Overdose, poisoning and drug abuse

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CHAPTER 9 OVERDOSE, POISONING AND DRUG ABUSE

OVERDOSE AND POISONING

The problems associated with overdose and poisoning (deliberate or accidental) are responsible for a significant portion of the acute medical workload in hospitals. While most overdoses and poisonings are not serious and can be managed on medical wards, some patients will require admission to intensive care. This may be the result of the specific nature and effects of the substance involved, respiratory or cardiovascular complications or occasionally due to the onset of multiorgan failure. Common complications associated with overdose and poisonings are shown in Table 9.1.

TABLE 9.1 Potential complications of overdose

General	Hypothermia/hyperthermia Pressure sores Crush syndrome/rhabdomyolysis Dehydration
Cardiovascular	Hypotension/hypertension Dysrhythmias Cardiac arrest
Respiratory	Respiratory depression Aspiration Pneumonia
CNS	Coma Hypoxic brain damage Seizures Confusional states/aggression
Renal	ATN secondary to hypotension/dehydration Effects of rhabdomyolysis Direct toxic effects
Gastrointestinal/liver	Diarrhoea/vomiting Acute gastric erosions/gastrointestinal haemorrhage Acute liver failure

This chapter provides general advice only. The UK National Poisons Information service (http://www.npis.org) operates TOXBASE®, which is an on-line poisons information service available at http://www.toxbase.org. This requires registration but should be available in most centres and should be consulted in the first instance. If additional advice is needed, this can be obtained from one of the regional poisons information services by telephone. Telephone numbers will be available through local hospital switch boards, via Toxbase® and from the British National Formulary (BNF: available on line at www.bnf.org).

INVESTIGATIONS

In the unconscious patient it is essential to exclude other treatable causes of loss of consciousness (e.g. head injury, subarachnoid haemorrhage, hypoglycaemia, meningitis), even if the patient has left a suicide note or is known to have taken an overdose previously. If in doubt, organize a CT scan of the brain and consider lumbar puncture and other investigations as appropriate.

The response to a (cautious) challenge of naloxone or flumazenil may occasionally be helpful in identifying opioid and benzodiazepine overdose, respectively (see below).

Aspirin (salicylate) and paracetamol assays should be performed in all cases. Alcohol levels can be measured in most centres and may be useful to distinguish intoxication from brain injury. The majority of other assays are unavailable at short notice, and the samples should be sent to regional centres. Aside from paracetamol, it is rare for assays to alter clinical management. Ask the laboratory to save serum in uncertain cases for later analysis and send urine for a toxicology screen. These samples may be invaluable if the patient subsequently dies and there is a Coroner’s inquest or other inquiry.

MEASURES TO REDUCE ABSORPTION/INCREASE ELIMINATION OF DRUGS

Gastric lavage

Historically, gastric lavage was frequently performed in an attempt to remove tablet debris from the stomach. This is no longer a routine procedure, as evidence suggests it is largely ineffective, does not improve survival and is associated with potentially serious adverse events including aspiration, airway compromise, hypoxia and death.

Gastric lavage should therefore only be performed when recommended by a poisons information centre. It is usually only indicated when patients present within one hour of ingestion of life threatening quantities of drugs. Contraindications include ingestion of corrosives or substances liable to cause lipoid pneumonias and refusal of consent. It is not usually performed in children.

In the rare cases where gastric lavage is indicated, the airway should be protected by endotracheal intubation. If necessary, seek help from an experienced anaesthetist.

If the patient is very obtunded, it may be possible to intubate the trachea without any anaesthetic drugs.

If not, perform a rapid sequence induction with preoxygenation, cricoid pressure, an intravenous induction agent and suxamethonium.

Pass the gastric tube under direct vision and then perform lavage.

Consider extubation in head-down, left lateral position.

If the patient is not fit to extubate and/or send to the ward, keep the patient intubated and transfer to ICU.

If respiratory effort is feeble, it is better to support ventilation for a few hours than leave the patient to breathe spontaneously with poor tidal volumes. This helps to maintain lung expansion, minimizes the tendency to atelectasis and provides ongoing airway protection.

Forced alkaline diuresis

Traditionally, this has been used to increase the renal clearance of soluble, acidic drugs, particularly salicylates and barbiturates. It is now controversial due to problems with fluid overload and acid–base disturbance. Seek senior advice. A typical regimen is as follows:

Use CVP to guide volume loading with normal saline/colloid.

