Ignite Creation Date:
2024-05-05 @ 5:13 PM
Last Modification Date:
2024-10-26 @ 9:29 AM
Study NCT ID:
NCT00416260
Status:
COMPLETED
Last Update Posted:
2014-06-24
First Post:
2006-12-26
Brief Title:
Combined High Frequency Oscillation and Tracheal Gas Insufflation for Severe Acute Respiratory Distress Syndrome
Sponsor:
University of Athens
Organization:
University of Athens
Study Overview
Official Title:
Phase 1Phase 2 Single-Center Controlled Study of the Effectiveness of Combined High Frequency Oscillation and Tracheal Gas Insufflation in Improving the Clinical Course of Patients With Severe Acute Respiratory Distress Syndrome
Status:
COMPLETED
Status Verified Date:
2014-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
In the past five years there is a growing body of published evidence on the feasibility and oxygenation and lung protection benefits of high frequency oscillation HFO in the acute respiratory distress syndrome ARDS The investigators have recently demonstrated the short term feasibility and additional benefits with respect to oxygenation of HFO combined with tracheal gas insufflation TGI In the present clinical trial the investigators intend to test the hypothesis that HFO-TGI may result in improved respiratory physiology and clinical course compared to low tidal volume conventional mechanical ventilation in patients with severe ARDS
Detailed Description:
OBJECTIVES AND UNDERLYING HYPOTHESIS
High frequency oscillation HFO has beneficial physiological effects in acute respiratory distress syndrome ARDS 1-4 A recent randomized controlled trial of HFO versus conventional mechanical ventilation CMV with traditional tidal volumes 101 28 mLkg-1 predicted body weight reported a trend toward reduced 30-day mortality in the HFO arm 37 versus 52 in the CMV group P 010 3 To-date HFO has not been compared to CMV with low tidal volumes 62 11 mLkg-1 predicted body weight in ARDS 5 with respect to respiratory physiology and clinical course
The main mechanisms of gas exchange during CMV are bulk convection and diffusion 4 6 Tracheal gas insufflation TGI promotes CO2 elimination during CMV 7-9 During HFO additional gas exchange mechanisms comprise asymmetric velocity profiles Taylor dispersionturbulence cardiogenic mixing pendelluft effect and collateral ventilation 4 6
We have recently shown that in patients with moderate-to-severe primary ARDS HFO combined with TGI HFO-TGI substantially improves oxygenation relative to both standard HFO and CMV according to the ARDS network protocol 5 10 Mean airway pressure mPaw was set at 1 cm H2O above the point of maximal curvature PMC of the expiratory pressure volume curve During HFO-TGI it is probably feasible to reduce mPaw while still achieving PaO2 and peripheral oxygen saturation SaO2 targets similar to those set by the ARDS network protocol 5 This may result in reduced and non-traumatic ventilation pressures during HFO-TGI Furthermore if HFO-TGI-related gas exchange benefits are maintained during post-HFO-TGI CMV 10 then a reduction of ventilation pressures relative to the pre-HFO-TGI CMV may be feasible as well However the use of reduced ventilation pressures may minimize ventilator associated lung injury In this study we will test the hypothesis that HFO-TGI may improve the respiratory physiology and clinical course of patients with severe ARDS
METHODS Patients
The protocol has been approved by the Scientific Committee of Evaggelismos Hospital Informed consent will be requested from the next-of-kin of participation-eligible patients Eligible patients should fulfill the criteria 1 early diagnosis established within the preceding 72 h ARDS according to the American-European Consensus Conference Criteria 11 2 severe oxygenation disturbances defined as PaO2inspired oxygen fraction FiO2 150 mm Hg while ventilated with a positive end-expiratory pressure PEEP of 8 cm H2O criterion for severe ARDS 3 age 18-75 years body weight 40 kg and absence of a severe air leak ie 