Dexamethasone doses in patients with COVID-19 and hypoxia: A systematic review and meta-analysis.

BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.

Update on Therapeutic Drug Monitoring of Beta-Lactam Antibiotics in Critically Ill Patients-A Narrative Review.

Beta-lactam antibiotics remain one of the most preferred groups of antibiotics in critical care due to their excellent safety profiles and their activity against a wide spectrum of pathogens. The cornerstone of appropriate therapy with beta-lactams is to achieve an adequate plasmatic concentration of a given antibiotic, which is derived primarily from the minimum inhibitory concentration (MIC) of the specific pathogen. In a critically ill patient, the plasmatic levels of drugs could be affected by many significant changes in the patient's physiology, such as hypoalbuminemia, endothelial dysfunction with the leakage of intravascular fluid into interstitial space and acute kidney injury. Predicting antibiotic concentration from models based on non-critically ill populations may be misleading. Therapeutic drug monitoring (TDM) has been shown to be effective in achieving adequate concentrations of many drugs, including beta-lactam antibiotics. Reliable methods, such as high-performance liquid chromatography, provide the accurate testing of a wide range of beta-lactam antibiotics. Long turnaround times remain the main drawback limiting their widespread use, although progress has been made recently in the implementation of different novel methods of antibiotic testing. However, whether the TDM approach can effectively improve clinically relevant patient outcomes must be proved in future clinical trials.

Cryptococcal Pneumonia: An Unusual Complication in a COVID-19 Patient.

Cryptococcal superinfection is a rare but potentially fatal complication, especially if its detection and subsequent treatment are delayed. Histopathological findings of pulmonary parenchyma from a deceased patient with these complications were acquired. Quite interestingly, only a minimal inflammatory reaction could be seen in an individual with no previously known immune suppression, indicating a disturbance of the immune system. This finding was well in concordance with the described changes in cellular immunity in COVID-19. We report the case of a 60 year old male with critical coronavirus disease 2019 (COVID-19) complicated by cryptococcal pneumonia and multiorgan failure. Both X-ray and CT scans revealed lung infiltrates corresponding with COVID-19 infection early after the onset of symptoms. Despite receiving standard treatment, the patient progressed into multiple organ failure, requiring mechanical ventilation, circulatory support, and haemodialysis. Cryptococcus neoformans was detected by subsequent BAL, and specific antifungal treatment was instituted. His clinical status deteriorated despite all treatment, and he died of refractory circulatory failure after 21 days from hospital admission. Histopathological findings confirmed severe diffuse alveolar damage (DAD) caused by COVID-19 and cryptococcal pneumonia. Timely diagnosis of cryptococcal superinfection may be challenging; therefore, PCR panels detecting even uncommon pathogens should be implemented while taking care of critical COVID-19 patients.

Palliative care practice and moral distress during COVID-19 pandemic (PEOpLE-C19 study): a national, cross-sectional study in intensive care units in the Czech Republic.

BACKGROUND: Providing palliative care at the end of life (EOL) in intensive care units (ICUs) seems to be modified during the COVID-19 pandemic with potential burden of moral distress to health care providers (HCPs). We seek to assess the practice of EOL care during the COVID-19 pandemic in ICUs in the Czech Republic focusing on the level of moral distress and its possible modifiable factors. METHODS: Between 16 June 2021 and 16 September 2021, a national, cross-sectional study in intensive care units (ICUs) in Czech Republic was performed. All physicians and nurses working in ICUs during the COVID-19 pandemic were included in the study. For questionnaire development ACADEMY and CHERRIES guide and checklist were used. A multivariate logistic regression model was used to analyse possible modifiable factors of moral distress. RESULTS: In total, 313 HCPs (14.5% out of all HCPs who opened the questionnaire) fully completed the survey. Results showed that 51.8% (n = 162) of respondents were exposed to moral distress during the COVID-19 pandemic. 63.1% (n = 113) of nurses and 71.6% of (n = 96) physicians had experience with the perception of inappropriate care. If inappropriate care was perceived, a higher chance for the occurrence of moral distress for HCPs (OR, 1.854; CI, 1.057-3.252; p = 0.0312) was found. When patients died with dignity, the chance for moral distress was lower (OR, 0.235; CI, 0.128-0.430; p < 0.001). The three most often reported differences in palliative care practice during pandemic were health system congestion, personnel factors, and characteristics of COVID-19 infection. CONCLUSIONS: HCPs working at ICUs experienced significant moral distress during the COVID-19 pandemic in the Czech Republic. The major sources were perceiving inappropriate care and dying of patients without dignity. Improvement of the decision-making process and communication at the end of life could lead to a better ethical and safety climate. TRIAL REGISTRATION: NCT04910243 .

Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study.

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2'-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker's ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin.

