Oxford Handbook of Critical Care (3 edn)
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Poisoning—general principles
Consider poisoning in patients presenting with altered consciousness, respiratory or cardiovascular depression, vomiting, hypothermia, or seizures. Diagnosis is often obvious though the obtunded or truly suicidal patient may prevent an accurate history being taken. Clinical signs may be confused due to ingestion of multiple poisons or absent if effects are delayed. Poisons may also enter the body via routes other than ingestion, e.g. inhalation or transdermally. Salicylate and paracetamol are extremely common agents in self‐poisoning and patients often present without alteration in conscious level.
Investigation
All patients require urea and electrolyte, baseline liver function, coagulation studies, blood glucose, and blood gas estimations. Urine samples and gastric aspirate should be saved for possible later toxicology analysis. Obtain salicylate and paracetamol levels urgently due to the common lack of early signs and to direct specific early treatment. Other drug levels may help in diagnosis but treatment is often supportive. Early support from the local Poisons Information Service should be solicited.
Supportive treatment
Treat cardiovascular and respiratory compromise and neurological disturbance as by standard intensive care methods. In the unconscious patient, opiates and benzodiazepines may be reversed temporarily to allow assessment of underlying neurological status though caution should be applied in epileptics.
Gastric emptying
Despite previous widespread use, there is little supporting evidence and it carries significant complication risks. Consider gastric emptying if the poison is not a corrosive or hydrocarbon, has been ingested <60min previously, and cannot be eliminated by other means (e.g. iron). Forced emesis (ipecacuanaha 30mL in 200mL water) is no longer recommended as vomiting may be delayed for 30min and may be intractable. Aspiration is a serious risk with either form of gastric emptying therapy; intubate the patient for airway protection if consciousness is at all impaired.
Prevention of absorption
Activated charcoal is probably more effective than gastric emptying to prevent drug absorption. A charcoal:poison weight ratio of 10:1 is recommended. Give activated charcoal (50–100g as a single dose) NG to adsorb poison remaining in the gut ± a cathartic agent.
Enhanced elimination
Forced diuresis is no longer recommended. Fluid repletion with mild urinary alkalinisation is useful for salicylates. Small molecules may be removed by haemodialysis (e.g. ethylene glycol, methanol, oxalic acid, formic acid, salicylates, lithium). Activated charcoal given to prevent absorption may also adsorb poison returned to the small bowel via the enterohepatic circulation. This may be useful in carbamazepine, phenobarbital, theophylline, quinine, and dapsone poisoning. Multiple doses of activated charcoal are probably ineffective.
See also:
Airway maintenance, p40; Endotracheal intubation, p42; Urea and creatinine, p210; Electrolytes (Na+, K+, Cl−, HCO3 −), p212; Liver function tests, p218; Toxicology, p228; Salicylate poisoning, p522; Paracetamol poisoning, p524; Sedative poisoning, p526; Tricyclic antidepressant poisoning, p528; Amphetamines and ecstasy, p530; Cocaine poisoning, p532; Inhaled poisons, p534; Household chemicals, p536; Methanol and ethylene glycol, p538; Organophosphate poisoning, p540.
Salicylate poisoning
Serious, life‐threatening toxicity is likely after ingestion of >7.5g salicylate. Aspirin (acetyl salicylic acid) is the most common form ingested.
Loss of consciousness is rare but metabolic derangements are complex (e.g. respiratory alkalosis due to respiratory centre stimulation, dehydration due to salt and water loss, renal bicarbonate excretion and hyperthermia, hypokalaemia, metabolic acidosis due to interference with carbohydrate, lipid and amino acid metabolism, hyperthermia due to uncoupling of oxidative phosphorylation and increased metabolic rate).
There may also be pulmonary oedema due to capillary leak and bleeding due to reduced prothrombin levels. Although gastric erosions are common with aspirin treatment, bleeding from this source is rare in acute poisoning.
Management
Prevention of absorption
Give activated charcoal (50–100g) NG to adsorb salicylate remaining in the gut.
Salicylate levels
Repeat blood levels as they may continue to rise as absorption continues. Levels taken after 12h may underestimate the degree of toxicity due to tissue binding. If salicylate levels are <3.1mmol/L after 1h of ingestion and there is no metabolic derangement, then observation, fluids, and repeat levels are all that is required. Urine alkalinisation is required if levels >3.6mmol/L or there is metabolic derangement but no renal failure. Levels >5.1mmol/L (or >3.6mmol/L with renal failure) require haemodialysis.
