The Effects of Different Ventilator Strategies on Inflammation and Injury in Normal Lungs

• arterial blood gases [ Time Frame: during the operative procedure ] [ Designated as safety issue: Yes ]
• subject post-operative outcome:mortality, pulmonary complications, major cardiac morbidity, LOS, readmission [ Time Frame: wothin 30 days of surgery ] [ Designated as safety issue: No ]

This research is being done to determine if there is a way the investigators can improve the techniques that they use to assist patients with their breathing during surgery. The majority of surgeries require patients to concurrently undergo general anesthesia. This usually includes a breathing tube and a machine that breathes for the patient during the duration of the surgery. The doctors would like to investigate the effects of this type of anesthesia to healthy adult patients and whether they can improve the way they give general anesthesia to patients. The investigators plan to ask approximately 200 patients to participate. If the patients decide to participate in the study,some additions will be made to the standard anesthetic care they receive. The patients will additionally be monitored for adequate oxygenation in their blood as well as level of inflammation in their blood and lungs. The patients' breathing tube will be bathed with warm normal saline and suctioned twice during the operation. When these procedures are done the patients will be asleep and not be aware of what is happening.

The ability to provide mechanical ventilation that will not injure and may protect normal lungs during major surgical procedures of long duration may improve postoperative outcomes and decrease morbidity and mortality. The aim of the current study was to identify ventilator strategies that are less damaging to normal lungs. The investigators plan to compare three ventilation strategies commonly utilized in the operating room in normal lungs. One group will be ventilated with high tidal volume (15 mL/kg PBW) and low PEEP (3 cm H2O), another group ventilated with low tidal volume (6 mL/kg PBW) and low PEEP (3 cm H2O) and the final group ventilated with low tidal volume (6 mL/kg PBW) and high PEEP (10 cm H2O). This study will show the effects of these commonly used methods of ventilation on pulmonary mechanics, systemic and pulmonary inflammatory markers and outcomes in patients with normal lungs undergoing surgery of long duration.

• Active Comparator: 1
  High tidal volume (15mL/kg PBW0 with low PEEP (3cm H2O
  Intervention: Other: Ventilator settings
• Active Comparator: 2
  Low tidal volume (6mL/kg PBW) and high PEEP (3cm H2O)
  Intervention: Other: Ventilator settings
• Active Comparator: 3
  low tidal volume (6mL/kg PBW) and high PEEP (10cm H2O)
  Intervention: Other: Ventilator settings

• Wrigge H, Zinserling J, Stüber F, von Spiegel T, Hering R, Wetegrove S, Hoeft A, Putensen C. Effects of mechanical ventilation on release of cytokines into systemic circulation in patients with normal pulmonary function. Anesthesiology. 2000 Dec;93(6):1413-7.
• Wrigge H, Uhlig U, Baumgarten G, Menzenbach J, Zinserling J, Ernst M, Drömann D, Welz A, Uhlig S, Putensen C. Mechanical ventilation strategies and inflammatory responses to cardiac surgery: a prospective randomized clinical trial. Intensive Care Med. 2005 Oct;31(10):1379-87. Epub 2005 Aug 17.

Inclusion Criteria:

• Elective surgery under general anesthesia expected to take 4 hours or more positioned supine for surgery

Exclusion Criteria:

• Subjects who have HIV or who have had Radiation or chemotherapy for cancer
• Subjects undergoing surgery on chest or lings
• Subjects who have obstructive sleep apnea (OSA), asthma, tuberculosis, chronic obstructive pulmonary disease