Major Publications in the Critical Care Pharmacotherapy Literature: 2021.

To summarize the most impactful articles relevant to the pharmacotherapy of critically ill adult patients published in 2021. DATA SOURCE: PubMed/MEDLINE. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021. DATA EXTRACTION: Candidate articles were organized by clinical domain based on the emerging themes from all studies. A modified Delphi process was applied to obtain consensus on the most impactful publication within each clinical domain based on overall contribution to scientific knowledge and novelty to the literature. DATA SYNTHESIS: The search revealed 830 articles, of which 766 were excluded leaving 64 candidate articles for the Delphi process. These 64 articles were organized by clinical domain including: emergency/neurology, cardiopulmonary, nephrology/fluids, infectious diseases, metabolic, immunomodulation, and nutrition/gastroenterology. Each domain required the a priori defined three Delphi rounds. The resultant most impactful articles from each domain included five randomized controlled trials and two systematic review/meta-analyses. Topics studied included sedation during mechanical ventilation, anticoagulation in COVID-19, extended infusion beta-lactams, interleukin-6 antagonists in COVID-19, balanced crystalloid resuscitation, vitamin C/thiamine/hydrocortisone in sepsis, and promotility agents during enteral feeding. CONCLUSIONS: This synoptic review provides a summary and perspective of the most impactful articles relevant to the pharmacotherapy of critically ill adults published in 2021.

Successful Use of Aspirin, Apixaban, and Viscoelastography in a Patient with Severe COVID Disease and Allergy to Porcine Products.

Coagulation abnormalities are frequently described in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Common thromboprophylaxis and anticoagulation treatment strategies include the use of heparinoid therapy. We describe a 57-year-old woman with an allergy to porcine products that was started on apixaban for anticoagulation therapy given her allergy profile and need for venous thromboembolism prophylaxis. Apixaban and aspirin therapy were optimized with the support of serial viscoelastography and platelet function assays. Our patient experienced respiratory failure requiring intubation for 7 days but was successfully weaned to room air, tolerated a regular diet, and ultimately discharged to home after a 17-day hospital course. Here we report the safe and successful use of aspirin, apixaban, and viscoelastography for COVID-19-associated coagulopathy.

Anticoagulation Monitoring in the Intensive Care Unit.

Patients with critical illness often display variable hypo- and hypercoagulable sequalae requiring intense monitoring and anticoagulation pharmacotherapy to prevent or treat inappropriate clot formation. It is imperative to understand the various stages of the clotting cascade and where each pharmacotherapy agent exerts its therapeutic effect. Common coagulation tests are utilized to monitor the areas of the clotting cascade and the effects that anticoagulant pharmacotherapy exhibits. Many novel coagulation tests are also in development. The purpose of this narrative review is to evaluate commonly utilized coagulation tests that monitor anticoagulation while in the intensive care unit.

Utilization of 4-Factor Prothrombin Complex Concentrate for Reversal of Oral Factor Xa Inhibitor-Associated Acute Major Bleeding: A Case Series.

OBJECTIVE: In cases of oral factor Xa (FXa) inhibitor-associated acute major bleeding, several reversal strategies are available. Current guidelines recommend a dose of 50 U/kg if using 4-factor prothrombin complex concentrate (4F-PCC). A paucity of data exists with the use of 4F-PCC for FXa inhibitor reversal for acute major bleeding, specifically the most efficacious dosing regimens and safety data. The purpose of this case series is to describe the utilization of 4F-PCC for reversal of oral FXa inhibitor-associated acute major bleeding. METHODS: This retrospective case series included all admitted patients 18 years and older who received 4F-PCC for oral FXa inhibitor-associated major bleeding. Major bleeding was defined using the International Society of Thrombosis and Hemostasis definition for major bleeding in nonsurgical patients. The primary outcome was achievement of hemostasis. RESULTS: A total of 31 patients met inclusion criteria, with 17 receiving rivaroxaban and 14 receiving apixaban. Intracranial hemorrhage was the most common type of bleeding occurring in 15 (55%) patients. The median dose of 4F-PCC was 37 U/kg. Of the patients evaluated in the primary end point analysis, 68% achieved effective hemostasis. Four (12.9%) patients experienced a documented thrombotic event within 7 days of receiving 4F-PCC. CONCLUSION: The use of 4F-PCC for FXa inhibitor-associated acute major bleeding was effective for the majority of patients. The rate of thrombotic events appears higher compared to previously published studies, although major confounders exist and larger studies are needed to fully evaluate the safety of 4F-PCC for this indication.

Utilization of thromboelastography and a low molecular weight heparin anti-Xa assay for guidance in apixaban reversal: A case report.

Reversal of oral factor Xa (FXa) inhibitors, such as apixaban, remains a controversial topic. However, the controversy goes beyond what reversal agent to utilize. Often times these patients present with an acute major bleed and are difficult to assess whether reversal is warranted or not. Furthermore, it is difficult to assess whether reversal was successful in a timely manner. A paucity of literature exists regarding the utilization of low molecular weight heparin (LMWH) anti-Xa assays and thromboelastography for identifying coagulopathies associated with oral FXa inhibitors. We report a case of apixaban induced coagulopathy utilizing thromboelastography and a LMWH anti-Xa assay as a guide for reversal.