RESUMO
OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours. STUDY DESIGN: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age. RESULTS: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively. CONCLUSIONS: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00614744.
Assuntos
Deficiências do Desenvolvimento/diagnóstico por imagem , Hipóxia-Isquemia Encefálica/terapia , Imageamento por Ressonância Magnética , Deficiências do Desenvolvimento/etiologia , Feminino , Humanos , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/métodos , Hipóxia-Isquemia Encefálica/complicações , Hipóxia-Isquemia Encefálica/diagnóstico por imagem , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Valor Preditivo dos Testes , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: To determine the characteristics of term infants with persistent pulmonary hypertension of the newborn (PPHN) associated with moderate or severe hypoxic ischemic encephalopathy (HIE). METHODS: We compared infants with and without PPHN enrolled in 2 randomized trials of therapeutic hypothermia: the induced hypothermia trial of cooling to 33.5°C for 72 hours vs normothermia, and the "usual-care" arm (33.5°C for 72 hours) of the optimizing cooling trial. RESULTS: Among 303 infants with HIE from these 2 studies, 67 (22%) had PPHN and 236 (78%) did not. We compared infants with PPHN with those without PPHN. The proportion of patients treated with therapeutic hypothermia was similar in PPHN and no-PPHN groups (66% vs 65%). Medication use during resuscitation (58% vs 44%), acidosis after birth (pH: 7.0 ± 0.2 vs 7.1 ± 0.2), severe HIE (43% vs 28%), meconium aspiration syndrome (39% vs 7%), pulmonary hemorrhage (12% vs 3%), culture-positive sepsis (12% vs 3%), systemic hypotension (65% vs 28%), inhaled nitric oxide therapy (64% vs 3%), and extracorporeal membrane oxygenation (12% vs 0%) were more common in the PPHN group. Length of stay (26 ± 21 vs 16 ± 14 days) and mortality (27% vs 16%) were higher in the PPHN group. CONCLUSIONS: PPHN is common among infants with moderate/severe HIE and is associated with severe encephalopathy, lung disease, sepsis, systemic hypotension, and increased mortality. The prevalence of PPHN was not different between those infants receiving therapeutic hypothermia at 33.5°C in these 2 trials (44/197 = 22%) compared with infants receiving normothermia in the induced hypothermia trial (23/106 = 22%).
Assuntos
Asfixia Neonatal/terapia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/terapia , Acidose , Comorbidade , Interpretação Estatística de Dados , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipóxia-Isquemia Encefálica/complicações , Recém-Nascido , Tempo de Internação , Masculino , Idade Materna , Síndrome de Aspiração de Mecônio/complicações , Síndrome de Aspiração de Mecônio/diagnóstico , Síndrome de Aspiração de Mecônio/terapiaAssuntos
Dano Encefálico Crônico/prevenção & controle , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/terapia , Animais , Biomarcadores/análise , Temperatura Corporal , Encéfalo/patologia , Ensaios Clínicos como Assunto , Terapia Combinada , Eletroencefalografia , Humanos , Recém-Nascido , Capacitação em Serviço , Imageamento por Ressonância Magnética , Exame Neurológico , Fármacos Neuroprotetores/uso terapêutico , Segurança do Paciente , Sistema de Registros , Fatores de Tempo , Transporte de PacientesRESUMO
OBJECTIVE: To develop and validate a 48-hour gentamicin dosing regimen for infants born at <28 weeks' gestation. STUDY DESIGN: Using previously published pharmacokinetic data, we performed Monte Carlo simulations for several candidate gentamicin dosing regimens. On the basis of these simulations, we changed dosing for infants born at <28 weeks to 4.5 mg/kg every 48 hours. We then conducted an observational study of 30 infants on this new regimen and compared serum gentamicin levels with 60 historical control subjects who received 2.5 mg/kg every 24 hours. RESULTS: Infants in the 48-hour group achieved higher gentamicin peaks (mean 9.43 microg/mL vs 6.0 microg/mL, P < .001) and lower gentamicin troughs (mean 1.08 microg/mL vs 1.54 microg/mL, P < .001) compared with the 24-hour group. Seven percent of the 48-hour group infants had a gentamicin peak <6 microg/mL versus 43% in the 24-hour group. With a goal for peaks of 6 to 12 microg/mL and for troughs of <1.5 microg/mL, infants in the 48-hour group required fewer adjustments of their dosing regimens compared with the 24-hour group (26.7% vs 78.3%). CONCLUSIONS: Gentamicin given every 48 hours to infants born at <28 weeks achieves optimal blood concentrations more frequently than does once-daily dosing. Monte Carlo simulations on the basis of pharmacokinetic modeling are useful to optimize drug dosing in premature infants.