Previous Studies & Results

ABC PICU: The Age of Blood in Children in Pediatric Intensive Care Units

• Principal Site Investigator: Katri Typpo, MD, MPH
• ABC PICU was a randomized clinical trial that compared the clinical consequences of red blood cell (RBC) storage duration in 1538 critically ill children. Physicians and institutions have been systematically transfusing fresh RBCs to some pediatric patients primarily because of beliefs that the use of fresh RBCs improve outcomes. Conversely, the standard practice of blood banks is to deliver the oldest RBC unit in order to decrease blood wastage. To determine if RBCs of reduced storage duration improved outcomes, ABC PICU conducted a trial comparing development of New or Progressive Multiple Organ Dysfunction Syndrome (NPMODS) in critically ill children transfused with either RBCs stored ≤ 7 days or standard issue RBCs (expected mean RBC storage duration of 17-21 days).
• More information and publications for ABC PICU can be found here.

BACON: Bronchiolitis and Co-Detection Study

• Principal Site Investigator: Mary Gaspers, MD, MPH
• It is important to investigate bacterial co-detection, or the detection of multiple bacterial pathogens, in a systematic and multicenter fashion. Understanding the true prevalence of co-detection and its clinical impact could alter how we choose to treat these patients, particularly from an antibiotic standpoint. This large, multi-center study allowed investigators to account for the wide variability in clinical practice seen in critical bronchiolitis and may facilitate a better understanding of who may truly benefit from antibiotics or other specific therapies. Given the large number of infants with bronchiolitis admitted to the PICU annually and the lack of evidence to support most ICU practices in bronchiolitis, development of this type of research framework is essential to improve care for this important group of patients.
• Publication are in progress. More information on the BACON study can be found on their Twitter page, here.

BALI: Genetic Variation and Biomarkers in Acute Lung Injury

• Principal Site Investigator: Marc Berg, MD
• As an ancillary study to RESTORE, acute lung injury (ALI) and the more pediatric severe acute respiratory distress syndrome (PARDS) are a significant problem in Pediatric Intensive Care Units, affecting up to 16 of every 1000 children admitted to these units. These disorders carry with them high mortality rates as well as numerous long-term effects for the surviving children. There are a wide range of problems which make certain PICU patients more likely to develop either ALI or PARDS. This research aimed to determine which of these children are at the greatest risk for ALI/PARDS by examining differences in plasma biomarkers and in DNA of a large number of PICU patients. The project hypothesized that significant differences in the level of specific plasma biomarkers or in the frequency of specific DNA variants existed in children who develop ALI/PARDS.
• More information for BALI can be found here.

EPIC-Cardiac: Epithelial Permeability in Children after Cardiopulmonary Bypass

• Principal Site Investigator: Katri Typpo, MD, MPH
• Children with congenital heart disease have loss of intestinal epithelial barrier function, which increases their risk for postoperative sepsis and organ dysfunction. The study was conducted to understand how postoperative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass might alter intestinal epithelial barrier function. EPIC-Cardia examined variation in a panel of plasma biomarkers to reflect intestinal epithelial barrier function (cellular and paracellular) after cardiopulmonary bypass and in response to routine ICU care.
• Results from EPID-Cardiac can be found here.

HIP: Hypothermia’s Impact on Pharmacology

• Principal Site Investigator: Andreas Theodorou, MD
• Site Co-Investigator: Katri Typpo, MD, MPH
• Following cardiac arrest, multiple organ dysfunction syndrome, especially renal and hepatic dysfunction, is common and affects the metabolism and excretion of drugs. Very little is known about the impact of hypothermia on a child's ability to metabolize medications. Dose adjustments may be required in the setting of hypothermia to avoid under-dosing and over-dosing of medications. Improper dosing and drug accumulation of sedatives and opiates can worsen existing neurologic, circulatory and respiratory failure. The purpose of the study was to understand the complex interaction between hypothermia (cooling) and pharmacogenetics (how specific genes effect how drugs are handled), and their impact on how routinely given sedation drug are broken down and used by the body when given to children after cardiac arrest (when heart stops pumping blood) and are critically ill.
• More information and publications for HIP can be found here.

