Neonatal Hypotension Research Articles

Effects of hydroxyethyl starch on cardiac output in hypotensive neonates: A comparison with isotonic saline and 5% albumin

To evaluate the effects of hydroxyethyl starch (6% HES 200/0.5) on cardiac output in hypotensive neonates with low cardiac output and absence of myocardial dysfunction. In a prospective randomized blinded trial, 21 hypotensive neonates (mean gestational age of 29+/-3 wk) were randomly allocated to receive infusions of either 5% albumin (albumin group), isotonic saline (saline group) or hydroxyethyl starch (HES group). Infants had to show low cardiac output and an absence of myocardial dysfunction for inclusion in the study. Cardiac output was assessed by Doppler-derived mean aortic flow velocity. Ten minutes after infusion, 67% of all infants had more than a 10% increase in cardiac output. Increases in mean aortic flow velocity (m/s; median and range) were 0.05 (-0.02, +0.07), 0.03 (-0.03, +0.12) and 0.03 (-0.04, +0.11) for the albumin, saline and HES groups, respectively (p = 0.79). The percentage of blood pressure normalization (95% confidence interval) was 86% (60-100) in the albumin group, 57% (20-94) in the saline group and 71% (37-100) in the HES group (p = 0.50). This study did not provide evidence that hydroxyethyl starch is more efficient than isotonic saline or albumin.

Treated Hypotension Is Associated With Neonatal Morbidity and Hearing Loss in Extremely Low Birth Weight Infants

Neonatal hypotension may be a risk factor for neurologic impairment. Few studies have examined the impact of low blood pressure in extremely low birth weight (ELBW) infants weighing 400 to 999 g on neurodevelopmental outcome. We set out to explore the relationship between treated hypotension in the first 72 hours of life and perinatal factors, morbidity, and mortality in ELBW infants and then to compare neurosensory outcome in ELBW infants with treated hypotension and those who never received treatment for hypotension. We performed chart review of all 156 ELBW infants admitted to our level III NICU in 1998-1999. Infants had "treated hypotension" if they received fluid pushes, corticosteroids, and/or vasopressors during the first 72 hours of life in an attempt to increase blood pressure. Follow-up included neurologic examination, Bayley Scales of Infant Development, vision and hearing evaluation. Statistical analysis was performed by using SPSS 11.0. Univariate and multivariate analyses were conducted to determine morbidities associated with treated hypotension. Fifty-nine infants received treatment for hypotension. Ninety-seven infants did not. The groups had similar race, gender, delivery mode, chorioamnionitis, and maternal socioeconomic status. Thirty-eight (24%) infants expired, including 20 who received treatment for hypotension. Of the 156 infants in the study group, 110 underwent neurodevelopment testing, and 103 were able to undergo complete neurodevelopment testing and Bayley examination. Multivariate analysis controlling for socioeconomic status and neonatal morbidity revealed that treated hypotension is associated with delayed motor development and hearing loss. Treated hypotension in ELBW infants in the first 72 hours of life is associated with significant short-term and long-term morbidity. Infants with treated hypotension are more likely to have delayed motor development, hearing loss, and death.

Moderate to severe Alzheimer disease

<h3>Background</h3> The use of vasoactive agents like arginine vasopressin (AVP) and terlipressin to treat hypotension or persistent pulmonary hypertension in critically ill preterm neonates is increasing. Therefore, a systematic review of the available data on dosing, efficacy and safety of AVP and terlipressin in this patient population appears beneficial. <h3>Methods</h3> We will conduct a systematic review of the available evidence on the use of AVP and terlipressin for the treatment of hypotension or persistent pulmonary hypertension in preterm neonates. We will search Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Google Scholar from inception to March 2021. Two reviewers will independently screen titles and abstracts, review the full text of eligible studies, extract data, assess the risk of bias and judge the certainty of the evidence. Our primary outcome will be an (1) improvement of end-organ perfusion after initiation of AVP or terlipressin and (2) mortality prior to discharge. Our secondary outcomes will include (1) major neurosensory abnormality and (2) the occurrence of adverse events. <h3>Discussion</h3> The currently available evidence on the efficacy and safety of AVP and terlipressin in preterm neonates is limited. Yet, evidence on the pharmacology of these drugs and the pathophysiology of vasoplegic shock support the biological plausibility for their clinical effectiveness in this population. Therefore, we aim to address this gap concerning the use of vasopressin and terlipressin among critically ill preterm neonates. <h3>Trial registration</h3> This protocol has been submitted for registration to the international database of prospectively registered systematic reviews (PROSPERO, awaiting registration number).

