Hypotension In Preterm Infants Research Articles

Time‐course effect of a single dose of hydrocortisone for refractory hypotension in preterm infants

The aim of this study was to determine the time-course effect of a single dose of hydrocortisone (HC) on arterial blood pressure in extremely low gestational age newborns (ELGAN) with refractory hypotension during the first 3 days of life. We carried out a matched case-control study of a cohort of 116 infants born between 23 and 27 weeks' gestation at a tertiary center. Twelve infants (10%) were treated with HC for refractory hypotension (HC group). HC was administered at a dose of 2 mg/kg when mean arterial pressure (MAP) was below 30 mmHg (25 mmHg for infants <25 weeks of gestational age) despite the use of inotropes and volume expanders. Changes in the MAP after the HC administration were compared with those in the infants who were not treated with HC and matched for gestational age (Control group). The mean MAP before administration of HC was significantly lower in the HC group than that in the control group (24.0 ± 3.2 vs 33.3 ± 4.8 mmHg; P < 0.01). The mean MAP in the HC group increased significantly at 2 h after HC treatment, and then reached levels comparable to those in the Control group at 5 h (31.3 ± 4.0 vs 33.9 ± 4.7 mmHg; P= 0.18), and remained at normal levels until 12 h after HC treatment. A single dose of HC treatment induces a rapid and sustained improvement in blood pressure in ELGAN with refractory hypotension.

Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm infants

Pediatric AnesthesiaVolume 21, Issue 6 p. 711-712 CORRESPONDENCE Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm infants Marieke Nauta, Marieke Nauta Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The NetherlandsEmail: w.onland@amc.uva.nlSearch for more papers by this authorWes Onland, Wes Onland Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The NetherlandsEmail: w.onland@amc.uva.nlSearch for more papers by this authorAnne De Jaegere, Anne De Jaegere Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The NetherlandsEmail: w.onland@amc.uva.nlSearch for more papers by this author Marieke Nauta, Marieke Nauta Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The NetherlandsEmail: w.onland@amc.uva.nlSearch for more papers by this authorWes Onland, Wes Onland Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The NetherlandsEmail: w.onland@amc.uva.nlSearch for more papers by this authorAnne De Jaegere, Anne De Jaegere Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The NetherlandsEmail: w.onland@amc.uva.nlSearch for more papers by this author First published: 25 April 2011 https://doi.org/10.1111/j.1460-9592.2011.03552.xCitations: 17Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume21, Issue6June 2011Pages 711-712 RelatedInformation

A meta-analysis of dopamine use in hypotensive preterm infants: blood pressure and cerebral hemodynamics

Dopamine administration results in variable effects on blood pressure in hypotensive preterm infants. The clinical benefits of dopamine administration in increasing cerebral blood flow (CBF) and reducing adverse neurological outcomes in hypotensive preterm neonates are unclear. The objective of this study was to examine the efficacy of dopamine for treatment of hypotension and investigate the changes in cerebral hemodynamics and central nervous system injury in hypotensive preterm infants following dopamine administration. Standard meta-analytic techniques, including random and fixed effects models, were used to calculate combined effect size correlations and significance levels. Random effects meta-analysis found that dopamine increases mean arterial blood pressure (12 studies; N=163; r=0.88, 95% confidence interval (CI)=0.76 to 0.94) and systolic blood pressure (8 studies; N=142; r=0.81, 95% CI=0.42 to 0.94). For the increase in blood pressure, dopamine administration was associated with a significantly greater overall efficacy than dobutamine (seven studies; N=251; r=0.26; 95% CI=0.20 to 0.32), colloid (two studies; N=67; r=0.60; 95% CI=0.41 to 0.74) and hydrocortisone (one study; N=28; r=0.40; 95% CI=0.034 to 0.67). CBF increased following dopamine administration (five studies; N=75; r=0.36; 95% CI=-0.059 to 0.67) and the increase in CBF was greater in hypotensive than normotensive preterm infants (eight studies; N=153; r=0.16; 95% CI=-0.0080 to 0.32). There were no statistically significant differences in adverse neurological outcome between dopamine and dobutamine (three studies; N=118; r=-0.13; 95% CI=-0.31 to 0.059), epinephrine (two studies; N=46; r=0.06; 95% CI=-0.23 to 0.34), colloid (two studies; N=80; r=0.0070; 95% CI=-0.218 to 0.23) or hydrocortisone administration (one study; N=40; r=-0.10; 95% CI=-0.40 to 0.22). Dopamine administration increases mean and systolic blood pressure in hypotensive preterm infants, and is more effective than dobutamine, colloid or hydrocortisone alone. Dopamine administration is associated with increased CBF, with greater increases in CBF in hypotensive than in normotensive preterm infants. Dopamine is not associated with a greater incidence of adverse effects than other therapies used to treat hypotension.

