necessary if adequate oxygenation cannot be obtained or hypercapnia ensues.
• Hypotension: this is common in poisoning and, in addition to the resuscitative measures indicated above, conventional inotropic support may be required.
• In addition: there is recent interest in the use of high dose insulin infusions with euglycaemic clamping as a positive inotrope in the context of overdose with myocardial depressant agents. The very high insulin doses given (0.5–2 units/kg/h) have so far deterred physicians from the routine use of such therapy. There are, however, a number of case reports that support such an approach. Many of these are in the context of overdosage with non-dihydropyridine calcium channel blockers that are often resistant to conventional inotropic agents.
• Convulsions should be treated if they are persistent or protracted. Intravenous benzodiazepine (diazepam or lorazepam) is the first choice.
• Cardiac arrhythmia frequently accompanies poisoning, e.g. with tricyclic antidepressants, theophylline, β-adrenoceptor blockers.
• Acidosis, hypoxia and electrolyte disturbance are often important contributory factors and it is preferable to observe the effect of correcting these before considering resort to an antiarrhythmic drug. If arrhythmia does lead to persistent peripheral circulatory failure, an appropriate drug may be cautiously justified, e.g. a β-adrenoceptor blocker for poisoning with a sympathomimetic drug.
• Hypothermia may occur if CNS depression impairs temperature regulation. A low-reading rectal thermometer is used to monitor core temperature and the patient is nursed in a heat-retaining ‘space blanket’.
• Immobility may lead to pressure lesions of peripheral nerves, cutaneous blisters, necrosis over bony prominences, and increased risk of thromboembolism warrants prophylaxis.
• Rhabdomyolysis may result from prolonged pressure on muscles from agents that cause muscle spasm or convulsions (phencyclidine, theophylline); may be aggravated by hyperthermia due to muscle contraction, e.g. with MDMA (‘ecstasy’). Aggressive volume repletion and correction of acid–base abnormality are needed; urine alkalinisation and/or diuretic therapy may be helpful in preventing acute tubular necrosis but evidence is not conclusive.
Patients die from overdose:
• Early – from direct respiratory depression, fatal cardiac arrhythmias, fatal convulsions.
• Delayed – from organ damage consequent upon poorly managed cardiorespiratory support.
• Late – from delayed toxicity of the drug causing severe direct end organ damage, e.g. liver failure.
Preventing further absorption of the poison
From the environment
When a poison has been inhaled or absorbed through the skin, the patient should be taken from the toxic environment, the contaminated clothing removed and the skin cleansed.
From the alimentary tract (‘gut decontamination’)1
Gastric lavage should not be employed routinely, if ever, in the management of poisoned patients. Serious risks of the procedure include hypoxia, cardiac arrhythmias, laryngospasm, perforation of the GI tract or pharynx, fluid and electrolyte abnormalities and aspiration pneumonitis. Clinical studies show no beneficial effect. The procedure may be considered in very extraordinary circumstances for the hospitalised adult who is believed to have ingested a potentially life-threatening amount of a poison within the previous hour, and provided the airways are protected by a cuffed endotracheal tube. It is contraindicated for corrosive substances, hydrocarbons with high aspiration potential and where there is risk of haemorrhage from an underlying gastrointestinal condition.
Emesis using syrup of ipecacuanha is no longer practised in hospital, as there is no clinical trial evidence that the procedure improves outcome.
Oral adsorbents
Activated charcoal (Carbomix) consists of a very fine black powder prepared from vegetable matter, e.g. wood pulp, coconut shell, which is ‘activated’ by an oxidising gas flow at high temperature to create a network of small (10–20 nm) pores with an enormous surface area in relation to weight (1000 m2/g). This binds to, and thus inactivates, a wide variety of compounds in the gut. Indeed, activated charcoal comes nearest to fulfilling the long-sought notion of a ‘universal antidote’.2 Thus it is simpler to list the exceptions, i.e. substances that are poorly adsorbed by charcoal:
• Metal salts (iron, lithium).
• Cyanide.
• Alcohols (ethanol, methanol, ethylene glycol).
• Petroleum distillates.
• Clofenotane (dicophane, DDT).
• Malathion.
• Strong acids and alkalis.
• Corrosive agents.
To be most effective, five to ten times as much charcoal as poison, weight for weight, is needed. In the adult an initial dose of 50 g is usual, repeated if necessary. If the patient is vomiting, give the charcoal through a nasogastric tube. Unless a patient has an intact or protected airway its administration is contraindicated.
Activated charcoal is most effective when given soon after ingestion of a potentially toxic amount of a poison and while a significant amount remains yet unabsorbed. Volunteer studies suggest that administration within 1 h can be expected to prevent up to 40–50% of absorption. There are no satisfactorily designed clinical trials in patients to assess the benefit of single dose activated charcoal. Benefit after 1 h cannot be excluded and may be sometimes be indicated. Charcoal in repeated doses accelerates the elimination of poison that has been absorbed (see later). Activated charcoal, although unpalatable, appears to be relatively safe but constipation or mechanical bowel obstruction may follow repeated use. In the drowsy or comatose patient there is particular risk of aspiration into the lungs causing hypoxia through obstruction and arteriovenous shunting. Methionine, used orally for paracetamol poisoning, is adsorbed by the charcoal.
Other oral adsorbents have specific uses. Fuller's earth (a natural form of aluminium silicate) binds and inactivates the herbicides paraquat (activated charcoal is superior) and diquat; colestyramine and colestipol will adsorb warfarin.
