Special caution is needed when using dopaminergic agents in neonatal practice because during maturation adrenergic receptors continue to develop and increase in number and activity. In hypotensive premature babies, even relatively low doses of DA (2 ug/kg per min) increase MAP, probably because of the high sensitivity of a-receptors in these preterm infants [83]. The inotropic action of DA is less effective in neonates than at a later age, because of incomplete sympathetic innervation of the fetal and neonatal heart [79].
DA may be used in combination with other medications, for example furosemide (FM). Premature babies with RDS and FM-resistant oliguria responded with a marked increase in natriuresis and diuresis when DA was added to the therapeutic regimen [84]. Whether or not DA treatment is helpful in indomethacin-induced renal dysfunction is still open to debate [85, 86]. There is, however, no objection to trying low doses of DA in this situation [87]. The improvement in kidney function with DA alone, or in combination with FM, strongly suggests that full-term human neonates, and even premature neonates, have functional renal dopaminergic receptors. The effectiveness of low i.v. doses of DA (2 ug/kg per min) in combating hypotension and oliguria in sick preterm babies can probably be explained by the prolonged half-life and better bioavailability of DA, due to decreased metabolic clearance by the liver. This of course carries the risk of significant adverse effects to the drug, such as cardiac arrhythmia, depression of peripheral chemore-ceptor activity, and an increase in peripheral vascular resistance, particularly in the pulmonary vascular bed [82, 88, 89].
Dobutamine has been synthesized in an attempt to find an inotropic agent devoid of a- and [32-adrenergic activity. The absence of these activities avoids the chronotropic and hypertensive effects of other catecholamines [90]. Dobutamine is less effective than DA in the treatment of hypotension in premature infants with RDS; this is due to its receptor selectivity [91]. The DA-induced blood pressure effect in the newborn contributes significantly to the renal effects of DA. Dobutamine will probably have little impact on immature renal function [79].
Dopexamine is another dopaminergic agent, preferentially stimulating the pVadrenergic receptors, and devoid of a-adrenergic receptor action. In the adult it is effective in protecting and/or restoring renal function in ARF [92]. In contrast, no protective effect of dopexamine could be demonstrated on glomerular dysfunction of the newborn hypoxemic rabbit [80]. It should, however, be
emphasized that similar disappointing results with experimental animals were initially obtained with DA, whereas later the drug proved to be very promising in clinical trials in the human. Before making final conclusions on the efficacy of dopexamine treatment in VMNP of the human neonate, one has to await the results of similar future clinical trials.
Diuretics
Incipient or established fluid overload, such as seen in CHF, can be treated with diuretics that reduce the volume overload and improve cardiac function [93]. In other situations, such as oliguric or non-oliguric ARF, the beneficial effects of diuretics are rather limited, because they induce only a minor and transient increase in urine flow rate, generally without accompanying improvement in renal glomerular function. However, it cannot be stressed too strongly that the overall management of a newborn with some diuresis (non-oliguric ARF) is much easier than a severely oliguric or anuric patient.
FM has remained the most frequently used diuretic in the neonatal period. Approximately 25% of neonates admitted to neonatal intensive care units
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