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

BACKGROUND: Since December 2019, SARS-CoV-2 virus has infected millions of people worldwide. In patients with COVID-19 pneumonia in need of oxygen therapy or mechanical ventilation, dexamethasone 6 mg per day is currently recommended. However, the dose of 6 mg of dexamethasone is currently being reappraised and may miss important therapeutic potential or may prevent potential deleterious effects of higher doses of corticosteroids. METHODS: REMED is a prospective, open-label, randomised controlled trial testing the superiority of dexamethasone 20 mg (dexamethasone 20 mg on days 1-5, followed by dexamethasone 10 mg on days 6-10) vs 6 mg administered once daily intravenously for 10 days in adult patients with moderate or severe ARDS due to confirmed COVID-19. Three hundred participants will be enrolled and followed up for 360 days after randomization. Patients will be randomised in a 1:1 ratio into one of the two treatment arms. The following stratification factors will be applied: age, Charlson Comorbidity Index, CRP levels and trial centre. The primary endpoint is the number of ventilator-free days (VFDs) at 28 days after randomisation. The secondary endpoints are mortality from any cause at 60 days after randomisation; dynamics of the inflammatory marker, change in WHO Clinical Progression Scale at day 14; and adverse events related to corticosteroids and independence at 90 days after randomisation assessed by the 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. The study will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. DISCUSSION: We aim to compare two different doses of dexamethasone in patients with moderate to severe ARDS undergoing mechanical ventilation regarding efficacy and safety. TRIAL REGISTRATION: EudraCT No. 2020-005887-70. ClinicalTrials.gov NCT04663555. Registered on December 11, 2020.

Prognostic value of oxidative stress in patients with acute myocardial infarction complicated by cardiogenic shock: A prospective cohort study.

INTRODUCTION: Cardiogenic shock is a frequent complication of acute myocardial infarction. Similar to ischemia/reperfusion injury, excessive production of reactive oxygen species can be expected in those who experience cardiogenic shock. The aims of this study were to describe the extent and time course of oxidative stress and evaluate the prognostic value of oxidative stress markers in patients who experienced ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. METHODS: Plasma/serum levels of selected biomarkers of oxidative stress (oxidised guanine species (OGS), malondialdehyde, and glutathione peroxidase 3) and markers, which simultaneously reflect severe cellular damage (ferric ion reducing antioxidant power (FRAP), Cu/Zn-superoxide dismutase (SOD), and glutathione) were measured seven times per week in a prospective cohort of 82 patients with STEMI complicated by cardiogenic shock. RESULTS: We found elevated OGS levels in patients who died during three months, which persisted significantly increased the next 12 h compared to surviving patients. A similar time course pattern also exhibited concentrations of FRAP and SOD. The other markers did not change significantly and did not show differences between surviving and non-surviving patients during the monitored period. In addition, a strong relationship between OGS, FRAP, and SOD levels (on admission and 12 h after admission) and 3-month mortality was found. CONCLUSION: Levels of OGS, FRAP, and SOD within 12 h after hospital admission were revealed as early predictors of the adverse development of STEMI complicated by cardiogenic shock.

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.

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 - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 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.

Ischemic stroke in paediatrics - narrative review of the literature and two cases.

Stroke is a rare condition in childhood with an estimated incidence of between 1.3-13/100.000 patients. Clinical manifestation and risk factors for paediatric stroke are different from those of adults. The uncommon incidence, age-associated difference and plethora of clinical symptoms make the diagnosis of such strokes extremely difficult and often delayed. The history and clinical examination should point to diseases or predisposing factors. Neuroimaging (DWI MR) is the golden standard for diagnosis of paediatric stroke and other investigations can be considered according to the clinical condition. Despite advances in paediatric stroke research and clinical care, questions remain unanswered regarding acute treatment, secondary prevention and rehabilitation. The treatment recommendations are mainly extrapolated from studies on adult populations. In the review authors summarized the clinical characteristics and diagnostic steps for stroke in children/adolescents based on the most recent international guidelines and practical directions for recognising and managing the child/adolescent with stroke in paediatric emergency. In the two case reports, we describe the clinical course in both stroke patients.

Infectious Complications and Immune/Inflammatory Response in Cardiogenic Shock Patients: A Prospective Observational Study.

INTRODUCTION: Patients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers. METHODS: Eighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock. RESULTS: Infection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875. CONCLUSION: The prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections did not prolong statistically significantly the duration of mechanical ventilation and did not increase the prevalence of hospital mortality in this high-risk CS population. CS due to acute myocardial infarction was accompanied by a strong and highly variable inflammatory response, but it did not reach the intensity of the inflammatory response observed in patients with septic shock. An extensive immune/inflammatory response in patients with CS is linked to a poor prognosis.

Epidemiology of hospital-acquired pneumonia: Results of a Central European multicenter, prospective, observational study compared with data from the European region.

