Publications by authors named "Lakshmi Raman"

56 Publications

3-Hydroxypropane-1,2-Diyl Dipalmitoleate-A Natural Compound with Dual Roles (CB1 Agonist/FAAH1 Blocker) in Inhibiting Ovarian Cancer Cell Line.

Pharmaceuticals (Basel) 2021 Mar 12;14(3). Epub 2021 Mar 12.

Department of Biotechnology, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research (SRIHER), Deemed to be University (DU), Porur, Chennai, Tamil Nadu 600 116, India.

Though it was once known that upregulated Cannabinoid Receptor (CB1) and downregulated Fatty Acid Amide Hydrolase (FAAH1) are associated with tumour aggressiveness and metastasis, it is now clear that upregulated CB1 levels more than a certain point cause accumulation of ceramide and directs cells to apoptosis. Hence, CB1 analogues/FAAH1 blockers are explored widely as anticancer drugs. There are reports on CB1-agonists and FAAH1-blockers separately, however, dual activities along with ovarian cancer-specific links are not established for any natural compound. With this setting, we describe for the first time the isolation of 3-hydroxypropane-1,2-diyl dipalmitoleate (564.48 Da) from a marine snail, which binds to both CB1 and FAAH1 (glide energies: -70.61 and -30.52 kcal/mol, respectively). MD simulations indicate stable compound-target interaction for a minimum of 50 nanoseconds with relative invariabilities in . The compound inhibited ovarian cancer cell line, PA1 at 1.7 μM. Structural and chemical interpretation of the compound () was done using FT-IR, GC-MS, ESI-MS, H and C-NMR (1 and 2D). Furthermore, a probable route for gram-scale synthesis of is hinted herein. With the available preliminary data, molecular mechanisms involving dual roles for this potent molecule must be elucidated to understand the possibilities of usage as an anticancer drug.
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http://dx.doi.org/10.3390/ph14030255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998876PMC
March 2021

Guidelines for Pediatric Cardiac Failure Extracorporeal Life Support Organization ECLS Guidelines 2020.

ASAIO J 2021 Mar 29. Epub 2021 Mar 29.

From the Cardiac Intensive Care Unit, The Royal Children's Hospital, Melbourne, Australia Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, Maryland Cardiorespiratory and Critical Care Division, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Department of Pediatrics, Critical Care Division, Le Bonheur Children's Hospital, University of Tennessee, Memphis, Tennessee Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota Pediatric Cardiology Division, Heart Transplant and Advanced Cardiac Therapies Program, Children's National Heart Institute, Washington, D.C. Children's Intensive Care Unit, Department of Paediatric Subspecialties, KK Women's and Children's Hospital, Singapore Department of Critical Care, University of Texas Southwestern Medical Center, Texas Leiden University Medical Centre, Leiden, Netherlands National University Heart Centre, Singapore UF Shands Children's Hospital, Gainesville, Florida.

These guidelines are applicable to neonates and children with cardiac failure as indication for extracorporeal life support (ELSO). These guidelines address patient selection, management during extracorporeal membrane oxygenation, and pathways for weaning support or bridging to other therapies. Equally important issues, such as personnel, training, credentialing, resources, follow-up, reporting, and quality assurance, are addressed in other ELSO documents or are center-specific.
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http://dx.doi.org/10.1097/MAT.0000000000001431DOI Listing
March 2021

ECMO for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization (ELSO).

ASAIO J 2021 Feb 26. Epub 2021 Feb 26.