Diagnosis and treatment of neonatal hypotension outside the transitional period

The etiology and pathophysiology of the circulatory compromise are among the primary determinants of the clinical presentation of patients with neonatal shock. Therefore, in the absence of direct assessment of cardiac output and organ blood flow, the characteristic clinical presentation itself may guide the initial management of the circulatory compromise. This chapter discusses different pathophysiology-driven management approaches to a number of characteristic clinical presentations of neonatal shock. The clinical presentations discussed in detail are the hypotensive very low birth weight neonate with a hemodynamically significant patent ductus arteriosus, and the preterm or term neonate with perinatal depression, pressor/inotrope resistance and relative adrenal insufficiency, and with specific systemic inflammatory response syndrome. In the absence of information from appropriately designed, randomized clinical trials, management of neonatal shock remains based on pathophysiology and experience. Thus, as there is little evidence for the effectiveness of these management approaches to improve mortality and short-and long-term outcome, the therapeutic approaches described in this chapter should be carefully evaluated and cautiously entertained when treating a neonate with circulatory compromise.

A Randomized-Controlled Trial of Prophylactic Hydrocortisone Supplementation for the Prevention of Hypotension in Extremely Low Birth Weight Infants

Extremely low birth weight (ELBW) infants are at risk for hypotension. Abnormal adrenal function may play a role in the pathogenesis of hypotension, and therefore, the administration of hydrocortisone (HC) may be an effective treatment for hypotension in some infants. However, the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied. We conducted a randomized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants. Infants were assigned to receive either HC or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors (VP) was standardized based on an a priori protocol. A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the HC group 25% received VP at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the HC group received VP compared to 39% of the placebo group (p<0.05). Prophylactic treatment with HC reduces the incidence of hypotension, defined by treatment with VP, among ELBW infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established.

Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

Objectives: A proportion of preterm, very low birthweight (VLBW, < 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone...

Transient adrenocortical insufficiency of prematurity and systemic hypotension in very low birthweight infants

<b>Objectives:</b> A proportion of preterm, very low birthweight (VLBW, &lt; 1500 g) infants may show inadequate adrenal response to stress in the immediate postnatal period. The human corticotrophin releasing hormone (hCRH) stimulation test was used to: (<i>a</i>) determine the relation between pituitary-adrenal response and systemic blood pressure in these infants; (<i>b</i>) characterise the endocrinological features of transient adrenocortical insufficiency of prematurity (TAP). <b>Study design:</b> A total of 226 hCRH tests were performed on 137 VLBW infants on day 7 and 14 of life in a tertiary neonatal centre. <b>Results:</b> Basal, peak, and incremental rise in serum cortisol (ΔCort_0–30) on day 7 were associated significantly with the lowest systolic, mean, and diastolic blood pressures recorded during the first two weeks of life (<i>r</i> &gt; 0.25, p &lt; 0.005). These cortisol concentrations also correlated significantly but negatively with the maximum and total cumulative dose of dopamine (<i>r</i> &gt; −0.22, p &lt; 0.02), dobutamine (<i>r</i> &gt; −0.18, p &lt; 0.04), and adrenaline (<i>r</i> &gt; −0.26, p &lt; 0.004), total volume of crystalloid (<i>r</i> &gt; −0.22, p &lt; 0.02), and duration of inotrope treatment (<i>r</i> &gt; −0.25, p &lt; 0.006). Multivariate regression analysis of significant factors showed that the lowest systolic, mean, and diastolic blood pressures remained independently associated with serum cortisol (basal, peak, and ΔCort_0–30) on day 7. Hypotensive infants requiring inotropes (group 2) were significantly less mature and more sick than infants with normal blood pressure (group 1). The areas under the ACTH response curves were significantly greater in group 2 than in group 1, on both day 7 (p = 0.004) and day 14 (p = 0.004). In contrast, the area under the cortisol response curve was significantly greater in group 1 than in group 2 on day 7 (p = 0.001), but there was no significant difference between the two groups on day 14. In addition, serum cortisol at the 50th centile in hypotensive infants had high specificity and positive predictive value (0.80–0.93 and 0.81–0.89 respectively) for predicting early neonatal hypotension. <b>Conclusions:</b> This study characterises the fundamental endocrinological features of TAP: normal or exaggerated pituitary response; adrenocortical insufficiency; good recovery of adrenal function by day 14 of postnatal life. The results also provide the centiles of serum cortisol for hypotensive patients and infants with normal blood pressure, and show a significant relation between serum cortisol and blood pressure in VLBW infants.

