Episodic Hypoxemia in Mechanically Ventilated Preterm Infants
Conditions
Keywords
hypoxemia, desaturation, mechanical ventilation, preterm infants, volume guarantee ventilation
Brief summary
Preterm infants undergoing mechanical ventilation often present with respiratory instability which leads to fluctuations in ventilation and oxygenation. In conventional modes of mechanical ventilation used in these patients, the ventilator delivers breaths at a set rate and a constant peak inspiratory pressure. We have demonstrated that spontaneous episodes of hypoxemia in mechanically ventilated preterm infants are frequently triggered by a loss in end-expiratory lung volume followed by decrease in tidal volume. This is due to a reduction in respiratory system compliance and increase in airway resistance. Volume Guarantee ventilation is a mode of ventilation in which ventilator measures the exhaled tidal volume of each ventilator breath and automatically adjusts the peak inspiratory pressure to deliver the set tidal volume. We have previously shown that Volume Guarantee reduced the severity and duration of hypoxemia episodes during a period of 2 hours in preterm infants The study hypothesis is that Volume Guarantee ventilation will decrease the duration of episodes of hypoxemia when compared to conventional mechanical ventilation during routine clinical conditions and over longer periods of time. The objective of the study is to evaluate the effects of Volume Guarantee on the duration, severity and frequency of episodes of hypoxemia in mechanically ventilated preterm infants who present with frequent hypoxemia episodes in comparison to conventional ventilation over two periods of 24 hours each and under routine clinical conditions.
Interventions
DEVICESequence A: Conventional-Volume Guarantee
This is a crossover study. Infants will be randomly assigned to one of two sequences. In sequence A, the infant will undergo a 24-hour period of conventional mechanical ventilation followed by a 24 hour period of volume guarantee ventilation. Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA). During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team. During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.
DEVICESequence B: Volume Guarantee-Conventional
This is a crossover study. Infants will be randomly assigned to one of two sequences. In sequence B, the infant will undergo a 24-hour period of volume guarantee ventilation followed by a 24 hour period of conventional mechanical ventilation. Both conventional mechanical ventilation and volume guarantee ventilation will be provided by the same neonatal ventilator (AVEA, CareFusion Inc, Yorba Linda, CA). During the 24 hour period of conventional mechanical ventilation, the infant will receive mechanical ventilation with the settings determined by the clinical team. During volume guarantee ventilation, the set tidal volume to be maintained by the ventilator will be the average tidal volume delivered by the ventilator prior to start of study.
Sponsors
University of Miami
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Born at less than 32 weeks of gestational age. * Requiring mechanical ventilation on a mandatory ventilator rate greater than or equal to 20 per minute and receiving a mean tidal volume of at least 4 ml/kg. * Presenting with 4 or more episodes of hypoxemia, defined as oxygen saturation less than 75%, in the 8 hours prior to the study.
Exclusion criteria
* Major congenital anomalies. * Hemodynamic instability requiring inotropes within 72 hours prior to the study * Culture proven sepsis within 72 hours prior to the study. * Diagnosis of pulmonary interstitial emphysema or pneumothorax within the 72 hours prior to the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time Spent With Arterial Oxygen Saturation < 75% | 24 hours | Percentage of time spent with arterial oxygen saturation \< 75% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Severe Hypoxemia Episodes | 24 hours | Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 \< 75% lasting for at least 20 seconds. |
| Frequency of Hypoxemia Episodes | 24 hours | Frequency of hypoxemia episodes defined as episodes with arterial saturation \< 85% for at least 20 seconds |
| Duration of Hypoxemia Episodes | 24 hours | Duration of hypoxemia episodes of arterial saturation \< 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Fraction of Inspired Oxygen (FiO2) | 24 hours | Calculated as the mean value of the recorded fraction of inspired oxygen for each subject during each of the two 24 hour periods. Reported as median and inter-quartile range of all subjects. |
| Tidal Volume | 24 hours | The mean exhaled tidal volume of mechanical breaths. |
Countries
United States
Participant flow
Recruitment details
This study was conducted at the Project NewBorn Neonatal Intensive Care Unit of the Jackson Memorial Hospital/University of Miami Medical Center. Subjects were recruited into the study between December, 2012 and September, 2014.
Pre-assignment details
42 infants were screened. Of these, 9 declined participation and 3 did not meet inclusion criteria. 30 infants were enrolled (consented). Of these, 4 infants became ineligible after consent and were not studied. 26 enrolled infants were studied.
