PassFinals
Pharmacology & Therapeutics

Opioid Overdose

Excess mu-opioid activation blunts the brainstem response to carbon dioxide, so ventilation fails first; naloxone displaces the opioid, but for less time than the opioid lasts.

In a nutshell

Opioid overdose is respiratory failure caused by a drug: a rate of 8 breaths per minute or less, barely rousable, pupils pinpoint. Ventilate first, then give naloxone 400 micrograms IV and titrate up until breathing is adequate, not until the patient is awake.

Classic presentation

A man found unresponsive beside used needles, breathing 6 times a minute, with pinpoint pupils and a fentanyl patch on his chest.

Key points

  • Naloxone is a competitive antagonist, so its effect is graded by dose. That is why titration works and why an all-or-nothing bolus is the wrong instinct.
  • The BNF carries two regimens, not one. High-dose for the patient who is dying now, low-dose when acute withdrawal or loss of analgesia is the bigger danger.
  • Pinpoint pupils are supportive, not required. Co-ingestion, hypoxia and some synthetic opioids leave the pupils normal or dilated.
  • Intramuscular naloxone comes only as 400 micrograms, so community dosing is one syringe repeated rather than one dose titrated.
  • NHS England logged three wrong-dose naloxone incidents, two of them fatal, and issued a national patient safety alert in 2014.
  • Naloxone stays a prescription-only medicine, but the 2024 regulations let trained services and named professionals hand it out to save a life.

First-line investigation

Clinical: respiratory rate, oxygen saturation, conscious level and pupils, plus a capillary glucose to exclude hypoglycaemia. No test delays treatment; a blood gas quantifies the hypercapnia afterwards.

Management

Ventilate before you reverse

  • ABCDE (airway, breathing, circulation, disability, exposure). Open the airway, oxygen to saturations 94 to 98% (88 to 92% in COPD), bag-valve-mask if breathing is inadequate.2
  • Unresponsive and not breathing normally: start CPR (cardiopulmonary resuscitation) and run the standard advanced life support algorithm. Naloxone never replaces ventilation.2,3
  • Capillary glucose in every reduced conscious level; treat a value below 4.0 mmol/L.2

Naloxone, titrated to breathing

  • BNF staged IV example for life-threatening overdose: 400 micrograms, then 800 micrograms up to twice at 1-minute intervals, then 2 mg once; up to 4 mg if seriously poisoned.5
  • BNF staged IV example for opioid-dependent, palliative or postoperative use: 100 to 200 micrograms, then 100 micrograms up to twice at 1-minute intervals, titrating to 2 mg.5,1
  • Endpoint: adequate ventilation, not consciousness. BNF staged IV examples use 1-minute intervals; SPS permits IV repeats every 2 to 3 minutes. Follow one selected local or BNF protocol and do not hybridise timings.5,1,4
  • No IV access: 400 micrograms IM in successive 2- to 3-minute resuscitation cycles, or intranasal 1.8 mg with a second dose after 2 to 3 minutes, alternating nostrils.5,1
  • Still nothing after the full sequence? Review the diagnosis. Naloxone does nothing to a coma that is not opioid-driven.5,1

When naloxone runs out before the opioid does

  • Naloxone's half-life is 1 to 1.5 hours. Modified-release, long-acting (buprenorphine) or potent (oxycodone) opioids and very large overdoses need a continuous infusion.1,5
  • Start the infusion at 60% of the effective bolus per hour: the bolus that held satisfactory respiratory effort for at least 15 minutes.5
  • Dilute to at most 200 micrograms/mL in glucose 5% or sodium chloride 0.9% and run through a pump, titrating to response.5
  • Buprenorphine may reverse only partly. Escalating naloxone will not fix that: secure the airway and ventilate mechanically.1

The rest of the poisoning

  • Look for co-ingested alcohol, benzodiazepines and paracetamol, and for aspiration, arrhythmia and rhabdomyolysis. A blood gas quantifies the hypercapnia.1,4
  • Phone the National Poisons Information Service (NPIS) on 0344 892 0111 for agent-specific advice. Its TOXBASE database requires professional registration.7,3
  • Once breathing is restored, monitor blood gases, oxygen saturation and respiratory rate for recurrence.1

Observation and discharge

  • Observe at least 4 hours from the last naloxone bolus or from stopping the infusion; longer for modified-release, long-acting or uncertain exposures.1
  • Intentional self-poisoning gets a psychosocial assessment alongside the physical care. Suicide risk rises 30 to 50 fold in the year after presentation.8
  • Offer take-home naloxone: Prenoxad intramuscular injection, Nyxoid 1.8 mg nasal spray or naloxone 1.26 mg nasal spray. Nyxoid is licensed from 14 years.6
  • Drug services, pharmacists, pharmacy technicians, registered nurses, midwives and paramedics can supply naloxone without a prescription if trained.6

