Intensive Alveolar Recruitment Protocol After Cardiac Surgery

• Sponsor: University of Sao Paulo (Other)
• Overall Status: Completed
• CT.gov ID: NCT01502332
• Collaborator: InCor Heart Institute (Other)
• Enrollment: 320
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 11.9

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate prospectively the impact of two protective mechanical ventilation strategies, both using low tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery. The study selected patients presenting signals of deficient gas exchange (PaO2/FIO2 < 250 at a PEEP [positive end expiratory pressure] of 5 cmH2O) in the immediate post-operative period. An aggressive alveolar recruitment protocol applying opening pressures of 45 cmH2O, followed by ventilation with PEEP = 13 cmH2O, was compared to the standard alveolar recruitment protocol of the institution, where an opening pressure of 20 cmH2O in the airways is followed by ventilation with PEEP = 8 cmH2O. After a stabilizing period of four hours of controlled mechanical ventilation, the patients followed the routine weaning protocol and physiotherapy protocol of the institution.

Condition or Disease	Intervention/Treatment	Phase
Ventilator Induced Lung Injury; Cardiac Disease; Acute Lung Injury	Other: Intensive Alveolar Recruitment; Other: Moderate Alveolar Recruitment	N/A

Detailed Description

The postoperative period of cardiac surgery is associated with the development of pulmonary complications. Functional residual capacity can be reduced up to 50% and pulmonary volumes may be decreased until three months after surgery.

Lung injury is the result of pulmonary inflammation (activated by cardiopulmonary bypass, the surgical procedure itself and ischemia-reperfusion injury), the adopted mechanical ventilation strategy and a consequence of previous cardiac and/or pulmonary dysfunction.

The use of protective mechanical ventilation strategies with low tidal volumes since the immediate postoperative period, or since the operating room, has been shown to attenuate and prevent lung injury in previous studies selecting with high-risk patients.

A more complex topic, however, has been the proof of the additional benefit of alveolar recruitment maneuvers during the brief period of mechanical ventilation after surgery. While the experimental evidence suggests that the use of an open lung approach could minimize the shearing forces in the lung parenchyma, enhancing the protection afforded by low tidal volume ventilation, innumerous concerns about the hemodynamic side effects, and the possibility of barotrauma have prevented the routine use of intensive alveolar recruitment protocols. Another matter of concern is the net efficacy of a recruitment maneuver applied in the post-operative period, instead of the intra-operative period.

Thus, this study compared the impact of two protective mechanical ventilation strategies, both using low-tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery, in a selective population of patients presenting signals of deficient gas exchange (PaO2/FIO2 < 250 at a PEEP of 5 cmH2O) in the immediate post-operative period. In a previous study at this institution, this subgroup of patients was shown to be at higher risks of postoperative pulmonary complications.

During the short period of controlled mechanical ventilation after the patient arrival from the operating theater, an aggressive alveolar recruitment protocol applying opening pressures of 45 cmH2O, followed by ventilation with PEEP = 13 cmH2O, was compared to the standard alveolar recruitment protocol of the institution, where an opening pressure of 20 cmH2O in the airways is followed by ventilation with PEEP = 8 cmH2O. After an stabilizing period of four hours of controlled mechanical ventilation, the patients followed the routine weaning protocol and physiotherapy protocol of the institution.

Our hypothesis was that the aggressive alveolar recruitment strategy might help in the reversal of collapse created during the surgery and short term mechanical ventilation during anesthesia and patient transportation. Previous studies have shown that this effect may extend to the post-extubation period, impairing lung function for a few days.

Thus, we tested if the effect of an aggressive alveolar recruitment protocol was translated in a better lung compliance, better gas exchange, and fewer pulmonary complications in the post-operative periods (this latter was our primary outcome). Analysis of the length of stay was also scrutinized, consisting in our secondary outcome. All hemodynamic complications was reported, since we also anticipated that events of hemodynamic impairment might be more frequent in the aggressive recruitment arm, eventually obscuring the expected benefits .

