Showing papers by "Ravi R. Thiagarajan published in 2021"

Variability in the Hemodynamic Response to Fluid Bolus in Pediatric Septic Shock.

Abstract: Objectives Fluid boluses are commonly administered to improve the cardiac output and tissue oxygen delivery in pediatric septic shock. The objective of this study is to evaluate the effect of an early fluid bolus administered to children with septic shock on the cardiac index and mean arterial pressure, as well as on the hemodynamic response and its relationship with outcome. Design, setting, patients, and interventions We prospectively collected hemodynamic data from children with septic shock presenting to the emergency department or the PICU who received a fluid bolus (10 mL/kg of Ringers Lactate over 30 min). A clinically significant response in cardiac index-responder and mean arterial pressure-responder was both defined as an increase of greater than or equal to 10% 10 minutes after fluid bolus. Measurements and main results Forty-two children with septic shock, 1 month to 16 years old, median Pediatric Risk of Mortality-III of 13 (interquartile range, 9-19), of whom 66% were hypotensive and received fluid bolus within the first hour of shock recognition. Cardiac index- and mean arterial pressure-responsiveness rates were 31% and 38%, respectively. We failed to identify any association between cardiac index and mean arterial pressure changes (r = 0.203; p = 0.196). Cardiac function was similar in mean arterial pressure- and cardiac index-responders and nonresponders. Mean arterial pressure-responders increased systolic, diastolic, and perfusion pressures (mean arterial pressure - central venous pressure) after fluid bolus due to higher indexed systemic vascular resistance and arterial elastance index. Mean arterial pressure-nonresponders required greater vasoactive-inotrope support and had higher mortality. Conclusions The hemodynamic response to fluid bolus in pediatric septic shock was variable and unpredictable. We failed to find a relationship between mean arterial pressure and cardiac index changes. The adverse effects of fluid bolus extended beyond fluid overload and, in some cases, was associated with reduced mean arterial pressure, perfusion pressures and higher vasoactive support. Mean arterial pressure-nonresponders had increased mortality. The response to the initial fluid bolus may be helpful to understand each patient's individualized physiologic response and guide continued hemodynamic management.

Coagulations Studies Do Not Correlate With Each Other or With Hematologic Complications During Pediatric Extracorporeal Membrane Oxygenation.

Abstract: OBJECTIVES Anticoagulation plays a key role in the management of children supported with extracorporeal membrane oxygenation. However, the ideal strategy for monitoring anticoagulation remains unclear. Our objective was to evaluate the utility of laboratory measures of anticoagulation in pediatric extracorporeal membrane oxygenation. DESIGN Retrospective cohort study. SETTING Quaternary care academic children's hospital. PATIENTS Children in a noncardiac PICU cannulated to extracorporeal membrane oxygenation in 2010-2016. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Demographic data, laboratory values, and heparin doses were extracted from the enterprise data warehouse. Primary diagnoses, indications for cannulation, hemorrhagic and thrombotic complications, and survival outcomes were abstracted from the local registry used for Extracorporeal Life Support Organization reporting. Statistical models accounting for repeated measures using generalized estimating equations were constructed to evaluate correlations between heparin doses and laboratory values; among laboratory values; and between heparin dose or laboratory values and clinical outcomes. One hundred thirty-three unique patients-78 neonates and 55 older patients-were included in the study. There was no significant association between antifactor Xa level, activated partial thromboplastin time, activated clotting time, or heparin dose with hemorrhage or thrombosis (odds ratio ≅ 1 for all associations). There was weak-to-moderate correlation between antifactor Xa, activated partial thromboplastin time, and activated clotting time in both neonates and older pediatric patients (R2 < 0.001 to 0.456). Heparin dose correlated poorly with laboratory measurements in both age groups (R2 = 0.010-0.063). CONCLUSIONS In children supported with extracorporeal membrane oxygenation, heparin dose correlates poorly with common laboratory measures of anticoagulation, and these laboratory measures correlate poorly with each other. Neither heparin dose nor laboratory measures correlate with hemorrhage or thrombosis. Further work is needed to identify better measures of anticoagulation in order to minimize morbidity and mortality associated with extracorporeal membrane oxygenation.

Risk Factors for Severe Primary Graft Dysfunction in Infants Following Heart Transplant

Abstract: Background Previous studies suggest that infant heart transplant (HT) recipients are at higher risk of developing severe primary graft dysfunction (PGD) than older children. We sought to identify r...