Clinical Picture of Adrenal Insufficiency-associated Hypotension in Preterm Infants

Clinical Picture of Adrenal Insufficiency-associated Hypotension in Preterm Infants

Early Postnatal Blood Pressure in Preterm Infants: Effects of Chorioamnionitis and Timing of Antenatal Steroids

Previous studies suggest postnatal blood pressure in preterm infants to be decreased by chorioamnionitis and increased by antenatal steroids (AS). We examined the adjusted effects of both antenatal modulators on postnatal blood pressure (BP), with separate effects reported for histologic chorioamnionitis with or without fetal involvement and timing of AS. General characteristics, BP, and heart rate values during the first 72 h after birth were obtained from 271 infants with gestational age <or=32.0 wk. In unadjusted analyses, chorioamnionitis was associated with lower BP, most prominently so in infants with fetal involvement, without an effect on hypotension incidence. AS increased BP and decreased the incidence of hypotension when administered within 7 d before birth. In a multivariable mixed model analysis, the AS effect remained significant, whereas chorioamnionitis was not independently predictive of postnatal BP. Other variables associated with increased postnatal BP were gestational age and umbilical artery pH, whereas hemolysis, elevated liver enzymes, low platelets syndrome was associated with decreased BP. In conclusion, AS seem to increase postnatal BP and decrease hypotension in preterm infants when given within 7 d before birth. Conversely, chorioamnionitis did not significantly affect postnatal BP after multivariable adjustment.

The endocrine effects of dopamine and dobutamine in hypotensive preterm infants

UENPS.311 The endocrine effects of dopamine and dobutamine in hypotensive preterm infants Huiqing Sun⁎, Hong Xiong, Wenqing Kang Department of Pediatrics, Zhengzhou Children's Hospital, Zhengzhou, China

Is refractory hypotension in preterm infants a manifestation of early ductal shunting?

Clinicians frequently use hydrocortisone (HC) to treat vasopressor-resistant hypotension even before establishing its cause. To identify the etiologic factors leading to development of refractory hypotension, and to assess if patent ductus arteriosus (PDA) is associated with refractory hypotension during the first week of life. The medical records of 290 consecutively born infants <or=30 weeks' gestational age (GA) were reviewed to identify the escalating need for vasopressors to maintain mean arterial blood pressure (MABP) at or above a level equal to the GA in completed weeks. Refractory hypotension was defined as MABP unresponsive to fluid boluses and high-dose vasopressors (dopamine and dobutamine at doses 20 microg/kg/min each and/or epinephrine) prompting the use of HC. Eighty-nine (30.7%) of 290 infants had refractory hypotension between postnatal days 2 and 7. Infants with refractory hypotension were more likely to have a lower birth weight and GA (P<0.001), been treated with surfactant (P=0.004) and received indomethacin for a symptomatic PDA (P<0.001). To identify the etiologic factors, a univariate analysis revealed that the use of high-frequency oscillatory ventilation, presence of air leaks, PDA, sepsis, hyperkalemia and intraventricular hemorrhage (IVH) were significantly associated with refractory hypotension. However, multivariate analysis confirmed the independent association of only PDA (odds ratio (OR) 7.6, 95% confidence interval (CI) 3.3-17.7, P=0.000), severe IVH (OR 2.6, 95% CI 1.1-6.4, P=0.03) and GA (OR 0.7, 95% CI 0.6-0.8, P=0.001). Evaluation for early ductal shunting and closure of the ductus, if patent, should be attempted before HC is considered in hypotensive infants with escalating needs for vasopressors.

A Double-Blind, Randomized, Controlled Study of a “Stress Dose” of Hydrocortisone for Rescue Treatment of Refractory Hypotension in Preterm Infants

A Double-Blind, Randomized, Controlled Study of a “Stress Dose” of Hydrocortisone for Rescue Treatment of Refractory Hypotension in Preterm Infants

DOES THE USE OF EPINEPHRINE AS AN ADJUNCT INOTROPIC THERAPY IN PRETERM INFANTS REDUCE MORTALITY?

