February 1999

Regional Hemodynamic Effects of Dopamine in the Sick Preterm Neonate.
Seri I; Abbasi S; Wood DC; Gerdes JS.
J Pediatr. 1998 Dec;133(6):728-734.
Commentary by Charles Coté,

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[ see abstract below ]

Seri et al examined the regional hemodynamic responses of sick preterm infants to dopamine infusions. Since the vast majority of medications (approximately 80 percent) are not approved in some age population of children (meaning no pharmaceutical industry-sponsored study was performed with sufficient supporting data submitted to the FDA to allow labeling), this paper represents an important contribution to our knowledge.

The response of the preterm neonate to most medications is affected by (1) differences in protein binding (both reduced albumen and alpha-1-acid glycoprotein) that make more free drug available to cross biologic membranes, (2) immaturity of hepatic and renal function leading to altered drug metabolism, and (3) immaturity of the heart and central nervous system leading to drug sensitivity for certain classes of drugs. In addition, it is extremely difficult to perform pharmacology research in this age group because of both the limited ability to obtain blood samples (thus the need for population-based pharmacokinetic and pharmacodynamic modeling) and the difficulty in obtaining consent for study of this population. Thus we are often left with the only alternative, which is to use drugs cautiously in this age group and extrapolate from the experience in older patients.

Previous studies have suggested that sick preterm infants are resistant to the effects of vasopressors due to down-regulation of adrenergic receptors. In this pharmacodynamic study of dopamine, the authors focused upon regional blood flow in a preterm population at the time of initiation of dopamine for the treatment of oliguria and poor peripheral perfusion. The authors also compared extremely premature infants (23-27 weeks gestational age) vs more mature infants (28-31 weeks gestational age). Seri et al found a normal renovascular response (increased renal blood flow with resultant increased urine output) due to decreased renal vascular resistance. This effect was similar in both age groups, indicating a normal (mature) renal vascular response to dopamine regardless of age. There was no effect on mesenteric artery blood flow, indicating an immaturity of response in this vascular bed. Cerebral (middle cerebral artery) blood flow did not change indicating a maturity of the cerebrovascular system response to dopamine (normal autoregulation). Interestingly, the response in blood pressure appeared to be age-dependent, with the more immature infants responding with an increase in blood pressure and the older infants experiencing no change-suggesting, perhaps, an enhanced alpha-adrenergic sensitivity in the younger infants.

The clinical importance of this paper is that it demonstrates clearly the effectiveness of dopamine in improving renal function regardless of the gestational age of the infant. In addition, because there was no change in mesenteric blood flow in any age group, low-dose dopamine may be ineffective in improving mesenteric blood flow to non-hypotensive infants with necrotizing enterocolitis. The authors suggest that appropriate vasopressor support be used to treat hypotension-induced decreases in mesenteric blood flow. The authors are to be congratulated for their continuing efforts in defining drug responses in this difficult-to-study population. This study emphasizes the need for further research to more precisely define how neonates differ from older more mature patients.

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