3 Poisoning 164-184

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Home > 1 PRINCIPLES OF MEDICAL PRACTICE > 3 Poisoning
3 Poisoning
A.L. JONES
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Acute poisoning remains one of the most common medical emergencies in the UK, accounting for 10-20% of all acute medical admissions. At least 50% involve more than one drug, with alcohol being the most frequent second agent.
Substances involved in poisoning vary widely between different countries (see Box 3.1). In the UK, poisoning with paracetamol accounts for 48% of all overdoses. By contrast, in the USA only 7% of all cases of poisoning are due to paracetamol, and in Nepal it is very rare. Poisoning with tricyclic antidepressants, selective serotonin (5-hydroxytryptamine, 5-HT) re-uptake inhibitors and drugs of misuse is very common in the UK and USA. Australia has a similar range of ingested toxins to the UK but envenomation with snakes, spiders and marine creatures is also very common. In South and South-east Asia, pesticide ingestion is endemic, and is the most common cause of death by poisoning. The toxicity of available poisons and the paucity of medical facilities in the developing world mean that the mortality rate for self-poisoning is high at 10-20%. This compares with a mortality rate of 0.5-1% in most industrialised countries. Reducing deaths from self-harm requires interventions both to reduce the incidence of harmful behaviour and to improve the medical management of acute poisoning. Clinical features of poisoning with specific agents and their management are discussed later in this chapter.
3.1 SUBSTANCES FREQUENTLY INVOLVED IN POISONING
In the United Kingdom
Analgesic drugs, including paracetamol and non-steroidal anti-inflammatory drugs
Cardiovascular toxic drugs, especially tricyclic antidepressants
Drugs of misuse
Carbon monoxide
Alcohol

In South and South-east Asia
Organophosphorusand carbamate insecticides
Aluminium and zinc phosphide
Snake bites
Antimalarial drugs such as chloroquine
Antidiabetic medication


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Home > 1 PRINCIPLES OF MEDICAL PRACTICE > 3 Poisoning > GENERAL APPROACH TO THE POISONED PATIENT
GENERAL APPROACH TO THE POISONED PATIENT
TAKING A HISTORY
In most cases, the diagnosis of poisoning is apparent on the basis of the history given by the patient. However, such information may not always be forthcoming, either because patients do not know what has been taken or because they may have been under the influence of alcohol or the drug itself at the time of ingestion. A few patients deliberately mislead doctors but in our experience this is very rare, with the exception of drug misusers.
Full details of the amount and type of substance that has been taken must be recorded, as well as the timing of ingestion or exposure. Whether the drugs belonged to the patient, or to a friend or relative, and the source of the drug (i.e. over the counter, prescription, street) are important in the prevention of future poisoning. The nature of any drug taken should be corroborated or identified from descriptions of the tablets or remaining pills (or their packets or bottles) by the use of drug identification software (e.g. TICTAC®), which can be accessed by many pharmacies and poisons information centres.
Ask the patient why the overdose was taken and take time to listen to the explanation. Reasons often include relationship difficulties, work- or school-related difficulties, drug addiction, psychiatric illness or bereavement. Whilst 'accidental overdose' can occur, in general all patients presenting with poisoning should undergo psychiatric evaluation (see p. 252).
Details of the past medical history should be recorded. In particular, a history of asthma, jaundice, drug misuse (and by which routes), head injury, epilepsy, cardiovascular problems, previous psychiatric illness and self-harm should be taken. It is important to ask about allergies and alcohol history. Identifying family problems and taking a good social history are also very important.
CLINICAL FEATURES OF POISONING
First ensure that:
the Airway is clear
the patient is Breathing adequately
the Circulation is not compromised.

If the patient is alert and has a stable circulation, proceed to an examination. The only exception is where immediate eye or skin decontamination is required (see Fig. 3.2, p. 169). A standard clinical examination should be carried out on every poisoned patient. Particular care should be taken to look for needle marks or previous evidence of self-harm, e.g. razor marks on forearms. Examination findings such as pupil size, respiratory rate and heart rate may support the diagnosis in an unconscious patient but on their own may merely help to narrow down the potential list of toxins. Clinical signs that can help identify which toxin has been taken are shown in Figure 3.1. The weight of the patient is also important as it is often critical in determining whether (given the dose ingested) toxicity is likely to occur, and allows the dose of any antidote to be calculated (e.g. N-acetylcysteine in paracetamol poisoning).
The Glasgow Coma Scale (GCS, see p. 1143) is the method most frequently used to assess the degree of impaired consciousness, though remarkably it has never been validated for use in poisoned patients. When patients are unconscious and no history is available, the diagnosis of poisoning depends on the exclusion of other causes of coma (especially meningitis, intracerebral bleeds, hypoglycaemia, diabetic ketoacidosis, uraemia and encephalopathy-see p. 1143) and consideration of circumstantial evidence.
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Figure 3.1 Clinical signs of poisoning by pharmaceutical agents or drugs of misuse.
ROLE OF THE TOXICOLOGY LABORATORY
In most patients the diagnosis of poisoning is made on the history and clinical signs alone. In some cases, such as poisoning with paracetamol (see p. 170), aspirin (see p. 171) or iron (see Box 3.7, p. 174), subsequent management of the patient depends on measurement of the amount of toxin in the blood.
In unconscious patients, a qualitative screen of the urine (e.g. urine immunofluorescence drugs of misuse screening test) is an effective way to confirm recent use of drugs such as benzodiazepines, cocaine, ecstasy, opioids and cannabis. Routine screens may not, however, detect fentanyl derivatives, tramadol and other synthetic opioids. Occasionally, measuring drugs of misuse and their metabolites in blood by gas chromatography-mass spectroscopy (GC-MS) is required for medico-legal purposes, particularly where there is a fatality, and in such cases urine and serum should be saved for later analysis.
PSYCHIATRIC ASSESSMENT OF THE POISONED PATIENT
In order to decide on the most appropriate placement and staffing ratios for a self-poisoned patient, an initial assessment of suicidal intent must be made. Use of the Beck's depression scale or similar may be valuable for this (see Box 3.2). If the sum of all the scores for each parameter is greater than 4 (e.g. suicide note left and no one likely to find patient after overdose), this indicates significant suicidal intent and means that the patient is at risk of further self-harm and should have a nurse with him or her at all times whilst an inpatient.
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3.2 BECK'S SCORING SYSTEM
Parameter Beck's score (add up all those relevant below) Scoring
Isolation 0 Someone present
1 Someone nearby or in vocal contact
2 No one nearby or in visual/vocal contact
Timing 0 Intervention probable
1 Intervention not likely
2 Intervention highly unlikely
Precautions against discovery or interruption 0 None
1 Passive precautions (avoiding others but doing nothing to prevent intervention)
2 Active precautions, e.g. locking door
Acting to gain help after the attempt 0 Notified potential helper regarding the attempt
1 Contacted but did not specifically notify helper regarding the attempt
2 Did not contact or notify helper
Final acts in anticipation of death 0 None
1 Thought about or made some arrangement
2 Definite plans made, e.g. changing will
Active preparation for attempt 0 None
1 Minimal
2 Extensive
Suicide note 0 None
1 Note written but torn up or note thought about
2 Note present
Overt communication of intent before attempt 0 None
1 Equivocal communication
2 Unequivocal attempt

Suicide attempts were once much more common in women than in men but now the ratios are more equal. There is a higher incidence in lower socio-economic groups, those who lost a parent at an early age, those with alcohol or drug misuse, recipients of child abuse, the unemployed and those with recent broken relationships. A thorough psychiatric and social assessment should be carried out in all patients once sufficient time has elapsed to allow the toxic effects of any drugs to wear off. This can be performed by nurses, physicians or psychiatrists. The interviewer needs to assess the severity of any current symptoms of psychiatric illness and to determine what personal or social supports need to be provided. Most patients have depressive and anxiety symptoms which are reactive to an acute life crisis superimposed on a background of chronic social and personal difficulties. They need neither psychotropic medication nor specialised psychiatric treatment but do need support, e.g. from social workers. Admission to a psychiatric ward is necessary for patients with major psychiatric illness (see p. 252) who remain intent on suicide. In our unit, about 20% of patients make a repeat suicide attempt during the following 12 months and 1% actually kill themselves. Factors associated with an increased risk of suicide include male sex, age over 45, living alone, unemployment, recent bereavement, divorce or separation, chronic ill health, drug or alcohol misuse, violent method used, suicide note written and a history of previous attempts.
Preventing poisoning is much better than curing it, and a number of important measures have been taken to achieve this (see Box 3.3).
3.3 METHODS OF POISONING PREVENTION
Method Mode of action
Addition of 'Bitrex' and other bittering agents to household products Prevents significant quantities being ingested as it tastes very bitter
Adding the antidote to the toxin, e.g. combination tablets of methionine and paracetamol Antidote is present so glutathione remains replete and hepatocellular injury is prevented
Child-resistant containers Reduce chance of ingestion by children
Secure location, e.g. locked cupboard Reduces chance of ingestion
Hazard warning labels Warn of potential toxicity, routes of exposure and appropriate protective equipment
Education Warning on safe storage and handling of chemicals and drugs
Supervision The key to reduced exposure for children
Legislation, e.g. Health and Safety regulations Makes a safer workplace with safeguards in the use of dangerous chemicals

