Educational draft · awaiting clinical reviewThe full textbook explains uncertainty but does not replace live national or local guidance, specialist advice, or current prescribing information.
Opioid intoxication, withdrawal and naloxone
Psychiatry · UK scope · Sources checked 27 Aug 2026 · Clinical review pending
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Respiratory depression is the opioid emergency
Unresponsiveness, very slow or absent breathing, cyanosis, pinpoint pupils, snoring or gurgling in a person with possible opioid exposure is an overdose until proved otherwise; potent synthetic or long-acting opioids may outlast initial naloxone.
Action: Call 999, open the airway, provide rescue breathing or CPR according to responsiveness and breathing, give available naloxone, and repeat the product-specific dose after 2–3 minutes if breathing has not recovered. Stay with the person, place them in the recovery position once breathing adequately, and continue observation because respiratory depression can recur.
Overview
Distinguish life-threatening opioid toxicity from withdrawal, restore ventilation with airway support and correctly dosed naloxone, anticipate recurrent respiratory depression, and reduce overdose risk before and after detoxification or treatment transitions.
Opioid toxicity kills by suppressing brainstem respiratory drive. Look for reduced consciousness, slow shallow or absent breathing, cyanosis, small pupils and reduced bowel sounds, while remembering that hypoxia, co-ingestion or certain opioids can alter the pupil finding. Street drug names and appearance are unreliable because heroin, counterfeit tablets and powders may contain fentanyl analogues or nitazenes. Ask what, how much, by which route and when only after airway and ventilation are being managed. Check glucose, temperature, oxygenation, injury and evidence of alcohol, benzodiazepines, gabapentinoids or stimulants.
Naloxone displaces opioids at receptors but does not correct hypoxia already present. Begin basic life support and summon emergency help, then give the formulation available. Take-home intranasal
Practice
Two practice questions
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Question 1 of 2
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PsychiatryOriginal SBA
Recurrent respiratory depression
A bystander gives one Nyxoid spray to an unresponsive adult with slow breathing. He initially breathes normally but becomes drowsy and bradypnoeic again before the ambulance arrives. What should happen next?
Sources and review status6 sources · checked 27 Aug 2026 · clinical review pending+
Sources
Sources and review status
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
is a single 1.8 mg spray into one nostril; use a second device after two to three minutes if no response or immediately if breathing deteriorates again.
Prenoxad
supplies 400 microgram intramuscular increments repeated every two to three minutes. Someone must keep supporting breathing, because drug absorption and circulation may be poor and naloxone is not instantaneous.
The aim is adequate spontaneous ventilation and airway protection, not full arousal. A large antagonist dose can abruptly precipitate pain, vomiting, agitation and severe withdrawal in a dependent person. In clinical care, intravenous naloxone can be titrated in small or product-directed doses with close monitoring; the current injectable SmPC permits 400–2,000 micrograms initially and repetition every two to three minutes. Response may fade after naloxone clears. Methadone, sustained-release products and highly potent synthetic opioids can require repeated doses or a monitored infusion based on the effective bolus dose and local toxicology guidance.
Withdrawal is the mirror image of intoxication: dilated pupils, yawning, watering eyes, runny nose, sweating, gooseflesh, restlessness, muscle and abdominal pain, vomiting, diarrhoea, insomnia and intense craving. Symptoms are unpleasant and can drive rapid return to use, but uncomplicated opioid withdrawal usually does not cause the seizures or delirium characteristic of alcohol or benzodiazepine withdrawal. Assess pregnancy, cardiovascular and other illness, fluid loss, pain, mental state, safeguarding and concurrent dependence. An emergency department should treat the emergency and withdrawal symptoms but not routinely initiate an unplanned detoxification episode.
The period after abstinence is hazardous because tolerance falls faster than conditioned expectations. Risk is especially high after prison release, hospital admission, residential treatment, detoxification or any interruption in opioid substitution treatment. Explain the danger of returning to a previous dose, sedative combinations, using alone and variable illicit potency. Offer opioid substitution treatment where dependence is present, take-home naloxone to the person and likely witnesses, hepatitis and HIV services, sterile injecting equipment and continuity of care. A non-fatal overdose is a critical opportunity for active treatment linkage rather than discharge with warning alone.
