Pharmacology & Poisoning
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A 21 year old known drug user is brought to the Emergency Department with a GCS of 7 and a respiratory rate of 6 breaths per minute. He receives incremental IV naloxone 100–200 micrograms every 60 seconds, requiring a total of 800 micrograms before his respiratory rate improves to 12 breaths per minute. Ninety minutes later his respiratory rate falls to 8 breaths per minute. Further incremental IV naloxone is administered, and a total of 600 micrograms is required to restore his respiratory rate to 12 breaths per minute. Your consultant asks you to commence a naloxone infusion. What is the most appropriate starting infusion rate?
Answer:
- Following an initial response, if the patient subsequently deteriorates and requires further IV boluses of naloxone to maintain adequate ventilation, they will require a naloxone infusion.
- Start an hourly infusion rate of naloxone at 60% of the total naloxone dose that was required to adequately reverse the respiratory depression during the second dosing of naloxone.
Acute Opioid Toxicity
Pharmacology & Poisoning
Last Updated: 24th February 2026
Acute opioid toxicity is a common presentation to Emergency Departments in the UK and represents a significant burden on emergency healthcare services.
The severity and duration of toxicity vary depending on:
- the amount ingested
- the potency of the opioid(s)
- the patient’s opioid tolerance
- the route of use (oral, inhaled, intravenous)
Opioids are frequently co-ingested with other substances, including:
- alcohol
- benzodiazepines
- GABA-ergic drugs (e.g. pregabalin)
- stimulants (e.g. cocaine or methamphetamine)
- synthetic cannabinoids
Clinical Features
- Classic triad
- CNS depression - drowsiness, reduced GCS
- Respiratory depression - hypoventilation, reduced respiratory rate
- Pupillary miosis
- Other symptoms and signs
- Nausea and vomiting
- Neuropsychiatric features - nightmares, anxiety, agitation, euphoria, dysphoria, depression, paranoia, hallucinations
- Urticaria and pruritus
- Convulsions
- Hypotension and bradycardia
- Hypothermia (secondary to environmental exposure)
Co-ingestion may mask the typical opioid toxidrome and/or result in additional adverse effects.
Diagnosis
- Diagnosis is clinical and should be based on history, symptoms, and signs.
- Urine drug screening has no role in immediate ED management and should not delay treatment.
- Naloxone can be used as a diagnostic and therapeutic trial in patients with drowsiness and significant respiratory depression where opioid toxicity is suspected.
- Where there is uncertainty regarding the presentation, discussion with a clinical toxicologist via the National Poisons Information Service (NPIS) is recommended.
- Alternative diagnoses must be considered, particularly if there is no response after a cumulative 2 mg of naloxone. Investigations should include:
- Capillary blood glucose
- Venous blood gas
- Paracetamol concentration
- +/- CT head if clinically indicated
Management
Naloxone, competitive mu-opioid receptor antagonist, is widely accepted as the antidote for opioid toxicity. The preferred route in the Emergency Department is intravenous. Alternative routes (IM, IN, IO) should be considered if IV access is difficult or not possible. IM and IN routes have a longer time to peak blood concentrations.
Treatment Goal
The primary aim of treatment is reversal of respiratory depression and preservation of airway protective reflexes, not full restoration of consciousness.
Although level of consciousness (e.g. AVPU, GCS) can be useful to monitor, therapeutic targets are:
- Respiratory rate > 10 breaths per minute
- Oxygen saturations > 92% on room air (or 88-92% if chronic respiratory disease)
Where available and clinicians are experienced in its use, nasal end-tidal CO2 monitoring can be used as an adjunct to clinical assessment of ventilatory status.
Patients with RR > 10/min and SpO2 > 92% on presentation do not require naloxone. Observations should be assessed every 30 mins. If RR, SpO2, ETCO2 and AVPU are within normal limits for 6 hours after suspected time of overdose, consider discharge.
Acute Opioid Withdrawal
Smaller, titrated IV doses are preferable in non-respiratory arrest patients to reverse respiratory depression while minimising acute iatrogenic opioid withdrawal. Overzealous reversal may unmask stimulant toxicity in mixed overdose and can lead to agitation requiring restraint or sedation. Withdrawal is distressing and may discourage future engagement with healthcare.
