Publications by authors named "Michael Joannidis"

208 Publications

Discontinuation versus continuation of renin-angiotensin-system inhibitors in COVID-19 (ACEI-COVID): a prospective, parallel group, randomised, controlled, open-label trial.

Lancet Respir Med 2021 Jun 11. Epub 2021 Jun 11.

Department of Internal Medicine I (Cardiology), University Hospital Aachen, Aachen, Germany.

Background: SARS-CoV-2 entry in human cells depends on angiotensin-converting enzyme 2, which can be upregulated by inhibitors of the renin-angiotensin system (RAS). We aimed to test our hypothesis that discontinuation of chronic treatment with ACE-inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) mitigates the course o\f recent-onset COVID-19.

Methods: ACEI-COVID was a parallel group, randomised, controlled, open-label trial done at 35 centres in Austria and Germany. Patients aged 18 years and older were enrolled if they presented with recent symptomatic SARS-CoV-2 infection and were chronically treated with ACEIs or ARBs. Patients were randomly assigned 1:1 to discontinuation or continuation of RAS inhibition for 30 days. Primary outcome was the maximum sequential organ failure assessment (SOFA) score within 30 days, where death was scored with the maximum achievable SOFA score. Secondary endpoints were area under the death-adjusted SOFA score (AUC), mean SOFA score, admission to the intensive care unit, mechanical ventilation, and death. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT04353596.

Findings: Between April 20, 2020, and Jan 20, 2021, 204 patients (median age 75 years [IQR 66-80], 37% females) were randomly assigned to discontinue (n=104) or continue (n=100) RAS inhibition. Within 30 days, eight (8%) of 104 died in the discontinuation group and 12 (12%) of 100 patients died in the continuation group (p=0·42). There was no significant difference in the primary endpoint between the discontinuation and continuation group (median [IQR] maximum SOFA score 0·00 (0·00-2·00) vs 1·00 (0·00-3·00); p=0·12). Discontinuation was associated with a significantly lower AUC (0·00 [0·00-9·25] vs 3·50 [0·00-23·50]; p=0·040), mean SOFA score (0·00 [0·00-0·31] vs 0·12 [0·00-0·78]; p=0·040), and 30-day SOFA score (0·00 [10-90th percentile, 0·00-1·20] vs 0·00 [0·00-24·00]; p=0·023). At 30 days, 11 (11%) in the discontinuation group and 23 (23%) in the continuation group had signs of organ dysfunction (SOFA score ≥1) or were dead (p=0·017). There were no significant differences for mechanical ventilation (10 (10%) vs 8 (8%), p=0·87) and admission to intensive care unit (20 [19%] vs 18 [18%], p=0·96) between the discontinuation and continuation group.

Interpretation: Discontinuation of RAS-inhibition in COVID-19 had no significant effect on the maximum severity of COVID-19 but may lead to a faster and better recovery. The decision to continue or discontinue should be made on an individual basis, considering the risk profile, the indication for RAS inhibition, and the availability of alternative therapies and outpatient monitoring options.

Funding: Austrian Science Fund and German Center for Cardiovascular Research.
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http://dx.doi.org/10.1016/S2213-2600(21)00214-9DOI Listing
June 2021

Provision of critical care for the elderly in Europe: a retrospective comparison of national healthcare frameworks in intensive care units.

BMJ Open 2021 Jun 3;11(6):e046909. Epub 2021 Jun 3.

Division of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Dusseldorf, Dusseldorf, Germany

Objectives: In Europe, there is a distinction between two different healthcare organisation systems, the tax-based healthcare system (THS) and the social health insurance system (SHI). Our aim was to investigate whether the characteristics, treatment and mortality of older, critically ill patients in the intensive care unit (ICU) differed between THS and SHI.

Setting: ICUs in 16 European countries.

Participants: In total, 7817 critically ill older (≥80 years) patients were included in this study, 4941 in THS and 2876 in the SHI systems.

Primary And Secondary Outcomes Measures: We chose generalised estimation equations with robust standard errors to produce population average adjusted OR (aOR). We adjusted for patient-specific variables, health economic data, including gross domestic product (GDP) and human development index (HDI), and treatment strategies.

Results: In SHI systems, there were higher rates of frail patients (Clinical Frailty Scale>4; 46% vs 41%; p<0.001), longer length of ICU stays (90±162 vs 72±134 hours; p<0.001) and increased levels of organ support. The ICU mortality (aOR 1.50, 95% CI 1.09 to 2.06; p=0.01) was consistently higher in the SHI; however, the 30-day mortality (aOR 0.89, 95% CI 0.66 to 1.21; p=0.47) was similar between THS and SHI. In a sensitivity analysis stratifying for the health economic data, the 30-day mortality was higher in SHI, in low GDP per capita (aOR 2.17, 95% CI 1.42 to 3.58) and low HDI (aOR 1.22, 95% CI 1.64 to 2.20) settings.

Conclusions: The 30-day mortality was similar in both systems. Patients in SHI were older, sicker and frailer at baseline, which could be interpreted as a sign for a more liberal admission policy in SHI. We believe that the observed trend towards ICU excess mortality in SHI results mainly from a more liberal admission policy and an increase in treatment limitations.