Study Design

• Study Type: Interventional
• Actual Enrollment: 320 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparison of Two Protective Mechanical Ventilation Strategies After Cardiac Surgery: Aggressive Versus Moderate Alveolar Recruitment Strategies
• Study Start Date: Dec 1, 2011
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intensive Alveolar Recruitment Recruitment with opening pressures of 45 cmH2O in the airways.	Other: Intensive Alveolar Recruitment; Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with tidal volume (VT) = 6 mL/kg/pbw.
Active Comparator: Moderate Alveolar Recruitment Recruitment with opening pressures of 20 cmH2O in the airways.	Other: Moderate Alveolar Recruitment; Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.

Outcome Measures

Primary Outcome Measures

1. Severity of Pulmonary Complications in the Post-operative Period [Participants were followed for the duration of hospital stay.]

   Score of pulmonary complications adapted from previous publications, with 5 degrees, where the higher one means death before hospital discharge, degree (4) means the need of mechanical ventilation for more than 48 hours after surgery or after reintubation, degree (3) means pneumonia or intense noninvasive ventilation need, degree (2) means hypoxemia and abnormal lung findings, degree 1 means simple atelectasis and degree (0) means no complication. The comparison used this ordinal variable, representing the highest score achieved during the post-operative period. The comparison between arms was made through the Mann-Whitney U test. Data shown are percentage of participants with pulmonary complications grade ≥ 3.

Secondary Outcome Measures

1. Length of ICU Stay [From the day of surgery up to ICU discharge, maximum censoring at day 28 after surgery]

   Days since surgery until ICU discharge, analyzed through Kaplan-Meyer curves (log-Rank test), where the time to event is the time of discharge from the ICU. The censoring was performed at 28 days. Patients dying before leaving the ICU were censored as not discharged from ICU at day 28.

2. Length of Hospital Stay [From the day of surgery up to Hospital discharge, maximum censoring at day 28 after surgery]

   Days since surgery until Hospital discharge, analyzed through Kaplan-Meyer curves (log-Rank test), where the time to event is the time of discharge from the Hospital. The censoring was performed at 28 days. Patients dying before leaving the Hospital were censored as not discharged from Hospital at day 28.

3. Incidence of Barotrauma [Five days after surgery]

   Confirmed by X-ray. Test with logistic regression

4. Hospital Mortality [From the day of surgery up to Hospital discharge or death, with no maximum censoring.]

   Deaths occurred during hospital stay, tested with logistic regression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Immediate postoperative period of myocardial revascularization and/or heart valve surgery (aortic and/or mitral)

• Age > 18 years and < 80 years

• No previous pulmonary disease

• Left ventricular ejection fraction > 35%

• Body mass index < 40 kg/m2

• Oxygen index (PaO2/FiO2) < 250

• Corrected volemic status (negative raising legs mean arterial pressure [MAP] variation < 10%)

• Written inform consent

Exclusion Criteria:

• MAP (mean arterial pressure) < 60 mmHg

• Noradrenaline > 2 micrograms/Kg/min

• Acute arrhythmias

• Blooding associated to hemodynamic instability

• Need of re-surgery and/or mechanical circulatory assistance

• Suspicion of neurological alteration

• Chest tube with persistent air leak

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Instituto do Coração (Incor) - University of São Paulo	São Paulo		Brazil

Sponsors and Collaborators

• University of Sao Paulo
• InCor Heart Institute

Investigators

• Study Director: Marcelo BP Amato, PhD, University of Sao Paulo

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alcino Costa Leme, Supervisor of respiratory post-operative care - Incor Heart Institute, University of Sao Paulo
• ClinicalTrials.gov Identifier: NCT01502332
• Other Study ID Numbers: InCor-OLA
• First Posted: Dec 30, 2011
• Last Update Posted: Nov 23, 2016
• Last Verified: Oct 1, 2016

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Alcino Costa Leme, Supervisor of respiratory post-operative care - Incor Heart Institute, University of Sao Paulo: Mechanical ventilation; Open lung approach; Blood gases; Cardiac surgery; Pulmonary complications
• Additional relevant MeSH terms: Lung Injury; Acute Lung Injury; Ventilator-Induced Lung Injury; Heart Diseases; Wounds and Injuries