Pharmacology Review

After completing this article, readers should be able to: 1. Describe the primary cardiovascular effects of dobutamine in neonates. 2. Delineate the monitoring that is required in neonates to whom dobutamine is administered. Dobutamine was introduced for the management of neonatal cardiovascular compromise 2 decades ago in an attempt to provide an alternative to dopamine and improve outcomes in preterm and term neonates presenting with hypotension. However, as with dopamine, dobutamine was introduced in neonatal intensive care without appropriately designed clinical trials. Furthermore, most of the randomized studies have investigated the effectiveness of the agent in treating hypotension; organ blood flow changes and tissue perfusion have become the primary outcome measures only in more recent studies. Finally, because there is virtually no information from prospective, randomized trials on the impact of treating neonatal hypotension on mortality and neurodevelopmental outcome, evidence that use of dobutamine or the other sympathomimetic amines (dopamine, epinephrine, norepinephrine) improves neonatal mortality or morbidity is only suggestive and indirect. Dobutamine, an analog of isoproterenol, is a synthetic sympathomimetic amine originally developed for the treatment of congestive heart failure. Unlike dopamine, dobutamine is a relatively cardioselective agent, with significant cardiac alpha1- and beta1/beta2-adrenoreceptor-mediated direct inotropic effects and limited chronotropic actions. Because dobutamine contains an asymmetric carbon atom, there are two enantiomers of the drug. The available preparation is a 1:1 racemic mixture of the (−)- and (+)-enantiomers. However, the adrenoreceptor affinity of the two optical isomers differs substantially. The (−)-dobutamine is a highly selective alpha1-adrenoreceptor agonist, and the (+)-dobutamine exerts a potent and selective beta1- and beta2-adrenoreceptor stimulatory effect. In addition, (+)-3-O-methyldobutamine, the (+) optical isomer of the major dobutamine metabolite, is a relatively potent and highly selective alpha1-adrenoreceptor blocker. Thus, the interaction of the two …

Hypotension in the Neonate

After completing this article, readers should be able to: 1. Describe the relationship between blood pressure and birthweight, gestational age, and postnatal age. 2. Delineate potential negative consequences of treating hypotension in the neonate. 3. Characterize the evaluation of a neonate prior to treating suspected hypotension. 4. Describe current and potential future therapeutic options for treatment of neonatal hypotension. Deciding which neonates require treatment for a low arterial blood pressure (BP) often is difficult. To some extent, this has been due to a lack of normative BP data, particularly among preterm neonates. However, we now have reliable data relating birthweight, gestational age, and postnatal age to BP in term and preterm neonates. Nevertheless, the management of suspected hypotension in various neonatal intensive care units differs. Although there are good studies comparing various modes of therapy, prospective trials relating long-term outcome to treatment versus no treatment at various BP values have not been performed. Concern about the deleterious effects of hypotension is greater for preterm neonates primarily because of the relative inability to regulate cerebral blood flow in preterm neonates compared with infants who are born at term. ### Preterm Neonates Clearly, the primary issue surrounding possible hypotension in preterm neonates is the concern that these infants may experience impaired central nervous system perfusion, leading to ischemic damage. Low arterial BP has been associated with a decrease in cerebral blood flow, and the apparent impairment of autoregulation of cerebral blood flow in distressed infants emphasizes the importance of preventing both hypotension and rapid increases in BP in preterm neonates. Impaired autoregulation, demonstrated by near-infrared spectroscopy, and BP have been shown to be predictive of germinal matrix-intraventricular hemorrhage, periventricular leukomalacia, or both. When mean blood pressure (MBP) was measured continuously in neonates at gestational ages 26 to 30 weeks, a highly significant relationship was demonstrated between MBP less than …

