Jarinda A Poppe1, Willem van Weteringen2,3, Swantje Völler2,4, Sten P Willemsen2,5, Tom G Goos2, Irwin K M Reiss2, Sinno H P Simons2. 1. Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands, j.poppe@erasmusmc.nl. 2. Department of Pediatrics, Division of Neonatology, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands. 3. Department of Pediatric Surgery, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands. 4. Systems Biomedicine and Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands. 5. Department of Biostatistics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract
INTRODUCTION: Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. METHODS: In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio and the area under the 89% SpO2 curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation). RESULTS: Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6-30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO2 and SpO2/FiO2 ratio as well as a decrease in episodes with saturations below target (SpO2 <89%). The SpO2/FiO2 ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83). CONCLUSION: The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO2/FiO2 ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.
INTRODUCTION: Evaluation of pharmacotherapy during intensive care treatment is commonly based on subjective, intermittent interpretations of physiological parameters. Real-time visualization and analysis may improve drug effect evaluation. We aimed to evaluate the effects of the respiratory stimulant doxapram objectively in preterm infants using continuous physiological parameters. METHODS: In this longitudinal observational study, preterm infants who received doxapram therapy were eligible for inclusion. Physiological data (1 Hz) were used to assess respiration and to evaluate therapy effects. The oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) ratio and the area under the 89% SpO2 curve (duration × saturation depth below target) were calculated as measures of hypoxemia. Regression analyses were performed in 1-h timeframes to discriminate therapy failure (intubation or death) from success (no intubation). RESULTS: Monitor data of 61 patients with a median postmenstrual age (PMA) at doxapram initiation of 28.7 (IQR 27.6-30.0) weeks were available. The success rate of doxapram therapy was 56%. Doxapram pharmacodynamics were reflected in an increased SpO2 and SpO2/FiO2 ratio as well as a decrease in episodes with saturations below target (SpO2 <89%). The SpO2/FiO2 ratio, corrected for PMA and mechanical ventilation before therapy start, discriminated best between therapy failure and success (highest AUC ROC of 0.83). CONCLUSION: The use of continuous physiological monitor data enables objective and detailed interpretation of doxapram in preterm infants. The SpO2/FiO2 ratio is the best predictive parameter for therapy failure or success. Further implementation of real-time data analysis and treatment algorithms would provide new opportunities to treat newborns.