Study Results

Participant Flow

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment
Arm/Group Description	Intensive Alveolar Recruitment ARM: recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Moderate alveolar recruitment ARM: recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
Period Title: Overall Study
STARTED	157	163
COMPLETED	157	163
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment	Total
Arm/Group Description	Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Total of all reporting groups
Overall Participants	157	163	320
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	100 63.7%	100 61.3%	200 62.5%
>=65 years	57 36.3%	63 38.7%	120 37.5%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	62	63	62
Sex: Female, Male (Count of Participants)
Female	59 37.6%	66 40.5%	125 39.1%
Male	98 62.4%	97 59.5%	195 60.9%
Region of Enrollment (participants) [Number]
Brazil	157 100%	163 100%	320 100%

Outcome Measures

1. Primary Outcome

Title	Severity of Pulmonary Complications in the Post-operative Period
Description	Score of pulmonary complications adapted from previous publications, with 5 degrees, where the higher one means death before hospital discharge, degree (4) means the need of mechanical ventilation for more than 48 hours after surgery or after reintubation, degree (3) means pneumonia or intense noninvasive ventilation need, degree (2) means hypoxemia and abnormal lung findings, degree 1 means simple atelectasis and degree (0) means no complication. The comparison used this ordinal variable, representing the highest score achieved during the post-operative period. The comparison between arms was made through the Mann-Whitney U test. Data shown are percentage of participants with pulmonary complications grade ≥ 3.
Time Frame	Participants were followed for the duration of hospital stay.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment
Arm/Group Description	Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
Measure Participants	157	163
Number [percentage of participants]	15 9.6%	26 16%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Alveolar Recruitment, Moderate Alveolar Recruitment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Length of ICU Stay
Description	Days since surgery until ICU discharge, analyzed through Kaplan-Meyer curves (log-Rank test), where the time to event is the time of discharge from the ICU. The censoring was performed at 28 days. Patients dying before leaving the ICU were censored as not discharged from ICU at day 28.
Time Frame	From the day of surgery up to ICU discharge, maximum censoring at day 28 after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment
Arm/Group Description	Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
Measure Participants	157	163
Median (Inter-Quartile Range) [days]	3	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Alveolar Recruitment, Moderate Alveolar Recruitment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Length of Hospital Stay
Description	Days since surgery until Hospital discharge, analyzed through Kaplan-Meyer curves (log-Rank test), where the time to event is the time of discharge from the Hospital. The censoring was performed at 28 days. Patients dying before leaving the Hospital were censored as not discharged from Hospital at day 28.
Time Frame	From the day of surgery up to Hospital discharge, maximum censoring at day 28 after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment
Arm/Group Description	Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
Measure Participants	157	163
Median (Inter-Quartile Range) [days]	8	9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Alveolar Recruitment, Moderate Alveolar Recruitment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	Log Rank
	Comments

4. Secondary Outcome

Title	Incidence of Barotrauma
Description	Confirmed by X-ray. Test with logistic regression
Time Frame	Five days after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment
Arm/Group Description	Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
Measure Participants	157	163
Number [percentage of participants]	0 0%	1 0.6%

5. Secondary Outcome

Title	Hospital Mortality
Description	Deaths occurred during hospital stay, tested with logistic regression.
Time Frame	From the day of surgery up to Hospital discharge or death, with no maximum censoring.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intensive Alveolar Recruitment	Moderate Alveolar Recruitment
Arm/Group Description	Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.	Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
Measure Participants	157	163
Number [percentage of participants]	3 1.9%	5 3.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Intensive Alveolar Recruitment, Moderate Alveolar Recruitment
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.267
	Comments
	Method	Regression, Logistic
	Comments

Adverse Events

Arm/Group Title	Intensive Alveolar Recruitment ARM		Moderate Alveolar Recruitment ARM
Arm/Group Description	Mechanical ventilation strategy: Intensive Alveolar Recruitment ARM: recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.		Mechanical ventilation strategy: Moderate alveolar recruitment ARM: recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
All Cause Mortality
	Intensive Alveolar Recruitment ARM		Moderate Alveolar Recruitment ARM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intensive Alveolar Recruitment ARM		Moderate Alveolar Recruitment ARM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/157 (0%)		0/163 (0%)
Other (Not Including Serious) Adverse Events
	Intensive Alveolar Recruitment ARM		Moderate Alveolar Recruitment ARM
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/157 (0%)		0/163 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.