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DOI: 10.1542/peds.2012-0587
; originally published online January 6, 2013; 2013;131;e626 Pediatrics
Andrew Peter Maxted, Abigail Hill and Patrick Davies
Crisis
Oral Sildenafil as a Rescue Therapy in Presumed Acute Pulmonary Hypertensive
 
 
 
http://pediatrics.aappublications.org/content/131/2/e626.full.html
located on the World Wide Web at:
The online version of this article, along with updated information and services, is
 
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
publication, it has been published continuously since 1948. PEDIATRICS is owned,
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
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Oral Sildenafil as a Rescue Therapy in Presumed Acute
Pulmonary Hypertensive Crisis
abstract
A 23-week-old baby, born at 26
+2
weeks, presented to the hospital with
critical respiratory failure, which was impossible to stabilize. She had
unstable oxygen saturations between 35% and 95%. A presumptive
diagnosis of bronchopulmonary dysplasia with associated pulmonary
hypertensive crisis was made. In the absence of inhaled nitric oxide, 2
oral doses of 1 mg/kg sildenafil were given, with a dramatic improve-
ment 30 to 45 minutes later. Her oxygenation index fell from 43 to 14.
She made a full recovery and was discharged from the hospital 2
weeks later. Pediatrics 2013;131:e626–e628
AUTHORS: Andrew Peter Maxted, BMBS, Abigail Hill, MN,
and Patrick Davies, BMBS, MRCPCH
Paediatric Intensive Care Unit, Nottingham Children’s Hospital,
Queens Medical Centre, Nottingham, United Kingdom
KEY WORDS
pulmonary hypertension, intensive care, sildenafil, crisis
ABBREVIATIONS
CLD—chronic lung disease
NO—nitric oxide
www.pediatrics.org/cgi/doi/10.1542/peds.2012-0587
doi:10.1542/peds.2012-0587
Accepted for publication Oct 1, 2012
Address correspondence to Andrew Maxted, BMBS, Paediatric
Intensive Care Unit, Nottingham Children’s Hospital, Queen’s
Medical Centre, Derby Rd, Nottingham, NG7 2UH United Kingdom.
E-mail: [email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2013 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have
no financial relationships relevant to this article to disclose.
FUNDING: No external funding.
e626 MAXTED et al
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Pulmonary hypertension occurs when
there is an increase in pulmonary vas-
cular pressure, which can then lead to
a right to left shunt. Recognized treat-
ment optionsincludeinhalednitricoxide
(NO), prostacyclin, and oral sildenafil,
with supportive care as needed.
1–4
Sildenafil has been used in pulmonary
hypertension since 1999.
1
It is becoming
standard treatment of patients with
chronic pulmonary hypertension and is
also used to aid weaning from inhaled
NO therapy.
1,2
The use of oral sildenafil
has also been documented as an ad-
junctive therapy when previous treat-
ment options have failed;
3–6
however, its
use as an emergency treatment of pul-
monary hypertension is limited to a sin-
gle case report of persistent pulmonary
hypertension of the newborn and news
articles.
7,8
We discuss a patient treated
at a local hospital where inhaled NO was
not available and rescue oral sildenafil
was used to excellent effect.
PATIENT
The patient was born at 26
+2
weeks
by emergency caesarean delivery for
severe maternal preeclampsia, with
a birth weight of 599 g. She was venti-
lated for 31 days and then needed 11
days of noninvasive ventilation. She was
diagnosed with chronic lung disease
(CLD) and needed oxygen at discharge.
Her other comorbidities included a pat-
ent ductus arteriosus and retinopathy
of prematurity. She was discharged at
2 months’ corrected age with a weight
of 3455 g, requiring 0.2 L of oxygen
and nasogastric feed.
The patient presented to her local hos-
pital the morning after discharge aged
23 weeks with a history of respiratory
arrest. During an overnight feed, the
baby stopped breathing and mother
started cardiopulmonary resuscitation.
Onarrival totheemergencydepartment,
her heart rate was .100, but she was
cold and blue with unrecordable oxygen
saturations. Her initial capillary blood
gas showed a pH of 6.99 with a pCO
2
of
14.9 kPa. After limited improvement
following a fluid bolus, antibiotics, and
oxygen therapy, she was intubated and
ventilated.
On arrival of the regional pediatric in-
tensive care retrieval team, the satu-
rations were 89% in 85% oxygen. After
initial stabilization, difficulties were en-
countered in maintaining adequate ox-
ygenation. Despite hand ventilating the
patient in 100% oxygen, her oxygen sat-
urations were fluctuating between 35%
and95%. Anotherchest radiographruled
out a pneumothorax and showed severe
CLD but no gross consolidation. The pa-
