Biomedical subjects
Publications and source records attributed to Brahm Goldstein.
We designed a new methodology to estimate the pulse pressure variation index (deltaPP) in arterial blood pressure (ABP). The method uses automatic detection algorithms, kernel smoothing, and rank-order filters to continuously estimate deltaPP. The technique can be used to estimate deltaPP from ABP alone, eliminating the need for simultaneously acquiring airway pressure.
OBJECTIVE: In a phase 3 trial, recombinant human activated protein C (drotrecogin alfa [activated]) significantly reduced mortality in adult patients with severe sepsis. We have now performed a preliminary analysis of the safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in pediatric patients with severe sepsis. DESIGN AND SETTING: Open-label, nonrandomized, sequential, 2-part study conducted in 11 medical centers in the United States and United Kingdom. PATIENTS: Eighty-three pediatric patients with severe sepsis aged term newborn (>or=38 weeks' gestation) to <18 years old. INTERVENTION: In part 1, drotrecogin alfa (activated) was administered as escalating doses of 6, 12, 24, and 36 micro g/kg per hour for 6 hours for each patient (n = 21). In part 2, drotrecogin alfa (activated) was infused at a rate of 24 micro g/kg per hour for 96 hours in 62 patients. MAIN OUTCOME MEASURES: Plasma clearance, plasma concentration, D-dimer, protein C, and antithrombin levels were measured, and adverse events were monitored. RESULTS: The trial enrolled 83 pediatric patients with severe sepsis, aged term newborn (>or=38 weeks' gestation) to <18 years. In part 1, a dose of 24 micro g/kg per hour produced steady-state plasma concentrations of activated protein C similar to those attained in equivalently dosed adult severe sepsis patients. For all pediatric patients dosed at 24 micro g/kg per hour, the median weight-normalized clearance was 0.45 L/hour/kg and the median steady-state concentration was 51.3 ng/mL. The mean plasma half-life was 30 minutes. Weight-normalized clearance in pediatric and adult patients did not differ significantly with age or weight. D-dimer levels decreased 26% from baseline to end of infusion. Baseline levels of protein C and antithrombin increased 79% and 24%, respectively, over the 96-hour treatment period in part 2. The incidence of serious bleeding during infusion and during the entire study period was 2.4% and 4.8%, respectively. CONCLUSIONS: Pediatric patients with severe sepsis manifest sepsis-induced coagulopathy including protein C deficiency comparable to that seen in adults with severe sepsis. The pharmacokinetics, pharmacodynamic effects, and safety profile of drotrecogin alfa (activated) in pediatric patients are similar to those previously published for adult patients. A large, phase 3, randomized, placebo-controlled study is ongoing to confirm these results and formally assess the safety and efficacy of drotrecogin alfa (activated) in children.
OBJECTIVE: To describe a real-time, continuous physiologic data acquisition system for the study of disease dynamics in the intensive care unit. DESIGN: Descriptive report. SETTING: A 16-bed pediatric intensive care unit in a tertiary care children's hospital. PATIENTS: A total of 170 critically ill or injured pediatric patients. INTERVENTIONS: None. MAIN OUTCOME MEASURES: None. RESULTS: We describe a computerized data acquisition and analysis system for the study of critical illness and injury from the perspective of complex dynamic systems. Both parametric (1 Hz) and waveform (125-500 Hz) signals are recorded and analyzed. Waveform data include electrocardiogram, respiration, systemic arterial pressure (invasive and noninvasive), central venous pressure, pulmonary arterial pressure, left and right atrial pressures, intracranial pressure, body temperature, and oxygen saturation. Details of the system components are explained and examples are given from the resultant physiologic database of signal processing algorithms and signal analyses using linear and nonlinear metrics. CONCLUSIONS: We have successfully developed a real-time, continuous physiologic data acquisition system that can capture, store, and archive data from pediatric intensive care unit patients for subsequent time series analysis of dynamic changes in physiologic state. The physiologic signal database generated from this system is available for analysis of dynamic changes caused by critical illness and injury.
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OBJECTIVE: To determine whether heart rate variability metrics provide an accurate method of monitoring depth of anesthesia, assessing the response to painful stimuli, and assessing neuroautonomic regulation of cardiac activity in children receiving propofol anesthesia for short-duration procedures. DESIGN: Prospective, case series. SETTING: Sixteen-bed pediatric intensive care unit, oncology unit, and endoscopy suite in a tertiary care children's hospital and ophthalmology examination rooms in an associated eye institute. PATIENTS: Thirty-three pediatric patients undergoing propofol anesthesia for short procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate variability metrics studied included mean, SD, low- and high-frequency power, detrended fluctuation analysis (represented by correlation coefficient, alpha), and approximate entropy. Compared with the initial anesthetized state, we found increased heart rate SD (3.17 +/- 1.31 vs. 7.05 +/- 0.26 bpm, p <.0001), heart rate low-frequency power (3.69 +/- 0.36 vs. 4.48 +/- 0.41 bpm(2)/Hz, p <.0001), heart rate low-/high-frequency ratio (1.47 +/- 0.26 vs. 1.26 +/- 0.24, p =.001), and heart rate alpha (1.12 +/- 0.24 vs. 1.35 +/- 0.21, p <.0001) during painful procedure. Mean heart rate (105.8 +/- 13.4 vs. 101.5 +/- 12.4 bpm, p =.005) and heart rate approximate entropy decreased with painful procedure (0.75 +/- 0.19 vs. 0.53 + 0.16, p <.001), whereas there was no significant change in heart rate high-frequency power (3.04 +/- 0.63 vs. 3.16 +/- 0.71 bpm(2)/Hz, p =.26). CONCLUSIONS: We conclude that power spectral analysis of heart rate variability may be an accurate and clinically useful measure of depth of propofol anesthesia. We speculate that high-frequency heart rate power during propofol anesthesia correlates with depth of anesthesia, whereas low-frequency power allows for assessment of the patient's sympathetic response to pain.
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