Echocardiographic Detection of Extravascular Lung Water Increase During Weaning From Mechanical Ventilation
Condition: Ventilator Weaning
Study type: Interventional

Summary: 
      Switching from positive airway pressure ventilation to spontaneous ventilation during weaning
      from mechanical ventilation, pulmonary edema may occur and in this case, doppler
      echocardiographic (U/S) indices of cardiac dysfunction correlates with the concentration of
      fluid in interstitial space.

      Forty consecutive mechanically ventilated critical ill patients who fulfill criteria for
      weaning from mechanical ventilation, will be included in this study. All patients will be
      evaluated daily and when the patients fulfill weaning criteria them they will undergo a
      2-hour spontaneous breathing trial (SBT) through a T-piece.

      Before and after SBT cardiopulmonary function will be assessed by thermodilution and
      echocardiography. In patients with preserved LV systolic function, an echocardiographic index
      of diastolic dysfunction (E/Em ratio) before preforming SBT may identify high risk patients
      for increasing extravascular water in weaning.

      In addition, the investigators expect to find positive correlations (p<0.05) between
      pulmonary extravascular lung water and echocardiographic indices (such as E/Em ratio) during
      SBT.
    

Detailed description: 
      Pulmonary edema (PE) is an underestimated factor of weaning failure. The interruption of
      mechanical ventilation

        1. increases left ventricular (LV) afterload, sympathetic tone and may provoke myocardial
           schema, LV dysfunction and

        2. augments blood in-flow into the thorax and may cause right ventricular dilation and
           intraventricular septum left shift.

      These events may impair LV compliance during weaning, increase intra-capillary pulmonary
      pressures and cause cardiogenic PE (CPE). The investigators have recently shown that LV
      diastolic dysfunction may predispose to weaning failure, while echocardiographic markers of
      CPE may provide further insight in weaning process. Notably, this could be especially true in
      chronic obstructive pulmonary disease patients where strategies aiming to manage heart
      failure (i.e. diuretics, nitroglycerin) has been shown to improve weaning outcomes.

      In addition, vigorous inspiratory efforts against the endotracheal tube during spontaneous
      weaning trials may reduce excessively extracapillary pressures in pulmonary interstitial
      spaces, causing an intra-pulmonary fluid shift known as negative pressure PE (NPPE).

      Primary aim: To study whether echocardiographic parameters of left and right ventricular
      function, and echocardiographic surrogates of cardiogenic PE (markers of elevated LV filling
      pressures, such as E/Em) are associated to weaning-induced alterations in extravascular lung
      water index (EVLWI).

      Hypothesis A) Switching from positive airway pressure ventilation to spontaneous ventilation
      during weaning from mechanical ventilation, pulmonary edema may occur and in this case,
      doppler echocardiography (U/S) indices of cardiac dysfunction correlates with the
      concentration of fluid in interstitial space.

      B) These events can be further provoked after Maximum Inspiratory Pressure (MIP) trials.

      C) Pulmonary edema is a major cause of weaning failure in chronic obstructive pulmonary
      disease (COPD) patients, even in those without known cardiac disease.

      SUBJECTS Thirty-five consecutive mechanically ventilated critical ill patients who fulfil
      criteria for weaning, will be included.

      METHODS All patients will be evaluated daily for the aforementioned weaning criteria and when
      the patients fulfill them they will undergo A) a 2-hour spontaneous breathing trial (SBT)
      through a T-piece and B) MIP trial.

      Before and after SBT and MIP trials cardiopulmonary function will be assessed by
      thermodilution and echocardiography.

      Extravascular Lung Water Index (EVLWI) study. EVLWI will be assessed by transpulmonary
      thermodilution (PiCCO plus system, Pulsion Medical Systems and Philips Medical Systems, USA).
      Transpulmonary thermodilution measures left-side CO by injection of a cold injectate (15-20
      ml,10C lower than blood temperature) via subclavian or internal jugular vein and by the
      detection of the change in temperature in the arterial system via femoral access. Analysis of
      the thermodilution curve in terms of mean transit time (MTt) and downslope time (DSt) will be
      used for determination of intra and extra vascular fluid volumes. EVLW correlates to the
      extravascular thermal volume in the lungs and it is evaluated through the MTt.

      Principle parameters obtained by transpulmonary thermodilution are following

        -  cardiac output (absolute/indexed parameters, CO/CI)

        -  cardiac function index (CFI)

        -  extravascular lung water (EVLW/EVLWI)

        -  pulmonary vascular permeability index (PVPI)

        -  global ejection fraction (GEF)

      Echocardiographic study. Baseline Doppler echocardiographic measurements will be obtained
      before SBT initiation, while participants will be in pressure support ventilation (pre-SBT).
      Follow up measurements (end-SBT) in patients who succeeded in the trial, will be collected
      120 minutes after SBT initiation. In those participants who fail the procedure, measurements
      will obtained before reconnection to the ventilator. Doppler echocardiography will be
      performed as previously described (Philips i33, U.S.A.). Mitral inflow pulsed-wave Doppler
      signals [peak velocities of early (E) and late (A) LV diastolic filling, E-wave deceleration
      time (DTE)], Tissue Doppler Imaging(TDI)-derived peak systolic (Sm)/early diastolic (Em)/late
      diastolic (Am) velocities at the lateral/septal mitral annulus and lateral tricuspid annulus,
      and color M-mode Doppler velocity of propagation (Vp) will be obtained from the apical
      4-chamber view. Analysis will be also performed for "conventional" (E/A ratio) and "advanced"
      (E/Em, ) echocardiographic indices of LV filling pressures.

      Expected Results Recruitment period: three months Analysis of results: three months Based on
      a previous study contacted by the investigators, echocardiographic variables of LV diastolic
      dysfunction is expected to be found associated with direct measurements of pulmonary edema
      (EVLWI). In participants with preserved LV systolic function, an E/Em ratio>7.8 before
      preforming SBT may identify high risk patients for increasing extravascular water in weaning.

      Based on preliminary findings EVLWI values measured in critical patients by the investigators
      were 2-11 ml/Kg.

      The investigators expect to find positive correlations (p<0.05) between EVLWI and E/Em during
      SBT and MIP trials.

      Implications:

      The findings of the study will provide further insights in the pathophysiology of weaning.
      This could be especially true in COPD patients where failure rates are high.

      Diagnosis of weaning failure and identification of those patients who are prone to develop LV
      dysfunction during weaning and weaning outcomes may improve with the application of
      strategies aiming to manage heart failure (i.e diuretics, nitroglycerin).

      EVLW measurements and DE indices will be use as an aid to diagnose and to determine the
      etiology of pulmonary edema in critical care patients.

      These indices may retain the predictive value even in the subset of patients who initially
      pass SBT; therefore, E/Em pre-SBT could identify patients who will probably fail to remain in
      SBT.

      The relationship between DE indices and EVLWI could be advantageous compared to EVLWI
      measurement alone, for the quantification of lung edema and the guidance of therapy.
    

Intervention name(s): Monitoring of pulmonary oedema induced by weaning from mechanical ventilation
Intervention type(s): Other
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic