Pulmonary Vascular Effects of Respiratory Rate & Carbon Dioxide

Acute Respiratory Distress Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01927237
• Other study ID #: 2013P000222
• Status: Withdrawn
• Phase: N/A
• First received: August 20, 2013
• Last updated: February 24, 2017
• Start date: September 2013
• Est. completion date: August 2014

Study information

• Verified date: August 2014
• Source: Beth Israel Deaconess Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Low Tidal Volume Ventilation
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Other:
• HLR

• EHR

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Beth Israel Deaconess Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (5)

Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. — View Citation

Malhotra A. Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 2007 Sep 13;357(11):1113-20. Review. — View Citation

Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. — View Citation

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012 Oct 24;308(16):1651-9. doi: 10.1001/jama.2012.13730. — View Citation

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. N Engl J Med. 2000 May 4;342(18):1301-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	mean pulmonary artery pressure (mPAP)	Pulmonary artery pressure will be measured directly by transducing the pulmonary artery catheter, and will include systolic (PASP) and diastolic (PADP) Ppa. The mean pulmonary artery pressure (mPAP) will be calculated according to the formula: mPAP = 1/3 PASP + 2/3 PADP	4 hours
Secondary	Right ventricular systolic function	Right ventricular systolic function will be assessed using strain echocardiography or peak tricuspid annular systolic velocity.	4 hours