Citrulline, Intestinal Fatty Acid-Binding Protein and the Acute Gastrointestinal Injury Score as Predictors of Gastrointestinal Failure in Patients with Sepsis and Septic Shock.

Gastrointestinal (GI) failure can be both a cause of sepsis and a consequence of the systemic pro-inflammatory response in sepsis. Changes in biomarkers of enterocyte damage, citrulline and I-FABP (intestinal fatty acid binding protein), may indicate altered intestinal permeability and damage. The study group consisted of patients with sepsis (N = 28) and septic shock (N = 30); the control group included patients without infection (N = 10). Blood samples were collected for citrulline and I-FABP and a 4-point AGI score (acute GI injury score) was calculated to monitor GI function on days 1, 3, 5, 7, and 10. Citrulline concentrations in the study group were lower than in the control. Lower values were also noted in septic patients with shock when compared to the non-shock group throughout the study period. I-FABP was higher in the septic shock group than in the sepsis group only on days 1 and 3. Citrulline was lower in patients with GI failure (AGI III) when compared to AGI I/II, reaching significance on days 7 (p = 0.034) and 10 (p = 0.015); moreover, a higher AGI score was associated with an increased 28 day mortality (p = 0.038). The results indicate that citrulline measurements, along with the AGI assessment, have clinical potential in monitoring GI function and integrity in sepsis.

Inflammasome-related Markers upon ICU Admission do not Correlate with Outcome in Critically Ill COVID-19 Patients.

PURPOSE: The development of targeted biological therapies for coronavirus disease 2019 (COVID-19) requires reliable biomarkers that could help indicate how patients are responding. The hyperactivation of inflammasomes by the SARS-CoV2 virus is hypothesized to contribute to a more severe course of the COVID-19 disease. Therefore, we aimed to evaluate the prognostic value of several inflammasome-related cytokines and proteins upon admission to the intensive care unit (ICU). PATIENTS AND METHODS: We performed a prospective cohort study. Plasma samples were obtained from 45 critically ill COVID-19 patients and 10 patients without any signs of infection (traumatic brain injury [TBI]) on admission to the ICU. Concentrations of IL-1a, IL-1ß, IL-18, IL-1RA, galectin-1, apoptosis-associated speck-like proteins, LDH, ferritin, and gasdermin D were analyzed. A cell-free caspase-1 plasma assay was done by inhibitor-based immunoprecipitation followed by a Western Blot. Demographic and clinical characteristics were recorded. RESULTS: Inhospital mortality in COVID-19 patients was 62%. Galectin-1 was 1.8-fold lower in COVID-19 than in TBI patients (17101.84 pg/mL vs. 30764.20 pg/mL, P = 0.007), but other inflammasome-related biomarkers had similar concentrations. Patients with a Sequential Organ Failure Assessment (SOFA) score of > 9 on admission who were at high risk of death had significantly higher galectin-1 but lower IL-1RA in comparison with low-risk patients (25551.3 pg/mL vs. 16302.7 pg/mL, P = 0.014; 14.5 pg/mL vs. 39.4pg/mL, P = 0.04, respectively). Statistically significant correlations were observed between: IL-1a and platelets (r = -0.37), IL-1 ß and platelets (r = -0.36), ferritin and INR (r = 0.39). Activated caspase-1 p35, whose presence was related to higher fibrinogen and lower D-dimers, was detected in 12 out of 22 COVID-19 patients and in none of the TBI patients. Moreover, densitometric analysis showed a significantly higher amount of p35 in patients with a SOFA score > 9. CONCLUSION: We found that the systemic markers of activation of inflammasomes in critically ill COVID-19 patients were not directly related to outcome. Therefore, potential interventions aimed at the inflammasome pathway in this group of patients may be of limited effectiveness and should be biomarker-guided.

Extracorporeal membrane oxygenation for severe COVID-19-associated acute respiratory distress syndrome in Poland: a multicenter cohort study.

BACKGROUND: In Poland, the clinical characteristics and outcomes of patients with COVID-19 requiring extracorporeal membrane oxygenation (ECMO) remain unknown. This study aimed to answer these unknowns by analyzing data collected from high-volume ECMO centers willing to participate in this project. METHODS: This retrospective, multicenter cohort study was completed between March 1, 2020, and May 31, 2021 (15 months). Data from all patients treated with ECMO for COVID-19 were analyzed. Pre-ECMO laboratory and treatment data were compared between non-survivors and survivors. Independent predictors for death in the intensive care unit (ICU) were identified. RESULTS: There were 171 patients admitted to participating centers requiring ECMO for refractory hypoxemia due to COVID-19 during the defined time period. A total of 158 patients (mean age: 46.3 ± 9.8 years) were analyzed, and 13 patients were still requiring ECMO at the end of the observation period. Most patients (88%) were treated after October 1, 2020, 77.8% were transferred to ECMO centers from another facility, and 31% were transferred on extracorporeal life support. The mean duration of ECMO therapy was 18.0 ± 13.5 days. The crude ICU mortality rate was 74.1%. In the group of 41 survivors, 37 patients were successfully weaned from ECMO support and four patients underwent a successful lung transplant. In-hospital death was independently associated with pre-ECMO lactate level (OR 2.10 per 1 mmol/L, p = 0.017) and BMI (OR 1.47 per 5 kg/m2, p = 0.050). CONCLUSIONS: The ICU mortality rate among patients requiring ECMO for COVID-19 in Poland was high. In-hospital death was independently associated with increased pre-ECMO lactate levels and BMI.