1 chest tube per hemithorax with a persistent airleak for 72 h b systolic arterial pressure of 90 mm Hg while receiving fluids and norepinephrine at 05 μgkgmin c significant heart disease ie ejection fraction 40 history of pulmonary edema and active coronary ischemia or myocardial infarction d significant chronic obstructive pulmonary disease COPD or asthma 10 e intracranial abnormalities causing uncontrollable intracranial hypertension f chronic interstitial lung disease associated with bilateral pulmonary infiltrates g lung biopsy or resection on current admission h previous lung or bone marrow transplant or presence of immunosuppression i inability to wean from prone positioning or inhaled nitric oxide k pregnancy or morbid obesity ie body mass index 40 kgm2 and l enrollment in another interventional study Patient monitoring will include electrocardiographic lead II hemodynamics and SaO2 Deep sedationneuromuscular blockade will be employed as previously described 10 12
CMV strategy In the 37-bed intensive care unit ICU of Evaggelismos hospital a ventilatory strategy similar to the ARDS network protocol is routinely employed Consequently before randomization patients will already be ventilated Siemens 300C ventilator or Galileo Gold Hamilton Medical with one of the network-protocol allowable combinations of FiO2 and PEEP 5 Administered tidal volumes will be 55-75 mLkg-1 predicted body weight ventilatory rate eg 20-35min-1 will be adjusted so that pHa is kept within 720-745 the inspiration to expiration duration ratio will be 11 to 13 and the target plateau inspiratory pressure will be 30-35 cm H2O Oxygenation goals will be PaO2 55-80 mm Hg or SaO2 88-95
Randomization Patients will be randomly assigned to either the CMV-group or the HFO-TGI-group CMV-group patients will continue to receive CMV as described above In the HFO-TGI-group 30 min prior to HFO-TGI initiation an inspiratory and an expiratory pressure volume curve will be consecutively constructed with the linear pressure ramp technique whenever clinically feasible 10 13
HFO-TGI strategy The Sensormedics 3100B ventilator 10 will be connected to the endotracheal tube Also a thin Vygon TGI catheter internal external diameter 10 20 mm respectively 10 will be introduced into the endotracheal tube TGI catheter tip will be placed 05-1 cm beyond the endotracheal tube tip The proximal end of the TGI catheter will be connected to an O2 flowmeter Initial HFO settings will be as follows 1 FiO2 100 later-on titrated toward the FiO2 of preceding CMV 2 bias flow 30 Lmin-1 3 oscillation frequency 40-50 Hz 4 oscillatory pressure amplitude arithmetical PaCO2 value during preceding CMV 20-30 cm H2O maximal acceptable value 95-100 cm H2O 10 5 inspiratory to expiratory time ratio 12 and 6 mPaw adjusted so that mean tracheal pressure 2-3 cm H2O above the mean tracheal pressure of the preceding CMV corresponding to an HFO mPaw of 9-10 cm H2O above the preceding CMV mPaw Sixty to 120 secs after HFO initiation a recruitment maneuver will be performed by pressurizing the HFO circuit at 40-45 cm H2O for 20-30 secs with oscillator piston off HFO will then be resumed a 3-5 cm H2O endotracheal tube cuff leak will be placed Immediately thereafter continuous forward thrust TGI flow 50 of the minute ventilation of the preceding CMV 10 will be superimposed on the HFOThe mPaw control knob will then be adjusted to return mPaw to its originally set value Fifteen min thereafter arterial blood gas analysis will be performed and oscillatory pressure amplitude and oscillation frequency will be adjusted in order to achieve a PaCO2 of 10-15 mm Hg above the PaCO2 of the preceding CMV and to keep pHa 720 After another 30-60 min blood gas analysis will be repeated and then mPaw will be gradually reduced estimated reduction rate 0-1 cm H2Oh-1 toward a target mean tracheal pressure of up to 2-3 cm H2O lower than the mean tracheal pressure of the preceding CMV corresponding to an HFO mPaw of 3-4 cm H2O above preceding CMV mPaw Subsequently TGI will be discontinued and standard HFO will be continued for 30 min The aforementioned adjustments should permit maintenance of SaO2 88-95 or PaO2 55-80 mm Hg and of the above-described target PaCO2pHa
