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1.
Arch Dis Child Fetal Neonatal Ed ; 105(2): 184-189, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31201254

RESUMO

OBJECTIVE: The aim of our study was to determine if a genetic background of high blood pressure is a survival factor in preterm infants. DESIGN: Prospective cohort study. SETTING: Patients were enrolled in 53 neonatal intensive care units. PATIENTS: Preterm infants with a birth weight below 1500 g. EXPOSURES: Genetic score blood pressure estimates were calculated based on adult data. We compared infants with high genetic blood pressure estimates (>75th percentile of the genetic score) to infants with low genetic blood pressure estimates (<25th percentile of the genetic score). MAIN OUTCOME MEASURES: Lowest blood pressure on the first day of life and mortality. RESULTS: 5580 preterm infants with a mean gestational age of 28.1±2.2 weeks and a mean birth weight of 1022±299 g were genotyped and analysed. Infants with low genetic blood pressure estimates had significantly lower blood pressure if compared with infants with high genetic blood pressure estimates (27.3±6.2vs 27.9±6.4, p=0.009, t-test). Other risk factors for low blood pressure included low gestational age (-1.26 mm Hg/week) and mechanical ventilation (-2.24 mm Hg, p<0.001 for both variables, linear regression analysis). Mortality was significantly reduced in infants with high genetic blood pressure estimates (28-day mortality: 21/1395, 1.5% vs 44/1395, 3.2%, p=0.005, Fisher's exact test). This survival advantage was independent of treatment with catecholamines. CONCLUSIONS: Our study provides first evidence that a genetic background of high blood pressure may be beneficial with regard to survival of preterm infants.

3.
Cochrane Database Syst Rev ; 9: CD003248, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31529790

RESUMO

BACKGROUND: Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012. OBJECTIVES: To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: This update includes forty-eight studies, involving 5721 babies and their mothers, with data available from 40 studies involving 4884 babies and their mothers. Babies were between 24 and 36+6 weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty). AUTHORS' CONCLUSIONS: Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.


Assuntos
Recém-Nascido Prematuro , Circulação Placentária/fisiologia , Cordão Umbilical , Transfusão de Sangue/estatística & dados numéricos , Hemorragia Cerebral/prevenção & controle , Parto Obstétrico , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Gravidez , Resultado da Gravidez , Nascimento Prematuro , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
4.
Arch Dis Child ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471281

RESUMO

OBJECTIVE: To evaluate whether changing dopamine infusions every 12 hours and preparing these infusions 30 min before administration reduces blood pressure fluctuations in preterm and term neonates. DESIGN: This was a retrospective study using data from live patients on the neonatal unit and prospective study exploring stability of infusions in a laboratory-based neonatal ward simulation. SETTING: Single-centre study in a tertiary neonatal surgical unit in a university teaching hospital. PATIENTS: Neonates who received more than one subsequent dopamine infusion and had invasive arterial blood pressure monitoring, during their admission in the neonatal unit, were included. INTERVENTIONS: As part of the Quality Improvement project, the standard operating procedure (SOP) was changed, and dopamine infusions were prepared by nursing staff and left to rest for 30 min before administering to the neonate. Additionally, infusions were replaced every 12 hours. MAIN OUTCOME MEASURES: The percentage change in mean arterial pressure (MAP) and the percentage loss in the drug concentration during infusion during changeover. RESULTS: Our findings indicate that up to 15% of the initial dopamine concentration is lost after 24 hours. This results in a sharp variation in the dopamine concentration during infusion changeover that correlates with observed rapid fluctuations in MAP. In changing the SOP, no significant difference in the concentration of dopamine and MAP were observed over 12 hours. CONCLUSIONS: Delaying administration of dopamine infusions by 30 min after preparation combined with changing infusions 12 hourly has reduced MAP fluctuations. Therefore, the risks associated with MAP fluctuations, including intraventricular haemorrhages, are reduced.