Exam traps

  • Titrating to full consciousness in a dependent patient is the classic error: it strips analgesia and can cause pulmonary oedema, arrhythmia and cardiac arrest.
  • A good response is not the end of it. Naloxone outlasts nothing except itself, so re-sedation follows when the opioid is longer-acting.
  • Buprenorphine binds the receptor tightly, so more naloxone is not the answer. Ventilate instead.
  • No response to the full naloxone sequence means the diagnosis is wrong, not that the dose is too small.
  • Potent synthetics such as nitazenes and fentanyl may need more doses, but the graduated approach still applies. Do not abandon titration.
  • Observation is timed from the last naloxone dose, not from arrival, and it must outlast the naloxone rather than the patient's mood.

Illustrations

Mu-receptor mechanism of the opioid toxidromeDiagram showing mu-opioid receptor activation in the brainstem respiratory centres and pupillary pathway producing respiratory depression and miosis.PassFinals · original
Naloxone versus opioid duration of actionTimeline graphic showing naloxone's shorter duration of action against a longer-acting opioid, illustrating the mechanism behind re-sedation.PassFinals · original
The opioid toxidrome triadIllustration of the classic triad of respiratory depression, miosis and reduced consciousness in opioid overdose.PassFinals · original

Key sources

  1. NHS Specialist Pharmacy Service: Reversing an adult opioid overdose with naloxone (UK professional medicines guidance. Sections used: 'Aim of naloxone treatment' for respiratory depression; 'Selecting a naloxone regimen' for high-dose and low-dose choice; 'How to administer naloxone' for repeat intravenous doses and intramuscular rescue cycles at 2 to 3 minute intervals, and the 1 to 1.5 hour half-life; 'Monitoring' for at least 4 hours after the last dose or stopping an infusion. Current BNF staged intravenous examples use 1-minute intervals; select one local or BNF protocol rather than combining timings.)Published 18 Oct 2022 | Updated 13 Mar 2026
  2. Resuscitation Council UK: First Aid Guidelines 2025 (Sections used: 'Opiate/Opioid poisoning' under Medical emergencies for the recognition features and the call 999, CPR, naloxone sequence; 'Use of pulse oximetry and use of oxygen for acute difficulty breathing' for oxygen saturation targets of 94 to 98%, or 88 to 92% in chronic obstructive pulmonary disease; 'Hypoglycaemia' for the 4.0 mmol/L threshold.)Published 27 Oct 2025
  3. Resuscitation Council UK: Special Circumstances Guidelines 2025 (The 'Toxins' section: resuscitate on the standard advanced life support algorithm, assess every patient in cardiac arrest for poisoning, give antidotes as soon as possible, be prepared to resuscitate for a prolonged period, and consult a national poisons centre.)Published 27 Oct 2025
  4. NHS England Patient Safety Alert: Risk of distress and death from inappropriate doses of naloxone in patients on long-term opioid treatment (Alert reference NHS/PSA/W/2014/016, stage one warning. Naloxone given where it is not indicated, or in larger than recommended doses, causes intense pain and distress and an acute withdrawal syndrome, and hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest may follow. Three reported wrong-dose incidents included two deaths. The dose figures quoted inside the alert come from the September 2014 BNF and are superseded; the doses in this chapter come from the current BNF monograph.)Published 20 Nov 2014
  5. BNF: Naloxone hydrochloride (Indications and dose: the adult high-dose and low-dose intravenous regimens, the continuous intravenous infusion rate of 60% of the initial resuscitative injection dose per hour, the intramuscular and intranasal doses, and the dilution instructions under directions for administration. BNF content changes continuously; check the monograph before prescribing.)
  6. Department of Health and Social Care: Supplying take home naloxone without a prescription (UK government guidance on the 2015, 2019 and 2024 Human Medicines Regulations amendments: who may supply naloxone without a prescription, the three available products and their licensed age ranges, and the graduated dosing advice for potent synthetic opioids such as nitazenes and fentanyl.)Published 23 Apr 2025 | Updated 12 Sept 2025
  7. TOXBASE and the UK National Poisons Information Service (NPIS) (The primary UK clinical toxicology database. Its public page states that TOXBASE is for registered health professionals only and gives the UK NPIS telephone number 0344 892 0111. The database itself sits behind a login and was not consulted for this chapter; nothing here rests on it except the contact route.)
  8. NICE NG225: Self-harm: assessment, management and preventing recurrence (Context chapter: self-harm is defined as intentional self-poisoning or self-injury; most of the roughly 200,000 hospital presentations in England each year are for self-poisoning; suicide risk is increased 30 to 50 fold in the year after a hospital presentation; only about half of people attending an emergency department after self-harm are assessed by a mental health professional.)Published 7 Sept 2022

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.