Ventilator-associated pneumonia in children after cardiac surgery in The Netherlands

We performed a retrospective cohort study of VAP in PICU patients following cardiac surgery. Only a few previous studies have looked at VAP in this specific patient population [3, 9, 10]. This is the first study to characterize VAP in a PICU population in The Netherlands. Of the 125 patients included in the study, 11 (8.8%) developed VAP giving a rate of 17.1 episodes of VAP per 1,000 ventilator days. Fischer et al. [9] found a comparable rate of 9.6%. Tang et al. [3] reported a higher incidence of 13% and 21.6 episodes of VAP per 1,000 ventilator days, despite a 3-day prophylaxis with cefazoline and gentamicin compared to our 24-h prophylaxis with cefazoline. Our use of cuffed tubes might be an explanation for the lower VAP incidence. Even though modern microcuffed tubes do not necessarily provide an isolated airway and tracheal soiling can probably still occur, in adults the use of cuffed endotracheal tubes has been shown to reduce the incidence of VAP [13, 14].

Tan et al. [10] reported an even higher incidence of 21.5% for acquired nosocomial pneumonia in children after cardiac surgery. However, this incidence probably does not reflect the incidence of true VAP, as they did not comment on the temporal relationship with mechanical ventilation. Rates reported in general PICU populations are generally lower than those found in our study: between 2.9 and 11.6 per 1,000 ventilator days [2, 6]. Higher VAP rates for surgical and trauma ICUs versus medical ICUs were reported in the 2004 NNIS survey in both adult and pediatric studies [4, 7, 8, 15].

There is no gold standard for the diagnosis of VAP in pediatric patients. The diagnostic criteria of VAP remain contentious. We adhered to the criteria proposed by Horan et al. [11] which place an emphasis on identifying a progressive infiltrate in two consecutive chest radiographs in patients with underlying disease. However, in postoperative pediatric cardiac surgical patients it is very difficult to differentiate between infectious infiltrates and pulmonary over-circulation, fluid overload, atelectases and pleural effusion on chest radiographs. This indicates that the criteria proposed by Horan et al. [11] may not be fully applicable to pediatric patients after cardiac surgery. Other criteria include worsening gas exchange, reflected in a worsening PaO₂/FiO₂ ratio and/or an A–a gradient which are already abnormal due to fluid overload, atelectases or intracardiac shunts in many patients after cardiac surgery. In our patients with VAP without shunting (8 of 11) the PaO₂/FiO₂ ratio decreased by an average of 16% (from 225 to 188 mmHg) and the A–a gradient doubled on average from 120 to 249 mmHg. Further research is needed to address the issue of diagnosing VAP, especially in this specific patient group. We are currently performing a prospective review of the incidence of VAP.

The most common etiological agents in VAP in pediatric patients reported previously are P. aeruginosa and S. aureus [2, 16]. We identified these bacterial species in 9.1 and 18.2%, respectively. No methicillin-resistant S. aureus species were identified. The most commonly isolated organisms in our population were H. influenzae (45.5%) and M. catarrhalis (27.3%), probably representing nasopharyngeal flora as associated agents of VAP. All the cultured bacteria were sensitive to our empirical antibiotic regimen. Tan et al. [10] also reported gram-negative bacilli as the most frequent isolates (86.1%), followed by fungi (7.6%), and gram-positive cocci (6.3%). The incidence of polymicrobial VAP was 36.4%, similar to that reported by Srinivasan et al. [7]. No organisms were cultured from the samples from two patients (18.2%), and rhinovirus was found by PCR in two patients (18.2%), although it is unclear what role this played in the etiology of VAP. Of 11 patients with VAP, 9 had positive endotracheal cultures, obtained by standard endotracheal suction.

