Recovery of Ventilation After General Anesthesia in Morbidly Obese Patients
Recovery of Ventilation After General Anesthesia in Morbidly Obese Patients
This is an observational study of morbidly obese patients recovering from general anesthesia
 after weight-loss surgery. The investigators aim to assess ventilatory function and how this
 is influenced by the diagnosis of obstructive sleep apnea (OSA), baseline ventilatory status,
 as well as pharyngeal collapsibility of patients who are recovering from anesthesia and
 treated for pain with opioids. The investigators hypothesize that patients with OSA, chronic
 (baseline) hypoventilation and increased pharyngeal collapsibility, will be more vulnerable
 to opioid-induced ventilatory depression.
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.
Inclusion Criteria:

 -  Body mass index (BMI) equal or greater than 35 kg/m2.

 -  American Society of Anesthesiologists (ASA) physical status I - III patients.

 -  Scheduled to undergo laparoscopic roux-en-Y gastric bypass or gastric sleeve placement
 surgery for weight loss.

 Exclusion Criteria:

 -  Chronic obstructive pulmonary disorder (COPD).

 -  Treatment with continuous positive airway pressure (CPAP) in the past three months.

 -  Severe neurological, cardiopulmonary, psychiatric, or untreated thyroid disorder.

 -  Chronic pain condition that was being treated with opioids.

 -  Patients with a hematocrit lower than 35%.