Background Cardiopulmonary bypass [CPB] in small size bodies can result in decreased peripheral perfusion. This results in anaerobic metabolism as evidenced by lactic acidosis. High flow results in systemic hypertension which is accentuated by moderate hypothermia commonly used during cardiopulmonary bypass. Phenoxybenzamine [PBZ] is an arteriolar vasodilator that acts by irreversibly blocking the alpha adrenergic receptors. It causes vasodilatation allowing high flow, low pressure CPB. It has been used extensively outside US in Canada, Europe and Australia. In the US oral PBZ is FDA approved, whereas intravenous PBZ is only available as an investigational drug. At the Cleveland Clinic this medication has been used under this protocol since 1994 in >1000 without any significant or serious adverse outcome. The drug is also used at Texas Children's Hospital, Hospital for Sick Children in Toronto, Children's Hospital of Wisconsin and a number of centers throughout Europe, Australia and Asia. The drug has helped reduce the mortality of children undergoing cardiopulmonary bypass.~The theoretic benefit of PBZ in this patient population is uniform and smooth reduction fo systemic vascular resistance in the perioperative period. This uniform systemic vasodilation allows low pressure, high flow systemic perfusion on cardiopulmonary bypass. We feel that this ins in part responsible for improved outcome after cardiopulmonary bypass, including less end-organ edema formation and dysfunction. Due to experience in this and other centers we strongly believe that the use of PBZ in the bypass management protocol of these patients represents the state-of-the-art and not an experimental investigation. Since in the US the drug is not available except as an investigational drug, we have been required to use it as an investigational new drug [IND] PBZ[oral] is currently used in the US for the management of pheochromocytoma. It has a proven track record and known to be safe. Use in a large number of patients worldwide has shown no serious side-effects except hypotension [which is an effect indeed] requiring norepinephrine [an alpha agonist commonly used after cardiopulmonary bypass in these patients anyway].~Patients~The following patients are candidates for receiving PBZ for HFLPP. These include:~All patients under 16 kg.~Those patients between 16-18 kg whose pre bypass hemoglobin is <16 g/dl~All patients are less than 18 years of age.~Use of Phenoxybenzamine:~Loading dose given at the time of going on CPB:~For patients with obstructing lesions on systemic side:~0.25 mg/kg dose in the bypass circuit~None intravenous~For patients without obstructing left sided lesions:~0.5 mg/kg in the bypass circuit~0.5 mg/kg I.V. at cannulation~Maintenance dose given in the post-operative period:~0.3 mg/kg I.V. every 8 hours till oral intake is started or for first 48 hours~0.3 mg/kg P.O. every 8 hours for next 24 hours~0.15 mg/kg P.O. every 8 hours for next 24 hours and then stop~Hold PBZ if the patient is on norepinephrine infusion or the mean arterial pressure is lower than that allowed for the age group~Do not use maintenance dose in the following patients unless they are on maximum dose of sodium nitroprusside infusion and still hypertensive:~Norwood patients~Fontan patients~Patients with residual left ventricular obstructive lesions - don't use at all in the post operative period~Data collected and monitored for the purpose of this study only:~Demographic information, side effects and mortality data would be recorded and kept in a password protected computer in a secure-access-only physician office. Only composite data without individual identifiers will be reported to the IRB and FDA. No publication is planned from this study and no follow-up will be done after the patient is discharged from the hospital.~Side effects to be monitored:~Hypotension requiring norepinephrine in excess of usual dose [0.2 micrograms/kg/min]~Death from such hypotension in the absence of other causes [such as bleeding, sepsis]~Effects occuring within 12 hours of I.V. dose administration or within 24 hours of P.O. dose administration~Any unanticipated or unusual side effects [none noted since 1994] Consent Informed consent would be obtained from the parents/guardians of all patients. Assent will be obtained from children of >7 years age.
Cardiopulmonary bypass [CPB] in small size bodies can result in decreased peripheral perfusion. This results in anaerobic metabolism as evidenced by lactic acidosis. High flow perfusion results in systemic hypertension which is accentuated by moderate hypothermia commonly used during cardiopulmonary bypass. Phenoxybenzamine [PBZ] is an arteriolar vasodilator that acts by irreversibly blocking the alpha adrenergic receptors. It causes vasodilatation allowing high flow, low pressure CPB. It has been used extensively outside US in Canada, Europe and Australia. In the US oral PBZ is FDA approved, whereas intravenous PBZ is only available as an investigational drug