Pulmonary Vascular Effects of Respiratory Rate & Carbon Dioxide

NCT01927237 | Withdrawn

• 1 other identifier: 2013P000222
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Low Tidal Volume Ventilation; Acute Respiratory Distress Syndrome

Keywords

pulmonary artery pressure; ARDS; alveolar hypoventilation; hypercapnic acidosis; permissive hypercapnia; myocardial strain

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Right ventricular systolic function

  4 hours

Study Arms (2)

HLR-first

EXPERIMENTAL

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: EHR

EHR-first

EXPERIMENTAL

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: EHR

Interventions

HLR OTHER

Also known as: hypercapnia with low respiratory rate

EHR-first; HLR-first

EHR OTHER

Also known as: eucapnia with high respiratory rate

EHR-first; HLR-first

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02122, United States

Location

Related Publications (5)

• Malhotra A. Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 2007 Sep 13;357(11):1113-20. doi: 10.1056/NEJMct074213.

  PMID: 17855672 BACKGROUND

• Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Esposito 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.

  PMID: 23093163 BACKGROUND

• 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. doi: 10.1056/NEJM199802053380602.

  PMID: 9449727 BACKGROUND

• 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. doi: 10.1056/NEJMoa050333.

  PMID: 16236739 BACKGROUND

• Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.

  PMID: 10793162 BACKGROUND

MeSH Terms

Conditions

Respiratory Distress Syndrome; Hypoventilation; Acidosis, Respiratory

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Daniel Talmor, MD MPH

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Edward Lowenstein Professor of Anaesthesia

Study Record Dates

• First Submitted: August 20, 2013
• First Posted: August 22, 2013
• Study Start: September 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: February 27, 2017

Record last verified: 2014-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)