Treatments for hypotensive preterm infants include volume expansion, inotropic agents, and corticosteroids. Common inotropic agents include dopamine, dobutamine, and epinephrine. There are few studies describing the effects and efficacy of inotropes, particularly in terms of survival. This paucity of information led to the hypothesis that in infants ≤ 1,500 g or ≤ 32 weeks9 gestation receiving inotropic support, there will be no difference in mortality when epinephrine is added as an adjunctive inotropic agent. A retrospective chart review of patients admitted to Kosair Children9s Hospital NICU from December 2002 to December 2005 was performed. Preterm infants ≤ 1,500 g or ≤ 32 weeks gestation who received inotropic support were included. Patients were excluded for life-threatening congenital defects. Those infants who received epinephrine (epi) as an adjunctive inotropic agent were compared with infants who did not receive epinephrine (no-epi). Admission demographic data, BP, ABGs, and UOP were recorded. SNAPPE-II and CRIB-II scores were calculated. BP, HR, and ABGs were recorded prior to initiation and during inotropic support. The primary outcome variable was death. Data were analyzed with SPSS for Windows (V. 14; SPSS Inc). Eighty-eight infants were considered for analysis. There was a significant difference in BW and EGA between the groups; however, there was no difference in admitting diagnoses, BP, ABG, or UOP. There was a trend toward higher predicted mortality in the epi group. Prior to intervention, there was no difference in BP, HR, or ABGs. With intervention, the epi group demonstrated a higher maximum HR (p

Autoregulation of Cerebral Blood Flow

Autoregulation is a result of an intrinsic character of vascular smooth muscle cells. Other factors interact with pressure to define the degree of contraction of the smooth muscle cell. The final common pathway involves plasma membrane potassium conductance, smooth cell membrane potential, and cytoplasmatic calcium concentration. The molecular mechanisms are too complex to allow quantitative predictions. Autoregulation operates in most newborn infants (even the most immature), although the cerebral blood flow (CBF)-pressure relation is not likely to be strictly flat. In severely asphyxiated neonates, in preterm neonates who eventually develop major intracranial hemorrhage, and in hypotensive preterm infants treated with dopamine, the CBF-pressure relation is significantly above zero and may be as high as 4% per millimeter of mercury, corresponding to complete pressure passiveness. The lower threshold for cerebral autoregulation can be assumed to be 30 mm Hg or below. When blood pressure falls below this threshold, CBF decreases more than in proportion to pressure due to the elastic reduction in vascular diameter, but significant blood flow can be assumed to continue until the blood pressure is well below 20 mm Hg. The clinical relevance of autoregulation of CBF is the ability of cerebral arteries and arterioles to dilate to compensate for low blood pressure and protect against ischemic brain injury. The importance of the ability to constrict to protect against cerebral hemorrhage is not supported by clinical research.

Hydrocortisone is effective in treatment of vasopressor-resistant hypotension in very low birth weight neonates

Ng PC, Lee CH, Bnur FL, Chan IHS, Lee AWY, Wong E, et al. A double-blind, randomized, controlled study of a “stress dose” of hydrocortisone for rescue treatment of refractory hypotension in preterm infants. Pediatrics 2006;117:367-75.

A Double-Blind, Randomized, Controlled Study of a “Stress Dose” of Hydrocortisone for Rescue Treatment of Refractory Hypotension in Preterm Infants

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.

Cardiovascular Effects of Low-Dose Dexamethasone in Very Low Birth Weight Neonates with Refractory Hypotension

Background: Administration of hydrocortisone and relatively high doses of dexamethasone increase blood pressure in volume- and pressor-resistant hypotensive preterm infants. However, little is known about the temporal relationship of dexamethasone administration and the improvement in blood pressure and the weaning of pressors/inotropes. Furthermore, there are no sufficient data available on whether a smaller dose of dexamethasone would also be effective in treating refractory hypotension. Objective: To study the cardiovascular responses to low-dose dexamethasone in very low birth weight neonates with volume- and pressor-resistant hypotension. Methods: Retrospective database review. Twenty-four preterm neonates (gestational age 26 (23–34) weeks; birth weight 801 (457–1,180) g; postnatal age 2 (1–24) days, medians (ranges)) who remained hypotensive despite volume administration and combined dopamine and dobutamine treatment at ≧30 µg/kg/min received dexamethasone 0.1 mg/kg followed by 0.05 mg/kg intravenously every 12 h for 5 additional doses if still on pressors ≧8 µg/kg/min. Results: Two hours after the first dose of dexamethasone the mean blood pressure increased from 30 ± 5 to 34 ± 6 mm Hg (p < 0.001) and remained elevated at 4, 6, 12, and 24 h after treatment was started (p < 0.001). Six hours after the initial dose of dexamethasone the pressor/inotrope requirement decreased from 34 ± 9 to 24 ± 13 µg/kg/min (p = 0.001) and continued to decrease at 12 and 24 h (p < 0.001). Urine output also increased significantly during the first 6 h after dexamethasone (p < 0.001). Conclusions: Low-dose dexamethasone rapidly increases blood pressure and decreases pressor requirements in very low birth weight neonates with volume- and pressor-resistant hypotension.

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. See Review Group details for more information. This was supplemented by additional searches of the Oxford Database of Perinatal Trials, and updated search performed of the Cochrane Central Register of Controlled Trials (CENTRAL, Cochrane Library Issue 1, 2004), MEDLINE (1996-January 2004), EMBASE (1980-January 2004), previous reviews including cross references (all articles referenced), abstracts and conferences (Perinatal Society of Australia and New Zealand, and Pediatric Academic Societies and American Academy of Pediatrics meetings 1998-2003). 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. Comparing albumin and saline in hypotensive infants, one study (Lynch 2002) reported a significant increase in mean BP and reduced incidence of treatment failure (persistent hypotension). The other study (So 1997) and the meta-analysis of the two studies found no significant difference in treatment failure (RR 0.75, 95% CI 0.53, 1.06) or in any other clinical outcome. 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 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 significance of the finding of a significant increase in blood pressure in hypotensive preterm infants in one trial comparing albumin and saline is unclear, but the overall meta-analyses found no other significant clinical benefit in using albumin compared to saline.

Diagnosis and Treatment of Low Systemic Blood Flow in Preterm Infants

After completing this article, readers should be able to: 1. Delineate the short- and long-term adverse outcomes associated with low systemic blood flow. 2. Explain why it is not appropriate to use blood pressure and population criteria for hypotension to determine which infants who have low systemic blood flow need cardiovascular support. 3. Describe the various hemodynamic states in neonates and the assessment that is useful in allowing discrimination between these states. 4. Characterize the hemodynamic effects of dopamine and dobutamine in neonates. 5. Delineate the most common characteristics of infants who fail to maintain superior vena cava flows despite the use of inotropes. Low systemic blood flow (SBF) commonly occurs in preterm infants who have respiratory distress in the first postnatal day. Such low flows are strongly associated with neonatal morbidity, including peri/intraventricular hemorrhage (P/IVH), developmental impairments, and mortality. Diagnosing which infants have low SBF is problematic; use of blood pressure (BP) and signs of poor tissue perfusion, including capillary refill times (CRT), poor renal function, and acidosis, results in substantial delays in the initiation of cardiovascular support and a proportion of affected infants missing treatment. The traditional approach to cardiovascular support of the preterm infant has been to identify infants who have hypotension and to use agents, particularly dopamine, titrated to improve BP. However, this strategy may not be the best for improving SBF, and it is yet to be demonstrated that this approach improves neonatal outcomes. This review focuses on identifying which infants have low SBF or organ blood flow, discusses mechanisms for low flows, and examines potential therapies for treating or preventing low flow. Cardiovascular compromise occurs in a number of clinical scenarios in preterm infants, but it is most common on the first postnatal day. Not all infants who have low SBF will be suspected based on clinical signs, including …

Is hypotension a major risk factor for neurological morbidity at term age in very preterm infants?

Objective: To investigate the influence of perinatal risk factors, especially hypotension, on neuromotor status at term in surviving preterm infants born before 32 weeks of gestation. Methods: This study is part of the Leiden Follow-Up Project on Prematurity: a prospective, regional study of 266 live born infants with a gestational age (GA) <32 weeks born in 1996–1997. Twenty-eight infants died before term age. Two hundred and eleven infants were examined neurologically at term according to Prechtl. The findings were classified as normal (N), mildly abnormal (MA) or definitely abnormal (DA). Hypotension was defined as a mean arterial blood pressure (MABP) <30 mm Hg on at least two occasions. Results: One hundred and six (50%) infants were classified as neurologically N, 92 (44%) infants were classified as MA and 13 (6%) infants as DA. Hypotension, bronchopulmonary dysplasia (BPD), flaring and cystic periventricular leucomalacia (PVL) were risk factors for neurological morbidity. Of the 68 infants with hypotension, 33 (49%) were classified as MA and 7 (10%) as DA. Of the 141 infants without hypotension, 58 (41%) were MA, and 5 (4%) were DA. The odds ratio of hypotension for neurological morbidity was 1.9 (95% CI 1.06–3.40), adjusted for gestational age, birth weight, small for gestational age (SGA) and gender, it was 1.96 (95% CI 1.02–3.77). The adjusted odds ratio of PVL was 18.6 (4.4–78.5), of flaring was 2.37 (1.18–4.74) and of BPD was 2.44 (1.08–5.5). Conclusions: Apart from gestational age, periventricular leucomalacia, and bronchopulmonary dysplasia, hypotension in preterm infants is a major risk factor for neurological morbidity at term.

