DOI: 10.1542/peds.2012-0587; originally published online January 6, 2013; 2013;131;e626Pediatrics

Andrew Peter Maxted, Abigail Hill and Patrick DaviesCrisis

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 Pointpublication, 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 AcutePulmonary Hypertensive Crisis

abstractA 23-week-old baby, born at 26+2 weeks, presented to the hospital withcritical respiratory failure, which was impossible to stabilize. She hadunstable oxygen saturations between 35% and 95%. A presumptivediagnosis of bronchopulmonary dysplasia with associated pulmonaryhypertensive crisis was made. In the absence of inhaled nitric oxide, 2oral 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 2weeks 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 WORDSpulmonary hypertension, intensive care, sildenafil, crisis

ABBREVIATIONSCLD—chronic lung diseaseNO—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, PaediatricIntensive Care Unit, Nottingham Children’s Hospital, Queen’sMedical Centre, Derby Rd, Nottingham, NG7 2UH United Kingdom.E-mail: andrewmaxted@nhs.net

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2013 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated they haveno financial relationships relevant to this article to disclose.

FUNDING: No external funding.

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Pulmonary hypertension occurs whenthere is an increase in pulmonary vas-cular pressure, which can then lead toa right to left shunt. Recognized treat-mentoptions include inhalednitricoxide(NO), prostacyclin, and oral sildenafil,with supportive care as needed.1–4

Sildenafil has been used in pulmonaryhypertension since 1999.1 It is becomingstandard treatment of patients withchronic pulmonary hypertension and isalso used to aid weaning from inhaledNO therapy.1,2 The use of oral sildenafilhas also been documented as an ad-junctive therapy when previous treat-ment options have failed;3–6 however, itsuse as an emergency treatment of pul-monary hypertension is limited to a sin-gle case report of persistent pulmonaryhypertension of the newborn and newsarticles.7,8 We discuss a patient treatedat a local hospital where inhaled NO wasnot available and rescue oral sildenafilwas used to excellent effect.

PATIENT

The patient was born at 26+2 weeksby emergency caesarean delivery forsevere maternal preeclampsia, witha birth weight of 599 g. She was venti-lated for 31 days and then needed 11days of noninvasive ventilation. She wasdiagnosed with chronic lung disease(CLD) and needed oxygen at discharge.Her other comorbidities included a pat-ent ductus arteriosus and retinopathyof prematurity. She was discharged at2 months’ corrected age with a weightof 3455 g, requiring 0.2 L of oxygenand nasogastric feed.

The patient presented to her local hos-pital the morning after discharge aged23 weeks with a history of respiratoryarrest. During an overnight feed, thebaby stopped breathing and motherstarted cardiopulmonary resuscitation.Onarrival to theemergencydepartment,her heart rate was .100, but she wascold and blue with unrecordable oxygensaturations. Her initial capillary blood

gas showed a pH of 6.99 with a pCO2 of14.9 kPa. After limited improvementfollowing a fluid bolus, antibiotics, andoxygen therapy, she was intubated andventilated.

On arrival of the regional pediatric in-tensive care retrieval team, the satu-rations were 89% in 85% oxygen. Afterinitial stabilization, difficulties were en-countered in maintaining adequate ox-ygenation. Despite hand ventilating thepatient in 100% oxygen, her oxygen sat-urations were fluctuating between 35%and95%.Anotherchestradiographruledout a pneumothorax and showed severeCLD but no gross consolidation. The pa-tient continued to deteriorate, and highpressures were needed to keep satu-rations.75%butwere commonly in the50s. Parents were advised that the babywas unlikely to survive the transfer.

In the absence of inhaled NO and facedwith a severely sick patient with riskfactors for pulmonary hypertension, arescue dose of sildenafil 1 mg/kg wasgiven via the nasogastric tube (Fig 1).Within 20 to 30 minutes a slight im-provementwas seen, but the saturationswere still low, so an additional 1 mg/kgdose was given. Within 15 minutes, therewas a marked improvement in thesaturations, which remained .95%for the rest of the transfer. No sideeffects were observed; her bloodpressure remained stable with heroxygenation index dropping from 43

to 14. On arrival to the regional pedi-atric ICU, the patient was started onhigh-frequency oscillation ventilation andinhaled NO. She made a good recoveryand was transferred back to her localhospital within 2 weeks.

DISCUSSION

Sildenafil is a selective phosphodies-terase inhibitor and has been shown instudies to improve pulmonary hyper-tension in both adult and pediatricpopulations.9–11 The dosing regimen foracute pulmonary hypertension is notclear, and data are limited. One studydemonstrated that plasma levels afterdoses of 0.5 to 2 mg/kg are similar tomaximum plasma concentrations inadults on sildenafil.12 Potential reportedside effects include arterial hypoxemia(due to increased intrapulmonary shunt)and hypotension.1,2,7,13,14 Sildenafil hasbeen shown to have an onset of action in30 to 120 minutes (mean 60 min)10 andhas been shown to improve pulmonaryarterial pressures, systemic saturations,and oxygen index and maintain V/Qmatching.5,10,11 Theoretically, V/Q mis-matching may occur due to globalpulmonary vasodilatation, but no evi-dence of this was seen.