BACKGROUND: Hospital-acquired pneumonia (HAP) is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of HAP. This project was aimed at collecting multicenter epidemiological data on patients with HAP in the Czech Republic and comparing them with supraregional data. METHODS: This prospective, multicenter, observational study processed data from a database supported by a Czech Ministry of Health grant project. Included were all consecutive patients aged 18 and over who were admitted to participating intensive care units (ICUs) between 1 May 2013 and 31 December 2014 and met the inclusion criterion of having HAP. The primary endpoint was to analyze the relationships between 30-day mortality (during the stay in or after discharge from ICUs) and the microbiological etiological agent and adequacy of initial empirical antibiotic therapy in HAP patients. RESULTS: The group dataset contained data on 330 enrolled patients. The final validated dataset involved 214 patients, 168 males (78.5%) and 46 females (21.5%), from whom 278 valid lower airway samples were obtained. The mean patient age was 59.9 years. The mean APACHE II score at admission was 21. Community-acquired pneumonia was identified in 13 patients and HAP in 201 patients, of whom 26 (12.1%) had early-onset and 175 (81.8%) had late-onset HAP. Twenty-two bacterial species were identified as etiologic agents but only six of them exceeded a frequency of detection of 5% (Klebsiella pneumoniae 20.4%, Pseudomonas aeruginosa 20.0%, Escherichia coli 10.8%, Enterobacter spp. 8.1%, Staphylococcus aureus 6.2% and Burkholderia cepacia complex 5.8%). Patients infected with Staphylococcus aureus had significantly higher rates of early-onset HAP than those with other etiologic agents. The overall 30-day mortality rate for HAP was 29.9%, with 19.2% mortality for early-onset HAP and 31.4% mortality for late-onset HAP. Patients with late-onset HAP receiving adequate initial empirical antibiotic therapy had statistically significantly lower 30-day mortality than those receiving inadequate initial antibiotic therapy (23.8% vs 42.9%). Patients with ventilator-associated pneumonia (VAP) had significantly higher mortality than those who developed HAP with no association with mechanical ventilation (34.6% vs 12.7%). Patients having VAP treated with adequate initial antibiotic therapy had lower 30-day mortality than those receiving inadequate therapy (27.2% vs 44.8%). CONCLUSIONS: The present study was the first to collect multicenter data on the epidemiology of HAP in the Central European Region, with respect to the incidence of etiologic agents causing HAP. It was concerned with relationships between 30-day patient mortality and the type of HAP, etiologic agent and adequacy of initial empirical antibiotic therapy.

Patient survival, predictive factors and disease course of severe sepsis in Czech intensive care units: A multicentre, retrospective, observational study.

BACKGROUND: Severe sepsis/septic shock is associated with high mortality. In Central Europe, there is a dearth of information on the prevalence and treatment of severe sepsis. The EPOSS (Data-based Evaluation and Prediction of Outcome in Severe Sepsis) project launched in 2011 was aimed at collecting data on patients with severe sepsis/septic shock. METHODS: The EPOSS study processes data from the EPOSS project database, and is a retrospective, multicentre, observational study. This included all consecutive patients aged 18 and over who were admitted to participating ICUs from 1 January 2011 to 5 November 2013 and met the inclusion criteria of severe sepsis/septic shock. The primary endpoint was to analyse the relationship between in-hospital mortality (either in ICU or after discharge from ICU) and the type and number of fulfilled diagnostic and treatment interventions during the first 6 h after the diagnosis of severe sepsis/septic shock. RESULTS: The collected dataset involved 1082 patients meeting the criteria of severe sepsis/septic shock. Following data validation, a final dataset of 897 patients was obtained. The average age of the patient group was 64.7 years; mortality at discharge from EPOSS ICUs was 35.5% and from hospital 40.7%. Of the 10 evaluated diagnostic and treatment interventions within the initial 6 hours of identifying severe sepsis/septic shock (i.e. fulfilment of SSC bundles), four or five diagnostic and treatment interventions were administered to 58.4% patients. Combined diagnostic and treatment interventions associated with the lowest in-hospital mortality were: CVP of ≥8-12 mm Hg & MAP of ≥65 mm Hg & Urine output at ≥0.5 mL/kg/h & Lactate of ≤4.0 mmol/L & Initial lactate measured & Antibiotics in the first hour. Lactate at <4 mmol/L and MAP of ≥65 mm Hg remained statistically significant even after adjustment for patient age and APACHE II score. Statistically significantly increased in-hospital mortality was found in patients admitted from general departments (45.7%) or from other ICUs (41.6%), compared to a lower in-hospital mortality of patients transferred from outpatient clinics (26.5%) or Emergency (38.0%). Severe sepsis/septic shock patients transferred from the department of internal medicine were associated with a higher in-hospital mortality (45.1%) than surgical patients (35.5%). CONCLUSIONS: The most effective measures associated with the lowest in-hospital mortality in septic shock patients were CVP of ≥8-12 mm Hg, MAP of ≥65 mm Hg, urine output at ≥0.5 mL/kg/h, initial lactate level of ≤4.0 mmol/L and administration of antibiotics within the first hour.