Return to CMV will be considered at the following HFO settings mPaw adjusted so that HFO-mean tracheal pressure up to 2-3 cm H2O lower than tracheal pressure of preceding CMV corresponding to an HFO mPaw of 3-4 cm H2O above preceding CMV mPaw FiO2 FiO2 of preceding CMV and TGI 0 Lmin-1 CMV will be resumed and continued provided that PaO2FiO2 is maintained at 150 mm Hg at a PEEP of 8 cm H2O Return to HFO-TGI will be considered necessary if after 12-16 h of CMV PaO2FiO2 is 150 mm Hg at a PEEP of 8 cm H2O In the HFO-TGI-group patients will receive repeated daily sessions of HFO-TGI until they no longer satisfy the severe ARDS criterion during CMV for 24 h Predicted minimum duration of HFO-TGI sessions is 6 h For HFO-TGI-group members total HFO-TGI duration will have to be 12 h
Recruitment Maneuvers
Recruitment maneuvers with continuous positive airway pressure of 40-50 cm H2O and a duration of 20-30 secs will be performed as follows
In the HFO-TGI group recruitment maneuvers will be performed at the onset and at 3 h following the onset of each HFO-TGI session and just prior to return to CMV In the CMV-group 3 recruitment maneuvers one every 3 h first maneuver at 900 am will be performed daily In both groups recruitment maneuvers will be continued as part of the early intervention period of the study protocol until resolution of severe ARDS if achieved or death
Weaning from CMV
Weaning from CMV will be by pressure-supported ventilation when a PaO2 of 60 mm Hg can be maintained at an FiO2 of 50 and a PEEP of 8 cm H2O
Data Collection Data on demographic physiologic and radiographic characteristics coexisting conditions and medication will be recorded within 4 h prior to randomization Physiologic laboratory and radiographicimaging data will be collected daily up to 28 days post-randomization Patients will be monitored daily for signs of failure of nonpulmonary organs and systems
Outcome Measures are reported in the dedicated section
In concordance with a suggestion of a recent Editorial Intensive Care Med 2014 40743-745 the Original and its revision to the Final Form of the Study Protocol also corresponding to NCT00637507 detailing the Pre-specified Study Planning which explains the reason for any prior changes in the current registration data can be found by scrolling down to the end of the following webpage httpwwwevaggelismos-hospgr0010000688CEB9CF83CF84CEBFCF81CEB9CEBACEBF-CEB5CEB5CF80CEBDCEB5html
High frequency oscillation HFO has beneficial physiological effects in acute respiratory distress syndrome ARDS 1-4 A recent randomized controlled trial of HFO versus conventional mechanical ventilation CMV with traditional tidal volumes 101 28 mLkg-1 predicted body weight reported a trend toward reduced 30-day mortality in the HFO arm 37 versus 52 in the CMV group P 010 3 To-date HFO has not been compared to CMV with low tidal volumes 62 11 mLkg-1 predicted body weight in ARDS 5 with respect to respiratory physiology and clinical course
The main mechanisms of gas exchange during CMV are bulk convection and diffusion 4 6 Tracheal gas insufflation TGI promotes CO2 elimination during CMV 7-9 During HFO additional gas exchange mechanisms comprise asymmetric velocity profiles Taylor dispersionturbulence cardiogenic mixing pendelluft effect and collateral ventilation 4 6
