Overdose Flashcards
Other specific antidotes
- Opiates: Naloxone (specific antagonist)
- Benzodiazepines: Flumazenil (specific antagonist) can cause seizures so not used as often
- Ethylene glycol, methanol: Ethanol, Fomepizole (alcohol dehydrogenase inhibitors)
- Dapsone: Methylene blue (reducing agents) turns haemoglobin back to normal state
- Organophosphates: Pralidoxime (Cholinesterase reactivators)
- Digoxin: Digibind (antibody fragments)
- Snake bites: Zagreb antivenom
- Paracetamol poisoning: Acetylcysteine, Methionine (Glutathione repleters)
Benzodiazepines MoA
Work by enhancing the effects of the inhibitory neurotransmitter GABA, particularly at the GABAa receptor by increasing the frequency of chloride channels. Causes sedation, anti-anxiety, anti-seizure, and generalized muscle relaxant effects. Used for sedation and as hypnotics
Features of Benzodiazepine overdose and withdrawal
Features of Benzodiazepine overdose: drowsiness, ataxia, dysarthria, hypotension, bradycardia, respiratory depression and coma.
Benzodiazepine withdrawal symptoms: insomnia, irritability, anxiety, tremor, loss of appetite, tinnitus, perspiration
Features of Benzodiazepine overdose management
- Airway, breathing and circulation
- Oral activated charcoal
- Monitor vital signs
- 12 Lead ECG
- Supportive care
- Antidote - flumazenil (not often used, supportive care often adequate)
Flumazenil
- Has a shorter half life the benzos and repeated administration may be required
- Bolus administration is IV over 15s, may have to give further doses
- Contraindicated in TCA overdose, receiving benzos for seizure control or raised intracranial pressure. Increases seizure risk. Best to avoid if you don’t know what’s been co-ingested
- Can be used in iatrogenic overdose or in patients with chronic respiratory disease to avoid intubation and ventilation
- Reverses effects of Benzos in minutes
When to use Flumazenil and contraindications
- Used in severe OD with marked respiratory impairment of consciousness or respiratory distress
- Contraindications: Benzodiazepine dependent, mixed TCA OD, history of epilepsy
- When given monitor with ECG
Timings of iron overdose
Uncommon, may be serious especially in children
Timings of iron overdose
- Early (0-6hrs): N+V, abdo pain, diarrhoea (bloody), massive GI fluid loss
- Delayed (2-72 hours): black offensive stools, drowsiness/coma, fits, circulatory collapse
- Late (2-4 days): acute liver necrosis (hepatocellular necrosis), renal failure
- Very late (2-5 weeks): Gastric strictures
Investigations into iron overdose
- History - establish amount of elemental iron taken (differs between ferrous sulphate and ferrous fumerate), serious overdose >10mg/kg
- Iron concentration: After at least 4 hours, Repeat after 2-3 hours
- Blood count: raised WCC
- U&E’s
- Bicarbonate - monitor daily to check for metabolic acidosis
- Glucose [usually see hyperglycaemia]
- Clotting - monitor daily
- LFT’s
Treatment of iron overdose
- Gastric decontamination (Gastric lavage): if large OD and presenting early
- Activated charcoal is ineffective
- Desferrioxamine
Desferrioxamine
- Chelates iron and reduces toxicity
- Chelate iron ( forms ferrioxamine) is water soluble and excreted in urine (red discolouration)
- Can cause adverse effects, e.g. hypotension and pulmonary oedema
- Contraindicated in renal failure
- Used for patients with severe toxicity: Fits, coma, circulatory collapse. GI symptoms, leucocytosis, or hyperglycaemia and high iron concentration (>3 mg/l)
Supportive care for iron overdose
- Hypotension - I.V fluids
- Vomiting - Antiemetics
- Fits - Diazepam / Lorazepam
- Acidosis - Correct with bicarbonate
- Renal failure - Dialysis
Examples of opiates/opioids
- Heroin
- Morphine
- Methadone
- Dihydrocodeine
- Codeine
- Pethidine
- Dipipanone
- Dextropropoxyphene
- Tramadol
- Buprenorphine
- Opiates are naturally derived from the poppy plant whilst opioids are synthetic
Illegal Opiates effects and administration
Opiates administration: Oral, smoked, IV, inhaled
Opiates effects:
- CNS and respiratory depression: coma
- ‘Pin-point’ pupils
- Hypotension, tachycardia
- Hallucinations
- Rhabdomyolysis
- Non-cardiac pulmonary oedema
Opiate overdose management
- Airway management if reduced GCS or respiratory rate
- Breathing: Consider Opioid receptor antagonist (Naloxone), Ventilation
- Circulation
- Disability – reduced GCS. Consider Opioid receptor antagonist (Naloxone)
- Hepatitis B,C and HIV precautions (IV users)
Naloxone
- Used in suspected opiate intoxification for diagnosis and treatment
- Diagnosis: if responds to naloxone confirms opioid toxicity
- Indications: Reduced respiratory rate (<10/min), Reduced conscious level (<10/15)
