ABSTRACT
BACKGROUND: The pressures exerted by the coronavirus disease 2019 (COVID-19) pandemic pose an unprecedented demand on healthcare services. Hospitals become rapidly overwhelmed when patients requiring life-saving support outpace available capacities. OBJECTIVE: We describe methods used by a university hospital to forecast case loads and time to peak incidence. METHODS: We developed a set of models to forecast incidence among the hospital catchment population and to describe the COVID-19 patient hospital-care pathway. The first forecast utilized data from antecedent allopatric epidemics and parameterized the care-pathway model according to expert opinion (ie, the static model). Once sufficient local data were available, trends for the time-dependent effective reproduction number were fitted, and the care pathway was reparameterized using hazards for real patient admission, referrals, and discharge (ie, the dynamic model). RESULTS: The static model, deployed before the epidemic, exaggerated the bed occupancy for general wards (116 forecasted vs 66 observed), ICUs (47 forecasted vs 34 observed), and predicted the peak too late: general ward forecast April 9 and observed April 8 and ICU forecast April 19 and observed April 8. After April 5, the dynamic model could be run daily, and its precision improved with increasing availability of empirical local data. CONCLUSIONS: The models provided data-based guidance for the preparation and allocation of critical resources of a university hospital well in advance of the epidemic surge, despite overestimating the service demand. Overestimates should resolve when the population contact pattern before and during restrictions can be taken into account, but for now they may provide an acceptable safety margin for preparing during times of uncertainty.
Subject(s)
COVID-19/epidemiology , Hospital Bed Capacity , Hospitals, University/organization & administration , COVID-19/prevention & control , Cross Infection/prevention & control , Forecasting , Germany/epidemiology , Hospitals, University/statistics & numerical data , Humans , Incidence , Models, Statistical , Patient SafetyABSTRACT
BACKGROUND: Increasing evidence suggests that some patients suffer from persistent symptoms for months after recovery from acute COVID-19.âHowever, the clinical phenotype and its pathogenesis remain unclear. We here present data on complaints and results of a diagnostic workup of patients presenting to the post-COVID clinic at the University Medical Center Freiburg. METHODS: Retrospective data analysis of persistently symptomatic patients presenting to our clinic at least 6 months after onset of acute COVID-19.âAll patients were assessed by a doctor and routine laboratory analysis was carried out. Quality of life was assessed using SF-36 questionnaire. In case of specific persisting symptoms, further organ-specific diagnostic evaluation was performed, and patients were referred to respective departments/specialists. FINDINGS: 132 Patients (58 male, 74 female; mean age 53.8 years) presented to our clinic at least 6 months after COVID-19. 79 (60â%) had been treated as outpatients and 53 (40â%) as inpatients. Most common complaints were persistent fatigue (82â%) and dyspnea on exertion (61â%). Further common complaints were impairments of concentration (54â%), insomnia (43â%), and impairments of smell or taste (35â%). Quality of life was reduced in all sections of the SF-36 questionnaire, yielding a reduced working capacity. Significant pathological findings in laboratory, echocardiographic and radiological work-up were rare. Impairments in lung function tests were more common in previously hospitalized patients. CONCLUSION: Patients presenting 6 months after onset of acute COVID-19 suffer from a diverse spectrum of symptoms with impaired quality of life, also referred to as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Further research is needed to determine the frequency of these post-COVID syndromes and their pathogenesis, natural course and treatment options. Evaluation and management should be multi-disciplinary.
