Therapy with lopinavir/ritonavir and hydroxychloroquine is associated with acute kidney injury in COVID-19 patients.

BackgroundAcute kidney injury (AKI) is an independent risk factor for mortality, which affects about 5% of hospitalized coronavirus disease-2019 (COVID-19) patients and up to 25-29% of severely ill COVID-19 patients. Lopinavir/ritonavir and hydroxychloroquine show in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have been used for the treatment of COVID-19. Both, lopinavir and hydroxychloroquine are metabolized by cytochrome P450 (CYP) 3A4. The impact of a triple therapy with lopinavir/ritonavir and hydroxychloroquine (triple therapy) on kidney function in COVID-19 is currently not known.MethodsWe retrospectively analyzed both non-ICU and ICU patients with COVID-19 receiving triple therapy for the incidence of AKI. Patients receiving standard therapy served as a control group. All patients were hospitalized at the University Hospital of Freiburg, Germany, between March and April 2020. A matched-pair analysis for the National Early Warning Score (NEWS) 2 was performed to control for the severity of illness among non-intensive care unit (ICU) patients.ResultsIn non-ICU patients, the incidence of AKI was markedly increased following triple therapy (78.6% vs. 21.4% in controls, p = 0.002), while a high incidence of AKI was observed in both groups of ICU patients (triple therapy: 80.0%, control group: 90.5%). ICU patients treated with triple therapy showed a trend towards more oliguric or anuric kidney injury. We also observed a linear correlation between the duration of the triple therapy and the maximum serum creatinine level (p = 0.004, R2 = 0.276, R = 0.597).ConclusionTriple therapy is associated with an increase in the incidence of AKI in non-ICU COVID-19 patients. The underlying mechanisms may comprise a CYP3A4 enzyme interaction, and may be relevant for any future therapy combining hydroxychloroquine with antiviral agents

Dual Antiplatelet Therapy (DAPT) versus No Antiplatelet Therapy and Incidence of Major Bleeding in Patients on Venoarterial Extracorporeal Membrane Oxygenation

<div><p>Aims</p><p>Bleeding is a frequent complication in patients on venoarterial extracorporeal membrane oxygenation (VA-ECMO). An indication for dual antiplatelet therapy due to coronary stent implantation is present in a considerable number of these patients. The objective of this retrospective study was to evaluate if dual antiplatelet therapy (DAPT) significantly increases the high intrinsic bleeding risk in patients on VA-ECMO.</p><p>Methods and Results</p><p>A total of 93 patients were treated with VA-ECMO between October 2010 and October 2013. Average time on VA-ECMO was 58.9 ± 1.7 hours. Dual antiplatelet therapy was given to 51.6% of all patients. Any bleeding was recorded in 60.2% of all patients. There was no difference in bleeding incidence in patients on DAPT when compared to those without any antiplatelet therapy including any bleeding (66.7% vs. 57.1%, p = 0.35), BARC3 bleeding (43.8% vs. 33.3%, p = 0.31) or pulmonary bleeding (16.7% vs. 19.0%, p = 0.77). This holds true after adjustment for confounders. Rate of transfusion of red blood cells were similar in patients with or without DAPT (35.4% vs. 28.6%, p = 0.488).</p><p>Conclusions</p><p>Bleeding on VA-ECMO is frequent. This registry recorded no statistical difference in bleeding in patients on dual antiplatelet therapy when compared to no antiplatelet therapy. When indicated, DAPT should not be withheld from VA ECMO patients.</p></div

Bleeding and transfusions.

<p>Bleeding and transfusions.</p

Transfusions of platelets, red blood cells and fresh frozen plasma; Percentage of patients requiring any transfusion (A), Average number of transfused blood products in all patients (B), Average number of transfused blood products in patients receiving at least one transfusion (C).

<p>Transfusions of platelets, red blood cells and fresh frozen plasma; Percentage of patients requiring any transfusion (A), Average number of transfused blood products in all patients (B), Average number of transfused blood products in patients receiving at least one transfusion (C).</p

Bleeding incidence on venoarterial extracorporeal membrane oxygenation therapy, bleeding incidence during venoarterial extracorporeal membrane oxygenation therapy is given as percentage of patients with bleeding to total patients treated.