Key points
Prioritise breathing: the clinically important overdose triad is depressed consciousness, respiratory depression and usually small pupils, but pupils may be atypical in mixed poisoning.
Naloxone is a competitive opioid antagonist and should be titrated to restore adequate ventilation, not used to force complete alertness at the cost of severe precipitated withdrawal.
Nyxoid delivers 1.8 mg into one nostril for adults and adolescents aged 14 or over; if there is no response give a second dose after 2–3 minutes, or immediately if respiratory depression returns, using alternate nostrils.
Prenoxad take-home injection gives 400 micrograms intramuscularly into the outer thigh or upper arm, repeated every 2–3 minutes through resuscitation cycles until breathing recovers, help arrives or the syringe is used.
In a clinical setting, one injectable naloxone SmPC permits 400–2,000 micrograms intravenously initially, repeated every 2–3 minutes; if 10 mg total gives no response, reconsider the diagnosis, while long-acting opioids may require infusion.
Every community naloxone dose accompanies a 999 call and airway support; nasal and injectable products have different strengths and instructions, so teach the supplied device.
Aetiology
01
Excess receptor agonism
A large opioid exposure, potent contaminant or reduced tolerance can suppress respiratory drive even when the intended amount seems familiar.
02
Sedative combination
Alcohol, benzodiazepines, gabapentinoids and other central depressants add substantial respiratory and consciousness impairment to the underlying opioid effects.
03
Abrupt receptor under-stimulation
Stopping a regular opioid, giving an antagonist or introducing buprenorphine too early produces withdrawal when receptor activation falls rapidly.
Pathophysiology
1
Brainstem suppression
Mu-opioid receptor activation reduces the ventilatory response to rising carbon dioxide, causing progressively slower, shallower and ineffective spontaneous breathing.
2
Upper-airway compromise
Reduced consciousness and muscle tone permit obstruction, aspiration and hypoxic injury in addition to central respiratory depression.
3
Antagonist displacement
Naloxone competitively displaces opioid agonists, rapidly restoring respiratory drive but potentially triggering abrupt withdrawal in dependent people.
4
Autonomic rebound
Loss of opioid signalling increases noradrenergic and gastrointestinal activity, producing sweating, restlessness, pain, vomiting and diarrhoea.
Clinical features and red flags
Opioid respiratory toxidrome
Reduced consciousness with slow, shallow or absent breathing is the decisive pattern; pinpoint pupils support but are not required.
Mixed-drug poisoning
Alcohol, benzodiazepines, gabapentinoids or other sedatives deepen coma and may leave impairment after naloxone restores the opioid component.
Abrupt severe vomiting, pain, agitation and autonomic symptoms after naloxone or buprenorphine suggests rapid antagonist or partial-agonist displacement.
Loss of tolerance
A recent period of abstinence, custody, hospitalisation or detoxification markedly increases overdose risk on return to a previously tolerated amount.
Red flags requiring action
A respiratory rate below normal with reduced consciousness, cyanosis, apnoea, snoring or gurgling requires immediate ventilation support and naloxone, not a prolonged history.
Failure to respond after appropriately repeated naloxone requires continued resuscitation and reconsideration of airway obstruction, non-opioid poisoning, hypoglycaemia, stroke, trauma and seizure.
Investigations
01Airway and respiratory assessmentFirst step
Why
Determine whether immediate ventilation, advanced airway support and naloxone are required.
Interpretation and limitations
Respiratory rate, depth, oxygen saturation and consciousness drive treatment; normal saturation on oxygen does not prove adequate ventilation.
02Bedside glucose and temperature
Why
Identify common reversible mimics or complications of reduced consciousness.
Interpretation and limitations
Correct hypoglycaemia immediately and evaluate hypothermia or fever rather than assuming every abnormality is opioid related.
03Electrocardiogram and targeted blood tests
Why
Assess arrhythmia, methadone-related QT risk, acidosis, renal injury, infection and co-ingestion when clinically indicated.
Interpretation and limitations
Testing follows resuscitation and helps determine observation, admission and complications; it must not delay ventilation or naloxone.
