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EMA Cited · Toxicology

Opioid overdose

Updated Oct 24, 2026Adults · ED management16 sources · 13 checked in PubMed3 figuresRCEM/NPIS 2024

Bottom line

  • Treat the breathing, not the coma. Titrate naloxone to a respiratory rate over 10 and oxygen saturation over 92% with protected airway reflexes. Full wakefulness is not the goal.1
  • Start small and repeat. The UK guideline gives 100–200 micrograms IV every 60 seconds. Some patients still need a total of 2–4 mg.1 The US label allows 0.4–2 mg IV, repeated every 2–3 minutes.2
  • Overshooting has a cost. Too much naloxone causes withdrawal and can unmask stimulant toxicity.1 Prehospital totals over 4.4 mg were associated with more pulmonary complications (42% vs 26%).3
  • Observation time is disputed. The UK guideline advises at least 4 hours after the last naloxone dose and 6 hours after use.1 The St. Paul's rule allows discharge after a normal check 1 hour after naloxone.4,5
  • The visit is a chance to prevent death. In Massachusetts, 5.5% of patients discharged after an overdose died within a year.6 ED-started buprenorphine nearly doubled engagement in addiction treatment at 30 days (78% vs 37%).7

Recognize

  • The classic triad is drowsiness, slow or shallow breathing, and pinpoint pupils.1
  • Other features include vomiting, itching or hives, hypotension, bradycardia, seizures, and hypothermia from exposure.1
  • Look for complications: aspiration pneumonia, rhabdomyolysis, compartment syndrome, skin necrosis and hypoxic brain injury.8
  • Expect co-ingestants. Alcohol, benzodiazepines and pregabalin deepen respiratory depression. Cocaine or synthetic cannabinoids can mask the toxidrome.1
  • The diagnosis is clinical. A urine drug screen has no role in immediate management. A trial of naloxone can help confirm it in a drowsy patient with poor breathing.1
  • Naloxone does not reverse non-opioid drugs. Partial agonists such as buprenorphine may reverse incompletely or need higher doses.2

First 10 minutes

  1. Support ventilation first. If naloxone gives an incomplete response, assist breathing mechanically.2
  2. Give naloxone IV in small steps: 100–200 micrograms every 60 seconds until the respiratory rate is over 10.1
  3. No IV access? Give it IM, intranasally or IO. These routes reach peak levels more slowly.1
  4. Aim for a respiratory rate over 10 and oxygen saturation over 92% on room air (88–92% in COPD). Nasal end-tidal CO₂ can help if your team uses it.1
  5. Needs more boluses after the first response? Start an infusion (below).1
  6. No response after 10 mg? Question whether opioids are the cause.2
FIG 1 · Decision flowCited
  1. Drowsy with respiratory depression. Open the airway and support ventilation.2
  2. IV access?
    No
    Give naloxone IM, intranasally or IO. Expect a slower peak.1
  3. Yes
    Naloxone 100–200 micrograms IV every 60 seconds.1
  4. Respiratory rate over 10, oxygen saturation over 92%?
    No, after 10 mg
    Question the diagnosis. Keep ventilating.2
  5. Yes
    Breathing stays adequate without more boluses?
    No: needs a second round
    Start an infusion: per hour, 60% of the second round's total dose.1
  6. Yes
    Observe. At least 4 hours after the last dose and 6 hours after use; longer for long-acting opioids.1
FIG 1Titrating naloxone. Drawn for this page from the RCEM/NPIS guideline and the US injection label. Each box carries its own citations.1,2

Naloxone

UseAdult doseNotes
Bolus
IV, ED titration100–200 micrograms every 60 sRepeat until respiratory rate > 10. Totals of 2–4 mg may be needed.1
IV, US label0.4–2 mg, repeat every 2–3 minIM or subcutaneous if IV is not available. Question the diagnosis after 10 mg.2
Intranasal spray4 mg per sprayOne spray per device.9 In the ED, use it only when IV access is difficult.1
Infusion
Starting rate60% of the second-round dose, per hourMix 4 mg in 40 mL total (100 micrograms/mL).1
Recurrent depression on infusionBolus 100–200 micrograms every 60 s, up to 2 mgThen raise the hourly rate by 60% of the bolus total.1
Withdrawal on infusionCut the rate by 50%If very agitated, stop. Restart after 30–60 min at half the rate.1

Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.

Sources disagree

Starting dose: the UK guideline titrates from 100–200 micrograms to avoid withdrawal.1 The US label starts at 0.4–2 mg.2 In one prehospital cohort, a first dose above 0.4 mg was associated with more pulmonary complications (27% vs 13%).3 Outside cardiac or respiratory arrest, start low.