Give 0.25–0.5 g / kg mannitol 20% to promote diuresis > 200 mL / h.

Give sodium bicarbonate (8.4%) 1 mmol / kg / h to achieve urinary pH > 7.5.

The role of loop diuretics to increase urine flow in this setting is controversial. Some authors recommend them if the response to mannitol is inadequate. They can, however, produce acidification in the renal tubule and promote precipitation of acid-soluble drugs and compounds such as myoglobin. (See Rhabdomyolysis, p. 320.)

Haemodialysis and haemoperfusion

Haemodialysis and haemoperfusion over activated charcoal are useful for some life-threatening overdoses. These are listed in Table 9.2. Seek specialist advice. There are also some reports of albumin dialysis (e.g. MARS®) being used in the treatment of heavy metal poisoning.

TABLE 9.2 Role of haemodialysis and haemoperfusion in overdose

Haemodialysis	Haemoperfusion
Ethylene glycol	Barbiturates
Methanol	Theophylline
Lithium
Salicylates

ANTIDOTES

Some overdoses / poisonings have specific antagonists or antidotes which reduce the toxic effects and mortality. These should generally only be used for potentially life-threatening situations when the nature of the overdose or poison is known. Available antagonists / antidotes are shown in Table 9.3.

TABLE 9.3 Commonly available antagonists and antidotes

Drug	Antagonist/antidote
Benzodiazepines	Flumazenil
Copper	Penicillamine
Digoxin	Digoxin-specific antibodies
Ethylene glycol	Ethanol, fomepizole
Heparin (unfractionated)	Protamine
Iron	Desferrioxamine
Lead	Sodium calcium edetate
Methanol	Ethanol, fomepizole
Opioids	Naloxone
Organophosphates	Atropine, pralidoxime
Paracetamol	N-acetylcysteine
Warfarin	Vitamin K, fresh frozen plasma, prothrombin complex concentrate (Beriplex)

INTENSIVE CARE MANAGEMENT

In the majority of overdoses/poisonings there is no specific antidote and care is supportive with the aim of preventing or reversing the onset of complications. Indications for admission to intensive care are shown in Box 9.2.

Secure the airway and support respiration with IPPV if necessary. Sedative drugs can usually be avoided if the patient is deeply comatose. Muscle relaxants may aid intubation. Extubate once the consciousness level improves.

Monitor ECG and blood pressure.

A number of common overdoses are associated with cardiac rhythm disturbances. Where possible avoid procedures or treatments that may precipitate dysrhythmias. Most patients admitted to intensive care following self-poisoning are admitted for a relatively short period, and remain stable (generally suffering only a depressed level of consciousness). It is usually neither necessary nor desirable to insert a central venous catheter. If central venous access is required, avoid precipitating cardiac rhythm disturbances by inserting the guide wire too far.

Use fluid in the first instance to manage hypotension. Some patients may be severely dehydrated and require significant fluid therapy.

Monitor body temperature. Hypothermia is common following prolonged unconsciousness and after overdose with some centrally acting drugs while hyperthermia may follow some specific overdoses.

Single short convulsions do not require treatment. Prolonged seizure activity should be treated; seek specialist advice. (See Seizures, p. 296.)

Beware of pressure-related injuries from prolonged immobilization. Pressure sores, tissue necrosis and compartment syndromes are common following prolonged unconsciousness. Rhabdomyolysis and myoglobinuria can precipitate renal failure. (See Peripheral compartment syndromes, p. 319 and Rhabdomyolysis, p. 320.)

Box 9.2 Indications for admission to intensive care following overdose/poisoning

Need for tracheal intubation/assisted ventilation

Reduced conscious level (GCS < 8) or seizures

Need for invasive monitoring/cardiovascular support

Dysrhythmias ^*

2nd or 3rd degree heart block ^*

QRS > 0.12 s or QTc > 420 ms ^*

Need for renal replacement therapy or other organ support

^* Need for continuous cardiac monitoring. Depending on local policies may be admitted to coronary care unit or HDU.

Typically, a patient who has taken an overdose of sedative or analgesic agents needs between 12 and 24 h of supportive care (possibly including ventilation) before discharge to the ward.

All patients who are admitted following deliberate overdose should be referred to a liaison psychiatrist. The psychiatric consultation will not normally take place until the patient is sufficiently well for this to be meaningful, and this may therefore not occur until after the patient has returned to the ward. Nevertheless, it is important to make the referral at an early stage so that it is not overlooked. This is particularly important as many patients who have taken an overdose may discharge themselves from hospital against medical advice.

