Poisoning by drugs and chemicals - general management - technical
Antidotes and methods to enhance elimination are available for only very small number of poisons, and the management of the great majority of poisoned patients is based on what has been called ‘an orderly if unspectacular regimen of supportive therapy’.
A small but significant number of poisoned patients arrive at hospital with respiratory obstruction, ventilatory failure, or in cardiorespiratory arrest. In these cases, conventional resuscitation takes precedence over detailed assessment of the patient and attempts to obtain a history. The opioid antagonist naloxone is safe and should be used whenever there is the slightest suspicion that an opioid is involved. Its use intravenously will resurrect a comatose, hypoventilating patient within seconds and, even if it is given inappropriately, it is highly unlikely to have adverse effects.
Unconscious patients need scrupulous attention to respiration, hypotension, hypothermia, and other complications, if they are to survive. Expert nursing is as important as medical measures.
Establishment and maintenance of an adequate airway is of paramount importance in the management of unconscious poisoned patients. The airway may be obstructed by the tongue falling back, dental plates being dislodged, other foreign bodies, buccal secretions, vomitus, and flexion of the neck. In the first instance, the neck should be extended and the tongue and jaw held forward. Secretions in the oropharynx must be removed, and an oropharyngeal airway should be inserted before turning the patient into a semiprone position. If the cough reflex is absent, an endotracheal tube should be inserted to prevent aspiration into the lungs and allow regular aspiration of bronchial secretions. It is then important to ensure that the inspired air is adequately warmed and humidified.
Once a clear airway has been established, the adequacy of spontaneous ventilation should be assessed. Pulse oximetry can be used to measure oxygen saturation. The displayed reading may be inaccurate when the saturation is below 70%, when peripheral perfusion is poor, and in the presence of carboxyhaemoglobin or methaemoglobin. Only measurement of arterial blood gases, however, indicates the presence both of hypercapnia and hypoxia. The presence of ventilatory insufficiency (as determined by arterial partial pressure of oxygen ≤9 kPa on air and/or arterial partial pressure of CO2 ≥6 kPa) should lead to consideration of immediate intubation and assisted ventilation, if the central respiratory depression cannot be reversed by administration of a specific antidote such as naloxone.
Unconscious poisoned patients often have a mild, mixed respiratory and metabolic acidosis with CO2 tensions at the upper limit of normal, and oxygen tensions that fall with increasing depth of coma. Increasing the oxygen contents of the inspired air is often sufficient to correct hypoxia. High inspired oxygen concentrations are imperative in patients with carbon monoxide and cyanide poisoning and in pulmonary oedema resulting from inhalation of irritant gases.
Cardiovascular function should be assessed by measuring pulse, blood pressure, and temperature (core and peripheral). ECG should be monitored in moderately or severely poisoned patients, particularly when a drug with a cardiotoxic action (e.g. a tricyclic antidepressant that produces QRS prolongation) has been ingested.
Although hypotension (systolic blood pressure <80 mmHg) is a recognized feature of acute poisoning, the classical features of shock (tachycardia and pale, cold skin) are seen only rarely because only a minority of patients are severely poisoned.
Hypotension and shock occur in many severely poisoned patients and may be caused by a direct cardiodepressant action of the poison (e.g. β-blockers, calcium channel blockers, tricyclic antidepressants); vasodilatation and venous pooling in the lower limbs (e.g. angiotensin converting enzyme (ACE) inhibitors, phenothiazines); decrease in circulating blood volume because of gastrointestinal losses (e.g. theophylline), increased insensible losses (e.g. salicylates), increased renal losses (e.g. diuretics), and increased capillary permeability. Hypotension may be exacerbated by coexisting hypoxia, acidosis, and dysrhythmias.
Correct management of individual cases depends on accurate identification of the cause. Young patients are generally not at risk of cerebral or renal damage unless the systolic blood pressure falls below 80 mmHg, but in those over the age of 40 years, it is preferable to keep the systolic blood pressure above 90 mmHg.
Hypotension often responds to elevation of the foot of the bed by 15 cm and, if this is unsuccessful, sodium chloride or other plasma expander should be administered. In more severe cases, it is helpful to undertake invasive haemodynamic monitoring to confirm that adequate volume replacement has been administered.