Whole-bowel irrigation3
should not be used routinely in the management of the poisoned patient. While volunteer studies have shown marked reductions in the bioavailability of ingested drugs, there is no evidence from controlled clinical trials in patients. It should be used for the removal of sustained-release or enteric-coated formulations from patients who present more than 2 h after ingestion, e.g. iron, theophylline, aspirin. Evidence of benefit is conflicting. Activated charcoal in frequent (50 g) doses is generally preferred. Sustained-release formulations are common, and patients have died from failure to recognise the danger of continued release of drug from such products. Whole-bowel irrigation is also an option for the removal of ingested packets of illicit drugs. It is contraindicated in patients with bowel obstruction, perforation or ileus, with haemodynamic instability and with compromised unprotected airways.
Whole bowel irrigation should be used with special care in patients who are debilitated or who have significant concurrent medical conditions. The effectiveness of activated charcoal may be reduced by co-administration with whole bowel irrigation.
Cathartics have no routine role in gut decontamination, but a single dose of an osmotic agent (sorbitol, magnesium sulphate) may be justified on occasion.
Accelerating elimination of the poison
Techniques for eliminating absorbed poisons have a role that is limited, but important when applicable. Each method depends, directly or indirectly, on removing drug from the circulation and successful use requires that:
• The poison should be present in high concentration in the plasma relative to that in the rest of the body, i.e. it should have a small volume of distribution.
• The poison should dissociate readily from any plasma protein binding sites.
• The effects of the poison should relate to its plasma concentration.
Methods used are:
Repeated doses of activated charcoal
Activated charcoal by mouth not only adsorbs ingested drug in the gut, preventing absorption into the body (see above), it also adsorbs drug that diffuses from the blood into the gut lumen when the concentration there is lower. As binding is irreversible, the concentration gradient is maintained and drug is continuously removed; this has been called ‘intestinal dialysis’. Charcoal may also adsorb drugs that secrete into the bile, i.e. by interrupting an enterohepatic cycle. The procedure is effective for overdose of carbamazepine, dapsone, phenobarbital, quinine, salicylate and theophylline.
Repeated-dose activated charcoal is increasingly preferred to alkalinisation of urine (below) for phenobarbital and salicylate poisoning. In adults, activated charcoal 50 g is given initially, then 50 g every 4 h. Vomiting should be treated with an antiemetic drug because it reduces the efficacy of charcoal treatment. Where there is intolerance, the dose may be reduced and the frequency increased, e.g. 25 g every 2 h or 12.5 g every hour, but efficacy may be compromised.
Alteration of urine pH and diuresis
It is useful to alter the pH of the glomerular filtrate such that a drug that is a weak electrolyte will ionise, become less lipid soluble, remain in the renal tubular fluid, and leave the body in the urine (see p. 80).
Maintenance of a good urine flow (e.g. 100 mL/h) helps this process, but the alteration of tubular fluid pH is the important determinant. The practice of forcing diuresis with furosemide and large volumes of intravenous fluid does not add significantly to drug clearance but may cause fluid overload; it is obsolete.
The objective is to maintain a urine pH of 7.5–8.5 by an intravenous infusion of sodium bicarbonate. Available preparations of sodium bicarbonate vary between 1.2% and 8.4% (1 mL of the 8.4% preparation contains 1 mmol sodium bicarbonate) and the concentration given will depend on the patient's fluid needs.
Alkalinisation4 may be used for: salicylate (> 500 mg/L + metabolic acidosis, or in any case > 750 mg/L) phenobarbital (75–150 mg/L); phenoxy herbicides, e.g. 2,4-D, mecoprop, dichlorprop; moderately severe salicylate poisoning that does not meet the criteria for haemodialysis.
Acidification may be used for severe, acute poisoning with: amfetamine; dexfenfluramine; phencyclidine. The objective is to maintain a urine pH of 5.5–6.5 by giving an intravenous infusion of arginine hydrochloride (10 g) over 30 min, followed by ammonium chloride (4 g) every 2 h by mouth. It is very rarely indicated. Hypertension due to amfetamine-like drugs, for example, will respond to phenoxybenzamine (by α-adrenoceptor block).
Haemodialysis
The system requires a temporary extracorporeal circulation, e.g. from an artery to a vein in the arm. A semipermeable membrane separates blood from dialysis fluid; the poison passes passively from the blood, where it is present in high concentration, to enter the dialysis fluid, which is flowing and thus constantly replaced.
Haemodialysis significantly increases the elimination of: salicylate (> 750 mg/L + renal failure, or in any case > 900 mg/L); isopropanol (present in aftershave lotions and window-cleaning solutions); lithium; methanol; ethylene glycol; ethanol.
Haemofiltration
An extracorporeal circulation brings blood into contact with a highly permeable membrane. Water is lost by ultrafiltration (the rate being dependent on the hydrostatic pressure gradient across membrane) and solutes by convection; the main change in plasma concentrations results from replacement of ultrafiltrate with an appropriate solution.
Haemofiltration is effective for: phenobarbital (> 100–150 mg/L, but repeat-dose activated charcoal by mouth appears to be as effective; see above) and other barbiturates; ethchlorvynol; glutethimide; meprobamate; methaqualone; theophylline; trichloroethanol derivatives.
Peritoneal dialysis
This involves instilling appropriate fluid into the peritoneal cavity. Poison in the blood diffuses down the concentration gradient into the dialysis fluid, which undergoes repeated drainage and replacement. The technique requires little equipment; it may be worth using for lithium and methanol poisoning.
Haemofiltration and peritoneal dialysis are more readily available but are less efficient (one-half to one-third) than haemodialysis.
