Opioid Toxidrome

Introduction

Opioids are a diverse group of substances which are used mostly for their analgesic properties but can be abused for their euphoric properties. Drugs in this class include morphine, codeine, fentanyl, oxycodone, methadone, pethidine, hydromorphone, tramadol, tapentadol, buprenorphine and heroin.

The opioid toxidrome consists of miosis, vomiting, respiratory depression, sedation and coma.

Toxicokinetics

Opioids are agonists at the opioid receptor which act centrally to provide analgesia and sedation in a dose dependent manner.

Oral immediate release preparations are rapidly absorbed with peak concentrations within 2 hours.  Controlled release preparations are common and available for oxycodone, morphine, hydromorphone, tramadol and tapentadol.  In general, if these controlled release compounds are crushed, they lose their slow release properties.  This includes if they are injected.  Some preparations have added properties (eg they form a gel when crushed and added to water) to limit recreational misuse.

Opioids primarily undergo hepatic metabolism. Most opioids have half-lives between 1 and 5 hours. Notable exceptions include heroin with a short half-life of 15 to 30 mins, and longer acting agents like methadone and buprenorphine with half-lives of approximately 24 and 36 hours respectively.

Risk Assessment

Clinical examination should focus on examining for an opioid toxidrome.

Opioid naïve patients will exhibit more severe toxicity.

Complications of opioid poisoning include:

  • Aspiration
  • Pressure injuries from long lie, rhabdomyolysis
  • Prolonged QT (methadone)
  • Serotonin Toxicity (fentanyl, tramadol, tapentadol)
  • Seizures (tramadol, tapentadol, pethidine)

There is little role for a spot urine drug screen.

Management

Good supportive care is sufficient in the majority of cases of opioid poisoning.  Patients should be observed in a visual area with continuous oximetry to detect hypoxia due to ventilatory insufficiency.  Avoid supplemental oxygen where possible.

Toxicity with respiratory insufficiency should prompt administration of the opioid reversal agent naloxone.  End points are a RR > 10, Sats > 92% on room air and if measured a pCO< 60mmHg.  Ideally the patient should be rousable to voice, however if they have taken other sedating co-ingestions this may not be possible.

Resuscitation

Antidote

Naloxoneis an effective antidote and should be administered to people presenting with hypoventilation due to opioid toxicity.  It can be administered IM, IV, IN or SL routes. The most effective dosing regimen is not clearly established.

Large IM boluses are effective and decrease the need for naloxone infusions.  They are most appropriate for short acting opioid overdoses such as heroin.

Give 0.8 – 1.6mg IM naloxone q30min PRN

Titrated IV aliquots are preferred by some in an effort to minimise acute opioid withdrawal and in particular acute behavioural disturbance.

Give 50 – 100mcg IV naloxone q2min PRN

If a patient redevelops hypoventilation an infusion may be required.  The initial hourly rate is the same amount as the total of IV aliquotsthe patient required to achieve a RR > 10 and Sats > 92% on RA. 

This hourly rate can then be titrated depending on the progression of toxicity.  If the infusion needs to be increased due to the recurrence of opioid toxicity, ensure the patient receives a bolus of naloxone first to ensure RR > 10 and Sats > 92% prior to increasing infusion rate.  Avoid weaning/ceasing the infusion overnight.

Poisonings with controlled release substances, or those with longer half-lives such as methadone will likely require a prolonged infusion.  Naloxone infusions should not be ceased overnight unless discussed with the toxicology team prior.

Naloxone infusion: 4mg naloxone in 100mL N/Saline; titrated to achieve a RR > 10 and Sats > 92%

Specific therapy

Decontamination 

Activated charcoal can be offered to patients presenting within 2 hours of an immediate release preparation ingestion and 6 hours following a slow release opioid overdose.  

Supportive therapy 

Supportive measures are the mainstay of therapy in addition to naloxone if there is respiratory insufficiency. Patients should be in a visual area with continuous oximetry.  Supplemental oxygen should not be applied unless there is an oxygen requirement due to aspiration.

Ensure the patient is well hydrated.  Similarly, bladder care and the consideration of thromboprophylaxis (as per the Toxicology Unit guidelines) is advised for patients with significant sedation, particularly if it is expected to be prolonged.

Disposition

Most patients are suitable for a SSU admission under the toxicology team for observation and naloxone therapy if necessary.  

The minimum observation period following naloxone is controversial and depends on the opioid taken, its dose, the naloxone requirement and its route.  Discussion with the toxicology team is recommended prior to discharge.

In general patients should be observed;

  • For at least 2 hours following their last IV dose
  • For at least 4 hours following their last IM dose
  • For at least 6 hours following a naloxone infusion

Patient should be alert, mobilising safely, have eaten and passed urine prior to discharge.  Once the symptoms of the opiate toxidrome subside, referral to drug and alcohol services should be made if the patient is willing.  

Discharge naloxone should be offered to all patients presenting with opioid poisoning.See additional information  

Patients should be instructed not to drive for 3 days due to the increased risk of MVA.  A discharge proforma stating the same should be provided.  These are available on the Toxicology Resource Wall in the SSU.

Additional Information

  • Prenoxad is the currently available discharge naloxone preparation.  It is available in 2mg/2mL and costs $38 ($6.90 with a concession card).  Script instructions should state;
    • give 2mg IM stat if the patient is unconscious and not breathing following opioid overdose.  
  • The Pharmacist is available to educate the patient and their family prior to discharge regarding the administration of Prenoxad.

Further reading

  • Sivilotti M.  “Flumazenil, naloxone and the ‘coma’ cocktail” Br J Clin Pharmacol2016 Mar;81(3):428-36

References

  1. Sivilotti M.  “Flumazenil, naloxone and the ‘coma’ cocktail” Br J Clin Pharmacol2016 Mar;81(3):428-36