ABSTRACT
ECMO has become a widely recognized support modality for patients with severe cardiac or respiratory failure, and has been increasingly utilized in the ongoing severe acute respiratory syndrome due to coronavirus-2 (SARS-CoV-2) pandemic. Long-term support on ECMO for acute respiratory distress syndrome (ARDS) is also becoming more commonplace with eventual lung recovery, obviating the need for lung transplantation. However, long-term ECMO support has not been well studied for SARS-CoV-2 ARDS patients. We report the case of a 39-year-old female with severe SARS-CoV-2-induced ARDS successfully supported on venovenous ECMO (V-V ECMO) for 5,208 hours (217 days) in a high ECMO-volume, quaternary care children's hospital in 2021. At the time of this writing, this is the longest reported patient successfully supported on ECMO for SARS-CoV-2 ARDS. Our patient was initially cannulated at our children's hospital with dual-site V-V ECMO, via the right internal jugular vein (RIJ) and right common femoral vein. Bedside tracheostomy was performed on ECMO day 40, for early mobility, oral feeding, interaction, and pulmonary rehabilitation planning. Unfortunately, during her course she suffered multiple complications including bacterial co-infections, bleeding requiring anticoagulant changes from unfractionated heparin (UFH) to bivalirudin, multiple ECMO circuit changes due to blood product consumption and coagulopathy, and pneumothoraces requiring thoracostomy tube placements. Approximately 1.5 months into her ECMO course, she suffered acute hypoxemia and echocardiography revealed indirect evidence of pulmonary hypertension with right heart failure. Initial right heart catheterization while on V-V ECMO revealed elevated right ventricular end-diastolic pressure (RVEDP=15-20 mmHg) and severe systemic desaturation with main pulmonary artery (MPA) pressure of 30 mmHg. Pulmonary hypertension and right heart support was initiated in the form of inhaled nitric oxide (iNO), inotropes, phosphodiesterase inhibitors, nitrates, angiotensin-converting enzyme inhibitors, and diuresis. Ultimately, due to necessity of right-heart decompression and support, on ECMO day 86 she was transitioned to single-site V-V ECMO utilizing a 31 Fr dual-lumen venovenous cannula (ProtekDuo (LivaNova, UK)) placed via her RIJ through her right atrium (RA) into the MPA in the cardiac catheterization laboratory. Subsequent heart catheterization more than 2 months later revealed severe right ventricular (RV) diastolic dysfunction (RVEDP=35 mmHg) and moderate left ventricular (LV) diastolic dysfunction (pulmonary capillary wedge pressure (PCWP=24 mmHg)). During her course, multiple trials off ECMO were attempted with varying lengths of time off ECMO support, but ultimately required ongoing ECMO support. She developed evidence of end-organ dysfunction from her cor pulmonale, including oliguric renal failure requiring renal replacement therapy (RRT), hepatic injury with elevated transaminases and hyperammonemia leading to depressed mental state, feeding intolerance, and coagulopathy. Additionally, due to long-term nasogastric enteral tube placement for caloric supplementation and enteral medication administration, she developed concerns for invasive sinusitis with erosion into ethmoid and maxillary sinuses. As she was an adult patient being cared for in a free-standing academic children's hospital, multiple adult medicine consultants were involved in her care. Specifically, adult nephrology, cardiology, cardiothoracic surgery (for ProtekDuo cannula placement), and gastroenterology/ hepatology were integral into her care, along with our pediatric critical care medicine and ECMO teams. Notably, this was the first patient supported on ECMO to receive tracheostomy, RA-MPA dual-lumen VV cannula, and full autonomous mobility outside of the ICU at our well-established ECMO program, which has served as the index patient leading to future advances in the care of our ECMO patients. Over time and with multiple therapies to alleviate her cor pulmonale, the patient's echocardiograms evealed improved, half-systemic right-sided cardiac pressures. She was ultimately decannulated from ECMO at our center before being transferred back to the referring adult facility, and discharged to home 8 months after her initial presentation with acute respiratory failure.
ABSTRACT
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that causes the disease entity COVID- 19. Initially, reports showed children had generally mild disease, with few requiring hospitalization. However, as of December 2021 in Arkansas, USA, children and young adults aged 24 years and younger accounted for approximately 166,000 cases with over 1,800 hospitalizations and 27 deaths (3 deaths under age 17). Comparatively, there have been over 6 million cases nationally in children and young adults, with over 1,000 deaths. Bacterial, viral, and fungal co-infections are known complications of viral respiratory illnesses that can lead to increased mortality. There have been multiple reports in adults on the incidence and type of co-infections seen with COVID-19, but few in pediatric patients. Adult data shows that co-infections are present in approximately 13-45% of patients with COVID-19, most commonly with bacterial pathogens of Mycoplasma pneumoniae and Haemophilus influenzae. Methods: We describe four patients with acute SARS-CoV-2 infection, requiring intubation, mechanical ventilation, and extracorporeal membrane oxygenation (ECMO), all of whom had methicillin-sensitive Staphylococcus aureus(MSSA) infections discovered within 24 hours of escalating respiratory support. This case series was determined as exempt by the Institutional Review Board at our institution. Results: Our cohort includes 4 patients with a median age of 18 years (range 16-19 years), all of whom required ECMO for acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 pneumonia. The median time from intubation to ECMO cannulation was 139 hours (range 3-319 hours). All patients received targeted COVID-19 therapy with dexamethasone, remdesivir, and either tociluzimab or baricitinib during their hospitalization. These patient also all had culture positive MSSA infections from blood and mini-BAL cultures. Three of the four patients had a positive culture within 24 hours of requiring ECMO and one patient had a positive culture within 24 hours of requiring intubation. All of the patients were initially placed on venovenous (V-V) ECMO and three (75%) later required transition to venoarterial venous (VA-V) ECMO for worsening hemodynamics. All were initially cannulated with dual site femoral-internal jugular configuration. Femoral arterial cannulas were used for the transition to VA-V. Complications encountered during ECMO for these patients included GI bleeding (n=1), atrial flutter requiring cardioversion (n=1), lower extremity compartment syndrome (n=1), and dislodgement of a venous ECMO cannula (n=1). One patient received a tracheostomy while on ECMO. The median ECMO duration was 19.35 days (range 11-48.5 days). All patients were successfully decannulated from ECMO and all were discharged from the hospital alive, except one who is still requiring inpatient rehabilitation services. Discussion: We describe 4 pediatric patients with acute SARS-CoV-2 respiratory infections who were found to have MSSA co-infection within 24 hours of escalating respiratory support, all of whom eventually required ECMO support. In a recently published study, Pickens, et al reported that 25% of recently intubated adult COVID-19 patients have a bacterial co-infection. Limited data is available in pediatric patients. Staphylococcus aureus infections are among the most common bacterial infections worldwide. They are responsible for over 100,000 infections in the United States each year and lead to increased morbidity and mortality. All of our patients received immunemodulating therapies with either tociluzimab or baricitinib, which carry the risk of secondary infections due to immunosuppressive effects. Clinicians should maintain a high index of suspicion and be aware of the possibility of secondary bacterial infections in COVID- 19 patients, especially in those treated with immune-modulators. MSSA co-infection can lead to increased morbidity and mortality in patients with SARS-CoV-2, as seen in our cohort. More investigation s needed to further describe co-infections in patients with COVID- 19 and to identify risk factors for the development of co-infections.