Urine alkalinisation
Alkalinisation rather than forced diuresis is more important for salicylate excretion. Urinary pH must be >7.0 without arterial alkalosis (pH <7.5). Potassium loss occurs with a bicarbonate infusion due to the diuresis and as a toxic effect of the salicylate. Monitor and correct potassium levels in a high dependency environment. Fluid repletion is essential. Alkalinisation, if successful, should continue until salicylate levels fall <3.6mmol/L. Calcium levels may drop with prolonged alkalinisation.
Haemodialysis
Indications include salicylate levels >5.1mmol/L, renal failure, or marked metabolic acidosis.
See also:
Paracetamol poisoning
Serious, life‐threatening toxicity is likely after ingestion of >10–15g paracetamol, particularly with co‐ingestion of enzyme‐inducing drugs (e.g. anticonvulsants, anti‐TB therapy) and/or alcohol.
Paracetamol is rapidly absorbed and metabolised by conjugation in the liver. Hepatic necrosis occurs due to toxicity of an alkylating metabolite normally removed by conjugation with glutathione; glutathione is rapidly depleted with overdose and may already be low in starvation, alcoholics, and HIV disease, thus predisposing these groups to an increased risk of toxicity.
Toxicity is usually asymptomatic for 1–2 days although laboratory assessment of liver function may become abnormal after 18h.
Hepatic failure develops after 2–7 days.
Management
If ingestion of >12g has occurred <1h previously, activated charcoal (50–100g) should be given NG to adsorb paracetamol remaining in the bowel. Take blood levels to confirm ingestion, but should not be interpreted for toxicity unless taken four or more hours from ingestion. The mainstay of treatment is with N‐acetylcysteine (NAC) to restore hepatic glutathione levels by increasing intracellular cysteine levels.
N‐acetylcysteine
Treatment is most effective if started within 8h of ingestion, but is currently advised for up to 36h of ingestion. Start NAC if paracetamol levels are in the toxic range (see figure 30.1) or >12g paracetamol has likely been ingested. Continue NAC until paracetamol is not detected in the blood. It is given by continuous IV infusion (150mg/kg over 15min, 50mg/kg in 500mL 5% glucose over 4h, then 50mg/kg in 500mL 5% glucose 8‐hourly).
Methionine
Methionine is an alternative to NAC, but absorption is unreliable if there is vomiting or activated charcoal administration. Give 2.5g methionine PO 4‐hourly for four doses within 12h of ingestion.
Complications
The major complication is hepatic (9 renal) failure. A rise in prothrombin time, INR, and bilirubin are early warning signs of significant hepatic damage and this should prompt early referral to a specialist centre.
Guidelines for referral to a Specialist Liver centre
Arterial pH <7.3.
INR >3 on day 2 or >4 thereafter.
Oliguria and/or rising creatinine.
Altered conscious level.
Hypoglycaemia.
Guidelines for liver transplantation
Arterial pH <7.3.
Or all the following:
PT >100, INR >6.5.
Creatinine >200 mol/L.
Grade 3–4 encephalopathy.
High lactate levels (>3.5mmol/L at 4 and 12h) and low factor V levels are also associated with a poor outcome if not transplanted.
Graph for predicting treatment requirement.
Treatment is required at lower levels if the patient is a known alcoholic, protein‐depleted, HIV‐positive, or is taking enzyme‐inducing drugs, e.g. phenytoin.
See also:
Sedative poisoning
Patients can present with alterated consciousness, respiratory failure, and sometimes, cardiovascular disturbance. Treatment is usually supportive. Consider the possibility of rhabdomyolysis after prolonged immobility.
Benzodiazepine poisoning
Benzodiazepines are common agents used for self‐poisoning, but severe features are uncommon, except at extremes of age.
Flumazenil may be used as a specific antidote (0.2–1.0mg IV given in 0.1mg increments), but is dangerous in benzodiazepine dependence and mixed poisoning with tricyclic antidepressants.
Flumazenil is short‐acting so benzodiazepine reversal may be temporary.
Rapid reversal of benzodiazepines may lead to anxiety attacks or seizures.
Opioid poisoning
Treatment is supportive with attention particularly to respiratory depression and cardiovascular disturbance.
Naloxone may be used as an antidote (0.2–0.4mg IV) although rapid reversal is not desired in opioid abusers.
Naloxone is short‐acting so reversal may be temporary.
Consider HIV or other viral infection, and endocarditis in IV drug abusers.