Haemodialysis is invasive, demands skill and experience on the part of the operator, and is costly in terms of staffing. Its use should be confined to cases of severe, prolonged or progressive clinical intoxication, when high plasma concentration indicates a dangerous degree of poisoning, and its effect constitutes a significant addition to natural methods of elimination.
Specific antidotes5
Specific antidotes reduce or abolish the effects of poisons through a variety of general mechanisms, as indicated in Table 10.3.
Table 10.3 General mechanisms of the action of antidotes
|
Mechanism |
Examples |
|
Removal of circulating poison from plasma |
• Chelating agents for heavy metal poisoning, e.g. desferrioxamine for iron poisoning • Chemical binding or precipitation, e.g. calcium gluconate for fluoride poisoning, binding to specific antibody, e.g. digoxin-specific antibody fragments in cardiac glycoside poisoning |
|
Receptor agonism |
• Direct agonism, e.g.isoprenaline in β-adrenoceptor antagonist poisoning • Indirect agonism, e.g. glucagon in β-adrenoceptor poisoning |
|
Receptor antagonism |
• Direct antagonism, e.g. atropine in organophosphate poisoning and many other examples |
|
Replenish depleted natural ‘protective’ compound |
• Replenish protective species, e.g. N-acetylcysteine in paracetamol poisoning • Bypass block in metabolism, e.g. folinic acid in methotrexate poisoning, vitamin K in warfarin poisoning |
|
Prevent conversion to toxic metabolite |
• Ethanol in methanol poisoning |
|
Protective action on target enzyme |
• Pralidoxime competitively reactivates cholinesterase |
Table 10.4 illustrates these mechanisms with antidotes that are of therapeutic value.
Table 10.4 Specific antidotes useful in clinical practice
|
Some specific antidotes, indications and modes of action (see Index for a fuller account of individual drugs) |
||
|
Antidote |
Indication |
Mode of action |
|
Acetylcysteine |
Paracetamol, chloroform, carbon tetrachloride, radiocontrast nephropathy |
Replenishes depleted glutathione stores |
|
Atropine |
Cholinesterase inhibitors, e.g. organophosphorus insecticides |
Blocks muscarinic cholinoceptors |
|
β-Blocker poisoning |
Vagal block accelerates heart rate |
|
|
Benzatropine |
Drug-induced movement disorders |
Blocks muscarinic cholinoceptors |
|
Calcium gluconate |
Hydrofluoric acid, fluorides |
Binds or precipitates fluoride ions |
|
Desferrioxamine |
Iron |
Chelates ferrous ions |
|
Dicobalt edetate |
Cyanide and derivatives, e.g. acrylonitrile |
Chelates to form non-toxic cobalti- and cobalto-cyanides |
|
Digoxin-specific antibody fragments (FAB) |
Digitalis glycosides |
Binds free glycoside in plasma, complex excreted in urine |
|
Dimercaprol (BAL) |
Arsenic, copper, gold, lead, inorganic mercury |
Chelates metal ions |
|
Ethanol (or fomepizole) |
Ethylene glycol, methanol |
Competes for alcohol and acetaldehyde dehydrogenases, preventing formation of toxic metabolites |
|
Flumazenil |
Benzodiazepines |
Competes for benzodiazepine receptors |
|
Folinic acid |
Folic acid antagonists, e.g. methotrexate, trimethoprim |
Bypasses block in folate metabolism |
|
Glucagon |
β-Adrenoceptor antagonists |
Bypasses blockade of the β-adrenoceptor; stimulates cyclic AMP formation with positive cardiac inotropic effect |
|
Isoprenaline |
β-Adrenoceptor antagonists |
Competes for and activates β-adrenoceptors |
|
Methionine |
Paracetamol |
Replenishes depleted glutathione stores |
|
Naloxone |
Opioids |
Competes for opioid receptors |
|
Neostigmine |
Antimuscarinic drugs |
Inhibits acetylcholinesterase, causing acetylcholine to accumulate at cholinoceptors |
|
Oxygen |
Carbon monoxide |
Competitively displaces carbon monoxide from binding sites on haemoglobin |
|
Penicillamine |
Copper, gold, lead, elemental mercury (vapour), zinc |
Chelates metal ions |
|
Phenoxybenzamine |
Hypertension due to α-adrenoceptor agonists, e.g. with MAOI, clonidine, ergotamine |
Competes for and blocks α-adrenoceptors (long acting) |
|
Phentolamine |
As above |
Competes for and blocks α-adrenoceptors (short acting) |
|
Phytomenadione (vitamin K1) |
Coumarin (warfarin) and indanedione anticoagulants |
Replenishes vitamin K |
|
Pralidoxime |
Cholinesterase inhibitors, e.g. organophosphorus insecticides |
Competitively reactivates cholinesterase |
|
Propranolol |
β-Adrenoceptor agonists, ephedrine, theophylline, thyroxine |
Blocks β-adrenoceptors |
|
Protamine |
Heparin |
Binds ionically to neutralise |
|
Prussian blue (potassium ferric hexacyanoferrate) |
Thallium (in rodenticides) |
Potassium exchanges for thallium |
|
Sodium calcium edetate |
Lead |
Chelates lead ions |
|
Unithiol |
Lead, elemental and organic mercury |
Chelates metal ions |
Psychiatric and social assessment
Patients require a psychosocial assessment when they have recovered from the medical aspects of the overdose. The immediate risk and subsequent risk of suicide should be assessed. Even ‘minor’ cases of deliberate self-harm should not be dismissed, as 20–25% of patients who die from deliberate self-harm will have presented to hospital with an episode of self-harm in the previous year. Interpersonal or social problems precipitate most cases of self-poisoning and require attention. Identify and treat any significant psychiatric illness. Consider the impact of any associated medical problems and their symptom control. Obtain information on associated alcohol and substance abuse. In UK hospitals such assessments are usually performed by the hospital psychiatric liaison service prior to discharge of the patient from the hospital. Most patients can be discharged without psychiatric follow-up. Rarely, patients with a high suicide risk and/or an underlying severe psychiatric illness may require transfer to an inpatient psychiatric facility, either voluntarily or under the appropriate section of the 1983 Mental Health Act. More commonly, patients may benefit from community psychiatric support as outpatients.
