PERINATAL/NEONATAL CASE PRESENTATION
Endotracheal DNase for atelectasis in ventilated neonates
R MacKinnon, KI Wheeler and J Sokol
Neonatal Unit, The Royal Women’s Hospital, Parkville, Victoria, Australia
Management of atelectasis and lung collapse in ventilated neonates remains
a common challenge in the neonatal intensive care unit. Recombinant
human DNase (rhDNase) is an established treatment of atelectasis in cystic
ﬁbrosis and its use is also reported in the management of asthma,
respiratory syncitial virus bronchiolitis and bronchiectasis to liquefy sputum
and aid its clearance from the lungs. We report the use of rhDNase in a
subgroup of ventilated neonates with severe end-stage respiratory failure and
atelectasis. Three of the four patients showed clinical improvement. A
previously undiagnosed lung anomaly was subsequently identiﬁed in the
fourth patient. Future randomized studies could examine any potential
beneﬁts of this emerging therapy.
Keywords: DNase; atelectasis; neonatal ventilation
Despite the ongoing trend away from invasive ventilation toward
continuous airway pressure (CPAP) in the neonatal intensive care
unit, a number of patients still require ventilation. In a proportion
of these patients, ventilation may become difﬁcult because of the
presence of viscous sections, resulting in areas of collapse,
increased risk of pneumonia, prolonged ventilation and potential
damage to lung parenchyma.
Pulmonary secretions attain their
viscosity from the presence of extracellular DNA from degenerating
polymorphonuclear lymphocytes. Recombinant human DNase
(rhDNase) reduces sputum viscosity by hydrolyzing extracellular
DNA, thus allowing it to ﬂow and be easily cleared.
Use of rhDNase is an established pediatric therapy in patients
with cystic ﬁbrosis and has been reported in pediatric populations
with bronchiolitis, respiratory syncitial virus and asthma.
data are available regarding the use of rhDNase in the neonatal
We therefore summarize our experience with this
therapy in four patients over the last 2 years. This study was
approved by the Royal Women’s Hospital Research and Ethics
Patient 1 was born at 25-week gestational age. She was intubated
at birth, received surfactant (poractant alfa) and remained
ventilated for 7 weeks. She required reintubation at 9 weeks of life
for an acute deterioration associated with sepsis. Oxygenation was
problematic and showed no response to high-frequency oscillatory
ventilation or to a trial of nitric oxide inhalation. Endotracheal
tube (ETT) secretions were copious, requiring several reintubations
for tube blockage. ETT aspirate supported the growth of
Enterococcus faecalis, and thus antibiotic therapy was revised
appropriately. Serial chest radiographs showed extensive
consolidation of both lung ﬁelds with alternating collapse of the
dependent lung. At 10 weeks of life, although showing no
improvement on conventional ventilation, she was subjected to a
trial of 2.5-mg nebulized DNase (Pulmozyme 227 Roche, Basel,
Switzerland). Her inspired oxygen concentration (FiO
from 0.9 to 0.4 over a period of 5 days; during this time, minimal
set tidal volumes were also weaned until day 6 of treatment when
she was successfully extubated to CPAP. Repeated chest radiographs
showed resolution of atelectasis after 3 days of DNase treatment.
Patient 2 was delivered at 25-week gestational age; he was
ventilator dependent for the ﬁrst 8 weeks of life. He suffered a
number of episodes of presumed sepsis, and Klebsiella oxytoca and
Enterobacter spp. were isolated on separate ETT aspirate cultures;
these were treated with appropriate antibiotics. Serial chest
radiographs showed hyperinﬂation, cystic lung changes and
alternating collapse of the dependent lung, which varied with
changes in the baby’s position. At 6 weeks of life, he had worsening
hypercarbia and required 100% oxygen that showed no response to
a trial of high-frequency oscillatory ventilation. The patient then
received a trial of 2.5-mg rhDNase that was instilled undiluted
endotracheally every 8 h. Oxygenation index was 29.5 before
treatment was started. This reduced to 20.9 at 24 h after DNase
treatment was started. After 3 days of rhDNase treatment, the
radiographic appearance of the patient’s chest improved, FiO
reduced to 0.35 and rhDNase was ceased. The patient’s FiO
returned to 0.6 and rhDNase treatment was recommenced. Over the
following week, his FiO
remained static at 0.6, whereas other
Received 10 October 2010; revised 21 March 2011; accepted 22 March 2011
Journal of Perinatology (2011) 31, 799–801
2011 Nature America, Inc. All rights reserved. 0743-8346/11
Fset tidal volume and peak inspiratory
Fwere successfully weaned off. He was extubated to CPAP
and was FiO
-weaned over the subsequent 4 weeks.
Patient 3 was born at 24 weeks and was ventilated from birth. He
became unwell on day 4 of life owing to the infection from sepsis-
causing Escherichia coli, and was therefore treated with a
prolonged course of antibiotics. The patient’s ventilation and FiO
requirements increased, requiring high-frequency oscillatory
ventilation and 100% oxygen. A chest radiograph showed left-sided
collapse after the preceding image had demonstrated right-sided
collapse, prompting the patient to be nursed left side up. He did not
respond to ventilation changes, and rhDNase treatment was
commenced on day 8 of life, receiving 2.5 mg of rhDNase that was
instilled endotracheally every 8 h for 5 days. On day 2 of this
regimen, his FiO
was weaned from 0.9 to 0.45; oxygenation index
decreased from 29.3 to 14.7 over the same time period; and after 4
days high-frequency oscillatory ventilation was changed to
conventional ventilation. A chest radiograph taken 5 days after
commencement of treatment demonstrated signiﬁcant
improvement in consolidation. The patient was extubated to CPAP
at 9 weeks of age.