5.
Neonatology ; 116(3): 199-210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31247620

RESUMO

BACKGROUND: Around 10% of newborn infants require assistance during transition after birth. Heart rate (HR) is the most important clinical indicator to evaluate the clinical status of a newborn. AIM: Our study aimed to review all established and novel methods to detect HR in babies giving special consideration to non-invasive techniques. METHODS: We performed a systematic literature search on the following databases: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and CINAHL. The inclusion criteria were studies on methods to detect HR in both term and preterm infants in comparison to one of the current gold standards: pulse oximetry (PO) or electrocardiography (ECG) published in the last 15 years. Two independent reviewers screened titles and abstracts for eligibility. Data extracted in an Excel table were analysed to produce a narrative review structured around the type of monitoring, identified obstacles in use, as well as methods to overcome these limitations. RESULTS: The search revealed 649 studies after duplicates were removed. Full article analysis was performed on 26 studies of which 25 met the inclusion criteria. Well established methods such as auscultation and palpation, although rapid and easily available, have been shown to be inaccurate. ECG and PO were both more precise but the delay in obtaining a reliable HR signal from birth often exceeded 1-2 min. Novel sensors offered the advantages of minimally obtrusive technologies but have limitations mainly due to movement artefact, bad sensor coupling, intermittent measurement, and poor-quality recordings. CONCLUSIONS: The limitations of existing methods have a potential impact on short- and long-term morbidity and mortality outcomes. The development of a technological solution to determine HR accurately and quickly in babies at birth has immense implications for further research and can guide interventions, such as placental transfusion and resuscitation.

6.
Front Pediatr ; 7: 212, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192178

RESUMO

Objectives: The definition of circulatory impairment in the premature infant is controversial. Current research suggests overdiagnosis and overtreatment. We aimed to analyse which biomarkers move clinicians to initiate cardiovascular treatment (CVT). The prognostic capacity for adverse outcome (death and/or moderate-severe brain damage by cranial ultrasound at term equivalent) of these biomarkers was evaluated. Study Design: Retrospective data analysis from preterm infants enrolled in a placebo-controlled trial on dobutamine for low superior vena cava (SVC) flow, who showed normal SVC flow within the first 24 h (not randomized). Five positive biomarkers were considered: MABP < gestational age (GA)-1 mmHg; MABP < GA-5 mmHg; lactate > 4 mmol/L; BE < -9 mmol/L; SVC flow <51 ml/kg/min. Results: Ninety eight infants formed the study cohort. Thirty six received CVT (2-95 h). Logistic regression models adjusted for gestational age showed a positive association between CVT and the risk of death or moderate-severe abnormal cranial ultrasound at term equivalent [(OR 5.2, 95%CI: 1.8-15.1) p = 0.002]. MABP < GA-1 mmHg and lactate > 4 mmol/L were the most prevalent biomarkers at start of treatment. Low BE, high serum lactate and low SVC flow at first echocardiography showed a trend toward being associated with adverse outcome, although not statistically significant. Conclusions: Low blood pressure and high lactate are the most prevalent biomarkers used for CVT prescription. Lactic acidosis and low SVC flow early after birth showed a trend toward being associated with adverse outcome. These findings support using a combination of biomarkers for inclusion in a placebo-controlled trial on CVT during transitional circulation.

7.
Early Hum Dev ; 134: 31-33, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31154051

RESUMO

Early identification of neonatal sepsis may help reduce morbidity. From Heart Rate Variability (HRV) visually assessed in preterm infants, eight of nine recordings in babies with positive blood cultures had low HRV and six infants without positive cultures had normal HRV. Straightforward HRV display could help identify infection in infants.


Assuntos
Frequência Cardíaca , Recém-Nascido Prematuro , Sepse Neonatal/diagnóstico , Carga Bacteriana , Proteína C-Reativa/metabolismo , Feminino , Humanos , Recém-Nascido , Masculino , Sepse Neonatal/sangue , Sepse Neonatal/epidemiologia
8.
Clin Perinatol ; 46(2): 273-290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010560

RESUMO

There is a distinct lack of age-appropriate cardiotonic drugs, and adult derived formulations continue to be administered, without evidence-based knowledge on their dosing, safety, efficacy, and long-term effects. Dopamine remains the most commonly studied and prescribed cardiotonic drug in the neonatal intensive care unit (NICU), but evidence of its effect on endorgan perfusion still remains. Unlike adult and pediatric critical care, there are significant gaps in our knowledge on the use of various cardiotonic drugs in various forms of circulatory failure in the NICU.