Department of Emergency Medicine, University of Washington, USA Division of Pulmonary Critical Care and Sleep Medicine, University of Washington, USA General ICU, University Hospital of Parma, Italy Department of Biomedical, Metabolic and Neural Sciences, University of Modena & Reggio Emilia, Italy Extracorporeal Life Support Organization Texas Children's Hospital, Baylor College of Medicine Children's Medical Center of Dallas, University of Texas Southwestern Medical Center Extracorporeal Life Support Organization, President; Children's Healthcare of Atlanta, Emory University Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, USA University of Michigan Department of Critical Care, Guy's and St. Thomas' NHS Foundation Trust Centre for Human & Applied Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London Sorbonne Université, INSERM, Institute of Cardiometabolism and Nutrition Service de médecine intensive-réanimation, Institut de Cardiologie, APHP Sorbonne Université Hôpital Pitié-Salpêtrière, F-75013 PARIS, France Department of Cardio-Thoracic Surgery - Maastricht University Medical Centre - Cardiovascular Research Institute Maastricht Maastricht, The Netherlands Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany Nemours Children's Health System Congenital Heart Center, Departments of Surgery and Pediatrics, University of Florida, Gainesville, USA Intensive Care Unit, Alfred Health Melbourne, Victoria, Australia Critical Care ECMO service, King Saud Medical City - Ministry Of Health (MOH), Riyadh - Saudi Arabia. Fundación Cardiovascular de Colombia Service de Médecine Intensive-Réanimation, Institut de Cardiologie, AP-HP, Sorbonne Université Hôpital Pitié-Salpêtrière, Paris, France. Sorbonne Université, GRC n°30, GRC RESPIRE, INSERM, UMRS_1166-ICAN, Institute of Cardiometabolism and Nutrition, Paris, France. Adult Intensive Care Services, The Prince Charles Hospital, Brisbane, Queensland, Australia National University Hospital, Singapore Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA Center for Acute Respiratory Failure, New York-Presbyterian Hospital, New York, USA.

This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.
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http://dx.doi.org/10.1097/MAT.0000000000001422DOI Listing
February 2021

Pediatric Extracorporeal Cardiopulmonary Resuscitation ELSO Guidelines.

ASAIO J 2021 03;67(3):229-237

Department of Pediatrics, UTSouthwestern Medical Center, Dallas, Texas.

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http://dx.doi.org/10.1097/MAT.0000000000001345DOI Listing
March 2021

Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization.

ASAIO J 2021 03;67(3):221-228

From the The Alfred Hospital, Melbourne, Australia.

Disclaimer: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.
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http://dx.doi.org/10.1097/MAT.0000000000001344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984716PMC
March 2021

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

Crit Care Med 2021 04;49(4):682-692

University of Texas Southwestern Medical Center, Dallas, TX.

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.
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http://dx.doi.org/10.1097/CCM.0000000000004882DOI Listing
April 2021

Role of extracorporeal membrane oxygenation in children with sepsis: a systematic review and meta-analysis.

Crit Care 2020 12 7;24(1):684. Epub 2020 Dec 7.

Cardiothoracic Intensive Care Unit, Department of Cardiothoracic Surgery, National University Hospital, Singapore, 119228, Singapore.

Background: The benefits of extracorporeal membrane oxygenation (ECMO) in children with sepsis remain controversial. Current guidelines on management of septic shock in children recommend consideration of ECMO as salvage therapy. We sought to review peer-reviewed publications on effectiveness of ECMO in children with sepsis.

Methods: Studies reporting on mortality in children with sepsis supported with ECMO, published in PubMed, Scopus and Embase from 1972 till February 2020, were included in the review. This study was done in adherence to Preferred Reporting Items for Systematic Review and Meta-Analysis statement after registering the review protocol with PROSPERO. Study eligibility was independently assessed by two authors and disagreements resolved by a third author. Publications were reviewed for quality using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Random-effects meta-analyses (DerSimonian and Laird) were conducted, and 95% confidence intervals were computed using the Clopper-Pearson method. Outliers were identified by the Baujat plot and leave-one-out analysis if there was considerable heterogeneity. The primary outcome measure was survival to discharge. Secondary outcome measures included hospital length of stay, subgroup analysis of neonatal and paediatric groups, types and duration of ECMO and complications .

Results: Of the 2054 articles screened, we identified 23 original articles for systematic review and meta-analysis. Cumulative estimate of survival (13 studies, 2559 patients) in the cohort was 59% (95%CI: 51-67%). Patients had a median length of hospital stay of 28.8 days, median intensive care unit stay of 13.5 days, and median ECMO duration of 129 h. Children needing venoarterial ECMO (9 studies, 208 patients) showed overall pooled survival of 65% (95%CI: 50-80%). Neonates (< 4 weeks of age) with sepsis needing ECMO (7 studies, 85 neonates) had pooled survival of 73% (95%CI: 56- 87%). Gram positive organisms were the most common pathogens (47%) in septic children supported with ECMO.

Conclusion: Survival rates of children with sepsis needing ECMO was 59%. Neonates had higher survival rates (73%); gram positive organisms accounted for most common infections in children needing ECMO. Despite limitations, pooled survival data from this review indicates consideration of ECMO in refractory septic shock for all pediatric age groups.
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http://dx.doi.org/10.1186/s13054-020-03418-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720382PMC
December 2020

Surveying the Scene: Timing Is Everything.

