Poisoning

S.H.L. Thomas

J. White

Comprehensive evaluation of the poisoned patient

Taking a history in poisoning

• What toxin(s) have been taken and how much?

• What time were they taken and by what route?

• Has alcohol or any drug of misuse been taken as well?

• Obtain details from witnesses of the circumstances of the overdose (e.g. family, friends ambulance personnel)

• Ask the general practitioner for background and details of prescribed medication

• Assess suicide risk (full psychiatric evaluation when patient has physically recovered)

• Assess capacity to make decisions about accepting or refusing treatment

• Establish past medical history, drug history and allergies, social and family history

• Record all information carefully

Evaluation of the envenomed patient

Assessment of type and extent of envenoming

Neurotoxic paralysis

• ‘Sleepy’ or drooping eyelids

• Difficulty swallowing, dysarthria and drooling

• Limb weakness

• Respiratory distress

Excitatory neurotoxicity

• Sweating, salivation, piloerection

• Tingling around mouth or tongue, muscle twitching

• Dyspnoea (pulmonary oedema)

Myolysis

• Muscle pain or weakness

Coagulopathy

• Blood oozing from bite site and/or gums

• Bruising

• Melaena, haematemesis

Local effects

• Pain, sweating, blistering, bruising etc.

Taking a history in envenoming

• When was the patient exposed to a bite/sting?

• Was the organism causing it seen and what did it look like (size, colour)?

• What were the circumstances (on land, in water etc.)?

• Was there more than one bite/sting?

• What first aid was used, when and for how long?

• What symptoms has the patient had (local and systemic)?

• Are there symptoms suggesting systemic envenoming (paralysis, myolysis, coagulopathy etc.)?

• Past medical history and medications?

• Past exposure to antivenom/venom and allergies?

Acute poisoning is common, accounting for about 1% of hospital admissions in the UK. Common or otherwise important substances involved are shown in Box 9.1. In developed countries, the most frequent cause is intentional drug overdose in the context of self-harm and usually involves prescribed or ‘over-the-counter’ medicines. Accidental poisoning is also common, especially in children and the elderly (Box 9.2). Toxicity also may occur as a result of alcohol or recreational substance use, or following occupational or environmental exposure. Poisoning is a major cause of death in young adults, but most deaths occur before patients reach medical attention, and mortality is much lower than 1% in those admitted to hospital.

9.1 Important substances involved in poisoning

In the UK

• Analgesics: paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs)

• Antidepressants: tricyclic antidepressants (TCAs), selective serotonin re-uptake inhibitors (SSRIs) and lithium

• Cardiovascular agents: β-blockers, calcium channel blockers and cardiac glycosides

• Drugs of misuse: opiates, benzodiazepines, stimulants (e.g. amphetamines, MDMA, cocaine)

• Carbon monoxide

• Alcohol

In South and South-east Asia

• Organophosphorus and carbamate insecticides

• Aluminium and zinc phosphide

• Oleander

• Snake venoms

• Antimalarial drugs: chloroquine

• Antidiabetic medication

9.2 Poisoning in old age

• Aetiology: commonly results from accidental poisoning (e.g. due to confusion or dementia) or drug toxicity as a consequence of impaired renal or hepatic function or drug interaction. Toxic prescription medicines are more likely to be available.

• Psychiatric illness: self-harm is less common than in younger adults but more frequently associated with depression and other psychiatric illness, as well as chronic illness and pain. There is a higher risk of subsequent suicide.

• Severity of poisoning: increased morbidity and mortality result from reduced renal and hepatic function, reduced functional reserve, increased sensitivity to sedative agents and frequent comorbidity.

In developing countries, the frequency of self-harm is more difficult to estimate. Household and agricultural products, such as pesticides and herbicides, are more freely available, are common sources of poisoning and are associated with a much higher case fatality. In China and South-east Asia, pesticides account for about 300 000 suicides each year.

General approach to the poisoned patient

A general approach is shown on pages 206–207.