Poisoning by (non-drug) chemicals
Heavy metal poisoning and use of chelating agents
Acute or chronic exposure to heavy metals can harm the body.6 Treatment is with chelating agents which incorporate the metal ions into an inner ring structure in the molecule (Greek: chele, claw) by means of structural groups called ligands (Latin: ligare, to bind). Effective agents form stable, biologically inert complexes that pass into the urine.
Dimercaprol (British Anti-Lewisite, BAL). Arsenic and other metal ions are toxic in low concentration because they combine with the SH-groups of essential enzymes, thus inactivating them. Dimercaprol provides SH-groups, which combine with the metal ions to form relatively harmless ring compounds that pass from the body, mainly in the urine. As dimercaprol itself is oxidised in the body and excreted renally, repeated administration is necessary to ensure that an excess is available to eliminate all of the metal.
Dimercaprol may be used in cases of poisoning by antimony, arsenic, bismuth, gold and mercury (inorganic, e.g. HgCl2).
Adverse effects are common, particularly with larger doses, and include nausea, vomiting, lachrymation, salivation, paraesthesiae, muscular aches and pains, urticarial rashes, tachycardia and raised blood pressure. Gross overdosage may cause over-breathing, muscular tremors, convulsions and coma.
Unithiol (dimercaptopropanesulphonate, DMPS) effectively chelates lead and mercury; it is well tolerated.
Sodium calcium edetate is the calcium chelate of the disodium salt of ethylenediaminetetra-acetic acid (calcium EDTA). It is effective in acute lead poisoning because of its capacity to exchange calcium for lead: the kidney excretes the lead chelate, leaving behind a harmless amount of calcium. Dimercaprol may usefully be combined with sodium calcium edetate when lead poisoning is severe, e.g. with encephalopathy.
Adverse effects are fairly common, and include hypotension, lachrymation, nasal stuffiness, sneezing, muscle pains and possible nephrotoxicity.
Dicobalt edetate. Cobalt forms stable, non-toxic complexes with cyanide (see p. 130). It is toxic (especially if the wrong diagnosis is made and no cyanide is present), causing hypertension, tachycardia and chest pain. Cobalt poisoning is treated by giving sodium calciumedetate and intravenous glucose.
Penicillamine (dimethylcysteine) is a metabolite of penicillin that contains SH-groups; it may be used to chelate lead and copper (see Wilson's disease, p. 366). Its principal use is for rheumatoid arthritis (see Index).
Desferrioxamine (see Iron, p. 500).
Cyanide
poisoning results in tissue anoxia by chelating the ferric part of the intracellular respiratory enzyme, cytochrome oxidase. It thus uncouples mitochondrial oxidative phosphorylation and inhibits cellular respiration in the presence of adequate oxygenation. Poisoning may occur as a result of: self-administration of hydrocyanic (prussic) acid; accidental exposure in industry; inhaling smoke from burning polyurethane foams in furniture; ingesting amygdalin which is present in the kernels of several fruits including apricots, almonds and peaches (constituents of the unlicensed anticancer agent, laetrile); excessive use of sodium nitroprusside for severe hypertension.7
The symptoms of acute poisoning are due to tissue anoxia, with dizziness, palpitations, a feeling of chest constriction and anxiety. Characteristically the breath smells of bitter almonds. In more severe cases there is acidosis and coma. Inhaled hydrogen cyanide may lead to death within minutes, but with the ingested salt several hours may elapse before the patient is seriously ill.
Cyanide toxicity is suggested by a metabolic acidosis, reduced arterial/venous oxygen saturation difference and markedly elevated plasma lactate. The presence of these findings in the context of smoke inhalation should alert the physician to the possibility that cyanide poisoning has occurred and needs urgent treatment.
The principles of specific therapy are as follows:
Hydroxocobalamin (5 g for an adult) combines with cyanide to form cyanocobalamin and is excreted by the kidney. Adverse effects include transient hypertension (may be beneficial) and rare anaphylactic and anaphylactoid reactions. Co-administration with sodium thiosulphate (through a separate intravenous line or sequentially) may have added benefit. The use of hydroxocobalamin has largely superseded that of the alternative, dicobalt edetate.
• Dicobalt edetate. The dose is 300 mg given intravenously over 1 min (5 min if condition is less serious), followed immediately by a 50 mL intravenous infusion of 50% glucose; a further 300 mg dicobalt edetate should be given if recovery is not evident within 1 min.
• Alternatively, a two-stage procedure may be followed by intravenous administration of:
1. Sodium nitrite, which rapidly converts haemoglobin to methaemoglobin, the ferric ion of which takes up cyanide as cyanmethaemoglobin (up to 40% methaemoglobin can be tolerated).
2. Sodium thiosulphate, which more slowly detoxifies the cyanide by permitting the formation of thiocyanate. When the diagnosis is uncertain, administration of thiosulphate plus oxygen is a safe course.
