Poisoning Flashcards
Main causes of death from drug poisoning (Eng + Wales)?
Peak ages?
Deaths related to drug poisoning in England & Wales:
- Opioids
- Paracetamol
- Antidepressants
Alcohol often a significant factor in many drug related deaths. Peak age for overdose death is 15-24 in women and 15-34 in men.
If suspecting poisoning, what should you establish?
- Other agent(s) involved including co-agents e.g. alcohol, paracetamol
- Route of exposure
- Time of ingestion
- Quantity ingested
- Whether exposure was single overdose, staggered or chronic
What is a benzodiazepine antagonist and when is it used?
Flumazenil
Not advised as routine diagnostic test in patients with reduced consciousness
Not necessary or appropriate in cases of poisoning to fully reverse the CNS effects – it may precipitate withdrawal in patients who are dependent.
May sometimes be used as an alternative to ventilation in children who are naïve to benzodiazepines, or in patients with COPD to avoid the need for ventilation
How to approach management of poisoned patient?
ABDCE
o Airway: laryngeal reflexes, vomitus etc.
o Disability: consciousness & neurological status (AVPU), aspiration risk?
o Exposure: other sites of injury? Attempts at self harm? Does the patient abuse drugs?
Ensure wearing PPE and be aware of any sharps.
Overdose can mimic many different conditions – Hx also often sparse (aim for 5 key points). May require discussion with bystanders, ambulance crew, relatives, friends, GP, patients belongings. Contact Trust Medicines Informations Department if recover an agent you cannot identify (they can use TICTAC database).
Examination may also reveal cause of poisoning (e.g. puncture sites) or deliberate cutting + if taken sedatives (including alcohol) may have significant injuries without being aware of them.
Toxidrome for TCAs? e.g. amitryptilline
Coma Hypertonia Dilated pupils Urinary retention Sinus tachycardia Hyperreflexia
Toxidrome for opioids? e.g. heroin
Coma
constricted pupils
↓ resp rate
Toxidrome for amphetamines? e.g. ecstasy
Delirium Tachycardia Agitation Dilated pupils Hyperthermia
Toxidrome for organophosphorous compunds?
e.g. malathion
Miosis Hypersalivation Vomiting Lacrimation Bradycardia
Toxidrome for barbiturates?
e.g. phenobarbital
Coma
Hypoxia
Hyporeflexia
Hypotension
Significant depressive activity, some used as anaesthetic agents
Investigations for poisoning?
After provisional diagnosis, may consider specific antidote trial - usually only trial that can be safely prescribed is naloxone in opioid poisoning, or glucose to reverse hypoglycaemic coma.
If any uncertainty: exclude paracetamol poisoning as delayed Tx can be fatal. Urgent drug screens not usually needed for unconscious patients in ED (as it won’t change their management). Care is usually supportive.
If diagnostic clues suggest poisoning with any of the following, samples should measure concentrations:
- Ethylene glycol
- Iron salts
- Lithium salts
- Methanol
- Paracetamol
- Salicyclates (e.g. aspirin)
- Theophylline
Important to know interval between substance taken + sample taken (to identify the amount taken + probable prognosis - see Toxbase for when samples should be taken + their potential prognostic significance).
Carboxyhaemoglobin may also be useful and will usually be reported when ABGs are performed.
What are three main aims of management in poisoning?
- Reduce absorption
- Give an antidote
- Increase elimination
How can reduced absorption be achieved in poisoning?
Activated charcoal binds many poisons in the GI tract, reducing absorption if given soon after ingestion (only likely useful if given within 1 hour). Although it reduces amount of poison absorbed, no clinical trials to show it substantially alters the outcome. It’s NOT effective at adsorbing strongly ionised drugs or alcohols e.g.
- Inorganic acids
- Strong alkalis
- Iron salts
- Lithium salts
- Methanol
- Ethanol
- Ethylene glycol
Gastric lavage also been used but no evidence of benefit, and can be harmful (poison washed into duodenum thereby speeding up absorption, also increases aspiration risk)
Whole bowel irrigation can be useful in specific circumstances e.g. Tx of those that have ingested large numbers of modified-release preparations and in body-packers e.g. drug smugglers who have swallowed packets of drugs. It also increases the risk of aspiration.
Ipecacuanha-induced emesis can increase risk of aspiration and has no role in management.
What antidotes are available for poisoning?
