ABSTRACT
Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.
Subject(s)
Lipoproteins , Shock, Septic , Thromboplastin , Humans , Shock, Septic/blood , Shock, Septic/metabolism , Thromboplastin/metabolism , Male , Female , Lipoproteins/blood , Lipoproteins/metabolism , Middle Aged , Aged , Multiple Organ Failure/blood , Multiple Organ Failure/etiology , Disseminated Intravascular Coagulation/blood , Case-Control Studies , Adult , Biomarkers/bloodABSTRACT
Acute kidney injury (AKI) is a common problem in critically ill patients and is associated with increased morbidity and mortality. Since 2012, AKI has been defined according to the KDIGO (Kidney Disease Improving Global Outcome) guidelines. As some biomarkers are now available that can provide useful clinical information, a new definition including a new stage 1S has been proposed by an expert group of the Acute Disease Quality Initiative (ADQI). At this stage, classic AKI criteria are not yet met, but biomarkers are already positive defining subclinical AKI. This stage 1S is associated with a worse patient outcome, regardless of the biomarker chosen. The PrevAKI and PrevAKI-Multicenter trial also showed that risk stratification with a biomarker and implementation of the KDIGO bundle (in the high-risk group) can reduce the rate of moderate and severe AKI. In the absence of a successful clinical trial, conservative management remains the primary focus of treatment. This mainly involves optimization of hemodynamics and an individualized (restrictive) fluid management. The STARRT-AKI trial has shown that there is no benefit from accelerated initiation of renal replacement therapy. However, delaying too long might be associated with potential harm, as shown in the AKIKI2 study. Prospective studies are needed to determine whether artificial intelligence will play a role in AKI in the future, helping to guide treatment decisions and improve outcomes.
Subject(s)
Acute Kidney Injury , Biomarkers , Acute Kidney Injury/therapy , Acute Kidney Injury/diagnosis , Acute Kidney Injury/classification , Biomarkers/blood , Humans , Prognosis , Renal Replacement Therapy , Phenotype , Fluid TherapyABSTRACT
Direct thrombin inhibitors, including argatroban, are increasingly used for anticoagulation during venovenous extracorporeal membrane oxygenation (VV ECMO). In many centers activated partial thromboplastin time (aPTT) is used for monitoring, but it can be affected by several confounders. The aim of this study was to evaluate the safety and efficacy of anticoagulation with argatroban titrated according to diluted thrombin time targets (hemoclot™ assay) compared to anti-Xa guided anticoagulation with unfractionated heparin (UFH). METHODS: This cohort study included adults at two tertiary care centers who required VV ECMO for severe COVID-19-related acute respiratory distress syndrome (CARDS). Patients received center-dependent argatroban or UFH for anticoagulation during ECMO. Argatroban was guided following a hemoclot™ target range of 0.4-0.6 µg/ml. UFH was guided by anti-factor Xa (antiXa) levels (0.2-0.3 IU/ml). The primary outcome was safety of argatroban compared to UFH, assessed by time to first clinically relevant bleeding event or death during ECMO. Secondary outcomes included efficacy (time to thromboembolism) and feasibility (proportion of anticoagulation targets within range). RESULTS: From 2019 to 2021 57 patients were included in the study with 27 patients (47 %) receiving argatroban and 30 patients (53 %) receiving UFH. The time to the first clinically relevant bleeding or death during ECMO was similar between groups (HR (argatroban vs. UFH): 1.012, 95 % CI 0.44-2.35, p = 0.978). Argatroban was associated with a decreased risk for thromboembolism compared to UFH (HR 0.494 (95 % CI 0.26-0.95; p = 0.034)). The overall proportion of anticoagulation within target ranges was not different between groups (46 % (23-54 %) vs. 46 % (37 %-57 %), p = 0.45). CONCLUSION: Anticoagulation with argatroban according to hemoclot™ targets (0.4-0.6 µg/ml) compared to antiXa guided UFH (0.2-0.3 IU/ml) is safe and may prolong thromboembolism-free time in patients with severe ARDS requiring VV ECMO.