[Dynamics of interleukin 6 levels in the patients with cardiogenic and septic shock and in a control group of patients with uncomplicated AMI]. / Dynamika hladiny interleukinu 6 u pacientu v septickém a kardiogenním soku a u pacientu s akutním infarktem myokardu s elevacemi ST.

INTRODUCTION: Cardiogenic shock (CS) is the leading cause of mortality in patients with acute myocardial infarction (AMI). Inflammatory response seems to be common response in patients with AMI, especially those with CS. We have therefore conducted a study to determine diagnostic and prognostic utility of interleukin 6 (IL6) levels in the cohort of patients with cardiogenic and septic shock (SS) and in a control group of patients with uncomplicated AMI. METHODS: In this prospective study 71 patients fulfilled the inclusion criteria: 30 patients with cardiogenic shock, 21 patients with septic shock and 20 patients with ST elevation myocardial infarction (STEMI). Plasma levels of IL6 were measured at 8 time points. The main endpoint was 3 month mortality. RESULTS: We have shown that the highest IL6 levels during the first week were recorded in patients with septic shock with peak value at admission. The maximum level of IL6 was detected between 12 to 24 hours after the onset of MI among patients with cardiogenic shock. According to Receiver operating characteristic (ROC) statistics levels of IL6 > 357 pg/ml at admission (AUC 0.730, p = 0.031) were typical for patients with CS in comparison with control group of STEMI patients. Values of IL6 > 1 237 pg/ml at admission and > 1 071 pg/ml at 24 hours (after admission?) were typical for thouse in septic shock in comparison with CS patients. We found only a non-significant trend of IL6 for the prediction of mortality in the cohort of CS patients for levels 1 854 pg/ml (AUC 0.769, p = 0.066) sampled 12 hours after admission. There was no association of plasma levels of IL6 with mortality in septic shock patients. CONCLUSIONS: Patients with cardiogenic shock demonstrated more pronounced cytokine response as evidenced by increased levels of IL6 compared to patients with uncomplicated STEMI. Levels of IL6 peaked in SS patients at admission, in CS patients 12-24 hours after admission. In daily clinical practice routine measurement of IL6 levels for prediction of prognosis both in cardiogenic and septic shock are of little value mainly due to significant interindividual variability of IL6 values.

Soluble ST2 levels in patients with cardiogenic and septic shock are not predictors of mortality.

BACKGROUND: Soluble ST2 (sST2) is an interleukin-33 receptor. sST2 was found to be an independent prognostic factor in patients with myocardial infarction, sepsis and heart failure. OBJECTIVES: To assess sST2 levels in patients with cardiogenic shock (CS) and septic shock (SS), and to evaluate the prognostic value of sST2 for short-term mortality. METHODS: The present prospective observational study evaluated 32 patients with CS, 17 patients with SS and 61 patients with ST segment elevation myocardial infarction (STEMI )(control group). Samples of serum were collected eight times and the follow-up time was three months. RESULTS: sST2 levels were elevated from admission in SS patients relative to patients with CS and STEMI, who exhibited peak sST2 levels 24 h after admission. On admission, CS patients had a median (5th percentile; 95th percentile) sST2 level of 62.5 pg/mL (8.3 pg/mL; 315.8 pg/mL) and SS patients had a median sST2 level of 216.4 pg/mL (46.8 pg/mL; 364.4 pg/mL). ROC analysis found sST2 to be a biomarker that could distinguish between CS and SS at admission (area under the curve [AUC] 0.813; P<0.01) with a cut-off value of 210.4 pg/mL. Patients with STEMI had significantly lower sST2 levels at admission (20.3 pg/mL (4.2 pg/mL; 339.8 pg/mL) compared with CS patients. The AUC of the ROC analysis was 0.671 (P=0.007) for the detection of CS in patients with STEMI. Only a weak correlation was observed between sST2 and B-type natriuretic peptide (r=0.376, P=0.05) and sST2 and N-terminal pro-B-type natriuretic peptide (r=0.496, P=0.019). No statistically significant differences were observed in sST2 levels in patients with CS and SS relative to three-month mortality. CONCLUSION: Levels of sST2 at admission are significantly higher in patients with SS compared with CS. sST2 could be a diagnostic marker to distinguish SS and CS as well as CS and STEMI at the time of admission. Levels of sST2 are related to levels of natriuretic peptides in CS but not in SS. sST2 levels are not a suitable prognostic marker for patients with CS and SS.