PARACETAMOL

Paracetamol poisoning is important, as it is the commonest overdose referred to the UK National Poisons Information Service, accounting for over 1000 calls per year. Despite legislation to reduce the amount of paracetamol which can be bought at any one time, in the UK, 48% of all hospital admissions for poisoning are due to paracetamol. It remains a leading cause of hyperacute liver failure in intensive care units, and results in 300 deaths in the UK annually.

Relatively low doses of drug may produce fatal liver failure in susceptible patients, such as those with pre-existing liver disease. In addition, the ingestion of other drugs (e.g. anticonvulsants) may increase the toxicity of paracetamol.

The need for treatment is determined by plasma paracetamol concentrations. For those who fall above treatment thresholds, intravenous N-acetylcysteine is an effective antidote if started within 10–12 h of ingestion. For treatment thresholds and dosage schedules, see BNF or contact poisons advice centre.

For those patients who present more than 12 h after significant ingestion of paracetamol, N-acetylcysteine may still be of some benefit. Advice should be obtained from the poisons centre and/or the local liver unit.

Patients who develop liver failure often have few visible signs of problems for about 48 hours, and then deteriorate rapidly. Fulminant liver failure follows, with hepatic encephalopathy, increasing prothrombin time and INR, falling platelet count, jaundice, acidosis and renal dysfunction. These patients must be urgently transferred to a regional liver unit for further management, including possible acute transplantation. As patients with fulminant paracetamol-induced liver failure deteriorate extremely quickly, it is important to discuss such cases with your local liver unit as soon as possible, and carry out the transfer before the patient succumbs to multiple organ failure. (See Hepatic failure, p. 176.) Indications for urgent transplantation (within 24 h) are shown in Table 9.4.

TABLE 9.4 Indications for liver transplant following paracetamol overdose

Either (any one of the following)	Or (all of the following)
pH < 7.3 after fluid resuscitation	Creatinine > 300 μmol/l
Lactate > 3.5 (pre-resuscitation)	PT > 100 s
Lactate > 3.0 (post-resuscitation)	Grade III or IV encephalopathy

SALICYLATES (ASPIRIN)

The features of salicylate poisoning are hyperventilation, tinnitus, deafness, vasodilatation and sweating. Hyperventilation and sweating result in dehydration. Coma is uncommon but indicates severe overdose. Gastric emptying is delayed and gastric lavage is useful to retrieve tablet debris up to 4 h after ingestion. For the same reason, plasma levels may be misleading if taken within 6 h.

Blood gases and electrolytes should be monitored. Treatment is by rehydration. If plasma levels are above 500 mg/L (3.6 mmol/L) in adults or 350 mg/L (2.5 mmol/L) in children then forced alkaline diuresis with 1.26% sodium bicarbonate should be used to improve urinary excretion. In very severe cases, levels above 700 mg/L (5.1 mmol/L), haemodialysis is the treatment of choice.

BENZODIAZEPINES AND OPIODS

Benzodiazepines or opioid overdose generally requires no specific therapy other than supportive care and airway protection, with or without assisted ventilation until conscious level and respiratory drive improve. Flumazenil and naloxone may be used to confirm the diagnosis in benzodiazepine and opioid overdose, but may precipitate seizures, arrhythmias and hypertension. Do not use these antidotes in an attempt to avoid the need for tracheal intubation, assisted ventilation and ICU admission. They are short acting. If the infusion stops or the cannula is pulled out, then the patient’s conscious level may rapidly deteriorate, potentially with fatal consequences. Cases have also been reported where, following administration of these antagonist agents, the patient has rapidly woken up, become aggressive and taken hospital discharge, only to collapse again once outside the hospital. (See Intravenous drug abusers, p. 243.)

ANTIDEPRESSANTS

Tricyclic antidepressants

The tricyclic and related antidepressant drugs, in addition to sedative properties, have anticholinergic/sympathomimetic effects, which cause significant problems following overdose. Potential effects are shown in Box 9.3.

Box 9.3 Effects of tricyclic overdose

Tachycardia/dysrhythmias

Widely dilated pupils

Hyperthermia

Treatment is supportive, with resuscitation, control of seizures and rehydration. Tachydysrhythmias are common and may require repeated cardioversion. Antidysrhythmic drugs are best avoided. Once hypoxia, acidosis and dehydration are corrected, cardiac rhythm usually settles to a sinus tachycardia. Correction of acidosis with bicarbonate is thought to help by reducing unbound free drug (pKa effect). Typically, even after severe problems (e.g. dysrhythmias requiring repeated cardioversion), patients are stable enough to be extubated after 12–24 h. Often the patient will require no sedation for the first few hours. Short-acting sedatives/anticonvulsants (e.g. propofol infusion) may be required for a few hours until the patient is stable.

