Hypotension In Preterm Infants Research Articles

Early volume expansion for prevention of morbidity and mortality in very preterm infants.

Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. In very preterm infants, does early volume expansion reduce morbidity and mortality. If volume expansion is effective, what type of volume expansion is most effective. The standard search strategy of the Neonatal Review Group was used. Searches were conducted of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts and conference proceedings. Randomised trials of early volume expansion with normal saline, fresh frozen plasma, albumin, plasma substitutes or blood compared to no treatment or another form of volume expansion in preterm infants < 32 weeks gestation or < 1500g were included. Volume expansion was defined as at least 10 mls/kg given in the first 72 hours of life. Standard methods of the Neonatal Review Group with use of relative risk (RR), risk difference (RD) and weighted mean difference (WMD). The fixed effects model using RevMan 4.1 was used for meta-analysis. Data from individual studies were only eligible for inclusion if a least 80% of infants were reported for that outcome. Seven studies were included. Five studies, four with data for mortality, compared volume to no treatment. Most studies enrolled very preterm infants on the basis of gestation or birthweight. Two studies comparing different types of volume expansion enrolled very preterm infants with hypotension. No study enrolled infants on the basis of low blood flow. One study examined the effect of volume expansion on blood flow but in normotensive very preterm infants. Comparing volume and no treatment, 4 studies with a total of 940 very preterm infants reported no significant difference in mortality (RR 1.11, 95% CI 0.88, 1.40). The large NNNI 1996 study reported no significant difference in severe disability (RR 0.80, 95% CI 0.52, 1.23), cerebral palsy (RR 0.76, 95% CI 0.48, 1.20) and combined death or severe disability (RR 1.00, 95% CI 0.80, 1.24). Although one small study (Beverley 1985) reported reduced P/IVH with volume expansion, this was not supported by any other study. No significant difference was reported in grade 3-4 P/IVH and combined death or grade 3-4 P/IVH. One study (NNNI 1996) reported no significant difference in the incidence of hypotension. The finding of decreased necrotising enterocolitis and increased sepsis in infants who received fresh frozen plasma compared to a gelatin-based plasma substitute or no treatment in one study should be treated with caution. No significant differences in mortality or disability were found in this study. In one small study, there were no significant differences in outcomes between hypotensive infants who received colloid (albumin) or crystalloid (saline). There is no evidence from randomised trials to support the routine use of early volume expansion in very preterm infants without cardiovascular compromise. There is insufficient evidence to determine whether infants with cardiovascular compromise would benefit from volume expansion. There is insufficient evidence to determine what type of volume expansion should be used in preterm infants (if at all) or for the use of early red cell transfusions. The trial comparing colloid (albumin) and crystalloid (saline) in hypotensive preterm infants found no benefit in using a more expensive blood product compared to saline, but is insufficiently powered to detect an important clinical difference.

Early volume expansion versus inotrope for prevention of morbidity and mortality in very preterm infants.

Reduced perfusion of organs such as the brain, heart, kidneys and the gastrointestinal tract may lead to acute dysfunction and be associated with permanent injury. Various strategies have been used to provide cardiovascular support to preterm infants including inotropes, corticosteroids and volume expansion. In very preterm infants, to determine the effect of early volume expansion compared to inotrope in reducing morbidity and mortality. Subgroup analysis was planned according to method of diagnosis of poor perfusion, postnatal age of treatment and type of volume expansion and inotrope used. The standard search strategy of the Cochrane Neonatal Review Group was used. All randomised trials that compared volume expansion to an inotrope in preterm infants in the first days of life were included. Data were extracted independently by each author and analysed using the standard methods of the Cochrane Collaboration and its Neonatal Review Group using relative risk (RR), risk difference (RD) and weighted mean difference (WMD). Two small studies comparing volume expansion, using albumin, with dopamine were included. Both studies were adequately randomised, unblinded studies of albumin versus dopamine with no losses to follow up and analysed by intention to treat. Data for clinical outcomes were available from one study in hypotensive preterm infants in the first day of life. In this study, albumin had a higher failure rate for correcting hypotension (RR 5.2, 95% CI 1.3, 20.6). As 49% of these infants had already been given volume, the question of which treatment should be given first was not answered. A second study compared albumin with dopamine in preterm infants with a normal mean blood pressure at a mean age of 32 hours. Dopamine produced a significant increase in mean blood pressure when compared to infants who received albumin or no treatment, although the difference between the dopamine and albumin groups did not reach significance. Albumin and dopamine produced similar increases in left ventricular output but no significant change in cerebral blood flow. No difference was found in mortality (RR 1.5, 95% CI 0.5, 4.0) or morbidity including any P/IVH, chronic lung disease or retinopathy. There was a higher rate of grade 2-4 P/IVH of borderline statistical significance in infants who received albumin in one study (RR 1.47; 95% CI 0.96 to 2.25: RD 0.27, 95% CI 0.00 to 0.54). No data were available for neurodevelopmental outcomes. Dopamine was more successful than albumin at correcting low blood pressure in hypotensive preterm infants, many of whom had already received volume. Neither intervention has been shown to be superior at improving blood flow, or in improving mortality and morbidity in preterm infants. The trials do not allow any firm conclusions to be made as to whether or when volume or dopamine should be used in preterm infants.

