Publications by authors named "Martin Balik"

54 Publications

Bacteremia in critically ill immunocompromised patients with acute hypoxic respiratory failure: A post-hoc analysis of a prospective multicenter multinational cohort.

J Crit Care 2021 Aug 17;64:114-119. Epub 2021 Apr 17.

Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology and Biostatistics, Sorbonne Paris Cité, CRESS, INSERM, Paris Diderot Sorbonne University, Paris, France.

Purpose: The characteristics and impact of bacteremia have not been widely investigated in immunocompromised patients with acute respiratory failure (ARF).

Methods: We performed a secondary analysis of a prospective cohort of immunocompromised patients with ARF (EFRAIM study). After exclusion of blood cultures positive for coagulase negative Staphylococci, we compared patients with (n = 236) and without (n = 1127) bacteremia.

Results: The incidence of bacteremia was 17%. Bacterial pneumonia and extra-pulmonary ARDS were the main causes of ARF in bacteremic patients. Bacteremia involved gram negative rods (48%), gram positive cocci (40%) or were polymicrobial (10%). Bacteremic patients had more hematological malignancy, higher SOFA scores and increased organ support within 7 days. Bacteremia was associated with higher crude ICU mortality (40% versus 32%, p = 0.02), but neither hospital (49% versus 44%, p = 0.17) nor 90-day mortality (60% versus 56%, p = 0.25) were different from non-bacteremic patients. After propensity score matching based on baseline characteristics, the difference in ICU mortality lost statistical significance (p = 0.06), including in a sensitivity analysis restricted to patients with pneumonia.

Conclusions: We analyzed a large population of immunocompromised patients with ARF and an incidence of bacteremia of 17%. We could not demonstrate an impact of bacteremia on mortality after adjusting for baseline characteristics.
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http://dx.doi.org/10.1016/j.jcrc.2021.03.014DOI Listing
August 2021

Effect of dexamethasone in patients with ARDS and COVID-19 - prospective, multi-centre, open-label, parallel-group, randomised controlled trial (REMED trial): A structured summary of a study protocol for a randomised controlled trial.

Trials 2021 Mar 1;22(1):172. Epub 2021 Mar 1.

Bloomsbury Institute of Intensive Care Medicine, Division of Medicine, University College London, Gower Street, London, WC1E 6BT, UK.

Objectives: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days.

Trial Design: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice.

Participants: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic.

Inclusion Criteria: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria:  • Moderate - PaO/FiO 100-200 mmHg;  • Severe - PaO/FiO < 100 mmHg; 5. Admission to ICU in the last 24 hours.

Exclusion Criteria: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history:  a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days;  b) Systemic corticosteroid use before hospitalization;  c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment;  d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g.  • intractable hyperglycaemia;  • active gastrointestinal bleeding;  • adrenal gland disorders;  • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days.

Intervention And Comparator: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used.

Main Outcomes: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index.

Randomisation: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day.

Blinding (masking): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed.

Numbers To Be Randomised (sample Size): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled.

Trial Status: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021.

Trial Registration: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021.

Full Protocol: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
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http://dx.doi.org/10.1186/s13063-021-05116-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917377PMC
March 2021

Dual veno-arterial extra-corporeal membrane oxygenation support in a patient with refractory hyperdynamic septic shock: a case report.

Perfusion 2021 Feb 26:267659121998962. Epub 2021 Feb 26.

Department of Anaesthesiology, Resuscitation and Intensive Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.

The hypodynamic septic shock appears to be a promising indication to veno-arterial membrane oxygenation (VA-ECMO) support of a patient with insufficient cardiac output. With cardiac recovery most of those patients progress into a hyperdynamic septic shock with cardiac output, which may not match critically low systemic vascular resistance to maintain perfusion pressures. Such refractory distributive shock represents a challenging indication to VA-ECMO. We report a rare case of a 27-year old patient who developed severe refractory hypodynamic septic shock due to the bilateral staphylococcal pneumonia and had to be initially rescued by femoro-femoral VA-ECMO. Despite extensive measures, he remained in intractable hypotension and profound tissue hypoperfusion with imminent multiorgan failure. The commencement of a second jugulo-axillary VA ECMO secured a total blood flow of 14.3 L/min, which restored perfusion pressure and successfully bridged patient over the period of critical haemodynamic instability and ultimately may have facilitated recovery.
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http://dx.doi.org/10.1177/0267659121998962DOI Listing
February 2021

Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus.

Crit Care 2020 12 24;24(1):702. Epub 2020 Dec 24.

Ospedale Niguarda C' Grande, Milan, Italy.

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
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http://dx.doi.org/10.1186/s13054-020-03369-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759024PMC
December 2020

The PRICES statement: an ESICM expert consensus on methodology for conducting and reporting critical care echocardiography research studies.

Intensive Care Med 2021 01 4;47(1):1-13. Epub 2020 Dec 4.

Intensive Care Medicine Unit, Assistance Publique-Hôpitaux de Paris, University Hospital Ambroise Paré, 92100, Boulogne-Billancourt, France.

Purpose: Echocardiography is a common tool for cardiac and hemodynamic assessments in critical care research. However, interpretation (and applications) of results and between-study comparisons are often difficult due to the lack of certain important details in the studies. PRICES (Preferred Reporting Items for Critical care Echocardiography Studies) is a project endorsed by the European Society of Intensive Care Medicine and conducted by the Echocardiography Working Group, aiming at producing recommendations for standardized reporting of critical care echocardiography (CCE) research studies.

Methods: The PRICE panel identified lists of clinical and echocardiographic parameters (the "items") deemed important in four main areas of CCE research: left ventricular systolic and diastolic functions, right ventricular function and fluid management. Each item was graded using a critical index (CI) that combined the relative importance of each item and the fraction of studies that did not report it, also taking experts' opinion into account.

Results: A list of items in each area that deemed essential for the proper interpretation and application of research results is recommended. Additional items which aid interpretation were also proposed.

Conclusion: The PRICES recommendations reported in this document, as a checklist, represent an international consensus of experts as to which parameters and information should be included in the design of echocardiography research studies. PRICES recommendations provide guidance to scientists in the field of CCE with the objective of providing a recommended framework for reporting of CCE methodology and results.
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http://dx.doi.org/10.1007/s00134-020-06262-5DOI Listing
January 2021

ICU-acquired pneumonia in immunosuppressed patients with acute hypoxemic respiratory failure: A post-hoc analysis of a prospective international cohort study.