GENERAL MANAGEMENT OF THE POISONED PATIENT
The majority of patients who present after poisoning have taken an overdose. Some present with eye or skin contamination and these are treated with appropriate washing methods (see Fig. 3.2). Only patients who have ingested significant overdoses need further measures such as gastric decontamination and methods to increase elimination. In the seriously poisoned patient, meticulous supportive care, including the treatment of seizures, coma and cardiovascular complications, is critical to good outcome. Seizures are seen most commonly in poisoning by theophyllines, non-steroidal anti-inflammatory drugs (NSAIDs), anticonvulsants and tricyclic antidepressants, and are best treated by airway management and i.v. diazepam (10 mg for an adult, repeated as necessary; see p. 1127). Cardiovascular support measures are discussed on page 201. Ventilatory support may be required until consciousness returns, and complications such as aspiration pneumonia should be treated promptly. It is important that patients are observed closely for signs of deterioration whilst the effects of the toxin they have taken wear off. This often approximates to five half-lives of the drug concerned.
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Figure 3.2 Routes of exposure to toxins and methods of preventing absorption or enhancing elimination.
EBM
SINGLE-DOSE ACTIVATED CHARCOAL AFTER POISON INGESTION
'A position statement based on available RCT data recommends that activated charcoal should be given to all patients who present within 1 hour of ingestion of a potentially toxic amount of poison which binds to charcoal.'
Chyka PA, Seger D. Position Statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poison Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:721-741.


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3.4 SUBSTANCES WHICH DO NOT BIND TO ACTIVATED CHARCOAL
Acids
Alkalis
Iron
Lithium
Ethanol
Methanol
Ethylene glycol


EBM
IPECACUANHA ADMINISTRATION AFTER POISON INGESTION
'Systematic review of clinical trials has demonstrated that ipecacuanha (ipecac) does not improve the outcome of poisoned patients and may delay the administration or reduce the effectiveness of activated charcoal, oral antidotes and whole bowel irrigation. Ipecacuanha-induced emesis is therefore no longer recommended.'
Krenzelok EP, McGuigan M, Lheureux P. Position Statement: ipecac syrup. American Academy of Clinical Toxicology; European Association of Poison Control Centres and Clinical Toxicologists. J Toxicol Clin Toxicol 1997; 35:699-709.
Pond SM, Lewis-Driver DJ, Williams GM, et al. Gastric emptying in acute overdose: a prospective randomised controlled trial. Med J Aust 1995; 163:345-349.


Activated charcoal is the most common method used to prevent drug absorption and is given orally as a black slurry; owing to its large surface area and porous structure, this is highly effective in adsorbing most toxins (see EBM panel). There are, however, a few agents that do not bind to activated charcoal (see Box 3.4). It should not be mixed with ice-cream or flavouring agents as these reduce its adsorptive capacity. In patients who cannot swallow or who have a reduced level of consciousness the activated charcoal should be given via a nasogastric tube. In all cases the airway must be adequately protected to avoid aspiration pneumonitis. Poisoning with certain drugs is best treated with multiple doses of activated charcoal (see Fig. 3.2), and in such circumstances it is important that a laxative is given to avoid obstruction due to charcoal 'briquette' formation in the gastrointestinal tract. Ipecacuanha administration is no longer recommended in the management of the poisoned patient.
Whole bowel irrigation is most effectively performed by asking patients to drink 1 litre of polyethylene glycol every hour until their rectal effluent is clear. Such preparations are not associated with osmotic changes. Contraindications include gastrointestinal haemorrhage or obstruction.
Despite popular misconceptions, specific antidotes are only available for a small number of poisons (see Box 3.5).
3.5 ANTIDOTES AVAILABLE FOR THE TREATMENT OF SPECIFIC POISONINGS
Poison Antidote
Anticoagulants (e.g. warfarin, rodenticides) Vitamin K, fresh frozen plasma
ß-adrenoceptor antagonists (ß-blockers) Glucagon, adrenaline (epinephrine)
Calcium channel blockers Calcium gluconate
Cyanide Oxygen, dicobalt edetate, nitrites, sodium thiosulphate, hydroxocobalamin
Ethylene glycol/methanol Ethanol, 4-methylpyrazole
Lead DMSA (2,3-dimercaptosuccinic acid), disodium calcium edetate
Mercury DMPS (2,3-dimercapto-1-propane sulphonate)
Iron salts Desferrioxamine
Opioids Naloxone
Organophosphorus insecticides, nerve agents Atropine, pralidoxime (P2S)
Paracetamol N-acetylcysteine, methionine
Cardiac glycosides Digoxin-specific antibody fragments (F(ab))

Substances of low toxicity
Every substance, even water, is a potential toxin, but the dose is the critical feature predicting risk of toxicity. However, for practical purposes, some substances can be ingested by man in large amounts without serious sequelae (see Box 3.6).
3.6 SUBSTANCES OF LOW TOXICITY
Antibiotics-but NOT tetracyclines or antituberculous drugs, which are toxic
Anti-ulcer drugs: H2-blockers or proton pump inhibitors
Chalk
Paper glues and wallpaper paste
Washing-up liquid-but NOT dishwasher tablets, which are highly corrosive
Household plants
Oral contraceptive pills
'Lead' pencils and 'felt-tip' pens
Silica gel
Emollient and zinc oxide creams


ISSUES IN OLDER PEOPLE
POISONING IN THE ELDERLY
Drugs that are renally cleared accumulate more rapidly and to higher levels in elderly patients due to reduced glomerular filtration rate.
CNS depressant drugs have a greater sedative action in the elderly and may precipitate confusion.
Suicide rates in most countries are highest in older people, and in the UK attempts in old age are usually by overdose.
There is a close association between depression and self-harm in old age, so all overdoses should be taken seriously in older people and aggressive treatment given for any underlying depressive illness.