Pediatr Crit Care Med 2020 10;21(10):902-903

Pediatric Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX INOVA Fairfax Medical Center; Program Development and Research, ECLS; Pediatrics; and Heart and Vascular Institute Falls Church, VA.

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http://dx.doi.org/10.1097/PCC.0000000000002518DOI Listing
October 2020

Neural Networks to Predict Radiographic Brain Injury in Pediatric Patients Treated with Extracorporeal Membrane Oxygenation.

J Clin Med 2020 Aug 22;9(9). Epub 2020 Aug 22.

Children's Health Dallas, Dallas, TX 75201, USA.

Brain injury is a significant source of morbidity and mortality for pediatric patients treated with Extracorporeal Membrane Oxygenation (ECMO). Our objective was to utilize neural networks to predict radiographic evidence of brain injury in pediatric ECMO-supported patients and identify specific variables that can be explored for future research. Data from 174 ECMO-supported patients were collected up to 24 h prior to, and for the duration of, the ECMO course. Thirty-five variables were collected, including physiological data, markers of end-organ perfusion, acid-base homeostasis, vasoactive infusions, markers of coagulation, and ECMO-machine factors. The primary outcome was the presence of radiologic evidence of moderate to severe brain injury as established by brain CT or MRI. This information was analyzed by a neural network, and results were compared to a logistic regression model as well as clinician judgement. The neural network model was able to predict brain injury with an Area Under the Curve (AUC) of 0.76, 73% sensitivity, and 80% specificity. Logistic regression had 62% sensitivity and 61% specificity. Clinician judgment had 39% sensitivity and 69% specificity. Sequential feature group masking demonstrated a relatively greater contribution of physiological data and minor contribution of coagulation factors to the model's performance. These findings lay the foundation for further areas of research directions.
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http://dx.doi.org/10.3390/jcm9092718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565544PMC
August 2020

EEG is A Predictor of Neuroimaging Abnormalities in Pediatric Extracorporeal Membrane Oxygenation.

J Clin Med 2020 Aug 4;9(8). Epub 2020 Aug 4.

Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.

The goal of this project was to evaluate if severity of electroencephalogram (EEG) during or shortly after being placed on extracorporeal membrane oxygenation (ECMO) would correlate with neuroimaging abnormalities, and if that could be used as an early indicator of neurologic injury. This was a retrospective chart review spanning November 2009 to May 2018. Patients who had an EEG recording during ECMO or within 48 hours after being decannulated (early group) or within 3 months of being on ECMO (late group) were included if they also had ECMO-related neuroimaging. In the early EEG group, severity of the EEG findings of mild, moderate, and severe EEG correlated to mild, moderate, and severe neuroimaging scores. Patients on venoarterial (VA) ECMO were noted to have higher EEG and neuroimaging severity; this was statistically significant. There was no association in the late EEG group to neuroimaging abnormalities. Our study highlights that EEG severity can be an early predictor for neuroimaging abnormalities that can be identified by computed tomography (CT) and or magnetic resonance imaging (MRI). This can provide guidance for both the medical team and families, allowing for a better understanding of overall prognosis.
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http://dx.doi.org/10.3390/jcm9082512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7463499PMC
August 2020

Choice of ECMO as a Therapy in COVID-19?

ASAIO J 2020 08;66(8):e112

Division of Pediatric Critical Care, Emory University, Atlanta, Georgia.

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http://dx.doi.org/10.1097/MAT.0000000000001235DOI Listing
August 2020

Extracorporeal Life Support Organization (ELSO): 2020 Pediatric Respiratory ELSO Guideline.

ASAIO J 2020 Sep/Oct;66(9):975-979

From the Interdivisional Department of Critical Care Medicine, University of Toronto, Ontario, Canada.

Disclaimer: This guideline describes prolonged extracorporeal life support (ECLS) and extracorporeal membrane oxygenation (ECMO), applicable to Pediatric respiratory failure. These guidelines describe useful and safe practice, prepared by ELSO and based on extensive experience and are considered consensus guidelines. These guidelines are not intended to define standard of care and are revised at regular intervals as new information, devices, medications, and techniques become available.
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http://dx.doi.org/10.1097/MAT.0000000000001223DOI Listing
March 2021

Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers.