The Rationale and Current Status of Endotoxin Adsorption in the Treatment of Septic Shock.

Lipopolysaccharide, the main component of the outer membrane of Gram-negative bacteria is a highly potent endotoxin responsible for organ dysfunction in sepsis. It is present in the blood stream not only in Gram-negative infections, but also in Gram-positive and fungal infections, presumably due to sepsis-related disruption of the intestinal barrier. Various pathways, both extra- and intracellular, are involved in sensing endotoxin and non-canonical activation of caspase-mediated pyroptosis is considered to have a major role in sepsis pathophysiology. Endotoxin induces specific pathological alterations in several organs, which contributes to poor outcomes. The adverse consequences of endotoxin in the circulation support the use of anti-endotoxin therapies, yet more than 30 years of experience with endotoxin adsorption therapies have not provided clear evidence in favor of this treatment modality. The results of small studies support timely endotoxin removal guided by measuring the levels of endotoxin; unfortunately, this has not been proven in large, randomized studies. The presence of endotoxemia can be demonstrated in the majority of patients with COVID-19, yet only case reports and case series describing the effects of endotoxin removal in these patients have been published to date. The place of blood purification therapies in the treatment of septic shock has not yet been determined.

Influenza in patients with respiratory failure admitted to intensive care units in Poland and the use of extracorporeal respiratory support: a survey-based multicenter study.

BACKGROUND: In Poland, little is known about the most serious cases of influenza that need admittance to the intensive care unit (ICU), as well as the use of extracorporeal respiratory support. METHODS: This was an electronic survey comprising ICUs in two administrative regions of Poland. The aim of the study was to determine the number of influenza patients with respiratory failure admitted to the ICU in the autumn-winter season of 2018/2019. Furthermore, respiratory support, outcome and other pathogens detected in the airways were investigated. RESULTS: Influenza infection was confirmed in 76 patients. The A(H1N1)pdm09 strain was the most common. 34 patients died (44.7%). The median age was 62 years, the median sequential organ failure assessment (SOFA) score was 11 and was higher in patients who died (12 vs. 10, p = 0.017). Mechanical ventilation was used in 75 patients and high flow nasal oxygen therapy in 1 patient. Extracorporeal membrane oxygenation (ECMO) was used in 7 patients (6 survived), and extracorporeal carbon dioxide removal (ECCO2R) in 2 (1 survived). The prone position was used in 16 patients. In addition, other pathogens were detected in the airways on admittance to the ICU. CONCLUSION: A substantial number of influenza infections occurred in the autumn-winter season of 2018/2019 that required costly treatment in the intensive care units. Upon admission to the ICU, influenza patients had a high degree of organ failure as assessed by the SOFA score, and the mortality rate was 44.7%. Advanced extracorporeal respiratory techniques offer real survival opportunities to patients with severe influenza-related ARDS. The presence of coinfection should be considered in patients with influenza and respiratory failure.

Immunosuppression as a Hallmark of Critical COVID-19: Prospective Study.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/ß and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/ß and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

Analysis of management protocols regarding ineffective maintenance of organ functions in patients treated at the Intensive Care Unit of the University Hospital in Wroclaw.

BACKGROUND: Prolonged support of organ functions without therapeutic benefit represents a serious problem of therapy in intensive care units (ICUs). This kind of treatment, called "futile therapy", prolongs the process of dying and should be avoided. In Poland, the guidelines and protocol defining the best clinical practice for the avoidance of futile therapy in ICUs was published in 2014. The aim of study was to analyse the protocols concerning futile therapy in the general ICU in the University Hospital in Wroclaw, Poland during the years 2015-2018. METHODS: The content of protocols was analysed. The protocols contained information on clinical problems, ethical and social aspects, data on communication with relatives, and therapeutic procedures regarded as futile and consequently withheld or withdrawn. RESULTS: During the study 1660 patients were treated in the ICU, of whom 557 patients died. Protocols regarding futile therapy were analysed in 146 patients. The diagnosis before starting the protocol was multiorgan failure (56%), permanent CNS injury (39%), respiratory failure (3%), and circulatory failure (2%). The withholding of therapeutic procedures was preferred, and the cases of withdrawal were rare. All patients with protocols died during hospital stay, 81.5% of them in the ICU. CONCLUSIONS: The protocols concerning futile therapy were instituted in 1 in 10 patients treated in the ICU in Wroclaw, which comprised was nearly one-fifth of all ICU deaths. The withholding of futile therapeutic procedures was preferred in comparison to withdrawing. Communication with relatives was essential to the process of avoiding futile therapy.