Clinical Factors Influencing Blood Pressure in the Neonate

After completing this article, readers should be able to: 1. Describe the association between gestational age, birthweight, and postnatal age and blood pressure in the neonate. 2. Delineate the primary clinical consideration in an infant who has hypotension. 3. Describe the controversy surrounding the relationship between antenatal steroid therapy and neonatal blood pressure. 4. Delineate the aspects of management of respiratory illnesses in the neonate that may be associated with altered blood pressure. 5. List factors that may cause altered blood pressure in the neonate. Few aspects of neonatal care have generated as much controversy as the assessment of blood pressure (BP) and need for treatment of perceived abnormalities of this physiologic variable. Familiarity with clinical situations in which BP may be low should allow anticipation of this common clinical problem and timely intervention when such treatment is necessary (Tables 1 and 2). In this article, we review factors that have been shown to have the greatest effect on BP. View this table: Table 1. Some Risk Factors for Shock in the Newborn View this table: Table 2. Some Causes of Cardiogenic Shock in the Newborn A direct reading from an indwelling arterial catheter represents the “gold standard” for measuring BP in the neonate, and this method should be used whenever possible. Obviously, arterial access may not always be available, and the ability to monitor BP noninvasively using an oscillometric technique represents a major advancement in neonatal care. The correlation between direct and indirect methods generally has been good. Disparities in results have been related to various factors, including inappropriate cuff width-to-arm ratio or problems with the arterial catheter-transducer system, such as air bubbles or clots. In general, indirect determinations are higher than those obtained directly, often by 3 to 5 mm Hg. The individual contributions of birthweight and gestational age to BP are difficult to delineate. Several groups of investigators have shown that BP …

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.

Controversies in the diagnosis and management of hypotension in the newborn infant.

Although close to half of the newborns admitted to neonatal intensive care units receive treatment for "hypotension," the normal physiologic blood pressure range ensuring appropriate organ perfusion in the neonate is unknown. Thus, the decision to treat hypotension in the newborn is based on statistically defined gestational and postnatal age-dependent normative blood pressure values and physicians' beliefs rather than on data bearing physiologic reference. Dopamine is the most widely used sympathomimetic amine in the treatment of neonatal hypotension, and it is more effective than dobutamine in raising blood pressure. Volume administration is less effective in the immediate postnatal period, and its extensive use is associated with significant untoward effects, especially in preterm infants. During the course of their disease, some of the sickest hypotensive newborns become unresponsive to volume and pressor administration. This phenomenon is caused by the desensitization of the cardiovascular system to catecholamines by the critical illness and relative or absolute adrenal insufficiency. The findings that steroids rapidly up-regulate cardiovascular adrenergic receptor expression and serve as hormone substitution in cases of adrenal insufficiency explain their effectiveness in stabilizing the cardiovascular status and decreasing the requirement for pressor support in the critically ill newborn with volume-and pressor-resistant hypotension. Finally, despite recent advances in our understanding of the pathophysiology and management of neonatal hypotension, there are few data on the impact of the treatment on organ blood flow and tissue perfusion and on neonatal morbidity and mortality.

Circulatory support of the sick preterm infant

In the majority of preterm infants, especially during the immediate postnatal period, hypotension is primarily caused by abnormal peripheral vasoregulation and/or myocardial dysfunction and not by absolute hypovolemia. Therefore, aggressive volume resuscitation is not warranted and is potentially harmful. Volume support should be limited to 10–20ml/kg of isotonic saline administration and, if sustained normalization of the blood pressure cannot be achieved, early initiation of cardiovascular pharmacological support is recommended. However, in preterm infants who present with an identifiable volume loss, the kind of fluid lost should first be replaced. Due to its beneficial cardiovascular and renal actions, dopamine is the drug of choice in the treatment of neonatal hypotension. Dobutamine may be added if myocardial dysfunction persists or develops during dopamine treatment. In some critically ill preterm infants, escalation of dopamine therapy or addition of epinephrine is necessary yet not always effective indicating the development of pressor resistant hypotension. Downregulation of cardiovascular adrenergic receptors and some degree of adrenal insufficiency may explain this phenomenon. In these patients, a brief course of steroid treatment may be successful in stabilizing the cardiovascular status and decreasing the requirement for pressor/inotrope support. However, well-designed randomized and controlled clinical trials are needed in the future to determine the effectiveness and potential short- and long-term side effects of steroid administration in preterm infants with pressor-resistant hypotension. In summary, management of the critically ill hypotensive preterm infant remains challenging and requires a better understanding of the pathophysiology of neonatal shock and improvements in our ability to evaluate cardiac output, organ blood flow, and tissue perfusion at the bedside.