ASAIO J 2020 Jul;66(7):707-721

The Alfred, Melbourne, Victoria, Australia.

Disclaimer: The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.
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http://dx.doi.org/10.1097/MAT.0000000000001193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228451PMC
July 2020

Cerebral Hemodynamic Profile in Ischemic and Hemorrhagic Brain Injury Acquired During Pediatric Extracorporeal Membrane Oxygenation.

Pediatr Crit Care Med 2020 10;21(10):879-885

Children's Health in Dallas, Dallas, TX.

Objectives: To describe the cerebral hemodynamic profiles associated with ischemic and hemorrhagic brain injury during neonatal and pediatric extracorporeal membrane oxygenation.

Design: A retrospective cohort study.

Setting: Tertiary PICU.

Patients: Forty-seven neonatal and pediatric patients (0-15 yr of age) placed on extracorporeal membrane oxygenation from January 2014 to December 2018.

Measurements And Main Results: Continuous monitoring of mean arterial pressure and cerebral tissue oxygen saturation was conducted through entire extracorporeal membrane oxygenation run. Wavelet analysis was performed to assess changes in cerebral autoregulation and to derive pressure-dependent autoregulation curves based on the mean arterial pressure and cerebral tissue oxygen saturation data. Patients were classified into three brain injury groups: no-injury, ischemic injury, and hemorrhagic injury based on neuroimaging results. No-injury patients (n = 23) had minimal variability in the autoregulation curve over a broad range of blood pressure. Ischemic injury (n = 16) was more common than hemorrhagic injury (n = 8), and the former was associated with increased mortality and morbidity. Ischemic group showed significant abnormalities in cerebral autoregulation in the lower blood pressure range, suggesting pressure-dependent cerebral perfusion. Hemorrhagic group had highest average blood pressure as well as the lowest cerebral tissue oxygenation saturation, suggesting elevated cerebral vascular resistance. Mean heparin dose during extracorporeal membrane oxygenation was lower in both ischemic and hemorrhagic groups compared with the no-injury group.

Conclusions: This study outlines distinct differences in underlying cerebral hemodynamics associated with ischemic and hemorrhagic brain injury acquired during extracorporeal membrane oxygenation. Real-time monitoring of cerebral hemodynamics in patients acquiring brain injury during extracorporeal membrane oxygenation can help optimize their management.
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http://dx.doi.org/10.1097/PCC.0000000000002438DOI Listing
October 2020

Position Paper on Global Extracorporeal Membrane Oxygenation Education and Educational Agenda for the Future: A Statement From the Extracorporeal Life Support Organization ECMOed Taskforce.

Crit Care Med 2020 03;48(3):406-414

Department of Pediatrics, Division of Neonatology, Nemours Alfred I duPont Hospital for Children, Wilmington, DE.

Objectives: The purpose of this position paper is two-fold: first, to describe the state of extracorporeal membrane oxygenation education worldwide, noting current limitations and challenges; and second, to put forth an educational agenda regarding opportunities for an international collaborative approach toward standardization.

Design: Relevant medical literature was reviewed through literature search, and materials from national organizations were accessed through the Internet. Taskforce members generated a consensus statement using an iterative consensus process through teleconferences and electronic communication.

Setting: In 2018, the Extracorporeal Life Support Organization convened the ECMOed Taskforce at two structured, face-to-face meetings of 40 healthcare practitioners and educators with expertise in caring for the extracorporeal membrane oxygenation patient and in extracorporeal membrane oxygenation education.

Patients: None.

Interventions: None.

Measurements And Main Results: The ECMOed Taskforce identified seven educational domains that would benefit from international collaborative efforts. Of primary importance, the Taskforce outlined actionable items regarding 1) the creation of a standardized extracorporeal membrane oxygenation curriculum; 2) defining criteria for an extracorporeal membrane oxygenation course as a vehicle for delivering the curriculum; 3) outlining a mechanism for evaluating the quality of educational offerings; 4) utilizing validated assessment tools in the development of extracorporeal membrane oxygenation practitioner certification; and 5) promoting high-quality educational research to guide ongoing educational and competency assessment development.