- Adults: 400 micrograms up to 2.0mg or more, in children titrate up from 0.1mg
- Repeat as necessary or use a continuous infusion- 2/3 of initial dose required to rouse patients by IV infusion per hour, then titrate down
Investigations of opioid toxicity
- FBC
- U+E
- CK (?rhabdomyolysis)
- ABG: mixed acidosis
- urine drug screen
- CXR (?pulmonary oedema)
Naloxone risks
- Dose of naloxone should be titrated up gradually to reduce risk of sudden withdrawal symptoms
- Can cause acute withdrawal syndrome in long term uses: muscle aches, diarrhoea, palpitations, rhinorrhoea, yawning, irritability, nausea, fever, tremor, cramps
- Unmasking of pain if taken for pain
- Hypertension
- Behavioural disturbances (high doses)
- Rarely fits, arrhythmias, pulmonary oedema
Naloxone half life
- Naloxone has a half-life of 1hr which is less than many opioids (check for re sedation after this time)
- Self-discharge during alert phase with subsequent coma / death
Patients at risk of hepatotoxicity following a paracetamol overdose
- patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John’s Wort)
- malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days
- Chronic alcohol use
Mechanism of paracetamol overdose
- the usual paracetamol metabolism pathways (Para-glucuronide and Para-sulphate via bile) are rapidly saturated
- the other pathways via CYP 2E1 and CYP 3A4 generate toxic NAPQI
- the body can detoxify a small amount of NAPQI with endogenous glutathione but this gets rapidly saturated causing Hepatocellular injury
Paracetamol overdose presentation early and epidemiology
Almost half of overdoses presenting to hospital include paracetamol
Presentation of paracetamol overdose early: abdo pain, N/V, altered clotting (non-specific)
Presentation of Paracetamol overdose delayed
- Hepatic necrosis: takes 2-3 days. Get jaundice, RUQ pain, encephalopathy, coagulopathy, Fulminant hepatic failure, death (3-6 days after overdose)
- Renal failure (acute tubular necrosis): less common 2-7 days after poisoning, oliguria, loin pain, AKI
- Others: Hypoglycaemic, Metabolic acidosis
Paracetamol overdose investigations
- Paracetamol level (4 hours after overdose): best early predictor of prognosis, indicates antidotes
- Clotting: PT or INR- increased due to reduced clotting factor production
- U&E’s
- ABG: metabolic acidosis
- LFT’s: elevated
Paracetamol overdose: poor prognostic features
- PT or INR rising after day 3
- PT >100 s at any time
- Bilirubin > 70 micromol/l
- Metabolic acidosis
- Encephalopathy [III or IV]
- Raised Lactate: not resolved after fluid resus
- Creatinine > 300 micromol/L
Paracetamol overdose treatment
- Activated charcoal: within 1 hour
- supportive therapy: vitamin K, fluids, dialysis, glucose infusions
- consider liver transplant
- N-acetylcysteine (IV)
- Antidote second line N-acetylcysteine: Methionine (oral)
N-acetylcysteine
- Mechanism: glutathione precursor (allows detoxification of NAPQI by providing glutathione)
- Should be given within 8hrs of ingestion ideally but can be effective up to 24hr- but given at any time after severe poisoning
- Indicated if serum paracetamol is above treatment line after 4hrs
- Given in 3 IV infusions over 21 hours (the first over 1hr) mix with 5% glucose
- Effectiveness decreases with time
- Benefit in patients with fulminant hepatic failure
When to give N-acetylcysteine
- the plasma paracetamol concentration is on or above the treatment line regardless of risk factors for hepatotoxicity
- there is astaggered overdose or there is doubt over the time of paracetamol ingestion, regardless of the plasma paracetamol concentration;
- patients who present 8-24 hoursafter an acute overdose of more than 150 mg/kg of paracetamol
- patients who present > 24 hoursif they are clearly jaundiced or have hepatic tenderness, their ALT is above the upper limit of normal
Side effects of N-acetylcysteine
- Vomiting (give IV antiemetic)
- coagulopathy
- anaphylactoid reaction due to dose related histamine release, resulting in urticaria, wheeze, itch and hypotension (stop infusion, give antihistamine then restart). Not true allergic reactions
When is liver transplant indicated for paracetamol overdose
- pH below 7.3 after 24hrs
- INR above 6.5, creatinine above 300 and grade 3 or 4 HE
Supportive treatment for paracetamol overdose
- Vitamin K
- Fresh frozen plasma (for active bleeding only)
- Hepatic intensive care: Fluid balance, Inotropic support, Intracranial pressure monitoring in HE
- Dialysis for renal failure
- Orthotopic liver transplantation
Mechanism of salicyclate poisoning
- uncouples oxidative phosphorylation, causing metabolic acidosis
- also stimulates CNS respiratory centre causing increased RR and respiratory alkalosis