Trial Registration Numbers: NCT03134807 and NCT03370692.
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http://dx.doi.org/10.1136/bmjopen-2020-046909DOI Listing
June 2021

Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative.

Nat Rev Nephrol 2021 May 11. Epub 2021 May 11.

Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA, USA.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.
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http://dx.doi.org/10.1038/s41581-021-00418-2DOI Listing
May 2021

Pharmacokinetics and antifungal activity of echinocandins in ascites fluid of critically ill patients.

Antimicrob Agents Chemother 2021 May 10. Epub 2021 May 10.

Clinical Pharmacokinetics Unit, Division of Medical Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria

Pharmacokinetics and antifungal activity of the echinocandins anidulafungin (AFG), micafungin (MFG) and caspofungin (CAS) were assessed in ascites fluid and plasma of critically ill adults treated for suspected or proven invasive candidiasis. Ascites fluid was obtained from ascites drains or during paracentesis. The antifungal activity of the echinocandins in ascites fluid was assessed by incubation of and at concentrations of 0.03 to 16.00 μg/ml. In addition, ascites fluid samples obtained from our study patients were inoculated with the same isolates and evaluated for fungal growth. These patient samples had to be spiked with echinocandins to restore the original concentrations, because echinocandins had been lost during sterile filtration. In ascites fluid specimens of 29 patients, echinocandin concentrations were below the simultaneous plasma levels. Serial sampling in 20 patients revealed a slower rise and decline of echinocandin concentrations in ascites fluid than in plasma. Proliferation of in ascites fluid was slower than in culture medium and growth of was lacking, even in the absence of antifungals. In CAS-spiked ascites fluid samples, fungal CFU counts moderately declined, whereas spiking with AFG or MFG, had no relevant effect. In ascites fluid of our study patients, echinocandin concentrations achieved by therapeutic doses did not result in a consistent eradication of or Thus, therapeutic doses of AFG, MFG, or CAS may result in ascites fluid concentrations preventing relevant proliferation of and , but do not warrant reliable eradication.
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http://dx.doi.org/10.1128/AAC.02565-20DOI Listing
May 2021

Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial.

Intensive Care Med 2021 Jun 7;47(6):665-673. Epub 2021 May 7.

Department of Intensive Care, Austin Hospital, Melbourne, Australia.

Purpose: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation.

Methods: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization.

Results: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm.

Conclusions: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.
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http://dx.doi.org/10.1007/s00134-021-06401-6DOI Listing
June 2021

Outcomes in patients treated with chimeric antigen receptor T-cell therapy who were admitted to intensive care (CARTTAS): an international, multicentre, observational cohort study.

Lancet Haematol 2021 May;8(5):e355-e364

Critical Care Department, APHP, Hôpital Saint-Louis, University of Paris, Paris, France.

Background: Chimeric antigen receptor (CAR) T-cell therapy can induce side-effects such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome (ICANS), which often require intensive care unit admission. The aim of this study was to describe management of critically ill CAR T-cell recipients in intensive care.

Methods: This international, multicentre, observational cohort study was done in 21 intensive care units in France, Spain, the USA, the UK, Russia, Canada, Germany, and Austria. Eligible patients were aged 18 years or older; had received CAR T-cell therapy in the past 30 days; and had been admitted to intensive care for any reason. Investigators retrospectively included patients admitted between Feb 1, 2018, and Feb 1, 2019, and prospectively included patients admitted between March 1, 2019, and Feb 1, 2020. Demographic, clinical, laboratory, treatment, and outcome data were extracted from medical records. The primary endpoint was 90-day mortality. Factors associated with mortality were identified using a Cox proportional hazard model.

Findings: 942 patients received CAR T-cell therapy, of whom 258 (27%) required admission to intensive care and 241 (26%) were included in the analysis. Admission to intensive care was needed within median 4·5 days (IQR 2·0-7·0) of CAR T-cell infusion. 90-day mortality was 22·4% (95% CI 17·1-27·7; 54 deaths). At initial evaluation on admission, isolated cytokine release syndrome was identified in 101 patients (42%), cytokine release syndrome and ICANS in 93 (39%), and isolated ICANS in seven (3%) patients. Grade 3-4 cytokine release syndrome within 1 day of admission to intensive care was found in 50 (25%) of 200 patients and grade 3-4 ICANS in 38 (35%) of 108 patients. Bacterial infection developed in 30 (12%) patients. Life-saving treatments were used in 75 (31%) patients within 24 h of admission to intensive care, primarily vasoactive drugs in 65 (27%) patients. Factors independently associated with 90-day mortality by multivariable analysis were frailty (hazard ratio 2·51 [95% CI 1·37-4·57]), bacterial infection (2·12 [1·11-4·08]), and lifesaving therapy within 24 h of admission (1·80 [1·05-3·10]).

Interpretation: Critical care management is an integral part of CAR T-cell therapy and should be standardised. Studies to improve infection prevention and treatment in these high-risk patients are warranted.

Funding: Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique.
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http://dx.doi.org/10.1016/S2352-3026(21)00060-0DOI Listing
May 2021

Low bicarbonate replacement fluid normalizes metabolic alkalosis during continuous veno-venous hemofiltration with regional citrate anticoagulation.