Infusion rates

Total bolus that workedStart atRate at 100 micrograms/mL
200 micrograms120 micrograms/h1.2 mL/h
400 micrograms240 micrograms/h2.4 mL/h
800 micrograms480 micrograms/h4.8 mL/h
1,000 micrograms600 micrograms/h6.0 mL/h
2,000 micrograms1,200 micrograms/h12.0 mL/h

Selected rows from the RCEM/NPIS starting-rate table.1

  • Observe every 15 minutes for the first hour, then every 30 minutes. Restart that schedule whenever the rate changes.1
  • Hold the rate for at least 4 hours, then wean by 25% of the maximum rate every 2 hours.1
  • Don't stop it between midnight and 6 am unless the patient is in withdrawal. Recurrence is harder to spot in a sleeping patient.1

Harms of too much naloxone

  • Withdrawal: yawning, rhinorrhea, tearing, dilated pupils, tachycardia, hypertension, diarrhea, tremor, anxiety and restlessness.1
  • Unmasked stimulants: after cocaine or methamphetamine, reversal can leave an agitated patient who needs restraint or intubation. Withdrawal also makes people avoid care.1
  • Pulmonary complications: in 1,831 Pittsburgh patients, totals over 4.4 mg had higher odds after adjustment (OR 1.85). Pulmonary edema itself occurred in 1.1%. The study was retrospective and cannot show cause.3
  • Cardiac events such as pulmonary edema, ventricular arrhythmias and arrest are reported after abrupt postoperative reversal, mostly in patients with heart disease.2

Routes, fentanyl and newer opioids

  • Intranasal is slower than IM at the same dose. In a blinded trial at a supervised injecting site (n = 197), 800 micrograms intranasally needed a rescue dose more often than 800 micrograms IM (23.1% vs 8.6%).10
  • Nitazenes and other novel potent opioids can be stronger and longer acting than heroin. Isotonitazene is about twice as potent as fentanyl.1
  • In a small US cohort, patients with novel potent opioids needed more in-hospital naloxone boluses than fentanyl-only patients (9 vs 11 patients).11

Cardiac arrest

The role of naloxone once the heart has stopped is uncertain. The American Heart Association calls it a critical evidence gap.12 In 3,811 Californian arrests in adults under 50 that nobody witnessed, EMS naloxone was associated with higher survival to discharge (8.1% vs 4.4%; adjusted difference 2.75 points). Among patients who also got epinephrine, the benefit was not seen. The data are observational.12

Observation and disposition

  • UK standard: observe at least 4 hours after the last naloxone dose and at least 6 hours after the suspected time of use. Discharge when observations and mental state are normal.1
  • Long-acting opioids such as methadone or a novel synthetic opioid: extend observation up to 12 hours.1
  • How long toxicity lasts: about 6 hours for heroin, up to 12 hours for controlled-release products, and more than 24 hours for methadone and oxycodone.8
  • Ongoing infusion: admit. Weaning is rarely finished in the ED.1
  • Don't give IM naloxone alongside IV doses or just before discharge.1
St. Paul's rule: 1 hour after naloxoneDischarge if all are met
MobilityCan walk as usual
Oxygen saturation, room air> 92% (95% in the validation study)
Respiratory rate> 10 and < 20 /min
Temperature> 35.0 and < 37.5 °C
Heart rate> 50 and < 100 /min
Glasgow Coma Scale15
  • Derivation (Vancouver, n = 573): sensitivity 99% and specificity 40% for adverse events within 24 hours.4 No discharged patient had a serious adverse event within 24 hours.13
  • Validation (Buffalo, n = 538, after prehospital naloxone): adverse events in 15.4%. Sensitivity 84.1%, specificity 62.1%, negative predictive value 95.6%.5
  • Refusing transport: across observational studies of 5,443 patients treated without transport, 4 died of rebound toxicity.14
FIG 2How long to watch. Drawn for this page. Time zero is the last naloxone dose. The 1-hour check comes from the St. Paul's rule, the 4-hour minimum and 12-hour extension from the UK guideline. The UK guideline also requires at least 6 hours from opioid use, which this chart cannot show.1,4
Sources disagree

The UK guideline sets a 4–6 hour minimum and calls for research on safe discharge criteria.1 A systematic review concluded that 1 hour is enough if the patient walks normally, has normal vital signs and a GCS of 15.14 The St. Paul's rule was derived in 2000. Its validation, run as synthetic opioids emerged, found lower sensitivity (84% vs 99%).4,5