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Home > 1 PRINCIPLES OF MEDICAL PRACTICE > 3 Poisoning > POISONING BY SPECIFIC PHARMACEUTICAL AGENTS
POISONING BY SPECIFIC PHARMACEUTICAL AGENTS
ANALGESICS
PARACETAMOL
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Figure 3.3 The management of a paracetamol overdose patient.
Do not check a paracetamol concentration before 4 hours have elapsed; it is uninterpretable. If more than 8 hours have elapsed since ingestion, start the N-acetylcysteine immediately and only stop it if the concentration is below the treatment line. (INR = international normalised ratio)
Paracetamol causes hepatic damage in overdose. More rarely, it can also cause renal failure. The management of a patient with paracetamol overdose is summarised in Figure 3.3. If a patient presents within 1 hour of the paracetamol overdose, activated charcoal can be given in addition to the management shown in the figure. The antidote of choice is intravenous N-acetylcysteine, which provides complete protection against toxicity if given within 10 hours of the overdose; its efficacy declines thereafter. For this reason, if a patient presents more than 8 hours after ingestion, N-acetylcysteine administration should not be delayed to await a paracetamol blood concentration result but should be stopped if the paracetamol concentration is subsequently shown to be below the treatment line. Methionine 12 g orally 4-hourly, to a total of four doses, is a suitable alternative antidote for paracetamol poisoning when N-acetylcysteine is not available. If a patient presents more than 15 hours after ingestion, liver function tests, prothrombin ratio (or international normalised ratio-INR) and renal function tests should be carried out, the antidote started, and a poisons information centre or local liver unit contacted for advice. In some cases an arterial blood gas sample will need to be taken. Liver transplantation should be considered in individuals who develop acute liver failure due to paracetamol (see p. 845).
If multiple ingestions of paracetamol have taken place over several hours or days (i.e. a staggered overdose), there is no merit in measuring the plasma paracetamol concentration as it will be uninterpretable. Such patients should be given N-acetylcysteine if the paracetamol dose exceeds 150 mg/kg body weight in any one 24-hour period or 75 mg/kg body weight in 'high-risk groups' (as shown in Fig. 3.3).
SALICYLATES (ASPIRIN)
Salicylate ingestion at doses greater than 150, 250 and 500 mg aspirin/kg body weight produces mild, moderate and severe poisoning respectively. Salicylate poisoning can also occur with ingestion of oil of wintergreen or when salicylic ointment (e.g. verruca remover) is applied extensively to skin. Aspirin overdose commonly produces nausea, vomiting, tinnitus and deafness. Direct stimulation of the respiratory centre produces hyperventilation. Peripheral vasodilatation with bounding pulses and profuse sweating occurs in moderately severe poisoning. Petechiae and subconjunctival haemorrhages can occur due to reduced platelet aggregation but are self-limiting. Signs of serious salicylate poisoning include metabolic acidosis, renal failure and central nervous system (CNS) effects such as agitation, confusion, coma and fits. Rarely, pulmonary and cerebral oedema occur. Death can occur as a consequence of CNS depression and cardiovascular collapse. The development of a metabolic acidosis is a bad prognostic sign, not least because acidosis results in increased salicylate transfer across the blood-brain barrier.
It is important to measure a plasma salicylate concentration in all but the most trivial overdose. This is best undertaken at 6 hours or later after ingestion because of continued absorption of the drug. The salicylate concentration needs to be interpreted in conjunction with the clinical features and acid-base status of the patient. Any significant metabolic acidosis should be treated with intravenous sodium bicarbonate (8.4%), and the volume given titrated to give an arterial pH of 7.4-7.5. Patients are often very dehydrated, and it is important to replace fluid loss from vomiting and sweating. However, injudicious use of intravenous fluids may precipitate pulmonary oedema. The use of multiple doses of activated charcoal (see p. 168) in salicylate poisoning is controversial, but this approach is currently recommended until the salicylate concentration has peaked. Urinary alkalinisation (see Fig. 3.2, p. 169) is indicated for adult patients with salicylate concentrations of 600-800 mg/l. Haemodialysis is very effective at removing salicylate and correcting acid-base and fluid balance abnormalities and should be considered when serum concentrations are above 800 mg/l in adult patients and above 700 mg/l in the elderly. Other indications for haemodialysis in acute salicylate overdose are metabolic acidosis resistant to correction, severe CNS effects such as coma or convulsions, pulmonary oedema and acute renal failure.
NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs)
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Overdose of most NSAIDs usually causes little more than minor gastrointestinal upset including mild abdominal pain, vomiting and diarrhoea. However, 10-20% of such patients have convulsions; these are usually self-limiting and seldom need treatment other than airway protection and oxygen. Serious features include coma, prolonged fits, apnoea and bradycardia but these are very rare. Deaths have been reported after massive overdose of ibuprofen, but not with mefenamic acid. Rarely, renal failure ensues. Features of toxicity tend to occur early and are unlikely to develop later than 6 hours after the overdose. Liver and renal function may be affected, and therefore electrolytes, liver function tests and a full blood count should be taken in all but the most trivial overdoses. The half-lives of most NSAIDs are less than 12 hours, so elimination methods are not needed. Activated charcoal should be given if more than 100 mg/kg body weight of ibuprofen or more than 10 tablets of another NSAID have been taken in the last hour. Non-self-limiting seizures are treated with intravenous diazepam, and gastrointestinal irritation with oral H2-blockers (e.g. ranitidine).
CARDIOTOXIC DRUGS
An individual's response to a cardiotoxic drug overdose is highly variable, and those with cardiac disease are more at risk of toxicity, particularly of complications such as pulmonary oedema. Care should be taken to identify whether or not the preparation is modified-release since in such cases toxicity can be delayed and prolonged. The cardiac features and principles of management of poisoning with cardiotoxic drugs are shown in Figure 3.4. In many countries, the more cardiotoxic tricyclic antidepressants are being replaced with the less cardiotoxic selective serotonin re-uptake inhibitors (SSRIs) for the treatment of depression. However, in large doses SSRIs can still cause hypotension and arrhythmias.


Figure 3.4 Mechanisms and management of poisoning with cardiotoxic drugs.
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ANTIMALARIALS
CHLOROQUINE
Symptoms and signs of chloroquine overdose usually start within 1 hour of ingestion and include nausea, vomiting, agitation, drowsiness, hypokalaemia, headaches and visual disturbances. After large ingestions coma, convulsions, hypotension (due to the negative inotropic effect) and arrhythmias (widened QRS and QT intervals, ventricular tachycardia-including torsade de pointes, and ventricular fibrillation) occur.
Activated charcoal should be given and gastric lavage considered in all patients who present within 1 hour of ingestion of more than 15 mg/kg chloroquine. Cardiovascular complications can be managed by the techniques shown in Figure 3.4. The plasma potassium should be monitored, although hypokalaemia may have a protective effect and should not be corrected in the early stages of poisoning. If hypokalaemia persists beyond 8 hours, potassium should be replaced with caution. High-dose diazepam (2 mg/kg body weight i.v. over 30 minutes) may have a protective effect in chloroquine poisoning, but respiratory support should be available before it is given.
QUININE
Quinine salts are widely used in the treatment of malaria and nocturnal cramps. The average fatal dose in an adult is 8 g, although deaths have been reported with as little as 1.5 g in an adult and 900 mg in a child. Quinine causes retinal vasoconstriction and also has a direct toxic effect on retinal photoreceptor cells. At 6-10 hours after ingestion, blurred vision and impaired colour perception start and can progress to constriction of the visual field, scotoma and complete blindness. The pupils become dilated and unresponsive to light, and fundoscopy shows retinal artery spasm progressing to disc pallor and retinal oedema. Visual loss can be permanent. Other features include nausea, vomiting, tinnitus, deafness, headache and tremor. In large overdoses ataxia, drowsiness, coma, respiratory depression, haemolysis and cardiac effects can occur. The latter include hypotension, ECG changes (prolongation of the QRS and corrected QT interval (QTc), atrioventricular block) and arrhythmias (ventricular tachycardia-torsade de pointes and ventricular fibrillation).
Maintenance of the airway and ventilation is critical. Gastric lavage should be considered if a patient presents within 1 hour of ingestion of more than 15 mg/kg of quinine, and multiple-dose activated charcoal should be given to all patients who have ingested an amount of quinine above this threshold dose. All patients should have a 12-lead ECG, have blood taken for urea, electrolytes and glucose, and have cardiac monitoring. Visual effects of quinine are largely untreatable. In the past many measures were advocated, such as stellate ganglion block and retrobulbar or i.v. injections of vasodilators including nitrates; these measures are now obsolete. Cardiovascular complications can be managed by the techniques shown in Figure 3.4. Haemodialysis and haemoperfusion are ineffective in quinine poisoning.
ANTIDIABETIC AGENTS
These include the sulphonylureas (e.g. chlorpropamide, glibenclamide, gliclazide, glipizide, tolbutamide), biguanides (metformin) and insulin.
Antidiabetic agents can cause hypoglycaemia when taken in overdose, although insulin is non-toxic if ingested. The onset and duration of hypoglycaemia vary, but can last for several days with the longer-acting agents such as chlorpropamide and isophane and lente insulins. Hypoglycaemia may manifest as agitation, sweating, confusion, tachycardia, hypothermia, drowsiness, coma or convulsions (see p. 652). Permanent neurological damage can occur if the hypoglycaemia is prolonged. Metformin can cause a lactic acidosis in overdose, particularly when co-ingested with ethanol or in elderly patients and those with renal or hepatic impairment, and is associated with a high (> 50%) mortality. Other clinical effects observed after metformin overdose include nausea and vomiting, diarrhoea, abdominal pain, drowsiness, coma, hypotension and cardiovascular collapse.
Activated charcoal should be given (and gastric lavage considered) to all patients who present within 1 hour of ingestion of more than the normal therapeutic dose of an oral hypoglycaemic agent. Formal measurement of (venous) blood glucose (not just visually read strips or meter) and urea and electrolytes should be carried out and the tests repeated regularly. For medico-legal purposes, a blood sample may be required for subsequent measurement of insulin, pro-insulin and C-peptide levels. Hypoglycaemia should be corrected urgently with 50 ml 50% dextrose given i.v. if the patient is unconscious or with a sugary drink if the patient is conscious. This should be followed by an infusion of 10% or 20% dextrose titrated to the patient's blood glucose to prevent further hypoglycaemia. Patients may need dextrose infusions for several days, depending on the agent ingested/injected. Potassium replacement is necessary and should be guided by frequent measurement of urea and electrolytes. As a general rule, add 10-20 mmol potassium chloride to each litre of dextrose. Failure to regain consciousness within a few minutes of normalisation of the blood glucose can indicate that a CNS depressant has also been ingested, that the hypoglycaemia has been prolonged, that there is another cause for the coma (e.g. cerebral haemorrhage) or that the patient has cerebral oedema (see p. 846).
DRUGS LESS COMMONLY TAKEN IN OVERDOSE
Box 3.7 gives an overview of the clinical features and management of overdose of other drugs not discussed in detail above.
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3.7 DRUGS TAKEN LESS COMMONLY IN OVERDOSE
Drug Features Management
Anticonvulsants Cerebellar signs
Fits Multiple-dose activated charcoal
Coma
Cardiovascular toxicity Cardiovascular support (as Fig. 3.4) I.v. diazepam for fits
Antihistamines Drowsiness Activated charcoal within 1 hour
Cardiac arrhythmias Cardiovascular support (as Fig. 3.4)
Chlorpromazine/haloperidol Hypotension
Drowsiness Single-dose activated charcoal
Fits Cardiovascular support (as Fig. 3.4) I.v. diazepam for fits
Iron tablets Vomiting
Haematemesis
Abdominal pain
Coma Ingestion of < 30 mg elemental iron/kg body weight: no active treatment
Convulsions
Shock
Metabolic acidosis
Hepatic failure Ingestion of > 30 mg/kg:
Check abdominal radiograph
Perform gastric lavage/whole bowel irrigation
Check a serum iron concentration and above 90µmol/l treat with i.v. desferrioxamine, especially if clinical features are present
Isoniazid Peripheral neuropathy Activated charcoal
I.v. pyridoxine
Fits I.v. diazepam for fits
Lithium Nausea Does NOT bind to charcoal
Vomiting Whole bowel irrigation
Tremors
Fits Increased hydration, avoid diuretics
Confusion
Coma In severe cases: haemodialysis
Theophylline Cardiac arrhythmias
Fits Cardiovascular support (as Fig. 3.4)
Coma Multiple-dose activated charcoal
I.v. diazepam for fits
Thyroxine Tremor Check thyroid function
Tachycardia Treat symptomatically with propranolol p.o.
Zidovudine Drowsiness Activated charcoal
Nausea Regular full blood count
Bone marrow suppression Diazepam for fits
Fits

