Stephen J. Kimatian

Plasma Biomarkers in Pediatric Patients Undergoing Cardiopulmonary Bypass

It is critical to identify at-risk patients and minimize the deleterious effects of cardiopulmonary bypass (CPB) procedures in pediatric populations. The present study screened the plasma proteome of pediatric patients undergoing CPB procedures to identify potential clinical biomarkers related to tissue damage, inflammation, or other pathologies. Blood samples were collected at five different time points from 10 children undergoing a CPB procedure. Plasma was isolated and analyzed using two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption ionization time of flight mass spectrometry. Levels of differentially regulated proteins identified by two-dimensional differential in-gel electrophoresis, and related proteins were then measured in all time points and patients. As well, associated small molecules and ions were measured. The present study identified 13 proteins and protein isoforms altered in expression, including hemopexin, ceruloplasmin, inter-alpha inhibitor H4, and alpha-2-macroglobulin. Immunoblot analysis revealed significant decreases in each of these proteins during the CPB procedure. Significant changes in the levels of copper, iron, Hb, epinephrine, norepinephrine, and serotonin were observed. The potential markers of pathology (inflammation, oxidative stress) identified during this preliminary study may illuminate opportunities for preventative measures and/or treatments during and following CPB procedures in pediatric patients.

Transcranial Doppler ultrasonography: a reliable method of monitoring pulsatile flow during cardiopulmonary bypass in infants and young children.

Clinical symptoms are sudden chest pain, dyspnea, and, less commonly, dysphagia and hoarseness. Physically, subcutaneous air and a typical crunching sound are present. When chest pain and dyspnea are present, anxiety and panic attack are frequent. Panic disorders are often observed in anorexic patients: when chest pain and/or dyspnea or dysphagia appear, spontaneous PM should be considered. At present, 20 cases of spontaneous PM have been described in the literature. PM in anorexic patients is sometimes produced by selfinduced vomiting. Our patient had no history of vomiting, and the thorough diagnostic procedures (thoracic computed tomographic scan, esophageal radiologic evaluation, and laryngopharyngoscopy) showed no signs of esophageal or upper airway laceration. The pathophysiologic mechanism of PM in our patient can be explained by an alveolar wall rupture, with consequent air leak into the mediastinum. The air was interestingly confined to the mediastinum only: no signs of pneumothorax were evident. PM is sometimes observed in AN: self-induced vomiting causing an esophageal laceration is frequently the cause of PM in these patients. Anorexic patients with severe malnutrition are at high risk for PM or pneumothorax.

Plasma proteomics: a noninvasive window on pathology and pediatric cardiac surgery.

A challenge of pediatric research is the limited ability to obtain tissue samples from small patients. To confront this problem, blood biomarkers can be used as surrogate markers of disease processes and aid in patient monitoring and disease detection. Furthermore, proteomic analysis of plasma samples is one approach for large-scale discovery of disease biomarkers. This study examined the use of plasma for disease process biomarkers in pediatric patients undergoing cardiopulmonary bypass (CPB) surgery. Proteomic studies of plasma are limited by the presence of a few high abundance proteins that mask the presence of lower abundance proteins of interest. Plasma immunoaffinity depletion (removing 6 of the highest abundance proteins of little pathological importance) increases sensitivity of detection for proteins such as those related to inflammation, remodeling, and damage. Using two-dimensional in-gel fluorescence electrophoresis, changes in the expression levels of proteins that occur as a result of CPB can be identified. In the present study, plasma depletion removed 83% of the plasma protein mass, allowing approximately 1400 spots to be observed by two-dimensional in-gel fluorescence electrophoresis. Of the detected spots, 79 (5.7%) were altered by CPB. These data illuminate the strength of plasma proteomics in identification of candidate biomarkers of CPB-associated disease processes.

The influence of neurophysiologic monitoring on the management of pediatric cardiopulmonary bypass.

We describe a process by which we sought to determine how the addition of intraoperative neurophysiologic monitoring (IONM) impacted the management of cardiopulmonary bypass (CPB) during pediatric cardiac surgery. While maintaining a consistent team of surgeons, anesthesiologists, nurses, and perfusionists, a multi-modal, IONM program was established consisting of Near Infrared Spectroscopy, Transcranial Doppler, and eight channel electroencephalography. A retrospective review of cases from 1 year before the institution of the IONM program was compared with data obtained from cases performed after neurophysiologic monitoring was established as a standard of care for pediatric patients on CPB. This comparative analysis of CPB management revealed a significant increase in the use of donor blood added to the CPB circuit prime as well as in the maintenance of a higher hematocrit during the bypass period after the implementation of IONM. These changes in the management of pediatric CPB correlated with recommendations of previous studies that examined postoperative neurophysiologic outcomes, suggesting that these changes were not only consistent with best practices, but that the presence of IONM data facilitated a transition to evidence-based practice.