Outcomes of Pediatric Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

Abstract: OBJECTIVE The goal of this work is to provide insight into survival and neurologic outcomes of pediatric patients supported with extracorporeal cardiopulmonary resuscitation. DATA SOURCES A systematic search of Embase, PubMed, Cochrane, Scopus, Google Scholar, and Web of Science was performed from January 1990 to May 2020. STUDY SELECTION A comprehensive list of nonregistry studies with pediatric patients managed with extracorporeal cardiopulmonary resuscitation was included. DATA EXTRACTION Study characteristics and outcome estimates were extracted from each article. DATA SYNTHESIS Estimates were pooled using random-effects meta-analysis. Differences were estimated using subgroup meta-analysis and meta-regression. The Meta-analyses Of Observational Studies in Epidemiology guideline was followed and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation system. Twenty-eight studies (1,348 patients) were included. There was a steady increase in extracorporeal cardiopulmonary resuscitation occurrence rate from the 1990s until 2020. There were 32, 338, and 1,094 patients' articles published between 1990 and 2000, 2001 and 2010, and 2010 and 2020, respectively. More than 70% were cannulated for a primary cardiac arrest. Pediatric extracorporeal cardiopulmonary resuscitation patients had a 46% (CI 95% = 43-48%; p < 0.01) overall survival rate. The rate of survival with favorable neurologic outcome was 30% (CI 95% = 27-33%; p < 0.01). CONCLUSIONS The use of extracorporeal cardiopulmonary resuscitation is rapidly expanding, particularly for children with underlying cardiac disease. An overall survival of 46% and favorable neurologic outcomes add credence to this emerging therapy.

Hemostatic Challenges in Pediatric Critical Care Medicine-Hemostatic Balance in VAD

Abstract: Ventricular assist devices (VAD) are used more in children. Safe and effective anticoagulation is required for successful management of children supported with ventricular assist devices. Developmental hemostasis, device hemocompatibility, plastic to body ratio, surgical variable techniques, lack of knowledge on pharmacokinetics of anticoagulants, and wide variability in anticoagulation protocols have all contributed to increased incidence of bleeding and thromboembolic complications. New collaborative learning networks, such as the ACTION network, provide opportunities to define best practices, optimize, and reduce anticoagulation related adverse events. ACTION was established Dec 2017. It consists of expert clinicians in heart failure, as well as researchers, parents, and patients, with goals to improve outcomes, share data, improve education and standard practice for children with heart failure (, n.d). Changes in pediatric VAD anticoagulation strategy from using mainly heparin to DTI such as bivalirudin have helped reduce bleeding and clotting complications.

On the Academic Value of 30 Years of the Extracorporeal Life Support Organization Registry.

Abstract: From the *Division of Cardiothoracic Surgery, Department of Surgery, University of Utah Health, Salt Lake City, Utah; †Division of Emergency Medicine, Department of Surgery, University of Utah Health, Salt Lake City, Utah; ‡Department of Pediatrics, University of Michigan, Ann Arbor; Child Health Evaluation and Research Center, University of Michigan, Ann Arbor, Michigan; §Extracorporeal Life Support Organization, Ann Arbor, Michigan; ¶Department of Surgery, Virginia Commonwealth University, Richmond, Virginia; ||University of Texas Southwestern Medical Center, Dallas, Texas; #Division of Cardiac Anesthesia, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts; **Division of Pediatric Critical Care, Emory University, Atlanta, Georgia; ††Department of Cardiology, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts; ‡‡Inova Fairfax Medical Center, Fairfax, Virginia; §§Departments of Medicine, Emergency Medicine and Pediatrics, Louisiana State University Health Sciences Center, Shreveport, Louisiana; and ¶¶Department of Surgery, University of Michigan, Ann Arbor, Michigan. Submitted for consideration September 2020; accepted for publication in revised form September 2020. Disclosure: J.E.T. is Chair of the Scientific Oversight Subcommittee of the Extracorporeal Life Support Organization (ELSO) Registry. R.P.B. is Chair of the ELSO Registry. J.E.T. is supported by a Career Development Award from the National Institutes of Health/National Heart, Lung, And Blood Institute (K23 HL141596). J.E.T. received speaker fees and travel compensation from LivaNova and Philips Healthcare, unrelated to this work. R.P.B. reports grant support from the Training to Advance Care Through Implementation Science in Cardiac And Lung illnesses (TACTICAL) National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) K12 HL138039 and the Pediatric Implantable Artificial Lung National Institute of Health and Human Development (NICHD), NIH R01HD015434-34. This study was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR002538 (formerly 5UL1TR001067-05, 8UL1TR000105, and UL1RR025764). Copyright © ASAIO 2020 DOI: 10.1097/MAT.0000000000001318 On the Academic Value of 30 Years of the Extracorporeal Life Support Organization Registry

Stratification of Bleeding Risk Using Thromboelastography in Children on Extracorporeal Membrane Oxygenation Support.

