• Vital Signs [ Time Frame: At baseline, then every hour for the first 8 hours of therapy, followed by every 4 hours of therapy. ] [ Designated as safety issue: No ]
• Methemoglobin Levels [ Time Frame: at 2,4,6, and 8 hours after the start of therapy and then every 24 hours while on therapy. ] [ Designated as safety issue: Yes ]
• Need for analgesics [ Time Frame: baseline and throughout treatment. ] [ Designated as safety issue: No ]
• blood chemistry levels [ Time Frame: every 24 hours for the first 5 days after start of treatment. ] [ Designated as safety issue: No ]
• Lenght of hospitalization from admissions defined by the time of the discharge order is written [ Time Frame: study duration ] [ Designated as safety issue: No ]
• Rate of acute chest syndrome/pneumonia requiring blood transfusion [ Time Frame: study duration ] [ Designated as safety issue: No ]

This study will examine whether nitric oxide (NO) gas can reduce the time it takes for pain to go away in patients who are in sickle cell crisis. NO is important in regulating blood vessel dilation, and consequently, blood flow. The gas is continuously produced by cells that line the blood vessels. It is also transported from the lungs by hemoglobin in red blood cells.

Patients 10 years of age or older with sickle cell disease (known SS, S-beta-thalassemia or other blood problems causing sickle cell disease) may be eligible for this study. Patients whose disease is due to hemoglobin (Hgb) SC are excluded. Candidates are screened with blood tests and a chest x-ray to look at the lungs and heart.

Participants are admitted to the hospital in a pain crisis. They are evaluated and then randomly assigned to receive one of two treatments: 1) standard treatment plus NO, or 2) standard treatment plus placebo. The placebo used in this study is nitrogen, a gas that makes up most of the air we breathe and is not known to help in sickle cell disease.

For the first 8 hours of the study, patients receive placebo or NO through a facemask. The mask may be taken off for 5 minutes every hour and for not more than 20 minutes to eat a meal. After the first 8 hours, the gas is delivered through a nasal cannula (small plastic tubing that rests under the nose) that may be taken off only while showering or using the restroom. Patients are questioned about the severity of their pain when they start the study and then every few hours while they are in the hospital. Their vital signs (temperature, breathing rate, and blood pressure) and medicines are checked. Patients will breathe the gas for a maximum of 3 days, but will stay hospitalized until the patient feels well enough to go home. Patients are followed up about 1 month after starting the study by a return visit to the hospital or by a phone call.

The object of this study is to determine the safety and efficacy of nitric oxide for inhalation in the treatment of vaso-occlusive pain crisis (VOC) in patients with sickle cell disease. The study population will include patients with sickle cell disease (SS, S-beta-Thalassemia) presenting with vaso-occlusive pain crisis. Patients will be administered either placebo or inhaled nitric oxide to see if the experimental agent, inhaled nitric oxide, can reduce the time it takes for resolution of the vaso-occlusive crisis.

• Drug: Nitric Oxide
• Drug: Placebo

• Experimental: Inhaled nitric oxide
• Placebo Comparator: Nitrogen gas

INCLUSION CRITERIA:

Each subject must meet all of the following inclusion criteria during the screening process in order to participate in the study:

• Patient must have a diagnosis of SCD (known SS, S-Beta-thalassemia or other hemoglobinopathies causing sickle cell disease). Patients with disease due to Hgb SC are not permitted.
• Must present to the ED/EC or other appropriate unit in VOC.
• Greater than or equal to 10 years old.
• Written informed consent/assent has been obtained.

EXCLUSION CRITERIA:

Subjects meeting any of the following criteria during baseline evaluation will be excluded from entry into the study:

• Exposure to therapeutic nitric oxide within the past 12 hours.
• Patient has received sildenafil or other phosphodiesterase 5 inhibitors, therapeutic L-arginine, nitroprusside or nitroglycerine within the past 12 hours.
• Patient has received previous ED/EC or other appropriate unit treatment for a vaso-occlusive crisis less than 48 hours or hospitalization less than 14 days ago (patients transferred directly from another ED or clinic may be enrolled).
• Patient has visited the ED/EC or other appropriate unit greater than 10 times in the past year having a vaso-occlusive crisis.
• Patients presenting with clinically diagnosed bacterial infection (e.g., osteomyelitis, pneumonia, sepsis or meningitis).
• Patients who are currently enrolled in any other investigational drug study except for hydroxyurea studies.
• Pregnant women (urine HCG + )/ nursing mothers.
• Patients who have received an exchange transfusion (not simple transfusion) in the last 30 days or are on a chronic simple or exchange transfusion program.
• Suspected splenic sequestration.
• Acute chest syndrome or pneumonia: Abnormal new pulmonary infiltrate (alveolar infiltration and not atelectasis) and one or more pulmonary signs and/or symptoms (fever, rales, wheezing, cough, shortness of breath, retractions).
• Previous participation in this study.