Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01927237
First received: August 20, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Low Tidal Volume Ventilation
Acute Respiratory Distress Syndrome
Other: HLR
Other: EHR

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: The Pulmonary Vascular Consequences of Divergent Strategies for Low Tidal Volume Ventilation: Hypercapnia or High Respiratory Rate?

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • mean pulmonary artery pressure (mPAP) [ Time Frame: 4 hours ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Right ventricular systolic function [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    Right ventricular systolic function will be assessed using strain echocardiography or peak tricuspid annular systolic velocity.


Enrollment: 0
Study Start Date: September 2013
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HLR-first
Patients in this arm will have the "hypercapnia with low respiratory rate" (HLR) strategy first. Once hypercapnia is achieved via inspired carbon dioxide, no additional changes will be made to the ventilator. Once steady-state is achieved, physiological measurements will be taken. The patient will be returned to baseline settings for a 15-minute "rest period" before starting the EHR strategy per the cross-over design.
Other: HLR
Other Name: hypercapnia with low respiratory rate
Other: EHR
Other Name: eucapnia with high respiratory rate
Experimental: EHR-first
Patients in this arm will have the "eucapnia with high respiratory rate" (EHR) strategy first. Once hypercapnia is achieved via inspired carbon dioxide, respiratory rate will be increased until PetCO2 returns to baseline or up to 35 breaths per minute, as limited by the National Heart Lung and Blood Institute (NHLBI) ARDS Network protocol. fraction of inspired oxygen inspired oxygen fraction and set tidal volume will be maintained. Once steady-state is achieved, physiological measurements will be taken. The patient will be returned to baseline settings for a 15-minute "rest period" before starting the HLR strategy per the cross-over design.
Other: HLR
Other Name: hypercapnia with low respiratory rate
Other: EHR
Other Name: eucapnia with high respiratory rate

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01927237

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02122
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Daniel Talmor, MD MPH Beth Israel Deaconess Medical Center
  More Information

Publications:
Responsible Party: Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01927237     History of Changes
Other Study ID Numbers: 2013-P-000222
Study First Received: August 20, 2013
Last Updated: August 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
pulmonary artery pressure
ARDS
alveolar hypoventilation
hypercapnic acidosis
permissive hypercapnia
myocardial strain

Additional relevant MeSH terms:
Acute Lung Injury
Hypercapnia
Respiratory Distress Syndrome, Adult
Respiratory Distress Syndrome, Newborn
Infant, Newborn, Diseases
Infant, Premature, Diseases
Lung Diseases
Lung Injury
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms
Signs and Symptoms, Respiratory

ClinicalTrials.gov processed this record on November 25, 2014