J Pediatr Intensive Care 2023; 12(02): 148-153
DOI: 10.1055/s-0041-1730900
Original Article

Role of Sildenafil in Management of Pediatric Acute Respiratory Distress Syndrome

Monika Janagill
1   Department of Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
,
Puneet Aulakh Pooni
2   Department of Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
,
Siddharth Bhargava
2   Department of Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
,
Shibba Takkar Chhabra
3   Department of Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
› Author Affiliations

Abstract

Acute respiratory distress syndrome (ARDS) has high mortality and multiple therapeutic strategies have been used to improve the outcome. Inhaled nitric oxide (INO), a pulmonary vasodilator, is used to improve oxygenation. This study was conducted to determine the role of sildenafil, an oral vasodilator, to improve oxygenation and mortality in pediatric ARDS (PARDS). The prevalence of pulmonary hypertension in PARDS was studied as well. Inclusion criteria included children (1–18 years) with ARDS requiring invasive ventilation admitted to the pediatric intensive care unit of a teaching hospital in Northern India over a 1-year period of time. Thirty-five patients met the inclusion criteria. Pulmonary arterial pressure (PAP) was determined by echocardiogram. Patients with persistent hypoxemia were started on oral sildenafil. The majority of patients (77%) had a primary pulmonary etiology of PARDS. Elevated PAP (>25 mm Hg) was detected in 54.3% patients at admission. Sildenafil was given to 20 patients who had severe and persistent hypoxemia. Oxygenation improved in most patients after the first dose with statistically significant improvement in PaO2/FiO2 ratios at both 12 and 24 hours following initiation of therapeutic dosing of sildenafil. Improvement in oxygenation occurred irrespective of initial PAP. Outcomes included a total of 57.1% patients discharged, 28.6% discharged against medical advice (DAMA), and a 14.3% mortality rate. Mortality was related to the severity of PARDS and not the use of sildenafil. This is the first study to determine the effect of sildenafil in PARDS. Sildenafil led to improvement in oxygenation in nearly all the cases without affecting mortality. Due to unavailability of INO in most centers of developing countries, sildenafil may be considered as an inexpensive alternative in cases of persistent hypoxemia in PARDS. We recommend additional randomized controlled trials to confirm the effect of sildenafil in PARDS as determined in this study.



