Assess and Stabilise the Patient

Drug overdose should be treated as a medical emergency. Attend to the patient immediately and stabilise (maintain vital physiological parameters, e.g. oxygen saturation, blood pressure) the patient as a priority (Table 27.1).

Table 27.1 Clinical signs and management summary of some commonly ingested pharmaceutical agents

Drug class	Clinical effects	Toxic dose	Action	Comments
ACE inhibitors	Hypotension and tachycardia. Hyperkalaemia	Variable	Supportive care. Intravenous fluids
Amiodarone	Non-specific ECG changes, hypotension and bradycardia	Variable	AC and supportive care
Antihistamines	Nausea, vomiting, retention of urine, tachycardia	Cyclizine 5 mg/kg, Diphenhydramine >300 mg	Activated charcoal (AC) and supportive care
Antibiotics	Mainly gastrointestinal – variable signs depending on the agent		AC and supportive care	Some are teratogenic
Anticoagulants (warfarin)	Bleeding tendency and prolonged international normalised ratio (INR)	Variable	AC and vitamin K for up to 10 days	If mother is on long-term warfarin, correction should be gradual to prevent thrombosis
Barbiturates	Nystagmus, ataxia, small pupils, respiratory depression and coma		Manage airway. AC
Benzodiazepines	CNS and respiratory depression	Variable	Manage airway. AC	Do not give flumazenil
Bromocriptine	Nausea, vomiting and hypotension. Psychosis and hallucinations	50–75 mg	AC. IV fluids and supportive care
Clonidine	Drowsiness, coma, bradycardia and hypotension. Hypertension	Variable	AC. Supportive care, IV fluids
Ergotamines	Cold cyanotic peripheries, abdominal pain	Variable	AC, glyceryl trinitrate, nitroprusside and nifedipine	Increases uterine tone, fetal hypoxia
Lithium (acute ingestions)	Nausea, vomiting, ataxia, myoclonic twitches, confusion and coma		Whole bowel irrigation if >4 g of sustained release is ingested. Do lithium levels at 6 hours post ingestion. Observe for up to 24 hours. Manage airway and fluid balance	May induce congenital malformations. Haemodialysis if coma, convulsions and respiratory failure or levels >7.5 mmol/L
MAOI	Drowsiness, confusion, agitation, coma, hypertension, hyperthermia		Airway management, diazepam, fluids	Symptoms may occur 24 hours post-ingestion
Opioids	Drowsiness, respiratory depression, hypotension, pinpoint pupils, coma		AC, naloxone (0.4 mg IV, increased every 2–3 minutes to a maximum bolus dose of 2 mg – use 2/3 the dose required as a maintenance each hour), airway management	Observe for minimum of 6 hours. In addicted patients, naloxone may precipitate withdrawal
Non-steroidal anti-inflammatory drugs	Variable – no symptoms to CNS depression and acidosis in massive doses	Variable	AC, supportive care
SSRI	Nausea and vomiting.		AC. In serotonin syndrome –
	Drowsiness and serotonin		cooling, IV fluids, sedate with
	syndrome (hyperthermia,rigidity, rhabdomyolysis)		diazepam and cyproheptadine
Theophylline	Nausea, vomiting, tachycardia, convulsions, hypokalaemia	1 g	Multiple dose AC	Observe 4 hours or up to 24 hours if sustained-release drug is ingested

Use Standard Advanced Cardiac Life Support

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  Assess airway, breathing and circulation – use standard guidelines.

  
  
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  Assess airway – talk to the patient. If she responds, the airway is patent. If there is no response, carry out airway opening manoeuvres (head tilt and jaw thrust).

  
  
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  Assess breathing – look, feel and count respiratory rate – feel for air on palm. Cyanosis?

  
  
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  Assess circulation – presence of pulse, measure blood pressure.

  
  
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  Assess neurological disability – note score on Glasgow Coma Scale (GCS).

  
  
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  Connect the patient to an ECG monitor and pulse oximeter. Measure blood sugar and serum electrolytes.

All patients who present with a ‘threatened airway’ (i.e. at risk of aspiration into the lungs) and low GCS score should have endotracheal intubation.

Assess Risk

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  Ask for the name of the drug/s.

  
  
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  Determine number of tablets, strength and preparation (ordinary release or slow release).

  
  
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  Decide if the ingested dose is likely to cause toxicity. Examine to detect the presence of signs of toxicity.