ISSUES IN OLDER PEOPLE
POISONING BY SPECIFIC PHARMACEUTICAL AGENTS
In salicylate poisoning in the elderly haemodialysis should be started at lower serum drug levels (see p. 171).
Older people are more likely to develop lactic acidosis following metformin overdose.


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Home > 1 PRINCIPLES OF MEDICAL PRACTICE > 3 Poisoning > DRUGS OF MISUSE
DRUGS OF MISUSE
CANNABIS
The term 'cannabis' refers to all psychoactive substances derived from the dried leaves and flowers of the plant Cannabis sativa. Marijuana refers to any part of the plant used to induce effects, and hashish is the dried resin from the flower tops. Cannabis is usually dried and either smoked or eaten. Slang terms include grass, pot, ganja, spliff and reefer. When it is smoked, the onset of effect is 10-30 minutes; after ingestion the onset is 1-3 hours. The duration of effect is 4-8 hours. In low doses cannabis produces euphoria and perceptual alterations, followed by relaxation and drowsiness, hypertension, tachycardia, slurred speech and ataxia. High doses produce acute paranoid psychosis, anxiety, confusion, hallucinations and distortion of time and space. Intravenous misuse of the crude extract of cannabis may cause nausea and vomiting, diarrhoea, abdominal pain, fever, hypotension, pulmonary oedema, acute renal failure, disseminated intravascular coagulation and death.
Serious poisoning resulting from ingestion or smoking of cannabis is extremely rare. For patients with drug-induced psychosis reassurance is usually sufficient but i.v. diazepam may be used for sedation. Hypotension usually responds well to intravenous fluids. All patients who have injected cannabis should be admitted, and careful management of fluid and electrolyte balance is essential, owing to the risks of acute renal failure and pulmonary oedema.
BENZODIAZEPINES
In general, lone benzodiazepine overdoses are remarkably safe and near-full recovery takes place within 24 hours. Difficulties occur when other CNS depressants, such as tricyclic antidepressants, opioids or alcohol, are taken in addition or when an overdose occurs in susceptible groups such as the elderly or those with chronic obstructive pulmonary disease. Drowsiness and mid-position or dilated pupils are common and occur within 3 hours of ingestion. Ataxia, dysarthria, nystagmus and confusion are also observed. Coma may follow, but in lone benzodiazepine overdose a GCS grade below 10 (see p. 1143) is rare. Minor hypotension and respiratory depression may occur. Respiratory arrest is uncommon but can occur after shorter-acting agents such as midazolam.
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Gastric lavage is not advised in pure benzodiazepine overdose. Activated charcoal, if required, can be given within 1 hour of the overdose, particularly in a mixed overdose. Impaired consciousness is treated conventionally, with particular attention to maintenance of the airway. Observation should be for at least 6 hours post-ingestion, or for 24 hours in more serious cases. Oxygen saturation monitoring using a pulse oximeter is useful for ascertaining the adequacy of ventilation if significant CNS depression is present. Flumazenil is a specific benzodiazepine antagonist but it is not used in the vast majority of cases of poisoning with benzodiazepines. Flumazenil must never be used in patients with a history of convulsions or toxin-induced cardiotoxicity, or in those who have co-ingested tricyclic antidepressants. In such circumstances, seizures and ventricular arrhythmias can be precipitated.
CRACK/COCAINE
Cocaine (hydrochloride) is usually purchased as a white crystalline powder or colourless crystals and may be sniffed into the nose (snorted) or injected intravenously. 'Crack' is cocaine that has been separated from the hydrochloride base (free-base), melted and smoked in a pipe or mixed with tobacco in a cigarette. Crack is usually sold in 'rocks' containing 150 mg of cocaine or as a 'line' of cocaine for snorting that contains 20-30 mg of the drug. While the toxic dose is very variable and depends on individual tolerance, the presence of other drugs and the route of administration, ingestion of any amount over 1 g is potentially fatal.
After intranasal use effects are experienced within minutes and tend to last 20-90 minutes. With intravenous use or oral intake the peak 'high' occurs within 10 and 45-90 minutes respectively. Smoking crack causes a peak 'high' within 10 minutes. In most cases the effects begin to resolve in about 20 minutes post-onset, except when taken intranasally. In fatal poisoning the onset and progression of symptoms are accelerated and death may occur in minutes. Survival beyond 3 hours indicates that the patient is unlikely to die.
3.8 COMPLICATIONS AND MANAGEMENT OF ACUTE COCAINE INTOXICATION
Complication Management
Hypertension Oral diazepam, nifedipine or doxazosin
Hypertension with encephalopathy, infarction, stroke or proteinuria I.v. therapy: nitrates or sodium nitroprusside
Supraventricular tachycardia I.v. verapamil; avoid ß-blockers, which cause hypertension due to unopposed alpha stimulation
Cocaine-induced angina I.v. or buccal nitrates are treatment of choice; avoid ß-blockers
Cocaine-induced myocardial infarction Use of thrombolytic agents usually not necessary because mechanism is spasm rather than thrombosis
Hyperthermia > 39°C Cool i.v. fluids, dantrolene; paralyse and ventilate the patient if hyperthermia persists despite these measures
Agitation or psychosis Oral diazepam; phenothiazines and haloperidol should be avoided as they lower the threshold for convulsions

