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 10–20 ml/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.     

早产儿低血压诊治进展

低血压是新生儿重症监护室的常见疾病,早产儿更容易出现低血压.目前,对早产儿低血压的定义、何时开始治疗及如何治疗仍存在争议,治疗上除扩容外,主要的药物有多巴胺、多巴酚丁胺、肾上腺素、氢化可的松、米力农等,这些药物能否改善早产儿预后需要更多的临床研究加以证实.     

Neonatal shock in the first postnatal day.

Advances in neonatal medicine have markedly reduced mortality in preterm infants. Current emphasis should be placed on early detection and treatment of neonatal hypotension and shock. Ideal clinical management includes perinatal recognition of low birth weight infants at risk for hypotension. All critically ill preterm infants should be closely monitored for tachycardia, hypotension, and/or decreased urinary output. By use of noninvasive blood pressure screening techniques, hypotensive infants may be identified in the first hours of life. Judicious use of whole blood or balanced salt solutions will result in reduction of mortality from 50% to 10%.     

Hypotension and shock in the preterm infant

Between 16% and 98% of extremely preterm infants receive treatment for hypotension in the first few days of life. This enormous variation has arisen because of a lack of reliable information to create an evidence base for intervention. This review article provides the unique characteristics of the neonatal cardiovascular system, and addresses the definitions of hypotension and shock in the preterm infant, the indications for treatment and appropriate therapies in individual cases. The treatment of shock and hypotension in the preterm infant may be the area of neonatology where there is the greatest 'intervention/data imbalance'; more babies receive more treatments with less supportive evidence than in virtually any other domain. Treatment of hypotension in infants with good perfusion is probably unnecessary and may be harmful, but the assessment of adequate perfusion remains problematic. Infants with inadequate oxygen delivery to the tissues may benefit from treatment, but which treatments are effective are unknown. It is essential that better evidence be available to create a rational basis for intervention.     

Hypotension in preterm infants

PURPOSE: Hypotension is a frequent occurrence in sick preterm neonates. It is important to appropriately recognise and treat hypotension in preterm infants due to the possible association with short and long term adverse outcomes. SEARCH STRATEGY: An extensive search for relevant articles was carried out on PubMed, Embase and Cochrane database of systematic reviews. Cross references were hand searched. CONCLUSIONS: The pathophysiology hypotension in preterm infants is multifactorial. Hypovolemia plays only a minor role in the absence of overt fluid losses. Cardiac dysfunction seems to be a factor in some neonates. Assessment of hypotension should be based on an overall clinical condition. Overzealous fluid administration seems to be associated with adverse outcomes and should be avoided in the absence of obvious fluid losses. Inotropes should be used if fluid boluses fail to correct hypotension. Dopamine is the most effective inotrope. Dobutamine can be used as add on therapy or as first line if cardiac dysfunction is an obvious cause. Evidence points to hypocortisolism in at least some hypotensive infants. Steroids have been used successfully in inotrope-resistant hypotension in some infants. Steroids should be used judiciously since there have been concerns about adverse neurological outcome in preterm infants who received steroids in the neonatal period.     

Neonatal hypotension: two years' experience in a neonatal intensive care nursery

Routine measurement of blood pressure in high risk neonates admitted to the intensive care nursery during a 2 year period resulted in detection of 18 infants with persistent hypotension requiring definitive treatment. The perinatal events in these babies were compared to those in a control group of infants. No single well defined factor responsible for neonatal hypotension could be found in the antenatal period or during labour. However 14 of the 18 babies were asphyxiated at the time of admission compared to 6 of 18 controls (p less than 0.02). Seventeen of 18 babies were preterm. Treatment consisted of maintenance of ventilation, oxygenation and acid-base status, volume expansion when indicated and inotropic agents. Nine of the 18 hypotensive babies died compared to 1 of 18 controls. Failure to respond within a few hours of commencement of treatment indicated poor prognosis.     