Conclusions: Significant variability and limitations in global extracorporeal membrane oxygenation education exist. In this position paper, we outline a road map for standardizing international extracorporeal membrane oxygenation education and practitioner certification. Ongoing high-quality educational research is needed to evaluate the impact of these initiatives.
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http://dx.doi.org/10.1097/CCM.0000000000004158DOI Listing
March 2020

Successful Use of Pulmonary Cryotherapy for Tracheobronchial Thrombus Extraction and Recanalization of the Tracheobronchial Tree During a Pediatric Venovenous Extracorporeal Membrane Oxygenation Run.

Pediatr Allergy Immunol Pulmonol 2019 Mar 18;32(1):28-30. Epub 2019 Mar 18.

Division of Pediatric Intensive Care, Department of Pediatrics, University of Texas Southwestern, Dallas, Texas.

Impacted pediatric tracheobronchial thrombus is an uncommon diagnosis. There are no clearly proven therapeutic options for airway casts due to a similar process, plastic bronchitis. Cryotherapy, specifically cryoextraction, has shown potential as a therapeutic option in adults with tracheobronchial thrombus and cast. We describe the novel application of this method in a complex pediatric patient.
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http://dx.doi.org/10.1089/ped.2018.0911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733042PMC
March 2019

Neurodevelopmental Outcomes in Extracorporeal Membrane Oxygenation Patients: A Pilot Study.

ASAIO J 2020 04;66(4):447-453

From the Department of Pediatrics, University of Texas Southwestern Medical Center.

In this pilot study, we evaluated the long-term neurodevelopmental outcomes in neonatal and pediatric patients supported by extracorporeal membrane oxygenation (ECMO) and aimed to identify the role of post-ECMO magnetic resonance imaging (MRI) in predicting neurodevelopmental outcomes. Twenty-nine patients were evaluated using the Ages and Stages Questionnaire, Third Edition (ASQ-3) screening tool. Thirteen were evaluated during their visit at the neurodevelopmental clinic and 16 were interviewed via phone. We also reviewed the post-ECMO MRI brain of these patients and scored the severity of their injury based on the neuroimaging findings. In our cohort of 29 patients, 10 patients (34%) had developmental delay. Of those with developmental delay, 80% were newborns. Sixty-seven percent of patients with developmental delay had moderate to severe MRI abnormalities as compared with only 18% with no developmental deficits (p = 0.03). The younger the age at the time of placement on ECMO, the higher the chances of impaired neurodevelopmental outcome. Long-term follow-up of patients who have survived ECMO, with standardized neuropsychologic testing and post-ECMO imaging, should become the standard of care to improve long-term outcomes. Significant abnormalities on brain MRIs done before discharge correlated with developmental delay on follow-up.
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http://dx.doi.org/10.1097/MAT.0000000000001035DOI Listing
April 2020

The Use of Extracorporeal Membrane Oxygenation in Life-Threatening Foreign Body Aspiration: Case Series, Review of Extracorporeal Life Support Organization Registry Data, and Systematic Literature Review.

J Emerg Med 2019 May 14;56(5):523-529. Epub 2019 Mar 14.

Division of Critical Care Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center/Children's Health, Dallas, Texas.

Background: Foreign body aspiration (FBA) is a common cause of morbidity and mortality in children < 3 years of age. Guidelines recommend performing a bronchoscopy in any suspected or confirmed FBA. Extracorporeal membrane oxygenation (ECMO) can be used as a rescue mode of support in children with life-threatening FBA for stabilization before, during, and after removal.

Case Report: We present a series of children with life-threatening FBA who were placed on ECMO for stabilization before or after FB removal and a review of the literature and the Extracorporeal Life Support Organization database. Foreign bodies were removed without complications, and all patients survived ECMO support and were promptly discharged home. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: ECMO can be safely used in the stabilization of children with life-threatening FBA before, during, and after bronchoscopic removal. ECMO should be considered in the stabilization of children presenting with FBA to facilitate removal.
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http://dx.doi.org/10.1016/j.jemermed.2019.01.036DOI Listing
May 2019

A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury.

Crit Care Med 2019 03;47(3):e206-e213

Departments of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX.

Objectives: Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.

Design: A single center prospective observational study.

Setting: Pediatric and cardiac ICUs at a single tertiary care, academic center.

Patients: Twenty pediatric extracorporeal membrane oxygenation patients (0-14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patients INTERVENTIONS:: None.

Measurements And Main Results: Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10-23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n = 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p < 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation.

