Key Facts

Opioid overdose is the leading cause of drug-related death in the UK. Prompt recognition and treatment with naloxone can be life-saving. The majority of opioid-related deaths are preventable. Take-home naloxone programmes are a key public health intervention.

Epidemiology

• ~2,300 opioid-related deaths per year in England and Wales (2021 data); rising trend
• Drug poisoning deaths overall: ~4,900/year — highest on record
• Peak age: 40-49 years (reflecting ageing cohort of opioid users)
• Male:female ratio: approximately 3:1
• Risk period: first 4 weeks after prison release — 7-8× increased risk of drug-related death
• Approximately 70% of opioid-related deaths involve multiple substances

Aetiology

• Heroin (diamorphine): most common opioid in UK overdose deaths
• Methadone: second most common; risk during initiation and if diverted
• Prescription opioids: codeine, tramadol, oxycodone, fentanyl — increasingly involved
• Illicit fentanyl and analogues: extremely potent (fentanyl ~100× morphine potency); increasingly detected in UK drug supply
• Polydrug use: benzodiazepines, alcohol, pregabalin/gabapentin, cocaine synergistically increase risk

Pathophysiology

• Opioids bind μ receptors in brainstem respiratory centre (pre-Bötzinger complex) → reduced respiratory drive
• Progressive: reduced respiratory rate → hypoventilation → hypoxia → hypercapnia → respiratory arrest → cardiac arrest
• Hypoxic brain injury: irreversible if prolonged; even survivors may have permanent damage
• Non-cardiogenic pulmonary oedema: mechanism unclear; possibly related to acute negative intrathoracic pressure or direct alveolar membrane effects

Classical Presentation

• Respiratory depression: rate <12 breaths/min, may be apnoeic; shallow, irregular breathing
• Miosis: pinpoint pupils (bilateral) — may be absent with co-ingestants, hypoxia, or certain synthetic opioids
• Reduced consciousness: GCS reduced; may range from drowsiness to unresponsive (GCS 3)
• Cyanosis: peripheral and central in severe cases
• Bradycardia and hypotension
• Hypothermia: reduced metabolic activity
• Reduced or absent bowel sounds

Complications

• Aspiration pneumonia: vomiting while obtunded
• Non-cardiogenic pulmonary oedema: may develop hours after overdose or after naloxone administration
• Rhabdomyolysis: prolonged immobility on hard surface → crush injury
• Compartment syndrome: pressure on limbs during prolonged unconsciousness
• Hypoxic brain injury: anoxic encephalopathy if prolonged respiratory depression
• Needle-stick injury: risk to rescuers in the pre-hospital setting

Red Flags

• Apnoea or respiratory rate <8/min: immediate ventilatory support needed
• GCS ≤8: cannot protect airway
• No response to naloxone 2 mg total: consider non-opioid cause or massive overdose (fentanyl may require much larger doses)
• Recurrent sedation after naloxone wears off: especially with long-acting opioids (methadone)
• Pulmonary oedema: frothy pink sputum after naloxone; needs high-flow oxygen and possible CPAP/ventilation
• Body packing/stuffing: consider internal concealment — surgical emergency if packet rupture

Bedside

• Airway assessment: patent? Gag reflex? Vomit?
• Respiratory rate and SpO2: critical parameters
• GCS: serial monitoring
• Pupil size and reactivity: miosis supports opioid toxicity
• Capillary blood glucose: exclude hypoglycaemia
• Temperature: hypothermia common
• ECG: QTc prolongation (methadone), arrhythmias, ischaemia

Bloods

• ABG/VBG: assess oxygenation, ventilation (CO2), acid-base status, lactate
• U&Es: renal function, electrolytes (rhabdomyolysis risk)
• CK: rhabdomyolysis if immobile
• FBC: leucocytosis may suggest aspiration
• LFTs: paracetamol co-ingestion common
• Paracetamol and salicylate levels: always check in overdose
• Blood alcohol level: concurrent intoxication
• Urine drug screen: confirm opioid use, identify co-ingestants