Effects of inhaled corticosteroids on systemic blood pressure in preterm infants

OBJECTIVE: To assess the effect of inhaled fluticasone propionate on (i) systemic blood pressure, and (ii) the need for volume expanders (crystalloids and colloids) and inotropes for blood pressure support in preterm, very low birth weight (VLBW) infants. METHODS: Ventilated VLBW infants, less than 32 weeks of gestation, with respiratory distress syndrome were randomised to receive a 14-day course of either fluticasone propionate (500 microg/puff, 2 puffs every 12 h; n=27) or placebo (n=26) with a metered dose inhaler-spacer device. The response of treatment was assessed by comparing the use of volume expanders, inotropes, and the average and the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. RESULTS: There were no significant differences in the average or the lowest systolic, mean and diastolic blood pressures in 6 hourly epochs between the 2 groups. However, the total volume of crystalloids and colloids requirement was significantly greater in control than in treated infants (p=0.03). There was also a trend towards greater consumption of the total cumulative dose of dopamine in the control infants (p=0.10). CONCLUSIONS: Fluticasone-treated infants required significantly less volume of crystalloids and colloids for blood pressure support compared with control infants. Further larger scale studies are required to determine whether inhaled corticosteroids could minimise the use of volume replacement therapy and inotropes in the treatment of hypotension in preterm infants in the early postnatal period.     

Adding Hydrocortisone as 1st Line of Inotropic Treatment for Hypotension in Very Low Birth Weight Infants

In this pilot study the authors demonstrate the feasibility, effectiveness and safety of the combined early treatment with hydrocortisone and dopamine for refractory hypotension in preterm newborns. Very low birth weight infants born at gestational age < 30 wk or birth weight < 1250 g in the first 48 h of life with hypotension after receiving 10–20 mL/kg bolus of normal saline, were randomized to receive concurrently with the initiation of dopamine, intravenous hydrocortisone (11 infants) or an equivalent volume of placebo (11 infants). Despite no significant clinical difference between the groups including gestational age, birth weight, prevalence of chorioamnionitis, prenatal steroid treatment, cord PH, baseline cortisol level, there was a trend towards lower incidence of bronchopulmonary dysplasia (BPD), and higher survival without BPD rate in the hydrocortisone group. In this very sick small group of infants, hydrocortisone was not associated with more adverse effects, but rather showed a trend toward association with better outcome, including survival without BPD.     

Neonatal hypotension: two years'experience in a neonatal intensive care nursery

ABSTRACT. Routine measurement of blood pressure in high risk neonates admitted to the intensive care nursery during a 2 year period resulted in detection of 18 infants with persistent hypotension requiring definitive treatment. The perinatal events in these babies were compared to those in a control group of infants. No single well defined factor responsible for neonatal hypotension could be found in the antenatal period or during labour. However 14 of the 18 babies were asphyxiated at the time of admission compared to 6 of 18 controls (p<0.02). Seventeen of 18 babies were preterm. Treatment consisted of maintenance of ventilation, oxygenation and acid-base status, volume expansion when indicated and inotropic agents. Nine of the 18 hypotensive babies died compared to 1 of 18 controls. Failure to respond within a few hours of commencement of treatment indicated poor prognosis.     

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 micrograms/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.     

Diagnosis and treatment of preterm transitional circulatory compromise

AIM: To determine the evidence for detection and treatment of low systemic and organ blood flow in preterm infants in the first day after birth. REVIEW: Preterm infants are at risk of low systemic blood flow (SBF) in the first day, with almost all infants who develop low flows doing so by 12 h of age. Risk factors for low SBF include low gestational age, ventilation with higher mean airway pressures, large diameter ductus arteriosus, higher calculated systemic vascular resistance and poor myocardial contractility. Blood pressure and clinical signs such as capillary refill times do not accurately detect infants with low SBF, and result in delayed treatment when treatment is targeted at hypotension. Echocardiography in the first hours (including ventricular outputs and superior vena caval flow) is required to detect infants with low flows. Although dobutamine is better at increasing SBF and dopamine better at increasing blood pressure, neither has been shown to improve mortality or longer-term outcomes. Nearly 40% of infants with low SBF fail to respond to inotropes. Volume expansion should not be used routinely in preterm infants. In infants with refractory hypotension, adrenaline and corticosteroids should be considered. Further trials of echocardiographically directed cardiovascular treatments are required.     

