Dopamine versus epinephrine for cardiovascular support in low birth weight infants: analysis of systemic effects and neonatal clinical outcomes.
BACKGROUND
Early postnatal adaptation to transitional circulation in low birth weight infants frequently is associated with low blood pressure and decreased blood flow to organs. Catecholamines have been used widely as treatment, despite remarkably little empirical evidence on the effects of vasopressor/inotropic support on circulation and on clinically important outcomes in sick newborn infants.


OBJECTIVE
To explore the effectiveness of low/moderate-dose dopamine and epinephrine in the treatment of early systemic hypotension in low birth weight infants, evaluate the frequency of adverse drug effects, and examine neonatal clinical outcomes of patients in relation to treatment.


METHODS
Newborns of <1501-g birth weight or <32 weeks of gestational age, with a mean blood pressure lower than gestational age in the first 24 hours of life, were assigned randomly to receive dopamine (2.5, 5, 7.5, and 10 microg/kg per minute; n = 28) or epinephrine (0.125, 0.250, 0.375, and 0.5 microg/kg per minute; n = 32) at doses that were increased stepwise every 20 minutes until optimal mean blood pressure was attained and maintained (responders). If this treatment was unsuccessful (nonresponders), sequential rescue therapy was started, consisting first of the addition of the second study drug and then hydrocortisone.


METHODS
These included: (1) short-term changes (first 96 hours, only responders) in heart rate, mean blood pressure, acid-base status, lactate, glycemia, urine output, and fluid-carbohydrate debit; and (2) medium-term morbidity, enteral nutrition tolerance, gastrointestinal complications, severity of lung disease, patent ductus arteriosus, cerebral ultrasound diagnoses, retinopathy of prematurity, and mortality.


RESULTS
Patients enrolled in this trial did not differ in birth weight or gestational age (1008 +/- 286 g and 28.3 +/- 2.3 weeks in the dopamine group; 944 +/- 281 g and 27.7 +/- 2.4 weeks in the epinephrine group). Other main antenatal variables were also comparable. However, responders and nonresponders differed significantly with respect to the need for cardiorespiratory resuscitation at birth (3% vs 23%), Critical Risk Index for Babies score (3.8 +/- 3 vs 7 +/- 5), and premature rupture of membranes >24 hours (39.5% vs 13.6%), respectively. No differences were found in the rate of treatment failure (dopamine: 36%; epinephrine: 37%) or need for rescue therapy according to treatment allocation. Groups did not differ in age at initiation of therapy (dopamine: 5.3 +/- 3.9 hours; epinephrine: 5.2 +/- 3.3 hours), but withdrawal was significantly later in the dopamine group. For short-term changes, mean blood pressure showed a significant increase from baseline throughout the first 96 hours with no differences between groups. However, epinephrine produced a greater increase in heart rate than dopamine. After treatment began, epinephrine patients showed higher plasma lactate (first 36 hours) and lower bicarbonate and base excess (first 6 hours) and received more bicarbonate. Patients in the epinephrine group also had higher glycemia (first 24 hours) and needed insulin therapy more often. Groups did not differ in urine output or fluid-carbohydrate supply during the first 96 hours. For medium-term morbidity, there were no differences in neonatal clinical outcomes in responders. However, significant differences were found in the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, need for high-frequency ventilation, occurrence of necrotizing enterocolitis, and death between responders and nonresponders.


CONCLUSIONS
Low/moderate-dose epinephrine is as effective as low/moderate-dose dopamine for the treatment of hypotension in low birth weight infants, although it is associated with more transitory adverse effects.
Valverde
Eva
E
Department of Neonatology, La Paz University Hospital, Madrid, Spain.
Pellicer
Adelina
A
Madero
Rosario
R
Elorza
Dolores
D
Quero
José
J
Cabañas
Fernando
F
D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D004298:Dopamine / Q000008:administration & dosage* / Q000009:adverse effects*; D004837:Epinephrine / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007022:Hypotension / Q000188:drug therapy*; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000009:adverse effects*
D002316:Cardiotonic Agents; D014662:Vasoconstrictor Agents; D004298:Dopamine; D004837:Epinephrine