Before they leave

  • Risk of death is high, and early. Of 11,557 Massachusetts patients, 1.1% died within a month and 0.25% within 2 days.6 In Ontario, 5.3% died within a year, 1.9% from opioids.15
  • Higher-risk groups in Ontario: men, and people on opioid agonist therapy or benzodiazepines in the prior year.15
  • Offer brief intervention and referral to drug services. Offer blood-borne virus testing.1
  • Hand out take-home naloxone. It is known to reduce drug deaths.1
  • Offer buprenorphine. In 329 opioid-dependent ED patients, ED-started buprenorphine raised treatment engagement at 30 days to 78%, versus 37% with referral and 45% with brief intervention.7
  • Injectable or sublingual both work. In 1,994 patients, 76% of them fentanyl-positive, engagement at 7 days was 40.5% with 7-day extended-release injection vs 38.5% sublingual. Precipitated withdrawal occurred in under 1%.16
Open zip case labelled naloxone containing an amber bottle of naloxone ampules, a response card, gloves and a CPR face shield, beside three syringes and alcohol swabs
FIG 3A take-home naloxone kit. This injectable kit holds naloxone 0.4 mg/mL ampules, syringes, gloves, a face shield and a step-by-step response card. Nasal spray kits are another option.1James Heilman, MD · Wikimedia Commons · CC BY-SA 4.0

Pitfalls

  • Pushing naloxone until the patient is fully awake. The target is breathing and airway reflexes.1
  • Giving IM naloxone "for the road." The UK guideline actively discourages it.1
  • Discharging at 1 hour after methadone, a controlled-release product or a suspected novel opioid.1,8
  • Missing a co-ingested sedative or stimulant. Alcohol and benzodiazepines deepen respiratory depression.1
  • Forgetting the ECG after methadone or oxycodone, which can prolong the QT.8
  • Discharging without naloxone, a referral, or an offer of buprenorphine.1,7

How strong is the evidence?

The UK guideline is a best-practice consensus without graded recommendations, and it names discharge criteria as a research priority.1 Observation rules rest on two single-region cohorts.4,5 The link between high naloxone doses and lung complications is retrospective.3 Naloxone in cardiac arrest has only observational support.12 The strongest data are the randomized trials of intranasal naloxone and ED-started buprenorphine.10,7,16

On-shift teaching

Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.

Q1What are you titrating naloxone to?
A respiratory rate over 10 and oxygen saturation over 92% on room air (88–92% in COPD), with protected airway reflexes. Not full wakefulness.1
Q2A patient needed 800 micrograms to breathe, then slowed again and needed another 800. What infusion rate do you start?
480 micrograms per hour: 60% of the second round's total. At 100 micrograms/mL, that's 4.8 mL/h.1
Q3Why not just give 2 mg IV up front?
Big doses cause withdrawal and can unmask stimulant toxicity.1 In Pittsburgh, a first dose above 0.4 mg was associated with more pulmonary complications (27% vs 13%).3
Q4What are the six St. Paul's criteria for discharge 1 hour after naloxone?
Walks as usual, oxygen saturation over 92%, respiratory rate 10–20, temperature 35.0–37.5 °C, heart rate 50–100, and GCS 15.4 At validation, sensitivity was 84.1%.5
Q5When do you extend observation to 12 hours?
For methadone or a suspected novel synthetic opioid, which act longer than heroin.1 Methadone and oxycodone toxicity can last more than 24 hours.8
Q6How risky is the year after a nonfatal overdose?
In Massachusetts, 5.5% died within a year and 1.1% within a month.6 ED-started buprenorphine raised 30-day treatment engagement to 78% vs 37% with referral.7

References

Evidence base

What this page is built on

16 sources, cited 92 times. Dots are sources, filled by how far each was read; stronger color means a larger share of the citations. Tap a tier to see its sources.

Read in full · 4Abstract read · 12Record only · 0Link checked · 0

Checked by the writer, not a physician. The dots show how each source was read, not that anyone has confirmed the claims.

How this page was made
  • Written from scratch. No source text was copied; facts are restated and cited.
  • Anchored on the 2024 RCEM/NPIS guideline, read in full from the RCEM PDF. Its management flowchart is an image and was not used. The 2025 American Heart Association special-circumstances guideline (PMID 41122889) could not be accessed, so none of its recommendations are stated here.
  • Each PubMed citation was resolved through NCBI E-utilities and each number checked against that paper's abstract. Naloxone doses come from the guideline text and FDA labels on DailyMed.
  • Adults only. Observation periods for children differ and are not covered here. Patients on opioids for palliative or cancer pain are outside the guideline's scope.
  • Figures 1 and 2 were drawn for this page from cited data. Figure 3 is an openly licensed image from Wikimedia Commons, credited under it, and keeps its own license.
  • Not for clinical use.
Not for clinical use

AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms