Recovery of Ventilation After General Anesthesia in Morbidly Obese Patients

Obstructive sleep apnea (OSA) increases the risk for pulmonary complications in the first 24 hours after surgery, by more than 3-fold, suggesting an enhanced sensitivity to opioid-induced ventilatory depression (OIVD), in this patient population. Obesity and OSA, two highly comorbid conditions, are common among victims of postoperative life-threatening or fatal OIVD and increased somnolence preceding the onset of a critical event, is an almost ubiquitous clinical finding.

These clinical observations are in agreement with recent evidence that decreased wakefulness is an important contributory mechanism of OIVD in OSA patients who receive opioid analgesia in the postoperative period. Studies that examined the effect of opioids on breathing in awake, sleeping, or anesthetized patients with OSA, support overall that OSA is not associated with increased sensitivity to OIVD in awake subjects. In contrast, diminished wakefulness has been shown to worsen, leave unaffected, or even slightly improve breathing and oxygenation in patients with OSA, who are treated opioids.

Decrease in the tonic activity of the pharyngeal muscles with the progression from wakefulness to sleep, contributes to increased airway resistance and the predisposition to airway occlusion. This effect of sleep on the patency of pharyngeal airway seems to be more pronounced in patients with OSA, who present with increased genioglossus muscle activity during wakefulness taken as evidence for a neural compensation to maintain adequate airflow in the presence of anatomical airway narrowing.

It can thus be suggested that during pharmacological suppression of consciousness, like when recovering from anesthesia, patients with OSA will experience more severe sleep-disordered breathing and consequently be more vulnerable to OIVD, compared to normal subjects.

Specific Aims

Specific Aim 1: To assess opioid-induced ventilatory depression in morbidly obese patients with OSA, who recover from general anesthesia and are treated for pain with fentanyl. We will develop a pharmacodynamic model for OIVD to assess the effect of OSA status (i.e., moderate-to-severe OSA vs. no or mild OSA) on the probability for TcPCO2 to exceed a pre-specified threshold during recovery from anesthesia.

Specific Aim 2: To assess the effect of baseline TcPCO2 on the probability for TcPCO2 to exceed a pre-specified threshold during recovery from anesthesia, independently of the OSA status.

Specific Aim 3: To assess the effect of the minimum positive airway pressure (minPAP) that prevents obstructive breathing during sleep (estimated during in-lab polysomnography) on the probability for TcPCO2 to exceed a pre-specified threshold, during recovery from anesthesia.

Hypotheses:

1. Patients with moderate-to-severe OSA will demonstrate a higher probability for exceeding a pre-specified threshold for TcPCO2, compared to those with mild or no OSA, during recovery from general anesthesia.

2. Patients who present with higher TcPCO2 at baseline, will present with a higher probability to exceed a pre-specified threshold for TcPCO2, independently of their OSA status, compared to those with normal ventilatory control at baseline, during recovery from anesthesia.

3. Patients with higher therapeutic PAP level (hence more collapsible airway) will be more sensitive to fentanyl-induced ventilatory depression and will thus demonstrate a higher probability for exceeding a pre-specified threshold for TcPCO2 during recovery from anesthesia.