Clinical Trial: Physiological Study of Low-frequency HFO/HFO-TGI and High-frequency HFO

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Comparison of Cardio-respiratory Variables Between Low-frequency High Frequency Oscillation With/Without Tracheal Gas Insufflation and High-frequency High-frequency Oscillation in Severe ARDS.

Brief Summary: Recent data from large trials of high-frequency high frequency oscillation (HFO) without a cuff leak vs, lung-protective conventional ventialtion (CMV) failed to show any HFO-related benefit with respect to outcome. A possible explanation is that HFO increases the probability of right ventricular dysfunction due to the combination of high mean airway pressures (mPaws) and hypercapnia. In contrast, available preliminary data on low-frequency HFO-tracheal gas insufflation (TGI) with cuff leak vs. CMV are suggestive of an HFO-TGI related benefit. Low-frequency HFO-TGI with a cuff leak is associated with relatively low mean tracheal pressures and adequate control of PaCO2. Thus, the investigators intend to test the hypothesis that low frequency HFO +/- TGI with a cuff leak is associated with better right ventricular function relative to high-frequency HFO without a cuff leak.

Detailed Summary:

Rationale of the study Acute Respiratory Distress Syndrome (ARDS) is an acute inflammatory state of the pulmonary parenchyma that causes hypoxemia, atelectasis, pulmonary congestion, and reduction in pulmonary compliance. Mechanical ventilation is actually life-saving, but it may traumatize the lungs (e.g. volutrauma, barotrauma, atelectrauma, and biotrauma). The use of low tidal volumes and high positive end-expiratory pressure (PEEP), aims at attenuating ventilator-associated lung injury. However, ARDS mortality still remains high. High frequency oscillation (HFO) is an alternative ventilatory technique that employs very low tidal volumes (1-4 ml/kg) administered at high frequencies (3-15 Hz). Prior observational studies have reported improvements in oxygenation, whereas recent two-center data on severe ARDS suggest a survival benefit from the intermittent, combined use of low-frequency HFO with a cuff leak, Recruitment maneuvers (RMs), and tracheal gas insufflation (TGI). The addition of TGI improves oxygenation and CO2 elimination; however, it is still unclear whether it affects survival. Two recently published multicenter studies showed either neutral (10) or negative results (11) with respect to survival when high frequency HFO without a cuff leak was used in the treatment of early ARDS. However, these negative results may be partly due to right ventricular overload/dysfunction/failure caused by the combination of high intrathoracic pressures and hypercapnia, with consequent hemodynamic instability and increased need of inotropic/vasopressor support. Accordingly, the investigators hypothesize that a different HFO strategy [employing a combination of a low frequency and a cuff leak - which augments CO2 elimination and is associated with relatively low mean tracheal pressures - could lead to different results.

A high intrathoracic pressure may impede venous return and
Sponsor: University of Athens

Current Primary Outcome:

  • Right ventricular diastolic area, left ventricular diastolic area as determined by transesophageal echocardiography during the application of the tested ventilatory strategies. [ Time Frame: Within 6-7 hours after study enrollment ]
  • Eccentricity index as determined by transesophageal echocardiography during the application of the tested ventilatory strategies [ Time Frame: Within 6-7 hours after study enrollment ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • PaO2, PaCO2 and arterial pH during the application of the tested ventilatory strategies [ Time Frame: Within 6-7 hours after study enrollment ]
  • Mean arterial pressure during the application of the tested ventilatory strategies [ Time Frame: Within 6-7 hours after study enrollment ]
  • Cardiac index during the application of the tested ventilatory strategies [ Time Frame: Within 6-7 hours after study enrollment ]
  • Static Compliance of the Respiratory System before and after the application of the tested HFO strategies [ Time Frame: Within 6-7 hours after study enrollment ]


Original Secondary Outcome: Same as current

Information By: University of Athens

Dates:
Date Received: January 2, 2014
Date Started: January 2014
Date Completion:
Last Updated: October 3, 2016
Last Verified: October 2016