Conclusions: We show that pediatric extracorporeal membrane oxygenation patients with acquired brain injury exhibit an induction of pro-inflammatory cell signaling, a robust activation of adaptive immune cells, and CNS-targeting adaptive immune responses. As these patients experience developmental delays for years after extracorporeal membrane oxygenation, it is critical to identify and characterize adaptive immune cell mechanisms that target the developing CNS.
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http://dx.doi.org/10.1097/CCM.0000000000003621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6377324PMC
March 2019

Tau Is Elevated in Pediatric Patients on Extracorporeal Membrane Oxygenation.

ASAIO J 2020 01;66(1):91-96

*Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas.

Neurologic injury is a known and feared complication of extracorporeal membrane oxygenation (ECMO). Neurologic biomarkers may have a role in assisting in early identification of such. Axonal biomarker tau has not been investigated in the pediatric ECMO population. The objective of this study is to evaluate plasma levels of tau in pediatric patients supported with ECMO. Eighteen patients requiring ECMO support in a quaternary pediatric intensive care unit at a university-affiliated children's hospital from October 2015 to February 2017 were enrolled. Patients undergoing extracorporeal cardiopulmonary resuscitation or recent history of bypass were excluded. Plasma tau was measured using enzyme-linked immunosorbent assay. Neuroimaging was reviewed for acute neurologic injury, and tau levels were analyzed to assess for correlation. Tau was significantly higher in ECMO patients than in control subjects. Sixty-one percent of subjects had evidence of acute brain injury on neuroimaging, but tau level did not correlate with injury. Subjects with multifocal injury all experienced infarction and had significantly higher tau levels on ECMO day 3 than patients with isolated injury. In addition, peak tau levels of neuro-injured subjects were compared with controls and noninjured ECMO subjects using receiver operating curve analysis. This study demonstrates preliminary evidence of axonal injury in pediatric ECMO patients.
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http://dx.doi.org/10.1097/MAT.0000000000000923DOI Listing
January 2020

RBC Exposure in Pediatric Extracorporeal Membrane Oxygenation: Confusion Without Consensus.

Pediatr Crit Care Med 2018 08;19(8):787-788

Department of Child Health, Phoenix Children's Hospital, Phoenix, AZ Pediatric Intensive Care Unit, Stollery Children's Hospital, Edmonton, AB, Canada Department of Pediatrics, Section Critical Care Medicine, University of Texas Southwestern Medical Center at Dallas, Children's Medical Center at Dallas, Dallas, TX.

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http://dx.doi.org/10.1097/PCC.0000000000001623DOI Listing
August 2018

Highlights from the Extracorporeal Life Support Organization Registry: 2006-2017.

ASAIO J 2019 08;65(6):537-544

Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts.

Extracorporeal membrane oxygenation (ECMO) is a supportive therapy for patients with severe cardiovascular or respiratory failure refractory to conventional medical therapy. Improvements in ECMO technology, easy access to ECMO devices, and a greater understanding of care of ECMO patients have led to increased utilization of ECMO. The Extracorporeal Life Support Organization (ELSO) registry was established in 1984, to collect data on patients receiving ECMO support to help improve outcomes of these patients. The registry has grown to include over 400 contributing centers from 60 countries with data for more than 90,000 patients. Many investigators have used the ELSO registry to answer clinical questions on outcomes and care of this vulnerable patient population. This report provides a brief summary of 16 peer-reviewed articles that have advanced the knowledge and treatment of neonates, children, and adults supported with ECMO using data from the ELSO registry.
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http://dx.doi.org/10.1097/MAT.0000000000000863DOI Listing
August 2019

Pediatric Extracorporeal Membrane Oxygenation.

Crit Care Clin 2017 Oct 29;33(4):825-841. Epub 2017 Jul 29.

Department of Pediatrics, Adult and Pediatric ECMO, INOVA Fairfax Medical Center, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA; George Washington University, 2121 I Street Northwest, Washington, DC 20052, USA. Electronic address:

Extracorporeal life support is a modified form of cardiopulmonary bypass. Experience in extracorporeal membrane oxygenation (ECMO) has come largely from the neonatal population. Most centers have transitioned the ECMO pumps from roller pumps to centrifugal technology. Modes of support include venovenous for respiratory support and venoarterial for cardiac support. "Awake" ECMO is the trend with extubation and tracheostomy on the rise. Fluid overload is common and managed with diuretics or hemofiltration. Nutrition is important and provided enterally or via total parenteral nutrition. Overall survival for pediatric cardiac and respiratory ECMO has remained at approximately 50% to 60%.
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http://dx.doi.org/10.1016/j.ccc.2017.06.005DOI Listing
October 2017

Impairment of cerebral autoregulation in pediatric extracorporeal membrane oxygenation associated with neuroimaging abnormalities.