The increasing use of hydroxocobalamin as a first-line treatment is based upon animal studies that have shown a faster improvement of arterial blood pressure compared to sodium nitrate. No benefit in terms of mortality was seen in these studies.
There is evidence that oxygen, especially if at high pressure (hyperbaric), overcomes the cellular anoxia in cyanide poisoning; the mechanism is uncertain, but it is reasonable to administer high-flow oxygen.
Carbon monoxide (CO)
is a colourless, odourless gas formed by the incomplete combustion of hydrocarbons and poisoning results from its inhalation. The concentration (% saturation) of CO in the blood may confirm exposure (cigarette smoking alone may account for up to 10%) but is no guide to the severity of poisoning. CO binds reversibly to haemoglobin with about 250 times greater affinity than oxygen. Binding to one of the four oxygen binding sites on the haemoglobin molecule significantly increases the affinity of the other three binding sites for oxygen which further reduces the delivery of oxygen to hypoxic tissues. In addition CO has an even higher affinity for cardiac myoglobin, further worsening cardiac output and tissue oxygenation. Poor correlation between carboxyhaemoglobin in the blood and observed toxicity suggests that other mechanisms are involved.
Symptoms commence at about 10% carboxyhaemoglobin with a characteristic headache. Death may occur from myocardial and neurological injury at levels of 50–70%. Severe breathlessness is not a feature typical of severe intoxication. Delayed symptoms (2–4 weeks) include parkinsonism, cerebellar signs and psychiatric disturbances.
Investigations should include direct estimation of carboxyhaemoglobin in the blood. Consider the diagnosis even if the level is low and some time has passed since exposure or high flow oxygen has been given. PaO2 levels should be normal. Oxygen saturation is accurate only if directly measured (see above) and not calculated from the PaO2. Administer oxygen through a tight-fitting mask and continue for at least 12 h. Evidence for the efficacy of hyperbaric oxygen is conflicting and transport to hyperbaric chambers may present logistic problems, but it is advocated when the blood carboxyhaemoglobin concentration exceeds 40%, there is unconsciousness, neurological defect, ischaemic change on the ECG, pregnancy, or the clinical condition does not improve after 4 h of normobaric therapy.
Lead
poisoning arises from a variety of occupational (house renovation and stripping old paint), and recreational sources. Environmental exposure has been a matter of great concern, as witnessed by the protective legislation introduced by many countries to reduce pollution, e.g. by removing lead from petrol. Lead in the body comprises a rapidly exchangeable component in blood (2%, biological t½ 35 days) and a stable pool in dentine and the skeleton (95%, biological t½ 25 years). Lead binds to sulfhydryl groups and interferes with haem production. Since haem-containing proteins play a vital role in cellular oxidation, lead poisoning has wide-ranging effects, particularly in young children. With mild poisoning there is lethargy and abdominal discomfort; severe abdominal symptoms and peripheral neuropathy and CNS disturbances indicate more serious toxicity. Serum lead values over 100 micrograms/mL are associated with impaired cognitive development in children; levels above 1000 micrograms/mL are potentially fatal.
Mild lead poisoning (< 450 micrograms/mL) may be treated by removal from exposure and monitoring. Moderate poisoning requires oral chelation therapy such as D-penicillamine (unlicensed) or more recently with succimer(2,3-dimercaptosuccinic acid, DMSA), a water-soluble analogue of dimercaprol with a high affinity for lead. Severe lead poisoning calls for parenteral therapy to initiate excretion and sodium calcium edetate is commonly used to chelate lead from bone and the extracellular space; urinary lead excretion diminishes over 5 days as the extracellular store is exhausted. Redistribution of lead from bone to brain may account for subsequent worsening of symptoms (colic and encephalopathy).
Dimercaprol is more effective than sodium calcium edetate at chelating lead from the soft tissues such as brain, which is the rationale for combined therapy with sodium calcium edetate.
Methanol
Methanol is widely available as a solvent and in paints and antifreezes, and constitutes a cheap substitute for ethanol. Methanol itself has low toxicity but its metabolites are highly toxic. As little as 10 mL may cause permanent blindness and 30 mL may kill. Methanol, like ethanol, is metabolised by zero-order processes that involve the hepatic alcohol and aldehyde dehydrogenases, but, whereas ethanol forms ethanal and ethanoic acid (partly responsible for the unpleasant effects of ‘hangover’), methanol forms methanal and methanoic acid. Blindness may occur because aldehyde dehydrogenase present in the retina (for the interconversion of retinol and retinene) allows the local formation of methanal. Acidosis is due to the methanoic acid, which itself enhances pH-dependent hepatic lactate production, adding the problems of lactic acidosis.
The clinical features include severe malaise, vomiting, abdominal pain and tachypnoea (due to the acidosis). Loss of visual acuity and scotomata indicate ocular damage and, if the pupils are dilated and non-reactive, permanent loss of sight is probable. Coma and circulatory collapse may follow. The key laboratory finding is a high anion gap acidosis. Blood methanol can be measured but does not correlate closely with the clinical picture.
Therapy is directed at:
• Correcting the metabolic acidosis. Achieving this largely determines the outcome; sodium bicarbonate is given intravenously in doses up to 2 mol in a few hours, carrying an excess of sodium which must be managed. Methanol is metabolised slowly and relapse may accompany too early discontinuation of bicarbonate.
• Inhibiting methanol metabolism. Ethanol, which occupies the dehydrogenase enzymes in preference to methanol, competitively prevents metabolism of methanol to its toxic products. A single oral dose of ethanol 1 mL/kg (as a 50% solution or as the equivalent in gin or whisky) is followed by 0.25 mL/kg/h orally or intravenously, aiming to maintain the blood ethanol at about 100 mg/100 mL until no methanol is detectable in the blood. Fomepizole (4-methylpyrazole), another competitive inhibitor of alcohol dehydrogenase, is effective in severe methanol poisoning and is less likely to cause cerebral depression (it is available in the UK on a named-patient basis).
