Adverse birth outcomes such as preterm labour and low birth weight have been reported in a very small number of patients. Most drug overdoses require only supportive care. However, a few drugs which may cause severe overdose are discussed in this chapter. Treat the poison if an antidote is available, as the ‘poison’ is bound to be more toxic than the antidote to the fetus.
Physiological changes in pregnancy may be associated with changes in pharmacokinetics and toxicokinetics following overdose. The delay in gastric emptying time of up to 50% would result in lower peak plasma concentrations. Similarly, the increase in plasma volume during pregnancy and the associated increase in the volume of distribution would also result in reduced peak plasma concentrations of the drug.
Fetal: Effects on the fetus following overdose of the mother are sparse or non-existent at present.
Often effects on the fetus are considered to be directly related to maternal outcome.
Some drugs are known to be mutagenic and/or teratogenic. Others have the potential to be carcinogenic.
Key Diagnostic Signs
Anticholinergic signs: dilated pupils, sweating, warm and red peripheries – for example tricyclic antidepressant or belladonna alkaloid self-poisoning
Sympathomimetic signs: tachycardia, high blood pressure, sweating, dilated pupils – overdose of sympathomimetics, for example, amphetamines
Increased respiratory rate, sweating and tinnitus – salicylate self-poisoning
Bradycardia and hypotension – calcium channel blocker or beta-blocker self-poisoning
Depressed respiration, consciousness and small pupils – opioids (pinpoint pupils) or benzodiazepines self-poisoning
Hyperthermia and rigidity – selective serotonin reuptake inhibitors (SSRIs)
Hypoglycaemia – self-poisoning with anti-diabetic medications
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).
|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
|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|
|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
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).
Assess breathing – look, feel and count respiratory rate – feel for air on palm. Cyanosis?
Assess circulation – presence of pulse, measure blood pressure.
Assess neurological disability – note score on Glasgow Coma Scale (GCS).
Connect the patient to an ECG monitor and pulse oximeter. Measure blood sugar and serum electrolytes.
Determine number of tablets, strength and preparation (ordinary release or slow release).
Decide if the ingested dose is likely to cause toxicity. Examine to detect the presence of signs of toxicity.
In the absence of signs of toxicity, assess the probability of subsequent development of toxicity.
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.
Observe for tachyarrhythmias in patients with tricyclic antidepressants (TCA), digoxin poisoning.
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.
Decontamination may be effective for longer periods than the usually recommended 1 hour post-ingestion.
Gastric lavage is not routinely recommended for a pregnant patient with drug overdose. Use activated charcoal.
For ordinary-release medications in overdose:
Administer activated charcoal 1 g/kg (50 g) if the patient presents within 1 hour post-ingestion.
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
Multiple doses of activated charcoal may be given in some cases of overdose with drugs such as carbamazepine and salicylates .
Whole bowel irrigation should be carried out following overdose with drugs such as slow-release calcium channel blockers, lithium and iron.
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:
ECG: widened QRS (100 ms) complex in tricyclic antidepressant poisoning. Bradycardia and heart blocks in calcium channel blocker and beta-blocker poisoning.
Tachyarrhythmias in tricyclic antidepressants (TCA), digoxin poisoning.
Prolonged QT interval – beta-blockers poisoning.
Metabolic acidosis – metformin poisoning (lactic acidosis), salicylate and iron poisoning.
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.
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
The INR is >2 at 24 hours; >4 at 48 hours; >6 at 72 hours post-ingestion
The PT in seconds is greater than the number of hours since overdose
if the patient has any of the following:
An elevated plasma creatinine (>200 μmol/L).
Hypotension (mean arterial pressure less than 60 mm Hg) following accepted methods of resuscitation.
It is important to treat within 8 hours post-ingestion, as the recovery is almost 100% in this case. If a plasma paracetamol level could be obtained within 8 hours, start treatment after the plasma paracetamol level is available. If the level is unlikely to be available within 8 hours of ingestion, start treatment when the ingested dose is considered potentially toxic. Continue/discontinue treatment after receiving the plasma paracetamol level.
NAC is the antidote and it should be administered as follows:
150 mg/kg body weight in 200 mL of 5% dextrose by slow IV infusion over 15 minutes, followed by
50 mg/kg by IV infusion in 500 mL of 5% dextrose over 4 hours and 100 mg/kg in 1 L of 5% dextrose over the next 16 hours.
Two hours after completion of the infusion, repeat measurements of INR, serum creatinine and AST. If the INR is stable or declining, there is no need for further treatment with NAC. If the patient is symptomatic and has an elevated INR, the patient is likely to require further doses of NAC.