Abstract: OBJECTIVES Patients undergoing extracorporeal membrane oxygenation are at high risk for bleeding and thrombotic complications. Current laboratory methods for assessing the coagulation system may be imprecise and complicate clinical decision-making. We hypothesize that thromboelastography may be more strongly associated with bleeding events than traditional methods and can aid extracorporeal membrane oxygenation coagulation management. DESIGN In a retrospective study, 40 patients with congenital heart disease requiring extracorporeal membrane oxygenation support yielded a total of 159 patient days of data for thromboelastography analysis. SETTING Pediatric cardiac ICU at a single institution. SUBJECTS Pediatric patients (≤ 18 yr) with congenital heart disease requiring extracorporeal membrane oxygenation support. INTERVENTIONS None. METHODS Thromboelastography was performed on whole blood samples collected 6-12 hours following extracorporeal membrane oxygenation initiation and daily for the duration of extracorporeal membrane oxygenation. Bleeding during each 24-hour period was defined as need for re-exploration or need for blood transfusion. Associations between thromboelastography variables and bleeding over each 24-hour period (bleeding vs nonbleeding days) were assessed using mixed effects logistic regression and classification and regression tree analysis. MEASUREMENTS AND MAIN RESULTS Bleeding occurred in 25 patients (63%), contributing 87 bleeding days (55% extracorporeal membrane oxygenation days) for analysis. The probability of bleeding within the 24-hour period was not associated with activated partial thromboplastin time (p = 0.6) or anti-Xa levels (p = 0.3) on that day. The strongest correlate of bleeding was a maximum amplitude less than 55.4 mm on thromboelastography (odds ratio, 3.28; 95% CI, 1.63-6.60; p < 0.001). Bleeding occurred on 73% versus 35% of extracorporeal membrane oxygenation days for maximum amplitude less than 55.4 mm versus greater than or equal to 55.4 mm, respectively. Bleeding occurred on all days when a combination of maximum amplitude less than 55.4 mm and a reaction time greater than 12.9 minutes was present. The lowest risk of bleeding (28% of patient days) was associated with maximum amplitude greater than or equal to 55.4 mm and plasma fibrinogen greater than 345 mg/dL. CONCLUSIONS Thromboelastography-derived variables maximum amplitude and reaction time, along with plasma fibrinogen levels, can help predict bleeding events in children on extracorporeal membrane oxygenation support. Research based on larger patient samples is needed to confirm the specific thresholds identified for bleeding risk stratification for extracorporeal membrane oxygenation anticoagulation management.

Factors Associated With Initiation of Extracorporeal Cardiopulmonary Resuscitation in the Pediatric Population: An International Survey.

Abstract: Although extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly utilized in the pediatric critical care environment, our understanding regarding pediatric candidacy for ECPR remains unknown. Our objective is to explore current practice and indications for pediatric ECPR. Scenario-based, self-administered, online survey, evaluating clinical determinants that may impact pediatric ECPR initiation with respect to four scenarios: postoperative cardiac surgery, cardiac failure secondary to myocarditis, septic shock, and chronic respiratory failure in a former preterm child. Responders are pediatric critical care physicians from four societies. 249 physicians, mostly from North America, answered the survey. In cardiac scenarios, 40% of the responders would initiate ECPR, irrespective of CPR duration, compared with less than 20% in noncardiac scenarios. Nearly 33% of responders would consider ECPR if CPR duration was less than 60 minutes in noncardiac scenarios. Factors strongly decreasing the likelihood to initiate ECPR were out-of-hospital unwitnessed cardiac arrest and blood pH 10 doses of adrenaline, poor CPR quality, and lactate >18 mmol/l. Pediatric intensive care unit location for cardiac arrest, good CPR quality, 24/7 in-house extracorporeal membrane oxygenation (ECMO) team moderately increase the likelihood of initiating ECPR. This international survey of pediatric ECPR initiation practices reveals significant differences regarding ECPR candidacy based on patient category, location of arrest, duration of CPR, witness status, and last blood pH. Further research identifying prognostic factors measurable before ECMO initiation should help define the optimal ECPR initiation strategy.

Life-Threatening Hemoptysis in a Pediatric Referral Center.