Intrauterine growth restriction affects the preterm infant's hippocampus

The hippocampus is known to be vulnerable to hypoxia, stress, and undernutrition, all likely to be present in fetal intrauterine growth restriction (IUGR). The effect of IUGR in preterm infants on the hippocampus was studied using 3D magnetic resonance imaging at term-equivalent age Thirteen preterm infants born with IUGR after placental insufficiency were compared with 13 infants with normal intrauterine growth age matched for gestational age. The hippocampal structural differences were defined using voxel-based morphometry and manual segmentation. The specific neurobehavioral function was evaluated by the Assessment of Preterm Infants' Behavior at term and at 24 mo of corrected age by a Bayley Scales of Infant and Toddler Development. Voxel-based morphometry detected significant gray matter volume differences in the hippocampus between the two groups. This finding was confirmed by manual segmentation of the hippocampus with a reduction of hippocampal volume after IUGR. The hippocampal volume reduction was further associated with functional behavioral differences at term-equivalent age in all six subdomains of the Assessment of Preterm Infants' Behavior but not at 24 mo of corrected age. We conclude that hippocampal development in IUGR is altered and might result from a combination of maternal corticosteroid hormone exposure, hypoxemia, and micronutrient deficiency.     

Treating preterm infants at risk for chronic lung disease with dexamethasone leads to an impaired quality of general movements

Mortality rates do not decline markedly after postnatal corticosteroid therapy and concern has been raised about its neurological sequelae. We studied 37 preterm infants with Prechtl's method for the qualitative assessment of general movements before, during and after dexamethasone therapy and found that the quality of general movements was impaired in 9 of 13 initially normal infants (p = 0.004, McNemar test). The quality of fidgety movements at 3 months was abnormal in the majority of the infants and correlated strongly with neurological abnormalities at 2 years (Spearman r = 0.785, p < 0.001). Prechtl's method may prove useful for the early neurological evaluation of alternative corticosteroid treatment strategies for the treatment of chronic lung disease.     

低血压对胎龄<32周早产儿近期预后的影响

目的 探讨以平均动脉压(mean arterial pressure,MAP)<胎龄(周)和MAP<30 mmHg定义为低血压的2种定义的早期低血压对胎龄<32周早产儿近期预后的影响。方法 前瞻性纳入华中科技大学同济医学院附属湖北妇幼保健院2020年4月—2021年8月收治的符合纳入标准的早产儿320例,监测生后72 h内血压。低血压的定义与分组采取以下2种方式：(1)连续2次MAP<胎龄者为低血压组(n=104),其余病例为对照组(n=216);(2)连续2次MAP<30 mmHg者为低血压组(n=114),其余病例为对照组(n=206)。收集患儿围生期资料及住院期间的临床资料。近期预后不良定义为住院期间死亡和/或出生1周内发生Ⅲ～Ⅳ度脑室周围-脑室内出血。采用多因素logistic回归分析法评估上述2种定义下的低血压对近期预后的影响。结果 2种定义下的低血压组低灌注临床表现、预后不良、有血流动力学意义的动脉导管未闭、肺出血的发生率均高于对照组,差异有统计学意义(均P<0.05)。此外,MAP<30 mmHg定义下的低血压组脑室周围-脑室内出...     

Apnea of prematurity: risk factors and ambulatory treatment with caffeine citrate]

INTRODUCTION: Apnea of prematurity develop during the first days of life and usually resolve by the time the infant reaches 36-37 weeks postmenstrual age. In a few cases, they persist beyond term, especially in infants delivered at the youngest gestational ages (24-28 GA), and require specific care. In our unit, those preterm babies are discharged home with caffeine citrate treatment. Discontinuing the treatment is performed in hospital when they achieve a postmenstrual age of at least 42 weeks. OBJECTIVE: To identify predictive factors of persistent apnea in preterm babies. MATERIAL AND METHODS: Retrospective study comparing a population of 41 preterm infants discharged with treatment to 123 preterm babies discharged without treatment to identify predictors of persistent apnea. RESULTS: Factors significantly associated were: birth weight<1500 g, initial hypotension, gastroesophageal reflux, need for continuous positive airway pressure and multiparity. At home, no infant died and no adverse effect was reported by parents. CONCLUSION: Persistent apnea can be responsible for prolonged hospitalization. Risk factors can be identified in some children. Discharging with treatment can be an alternative to their hospitalization.     

Perfusion monitoring and intraventricular hemorrhage in preterm infants

Cardiovascular instability in preterm infants during the early postnatal period correlates with the development of intraventricular hemorrhage (IVH). Due to the correlation between hypotension and fluctuation of blood pressure, treatment was targeted specifically at hypotension to prevent IVH, but this was not successful. Recently, several novel perfusion markers have been found to be correlated with the development of IVH, and they are of current interest in cardiovascular management. In this review, the correlation between IVH and conventional, as well as novel, perfusion markers is examined.     

