Methods of reducing the risk of occurrence of pulmonary edema associated with inhalation of nitric oxide gas

• US 8,431,163 B2
• Filed: 10/15/2012
• Issued: 04/30/2013
• Est. Priority Date: 06/30/2009
• Status: Active Grant

• Current Assignee: Mallinckrodt Critical Care Finance Inc (Mallinckrodt plc), Mallinckrodt Pharma Ip Trading DAC (Mallinckrodt plc), Therakos, Inc (Mallinckrodt plc)
• Original Assignee: INO Therapeutics LLC (Mallinckrodt plc)
• Inventors: Baldassarre, James S., Rosskamp, Ralf
• Primary Examiner(s): Arnold, Ernst
• Application Number:
  US13/651,660
• Publication Number:
  US 20130040000A1
• Time in Patent Office: 197 Days
• Field of Search: None
• US Class Current: 424/718
• CPC Class Codes: A61B 5/02007 Evaluating blood vessel condition, e.g. elasticity, compliance
• CPC Class Codes: A61B 5/0205 Simultaneously evaluating both cardiovascular conditions and different types of body conditions, e.g. heart and respiratory condition
• CPC Class Codes: A61B 5/08 Detecting, measuring or recording devices for evaluating the respiratory organs A61B5/0205 takes precedence
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: A61B 8/0883 for diagnosis of the heart
• CPC Class Codes: A61B 8/48 Diagnostic techniques A61B8/13 takes precedence
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/04 Nitro compounds
• CPC Class Codes: A61K 31/21 Esters, e.g. nitroglycerine, selenocyanates
• CPC Class Codes: A61K 33/00 Medicinal preparations containing inorganic active ingredients
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 16/0057 Pumps therefor
• CPC Class Codes: A61M 16/104 specially adapted for anaesthetics A61M16/18 takes precedence
• CPC Class Codes: A61M 16/12 by mixing different gases
• CPC Class Codes: A61M 60/139 inside the aorta, e.g. intra-aortic balloon pumps
• CPC Class Codes: A61M 60/295 Balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/497 for balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/841 of balloon pumps for circulatory assistance
• CPC Class Codes: A61M 60/857 : Implantable blood tubes
• CPC Class Codes: A61P 11/00 : Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: F17C 2201/058 : portable (<30 l)
• CPC Class Codes: F17C 2203/0646 : Aluminium
• CPC Class Codes: F17C 2221/014 : Nitrogen
• CPC Class Codes: F17C 2221/03 : Mixtures
• CPC Class Codes: F17C 2223/0123 : gaseous, e.g. CNG, GNC
• CPC Class Codes: F17C 2223/036 : Very high pressure (>80 bar)
• CPC Class Codes: F17C 2270/025 : Breathing
• CPC Class Codes: G06Q 99/00 : Subject matter not provided for in other groups of this subclass
• CPC Class Codes: G16H 20/10 : relating to drugs or medications, e.g. for ensuring correct administration to patients

Abstract

Disclosed are methods of reducing the risk of occurrence of pulmonary edema associated with a medical treatment comprising inhalation of nitric oxide gas.

Claims

1. A method of reducing the risk of occurrence of pulmonary edema associated with a medical treatment comprising inhalation of 20 ppm nitric oxide gas, said method comprising:

(a) performing echocardiography to identify a term or near-term neonate patient in need of 20 ppm inhaled nitric oxide treatment for hypoxic respiratory failure, wherein the patient is not dependent on right-to-left shunting of blood;

(b) determining that the patient identified in (a) has left ventricular dysfunction consistent with a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and

(c) excluding the patient from inhaled nitric oxide treatment, based on the determination that the patient has left ventricular dysfunction and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

2. The method of claim 1, wherein the determination in (b) comprises performing echocardiography.

3. The method of claim 1, wherein the patient'"'"'s left ventricular dysfunction is attributable to congenital heart disease.

4. The method of claim 1, wherein the patient is determined to be at particular risk not only of pulmonary edema, but also of other serious adverse events, upon treatment with inhaled nitric oxide, and the patient is excluded from inhaled nitric oxide treatment based on the determination that the patient has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also of other serious adverse events, upon treatment with inhaled nitric oxide.

5. The method of claim 4, wherein the patient'"'"'s left ventricular dysfunction is attributable to congenital heart disease.

6. A method of treatment comprising:

(a) performing echocardiography to identify a plurality of term or near-term neonate patients who are in need of 20 ppm inhaled nitric oxide treatment for hypoxic respiratory failure, wherein the patients are not dependent on right-to-left shunting of blood;

(b) determining that a first patient of the plurality has left ventricular dysfunction consistent with a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide;

(c) determining that a second patient of the plurality does not have left ventricular dysfunction;

(d) administering the 20 ppm inhaled nitric oxide treatment to the second patient; and

(e) excluding the first patient from treatment with inhaled nitric oxide, based on the determination that the first patient has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

7. The method of claim 6, wherein the second patient has congenital heart disease.

8. The method of claim 6, wherein the left ventricular dysfunction of the first patient is attributable to congenital heart disease.