Dobutamine (2.5–10 µg/kg per min) or adrenaline (0.5–2.0 µg/kg per min) is indicated if hypotension is resistant to these measures; dopamine (2–5 µg/kg per min) is an alternative. A vasoconstrictor sympathomimetic drug (e.g. noradrenaline base 6.4–13.3 μg/min) may be necessary in severe cases, but it must be recognized that blood pressure may be raised at the expense of perfusion of vital organs such as the kidneys.
A few drugs when taken in overdose may produce systemic hypertension. If this is mild and associated with agitation, a benzodiazepine alone may suffice. In more severe cases, e.g. those due to a monoamine oxidase inhibitor, there may be a risk of arterial rupture, particularly intracranially. To prevent this, intravenous isosorbide dinitrate 2 to 10 mg/h, up to 20 mg/h if necessary, an α-adrenergic blocking agent (e.g. phentolamine, 5 mg intravenously every 10–15 min) or sodium nitroprusside (0.5–1.5 μg/kg per min by intravenous infusion) should be administered until blood pressure elevation is controlled.
Although many poisons are potentially cardiotoxic, the incidence of serious cardiac arrhythmias in acute poisoning is very low. Tricyclic antidepressants, β-adrenoceptor blocking drugs, calcium channel blockers, cardiac glycosides, amphetamines, cocaine, bronchodilators (particularly theophylline and its derivatives), and antimalarial drugs are the most likely causes. Cardiotoxicity usually occurs together with other features of severe poisoning, including metabolic acidosis, hypoxia, convulsions, respiratory depression, and abnormalities of electrolyte balance, which should be corrected before considering the use of antiarrhythmic drugs. The latter have narrow therapeutic ratios and their use may further impair myocardial function.
In general, drug therapy should only be given for persistent, life-threatening arrhythmias associated with peripheral circulatory failure. The drug used must be selected from knowledge of the pharmacology and toxicology of the poison involved and in such a way that it will not further compromise cardiac function. For example, in tricyclic antidepressant poisoning, arrhythmias are due to sodium channel blockade exacerbated by acidosis and are best treated with hypertonic sodium bicarbonate 50 to 100 mmol. Lidocaine (lignocaine) is probably the drug of choice for serious ventricular tachydysrhythmias in poisoning not corrected by reversal of acidosis, particularly where the offending drug is uncertain, since its half-life is short and the dose can be adjusted readily.
Convulsions are potentially life-threatening because they cause hypoxia and metabolic acidosis and may precipitate cardiac arrhythmias and arrest. Short, isolated convulsions do not require treatment but those which are recurrent or protracted should be suppressed with intravenous diazepam 10 to 20 mg in an adult (lorazepam 4 mg is an alternative). This drug is highly effective in adequate doses and alternatives are seldom needed. However, it is important to remember that giving benzodiazepines in this way may potentiate the respiratory depressant effects of other poisons and further complicate management. The combination of convulsions, coma, and vomiting, which may occur with overdosage of theophylline derivatives, is particularly dangerous, and in these circumstances, it may be preferable to paralyse the patient, insert an endotracheal tube, and start assisted ventilation. However, although this ensures control of the airway and oxygenation, thus avoiding the risk of inhalation of gastric contents, it does not suppress seizure activity; cerebral function must therefore be monitored and parenteral anticonvulsants given as required.
Any poison which depresses the central nervous system may impair temperature regulation and cause hypothermia, especially when discovery of the patient is delayed and environmental temperatures are low. This important complication may be missed unless temperature is recorded rectally using a low-reading thermometer. In severe cases, peripheral and core temperatures should be monitored. Treatment includes nursing the patient in a warm room (27–29 °C) and a heat-conserving ‘space blanket’. Cold intravenous fluids should be avoided and bottles for use should be stored in the room or the lines should pass through a heating device.
Rarely, body temperature may increase to potentially fatal levels after overdosage with central nervous system stimulants such as cocaine, amphetamines (including ecstasy (MDMA)), monoamine oxidase inhibitors, or theophylline. In such cases, muscle tone is often grossly increased and convulsions and rhabdomyolysis are common. Cooling measures should be instituted, sedation with diazepam should be given and, in severe cases, dantrolene 1 mg/kg body weight should be administered intravenously.
