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From the Department of Anesthesiology, Perioperative and Pain Medicine, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts.
Address correspondence and reprint requests to James A. DiNardo, M.D., Department of Anesthesiology, Children's Hospital Boston, 300 Longwood Avenue, Boston MA 02115. Address e-mail to james.dinardo{at}childrens.harvard.edu.
There is little doubt that afterload reduction is an essential component in optimizing systemic oxygen delivery in neonates after Norwood Stage 1 reconstruction (1). A comprehensive strategy using phenoxybenzamine (POB), as well as modified ultrafiltration and aprotinin, has been associated with improvement in outcomes after Stage 1 palliation in at least 2 institutions (2,3). However, similar outcomes have been reported from at least 2 institutions that have never used the POB strategy (4,5). Furthermore, no randomized, controlled trial has been conducted of POB versus more titratable methods of afterload control such as sodium nitroprusside or milrinone. A study conducted at 2 separate institutions compared sodium nitroprusside (2–5 (g/kg/min) to POB (1 mg/kg) in neonates and infants during cardiopulmonary bypass (CPB) (6). The study, which excluded neonates with Hypoplastic Left Heart Syndrome, demonstrated clinically insignificant differences in base deficit and left atrial pressure during and after CPB. Significant differences in CPB flow (180 mL/kg/min for POB versus 73 mL/kg/min for nitroprusside) were noted at a similar mean arterial blood pressure (40 mm Hg). Reduced systemic vascular resistance and increased flow rates during CPB (if desired) can be obtained with nitroprusside administered at a higher dose, administration of isoflurane, which may have neuroprotective effects, or with administration of a short-acting 
-adrenergic drug such as phentolamine (half-life of 19 min).
The intense and long duration -adrenergic blockade induced by POB administration often dictates that systemic vasoconstrictor agents be administered to prevent profound hypotension and subsequent myocardial ischemia. The vasodilatation and hypotension induced by POB in the postoperative period is often refractory to high doses of conventional -adrenergic drugs such as epinephrine and norepinephrine, and an infusion of arginine vasopressin is often necessary (7,8). Vasopressin administration is not totally benign; its use has been associated with compromise of splanchnic perfusion (9) and induction of coronary vasoconstriction (10). The inherent vulnerability of neonates with single ventricle physiology after Stage 1 palliation to both splanchnic hypoperfusion and coronary ischemia makes this drug particularly unappealing.
As survival after neonatal Stage 1 palliation has improved over the last two decades there has been increasing awareness that a significant number of survivors suffer perioperative neurologic insults leading to adverse neurodevelopmental sequalae (11). Periventricular leukomalacia (PVL) is the combination of diffuse injury to immature oligodendroglia and focal necrosis of deep cerebral white matter adjacent to the lateral ventricles (12). PVL is common after surgery for congenital heart disease and is associated with an increased incidence of developmental delay and attention deficit/hyperactivity disorder. In the critical 48-hour period immediately postoperatively an aortic diastolic pressure < 36 mm Hg, an aortic systolic pressure < 81 mm Hg, and a PaO2, 41 mm Hg are all associated with an increased incidence (50% or more) of PVL in neonates (13). Use of a long-acting vasodilator such as POB with hypotensive effects that can be difficult to reverse is, therefore, not desirable in the postoperative setting.
The cerebral and coronary vascular beds are heavily autoregulated and thus are less responsive to -adrenergic-induced changes in vascular tone. POB can redirect blood flow away from the coronary and cerebral vascular beds to the splanchnic, skin, and muscle beds. This redistribution is likely to be exacerbated by the increased cerebral vascular resistance and loss of cerebral autoregulation that occurs after hypothermic CPB and deep hypothermic circulatory arrest or regional low flow cerebral perfusion (14,15). The long-term effects of such redistribution remain to be determined.
In conclusion, the circulatory physiology after neonatal Stage 1 palliation has been well established (16,17). Intermittent or continuous monitoring of superior vena cava saturation has become fairly standard, as it is now appreciated that SaO2 is a poor surrogate measure of systemic oxygen delivery in this patient population (18). There is nothing magic about POB, a drug with distinctly unfavorable pharmacokinetic and pharmacodynamic properties. It should be emphasized that an investigation citing the uncoupling of arterial oxygen saturation from systemic oxygen delivery by POB studied 62 patients who received POB and 9 who did not (19). It is not at all clear that these nine patients received inotropic and vasodilator drug combinations similar to those used by institutions that forgo the use of POB. Since the desired physiologic end-points in this patient population can be easily reached with drugs such as isoflurane, milrinone, and sodium nitroprusside, the use of POB is unnecessary and potentially harmful.
Footnotes
Accepted for publication May 9, 2007.
REFERENCES
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