We have recently shown that in patients with moderate-to-severe primary ARDS HFO combined with TGI HFO-TGI substantially improves oxygenation relative to both standard HFO and CMV according to the ARDS network protocol 5 10 Mean airway pressure mPaw was set at 1 cm H2O above the point of maximal curvature PMC of the expiratory pressure volume curve During HFO-TGI it is probably feasible to reduce mPaw while still achieving PaO2 and peripheral oxygen saturation SaO2 targets similar to those set by the ARDS network protocol 5 This may result in reduced and non-traumatic ventilation pressures during HFO-TGI Furthermore if HFO-TGI-related gas exchange benefits are maintained during post-HFO-TGI CMV 10 then a reduction of ventilation pressures relative to the pre-HFO-TGI CMV may be feasible as well However the use of reduced ventilation pressures may minimize ventilator associated lung injury In this study we will test the hypothesis that HFO-TGI may improve the respiratory physiology and clinical course of patients with severe ARDS
METHODS Patients
The protocol has been approved by the Scientific Committee of Evaggelismos Hospital Informed consent will be requested from the next-of-kin of participation-eligible patients Eligible patients should fulfill the criteria 1 early diagnosis established within the preceding 72 h ARDS according to the American-European Consensus Conference Criteria 11 2 severe oxygenation disturbances defined as PaO2inspired oxygen fraction FiO2 150 mm Hg while ventilated with a positive end-expiratory pressure PEEP of 8 cm H2O criterion for severe ARDS 3 age 18-75 years body weight 40 kg and absence of a severe air leak ie 1 chest tube per hemithorax with a persistent airleak for 72 h b systolic arterial pressure of 90 mm Hg while receiving fluids and norepinephrine at 05 μgkgmin c significant heart disease ie ejection fraction 40 history of pulmonary edema and active coronary ischemia or myocardial infarction d significant chronic obstructive pulmonary disease COPD or asthma 10 e intracranial abnormalities causing uncontrollable intracranial hypertension f chronic interstitial lung disease associated with bilateral pulmonary infiltrates g lung biopsy or resection on current admission h previous lung or bone marrow transplant or presence of immunosuppression i inability to wean from prone positioning or inhaled nitric oxide k pregnancy or morbid obesity ie body mass index 40 kgm2 and l enrollment in another interventional study Patient monitoring will include electrocardiographic lead II hemodynamics and SaO2 Deep sedationneuromuscular blockade will be employed as previously described 10 12
CMV strategy In the 37-bed intensive care unit ICU of Evaggelismos hospital a ventilatory strategy similar to the ARDS network protocol is routinely employed Consequently before randomization patients will already be ventilated Siemens 300C ventilator or Galileo Gold Hamilton Medical with one of the network-protocol allowable combinations of FiO2 and PEEP 5 Administered tidal volumes will be 55-75 mLkg-1 predicted body weight ventilatory rate eg 20-35min-1 will be adjusted so that pHa is kept within 720-745 the inspiration to expiration duration ratio will be 11 to 13 and the target plateau inspiratory pressure will be 30-35 cm H2O Oxygenation goals will be PaO2 55-80 mm Hg or SaO2 88-95
Randomization Patients will be randomly assigned to either the CMV-group or the HFO-TGI-group CMV-group patients will continue to receive CMV as described above In the HFO-TGI-group 30 min prior to HFO-TGI initiation an inspiratory and an expiratory pressure volume curve will be consecutively constructed with the linear pressure ramp technique whenever clinically feasible 10 13
HFO-TGI strategy The Sensormedics 3100B ventilator 10 will be connected to the endotracheal tube Also a thin Vygon TGI catheter internal external diameter 10 20 mm respectively 10 will be introduced into the endotracheal tube TGI catheter tip will be placed 05-1 cm beyond the endotracheal tube tip The proximal end of the TGI catheter will be connected to an O2 flowmeter Initial HFO settings will be as follows 1 FiO2 100 later-on titrated toward the FiO2 of preceding CMV 2 bias flow 30 Lmin-1 3 oscillation frequency 40-50 Hz 4 oscillatory pressure amplitude arithmetical PaCO2 value during preceding CMV 20-30 cm H2O maximal acceptable value 95-100 cm H2O 10 5 inspiratory