Acid–base disturbances commonly accompany coma due to drugs. Acute respiratory acidosis is less common than might be expected, but some elevation of arterial CO2 tensions towards the upper limit of normal is usual. This, in combination with mild hypoxia in the deeper grades of coma, produces overall acidaemia. In general, acidosis should be prevented and managed by ensuring adequate ventilation, oxygenation, and tissue perfusion, and control of convulsions rather than by giving bicarbonate. However, a number of poisons, particularly methanol and ethylene glycol, cause life-threatening metabolic acidosis, which should be corrected by infusion of sodium bicarbonate.
Acute respiratory alkalosis, often in combination with a minor metabolic acidosis, is commonly found in acute salicylate poisoning. The metabolic component may require treatment if it is the dominant feature and is causing overall acidaemia. Respiratory alkalosis should not be treated.
Electrolyte abnormalities may result from acid–base disturbances or the direct effects of poisons. Massive tissue damage, usually rhabdomyolysis, may allow potassium to leak from cells leading to potentially lethal hyperkalaemia. Cardiac glycosides cause hyperkalaemia, secondary to loss from cells due to inhibition of the membrane sodium–potassium pump, while the reverse occurs with sympathomimetic drugs. Oxalic acid and ethylene glycol (which is metabolized to oxalic acid) may cause hypocalcaemia by leading to the formation of insoluble calcium oxalate, which is deposited in tissues. Similarly, ingestion of fluorides is also a possible cause of hypocalcaemia; but the amounts children tend to ingest in the form of tablets to prevent dental caries seldom cause serious problems. Ingestion of potassium salts, even in sustained release formulations, may lead to hyperkalaemia and fatal arrhythmias.
Urinary retention is a common complication of acute poisoning, particularly with tricyclic antidepressants and other drugs, which have marked anticholinergic actions. However, bladder catheterization is all too often an unconsidered measure in unconscious poisoned patients. Coma in inself is not an indication for bladder catheters in poisoned patients, the great majority of whom regain consciousness within 12 h. The bladder can usually be induced to empty reflexively (provided it is not allowed to become grossly over-distended) by applying gentle suprapubic pressure. Catheterization should be reserved for those patients in whom suprapubic pressure is insufficient to empty the bladder, and in those thought to be developing renal failure.
Skin, muscle, and nerve lesions
Bullous lesions should be left intact until they burst, to reduce the risk of infection. De-roofing should be performed when the blister bursts; a nonadhesive dressing is then applied.
Rhabdomyolysis is a further possible result of immobility and may occur in combination with skin lesions or independently. Poisoning is the most common nontraumatic cause of this condition and it may lead to acute renal failure and, rarely, to ischaemic muscle contractures and long-term disability. Urgent orthopaedic referral is indicated if a compartment syndrome is suspected. Peripheral nerves such as the radial, ulnar, and common peroneal may also be damaged by direct pressure while the patient is unconscious.
Unconscious patients should be turned from side to side at least every 2 h. Antidotes Antidotes may exert a beneficial effect by:
- forming an inert complex with the poison (e.g. desferrioxamine, D-penicillamine, dicobalt edetate, dimercaprol, digoxin-specific antibody fragments, HI-6, hydroxocobalamin, obidoxime, pralidoxime, protamine, Prussian (Berlin) blue, sodium calcium edetate, succimer (DMSA), unithiol (DMPS))
- accelerating detoxification of the poison (e.g. N-acetylcysteine, sodium thiosulphate)
- reducing the rate of conversion of the poison to a more toxic compound (e.g. ethanol, fomepizole)
- competing with the poison for essential receptor sites (e.g. oxygen, naloxone, phytomenadione)
- blocking essential receptors through which the toxic effects are mediated (e.g. atropine)
- bypassing the effect of the poison (e.g. oxygen, glucagon)
The most frequently used antidote in the developed world is N-acetylcysteine for paracetamol poisoning. Naloxone for opioid analgesics, oxygen for carbon monoxide, and, possibly, flumazenil for benzodiazepines are the only antidotes commonly needed in the management of unconscious poisoned patients. Other antidotes of proven value are listed in Table 1.
