Neuraxial Opioid-Induced Respiratory Depression

Neuraxial opioid induced respiratory depression is reduced respiratory rate, sedation and hypoventilation after intrathecal or epidural opioids. Early depression occurs within 2 hours (lipophilic opioids), and delayed depression occurs 6 to 18 hours after hydrophilic opioids such as morphine, through cephalad spread in cerebrospinal fluid.

Epidemiology. Incidence is about 0.1% to 0.9% with intrathecal morphine at usual doses (up to 1% to 3% with high doses and risk factors), and 0.1% to 0.4% with epidural morphine.

Risk factors. High dose (intrathecal morphine over 200 microgram), age over 70 years, obesity, obstructive sleep apnoea, systemic opioids or sedatives, lung disease, renal impairment, thoracic surgery, head down tilt, and concurrent gabapentinoids.

Pathophysiology.

Hydrophilic opioids reach the medulla via rostral cerebrospinal fluid flow, blunting respiratory centre response to carbon dioxide. Respiratory depression is dose dependent and can occur without sedation.

Slow respiratory rate (under 10/min), reduced consciousness, small pupils, shallow breathing, desaturation, hypercapnia, and apnoea in the worst case. Respiratory rate alone can be falsely reassuring, and sedation precedes it.

Red flags.

• Respiratory rate under 8/min.
• Sedation score 3 (hard to rouse).
• Saturation under 90%.
• Apnoea.

Clinical. Use respiratory rate, sedation score and capnography or oximetry. Blood gas shows hypercapnia. Exclude other causes: high block, systemic opioids, hypoxia, stroke and sepsis.

Differential diagnosis.

• Systemic opioid or sedative overdose.
• High neuraxial block.
• Residual anaesthetic.
• Sleep apnoea.
• Stroke.
• Hypercapnia from lung disease.

Stimulate the patient, give oxygen and support the airway.

• Naloxone: 40 to 100 microgram IV every 2 to 3 minutes titrated to respiratory rate over 10/min; maximum 400 microgram before reconsidering diagnosis; infusion 5 to 10 microgram/kg/h for up to 24 hours if the effect wanes (duration of naloxone is 30 to 60 minutes, shorter than morphine); monitor respiratory rate, pain and blood pressure; use small increments to avoid pulmonary oedema and severe pain.

Ventilate by bag mask and intubate for apnoea. Stop all other sedatives. Monitor for recurrence for 12 to 24 hours.

Prevention. Use the lowest dose of intrathecal morphine (50 to 150 microgram; up to 100 microgram in older adults), avoid concurrent systemic opioids and sedatives, and screen for sleep apnoea.

Monitoring. After intrathecal morphine, check respiratory rate, sedation and saturation hourly for 12 hours, then every 2 hours for the next 12 hours (continuous oximetry and capnography in high risk patients). Epidural morphine requires monitoring for 24 hours.

Referral and escalation. Critical care for naloxone infusion, recurrent depression or ventilatory failure.

Special groups. Older adults, patients with sleep apnoea and obesity require lower doses and continuous monitoring.