Assuntos
Cardiotônicos/uso terapêutico , Hipotensão/tratamento farmacológico , Choque/tratamento farmacológico , Vasoconstritores/uso terapêutico , Corticosteroides/uso terapêutico , Asfixia Neonatal/complicações , Dobutamina/uso terapêutico , Dopamina/uso terapêutico , Cardiopatias Congênitas/complicações , Humanos , Hipotensão/etiologia , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Milrinona/uso terapêutico , Sepse Neonatal/complicações , Norepinefrina/uso terapêutico , Síndrome da Persistência do Padrão de Circulação Fetal/complicações , Choque/etiologia , Simendana/uso terapêutico , Vasopressinas/uso terapêutico
9.
Pediatr Res ; 86(3): 355-359, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30965354

RESUMO

BACKGROUND: Developmental abnormalities of the corpus callosum (CC) are linked to multiple neuro-developmental disorders, for which neonatal neuroimaging may allow earlier diagnosis and intervention. MRI is often considered the most sensitive imaging modality to white matter changes, while neurosonogram (NS) remains the clinical staple. This study assesses the correlation between MRI and US measurements of the neonatal CC using a protocol derived from established methodologies. METHODS: MR and NS images from an existing cohort of term infants (≥37 weeks gestational age) were studied. Length and area measurements of the CC made with linear (LUS) and phased array US (PUS) data were compared to those from MRI. Intra-observer reliabilities were estimated. RESULTS: Moderate-to-strong correlation strengths were observed for length measurements and the total area of the CC. Sectional area measurements showed poorer correlations. Bland-Altman plots support improved correspondence of length and total area measurements. LUS data appeared to correspond closer to MRI. All three modalities showed comparable repeatability. CONCLUSION: NS correlates well with some MRI measurements of the CC and shows similar levels of repeatability, making them possibly interchangeable. Use of LUS, a technique rarely used for NS, may be preferable to the standard approach for morphological studies.

11.
Birth ; 46(3): 411-427, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30264508

RESUMO

BACKGROUND: Enhanced placental transfusion reduces adverse neonatal outcomes, including death. Despite being endorsed by the World Health Organization in 2012, the method has not been adopted widely in practice. METHODS: We performed a systematic literature search and included quality improvement projects on placental transfusion at birth and studies on barriers to implementation. We extracted information on population, methods of implementation, obstacles to implementation, and strategies to overcome them. RESULTS: We screened 99 studies out of which 18 were included in the review. The preferred methods of implementation were protocol development (86% of studies) reinforced by targeted education (64% of studies) and multidisciplinary team involvement (43% of studies). Barriers to implementation were mentioned in 12 studies and divided into four categories: general factors such as lack of staff awareness (5 studies) and professional resistance to change (5 studies); obstetrician-specific concerns, including the impact during cesarean (3 studies) and the risk of postpartum hemorrhage (3 studies); pediatrician-specific concerns, including the need for resuscitation (5 studies), risk of jaundice (3 studies), and polycythemia (2 studies); and logistical difficulties. The main strategies to facilitate placental transfusion at birth included effective multidisciplinary team collaboration, protocol development, targeted education, and constructive feedback sessions. CONCLUSIONS: Placental transfusion implementation requires a multidisciplinary approach, with obstetricians, midwives, nurses, and pediatricians central to adoption of the practice. Understanding the obstacles to implementation informs strategies to increase placental transfusion adoption of practice worldwide. We suggest a stepwise approach to implementation and enhancement of placental transfusion into practice.