KIND Heart: Kids Intestinal Dysfunction in Congenital Heart Disease

• Principal Investigator: Katri Typpo, MD, MPH
• Clinicians lack objective data to inform decisions regarding provision of enteral nutrition (EN), an area where subjective decision-making is currently the rule. Lack of standardized practices for post-operative feeding lead to EN practice variation, which may harm these infants with regard to septic morbidity and long-term neurocognitive outcomes. KIND Heart aimed to address gaps in knowledge regarding the emerging role of the gastrointestinal tract as a modulator of systemic inflammatory response syndrome (SIRS), sepsis, and organ dysfunction after cardiopulmonary bypass during childhood. This study also aimed to generate pilot and feasibility data for a future comparative effectiveness trial to compare the effect of a biomarker based decision rule to a clinical decision rule for EN initiation on daily percent of goal nutrition delivered, feeding intolerance, and incidence of gastrointestinal complications after surgical repair of left-sided congenital cardiac defects.
• More information and publications for KIND Heart can be found here.

NACHRI-CLABSI: Eliminating Catheter-Associated Bloodstream Infections in Pediatric ICUs

• Principal Investigator: Robyn Meyer, MD
• The NACHRI-CLABSI project was a national collaborative effort of pediatric intensive care units that are members of The National Association of Children’s Hospital and Related Institutions.  A quality improvement project focused on eliminating central line-associated blood stream infections (CLABSI), the project aimed to improve clinical care and maintain rigorous standards for central-line management. While some previous work has produced results in PICUs to reduce infections associated with central-line insertion, data from a number of children’s hospitals suggested that even after reliable implementation of sterile insertion practices, PICU patients could continue to experience infection. Despite these experiences, there are no pediatric specific evidence-based strategies related to catheter maintenance practices which focus upon reducing CLABSI.
• More information and publications for NACHRI-CLABSI can be found here.

NPO-NIV: Nutritional Practices and Outcomes in Non-Invasive Ventilation

• Principal Investigator: Katri Typpo, MD, MPH
• To understand nutrition practices and outcomes for children on non-invasive ventilation (NIV), Dr. Typpo conducted an international point-prevalence study and provider survey through the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network, encompassing 52 pediatric intensive care units worldwide. This study evaluated current nutrition practices and outcomes across global regions for enteral and parenteral nutrition for infants and children newly supported with NIV over the study period. The study also conducted a survey of providers to assess beliefs regarding enteral nutrition in patients with varying degrees of respiratory and hemodynamic stability on invasive and non-invasive ventilation.
• Publications are in progress.

PARDIE: Paediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology

• Principal Site Investigator: Katri Typpo, MD, MPH
• The PARDIE study was designed as a multi-center international observational, cross sectional study of new cases of PARDS involving 5 continuous days of screening and patient enrollment, occurring every 2 months for a year (6 total study weeks). Included patients had a new diagnosis of PARDS during the study week or were at risk for PARDS. The main goal of PARDIE is to better understand the implications of the new Pediatric Acute Lung Injury Consensus Conference (PALICC) definition of Pediatric ARDS on the incidence and epidemiology of Pediatric ARDS.
• Results from PARDIE can be found here.

PICU-COV: Pediatric Intensive Care Units and SARS-CoV-2

• Principal Investigator: Katri Typpo, MD, MPH
• PICU-COV consiusted of a series of surveys sendt to pediatric intensive care units (PICUs) worldwide to understand then-current clinical practices in PICUs during the COVID-19 pandemic. Covering clinical practices, adjuvant therapy usage, and institutional practices, this project met a need to generate rapid clinical practice-sharing networks among those caring for severe pediatric cases of SARS-CoV-2 and MIS-C using a novel delivery and distribution network.
• Publications are in progress.

PICFlu: Pediatric Intensive Care Influenza Network

• Principal Site Investigator: Katri Typpo, MD, MPH
• Seasonal influenza annually infects 5 to 20% of the population, leading to 200,000 hospitalizations and approximately 36,000 deaths. Older people, young children, and people with health conditions such as asthma and immune compromise are at high risk for serious influenza-related complications. The study hypothesized that infection with the influenza virus triggers hypercytokinemia and innate immunosuppression in a genetically susceptible host would lead to very severe and sometimes fatal infection. the study aimed to test this hypothesis in critically ill children with influenza LRTI. By understanding why children become seriously or fatally ill from influenza, we can identify potential treatment strategies. As the first very large multicenter study characterizing the role of innate immunity in life-threatening influenza in children, PICFlu focused on answering questions that could assist researchers in designing future clinical trials to prevent and ameliorate life-threatening influenza in children.
• More information and publications for PICFlu can be found here.

