A Randomized Controlled Trial of Synchronized Nasal Intermittent Positive Pressure Ventilation in RDS

V Bhandari; R G Gavino; J H Nedrelow; P Pallela; A Salvador; R A Ehrenkranz; N L Brodsky;

Disclosures

December 05, 2007

In This Article

Methods

Materials

The ventilators used for infants in the CV group were either the Bear Cub (Model BP 2001; Bear Medical Systems Inc., Riverside, CA, USA) or the Infant Star 500/950 (Infrasonics Inc., San Diego, CA, USA). The Infant Star with the synchronized intermittent mandatory ventilation (IMV) box (Star Sync; Infrasonics Inc.) was used in the infants assigned to SNIPPV primary or secondary modes.

Methods

Subjects. Preterm infants admitted to the neonatal intensive care unit (NICU) at Albert Einstein Medical Center (Philadelphia, PA, USA) (born from July 2000 to January 2002) or the Newborn Special Care Unit (NBSCU) at Yale-New Haven Children's Hospital (YNHCH) (New Haven, CT, USA) (born from July 2002 to March 2005), with the following inclusion/exclusion criteria formed the study group ( Table 1 ).

The clinical parameters listed above in the exclusion criteria were at the discretion of the clinical team. Approval for this RCT was obtained from the Institutional Review Boards (IRB) of the Albert Einstein Healthcare Network and Yale University School of Medicine. Randomization was not stratified by site and was done sequentially, first at AEMC, followed by Yale University School of Medicine. There was no crossover of patients at either site. The analysis was by intention to treat. Since this was a pragmatic study to show feasibility of the primary mode of SNIPPV, detailed data were not collected on babies who met eligibility criteria, but were not enrolled. The overall number of admissions of babies <32 weeks of GA and BW of 600 to 1250 g was 41 infants, with 23 having RDS at AEMC in the study period specified. Similarly, at the Yale site, the numbers were 240 and 153, respectively. Data were collected on the enrolled babies as per definitions mentioned below.

Definitions. Pregnancy-induced hypertension was defined as a maternal systolic blood pressure of >140 mm Hg and a diastolic pressure of >90 mm Hg in the presence of proteinuria (>300 mg/24 h) and non-dependent edema. Chorioamnionitis was defined as a positive culture from the amniotic fluid. In the absence of positive cultures, the presence of organisms on gram stain, sheets of leukocytes or low glucose in the amniotic fluid in the presence of any two of the following clinical symptomatologies: maternal fever, leukocytosis, uterine tenderness, pus from the cervix, fetal tachycardia was used. RDS was defined as the presence of respiratory distress and a characteristic chest radiograph (reticular-granular pattern with air bronchograms and low lung volumes). Air leaks were documented by radiographic evidence of pneumothorax, pneumomediastinum or pulmonary interstitial emphysema. Patent ductus arteriosus (PDA) was documented by echocardiography. Intraventricular hemorrhage (IVH) was determined according to Papile's classification of blood in the germinal matrix or ventricular system with or without ventricular dilatation and parenchymal extension.[18]Periventricular leukomalacia (PVL) was defined as cerebral ultrasound findings of increased echogenicity and cystic lesions in the periventricular white matter.[19] BPD was defined as the need for oxygen supplementation at 36 weeks of corrected GA in association with characteristic chest radiographic changes.[20] Sepsis was diagnosed by a positive blood culture. Necrotizing enterocolitis (NEC) was defined as ≥stage 2 as per modified Bell's criteria.[21] ROP was defined as per the international classification.[22] The diagnosis of clinical gastroesophageal reflux (GER) was made, as defined previously.[23]

Management of RDS. Infants in both groups were managed as per nursery standards for RDS. Initial ventilator settings of infants with RDS included peak inspiratory pressure (PIP) at 16 to 20 cm H2O, positive-end expiratory pressure (PEEP) at 4 to 6 cm H2O, an inspiratory time of 0.35 to 0.45 s, a rate of 40 to 60/min and FiO2 adjusted to keep saturations 90 to 96%. Exogenous surfactant (Infasurf, Forest Laboratories, St Louis, MO, USA or Curosurf, Dey Inc., Napa, CA, USA or Survanta, Ross Products Divison, Abbott Laboratories, Abbott Park, IL, USA) was administered only as rescue therapy. Prophylactic surfactant therapy (in the DR) was not used at either site. Administration of surfactant required the diagnosis of RDS and an FiO2 requirement of ≥0.4. Pre-medication for intubation or sedation was not routinely used at either site, as per nursery standards. All infants were started on aminophylline/caffeine within the first 24 h of life. Randomization to the SNIPPV or CV groups was done by opening sealed, opaque envelopes with the allotment having been previously done by a computer-generated random numbers table. Randomization to one or the other group was done after birth, after consent, if the infant fulfilled the inclusion criteria.