Dopamine versus dobutamine for hypotensive preterm infants.

Inotropes are widely used in preterm infants to treat systemic hypotension. The most commonly used drugs are dopamine and dobutamine. These agents have different modes of action which may result in different haemodynamic effects. To compare the effectiveness and safety of dopamine and dobutamine in the treatment of systemic hypotension in preterm infants. The standard search method of the Cochrane Neonatal Review Group was used. Searches of electronic and other databases were performed. Previous reviews were searched for references to relevant trials and leading authors in the field were contacted for information about other published and unpublished studies. Randomised controlled trials where short and/or long term effects of treatment with dopamine and dobutamine for the treatment of systemic arterial hypotension were compared were selected for this review. Trials studying newborn infants born before 37 completed weeks gestation and less than 28 days of age were eligible for inclusion. Systemic arterial hypotension was not defined specifically, but accepted as defined in individual studies. Studies were not limited by birthweight, lower gestational age threshold or by route or duration of administration of inotropic agents. Study quality and eligibility were assessed independently by each reviewer. The standard method of the Cochrane Collaboration described in the Cochrane Collaboration Handbook was used to perform this systematic review. Data extraction was performed independently by each reviewer, with differences being resolved by discussion. The following outcomes were determined: mortality in the neonatal period, long term neurodevelopmental outcome, radiological evidence of severe neurological injury, short term haemodynamic changes and incidence of adverse effects. The effect of interventions is expressed either as Relative Risk (RR), Risk Difference (RD) or as Weighted Mean Difference (WMD) with their 95% Confidence Interval (CI). Four trials met the pre-defined criteria for inclusion in this review. There was no evidence of a significant difference between dopamine and dobutamine in terms of neonatal mortality (RD 0.02 95% CI -0.12 to 0.16), incidence of periventricular leukomalacia (RD -0.08, 95% CI -0.19 to 0.04), or severe periventricular haemorrhage (RD -0.02, 95% CI -0.13 to 0.09). Dopamine was more successful than dobutamine in treating systemic hypotension, with fewer infants having treatment failure (RD -0.29, 95% CI -0.42 to -0.17; NNT = 3.5, 95% CI 2.4 to 5.9). There was no evidence of a significant difference in change in left ventricular output when dopamine was compared with dobutamine (WMD -83 ml/kg/min, 95% CI -174 to 8 ml/kg/min). There was no evidence of a significant difference between the two agents with respect to the incidence of tachycardia (RD -0.06, 95% CI -0.25 to 0.14). None of the studies reported the incidence of adverse long term neurodevelopmental outcome. 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.

Dopamine effects on pulmonary artery pressure in hypotensive preterm infants with patent ductus arteriosus

We investigated the effects of dopamine on pulmonary artery pressure in 18 ventilated hypotensive preterm neonates by using the flow characteristics of the ductal shunt. Dopamine has variable effects on pulmonary/systemic mean arterial pressure ratio with half the neonates showing an increase in pulmonary pressure relative to systemic pressure. ( J Pediatr 2002;140:373-5)

Right ventricular performance in hypotensive preterm neonates treated with dopamine.

Systemic hypotension with left ventricular dysfunction is a common complication of neonatal respiratory distress syndrome and is often treated with inotropic agents. Although pulmonary hypertension with elevated pulmonary vascular resistance is also an important pathophysiological finding in respiratory distress syndrome, the effect of inotropes on the right ventricle has not been studied. The aim of this study was to assess changes in right ventricular dimensions and function with inotropic therapy in hypotensive preterm infants. Hypotensive neonates with respiratory distress syndrome were studied before and 1 hour after the initiation of a dopamine infusion. Right ventricular performance was assessed by two-dimensional echocardiography using the ellipsoid approximation method. Eight hypotensive neonates were recruited with a median (interquartile range) gestation of 27 weeks (26 to 27 weeks). Right ventricular end systolic volume decreased significantly from a median (interquartile range) of 1.06 ml/kg (0.81-1.50 ml/kg) to 0.73 ml/kg (0.51-0.99 ml/kg) (p < 0.01) 1 hour following dopamine therapy. Right ventricular end diastolic volume did not change significantly. Right ventricular ejection fraction increased significantly from 0.36 (0.29-0.46) to 0.51 (0.43-0.53) ( p < 0.01). There was a trend toward an increase in right ventricular output from 90 ml/kg/min (67-115 ml/kg/min) to 112 ml/kg/min-143 ml/kg/min) (p=0.07). Dopamine increases right ventricular ejection fraction through a reduction in right ventricular end systolic volume.

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.