J Crit Care 2021 Jun 29;63:243-245. Epub 2020 Sep 29.

Medical Intensive Care Unit, APHP, Hôpital Saint-Louis, Famirea Study Group, ECSTRA Team, and Clinical Epidemiology, UMR 1153, Center of Epidemiology, France.

Objective: Intensive Care Units (ICU) acquired Pneumonia (ICU-AP) is one of the most frequent nosocomial infections in critically ill patients. Our aim was to determine the effects of having an ICU-AP in immunosuppressed patients with acute hypoxemic respiratory failure.

Design: Post-hoc analysis of a multinational, prospective cohort study in 16 countries.

Settings: ICU.

Patients: Immunosuppressed patients with acute hypoxemic respiratory failure.

Intervention: None.

Measurements And Main Results: The original cohort had 1611 and in this post-hoc analysis a total of 1512 patients with available data on hospital mortality and occurrence of ICU-AP were included. ICU-AP occurred in 158 patients (10.4%). Hospital mortality was higher in patients with ICU-AP (14.8% vs. 7.1% p < 0.001). After adjustment for confounders and centre effect, use of vasopressors (Odds Ratio (OR) 2.22; 95%CI 1.46-3.39) and invasive mechanical ventilation at day 1 (OR 2.12 vs. high flow oxygen; 95%CI 1.07-4.20) were associated with increased risk of ICU-AP while female gender (OR 0.63; 95%CI 0.43-94) and chronic kidney disease (OR 0.43; 95%CI 0.22-0.88) were associated with decreased risk of ICU-AP. After adjustment for confounders and centre effect, ICU-AP was independently associated with mortality (Hazard Ratio 1.48; 95%CI 14.-1.91; P = 0.003).

Conclusions: The attributable mortality of ICU-AP has been repetitively questioned in immunosuppressed patients with acute respiratory failure. This manuscript found that ICU-AP represents an independent risk factor for hospital mortality.
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http://dx.doi.org/10.1016/j.jcrc.2020.09.027DOI Listing
June 2021

Azithromycin added to hydroxychloroquine for patients admitted to intensive care due to coronavirus disease 2019 (COVID-19)-protocol of randomised controlled trial AZIQUINE-ICU.

Trials 2020 Jul 8;21(1):631. Epub 2020 Jul 8.

Czech Anaesthesia Clinical Trials and Audit Network and Department of Anaesthesia and Intensive Care, Masaryk's Hospital, Ústí nad Labem, Czech Republic.

Background: Novel coronavirus SARS-CoV-2 is known to be susceptible in vitro to exposure to hydroxychloroquine and its effect has been found to be potentiated by azithromycin. We hypothesise that early administration of hydroxychloroquine alone or in combination with azithromycin can prevent respiratory deterioration in patients admitted to intensive care due to rapidly progressive COVID-19 infection.

Methods: Design: Prospective, multi-centre, double-blind, randomised, controlled trial (RCT).

Participants: Adult (> 18 years) within 24 h of admission to the intensive care unit with proven or suspected COVID-19 infection, whether or not mechanically ventilated. Exclusion criteria include duration symptoms of febrile disease for ≥ 1 week, treatment limitations in place or moribund patients, allergy or intolerance of any study treatment, and pregnancy.

Interventions: Patients will be randomised in 1:1:1 ratio to receive Hydroxychloroquine 800 mg orally in two doses followed by 400 mg daily in two doses and azithromycin 500 mg orally in one dose followed by 250 mg in one dose for a total of 5 days (HC-A group) or hydroxychloroquine + placebo (HC group) or placebo + placebo (C-group) in addition to the best standard of care, which may evolve during the trial period but will not differ between groups. Primary outcome is the composite percentage of patients alive and not on end-of-life pathway who are free of mechanical ventilation at day 14.

Secondary Outcomes: The percentage of patients who were prevented from needing intubation until day 14, ICU length of stay, and mortality (in hospital) at day 28 and 90.

Discussion: Although both investigational drugs are often administered off label to patients with severe COVID-19, at present, there is no data from RCTs on their safety and efficacy. In vitro and observational trial suggests their potential to limit viral replication and the damage to lungs as the most common reason for ICU admission. Therefore, patients most likely to benefit from the treatment are those with severe but early disease. This trial is designed and powered to investigate whether the treatment in this cohort of patients leads to improved clinical patient-centred outcomes, such as mechanical ventilation-free survival.

Trial Registration: Clinical trials.gov: NCT04339816 (Registered on 9 April 2020, amended on 22 June 2020); Eudra CT number: 2020-001456-18 (Registered on 29 March 2020).
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http://dx.doi.org/10.1186/s13063-020-04566-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341702PMC
July 2020

Respiratory Mechanics and Outcomes in Immunocompromised Patients With ARDS: A Secondary Analysis of the EFRAIM Study.

Chest 2020 11 20;158(5):1947-1957. Epub 2020 Jun 20.

Division of Pulmonary and Critical Care, Penn State University College of Medicine, Hershey, PA.

Background: In view of the high mortality rate of immunocompromised patients with ARDS, it is important to identify targets for improvement.

Research Question: This study investigated factors associated with mortality in this specific ARDS population, including factors related to respiratory mechanics (plateau pressure [Pplat,rs], compliance [Crs], and driving pressure [ΔPrs]).

Study Design And Methods: This study consisted of a predefined secondary analysis of the EFRAIM data. Overall, 789 of 1,611 patients met the Berlin criteria for ARDS, and Pplat,rs, ΔPrs, and Crs were available for 494 patients. A hierarchical model was used to assess factors at ARDS onset independently associated with hospital mortality.

