Methods for improving the safety of treating 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 pulmonary hypertension in pediatric patients by reducing the risk of inducing pulmonary edema, the method comprising:
 (a) identifying a plurality of pediatric patients with pulmonary hypertension;   (b) determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;   (c) administering 20 ppm inhaled nitric oxide to the first patient;   (d) determining that a second patient of the plurality has pre-existing left ventricular dysfunction, and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and   (e) excluding the second patient from treatment with inhaled nitric oxide, based on the determination that the second patient is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.   
     
     
         32 . The method of  claim 31 , wherein the second patient is a neonate. 
     
     
         33 . The method of  claim 31 , wherein the pulmonary hypertension of the second patient is associated with hypoxic respiratory failure. 
     
     
         34 . The method of  claim 31 , wherein the second patient is treated with a therapy comprising mechanical ventilation. 
     
     
         35 . The method of  claim 32 , wherein the second patient is treated with a therapy comprising mechanical ventilation. 
     
     
         36 . The method of  claim 33 , wherein the second patient is treated with one or more therapies selected from vasodilators, intravenous fluids, bicarbonate therapy, and mechanical ventilation. 
     
     
         37 . The method of  claim 31 , wherein the exclusion 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. 
     
     
         38 . The method of  claim 32 , wherein the exclusion 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. 
     
     
         39 . 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 plurality of pediatric patients with pulmonary hypertension;   (b) determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;   (c) administering inhaled nitric oxide to the first patient;   (d) determining that a second patient of the plurality has pre-existing left ventricular dysfunction, and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and   (e) excluding the second patient from inhaled nitric oxide administration based on the determination in (d), or starting administration of inhaled nitric oxide to the second patient and then, despite the second patient's ongoing need for inhaled nitric oxide administration, discontinuing administration of inhaled nitric oxide to the second patient, the discontinuation being in view of the determination in (d).   
     
     
         40 . The method of  claim 39 , wherein the second patient is a neonate. 
     
     
         41 . The method of  claim 39 , wherein the pulmonary hypertension of the second patient is associated with hypoxic respiratory failure. 
     
     
         42 . The method of  claim 39 , wherein the second patient is treated with mechanical ventilation. 
     
     
         43 . The method of  claim 41 , wherein the second patient is treated with one or more therapies selected from vasodilators, intravenous fluids, bicarbonate therapy, and mechanical ventilation. 
     
     
         44 . The method of  claim 39 , wherein administration of inhaled nitric oxide to the second patient is started and discontinued. 
     
     
         45 . The method of  claim 39 , wherein the inhaled nitric oxide administered to the first patient is 20 ppm inhaled nitric oxide. 
     
     
         46 . The method of  claim 39 , wherein the exclusion or discontinuation 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. 
     
     
         47 . The method of  claim 40 , wherein the exclusion or discontinuation 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. 
     
     
         48 . 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) treating a pediatric patient having pulmonary hypertension and pre-existing left ventricular dysfunction with 20 ppm inhaled nitric oxide;   (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; and   (c) based on the determination of (b), discontinuing the inhaled nitric oxide treatment.   
     
     
         49 . The method of  claim 48 , wherein the patient is a neonate. 
     
     
         50 . The method of  claim 48 , wherein the pulmonary hypertension is associated with hypoxic respiratory failure. 
     
     
         51 . The method of  claim 48 , wherein the patient is treated with mechanical ventilation after discontinuing the inhaled nitric oxide treatment. 
     
     
         52 . The method of  claim 48 , wherein the discontinuation is based not only on a determination that the patient is at risk of 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. 
     
     
         53 . A method of improving the safety of administering inhaled nitric oxide to pediatric patients by reducing the risk of inducing pulmonary edema, the method comprising:
 (a) identifying a plurality of pediatric patients who are candidates for inhaled nitric oxide administration;   (b) determining that a first patient of the plurality does not have pre-existing left ventricular dysfunction;   (c) administering 20 ppm inhaled nitric oxide to the first patient;   (d) determining that a second patient of the plurality has pre-existing left ventricular dysfunction, and so is at particular risk of developing pulmonary edema upon administration of inhaled nitric oxide; and   (e) excluding the second patient from inhaled nitric oxide administration based on the determination in (d), or starting administration of inhaled nitric oxide to the second patient and then, despite the second patient's ongoing need for inhaled nitric oxide administration, discontinuing administration of inhaled nitric oxide to the second patient, the discontinuation being in view of the determination in (d).   
     
     
         54 . The method of  claim 53 , wherein the second patient is a neonate. 
     
     
         55 . The method of  claim 53 , wherein the second patient is excluded from inhaled nitric oxide administration. 
     
     
         56 . The method of  claim 53 , wherein the second patient is treated with mechanical ventilation. 
     
     
         57 . The method of  claim 53 , wherein administration of inhaled nitric oxide to the second patient is started and discontinued. 
     
     
         58 . The method of  claim 57 , wherein the second patient is treated with mechanical ventilation. 
     
     
         59 . The method of  claim 53 , wherein the exclusion or discontinuation 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. 
     
     
         60 . The method of  claim 54 , wherein the exclusion or discontinuation 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.