Triage and resuscitation

Patients who are seriously poisoned must be identified early so that appropriate management is not delayed. Triage involves:

• immediate assessment of vital signs

• identifying the poison(s) involved and obtaining adequate information about them

• identifying patients at risk of further attempts at self-harm and removing any remaining hazards.

Those with possible external contamination with chemical or environmental toxins should undergo appropriate decontamination (Fig. 9.1). Critically ill patients must be resuscitated (p. 180).

Fig. 9.1 Methods of external decontamination.

The Glasgow Coma Scale (GCS) is commonly employed to assess conscious level, although it has not been specifically validated in poisoned patients. The AVPU (alert/verbal/painful/unresponsive) scale is also a rapid and simple method. An electrocardiogram (ECG) should be performed and cardiac monitoring instituted in all patients with cardiovascular features or where exposure to potentially cardiotoxic substances is suspected. Patients who may need antidotes should be weighed when this is feasible, so that appropriate weight-related doses can be prescribed.

Substances that are unlikely to be toxic in humans should be identified so that inappropriate admission and intervention are avoided (Box 9.3).

9.3 Substances of very low toxicity

• Writing/educational materials

• Decorating products

• Cleaning/bathroom products (except dishwasher tablets, which are corrosive)

• Pharmaceuticals: oral contraceptives, most antibiotics (but not tetracyclines and antituberculous drugs), H₂-blockers, proton pump inhibitors, emollients and other skin creams, baby lotion

• Miscellaneous: plasticine, silica gel, household plants, plant food

Clinical assessment and investigations

History and examination are described on page 206. Occasionally, patients may be unaware or confused about what they have taken, or may exaggerate (or less commonly underestimate) the size of the overdose, but rarely mislead medical staff deliberately. In regions of the world where self-poisoning is illegal, patients may be reticent about giving a history.

Toxic causes of abnormal physical signs are shown on page 207. The patient may have a cluster of clinical features (‘toxidrome’) suggestive of poisoning with a particular drug type, e.g. anticholinergic, serotoninergic (see Box 9.11, p. 213), stimulant, sedative, opioid (see Box 9.12, p. 217) or cholinergic (see Box 9.14, p. 221) feature clusters. Poisoning is a common cause of coma, especially in younger people, but it is important to exclude other potential causes (p. 1159), unless the aetiology is certain.

Urea, electrolytes and creatinine should be measured in all patients with suspected systemic poisoning. Arterial blood gases should be checked in those with significant respiratory or circulatory compromise, or when poisoning with substances likely to affect acid–base status is suspected (Box 9.4). Calculation of anion and osmolar gaps may help to inform diagnosis and management (Box 9.5).

9.4 Causes of acidosis in the poisoned patient

Cause	Normal lactate*	High lactate
Toxic	Salicylates	Metformin
	Methanol	Iron
	Ethylene glycol	Cyanide
	Paraldehyde	Sodium valproate Carbon monoxide
Other	Renal failure Ketoacidosis Severe diarrhoea	Shock

^*Unless circulatory shock is present, when it will be high in any case.

9.5 Anion and osmolal gaps in poisoning

	Anion gap	Osmolal gap
Calculation	[Na⁺ + K⁺] − [Cl⁻ + HCO₃⁻]	[Osm (measured)] [2 × Na + Urea + Glucose (all mmol/L)]¹
Reference range	12–16 mmol/L	< 10 mOsm/kg
Common toxic causes of elevation2	Ethanol Ethylene glycol Methanol Salicylates Iron Cyanide	Ethanol Ethylene glycol Methanol

¹ Osm (measured) stands for measured osmolality. For non-SI units, the corresponding formula is [Osm (measured)] – [2 × Na (meq/L) + Urea/2.8 (mg/dL) + Glucose/18 (mg/dL)].

² Box 16.19 (p. 445) gives non-toxic causes.