<p>Bleeding incidence on venoarterial extracorporeal membrane oxygenation therapy, bleeding incidence during venoarterial extracorporeal membrane oxygenation therapy is given as percentage of patients with bleeding to total patients treated.</p

Patients’ characteristics.

<p>Patients’ characteristics.</p

Impact of pulse pressure on clinical outcome in extracorporeal cardiopulmonary resuscitation (eCPR) patients

Background!#!Hemodynamic response to successful extracorporeal cardiopulmonary resuscitation (eCPR) is not uniform. Pulse pressure (PP) as a correlate for myocardial damage or recovery from it, might be a valuable tool to estimate the outcome of these patients.!##!Methods!#!We report retrospective data of a single-centre registry of eCPR patients, treated at the Interdisciplinary Medical Intensive Care Unit at the Medical Centre, University of Freiburg, Germany, between 01/2017 and 01/2020. The association between PP of the first 10 days after eCPR and hospital survival was investigated. Moreover, patients were divided into three groups according to their PP [low (0-9 mmHg), mid (10-29 mmHg) and high (≥ 30 mmHg)] at each time point.!##!Results!#!One hundred forty-three patients (age 63 years, 74.1% male, 40% OHCA, average low flow time 49 min) were analysed. Overall hospital survival rate was 28%. A low PP both early after eCPR (after 1, 3, 6 and 12 h) and after day 1 to day 8 was associated with reduced hospital survival. At each time point (1 h to day 5) the classification of patients into a low, mid and high PP group was able to categorize the patients for a low (5-20%), moderate (20-40%) and high (50-70%) survival rate. A multivariable analysis showed that the mean PP of the first 24 h was an independent predictor for survival (p = 0.008).!##!Conclusion!#!In this analysis, PP occurred to be a valuable parameter to estimate survival and maybe support clinical decision making in the further course of patients after eCPR

Intracerebral Hemorrhage in COVID-19 Patients with Pulmonary Failure: A Propensity Score-Matched Registry Study

Background!#!Hypercoagulability in Coronavirus Disease 2019 (COVID-19) causes deep vein thrombosis and pulmonary embolism necessitating systemic anticoagulation. Case reports of intracerebral hemorrhages in ventilated COVID-19 patients warrant precaution. It is unclear, however, if COVID-19 patients with acute respiratory distress syndrome (ARDS) with or without veno-venous extracorporeal membrane oxygenation therapy (VV-ECMO) have more intracerebral hemorrhages (ICH) compared to other ARDS patients.!##!Methods!#!We conducted a retrospective observational single-center study enrolling all patients with ARDS from 01/2018 to 05/2020. PCR-positive SARS-CoV-2 patients with ARDS were allocated to the COVID-19 group. Propensity score matching was performed for age, VV-ECMO, and bleeding risk.!##!Results!#!A total of 163 patients with moderate or severe ARDS were identified, 47 (28.8%) in the COVID-19 group, and 116 (71.2%) in the non-COVID-19 group. In 63/163 cases (38.7%), VV-ECMO therapy was required. The ICU survival was 52.8%. COVID-19 patients were older, more often male, and exhibited a lower SOFA score, but the groups showed similar rates of VV-ECMO therapy. Treatments with antiplatelet agents (p = 0.043) and therapeutic anticoagulation (p = 0.028) were significantly more frequent in the COVID-19 patients. ICH was detected in 22 patients (13.5%) with no statistical difference between the groups (11.2 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.21). Propensity score matching confirmed similar rates of ICH in both groups (12.8 vs. 19.1% without and with SARS-CoV-2, respectively, p = 0.57), thus leveling out possible confounders.!##!Conclusions!#!Intracerebral hemorrhage was detected in every tenth patient with ARDS. Despite statistically higher rates of antiplatelet therapy and therapeutic anticoagulation in COVID-19 patients, we found a similar rate of ICH in patients with ARDS due to COVID-19 compared to other causes of ARDS