In iatrogenic poisoning, naloxone will reverse the pain relief that opioids were given for. In these cases, respiratory depression is better reversed by the non‐specific respiratory stimulant, doxapram (1.0–1.5mg/kg over 30s IV followed by 1.5–4.0mg/min).
Barbiturates
Treatment is supportive with particular attention to respiratory and cardiovascular depression. Vasodilatation may be extreme requiring fluid support and, in some cases, inotropic support. Phenobarbital may be eliminated by forced alkaline diuresis.
See also:
Tricyclic antidepressant poisoning
Tricyclic antidepressants are prescribed to patients who are at greatest risk of a suicide attempt. They are rapidly absorbed from the gastrointestinal tract although gastric emptying is delayed.
Clinical features
Anticholinergic effects (dilated pupils, dry mouth, ileus, urine retention).
Arrhythmias (often associated with prolonged QT interval and broad QRS complex).
Hypotension related to arrhythmias and/or cardiac depression through Na+ channel blockade.
Hyper‐reflexia with extensor plantars, visual hallucinations, coma, and seizures. Drug levels do not correlate with severity.
Metabolic acidosis in severe poisoning.
Metabolism is usually rapid and improvement is usually within 24h.
Management
There is no specific treatment for tricyclic antidepressant poisoning.
Patients require ECG monitoring during the first 24h and until ECG changes have disappeared for 12h.
Activated charcoal (50g) via a nasogastric tube will adsorb tricyclics remaining in the bowel.
Cardiac arrhythmias are more common if there is an acidosis. Give bicarbonate to achieve an arterial pH of 7.5. If arrhythmias occur with no acidosis and fail to respond to treatment with amiodarone or phenytoin, bicarbonate (25–50mL 8.4% IV) may still be useful.
Seizures are best managed with benzodiazepines and phenytoin.
See also:
Amphetamines and Ecstasy
Amphetamines, e.g. 3,4‐methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) and 3,4‐methylenedioxyethamphetamine (‘Eve’), are stimulants taken predominantly for recreational use or as appetite suppressants. They are hallucinogenic at higher doses. MDMA cause rapid decreases in central nervous system 5‐hydroxytryptamine and 5‐hydroxyindole‐3‐acetic acid levels and increases in dopamine release.
Clinical features of overdose
Agitation, hyperactivity, hypertension, hallucinations, paranoia followed by exhaustion, coma, convulsions, and hyperthermia.
Idiosyncratic responses to Ecstasy and Eve are more common with numerous reports of mortality and major morbidity following ingestion of just 1–2 tablets.
Ingestion in hot environments, e.g. nightclubs, and concurrent dehydration is more likely to be associated with idiosyncratic responses.
Features include profound hyperthermia (>40°C), agitation, seizures, muscle rigidity, hypertension, tachycardia, sweating, coma, disseminated intravascular coagulation, and rhabdomyolysis.
These complications lead to hypovolaemia, electrolyte imbalance (particularly hyperkalaemia), and a metabolic acidosis.
Some patients taking Ecstasy or Eve have been admitted with water intoxication and acute hyponatraemia following ingestion of large amounts of water.
Management
Supportive care, including airway protection, fluid resuscitation, electrolyte correction, and if needed, mechanical ventilation.
Early stages of amphetamine poisoning can be often controlled with tepid sponging, chlorpromazine, β‐blockade. Forced acid diuresis to increase urinary excretion is rarely needed.
Manage severe complications as they arise, e.g. rapid cooling for hyperpyrexia, anticonvulsants for seizures, urine alkalinisation ± fasciotomies for rhabdomyolysis, platelet, and fresh frozen plasma infusions for coagulopathy.
Dantrolene is sometimes given to treat hyperpyrexia at a dose of 1mg/kg IV, repeated to a cumulative maximum dose of 10mg/kg, particularly if the temperature is >40°C. However, no outcome benefit has been reported through its use and it can cause side effects.
See also:
Cocaine poisoning
Modes of action
Blocks reuptake of dopamine (causing euphoria, hyperactivity) and norepinephrine (causing vasoconstriction and hypertension). Arrhythmias may also result.
Blocks Na+ channels, resulting in a local anaesthetic action and myocardial depression.
Platelet activation.
Mitochondrial dysfunction leading to myocardial depression.
Complications
Chest pain related to myocardial ischaemia or infarction, or to coronary artery spasm.
Heart failure.
Seizures.
Cerebrovascular accidents.
Pneumothorax.
Rhabdomyolysis.
Premature labour—abruption.
Agitated delirium, hyperthermia.
