RESUMO
In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.
Assuntos
Displasia Broncopulmonar/etiologia , Permeabilidade do Canal Arterial/terapia , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Respiração Artificial , Displasia Broncopulmonar/epidemiologia , Permeabilidade do Canal Arterial/complicações , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de TempoRESUMO
The PDA: TO LEave it alone or Respond And Treat Early trial compared the effects of 2 strategies for treatment of patent ductus arteriosus (PDA) in infants <280/7 weeks of gestation; however 137 potentially eligible infants were not recruited and received treatment of their PDA outside the PDA-TOLERATE trial due to "lack-of-physician-equipoise" (LPE). Despite being less mature and needing more respiratory support, infants with LPE had lower rates of mortality than enrolled infants. Infants with LPE treated before day 6 had lower rates of late respiratory morbidity than infants with LPE treated ≥day 6. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.
Assuntos
Esquema de Medicação , Permeabilidade do Canal Arterial/tratamento farmacológico , Seleção de Pacientes , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Displasia Broncopulmonar/complicações , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Prematuro/terapia , Masculino , Idade Materna , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.
Assuntos
Acetaminofen/uso terapêutico , Tratamento Conservador , Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/terapia , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Pressão Positiva Contínua nas Vias Aéreas , Permeabilidade do Canal Arterial/classificação , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Prospectivos , Método Simples-Cego , Resultado do TratamentoRESUMO
OBJECTIVE: To determine whether a moderate-to-large patent ductus arteriosus (PDA) is responsible for vasopressor-dependent hypotension, occurring at the end of the first postnatal week. STUDY DESIGN: We performed a retrospective, double cohort controlled study of infants delivered at ≤27+6 weeks' gestation (n = 313). From January 2004 through April 2011, all infants were treated with prophylactic indomethacin ([PINDO] epoch). From May 2011 through December 2015, no infant was treated with indomethacin until at least 8 postnatal days (conservative epoch). Echocardiograms were performed on postnatal days 6 or 7. Hypotension was managed by a predefined protocol. The primary outcome was the incidence of dopamine-dependent hypotension, defined as having received at least 6 µg/kg/min dopamine for at least 24 hours during postnatal days 4-7. RESULTS: As expected, the incidence of moderate-to-large PDA at the end of the first week differed significantly between epochs (PINDO = 8%; conservative = 64%). In multivariate analyses, infants in the PINDO epoch had a significantly lower incidence of vasopressor-dependent hypotension (11%) than infants in the conservative epoch (21%; OR = 0.40, 95% CI 0.20-0.82). Infants in the PINDO epoch also required less mean airway pressure, had a lower respiratory severity score, and lower mode of ventilation score than infants in the conservative epoch during postnatal days 4-7. The effects of PINDO on both the incidence of vasopressor-dependent hypotension and the need for respiratory support were no longer significant when analyses were adjusted for "presence or absence of a moderate-to-large PDA." CONCLUSION: PINDO decreases vasopressor-dependent hypotension and the need for respiratory support at the end of the first postnatal week. These effects are mediated by closure of the PDA.
Assuntos
Fármacos Cardiovasculares/uso terapêutico , Dopamina/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Hipotensão/epidemiologia , Indometacina/uso terapêutico , Estudos de Coortes , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/epidemiologia , Ecocardiografia , Feminino , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Incidência , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. STUDY DESIGN: We performed a multicenter study of infants born at <32 weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0 µg/kg) stimulation test (performed before the ligation), and at 10-12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1 × dopamine [µg/kg/min] + 1 × dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. RESULTS: Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P = .006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. CONCLUSION: Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production.
Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Catecolaminas/administração & dosagem , Permeabilidade do Canal Arterial/cirurgia , Hidrocortisona/sangue , Hipotensão/etiologia , Recém-Nascido Prematuro , Hormônio Adrenocorticotrópico/metabolismo , Procedimentos Cirúrgicos Cardíacos/métodos , Estudos de Coortes , Resistência a Medicamentos , Permeabilidade do Canal Arterial/diagnóstico , Permeabilidade do Canal Arterial/mortalidade , Feminino , Seguimentos , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/fisiopatologia , Recém-Nascido , Ligadura/efeitos adversos , Ligadura/métodos , Masculino , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Medição de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To estimate the impact of the average daily dose of hydrocortisone (HC) on the amount of growth attained in children with congenital adrenal hyperplasia (CAH). The effect of glucocorticoid therapy on adult height (AH) in children with CAH has yet to be elucidated. STUDY DESIGN: Triple-logistic models estimating components of growth and maturation were fitted to longitudinal records of 104 patients with classic CAH from 3 pediatric medical centers in Minnesota between 1955 and 2012. A total of 3664 clinical encounters were examined. Random-effects longitudinal models with time-related covariates were used to estimate the effect of HC therapy on linear growth. RESULTS: The predicted AH z-score (-0.7) was similar between the sexes and among CAH subtypes. The mean growth period HC dose was 18.9 ± 5.6 mg/m(2)/day. In the final regression model, HC dose was negatively associated with predicted AH, with each mg/m(2)/day increase in average growth period HC dose predicting a 0.37-cm decrease in AH (P < .004). CONCLUSION: This study has quantified the fractional reduction in predicted final AH with an incremental increase in HC dose. These findings have important clinical implications in the decision making balance between HC replacement dose and adrenal androgen suppression in children with CAH.
Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Estatura/efeitos dos fármacos , Hidrocortisona/farmacologia , Adolescente , Adulto , Anti-Inflamatórios/uso terapêutico , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Humanos , Hidrocortisona/uso terapêutico , Lactente , Modelos Lineares , Modelos Logísticos , Masculino , Minnesota , Resultado do TratamentoRESUMO
OBJECTIVE: To examine the relationship between the cause or severity of hypotension and the development of severe ROP (sROP) (≥stage 3 or stage 2 with plus disease in zone I or II). STUDY DESIGN: Infants (<28 weeks' gestation, n = 242) were observed for hypotension and treated with a standardized hypotension-treatment protocol. Hypotension was classified as resulting from one of the following causes: (1) culture-positive infection and/or necrotizing enterocolitis; (2) patent ductus arteriosus ligation; or (3) "idiopathic" (no cause identified other than prematurity), and as being either dopamine responsive or dopamine resistant. Cortisol levels were measured for infants with dopamine-resistant hypotension. Eye examinations were performed until the retinopathy of prematurity resolved or the vasculature matured. Multivariable logistic regression analysis was performed to determine the relationship between the cause/severity of hypotension and sROP. RESULTS: Overall, 66% of infants developed hypotension (41% were dopamine responsive and 25% were dopamine resistant). sROP developed in 19% of infants. "Idiopathic" dopamine-resistant hypotension was the only cause significantly related to sROP. Of the infants with dopamine-resistant hypotension, 66% had low serum cortisol (≤10 µg/dL). Low cortisol, in the presence of dopamine-resistant hypotension, was significantly associated with sROP and accounted for the relationship between "idiopathic" hypotension and sROP. When low cortisol was included in statistical models, other known risk factors, such as immature gestation, were no longer significantly related to sROP. CONCLUSION: Low cortisol, in the presence of dopamine-resistant hypotension, has the greatest magnitude of association with sROP.
Assuntos
Dopamina/uso terapêutico , Hipotensão/complicações , Hipotensão/tratamento farmacológico , Retinopatia da Prematuridade/etiologia , Resistência a Medicamentos , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive "trophic" (15 mL/kg/d) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus. STUDY DESIGN: Infants were eligible for the study if they were 23(1/7)-30(6/7) weeks' gestation, weighed 401-1250 g at birth, received maximum enteral volumes ≤60 mL/kg/d, and were about to be treated with indomethacin or ibuprofen. A standardized "feeding advance regimen" and guidelines for managing feeding intolerance were followed at each site (N = 13). RESULTS: Infants (N = 177, 26.3 ± 1.9 weeks' mean ± SD gestation) were randomized at 6.5 ± 3.9 days to receive "trophic" feeds ("feeding" group, n = 81: indomethacin 80%, ibuprofen 20%) or no feeds ("fasting [nil per os]" group, n = 96: indomethacin 75%, ibuprofen 25%) during the drug administration period. Maximum daily enteral volumes before study entry were 14 ± 15 mL/kg/d. After drug treatment, infants randomized to the "feeding" arm required fewer days to reach the study's feeding volume end point (120 mL/kg/d). Although the enteral feeding end point was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the 2 groups. There were no differences between the 2 groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation, or other neonatal morbidities. CONCLUSION: Infants required less time to reach the feeding volume end point if they were given "trophic" enteral feedings when they received indomethacin or ibuprofen treatments.
Assuntos
Permeabilidade do Canal Arterial/terapia , Nutrição Enteral , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Terapia Combinada , Permeabilidade do Canal Arterial/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Masculino , Estudos Prospectivos , Fatores de TempoRESUMO
Although black race is considered protective against hyperbilirubinemia, black infants appear at increased risk of kernicterus. We found that although black infants have a lower risk of developing total serum bilirubin levels ≥ 20 mg/dL than white infants, they appear at greater risk of developing levels ≥ 30 mg/dL.
Assuntos
Bilirrubina/sangue , Hiperbilirrubinemia/complicações , Hiperbilirrubinemia/etnologia , Icterícia Neonatal/sangue , População Negra , Humanos , Lactente , Recém-Nascido , Icterícia Neonatal/complicações , Fatores de RiscoRESUMO
OBJECTIVE: To examine whether a change in the approach to managing persistent patent ductus arteriosus (PDA) from early ligation to selective ligation is associated with an increased risk of abnormal neurodevelopmental outcomes. STUDY DESIGN: In 2005, we changed our PDA treatment protocol for infants born at ≤27 6/7 weeks' gestation from an early ligation approach, with prompt PDA ligation if the ductus failed to close after indomethacin therapy (period 1: January 1999 to December 2004), to a selective ligation approach, with PDA ligation performed only if specific criteria were met (period 2: January 2005 to May 2009). All infants in both periods received prophylactic indomethacin. Multivariate analysis was used to compare the odds of a composite abnormal neurodevelopmental outcome (Bayley Mental Developmental Index or Cognitive Score <70, cerebral palsy, blindness, and/or deafness) associated with each treatment approach at age 18-36 months (n = 224). RESULTS: During period 1, 23% of the infants in follow-up failed indomethacin treatment, and all underwent surgical ligation. During period 2, 30% of infants failed indomethacin, and 66% underwent ligation after meeting prespecified criteria. Infants treated with the selective ligation strategy demonstrated fewer abnormal outcomes than those treated with the early ligation approach (OR, 0.07; P = .046). Infants who underwent ligation before 10 days of age had an increased incidence of abnormal neurodevelopmental outcome. The significant difference in outcomes between the 2 PDA treatment strategies could be accounted for in part by the earlier age of ligation during period 1. CONCLUSION: A selective ligation approach for PDAs that fail to close with indomethacin therapy is not associated with worse neurodevelopmental outcomes at age 18-36 months.