Subject(s)
COVID-19 , Male , Female , Humans , SARS-CoV-2 , Outpatients , Quality of Life , Retrospective Studies , Follow-Up Studies , Academic Medical Centers , Post-Acute COVID-19 SyndromeABSTRACT
Background: Severe infections are a major clinical challenge due to frequent complications and high mortality rates. Objective: The use and impact of antibiotic stewardship (ABS) strategies in the context of severe infections are explained using the examples of sepsis, gram-negative bloodstream infections and coronavirus disease 2019 (COVID-19). Material and methods: The current literature and recommendations are summarized with a focus on clinical ABS implications in severe infections, such as sepsis, gram-negative bloodstream infections and COVID-19. Results: Sepsis: the updated sepsis guidelines propose a differentiated approach concerning the start of antibiotic treatment in patients with sepsis and absence of shock. In patients with an uncertain diagnosis and no signs of shock in the time period before initiating antibiotic treatment can be extended to 3 h. Within this time frame, the differential diagnostic investigations including adequate microbiological sampling should be completed in order to initiate or alternatively reject the start of antibiotic treatment based on reliable results.Gram-negative bloodstream infections: for uncomplicated gram-negative bloodstream infections, 7 days of antibiotic treatment is sufficient. According to current data a regular combination treatment for bloodstream infections due to Pseudomonas aeruginosa is not indicated.COVID-19: bacterial co-infections in COVID-19 are rare. A prophylactic antibiotic treatment is therefore not justified. Secondary bacterial infections (> 48 h after hospitalization) occur primarily in critically ill COVID-19 patients. In the case of pulmonary coinfection or secondary infection, a therapeutic approach in accordance with the current pneumonia guidelines is recommended. Conclusion: Despite the severity and complexity of these severe infections, the basic principles of antibiotic stewardship (ABS) apply in terms of a rational anti-infective prescription with respect to the substance, dosage and duration of treatment.
ABSTRACT
Hintergrund Schwere Infektionen stellen aufgrund der häufigen Komplikationen und hohen Sterblichkeit eine große klinische Herausforderung dar. Ziel der Arbeit (Fragestellung) Am Beispiel der Sepsis, gramnegativer Blutstrominfektionen und COVID-19 sollen Anwendung und Bedeutung von Antibiotic Stewardship(ABS)-Strategien im Kontext schwerer Infektionen erläutert werden. Material und Methode Es erfolgen die Zusammenfassung der aktuellen Literatur und Empfehlungen mit Fokus auf klinische ABS-Implikationen bei schweren Infektionen wie Sepsis, gramnegativen Blutstrominfektionen und COVID-19. Ergebnisse Die aktualisierte Sepsis-Leitlinie schlägt ein differenziertes Vorgehen zum Beginn der Antibiotikatherapie bei Patient*innen mit Sepsis, aber ohne Schock vor. Bei unsicherer Diagnose und bei fehlendem Schock kann der Zeitraum bis zur Einleitung der Antibiotikatherapie auf 3 h ausgedehnt werden. In dieser Zeit gilt es, die Differenzialdiagnostik und ein adäquates mikrobiologisches Sampling zu komplettieren, um eine Antibiotikatherapie aufgrund belastbarer Befunde zu initiieren oder alternativ zu verwerfen. Bei unkomplizierten gramnegativen Blutstrominfektionen ist eine 7‑tägige antibiotische Therapie ausreichend. Eine regelhafte Kombinationstherapie bei Blutstrominfektionen mit Pseudomonas aeruginosa ist aufgrund der bisher vorliegenden Daten nicht erforderlich. Bakterielle Koinfektionen bei COVID-19 sind selten. Eine prophylaktische antibiotische Therapie ist daher nicht gerechtfertigt. Bakterielle Sekundärinfektionen (> 48 h nach Hospitalisierung) treten v. a. bei kritisch kranken COVID-19-Patient*innen auf. Bei pulmonalen Ko- oder Sekundärinfektion ist ein therapeutisches Vorgehen entsprechend den Pneumonie-Leitlinien geboten. Schlussfolgerungen Trotz der Schwere und Komplexität der genannten Infektionen gelten die grundlegenden Prinzipien des Antibiotic Stewardship (ABS) im Sinne einer rationalen Antiinfektivaverordnung hinsichtlich Substanz, Dosis und Dauer der Therapie.