tient continued to deteriorate, and high
pressures were needed to keep satu-
rations .75%but were commonly in the
50s. Parents were advised that the baby
was unlikely to survive the transfer.
In the absence of inhaled NO and faced
with a severely sick patient with risk
factors for pulmonary hypertension, a
rescue dose of sildenafil 1 mg/kg was
given via the nasogastric tube (Fig 1).
Within 20 to 30 minutes a slight im-
provement was seen, but the saturations
were still low, so an additional 1 mg/kg
dose was given. Within 15 minutes, there
was a marked improvement in the
saturations, which remained .95%
for the rest of the transfer. No side
effects were observed; her blood
pressure remained stable with her
oxygenation index dropping from 43
to 14. On arrival to the regional pedi-
atric ICU, the patient was started on
high-frequency oscillation ventilation and
inhaled NO. She made a good recovery
and was transferred back to her local
hospital within 2 weeks.
DISCUSSION
Sildenafil is a selective phosphodies-
terase inhibitor and has been shown in
studies to improve pulmonary hyper-
tension in both adult and pediatric
populations.
9–11
The dosing regimen for
acute pulmonary hypertension is not
clear, and data are limited. One study
demonstrated that plasma levels after
doses of 0.5 to 2 mg/kg are similar to
maximum plasma concentrations in
adults on sildenafil.
12
Potential reported
side effects include arterial hypoxemia
(due to increased intrapulmonary shunt)
and hypotension.
1,2,7,13,14
Sildenafil has
been shown to have an onset of action in
30 to 120 minutes (mean 60 min)
10
and
has been shown to improve pulmonary
arterial pressures, systemic saturations,
and oxygen index and maintain V/Q
matching.
5,
10,11
Theoretically, V/Q mis-
matching may occur due to global
pulmonary vasodilatation, but no evi-
dence of this was seen.
Pediatric intensive care teams un-
dertaking transfers of critically ill
children need to cope with critical sit-
uations in which advanced intensive
care therapies are often not available.
FIGURE 1
Oxygen saturations over time: the first dose of sildenafil was given at 14:10.
CASE REPORT
PEDIATRICS Volume 131, Number 2, February 2013 e627
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Such teams need to make difficult
choices as to the risks and benefits of
novel treatments based on the patient’s
pathophysiology.
Efficacy of this treatment is difficult to
prove because we did not have pre- and
posttreatment echocardiographic as-
sessment of the pulmonary artery
pressures. Although the improvement
in the patient’s saturations might have
been due to improved lung compli-
ance, her ventilator pressure needs
remained extremely high throughout
the transfer period and beyond. The
improvement was temporarily linked
to the sildenafil dose with no other
changes in management or physiologic
parameters.
The successful outcome of this pa-
tient underlines the difficult scenarios
undertaken by pediatric intensive care
transfer teams. In this patient’s case,
inaction would have probably led to the
patient’s death. Transfer teams take
risks on their patient’s behalf, making
difficult decisions in the absence of
a robust evidence base. For teams in
such situations, it is important that
their decisions are based on balancing
the acute pathophysiology and the re-
sources at hand and that they can be
justified after the event.
CONCLUSION
Sildenafil is known to help in cases
of chronic pulmonary hypertension, al-
though evidence of its use in emergency
situations is limited. We used a rescue
dose of two 1 mg/kg doses of oral
sildenafil in a case of presumed pul-
monary hypertensive crisis. Our patient
had a dramatic improvement in her
ventilation and saturations within 45
minutes. We conclude that the use of
sildenafil intheemergency treatment of
presumed pulmonary hypertension
was temporally associated with a life-
saving clinical improvement with no
evidence of side effects.
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e628 MAXTED et al
by guest on April 22, 2014 pediatrics.aappublications.org Downloaded from
DOI: 10.1542/peds.2012-0587
; originally published online January 6, 2013; 2013;131;e626 Pediatrics
Andrew Peter Maxted, Abigail Hill and Patrick Davies
Crisis
Oral Sildenafil as a Rescue Therapy in Presumed Acute Pulmonary Hypertensive
 
 
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rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
Grove Village, Illinois, 60007. Copyright © 2013 by the American Academy of Pediatrics. All
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly
by guest on April 22, 2014 pediatrics.aappublications.org Downloaded from

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