Abstract: OBJECTIVES Hemoptysis is uncommon in children, even among the critically ill, with a paucity of epidemiological data to inform clinical decision-making. We describe hemoptysis-associated ICU admissions, including those who were critically ill at hemoptysis onset or who became critically ill as a result of hemoptysis, and identify predictors of mortality. DESIGN Retrospective cohort study. Demographics, hemoptysis location, and management were collected. Pediatric Logistic Organ Dysfunction-2 score within 24 hours of hemoptysis described illness severity. Primary outcome was inhospital mortality. SETTING Quaternary pediatric referral center between July 1, 2010, and June 30, 2017. PATIENTS Medical/surgical (PICU), cardiac ICU, and term neonatal ICU admissions with hemoptysis during or within 24 hours of ICU admission. INTERVENTIONS No intervention. MEASUREMENTS AND MAIN RESULTS There were 326 hemoptysis-associated ICU admissions in 300 patients. Most common diagnoses were cardiac (46%), infection (15%), bronchiectasis (10%), and neoplasm (7%). Demographics, interventions, and outcomes differed by diagnostic category. Overall, 79 patients (26%) died inhospital and 109 (36%) had died during follow-up (survivor mean 2.8 ± 1.9 yr). Neoplasm, bronchiectasis, renal dysfunction, inhospital hemoptysis onset, and higher Pediatric Logistic Organ Dysfunction-2 score were independent risk factors for inhospital mortality (p < 0.02). Pharmacotherapy (32%), blood products (29%), computerized tomography angiography (26%), bronchoscopy (44%), and cardiac catheterization (36%) were common. Targeted surgical interventions were rare. Of survivors, 15% were discharged with new respiratory support. Of the deaths, 93 (85%) occurred within 12 months of admission. For patients surviving 12 months, 5-year survival was 87% (95% CI, 78-92) and mortality risk remained only for those with neoplasm (log-rank p = 0.001). CONCLUSIONS We observed high inhospital mortality from hemoptysis-associated ICU admissions. Mortality was independently associated with hemoptysis onset location, underlying diagnosis, and severity of critical illness at event. Additional mortality was observed in the 12-month posthospital discharge. Future directions include further characterization of this vulnerable population and management recommendations for life-threatening pediatric hemoptysis incorporating underlying disease pathophysiology.

Use of ecmo for cardiogenic shock in pediatric population

Abstract: In children with severe advanced heart failure where medical management has failed, mechanical circulatory support in the form of veno-arterial extracorporeal membrane oxygenation (VA ECMO) or ventricular assist device represents life-sustaining therapy. This review provides an overview of VA ECMO used for cardiovascular support including medical and surgical heart disease. Indications, contraindications, and outcomes of VA ECMO in the pediatric population are discussed.VA ECMO provides biventricular and respiratory support and can be deployed in rapid fashion to rescue patient with failing physiology. There have been advances in conduct and technologic aspects of VA ECMO, but survival outcomes have not improved. Stringent selection and optimal timing of deployment are critical to improve mortality and morbidity of the patients supported with VA ECMO.

Cardiopulmonary Resuscitation and Rescue Therapies.

Abstract: The history of cardiopulmonary resuscitation and the Society of Critical Care Medicine have much in common, as many of the founders of the Society of Critical Care Medicine focused on understanding and improving outcomes from cardiac arrest. We review the history, the current, and future state of cardiopulmonary resuscitation.

Elective Non-Urgent Balloon-Atrial Septostomy in Infants with d-Transposition of the Great Arteries Does Not Eliminate the Need for PGE1 Therapy at the Time of Arterial Switch Operation

Abstract: Once a mainstay in the treatment of neonates with d-transposition of the great arteries (d-TGA), the application of balloon atrial septostomy (BAS) in the d-TGA population has become more selective. Currently, there is no clear evidence for or against a selective BAS strategy. The aims of this single-center retrospective study were to determine the incidence of BAS in the neonatal d-TGA population in the current era, to measure the rate of procedural success, and to compare the outcomes and complication rates of patients who underwent BAS to those who underwent neonatal ASO alone. Between 2012 and 2018, 147 patients with d-TGA underwent initial medical management and ASO, 73 of which underwent BAS. The percentage of patients that underwent BAS decreased from 73 to 33% over the study time period. In patients with d-TGA with intact ventricular septum, 33% of patients remained off of PGE1 at the time of surgery regardless of BAS. In d-TGA with ventricular septal defect, 85.7% of those that underwent BAS and 54.1% of those who did not remained off of PGE1 at the time of surgery, however, this difference did not reach statistical significance. In this single institution retrospective cohort of patients with d-TGA, the performance of a technically successful balloon atrial septostomy did not eliminate the need for PGE1 therapy at the time of definitive ASO. This was true regardless of the presence or absence of a ventricular septal defect.