Respiratory Control and Narcotic Effects

The aim of this study is to provide data that will assess the role of ventilatory chemosensitivity (respiratory drive) in determining postoperative respiratory depression due to opioids. In a group of patients requiring surgery and admission to hospital, before surgery, ventilatory chemosensitivity will be assessed in the presence or absence of an infusion of remifentanil. Parameters will be correlated with ventilatory depression events after surgery. A secondary aim is to determine whether respiratory depression is more likely during specific phases of sleep.

The study aims to test the following hypotheses:

Low respiratory drive is predictive of opioid-induced respiratory depression as defined by end-tidal PCO2 (PETCO2) \>50 mmHg, ventilation \<20% below baseline or pulse oximeter reading (SpO2) \<90%.

Respiratory depression is more likely during certain sleep stages, specifically slow wave sleep.

Respiratory Drive. Before surgery each patient's hypercapnic ventilatory response under conditions of mild hypoxia and mild hyperoxia. Using this technique, the patient first voluntarily hyperventilates to a PETCO2 value of 20-25 mmHg, then undergoes a rebreathing test allowing the PCO2 to rise to 55-60 mmHg while end-tidal PO2 (PETO2) is maintained at 150 mmHg. The procedure is then repeated with PETO2 clamped at 50 mmHg. Parameters derived from this method include slopes of the ventilatory response during hyperoxia and hypoxia. The slope during mild hypoxia is felt to be an index of peripheral chemoreceptor function, while the hyperoxic slope is more indicative of central respiratory drive.

These two maneuvers will then be repeated during an infusion of the ultra-short acting opioid, remifentanil. Remifentanil will be administered to achieve a specified effect site concentration selected to produce a 30% decrease in ventilation using a standard pharmacokinetic model implemented on a widely-used shareware program (TIVATrainer, www.eurosaver.eu). Recovery from ventilatory depression occurs within 10 minutes of discontinuation of the infusion.

Sleep Test. During a night before surgery a sleep test based on peripheral arterial tone will be performed at home (WatchPAT™, Itamar Medical, Franklin, MA) and will provide a formal measure of obstructive sleep apnea. This test requires only a device mounted on a finger that assesses SpO2 and peripheral tone, and an accelerometer on the chest to assess breathing movements. Respiratory indices calculated using this technology correlates with those calculated from standard polysomnography. The same testing will be used postoperatively from the time the patient enters the post anesthesia care unit (PACU) until the following morning. Recording of the same variables will then continue: inter-breath interval, respiratory minute volume (using an electrical impedance device: ExSpiron™, Respiratory Motion, Waltham, MA), abdominal strain gauge recording, transcutaneous PCO2 (SenTec, Fenton, MO), and sleep measures. The data stream will then be divided into 5 minute epochs. During each epoch the sleep state (awake, stages 1-4 slow wave sleep, rapid eye movement (REM) sleep), opioid consumption, respiratory variables and apnea/hypopnea index (AHI) will be assessed. Subjects will have the option to opt in or out of participation in the overnight sleep study.

Long-Term Pulse Oximetry. For the entire postoperative period until discharge we will record opioid consumption and SpO2/heart rate using a wrist oximeter (WristOx™, Nonin Medical, Plymouth, MN).

Postoperative parameters of respiratory depression include hypercapnia (transcutaneous PCO2), hypoxemia, apneas, low respiratory minute volume and sleep state.

Eligibility Criteria:
Inclusion Criteria:

18 years of age or older, undergoing major abdominal or urological surgery requiring at least one overnight hospital stay

Exclusion Criteria:

Pregnancy Adverse reaction to remifentanil Opioid-use within the past month Dependency on supplemental oxygen Brain injury in the past year Coronary artery disease Sickle cell disease.