Doxapram and neurodevelopmental outcome.
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Biomedical subjects
Publications and source records attributed to Neil N Finer.
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OBJECTIVE: To examine the use of plasma lactate levels to predict mortality and neurodevelopmental outcome of neonates treated with extracorporeal membrane oxygenation. DESIGN: Prospective cohort study. SETTING: Two level III neonatal intensive care units in Canada and the United States. PATIENTS: Seventy-four neonates requiring extracorporeal membrane oxygenation in two neonatal intensive care units from 1994 to 1996. INTERVENTIONS: Differences in clinical and biochemical measurements, including serial lactate levels between three outcome groups (early deaths, adverse survivors, and normal survivors) were compared using analysis of variance. We also examined the predictive relationship between plasma lactate levels and the outcome at neonatal intensive care unit discharge and at 18-24 months postnatal age by backward, stepwise regression and Fisher's exact test. MEASUREMENTS AND MAIN RESULTS: Fifteen (20%) neonates died before neonatal intensive care unit discharge (early deaths), with seven additional deaths before follow-up, which are included in the adverse survivors group. Among 49 early childhood survivors (22 +/- 7 months), 27 were disabled or delayed with Mental and Performance Developmental Indices of 70 +/- 21 and 72 +/- 22, respectively. Early deaths had higher plasma lactate levels and were more acidemic than adverse and normal survivors, who were not different from each other (p <.05). Plasma lactate and the lowest arterial pH independently predicted 42% of the variance of the outcome ( p<.001). A peak lactate level of >or=25 mM predicted early mortality (sensitivity, 47%; specificity, 100%; positive and negative predictive values, 100% and 88%, respectively; p<.001), whereas a level of >or=15 mM predicted adverse outcome (sensitivity, 35%; specificity, 91%; positive and negative predictive values, 89% and 38%, respectively; p<.05). The predictability of plasma lactate was significantly improved in 45 neonates without congenital diaphragmatic hernia or lethal anomalies (sensitivity of 100% for early mortality, negative predictive value of 63% for adverse outcome). CONCLUSIONS In addition to assessing tissue oxygenation, plasma lactate may facilitate the decision-making process by providing early predictive information about the outcome of neonates treated with extracorporeal membrane oxygenation.
OBJECTIVE: The objective of this article is to conduct a cost-effectiveness analysis, based on data up to 18-24 months of follow-up, of the use of inhaled nitrogen oxide vs. oxygen, administered to near-term and term infants with severe respiratory failure who were referred for consideration for extracorporeal membrane oxygenation. DESIGN: The cost-effectiveness analysis was conducted alongside a randomized controlled trial conducted by the Canadian Inhaled Nitric Oxide Study Group for patients with severe respiratory distress. SETTING: Patients were cared for in Canadian regional neonatal intensive care units; follow-up treatment was based on standard care. PATIENTS: Term and near-term neonates with severe respiratory failure determined by at least two oxygenation indexes (oxygenation index = mean arterial pressure x Fio2/Pao2) >/=25 at least 15 mins apart. INTERVENTIONS: Patients were randomized to inhaled nitrogen oxide or oxygen. If conditions deteriorated, they qualified for extracorporeal membrane oxygenation. Not all who qualified received extracorporeal membrane oxygenation. Standard care followed after hospital discharge. MEASUREMENTS AND MAIN RESULTS: Timelines of analysis were from randomization until the follow-up, which occurred between 18 and 24 months after randomization. Costs included those for initial hospitalization (neonatal intensive care, medications, extracorporeal membrane oxygenation, transport) and standard medical services above routine care and developmental services received until follow-up. Outcomes included mortality rate, clinical outcomes, and a variety of neurodevelopmental indicators. Costs were not significantly different between interventions. While infants who received inhaled nitrogen oxide generally did better than those who received oxygen, the only variable that was significant was the number of seizure disorders. On economic grounds, inhaled nitrogen oxide was the preferred intervention.