Of 76 endotracheal cultures that were taken, 44 were positive, and 31 patients had positive endotracheal cultures without any clinical signs or symptoms of pulmonary infection and were retrospectively classified as colonization. However, lower respiratory tract infections often begin with tracheal colonization that may progress to ventilator-associated tracheobronchitis (VAT), which can be diagnosed on the basis of clinical signs (fever, leukocytosis, purulent sputum), microbiological information (sputum cultures), and the absence of infiltrates on chest radiographs. VAT can lead to VAP in some patients and treatment of VAT may be an important factor in preventing VAP [17]. In adult VAP it has also been shown that appropriate antimicrobial treatment of patients significantly improves outcome [4]. It is therefore important to obtain microbiological information. Protected specimen brush and bronchoalveolar lavage are recommended to avoid a high incidence of false-positive endotracheal cultures due to colonization [4] as they are a good alternative to bronchoalveolar lavage [18, 19].

The risk factors found in our study were different from those reported in general PICU populations (presence of a genetic syndrome, reintubation, enteral feeding, transport out of the PICU, duration of mechanical ventilation, and the presence of a central venous line) [3, 6‐8]. In our study, patients with VAP were more likely to have an admission PRISM III score of ≥10 (p = 0.033) as confirmed by multivariate analysis. This could indicate patients who were more unstable during surgery or required more complex surgery, which is reinforced by the fact that they also had longer aortic cross-clamp times. Tang et al. [3] have reported previously that patients with complex congenital heart disease are more likely to develop VAP than patients with simple congenital heart disease. However, the complexity of cardiac surgery as defined by the RACHS-1 score did not correlate with development of VAP in our study (Table 1), a finding also reported by Fischer et al. [9]. Furthermore, none of our patients who developed VAP had delayed sternum closure compared to 18.4% among the other 114 patients (Table 3) and steroids were given before cardiopulmonary bypass to approximately 80% of patients in both groups (p = 1.00), and neither could therefore be identified as a risk factor for VAP. Only two patients received continued steroids because of low cardiac output syndrome, but neither developed VAP. However, steroids have been reported as a risk factor for VAP in the adult literature [20]. Furthermore, patients with VAP were more likely to have received a transfusion of fresh frozen plasma, although in multivariate analysis the difference was not statistically significant. Unfortunately, our numbers were too small to comment on the temporal relationship between fresh frozen plasma transfusion and the development of VAP. An increased risk of infections in patients treated with fresh frozen plasma has been reported previously in adult ICU patients [21].

The age of the patients with VAP was higher (mean 28.8 vs. 15.4 months), although this was not statistically significant. Further analysis did not identify a specific age group at risk. Colonization of the upper airway in the normal population changes with age, but whether this plays a role in the development of VAP needs to be further investigated. We maintain oral hygiene with oral swabs using water. Whether chlorhexidine mouthwash would lower the incidence of VAP is the subject of further investigation. Preventive interventions based on evidence in adult settings [22] have been shown to lead to a reduction in the incidence of VAP in pediatric patients [23, 24]. Patients with VAP had significantly prolonged mechanical ventilation and PICU length of stay. This has also been reported in previous studies [6, 8, 9]. There were no deaths in the group of patients with VAP. Only a few studies in pediatric patients have demonstrated a significantly higher mortality rate in patients with VAP [3, 25]. Higher mortality due to VAP in adults is well documented [26].

The limitations of our study include the fact that it reflects a single-center experience, which may limit its generalizability. Due to the explorative character of this study, a formal power analysis was not performed. Because it was a retrospective study, the data collected could have been incomplete. However, all our data were prospectively gathered in our PDMS and were available for all patients. Possible misclassification was addressed by using very specific definitions. Therefore underestimation of our VAP rate, although possible, seems unlikely. However, the lack of a gold standard for the definition of VAP may limit the accuracy of the correlation with risk factors and outcomes. Despite these limitations the study has allowed us to establish a solid reference point for VAP in PICU patients in The Netherlands, and has provided us with valuable information for the setting up of future prospective studies.