Assuntos
Transfusão de Sangue/métodos , Parto Obstétrico/métodos , Equipe de Assistência ao Paciente , Placenta/irrigação sanguínea , Cordão Umbilical/irrigação sanguínea , Constrição , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Recém-Nascido , Gravidez
12.
Pediatr Res ; 85(7): 943-954, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30584262

RESUMO

Although seizures have a higher incidence in neonates than any other age group and are associated with significant mortality and neurodevelopmental disability, treatment is largely guided by physician preference and tradition, due to a lack of data from well-designed clinical trials. There is increasing interest in conducting trials of novel drugs to treat neonatal seizures, but the unique characteristics of this disorder and patient population require special consideration with regard to trial design. The Critical Path Institute formed a global working group of experts and key stakeholders from academia, the pharmaceutical industry, regulatory agencies, neonatal nurse associations, and patient advocacy groups to develop consensus recommendations for design of clinical trials to treat neonatal seizures. The broad expertise and perspectives of this group were invaluable in developing recommendations addressing: (1) use of neonate-specific adaptive trial designs, (2) inclusion/exclusion criteria, (3) stratification and randomization, (4) statistical analysis, (5) safety monitoring, and (6) definitions of important outcomes. The guidelines are based on available literature and expert consensus, pharmacokinetic analyses, ethical considerations, and parental concerns. These recommendations will ultimately facilitate development of a Master Protocol and design of efficient and successful drug trials to improve the treatment and outcome for this highly vulnerable population.

13.
J Ultrasound Med ; 37(9): 2181-2190, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29476553

RESUMO

OBJECTIVES: To explore the intra- and inter-rater agreement of superior vena cava (SVC) flow and right ventricular (RV) outflow in healthy and unwell late preterm neonates (33-37 weeks' gestational age), term neonates (≥37 weeks' gestational age), and neonates receiving total-body cooling. METHODS: The intra- and inter-rater agreement (n = 25 and 41 neonates, respectively) rates for SVC flow and RV outflow were determined by echocardiography in healthy and unwell late preterm and term neonates with the use of Bland-Altman plots, the repeatability coefficient, the repeatability index, and intraclass correlation coefficients. RESULTS: The intra-rater repeatability index values were 41% for SVC flow and 31% for RV outflow, with intraclass correlation coefficients indicating good agreement for both measures. The inter-rater repeatability index values for SVC flow and RV outflow were 63% and 51%, respectively, with intraclass correlation coefficients indicating moderate agreement for both measures. CONCLUSIONS: If SVC flow or RV outflow is used in the hemodynamic treatment of neonates, sequential measurements should ideally be performed by the same clinician to reduce potential variability.


Assuntos
Ecocardiografia , Doenças Vasculares/fisiopatologia , Veia Cava Superior/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Velocidade do Fluxo Sanguíneo , Estudos de Coortes , Feminino , Idade Gestacional , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Variações Dependentes do Observador , Estudos Prospectivos , Reprodutibilidade dos Testes , Doenças Vasculares/diagnóstico por imagem , Veia Cava Superior/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem
14.
Curr Pharm Des ; 23(38): 5850-5860, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28925895

RESUMO

BACKGROUND: Circulatory failure in preterm and term newborn infants is commonly treated with inotropes or vasoactive medications. In this structured literature review, the available data on pharmacodynamic effects of the inotropes adrenaline, dobutamine, dopamine, levosimendan, milrinone, noradrenaline, and the vasoactive drugs vasopressin and hydrocortisone are presented. METHODS: Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria which were human clinical trials published after 2000. RESULTS: Out of 101 identified eligible studies only 22 studies met the criteria for evidence based practice guidelines level I to IV. The most prevalent pharmacodynamic effects were increase in blood pressure and/or heart rate, which were also the most frequently studied circulatory parameters. CONCLUSION: This review demonstrates the need for further systematic studies on all reviewed drugs with incorporation of novel non-invasive biomarkers in this vulnerable patient group, for more timely and appropriate treatment for clinical efficacy.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Fármacos Cardiovasculares/farmacocinética , Doenças Cardiovasculares/tratamento farmacológico , Desenvolvimento Infantil/efeitos dos fármacos , Análise de Dados , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacocinética , Doenças Cardiovasculares/metabolismo , Desenvolvimento Infantil/fisiologia , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Recém-Nascido
15.
Arch Dis Child Fetal Neonatal Ed ; 102(6): F547-F550, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28818851