Subject(s)
Arginine/analogs & derivatives , Extracorporeal Membrane Oxygenation , Pipecolic Acids , Respiratory Distress Syndrome , Sulfonamides , Thromboembolism , Adult , Humans , Heparin/therapeutic use , Heparin/pharmacology , Anticoagulants/therapeutic use , Cohort Studies , Heparin, Low-Molecular-Weight , Hemorrhage , Respiratory Distress Syndrome/drug therapy , Retrospective StudiesABSTRACT
INTRODUCTION: A small percentage of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) showed severe respiratory deterioration requiring treatment with extracorporeal membrane oxygenation (ECMO). During the pandemic surges availability of ECMO devices was limited and resources had to be used wisely. The aim of this analysis was to determine the incidence and outcome of venovenous (VV) ECMO patients in Tyrol, when criteria based on the Extracorporeal Life Support Organization (ELSO) guidelines for VV-ECMO initiation were established. METHODS: This is a secondary analysis of the Tyrol-CoV-ICU-Reg, which includes all patients admitted to an intensive care unit (ICU) during the coronavirus disease 2019 (COVID-19) pandemic in Tyrol. Of the 13 participating departments, VV-ECMO was performed at 4 units at the University Hospital Innsbruck. RESULTS: Overall, 37 (3.4%) of 1101 patients were treated with VV-ECMO during their ICU stay. The hospital mortality rate was approximately 40% (nâ¯= 15). Multiorgan failure due to sepsis was the most common cause of death. No significant difference in survival rates between newly initiated and experienced centers was observed. The median survival time of nonsurvivors was 27 days (interquartile range, IQR: 22-36 days) after initiation of VV-ECMO. Acute kidney injury meeting the Kidney Disease: Improving Global Outcomes (KDIGO) criteria occurred in 48.6%. Renal replacement therapy (RRT) was initiated in 12 (32.4%) patients after a median of 18 days (IQR: 1-26 days) after VV-ECMO start. The median length of ICU and hospital stays were 38 days (IQR: 30-55 days) and 50 days (IQR: 37-83 days), respectively. DISCUSSION: Despite a rapidly increased demand and the resulting requirement to initiate an additional ECMO center, we could demonstrate that a structured approach with interdisciplinary collaboration resulted in favorable survival rates similar to multinational reports.
Subject(s)
COVID-19 , Critical Illness , Humans , Critical Illness/therapy , Transportation of Patients , Critical Care , Patient TransferABSTRACT
INTRODUCTION: Acute kidney injury is a frequent complication in critically ill patients with and without COVID-19. The aim of this study was to evaluate the incidence of, and risk factors for, acute kidney injury and its effect on clinical outcomes of critically ill COVID-19 patients in Tyrol, Austria. METHODS: This multicenter prospective registry study included adult patients with a SARS-CoV-2 infection confirmed by polymerase chain reaction, who were treated in one of the 12 dedicated intensive care units during the COVID-19 pandemic from February 2020 until May 2022. RESULTS: In total, 1042 patients were included during the study period. The median age of the overall cohort was 66 years. Of the included patients, 267 (26%) developed acute kidney injury during their intensive care unit stay. In total, 12.3% (n = 126) required renal replacement therapy with a median duration of 9 (IQR 3-18) days. In patients with acute kidney injury the rate of invasive mechanical ventilation was significantly higher with 85% (n = 227) compared to 41% (n = 312) in the no acute kidney injury group (p < 0.001). The most important risk factors for acute kidney injury were invasive mechanical ventilation (OR = 4.19, p < 0.001), vasopressor use (OR = 3.17, p < 0.001) and chronic kidney disease (OR = 2.30, p < 0.001) in a multivariable logistic regression analysis. Hospital and intensive care unit mortality were significantly higher in patients with acute kidney injury compared to patients without acute kidney injury (Hospital mortality: 52.1% vs. 17.2%, p < 0.001, ICU-mortality: 47.2% vs. 14.7%, p < 0.001). CONCLUSION: As in non-COVID-19 patients, acute kidney injury is clearly associated with increased mortality in critically ill COVID-19 patients. Among known risk factors, invasive mechanical ventilation has been identified as an independent and strong predictor of acute kidney injury.