早产儿脑室周围-脑室内出血预防的临床证据

目的 寻找与早产儿脑室周围-脑室内出血(PVH-IVH)预防相关的临床证据,并探讨其临床应用价值.方法 检索MEDLINE、EMBASE、Oxford围产新生儿组资料库和Cochrane图书馆关于PVH-IVH危险因素和预防相关的系统评价和随机(半随机)对照研究(randomised or quasi-randomised controlled trials,RCT),并进行分析.结果 产前母亲使用皮质激素、出生时延迟结扎脐带可显著降低早产儿PVH-IVH发生率,出生后预防性使用消炎痛可降低早产儿严重IVH的发生率,但对神经系统远期预后没有影响.结论 推荐产前母亲单次使用皮质激素预防早产儿PVH-IVH的发生,消炎痛和产前多次使用皮质激素尚待更多的前瞻性RCT来证实其安全性和有效性.     

Vor- und Nachteile einer postnatalen Glukokortikosteroidtherapie bei Frühgeborenen

Postnatal glucocorticosteroids are commonly used to support weaning of preterm infants from the ventilator and to prevent or treat chronic lung disease (CLD). However, recent follow-up studies have raised concerns that postnatal glucocorticosteroids may cause adverse neuro-developmental outcome. A systematic review of the literature was therefore performed. Data from randomised controlled trials were used to determine the benefits and risks of postnatal glucocorticosteroid treatment in preterm infants. Postnatal glucocorticosteroids reduce duration of mechanical ventilation and the risk of developing CLD without a significant impact on mortality. However, one single study without any “contamination” of the control group revealed a trend towards decreased mortality in the treatment group. Several studies show that postnatal corticosteroid treatment is associated with increased risk for adverse neuro-developmental outcome. Postnatal glucocorticosteroid treatment is associated with short-term benefits and an increased risk for adverse neuro-developmental outcome. Therefore, it should be used only in life-threatening situations.     

枸橼酸咖啡因治疗对呼吸暂停早产儿早期肺功能的影响

目的探讨枸橼酸咖啡因治疗早产儿呼吸暂停(AOP)对患儿早期肺功能的影响。方法 40例AOP患儿随机分为氨茶碱治疗组(20例)和咖啡因治疗组(20例)。2组患儿均在生后出现呼吸暂停时在经鼻持续气道正压通气(NCPAP)辅助通气的基础上给予氨茶碱或枸橼酸咖啡因治疗,停药后行肺功能检测,比较两组之间肺功能的变化。结果治疗后咖啡因治疗组潮气量、每分通气量、达峰时间比、达峰容积比、潮气呼吸呼气峰流速及75%、50%、25%潮气量时呼吸流速均高于氨茶碱治疗组(P0.05);咖啡因治疗组用氧时间、NCPAP使用时间均低于氨茶碱治疗组(P0.01)。与氨茶碱治疗组比较,咖啡因治疗组用药7d后呼吸暂停发生频率明显减少(P0.01)。结论枸橼酸咖啡因治疗AOP可以改善患儿早期肺功能,减少呼吸暂停的发生。     

Blood pressure disorders in the neonate: hypotension and hypertension

Although many sick newborns are treated for hypotension and hypertension, the normal physiologic blood pressure range ensuring appropriate organ perfusion is uncertain. Treatment decisions are based on statistically defined gestational and postnatal age-dependent normative blood-pressure values, combined with clinical intuition, because of difficulties evaluating organ perfusion and adequacy of cerebral oxygen delivery. Early-onset hypotension usually results from the combined effects of abnormal peripheral vasoregulation, myocardial dysfunction, and hypovolemia. Volume administration is the primary initial therapy but its use can be associated with significant untoward effects, especially in preterm infants, and should be limited to 10-20 mL/kg of isotonic saline. If the blood pressure cannot be normalized, dopamine should be added, and sometimes followed by adrenaline (epinephrine) and corticosteroids. Hypertension, most often caused by congenital or acquired renovascular disease or volume overload, needs a thorough search for the etiology and cautious treatment, so that blood pressure does not fall too quickly or too low.