Inhaled Nitric Oxide Title of Guideline Guideline for the Use of inhaled Nitric Oxide (NO) 1a 2a 2b Contact Name and Job Title (author) Directorate & Speciality Date of submission October 2015 Date when guideline reviewed October 2018 Guideline Number 1973 Explicit definition of patient group to which it applies (e.g. inclusion and exclusion criteria, diagnosis) Catarina Silvestre Prof. Harish Vyas Directorate: Family Health Children Speciality: Paediatric Intensive Care Patients with Pulmonary Hypertension or ARDS Abstract This guideline describes the indications and the methods for using NO Key Words Paediatrics. Children. Nitric Oxide. Pulmonary hypertension Statement of the evidence base of the guideline has the guideline been peer reviewed by colleagues? meta analysis of randomised controlled x trials at least one well-designed controlled study without randomisation at least one other type of well-designed quasi-experimental study 3 well designed non-experimental descriptive studies (ie comparative / correlation and case studies) 4 expert committee reports or opinions and / or clinical experiences of respected authorities 5 recommended best practise based on the clinical experience of the guideline developer Consultation Process Staff at Nottingham Children s Hospital PICU Target audience PICU staff This guideline has been registered with the trust. However, clinical guidelines are guidelines only. The interpretation and application of clinical guidelines will remain the responsibility of the individual clinician. If in doubt contact a senior colleague or expert. Caution is advised when using guidelines after the review date. Catarina Silvestre Page 1 of 5 October 2015
BACKGROUND: Inhaled Nitric oxide (NO) is well established as a highly effective selective pulmonary vasodilator synthesized by the enzyme nitric oxide synthase (NOS) by endothelial cells NO is a gas molecule that diffuses freely from the endothelium to vascular smooth muscle cell, that leads to pulmonary vasodilatation. Nitric oxide is currently used in newborns with Primary Pulmonary hypertension (PPHN) or congenital heart diseases associated pulmonary hypertension. In Paediatric and adults patients, there is no evidence of benefit of NO in acute respiratory syndrome or hypoxic respiratory failure. Despite the improvement of PaO 2 /FiO 2 in the first 4 days of the treatment, there is no reduction in mortality or other outcomes INDICATIONS: Neonatal conditions PPHN Congenital diaphragmatic hernia Neonatal Pulmonary Hypoplasia Pulmonary hypertension in postoperative patient with congenital heart disease Paediatric use Inhaled nitric oxide is not recommended for routine use in paediatric ARDS (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 bridge to extracorporeal life support. When used, assessment of benefit must be undertaken promptly and serially to minimize toxicity and to eliminate continued ADMINISTRATION: Optimize ventilation: Make sure that the strategy is appropriate for the underlying lung disease Calculate the Oxygenation Index (OI) and record sato 2 Echocardiography is a essential to assess pulmonary artery pressures and for evaluation of right ventricular function Start NO initially at 20 PPM and assess sato 2 After 30 minutes if there is no improvement in OI, STOP the NO Beware of transient drop of SaO 2 due to rebound pulmonary hypertension upon withdrawal. If a patient responds to NO, reduce to the lower effective dose after 12-24 hours Catarina Silvestre Page 2 of 5 October 2015
The required dose of NO will vary from patient to patient. The lowest efficacious dose should be used. Should not be used for greater than 48 hours WEANING: NO may be weaned in a step wise fashion, with a decrement of 5 ppm at a time until 5ppm. Once at 5 ppm it may be desirable to drop 1 ppm each time. At 1 ppm, increase FiO2 by 10% and stop NO. If saturation deteriorates, go back 2-3 ppm and wean 1ppm slowly (NO can be reduced at even slower rate) For the next weaning attempt considerer increasing the FiO2 20-30% and considerer use of oral phosphodiesterase-5-inhibitor (sildenafil 0,3mg/kg/dose 3-6 hourly, increasing as needed to maximum of 1 mg/kg/dose) NO 20 ppm 30 minutes Improvement PaO 2 / FiO 2 No improvement PaO 2 /FiO 2 STOP NO 12-24 h 5ppm/ 5ppm 5ppm 1ppm/ 1ppm 1 ppm FiO 2 10% STOP NO Failure to wean: Back to 2-3 ppm Wean slowly until 1ppm Increase FiO2 20-30% Sildenafil MONITORING Catarina Silvestre Page 3 of 5 October 2015
Methemoglobin (MetHb) levels should be recorded 1 and 6 hours after starting and then twice a day.). Half-life of NO is 5 hours Normal range of MetHb: <1-3 % optimal 5-10% reduce NO dose by 50%. >10 % stop NO >20% Methylene blue 1-2 mg/kg IV. NO2 and peroxynitrite: toxic products produced by spontaneous conversion of NO in presence of O 2, or reaction to the presence of free radicals. Clinical trials have stablished low levels of exhaled NO 2, but the effects of NO 2 in poor perfused areas of the lung my cause deleterious effects CONTRAINDICATIONS 1. Methemoglobin reductase deficiency 2. Glucose 6 phosphate dehydrogenase deficiency 3. Neonates dependent on right- to-left shunting of blood Catarina Silvestre Page 4 of 5 October 2015
REFERENCES: Barr FE, Macrae D. Inhaled Nitric Oxide and Related Therapies. Pediatr Crit Care Med. 2010; 11(2): S30-36. Steinhorn RH. Therapeutic approaches using nitric oxide in infants and children. Radic Biol Med. 2011; 51(5): 1027-1034. Adhikari NK, Dellinger RP, Lundin S, Payen D, Vallet B, Gerlach H, Park KJ, Mehta S, Slutsky AS, Friedrich JO. Inhaled Nitric Oxide Does Not reduce Mortality in Patients With Acute Respiratory Distress Syndrome Regardless of Severity: Systemic Review and Meta- Analysis. Crit Care Med. 2014; 42(20): 405-412. Scheider J, Sweberg T. Acute Respiratory Failure. Crit Care Clin. 2013; 29: 168-183 Afshari A, Brok J, Møller AM, Wetterslev J. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) and acute lung injury in children and adults (Review). Cochrane Collaboration. 2013;1-99. http://www.thecochranelibrary.com Valentine S, Nadkarni V, Curley M, for the Paediatric Acute Lung Injury Consensus Conference Group. Ped Crit Care Med. 2015;16 (5 Sup):S73-S85 Catarina Silvestre Page 5 of 5 October 2015