Methods for improving the safety of treating pediatric patients who are candidates for inhaled nitric oxide treatment

Abstract

Disclosed are methods of reducing the risk that a medical treatment comprising inhalation of nitric oxide gas will induce an increase in pulmonary capillary wedge pressure in pediatric patients, leading to pulmonary edema. The methods include avoiding or discontinuing administration of inhaled nitric oxide to a pediatric patient determined to have pre-existing left ventricular dysfunction but who otherwise is a candidate for inhaled nitric oxide treatment (e.g., for pulmonary hypertension), and administering inhaled nitric oxide to pediatric patients who are candidates for such treatment and who are determined not to have pre-existing left ventricular dysfunction.

1 - 30 . (canceled) 
     
     
         31 . A method of improving the safety of treating hypoxic respiratory failure in neonates by reducing the risk of inducing pulmonary edema, the method comprising:
 (a) identifying a plurality of neonatal patients who have hypoxic respiratory failure;   (b) determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;   (c) administering a first treatment regimen to the first patient, wherein the first treatment regimen comprises administration of 20 ppm inhaled nitric oxide for 14 days or until the first patient's hypoxia has resolved;   (d) determining that a second patient of the plurality has pre-existing left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and   (e) based on the determination of (d), selecting and administering a second treatment regimen to the second patient, wherein the second treatment regimen does not comprise either (i) administration of inhaled nitric oxide for 14 days or (ii) administration of inhaled nitric oxide until the second patient's hypoxia has resolved, and does comprise one or more other therapies selected from vasodilators, intravenous fluids, bicarbonate therapy and mechanical ventilation.   
     
     
         32 . The method of  claim 31 , wherein the second treatment regimen comprises mechanical ventilation. 
     
     
         33 . The method of  claim 31 , wherein the second treatment regimen does not comprise administration of inhaled nitric oxide. 
     
     
         34 . The method of  claim 31 , wherein the second treatment regimen comprises beginning administration of inhaled nitric oxide, but discontinuing the administration upon determining that inhaling nitric oxide has increased the second patient's pulmonary capillary wedge pressure (PCWP), the discontinuation being at a point before the second patient has received 14 days of inhaled nitric oxide administration and before the second patient's hypoxia has resolved. 
     
     
         35 . The method of  claim 31 , wherein the second treatment regimen comprises beginning administration of inhaled nitric oxide, but discontinuing the administration upon determining that inhaling nitric oxide has induced pulmonary edema in the second patient, the discontinuation being at a point before the second patient has received 14 days of inhaled nitric oxide administration and before the second patient's hypoxia has resolved. 
     
     
         36 . The method of  claim 31 , comprising performing a diagnostic process to identify the second patient as having hypoxic respiratory failure. 
     
     
         37 . The method of  claim 36 , wherein the diagnostic process comprises echocardiography. 
     
     
         38 . The method of  claim 31 , wherein the first and second patients are term or near-term neonates. 
     
     
         39 . The method of  claim 31 , wherein the selection of the second treatment regimen is based not only on a determination that the second patient is at particular risk of pulmonary edema, but also on a determination that the second patient is at particular risk of other serious adverse events, upon treatment with inhaled nitric oxide. 
     
     
         40 . A method of improving the safety of treating hypoxic respiratory failure in neonates by reducing the risk of inducing pulmonary edema, the method comprising:
 (a) identifying a plurality of neonatal patients who have hypoxic respiratory failure;   (b) determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;   (c) administering a first treatment regimen to the first patient, wherein the first treatment regimen comprises administration of 20 ppm inhaled nitric oxide;   (d) determining that a second patient of the plurality has pre-existing left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and   (e) based on the determination of (d), selecting and administering a second treatment regimen to the second patient, wherein the second treatment regimen does not comprise administration of inhaled nitric oxide, and does comprise one or more other therapies selected from vasodilators, intravenous fluids, bicarbonate therapy and mechanical ventilation.   
     
     
         41 . The method of  claim 40 , wherein the second treatment regimen comprises mechanical ventilation. 
     
     
         42 . The method of  claim 40 , comprising performing a diagnostic process to identify the second patient as having hypoxic respiratory failure. 
     
     
         43 . The method of  claim 42 , wherein the diagnostic process comprises echocardiography. 
     
     
         44 . The method of  claim 40 , wherein the second patient is a term or near-term neonate. 
     
     
         45 . The method of  claim 40 , wherein the selection of the second treatment regimen is based not only on a determination that the second patient is at particular risk of pulmonary edema, but also on a determination that the second patient is at particular risk of other serious adverse events, upon treatment with inhaled nitric oxide. 
     
     
         46 . A method of improving the safety of treating pulmonary hypertension in pediatric patients by reducing the risk of inducing pulmonary edema, the method comprising:
 (a) identifying a pediatric patient having pulmonary hypertension and pre-existing left ventricular dysfunction;   (b) determining that, because the patient has pre-existing left ventricular dysfunction, the patient is at particular risk of increased PCWP leading to pulmonary edema, when treated with inhaled nitric oxide;   (c) treating the patient with 20 ppm inhaled nitric oxide;   (d) determining that the patient's PCWP increased during the treatment; and   (e) based on the determinations of (b) and (d), discontinuing the inhaled nitric oxide treatment.   
     
     
         47 . The method of  claim 46 , wherein the pulmonary hypertension is associated with hypoxia, and the discontinuation occurs at a point before the patient has received 14 days of inhaled nitric oxide administration and before the patient's hypoxia has resolved. 
     
     
         48 . The method of  claim 46 , wherein the discontinuation is based not only on a determination that the patient is at particular risk of increased PCWP leading to pulmonary edema, but also on a determination that the patient is at particular risk of other serious adverse events, upon treatment with inhaled nitric oxide. 
     
     
         49 . The method of  claim 46 , comprising performing a diagnostic process to identify the patient as having pulmonary hypertension. 
     
     
         50 . The method of  claim 46 , wherein the patient is a neonate. 
     
     
         51 . The method of  claim 46 , wherein the patient is a term or near-term neonate. 
     
     
         52 . The method of  claim 46 , wherein the patient's pulmonary hypertension is associated with hypoxic respiratory failure. 
     
     
         53 . The method of  claim 52 , wherein the patient is a neonate. 
     
     
         54 . A method of improving the safety of treating hypoxic respiratory failure in neonates by reducing the risk of inducing pulmonary edema, the method comprising:
 (a) identifying a neonatal patient as having hypoxic respiratory failure and pre-existing left ventricular dysfunction;   (b) determining that, because the patient has pre-existing left ventricular dysfunction, the patient is at particular risk of pulmonary edema when treated with inhaled nitric oxide;   (c) treating the patient with 20 ppm inhaled nitric oxide; and   (d) discontinuing the inhaled nitric oxide treatment due to the determination of (b).   
     
     
         55 . The method of  claim 54 , wherein the discontinuation occurs at a point before the patient has received 14 days of inhaled nitric oxide administration and before the patient's hypoxia has resolved. 
     
     
         56 . The method of  claim 54 , comprising performing a diagnostic process to identify the patient as having hypoxic respiratory failure. 
     
     
         57 . The method of  claim 56 , wherein the diagnostic process comprises echocardiography. 
     
     
         58 . The method of  claim 54 , wherein the patient is a term or near-term neonate. 
     
     
         59 . The method of  claim 55 , wherein the patient is a term or near-term neonate. 
     
     
         60 . The method of  claim 54 , wherein the discontinuation is due not only to the determination that the patient is at particular risk of pulmonary edema, but also due to a determination that the patient is at particular risk of other serious adverse events, upon treatment with inhaled nitric oxide.