Mild to moderate intoxication with cocaine causes euphoria, agitation, aggression, cerebellar signs (see p. 1135), dilated pupils, vomiting, pallor, headache, cold sweats, twitching, pyrexia, tachycardia, hallucinations and hypertension. Features of severe intoxication include convulsions, coma, muscular paralysis, severe hypertension and stroke. Coronary artery spasm may result in myocardial ischaemia or infarction, even in patients with normal coronary arteries, and this leads to hypotension, cyanosis and ventricular arrhythmias. Hyperthermia associated with rhabdomyolysis, acute renal failure and disseminated intravascular coagulation may also occur.
Activated charcoal should be given in any patient presenting within 1 hour of oral ingestion, irrespective of the amount taken. All patients should be observed with ECG monitoring for a minimum of 2 hours. Blood pressure, heart rate and body temperature should also be monitored and the patient observed carefully for the development of specific complications (see Box 3.8).
ECSTASY/AMPHETAMINES
MDMA (3,4-methylenedioxymethamphetamine, ecstasy) is a 'designer' amphetamine also known as E, Adam, white dove, white burger, or red and black. Amphetamines and the newer designer amphetamines are virtually indistinguishable in their clinical effects. Effects occur within 1 hour of ingestion and last 4-6 hours following doses of 75-150 mg but up to 48 hours after the ingestion of 100-300 mg. However, tolerance is common, and most regular users need to take considerably higher doses.
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Supraventricular and ventricular arrhythmias are common and may cause death. Agitation or drowsiness is also common. Whilst the vast majority of patients who have taken ecstasy are profoundly dehydrated, a small proportion develop hyponatraemia, usually through drinking excessive amounts of water in the absence of sufficient exertion to sweat off the fluid. Antidiuretic hormone secretion may also contribute to the development of hyponatraemia. Other features of intoxication with amphetamines or ecstasy include nausea, hyper-reflexia, muscle pain, trismus (jaw-clenching), dilated pupils, blurred vision, sweating, dry mouth, agitation, visual hallucinations and anxiety. Severe intoxication is characterised by coma, convulsions, hypertension and cardiac arrhythmias. A hyperthermic (5-HT-like) syndrome may develop with rigidity, hyper-reflexia and hyperpyrexia (> 39°C) leading to hypotension, rhabdomyolysis, metabolic acidosis, acute renal failure, disseminated intravascular coagulation, hepatocellular necrosis, acute respiratory distress syndrome and cardiovascular collapse. In view of this it is important to measure urea and electrolytes, creatine kinase and blood glucose, carry out a full blood count and liver function tests, and observe all symptomatic cases with ECG, blood pressure and temperature monitoring for at least 6 hours post-exposure. A 12-lead ECG is required. The complications described above should be treated in the same way as for cocaine (see Box 3.8). Selective serotonergic antagonists (e.g. cyproheptadine/ketanserin) may become available for use in patients with a 5-HT-like syndrome to reduce temperature and rigidity by central mechanisms.
GAMMAHYDROXYBUTYRATE (GHB)
GHB is marketed illegally for body building and weight loss and as a replacement for L-tryptophan. Slang terms include liquid X, cherry meth, easy lay, scoop and GBH. It is commonly dissolved in water to produce a clear, colourless liquid that tastes of seaweed. Many misusers simply 'guzzle' it until they reach an adequate high, which is often achieved shortly before becoming unconscious. Owing to the drowsiness that may occur, it is sometimes mixed with amphetamines to prolong the 'high' for several hours. The severity and duration of effects seem to be dose-dependent. Doses of 10-30 mg/kg cause mild effects such as nausea, diarrhoea, confusion, vertigo, tremor, extrapyramidal signs, agitation and euphoria, whereas higher doses (30-50 mg/kg) cause drowsiness, coma, bradycardia, hypotension and respiratory depression. More than 50 mg/kg causes decreased cardiac output and increasingly severe respiratory depression, fits and coma. The effects are potentiated by other CNS depressants (e.g. alcohol, benzodiazepines, opioids and neuroleptic drugs). Bizarrely, patients often recover quickly (within 1-2 hours), with scenarios such as self-extubation and rapid reversal of coma seen. Coma usually resolves spontaneously within 2-4 hours, but may on occasion persist for as long as 96 hours.
Urea and electrolytes and glucose should be measured in all but the most trivial of cases. Activated charcoal treatment is recommended within 1 hour for ingestions of more than 20 mg/kg. All patients should be observed for a minimum of 2 hours, monitoring blood pressure, heart rate, respiratory rate and oxygenation. Patients who remain symptomatic after this time should be admitted and observed until symptoms resolve, but require supportive care only.
LSD
d-Lysergic acid diethylamide (LSD) is a synthetic hallucinogen. Common slang terms are acid, trips, dots, paper mushrooms or 'L'. LSD is usually ingested as small squares of impregnated absorbent paper, which are often printed with a distinctive design, or as 'microdots'. Patients presenting to hospital usually do so as a result of a 'bad trip', panic reaction, vivid visual hallucinations or aggression, or after a suicide attempt. The individual may be found wandering in a confused, agitated state. Dilated pupils are common. Peak effects are seen within 30-60 minutes of an oral dose. LSD itself is of low acute toxicity; fatalities are a result of behavioural changes induced by LSD, leading to accidents such as drowning. Flashbacks can occur within hours or months after acute or chronic misuse. These may be precipitated by physical or emotional stress.
Patients with psychotic reactions or CNS depression should be observed in hospital. The patient should be placed in a quiet, dimly lit room to minimise external stimulation. Where sedation is required, diazepam is the drug of choice; haloperidol is used as the second agent if diazepam is ineffective. The use of chlorpromazine has been associated with cardiovascular collapse in LSD intoxication.
OPIOIDS
These include heroin, morphine, methadone, codeine, pethidine, dihydrocodeine and dextropropoxyphene. The hallmarks of opioid analgesic poisoning are:
depressed respiration
pinpoint or small pupils
depressed conscious level
signs of intravenous drug misuse (e.g. needle track marks).

Severe poisoning is indicated by respiratory depression, hypotension, non-cardiogenic pulmonary oedema and hypothermia. Death occurs by respiratory arrest or from aspiration of gastric contents. Poisoning with dextropropoxyphene (the opioid moiety of co-proxamol) may also result in cardiac conduction effects, particularly QRS prolongation, ventricular arrhythmias and heart block. Unconscious patients should always have their paracetamol concentration checked because of the prevalence of combination opioid/paracetamol drugs. Symptoms of opioid poisoning can be prolonged for up to 48 hours, particularly after ingestion of methadone, which has a long half-life.
Steps should be taken to ensure a clear airway and, if necessary, provide respiratory support. Supplementary high-flow oxygen should be administered. The need for endotracheal intubation can often be avoided by prompt administration of adequate doses of the opioid antagonist naloxone (see below). Oxygen saturation monitoring and arterial blood gases demonstrate the adequacy of ventilation in those whose respiration has been compromised. The treatment of coma (see p. 1143), fits (see p. 1121) and hypotension (see Fig. 3.4, p. 172) is detailed elsewhere. Non-cardiogenic pulmonary oedema in severe cases does not usually respond to diuretic therapy, and CPAP and/or PEEP (see p. 204) may be required.
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Naloxone is a specific opioid antagonist that reverses the above features of opioid toxicity. It should be used as a bolus dose (0.8-2 mg i.v.) in adults. This should be repeated every 2 minutes as necessary until the level of consciousness and respiratory rate increase and the pupils dilate. A total dose of as much as 10-20 mg may be required in some cases. Administration of too much naloxone should be avoided as it can precipitate a withdrawal reaction, characterised by gastrointestinal effects, sweating and fits. It is best to titrate repeat bolus doses, aiming for a GCS of 13-14 (not 15). After the initial i.v. bolus, an infusion of naloxone may be needed because the half-life of the antidote is much shorter than the half-lives of most opioids. As a guide, two-thirds of the bolus dose initially required to wake the patient should be infused each hour. Patients must be carefully observed for recurrence of coma and respiratory depression, usually for at least 18-24 hours. It is particularly important that patients are observed for recurrence of CNS depression for at least 4-6 hours after the last dose of naloxone is given. Naloxone has been reported to cause pulmonary oedema and ventricular arrhythmias, but such events are infrequent and not enough to outweigh its use.
MANAGEMENT OF BODYPACKERS
Bodypackers ingest drugs of misuse (particularly cocaine and heroin) wrapped in clingfilm or packed into condoms for the purpose of drug smuggling. It is important to ask the patient exactly what is in the packets and to obtain an abdominal radiograph to help establish where the packets are located and how many are present (see Fig. 3.5). If they are in the stomach, they can be removed endoscopically, taking extreme care not to rupture the packages. Alternatively, they can be allowed to pass through with the help of a laxative such as lactulose. Paraffin-based laxatives should not be used, as this may increase the risk of packet rupture. If packages are in the small or large bowel, either laxatives can be given, or whole bowel irrigation can be performed to aid their speedy recovery (see p. 170). Patients should be admitted and observed closely until all packets are recovered. Rupture of the packets can be fatal and rapid because of the large doses carried. Packets carried in the vagina or rectum should be removed manually.