9. The method of claim 6, wherein the first patient is determined to be at particular risk not only of pulmonary edema, but also of other serious adverse events, upon treatment with inhaled nitric oxide, and the first patient is excluded from inhaled nitric oxide treatment based on the determination that the first patient has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other serious adverse events, upon treatment with inhaled nitric oxide.

10. The method of claim 9, wherein the left ventricular dysfunction of the first patient is attributable to congenital heart disease.

11. The method of claim 6, wherein determining that the first patient of the plurality has pre-existing left ventricular dysfunction and the second patient of the plurality does not have pre-existing left ventricular dysfunction comprises performing echocardiography on the first and second patients.

12. A method of reducing the risk of occurrence of pulmonary edema associated with a medical treatment comprising inhalation of 20 ppm nitric oxide gas, said method comprising:

(a) performing echocardiography to identify a term or near-term neonate patient in need of 20 ppm inhaled nitric oxide treatment for hypoxic respiratory failure, wherein the patient is not dependent on right-to-left shunting of blood;

(b) determining that the patient identified in (a) has left ventricular dysfunction consistent with a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide; and

(c) excluding the patient from inhaled nitric oxide treatment, or, despite the patient'"'"'s ongoing need for treatment for hypoxic respiratory failure, discontinuing the treatment after it has begun, the exclusion or discontinuation being based on the determination that the patient has left ventricular dysfunction and so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

13. The method of claim 12, wherein the determination in (b) comprises performing echocardiography.

14. The method of claim 12, wherein the left ventricular dysfunction is attributable to congenital heart disease.

15. The method of claim 12, wherein the patient is determined to be at particular risk not only of pulmonary edema, but also of other serious adverse events, upon treatment with inhaled nitric oxide, and the patient is excluded from inhaled nitric oxide treatment, or, despite the patient'"'"'s ongoing need for treatment for hypoxic respiratory failure, the patient'"'"'s treatment with inhaled nitric oxide is discontinued after it was begun, the exclusion or discontinuation being based on the determination that the patient has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other serious adverse events, upon treatment with inhaled nitric oxide.

16. The method of claim 15, wherein the left ventricular dysfunction of the patient is attributable to congenital heart disease.

17. The method of claim 13, wherein the left ventricular dysfunction of the patient is attributable to congenital heart disease.

18. The method of claim 13, wherein the patient is determined to be at particular risk not only of pulmonary edema, but also of other serious adverse events, upon treatment with inhaled nitric oxide, and the patient is excluded from inhaled nitric oxide treatment, or, despite the patient'"'"'s ongoing need for treatment for hypoxic respiratory failure, the patient'"'"'s treatment with inhaled nitric oxide is discontinued after it was begun, the exclusion or discontinuation being based on the determination that the patient has pre-existing left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other serious adverse events, upon treatment with inhaled nitric oxide.

19. The method of claim 18, wherein the left ventricular dysfunction of the patient is attributable to congenital heart disease.

20. A method of treatment comprising:

(a) performing echocardiography to identify a plurality of term or near-term neonate patients who are in need of 20 ppm inhaled nitric oxide treatment for hypoxic respiratory failure, wherein the patients are not dependent on right-to-left shunting of blood;

(b) determining that a first patient of the plurality has left ventricular dysfunction consistent with a pulmonary capillary wedge pressure greater than or equal to 20 mm Hg, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide;

(c) determining that a second patient of the plurality does not have left ventricular dysfunction;

(d) administering the 20 ppm inhaled nitric oxide treatment to the second patient; and

(e) excluding the first patient from treatment with inhaled nitric oxide, or, despite the first patient'"'"'s ongoing need for treatment for hypoxic respiratory failure, discontinuing the first patient'"'"'s treatment with inhaled nitric oxide after it was begun, the exclusion or discontinuation being based on the determination that the first patient has left ventricular dysfunction, so is at particular risk of pulmonary edema upon treatment with inhaled nitric oxide.

21. The method of claim 20, wherein the second patient has congenital heart disease.

22. The method of claim 20, wherein the left ventricular dysfunction of the first patient is attributable to congenital heart disease.

23. The method of claim 20, wherein the first patient is determined to be at particular risk not only of pulmonary edema, but also of other serious adverse events, upon treatment with inhaled nitric oxide, and the first patient is excluded from inhaled nitric oxide treatment, or, despite the first patient'"'"'s ongoing need for treatment for hypoxic respiratory failure, the first patient'"'"'s treatment with inhaled nitric oxide is discontinued after it was begun, the exclusion or discontinuation being based on the determination that the first patient has left ventricular dysfunction and so is at particular risk not only of pulmonary edema, but also other serious adverse events, upon treatment with inhaled nitric oxide.

24. The method of claim 23, wherein the left ventricular dysfunction of the first patient is attributable to congenital heart disease.

25. The method of claim 20, wherein determining that the first patient of the plurality has pre-existing left ventricular dysfunction and the second patient of the plurality does not have pre-existing left ventricular dysfunction comprises performing echocardiography on the first and second patients.