Evaluation of the applicability of the current CDC pediatric ventilator-associated events (PedVAE) surveillance definition in the neonatal intensive care unit population

Mechanical ventilation is an essential, life-saving therapy for infants with critical illness and respiratory failure [1]. However, mechanically ventilated neonates are at high risk for complications including bronchopulmonary dysplasia (BPD), ventilator-associated pneumonia (VAP), septicemia, pulmonary edema, and acute respiratory distress syndrome, which can prolong the duration of mechanical ventilation, length of hospitalization, and contribute significantly to neonatal morbidity and mortality [2, 3]. Surveillance for ventilator-associated events (VAEs) is a critical component of patient safety and quality improvement initiatives in health care facilities and is an integral part of the safety surveillance systems managed by the Centers for Disease Control and Prevention (CDC) [4].

Traditionally, surveillance for VAEs was limited to VAP alone, but the most widely accepted VAP definitions are neither sensitive nor specific, due to the subjectivity of clinical and chest radiographic findings of pneumonia, key requirements of the CDC’s VAP definition [5, 6]. The lack of a precise, reproducible and clinically meaningful definition has implications for assessing effectiveness of prevention strategies. In 2013, the CDC introduced the VAE surveillance definition to address these limitations in the adult populations [7]. These new definitions eliminated the subjectivity and variability associated with diagnosing VAP and broadened the range of surveillance to include both infectious and non-infectious etiologies associated with deterioration on the ventilator.

VAE surveillance was initially not used in neonatal and pediatric locations based on recommendations of a separate working group the CDC organized in 2012 [7]. Subsequently, pediatric and neonatal adaptations for VAE surveillance criteria were defined based on increase in the fraction of inspired oxygen (FiO₂) and/or mean airway pressure (MAP) after a period of stability or improvement on the ventilator [8, 9].

In a retrospective cohort study involving adult patients, VAEs were associated with more days to extubation, more days to hospital discharge, and higher mortality risk [10]. In addition, antimicrobial use is common in pediatric ventilator associated conditions, which include both infectious and non-infectious complications [10, 11]. PedVAE is a surveillance definition and is not intended for use in clinical management of infants. State-mandated reporting of PedVAE started in 2019 and is not standardized. Research on pediatric VAEs focuses on the pediatric intensive care unit (PICU) setting [4, 6]. Therefore, epidemiology of PedVAE in the neonatal intensive care unit (NICU) is limited. We sought to describe PedVAE rates and event characteristics in the NICU population from a single 39-bed level IV NICU before and after the implementation of the state-mandated reporting of CDC PedVAE surveillance definition in January 2019. In addition, risk factors to develop PedVAEs were determined. Finally, we analyzed infants who were mechanically ventilated for at least 4 days and had a new antibiotic treatment course initiated during the time of mechanical ventilation as a surrogate marker of events that require quality improvement interventions.

NICU-specific PedVAE data are limited, with most studies of PedVAE occurring in the PICU or other acute care settings such as the CICU. In this single-center case-control study of ventilated infants, 2 patients met the PedVAE surveillance definition based on the CDC criteria with a total of 3 events. The PedVAE definition is based on an increase in the daily minimum FiO₂ by ≥25% or MAP by ≥4 cmH₂0 after a 2-day period of stability on the ventilator. Ventilator-associated conditions specific to pediatrics have been defined based on modification of the adult definition to use MAP instead of positive end-expiratory pressure (PEEP) [8]. PEEP can be difficult to measure in pediatric high frequency ventilator modes, and MAP may better represent lung compliance in the neonatal and pediatric population [8].

In the adult population, most VAEs are because of pneumonia, pulmonary edema, atelectasis or acute respiratory distress syndrome [10]. The low incidence of PedVAE in our study population could be attributed to the intrinsic differences in respiratory physiology and ventilation management strategies between adults and children. For example, patients in the NICU are more likely to be ventilated due to prematurity or bronchopulmonary dysplasia, as opposed to pneumonia or pulmonary edema.

Although many patients had episodes of significant FiO₂ increase on the ventilator, the event did not qualify because the definition is based on the daily minimum value for the day. Other reasons for exclusion included no 2-day period of stability or decreasing FiO₂ prior to the increase. This was evidenced by an increase in the number of potential events once the period of stability or decrease was removed. Different thresholds of fraction of inspired oxygen (FiO₂) and PEEP can result in increased sensitivity and better correlation between the VAE definition in children and clinical outcomes in ventilated critically ill children [13].

An increase in MAP of 4 cmH₂0 in the NICU population is very unlikely unless the patient is being transitioned from the conventional ventilator to high frequency oscillatory ventilation, which was the case in the patient who developed 2 PedVAEs based on the increase in her MAP. There were 2 potential events when the period of stability or decrease was removed and the threshold for increase in MAP was reduced to 2 cmH₂0.

In the NICU population, infants who have a clinical deterioration and require increased ventilator settings frequently are initiated on empiric antibiotics and a blood culture is obtained to rule out sepsis. Therefore, initiation of a new course of antibiotics while mechanically ventilated was used to identify an additional 30 patients with 79 potential PedVAEs. There is poor correlation between clinician diagnosed ventilator-associated infection in PICUs and the proposed PedVAE definition [14].

Out of these 79 events, only 3 events (4%) had culture-proven sepsis with Staphylococcus epidermidis in 2 events and Candida albicans in 1 event. The primary indication for antibiotic use in our study population was tracheitis and the most common organism isolated in tracheal aspirate cultures was Pseudomonas aeruginosa. Similarly, 60% of tracheal aspirates in a Canadian PICU grew Haemophilus influenzae and Pseudomonas aeruginosa [15]. Antibiotic need and duration for ventilator-associated tracheitis in the pediatric population are not well defined [16, 17].

Patients with potential PedVAE/PedVAE were more likely to be born preterm, and there was a statistically significant increase in complications of prematurity such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and retinopathy of prematurity in this population. Of note, patients with potential PedVAE/ PedVAE were admitted at an older age compared to those without PedVAE. This study was conducted at a Level IV NICU with all admitted infants transferred from peripheral Level II and III NICUs. Therefore, these patients have usually had complicated hospital courses at the referral sites, which culminates in transfer.

Age-specific comorbidities such as RDS, BPD and necrotizing enterocolitis in neonates and infants can independently result in prolonged duration of mechanical ventilation, and complicate clinical and laboratory diagnostic criteria of VAP [18]. To remove these confounding factors, a logistic regression was performed to determine if potential PedVAE/PedVAE cases could be explained by the duration of mechanical ventilation, gestational age, and birth weight. This showed a significant association between potential PedVAE/PedVAE and the duration of mechanical ventilation, which is consistent with the adult literature [10].

The rate of PedVAE in our study was 0.9 per 1000 ventilator days, and thus difficult to assess the attributable morbidity and mortality in our patient population. Only 2 infants met current PedVAE criteria in the 3-year study period. However, about one-quarter of ventilated infants received multiple sepsis evaluations and antibiotic courses associated with increased ventilator settings. The current PedVAE definition offers little guidance relating to antibiotic use, and might be inadequate to identify actionable VAE events to inform prevention efforts in the NICU population. To the best of our knowledge, there have been no studies on PedVAE in the neonatal population since the implementation of mandatory reporting of these events by the CDC in January 2019. Screening daily ventilator settings is feasible and efficient, however, this study reveals the challenges with the current surveillance definition and the need to identify alternate indices which could better characterize these events in the NICU population and predict adverse outcomes.