Acetylcysteine (paracetamol)
Atropine (cholinergic excess – also for inhibiting parasympathetic action of vagus nerve in poisonings causing bradycardia, e.g. beta-blockers, digoxin, calcium-channel blockers)
Desferrioxamine (iron poisoning)
Digoxin-specific antibody fragments i.e. Fab fragments (digoxin toxicity – binds digoxin and blocks it from acting at Na/K ATPase pump, digoxin-antibody complex renally excreted)
Flumazenil (benzodiazepines – not given as a diagnostic trial as can precipitate seizures)
Fomepizole (methanol & ethylene glycol- blocks alcohol dehydrogenase so ↓ toxic metabolites)
Glucagon (beta-blocker toxicity)
Naloxone (opioid poisoning)
Phytomenadione i.e. Vitamin K (warfarin poisoning – ensure adequate thromboprophylaxis for their underlying condition, complete reversal of effects of warfarin can put patients at risk)
How can elimination be increased in poisoning?
Multiple-dose activated charcoal can increase elimination rate of drugs that undergo enterohepatic circulation: • Carbamazepine • Dapsone • Phenobarbital • Quinine • Theophylline
Urine alkalisation with sodium bicarbonate increases renal clearance of salicylate.
Dialysis & haemoperfusion may be useful for poisons that have a low Vd – remaining predominantly in plasma compartment – therefore effective for: • Ethanol • Ethylene glycol • Lithium salts • Methanol • Salicylates
What are key risk factors for overdose?
Peak age 15-24 women, 15-34 men
Older people more likely to die if they take an overdose (intent and physical characteristics)
Co-ingestion of alcohol common factor in many self-harm episodes
Teenagers: relationship break-ups common precipitant for tablet taking
Single + divorced individuals higher risk of suicide & overdose than other marital categories
Psychiatric disorders (depression, alcoholism, schizophrenia, sociopathic personality disorders) have increased risk of suicide
What is the best predictor of the severity of paracetamol poisoning?
Plasma-paracetamol concentration: single measurement taken 4-15 hours after ingestion, reasonably accurate predictor of liver damage. Sample taken any earlier than 4 hours may be misleading and prognostic accuracy of a concentration taken after 15 hours is uncertain.
Prolonged PT, raised creatinine, low blood pH: all associated with poor prognosis 24 hours post-ingestion. Values often normal for first 12-18 hours post-ingestion.
What is the mechanism of paracetamol poisoning?
60-90% metabolised in liver at therapeutic doses (conjugation –> paracetamol glucuronide + sulphate).
Small amount oxidised to form highly reactive free radical called N-acetyl-p-benzo-quinone-imine (NAPQI or NABQI) – reacts immediately with -SH groups (in glutathione, and then cysteine and mercapturate).
In overdose, more of the drug forms the highly reactive species as usual route is saturated. As liver depleted of glutathione, the free radical causes liver damage by directly attacking SH groups in liver cell proteins and depletes their normal defences against oxidative damage.
Maximal liver damage in untreated patients occurs 72-96 hours after ingestion, kidney damage can also occur (probably by a similar mechanism).
How can paracetamol overdose be classified?
Acute: hepatotoxicity may occur after single ingestion >150mg/kg taken in <1 hour. All patients who have taken >75mg/kg should be referred to hospital.
Staggered: potentially toxic dose ingested over > 1 hour (BNF), where there is uncertainty over the time of the ingestion, patients should be managed as per staggered overdose
Therapeutic excess: inadvertent ingestion of potentially toxic dose of paracetamol during clinical use
Early management of paracetamol poisoning?
If present within 1 hour of ingestion, activated charcoal may be of benefit. Plasma-paracetamol concentration will indicate severity of poisoning and the degree of liver toxicity. Take a sample between 4-15 hours post-ingestion.
Risk of significant liver damage is very low if acetylcysteine administered within 10 hours of ingestion. Left untreated, liver injury (occasionally renal problems) will be seen after ~ 48 hours.
Toxbase: there is normally no indication to start acetylcysteine without a paracetamol blood concentration provided the result can be obtained and acted upon within 8 hours of ingestion. If there is going to be undue delay in obtaining the concentration, Tx should be started if >150mg/kg has been ingested.
When are the circumstances in which acetylcysteine can be commenced?
- If conc on or above treatment line (and if acetylcysteine cannot be used, can give methionine by mouth as long as overdose within 10-12 hours and not vomiting)
- Before plasma-paracetamol concentration is known if:
8-24 hours elapsed since overdose of >150mg/kg
Staggered overdose (i.e. over period >1 hour, value not interpretable, Tx graph unreliable in these patients)
Doubt over time of paracetamol ingestion
Prognostic accuracy after 15 hours is uncertain, but plasma-paracetamol concentration on or above the treatment line should be regarded as carrying a serious risk of liver damage.