For the CV group, infants were weaned from CV and monitored by serial blood gas analyses (see below) at the discretion of the clinical team. The criteria for extubation were PIP≤16 cm H2O, PEEP≤5 cm H2O, IMV rate 15 to 25, FiO2≤0.35. Infants were extubated to SNIPPV (secondary mode), standard practice in our NICUs following the previous study.[8]

Infants in the SNIPPV group were extubated to SNIPPV (primary mode) within 90 min after surfactant administration. We used nasopharyngeal prongs (V-SIL binasal airway, 3.0 mm outer diameter, 4 cm length attached to the infant's cheeks by a Neobar; Neotech Products Inc., Chatsworth, CA, USA) for the babies in the SNIPPV group (primary mode). Babies extubated to SNIPPV received synchronized IMV at the same rate as they were receiving before extubation, PIP was increased by 2 to 4 cm H2O, whereas the PEEP was kept ≤5 cm H2O. FiO2 was adjusted to maintain oxygen saturations 90 to 96% on pulse oximetry. The flow rate was kept at 8 to 10 l/min. To avoid excessive leak of pressure, attempt was made on all babies on SNIPPV to have their mouths closed (using pacifiers and/or chin-straps). All babies on SNIPPV had a large-bore nasogastric tube placed, open to the atmosphere, to avoid distension of the stomach.

In both groups, blood gas analyses were done at 1, 6, 24 and 48 h post-surfactant and as clinically indicated, from samples obtained from indwelling arterial lines or arterialized capillary blood obtained from a warmed heel. Ventilator settings were adjusted to maintain blood gas parameters as follows: pH 7.25 to 7.45; PaCO2 40 to 55 mm Hg; PaO2 50 to 80 mm Hg. Ventilator settings could be increased or decreased in the SNIPPV mode, if needed, to maintain the target blood gases.

Infants were weaned to NCPAP once they had ventilator settings of PIP/PEEP 14/4 cm H2O, rate of ≤20/min and FiO2≤0.3 with acceptable blood gas values. They were then further weaned to nasal cannula, when they were on NCPAP of 4 cm H2O, FiO2≤0.3, with acceptable blood gases. Once the child was on nasal cannula flow of 1 l/min, the FiO2 was weaned to room air while maintaining oxygen saturations 90 to 96% on pulse oximetry with acceptable blood gases.

Re-intubation was performed in the presence of any of the following: a pH<7.25, PaCO2>60 mm Hg, a single episode of apnea needing bag and mask resuscitation; frequent (>2 to 3/h) apnea/bradycardia spells (cessation of respiration for >20 s associated with a heart rate <100/min) on therapeutic serum aminophylline/caffeine levels; frequent desaturations (<85%)≥3 episodes/h not responding to increased ventilatory settings; or an increase in FiO2 to 1.0, or a PaO2<50 mm Hg despite an FiO2 of 1.0.

Thus, if an infant belonging to the SNIPPV group was re-intubated and then extubated, the infant would be managed with 'secondary mode' SNIPPV, similar to what would be done for an infant in the CV group who was extubated. The CPAP kit (Argyle CPAP Nasal Cannula Kit; Sherwood Medical, St Louis, MO, USA) was used for this purpose. The size of the prongs to be used for each infant was determined by their weight as follows: 'small' for infants 1000 to 1250 g and 'x-small' for infants <1000 g. Any subsequent re-intubations would also be followed by extubation to 'secondary mode' SNIPPV in both groups.

Infants were monitored as per standard NICU nursing protocols. The medical management of these babies was as per the attending neonatologist. Cranial ultrasounds were done on all infants at days 1 to 3, 7 to 10, at discharge, and as indicated. Radiographs, cardiac echocardiography and sepsis evaluations were done when clinically indicated. Eye exams for ROP were performed on the infants by pediatric ophthalmologists at 4 to 6 weeks of age and repeated every 1 to 2 weeks, as indicated. Cranial ultrasounds, echocardiographic and eye examinations were interpreted by clinicians unaware of the infant's study group assignment.

Discharge criteria for the infants in both groups were uniform and included the ability to maintain their temperature in a crib, apnea-free for 1 week (off aminophylline/caffeine) with a normal pneumocardiogram (the 'normal pneumocardiogram' criterion only for babies at AEMC), accepting feeds orally and maintaining weight gain, and free from any active infection. No specific GA or weight limitations were used to dictate the decision to discharge any infant. Surviving infants (all for AEMC, only babies with BW≤1000 g at Yale site) were invited back for neurodevelopmental assessments in the respective neonatal follow-up clinics at both institutions.

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