espiratory depression following administration of neuraxial opioids remains an underappreciated but significant source of morbidity and mortality. Observational studies report that the frequency of respiratory depression ranges from 0.01 percent to 7 percent when single-injection intrathecal morphine is administered and from 0.08 percent to 3 percent when single-injection epidural morphine is administered. Despite advances in clinical practice and monitoring, cases of respiratory depression and arrest continue to occur. A recent closed claims analysis revealed 15 cases of respiratory depression involving patient-controlled analgesia (PCA) and 16 cases involving neuraxial opioids.¹ The event occurred in the first 24 hours in 50 percent of the PCA and 62 percent of the neuraxial claims. Nearly three-fourths of the patients died or suffered permanent brain damage. The majority of these cases may have been prevented with proper and effective use of monitoring.

In response to concerns regarding the safety of neuraxial opioids, the ASA Committee on Standards and Practice Parameters established a task force to determine practice guidelines for the prevention, detection and management of respiratory depression associated with neuraxial opioid administration. The task force’s preliminary recommendations are presented here for membership review and comment. They will be further discussed within reference committees at the upcoming ASA Annual Meeting in San Francisco, California, on October 13-17, 2007.

The guidelines focus on the management of all patients receiving epidural or spinal opioids in inpatient (operating rooms, intensive care units, labor and delivery suites, postoperative surgical floors, hospital wards) or ambulatory settings (stand-alone outpatient facilities). The guidelines do not apply to chronic pain or cancer pain patients (except those with acute postoperative pain), patients with pre-existing implantable drug delivery systems or patients with contraindications to spinal/epidural opioids (e.g., coagulopathy, sepsis).

Risk factors for respiratory depression were identified through review of randomized clinical trials and observational series [Table 1]. The following preliminary recommendations are derived from an evidence-based review of the literature, expert opinion, open forum commentary and clinical feasibility data.

Summary of Preliminary Recommendations

I. Prevention

• The anesthesiologist should conduct a focused history and physical examination before administering neuraxial opioids.

– Particular attention should be directed toward signs, symptoms or a history of sleep apnea, co-existing diseases, current medications (including preoperative opioids) and adverse effects following opioid administration.

– A physical examination should include, but is not limited to, baseline vital signs, airway, heart, lung and cognitive function.

– Patients with a history of sleep apnea treated with noninvasive positive airway pressure should be encouraged to bring their own equipment to the hospital for periprocedural use.

• Single-injection neuraxial opioids may be safely used in place of parenteral opioids without increasing the risk of respiratory depression or hypoxemia.

• Given the unique pharmacokinetic effect of the various neuraxially administered opioids, appropriate duration of monitoring should be matched with the drug.

• When clinically suitable, extended-release epidural morphine may be used in place of intravenous or conventional (i.e., immediate-release) epidural morphine, although extended monitoring may be required.

• Continuous epidural opioids are preferred to parenteral opioids for anesthesia and analgesia for reducing the risk of respiratory depression.

• When clinically suitable, continuous epidural infusion of fentanyl or sufentanil may be used in place of continuous epidural infusion of morphine or hydromorphone without increasing the risk of respiratory depression.

• Neuraxial morphine or hydromorphone should not be given to surgical outpatients.

• The lowest efficacious dose of neuraxial opioids should be administered to minimize the risk of respiratory depression.

• Parenteral opioids or hypnotics should be cautiously administered in the presence of neuraxial opioids.

• The concomitant administration of neuraxial opioids and parenteral opioids, hypnotics or magnesium requires increased monitoring (e.g., intensity, duration or additional methods of monitoring).

II. Detection:

• All patients receiving neuraxial opioids should be monitored for adequacy of ventilation (e.g., respiratory rate, depth of respiration [assessed without disturbing a sleeping patient]), oxygenation (e.g., pulse oximetry when appropriate) and level of consciousness.

– In the case of single-injection neuraxial lipophilic opioids, continual monitoring should be performed for a minimum of two hours following administration.

– In the case of single-injection hydrophilic neuraxial opioids and all continuous neuraxial opioid infusions, hourly monitoring should be performed during the first 12 hours, and every two hours for the next 12 hours (i.e., 12-24 hours) after administration of the neuraxial opioid.

– For patients administered continuous neuraxial opioids, monitoring after 24 hours should be performed at least once every four hours for the duration of the infusion.

• Increased monitoring (e.g., intensity, duration or additional methods of monitoring) may be warranted in patients at increased risk for respiratory depression (e.g., unstable medical condition, obesity, obstructive sleep apnea, concomitant administration of opioid analgesics or hypnotics by other routes, extremes of age).

• When sustained or extended-release epidural morphine is administered, hourly monitoring should be performed during the first 12 hours and every two hours for the next 12 hours (i.e., 12-24 hours) after administration. Subsequent monitoring should be performed at least once every four hours for a minimum of 48 hours.

III. Management/Treatment:

• For patients receiving neuraxial opioids, supplemental oxygen should be available.

• Supplemental oxygen should be administered to patients with altered level of consciousness, respiratory depression or hypoxemia and continued until the patient is alert and no respiratory depression or hypoxemia is present.

• Routine use of supplemental oxygen may increase the duration of apneic episodes and may hinder detection of atelectasis, transient apnea and hypoventilation.

• In the presence of severe respiratory depression, appropriate resuscitation should be initiated.

Of note, in October 2006, the Anesthesia Patient Safety Foundation (APSF) also convened a workshop that focused on the detection of postoperative (parenteral and neuraxial) opioid-induced respiratory depression [Table 2].

The membership is encouraged to review the summary of the APSF workshop proceedings at www.apsf.org as well as participate in the reference committee discussions of the ASA Practice Guidelines for the Prevention, Detection and Management of Respiratory Depression Associated with Neuraxial Opioid Administration. The complete task force draft document is available on the Society’s Web site www.ASAhq.org/publicationsAndServices/neuraxialopioids.pdf.

Terese T. Horlocker, M.D., is Consultant in Anesthesiology and Professor of Anesthesiology and Orthopedics, Mayo Clinic College of Medicine, Rochester, Minnesota.