Inhaled NO as an Anti-inflammatory and Anti-reperfusion Agent in Infants and Children Undergoing Cardiopulmonary Bypass

• Status: Completed
• Trial end date: 2011-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Each year, there are over 400,000 cardiac surgical operations performed in the United States; of which 10,000 are performed on children. These operations are made possible by the use of the heart-lung bypass machine, also known as cardiopulmonary bypass. This machine allows for the body to be supported while the heart is repaired. While this machine has been life saving, it has risks and can lead to a variety of complications.

One such complication results from the fact that the patient's blood is exposed to the foreign material of the machine, such as plastic tubing. In nearly all cases of cardiac surgery, this leads to a whole body response in the patient following the operation. This response, inflammation, is characterized by alterations in the function of the heart and lungs, fever, fluid retention, and bleeding disorders in the postoperative period. While this is usually temporary and self limiting, significant morbidity occurs in approximately 1-2% of cases where this inflammatory response is present. Additionally, children appear to be more susceptible to this response. This can lead to significant postoperative complications that are not associated with the actually surgical procedure performed on the heart.

The exact cause of this response is not fully understood. However, it is important to understand the triggers, timing, and pattern of this complex inflammatory response in order to modify or arrest it. Unlike other situations associated with this type of whole-body inflammatory reaction such as trauma or overwhelming infection, cardiac surgical teams have the advantage of knowing when the trigger will occur (i.e. during the cardiac operation) and hence have the opportunity for preemptive intervention in an effort to minimize the response. One such effort is the focus of this proposal.

Nitric oxide (NO) is a gas that has been used for years in the treatment of lung disease in infants. It has been life saving and safe. Recently, it has been investigated for its anti-inflammatory effects outside the lungs. We propose delivering NO to the source of the greatest inflammation in cardiac surgery, the cardiopulmonary bypass machine. It is our intention to show that in doing so; we can minimize the inflammation found in the first 24 hours following cardiac surgery in children. If we are correct, the reduction of this inflammation will result in less damage to other organs of the child's body and improved outcome following surgery.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: Mallinckrodt
• Treatments: Anti-Inflammatory Agents; Nitric Oxide

Criteria

Inclusion Criteria:

• Patients with the following congenital heart lesions who require cardiopulmonary bypass for surgical repair or palliation will be eligible:

• D-transposition of the great vessels (D-TGA)

• Tetralogy of Fallot (TOF)

• Children of age less than 16 years

Exclusion Criteria:

• Signs of persistently elevated pulmonary vascular resistance preoperatively

• Cardiac arrest one week prior to surgery

• Prior surgical procedure that required use of cardio-pulmonary bypass

• Acute or chronic infection such as sepsis or wound infections

• History of any pulmonary condition such as pneumonia or respiratory distress syndrome

• Patients that have received steroid treatment within the last month

• DiGeorge syndrome

• Active bleeding disorder

• Any other condition associated with non-cardiac morbidity

• Use of another investigational drug

• Age over 16 years.