Figure 3.5 Abdominal radiograph of a bodypacker showing multiple drug-filled condoms.

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Home > 1 PRINCIPLES OF MEDICAL PRACTICE > 3 Poisoning > CHEMICALS AND PESTICIDES
CHEMICALS AND PESTICIDES
Features of poisoning on clinical examination that point to the chemical, gas or pesticide responsible are shown in Figure 3.6.
CARBON MONOXIDE AND SMOKE
Carbon monoxide is a colourless, non-irritant, odourless gas; sources include smoke from fires, car exhausts and the incomplete burning of gas fires or cookers. The risk of carbon monoxide poisoning is greatest where ventilation is poor. As well as carbon monoxide, smoke produced in house fires contains a mixture of soot and organic particles, together with other gases such as hydrogen sulphide. Carbon monoxide is the major cause of death by poisoning in the United Kingdom and many other countries. It reduces the oxygen-carrying capacity of the blood by binding to haemoglobin to form carboxyhaemoglobin, and impairs the function of cytochrome oxidases. This impairs oxygen delivery from blood to tissues and its utilisation within tissues. Death may result from the acute cardiac and neurological sequelae, and there are also concerns over long-term effects from acute and chronic exposure.
The early clinical features of acute carbon monoxide poisoning are headache, nausea and vomiting, ataxia and nystagmus. Later features include drowsiness, hyperventilation, hyper-reflexia and shivering. Central and peripheral cyanosis occurs. Some patients are disinhibited, agitated or aggressive rather than drowsy. Convulsions, coma, hypotension, respiratory depression, ECG changes (ST segment depression, T-wave abnormalities, ventricular tachycardia or ventricular fibrillation) and cardiovascular collapse may occur in severe cases. Cerebral oedema is common and focal neurological signs can be present. Carbon monoxide-induced rhabdomyolysis leading to myoglobinuria and renal failure has been reported. Significant abnormalities on physical examination include impaired short-term memory and cerebellar signs (past-pointing and unsteadiness of gait, particularly heel-toe walking). Any one of these signs would classify the episode as severe. Rigidity, hyper-reflexia and extensor plantars may occur in mild, moderate or severe cases. Carbon monoxide poisoning in pregnancy is likely to cause miscarriage or premature labour due to fetal hypoxia. Patients recovering from carbon monoxide poisoning may suffer neurological sequelae including tremor, personality changes, memory impairment, visual loss, inability to concentrate and Parkinsonian features. Chronic carbon monoxide poisoning gives symptoms which are difficult to distinguish from influenza, i.e. nausea, vomiting, headache, lethargy, and aches and pains.
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Figure 3.6 Clinical signs of poisoning by chemicals, pesticides or gases.
The carboxyhaemoglobin (COHb) concentration is of value in confirming the diagnosis of acute carbon monoxide poisoning, although it may not be elevated sufficiently to be diagnostic in chronic cases. However, the degree of COHb elevation does not correlate well with the severity of poisoning, even acutely. Normal values are up to 3-5% and can be as high as 6-10% in smokers. An ECG should be performed in anyone with acute poisoning, especially in patients with pre-existing heart disease. Anyone with serious poisoning also requires arterial blood gas analysis. Oxygen saturation readings by pulse oximetry are misleading (see below).
3.9 INDICATIONS FOR CONSIDERING HYPERBARIC OXYGEN THERAPY IN CARBON MONOXIDE POISONING
Focal neurological signs, especially cerebellar ones
COHb at any time > 40%
Patient is pregnant
Patient is unconscious at any time


The most important first step in treating carbon monoxide poisoning is to move the patient away from the source of exposure. It is vital to ensure that the airway, breathing and circulation are adequately maintained and give supplementary oxygen as soon as possible. Oxygen should be given in high flow, e.g. 12 litres per minute, ideally through a tightly fitting facemask such as a CPAP mask. It should be continued until the COHb is less than 5% and for at least 6 hours after exposure. Sometimes 12-20 hours are required for this to take place. Unfortunately, pulse oximeters measure both carboxyhaemoglobin and oxyhaemoglobin and so a normal saturation value does not give grounds for reassurance. The use of sodium bicarbonate intravenously should be avoided, as this will impair oxygen release to tissues. Care should be taken to avoid excessive intravenous fluid administration, particularly in the elderly, because of the risk of pulmonary oedema. Most deaths occur in those who have arrested at the scene or who are unconscious on arrival in hospital. Blood pressure should be monitored and convulsions controlled with diazepam. The use of hyperbaric oxygen is controversial; Box 3.9 lists the current indications for such therapy. The logistical difficulties of transporting sick patients to hyperbaric chambers should not be under-estimated.
ORGANOPHOSPHORUS INSECTICIDES/NERVE GASES
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Organophosphorus compounds were initially developed as chemical warfare agents, e.g. sarin. Although they have numerous complex actions, their principal effect is inhibition of cholinesterase enzymes, particularly acetylcholinesterase (AChE) (see Fig. 3.7), which is very slow to 'age', yielding the active enzyme once again. This leads to accumulation of acetylcholine at muscarinic receptors (cholinergic effector cells), nicotinic receptors (skeletal neuromuscular junction and autonomic ganglia) and in the CNS. Organophosphorus compounds are well absorbed by ingestion and inhalation, and through the skin. The onset, severity and duration of poisoning depend on the route of exposure and the agent involved; onset can be as early as 5 minutes after exposure or be delayed for up to 12 hours.
Features of acute ingestion include muscarinic effects (vomiting, abdominal pain, diarrhoea, miosis, sweating, hypersalivation and dyspnoea due to bronchoconstriction and excessive bronchial secretions), nicotinic effects (muscle fasciculation, tremor and later weakness) and CNS effects (anxiety, headache, loss of memory, drowsiness and coma). Although bradycardia would be predicted from the mechanism of action, tachycardia occurs in about one-third of cases. Later, flaccid muscle paralysis with paralysis of limb muscles, respiratory muscles and sometimes extra-ocular muscles occurs. Respiratory muscle paralysis, bronchial constriction and the presence of copious respiratory secretions contribute to respiratory failure, but depression of respiratory drive is probably the single most important factor and respiratory complications are the major cause of death in severely poisoned patients. Coma is present in severely poisoned patients; rarely, hyperglycaemia, complete heart block and arrhythmias may occur.
A minority of patients develop the intermediate syndrome. This is characterised by cranial nerve and brain-stem lesions and a proximal neuropathy commencing 1-4 days after acute poisoning and lasting for approximately 3 weeks. Respiratory depression is a complication and ventilatory support is required as the intermediate syndrome is unresponsive to atropine and oximes.