Results: Hospital mortality was 56.3%. After adjustment, variables independently associated with hospital mortality included ARDS of undetermined etiology (OR, 1.66; 95% CI, 1.01-2.72), need for vasopressors (OR, 1.91; 95% CI, 1.27-2.88), and need for renal replacement therapy (OR, 2.02; 95% CI, 1.37-2.97). ARDS severity according to the Berlin definition, neutropenia on admission, and the type of underlying disease were not significantly associated with mortality. Before adjustment, higher Pplat,rs, higher ΔPrs, and lower Crs were associated with higher mortality. Addition of each of these individual variables to the final hierarchical model revealed a significant association with mortality: ΔPrs (OR, 1.08; 95% CI, 1.05-1.12), Pplat,rs (OR, 1.07; 95% CI, 1.04-1.11), and Crs (OR, 0.97; 95% CI, 0.95-0.98). Tidal volume was not associated with mortality.

Interpretation: In immunocompromised patients with ARDS, respiratory mechanics provide additional prognostic information to predictors of hospital mortality. Studies designed to define lung-protective ventilation guided by these physiological variables may be warranted in this specific population.
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http://dx.doi.org/10.1016/j.chest.2020.05.602DOI Listing
November 2020

Vasopressin in Patients with Septic Shock and Dynamic Left Ventricular Outflow Tract Obstruction.

Cardiovasc Drugs Ther 2020 10;34(5):685-688

Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, Unit of Anaesthesia and Intensive Care Fondazione Policlinico San Matteo, IRCCS, University of Pavia, Pavia, Italy.

Purpose: Left ventricular outflow tract obstruction (LVOTO) is a relatively uncommon but severe condition that may lead to hemodynamic impairment. It can be elicited by morphological (left ventricular hypertrophy, sigmoid septum, prominent papillary muscle, prolonged anterior mitral valve leaflet) and functional (hypovolemia, low afterload, hypercontractility, catecholamines) factors. We sought to determine the incidence of the most severe form of LVOTO in septic shock patients and describe the therapeutic effects of vasopressin.

Methods: Over a period of 29 months, 527 patients in septic shock were screened for LVOTO. All were mechanically ventilated and treated according to sepsis bundles, including pre-load optimization and norepinephrine infusion. Vasopressin was added in addition to norepinephrine to reduce the adrenergic burden and decrease LVOTO.

Results: Ten patients were diagnosed with the most severe form of LVOTO, including systolic anterior mitral valve motion (SAM) and severe mitral regurgitation (MR) with pulmonary oedema. The median norepinephrine dosage to obtain a mean arterial pressure of ≥70 mmHg was 0.58 mcg/Kg/min (IQR 0.40-0.78). All patients had a hyper-contractile left ventricle, septal hypertrophy, significant LVOTO (peak gradient 78 [56-123] mmHg) associated with SAM and severe MR with pulmonary oedema. Vasopressin (median 4 IU/h) allowed a significant reduction of norepinephrine (0.18 [0.14-0.30] mcg/kg/min; p = 0.01), LVOT gradient (35 [24-60] mmHg; p = 0.01) and MR with a significant paO/FiO increase (174 [125-213] mmHg; p = 0.01).

Conclusion: Vasopressin allowed a reduction of norepinephrine with subsequent LVOTO reduction and hemodynamic improvement of the most severe form of LVOTO, which represented 1.9% of all septic shock patients.
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http://dx.doi.org/10.1007/s10557-020-06998-8DOI Listing
October 2020

Methylene blue administration in patients with refractory distributive shock - a retrospective study.

Sci Rep 2020 02 4;10(1):1828. Epub 2020 Feb 4.

General University Hospital, Department of Anaesthesiology, Resuscitation and Intensive Medicine, First Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.

Hemodynamic effectiveness of methylene blue (MB) was tested in patients with refractory distributive shock. A retrospective analysis of 20 critically-ill patients who developed refractory shock was performed. Patients were divided into two study groups as responders with positive hemodynamic response to MB administration (defined as 10% decrease of norepinephrine dose) and non-responders. Hemodynamic, outcome data and baseline tissue hypoxia-related parameters including ratio of central venous-to-arterial carbon dioxide tension to arterio-venous oxygen content (P(v-a)CO/C(a-v)O) were compared between the groups. There were 9 (45%) responders and 11 (55%) non-responders to single bolus of MB administration. Dose of MB did not differ between responders and non-responders (1.3 ± 0.5 vs. 1.3 ± 0.4 mg/kg respectively, P = 0.979). MB responders had lower baseline P(v-a) CO/C(a-v)O (1.79 ± 0.73 vs. 3.24 ± 1.18, P = 0.007), higher pH (7.26 ± 0.11 vs. 7.16 ± 0.10, P = 0.037) and lower lactate levels at 12 hours post MB administration (3.4 ± 2.7 vs. 9.9 ± 2.2 mmol/L, P = 0.002) compared to non-responders. Methylene blue represents a non-adrenergic vasopressor with only limited effectiveness in patients with refractory distributive shock. Profound tissue hypoxia with high degree of anaerobic metabolism was associated with the loss of hemodynamic responsiveness to its administration.
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http://dx.doi.org/10.1038/s41598-020-58828-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7000741PMC
February 2020

High resolution respirometry to assess function of mitochondria in native homogenates of human heart muscle.

PLoS One 2020 15;15(1):e0226142. Epub 2020 Jan 15.

OXYLAB - Laboratory of Mitochondrial Physiology, Department of Anaesthesia and Intensive Care, Third Faculty of Medicine, Charles University and FNKV University Hospital, Prague, Czech Republic.

Impaired myocardial bioenergetics is a hallmark of many cardiac diseases. There is a need of a simple and reproducible method of assessment of mitochondrial function from small human myocardial tissue samples. In this study we adopted high-resolution respirometry to homogenates of fresh human cardiac muscle and compare it with isolated mitochondria. We used atria resected during cardiac surgery (n = 18) and atria and left ventricles from brain-dead organ donors (n = 12). The protocol we developed consisting of two-step homogenization and exposure of 2.5% homogenate in a respirometer to sequential addition of 2.5 mM malate, 15 mM glutamate, 2.5 mM ADP, 10 μM cytochrome c, 10 mM succinate, 2.5 μM oligomycin, 1.5 μM FCCP, 3.5 μM rotenone, 4 μM antimycin and 1 mM KCN or 100 mM Sodium Azide. We found a linear dependency of oxygen consumption on oxygen concentration. This technique requires < 20 mg of myocardium and the preparation of the sample takes <20 min. Mitochondria in the homogenate, as compared to subsarcolemmal and interfibrillar isolated mitochondria, have comparable or better preserved integrity of outer mitochondrial membrane (increase of respiration after addition of cytochrome c is up to 11.7±1.8% vs. 15.7±3.1%, p˂0.05 and 11.7±3.5%, p = 0.99, resp.) and better efficiency of oxidative phosphorylation (Respiratory Control Ratio = 3.65±0.5 vs. 3.04±0.27, p˂0.01 and 2.65±0.17, p˂0.0001, resp.). Results are reproducible with coefficient of variation between two duplicate measurements ≤8% for all indices. We found that whereas atrial myocardium contains less mitochondria than the ventricle, atrial bioenergetic profiles are comparable to left ventricle. In conclusion, high resolution respirometry has been adapted to homogenates of human cardiac muscle and shown to be reliable and reproducible.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226142PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961865PMC
April 2020

