Oliver Karam, MD, PhD

Bleeding: Bleeding is a frequent complication of critical illness that is associated with significant mortality and morbidity. However, very little is known about bleeding in critically ill children. Dr. Karam's main research focus pertains to the epidemiology of bleeding in critically ill children. In a systematic review, he has shown that, although there are numerous definitions related to bleeding's clinical significance, none are designed for critically ill children. He then used an internationally distributed survey to explore the perceived severity of bleeding in critically ill children. He showed that characteristics most frequently identified as clinically relevant were bleeding in critical locations (e.g., pericardium, pleural space, CNS, and lungs); requiring interventions; leading to physiologic repercussions, including organ failure; and prolonged duration. He then designed an international consensus definition; with the help of 31 experts, he defined bleeding in critically ill children, which was the first definition to be validated in this specific population. He then further explored the relationship between bleeding and poor outcome, examining chest tube bleeding in children on ECMO. He showed a dose-response relationship between bleeding and mortality. These studies have allowed him to develop a new, operationalizable, bleeding definition that is now used in clinical studies. He has set the foundation for future studies, by establishing a consensus definition that is applicable to this patient population.

Thrombosis: The other side of Dr. Karam's research on bleeding is on thrombotic complications, as most therapies that aim to decrease bleeding put patients at increased thrombotic risk. He has evaluated antithrombin's effect on thrombotic complications after pediatric liver transfusion. He has also designed an international survey that identified the heterogeneity of antithrombotic strategies in various transplantation teams around the world. Finally, he evaluated the effect of transfusions on thrombotic complications in an extensive dataset of more than 400,000 children. He showed that perioperative red blood cell transfusions were independently associated with postoperative thrombotic events in children.

Extracorporeal life support: Dr. Karam has two leading research focuses within extracorporeal life support. First, as the extracorporeal circuit is very pro-thrombotic, virtually all patients require anticoagulation, which puts patients at risk of bleeding. In a systematic review and meta-analysis, he has identified the optimal test to guide anticoagulation. He is currently leading an international randomized controlled trial that evaluates two platelet transfusion thresholds in children on extracorporeal life support (the ECSTATIC trial). Second, although thousands of children are placed on ECMO during active cardiopulmonary resuscitation, the indications remain unclear. He has designed a score that should help identify ECMO's appropriate indications when the benefits outweigh the risks.

Parental outcomes after ECMO: Dr. Karam's research explores the psychological toll of extracorporeal membrane oxygenation (ECMO) on parents, with the goal of identifying modifiable risk factors to improve outcomes. Through the Post-ECMO Parental Stress Investigation (PEPSI) research program, he is addressing the critical gaps in understanding PTSD, anxiety, and depression in this population. The first study, a systematic review and meta-analysis, evaluates the prevalence of parental psychopathologies and identifies potential risk factors. This work, currently under peer review, will serve as the foundation for future studies. The second study involves qualitative interviews with parents, including those who experienced the loss of a child, to explore communication during ECMO, access to resources, and decision-making regret. Additionally, Dr. Karam is spearheading a global point-prevalence study across 40 ECMO centers to survey over 400 parents on symptoms of PTSD, depression, and anxiety, with plans to present findings at the upcoming ELSO meeting. These efforts lay the groundwork for future NIH-funded studies, including a large observational study to follow parents during and after ECMO, and a step-wedged cluster randomized trial designed to test interventions aimed at reducing parental psychopathologies and improving long-term outcomes.