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 (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.