Health-related quality of life determinants in survivors of a mass methanol poisoning outbreak: six-year prospective cohort study.

Clin Toxicol (Phila) 2020 09 8;58(9):870-880. Epub 2020 Jan 8.

Department of Occupational Medicine, First Faculty of Medicine, Charles University, Prague, Czech Republic.

The effect of acute methanol poisoning on the follow-up quality of life of survivors in mass poisoning outbreaks is not known. The objective of this is to study the impact of visual and central nervous system (CNS) sequelae of methanol poisoning on long-term health-related quality of life (QoL) of survivors, its clinical determinants, and dynamics. A total of 54 patients with confirmed methanol poisoning (mean age 46.7 ± 13.4 years, 9 females) were examined consequently three times within six-year prospective cohort study and compared to 23 controls with the history of chronic alcohol abuse. The following tests were performed: SF-36 QoL questionnaire, visual evoked potentials (VEP) of optic nerve, ocular examination with retinal nerve fiber layer (RNFL) thickness measurement, brain magnetic resonance imaging (MRI), and biochemical and toxicological tests. Acute methanol poisoning led to significant decrease in physical component summary (PCS) compared to PCS of age-adjusted controls (mean score with SD 46.8 ± 11.0 versus 52.3 ± 9.4 points;  = .003). In 17/40 (42.5%) patients with three rounds of examination, signs of severe disability (≤30 points in at least one score) were present six years after discharge, with negative dynamics of PCS score during the observation period. The patients with abnormal RNFL thickness had lower PCS (mean difference 10.5 points; 95%CI 3.5-17.5,  = .004) and mental component summary score (9.5 points; 95%CI 1.9-17.1,  = .015) compared to the patients with normal RNFL. Signs of physical and mental adaptation to long-term visual sequelae were registered with gradual reduction of difference in most of physical and mental components scores compared to the patients with normal RNFL during six years of observation. Signs of hemorrhagic brain lesions were associated with permanent decrease of PCS score (mean difference 7.4 points; 95%CI 0.6-14.0;  = .033), bodily pain (8.7 points; 95%CI 1.6-17.6;  = .018), and social functioning (8.2 points; 95%CI 3.0-17.4;  = .005) six years after discharge. No effect of type of antidote (fomepizole versus ethanol) and extracorporeal enhanced elimination modality (intermittent hemodialysis versus continuous renal replacement therapy) applied in hospital on long-term QoL was found (all  > .05). Acute methanol poisoning was associated with a significant decrease of health-related quality of life of survivors persisting for at least six years after discharge. The more pronounced decrease in QoL scores was observed in the patients with hemorrhagic brain lesions and visual sequelae of poisoning with abnormal RNFL thickness.
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http://dx.doi.org/10.1080/15563650.2019.1702994DOI Listing
September 2020

Efficacy and safety of 1C class antiarrhythmic agent (propafenone) for supraventricular arrhythmias in septic shock compared to amiodarone: protocol of a prospective randomised double-blind study.

BMJ Open 2019 09 3;9(9):e031678. Epub 2019 Sep 3.

Anaesthesia and Intensive Care, 1st Medical Faculty, Charles University and General University Hospital in Prague, Prague, Czech Republic, EU.

Introduction: Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy.

Methods And Analysis: The trial includes septic shock patients with new-onset arrhythmia, but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient is randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the percentages of patients that needed rescue treatments (DC cardioversion or unblinding and crossover of the antiarrhythmics), the recurrence of arrhythmias, intensive care unit mortality, 28-day and 1-year mortality. In the posthoc analysis, we separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction. In the exploratory part of the study, we assess whether the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical SR and whether the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Considering that the restoration of SR within 24 hours occurred in 74% of the amiodarone-treated patients and in 89% of the patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05.

Ethics And Dissemination: The trial is recruiting patients according to its second protocol version approved by the University Hospital Ethical Board on the 6 October 2017 (No. 1691/16S-IV). The results will be disseminated through peer reviewed publications and conference presentations.

Trial Registration Number: NCT03029169.
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http://dx.doi.org/10.1136/bmjopen-2019-031678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731952PMC
September 2019

Diagnosis and outcome of acute respiratory failure in immunocompromised patients after bronchoscopy.

Eur Respir J 2019 07 25;54(1). Epub 2019 Jul 25.

Medical ICU, First Dept of Internal Medicine, Teaching Hospital, Faculty of Medicine and Biomedical Center in Pilsen, Charles University, Pilsen, Czech Republic.

Objective: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain.

Patients And Methods: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching.

Results: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% 28%; p<0.0001) and hospital mortality (49% 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81).

Conclusions: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.
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http://dx.doi.org/10.1183/13993003.02442-2018DOI Listing
July 2019

Importance of ultrasound examination in diagnosing acute conditions.