04Clinical response to naloxone
Why
Support opioid involvement while restoring breathing.
Interpretation and limitations
Improved ventilation supports the diagnosis, but incomplete arousal can reflect hypoxic injury, another sedative or an independent neurological emergency.
Differential diagnosis
01
Other sedative poisoning
Alcohol, benzodiazepines, gabapentinoids, clonidine and antipsychotics can produce coma and may coexist with an opioid exposure.
02
Neurological emergency
Intracranial haemorrhage, stroke, seizure, meningitis and head injury require consideration when recovery is incomplete or focal signs occur.
03
Metabolic unconsciousness
Hypoglycaemia, hypoxia, hypercapnia, renal failure and severe systemic infection may mimic the opioid toxidrome or compound its effects.
04
Alternative withdrawal
Alcohol, benzodiazepine, gabapentinoid and GHB withdrawal may cause agitation, autonomic symptoms and greater seizure or delirium risk.
Management
01Community overdoseCall, breathe, give naloxoneFirst stepA person is unresponsive or inadequately breathing after known or possible opioid use.+
1Call 999, open the airway and provide rescue breathing or CPR according to current life-support guidance.
2Give the supplied intranasal or intramuscular naloxone exactly as trained and repeat after 2–3 minutes if needed while resuscitation continues.
3Stay until emergency services take over, use the recovery position once appropriate and give further dose immediately if respiratory depression returns.
02Clinical overdoseRestore and sustain ventilationOpioid toxicity is managed by trained clinicians with monitoring and injectable naloxone.+
1Provide oxygen and ventilation, gain access, check glucose and titrate naloxone to effective breathing using the local emergency protocol.
Complications
01
Hypoxic brain injury
Prolonged inadequate ventilation can cause irreversible neurological disability or death even if naloxone is later effective.
02
Aspiration and lung injury
Vomiting, reduced protective airway reflexes and prolonged unconsciousness can cause aspiration pneumonitis, pneumonia or non-cardiogenic pulmonary oedema.
03
Recurrent toxicity
Naloxone may clear before a long-acting opioid, allowing respiratory depression to return after an apparently successful reversal.
04
Post-detox overdose
Reduced tolerance makes return to a former dose especially dangerous after custody, admission, residential care or planned detoxification.
Monitoring and follow-up
Continue respiratory rate, depth, oxygenation, consciousness and airway observations after every dose and after apparent recovery.
Extend observation when methadone, modified-release opioids, nitazenes, fentanyl analogues or mixed sedatives may outlast naloxone.
Monitor vomiting, aspiration, agitation, chest pain, pulmonary oedema and recurrent pain or withdrawal after reversal.
During withdrawal, review hydration, electrolytes when indicated, sleep, mental state, pregnancy, infection and concurrent alcohol or sedative dependence.
At transition, confirm substitution prescribing, take-home naloxone training, safer-use information and direct connection with community treatment.
Special situations
Breathing is the target
A person need not be fully awake for naloxone to have succeeded; adequate spontaneous ventilation is the immediate physiological goal.
Pupils can mislead
Hypoxia, stimulants, eye disease and mixed poisoning may alter pupil size, so respiratory depression carries more weight.
Naloxone wears off
Recovery can reverse when a short antagonist effect ends while methadone, fentanyl, nitazenes or sustained-release opioids remain active.
Withdrawal differs in danger
Opioid withdrawal is usually not intrinsically fatal, but dehydration, pregnancy, comorbidity, suicide risk and rapid return to use can be serious.
Witnesses save lives
Supplying naloxone to friends, family and outreach workers matters because an unconscious person cannot administer their own kit.
Common pitfalls
01
Delaying ventilation while searching for drug history, pupils or a naloxone kit.
02
Assuming naloxone replaces a 999 call or that one response makes further observation unnecessary.
03
Using the dose from one nasal or injectable product for a differently concentrated device.
04
Trying to force complete wakefulness with repeated large doses despite restored breathing.
05
Calling persistent coma non-opioid without considering co-ingestion or hypoxic brain injury after ventilation improves.
