The efficacy of intratracheal rhDNase therapy in the treatment of severe hypercapnoeic respiratory acidosis in ventilated children with status asthmaticus and bronchiolitis

Objective

Successful rescue therapy with intratracheal recombinant (rh) DNAse has been documented in case reports of severe status asthmaticus with life-threatening mucus plugging [1]. Benefit may occur via its mucolytic properties or enhancement of mucociliary transport. The aim of this study was to report the efficacy of rhDNAse in terms of CO₂ clearance in a cohort of ventilated children with severe airflow obstruction secondary to either status asthmaticus or viral bronchiolitis unresponsive to conventional therapy.

Method

We reviewed retrospectively the case notes of 19 ventilated patients admitted to a tertiary paediatric ICU with a clinical diagnosis of asthma or bronchiolitis who received rhDNAse therapy for severe persisting hypercarbic acidosis (pCO₂ > 10 kPa, pH < 7.2) despite optimising conventional ventilation (peak inspiratory pressure > 28 cmH₂O, pressure control mode). One millilitre per kilogram of rhDNAse (0.25 mg/ml concentration in 0.9% saline) was instilled bronchoscopically (n = 4) or blindly (n = 15) into the trachea followed by percussive physiotherapy with adequate patient sedation and muscle relaxation. Ventilator settings (Servo 300) and arterial blood gases were recorded pre-DNAse and at 4 and 8 hours after therapy according to our standard DNAse protocol. Tidal volumes were not measured due to known inaccuracy of the Servo 300 ventilators. Data were analyzed using two-way, repeated-measures ANOVA. Significance levels for group (asthma vs bronchiolitis), time (0, 4 and 8 hours) and interaction effects are reported.

Results

Patient demographics are presented in Table 1. There was a significant fall in arterial pCO₂ in both groups over the 8 hours after DNAse therapy (time effect P = 0.01, group effect P = 0.03; Fig. 1), which was mirrored by a rise in pH (time effect P = 0.002). This was associated with a reduction in peak inspiratory pressure (time effect P = 0.03; Fig. 2) which was more pronounced in asthma (interaction effect P = 0.004; Fig. 2). Patients with bronchiolitis were ventilated at a higher rate than asthma (group effect P = 0.001), which did not change with time (time effect P = 0.4), suggesting the reduced pCO₂ was a function of improved tidal volumes.

Table 1 (abstract P52)

Figure 1

(abstract P52)

Figure 2

(abstract P52)

Conclusion

Intratracheal DNAse with percussive physiotherapy may offer an effective method to improve ventilation in status asthmaticus and bronchiolitis patients with severe hypercarbic acidosis. Further studies are warranted.