Pediatric intensive care teams un-dertaking transfers of critically illchildren need to cope with critical sit-uations in which advanced intensivecare therapies are often not available.

FIGURE 1Oxygen saturations over time: the first dose of sildenafil was given at 14:10.

CASE REPORT

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Such teams need to make difficultchoices as to the risks and benefits ofnovel treatments based on the patient’spathophysiology.

Efficacy of this treatment is difficult toprove because we did not have pre- andposttreatment echocardiographic as-sessment of the pulmonary arterypressures. Although the improvementin the patient’s saturations might havebeen due to improved lung compli-ance, her ventilator pressure needsremained extremely high throughoutthe transfer period and beyond. Theimprovement was temporarily linkedto the sildenafil dose with no other

changes in management or physiologicparameters.

The successful outcome of this pa-tient underlines the difficult scenariosundertaken by pediatric intensive caretransfer teams. In this patient’s case,inaction would have probably led to thepatient’s death. Transfer teams takerisks on their patient’s behalf, makingdifficult decisions in the absence ofa robust evidence base. For teams insuch situations, it is important thattheir decisions are based on balancingthe acute pathophysiology and the re-sources at hand and that they can bejustified after the event.

CONCLUSION

Sildenafil is known to help in casesof chronic pulmonary hypertension, al-though evidence of its use in emergencysituations is limited.We used a rescuedose of two 1 mg/kg doses of oralsildenafil in a case of presumed pul-monaryhypertensive crisis. Ourpatienthad a dramatic improvement in herventilation and saturations within 45minutes. We conclude that the use ofsildenafil in theemergency treatmentofpresumed pulmonary hypertensionwas temporally associated with a life-saving clinical improvement with noevidence of side effects.

REFERENCES

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2. Namachivayam P, Theilen U, Butt WW, CooperSM, Penny DJ, Shekerdemian LS. Sildenafilprevents rebound pulmonary hypertensionafter withdrawal of nitric oxide in children.Am J Respir Crit Care Med. 2006;174(9):1042–1047

3. Chaudhari M, Vogel M, Wright C, Smith J,Haworth SG. Sildenafil in neonatal pulmonaryhypertension due to impaired alveolarisationand plexiform pulmonary arteriopathy. ArchDis Child Fetal Neonatal Ed. 2005;90(6):F527–F528

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5. Hon KL, Cheung KL, Siu KL, et al. Oral sil-denafil for treatment of severe pulmonaryhypertension in an infant. Biol Neonate.2005;88(2):109–112

6. Lammers AE, Haworth SG, Pierce CM. In-travenous sildenafil as an effective treat-ment of pulmonary hypertensive crisesduring acute intestinal malabsorption[published correction appears in CariolYoung. 2006;16(3)328]. Cardiol Young. 2006;16(1):84–86

7. Juliana AE, Abbad FC. Severe persistentpulmonary hypertension of the newborn ina setting where limited resources excludethe use of inhaled nitric oxide: successfultreatment with sildenafil. Eur J Pediatr.2005;164(10):626–629

8. Kumar S. Indian doctor in protest afterusing Viagra to save “blue babies.” BMJ.2002;325(7357):181

9. Zhao L, Mason NA, Morrell NW, et al. Sil-denafil inhibits hypoxia-induced pulmonaryhypertension. Circulation. 2001;104(4):424–428

10. Huddleston AJ, Knoderer CA, Morris JL,Ebenroth ES. Sildenafil for the treatmentof pulmonary hypertension in pediatric

patients. Pediatr Cardiol. 2009;30(7):871–882

11. Ghofrani HA, Wiedemann R, Rose F, et al.Sildenafil for treatment of lung fibrosisand pulmonary hypertension: a randomisedcontrolled trial. Lancet. 2002;360(9337):895–900

12. Karatza AA, Bush A, Magee AG. Safety andefficacy of Sildenafil therapy in childrenwith pulmonary hypertension. Int J Cardiol.2005;100(2):267–273

13. Khorana M, Yookaseam T, Layangool T,Kanjanapattanakul W, Paradeevisut H. Out-come of oral sildenafil therapy on persistentpulmonary hypertension of the newborn atQueen Sirikit National Institute of ChildHealth. J Med Assoc Thai. 2011;94(suppl 3):S64–S73

14. Kloner RA. Cardiovascular effects of the3 phosphodiesterase-5 inhibitors ap-proved for the treatment of erectiledysfunction. Circulation. 2004;110(19):3149–3155

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DOI: 10.1542/peds.2012-0587; originally published online January 6, 2013; 2013;131;e626Pediatrics

Andrew Peter Maxted, Abigail Hill and Patrick DaviesCrisis

Oral Sildenafil as a Rescue Therapy in Presumed Acute Pulmonary Hypertensive  

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