06
Completing detoxification without warning about tolerance loss, providing naloxone and arranging continuing treatment.
Clinical stateAwaiting review
JurisdictionUnited Kingdom
Opioid withdrawal causes yawning, lacrimation, rhinorrhoea, piloerection, mydriasis, cramps, diarrhoea, vomiting, insomnia and dysphoria; it is intensely distressing but usually less medically dangerous than alcohol or benzodiazepine withdrawal.
Detoxification lowers tolerance and increases overdose risk if opioid use resumes; offer continued psychosocial care, opioid substitution treatment where appropriate and take-home naloxone.
Recurrent drowsiness or slow breathing after initial recovery suggests that naloxone has worn off before the opioid and demands further treatment and monitoring.
Methadone, fentanyl, nitazenes, modified-release products or mixed sedative exposure increases the likelihood of prolonged toxicity and multiple naloxone doses.
Pregnancy, severe dehydration, persistent vomiting or diarrhoea, acute pain, infection, suicidality or a concurrent alcohol or benzodiazepine withdrawal complicates an otherwise usually non-fatal opioid withdrawal.
05
Dependence and treatment history
Why
Separate intoxication, withdrawal and interrupted prescribed treatment and estimate post-discharge overdose risk.
Interpretation and limitations
Verify current methadone or buprenorphine dose with the dispensing service before administration; self-report alone cannot establish a safe dose.
2
Observe for recurrent depression and identify long-acting opioid or mixed poisoning; use a naloxone infusion when toxicology or critical-care guidance indicates.
3Investigate aspiration, pulmonary oedema, rhabdomyolysis, infection, injury and suicidal intent, then arrange treatment and take-home naloxone before discharge.
03WithdrawalRelieve symptoms without unsafe detoxA dependent person has withdrawal symptoms but no current respiratory toxicity.+
1Assess severity, fluid loss, pregnancy, pain, mental state, co-dependence and the person's current or previous substitution prescription.
2First lineOffer specialist opioid treatment; methadone or buprenorphine are NICE first-line detoxification medicines when detoxification is a planned informed goal.
3Explain tolerance loss, provide naloxone and ongoing psychosocial care, and avoid a stand-alone acute detoxification that ends without continuity.
Key medicines and prescribing safety3 treatments · regimens, roles and cautions+
Take-home emergency reversal of respiratory and central nervous system depression from known or suspected opioid overdose.
Naloxone intranasal, Nyxoid
Adults and adolescents aged 14 years or over: give one 1.8 mg spray into one nostril. If there is no response, give a second spray after 2–3 minutes; if the person initially responds but respiratory depression returns, give the second dose immediately. Use alternate nostrils for further available doses while awaiting emergency services.
It does not replace 999 care, airway opening or ventilation. Expect acute withdrawal, vomiting or agitation, monitor continuously for relapse, and recognise that potent or long-acting opioids may require several doses and hospital treatment.
A reusable take-home prefilled syringe permits graduated emergency reversal while basic life support continues.
Naloxone intramuscular, Prenoxad
Give 400 micrograms, equivalent to 0.4 mL, intramuscularly into the outer thigh or upper arm, then repeat 400 micrograms every 2–3 minutes in successive resuscitation cycles until breathing recovers, the ambulance arrives or the prefilled syringe is empty.
Training must match the exact device. Avoid needlestick injury, call 999 before or alongside use, do not leave the person after apparent recovery, and anticipate precipitated withdrawal and recurrent respiratory depression.
Clinicians can titrate antagonist exposure to restore ventilation and maintain reversal beyond a short bolus effect.
Naloxone injection in clinical care
One current injectable SmPC recommends 400–2,000 micrograms intravenously initially for adults, repeated every 2–3 minutes according to response; if a cumulative 10 mg produces no response, reconsider the diagnosis. Use intramuscular or subcutaneous administration if intravenous access is unavailable and consider monitored infusion for long-acting opioids.
Dose and infusion must follow the stocked product and local resuscitation or toxicology protocol. Rapid full reversal can trigger severe withdrawal, hypertension, arrhythmia or pulmonary complications; ongoing airway and cardiorespiratory monitoring remains essential.