Pulmonary Vascular Effects of Respiratory Rate & Carbon Dioxide

The Pulmonary Vascular Consequences of Divergent Strategies for Low Tidal Volume Ventilation: Hypercapnia or High Respiratory Rate?

The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia and hypercapnia in the same patient. We will be testing two hypotheses: (1) while administering inspired carbon dioxide (CO2), eucapnia achieved by high respiratory rate (EHR) significantly decreases pulmonary artery pressures compared to hypercapnia with a lower respiratory rate (HLR), and (2) that EHR decreases myocardial strain compared to HLR.

The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia (maintaining alveolar ventilation to target carbon dioxide partial pressure (pCO2) 35-40 mm Hg) and hypercapnia (providing inspired CO2 to target pCO2 55-60 mm Hg) in the same patient. This prospective clinical study will enroll consenting adult patients scheduled for elective cardiac surgery and who require postoperative mechanical ventilation, pulmonary artery (Swan-Ganz) catheter monitoring, and arterial catheterization as part of routine standard care during the immediate postoperative period. The study will perform measurements using available ventilator monitors, ventilator in-line pneumotachograph and capnograph, measurements from the indwelling pulmonary artery catheter, transesophageal echocardiography, and other measurements available as part of routine care. The entire experimental protocol will be performed in one day over 2-4 hours, and the protocol will not interfere with routine postoperative care, nor prolong the need for mechanical ventilation, pulmonary artery catheterization, arterial catheterization, or intensive care unit length of stay.

Ventilation with low tidal volumes has been shown definitively to improve mortality from acute respiratory distress syndrome (ARDS)1 and may provide benefit even in patients without ARDS.2 During low tidal volume ventilation, practice varies on whether to allow some degree of alveolar hypoventilation with incidental hypercapnic acidosis (termed "permissive hypercapnia"),3 or to increase respiratory rate to maintain alveolar ventilation and target eucapnia, often requiring respiratory rates > 30/min.4 The physiological consequences of these divergent strategies remain to be fully elucidated. We propose the following study to distinguish the effects of a eucapnic high respiratory rate (EHR) strategy from a hypercapnic low respiratory rate (HLR) strategy on pulmonary hemodynamics during low tidal volume ventilation.

Specific Aim: To test the hypothesis that, while administering inspired CO2, eucapnia achieved by high respiratory rate (EHR) significantly decreases pulmonary artery pressures compared to hypercapnia with a lower respiratory rate (HLR).

Specific Aim: To test the hypothesis that EHR decreases myocardial strain compared to HLR.

Inclusion Criteria:

• Age ≥ 18 years old.
• Able to consent pre-operatively prior to scheduled cardiac surgery.
• Intubation on mechanical ventilation post-operatively.
• Presence of a pulmonary artery catheter and/or central venous catheter as part of usual care post-operatively.
• Presence of a radial, brachial, or femoral arterial catheter as part of usual care post-operatively.

Exclusion Criteria:

• Significant intra-operative or immediate post-operative complications, such as uncontrolled bleeding or persistent hemodynamic instability.

• Intra-cardiac or intrapulmonary shunt.

• Persistent post-operative moderate or severe hypoxemia, defined as PaO2/FiO2 < 200 mmHg.

• Moderate or severe lung disease, including moderate or severe chronic obstructive pulmonary disease (COPD) or asthma.

• Recently treated for bleeding varices, stricture, or hematemesis, esophageal trauma, recent esophageal surgery, or other contraindication to transesophageal echocardiography.

• Severe coagulopathy (platelet count < 10,000 or international normalized ratio [INR] > 4).

• History of lung, heart, or liver transplant.

• Elevated intracranial pressure or conditions where hypercapnia-induced elevations in intracranial pressure should be avoided, including:

  • Intracranial hemorrhage
  • Cerebral contusion
  • Cerebral edema
  • Mass effect (midline shift on head CT)
  • Flat EEG for > 2 hours

• Evidence of active air leak from the lung, such as broncho-pleural fistula or ongoing air leak from an existing chest tube.

• Treating physician refusal.

• Inability to obtain informed consent directly from the subject prior to surgery.