Management
Local chest pain guidelines should be followed. ECG abnormalities often resolve within 12h. Arrhythmias should be treated conventionally, but avoiding β‐blockers (leaving an unopposed α‐action).
Verapamil or phentolamine may be useful for treating hypertension.
Oxygen.
Give benzodiazepine for agitation, delirium, chest pain.
Aspirin for chest pain, CVA.
Nitrates for chest pain.
Low molecular weight heparin or clopidogrel may also be given unless the blood pressure is very high.
Urinary alkalinisation for rhabdomyolysis.
See also:
Pneumothorax, p368; Hypertension, p382; Acute coronary syndrome (1), p388; Acute coronary syndrome (2), p390; Heart failureassessment, p392; Heart failuremanagement, p394; Delirium, p442; Generalised seizures, p444; Stroke, p452; Poisoning—general principles, p520; Hyperthermia, p600; Rhabdomyolysis, p612.
Inhaled poisons
Carbon monoxide (CO)
CO poisoning should be considered in anyone found in a smoke‐filled, enclosed space. CO displaces oxygen from haemoglobin to which it has 200 times greater affinity and thus prevents oxygen carriage. There is also a direct toxic effect on mitochondrial oxidative phosphorylation as it competes with oxygen for the same binding site on cytochrome oxidase.
Clinical features
Fatigue, headache, vomiting, dizziness, confusion, dyspnoea, cerebral oedema in severe poisoning.
A cherry red appearance of the skin and mucosae are classical.
PaO2 will be normal unless there is respiratory depression and pulse oximetry is misleading.
The half‐life of carboxyhaemoglobin is 4h when breathing room air and 50min when breathing 100% oxygen.
Management
Carboxyhaemoglobin levels should be measured by a co‐oximeter and treatment started immediately with oxygen at the maximum concentration that can be delivered (ideally FIO2 1.0).
If carboxyhaemoglobin levels >25% or there is associated mental disturbance, the optimal treatment is hyperbaric oxygen at 3 atmospheres for 30min, repeated 6‐hourly if levels remain >25%. Death is likely with carboxyhaemoglobin levels >60%.
High concentration oxygen treatment should continue until carboxyhaemoglobin levels <10%.
Cyanide
Severe cyanide poisoning has an extremely rapid onset and occurs in some cases of smoke inhalation. Survival may be associated with anoxic brain damage.
Diagnosis must be made clinically; cyanide levels take >3h to perform.
Clinical features
Clinical features include anxiety, agitation, hyperventilation, headache, loss of consciousness, dyspnoea, weakness, dizziness, and vomiting. The skin remains pink and hypotension may be severe. An unexplained metabolic acidosis is suggestive.
Management
High concentration oxygen should be given, but is only truly effective when given at hyperbaric pressures.
In mild cases, rapid, natural detoxification reduces cyanide levels by 50% within 1h, allowing supportive therapy only.
Sodium thiosulphate (150mg/kg IV followed by 30–60mg/kg/h) converts cyanide to thiocyanate and should be used if there is unconsciousness. However, it is slow‐acting.
Nitrites produce methaemoglobinaemia (metHb) and may potentially worsen cyanide toxicity.
Dicobalt edetate (300mg IV), the specific antidote is toxic (vomiting, urticaria, tachycardia, hypotension, dyspnoea, chest pain) in the absence of cyanide. It is best avoided unless cyanide toxicity is likely.
Key paper
See also:
Household chemicals
Corrosives
Strong acids and alkalis are increasingly available in the household and ingestion may lead to shock and bowel perforation. Avoid gastric elimination techniques since aspiration of corrosives may cause severe lung damage. Early surgical repair of perforation may be necessary.
Petroleum
Access to petroleum in the home is easy.
Clinical features
Gut ingestion and absorption gives clinical features similar to those of alcohol intoxication with more severe neurological depression.
Management
Avoid gastric elimination techniques since a few drops of petroleum spilling into the lungs can lead to a severe pneumonitis. This is due to the low surface tension and vapour pressure of petroleum allowing rapid spread through the lungs.
Treatment involves supportive therapy and 250mL liquid paraffin orally.
Paraquat
Paraquat is widely available as a selective weedkiller which is inactivated on contact with the soil. A dose of 2–3g is usually fatal (equivalent to 80–120g of granules or 10–15mL of industrial liquid concentrate). It inhibits mitochondria and generates superoxide which damages lipid membranes.
Clinical features
Very little of the ingested paraquat is absorbed from the gut, but a large dose will lead rapidly to shock with widespread tissue necrosis.