RESUMO

During the transition to extrauterine life, preterm infants are at high risk of developing circulatory failure. Currently, hypotension is used as major diagnostic criteria for starting treatments such as fluid boluses, inotropes or steroids. Most of these treatment options have not been studied in large randomised controlled trials for efficacy and safety and are under discussions. A wide variety in their use is reported in the literature and clear evidence about which inotrope or other treatment should be preferred is lacking. In addition, there is ongoing debate about the appropriate threshold values for blood pressure. Other diagnostic measures for poor circulation are functional echocardiography, near-infrared spectroscopy, capillary refill time, base excess and serum lactate. Large randomised controlled trials for the use of dopamine and dobutamine in preterm infants <32 weeks gestation are under way to fill the knowledge gaps on the assessment of circulatory compromise and on efficacy and safety of the studied age-appropriate drug formulations.


Assuntos
Cardiotônicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hipotensão/tratamento farmacológico , Insuficiência Cardíaca/diagnóstico , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Parto
16.
Paediatr Drugs ; 19(5): 487-495, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28516289

RESUMO

OBJECTIVES: Our objectives were to investigate the possible effects of temperature and light on the stability of dopamine and dobutamine continuous infusions over 24 h when prepared in a variety of dilution vehicles. METHODS: Syringe-driver infusion apparatuses were set up for dopamine and dobutamine diluted with either 0.9% sodium chloride (NaCl) or 5% glucose delivering 3 and 5 µg/kg/min, respectively, via 206-cm extension sets. All infusions were prepared for a neonate weight of 1 kg. Infusions were run over 24 h with approximately half the tubing within an incubator set at 35 °C. Cyclic voltammetry was used to monitor the concentration of the inotrope within the syringe and at the end of the extension set, both initially and after 24 h. RESULTS: The variation in the concentration of dopamine and dobutamine in the vials (n = 6) was 3.58 and 1.22%, respectively. This variation increased to 10.88% for dopamine and 5.76% for dobutamine in the syringe. After 24 h, a significant reduction in the concentration of dopamine was observed at the end of the extension set when prepared in 0.9% NaCl versus 5% glucose (p < 0.001; n = 6-7) and in dobutamine when prepared in 0.9% NaCl (p < 0.001; n = 6-7). No differences in the concentration of dopamine prepared in 0.9% NaCl were observed after 24 h in light-exposed and light-protected extension sets (n = 6-7). CONCLUSIONS: Dobutamine is more stable in dilution vehicles than dopamine, and inotropes are more stable in the 5% glucose dilution vehicle than in 0.9% NaCl. Such findings will provide guidance on the choice of inotropes.


Assuntos
Cardiotônicos , Dobutamina , Dopamina , Estabilidade de Medicamentos , Humanos , Recém-Nascido , Infusões Intravenosas , Luz , Temperatura Ambiente
18.
Pediatr Res ; 81(3): 511-518, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27886191

RESUMO

BACKGROUND: The aim of our study was to measure drug-related changes in hemodynamics and oxygen metabolism in response to different doses of an age-appropriate dobutamine formulation in hypoxic pigs. A secondary aim was to validate superior vena cava flow (SVCF) as a marker of cardiac index (CI) for subsequent clinical trials of this formulation in humans. METHODS: Newborn pigs (n = 18) were exposed to 2-h hypoxia (10-15% oxygen) followed by reoxygenation (21-30% oxygen 4 h). After 1-h reoxygenation, pigs were randomized to: control group (no treatment), dobutamine infusion at a rate of 10-15 or 15-20 µg/kg/min. Dobutamine groups received two dobutamine doses during 30 min with a 60 min washout period between doses. Cardiovascular profile and oxygen metabolism were monitored. In four animals, an ultrasonic perivascular flow probe was placed around superior vena cava to measure SVCF. RESULTS: Hypoxia significantly decreased CI, systemic vascular resistance and mean arterial blood pressure (MABP). Dobutamine doses significantly increased heart-rate, CI, and oxygen-delivery without changes in stroke-volume and MABP. Only 10-15 µg/kg/min increased oxygen consumption and peripheral tissue oxygenation measured by Near-infrared spectroscopy. A positive correlation was observed between SVCF and CI. CONCLUSION: The new pediatric dobutamine formulation improved hemodynamic status, with dose-specific differences in metabolic response. SVCF may be a useful surrogate for CI in subsequent clinical trials.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Dobutamina/administração & dosagem , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Cardiotônicos/administração & dosagem , Cardiotônicos/farmacologia , Dobutamina/farmacologia , Feminino , Hipóxia , Masculino , Oxigênio/administração & dosagem , Consumo de Oxigênio , Espectroscopia de Luz Próxima ao Infravermelho , Sus scrofa
19.
Pediatr Cardiol ; 37(1): 14-23, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26346024