ABSTRACT
BACKGROUND: The city of Freiburg has been among the most affected regions by the COVID-19 pandemic in Germany. In out of hospital cardiac arrest (OHCA) care, all parts of the rescue system were exposed to profound infrastructural changes. We aimed to provide a comprehensive overview of these changes in the resuscitation landscape in the Freiburg region. METHODS: Utstein-style quantitative data on OHCA with CPR initiated, occurring in the first pandemic wave between February 27th, 2020 and April 30th, 2020 were compared to the same time periods between 2016 and 2019. Additionally, qualitative changes in the entire rescue system were analyzed and described. RESULTS: Incidence of OHCA with attempted CPR did not significantly increase during the pandemic period (11.1/100.000 inhabitants/63 days vs 10.4/100.000 inhabitants/63 days, p = 1.000). In witnessed cases, bystander-CPR decreased significantly from 57.7% (30/52) to 25% (4/16) (p = 0.043). A severe pre-existing condition (PEC) was documented more often, 66.7% (16/24) vs 38.2% (39/102) there were longer emergency medical services (EMS) response times, more resuscitation attempts terminated on scene, 62.5% (15/24) vs. 34.3% (35/102) and less patients transported to hospital (p = 0.019). Public basic life support courses, an app-based first-responder alarm system, Kids Save Lives activities and a prehospital extracorporeal CPR (eCPR) service were paused during the peak of the pandemic. CONCLUSION: In our region, bystander CPR in witnessed OHCA cases as well as the number of patients transported to hospital significantly decreased during the first pandemic wave. Several important parts of the resuscitation landscape were paused. The COVID-19 pandemic impedes OHCA care, which leads to additional casualties. Countermeasures should be taken.
Subject(s)
COVID-19 , Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , COVID-19/epidemiology , Germany/epidemiology , Humans , Observational Studies as Topic , Out-of-Hospital Cardiac Arrest/epidemiology , Out-of-Hospital Cardiac Arrest/therapy , Pandemics , RegistriesABSTRACT
The pathophysiological course of COVID-19 can be distinguished in a phase of viral replication and an inflammatory phase. Hyperinflammatory processes promote the development of severe COVID-19. Therefore, immunomodulating agents came into focus. Dexamethasone has already become standard of care for treatment of severe COVID-19. Two large randomized trials and a meta-analysis of collectively nine randomized trials showed a reduced mortality in patients with severe COVID-19 if Tocilizumab - an IL-6-rezeptor antagonist - was added to standard of care. Treatment with Baricitinib - a JAK 1/2 inhibitor - may also be beneficial for patients without or on low oxygen supplementation. National and international guidelines recommend Tocilizumab for treatment of severe COVID-19. Treatment with JAK inhibitors is an option for hospitalized patients with moderate COVID-19. It should be emphasized that comedication of JAK inhibitors and Tocilizumab is not recommended. Further high quality research is required for the widespread use of immunomodulating agents in COVID-19.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Immunomodulating Agents/therapeutic use , Azetidines/therapeutic use , Humans , Purines/therapeutic use , Pyrazoles/therapeutic use , Sulfonamides/therapeutic useABSTRACT
BACKGROUND: Delirium complicating the course of Intensive care unit (ICU) therapy is a known driver of morbidity and mortality. It has been speculated that infection with the neurotrophic SARS-CoV-2 might promote delirium. METHODS: Retrospective registry analysis including all patients treated at least 48 h on a medical intensive care unit. The primary endpoint was development of delirium as diagnosed by Nursing Delirium screening scale ≥2. Results were confirmed by propensity score matching. RESULTS: 542 patients were included. The primary endpoint was reached in 352/542 (64.9%) patients, without significant differences between COVID-19 patients and non-COVID-19 patients (51.4% and 65.9%, respectively, p = 0.07) and correlated with prolonged ICU stay in both groups. In a subgroup of patients with ICU stay >10 days delirium was significantly lower in COVID-19 patients (p ≤ 0.01). After adjustment for confounders, COVID-19 correlated independently with less ICU delirium (p ≤ 0.01). In the propensity score matched cohort, patients with COVID-19 had significantly lower delirium incidence compared to the matched control patients (p ≤ 0.01). CONCLUSION: Delirium is frequent in critically ill patients with and without COVID-19 treated at an intensive care unit. Data suggests that COVID-19 itself is not a driver of delirium per se.
