RESUMO
OBJECTIVE: We investigated factors associated with isolated mental delay in infants weighing < 1250 g at birth. STUDY DESIGN: With a case-control design, matching variables for 40 cases included gestation, birth weight, sex, grade of intraventricular hemorrhage, and socioeconomic status. Case subjects had a mental developmental index < 70, and controls had a mental developmental index > or = 85, according to the Bayley Scales of Infant Development II at 18 months' corrected age. RESULTS: There were no differences between the case and control subjects for neonatal complications and antenatal or postnatal steroid use. There was a marked difference in the cumulative dosage and duration of doxapram therapy used for apnea of prematurity (total dose 2233 +/- 1927 mg vs 615 +/- 767 mg, P < .001; duration 45.2 +/- 32.5 days vs 19.4 +/- 23.4 days, P < .001 for case subjects and control subjects, respectively). Multivariate analysis did not identify additive predictive variables. CONCLUSION: Isolated mental delay in infants weighing < 1250 g at birth was associated with the total dosage and duration of doxapram therapy for severe apnea. Although this may be a marker for cerebral dysfunction manifesting as apnea of prematurity, possible adverse effects of doxapram or its preservative, benzyl alcohol, on the developing brain deserve further study.
Assuntos
Apneia/tratamento farmacológico , Deficiências do Desenvolvimento/induzido quimicamente , Doxapram/efeitos adversos , Recém-Nascido Prematuro/psicologia , Recém-Nascido de muito Baixo Peso/psicologia , Medicamentos para o Sistema Respiratório/efeitos adversos , Apneia/complicações , Apneia/psicologia , Estudos de Casos e Controles , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/complicações , Hemorragia Cerebral/psicologia , Desenvolvimento Infantil/efeitos dos fármacos , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/psicologia , Doxapram/administração & dosagem , Doxapram/uso terapêutico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Medicamentos para o Sistema Respiratório/administração & dosagem , Medicamentos para o Sistema Respiratório/uso terapêutico , Estudos Retrospectivos , Classe Social , Fatores de Tempo , Resultado do TratamentoRESUMO
In an attempt to determine physiologic responses to neonatal apnea, we evaluated changes in heart rate and oxygen saturation as measured by pulse oximetry during 2082 episodes of apnea lasting 15 seconds or more in 47 infants less than 34 weeks of gestational age with idiopathic apnea of prematurity. Of these episodes, 832 (39.9%) were central, 1032 (49.6%) were mixed, and 218 (10.5%) were obstructive. Oxygen saturation decreased with increasing duration of apnea regardless of type or treatment, and the decrease in saturation was correlated with preapnea saturation. The baseline heart rate was similar for all apnea types. Infants receiving doxapram had a lower baseline heart rate (137.8 +/- 10.5 beats/min) than did infants receiving no therapy (142.8 +/- 16.6 beats/min) and infants receiving theophylline (149.7 +/- 15.0 beats/min) (p = < 0.001). A heart rate fall to less than 100 beats/min was seen more frequently with central apnea than with mixed or obstructive events, and in infants who were not receiving therapy. Falls in heart rate were significantly less in infants receiving doxapram (27.8% +/- 18.0%) than in infants receiving theophylline (44.5% +/- 19.0%) or no therapy (48.4% +/- 18.3%) (p = < 0.001). The most common heart rate pattern overall was a gradual decrease interrupted by accelerations, whereas an initial heart rate acceleration was the most common pattern in obstructive apnea. We conclude that heart rate response to neonatal apnea is a complex and is dependent on therapy and on type and duration of apnea.
Assuntos
Doenças do Prematuro/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Análise de Variância , Doxapram/uso terapêutico , Quimioterapia Combinada , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/epidemiologia , Monitorização Fisiológica , Consumo de Oxigênio/efeitos dos fármacos , Consumo de Oxigênio/fisiologia , Estudos Prospectivos , Síndromes da Apneia do Sono/tratamento farmacológico , Síndromes da Apneia do Sono/epidemiologia , Teofilina/uso terapêutico , Fatores de TempoRESUMO
A blinded, randomized, placebo-controlled trial was conducted to evaluate the effectiveness of theophylline and doxapram therapy in 31 infants with significant apnea of prematurity. Of 10 infants, two had a short-term response to placebo, 8 of 10 infants to theophylline, and 7 of 11 infants to doxapram (placebo vs treatment with theophylline or doxapram: p = 0.01). The two infants who initially responded to placebo remained responsive for the duration of the study. Of the eight infants in whom treatment with placebo failed, five were randomly assigned to receive theophylline, for a total of 15 infants treated with theophylline, and two of the eight were randomly assigned to receive doxapram, for a total of 13 infants treated with doxapram; the remaining infant required tracheal intubation. Of the 15 infants randomly assigned to receive theophylline, seven responded for the duration of the study; of the eight infants who did not respond to treatment with theophylline, five responded to doxapram, one responded to a combination of theophylline and doxapram, and two remained resistant to treatment. Of the 13 infants randomly assigned to receive doxapram four responded for the duration of the study; of the nine who did not respond to doxapram, seven responded to theophylline, one responded to a combination of theophylline and doxapram, and one remained resistant to treatment. This study demonstrates that although therapy with theophylline or doxapram is associated with a significant short-term reduction in the incidence of apnea compared with that in placebo-treated infants, the long-term response to treatment is frequently incomplete and is not sustained more than 1 week.
Assuntos
Apneia/tratamento farmacológico , Doxapram/uso terapêutico , Recém-Nascido Prematuro , Teofilina/uso terapêutico , Apneia/prevenção & controle , Doxapram/administração & dosagem , Doxapram/sangue , Combinação de Medicamentos , Feminino , Humanos , Recém-Nascido , Infusões Intravenosas , Masculino , Placebos , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego , Teofilina/administração & dosagem , Teofilina/sangueAssuntos
Traumatismos Craniocerebrais/complicações , Síndromes da Apneia do Sono/etiologia , Criança , Terapia Combinada , Doxapram/uso terapêutico , Eletroencefalografia , Hematoma Epidural Craniano/complicações , Humanos , Masculino , Exame Neurológico , Respiração com Pressão Positiva , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Síndromes da Apneia do Sono/terapia , Sono REM/efeitos dos fármacos , Sono REM/fisiologiaAssuntos
Apneia/tratamento farmacológico , Doxapram/uso terapêutico , Doenças do Prematuro/tratamento farmacológico , Apneia/sangue , Apneia/diagnóstico , Doxapram/administração & dosagem , Doxapram/sangue , Humanos , Recém-Nascido , Doenças do Prematuro/sangue , Doenças do Prematuro/diagnóstico , Infusões ParenteraisRESUMO
Twelve premature infants with significant apnea of prematurity while receiving therapeutic doses of aminophylline were given an intravenous infusion of doxapram, 2 or 2.5 mg/kg/hr. The ventilatory effects of the medication were monitored by means of face mask spirometry and airway occlusion studies. Doxapram therapy was associated with significant increases in minute ventilation, tidal volume, mean inspiratory flow, and airway pressure 100 msec after occlusion. Respiratory frequency and the relative duration of inspiration and expiration were unchanged. Paco2 decreased significantly during the infusion. The apnea attack rate, monitored by continuous recording, was significantly reduced after the first 6 hours of therapy. Six hours after starting doxapram, mean arterial blood pressure was significantly elevated, and continued to increase during the 24 hours of therapy. Doxapram is effective in treatment of apnea of prematurity refractory to aminophylline, and appears to act by increasing respiratory center output.