• Eliminating methanol and its metabolites. Haemodialysis is two to three times more effective than is peritoneal dialysis and is indicated in severe cases.
Folinic acid 30 mg intravenously 6-hourly may protect against retinal damage by enhancing formate metabolism.
Ethylene glycol
Ethylene glycol is readily accessible as a constituent of antifreezes for car radiators (available as a 95% concentration). Its use to give ‘body’ and sweetness to white table wines was criminal. Metabolism to glycolate and oxalate causes acidosis and renal damage, a situation that is further complicated by lactic acidosis. The lethal dose for an adult is around 100 mL.
In the first 12 h after ingestion the patient appears as though intoxicated with alcohol but without the characteristic odour. Subsequently there is increasing acidosis, pulmonary oedema and cardiac failure. In 2–3 days renal pain and tubular necrosis develop because calcium oxalate crystals form in the urine. Intravenous sodium bicarbonate corrects the acidosis, and with calcium gluconate, the hypocalcaemia. As with methanol (above), ethanol or fomepizole competitively inhibit the metabolism of ethylene glycol and haemodialysis eliminates the poison.
Hydrocarbons
Common hydrocarbons include paraffin oil (kerosene), petrol (gasoline) and benzene. The specific toxic effects depend upon the chemical structure of the hydrocarbon, the dose and route of administration. In general, they cause CNS depression and pulmonary damage from inhalation. It is vital to avoid aspiration into the lungs with spontaneous vomiting.
Volatile solvent abuse
Solvent abuse or ‘glue sniffing’ is common among teenagers, especially males, although the prevalence has probably declined over the last 35 years. Data from 2004 suggested that 6% of 15-year-olds had engaged in the practice in the previous year. The success of the modern chemical industry provides easy access to these substances as adhesives, dry cleaners, air fresheners, deodorants, aerosols and other products. Viscous products are taken from a plastic bag, liquids from a handkerchief or plastic bottle.
The immediate euphoriant and excitatory effects give way to confusion, hallucinations and delusions as the dose is increased. Chronic abusers, notably of toluene, develop peripheral neuropathy, cerebellar disease and dementia; damage to the kidney, liver, heart and lungs also occurs with solvents. Evidence from 2006 suggested that one person per week dies in the UK from this practice and in 60% of these cases there was no previous history of abuse, suggesting that death commonly occurs on the first use. Over 50% of deaths from the practice follow cardiac arrhythmia, probably caused by sensitisation of the myocardium to catecholamines and by vagal inhibition from laryngeal stimulation due to aerosol propellants sprayed into the throat. Most deaths have been related to butane lighter fuel inhalation due to its particular tendency to induce cardiac arrhythmias. Death may also occur from acute intoxication impairing judgment, leading to accidents.
Acute solvent poisoning requires immediate cardiorespiratory resuscitation and anti-arrhythmia treatment. Toxicity from carbon tetrachloride and chloroform involves the generation of phosgene, a First World War gas, which is inactivated by cysteine and by glutathione, formed from cysteine. Recommended treatment is therefore with N-acetylcysteine, as for poisoning with paracetamol.
Herbicides and pesticides
Organophosphorus pesticides
are anticholinesterases; an account of poisoning and its management is given later. Organic carbamates are similar.
Dinitro-compounds
Dinitro-ortho-cresol (DNOC) and dinitrobutylphenol (DNBP) are selective weedkillers and insecticides, and cases of poisoning occur accidentally, e.g. by ignoring safety precautions. These substances can be absorbed through the skin and the hands, resulting in yellow staining of face or hair. Symptoms and signs indicate a very high metabolic rate (due to uncoupling of oxidative phosphorylation); copious sweating and thirst proceed to dehydration and vomiting, weakness, restlessness, tachycardia and deep, rapid breathing, convulsions and coma. Treatment is urgent and consists of cooling the patient and attention to fluid and electrolyte balance. It is essential to differentiate this type of poisoning from that due to anticholinesterases, because atropine given to patients poisoned with dinitro-compound will stop sweating and may cause death from hyperthermia.
Phenoxy herbicides
(2,4-D, mecoprop, dichlorprop) are used to control broad-leaved weeds. Ingestion causes nausea, vomiting, pyrexia (due to uncoupling of oxidative phosphorylation), hyperventilation, hypoxia and coma. Urine alkalinisation accelerates elimination. Organochlorine pesticides, e.g. dicophane (DDT), may cause convulsions in acute overdose. Treat as for status epilepticus.
Rodenticides
include warfarin and thallium (see Table 10.1); for strychnine, which causes convulsions, give diazepam.
Paraquat
is a widely used herbicide that is extremely toxic if ingested; a mouthful of the commercial solution taken and spat out may be sufficient to kill. It is highly corrosive and can be absorbed through the skin. A common sequence is: ulceration and sloughing of8 the oral and oesophageal mucosa, renal tubular necrosis (5–10 days later), pulmonary oedema and pulmonary fibrosis. Whether the patient lives or dies depends largely on the condition of the lung. Treatment is urgent and includes activated charcoal or aluminium silicate (Fuller's earth) by mouth as adsorbents. Haemodialysis may have a role in the first 24 h, the rationale being to reduce the plasma concentration and protect the kidney, failure of which allows the slow but relentless accumulation of paraquat in the lung.
