Assessment of therapy for arterial hypotension in critically ill preterm infants. Response to dobutamine and dopamine in the hypotensive very preterm infant. Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome. Impact on blood pressure and intestinal perfusion of dobutamine or dopamine in hypotensive preterm infants. A double-blind, randomized, controlled study of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Randomized trial comparing dopamine and dobutamine in preterm infants. Randomised trial of dopamine compared with hydrocortisone for the treatment of hypotensive very low birthweight infants. Left ventricular contractility in extremely premature infants in the first day and response to inotropes. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Multicentre trial of ethamsylate for prevention of periventricular haemorrhage in very low birthweight infants. Prenatal dexamethasone treatment in conjunction with rescue therapy of human surfactant: a randomized placebo-controlled multicenter study.
The aim of this paper is to assess the efficacy of albumin and dopamine compared with albumin and dobutamine in treating hypotension in preterm newborn infants (PNI). A randomized, open-label, prospective, cross-over study, was designed on 66 PNI whose weights were between 1,000 to 1,500 g, and persistent hypotension, defined as a mean arterial pressure (MAP) of < 30 mmHg. Infants were randomly allocated to two groups and received a 5% albumin infusion at a dosage of 20 mL/kg, in 30 min. Thereafter, one group received dopamine and the other dobutamine at doses of 5 microg/kg/min. If there was not an increase in MAP values > 30 mmHg, the infusions were increased every 20 min by 2.5 microg/kg/min, up to a maximum of 10 microg/kg/min. Treatment failure was considered when there was no pressure response within 2 hr after the infusion started; then patients were changed to the other catecholamine. Statistical analysis was done with student's t-test, x2, and Fisher's exact probability test. There were no differences between groups in initial features. Overall, MAP was normalized with dopamine in 29 of 33 infants and with dobutamine in 25 of 33 infants (p > 0.05). The initial dosage of 5 microg/kg/min, was adequate in 22 infants treated with dopamine and in 13 treated with dobutamine (p < 0.05). The change from dopamine to dobutamine was successful in three out of four patients, while changing from dobutamine to dopamine was adequate in seven out of eight patients. Dopamine is recognized as the drug of choice to treat hypotension in PNI. Since our results showed only small differences in responses, it is proposed that dobutamine is also as efficacious and useful as dopamine. A randomised double blind study was designed to evaluate haemodynamic response to dobutamine and dopamine in 20 hypotensive preterm infants of less than 32 weeks' gestation. Neonates initially received dopamine or dobutamine 5 micrograms/kg/min. If mean arterial pressure (MAP) remained below 31 mm Hg, the infusion rate was increased in increments of 5 micrograms/kg/min. If 20 micrograms/kg/min of the initial drug failed to achieve a MAP above 30 mm Hg, it was discontinued and the other drug was administered at the same infusion rate. Left ventricular output (LVO) was measured by pulsed Doppler echocardiography. Mean (SE) MAP increased significantly from 24.4 (1.0) to 32.0 (1.4) mm Hg at a median dobutamine dosage of 20 micrograms/kg/min and from 25.6 (1.2) to 37.7 (1.5) mm Hg at a median dopamine dosage of 12.5 micrograms/kg/min. The percentage LVO increase was +21 (7)% with dobutamine compared with -14 (8)% with dopamine. Dobutamine failed to increase MAP above 30 mm Hg in six infants out of 10, whereas dopamine succeeded in all 10 infants. Six switches from dobutamine to dopamine were thus performed, providing a rise in MAP (29.2 (0.5) to 41.2 (2.0) mm Hg) and drop in LVO (356 (40) to 263 (36) ml/kg/min). These data indicate that dopamine is more effective than dobutamine in raising and maintaining MAP above 30 mm Hg; however dopamine does not increase LVO. To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, < or = 30 mm Hg) in preterm (< or = 34 weeks of gestation) infants with respiratory distress syndrome in the first 24 hours of life, we enrolled 63 hypotensive preterm infants in a randomized, blind trial. Inclusion