Authors:
Martin Balík

Vnitr Lek 2019 ;65(3):177-186

Availability of an ultrasound device at the critical care setting significantly enhances possible diagnostic ways and makes the management of critically ill patients more effective. Growing amount of papers confirms that qualified intensivists with background in medicine and anaesthesiology may provide accurate, safe and extensive diagnosis of the haemodynamic system with the aid of echocardiography. Examination of lungs, pleural space, quantification of pleural fluid and eventual exclusion of ventral pneumothorax should be an integral part of transtoracic echocardiographic examination. Interrogation of abdomen in sepsis of unknown origin, acute abdominal syndrome or in acute renal failure may direct further diagnostic and therapeutic steps in critically ill patient. Time factor is particularly important in shock and during admission of severe trauma where patient´s survival depends on correctly launched diagnostic algorithm. Ultrasound plays a key role here. Interrogation with ultrasound helps also before performing a percutanneous dilatational tracheostomy. The same technique may locate a vessel before cannulation in high risk patient and avoid potential complication and also unnecessary transfusion of platelets. Ultrasound has an established role in exploration of vessels in perfusion disorders and suspected deep venous thrombosis. Transcranial Doppler ultrasonography is an important aid in diagnostics of cerebral blood flow particularly in subarachnoid bleeding and intracranial hypertension. The cost of multimodal ultrasonic device is substantial however, the device may save a life of a patient and save time, complications and costs for the department in the hands of a skilled intensivist.
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August 2019

Management of accidental hypothermia: an established extracorporeal membrane oxygenation centre experience.

Perfusion 2019 04;34(1_suppl):74-81

5 2nd Department of Internal Medicine - Department of Cardiovascular Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Introduction: Data on management of severe accidental hypothermia published from an established high-volume extracorporeal membrane oxygenation centre are scarce.

Methods: A total of 28 patients with intravesical temperature lower than 28°C on admission were either treated with veno-arterial extracorporeal membrane oxygenation or rewarmed conservatively.

Results: A total of 10 patients rewarmed on veno-arterial extracorporeal membrane oxygenation (age: 37 ± 12.6 years) and 18 conservatively (age: 55.2 ± 11.2 years) were collected over a course of 5 years. The dominant cause was alcohol intoxication with exposure to cold (39%), 12 patients were resuscitated prior to admission. The admission temperature in the extracorporeal membrane oxygenation group (23.8 ± 2.6°C) was lower than in the non-extracorporeal membrane oxygenation group (26.0 ± 1.5°C, p = 0.01). The peripheral percutaneous veno-arterial extracorporeal membrane oxygenation was always cannulated in malignant arrhythmias causing refractory cardiac arrest. The typical extracorporeal membrane oxygenation blood flow was 3-4 L/minute and sweep gas flow 2 L/minute, the median extracorporeal membrane oxygenation duration was 48.3 (28.1-86.7) hours. The median rates of rewarming did not differ (0.41 (0.35-0.7)°C/hour in extracorporeal membrane oxygenation and 0.77 (0.54-0.98)°C/hour in non-extracorporeal membrane oxygenation, p = 0.46) as well as the admission arterial lactate, pH and potassium. Their development was not different between the groups except for higher pH between the third and ninth hour of rewarming in the extracorporeal membrane oxygenation group. The hospital mortality was 10% in the extracorporeal membrane oxygenation group and 11.1% in the non-extracorporeal membrane oxygenation group with the median last Glasgow Coma Scale 15 and Cerebral Performance Score 1.

Conclusion: Veno-arterial extracorporeal membrane oxygenation for severe hypothermia shows promising outcome data collected in an extracorporeal membrane oxygenation/extracorporeal cardiopulmonary resuscitation centre located in a European urban area. Except for presence of refractory cardiac arrest, the established hypothermia-related prognostic indicators did not differ between patients in need for extracorporeal membrane oxygenation and those rewarmed without extracorporeal membrane oxygenation.
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http://dx.doi.org/10.1177/0267659119830551DOI Listing
April 2019

Immature granulocytes as a sepsis predictor in patients undergoing cardiac surgery.

Interact Cardiovasc Thorac Surg 2019 06;28(6):845-851

Department of Anaesthesiology, Resuscitation and Intensive Medicine, General University Hospital, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Objectives: Usefulness of immature granulocyte percentage (IG%) to discriminate between postoperative non-infective systemic inflammatory response syndrome (SIRS) and sepsis was tested in cardiac surgical patients.

Methods: A retrospective analysis of 124 patients who developed non-infective SIRS and sepsis after elective cardiac surgery was performed. Predictive ability of IG% to predict sepsis was compared to procalcitonin (PCT), white blood cell count, temperature and different biomarker combinations using receiver operating characteristic and logistic regression analysis. The optimal cut-off points, diagnosis sensitivity and specificity were calculated.

Results: There were 44 patients diagnosed with sepsis and 80 patients with non-infective SIRS. In receiver operating characteristic analysis, area under the curve was higher for IG% (0.71) and PCT (0.72) compared to white blood cell count (0.62) and temperature (0.58). The best cut-off value for IG% was 1.45% (sensitivity 70.5%, specificity 60%) and 1.43 µg/l for PCT (sensitivity 65.9%, specificity 75%). The combination of IG% and PCT provided the best sepsis prediction (area under the curve of 0.8, sensitivity 63.6% and specificity 88.8%).

Conclusions: In cardiac surgical patients, IG% is a helpful marker with the moderate ability to discriminate between sepsis and non-infective SIRS, comparable to serum PCT. A combination of these parameters increased the test's overall predictive ability by improving its specificity.
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http://dx.doi.org/10.1093/icvts/ivy360DOI Listing
June 2019

X-ray indices of chest drain malposition after insertion for drainage of pneumothorax in mechanically ventilated critically ill patients.

J Thorac Dis 2018 Oct;10(10):5695-5701

Department of Anesthesiology and Intensive Care, 1 Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Background: Chest drain (CD) migration in the pleural cavity may result in inadequate drainage of pneumothorax. The aim of this study was to assess several parameters that might help in diagnosing CD migration on chest X-ray (CXR).

Methods: Patients with a CD inserted from the safe triangle with a subsequent supine CXR and CT scan performed less than 24 hours apart were assessed for CD foreshortening, angle of inclination of the CD, and CD tortuosity. CD foreshortening was expressed as a ratio between CD length measured in coronal plane only and CD length inside the pleural cavity measured on CT. The angle of inclination of the CD was measured as the angle between the horizontal line and CD at the pleural space entry on CXR. CD tortuosity was calculated as a ratio between the distance from CD pleural space entry to the tip of the CD and the length of CD from the pleural space entry to its tip on CXR.