Features of acute opioid withdrawal:
- Yawning
- Coughing
- Sneezing
- Running nose
- Lacrimation
- Hypertension
- Tachycardia
- Dilated pupils
- Diarrhoea
- Cool, clammy skin
- Fine muscle tremor
- Nausea
- Irritability
- Restlessness
Adverse Effects
Clinically it is difficult to ascertain whether many of the reported adverse effects of naloxone relate to co-used drugs or the opioid toxicity itself.
Possible adverse effects of naloxone:
- Common - nausea, vomiting, sweating, tachycardia, tremor, hyperventilation, hypertension (more likely with excessive dosing)
- Less common - hypo/hypertension, pulmonary oedema, atrial or ventricular fibrillation, cardiac arrest
- Rare - convulsions
Naloxone Bolus
- In non-cardiac arrest patients, administer incremental IV boluses of 100-200 micrograms every 60 seconds until the respiratory rate is > 10 breaths per minute.
- Initial naloxone bolus doses should be 100 micrograms, if the patient does not respond to four 100 mcg boluses, subsequent bolus doses should be 200 mcg.
- Patients may require large cumulative doses (up to 2-4 mg), but titration is important to reduce the risk of withdrawal.
- Following an initial response, if the patient subsequently deteriorates and requires further IV boluses of naloxone to maintain adequate ventilation, they will require a naloxone infusion.
Naloxone Infusion
- Starting
- Start an hourly infusion rate of naloxone at 60% of the total naloxone dose that was required to adequately reverse the respiratory depression during the second dosing of naloxone.
- Mix 4 mg (10 x 400 microgram/1mL vials) of Naloxone with 30 mL of 0.9% sodium chloride solution (dextrose can be used as an alternative), to provide a final 40mL volume with a concentration of 100 microgram/mL, for infusion using an IV pump.
- Monitoring and titration
- Observations every 15 minutes for the first hour, then every 30 minutes.
- If respiratory depression recurs (RR < 10, SpO2 < 92% on room air, and/or concerning end-tidal CO2 trace), give further IV boluses of 100-200 micrograms every 60 seconds up to a maximum of 2 mg to restore RR > 10, then increase the infusion rate by 60% of the total additional bolus dose that was required.
- If acute opioid withdrawal occurs, reduce the infusion rate (often by 50% initially).
- If severe agitation occurs, stop the infusion temporarily and restart after 30-60 minutes, at 50% of the previous infusion rate once settled.
- If the infusion rate is changed, revert to more frequent monitoring (every 15 minutes for 1 hour, then every 30 minutes).
- Stopping
- Continue at the same rate for at least 4 hours before starting to down-titrate (if no recurrence of toxicity or withdrawal).
- Down-titrate by 25% of the maximum infusion rate every 2 hours with continued close observation.
- Avoid stopping the infusion overnight (00:00-06:00) unless withdrawal occurs, because recurrence may be harder to detect if the patient is sleeping.
Respiratory Arrest/Peri-arrest Management (RR ≤ 5, SpO2 < 85%)
- Call senior decision maker early
- Ventilate with 15 L/min oxygen via bag-valve-mask at 10–12 breaths per minute (as per ALS)
- Secure IV or IO access
- Administer naloxone 400 micrograms IV (or IM/IN if IV access not secured)
- Repeat every 60 seconds if no response
- Escalate doses (800 mcg → 800 mcg → 2 mg)
- If no response after 2 mg, reconsider diagnosis
- Consider advanced airway support and urgent critical care referral
Discharge Following Naloxone Use
Patients who respond to naloxone and have normal observations and mental state may be discharged after an appropriate observation period.
Ideally observe for at least:
- 4 hours after the last dose of naloxone, and
- 6 hours after the suspected time of opioid use
If longer-acting opioids are suspected (for example methadone or novel synthetic opioids), consider extending the observation period up to 12 hours.
Secondary Prevention
ED attendance with opioid intoxication and/or overdose should be used as an opportunity for brief intervention, onward referral to drug liaison services, and
encouraging engagement with community support services.
- Provide verbal or written harm-reduction advice
- Encourage engagement with opiate substitution therapy pathways
- Consider provision of take-home naloxone (IM or IN) and training where available
- Consider blood-borne virus testing
- Consider homelessness referral where applicable
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