For a limited number of specific substances, management may be facilitated by measurement of the amount of toxin in the blood (Box 9.6). Qualitative urine screens for potential toxins, including near-patient testing kits, have a limited clinical role.

9.6 Laboratory analysis in poisoning

Organophosphates

• Plasma cholinesterase is reduced more rapidly but is less specific than red cell cholinesterase (p. 222)

• Antidote use should not be delayed pending results

Carboxyhaemoglobin

• > 20% indicates significant carbon monoxide exposure

Digoxin

• Therapeutic range usually 1–2 ng/mL (1.28–2.46 mmol/L)

• Concentrations > 4 ng/mL (5.12 mmol/L) usually associated with toxicity, especially with chronic poisoning

Ethanol

• Toxicity at concentrations > 1.8 g/L

Iron

• Take sample ≥ 4 hrs after overdose or if clinical signs of toxicity

• Concentrations > 5 mg/L suggest severe toxicity

Lithium

• Take sample ≥ 6 hrs after overdose or if clinical signs of toxicity

• Usual therapeutic range 0.4–1.0 mmol/L

Methaemoglobin

• Poisoning with nitrites, benzocaine, dapsone, chloroquine and aniline dyes is associated with methaemoglobinaemia

• Concentrations > 20% may require treatment with methylthioninium chloride (methylene blue)

Paracetamol

• Take sample ≥ 4 hrs after overdose

• Use nomogram to determine need for antidotal treatment (see Fig. 9.2, p. 212)

Salicylate

• Take sample ≥ 2 hrs (symptomatic patients) or 4 hrs (asymptomatic patients) after overdose

• Concentrations > 500 mg/L suggest serious toxicity

• Repeat after 2 hrs if severe toxicity is suspected

Theophylline

• Take sample ≥ 4 hrs after overdose or if clinical signs of toxicity

• Repeat after 2 hrs if severe toxicity is suspected

• Concentrations > 60 mg/L suggest severe toxicity

Psychiatric assessment

All patients presenting with deliberate drug overdose should undergo psychiatric evaluation by a health professional with appropriate training prior to discharge (p. 238). This should take place once the patient has recovered from any features of poisoning, unless there is an urgent issue, such as uncertainty about their capacity to decline medical treatment.

General management

Patients presenting with eye/skin contamination should undergo local decontamination procedures (see Fig. 9.1).

Gastrointestinal decontamination

Patients who have ingested potentially life-threatening quantities of toxins may be considered for gastrointestinal decontamination if poisoning has been recent (Box 9.7). Induction of emesis using ipecacuanha is no longer recommended.

9.7 Use of gastric decontamination methods

‘Single-dose activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (known to be adsorbed to charcoal) up to 1 hr previously.’¹

‘Multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine or theophylline.’²

‘Gastric lavage should not be employed routinely, if ever, in the management of poisoned patients.’³

‘Whole bowel irrigation should be considered for:

• poisoning with sustained-release or emetic-coated drugs

• patients who have ingested substantial amounts of iron (as morbidity is high and other options are limited)

• removal of ingested packets of illicit drugs.

• American Academy of Clinical Toxicology and European Association of Poison Centres and Clinical Toxicologists Joint Position Statements on Gastric Decontamination Methods:

• ¹Clin Toxicol 2005; 43:61–87.

• ²Clin Toxicol 1999; 37:731–751.

• ³Clin Toxicol 2004; 42:933–943.

• ⁴J Toxicol Clin Toxicol 2004; 42:843–42854.

Activated charcoal

Given orally as slurry, activated charcoal absorbs toxins in the bowel as a result of its large surface area. If given sufficiently early, it can prevent absorption of an important proportion of the ingested dose of toxin. Efficacy decreases with time and current guidelines do not advocate use more than 1 hour after overdose in most circumstances (see Box 9.7). However, use after a longer interval may be reasonable when a delayed-release preparation has been taken or when gastric emptying may be delayed. Some toxins do not bind to activated charcoal (Box 9.8) so it will not affect their absorption. In patients with impaired swallowing or a reduced level of consciousness, activated charcoal, even via a nasogastric tube, carries a risk of aspiration pneumonitis, which can be reduced (but not eliminated) by protecting the airway with a cuffed endotracheal tube.

Multiple doses of oral activated charcoal (50 g 6 times daily in an adult) may enhance the elimination of some drugs at any time after poisoning and are recommended for serious poisoning with some substances (see Box 9.7). This interrupts enterohepatic circulation or reduces the concentration of free drug in the gut lumen, to the extent that drug diffuses from the blood back into the bowel to be absorbed on to the charcoal: so-called ‘gastrointestinal dialysis’. A laxative is generally given with the charcoal to reduce the risk of constipation or intestinal obstruction by charcoal ‘briquette’ formation in the gut lumen.

Evidence suggests that single or multiple doses of activated charcoal do not improve clinical outcomes after poisoning with pesticides or oleander.

9.10 Complications of poisoning and their management

	Examples of causative agents	Management
Coma	Sedative agents	Appropriate airway protection and ventilatory support Pressure area and bladder care Identification and treatment of aspiration pneumonia
Seizures	NSAIDs Anticonvulsants TCAs Theophylline	Appropriate airway and ventilatory support IV benzodiazepine (e.g. diazepam 10–20 mg, lorazepam 2–4 mg) Correction of hypoxia, acid–base and metabolic abnormalities
Acute dystonias	Typical antipsychotics Metoclopramide	Procyclidine, benzatropine or diazepam
Hypotension
Due to vasodilatation	Vasodilator antihypertensives Anticholinergic agents TCAs	IV fluids Vasopressors (rarely indicated; p. 191)
Due to myocardial suppression	β-blockers Calcium channel blockers TCAs	Optimisation of volume status Inotropic agents (p. 191)
Ventricular tachycardia
Monomorphic, associated with QRS prolongation	Sodium channel blockers	Correction of electrolyte and acid–base abnormalities and hypoxia Sodium bicarbonate
Torsades de pointes, associated with QT_c prolongation	Anti-arrhythmic drugs (quinidine, amiodarone, sotalol) Antimalarials Organophosphate insecticides Antipsychotic agents Antidepressants Antibiotics (erythromycin)	Magnesium sulphate, 2 g IV over 1–2 mins, repeated if necessary

Antidotes

Antidotes are available for some poisons and work by a variety of mechanisms: for example, by specific antagonism (isoprenaline for β-blockers), chelation (desferrioxamine for iron) or reduction (methylene blue for dapsone). The use of some antidotes is described in the management of specific poisons below.

Poisoning by specific pharmaceutical agents

Analgesics

Paracetamol

Paracetamol (acetaminophen) is the drug most commonly used in overdose in the UK. Toxicity results from formation of an intermediate reactive metabolite that binds covalently to cellular proteins, causing cell death. This results in hepatic and occasionally renal failure. In therapeutic doses, the toxic intermediate metabolite is detoxified in reactions requiring glutathione, but in overdose, glutathione reserves become exhausted.

Management

Management is summarised in Figure 9.2. Activated charcoal may be used in patients presenting within 1 hour. Antidotes for paracetamol act by replenishing hepatic glutathione and should be administered to all patients with paracetamol concentrations above the ‘treatment line’ provided on paracetamol poisoning nomograms. Acetylcysteine given intravenously (or orally in some countries) is highly efficacious if administered within 8 hours of the overdose. However, since efficacy declines thereafter, administration should not be delayed in patients presenting after 8 hours to await a paracetamol blood concentration result. The antidote can be stopped if the paracetamol concentration is shown to be below the nomogram treatment line.

The most important adverse effect of acetylcysteine is related to dose-related histamine release, the ‘anaphylactoid’ reaction, which causes itching and urticaria, and in occasional severe cases, bronchospasm and hypotension. Most cases can be managed by temporary discontinuation of acetylcysteine and administration of an antihistamine.

An alternative antidote is methionine 2.5 g orally (adult dose) every 4 hours to a total of 4 doses, but this is less effective, especially after delayed presentation. If a patient presents more than 15 hours after ingestion, liver function tests, prothrombin time (or international normalised ratio – INR), renal function tests and a venous bicarbonate should be measured, the antidote started, and a poisons information centre or local liver unit contacted for advice if results are abnormal. An arterial blood gas sample should be taken in patients with severe liver function abnormalities; metabolic acidosis indicates severe poisoning. Liver transplantation should be considered in individuals who develop life-threatening liver failure due to paracetamol poisoning (p. 932).

If multiple ingestions of paracetamol have taken place over several hours or days (i.e. a staggered overdose), acetylcysteine may be indicated. Recommended thresholds for treatment vary between countries.

Salicylates (aspirin)

Clinical features

Salicylate overdose commonly causes nausea, vomiting, sweating, tinnitus and deafness. Direct stimulation of the respiratory centre produces hyperventilation and respiratory alkalosis. Peripheral vasodilatation with bounding pulses and profuse sweating occurs in moderately severe poisoning. Serious salicylate poisoning is associated with metabolic acidosis, hypoprothrombinaemia, hyperglycaemia, hyperpyrexia, renal failure, pulmonary oedema, shock and cerebral oedema. Agitation, confusion, coma and fits may occur, especially in children. Toxicity is enhanced by acidosis, which increases salicylate transfer across the blood–brain barrier.

Management

Activated charcoal should be administered if the patient presents within 1 hour. Multiple doses of activated charcoal may enhance salicylate elimination but currently are not routinely recommended.

The plasma salicylate concentration should be measured at least 2 (in symptomatic patients) or 4 hours (asymptomatic patients) after overdose and repeated in suspected serious poisoning, since concentrations may continue to rise some hours after overdose. In adults, concentrations above 500 mg/L and 700 mg/L suggest serious and life-threatening poisoning respectively, although clinical status is more important than the salicylate concentration in assessing severity.

Dehydration should be corrected carefully, as there is a risk of pulmonary oedema, and metabolic acidosis should be identified and treated with intravenous sodium bicarbonate (8.4%), once plasma potassium has been corrected. Urinary alkalinisation is indicated for adults with salicylate concentrations above 500 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 700 mg/L in adults with severe toxic features, or when there is renal failure, pulmonary oedema, coma, convulsions or refractory acidosis.

Non-steroidal anti-inflammatory drugs

Clinical features

Overdose of most non-steroidal anti-inflammatory drugs (NSAIDs) usually causes little more than minor abdominal discomfort, vomiting and/or diarrhoea, but convulsions can occur occasionally, especially with mefenamic acid. Coma, prolonged seizures, apnoea, liver dysfunction and renal failure can occur after substantial overdose but are rare. Features of toxicity are unlikely to develop in patients who are asymptomatic more than 6 hours after overdose.

Management

Electrolytes, liver function tests and a full blood count should be checked in all but the most trivial cases. Activated charcoal may be given if the patient presents sufficiently early. Symptomatic treatment for nausea and gastrointestinal irritation may be necessary.

Antidepressants

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) are used frequently in overdose and carry a high morbidity and mortality relating to their sodium channel-blocking, anticholinergic and α-adrenoceptor-blocking effects.

Clinical features

Anticholinergic effects are common (Box 9.11). Life-threatening complications are frequent, including convulsions, coma, arrhythmias (ventricular tachycardia, ventricular fibrillation and, less commonly, heart block) and hypotension, which results from inappropriate vasodilatation or impaired myocardial contractility. Serious complications appear to be more common with dosulepin and amitriptyline.

9.11 Anticholinergic and serotonergic feature clusters

	Anticholinergic	Serotonin syndrome
Common causes	Benzodiazepines Antipsychotics TCAs Antihistamines Scopolamine Benzatropine Belladonna Jimson weed Mushrooms (some)	SSRIs Monoamine oxidase inhibitors (MAOIs) TCAs Amphetamines Buspirone Bupropion (especially in combination)
Clinical features
Cardiovascular	Tachycardia, hypertension	Tachycardia, hyper- or hypotension
CNS	Confusion, hallucinations, sedation	Confusion, delirium, hallucinations, sedation, coma
Muscle	Myoclonus	Shivering, tremor, myoclonus, raised creatine kinase
Temperature	Fever	Fever
Eyes	Diplopia, mydriasis	Normal pupil size
Abdomen	Ileus, palpable bladder	Diarrhoea, vomiting
Mouth	Dry
Skin	Flushing, hot, dry	Flushing, sweating
Complications	Seizures	Seizures Rhabdomyolysis Renal failure Metabolic acidosis Coagulopathies

Management

Activated charcoal should be administered if the patient presents within 1 hour. All patients with possible TCA overdose should have a 12-lead ECG and ongoing cardiac monitoring for at least 6 hours. Prolongation of the QRS interval (especially if > 0.16 s) indicates severe sodium channel blockade and is associated with an increased risk of arrhythmia (Fig. 9.3). QT interval prolongation may also occur. Arterial blood gases should be measured in suspected severe poisoning.

Fig 9.3 ECG in severe tricyclic antidepressant poisoning.
This rhythm strip shows a broad QRS complex due to impaired conduction.

In patients with arrhythmias, significant QRS or QT prolongation or acidosis, intravenous sodium bicarbonate (50 mL of 8.4% solution) should be administered and repeated to correct pH. The correction of the acidosis and the sodium loading that result is often associated with rapid improvement in ECG features and arrhythmias. Hypoxia and electrolyte abnormalities should also be corrected. Anti-arrhythmic drugs should only be given on specialist advice. Prolonged convulsions should be treated with intravenous benzodiazepines (see Box 9.10). There is anecdotal evidence of benefit from lipid emulsion therapy in severe intractable poisoning.

Selective serotonin and noradrenaline re-uptake inhibitors

Selective serotonin re-uptake inhibitors (SSRIs) are a group of antidepressants that include fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram and escitalopram. They are increasingly used to treat depression, partly because they are less toxic in overdose than TCAs. A related group of compounds termed serotonin–noradrenaline reuptake inhibitors (SNRIs), such as venlafaxine and duloxetine, are also in common use and are sometimes taken in overdose.

Clinical features and management

Overdose of SSRIs may produce nausea and vomiting, tremor, insomnia and sinus tachycardia. Agitation, drowsiness and convulsions occur infrequently and may be delayed for several hours after ingestion. Occasionally, features of serotonin syndrome may develop (see Box 9.11), especially if SSRIs are taken in combination or with other serotonergic agents. Cardiac arrhythmias occur infrequently and most patients require supportive care only. The toxic effects of SNRIs are similar but tachycardia, hypertension or hypotension and ECG changes (QRS and QT prolongation) may be more prominent and hypoglycaemia can also occur.

Lithium

Severe lithium toxicity is uncommon after intentional overdose and is more often encountered in patients taking therapeutic doses as the result of interactions with drugs such as diuretics or NSAIDs that can cause dehydration or renal impairment, or because an excessive dose has been prescribed. Severe toxicity is more common with acute overdose in patients taking chronic therapy (‘acute on chronic’ poisoning).

Clinical features

Nausea, diarrhoea, polyuria, dizziness and tremor may progress to muscular weakness, drowsiness, confusion, myoclonus, fasciculations, choreoathetosis and renal failure. Coma, convulsions, ataxia, cardiac dysrhythmias such as heart block, blood pressure disturbances and renal failure may all occur in severe poisoning.

Management

Activated charcoal is ineffective. Gastric lavage is of theoretical benefit if used early after overdose, but lithium tablets are likely to remain intact in the stomach and may be too large for aspiration via a lavage tube. Some advocate whole bowel irrigation after substantial overdose but efficacy is unknown.

