ABSTRACT
The Coronavirus disease (COVID-19) pandemic of 2019 has resulted in significant morbidity and mortality, especially from severe acute respiratory distress syndrome (ARDS). As of September 2022, more than 6.5 million patients have died globally, and up to 5% required intensive care unit treatment. COVID-19-associated ARDS (CARDS) differs from the typical ARDS due to distinct pathology involving the pulmonary vasculature endothelium, resulting in diffuse thrombi in the pulmonary circulation and impaired gas exchange. The National Institute of Health and the Society of Critical Care Medicine recommend lung-protective ventilation, prone ventilation, and neuromuscular blockade as needed. Further, a trial of pulmonary vasodilators is suggested for those who develop refractory hypoxemia. A review of the prior literature on inhaled pulmonary vasodilators in ARDS suggests only a transient improvement in oxygenation, with no mortality benefit. This narrative review aims to highlight the fundamental principles in ARDS management, delineate the fundamental differences between CARDS and ARDS, and describe the comprehensive use of inhaled pulmonary vasodilators. In addition, with the differing pathophysiology of CARDS from the typical ARDS, we sought to evaluate the current evidence regarding the use of inhaled pulmonary vasodilators in CARDS.
ABSTRACT
INTRODUCTION: Thrombosis and bleeding are recognized complications of the novel coronavirus infection (COVID-19), with a higher incidence described particularly in the critically ill. METHODS: A retrospective review of COVID-19 patients admitted to our intensive care units (ICU) between 1 January 2020 and 31 December 2020 was performed. Primary outcomes included clinically significant thrombotic and bleeding events (according to the ISTH definition) in the ICU. Secondary outcomes included mortality vis-a-vis the type of anticoagulation. RESULTS: The cohort included 144 consecutive COVID-19 patients with a median age of 64 years (IQR 54.5-75). The majority were male (85 (59.0%)) and Caucasian (90 (62.5%)) with a median BMI of 30.5 kg/m2 (IQR 25.7-36.1). The median APACHE score at admission to the ICU was 12.5 (IQR 9.5-22). The coagulation parameters at admission were a d-dimer level of 109.2 mg/mL, a platelet count of 217.5 k/mcl, and an INR of 1.4. The anticoagulation strategy at admission included prophylactic anticoagulation for 97 (67.4%) patients and therapeutic anticoagulation for 35 (24.3%) patients, while 12 (8.3%) patients received no anticoagulation. A total of 29 patients (20.1%) suffered from thrombotic or major bleeding complications. These included 17 thrombus events (11.8%)-8 while on prophylactic anticoagulation (7 regular dose and 1 intermediate dose) and 9 while on therapeutic anticoagulation (p-value = 0.02)-and 19 major bleeding events (13.2%) (4 on no anticoagulation, 7 on prophylactic (6 regular dose and 1 intermediate dose), and 8 on therapeutic anticoagulation (p-value = 0.02)). A higher thrombosis risk among patients who received remdesivir (18.8% vs. 5.3% (p-value = 0.01)) and convalescent serum (17.3% vs. 5.8% (p-value = 0.03%)) was noted, but no association with baseline characteristics (age, sex, race, comorbidity), coagulation parameters, or treatments (steroids, mechanical ventilation) could be identified. There were 10 pulmonary embolism cases (6.9%). A total of 99 (68.8%) patients were intubated, and 66 patients (45.8%) died. Mortality was higher, but not statistically significant, in patients with thrombotic or bleeding complications-58.6% vs. 42.6% (p-value = 0.12)-and higher in the bleeding (21.2%) vs. thrombus group (12.1%), p-value = 0.06. It did not significantly differ according to the type of anticoagulation used or the coagulation parameters. CONCLUSIONS: This study describes a high incidence of thrombotic and bleeding complications among critically ill COVID-19 patients. The findings of thrombotic events in patients on anticoagulation and major bleeding events in patients on no or prophylactic anticoagulation pose a challenging clinical dilemma in the issue of anticoagulation for COVID-19 patients. The questions raised by this study and previous literature on this subject demonstrate that the role of anticoagulation in COVID-19 patients is worthy of further investigation.