Neurophotonics 2017 Oct 19;4(4):041410. Epub 2017 Aug 19.

University of Texas Southwestern Medical Center, Department of Pediatrics, Dallas, Texas, United States.

Extracorporeal membrane oxygenation (ECMO) is a life-supporting therapy for critically ill patients with severe respiratory and/or cardiovascular failure. Cerebrovascular impairment can result in hemorrhagic and ischemic complications commonly seen in the patients supported on ECMO. We investigated the degree of cerebral autoregulation impairment during ECMO as well as whether it is predictive of neuroimaging abnormalities. Spontaneous fluctuations of mean arterial pressure (MAP) and cerebral tissue oxygen saturation ([Formula: see text]) were continuously measured during the ECMO run. The dynamic relationship between the MAP and [Formula: see text] fluctuations was assessed based on wavelet transform coherence (WTC). Neuroimaging was conducted during and/or after ECMO as standard of care, and the abnormalities were evaluated based on a scoring system that had been previously validated among ECMO patients. Of the 25 patients, 8 (32%) had normal neuroimaging, 7 (28%) had mild to moderate neuroimaging abnormalities, and the other 10 (40%) had severe neuroimaging abnormalities. The degrees of cerebral autoregulation impairment quantified based on WTC showed significant correlations with the neuroimaging scores ([Formula: see text]; [Formula: see text]). Evidence that cerebral autoregulation impairment during ECMO was related to the patients' neurological outcomes was provided.
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http://dx.doi.org/10.1117/1.NPh.4.4.041410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562949PMC
October 2017

Coagulation Profile Is Not a Predictor of Acute Cerebrovascular Events in Pediatric Extracorporeal Membrane Oxygenation Patients.

ASAIO J 2017 Nov/Dec;63(6):793-801

From the *Department of Pediatrics, Critical Care Division, University of Texas Southwestern Medical Center, Dallas, Texas; †Department of Pediatrics, Hematology-Oncology Division, University of Texas Southwestern Medical Center, Dallas, Texas; ‡Department of Pediatrics, Critical Care Division, University of Texas Health Science Center at Houston, Houston, Texas; §Department of Pediatrics, Neurology Division, University of Texas Southwestern Medical Center, Dallas, Texas; and ¶Trauma Services Children's Health Dallas, Dallas, Texas.

We performed a retrospective matched case-control study evaluating whether the traditional coagulation profile predicts cerebrovascular events in children on extracorporeal membrane oxygenation (ECMO) in a 71 bed intensive care unit at a tertiary children's hospital. Between 2009 and 2014, 241 neonates and children were initiated on ECMO. The cumulative 5 year incidence of intracranial hemorrhage and infarct was 9.2% and 7.9%, respectively. Thirty-six cases were individually matched 1:1 with control subjects based on age, primary diagnosis, ECMO type, cannulation site, and the presence of pre-ECMO coagulopathy. In-hospital mortality was higher among the cases compared with control subjects (78 vs. 22%, p < 0.01). The median laboratory values that assisted with heparin anticoagulation monitoring (activated clotting time, partial thromboplastin time, and antifactor Xa) and the laboratory data that assisted with blood product administration (platelet count, prothrombin time, fibrinogen, and d-dimer) during the 24 and 72 hour periods before the cerebrovascular event did not show any significant difference between the hemorrhage group and their controls or between the infarct group and their controls. The traditional coagulation profile did not predict acute cerebrovascular events in our cohort. Other markers of neurologic injury on ECMO are yet to be elucidated. Prospective studies to determine better predictors of cerebrovascular complications in pediatric ECMO patients are required.
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http://dx.doi.org/10.1097/MAT.0000000000000571DOI Listing
May 2018

Pediatric Extracorporeal Life Support Organization Registry International Report 2016.