Lithium concentrations should be measured immediately in symptomatic patients or after at least 6 hours in asymptomatic patients following acute overdose. Adequate hydration should be maintained with intravenous fluids. Convulsions should be treated as in Box 9.10.

In patients with features suggesting severe toxicity associated with high lithium concentrations (e.g. > 4.0 mmol/L after chronic or ‘acute on chronic’ poisoning, or > 7.5 mmol/L after acute poisoning), haemodialysis should be considered. Lithium concentrations are reduced substantially during dialysis but rebound increases occur after discontinuation, and multiple sessions may be required.

The major features of toxicity are bradycardia and hypotension. Heart block, pulmonary oedema and cardiogenic shock occur in severe poisoning. Beta-blockers with sodium channel-blocking effects may cause seizures, confusion and coma, while sotalol may be associated with repolarisation abnormalities (including QT_c prolongation) and torsades de pointes (p. 570).

Management

Intravenous fluids may reverse hypotension but care is required to avoid pulmonary oedema. Bradycardia and hypotension may respond to high doses of atropine (up to 3 mg in an adult). The adrenoceptor agonist isoprenaline may also be effective but high doses are often needed. Glucagon (5–10 mg over 10 mins, then 1–5 mg/hr by infusion), which counteracts the effect of β-blockers by stimulating intracellular production of cyclic adenosine monophosphate (cAMP), is now more commonly used. In severe cases, ‘hyperinsulinaemia euglycaemic therapy’ has been used, as described under calcium channel blockers. Lipid emulsion therapy may have a role in severe poisoning with lipid-soluble agents such as propranolol, carvedilol and oxprenolol.

Calcium channel blockers

Calcium channel blockers are highly toxic in overdose because of their inhibitory effects on L-type calcium channels. Dihydropyridines, such as nifedipine or amlodipine, affect vascular smooth muscle in particular, resulting in vasodilatation, whereas diltiazem and verapamil, which are used in the treatment of arrhythmias, have predominantly cardiac effects, including bradycardia and reduced myocardial contractility.

Clinical features

The usual presentation is with hypotension due to vasodilatation or myocardial depression. Bradycardias and heart block may also occur, especially with verapamil and diltiazem. Gastrointestinal disturbances, confusion, metabolic acidosis, hyperglycaemia and hyperkalaemia may also be present.

Management

Hypotension should be corrected with intravenous fluids, taking care to avoid pulmonary oedema. Persistent hypotension may respond to intravenous calcium gluconate (10 mg IV over 5 mins, repeated as required). Isoprenaline and glucagon may also be useful. Successful use of intravenous insulin with glucose (10–20% dextrose with insulin initially at 0.5–2.0 U/kg/hr, increasing to 5–10 U/kg/hr according to clinical response), so-called ‘hyperinsulinaemia euglycaemic therapy’, has been reported in patients unresponsive to other strategies. The mechanism of action remains to be fully elucidated, but in states of shock myocardial metabolism switches from use of free fatty acids to glucose. Calcium channel blocker poisoning is also associated with hypoinsulinaemia and insulin resistance, impeding glucose uptake by myocytes. High doses of insulin inhibit lipolysis and increase glucose uptake and the efficiency of glucose utilisation. Cardiac pacing may be needed for severe unresponsive bradycardias or heart block. Lipid emulsion therapy has been used in severe poisoning with apparent benefit, although evidence is largely anecdotal.

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Tags: Davidsons Principles and Practice of Medicine

Apr 9, 2017 | Posted by admin in GENERAL SURGERY | Comments Off

Medicines
• Iron	• Lithium
Chemicals
• Acids * • Alkalis * • Ethanol • Ethylene glycol	• Mercury • Methanol • Petroleum distillates *

Haemodialysis
• Ethylene glycol • Isopropanol • Methanol	• Salicylates • Sodium valproate • Lithium
Haemoperfusion
• Theophylline • Phenytoin • Carbamazepine	• Phenobarbital • Amobarbital

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