Refractory hypotension in preterm infants with adrenocortical insufficiency

Five preterm, very low birthweight infants with severe hypotension and adrenocortical insufficiency are described. The profound hypotension was resistant to volume expansion and inotrope treatment, but responded promptly to corticosteroid...

Single-dose dexamethasone treatment of hypotension in preterm infants

Objective: To test the efficacy of single-dose dexamethasone (DXM) in the management of severe arterial hypotension of newborn infants. Our hypothesis was that epinephrine infusions could be discontinued in 70% of patients within 12 hours after DXM administration compared with 10% in the placebo group. Study design: Twenty preterm infants (median birth weight 690 g, gestational age 28 weeks, age at intervention 2 days) who did not respond to a standardized treatment protocol (blood/colloid followed by dopamine infusion stepwise increased to 15 μg/kg and minute) were started on an epinephrine infusion and were randomly allocated to receive either DXM (0.25 mg/kg) or placebo intravenously. The primary outcome criterion was the need for an epinephrine infusion 12 hours after treatment. Results: Three infants were excluded. Epinephrine infusion was discontinued in 5 of 8 infants with DXM but in only 1 of 9 infants in the control group. The duration of epinephrine infusion was significantly shorter in the DXM group (exact log-rank test, P = .023). Conclusions: DXM was effective for the management of severe arterial hypotension in preterm infants not responding to standardized treatment. (J Pediatr 1999;134:701-5)

Randomised controlled trial of colloid or crystalloid in hypotensive preterm infants

AIMTo compare the efficacy of a colloid (5% albumin) and a crystalloid (isotonic saline) solution for treating hypotension in mechanically ventilated preterm infants.METHODSSixty three preterm infants weighing 540 to 1950...

Cerebral blood flow measured by near infrared spectroscopy in hypotensive preterm infants

Cerebral blood flow measured by near infrared spectroscopy in hypotensive preterm infants

ANTENATAL STEROIDS DO NOT AFFECT MEAN ARTERIAL BLOOD PRESSURE OR NEED FOR TREATMENT OF HYPOTENSION IN INFANTS ≤1250 GRAMS DURING THE FIRST DAY OF LIFE. † 1462

Recent reports suggest that antenatal steroids (ANS) reduce the need for treatment of hypotension in preterm infants. We analyzed data from a randomized, controlled trial of Exosurf® (Pediatrics 88:1, 1991) to determine the effect of ANS on mean arterial blood pressure (MABP) and on the need for treatment of hypotension during the first 24 h of life in small preterm infants. MABP was measured continuously and directly via an arterial catheter and all babies were managed with a consistent protocol for treatment of hypotension. We included all inborn infants with gestational age (GA)≤31 weeks and birthweight (BW) ≤1250 g except if they died in the first 48 h, were small for GA, had major congenital anomalies or incomplete courses of steroids. Babies who received at least 2 doses of steroids, with the first given between 24 h and 7 d before delivery, were considered to have received a complete course of steroids (CS); the no steroids (NS) group included infants who received no dose for at least 7 d before delivery. There were 57 babies, 38 received CS and 19 had NS. MABP in the first 24h of life showed significant positive correlation with BW and GA.

Impact on blood pressure and intestinal perfusion of dobutamine or dopamine in hypotensive preterm infants.

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.