PINS: Pediatric International Nutrition Study

• Principal Site Investigator: Katri Typpo, MD, MPH
• PINS was a multi-site cohort study of how nutrition is delivered to critically ill patients in PICUs around the world. Each participating site included mechanically ventilated children in their respective PICUs and record the details of what type and amount of nutrition was received. These details were be compared to goals designated by the clinicians caring for each patient. The project sought to generate a better understand how different types and amounts of nutrition impact important PICU outcomes such as length of stay, time on the ventilator, rate of infections, and mortality.
• More information and publications for PINS can be found here.

PISA: Pharmacologic Impact on Sedation Assessments

• Principal Site Investigator: Marc Berg, MD
• As another ancillary study to RESTORE, this study used sophisticated modeling and simulation techniques to evaluate the impact of genetics and other variables such as degree of illness, age, weight and organ dysfunction on the use of morphine and midazolam in children who are mechanically ventilated for respiratory failure.  Information learned through this project sought to design of a pharmacologic model that could be used to individualize therapy in children requiring mechanical ventilation with the goal of optimizing sedation while minimizing the duration of mechanical ventilation.
• More information for PISA can be found here.

RESTORE: Randomized Evaluation of Sedation Titration for Respiratory Failure

• Principal Site Investigator: Marc Berg, MD
• Ensuring the safety and comfort of critically ill infants and children supported on mechanical ventilation is integral to the practice of pediatric critical care. Yet, the medications required to keep patients comfortable and safe can cause other complications. Over time, children can develop a tolerance to the sedation medications and may experience undesired side effects requiring them to remain on the ventilator longer. This study was done to learn more about the best ways to keep children comfortable and safe during mechanical ventilation, while limiting undesired short-term and long-term risks. The purpose of the study was to evaluate if sedatives used in children with acute respiratory failure affects how long they need to be mechanically ventilated, how much it cost, and their quality of life and emotional health after hospital discharge.
• More information and publications for RESTORE can be found here.

SiRD: Sepsis-Induced Red Cell Dysfunction

• Principal Site Investigator: Katri Typpo, MD, MPH
• SiRD aimed to characterize red cell dysfunction that impairs oxygen delivery in septic children. The hypothesis of the project was that in sepsis the energetic support of RBC antioxidant systems fails, leading to unquenched reactive oxygen species generation during the course of hemoglobin binding and release of oxygen. By impairing microvascular flow regulation and impeding oxygen release to the tissue, sepsis-induced red cell dysfunction (SiRD) would exacerbate dysoxia and worsen the progression of multiple organ failure. SiRD aimed to define the biochemical and biophysical alterations to red blood cells that influence oxygen delivery, and characterize sepsis-induced alterations in red blood cell metabolism, antioxidant systems, and oxidative injury. The goals of this project were to study a national cohort of septic children without chronic co-morbidities to characterize sepsis-induced red cell dysfunction (SiRD) as a distinct form of organ failure that impairs O2 delivery in sepsis, elucidate SiRD's role in multiple organ failure (MOF) progression, and evaluate a mechanism-based therapy targeted to SiRD pathobiology.
• Publications are in progress.

SPROUT: Sepsis Prevelence, Outcomes, and Therapy

• Principal Site Investigator: Katri Typpo, MD, MPH
• Pediatric sepsis is a major source of morbidity, mortality, and expenditures in pediatric intensive care units (PICUs) worldwide. At the time of initiation, SPROUT addressed the need for a contemporary study examining the global epidemiology of pediatric sepsis. As such, SPROUT sought to characterize the global prevalence, therapies, and outcomes of severe sepsis in PICUs. As well, the study aimed to understand the generalizability of criteria used to identify pediatric sepsis and determine the feasibility of clinical trials in this population.
• Results for SPROUT can be found here.