ASAIO J 2017 Jul/Aug;63(4):456-463

From the *Department of Pediatrics, C.S. Mott Children's Hospital, Ann Arbor, Michigan; †Department of Pediatrics, School of Medicine, Emory University, Atlanta, Georgia; ‡Department of Surgery, University of California Irvine Medical Center, Irvine, California; §Department of Pediatrics, University of Texas Southwestern, Dallas, Texas; ¶Department of Pediatrics, Stollery Children's Hospital, Edmonton, Alberta, Canada; ‖Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; #Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts; **Department of Anesthesiology and Critical Care Medicine, John Hopkins University, Baltimore, Maryland; and ††Extracorporeal Life Support Organization, Ann Arbor, Michigan.

The purpose of this report is to describe the international growth, outcomes, complications, and technology used in pediatric extracorporeal life support (ECLS) from 2009 to 2015 as reported by participating centers in the Extracorporeal Life Support Organization (ELSO). To date, there are 59,969 children who have received ECLS in the ELSO Registry; among those, 21,907 received ECLS since 2009 with an overall survival to hospital discharge rate of 61%. In 2009, 2,409 ECLS cases were performed at 157 centers. By 2015, that number grew to 2,992 cases in 227 centers, reflecting a 24% increase in patients and 55% growth in centers. ECLS delivered to neonates (0-28 days) for respiratory support was the largest subcategory of ECLS among children <18-years old. Overall, 48% of ECLS was delivered for respiratory support and 52% was for cardiac support or extracorporeal life support to support cardiopulmonary resuscitation (ECPR). During the study period, over half of children were supported on ECLS with centrifugal pumps (51%) and polymethylpentene oxygenators (52%). Adverse events including neurologic events were common during ECLS, a fact that underscores the opportunity and need to promote quality improvement work.
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http://dx.doi.org/10.1097/MAT.0000000000000603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626007PMC
February 2018

An International Survey on Ventilator Practices Among Extracorporeal Membrane Oxygenation Centers.

ASAIO J 2017 Nov/Dec;63(6):787-792

From the *Department of Pediatrics, Baylor College of Medicine, Houston, Texas; †Department of Pediatrics, Texas Children's Hospital, Houston, Texas; ‡Children's Medical Center at Dallas part of Children's Health (SM), Dallas, Texas; §Department of Accounting, University of Texas at Arlington, Arlington, Texas; and ¶Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas.

Although the optimal ventilation strategy is unknown for patients placed on extracorporeal support, there are increasing reports of extubation being used. Our objective was to describe the change in ventilation strategies and use of tracheostomy and bronchoscopy practices among extracorporeal membrane oxygenation (ECMO) centers across the world. A descriptive, cross-sectional 22 item survey of neonatal, pediatric, and adult ECMO centers was used to evaluate ventilator strategies, extubation, bronchoscopy, and tracheostomy practices. Extubation practices are increasing among all types of ECMO centers, representing 27% of all patients in pediatric centers, 41% of all patients in mixed centers, and 52% of all patients in adult centers. The most common mode of ventilation during ECMO is pressure control. There is a trend toward increased use of bilevel ventilation particularly for lung recruitment. Additionally, there is a trend toward increase in performance of bronchoscopy (pediatrics: 69%, mixed centers: 81%, adults: 76%) and tracheostomy. Among the centers performing tracheostomies, 45% reported the percutaneous method (pediatric: 31%, mixed: 46%, adult: 57%), 19% reported the open method (pediatric: 9%, mixed: 27%, adult: 24%), and 10% reported using both types of tracheostomies (pediatric: 2%, mixed: 8%, adult: 16%). Our study shows that ECMO centers are extubating their patients, performing tracheostomies and bronchoscopies on their patients more than in the previous years. There remains significant variation in ECMO ventilator strategies and management internationally. Future studies are needed to correlate these changes in practices to outcome benefits.
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http://dx.doi.org/10.1097/MAT.0000000000000575DOI Listing
May 2018

High Hemoglobin Is an Independent Risk Factor for the Development of Hemolysis During Pediatric Extracorporeal Life Support.

J Intensive Care Med 2019 Mar 10;34(3):259-264. Epub 2017 May 10.

Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.

Objective: To evaluate risk factors for hemolysis in pediatric extracorporeal life support.

Design: Retrospective, single-center study.

Setting: Pediatric intensive care unit.

Patients: Two hundred thirty-six children who received extracorporeal membrane oxygenation.

Interventions: None.

Measurements And Main Results: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group.

Conclusions: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only.
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http://dx.doi.org/10.1177/0885066617708992DOI Listing
March 2019