Ann Intensive Care 2021 Apr 23;11(1):62. Epub 2021 Apr 23.

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstr. 35, 6020, Innsbruck, Austria.

Background: Metabolic alkalosis is a frequently occurring problem during continuous veno-venous hemofiltration (CVVH) with regional citrate anticoagulation (RCA). This study aimed to evaluate the effectiveness of switching from high to low bicarbonate (HCO) replacement fluid in alkalotic critically ill patients with acute kidney injury treated by CVVH and RCA.

Methods: A retrospective-comparative study design was applied. Patients who underwent CVVH with RCA in the ICU between 09/2016 and 11/2017 were evaluated. Data were available from the clinical routine. A switch of the replacement fluid Phoxilium (30 mmol/l HCO) to Biphozyl (22 mmol/l HCO) was performed as blood HCO concentration persisted ≥ 26 mmol/l despite adjustments of citrate dose and blood flow. Data were collected from 72 h before the switch of the replacement solutions until 72 h afterwards.

Results: Of 153 patients treated with CVVH during that period, 45 patients were switched from Phoxilium to Biphozyl. Forty-two patients (42 circuits) were available for statistical analysis. After switching the replacement fluid from Phoxilium to Biphozyl the serum HCO concentration decreased significantly from 27.7 mmol/l (IQR 26.9-28.9) to 25.8 mmol/l (IQR 24.6-27.7) within 24 h (p < 0.001). Base excess (BE) decreased significantly from 4.0 mmol/l (IQR 3.1-5.1) to 1.8 mmol/l (IQR 0.2-3.4) within 24 h (p < 0.001). HCO and BE concentration remained stable from 24 h till the end of observation at 72 h after the replacement fluid change (p = 0.225). pH and PaCO did not change significantly after the switch of the replacement fluid until 72 h.

Conclusions: This retrospective analysis suggests that for patients developing refractory metabolic alkalosis during CVVH with RCA the use of Biphozyl reduces external HCO load and sustainably corrects intracorporeal HCO and BE concentrations. Future studies have to prove whether correcting metabolic alkalosis during CVVH with RCA in critically ill patients is of relevance in terms of clinical outcome.
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http://dx.doi.org/10.1186/s13613-021-00850-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062940PMC
April 2021

Penetration of echinocandins into wound secretion of critically ill patients.

Infection 2021 Apr 20. Epub 2021 Apr 20.

Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

Purpose: Wound infections caused by Candida are life-threatening and difficult to treat. Echinocandins are highly effective against Candida species and recommended for treatment of invasive candidiasis. As penetration of echinocandins into wounds is largely unknown, we measured the concentrations of the echinocandins anidulafungin (AFG), micafungin (MFG), and caspofungin (CAS) in wound secretion (WS) and in plasma of critically ill patients.

Methods: We included critically ill adults with an indwelling wound drainage or undergoing vacuum-assisted closure therapy, who were treated with an echinocandin for suspected or proven invasive fungal infection. Concentrations were measured by liquid chromatography with UV (AFG and MFG) or tandem mass spectrometry detection (CAS).

Results: Twenty-one patients were enrolled. From eight patients, serial WS samples and simultaneous plasma samples were obtained within a dosage interval. AFG concentrations in WS amounted to < 0.025-2.25 mg/L, MFG concentrations were 0.025-2.53 mg/L, and CAS achieved concentrations of 0.18-4.04 mg/L. Concentrations in WS were significantly lower than the simultaneous plasma concentrations and below the MIC values of some relevant pathogens.

Conclusion: Echinocandin penetration into WS displays a high inter-individual variability. In WS of some of the patients, concentrations may be sub-therapeutic. However, the relevance of sub-therapeutic concentrations is unknown as no correlation has been established between concentration data and clinical outcome. Nevertheless, in the absence of clinical outcome studies, our data do not support the use of echinocandins at standard doses for the treatment of fungal wound infections, but underline the pivotal role of surgical debridement.
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http://dx.doi.org/10.1007/s15010-021-01604-xDOI Listing
April 2021

Human Tissue Distribution of Anidulafungin and Micafungin.

Antimicrob Agents Chemother 2021 Apr 19. Epub 2021 Apr 19.

Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria

Concentrations of anidulafungin and micafungin were determined in eight different tissues obtained during autopsy of four deceased who had been treated with anidulafungin and of seven who had obtained micafungin. The highest amounts were recovered from liver with anidulafungin concentrations of 11.01 - 66.50 μg/g and micafungin levels of 0.36 - 5.53 μg/g (0.65 μg/g 30 days after the last administration). The lowest anidulafungin levels were measured in skeletal muscle, lowest micafungin concentrations in kidney.
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http://dx.doi.org/10.1128/AAC.00169-21DOI Listing
April 2021

The impact of frailty on survival in elderly intensive care patients with COVID-19: the COVIP study.

Crit Care 2021 04 19;25(1):149. Epub 2021 Apr 19.

Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Equipe: épidémiologie hospitalière qualité et organisation des soins, 75012, Paris, France.