|Table 1 Poisons for which there are specific antidotes|
|Arsenic||Dimercaprol (BAL), succimer (DMSA)|
|β-adrenoceptor blocking drugs||Atropine, glucagon|
|Calcium channel blockers||Atropine|
|Copper||D-Penicillamine, unthiol (DMPS)|
|Cyanide||Dicobalt edetate, hydroxocobalamin, oxygen, sodium nitrite, sodium thiosulphate|
|Diethylene glycol||Fomepizole, ethanol|
|Digoxin and digitoxin||Digoxin-specific antibody fragments|
|Ethylene glycol||Fomepizole, ethanol|
|Iron salts||Desferrioxamine (deferoxamine)|
|Lead (inorganic)||Succimer (DMSA), sodium calcium edetate|
|Methaemoglobinaemia||Methylthioninium chloride (methylene blue)|
|Mercury (inorganic)||Unithiol (DMPS)|
|Nerve agents||Atropine, obidoxime, pralidoxime, HI-6|
|Oleander||Digoxin-specific antibody fragments|
|Organophosphorus insecticides||Atropine, obidoxime, pralidoxime|
|Thallium||Prussian (Berlin) blue|
|Warfarin and other anticoagulants||Phytomenadione (vitamin K1)|
Reduction of poison absorption
Prevention of absorption of volatile poisons through the lungs obviously requires removal from the toxic atmosphere and occasionally removal of soiled clothing as well. The latter is also necessary when absorption is thought to have been percutaneous. In addition, the contaminated skin should be thoroughly washed with soap and water.
Although it appears logical to assume that removal of unabsorbed drug from the gastrointestinal tract (‘gut decontamination’) will be beneficial, the efficacy of current methods remains unproven, and efforts to remove small amounts of ‘safe’ drugs are clearly not worthwhile or appropriate.
Activated charcoal adsorbs a wide variety of drugs and toxic agents; the exceptions are acids and alkalis, ethanol, ethylene glycol, iron, lithium, and methanol.
In studies in volunteers given 50 g activated charcoal, the mean reduction in absorption was 40%, 16%, and 21% at 60 min, 120 min, and 180 min, respectively, after ingestion. Based on these studies, activated charcoal should be considered in those who have ingested a potentially toxic amount of a poison (known to be adsorbed by charcoal) up to 1 h previously. There are insufficient data to support or exclude its use after 1 h. There is no evidence that administration of activated charcoal improves the clinical outcome.
Gastric aspiration and lavage
Gastric emptying studies in volunteers provide no support for the use of gastric lavage. In the single clinical study in which benefit was claimed for lavage within 1 h of overdose, patients also received activated charcoal. There was also selection bias, and hence conclusions based on these data are limited. Thus, gastric lavage should not be used routinely in the management of poisoned patients as there is no evidence that it improves outcome, and it may cause significant morbidity.
The efficacy with which lavage removes gastric contents decreases with time; therefore, lavage should be considered only in patients who have ingested life-threatening amounts of a toxic agent up to 1 h previously.
Emesis with syrup of ipecacuanha
Syrup of ipecacuanha contains the active alkaloids emetine and cephaeline. Although syrup of ipecacuanha is an effective emetic, there is no evidence that its use prevents significant absorption of toxic material and, moreover, its adverse effects (e.g. persistent vomiting, diarrhoea, lethargy, drowsiness) may complicate diagnosis. It is not recommended.
Theoretically, the more quickly a slowly absorbed poison passes through the gut, the less it is absorbed. The opposite may apply to rapidly absorbed drugs. Whole-bowel irrigation using polyethylene glycol electrolyte solutions does not result in absorption of fluid and electrolytes, even though large volumes are administered rapidly via a nasogastric tube. Some volunteer studies have shown substantial decreases in the bioavailability of ingested drugs, but no controlled clinical trials have been conducted and there is no evidence that whole-bowel irrigation improves outcome. Based on volunteer studies, whole-bowel irrigation may be considered following potentially toxic ingestion of sustained-release or enteric-coated drugs and in body packers.
Cathartics have been used alone and with activated charcoal. Cathartics alone have no role in the management of poisoned patients. Based on available data, routine use of a cathartic with activated charcoal is not endorsed.
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