OBJECTIVE: Carnitine is thought to be a conditionally essential biological cofactor for premature infants. A preliminary study suggested that carnitine could significantly reduce apnea of prematurity. The objective of this study was to evaluate critically the role of carnitine in idiopathic apnea of prematurity and to determine whether the use of carnitine would facilitate discontinuation of mechanical ventilatory support, shorten the duration of ventilatory support, and reduce the amount of time that such infants are exposed to both mechanical ventilation and oxygen. We also wanted to determine the effects of supplemental carnitine on weight gain, time to regain birth weight, time to achieve full enteral feedings, and length of hospital stay. METHODS: A prospective, randomized, blinded trial was conducted on 44 preterm infants who were from the same neonatal intensive care unit and who were < or =32 weeks' gestational age with a postnatal age <48 hours and a birth weight <1500 g and required total parenteral nutrition (TPN). Infants were randomized to receive carnitine supplementation or placebo without crossover. Carnitine-supplemented infants received 30 mg/kg/d carnitine in their TPN until the they were tolerating 120 mL/kg/d enteral feedings, and then they received 30 mg/kg/d oral carnitine. The placebo group received TPN without supplemental carnitine; when they tolerated 120 mL/kg/d enteral feedings, they received an oral placebo. The 2 groups continued on their respective supplemental carnitine or placebo until 34 weeks' adjusted age, at which time the study period was completed. Twelve-hour cardiorespiratorygrams to record heart rate, respiratory impedance, and oxygen saturation, and a nasal thermistor to detect expiratory airflow were performed every 4 days on 3 occasions and at 30 and 34 weeks' adjusted age. Plasma carnitine levels were measured at day 14. RESULTS: There were no significant differences between the 2 groups in the occurrence of apnea as detected by cardiorespiratorygram or nursing observation. There were no significant differences between the groups in regard to total days on ventilator, days of nasal continuous positive airway pressure, time to regain birth weight, time to reach enteral feedings of 120 mL/kg/d, discharge weight, adjusted age at discharge, need for oxygen at 28 days' and 36 weeks' adjusted age, or length of stay. The plasma carnitine level was a median of 15.5 micromol/L (range: 7.6-30.5) for the placebo infants compared with a median of 195.3 micromol/L (range: 71.7-343.6) for the carnitine infants. CONCLUSIONS: In this blinded, randomized, placebo-controlled study, we found that infants who received supplemental carnitine did not demonstrate any reduction in apnea of prematurity, ventilator or nasal continuous positive airway pressure days, or the need for supplemental oxygen therapy. Although carnitine may be of significant nutritional benefit for very low birth weight infants, our study does not support its use to reduce apnea of prematurity or decrease dependence on mechanical ventilation.
OBJECTIVE: Infants with meconium aspiration syndrome (MAS) have marked surfactant dysfunction. Airways and alveoli of affected neonates contain meconium, inflammatory cells, inflammatory mediators, edema fluid, protein, and other debris. The objective of this study was to compare treatment with bronchoalveolar lavage using dilute Surfaxin with standard therapy in a population of newborn infants with MAS. METHODS: Inclusion criteria were 1) gestational age > or =35 weeks, 2) enrollment within 72 hours of birth, 3) diagnosis of MAS, 4) need for mechanical ventilation, and 5) an oxygenation index > or =8 and < or =25. Subjects were randomized to either lavage with Surfaxin or standard care (2:1 proportion). In lavaged infants, a volume of 8 mL/kg dilute Surfaxin (2.5 mg/mL) was instilled into each lung over approximately 20 seconds followed by suctioning after 5 ventilator breaths. The procedure was repeated twice. The third and final lavage was with a more concentrated solution (10 mg/mL) of Surfaxin. RESULTS: Twenty-two infants were enrolled (15 Surfaxin and 7 control). Demographic characteristics were similar. There were trends (not significant) for Surfaxin-lavaged infants to be weaned from mechanical ventilation earlier (mean of 6.3 vs 9.9 days, respectively), as well as to have a more rapid decline in their oxygenation indexes compared with control infants, the latter difference persisting for the 96-hour-long study period. The therapy was safe and generally well tolerated by the infants. CONCLUSIONS: Dilute Surfaxin lavage seems to be a safe and potentially effective therapy in the treatment of MAS. Data from this investigation support future prospective, controlled clinical trials of bronchoalveolar lavage with Surfaxin in neonates with MAS.
BACKGROUND: The management of critically ill infants and neonates includes frequent determination of arterial blood gas, electrolyte, and hematocrit values. An objective of attached point-of-care patient monitoring is to provide clinically relevant data without the adverse consequences associated with serial phlebotomy. METHODS: We prospectively determined the mean difference (and SD of the difference) from laboratory methods of an in-line, ex vivo monitor, the VIA LVM Blood Gas and Chemistry Monitoring System (VIA LVM Monitor; Metracor Technologies, Inc.), in 100 critically ill neonates and infants at seven children's hospitals. In doing so, we examined monitor stability with continuous use. In vivo patient test results from laboratory benchtop analyzers were compared with those from the VIA LVM Monitor on paired samples. In a separate in vitro comparison, benchtop analyzer and monitor test results were compared on whole-blood split samples. RESULTS: A total of 1414 concurrent, paired-sample measurements were obtained. The mean differences (SD of differences) from laboratory methods and r values for the combined data for the VIA LVM Monitor from the seven sites were 0.001 (0.026) and 0.97 for pH, 0.7 (3.6) mmHg and 0.94 for PCO(2), 4.2 (9.6) mmHg and 0.98 for PO(2), 0.0 (2.9) mmol/L and 0.87 for sodium, 0.1 (0.2) mmol/L and 0.96 for potassium, and 0.3% (2.9%) and 0.90 for hematocrit. Performance results were similar among the study sites with increasing time of monitor use and between in vivo paired-sample and in vitro split-sample test results. CONCLUSION: The VIA LVM Monitor can be used to assess critically ill neonates and infants.