Selective serotonin reuptake inhibitors (SSI)

Selective serotonin reuptake inhibitors have been increasingly implicated in overdosage in recent years. Overdose with this class of drugs carries a much lower mortality than overdosage with tricyclic antidepressant agents. While all members of the class have presented as overdoses, the commonest is citalopram. Overdose with this class of drugs generally presents with drowsiness, though in severe cases there may be depression of consciousness, fitting, and prolonged QT_C. Very rarely, this leads to significant cardiac dysrhythmias. The literature includes sporadic cases of cardiac arrest. Admission to intensive care for management of the sedative side-effects is recommended. The effects of selective serotonin reuptake inhibitors in overdose may be prolonged, as drug elimination is reduced and normal pharmacokinetics appear not to apply.

INSULIN OVERDOSE

Relative overdose from unintentional mismatch between insulin dosage and insulin requirement is common. If managed in a timely fashion, the resulting mild hypoglycaemia is usually short lived and results in no harm to the patient (see Hypoglycaemia).

Deliberate overdose of insulin either by the patient or by a third party acting with criminal intent, although uncommon has been seen both inside and outside the hospital setting. Protracted severe hypoglycaemia leads to irreversible brain damage and frequently death. Insulin overdose (deliberate or otherwise) should always be considered as a cause of severe hypoglycaemia. Consider taking blood for later insulin assay. Treatment is by dextrose infusion. Survivors with brain damage have similar problems to those with hypoxic brain injury.

CARBON MONOXIDE AND CYANIDE POISONING

Carbon monoxide

Carbon monoxide is a product of incomplete combustion. Carbon monoxide poisoning may be seen in combination with burns, from smoke inhalation, from inadequately ventilated heating appliances (unexplained collapse) and following suicide attempts (car exhaust). Apparently unburned victims from house fires may present with carbon monoxide poisoning. Carbon monoxide bonds avidly to haemoglobin, resulting in carboxyhaemoglobin, which does not carry oxygen. Severe cases may suffer anoxic brain damage. The clinical features are shown in Box 9.4.

Box 9.4 Clinical features of carbon monoxide poisoning

Cherry red colour (unreliable)

Coma, confusional states

Diagnosis is made by measurement of carboxyhaemoglobin levels. Many blood gas analysers now include a co-oximeter that can measure carboxyhaemoglobin (normal levels < 5%). Some pulse oximeters also have this facility.

Treatment is supportive. If the inspired oxygen concentration is increased to 100% the half-life of carboxyhaemoglobin is 1 h; therefore, blood levels will quickly return to normal although tissue levels may remain elevated for longer. There is some evidence that, in patients who have had recorded carboxyhaemoglobin levels >20% and / or neurological symptoms at any time, the incidence of late neurological sequelae may be reduced by hyperbaric oxygen therapy. The benefits of hyperbaric oxygen need to be weighed against the risks of transfer to a specialist centre. Seek senior advice.

Not all hyperbaric facilities are based on hospital sites: check before agreeing to go, as you may find yourself in an isolated site with limited facilities and no backup.

Cyanide poisoning

Cyanide is a product of combustion of some foam materials. Cyanide poisoning may therefore occur in patients with smoke inhalation/carbon monoxide poisoning. The clinical features, which may be rapid in onset, include anxiety, vomiting, headache and reduced consciousness. Metabolic acidosis is common.

In mild cases, only supportive treatment is required. Give 100% oxygen. In severe cases with loss of consciousness, sodium thiosulphate is used to convert cyanide to thiocyanate. Seek advice. Typically:

Sodium thiosulphate 150 mg / kg i.v. followed by 30–60 mg / kg / h infusion.

METHANOL AND ETHYLENE GLYCOL

These agents may be ingested accidentally or deliberately.

Methanol

Methanol is available as a solvent, in methylated spirits and is present in de-icers and antifreeze solutions. Methanol may be taken as an alcohol substitute by patients who are unaware of the risks.

Clinical features are progressive confusion, ataxia and visual disturbances. Metabolism to formaldehyde and then formic acid leads to severe metabolic acidosis 12–18 h after ingestion. The direct toxic effects of formate on the optic nerve can result in blindness. Plasma osmolality and anion gap are increased (see Treatment below).