Figure 3.7 Mechanism of action of acetylcholinesterase (AChE) and its inhibitors at the neuromuscular junction.
Organophosphate-induced delayed neuropathy starts 2 weeks or more after exposure and is the result of degeneration of large myelinated motor and sensory fibres. Initial flaccidity and muscle weakness in the arms and legs give rise to a clumsy shuffling gait and are followed later by spasticity, hypertonicity, hyper-reflexia and clonus. In many patients recovery is limited to the arms and hands, and damage to lower extremities, such as foot drop, is permanent. Not all organophosphorus compounds cause delayed neuropathy and those that do have been phased out in most developed countries.
If possible, the diagnosis should be confirmed by measuring AChE activity, preferably in both erythrocytes and plasma; the availability of this assay is limited and clinical features are more helpful than red cell cholinesterase measurements in determining the severity of intoxication. However, there is an approximate correlation between cholinesterase activity and clinical effects (~50% cholinesterase activity in subclinical poisoning, 20-50% activity in mild poisoning and less than 10% activity in severe poisoning). An ECG should be carried out in all patients, and urea, electrolytes and glucose monitored.
The management of acute organophosphorus poisoning includes clearing the airway, ensuring adequate ventilation and giving high-flow oxygen. For skin exposure, soiled clothing should be removed and placed in double-sealed bags, and the skin washed thoroughly with soap and water. If the compound has been ingested, gastric lavage may be undertaken within an hour of intake, followed by activated charcoal administered via nasogastric tube. Patients who are severely poisoned with organophosphorus compounds should be managed in an intensive care unit. Convulsions and twitching should be controlled with intravenous diazepam. Atropine (2 mg i.v. for an adult) reduces bronchorrhoea, bronchospasm, salivation and abdominal colic, and should be repeated every 10 minutes until secretions have dried up and bradycardia has been abolished. Atropine toxicity (flushed red skin, tachycardia, dilated pupils and dry mouth) should be avoided. Up to 30 mg of atropine, rarely more, may be required in the first 24 hours and the drug may have to be continued for a prolonged period.
Cholinesterase reactivators, such as the oximes pralidoxime (P2S) and obidoxime (toxogonin), are helpful if given before the organophosphorus-cholinesterase enzyme complex 'ages'. In the UK, pralidoxime is given in addition to atropine to every symptomatic patient at a dose of 30 mg/kg body weight by slow i.v. injection. Clinical improvement (cessation of convulsions and fasciculation, improved muscle power and recovery of consciousness) usually occurs within 30 minutes. The need for further therapy is guided by clinical improvement together with monitoring of cholinesterase activity. If necessary, further doses of pralidoxime can be given 4-6-hourly or by continuous infusion. Adverse effects are seen at high doses and include tachycardia, muscular rigidity, neuromuscular blockade, hypertension and laryngospasm. Haemoperfusion and haemodialysis are of no benefit.
CARBAMATE INSECTICIDES
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Carbamate insecticides inhibit a number of tissue esterases, in particular cholinesterase enzymes and especially acetylcholinesterase (see Fig. 3.7). They have a very similar duration of action to organophosphorus compounds but it is much shorter, as the carbamate/cholinesterase complex dissociates spontaneously with a half-life of 30-40 minutes. Since carbamate insecticides act in the same way as organophosphorus compounds, the features of poisoning are similar but not usually so severe. However, deaths have occurred. Delayed neurotoxicity has been reported following acute exposure to carbamate insecticide, particularly sensory loss and weakness in arms and legs, accompanied by peripheral axonal neuropathy.
3.10 CHEMICALS AND TOXINS TAKEN LESS COMMONLY IN OVERDOSE
Toxin Features Management
Acids and alkalis Acid injures stomach but alkali injures oesophagus; aspiration causes pneumonitis
Serious GI injury can result
Later, strictures or malignant transformation can occur Gastric lavage contraindicated
Do not give neutralising chemicals
Chest radiograph needed to exclude perforation
Early endoscopy or Gastrografin studies advised to assess extent of damage and determine
whether surgery is necessary
Button batteries containing lithium or mercury Obstruction, corrosion of GI tract
Heavy metal toxicity Abdominal radiograph will locate position
Remove endoscopically if obstruction/not passed from stomach within 24 hours
Bleach Irritation around mouth
Serious GI corrosion if an adult has deliberately ingested a large amount Milk if small amounts have been ingested, e.g. accidental mouthful
Endoscopy for adults as per acid (see above)
Essential oils, e.g. clove oil Very toxic
Fits and hepatotoxicity Gastric lavage if even a few ml have been taken by a child
Ethanol, e.g. alcoholic drinks, mouthwashes, antiseptics, perfumes Fatal dose of absolute ethanol is 6-10 ml/kg body weight in adults
Blood alcohol concentrations of > 5 g/l associated with coma
Convulsions, hypotension, and respiratory depression and/or circulatory failure may follow Check blood alcohol concentration
Protect airway to prevent aspiration; intubation and ventilation may be required
Ensure patient is well hydrated; in a chronic alcoholic, give i.v. thiamine (Pabrinex) before dextrose
Consider haemodialysis if blood ethanol concentration is > 5 g/l or arterial pH < 7
Methanol or ethylene glycol, e.g. antifreeze Methanol metabolised to metabolic acidosis and ocular toxicity formate, causing profound
Ethylene glycol metabolised to acids, causing metabolic acidosis; oxalate causes renal damage due to calcium oxalate crystals in urine Ethylene glycol and methanol assays not widely available as an urgent assay
Diagnosis usually made on presence of a high anion gap, osmolal gap (> 10 mOsm) and presence of oxalate crystals in urine (ethylene glycol in 50% of cases)
Antidotal treatment inhibits alcohol dehydrogenase; includes oral ethanol, i.v. ethanol or i.v. 4-methylpyrazole (non-sedating)
Haemodialysis should be considered in severe cases, especially if methanol or ethylene glycol concentration in blood is > 500 mg/l
Paraquat Buccal ulceration
Progressive respiratory fibrosis
Respiratory failure
Renal failure Give multiple doses of activated charcoal if urine screen test is positive
Check blood Paraquat concentration; if above survivalcurve, patient will probably die, as no measures are effective
Petroleum distillates, white spirit Vomiting common
Aspiration into lungs results in severe pulmonary complications: cough, choking, wheeze and dyspnoea, which peak in 24 hours and settle 3-4 days later
In more severe cases chemical pneumonitis or lipoid pneumonia can develop; deaths have occurred Gastric lavage contraindicated
Activated charcoal ineffective
Oxygen and nebulised bronchodilators
Chest radiograph should be carried out to look for pulmonary effects

The management of acute carbamate insecticide poisoning is identical to that for organophosphates, except that rapid recovery tends to occur with supportive therapy alone (including atropine), and the use of oximes is unnecessary and may be detrimental. In severe carbamate poisoning atropine may be given intravenously in frequent small doses (0.5-1.0 mg i.v. for an adult) until signs of atropinisation develop. Diazepam may be used to relieve anxiety.
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ALUMINIUM AND ZINC PHOSPHIDE
These are commonly used as rat poisons in South-east Asia. Aluminium phosphide has recently become the most common means of self-poisoning in Northern India, with a mortality rate of 60%.
When ingested, either compound reacts with water in the stomach to yield phosphine-a potent pulmonary toxicant. Hepatic toxicity and myocarditis have been reported after zinc phosphide ingestion. Many physicians will undertake gastric lavage in patients who have swallowed any amount of these tablets, as even a few can be fatal. Alternatively, lavage can be carried out with vegetable oil rather than water, in theory to reduce the generation of toxic phosphine. Sadly, most patients die, despite optimal supportive care.
CHEMICALS AND PESTICIDES LESS COMMONLY TAKEN IN OVERDOSE
Box 3.10 gives an overview of the clinical features and management for other chemicals not discussed above.

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Home > 1 PRINCIPLES OF MEDICAL PRACTICE > 3 Poisoning > ENVENOMATION
ENVENOMATION
SNAKE BITES
Snake bite is common in rural areas throughout the tropics; farmers, hunters and rice-pickers are at particular risk and prompt medical treatment is vital. Poisonous species of snake all fall into the following families (see Fig. 3.8):
Viperidae-including true vipers such as Russell's viper, and the puff adder
Crotalidae-often considered a subfamily of Viperidae; includes the pit vipers
Elapidae-true elapids, including the cobras, kraits and coral snakes
Hydrophidae-the sea snakes
Colubridae-including the mangrove snake.