When should plasma salicyclate be measured in peak overdose
Every 2hrs until levels peak (can take up to 6hrs
Aspirin overdose symptoms and signs
Dizziness, Sweating, Tinnitus, Vomiting, Vasodilation, Hyperventilation, Hypertension, Agitation, Delirium, Coma (especially children)
Aspirin overdose clinical features
- Metabolic acidosis: Salicylic acid uncouples oxidative phosphorylation causing anaerobic metabolism
- Respiratory alkalosis: direct CNS ‘receptor centre’ stimulation initially before becoming metabolic acidosis
- Hypoglycaemia
- Hypokalaemia
Aspirin overdose investigations
- Plasma salicylate concentration
- Urea,electrolytes,bicarbonate
- Blood glucose
- Arterial blood gases
Aspirin overdose treatment
- Gastric decontamination: 50g activated charcoal within 1 hour. Gastric lavage and activated charcoal if very large overdose (rarely used)
- Sodium bicarbonate: prevention of CNS penetration
- MDAC (Multiple dose activated charcoal), Urinary alkalisation (sodium bicarbonate): enhanced elimination
- Haemodialysis
Aspirin overdose: Haemodialysis
- Highly effective at removing salicylate, also corrects metabolic abnormalities
- Consider if pH <7.3, salicylate level >700mg/l (600 mg/l in children), patients in renal failure
Supportive medication for aspirin overdose
- Airway
- I.V fluids
- Ventilation
- Glucose for hypoglycaemia
- KCl for hypokalaemia
Indications for Haemodialysis in salicyclate overdose
serum concentration > 700mg/L
metabolic acidosis resistant to treatment
acute renal failure
pulmonary oedema
seizures
coma
Aspirin overdose ABG
A mixed respiratory alkalosis and metabolic acidosis. Early stimulation of the respiratory centre leads to a respiratory alkalosis whilst later the direct acid effects of salicylates (combined with acute renal failure) may lead to an acidosis.
TCA overdose ECG changes
- sinus tachycardia
- widening of QRS
- prolongation of QT interval
Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias
Clinical features of a TCA overdose
- Anticholinergic effects (presenting features): hot dry skin, dilated pupils, tachycardia, urinary retention, agitation, delirium, fits, coma, hypertonia, hyperreflexia
- Sodium channel blocking effects: Cardiac Arrhythmias, conduction block, prolonged QRS and QT interval
- Alpha adrenoceptor antagonism: Hypotension and vasodilation
- Not very common but very fatal
TCA overdose: investigations
- Urea & electrolytes
- Blood glucose
- Arterial blood gases: metabolic acidosis due to tissue hypoxia
- ECG: wide QRS, long QT, long PR
- QRS duration >160ms (4 small squares) = very high risk of arrhythmia. >120ms (3 small squares) = requires specific urgent action
- Constant cardiovascular monitoring: CCU or ITU if large overdose or initial ECG abnormal
TCA overdose treatment
- Gastric decontamination: activated charcoal within 1 hour
- Multiple doses of activated charcoal: every two hours can enhance elimination of some tricyclics (amitryptiline, nortryptiline)
- IV bicarbonate: first line for hypotension or arrhythmias
How to correct Arrhythmias in TCA overdose
- More likely if pH < 7.4 (metabolic acidosis)
- Give Sodium Bicarbonate for: Acidosis, Wide QRS complex [>120ms], Arrhythmias (ventricular tachycardia), Hypotension not responding to fluids, cardiac arrest
- Correct K+ if hypokalaemia
- If bicarbonate fails and the patient is haemodynamically unstable consider DC cardioversion or overdrive pacing
- Don’t use anti-arrhythmics or dialysis
What to do in TCA overdose if bicarb fails
- DC cardioversion
- lidocaine
- MgSO4
- do not use anti-arrhythmic
TCA overdose: fits
- Use Diazepam or Lorazepam
- If fails consider paralysis and mechanical ventilation
Newer antidepressants
- SSRIs (specific serotonin reuptake inhibitors): citalopram, escitalopram , fluoxetine, paroxetine ,sertraline
- SNRI (serotonin noradrenergic reuptake inhibitors): Venlafaxine
- NaSSA (noradrenergic and specific serotonergic antidepressant): Mirtazapine
- NaRI (selective noradrenaline reuptake inhibitor): Reboxetine
- RIMA (reversible inhibitor of monoamine oxidase A): moclobemide
Serotonin syndrome
- Caused by excess MAOI, SSRI’s (with ST Johns Wort and Tramadol), ectasy and amphetamines
- Cognitive-behavioural changes: agitation, confusion, hallucinations, coma,
- Neuromuscular dysfunction: tremor, teeth grinding, myoclonus, hyperreflexia
- Autonomic dysfunction: tachycardia, fever, hyper or hypotension, flushing, diarrhoea
- Others: Vomiting, seizures, hyperpyrexia, rhabdomyolysis, renal failure, coagulopathies
Management of Serotonin syndrome
- supportive including IV fluids
- benzodiazepines
- more severe cases are managed using serotonin antagonists such ascyproheptadineand chlorpromazine