Background: The COVID-19 pandemic has led highly developed healthcare systems to the brink of collapse due to the large numbers of patients being admitted into hospitals. One of the potential prognostic indicators in patients with COVID-19 is frailty. The degree of frailty could be used to assist both the triage into intensive care, and decisions regarding treatment limitations. Our study sought to determine the interaction of frailty and age in elderly COVID-19 ICU patients.

Methods: A prospective multicentre study of COVID-19 patients ≥ 70 years admitted to intensive care in 138 ICUs from 28 countries was conducted. The primary endpoint was 30-day mortality. Frailty was assessed using the clinical frailty scale. Additionally, comorbidities, management strategies and treatment limitations were recorded.

Results: The study included 1346 patients (28% female) with a median age of 75 years (IQR 72-78, range 70-96), 16.3% were older than 80 years, and 21% of the patients were frail. The overall survival at 30 days was 59% (95% CI 56-62), with 66% (63-69) in fit, 53% (47-61) in vulnerable and 41% (35-47) in frail patients (p < 0.001). In frail patients, there was no difference in 30-day survival between different age categories. Frailty was linked to an increased use of treatment limitations and less use of mechanical ventilation. In a model controlling for age, disease severity, sex, treatment limitations and comorbidities, frailty was independently associated with lower survival.

Conclusion: Frailty provides relevant prognostic information in elderly COVID-19 patients in addition to age and comorbidities. Trial registration Clinicaltrials.gov: NCT04321265 , registered 19 March 2020.
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http://dx.doi.org/10.1186/s13054-021-03551-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054503PMC
April 2021

COPD exacerbations are related to poor air quality in Innsbruck: A retrospective pilot study.

Heart Lung 2021 Jul-Aug;50(4):499-503. Epub 2021 Apr 6.

Department of Internal Medicine II, Infectious Diseases, Pneumology, Rheumatology, Medical University of Innsbruck, Anichstraße 35, 6020 Innsbruck, Austria. Electronic address:

Background: Triggers of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are diverse, potentially including airborne pollutants.

Objectives: To analyze whether daily air pollution levels correlate with AECOPD frequency.

Methods: In this retrospective pilot-study, AECOPD frequency was recorded between 2010 and 2016 at the University Hospital of Innsbruck's emergency department and correlated with daily air quality parameters. Data was compared to pulmonary embolism (PE) frequency, a disease not directly involving the airways.

Results: In total, 669 AECOPD and 857 PE events were registered. Days with AECOPD revealed significantly higher concentrations of CO and SO, whereas days with PE displayed an elevation of NO. Higher frequencies of AECOPD during winter months correlated with higher CO and SO levels, disclosing a seasonal trend, while no such pattern was observed for PE.

Conclusion: Air pollution is linked to AECOPD frequency, however, prospective studies are needed to confirm this possible, underrecognized trigger of AECOPD.
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http://dx.doi.org/10.1016/j.hrtlng.2021.02.012DOI Listing
April 2021

Death of unknown cause? Post-mortem diagnosis of fulminant course of an EBV-associated secondary hemophagocytic lymphohistiocytosis.

Memo 2021 Apr 1:1-5. Epub 2021 Apr 1.

Department of Hematology and Oncology, Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

HLH is a life-threatening disease, which is characterized by a dysregulated immune response with uncontrolled T cell and macrophage activation. The often fulminant course of the disease needs a fast diagnostic work-up to initiate as soon as possible the appropriate therapy. We present herein the case of a 71-year-old patient with rapidly progressive hyperinflammatory syndrome, which post mortem resulted in the diagnosis of EBV-associated HLH. With this case report, we intend to highlight the relevance of the HScore in the diagnosis of HLH, to create a greater awareness for EBV as a trigger of HLH, and to demonstrate the importance of treating EBV-associated HLH as early as possible.
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http://dx.doi.org/10.1007/s12254-021-00701-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015738PMC
April 2021

Frailty is associated with long-term outcome in patients with sepsis who are over 80 years old: results from an observational study in 241 European ICUs.

Age Ageing 2021 Mar 20. Epub 2021 Mar 20.

Department of Intensive Care Medicine, University Medical Center, University Utrecht, Utrecht, The Netherlands.

Background: Sepsis is one of the most frequent reasons for acute intensive care unit (ICU) admission of very old patients and mortality rates are high. However, the impact of pre-existing physical and cognitive function on long-term outcome of ICU patients ≥ 80 years old (very old intensive care patients (VIPs)) with sepsis is unclear.

Objective: To investigate both the short- and long-term mortality of VIPs admitted with sepsis and assess the relation of mortality with pre-existing physical and cognitive function.

Design: Prospective cohort study.

Setting: 241 ICUs from 22 European countries in a six-month period between May 2018 and May 2019.

Subjects: Acutely admitted ICU patients aged ≥80 years with sequential organ failure assessment (SOFA) score ≥ 2.

Methods: Sepsis was defined according to the sepsis 3.0 criteria. Patients with sepsis as an admission diagnosis were compared with other acutely admitted patients. In addition to patients' characteristics, disease severity, information about comorbidity and polypharmacy and pre-existing physical and cognitive function were collected.