RESUMO

Since its discovery in 1975 dobutamine has been used off-label for treating hemodynamic insufficiency in newborns and children. We present a structured literature review of pharmacokinetic and pharmacodynamic data for dobutamine in the pediatric population. Structured searches were conducted to identify relevant articles according to pre-defined inclusion criteria. Where possible, results for the pharmacodynamic and pharmacokinetic effect of dobutamine were reported as pooled data. Forty-six papers met the inclusion criteria. With regard to pharmacodynamic data a number of studies reported significant increases in a number of clinical parameters such as heart rate, blood pressure, cardiac output across a wide range of pediatric populations. With regard to pharmacokinetic data studies reported that the infusion rate was positively correlated to plasma dobutamine concentration. There was great variability with regard to dobutamine clearance between individuals and as to whether it followed first- or zero-order elimination kinetics. While the pharmacodynamic effects of dobutamine appear to reflect the pharmacological profile of the drug, the pharmacokinetic data are difficult to interpret due to inhomogeneity between study populations ages, comorbidities, dobutamine dosages and methodologies. High-quality prospective pharmacokinetic and pharmacodynamic data especially in newborns are urgently required prior to a large randomized study.


Assuntos
Dobutamina/farmacologia , Dobutamina/farmacocinética , Hipotensão/tratamento farmacológico , Simpatomiméticos/farmacologia , Simpatomiméticos/farmacocinética , Pressão Sanguínea/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Criança , Relação Dose-Resposta a Droga , Frequência Cardíaca/efeitos dos fármacos , Humanos , Lactente , Recém-Nascido
20.
Neonatology ; 109(2): 113-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26650133

RESUMO

BACKGROUND: Guidelines published by the International Liaison Committee for Resuscitation and by the World Health Organization recommend delaying cord clamping at birth as part of routine care for infants. OBJECTIVE: To study the use of milking of the cord 4 times as an alternative to enhance the redistribution of placental blood into the baby. METHODS: This is a prospective cohort study of neurodevelopmental assessment by the Bayley III method of very preterm infants who had participated in a trial of delayed cord clamping versus cord milking at birth that was conducted in a neonatal tertiary care hospital. The primary outcomes were differences in cognitive, motor and language development at 2 and 3.5 years. Two-tailed analyses were performed with the x03C7;2 test, Fisher's exact test, t test, Mann-Whitney U test and ANCOVA. RESULTS: Out of the 58 infants enrolled in the original study, 39 infants (67%) were assessed at 2 years and 29 (50%) at 3.5 years of age. Neurodevelopmental outcomes at 2 and 3.5 years did not significantly differ between the two groups for the three Bayley III composite scores. At 3.5 years there was a trend towards higher scores for girls in the language composite scores (girls: mean = 121.6, SD = 15.22; boys: mean = 101.07, SD = 19.84) and on the motor scale (girls: mean = 124.60, SD = 18.15; boys: mean = 97.86, SD = 17.23). CONCLUSIONS: In this small number of participants followed up at 2 and 3.5 years of age, milking of the cord 4 times did not have any long-term adverse effect on neurodevelopmental outcome, suggesting that cord milking could be used as an alternative to delayed cord clamping.


Assuntos
Desenvolvimento Infantil , Parto Obstétrico/métodos , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Transtornos do Neurodesenvolvimento/prevenção & controle , Testes Neuropsicológicos , Cordão Umbilical , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/prevenção & controle , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Transtornos do Desenvolvimento da Linguagem/diagnóstico , Transtornos do Desenvolvimento da Linguagem/prevenção & controle , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Avaliação de Resultados da Assistência ao Paciente , Organização Mundial da Saúde
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