SuPPeR: Supplemental Parenteral Nutrition in Pediatric Respiratory Failure

• Principal Investigator: Katri Typpo, MD, MPH
• Acute hypoxemic respiratory failure (AHRF) accounts for 10% of all pediatric intensive care unit (PICU) admissions. Nutritional support is central to appropriate PICU management of AHRF, and yet fundamental gaps in knowledge exist regarding best practice for timing, route, dose, and type of nutrition. Optimized nutritional support is a way to improve morbidity for survivors of pediatric critical illness. The central hypothesis of this proposal was that optimized early protein and calorie delivery will improve nutritional outcomes and intestinal barrier function for critically ill infants and children. The overall goals of this project was to evaluate the efficacy and safety of an early parenteral nutrition strategy to improve nutritional delivery, nutritional outcomes, and intestinal barrier function for mechanically ventilated children in the PICU.
• More information and publications for SuPPeR can be found here.

THAPCA: Therapeutic Hypothermia After Pediatric Cardiac Arrest

• Principal Site Investigator: Andreas Theodorou, MD
• Site Co-Investigator: Katri Typpo, MD, MPH
• Acute hypoxemic respiratory failure (AHRF) accounts for 10% of all pediatric intensive care unit (PICU) admissions. Nutritional support is central to appropriate PICU management of AHRF, and yet fundamental gaps in knowledge exist regarding best practice for timing, route, dose, and type of nutrition. Optimized nutritional support is a way to improve morbidity for survivors of pediatric critical illness. The central hypothesis of this proposal was that optimized early protein and calorie delivery will improve nutritional outcomes and intestinal barrier function for critically ill infants and children. The overall goals of this project was to evaluate the efficacy and safety of an early parenteral nutrition strategy to improve nutritional delivery, nutritional outcomes, and intestinal barrier function for mechanically ventilated children in the PICU.
• More information and publications for THAPCA can be found here.

VAIN: Ventilator-Associated Infectious Point Prevelence Study

• Principal Site Investigator: Katri Typpo, MD, MPH
• Ventilator-associated infections (pneumonia, tracheitis, lower respiratory infection) are among the most common nosocomial infections in the pediatric intensive care unit and are responsible for over half of all antibiotic use. No gold standard for diagnosis is available and this is reflected in the variability of the reported incidence.The existing Centers for Disease Control criteria are ambiguous and appear to be variably applied. Consequently, antibiotic treatment for “suspicion of ventilator-associated infection (VAI)” is also variable. This study aimed to identify the prevalence of “clinically suspected VAI”, the diagnostic criteria employed, and subsequent antibiotic treatment across participating institutions. VAIN also determined the clinical characteristics associated with antibiotic continuation beyond the usual “48 hour rule-out” and assess whether continuation of treatment is associated with any differences in outcomes.
• Results from VAIN can be found here.

VAIN2: Decreasing Antibiotic Exposure in Infants with Suspected Ventilator-Associated Infection

• Principal Site Investigator: Katri Typpo, MD, MPH
• The ventilator-associated infectious point prevelence study (VAIN) demonstrated the variability of treatment for suspected ventilator-associated infection in children. A more rational approach to antibiotic use for this condition was desperately needed. Specifically, pediatric intensivists need a consensus guideline for evaluation and treatment of VAI in infants and young children. The proposal for VAIN2 developed and tested a guideline for ventilator-associated infections evaluation and treatment and will collect information critical to understanding VAI in the pediatric critical care setting.
• Results from VAIN2 can be found here.

VESIP: Vaccine Effectiveness against Severe Influenza in Pediatrics

• Principal Site Investigator: Mary Gaspers, MD, MPH
• Site Co-Investigator: Katri Typpo, MD, MPH
• The PICFlu Study reported that influenza vaccination was approximately 74% effective for preventing influenza critical illness in children in 2010-2012. The effectiveness of live and inactivated influenza vaccines to consistently prevent severe influenza-related illness is unclear, especially in high risk children 6-24 months old. The primary aim of the VESIP study was to evaluate influenza vaccine efficacy for preventing severe and life-threatening influenza-associated illness in children 6 months to 17 years of age. VESIP aimed to address an unmet scientific and public health need to understand influenza infection and influenza vaccine efficacy in patients with the most severe manifestations of influenza.
• More information and publications for VESIP can be found here.