Subject(s)
Delirium/etiology , Respiratory Distress Syndrome/complications , Chi-Square Distribution , Delirium/virology , Humans , Influenza, Human/complications , Influenza, Human/etiology , Influenza, Human/physiopathology , Registries/statistics & numerical data , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/virology , Retrospective Studies , SARS-CoV-2/pathogenicityABSTRACT
BACKGROUND: Increasing evidence suggests that some patients suffer from persistent symptoms for months after recovery from acute COVID-19. However, the clinical phenotype and its pathogenesis remain unclear. We here present data on complaints and results of a diagnostic workup of patients presenting to the post-COVID clinic at the University Medical Center Freiburg. METHODS: Retrospective data analysis of persistently symptomatic patients presenting to our clinic at least 6 months after onset of acute COVID-19. All patients were assessed by a doctor and routine laboratory analysis was carried out. Quality of life was assessed using SF-36 questionnaire. In case of specific persisting symptoms, further organ-specific diagnostic evaluation was performed, and patients were referred to respective departments/specialists. FINDINGS: 132 Patients (58 male, 74 female; mean age 53.8 years) presented to our clinic at least 6 months after COVID-19. 79 (60â%) had been treated as outpatients and 53 (40â%) as inpatients. Most common complaints were persistent fatigue (82â%) and dyspnea on exertion (61â%). Further common complaints were impairments of concentration (54â%), insomnia (43â%), and impairments of smell or taste (35â%). Quality of life was reduced in all sections of the SF-36 questionnaire, yielding a reduced working capacity. Significant pathological findings in laboratory, echocardiographic and radiological work-up were rare. Impairments in lung function tests were more common in previously hospitalized patients. CONCLUSION: Patients presenting 6 months after onset of acute COVID-19 suffer from a diverse spectrum of symptoms with impaired quality of life, also referred to as Long COVID or Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Further research is needed to determine the frequency of these post-COVID syndromes and their pathogenesis, natural course and treatment options. Evaluation and management should be multi-disciplinary.
Subject(s)
COVID-19/complications , SARS-CoV-2/immunology , Adult , Aged , Aged, 80 and over , Anosmia , Antibodies, Viral/blood , COVID-19/epidemiology , Dyspnea , Fatigue , Female , Follow-Up Studies , Germany/epidemiology , Humans , Male , Middle Aged , Quality of Life , Retrospective Studies , Sleep Initiation and Maintenance Disorders , Surveys and Questionnaires , Taste Disorders , Young Adult , Post-Acute COVID-19 SyndromeABSTRACT
Prognosis of patients suffering from acute respiratory distress syndrome (ARDS) is poor. This is especially true for immunosuppressed patients. It is controverisal whether these patients should receive veno-venous extracorporeal membrane oxygenation (VV ECMO) while evidence on this topic is sparse. We report retrospective data of a single-center registry of patients with severe ARDS requiring ECMO support between October 2010 and June 2019. Patients were analyzed by their status of immunosuppression. ECMO weaning success and hospital survival were analyzed before and after propensity score matching (PSM). Moreover, ventilator free days (VFD) were compared. A total of 288 patients were analyzed (age 55 years, 67% male), 88 (31%) presented with immunosuppression. Survival rates were lower in immunosuppressed patients (27% vs. 53%, P < .001 and 27% vs. 48% after PSM, P = .006). VFD (60 days) were lower for patients with immunosuppression (11.9 vs. 22.4, P < .001), and immunosuppression was an independent predictor for mortality in multivariate analysis. Hospital survival was 20%, 14%, 35%, and 46% for patients with oncological malignancies, solid organ transplantation, autoimmune diseases, and HIV, respectively. In this analysis immunosuppression was an independent predictor for mortality. However, there were major differences in the weaning and survival rates between the etiologies of immunosuppression which should be considered in decision making.
