Adjunct Therapies for Pediatric ARDS: Where are the Data?

Adjunct Therapies for Pediatric ARDS: Where are the Data? Alexandre T. Rotta, MD, FCCM Professor of Pediatrics, Linsalata Family Endowed Chair in Pediatric Critical Care and Emergency Medicine Rainbow Babies & Children s Hospital Case Western Reserve University, Cleveland, OH

Pressure-Volume Zones 50 Zone of Volutrauma 40 Volume (ml) 30 20 10 0 Zone of Atelectrauma 0 10 20 30 40 50 Pressure (cm H 2 O)

Effect of a Protective-Ventilation Strategy on Mortality in the Acute Respiratory Distress Syndrome Amato, MBP, et al. N Engl J Med 1998

Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome ARDS Network, N Engl J Med 2000

Adjunct Therapies in ARDS HFOV Inhaled Nitric Oxide Corticosteroids Exogenous Surfactant Neuromuscular Blockers Prone Position ETT Suctioning Chest Physiotherapy Epoprostenol 2 -agonists Heliox N-acetylcysteine ECMO 9

Adjunct Therapies in ARDS Inhaled Nitric Oxide Corticosteroids Exogenous Surfactant Neuromuscular Blockers Prone Position 12

Inhaled Nitric Oxide Griffiths MJD, Timothy W. Evans TW. N Engl J Med 2005; 353:2683-2695

Griffiths MJD, Timothy W. Evans TW. N Engl J Med 2005; 353:2683-2695

Acute Respiratory Distress Syndrome

Adhikari NKJ et al, BMJ 2007 Effect of nitric oxide on PaO 2 /FiO 2 ratio at 24 hours

Adhikari NKJ et al, BMJ 2007 Effect of nitric oxide on Mortality

Dellinger RP, et al. Crit Care Med 1998;26:15 23

Inhaled NO in Children with Acute Hypoxemic Respiratory Failure Day RW et al, Chest 1997

Dobyns EL, et al. J Pediatr 1999;134:406 12)

Patients with OI>25 at enrollment Immunocompromised Patients Dobyns EL, et al. J Pediatr 1999;134:406 12)

Adhikari NKJ et al, Crit Care Med 2013

Ruan SY et al, Critical Care Med 2015

PALICC Recommendations ino is not recommended for routine use in PARDS. Its use may be considered in patients with documented pulmonary hypertension or severe right ventricular dysfunction. It may be considered in severe cases of PARDS as a rescue from or bridge to extracorporeal life support. When used, assessment of benefit must be undertaken promptly and serially to minimize toxicity and to eliminate continued use without established effect. Tamburro RS, Kneyber MC, for the PALICC Group, 2015

How do I Use ino in the PARDS? Rarely, and when forced to Cosmetic therapy: buys 24 48 hrs of improved oxygenation Start at 20 ppm and attempt to decrease FiO 2 to < 0.6 Monitor frequent ABGs Follow methemoglobin Follow NO 2 measurements Wean by 5 ppm once evidence of improvement Wean by 1 ppm when dose is at 5 ppm Watch for rebound hypoxemia

Adjunct Therapies in ARDS Inhaled Nitric Oxide Corticosteroids Exogenous Surfactant Neuromuscular Blockers Prone Position 34

Corticosteroids in PARDS No RCTs evaluating glucocorticoids in pediatric ARDS Case reports and small case series Adult data are conflicting

PALICC Recommendations At this time, corticosteroids cannot be recommended as routine therapy in PARDS. Further study should focus on specific patient populations that are likely to benefit from corticosteroid therapy and specific dosing and delivery regimens. (Strong agreement) Tamburro RS, Kneyber MC, for the PALICC Group, 2015

Do I use Steroids in the PARDS? Not routinely Have used methylprednisolone for the very rare and occasional patient if I can find a reasonable justification ARDS in a patient with chronic lung disease Last effort when family not agreeable to ECLS escalation

Adjunct Therapies in ARDS Inhaled Nitric Oxide Corticosteroids Exogenous Surfactant Neuromuscular Blockers Prone Position 40

Surfactant Control Surfactant 42 children in 8 ICUs Well tolerated Earlier extubation (4.2 days sooner) Earlier discharge from ICU (5 days sooner) No difference in mortality Willson DF, et al Crit Care Med 1999;27:188 195

Proportion of Calfactant Compared With Placebo Patients Successfully Extubated in the 28 Days After Study Entry

Thomas NJ et al. Pediatr Crit Care Med, 2012 47

PALICC Recommendations At this time, surfactant therapy cannot be recommended as routine therapy in PARDS. Further study should focus on specific patient populations that may be likely to benefit and specific dosing and delivery regimens. (Strong agreement) Tamburro RS, Kneyber MC, for the PALICC Group, 2015

Do I use Surfactant in the PARDS? Not routinely Have used exogenous surfactant in children who are stuck on ECLS with non-recruitable lungs. Have used it as part of a clinical trial

Adjunct Therapies in ARDS Inhaled Nitric Oxide Corticosteroids Exogenous Surfactant Neuromuscular Blockers Prone Position 50

PALICC Recommendations We recommend that if sedation alone is inadequate to achieve effective mechanical ventilation, NMB should be considered. When used, pediatric patients with PARDS should receive minimal yet effective NMB with sedation to facilitate their tolerance to mechanical ventilation and to optimize oxygen delivery, oxygen consumption, and work of breathing. (Strong agreement) Valentine SL, for the PALICC Group, 2015

PALICC Recommendations NMB use should be monitored and titrated to goal Consider a daily holiday Clinical trials should report their NMB strategy Further studies are needed (Strong agreement) Valentine SL, for the PALICC Group, 2015

Do I use NMB in the PARDS? Yes, my usage matches the PALICC recommendations

Adjunct Therapies in ARDS Inhaled Nitric Oxide Corticosteroids Exogenous Surfactant Neuromuscular Blockers Prone Position 57

Prone Positioning Supine Prone

Gattinoni L, et al. NEJM 2001;234:568 73

PALICC Recommendations Prone positioning cannot be recommended as routine therapy in PARDS. However, it should be considered an option in cases of severe PARDS. Further pediatric study is warranted, particular study stratifying on the basis of severity of lung injury. (Weak agreement) Tamburro RS, Kneyber MC, for the PALICC Group, 2015

Do I use Prone Positioning in the PARDS? Yes, my usage matches the PALICC recommendations

Thank You! Alex.Rotta@UHhospitals.org 72