Results: Altogether 28 patients were included in the study. The median time between the CXR and CT examinations was 5.4 hours (IQR, 3.8-6.9 hours). CD foreshortening was the best clue of a misplaced CD with AUC of 0.93, 100% sensitivity and 88% specificity for a cut-off value of 82%. The angle of CD inclination was greater in patients with misplaced CD with AUC of 0.83, 75% sensitivity and 92% specificity for a cut-off of 50 degrees. The performance of CD tortuosity was poor.

Conclusions: Greater foreshortening of the CD and a steep angle of inclination of the CD above the horizontal at chest entry should raise suspicion of CD migration and mandate further investigation by chest ultrasound to rule out residual pneumothorax occult on CXR.
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http://dx.doi.org/10.21037/jtd.2018.09.64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236183PMC
October 2018

Air Embolism into Superior Mesenteric Artery Following Replacement of Ascending Aorta for Aortic Dissection - A Rare and Fatal Case.

J Belg Soc Radiol 2018 Oct 18;102(1):68. Epub 2018 Oct 18.

Department of Surgery, First Faculty of Medicine, Charles University in Prague, CZ.

We report an unusual case of fatal air embolism into the superior mesenteric artery in a patient, who underwent replacement of the ascending aorta for aortic dissection type A. CT performed twice on the first postoperative day showed abundant air in the superior mesenteric artery and its branches (but not in the portal-venous system) indicating air embolism with no signs of bowel necrosis. On the second postoperative day, the patient underwent extensive bowel resection due to bowel ischemia and died on the third postoperative day on MODS/SIRS.
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http://dx.doi.org/10.5334/jbsr.822DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196575PMC
October 2018

A Rare Case of Severe Metabolic Alkalosis with Unusual Hyperproteinemia Treated with Continuous Renal Replacement Therapy and Regional Citrate Anticoagulation.

Case Rep Nephrol Dial 2018 May-Aug;8(2):138-146. Epub 2018 Aug 3.

Department of Anaesthesiology and Intensive Care, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

A 23-year-old woman was referred to the tertiary centre with acute kidney injury and severe metabolic alkalosis following an accidental ethylene glycol poisoning. The patient had been treated with continuous haemodiafiltration and regional citrate anticoagulation, and a tracheostomy was performed due to pneumonia. Besides severe metabolic alkalosis and hypernatremia, the laboratory tests revealed total protein of 108 g/L on admission to the tertiary centre. The haemodiafiltration with regional citrate anticoagulation continued with parallel correction of the alkalosis and normalisation of the total plasma protein. The tracheostomy was decannulated and the patient was discharged to the district hospital. The case demonstrates the usefulness of regional citrate anticoagulation even in severe metabolic alkalosis which was likely related to the method setting prior to admission and to an overcompensation of the initial severe metabolic acidosis. The unusual hyperproteinaemia might be interpreted with the aid of the Stewart-Fencl model of the acid-base regulation.
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http://dx.doi.org/10.1159/000491628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120368PMC
August 2018

Landiolol for managing post-operative atrial fibrillation.

Eur Heart J Suppl 2018 Jan 8;20(Suppl A):A10-A14. Epub 2018 Jan 8.

Abteilung für Kardiologie-Intensivstation 13H3, AKH Wien, Währinger Gürtel 18-20, Wien, Österreich.

Beta-blockers are a potential option to manage peri-operative atrial fibrillation. Landiolol is a new ultra-short beta-blocker with a half-life of only 4 minutes and very high beta-1 selectivity which has been used for treatment and prevention of atrial fibrillation in pulmonary surgery and gastro-intestinal surgery. Due to its limited negative inotropic effect and high beta-1 selectivity landiolol allows for control of heart rate with minimal impact on blood pressure. Landiolol is well tolerated by the respiratory system. Additional benefits are related to the regulation of the inflammatory response and blunting of the adrenergic pathway. There is a limited number of trials with total of 61 patients undergoing lung resection or oesophagectomy who developed post-operative atrial fibrillation and were treated with landiolol. The experience with landiolol for prevention is more documented than landiolol application for treatment of post-operative atrial fibrillation. There are 9 comparative studies with a total of 450 patients administered landiolol for prevention of post-operative atrial fibrillation. The use of low dosage (5-10mcg/kg/min) is usually sufficient to rapidly control heart rate which is associated with earlier and higher rate of conversion to sinus rhythm as compared to the controls. The excellent tolerance of landiolol at lower dosage (3-5mcg/kg/min) allows to initiate prophylactic use during surgery and postoperatively. Landiolol prophylaxis is associated with reduced incidence of post-operative atrial fibrillation without triggering adverse events related to a beta-blockade.
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http://dx.doi.org/10.1093/eurheartj/sux036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909769PMC
January 2018

Echocardiography in extracorporeal life support: A key player in procedural guidance, tailoring and monitoring.

Perfusion 2018 05;33(1_suppl):31-41

9 2nd Department of Medicine, Department of Cardiovascular Medicine, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

Extracorporeal life support (ECLS) is a mainstay of current practice in severe respiratory, circulatory or cardiac failure refractory to conventional management. The inherent complexity of different ECLS modes and their influence on the native pulmonary and cardiovascular system require patient-specific tailoring to optimize outcome. Echocardiography plays a key role throughout the ECLS care, including patient selection, adequate placement of cannulas, monitoring, weaning and follow-up after decannulation. For this purpose, echocardiographers require specific ECLS-related knowledge and skills, which are outlined here.
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http://dx.doi.org/10.1177/0267659118766438DOI Listing
May 2018

Arterialized blood from a central venous catheter after cardiac surgery: a puzzle for the intensivist.

Can J Anaesth 2018 08 27;65(8):951-952. Epub 2018 Feb 27.

Department of Anaesthesiology, Resuscitation and Intensive Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

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http://dx.doi.org/10.1007/s12630-018-1098-yDOI Listing
August 2018

Catastrophic Left Ventricular Thrombosis Complicating Extra-corporeal Membrane Oxygenation: A Case Report.

Prague Med Rep 2017;118(4):139-146

Department of Anaesthesiology, Resuscitation and Intensive Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

A massive left ventricular thrombosis represents a rare however, catastrophic complication of a central veno-arterial extra-corporeal membrane oxygenation. We report a case of such complication in a patient with severe left ventricular dysfunction after cardiac surgery. Its management and preventive measures are described and discussed.
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http://dx.doi.org/10.14712/23362936.2017.15DOI Listing
April 2018

Six-Month Outcome of Immunocompromised Patients with Severe Acute Respiratory Distress Syndrome Rescued by Extracorporeal Membrane Oxygenation. An International Multicenter Retrospective Study.