Publication History

Received: 18 January 2021

Accepted: 30 March 2021

Article published online:
19 June 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. Lancet 1967; 2 (7511): 319-323
  • 2 Tomashefski Jr JF. Pulmonary pathology of acute respiratory distress syndrome. Clin Chest Med 2000; 21 (03) 435-466
  • 3 Payen DM. Is nitric oxide inhalation a “cosmetic” therapy in acute respiratory distress syndrome?. Am J Respir Crit Care Med 1998; 157 (5 Pt 1): 1361-1362
  • 4 Moloney ED, Evans TW. Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome. Eur Respir J 2003; 21 (04) 720-727
  • 5 Kaisers U, Busch T, Deja M, Donaubauer B, Falke KJ. Selective pulmonary vasodilation in acute respiratory distress syndrome. Crit Care Med 2003; 31 (Suppl. 04) S337-S342
  • 6 Blanch L, Joseph D, Fernández R. et al. Hemodynamic and gas exchange responses to inhalation of nitric oxide in patients with the acute respiratory distress syndrome and in hypoxemic patients with chronic obstructive pulmonary disease. Intensive Care Med 1997; 23 (01) 51-57
  • 7 Dhariwal AK, Bavdekar SB. Sildenafil in pediatric pulmonary arterial hypertension. J Postgrad Med 2015; 61 (03) 181-192
  • 8 Akmal AH, Hasan M. Role of nitric oxide in management of acute respiratory distress syndrome. Ann Thorac Med 2008; 3 (03) 100-103
  • 9 Ranieri VM, Rubenfeld GD, Thompson BT. et al; ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition. JAMA 2012; 307 (23) 2526-2533
  • 10 Desai AR, Deep A. Ventilatory strategies and adjunctive therapy in ARDS. Indian J Pediatr 2006; 73 (08) 661-668
  • 11 Erickson S, Schibler A, Numa A. et al; Paediatric Study Group, Australian and New Zealand Intensive Care Society. Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study. Pediatr Crit Care Med 2007; 8 (04) 317-323
  • 12 Dahlem P, van Aalderen WMC, Hamaker ME, Dijkgraaf MGW, Bos AP. Incidence and short-term outcome of acute lung injury in mechanically ventilated children. Eur Respir J 2003; 22 (06) 980-985
  • 13 Wong JJ, Loh TF, Testoni D, Yeo JG, Mok YH, Lee JH. Epidemiology of pediatric acute respiratory distress syndrome in Singapore: risk factors and predictive respiratory indices for mortality. Front Pediatr 2014; 2: 78
  • 14 Wong JJ, Jit M, Sultana R. et al. Mortality in pediatric acute respiratory distress syndrome: a systematic review and meta-analysis. J Intensive Care Med 2019; 34 (07) 563-571
  • 15 Chakravarty A, Mohapatra J, Garg R, Kumar S. Outcome analysis of a newly setup pediatric intensive care unit in a teaching hospital of northern India. Int J Contemp Pediatrics 2019; 6 (05) 2147-2151
  • 16 Ashrafi E, Nobakht S, Keykaleh MS, Kakemam E, Hasanpoor E, Sokhanvar M. Discharge against medical advice (DAMA): causes and predictors. Electron Physician 2017; 9 (06) 4563-4570
  • 17 Gautam N, Sharma JP, Sharma A, Verma V, Arora P, Gautam PL. Retrospective evaluation of patients who leave against medical advice in a Tertiary Teaching Care Institute. Indian J Crit Care Med 2018; 22 (08) 591-596
  • 18 Hasan O, Samad MA, Khan H. et al. Leaving against medical advice from in-patients departments rate, reasons and predicting risk factors for re-visiting hospital retrospective cohort from a tertiary care hospital. Int J Health Policy Manag 2019; 8 (08) 474-479
  • 19 Chetan G, Rathisharmila R, Narayanan P, Mahadevan S. Acute respiratory distress syndrome in pediatric intensive care unit. Indian J Pediatr 2009; 76 (10) 1013-1016
  • 20 Khilnani P, Sarma D, Singh R. et al. Demographic profile and outcome analysis of a tertiary level pediatric intensive care unit. Indian J Pediatr 2004; 71 (07) 587-591
  • 21 Trachsel D, McCrindle BW, Nakagawa S, Bohn D. Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2005; 172 (02) 206-211
  • 22 Hammond BG, Garcia-Filion P, Kang P, Rao MY, Willis BC, Dalton HJ. Identifying an oxygenation index threshold for increased mortality in acute respiratory failure. Respir Care 2017; 62 (10) 1249-1254
  • 23 Prasertsan P, Anuntaseree W, Ruangnapa K, Saelim K, Geater A. Severity and mortality predictors of pediatric acute respiratory distress syndrome according to the pediatric acute lung injury consensus conference definition. Pediatr Crit Care Med 2019; 20 (10) e464-e472
  • 24 Zapol WM, Snider MT. Pulmonary hypertension in severe acute respiratory failure. N Engl J Med 1977; 296 (09) 476-480
  • 25 Ñamendys-Silva SA, Santos-Martínez LE, Pulido T. et al. Pulmonary hypertension due to acute respiratory distress syndrome. Braz J Med Biol Res 2014; 47 (10) 904-910
  • 26 Guzmán MC, Izquierdo LM, Carvajal D, Duque B, Rodriguez-Martinez MC. Clinical outcomes of pulmonary hypertension in children with pneumonia and respiratory failure. J Respir Dis 2017; 1: 107
  • 27 Yaseen H, Darwich M, Hamdy H. Is sildenafil an effective therapy in the management of persistent pulmonary hypertension?. J Clin Neonatol 2012; 1 (04) 171-175
  • 28 Ikeda D, Tsujino I, Ohira H. et al. Addition of oral sildenafil to beraprost is a safe and effective therapeutic option for patients with pulmonary hypertension. J Cardiovasc Pharmacol 2005; 45 (04) 286-289
  • 29 Erickson S, Reyes J, Bohn D, Adatia I. Sildenafil (Viagra) in childhood and neonatal pulmonary hypertension. J Am Coll Cardiol 2002; 39: 402
  • 30 Cornet AD, Hofstra JJ, Swart EL, Girbes ARJ, Juffermans NP. Sildenafil attenuates pulmonary arterial pressure but does not improve oxygenation during ARDS. Intensive Care Med 2010; 36 (05) 758-764
  • 31 Tarry D, Powell M. Hypoxic pulmonary vasoconstriction. BJA Educ 2017; 17 (06) 208-213
  • 32 Blanch L, Albaiceta GM. Sildenafil for pulmonary hypertension in ARDS: a new pleasant effect?. Intensive Care Med 2010; 36 (05) 729-731