criteria required an arterial catheter for measurement of mean arterial blood pressure, treatment with exogenous surfactant, and persistent hypotension after volume expansion with 20 ml/kg (packed erythrocytes if hematocrit < 0.40, 5% albumin if > or = 0.40). Intravenous study drug infusions were initiated at 5 micrograms/kg per minute and then increased in increments of 5 micrograms/kg per minute at 20-minute intervals until a mean arterial blood pressure > 30 mm Hg was attained and sustained for > or = 30 minutes (success) or a maximum rate of 20 micrograms/kg per minute was reached without resolution of hypotension (failure). The study groups at entry were comparable for birth weight, gestational age, postnatal age, gender, birth depression, hematocrit < 0.40, heart rate, oxygenation index, delivery route, maternal chorioamnionitis, and maternal magnesium or ritodrine therapy. No infants in the dopamine group had a treatment failure (0/31; 0%); (16%) of 32 infants failed to respond to dobutamine (p = 0.028). Success was attained at < or = 10 micrograms/kg per minute in 30 (97%) of 31 infants given dopamine and in 22 (69%) of 32 infants given dobutamine (p < 0.01). Among those treated successfully, the increase in mean arterial blood pressure was significantly higher in those given dopamine (mean, 11.3 vs 6.8 mm Hg; p = 0.003). We conclude that dopamine is more effective than dobutamine for the early treatment of hypotension in preterm infants with respiratory distress syndrome. In a prospective study hemodynamic effects of dobutamine or dopamine (10 micrograms/kg/min) were investigated in 20 preterm infants who had protracted arterial hypotension refractory to volume therapy. Doppler ultrasonography of the superior mesenteric artery (SMA) was applied to verify intestinal perfusion and blood pressure was recorded in parallel. Mean arterial pressure (MAP) raised significantly in both groups (from 31.0 +/- 6.8 to 37.7 +/- 9.8 mm Hg during dobutamine and from 27.7 +/- 3.6 to 36.0 +/- 9.3 mm Hg during dopamine). Mean blood flow velocity increased from 25.8 +/- 13.5 to 31.5 +/- 16 cm/s with dobutamine and from 16.3 +/- 5.0 to 19.0 +/- 6.0 cm/s with dopamine (significant for dobutamine). Vascular resistance of SMA (indicated by resistance index; RI) decreased from 0.81 +/- 0.07 to 0.74 +/- 0.11 for dobutamine and from 0.89 +/- 0.06 to 0.79 +/- 0.07 for dopamine (significant for both groups). These data indicate that in the dose tested here both catecholamines are equally effective in raising MAP and lead to a significant increase of intestinal perfusion. Thus, a negative impact on mesenteric blood supply, predisposing to necrotizing enterocolitis, is not probable. To assess the effectiveness of a "stress dose" of hydrocortisone for rescue treatment of refractory hypotension and adrenocortical insufficiency of prematurity in very low birth weight (VLBW) infants. We hypothesized that significantly more VLBW infants who were receiving dopamine > or =10 microg/kg per min could wean off vasopressor support 72 hours after treatment with hydrocortisone.
                A double-blind, randomized, controlled study was conducted in a university neonatal center. Forty-eight VLBW infants who had refractory hypotension and required dopamine > or =10 microg/kg per min were randomly assigned to receive a stress dose of hydrocortisone (1 mg/kg every 8 hours for 5 days; n = 24) or an equivalent volume of the placebo solution (isotonic saline; n = 24).
                The baseline clinical characteristics were similar between the groups. Serum cortisol concentrations were very low immediately before randomization in both groups of infants. Significantly more VLBW infants who were treated with hydrocortisone weaned off vasopressor support 72 hours after starting treatment. The use of volume expander, cumulative dose of dopamine, and dobutamine were significantly less in hydrocortisone-treated infants compared with control infants. In addition, the median duration of vasopressor treatment was halved in hydrocortisone-treated patients. Two versus 11 infants in the hydrocortisone and control groups required a second vasopressor for treatment of refractory hypotension. The trend (linear and quadratic) of the mean arterial blood pressure was also significantly and consistently higher in hydrocortisone-treated infants.