High Dose Dopamine for the Treatment of Neonatal Hypotension

High Dose Dopamine for the Treatment of Neonatal Hypotension

Randomized Trial of Normal Saline (NS) Versus 5% Albumin (ALB) for the Treatment of Neonatal Hypotension

Randomized Trial of Normal Saline (NS) Versus 5% Albumin (ALB) for the Treatment of Neonatal Hypotension

Cardiorespiratory stability of very low birth weight premature neonates following postoperative administration of morphine

Abstract The cardiac and respiratory status of mechanically ventilated premature neonates, who received intraoperative fentanyl during thoracotomy for ligation of a patent ductus arteriosus ( n =24), were evaluated before and after administration of the first postoperative dose of morphine. The neonates were 26.1 ± 2.1 (mean ± SD) weeks gestational age and 13.8 ± 8.1 (mean ± SD) days of age at the time of surgery. Changes in heart rate, arterial blood pressure, respiratory rate and oxygen saturation were measured preoperatively and immediately before and 20 and 60 minutes after parenteral administration of the morphine dose. Heart rate values increased (mean increase 6%; p=0.02) and respiratory rate values decreased (mean decrease 23%; p=0.01) postoperatively. There were no significant differences in heart rate, respiratory rate, blood pressure and oxygen saturation following administration of morphine. Mean arterial blood pressure decreased following the administration of morphine in a few neonates already being treated for hypotension. However, given the severity of illness of these neonates during the immediate postoperative period, it is difficult to directly attribute clinically significant hypotension to morphine administration alone. The findings from this study suggest that fears of morphine-induced bradycardia and hypotension in normovolaemic critically ill premature neonates during the immediate postoperative period are not warranted and should not be used as reasons for withholding opioid analgesia from these neonates. Use of a continuous infusion of morphine or fentanyl may be more appropriate methods of postoperative analgesia for hypotensive neonates or those at risk for hypotension.

High Dose Dopamine for Treatment of Neonatal Hypotension 1111

Dopamine doses of 10-20 mcg/kg/min are often avoided because alpha-adrenergic effects may decrease renal perfusion and impair urine output. However, some hypotensive neonates do not respond even to these doses, and require greater pressor support. Of 130 neonates treated with dopamine in 1991-1995, 24 (18.5%) required dopamine > 20 mcg/kg/min to achieve adequate blood pressure. We reviewed the data on these 24 infants. Doses of dopamine were 26 to 250 mcg/kg/min. Gestational age was 22-41 (29±6) weeks, and birth weight was 450 to 3845 (1505±1086) gr. The most common associated diagnosis included: RDS (n=18), pulmonary hypertension (n=5), sepsis (n=7), and barotrauma (n=10). Dopamine was infused at gradually increasing doses until adequate values of blood pressure (BP) were achieved. Urine output (UO) was also assessed. We compared results pre-treatment, while on“conventional” pressor doses, and while on “high-dose” dopamine. UO and BP were significantly higher (P <0.001) while on“high-dose” dopamine vs. the two preceding epochs. Data analyzed for the subgroup with birth weight <1500 gr. (n=15) was similar to the above. Overall survival was 45% (40% in the group with birth weight<1500gr). Incidence of severe IVH (grades 3 & 4) was 16% in the surviving infants with weight < 1500 gr. We conclude that there is an increasing pressor response to dopamine beyond 20 mcg/kg/min., and that urine output (UO) is not suppressed by these high doses; in fact, hemodynamic improvement may have a beneficial net effect on renal function. Table

Risk Factors for Cerebral Palsy (CP) in Very Low Birth Weight (VLBW) Infants without Major Cranial Ultrasound (CUS) Abnormalities. † 1309

