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 Dilated pupils Dry, flushed skin Urinary retention Decreased bowel sounds Mild increase in body temperature Confusion Cardiac arrhythmias Seizures	Antipsychotics Tricyclic antidepressants Antihistamines Antispasmodics Many plant toxins
Muscarinic	Salivation Lachrymation Abdominal cramps Urinary and faecal incontinence Vomiting Sweating Miosis Muscle fasciculation and weakness Bradycardia Pulmonary oedema Confusion CNS depression Seizures	Anticholinesterases Organophosphorus insecticides Carbamate insecticides Galantamine Donepezil
Sympathomimetic	Tachycardia Hypertension Hyperthermia Sweating Mydriasis Hyperreflexia Agitation Delusions Paranoia Seizures Cardiac arrhythmias

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

• 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 irrigation ³

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 antidotes ⁵

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.

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.

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 of ⁸ 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.