                A stress dose of hydrocortisone was effective in treating refractory hypotension in VLBW infants. Although routine and prophylactic use of systemic corticosteroids could not be recommended because of their potential adverse effects, this relatively low dose of hydrocortisone would probably be preferable to high-dose dexamethasone for treatment of refractory hypotension in emergency and life-threatening situations. The aim of this study was to compare the efficacy of two inotropic infusions in treating low BP in preterm neonates. Forty infants with median gestational age 27 weeks (range 23-33) were studied. At trial entry the infants, who all had a systolic BP < 40 mmHg despite receiving a colloid infusion, were randomized to receive either a dopamine or dobutamine infusion. The infusions were commenced at a rate of 5 micrograms/kg per min and, if necessary, this was increased over the 3 h study period to 15 micrograms/kg per min. There was no significant difference in the gestational or postnatal age or baseline BP of the 20 infants who received dopamine and those 20 who received dobutamine. Three hours after commencing the infusions, although there was no difference in the rate of inotrope infusion between the two groups, the infants who received dopamine had a significantly higher systolic BP, a median of 39 mmHg (range 30-58) compared to a median of 34 mmHg (range 21-46) in the dobutamine group, P < 0.05. In addition, 10 infants who received dopamine, but only 3 who received dobutamine, had a systolic BP > 40 mmHg (P < 0.05). We conclude that dopamine rather than dobutamine infusion is more efficacious in improving the BP of preterm neonates. To compare the efficacy of hydrocortisone with dopamine for the treatment of hypotensive, very low birthweight (VLBW) infants.
                Forty infants were randomly allocated to receive either hydrocortisone (n = 21) or dopamine (n = 19).
                All 19 infants randomised to dopamine responded; 17 of 21 (81%) did so in the hydrocortisone group. Three of the four non-responders in the hydrocortisone group had clinically significant left to right ductal shunting. The incidence of bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular haemorrhage, necrotising enterocolitis, symptomatic patent ductus arteriosus, hyperglycaemia, sepsis (bacterial or fungal) or survival did not differ between groups. The adrenocorticotrophic hormone (ACTH) stimulated plasma cortisol activity, either before or after treatment, did not differ between the two groups of infants. Although a significant difference in efficacy between dopamine and hydrocortisone was not noted (P = 0.108), there were four treatment failures in the hydrocortisone group, compared with none in the dopamine group.
                Both hydrocortisone and dopamine are effective treatments for hypotension in very low birthweight infants. The aim was to assess myocardial contractility in infants born <30 wk gestation developing low systemic blood flow (SBF) in the first day, and the effect of dobutamine versus dopamine. Superior vena cava (SVC) flow was used as a measure of SBF at 3, 10, and 24 h (n = 106). Infants with low SVC flow randomized to dopamine or dobutamine. Myocardial contractility was determined by the relationship between left ventricular (LV) mean velocity of circumferential fiber shortening (mVcfs) and wall stress. Infants who developed low SVC flow had significantly worse myocardial contractility at 3 h, but not 10 h. At 24 h, low-flow infants had lower than expected mVcfs for any given LV stress. In 37 infants randomized to inotrope, there was no significant difference in contractility at 10 microg/kg/min. At 20 microg/kg/min (n = 21), dopamine increased whereas dobutamine decreased LV stress. Infants on dobutamine had significantly lower than expected mVcfs for any given LV stress compared with infants on dopamine. Contractility was not improved by either inotrope at either dose. In conclusion, infants developing low SVC flow in the first day have worse myocardial contractility at 3 h. Neither inotrope increased contractility, but dopamine increased LV stress at 20 microg/kg/min. The purpose of this study was to determine whether the use of antenatal magnesium sulfate prevents adverse outcomes (neonatal intraventricular hemorrhage, periventricular leucomalacia, death, and cerebral palsy).
                In a controlled trial, we randomized mothers in preterm labor to magnesium sulfate, "other" tocolytic, or placebo. At delivery, umbilical cord blood was collected for the later determination of serum ionized magnesium levels. Neonatal cranial ultrasound scans were obtained periodically for the diagnosis of intraventricular hemorrhage and periventricular leucomalacia. Among survivors, the diagnosis of cerebral palsy was made at age 18 months.