Randomized, blind trial of dopamine versus dobutamine for treatment of hypotension in preterm infants with respiratory distress syndrome

To compare the efficacy of dopamine and dobutamine for the treatment of hypotension (mean arterial blood pressure, ≤30 mm Hg) in preterm (≤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 ≥0.40). Intravenous study drug infusions were initiated at 5 μg/kg per minute and then increased in increments of 5 μg/kg per minute at 20-minute intervals until a mean arterial blood pressure >30 mm Hg was attained and sustained for ≥30 minutes (success) or a maximum rate of 20 μg/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 ≤10 μg/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. (J P EDIATR 1994;125:117-22)

136 THE EFFECT OF EITHER DOPAMINE OR VOLUME-EXPANSION ON BLOOD PRESSURE AND CARDIAC FUNCTION IN MODERATELY HYPOTENSIVE, PRETERM INFANTS

Hypotension is a wellknown risk factor for adverse outcome in preterm infants. This study examines the cardiac function in moderately lypotensive, preterm infants and the effect of either volume expansion or dopamine infusion in these patients.Design Inclusion criteria: GA<33 weeks, 29mmHg<Mean Arterial blood Pressure(MAP)<40mmHg. The infants (n=26) were randomly assigned to receive an infusion of dopamine; 5 μg/kg/min or a bolus of plasma; 15 mL/kg. Measurements of left ventricular output(LVO) and MAP were taken before treatment(T0) and two hours later. Data were analysed using ANOVA.Methods LVO was calculated by measuring the internal aortic diameter jsing combined B- and M-mode echocardiography, and measuring the blood flow velocity at the same site using Doppler ultrasound. Blood pressure was measured invasively through an indwelling arterial catheter.Results Patients (median(range)) : GA 28(25-32) wks BW 1183(680-2140) gm T0 values (mean(range)): LVO 203 (85-368) mL/kg/min. MAP 34 (30-39) mmHg. At T0 no differences were found between the groups.Conclusions 1. LVO may be low in moderately hypotensive preterm infants md therefore warrant treatment. 2. Dopamine is more effective than volume expansion at increasing blood pressure, though both treatments are equally effective at increasing LVO. Further comparison of the two treatment regimes require assesment of organ perfusion.

Response to dopamine and dobutamine in the preterm infant less than 30 weeks gestation.

Mean arterial pressure (MAP) and heart rate (HR) were studied in 12 hypotensive preterm neonates given dopamine. A significant, although temporary, elevation in MAP (8 +/- 3 mm Hg; p less than .01) occurred in five neonates in response to 5 micrograms/kg.min, but an increase in MAP was found in all infants (11 +/- 6 mm Hg; p less than .01) when the infusion rate was doubled. This elevation was sustained only in five who previously showed some response to the slower infusion. HR was unaffected except for an increase of 22 +/- 12 beat/min (p less than .01) in the five showing sustained MAP elevation with 10 micrograms/kg.min. Dobutamine failed to raise MAP in the seven who relapsed, and refractory shock resulted. We conclude that time should not be wasted when starting dopamine at less than 10 micrograms/kg.min in hypotensive preterm infants, as lower rates are unlikely to produce a response and delay may cause further compromise.

644 RED CELL SEQUESTRATION IN PRETERM INFANTS

No previous studies have evaluated the response of red cell volume (RCV) to blood transfusion (Tx) in hypotensive preterm infants. We measured RCV in 69 hypotensive infants with respiratory distress syndrome (RDS) using Tc-99m and 51 Cr red cell leveling. All patients received Tx in amounts estimated by initial RCV to be sufficient to restore the volume to normal (55-60 ml/kg). Following Tx, RCVs were repeated in 27 patients; 2-7 serial values were obtained. Sixty-five infants responded to Tx with a rise in blood pressure (BP) and/or RCV; 4 had no rise in RCV (3 expired). Serial measurements in non-asphyxiated infants demonstrated a rise to expected RCV. However, the rise observed in asphyxiated preterm infants was disproportionate to the volume Tx, and only 37% of the Tx appeared in the circulating RCV, as shown in the table: Conclusions: Asphyxiated preterm infants have RCVs lower than those born without asphyxia. Tx to all hypotensive preterm infants produces a rise in BP and/or RCV but infants subjected to asphyxia may sequester a portion of the Tx. We speculate that the hypotension observed in patients with RDS results from red cell sequestration as a result of perinatal asphyxia.