Am J Respir Crit Care Med 2018 May;197(10):1297-1307

Sorbonne Universités, UPMC University Paris 06, INSERM UMRS_1166, Institute of Cardiometabolism and Nutrition, Paris, France.

Because encouraging rates for hospital and long-term survival of immunocompromised patients in ICUs have been described, these patients are more likely to receive invasive therapies, like extracorporeal membrane oxygenation (ECMO). To report outcomes of immunocompromised patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and to identify their pre-ECMO predictors of 6-month mortality and main ECMO-related complications. Retrospective multicenter study in 10 international ICUs with high volumes of ECMO cases. Immunocompromised patients, defined as having hematological malignancies, active solid tumor, solid-organ transplant, acquired immunodeficiency syndrome, or long-term or high-dose corticosteroid or immunosuppressant use, and severe ECMO-treated ARDS, from 2008 to 2015 were included. We collected demographics, clinical data, ECMO-related complications, and ICU- and 6 month-outcome data for 203 patients (median Acute Physiology and Chronic Health Evaluation II score, 28 [25th-75th percentile, 20-33]; age, 51 [38-59] yr; Pa/Fi, 60 [50-82] mm Hg before ECMO) who fulfilled our inclusion criteria. Six-month survival was only 30%, with a respective median ECMO duration and ICU stay of 8 (5-14) and 25 (16-50) days. Patients with hematological malignancies had significantly poorer outcomes than others (log-rank  = 0.02). ECMO-related major bleeding, cannula infection, and ventilator-associated pneumonia were frequent (36%, 10%, and 50%, respectively). Multivariate analyses retained fewer than 30 days between immunodeficiency diagnosis and ECMO cannulation as being associated with lower 6-month mortality (odds ratio, 0.32 [95% confidence interval, 0.16-0.66];  = 0.002), and lower platelet count, higher Pco, age, and driving pressure as independent pre-ECMO predictors of 6-month mortality. Recently diagnosed immunodeficiency is associated with a much better prognosis in ECMO-treated severe ARDS. However, low 6-month survival of our large cohort of immunocompromised patients supports restricting ECMO to patients with realistic oncological/therapeutic prognoses, acceptable functional status, and few pre-ECMO mortality-risk factors.
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http://dx.doi.org/10.1164/rccm.201708-1761OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7252852PMC
May 2018

Diagnostic and prognostic value of presepsin vs. established biomarkers in critically ill patients with sepsis or systemic inflammatory response syndrome.

Clin Chem Lab Med 2018 03;56(4):658-668

Department of Anesthesiology, University of Pittsburgh School of Medicine, UPMC Presbyterian Hospital, 200 Lothrop St. Suite C220, Pittsburgh, PA 15213, USA.

Background: Inflammatory biomarkers may aid to distinguish between systemic inflammatory response syndrome (SIRS) vs. sepsis. We tested the hypotheses that (1) presepsin, a novel biomarker, can distinguish between SIRS and sepsis, and (2) higher presepsin levels will be associated with increased severity of illness and (3) with 28-day mortality, outperforming traditional biomarkers.

Methods: Procalcitonin (PCT), C-reactive protein (CRP), presepsin, and lactate were analyzed in 60 consecutive patients (sepsis and SIRS, n=30 per group) on day 1 (D1) to D3 (onset sepsis, or after cardiac surgery). The systemic organ failure assessment (SOFA) score was determined daily.

Results: There was no difference in mortality in sepsis vs. SIRS (12/30 vs. 8/30). Patients with sepsis had higher SOFA score vs. patients with SIRS (11±4 vs. 8±5; p=0.023), higher presepsin (AUC=0.674; p<0.021), PCT (AUC=0.791; p<0.001), CRP (AUC=0.903; p<0.0001), but not lactate (AUC=0.506; p=0.941). Unlike other biomarkers, presepsin did not correlate with SOFA on D1. All biomarkers were associated with mortality on D1: presepsin (AUC=0.734; p=0.0006; best cutoff=1843 pg/mL), PCT (AUC=0.844; p<0.0001), CRP (AUC=0.701; p=0.0048), and lactate (AUC=0.778; p<0.0001). Multiple regression analyses showed independent associations of CRP with diagnosis of sepsis, and CRP and lactate with mortality. Increased neutrophils (p=0.002) and decreased lymphocytes (p=0.007) and monocytes (p=0.046) were also associated with mortality.

Conclusions: Presepsin did not outperform traditional sepsis biomarkers in diagnosing sepsis from SIRS and in prognostication of mortality in critically ill patients. Presepsin may have a limited adjunct value for both diagnosis and an early risk stratification, performing independently of clinical illness severity.
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http://dx.doi.org/10.1515/cclm-2017-0839DOI Listing
March 2018

Management of arrhythmia in sepsis and septic shock.

Anaesthesiol Intensive Ther 2017;49(5):419-429. Epub 2017 Nov 18.

Department of Anaesthesiology and Intensive Care, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Czechia.

The occurrence of supraventricular arrhythmias is associated with an unfavourable prognosis in septic shock. Available trials are difficult to apply in sepsis and septic shock patients due to included cohorts, control groups and because "one size does not fit all". The priorities in the critically ill are maintenance of the sinus rhythm and diastolic ventricular filling. The rate control modality should be reserved for chronic AF and in situations when the sinus rhythm is difficult to maintain due to extreme stress conditions resulting from a high dosage of vasoactive agents. Electric cardioversion is indicated in unstable patients with an absence of contraindications and is more feasible in combination with an antiarrhythmic agent. Besides amiodarone being preferred for its lower cardiodepressant side effect compared to other agents, drugs with a different degree of betablocking activity are very useful in supraventricular arrhythmias and septic shock, providing echocardiography is routinely used to support their indications within the current summary of product characteristics. A typical patient benefiting from propafenone is without significant structural heart disease, i.e. typically with normal to moderately reduced left ventricular systolic function. Future research should be channelled towards echocardiography-guided prospective controlled trials on antiarrhythmic therapy which may clarify the issue of rhythm versus rate control, the effects of various antiarrhythmic drugs, and a place for electric cardioversion in critically ill patients in septic shock.
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http://dx.doi.org/10.5603/AIT.a2017.0061DOI Listing
November 2018

Is the mechanism of re-expansion pulmonary oedema in a heart-lung interaction?