                Children with adverse outcomes had higher umbilical cord magnesium levels at delivery. In regression models that controlled for confounders, which included very low birth weight, magnesium remained a significant risk factor (adjusted odds ratio, 3.7; 95% CI, 1.1-11.9; P =.03).
                Contrary to original hypotheses, this randomized trial found that the use of antenatal magnesium sulfate was associated with worse, not better, perinatal outcome in a dose-response fashion. The effectiveness of ethamsylate in the prevention of periventricular haemorrhage (PVH) in very low birthweight infants was evaluated by means of a multicentre, placebo-controlled, double-blind trial. In 330 infants without evidence of PVH on initial cranial ultrasound examination there was little difference between ethamsylate and placebo groups with respect to subependymal haemorrhage, but intraventricular and parenchymal haemorrhages developed in 30/162 infants (18.5%) in the treated group, compared with 50/168 (29.8%) in the control group (p less than 0.02). The incidence of intraventricular and parenchymal haemorrhage in survivors was 20/137 (14.6%) in the ethamsylate group and 37/146 (25.3%) in the controls (p less than 0.05). In 30 infants with evidence of PVH on the initial scan, ethamsylate treatment seemed to limit parenchymal extension. Analysis of the total cohort of 360 infants showed that the proportion of infants in whom an increase of two or more grades of severity of PVH was recorded during the trial was lower in the treated than in the placebo group (p less than 0.01). No adverse effects were attributed to ethamsylate therapy. The reported incidence of patent ductus arterious was lower in the treated than in the placebo group (p less than 0.02). Mortality was similar in the two groups. A placebo-controlled, randomized, double-blind study was performed to determine whether prenatal dexamethasone (DEX) treatment improves the outcome of the preterm infant when exogenous surfactant is available.
                157 pregnant women at five hospitals with threatened preterm delivery and with lengths of gestation < 32 weeks received either DEX (dose 6 mg four times at 12-hour intervals) or placebo (PL). Prenatal treatment was not repeated. Preterm infants received rescue therapy of human surfactant (maximum four doses) if they required ventilatory support and at least 40% oxygen for the treatment of respiratory distress syndrome (RDS).
                Enrolled pregnant women delivered 188 live-born neonates, of whom 79 (DEX 41 and PL 38 neonates) were born 1 to 14 days after the prenatal treatment. Neonates born within 1 to 14 days after the initial DEX treatment had a lower incidence of RDS (DEX, 44%; PL, 79%; P < .01), lower requirements of surfactant (DEX, 22%; PL, 53%; P < .01), shorter duration of ventilatory support (DEX, 2.0 days; PL, 5.3 days; P < .05) and oxygen therapy (DEX, 2.0 days; PL, 7.0 days; P < .01), and a higher neonatal survival without ventilatory support (P < .05) than PL-treated neonates. DEX-treated neonates had higher mean blood pressure than PL-treated neonates during the first 3 days after birth. Among all neonates treated with DEX, there was a lower incidence of intraventricular hemorrhage or periventricular leucomalacia (DEX, 13%; PL, 33%; P < .01). Reduction in the incidence of intraventricular hemorrhage or periventricular leucomalacia in DEX-treated neonates was particularly associated with exogenous human surfactant therapy (DEX+surfactant 10%; PL+surfactant 48%; P < .01).
                Prenatal DEX treatment combined with exogenous human surfactant therapy in preterm infants decreases pulmonary morbidity and cerebral complications, and increases survival without severe morbidity.
Dopamine is more effective than dobutamine in the short term treatment of systemic hypotension in preterm infants. There was no evidence of an effect on the incidence of adverse neuroradiological sequelae (severe periventricular haemorrhage and/or periventricular leucomalacia), or on the incidence of tachycardia. However, in the absence of data confirming long term benefit and safety of dopamine compared to dobutamine, no firm recommendations can be made regarding the choice of drug to treat hypotension.