Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05150600 |
| Other study ID # |
FMASU R172/2021 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 15, 2021 |
| Est. completion date |
June 30, 2022 |
Study information
| Verified date |
July 2022 |
| Source |
Ain Shams University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background and Objectives: Maintaining oxygenation during neonatal open repair of esophageal
atresia is difficult. Inverse ratio ventilation can be used during one lung ventilation (OLV)
to improve the oxygenation and lung mechanics. The investigators will compare inverse ratio
to conventional ratio ventilation during OLV in neonatal open repair of esophageal atresia
regarding effect in oxygenation, hemodynamic variables, incidence of complications, and
easiness of procedure.
Methods: The investigators will enroll 40 term neonates undergoing open right thoracotomy for
esophageal atresia repair in this prospective randomized study. The patients will be randomly
assigned into 2 groups based on inspiratory to expiratory (I:E) ratio of mechanical
ventilation parameters (I:E ratio will be 2:1 in IRV and 1:2 in CRV). The incidence of
desaturation episodes that needs to stop the procedure and reinflation of the lung will
recorded as the primary outcome while hemodynamic parameters, incidence of complications, and
length of surgical procedure will be recorded as the secondary outcomes.
Description:
INTRODUCTION:
Maintaining adequate oxygenation after lung retraction and one lung ventilation (OLV) in open
thoracotomy during neonatal repair of esophageal atresia/ tracheoesophageal fistula is
extremely difficult and usually required stopping the procedure and reinflation of the
retracted lung which prolong the surgery time, stopping the procedure during critical
situations and endanger the fragile neonate from hypoxemia.
Inverse ratio ventilation has been used originally for long time in patients with acute
respiratory distress syndrome (ARDS) to improve the oxygenation and lung function. The
mechanism with inverse ratio ventilation is to prolong the inspiratory time with reducing the
airway pressure and elevate the mean airway pressure preventing the alveoli from collapse.
Also inverse ratio ventilation (IRV) used in many studies in adults during OLV with better
oxygenation and lung mechanics.
Despite the standard ventilatory sitting in neonatal anesthesia is to adjust the inspiratory
time to achieve inspiratory to expiratory (I:E) ratio of 1:2 to 1:3, but inverse I:E ratio
(with inspiratory time longer than expiratory time) up to 4:1 in neonatal mechanical
ventilation has been shown to be effective in improving oxygenation, PaO2, and gas
distribution in atelectatic lungs. Inverse I:E ratio in neonatal mechanical ventilation
should be used in caution and for a short period of time to avoid possible complications as
air trapping/auto PEEP, volutrauma, air leaks, decrease venous return, and increase pulmonary
vascular resistance.
AIM/ OBJECTIVES:
1. To compare the incidence of desaturation episodes that needs to stop the procedure and
reinflation of the lung using inverse ratio ventilation versus conventional ratio
ventilation during one lung ventilation in neonatal open repair of esophageal
atresia/tracheoesophageal fistula.
2. To determine the effect of inverse ratio ventilation on hemodynamic parameters,
incidence of complications, and length of surgical procedure as compared to conventional
ratio ventilation.
METHODOLOGY:
The study will be conducted at Ain Shams University Hospitals after ethical committee
approval and obtaining an informed written consent from patients' parents or legal guardian.
- Type of Study Prospective randomized controlled clinical trial.
- Study Setting Pediatric surgery operating theatre in Ain shams university hospital,
Cairo, Egypt.
- Study Period The study will be started immediately after ethical committee approval
starting from October 2021 aiming to be completed within 6 months.
- Study Population
- Inclusion Criteria: The patients will be of ASA physical status II-III, neonates
aged less than 28 days and undergoing open repair of esophageal atresia/
tracheoesophageal fistula with right thoracotomy. All patients' will be full term
with gestational age ≥ 36 weeks and weigh ≥ 2.5 kilograms.