Subject(s)
Acute Kidney Injury , COVID-19 , Adult , Aged , Humans , Acute Kidney Injury/epidemiology , Acute Kidney Injury/therapy , Austria/epidemiology , COVID-19/complications , COVID-19/epidemiology , COVID-19/therapy , Critical Illness/therapy , Incidence , Intensive Care Units , Pandemics , Respiration, Artificial , Retrospective Studies , Risk Factors , SARS-CoV-2 , Middle AgedABSTRACT
BACKGROUND: Many articles described a massive decline in surgical procedures during the COVID-19 pandemic waves. Especially the reduction in oncologic and emergency procedures led to the concern that delays and cancelling surgical activity might lead to a substantial increase in preventable deaths. METHODS: Overall numbers and types of surgery were analysed in a tertiary hospital in Austria during the winter period (October-April) from 2015/16 to 2021/22. The half-years 2019/20, 2020/21 and 2021/22 were defined as pandemic half-years and were compared with the mean results of the previous, four, pre-pandemic half-years. RESULTS: A reduction was found for overall numbers and elective surgeries during 2019/20 (4.62%; p < 0.0001 and 12.14; p < 0.0001 respectively) and 2021/22 (14.94%; p < 0.0001 and 34.27; p < 0.0001 respectively). Oncologic surgery increased during 2021/22 (- 12.59%; p < 0.0001) and remained unchanged during the other periods. Emergency surgeries increased during 2019/20 (- 6.97%; p < 0.0001) and during 2021/22 (- 9.44%; p < 0.0001) and remained unchanged during 2020/21. CONCLUSIONS: The concern that the pandemic led to a decrease in oncologic and emergency surgeries cannot be supported with the data from our hospital. A flexible, day-by-day, resource allocation programme with central coordination adhering to hospital resilience recommendations may have helped to adapt to the impact of the COVID-19 pandemic during the first three pandemic half-years.
ABSTRACT
BACKGROUND: Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. METHODS: This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan-Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. RESULTS: This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06-1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. CONCLUSION: Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. STUDY REGISTRATION: NCT04321265, registered March 19th, 2020.
Subject(s)
COVID-19 , Diabetes Mellitus , Humans , Aged , Aged, 80 and over , Prospective Studies , SARS-CoV-2 , Critical Illness , Diabetes Mellitus/epidemiology , Intensive Care UnitsABSTRACT
The administration of fluids is one of the most common interventions in the intensive care unit. The effects and side effects of intravenous fluids depend on the amount administered and their specific composition. Intravenous fluid solutions are either considered crystalloids (for example 0.9% saline, lactated Ringer's solution) or colloids (artificial colloids such as gelatins, and albumin). This narrative review summarizes the physiological principles of fluid therapy and reviews the most important studies on crystalloids, artificial colloids and albumin in the context of critically ill patients.
Subject(s)
Albumins , Colloids , Humans , Isotonic Solutions/therapeutic use , Isotonic Solutions/adverse effects , Crystalloid Solutions , Albumins/therapeutic use , Colloids/therapeutic use , Intensive Care UnitsABSTRACT
Coronavirus disease 2019 (COVID-19)-associated acute kidney injury (AKI) is common in critically ill patients. Renal tropism of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) appears to play only a minor role, whereas the pathological inflammatory response associated with severe COVID-19 is highly relevant. Both the consequences of invasive ventilation and acute respiratory distress syndrome (ARDS) caused by COVID-19 have a significant impact on the pathogenesis of AKI. High ventilation pressures compromise renal perfusion and, thus, may contribute to the development of AKI. The inflammatory response caused by ARDS, as well as the endothelial dysfunction typical of COVID-19 in combination with hypercoagulability are further factors that affect the kidney.
Subject(s)
Acute Kidney Injury , COVID-19 , Respiratory Distress Syndrome , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , COVID-19/complications , Humans , Inflammation/complications , Kidney , Lung , Respiration, Artificial/adverse effects , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , SARS-CoV-2ABSTRACT
Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns as to whether it contributes to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. We implemented a routine screening of respiratory specimens in COVID-19 ICU patients for Aspergillus species using culture and galactomannan (GM) detection from serum and/or bronchoalveolar lavages (BAL). Out of 329 ICU patients treated during March 2020 and April 2021, 23 (7%) suffered from CAPA, 13 of probable, and 10 of possible. In the majority of cases, culture, microscopy, and GM testing were in accordance with CAPA definition. However, we saw that the current definitions underscore to pay attention for fungal microscopy and GM detection in BALs, categorizing definitive CAPA diagnosis based on culture positive samples only. The spectrum of Aspergillus species involved Aspergillus fumigatus, followed by Aspergillus flavus, Aspergillus niger, and Aspergillus nidulans. We noticed changes in fungal epidemiology, but antifungal resistance was not an issue in our cohort. The study highlights that the diagnosis and incidence of CAPA is influenced by the application of laboratory-based diagnostic tests. Culture positivity as a single microbiological marker for probable definitions may overestimate CAPA cases and thus may trigger unnecessary antifungal treatment.
