1. The incidence of respiratory depression from opioid treatment, acute or chronic, is poorly documented. (Respiratory depression from opioids frequently goes undetected and therefore is underreported) (Table 19-3: Patients at Higher Risk for Opioid-Related Respiratory Depression).
2. The respiratory depressant effects of opioids may be divided into two components.
   1. Suppression of the ventilatory drive (true respiratory depression from the inactivation of respiratory neurons in the brain stem).
   2. Occlusion of the upper airways from either a direct suppression of neurons in the brain stem involved in maintaining the upper airway muscle tone or from the loss of muscle tone related to sedation.
3. Patients receiving opioids, whether diagnosed with obstructive sleep apnea syndrome or not, often develop both central and obstructive apneic events, resulting in recurrent hypoxemia during the first 3 to 5 nights postoperatively.
   1. Although supplemental oxygen results in fewer hypoxic events, it has a serious disadvantage because it masks hypoventilation and early detection of an obstructive respiratory event (the lungs are primed with supplemental oxygen).
   2. Use of a pulse oximeter, especially in the presence of supplemental oxygen administration, is not a valid measure of the adequacy of ventilation.
4. Current methods for monitoring of the electrocardiographic and oxygen saturation and regular nurse visits are insufficient to predict the occurrence of life-threatening respiratory events.
   1. Arousal is wake up from a state of sleep or sedation, allowing the patient to open his or her throat and hyperventilate to overcome the period of hypoxemia. Arousal is triggered by hypoxia and depressed by opioids and sedatives.
   2. Postoperative (nightly) respiratory events are often episodic with arousals and hyperventilation in between events. These events cause repetitive triggering of the oxygen saturation monitoring alarm and possibly alarm fatigue of the nursing staff.
   3. When the alarm is then inactivated or unattended, an arousal failure may occur, which is potentially fatal (Fig. 19-7: Breathing Pattern in Sleep Apnea).
   4. Alarms that give a direct indication of breathing activity are preferable.

Opioids

1. Short History
2. The Endogenous Opioid System
3. Opioid Receptor Knockout Mice
4. Classification of Exogneous Opioids
5. Opioids Acting at Opioid and Nonopioid Receptors
6. Opioid Mechanisms
7. Routes of Administration
8. Pharmcokinetics (PK) and Pharmacodynamics (PD)
9. PKPD Models for Opioid Effect: which End Point Serves the Clinician Best?
10. Pharmacodynamics: Dose Effect on Pain Relief
11. Pharmacogenetics
12. Opioid-Induced Respiratory Depression
13. Other Opioid-Related Side Effects
14. Remifentanil for Obstetric Labor Pain
15. Gender Differences