to expiratory time ratio 12 and 6 mPaw adjusted so that mean tracheal pressure 2-3 cm H2O above the mean tracheal pressure of the preceding CMV corresponding to an HFO mPaw of 9-10 cm H2O above the preceding CMV mPaw Sixty to 120 secs after HFO initiation a recruitment maneuver will be performed by pressurizing the HFO circuit at 40-45 cm H2O for 20-30 secs with oscillator piston off HFO will then be resumed a 3-5 cm H2O endotracheal tube cuff leak will be placed Immediately thereafter continuous forward thrust TGI flow 50 of the minute ventilation of the preceding CMV 10 will be superimposed on the HFOThe mPaw control knob will then be adjusted to return mPaw to its originally set value Fifteen min thereafter arterial blood gas analysis will be performed and oscillatory pressure amplitude and oscillation frequency will be adjusted in order to achieve a PaCO2 of 10-15 mm Hg above the PaCO2 of the preceding CMV and to keep pHa 720 After another 30-60 min blood gas analysis will be repeated and then mPaw will be gradually reduced estimated reduction rate 0-1 cm H2Oh-1 toward a target mean tracheal pressure of up to 2-3 cm H2O lower than the mean tracheal pressure of the preceding CMV corresponding to an HFO mPaw of 3-4 cm H2O above preceding CMV mPaw Subsequently TGI will be discontinued and standard HFO will be continued for 30 min The aforementioned adjustments should permit maintenance of SaO2 88-95 or PaO2 55-80 mm Hg and of the above-described target PaCO2pHa
Return to CMV will be considered at the following HFO settings mPaw adjusted so that HFO-mean tracheal pressure up to 2-3 cm H2O lower than tracheal pressure of preceding CMV corresponding to an HFO mPaw of 3-4 cm H2O above preceding CMV mPaw FiO2 FiO2 of preceding CMV and TGI 0 Lmin-1 CMV will be resumed and continued provided that PaO2FiO2 is maintained at 150 mm Hg at a PEEP of 8 cm H2O Return to HFO-TGI will be considered necessary if after 12-16 h of CMV PaO2FiO2 is 150 mm Hg at a PEEP of 8 cm H2O In the HFO-TGI-group patients will receive repeated daily sessions of HFO-TGI until they no longer satisfy the severe ARDS criterion during CMV for 24 h Predicted minimum duration of HFO-TGI sessions is 6 h For HFO-TGI-group members total HFO-TGI duration will have to be 12 h
Recruitment Maneuvers
Recruitment maneuvers with continuous positive airway pressure of 40-50 cm H2O and a duration of 20-30 secs will be performed as follows
In the HFO-TGI group recruitment maneuvers will be performed at the onset and at 3 h following the onset of each HFO-TGI session and just prior to return to CMV In the CMV-group 3 recruitment maneuvers one every 3 h first maneuver at 900 am will be performed daily In both groups recruitment maneuvers will be continued as part of the early intervention period of the study protocol until resolution of severe ARDS if achieved or death
Weaning from CMV
Weaning from CMV will be by pressure-supported ventilation when a PaO2 of 60 mm Hg can be maintained at an FiO2 of 50 and a PEEP of 8 cm H2O
Data Collection Data on demographic physiologic and radiographic characteristics coexisting conditions and medication will be recorded within 4 h prior to randomization Physiologic laboratory and radiographicimaging data will be collected daily up to 28 days post-randomization Patients will be monitored daily for signs of failure of nonpulmonary organs and systems
Outcome Measures are reported in the dedicated section
In concordance with a suggestion of a recent Editorial Intensive Care Med 2014 40743-745 the Original and its revision to the Final Form of the Study Protocol also corresponding to NCT00637507 detailing the Pre-specified Study Planning which explains the reason for any prior changes in the current registration data can be found by scrolling down to the end of the following webpage httpwwwevaggelismos-hospgr0010000688CEB9CF83CF84CEBFCF81CEB9CEBACEBF-CEB5CEB5CF80CEBDCEB5html
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None