Results: Out of 3,596 acutely admitted VIPs with SOFA score ≥ 2, a group of 532 patients with sepsis were compared to other admissions. Predictors for 6-month mortality were age (per 5 years): Hazard ratio (HR, 1.16 (95% confidence interval (CI), 1.09-1.25, P < 0.0001), SOFA (per one-point): HR, 1.16 (95% CI, 1.14-1.17, P < 0.0001) and frailty (CFS > 4): HR, 1.34 (95% CI, 1.18-1.51, P < 0.0001).

Conclusions: There is substantial long-term mortality in VIPs admitted with sepsis. Frailty, age and disease severity were identified as predictors of long-term mortality in VIPs admitted with sepsis.
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http://dx.doi.org/10.1093/ageing/afab036DOI Listing
March 2021

Reliability of the Clinical Frailty Scale in very elderly ICU patients: a prospective European study.

Ann Intensive Care 2021 Feb 3;11(1):22. Epub 2021 Feb 3.

Department of Intensive Care Medicine, Dutch Poisons Information Center (DPIC), University Medical Center, University Utrecht, Utrecht, The Netherlands.

Purpose: Frailty is a valuable predictor for outcome in elderly ICU patients, and has been suggested to be used in various decision-making processes prior to and during an ICU admission. There are many instruments developed to assess frailty, but few of them can be used in emergency situations. In this setting the clinical frailty scale (CFS) is frequently used. The present study is a sub-study within a larger outcome study of elderly ICU patients in Europe (the VIP-2 study) in order to document the reliability of the CFS.

Materials And Methods: From the VIP-2 study, 129 ICUs in 20 countries participated in this sub-study. The patients were acute admissions ≥ 80 years of age and frailty was assessed at admission by two independent observers using the CFS. Information was obtained from the patient, if not feasible, from the family/caregivers or from hospital files. The profession of the rater and source of data were recorded along with the score. Interrater variability was calculated using linear weighted kappa analysis.

Results: 1923 pairs of assessors were included and background data of patients were similar to the whole cohort (n = 3920). We found a very high inter-rater agreement (weighted kappa 0.86), also in subgroup analyses. The agreement when comparing information from family or hospital records was better than using only direct patient information, and pairs of raters from same profession performed better than from different professions.

Conclusions: Overall, we documented a high reliability using CFS in this setting. This frailty score could be used more frequently in elderly ICU patients in order to create a more holistic and realistic impression of the patient´s condition prior to ICU admission.
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http://dx.doi.org/10.1186/s13613-021-00815-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856616PMC
February 2021

Impaired fibrinolysis in critically ill COVID-19 patients.

Br J Anaesth 2021 03 9;126(3):590-598. Epub 2020 Dec 9.

Department of Anaesthesiology and Critical Care Medicine, Innsbruck, Austria.

Background: Critically ill coronavirus disease 2019 (COVID-19) patients present with a hypercoagulable state with high rates of macrovascular and microvascular thrombosis, for which hypofibrinolysis might be an important contributing factor.

Methods: We retrospectively analysed 20 critically ill COVID-19 patients at Innsbruck Medical University Hospital whose coagulation function was tested with ClotPro® and compared with that of 60 healthy individuals at Augsburg University Clinic. ClotPro is a viscoelastic whole blood coagulation testing device. It includes the TPA test, which uses tissue factor (TF)-activated whole blood with added recombinant tissue-derived plasminogen activator (r-tPA) to induce fibrinolysis. For this purpose, the lysis time (LT) is measured as the time from when maximum clot firmness (MCF) is reached until MCF falls by 50%. We compared COVID-19 patients with prolonged LT in the TPA test and those with normal LT.

Results: Critically ill COVID-19 patients showed hypercoagulability in ClotPro assays. MCF was higher in the EX test (TF-activated assay), IN test (ellagic acid-activated assay), and FIB test (functional fibrinogen assay) with decreased maximum lysis (ML) in the EX test (hypofibrinolysis) and highly prolonged TPA test LT (decreased fibrinolytic response), as compared with healthy persons. COVID-19 patients with decreased fibrinolytic response showed higher fibrinogen levels, higher thrombocyte count, higher C-reactive protein levels, and decreased ML in the EX test and IN test.

Conclusion: Critically ill COVID-19 patients have impaired fibrinolysis. This hypofibrinolytic state could be at least partially dependent on a decreased fibrinolytic response.
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http://dx.doi.org/10.1016/j.bja.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833514PMC
March 2021

Cardiopulmonary recovery after COVID-19: an observational prospective multicentre trial.

Eur Respir J 2021 04 29;57(4). Epub 2021 Apr 29.

Dept of Cardiac Surgery, Medical University of Innsbruck, Innsbruck, Austria.

Background: After the 2002/2003 severe acute respiratory syndrome outbreak, 30% of survivors exhibited persisting structural pulmonary abnormalities. The long-term pulmonary sequelae of coronavirus disease 2019 (COVID-19) are yet unknown, and comprehensive clinical follow-up data are lacking.

Methods: In this prospective, multicentre, observational study, we systematically evaluated the cardiopulmonary damage in subjects recovering from COVID-19 at 60 and 100 days after confirmed diagnosis. We conducted a detailed questionnaire, clinical examination, laboratory testing, lung function analysis, echocardiography and thoracic low-dose computed tomography (CT).

Results: Data from 145 COVID-19 patients were evaluated, and 41% of all subjects exhibited persistent symptoms 100 days after COVID-19 onset, with dyspnoea being most frequent (36%). Accordingly, patients still displayed an impaired lung function, with a reduced diffusing capacity in 21% of the cohort being the most prominent finding. Cardiac impairment, including a reduced left ventricular function or signs of pulmonary hypertension, was only present in a minority of subjects. CT scans unveiled persisting lung pathologies in 63% of patients, mainly consisting of bilateral ground-glass opacities and/or reticulation in the lower lung lobes, without radiological signs of pulmonary fibrosis. Sequential follow-up evaluations at 60 and 100 days after COVID-19 onset demonstrated a vast improvement of symptoms and CT abnormalities over time.

Conclusion: A relevant percentage of post-COVID-19 patients presented with persisting symptoms and lung function impairment along with radiological pulmonary abnormalities >100 days after the diagnosis of COVID-19. However, our results indicate a significant improvement in symptoms and cardiopulmonary status over time.
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http://dx.doi.org/10.1183/13993003.03481-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736754PMC
April 2021

Correlation of interleukin-6 with Epstein-Barr virus levels in COVID-19.

Crit Care 2020 11 23;24(1):657. Epub 2020 Nov 23.

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.

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http://dx.doi.org/10.1186/s13054-020-03384-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7682685PMC
November 2020

Structured ICU resource management in a pandemic is associated with favorable outcome in critically ill COVID‑19 patients.

Wien Klin Wochenschr 2020 Nov 10;132(21-22):653-663. Epub 2020 Nov 10.

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.

Introduction: On February 25, 2020, the first 2 patients were tested positive for severe acute respiratory syndrome coronavirus‑2 (SARS-CoV-2) in Tyrol, Austria. Rapid measures were taken to ensure adequate intensive care unit (ICU) preparedness for a surge of critically ill coronavirus disease-2019 (COVID-19) patients.

Methods: This cohort study included all COVID-19 patients admitted to an ICU with confirmed or strongly suspected COVID-19 in the State of Tyrol, Austria. Patients were recorded in the Tyrolean COVID-19 intensive care registry. Date of final follow-up was July 17, 2020.

Results: A total of 106 critically ill patients with COVID-19 were admitted to 1 of 13 ICUs in Tyrol from March 9 to July 17, 2020. Median age was 64 years (interquartile range, IQR 54-74 years) and the majority of patients were male (76 patients, 71.7%). Median simplified acute physiology score III (SAPS III) was 56 points (IQR 49-64 points). The median duration from appearance of first symptoms to ICU admission was 8 days (IQR 5-11 days). Invasive mechanical ventilation was required in 72 patients (67.9%) and 6 patients (5.6%) required extracorporeal membrane oxygenation treatment. Renal replacement therapy was necessary in 21 patients (19.8%). Median ICU length of stay (LOS) was 18 days (IQR 5-31 days), median hospital LOS was 27 days (IQR 13-49 days). The ICU mortality was 21.7% (23 patients), hospital mortality was 22.6%. There was no significant difference in ICU mortality in patients receiving invasive mechanical ventilation and in those not receiving it (18.1% vs. 29.4%, p = 0.284). As of July 17th, 2020, two patients are still hospitalized, one in an ICU, one on a general ward.

Conclusion: Critically ill COVID-19 patients in Tyrol showed high severity of disease often requiring complex treatment with increased lengths of ICU and hospital stay. Nevertheless, the mortality was found to be remarkably low, which may be attributed to our adaptive surge response providing sufficient ICU resources.
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http://dx.doi.org/10.1007/s00508-020-01764-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653454PMC
November 2020

Sex-specific outcome disparities in very old patients admitted to intensive care medicine: a propensity matched analysis.

Sci Rep 2020 10 29;10(1):18671. Epub 2020 Oct 29.

Alkhums Hospital, ICU, Tripoli, Libya.

Female and male very elderly intensive patients (VIPs) might differ in characteristics and outcomes. We aimed to compare female versus male VIPs in a large, multinational collective of VIPs with regards to outcome and predictors of mortality. In total, 7555 patients were included in this analysis, 3973 (53%) male and 3582 (47%) female patients. The primary endpoint was 30-day-mortality. Baseline characteristics, data on management and geriatric scores including frailty assessed by Clinical Frailty Scale (CFS) were documented. Two propensity scores (for being male) were obtained for consecutive matching, score 1 for baseline characteristics and score 2 for baseline characteristics and ICU management. Male VIPs were younger (83 ± 5 vs. 84 ± 5; p < 0.001), less often frail (CFS > 4; 38% versus 49%; p < 0.001) but evidenced higher SOFA (7 ± 6 versus 6 ± 6 points; p < 0.001) scores. After propensity score matching, no differences in baseline characteristics could be observed. In the paired analysis, the mortality in male VIPs was higher (mean difference 3.34% 95%CI 0.92-5.76%; p = 0.007) compared to females. In both multivariable logistic regression models correcting for propensity score 1 (aOR 1.15 95%CI 1.03-1.27; p = 0.007) and propensity score 2 (aOR 1.15 95%CI 1.04-1.27; p = 0.007) male sex was independently associated with higher odds for 30-day-mortality. Of note, male gender was not associated with ICU mortality (OR 1.08 95%CI 0.98-1.19; p = 0.14). Outcomes of elderly intensive care patients evidenced independent sex differences. Male sex was associated with adverse 30-day-mortality but not ICU-mortality. Further research to identify potential sex-specific risk factors after ICU discharge is warranted.Trial registration: NCT03134807 and NCT03370692; Registered on May 1, 2017 https://clinicaltrials.gov/ct2/show/NCT03370692 .
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http://dx.doi.org/10.1038/s41598-020-74910-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596065PMC
October 2020

Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement Therapy.

