Key facts:
Authors: Andrew Stein and Caroline Leech
Top Tip: Most overdoses cause no long term harm, if managed correctly; watch for the ones with high morbidity/mortality
Key Differential Diagnoses
- Other causes reduced conscious level, including hypogylcaemia
- Psychiatric conditions
Key Investigations
- Glucose (BM)
- Paracetamol + Salicylate (at 4h, or immediately)
- FBC, INR, U+E, LFT, Glucose ± CK
- ± VBG/ABG, if unwell
- ± ECG, esp if Tricyclic Antidepressant
- Use TOXBASE (http://www.toxbase.org/)
Key Treatments
- If GCS <8, or unwell, ABC + Call Senior
- Paracetamol: IV N-ACETYLCYSTEINE (NAC), according to levels, or immediately if presenting late with staggered/high dose OD
- Benzodiazepine: IV FLUMAZENIL 200 mcg over 15 secs, as first dose
- Opiate: IV NALOXONE 400 mcg
- Salicylate: urinary alkalinisation (>500 mg/kg) or dialysis (>700 mg/kg)
Key Management Decisions
- Dialysis
- Intubation and ventilation
Background
Most patients are well (at least initially); but may deteriorate rapidly. If your patient is unconscious, start your assessment with ABC
Introduction
- This section will largely deal with paracetamol, salicylate (eg aspirin), benzodiazepine and opiate ODs. Tricyclic ODs are very dangerous and discussed here
- Paracetamol OD: the commonest cause of self poisoning in the UK is paracetamol. Hepatotoxicity usually apparent at 48 hrs. 12g (24 tablets) or 150 mg/kg can be fatal (75 mg/kg in 'high risk' patients). Presentation within eight hours of ingestion can be successfully treated with the antidote N-acetylcysteine (NAC)
- In cases where the time of ingestion or amount of paracetamol ingested is unclear it is safest to treat the patient with NAC. Patients with signs of acute liver dysfunction should receive further NAC and be discussed with a specialist liver unit
- Salicylate OD: can cause severe metabolic acidosis and ARF
Note: paracetamol can also cause ARF - Benzodiazepine OD: The use of flumazenil is debated. Some say that it should not routinely be used to treat benzodiazepine poisoning because of the risk of significant adverse events (especially fits); and most patients can be successfully treated with good supportive care. Others say that the side-effects are exaggerated
- Opiate OD: Naloxone is a safe antidote that can be used as a diagnostic and therapeutic agent in treating opiate poisoning
- There is no evidence that gastric lavage improves patient outcome, in any overdose
Internet advice
- Internet based information services such as Toxbase (http://www.toxbase.org/) and Isabel
(http://www.isabel.org.uk) can help identify patients who may benefit from immediate intervention (eg activated charcoal)
Definition
- The term drug overdose (or simply overdose or 'OD') describes the ingestion or application of a drug or other substance in quantities greater than are recommended or generally practiced
Epidemiology
- 10% ODs are serious suicide attempt; 30% multiple drugs; 50% also involve alcohol
5%–10% ED admissions. Rates of self poisoning in the UK are among the highest in Europe
Non-accidental poisoning - ED attendances in the UK are 347 per 100 000/yr; they are increasing and result in more than 2000 deaths each year. 150-200 deaths are due to ALF secondary to paracetamol; 300 due to opiates
- 70% deaths occur out of hospital
Accidental poisoning - Accounts for about 80,000 annual ED attendances in England and is most common in children under 5 years of age; although most do not develop significant clinical features. There are about 1000 deaths each year in the UK from accidental poisoning, predominantly in adults (50% due to opiates)
Note: Common Law, or the Mental Health Act (2004) enables you to detain a patient against their will. This is not usually necessary
Commonest drugs (non-accidental)
- 50% Paracetamol
- NSAIDs (including aspirin) + compound analgesics
- Benzodiazepines/zopiclone,
- Opiates
- Tricyclic antidepressants (TCAs),
- Selective serotonin reuptake inhibitors (SSRIs)
Risk factors (suicide) = SADPERSONS
- Sex (male)
- Age (44 yrs)
- Depression
- Past history of deliverate self-harm
- Ethanol - alcohol or drug use
- Rational thinking loss
- Social isolation - no current supportive family or friends
- Organsied attempt (eg suicide note)
- No partner
- Sickness (chronic illness)
Key questions
- “When did you take the tablets?”