Subject(s)
Extracorporeal Membrane Oxygenation , Immunosuppression Therapy , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Adult , Female , Hospital Mortality , Humans , Immunocompromised Host , Male , Middle Aged , Prognosis , Propensity Score , Retrospective Studies , Survival RateABSTRACT
BACKGROUND: We sought to clarify the benefit of cytokine adsorption in patients with COVID-19 supported with venovenous extracorporeal membrane oxygenation (ECMO). METHODS: We did a single-centre, open-label, randomised, controlled trial to investigate cytokine adsorption in adult patients with severe COVID-19 pneumonia requiring ECMO. Patients with COVID-19 selected for ECMO at the Freiburg University Medical Center (Freiburg, Germany) were randomly assigned (1:1) to receive cytokine adsorption using the CytoSorb device or not. Randomisation was computer-generated, allocation was concealed by opaque, sequentially numbered sealed envelopes. The CytoSorb device was incorporated into the ECMO circuit before connection to the patient circuit, replaced every 24 h, and removed after 72 h. The primary endpoint was serum interleukin-6 (IL-6) concentration 72 h after initiation of ECMO analysed by intention to treat. Secondary endpoints included 30-day survival. The trial is registered with ClinicalTrials.gov (NCT04324528) and the German Clinical Trials Register (DRKS00021300) and is closed. FINDINGS: From March 29, 2020, to Dec 29, 2020, of 34 patients assessed for eligibility, 17 (50%) were treated with cytokine adsorption and 17 (50%) without. Median IL-6 decreased from 357·0 pg/mL to 98·6 pg/mL in patients randomly assigned to cytokine adsorption and from 289·0 pg/mL to 112·0 pg/mL in the control group after 72 h. One patient in each group died before 72 h. Adjusted mean log IL-6 concentrations after 72 h were 0·30 higher in the cytokine adsorption group (95% CI -0·70 to 1·30, p=0·54). Survival after 30 days was three (18%) of 17 with cytokine adsorption and 13 (76%) of 17 without cytokine adsorption (p=0·0016). INTERPRETATION: Early initiation of cytokine adsorption in patients with severe COVID-19 and venovenous ECMO did not reduce serum IL-6 and had a negative effect on survival. Cytokine adsorption should not be used during the first days of ECMO support in COVID-19. FUNDING: None.
Subject(s)
COVID-19/therapy , Cytokines , Extracorporeal Membrane Oxygenation , Adsorption , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
BACKGROUND: Acute 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. METHODS: We 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. RESULTS: In 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). CONCLUSION: Triple 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.
Subject(s)
Acute Kidney Injury/etiology , Antiviral Agents/adverse effects , COVID-19 Drug Treatment , Hydroxychloroquine/adverse effects , Lopinavir/adverse effects , Acute Kidney Injury/epidemiology , Aged , Antiviral Agents/therapeutic use , COVID-19/virology , Creatinine/blood , Drug Therapy, Combination , Female , Germany/epidemiology , Humans , Hydroxychloroquine/therapeutic use , Incidence , Intensive Care Units , Lopinavir/therapeutic use , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/isolation & purificationABSTRACT
Both antiviral treatment with remdesivir and hemoadsorption using a CytoSorb® adsorption device are applied in the treatment of severe COVID-19. The CytoSorb® adsorber consists of porous polymer beads that adsorb a broad range of molecules, including cytokines but also several therapeutic drugs. In this study, we evaluated whether remdesivir and its main active metabolite GS-441524 would be adsorbed by CytoSorb® . Serum containing remdesivir or GS-441524 was circulated in a custom-made system containing a CytoSorb® device. Concentrations of remdesivir and GS-441524 before and after the adsorber were analyzed by liquid chromatography-tandem mass spectrometry. Measurements of remdesivir in the outgoing tube after the adsorber indicated almost complete removal of remdesivir by the device. In the reservoir, concentration of remdesivir showed an exponential decay and was not longer detectable after 60 mins. GS-441524 showed a similar exponential decay but, unlike remdesivir, it reached an adsorption-desorption equilibrium at ~48 µg/L. Remdesivir and its main active metabolite GS-441524 are rapidly eliminated from the perfusate by the CytoSorb® adsorber device in vitro. This should be considered in patients for whom both therapies are indicated, and simultaneous application should be avoided. In general, plasma levels of therapeutic drugs should be closely monitored under concurrent CytoSorb® therapy.
Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/therapy , Hemoperfusion/instrumentation , Adenosine/analogs & derivatives , Adenosine Monophosphate/blood , Adenosine Monophosphate/pharmacokinetics , Alanine/blood , Alanine/pharmacokinetics , Blood Chemical Analysis , COVID-19/blood , Chromatography, Liquid , Combined Modality Therapy , Furans/blood , Furans/pharmacokinetics , Hemoperfusion/adverse effects , Humans , Pyrroles/blood , Pyrroles/pharmacokinetics , Tandem Mass Spectrometry , Triazines/blood , Triazines/pharmacokineticsABSTRACT
BACKGROUND: Germany reported sufficient intensive care unit (ICU) resources throughout the first wave of coronavirus disease 2019 (COVID-19). The treatment of critically ill COVID-19 patients without rationing may improve the outcome. We therefore analyzed ICU resources allocated to COVID-19 patients with respiratory failure and their outcomes. METHODS: Retrospectively, we enrolled severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR)-positive patients with respiratory failure from 03/08/2020 to 04/08/2020 and followed until 05/28/2020 in the university hospital of Freiburg, Germany. RESULTS: In the defined interval, 34 COVID-19 patients were admitted to the ICU with median age of 67±13 (31-86) years. Six of 34 (17.6%) were female. All patients suffered from moderate or severe acute respiratory distress syndrome (ARDS), 91.2% of the patients were intubated and 23.5% required extracorporeal membrane oxygenation (ECMO). Proning was performed in 67.6%, renal replacement therapy (RRT) was required in 35.3%. Ninety-six percent required more than 20 nursing hours per day. Mean ICU stay was 21±19 (1-81) days. Sixty-day survival of critically ill COVID-19 patients was 50.0% (17/34). Causes of death were multi-organ failure (52.9%), refractory ARDS (17.6%) and intracerebral hemorrhage (17.6%). CONCLUSIONS: Treatment of critically ill COVID-19 patients is protracted and resource-intense. In a context without resources shortage, 50% of COVID-19 with respiratory failure survived up to 60 days.
ABSTRACT
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.
Subject(s)
COVID-19/complications , Cerebral Hemorrhage/epidemiology , Cerebral Hemorrhage/virology , Respiratory Distress Syndrome/virology , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/therapy , Cerebral Hemorrhage/therapy , Critical Care , Extracorporeal Membrane Oxygenation , Female , Germany , Humans , Length of Stay , Male , Middle Aged , Propensity Score , Registries , Respiration, Artificial , Respiratory Distress Syndrome/mortality , Respiratory Distress Syndrome/therapy , Retrospective Studies , Risk Factors , Survival Rate , Young AdultABSTRACT
Corticosteroids have been found as useful adjunctive therapy in patients with various infections and hyperinflammation-associated disease. They are recommended in practice guidelines for patients with tuberculous and pneumococcal meningitis and patients with immune reconstitution syndrome associated with antiretroviral therapy. A new indication is severe COVID-19. Evidence from clinical trials is insufficient to allow the routine use of steroids among patients with septic shock, community-acquired pneumonia or tuberculous pericarditis.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19 Drug Treatment , HIV Infections/complications , Immune Reconstitution Inflammatory Syndrome/drug therapy , Meningitis, Pneumococcal/drug therapy , Tuberculosis, Meningeal/drug therapy , Brain Abscess/drug therapy , Chemotherapy, Adjuvant , HIV Infections/drug therapy , Humans , Sepsis/drug therapy , Severity of Illness Index , Shock, Septic/drug therapy , Spirochaetales Infections/drug therapy , Tuberculosis/drug therapyABSTRACT
BACKGROUND: Critically ill coronavirus disease 2019 (COVID-19) patients have a high risk of acute kidney injury (AKI) that requires renal replacement therapy (RRT). A state of hypercoagulability reduces circuit life spans. To maintain circuit patency and therapeutic efficiency, an optimized anticoagulation strategy is needed. This study investigates whether alternative anticoagulation strategies for RRT during COVID-19 are superior to administration of unfractionated heparin (UFH). METHODS: Retrospective cohort study on 71 critically ill COVID-19 patients (≥18 years), admitted to intensive care units at a tertiary health care facility in the southwestern part of Germany between February 26 and May 21, 2020. We collected data on the