Clin J Am Soc Nephrol 2021 May 28;16(5):820-828. Epub 2020 Oct 28.

Division of Nephrology, Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.
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http://dx.doi.org/10.2215/CJN.09670620DOI Listing
May 2021

COVID-19-associated acute kidney injury: consensus report of the 25th Acute Disease Quality Initiative (ADQI) Workgroup.

Nat Rev Nephrol 2020 12 15;16(12):747-764. Epub 2020 Oct 15.

Division of Nephrology, Department of Medicine, University of Alabama, Birmingham, AL, USA.

Kidney involvement in patients with coronavirus disease 2019 (COVID-19) is common, and can range from the presence of proteinuria and haematuria to acute kidney injury (AKI) requiring renal replacement therapy (RRT; also known as kidney replacement therapy). COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and serves as an independent risk factor for all-cause in-hospital death in patients with COVID-19. The pathophysiology and mechanisms of AKI in patients with COVID-19 have not been fully elucidated and seem to be multifactorial, in keeping with the pathophysiology of AKI in other patients who are critically ill. Little is known about the prevention and management of COVID-19 AKI. The emergence of regional 'surges' in COVID-19 cases can limit hospital resources, including dialysis availability and supplies; thus, careful daily assessment of available resources is needed. In this Consensus Statement, the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI based on current literature. We also make recommendations for areas of future research, which are aimed at improving understanding of the underlying processes and improving outcomes for patients with COVID-19 AKI.
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http://dx.doi.org/10.1038/s41581-020-00356-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561246PMC
December 2020

Correction to: Accumulation of hydroxyethyl starch in human and animal tissues: a systematic review.

Intensive Care Med 2021 Feb;47(2):263

Division of Emergency and Intensive Care Medicine, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.

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http://dx.doi.org/10.1007/s00134-020-06269-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880929PMC
February 2021

Correction to: Hypoalbuminemia and acute kidney injury: a meta-analysis of observational clinical studies.

Intensive Care Med 2021 Feb;47(2):262

Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.

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http://dx.doi.org/10.1007/s00134-020-06268-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880927PMC
February 2021

Correction to: The Boldt scandal still in need of action: the example of colloids 10 years after initial suspicion of fraud.

Intensive Care Med 2021 Feb;47(2):264

Division of Medical Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.

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http://dx.doi.org/10.1007/s00134-020-06270-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880920PMC
February 2021

Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest: a statistical analysis plan.

Trials 2020 Oct 7;21(1):831. Epub 2020 Oct 7.

Department of Clinical Sciences Lund, Anesthesia & Intensive Care, Lund University, Helsingborg Hospital, Lund, Sweden.

Background: To date, targeted temperature management (TTM) is the only neuroprotective intervention after resuscitation from cardiac arrest that is recommended by guidelines. The evidence on the effects of TTM is unclear.

Methods/design: The Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) trial is an international, multicentre, parallel group, investigator-initiated, randomised, superiority trial in which TTM with a target temperature of 33 °C after cardiac arrest will be compared with a strategy to maintain normothermia and active treatment of fever (≥ 37.8 °C). Prognosticators, outcome assessors, the steering group, the trial coordinating team, and trial statisticians will be blinded to treatment allocation. The primary outcome will be all-cause mortality at 180 days after randomisation. We estimate a 55% mortality in the targeted normothermia group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The secondary neurological outcome will be poor functional outcome (modified Rankin scale 4-6) at 180 days after cardiac arrest. In this paper, a detailed statistical analysis plan is presented, including a comprehensive description of the statistical analyses, handling of missing data, and assessments of underlying statistical assumptions. Final analyses will be conducted independently by two qualified statisticians following the present plan.

Discussion: This SAP, which was prepared before completion of enrolment, should increase the validity of the TTM trial by mitigation of analysis-bias.
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http://dx.doi.org/10.1186/s13063-020-04654-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542893PMC
October 2020

Recommendations on Acute Kidney Injury Biomarkers From the Acute Disease Quality Initiative Consensus Conference: A Consensus Statement.

JAMA Netw Open 2020 10 1;3(10):e2019209. Epub 2020 Oct 1.

Department of Medicine, University of Padova, Padova, Italy.

Importance: In the last decade, new biomarkers for acute kidney injury (AKI) have been identified and studied in clinical trials. Guidance is needed regarding how best to incorporate them into clinical practice.

Objective: To develop recommendations on AKI biomarkers based on existing data and expert consensus for practicing clinicians and researchers.