Imaging

• Chest X-ray: aspiration pneumonia, non-cardiogenic pulmonary oedema
• CT head: if GCS does not improve with naloxone — exclude intracranial pathology
• Abdominal X-ray/CT: if body packing suspected

Special Tests

• Serum drug levels: specific quantification rarely influences acute management
• Carboxyhaemoglobin: if CO poisoning considered
• Toxicology consultation: National Poisons Information Service (TOXBASE) for complex overdoses

Non-pharmacological — Immediate Actions (ABCDE Approach)

• Airway: open airway (head tilt, chin lift, jaw thrust); suction if needed; recovery position if breathing
• Breathing: if respiratory rate <8/min or SpO2 <92% — bag-valve-mask ventilation with high-flow oxygen
• Rescue breaths: 5 initial rescue breaths if apnoeic (bystander or EMS)
• Call 999: early activation of emergency services
• Do not leave patient alone: monitor continuously

Pharmacological — Naloxone

• Naloxone (opioid antagonist):
  • IV route: 400 mcg (0.4 mg) bolus; repeat every 2-3 minutes up to 10 mg total
  • IM/SC route: 400 mcg (0.4 mg); repeat every 2-3 minutes; slightly slower onset (~5 minutes)
  • Intranasal (Nyxoid): 1.8 mg per nostril; no needle required; increasingly used pre-hospital
  • Goal: restore adequate spontaneous respiration (RR >12) — do NOT aim to fully reverse opioid effect (precipitates severe withdrawal)
  • Naloxone infusion: if repeated boluses needed — 10 mg in 50 mL 0.9% NaCl at rate guided by clinical response (typically 2/3 of initial response dose per hour)
  • Observation period: minimum 2 hours after last naloxone dose for short-acting opioids; minimum 4-6 hours (or longer) for methadone, slow-release preparations, or fentanyl patches
• Take-home naloxone:
  • Prenoxad: pre-filled syringe with 5 × 400 mcg doses for IM injection
  • Nyxoid: nasal spray, 1.8 mg per dose; available without prescription in some settings
  • Should be offered to all patients at risk of opioid overdose, their families, and carers (NICE NG225)

Additional Pharmacological Management

• Atropine 0.5-1 mg IV: for symptomatic bradycardia
• IV fluids: for hypotension and rhabdomyolysis
• Sodium bicarbonate: for rhabdomyolysis-related acidosis
• Antibiotics: if aspiration pneumonia suspected

Surgical

• Intubation and mechanical ventilation: if airway compromise or persistent respiratory failure despite naloxone
• Surgical removal of drug packets: body packing with suspected rupture — emergency laparotomy

Referral Criteria

• Resuscitation team/ICU: refractory respiratory depression, intubated, multiorgan failure
• Drug and alcohol services: all patients surviving opioid overdose — assess for OST
• Mental health assessment: if intentional overdose
• Take-home naloxone provision: before discharge from ED
• Prison in-reach/release planning: if overdose relates to prison discharge

Outcomes

• Prompt naloxone administration: near-complete reversal of respiratory depression in majority of cases
• Survival to hospital discharge: >95% if naloxone given promptly
• Hypoxic brain injury: if prolonged respiratory depression before treatment — variable outcome from mild cognitive impairment to persistent vegetative state
• Recurrent overdose: approximately 20-30% of individuals who survive overdose will experience another within 12 months

Complications

• Aspiration pneumonia: occurs in ~10-15% of patients with reduced consciousness
• Non-cardiogenic pulmonary oedema: may develop up to 24 hours after overdose
• Rhabdomyolysis: CK >5,000 IU/L; risk of acute kidney injury; requires aggressive IV fluid resuscitation
• Naloxone-precipitated withdrawal: agitation, nausea, vomiting, tachycardia, hypertension; rarely dangerous but distressing
• Death: opioid overdose is the leading cause of preventable death in drug misusers

Naloxone Dosing Summary

Risk Factors for Opioid Overdose Death

Take-Home Naloxone — Who Should Receive It