Ethylene glycol

Ethylene glycol is a sweet-tasting liquid used alone or in combination with other alcohols in antifreeze. Clinical features are similar to alcohol intoxication, followed by nausea, vomiting and haematemesis. Focal neurological signs, seizures and a gradual deterioration in conscious level then occur. While most of the ethylene glycol is excreted unchanged in the urine, metabolites include oxalic acid. This accumulates, resulting in severe metabolic acidosis, increased anion gap and hypocalcaemia. Oxalate excretion in the urine leads to the formation of oxalate crystals and renal failure.

Treatment of both methanol and ethylene glycol poisoning is based on supportive care, correction of the underlying acidosis and inhibition of the metabolism with ethanol or fomepizole. Ethanol competes with methanol / ethylene glycol as a substrate in the metabolic pathway. High percentage proof ethanol ampoules are available from most hospital pharmacy departments. Fomepizole is an expensive, newly introduced alcohol dehydrogenase inhibitor. In both cases, the metabolism of methanol / ethylene glycol and the production of toxic metabolites are reduced. Haemodialysis to remove methanol / ethylene glycol should be considered in severe cases. Seek specialist advice.

ALCOHOL

Alcohol (ethanol) is the most commonly used and abused non-prescription drug. Acute alcohol intoxication is a factor in many patients admitted to intensive care, particularly following trauma.

Acute alcohol intoxication

Acute alcohol intoxication produces coma, hypothermia, hypoglycaemia and in severe cases metabolic acidosis. Other causes of coma (e.g. extradural haemorrhage) must be excluded. Other injuries should also be excluded. Treatment is supportive. Consider:

intubation to protect the airway and ventilation as necessary

gastric lavage to reduce alcohol absorption (alcohol delays gastric emptying)

dextrose infusion to correct hypoglycaemia.

In severe life threatening cases of alcohol intoxication, an alcohol dehydrogenase inhibitor such as fomepizole may be of value. Seek specialist advice. Haemodialysis has also been used to remove alcohol, although only sporadic cases have been reported.

Management of alcohol withdrawal on ICU

Acute withdrawal from alcohol may result in insomnia, tremor, agitation and seizures. Delirium tremens, in which patients develop visual hallucinations, is the most serious withdrawal phenomenon. Symptoms develop 1–5 days after withdrawal and may be life-threatening. Treatment comprises adequate sedation, together with supportive care:

Standard ICU sedative regimens (particularly benzodiazepine based) are usually adequate. Chlormethiazole given by infusion is difficult to titrate, provides a substantial fluid load, and is probably best avoided. (See Sedation and analgesia, p. 34.)

RECREATIONAL DRUG ABUSE

The abuse of drugs by all routes is widespread. Some of the commonly abused ‘recreational’ drugs and their effects are shown in Table 9.5.

TABLE 9.5 Common drugs of abuse and their effects

Substance	Effects
Amphetamines	Stimulant effects, increased metabolic rate, weight loss, tachycardia, hypertension, dysrhythmias, hallucinations, paranoia, aggression
Anabolic steroids	No intoxication effects. Occasional acute psychosis; long-term risks associated with steroids, cardiomyopathy and sudden death
Cannabinoids	Euphoria, slowed reaction time, impaired balance/co-ordination/anxiety and panic attacks
Cocaine	Stimulant effects similar to amphetamines. Tachycardia, hypertension, seizures, CVA, coma
Gamma-hydroxybutyrate (GHB)	Reduced pain and anxiety, feeling of well-being, drowsiness, nausea/vomiting, loss of consciousness, depressed reflexes, seizures, coma and death
Ketamine	Tachycardia, hypertension, impaired motor function; high doses, respiratory depression
Lysergic acid diethylamide (LSD)	Altered states of perception, hyperthermia, tachycardia, hypertension
Methylenedioxymetam-phetamine (MDMA) (group includes ecstasy)	Similar to amphetamines. Mild hallucinogenic effects, impaired memory and learning, hyperthermia, idiosyncratic hyperacute liver failure
Opioids	Pain relief, euphoria, drowsiness, unconsciousness, respiratory depression/arrest
Phencyclidine (PCP)	Panic, aggression, violence, bradycardia, hypotension
Solvents	Stimulants. Headaches, loss of co-ordination, nausea/vomiting, dysrhythmias, sudden death