- Exclusion Criteria: Significant congenital heart disease including cyanotic heart
disease, single ventricle pathology, large intracardiac defect with significant
left to right shunt, and severe pulmonary hypertension more than 50 mmHg. Other
exclusion criteria included prematurity, pneumonia or severe chest infection prior
to the surgery, and parent or guardian refusal.
- Sampling Method Based on inspiratory to expiratory (I:E) ratio used in positive pressure
ventilation, patients will be randomly and evenly assigned to one of two groups (20
patients each) using a computer-generated list: experimental group IRV (inverse ratio
ventilation) and control group CRV (conventional ratio ventilation).
Group IRV: the I:E ratio in this group will be 2:1 with the maximum inspiratory time (Ti) of
1.3 seconds.
Group CRV: the I:E ratio in this group will be 1:2 with the minimum inspiratory time (Ti) of
0.4 seconds.
- Sample Size Sample size was calculated using PASS 11.0 and based on a study carried out
by Son et al., 2020. Group sample size of 20 patients in Group one and 20 patients in
Group two achieve 82% power to detect a difference between the group proportions of
0.4000. The proportion in group one (the treatment group) is assumed to be 0.1000 under
null hypothesis and 0.5000 under the alternative hypothesis. The proportion in group two
(the control group) is 0.1000. The test statistic used is the two-sided Z test with
pooled variance. The significance level of the test was targeted at 0.0500. The
significance level actually achieved by this design is 0.0361. The sample size was
inflated by 10% to account for attrition problem in prospective studies.
- Ethical Considerations After acquiring local medical ethics committee approval and
informed written consent from the parent or guardian, The investigators will enroll 40
patients in this study.
- Study Tools AND/ OR Study Procedures AND/OR Study Interventions All included patients
will be admitted to neonatal intensive care unit (NICU) and kept Nil Per Os (NPO) after
establishing the diagnosis of esophageal atresia/tracheoesophageal fistula, had a
secured venous access and received dextrose containing intravenous fluid according to
the orders given by the neonatologist. An umbilical artery catheter will be inserted by
the neonatologist prior to the surgery, also an orogastric tube (OGT) will be inserted
in the proximal esophageal pouch and a low negative pressure suction will be applied to
suck any secretions in the esophagus and decrease risk of aspiration.
Another intravenous (iv) cannula will be inserted after induction of anesthesia and a femoral
22 gauge (G) arterial line will be inserted in any patient without an umbilical artery
catheter.
After applying standard monitors (non-invasive blood pressure, 5-lead ECG and 2 pulse
oximetry; one pre-ductal and one post-ductal, 2 temperature probes; one oropharyngeal and one
axillary), anesthesia induction will be started with inhalational anesthetics sevoflurane 2%
in 100% oxygen and increasing gradually till end-tidal sevoflurane reach 4-6% with
maintaining spontaneous breathing to avoid gastric distension with positive pressure
ventilation (PPV) then tracheal intubation will be facilitated with lidocaine 10% topical
spray one puff applied to the glottic opening just before insertion of 3 or 3.5 mm non-cuffed
endotracheal tube (ETT), then ETT will be fixed just above the tracheal carina (confirmed by
auscultation -the ETT will be initially pushed endobronchial then gradually withdrawn till
bilateral breath sound heard- and absence of gastric distension with gentle positive pressure
ventilation).
After ensure the correct position of ETT just above the carina and below the
tracheoesophageal fistula and the patient hemodynamically stable, positive pressure
ventilation will be started after establishing muscle relaxation with atracurium 0.5 mg/kg.
Anesthesia will be maintained with sevoflurane 1-2% in oxygen/air mixture and fentanyl
infusion of 1-2 mcg/kg/h. Fraction of inspired oxygen (FiO2) will be maintained to the lower
limit to keep oxygen saturation (SpO2) ≥ 92% with minimum FiO2 of 0.3. IV fluids will be
maintained as preoperative rate with boluses of normal saline will be given to replace blood
loss and third space loss. Blood transfusion will be given in cases lost more than 10% of
their total blood volume.