Diquat
is similar to paraquat but the late pulmonary changes may not occur.
Incapacitating agents
CS
(chlorobenzylidene malononitrile, a tear ‘gas’). It is possible that a physician will be called upon to treat individuals who have been exposed to incapacitating agents. Such agents are designed to cause a temporary disablement that lasts for little longer than the period of exposure. CS is a solid that is disseminated as an aerosol (particles of 1 micron in diameter) by including it in a pyrotechnic mixture. It is an aerosol or smoke, not a gas. The particles aggregate and settle to the ground in minutes, so that the risk of prolonged exposure out of doors is not great. The onset of symptoms occurs immediately on exposure and they disappear dramatically.
According to the concentration of CS to which a person is exposed, the effects vary from a slight pricking or peppery sensation in the eyes and nasal passages up to the maximal symptoms of streaming from the eyes and nose, spasm of the eyelids, profuse lachrymation and salivation, retching and sometimes vomiting, burning of the mouth and throat, cough and gripping pain in the chest.9 Exposed subjects absorb small amounts only, and the plasma t½ is about 5 s. There appear to be no long-lasting sequelae but, plainly, it would be prudent to assume that patients with asthma or chronic bronchitis could suffer an exacerbation from high concentrations.
CN
(chloroacetophenone, a tear gas) is generally used as a solid aerosol or smoke; solutions (Mace) are used at close quarters.
CR
(dibenzoxazepine) entered production in 1973 after testing on army volunteers. In addition to the usual properties (above) it may induce a transient rise in intraocular pressure. Its solubility allows use in water ‘cannons’.
Poisoning by biological substances
Many plants form substances that are important for their survival either by enticing animals, which disperse their spores, or by repelling potential predators. Poisoning occurs when children eat berries or chew flowers, attracted by their colour; adults may mistake non-edible for edible varieties of salad plants and fungi (mushrooms) for they may resemble one another closely and some are greatly prized by epicures. Ingestion of plants is responsible for a significant number of calls to poison information services (10% in US and German surveys) but serious poisonings are rare. Deaths from plant poisoning are thus very rare in industrialised societies. A recent study from the USA covering the period 1983–2000 identified only 30 fatalities over this 18-year period. Plant poisoning is, however, a significant problem in the developing world. Such deaths are almost exclusively deliberate suicide or homicide.10
The range of toxic substances that these plants produce is exhibited in a diversity of symptoms that may be grouped broadly as shown in Table 10.5.
Table 10.5 Commonly encountered plant poisonings
|
Symptom complex |
Causative agent |
Active ingredient |
|
Atropenic • dilated pupils • blurred vision • dried mouth • flushing • confusion and delirium |
• Atropa belladonna (deadly nightshade) • Datura (thorn apple) |
Tropane alkaloids such as • atropine • hyoscine (scopolamine) • hyoscyamine |
|
Nicotinic • hypersalivation • pupil dilatation • vomiting • convulsions • respiratory paralysis |
• Conium (hemlock) • Laburnum |
• coniine • cytisine |
|
Muscarinic • salivation • lachrymation • meiosis • perspiration • bradycardia • bronchoconstriction • hallucinations |
• Inocybe mushrooms • Clitocybe mushrooms |
• muscarine • several rare species have hallucinogenic properties and produce psilocybin |
|
Hallucinogenic • (so called ‘magic mushrooms’) |
• Psilocybe mushrooms |
• psilocybin |
|
Cardiovascular • cardiac arrhythmias • vomiting • diarrhoea |
• Digitalis (foxglove) • Viscum album (mistletoe) • Convallaria (lily of the valley) • Thevetia peruviana (yellow oleander) • Strophanthus (twisted corn flower) |
Cardenolide cardiac glycosides such as • digoxin • digitoxin • ouabain • oleandrin |
|
Hepatotoxic |
• Amanita phalloides (death cap mushroom) • Senecio (ragwort) • Crotalaria (common ingredient in bush teas) |
• alpha amatin in mushrooms • pyrollizidine alkaloids in plants |
|
Convulsant |
• Oenanthe (water dropwort) • Cicuta (cowbane) |
GABA antagonists • oenanthotoxin and closely related • cicutoxin |
In addition many plants may cause cutaneous irritation, e.g. directly with nettle (Urtica), or dermatitis following sensitisation with Primula. Gastrointestinal symptoms, nausea, vomiting, diarrhoea and abdominal pain occur with numerous plants.
The treatment of plant poisonings consists mainly of giving activated charcoal to adsorb toxin in the gastrointestinal tract, supportive measures to maintain cardiorespiratory function, and control of convulsions with diazepam.
Specific measures. In ‘death cap’ (Amanita phalloides) mushroom poisoning, high dose penicillin or silibinin (an extract of the milk thistle) may be used to inhibit amatoxin uptake by the liver and its enterohepatic circulation. Antitoxins, e.g. Digibind, are used for poisoning with plants that produce toxic cardiac glycosides.
Guide to further reading
Bradbury S., Vale A. Poisons: epidemiology and clinical presentation. Clin. Med. (Northfield Il). 2008;8(1):86–88. (and subsequent papers in this issue)
Body R., Bartram T., Azam F., Mackway-Jones K. Guidelines in Emergency Medicine Network (GeMNet): guideline for the management of tricyclic antidepressant overdose. Emergency Medical Journal. 2011;28:347–368.
Buckley N.A., Juurlink D.N., Isbister G., et al. Hyperbaric oxygen for carbon monoxide poisoning. Cochrane Database Syst. Rev.. 2011;13:4.