Evidence Review: At the 23rd Acute Disease Quality Initiative meeting, a meeting of 23 international experts in critical care, nephrology, and related specialties, the panel focused on 4 broad areas, as follows: (1) AKI risk assessment; (2) AKI prediction and prevention; (3) AKI diagnosis, etiology, and management; and (4) AKI progression and kidney recovery. A literature search revealed more than 65 000 articles published between 1965 and May 2019. In a modified Delphi process, recommendations and consensus statements were developed based on existing data, with 90% agreement among panel members required for final adoption. Recommendations were graded using the Grading of Recommendations, Assessment, Development and Evaluations system.

Findings: The panel developed 11 consensus statements for biomarker use and 14 research recommendations. The key suggestions were that a combination of damage and functional biomarkers, along with clinical information, be used to identify high-risk patient groups, improve the diagnostic accuracy of AKI, improve processes of care, and assist the management of AKI.

Conclusions And Relevance: Current evidence from clinical studies supports the use of new biomarkers in prevention and management of AKI. Substantial gaps in knowledge remain, and more research is necessary.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.19209DOI Listing
October 2020

Linkage of alterations in systemic iron homeostasis to patients' outcome in sepsis: a prospective study.

J Intensive Care 2020 1;8:76. Epub 2020 Oct 1.

Department of Internal Medicine II, Medical University of Innsbruck, Anichstr. 35, Innsbruck, Austria.

Background: Sepsis, a dysregulated host response following infection, is associated with massive immune activation and high mortality rates. There is still a need to define further risk factors and laboratory parameters predicting the clinical course. Iron metabolism is regulated by both, the body's iron status and the immune response. Iron itself is required for erythropoiesis but also for many cellular and metabolic functions. Moreover, iron availability is a critical determinant in infections because it is an essential nutrient for most microbes but also impacts on immune function and intravascular oxidative stress. Herein, we used a prospective study design to investigate the putative impact of serum iron parameters on the outcome of sepsis.

Methods: Serum markers of iron metabolism were measured in a prospective cohort of 61 patients (37 males, 24 females) with sepsis defined by Sepsis-3 criteria in a medical intensive care unit (ICU) and compared between survivors and non-survivors. Regulation of iron parameters in patients stratified by focus of infection and co-medication as well as association of the markers with sepsis severity scores and survival were investigated with linear and logistic regression corrected for sex and age effects.

Results: Positive correlations of increased serum iron and ferritin concentrations upon ICU admission with the severity of organ failure (SOFA score) and with mortality were observed. Moreover, high TF-Sat, elevated ferritin and serum iron levels and low transferrin concentrations were associated with reduced survival. A logistic regression model consisting of SOFA and transferrin saturation (SOFA-TF-Sat) had the best predictive power for survival in septic ICU patients. Of note, administration of blood transfusions prior to ICU admission resulted in increased TF-Sat and reduced survival of septic patients.

Conclusions: Our study could show an important impact of serum iron parameters on the outcome of sepsis. Furthermore, we identified transferrin saturation as a stand-alone predictor of sepsis survival and as a parameter of iron metabolism which may in a combined model improve the prediction power of the SOFA score.

Trial Registration: The study was carried out in accordance with the recommendations of the Declaration of Helsinki on biomedical research. The study was approved by the institutional ethics review board of the Medical University Innsbruck (study AN2013-0006).
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http://dx.doi.org/10.1186/s40560-020-00495-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528491PMC
October 2020

Stress ulcer prophylaxis: Is mortality a useful endpoint?

Intensive Care Med 2020 11 28;46(11):2058-2060. Epub 2020 Sep 28.

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

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http://dx.doi.org/10.1007/s00134-020-06250-9DOI Listing
November 2020

SARS-CoV-2: recommendations for treatment in intensive care medicine.

Wien Klin Wochenschr 2020 Nov 18;132(21-22):664-670. Epub 2020 Sep 18.

Department of Anaesthesiology and Critical Care Medicine, Klinikum Klagenfurt am Wörthersee, Feschnigstraße 11, 9020, Klagenfurt am Wörthersee, Austria.

Coronavirus disease 2019 (COVID-19) progresses mildly in most of the cases; however, about 5% of the patients develop a severe acute respiratory distress syndrome (ARDS). Of all COVID-19 patients 3% need intensive care treatment, which becomes a great challenge for anesthesiology and intensive care medicine, medically, hygienically and for technical safety requirements. For these reasons, only experienced medical and nursing staff in the smallest grouping possible should be assigned. For these team members, a consistent use of personal protective equipment (PPE) is essential.Due to the immense medical challenges, the following treatment guidelines were developed by the ÖGARI (Österreichische Gesellschaft für Anästhesiologie, Reanimation und Intensivmedizin), FASIM (Federation of Austrian Societies of Intensive Care Medicine) and ÖGIAIN (Österreichische Gesellschaft für Internistische und Allgemeine Intensivmedizin und Notfallmedizin).The recommendations given in this article are to be understood as short snapshots of the moment; all basic guidelines are works in progress and will be regularly updated as evidence levels, new study results and additional experience are gathered.
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http://dx.doi.org/10.1007/s00508-020-01734-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500247PMC
November 2020