- “Why did you take it?; What were they? How many did you take?”
(Find out quantity taken, if you can) - “Have you ever done this before, or have any problems with your nerves before?”
- “Have you ever seen a psychiatrist?"
Note: often strong history of alcohol /recreational drug use too
Clinical assessment
- Paracetamol
Wide range from no clinical signs, to N&V, to abdominal pain, to acute liver failure in 2-3 days - Salicylate (eg Aspirin)
Unlike paracetamol, may have early clinical features. Tinnitus, reduced conscious level, hyperventilation (vs benzodiazepines/opiates), N/V. Initially respiratory alkalosis, then metabolic acidosis. May get hypo/hyperglycaemia - Benzodiazepine
Reduced conscious level, and mid-sized or dilated pupils. Hypoventilation (vs salicylate), bradycardia and hypotension. Dysarthria, ataxia, nystagmus, agitation, and confusion can occur - Opiate
Pin-point pupils, hypoventilation (vs salicylate), and reduced conscious level, leading to respiratory arrest
Note 1: mixed pharmacological effects arising from preparations containing an opiate and a stimulant drug (cocaine and heroin combined as a ‘‘speedball’’) may cloud the typical clinical picture
Note 2: do a brief neurological examination and record the GCS; focus on pupils, fundi and plantars; also check for signs alcohol/recreational drug use; check PMH on Trust's computer; search for diabetic, steroid or hospital outpatient cards; IV drug users may be hepatitis B, C, HIV positive (wear gloves)
Investigation
If the patient looks unwell, do an ABG
Blood
- Glucose (BM)
- Paracetamol + salicylate levels (at 4h post-OD, or immediately)
Note: salicylate concentration at presentation can be an unreliable guide to the severity of poisoning, particularly after ingestion of enteric coated tablets, and levels may not peak until 12–18 hours after ingestion. So repeat every 2 hrs until the plasma concentration has peaked - FBC, clotting, U+E, LFT, Bone, Glucose ± CK (especially with opiates)
- ± VBG/ABG; if salicylate OD or unwell
Notes: salicylate poisoning initially leads to respiratory alkalosis (secondary to hyperventilation), then metabolic acidosis; salicylates, paracetamol and opiates can all cause ARF (latter two via ATN and rhabdomyolysis respectively)[Ref]
Other
- ECG, especially if Tricyclic Antidepressant
- ± CXR (if comatose; partly as baseline)
Key investigations
- Paracetamol + salicylate
- VBG/ABG, if unwell
Paracetamol treatment guideline
Differential diagnoses
- Other causes of reduced conscious level, including hypoglycaemia, ARF/metabolic acidosis, acute liver failure etc
- Psychiatric conditions
Treatment
5 Management Principles: ABC, Drug (remove), Drowsy patient (care of), Poisons centre/info, Psychiatric ('ADD Poisons and Psychs')
Treatment (general principles)
Procedures
- WEAR GLOVES
- IV access plus crystalloid fluids, if low BP
- OXYGEN, if hypoxic (SaO2 <95%)
- Monitor respiratory rate, SaO2, pulse, BP and GCS regularly
Treatment - Paracetamol
- PO ACTIVATED CHARCOAL 50mg, if patient has taken >150mg/kg in last hour (or >75mg/kg in high risk patient)
- IV N-ACETYLCYSTEINE (NAC) 150 mg/kg (in 200 ml 5% Dextrose) over 15 mins; then 50 mg/kg (in 500 ml 5% Dextrose) over 4 hours, then 100 mg/kg (in 1L 5% Dextrose) over 16h
- NAC is the antidote of choice for significant paracetamol poisoning. It acts as a glutathione donor and is almost 100% effective in preventing hepatotoxicity and nephrotoxicity if administered within eight hours of a non-staggered toxic paracetamol overdose. It should be noted that the evidence for all interventions for paracetamol overdose (including NAC) is weak: [Ref]
- IV VITAMIN K 10mg slowly, if INR raised
Treatment - Salicylate
Mild (Salicylate level )-Moderate (150-500 mg/kg)
- Oral or IV fluids
Severe (>500 mg/kg)
- IV fluids ± urinary alkalinisation, with 225 mls sodium bicarbonate (8.4%) over 30 mins
Life-threatening (>700 mg/kg is potentially fatal level)
- IV fluids ± haemodialysis
Treatment - Benzodiazepine
- IV FLUMAZENIL 200 mcg over 15 secs, wait 30 secs; then 300 mcg, wait 30 secs; then 500 mcg reperated doses up to maximum of 3 mg