Lack of Association between Blood Pressure Management by Anesthesia Residents and Competence Committee Evaluations or In-training Exam Performance: A Cohort Analysis.

Background:Prompt treatment of severe blood pressure instability requires both cognitive and technical skill. The ability to anticipate and respond to episodes of hemodynamic instability should improve with training. The authors tested the hypothesis that the duration of severe hypotension during anesthesia administered by residents correlates with concurrent adjusted overall performance evaluations by the Clinical Competence Committee and subsequent in-training exam scores. Methods:The authors obtained data on 70 first- and second-year anesthesia residents at the Cleveland Clinic. Analysis was restricted to adults having noncardiac surgery with general anesthesia. Outcome variables were in-training exam scores and subjective evaluations of resident performance ranked in quintiles. The primary predictor was cumulative systolic arterial pressure less than 70 mmHg. Secondary predictors were administration of vasopressors, frequency of hypotension, average duration of hypotensive episodes, and blood pressure variability. Results:The primary statistical approach was mixed-effects modeling, adjusted for potential confounders. The authors considered 15,216 anesthesia care episodes. A total of 1,807 hypotensive episodes were observed, lasting an average of 32 ± 20 min (SD) per 100 h of anesthesia, with 68% being followed by vasopressor administration. The duration of severe hypotension (systolic pressure less than 70 mmHg) was associated with neither Competence Committee evaluations nor in-training exam scores. There was also no association between secondary blood pressure predictors and either Competence Committee evaluations or in-training exam results. Conclusions:There was no association between any of the five blood pressure management characteristics and either in-training exam scores or clinical competence evaluations. However, it remains possible that the measures of physiologic control, as assessed from electronic anesthesia records, evaluate useful but different aspects of anesthesiologist performance.

Penn state hershey - Center for pediatric cardiovascular research: Guest editorial

With the creation of the Penn State Hershey - Center for Pediatric Cardiovascular Research, we strive to become one of the leading centers for the innovation and development of novel devices and treatments for congenital heart surgery. We also seek to educate more bioengineers, medical students, residents, post-doctoral fellows, and junior faculty members in pediatric cardiovascular research. Finally, we seek to continue the growth of our conference (The International Conference on Pediatric Mechanical Circulatory Support Systems and Pediatric Cardiopulmonary Perfusion - http://www.hmc.psu.edu/childrens/pedscpb/), in order to provide a scientific venue for the pioneering research being performed in pediatric mechanical circulatory support and cardiopulmonary perfusion. Our website (http://www.pennstatehershey.org/web/childrensheartgroup/research/overview) includes an overview of all of our current projects (clinical, basic science, and bioengineering), publications, presentations, as well as national and international collaborators affiliated with our center. Investigators interested in collaborating with us on current or new projects should send an e-mail to ude.usp@radnua. Special thanks go to all those who support our collaborative efforts, both intellectually and financially each year. This includes significant financial support from the Penn State Hershey Children’s Hospital and Penn State Hershey College of Medicine, the National Heart Lung and Blood Institute, and the National Institute of Health Office of Rare Diseases. Furthermore, we are most grateful to our dedicated students, sponsors, faculty, and national and international collaborators which make the formation of such an establishment possible.

Remediation and due process for trainees: setting the stage for future success.

When the words ‘‘remediation’’ and ‘‘due process’’ are used, the implication is that a failure has occurred and that we are transitioning from the formative state of feedback and education to the summative state of judgment and disposition. However, as this chapter seeks to discuss, if the goal is to help the resident overcome their perceived deficiencies, and not simply eject them from the program, then remediation and due process can, and should, be viewed as the elevation of feedback and education to a higher level. Although feedback and education are often discussed in the more personal interaction of teacher and student, elevating this process to a next level requires a team approach that harnesses the resources of the department as a whole. Dealing with a resident in this situation is much akin to treating a patient presenting with a new onset of symptoms in that there must first be a diagnosis, followed by a decision on the desired outcome or resolution, from which a treatment plan is implemented to attain the desired outcome.