A burning sensation in the mouth and abdomen, development of painful mouth ulcers and, after several days, a relentless, proliferative alveolitis leading to ARDS and death from pulmonary fibrosis. Liver, heart, and kidney may also be affected. Death may be slow and take up to 30 days following ingestion.
Management
Treatment should begin on clinical grounds in view of the severity of toxicity and the time taken for laboratory confirmation.
Remove patient from ongoing contact, decontaminate skin with large volumes of water, and remove their clothing. Staff should take care not to contaminate themselves.
Urgently instill 1000mL water containing 150g Fuller's earth via a nasogastric tube. Alternatively, 1g activated charcoal may be given.
A cathartic such as 25g magnesium sulphate should be given.
Severe diarrhoea may ensue, requiring careful fluid management.
If paraquat poisoning is confirmed, 200–500mL of 30% Fuller's earth is given 2‐hourly for 24h via a nasogastric tube.
Fluid repletion to encourage renal excretion.
Pulmonary fibrosis is more severe when breathing high FIO2. Oxygen should be avoided but, in severe hypoxaemia, give the lowest concentration possible accepting low PaO2. Liposomal superoxide dismutase and glutathione peroxidase are used experimentally.
See also:
Poisoning—general principles, p520.
Methanol and ethylene glycol
Methanol
Toxicity mainly due to oxidation of methanol to formic acid and formaldehyde. The oxidative pathway is an enzymatic process involving alcohol dehydrogenase, but proceeds at 20% of the rate of ethanol oxidation.
Clinical features
Clinical features of poisoning include blindness (due to concentration of methanol in the vitreous humour), severe metabolic acidosis, headache, nausea, vomiting, and abdominal pain.
Management
Metabolism of methanol is slow so treatment will need to be prolonged (several days).
Treatment includes ethanol or, preferably, fomepizole, to inhibit alcohol dehydrogenase.
On presentation 1mL/kg ethanol (50%) can given orally followed by 0.5mL/kg 2‐hourly for 5 days. Alternatively, an infusion can be given (7.5mL/kg ethanol (10%) over 30min followed by 0.5–1.0mL/kg/h aiming for blood ethanol levels of 100–150mg/dL). Levels need to be repeated frequently to avoid under‐ or overdosing.
Block metabolism with 4‐methyl pyrazole (fomepizole) infused or injected 12‐hourly IV. Though more expensive than alcohol, it is effective, well‐tolerated, and there is no need for therapeutic monitoring.
If methanol levels are >1000mg/L, haemodialysis is used until levels are <250mg/L.
Ethylene glycol
Ethylene glycol is partially metabolised by alcohol dehydrogenase to oxalic acid which is responsible for a severe metabolic acidosis, renal failure, and seizures.
Clinical features
Clinical suspicion is aroused by odourless drunkenness, oxalate crystals in the urine or blood, and the severe acidosis. As little as 50mL can be fatal.
Management
Treatment is as for methanol.
See also:
Organophosphate poisoning
Organophosphates in pesticides are the major cause of suicidal poisoning in developing countries and are used as nerve agents in terrorist attacks (e.g. Sarin, Tabun, VX, GF). They can be absorbed through intact skin, gut, or inhaled. Their mode of toxicity is via inhibiting cholinesterase.
Cholinergic (anticholinesterase) syndrome
Salivation, lacrimation, bronchorrhoea, sweating.
Anxiety and restlessness.
Vomiting, diarrhoea.
Bradycardia.
Bronchospasm.
Pulmonary oedema.
Miosis.
Hyperglycaemia.
Muscle weakness and fasciculation with paralysis.
Management
Skin decontamination should never be neglected or hurried but must occur prior to critical care admission. The patient's clothes should be removed. The patient's body should then be thoroughly washed with soap and water to prevent further absorption from the skin. Staff should be protected from the organophosphate by wearing gloves, gowns, and eye protectors.
The airway should be protected and oxygen given to avoid hypoxaemia (ventricular fibrillation more common with atropine in hypoxaemia).
Atropineantagonises acetylcholine at muscarinic receptors. A dose of 2mg should be given every 5–10 minutes until the mouth is dry. Severe poisoning may require >100mg atropine.
Pralidoximereactivates inhibited enzymes if given before the agent permanently binds to the enzyme. A dose of 30mg/kg, repeated every 4–6 hours or an infusion of 8mg/kg/h to a maximum dose of 12g in 24 hours should be given.
Diazepam—neuroprotection.