Budnitz D.S., Lovegrove M.C., Crosby A.E. Emergency department visits for acetaminophen-containing products. Am. J. Prev. Med.. 2011;40:585–592.
Chyka P.A., Erdman A.R., Christianson G., et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin. Toxicol.. 2007;45:95–131.
Evison D., Hinsley D., Rice P. Chemical weapons. Br. Med. J.. 2002;324:332–335.
Gawande A. When law and ethics collide – why physicians participate in executions. N. Engl. J. Med.. 2006;354(12):1221–1229.
Holger J.S., Engebretson K.M., Marini J.J. High dose insulin in toxic cardiogenic shock. Clin. Toxicol.. 2009;47(4):303–307.
Kales S.N., Christiani D.C. Acute chemical emergencies. N. Engl. J. Med.. 2004;350(8):800–808.
Kerins M., Dargan P.I., Jones A.L. Pitfalls in the management of the poisoned patient. J. R. Coll. Physicians Edinb.. 2003;33:90–103.
Ruben Thanacoody H.K., Thomas S.H.L. Antidepressant poisoning. Clin. Med. (Northfield Il). 2003;3(2):114–118.
Skegg K. Self-harm. Lancet. 2005;366:1471–1483.
Volans G., Hartley V., McCrea S., Monaghan J. Non-opioid analgesic poisoning. Clin. Med. (Northfield Il). 2003;3(2):119–123.
Wolf A.D., Erdman A.R., Nelson L.S., et al. Tricyclic antidepressant poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin. Toxicol.. 2007;45:203–233.
1 Joint position statements and guidelines agreed by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists review the therapeutic usefulness of various procedures for gut decontamination. These appear in the Journal of Toxicology, Clinical Toxicology from 1997 onwards, the latest position statements being in 2004 and 2005.
2 For centuries it was supposed not only that there could be, but that there actually was, a single antidote to all poisons. This was Theriaca Andromachi, a formulation of 72 (a magical number) ingredients among which particular importance was attached to the flesh of a snake (viper). The antidote was devised by Andromachus, whose son was physician to the Roman Emperor Nero (AD 37–68).
3 Irrigation with large volumes of a polyethylene glycol–electrolyte solution, e.g. Klean-Prep, by mouth causes minimal fluid and electrolyte disturbance (it was developed for preparation for colonoscopy). Magnesium sulphate may also be used.
4 Proudfoot A T, Krenzelok E P, Vale J A 2004 Position paper on urine alkalinisation. Journal of Toxicology, Clinical Toxicology 42:1–26.
5 Mithridates the Great (?132 BC – 63 BC), king of Pontus (in Asia Minor), was noted for ‘ambition, cruelty and artifice’. ‘He murdered his own mother … and fortified his constitution by drinking antidotes’ to the poisons with which his domestic enemies sought to kill him (Lemprière). When his son also sought to kill him, Mithridates was so disappointed that he compelled his wife to poison herself. He then tried to poison himself, but in vain; the frequent antidotes that he had taken in the early part of his life had so strengthened his constitution that he was immune. He was obliged to stab himself, but had to seek the help of a slave to complete his task. Modern physicians have to be content with less comprehensively effective antidotes, some of which are listed in Table 10.1.
6 Sometimes in unexpected ways; an initiation custom in an artillery regiment involved pouring wine through the barrel of a gun after several shots had been fired. A healthy 19-year-old soldier drank 250 mL of the wine and within 15 min convulsed and became unconscious. His plasma, urine and the wine contained high concentrations of tungsten. He received haemodialysis and recovered. Investigation revealed that the gun barrels had recently been hardened by the addition of tungsten to the steel. Marquet P, François B, Vignon P, Lachâtre G 1996 A soldier who had seizures after drinking a quarter of a litre of wine. Lancet 348:1070.
7 Or in other more bizarre ways. ‘A 23-year-old medical student saw his dog (a puppy) suddenly collapse. He started external cardiac massage and a mouth-to-nose ventilation effort. Moments later the dog died, and the student felt nauseated, vomited and lost consciousness. On the victim's arrival at hospital, an alert medical officer detected a bitter almonds odour on his breath and administered the accepted treatment for cyanide poisoning after which he recovered. It turned out that the dog had accidentally swallowed cyanide, and the poison eliminated through the lungs had been inhaled by the master during the mouth-to-nose resuscitation.’ Journal of the American Medical Association 1983 249:353.
8 A 19-year-old male was admitted to hospital in Sri Lanka, having ingested 250 mL of paraquat in an episode of deliberate self-harm. He was accompanied by his brother and friend. The unfortunate young man died within 8 h of admission. His brother and friend presented to the same hospital 2 days later with severe swelling and burns to the scrotal skin. They had originally brought the patient to hospital in a three-wheeled taxi with the patient lying across their laps. He had vomited on them several times. They had been wearing sarongs which they had been unable to change out of during their 8-hour vigil before he died. The brother went on to develop evidence of mild systemic toxicity with abnormalities of renal and hepatic function. Both made a complete recovery. The local and systemic toxicity had occurred from prolonged contact with the vomitus-stained clothes. (Premaratna R, Rathnasena B G N, de Silva H J 2008 Accidental scrotal burns from paraquat while handling a patient. Ceylon Medical Journal 53(3):102–103.)
9 Home Office Report (1971) of the enquiry into the medical and toxicological aspects of CS. Part II. HMSO, London: Cmnd 4775.
10 Eddleston M, Rezvi Sheriff M H, Hawton K 1998 Deliberate self-harm in Sri Lanka: an overlooked tragedy in the developing world. British Medical Journal 317:133–135.