ABSTRACT
(1) Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns to contribute to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. (2) Methods: Here, we assessed Aspergillus culture-positive and culture-negative respiratory tract specimens via direct fungal microscopy (gold standard) and compared the results with galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR. (3) Results: 241 respiratory samples from patients suffering from SARS-CoV-2 pneumonia were evaluated. Results showed both diagnostic tools, Aspergillus PCR and GM-EIA, to be positive or negative displaying a sensitivity of 0.90, a specificity of 0.77, a negative predictive value (NPV) of 0.95, and a positive predictive value (PPV) of 0.58 in Aspergillus sp. culture and microscopic-positive specimens. Non-bronchoalveolar lavage (BAL) samples, obtained within a few days from the same patient, showed a high frequency of intermittent positive or negative GM-EIA or Aspergillus PCR results. Positivity of a single biomarker is insufficient for a proper diagnosis. A broad spectrum of Aspergillus species was detected. (4) Conclusions: Our study highlights the challenges of combined biomarker testing as part of diagnosing CAPA. From the results presented, we highly recommend the additional performance of direct microscopy in respiratory specimens to avoid overestimation of fungal infections by applying biomarkers.
ABSTRACT
The Saline versus Albumin Fluid Evaluation (SAFE) study has demonstrated that the use of albumin as an infusion solution in volume therapy can be regarded as safe. An exception is hypo-oncotic albumin in traumatic brain injury. While clear indications of albumin exist for some patients with liver cirrhosis, large studies that demonstrate a clinically relevant advantage beyond hemodynamic effects and would therefore justify wider use in many other areas are still lacking. In large-volume paracentesis, spontaneous bacterial peritonitis, but also in hepatorenal syndrome, use of albumin is recommended and established due to clinical benefit in randomized controlled trials. In septic shock, use of albumin may be considered, with two large studies addressing this issue in Germany and Italy being still in the recruitment phase. For volume therapy, albumin can be used primarily when other measures for hemodynamic stabilization have been exhausted. This applies to volume resuscitation in hypovolemia as well as in conservative fluid management in the so-called "de-resuscitation" phase. The extent to which the correction of severe hypoalbuminemia with exogenous albumin can improve the impaired outcome of these patients is also part of ongoing studies. On the way to a more individualized medicine, hypoalbuminemia may serve as a parameter in future decision making for or against the use of albumin in volume therapy.
Subject(s)
Hepatorenal Syndrome , Peritonitis , Albumins , Ascites , Humans , Liver Cirrhosis/therapy , Peritonitis/drug therapyABSTRACT
BACKGROUND: Widely varying mortality rates of critically ill Coronavirus disease 19 (COVID-19) patients in the world highlighted the need for local surveillance of baseline characteristics, treatment strategies and outcome. We compared two periods of the COVID-19 pandemic to identify important differences in characteristics and therapeutic measures and their influence on the outcome of critically ill COVID-19 patients. METHODS: This multicenter prospective register study included all patients with a SARS-CoV2 infection confirmed by polymerase chain reaction, who were treated in 1 of the 12 intensive care units (ICU) from 8 hospitals in Tyrol, Austria during 2 defined periods (1 February 2020 until 17 July: first wave and 18 July 2020 until 22 February 2021: second wave) of the COVID-19 pandemic. RESULTS: Overall, 508 patients were analyzed. The majority (nâ¯= 401) presented during the second wave, where the median age was significantly higher (64 years, IQR 54-74 years vs. 72 years, IQR 62-78 years, pâ¯< 0.001). Invasive mechanical ventilation was less frequent during the second period (50.5% vs 67.3%, pâ¯= 0.003), as was the use of vasopressors (50.3% vs. 69.2%, pâ¯= 0.001) and renal replacement therapy (12.0% vs. 19.6%, pâ¯= 0.061), which resulted in shorter ICU length of stay (10 days, IQR 5-18 days vs. 18 days, IQR 5-31 days, pâ¯< 0.001). Nonetheless, ICU mortality did not change (28.9% vs. 21.5%, pâ¯= 0.159) and hospital mortality even increased (22.4% vs. 33.4%, pâ¯= 0.039) in the second period. Age, frailty and the number of comorbidities were significant predictors of hospital mortality in a multivariate logistic regression analysis of the overall cohort. CONCLUSION: Advanced treatment strategies and learning effects over time resulted in reduced rates of mechanical ventilation and vasopressor use in the second wave associated with shorter ICU length of stay. Despite these improvements, age appears to be a dominant factor for hospital mortality in critically ill COVID-19 patients.