Cardiovascular Support for Low Birth Weight Infants and Cerebral Hemodynamics: A Randomized, Blinded, Clinical Trial

Abstract

Maintaining adequate organ blood flow is the target of vasopressor treatment, but the impact of these measures on cerebral perfusion has not yet been evaluated systematically in a randomized, blinded, clinical trial. To explore the effects on brain hemodynamics of 2 different inotropic agents used to treat systemic hypotension among low birth weight (LBW) infants. Newborns of <1501 g birth weight or <32 weeks' gestational age, with a mean blood pressure (MBP) lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (DP) (2.5, 5, 7.5, or 10 microg/kg per minute; n = 28) or epinephrine (EP) (0.125, 0.250, 0.375, or 0.5 microg/kg per minute; n = 32), at doses that were increased in a stepwise manner every 20 minutes until the optimal MBP (MBP-OP) was attained and maintained. Continuous monitoring of quantitative changes in cerebral concentrations of oxyhemoglobin and deoxyhemoglobin, cerebral intravascular oxygenation (HbD) (the difference between oxyhemoglobin and deoxyhemoglobin), and cerebral blood volume (CBV) were assessed with near-infrared spectroscopy. MBP, heart rate, transcutaneous Pco2 and Po2, and peripheral oxygen saturation were recorded continuously and analyzed at baseline, 20 minutes after each dose increase (T1, T2, T3, and T4) until MBP-OP was reached, and then every 20 minutes up to 1 hour of stable MBP-OP. Fifty-nine infants were considered for analysis. Patients did not differ in birth weight or gestational age (1008 +/- 286 g and 28.3 +/- 2.3 weeks, respectively, in the DP group and 944 +/- 281 g and 27.7 +/- 2.4 weeks in the EP group). Studies were performed at a mean age of 5.3 +/- 3.7 hours of life (range: 2-16 hours). MBP-OP was attained for 96.3% of patients with DP and 93.7% with EP (responders). For those patients, MBP, heart rate, CBV, and HbD increased from baseline throughout the study period, with no differences between groups except for a higher heart rate with EP. Changes in MBP were correlated significantly with changes in HbD. Dose escalation of drugs produced no differences between groups in the behavior of the variables, except for a greater heart rate with EP from 20 minutes after dose 2 (T2) onward. Drug-induced changes in cerebral hemodynamics varied with gestational age; the EP-induced increase in CBV was greater among less mature patients (<28 weeks), whereas the DP-induced increase in CBV was greater among patients of > or =28 weeks. Among hypotensive LBW infants, cardiovascular support with low/moderate-dose DP or low-dose EP increased cerebral perfusion, as indicated by the increase in both CBV and HbD. Low-dose EP was as effective as low/moderate-dose DP in increasing MBP among LBW infants.