Patient 4 was born at 28 weeks; he was ventilated from birth until
extubation to CPAP on day 6. He required reintubation at the age
of 5 weeks for an episode of profound apnea. Blood cultures were
negative but ETT aspirate supported the growth of Klebsiella spp.
In the context of persisting right middle lobe collapse on serial
chest radiographs, he was treated with antibiotics for 14 days. His
was stable at 0.35 but the radiological abnormalities persisted.
RhDNase treatment (2.5 mg, instilled endotracheally every 8 h) was
commenced. There was no improvement in radiographic
appearance, and ventilation requirements needed to be increased
over 9 days of treatment; therefore rhDNase was discontinued.
Review of the patient’s chest radiographs suggested that the middle
lobe collapse was secondary to the right upper lobe hyperinﬂation.
A radiological diagnosis of right upper lobe emphysema was
conﬁrmed bronchoscopically; lobectomy was performed at 10 weeks
of life and the patient was ultimately extubated to CPAP.
The ﬁrst three patients were all preterm infants with severe,
end-stage respiratory failure requiring maximal ventilator support
and showed radiological evidence of changing patterns of collapse
and consolidation. Each patient failed to show an improvement
after optimization of ventilation strategies and each of them
substantially improved following rhDNase therapy. Our fourth
patient’s presentation differed as he remained on conventional
ventilation with modest oxygen requirements; he did not respond to
rhDNase and a congenital lung abnormality was subsequently
identiﬁed. We did not observe any of the previously reported side
effects of rhDNase (voice alteration, pharyngitis, dyspepsia or facial
) in any of our patients; however, we were limited by the
small number of patients and by the difﬁculties in assessing
A small number of reports of the use of rhDNase in neonates
have previously been published. El Hassan and Huysman
the use of nebulized rhDNase in three preterm patients, similar to
the treatment in our ﬁrst three patients. All patients had lung
disease that was unresponsive to conventional strategies such as
position change, suctioning and escalation of ventilator mode and
settings. The rescue use of rhDNase was successful, with all
showing a rapid reduction in oxygen and ventilation requirement,
as well as radiographic improvement, within hours of
administration. Erdeve et al.
also reported the use of rhDNase in
12 ventilated newborns, 10 of whom were preterm, who had not
responded to conventional escalations of ventilation and had
radiologically documented atelectasis and received nebulized
rhDNase. Ten patients showed rapid clinical and radiological
response; the two patients who did not show a rapid
clinical and radiological response were subsequently
administered a single dose that was instilled through ETT,
resulting in recovery.
Our infants received a dosage of 2.5 mg (2.5 ml) every 8 or 12 h.
Three infants received the dose directly instilled into the trachea.
One patient received a nebulized dose: 2.5-mg rhDNase was diluted
with normal saline to a total volume of 4 ml and nebulized using a
gas ﬂow of 8 l min
during ongoing ventilation. Because of the
high bias ﬂows and low tidal volumes, it is not recommended to
administer nebulized therapy during high-frequency ventilation.
During volume targeted ventilation mode, the nebulization may
affect ﬂow sensor function and tidal volume measurement;
therefore, the ﬂow sensor was removed and a non-volume targeted
mode of ventilation was used during administration
patients. Our usual practice is to frequently suction the infant
immediately after administration, in order to clear loosened
secretions. Our infants tolerated both nebulized and instilled
dosing well; however, there was one incidence of bradycardia
and desaturation associated with rapid instillation. This
responded to a period of manual intermittent positive-pressure
In previously published reports, dose and frequency of
administration differed greatly both within and between centers
that use rhDNase in ventilated premature infants. Erdeve’s group
administered a nebulized dose of 1.25 mg (half the recommended
pediatric dose) twice daily with 2 h between each dose, for up to
3 days. If this regimen failed to produce clinical improvement, a
single dose of 1.25 mg was instilled endoctracheally.
In the report
by Hendriks et al.
of rhDNase administration in the pediatric
DNase for atelectasis
R MacKinnon et al
Journal of Perinatology
population, 250 mg (10% of the nebulized dose used) was
administered endotracheally to ventilated patients and was still
reported to yield an effect. There is no consensus on the optimum
dose or means of administration in ventilated neonates.
There is a lack of randomized trials in this patient group. A
recent randomized controlled trial of rhDNase in 225 infants with
bronchiolitis did not identify an improvement in symptom score,
duration of oxygen therapy or hospital stay in the treatment
Well-designed randomized studies, adequately powered and
including appropriately selected neonates could assess whether the
reported effects are therapeutic beneﬁts or coincidental
improvements and therapeutic beneﬁt. Additional trials will
potentially identify the optimal therapeutic approaches in
In our series, three of the four neonatal patients with end-stage
respiratory failure showed clinical improvement following rhDNase
therapy. These patients were noted to have problematic secretions,
high ventilation requirements and radiographic collapse that
varied with position. The non-responder had a congenital lung
abnormality. Other case series have suggested that rhDNase may
beneﬁt selected neonatal patients. Because of the low incidence
of this problem in the preterm population, a multicentre,
randomized trial with this therapy could potentially ascertain its
efﬁcacy and safety.
Conﬂict of interest
The authors declare no conﬂict of interest.
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DNase for atelectasis
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