All patient will be mechanically ventilated with synchronized intermittent mandatory
ventilation-pressure controlled ventilation (SIMV-PCV) mode with the following parameters;
peak inspiratory pressure (PIP) 10-15 cmH2O above positive end-expiratory pressure (PEEP) of
5 cmH2O to achieve expired tidal volume (VTE) from 7-10 ml/kg, Respiratory rate (RR) ranging
from 30 to 50 breath/minute to achieve end-tidal CO2 (EtCO2) from 30 mmHg up to 50 mmHg, and
pressure support (PS) 12 cmH2O.
The same pediatric surgery team will perform all procedures. After positioning of the patient
in the right lateral position, the right hemithorax will be opened then the right lung will
be retracted to expose and ligate the fistula then end to end esophageal anastomosis will be
performed. The right lung will be re-inflated under direct vision to ensure full lung
expansion after finishing of esophageal anastomosis then the right hemithorax will be closed
with chest tube in situ. Patients in IRV group will resumed conventional I:E ratio
ventilation after resuming two lungs ventilation.
Hemodynamic variables including heart rate (HR), mean arterial pressure (MAP), and oxygen
saturation (SpO2) will be recorded: baseline (before induction of anesthesia), before
initiation of PPV, after the initiation of PPV, after initiation of OLV and every 10 min
until the end of the procedure.
The incidence of hypotension (as the lower limit of normal mean BP on the day of birth, in
mmHg, is approximately equal to the gestational age in weeks, so hypotension considered if
MAP is less than the gestational age in weeks); and bradycardia (defined as: HR< 90
beats/min, as the lower limit of normal HR in sleeping neonate is 90 beats/min) or hypoxemia
(oxygen saturation less than 90%) will be recorded.
In cases of hypotension, the patient will be treated initially with an IV fluid bolus of
10-20 ml/kg normal saline over 5-10 minutes. In case of estimated blood loss exceeded 10% of
TBV, transfusion of packed red blood cells (PRBCs) of 10-15 ml ml/kg over 10-20 minutes will
be given. If the hypotension persisted despite of volume loading, dopamine IV infusion will
be used in dose range 5-10 mcg/kg/min until the blood pressure normalize. Bradycardia will be
treated initially with stopping the surgery and manual reinflation of right lung if
associated with hypoxia and if persisted or not related to hypoxia will be treated with
intravenous atropine 0.02 mg/kg.
In the case of a drop in oxygen saturation of less than 90%, the FiO2 and the PEEP will be
increased to 1 and 7 cmH2O respectively, and if desaturation persist, the surgery will be
stopped with manual reinflation of right lung.
The incidence of stopping the procedure for manual reinflation of the lung will be recorded,
also the length of the surgical procedure starting from skin incision till skin closure will
be recorded.
Arterial blood gases (ABG) sample will be done two times during the procedure; first one
after established positive pressure ventilation by 10 minutes and before the surgical
incision, the second sample will be done after established OLV by 10 minutes but not during
desaturation episode. SaO2, PO2 and PCO2, will be recorded.
After completion of the procedure, patients will be transferred to the NICU intubated,
ventilated and sedated. In the NICU chest X-ray will be performed immediately after patient
arrival to exclude pneumothorax.
The incidence of complications including desaturation episodes that needs only increase FiO2
and/or PEEP, desaturation episodes that needs stop the procedure with lung reinflation,
hypotension, bradycardia, hypercapnia, needs for vasopressor and blood loss exceeding 10%
from TBV will be recorded.
Intraoperative and postoperative data will be collected by the an anesthesia resident not
participating in the study.
- Statistical Analysis Numerical data are presented as the mean (standard deviation) or
median (range) while categorical data are presented as the number of cases (percentage).
Between-group comparisons of numerical variables will be performed by the independent
sample T-test, or Mann-Whitney test as appropriate, while those of categorical variables
will be performed by the Chi-square test. For all tests, a P (probability) value < 0.05
will be considered statistically significant.
- Statistical Package The data collected will be analyzed with statistical program SPSS
(version 22.0 Chicago, Illinois, USA).
