creation date: 2026-03-02 23:45
tags: Pathologies
Opioid Toxicity
Background
Definitions
Opioids (and opiates) are medications used to relieve pain and can induce euphoria. Examples:
- Opiates: opium, morphine, diacetylmorphine (heroin), codeine
- Opioids: methadone, oxycodone, fentanyl, tramadol
Opioid toxicity refers to a complication of failure to adhere to opioid dosing and duration of use.
Etiology and Risk Factors
Causes of overdose include:
- Substance abuse
- Unintentional and intentional overdose
- Therapeutic drug error
Situations in which risk of overdose increases are:
- Taking escalating doses
- Returning to use after cessation
- Having severe medical and psychiatric conditions (eg. depression, HIV infection, lung/liver disease)
- Combining opioids with sedative medications
Other risk factors include:
- Male sex
- Younger age (20-40)
- White non-Hispanic race
Pathophysiology
Opioids act on 3 subtypes (mu, kappa, and delta) opioid receptors.
- Mu: analgesia, euphoria, sedation, respiratory depression, GI dysmotility, physical dependence
- Kappa: analgesia, diuresis, miosis, dysphoria
- Delta: analgesia, dopamine release inhibition, cough suppression
In the case of overdose, excessive stimulation of mu-opioid receptors in the brain results in respiratory depression and thus death by respiratory arrest.
Clinical Presentation
Signs & Symptoms
The classical “opioid overdose triad” is:
- Pinpoint pupils
- Respiratory depression
- Decreased level of consciousness
Findings on examination
Skin
- Needle track marks if IV use
- Itching
- Skin flushing
- Urticaria
Pulmonary - Respiratory distress and hypoxia
- Shallow breathing, hypopnea, bradypnea (4-6 breaths per min)
- Dyspnea, wheezing
- Frothy sputum production
Cardiovascular - Hypotension
Gastrointestinal - Nausea/vomiting
- Slow GI motility
Psychiatric - Generalized GNS depression
- Anxiety
- Agitation
- Depression
- Dysphoria
- Hallucination
- Nightmares, paranoia
Neurological - Seizures
- Auditory changes/deficit
History & Physical Exam
History may be difficulty to obtain due to lethargy or coma. Collateral history should be taken from family, friends, bystanders, or EMS providers.
Important points to note are:
- Amount of drug used
- Time of use
- If naloxone was administered and response to naloxone
Diagnosis
Criteria
Diagnosis is made clinically based on symptoms and can be confirmed by response to treatment.
Work-up
Laboratory studies
The following are used:
- CBC
- CMP
- Creatine kinase
- Arterial blood gas
- Blood glucose
- Pregnancy testing
- Acetaminophen and salicylate testing
Note that while drug screens are available, they typically do not alter management due to potential of false positives/negative.
Other
A chest radiograph can be performed if lung injury is suspected. If the suspected etiology is from body packing of substance, an abdominal x-ray.
An ECG is recommended for all patients as many coingestants have the potential to cause arrhythmias.
Differential
The primary differential for lethargy of unknown cause when patient is non-responsive to naloxone is co-ingestion of other substances (eg. benzodiazepines).
Red Flags / Complications
The major complication of overdose is respiratory arrest.
Management
Overdose reversal
Reversal of opioid toxicity is by administration of naloxone. In most cases, first responders will administer naloxone immediately and in some cases, further treatment will be refused.
Emergency Department Management
On arrival, management of airway and hemodynamics should be given priority. If necessary:
- Intubation
- Immobilization if suspicion of c-spine occult trauma
- CPR
- Assisted respiration (100% FiO2 should be administered with bag-valve ventilation prior to naloxone)
If necessary more naloxone can be administered:
- Starting dose (adults): 0.4-1 mg
- Starting dose (children): 0.1 mg/kg
- Administer gradually (0.04-0.4 mg IV q1-3min) if suspected chronic opioid user to avoid medically-induced withdrawal
In cases of contaminated gastrointestinal tract (eg. oral opioids or body packing):
- Activated charcoal (administered within 1 hour of ingestion)
- Bowel irrigation