disease course, AKI, RRT, and thromboembolic events. Four different anticoagulatory regimens were administered. Anticoagulation during continuous veno-venous hemodialysis (CVVHD) was performed with UFH or citrate. Anticoagulation during sustained low-efficiency daily dialysis (SLEDD) was performed with UFH, argatroban, or low molecular weight heparin (LMWH). Primary outcome is the effect of the anticoagulation regimen on mean treatment times of RRT. RESULTS: In patients receiving CVVHD, mean treatment time in the UFH group was 21.3 h (SEM: ±5.6 h), in the citrate group 45.6 h (SEM: ±2.7 h). Citrate anticoagulation significantly prolonged treatment times by 24.4 h (P = .001). In patients receiving SLEDD, mean treatment time with UFH was 8.1 h (SEM: ±1.3 h), with argatroban 8.0 h (SEM: ±0.9 h), and with LMWH 11.8 h (SEM: ±0.5 h). LMWH significantly prolonged treatment times by 3.7 h (P = .008) and 3.8 h (P = .002), respectively. CONCLUSIONS: UFH fails to prevent early clotting events in the dialysis circuit during COVID-19. For patients, who do not require effective systemic anticoagulation, regional citrate dialysis is the most effective strategy. For patients, who require effective systemic anticoagulation, the usage of LMWH results in the longest circuit life spans. The proposed anticoagulatory strategies are safe, can easily be monitored, and allow an individualized treatment.
Subject(s)
Acute Kidney Injury/therapy , Anticoagulants/administration & dosage , Betacoronavirus , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Renal Replacement Therapy/methods , Acute Kidney Injury/blood , Acute Kidney Injury/epidemiology , Adult , Aged , Arginine/analogs & derivatives , Blood Coagulation , COVID-19 , Citric Acid/administration & dosage , Comorbidity , Coronavirus Infections/blood , Critical Care , Critical Illness , Equipment Failure , Female , Germany/epidemiology , Heparin/administration & dosage , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Male , Middle Aged , Pandemics , Pipecolic Acids/administration & dosage , Pneumonia, Viral/blood , Renal Replacement Therapy/instrumentation , Retrospective Studies , SARS-CoV-2 , Sulfonamides , Tertiary Care CentersABSTRACT
BACKGROUND: Reported mortality of hospitalised Coronavirus Disease-2019 (COVID-19) patients varies substantially, particularly in critically ill patients. So far COVID-19 in-hospital mortality and modes of death under state of the art care have not been systematically studied. METHODS: This retrospective observational monocenter cohort study was performed after implementation of a non-restricted, dynamic tertiary care model at the University Medical Center Freiburg, an experienced acute respiratory distress syndrome (ARDS) and extracorporeal membrane-oxygenation (ECMO) referral center. All hospitalised patients with PCR-confirmed SARS-CoV-2 infection were included. The primary endpoint was in-hospital mortality, secondary endpoints included major complications and modes of death. A multistate analysis and a Cox regression analysis for competing risk models were performed. Modes of death were determined by two independent reviewers. RESULTS: Between February 25, and May 8, 213 patients were included in the analysis. The median age was 65 years, 129 patients (61%) were male. 70 patients (33%) were admitted to the intensive care unit (ICU), of which 57 patients (81%) received mechanical ventilation and 23 patients (33%) ECMO support. Using multistate methodology, the estimated probability to die within 90 days after COVID-19 onset was 24% in the whole cohort. If the levels of care at time of study entry were accounted for, the probabilities to die were 16% if the patient was initially on a regular ward, 47% if in the intensive care unit (ICU) and 57% if mechanical ventilation was required at study entry. Age ≥65 years and male sex were predictors for in-hospital death. Predominant complications-as judged by two independent reviewers-determining modes of death were multi-organ failure, septic shock and thromboembolic and hemorrhagic complications. CONCLUSION: In a dynamic care model COVID-19-related in-hospital mortality remained very high. In the absence of potent antiviral agents, strategies to alleviate or prevent the identified complications should be investigated. In this context, multistate analyses enable comparison of models-of-care and treatment strategies and allow estimation and allocation of health care resources.