Participants by arm
| Arm | Count |
|---|---|
| Study Population This is a crossover study. Infants were randomly assigned to one of two sequences.
Sequence A consisted of 24 hours of Conventional Mechanical Ventilation followed by 24 hours of Volume Guarantee Ventilation.
Sequence B consisted of 24 hours of Volume Guarantee Ventilation followed by 24 hours of Conventional Mechanical Ventilation. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First 24 Hours | Adverse Event | 0 | 1 |
| Second 24 Hours | Missing data | 0 | 1 |
Baseline characteristics
| Characteristic | Study Population |
|---|---|
| Age, Continuous | 32 days STANDARD_DEVIATION 22 |
| Birth weight | 685 grams STANDARD_DEVIATION 216 |
| Fraction of Inspired Oxygen | 0.38 fraction STANDARD_DEVIATION 0.09 |
| Gender Female | 13 Participants |
| Gender Male | 11 Participants |
| Gestational age | 25 weeks STANDARD_DEVIATION 1.5 |
| Peak inspiratory pressure | 19.4 cm H2O STANDARD_DEVIATION 1.5 |
| Positive end expiratory pressure | 5.3 cm H2O STANDARD_DEVIATION 0.47 |
| Pressure support | 10.4 cm H2O STANDARD_DEVIATION 1.7 |
| Ventilator mandatory rate | 33 breaths per minute STANDARD_DEVIATION 8.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 25 | 0 / 26 |
| serious Total, serious adverse events | 0 / 25 | 1 / 26 |
Outcome results
Primary
Percentage of Time Spent With Arterial Oxygen Saturation < 75%
Percentage of time spent with arterial oxygen saturation \< 75%
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Mechanical Ventilation Period | Percentage of Time Spent With Arterial Oxygen Saturation < 75% | 5 % of time |
| Volume Guarantee Ventilation Period | Percentage of Time Spent With Arterial Oxygen Saturation < 75% | 4.4 % of time |
p-value: 0.44Wilcoxon signed rank test
Secondary
Duration of Hypoxemia Episodes
Duration of hypoxemia episodes of arterial saturation \< 85% for at least 20 seconds. Calculated as the mean episode duration per subject per period. Reported as median and inter-quartile range of all subjects.
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Mechanical Ventilation Period | Duration of Hypoxemia Episodes | 76 seconds |
| Volume Guarantee Ventilation Period | Duration of Hypoxemia Episodes | 73 seconds |
p-value: 0.02Wilcoxon signed rank test
Secondary
Frequency of Hypoxemia Episodes
Frequency of hypoxemia episodes defined as episodes with arterial saturation \< 85% for at least 20 seconds
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Mechanical Ventilation Period | Frequency of Hypoxemia Episodes | 6.8 hypoxemia episodes per hour |
| Volume Guarantee Ventilation Period | Frequency of Hypoxemia Episodes | 6.5 hypoxemia episodes per hour |
p-value: 0.2Wilcoxon signed rank test
Secondary
Frequency of Severe Hypoxemia Episodes
Frequency of severe hypoxemia episodes defined as periods with arterial oxygen saturation SpO2 \< 75% lasting for at least 20 seconds.
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Mechanical Ventilation Period | Frequency of Severe Hypoxemia Episodes | 2.1 severe hypoxemia episodes per hour |
| Volume Guarantee Ventilation Period | Frequency of Severe Hypoxemia Episodes | 1.9 severe hypoxemia episodes per hour |
p-value: 0.75Wilcoxon signed rank test
Other Pre-specified
Fraction of Inspired Oxygen (FiO2)
Calculated as the mean value of the recorded fraction of inspired oxygen for each subject during each of the two 24 hour periods. Reported as median and inter-quartile range of all subjects.
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Conventional Mechanical Ventilation Period | Fraction of Inspired Oxygen (FiO2) | .42 fraction |
| Volume Guarantee Ventilation Period | Fraction of Inspired Oxygen (FiO2) | .41 fraction |
p-value: 0.049Wilcoxon signed rank test
Other Pre-specified
Tidal Volume
The mean exhaled tidal volume of mechanical breaths.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Conventional Mechanical Ventilation Period | Tidal Volume | 6.2 ml/Kg | Standard Deviation 1.6 |
| Volume Guarantee Ventilation Period | Tidal Volume | 5.6 ml/Kg | Standard Deviation 0.7 |
p-value: 0.006Paired t-test