Data from a population based cohort study [Pinto-Martin et al. Pediatrics 1995] suggests that almost one-half of VLBW infants with CP do not have antecedent major CUS abnormalities, such as periventricular echodensity or echolucency (PVED/EL). We performed a case-control study to identify risk factors for CP among VLBW infants without major CUS abnormality. 36 cases, who had CP and no major CUS abnormality, and 70 gestational-age matched controls were identified within a geographically based cohort, born 1985 to 1995, at the only tertiary perinatal referral center serving a 17-county region. 27 cases had normal CUS studies and 9 had uncomplicated subependymal hemorrhage(SEH), defined as SEH without post-hemorrhagic hydrocephalus, persistent ventricular enlargement, or PVED/EL. Medical records of mothers and neonates were reviewed to ascertain the occurrence of the following factors, which, in previous studies, have been associated with either CP or PVED/EL: multiple gestation, chorioamnionitis, pre-eclampsia, treatment of the mother with magnesium sulfate or betamethasone, neonatal sepsis, pneumothorax, acidosis, hypotension, hypocarbia, and bronchopulmonary dysplasia (BPD). In univariate analyses, betamethasone was associated with a lower risk [odds ratio (OR) 0.3(0.1-0.9)], while pneumothorax [OR 5.5 (1.0-29.9)], SEH[OR 11.3 (2.3, 55.9)], and BPD (defined as oxygen dependency at 28 days) [OR 10.2 (4.1-25.4)] were associated with an increased risk. The mean values for total time with PaCO2< 35 mm Hg, total time with systolic blood pressure < 35 mm Hg, and total time with pH < 7.15 were higher among cases, and mean arterial pH on the first postnatal blood gas was lower (all p < 0.05, Wilcoxon rank sum test]. When stepwise regression (with backward elimination) was used to select neonatal factors independently associated with CP, significant associations were found only for BPD [odds ratio 5.4 (2.1-14.1)] and uncomplicated SEH[odds ratio 8.3 (1.5-44.5)]. For the 27 cases of CP with normal CUS, the OR for BPD was 6.8 (2.4-19.3). If this association is assumed to be causal, then the estimated etiologic fraction for BPD is 0.66 (95% confidence limits 0.30-0.84). Thus among infants with normal CUS, a majority of CP may be attributable to BPD or unknown antecedents of BPD.

Rapid Increase of Blood Pressure after Low Dose Hydrocortison (HC) in Low Birth Weight Neonates with Hypotension Refractory to High Doses of Cardio-inotropics 210

Objective: The effect of HC on mean arterial blood pressure(MABP) was evaluated in a double-blind randomized study in 26 neonates with hypotension, despite high dose cardio-inotropics. Methods: 26 hypotensive neonates despite treatment with 20 μg/kg/min. dopamine and/or dobutamine, were randomized to receive either HC (5 mg/kg/day in 4 doses), or placebo (P). Hypotension was defined as MABP of less than nr. of gestational age in weeks in mmHg, during at least 30 minutes. During 24 hours MABP, heart rate, urine output, vasoactive medication and volume expanders were recorded.Results: Hypotension could be effectively treated within 24 hours in both HC- and P-treated neonates (table). No difference in additional vasoactive medication (dopamine, dobutamine, adrenaline or isoprenaline), or in volume expanders was found. However, in the HC-treated patients the increase in MABP to normal values occurred more rapidly (within 6 hours) than in the P-group (p<0.05). HC and P groups were comparable for gestational age and birth weight. No differences were found between groups for intracranial hemorrhage (7HC/7P) or flaring(5HC/5P).

Cortisol Production Rate is Related to Mean Arterial Blood Pressure in Neonates. † 811

There are few data on clinical factors that influence cortisol production rate (FPR) in neonates. This study aimed to provide such information. Blood samples for plasma cortisol (F) were taken via indwelling arterial lines at 15 min intervals for 6 hours in 42 clinically stable neonates (median ga 32 wks, range 25-41; median bw 1.95kg, range 0.64-3.88) studied in the first 9 postnatal days. None of the infants received vasopressor agents during the study and none received postnatal glucocorticoids prior to the study. We estimated FPR using deconvolution analysis. We prospectively collected data on antenatal steroid exposure, body surface area, gestational age, birth weight, the presence or absence of clinical interventions during the study, whether the neonate was intubated or extubated at time of study, mean arterial blood pressure (MABP), sex, SNAP score, and postnatal study day. MABP was recorded at 15 min intervals during the study and the values averaged to provide a single value for each neonate. The relationship between FPR and the above mentioned clinical factors was examined using univariate linear regression analysis (ULRA) and stepwise multiple linear regression analysis (SMLRA). Using ULRA, FPR correlated positively with postnatal study day (P = 0.0005, r= 0.51), MABP (P = 0.0006, r = 0.51) and being intubated (P = 0.011, r = 0.39). FPR did not significantly correlate with any other clinical factor. On SMLRA, these 3 clinical factors remained significantly correlated with FPR,(MABP, P = 0.0005; study day, P = 0.0085; intubated, P = 0.018). These 3 factors combined accounted for 51% of the variation in FPR (r2 = 0.51). We conclude that, assuming similar corticosteroid-binding globulin levels, FPR is related to MABP in neonates and to our knowledge this is the first time this relationship has been described. Our data support the concept that the low plasma F levels seen in association with hypotension in some premature neonates are consistent with cortisol insufficiency. We propose that this may be explained by decreased FPR in these neonates.