  
  
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  In the absence of signs of toxicity, assess the probability of subsequent development of toxicity.

  
  
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  Observed for widened QRS (100 ms) complex on the ECG in patients with tricyclic antidepressant poisoning. Similarly, observe for bradycardia and heart blocks in patients with calcium channel blocker and beta-blocker poisoning.

  
  
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  Observe for tachyarrhythmias in patients with tricyclic antidepressants (TCA), digoxin poisoning.

  
  
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  Patients with beta-blockers poisoning are at increased risk of Prolonged QT interval. Similarly metabolic acidosis may occur in patients with metformin poisoning (lactic acidosis), and salicylate and iron poisoning.

Decontaminate

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  Decontamination may be effective for longer periods than the usually recommended 1 hour post-ingestion.

  
  
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  Gastric lavage is not routinely recommended for a pregnant patient with drug overdose. Use activated charcoal.

For ordinary-release medications in overdose:

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  Administer activated charcoal 1 g/kg (50 g) if the patient presents within 1 hour post-ingestion.

  
  
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  The patient should have a protected airway and a verbal or written consent should be obtained for this if the clinical situation (i.e. conscious level) permits

  
  
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  Multiple doses of activated charcoal may be given in some cases of overdose with drugs such as carbamazepine and salicylates [1].

  
  
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  Whole bowel irrigation should be carried out following overdose with drugs such as slow-release calcium channel blockers, lithium and iron.

  
  
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  Method: Administer 1 L of oral polyethylene glycol hourly until the rectal effluent is clear.

Confirmation of Poisoning

Serum drug assays – limited use but a necessity in some instances, for example, instances e.g. overdose with paracetamol, iron, salicylates, digoxin or lithium.

Other indicators of toxicity, for example:

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  ECG: widened QRS (100 ms) complex in tricyclic antidepressant poisoning. Bradycardia and heart blocks in calcium channel blocker and beta-blocker poisoning.

  
  
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  Tachyarrhythmias in tricyclic antidepressants (TCA), digoxin poisoning.

  
  
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  Prolonged QT interval – beta-blockers poisoning.

  
  
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  Metabolic acidosis – metformin poisoning (lactic acidosis), salicylate and iron poisoning.

Paracetamol

Mechanisms of Toxicity

Paracetamol is largely metabolised in the liver to non-toxic glucuronide (60%) and sulphate (30%) conjugates, which are subsequently excreted in the urine.

A small fraction is also converted (by cytochrome P450-dependent mixed function oxidase enzymes) to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). The toxic metabolite is inactivated by conjugation with hepatic glutathione and eventually excreted as cysteine and mercapturic acid conjugates. In overdose, there is accumulation of this toxic metabolite.

In healthy women, a dose greater than 200 mg/kg or 10 g in total (whichever is less) may be hepatotoxic. In those considered as high-risk, that is, malnourished patients, patients on enzyme-inducing drugs (e.g. carbamazepine, phenytoin, rifampicin) or patients suffering from HIV, liver toxicity may occur at lower doses. The risk of liver damage is assessed using the paracetamol normogram (Figure 27.1) which plots the plasma paracetamol concentration in relation to the time of ingestion.

Figure 27.1 Paracetamol normogram.

Those on or above the treatment line will require treatment with N-acetylcysteine (NAC), without which severe liver damage could be expected in approximately 60% of patients. Where paracetamol has been taken chronically or in a staggered manner (e.g. >2 hours between doses), or where the time of ingestion is unknown, the plasma paracetamol concentration cannot accurately be interpreted using the normogram. If the total dose in 24 hours exceeds 200 mg/kg or 10 g, whichever is the smaller (> 100 mg/kg in high-risk patients), NAC should be administered.

Investigations

Measure plasma paracetamol level 4 hours after ingestion. Obtain baseline values for INR, serum creatinine, aspartate transaminase (AST) and alanine transaminase (ALT).

A specialist liver centre should be contacted if

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  The INR is >2 at 24 hours; >4 at 48 hours; >6 at 72 hours post-ingestion

  
  

       OR

  
  
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  The PT in seconds is greater than the number of hours since overdose

  
  

       OR

  
  
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    if the patient has any of the following:

  
  
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  An elevated plasma creatinine (>200 μmol/L).

  
  
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  Hypotension (mean arterial pressure less than 60 mm Hg) following accepted methods of resuscitation.

  
  
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  Encephalopathy.

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