- Flumazenil is a benzodiazepine antagonist acting on the GABA receptor. IT SHOULD NOT BE USED FOR MIXED OD, HISTORY OR SIGNS OF TCA OD, POST CARDIAC ARREST, OR AS A DIAGNOSTIC TEST
- Side effects include:
- BP, agitation, and N/V
- Convulsions in patients with epilepsy or head injury
- Arrthymias in patients who have taken a mixed OD with cardiotoxic drugs - In rare cases, where airway and ventilatory support are not available, lone benzodiazepine overdose is suspected, and the ingestion of any other drugs has been excluded, flumazenil may be used cautiously in small increments
- Others disagree with this caution, as in one large retrospective study the incidence of fits was 0.5%
Treatment - Opiate
- IV NALOXONE 400 mcg; repeat every 2 min; max 10 mg
- The bolus dose of naloxone required in patients presenting with opiate poisoning can be difficult to predict and it is best to give small (400 mcg) boluses initially, titrated against the level of consciousness (GCS 13–14/15), respiratory rate (RR 10–12), and oxygen saturation
- Naloxone can be safely used as a diagnostic tool in unconscious patients where opiate toxicity may be contributing to CNS depression. Naloxone has a short half life (30–100 minutes). Therefore repeated doses of naloxone or an infusion are sometimes required
- Patients who have ingested long acting opiates (such as methadone) or sustained release preparations (for example, MST continuous) may require naloxone infusions for up to 72 hours
Prescribing issues
- Use toxbase
Key management decisions
- Dialysis
- Intubation and ventilation
Admit?
- Usually
Bed plan
- Observation Ward (for
- ± ITU
Referrals
Medical
- Product information leaflets and older textbooks are often out of date and are not a reliable source of information in managing poisoned patients. Toxbase is better
- The National Poisons Information Service (NPIS) is a telephone based (0870 600 6266) resource available to all healthcare professionals. The NPIS provides 24 hour on call cover by clinical toxicologists
Psychiatric ± ITU
- All poisoned patients who have taken an intentional overdose should undergo a psychiatric assessment as a routine part of their treatment, prior to hospital discharge
The Rest
Ensure you treat patients with empathy and respect. It might be you next time
Complications
Paracetamol
- Acute liver failure; remember LFTs are not good markers of hepatocyte death; but if INR normal at 48 hrs, can usually go home; can cause ARF too (usually ATN, on day 3)
Salicylate
- Metabolic acidosis/ARF
Opiates
- Non-cardiac pulmonary oedema (poor prognosis); rhabdomyolysis/ARF
Follow-up
- Psychiatric, if necessary
- Paracetamol: monitor liver function for 2 wks, if INR raised initially
Prognosis
- 10-20% take an OD again
- 70% deaths occur out-of-hospital
- In-hospital mortality is low (0.5%): [Ref]
Paracetamol: indications for
referral to liver centre
- INR >2 at 24 hours, >4 at 48 hours, >6 at 72 hours; so measure INR 12 hrly
- ARF (creatinine >300 mcmol/l)
- Hypoglycaemia
- Metabolic acidosis (pH <7.3)
- Hypotension despite fluid resuscitation
- Hepatic encephalopathy, grade 3 or
- Lactate >3.5 on admission
2° Prevention + Health promotion
- Nearly one third of children under the age of 6 years who present after accidental poisoning will subsequently experience a second episode. Providing poison prevention education to parents at the time of the first presentation is an important method of reducing the number of paediatric poisonings
- Preventative measures include correct medication labelling, child-proof containers and keeping medications out of the reach of children
- Ensure every child with non-accidental poisoning is referred to the health visitor or school nurse
- Where there are concerns about the safetly at home, social services should be contacted
- All deliberate overdoses in children should be admitted under paediatrics
Don't forget
- Psychiatric assessment
- BM
Red flags
- Reduced conscious level
- Acute liver failure (especially abnormal clotting eg INR)
- ARF
- Metabolic acidosis