Pathogenesis


Figure 3.8 The management of snake bites.
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Snake venoms are complex mixtures of proteins and small polypeptides with enzymatic activity (e.g. the mitochondrial-damaging enzyme phospholipase A2). Russell's viper venom contains procoagulants; other venoms block transmission at the neuromuscular junction. The arbitrary grouping of snake venoms into neurotoxins, haemotoxins and cardiotoxins is toxicologically misleading and can result in serious management errors. This is because a so-called neurotoxin can produce marked cardiovascular or direct haematological effects.
Clinical features
Box 3.11 gives the geography of the common venomous snakes. Key questions to ask a victim are: Where were you bitten, how long ago and by what sort of snake? Friends and relatives will frequently bring the snake with the patients; the snake should be handled as little as possible since it may only be injured and not dead. The amount of venom injected via a bite is highly variable; it depends on the length of time since the snake last ate and on its aggression. Local swelling, ecchymosis and blistering occur at the site of the bite; vomiting, hypotension and shock then follow, particularly with viper bites. Neuromuscular weakness and respiratory muscle paralysis can occur. Bleeding and clotting disturbances are also a feature of viper and rattlesnake bites. Intravascular haemolysis is rare but may occur with bites from Russell's viper in India and Sri Lanka. Cobra bites may be followed by complement activation. Renal failure is rare; rhabdomyolysis is seen with tiger snakes, rattlesnakes, vipers and sea snakes.
3.11 VENOMOUS SNAKE DISTRIBUTION
Area Snake type
Africa Vipers, adders, cobras, mambas
Middle East Vipers, mambas
India/South-east Asia Vipers, cobras, kraits
America Rattlesnakes

Management
All patients with suspected envenomation should be observed for 12-24 hours, as the initial manifestations may be delayed, especially with elapid bites. First-aid measures should be directed at reassuring the patient, immobilising the bitten area to minimise venom spread, and identifying the snake. Application of a firm bandage to occlude lymphatic drainage is appropriate; however, the use of tourniquets is discouraged since they do not prevent the spread of venom and are frequently used inappropriately. Incisions at the bite site and attempts to suck out the venom with the mouth should not be made. Pain and vomiting should be managed symptomatically and the patient's blood pressure, and coagulation, renal, neurological and cardiorespiratory status monitored. A large-bore intravenous cannula should be inserted on an unaffected limb. Hypotension, anaphylactic shock, renal failure and respiratory distress may all develop rapidly and should be appropriately managed. Aspirin should not be used for analgesia since this may aggravate bleeding.
The most appropriate therapy for a snake bite is timely administration of the correct, species-appropriate antivenin (see Fig. 3.8); this should be given to patients with a severe or progressing local reaction, or clinical or laboratory features of systemic envenomation. Before starting antivenin therapy, enquiry must be made into any history of allergy and an intradermal sensitivity test performed by injecting 0.02 ml of saline-diluted antiserum at a site distant from the bite. The injection site is then observed for at least 10 minutes for the development of redness, hives, pruritus or other adverse effects. In general, the shorter the interval between injection and reaction, the greater the degree of sensitivity. A syringe containing 0.5 ml 1:1000 adrenaline (epinephrine) must be available whenever antivenin is administered. Unfortunately, a negative skin test does not always rule out a reaction following administration of the full antivenin dose. The rate of administration of antivenin should be based on the severity of the case and the patient's tolerance to the antivenin. The entire initial dose should be given as soon as possible and preferably within 4 hours of the bite. However, in severe envenomations, antivenin may be given up to 24 hours after the time of the bite and has been shown to reverse coagulation deficits even at 30 hours.
If an immediate hypersensitivity reaction to the venom occurs, administration of the antivenin should be immediately discontinued and the patient given an oral antihistamine or intramuscular adrenaline (epinephrine) as appropriate. If infusion of the antivenin is restarted, administration should be at a slower rate. Steroids are commonly given to treat serum sickness reactions, although their true value remains to be established. Bites by large snakes may need relatively high antivenin doses, particularly in children or small adults. If swelling continues to progress, if systemic features of envenomation increase in severity, or if new manifestations such as hypotension or reduced haematocrit appear, additional antivenin (e.g. the contents of 1-5 vials) should be administered.
Bitten limbs should also be regularly inspected; if the pulses are lost, then compartment syndrome should be suspected and surgical colleagues should be involved. Wound débridement and later skin grafting are occasionally required, especially in cobra and viper bites. Awareness and avoidance of the habitat of snakes are the major means of preventing snake bite.
SPIDER BITES
Spider bites are common, particularly in the USA and Australia. Optimum management requires a high index of suspicion in making the diagnosis and timely administration of appropriate antivenin (see Box 3.12).
SCORPION STINGS
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3.12 SPIDER BITES
Location/appearance of spider Clinical response Management
Black widow spider (Lactrodectus mactans) USA and Australia
Jet-black body with red hourglass mark on underside of abdomen Most bites painless; generalised pain in back or abdomen is most frequent presenting complaint Abdominal muscles become rigid, and severe cramps develop Nausea, vomiting, tremors, speech defects, sweating, periorbital oedema, skin rash, and rise in body temperature or blood pressure may be noted
Severely poisoned patients may lapse into coma
Respiratory muscle paralysis and cardiovascular collapse may also occur Oxygen, i.v. access and cardiac monitoring indicated in symptomatic patients
Oral diazepam may help with muscle cramps
Black widow spider equine antivenin is given to those who have heart disease or respiratory distress, are pregnant, are <16> 65 years of age, or show signs of envenomation or serious poisoning 1 vial of antivenin can be added to 15-100 ml of 0.9% (w/v) sodium chloride solution and then infused over 20-30 mins; normal dose is 1-2 vials
Prompt resolution of features of poisoning characteristic within 1 hr
Funnel-web spider Australia Venom is a neurotoxin causing widespread release of acetylcholine at motor end plates, and acetylcholine, adrenaline and noradrenaline (also calcium channel blockers in Agelenopsis aperta) through the autonomic nervous system
Clinical features include neuromuscular paralysis and hypertension Funnel-web spider antivenin covers the species Atrax robustus, Hadronyche and Missulena, and should be used for any patient developing more than a local bite reaction
Brown recluse spider (Loxosceles reclusa)
USA
Adults vary from yellow to dark brown; have dark, violin-shaped markings immediately behind eye Venom induces injury to arteries and veins, which become occluded with thrombus and capillary stasis; tissue infarction ensues
Clinical response varies from mild local stinging reaction to severe systemic involvement and death due to circulatory or renal failure
Other features include urticaria, morbilliform rash, fever and haemolysis Red blood cell transfusions, maintenance of good hydration and monitoring of renal function help ensure that haemoglobinuria does not cause renal failure
A goat-derived specific antivenin to the brown recluse spider administered within 24 hrs of the bite prevents or markedly attenuates toxicity (Titus phonentria, Loxosceles spider antivenin)
Redback spider (Latrodectus hasselti) Often found in urban habitats in Australia Bites can be painful and therefore bite and spider are recognised at the time of the bite CSL redback spider antivenin is the most commonly used antivenin in Australia
Reported as efficacious in 94% of cases 1 ampoule usually sufficient

The scorpion is characterised by its long segmented tail with a conspicuous stinger at the tip and can vary from 1.5 cm to 20 cm in length. Movement and particularly situations in which the scorpion becomes trapped in clothing or shoes trigger the sting.
Two types of scorpion venom exist. The first, produced by species of the genera Hadrurus, Vejovis and Uroctonus, has local effects only. Such effects include sharp burning, swelling and discoloration at the skin site. Very rarely, anaphylaxis occurs. If local symptoms are present, such as swelling with or without discoloration, the sting is most likely from less lethal species. However, in Leiurus envenomation, which is common in the Middle East, localised reactions can occur in up to 90% of victims. Thus in countries where Leiurus species exist, more protracted surveillance is required, and if systemic manifestations develop, transfer to an area with better intensive care facilities should take place.
The second type of venom, produced by the genera of the poisonous varieties Centruroides, Mesobuthus and Leiurus, consists of protein and polypeptide neurotoxins. They block sodium channels, leading to spontaneous depolarisation of nerves of the parasympathetic and sympathetic systems, with resultant tachycardia, hypertension, pulmonary oedema (especially with Mesobuthus species) and seizures, as well as sweating, piloerection and hyperglycaemia. The sharp pain first produced by the sting is quickly followed by paraesthesiae and numbness in the sting area due to peripheral nerve effects, muscle fasciculations and finally drowsiness. With Centruroides and Mesobuthus species, there is no swelling at the sting site.
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Figure 3.9 An approach to the management of environmental illness.
Local pain and paraesthesiae, both at the sting site and peripherally, are best treated with local compresses and oral analgesics. Patients with significant envenomation should be hospitalised for at least 12 hours and observed for cardiovascular and neurological sequelae of envenomation. More severe symptoms may require airway support, as well as 1-2 vials of intravenous antivenin. The use of antivenin is controversial because evidence of its effectiveness in the clinical setting is lacking, but its use is considered for the very young, the elderly or those individuals with severe hypertension. True anaphylaxis to the antivenin can occur but is rare. Serum sickness is common after antivenin administration but is usually self-limited and easily controlled with steroids and histamines. Tachyarrhythmias can be treated with standard doses of intravenous metoprolol or esmolol, with the addition of a-adrenoceptor antagonists such as prazosin, if hypertension or pulmonary oedema develops. Other treatments, such as calcium or sympathomimetic drugs, have been shown to be of little value.

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