BMJ Case Rep 2017 Jul 18;2017. Epub 2017 Jul 18.

Department of Anaesthesia and Intensive Care, 1st Medical Faculty, Charles University, Prague, Czech Republic.

The mechanism of re-expansion pulmonary oedema (Re-PE) is unclear. There are multiple variables in play when evaluating the response to evacuation of pleural fluid. We present an educational case of a critically ill patient admitted for respiratory failure who was fully dependent on ventricular pacing set at a constant rate throughout the episode of Re-PE. The transthoracic echocardiography (TTE) showed an ejection fraction of 38%, moderate mitral regurgitation (MR), mildly dilated right ventricle and moderate pulmonary hypertension. A pleural tap evacuated 850 mL of transudate, which was followed by tachypnoea and deteriorating oxygenation. Another repeat TTE revealed a Re-PE with elevated left ventricular end-diastolic pressure, severe MR, increased pulmonary hypertension and a decrease in stroke volume. There were no parallel changes in ventilation modality, heart rate, fluid therapy and vasopressor dosage. The treatment was initiated with dobutamine. The patient was extubated the next day and was later discharged to the cardiology department.
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http://dx.doi.org/10.1136/bcr-2017-219340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534756PMC
July 2017

A rationale for early extracorporeal membrane oxygenation in patients with postinfarction ventricular septal rupture complicated by cardiogenic shock.

Eur J Heart Fail 2017 05;19 Suppl 2:97-103

2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.

Aims: Ventricular septal rupture (VSR) became a rare mechanical complication of myocardial infarction in the era of percutaneous coronary interventions but is associated with extreme mortality in patients who present with cardiogenic shock (CS). Promising outcomes have been reported with the use of circulatory support allowing haemodynamic stabilization, followed by delayed repair. Therefore, we analysed our experience with an early use of Veno-Arterial Extracorporeal Membrane Oxygenation (V-A ECMO) for postinfarction VSR.

Methods And Results: We conducted a retrospective search of institutional database for patients presenting with postinfarction VSR from January 2007 to June 2016. Data from 31 consecutive patients (mean age 69.5 ± 9.1 years) who were admitted to hospital were analysed. Seven out of 31 patients with VSR who were in refractory CS received V-A ECMO support preoperatively. ECMO improved end-organ perfusion with decreased lactate levels 24 hours after implantation (7.9 mmol/L vs. 1.6 mmol/L, p = 0.01), normalized arterial pH (7.25 vs. 7.40, p < 0.04), improved mean arterial pressure (64 mmHg vs. 83 mmHg, p < 0.01) and lowered heart rate (115/min vs. 68/min, p < 0.01). Mean duration of ECMO support was 12 days, 5 out of 7 patients underwent surgical repair, 4 were weaned from ECMO, 3 survived 30 days and 2 survived more than 1 year. The most frequent complication (5 patients) and the cause of death (3 patients) was bleeding.

Conclusions: Our experience suggests that early V-A ECMO in patients with VSR and refractory CS might prevent irreversible multiorgan failure by improved end-organ perfusion. Bleeding complications remain an important limitation of this approach.
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http://dx.doi.org/10.1002/ejhf.852DOI Listing
May 2017

Cost-effectiveness of hospital treatment and outcomes of acute methanol poisoning during the Czech Republic mass poisoning outbreak.

J Crit Care 2017 06 6;39:190-198. Epub 2017 Mar 6.

Department of Occupational Medicine, 1st Faculty of Medicine, Charles University and General University Hospital, Toxicological Information Centre, Na Bojisti 1, 120 00 Prague 2, Czech Republic. Electronic address:

Purpose: During an outbreak of mass methanol poisoning in the Czech Republic in 2012-2014, we compared the total hospital costs and one-year medical costs in the patients treated with different antidotes (fomepizole versus ethanol) and modalities of hemodialysis (intermittent hemodialysis, IHD, versus continuous renal replacement therapy, CRRT).

Methods: Cross-sectional study in 106 patients with confirmed diagnosis treated in 30 ICU settings. For each patient, the following data were analyzed: admission laboratory data, GCS, PSS, ICU length of stay, organ failures, treatment, outcome, and total hospital costs. Of 83 survivors, in 54 (65%) patients the follow-up examination, quality of life measurement with SF36 questionnaire two years after discharge, and one-year medical costs analysis were performed.

Results: The median total hospital costs were 7200 (IQR 1500-10,900) euros and the median one-year medical costs were 1447 (IQR 133-1163) euros in the study population. The total hospital costs were higher in the patients treated with fomepizole comparing to ethanol: 12,890 (IQR 6910-16,210) versus 5590 (IQR 1430-6940) euros (p<0.001). The hospital costs in the patients treated with IHD were 5400 (IQR 1520-6910) versus 12,410 (IQR 5380-16,960) euros in the patients with CRRT (p=0.317). The geometric mean ratio for increased hospital costs in the patients treated with fomepizole versus ethanol adjusted for the severity of poisoning was 3.30 (1.70-3.80 CI 95%), p<0.001, and in the patients treated with IHD versus CRRT - 0.70 (0.60-0.99 CI 95%), p=0.047. The patients with visual sequelae had higher total hospital costs than those without sequelae: 10,419 (IQR 2984-14,355) versus 4605 (IQR 1303-4505) euros (p=0.009). The patients with GCS≤13 on admission had higher one-year medical costs as well (p<0.001). No difference was found in physical and mental condition scores in the patients treated with different antidotes and modalities of hemodialysis two years after discharge (both p>0.05).

Conclusion: The total hospital costs in the patients with acute methanol poisoning were more than three times higher in the patients treated with fomepizole than in the patients treated with ethanol after adjustment for the severity of poisoning. The dialysis modality did not affect the total hospital costs, but the trend to lower costs was present in IHD-group.
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http://dx.doi.org/10.1016/j.jcrc.2017.03.001DOI Listing
June 2017