Congenital diaphragmatic hernia (CDH) is associated with high mortality and morbidity. To date, there are no standardized protocols for the treatment of infants with this anomaly. However, protocols based on the literature and expert opinion might improve outcome. This paper is a consensus statement from the CDH EURO Consortium prepared with the aim of achieving standardized postnatal treatment in European countries. During a consensus meeting between high-volume centers with expertise in the treatment of CDH in Europe (CDH EURO Consortium), the most recent literature on CDH was discussed. Thereafter, 5 experts graded the studies according to the Scottish Intercollegiate Guidelines Network (SIGN) Criteria. Differences in opinion were discussed until full consensus was reached. The final consensus statement, therefore, represents the opinion of all consortium members. Multicenter randomized controlled trials on CDH are lacking. Use of a standardized protocol, however, may contribute to more valid comparisons of patient data in multicenter studies and identification of areas for further research.
The objective of this study was to prove the superiority of doxapram compared to theophylline therapy in apneas of prematurity in very low birth weight infants. Therefore all VLBW infants (gestational age < 35 weeks) were randomized if they had in a 2 hours-interval more than 2 apneas, 4 bradycardias or 4 oxygen desaturations. They received either theophylline (loading dose 5 mg/kg b. w., 3 mg/kg b. w. bid) or doxapram by continuous infusion of 0.5 mg/kg/h. Apneas, bradycardias and desaturations were recorded from the trend analysis of our monitoring system over the first 3-days and a 7 days period and compared statistically (Mann-Whitney U-test). Plasma levels of both drugs and a polysomnographic recording were obtained during steady state conditions in parallel to a behavioral observation according to Prechtl. The recorded events were again compared using the Mann-Whitney U-test. Twenty patients were treated with theophylline, 14 with doxapram. In 9 patients of each group we could perform a polysomnography and behavioral observation. The incidence of apneas, bradycardias and desaturations in a 7 days-interval was not significantly different between both groups. Analyzing the first 3 days of treatment, however, we could detect a significantly lower rate of apneas in the doxapram group (2.5 apneas compared to 7 in the theophylline group, p < 0.037). In the polysomnographic recording and in our behavioral observations we could not record any significant differences between both groups. Therefore we can conclude that theophylline and doxapram are comparable in the treatment of apneas of prematurity, however, doxapram is superior to theophylline in reducing the rate of apneas in the first 3 days of treatment.
Perioperative myocardial infarction (PMI) as diagnosed by standard electrocardiograms (appearance of persistent Q-waves of at least 0.4 sec duration) and/or autopsy, occurred in 51 (3.8%) out of 1341 consecutive patients undergoing coronary artery bypass surgery using saphenous vein grafts. Retrospective analysis of the available data revealed that preoperative factors like sex, age, history of myocardial infarction, functional class, coronary risk factors, number of vessels diseased, and ventricular function had no influence on the incidence of PMI. However, intraoperative parameters, e.g., type and duration of cardiac arrest as well as technical errors leading to graft occlusion, significantly affected the incidence of PMI. The clinical relevance of PMI is indicated by a high early mortality of 25.5% as compared to 2.3% in patients without PMI. Improvement as well as complete alleviation of angina pectoris was less frequent in patients with PMI than in patients without PMI. The decrease in the rate of PMI from more than 18% in 1970 to less than 1% in 1978/79 confirms that such incidents should not be regarded as an inevitable risk but as a complication which can largely be avoided by proper operative technique.
BackgroundPharmacodynamic evaluation is challenging in neonatal clinical care, and often based on subjective human interpretation of clinical signs and the available ‘snapshot’ of physiological parameters. High frequency data (≥ 1Hz) of bedside patient monitors provide the opportunity of continuous and objective drug evaluation.1 This study investigates the predictive value of continuously available vital and ventilatory parameters to evaluate doxapram therapy. Doxapram is a respiratory stimulant to avoid mechanical ventilation and adverse outcomes of hypoxemia in preterm infants.2 MethodsPreterm infants admitted to a level III NICU centre who received doxapram therapy were eligible for inclusion. Stored vital and ventilatory parameters were retrospectively analysed. Multivariate analysis was performed to identify variables that influenced therapy failure (intubation or death) or success. Variables with a p value < 0.1 in univariate analysis were included in the multivariate analysis. Additionally, the ΔSpO2/FiO2-ratio was calculated by subtracting the median SpO2/FiO2-ratio 1 day after therapy from the median SpO2/FiO2-ratio 1 day before therapy.ResultsThe first episode of doxapram treatment was analysed in a total of 61 preterm infants with a median postnatal age at therapy start (PNA) of 3.0 weeks (IQR; 2.0–3.6). The success rate of doxapram therapy was 57%. Out of all parameters, the SpO2/FiO2-ratio showed to be the most indicative for therapy outcome. The predictive model included the ΔSpO2/FiO2-ratio, the PNA, the administration of a loading dose at start, and intubation within 24 hours before the start of doxapram (area under the curve of 0.828). The ΔSpO2/FiO2-ratio was inversely associated with therapy outcome (OR 0.26, CI 95% 0.07–0.83; p = 0.03).ConclusionThe ΔSpO2/FiO2-ratio between 1 day before and 1 day after start of the therapy is predictive of failure or success of doxapram therapy. The use of physiological data shows potential in the pharmacodynamic evaluation of doxapram therapy.ReferencesFlint R, Weteringen WV, Voller S, Poppe JA, Koch BC, Groot R, et al. Big data analyses for continuous evaluation of pharmacotherapy: A proof of principle with doxapram in preterm infants. Curr Pharm Des. 2017.Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, et al. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015;314(6):595–603.Disclosure(s)Nothing to disclose
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