Surveillance of Antibiotic Prescribing in Intensive Care Units in Poland.

Antibiotic use and microbial resistance in health care-associated infections are increasing globally and causing health care problems. Intensive Care Units (ICUs) represent the heaviest antibiotic burden within hospitals, and sepsis is the second noncardiac cause of mortality in ICUs. Optimizing appropriate antibiotic treatment in the management of the critically ill in ICUs became a major challenge for intensivists. We performed a surveillance study on the antibiotic consumption in 108 Polish ICUs. We determined which classes of antibiotics were most commonly consumed and whether they affected the length of ICU stay and the size and category of the hospital. A total of 292.389 defined daily doses (DDD) and 192.167 patient-days (pd) were identified. Antibiotic consumption ranged from 620 to 3960 DDD/1000 pd. The main antibiotic classes accounted for 59.6% of the total antibiotic consumption and included carbapenems (17.8%), quinolones (14%), cephalosporins (13.7%), penicillins (11.9%), and macrolides (2.2%), respectively, whereas the other antibiotic classes accounted for the remainder (40.4%) and included antifungals (34%), imidazoles (20%), aminoglycosides (18%), glycopeptides (15%), and polymyxins (6%). The most consumed antibiotic classes in Polish ICUs were carbapenems, quinolones, and cephalosporins, respectively. There was no correlation between antibiotic consumption in DDD/1000 patient-days, mean length of ICU stay, size of the hospital, size of the ICU, or the total amount of patient-days. It is crucial that surveillance systems are in place to guide empiric antibiotic treatment and to estimate the burden of resistance. Appropriate use of antibiotics in the ICU should be an important public health care issue.

Occupational mercury vapour poisoning with a respiratory failure, pneumomediastinum and severe quadriparesis.

OBJECTIVES: Despite restrictions, mercury continues to pose a health concern. Mercury has the ability to deposit in most parts of the body and can cause a wide range of unspecific symptoms leading to diagnostic mistakes. METHODS AND RESULTS: We report the case of severe mercury vapour poisoning after occupational exposure in a chloralkali plant worker that resulted in life-threatening respiratory failure, pneumomediastinum and quadriparesis. CONCLUSIONS: Prolonged mechanical ventilation and treatment with penicillamine and spironolactone was used with successful outcome.

The importance of early detection of endotoxemia.

Endotoxin is considered a key signaling molecule in the pathogenesis of sepsis and septic shock. Anti-endotoxin therapies may result in the improvement of a patient's clinical condition and lower mortality. The pressing clinical challenge is to identify patients for whom endotoxin elimination would be the most beneficial. An endotoxin activity assay (EAA) has been available for detection of endotoxins, allowing selection of patients at high risk of endotoxemia in intensive care units (ICUs). We studied a cohort of 172 consecutive patients who had septic shock on admission to the ICU. Endotoxin activity (EA) was measured with a rapid chemiluminescent EAA, regarded as point-of-care testing. Endotoxemia with a mean EA of 0.59 ± 0.14 EAU was present in 104 patients (60%) and absent in 68 patients (EA = 0.25 ± 0.11 EAU). The risk of endotoxemia increased with the presence of a Gram-negative infection [odds ratio (OR) 3.1, 95% confidence interval (CI) 1.6-5.9; P = 0.001] and bacteremia (OR 3.8, 95% CI 1.6-8.9; P = 0.02) but did not change with a diagnosis of peritonitis (OR 1.03, 95% CI 0.54-1.97; P = 0.90). These findings indicate that anti-endotoxin interventions should be tailored to individual patients based on both clinical conditions and measured endotoxin levels.

Elevated Serum PCT in Septic Shock With Endotoxemia Is Associated With a Higher Mortality Rate.

To examine the effect of endotoxemia on the procalcitonin (PCT) serum levels and mortality rates of adult patients with septic shock diagnosed on the day of admission to the intensive care unit (ICU).A retrospective observational study was performed over a 2-year period. Levels of PCT were compared for septic shock patients with and without endotoxemia on admission to the ICU. Endotoxemia was identified with an Endotoxin Activity Assay.One hundred fifty-seven patients with septic shock were enrolled into the study. Group 1 consisted of patients with elevated endotoxin activity (EA) (n = 95, EA = 0.57 endotoxin activity unit [EAU] [0.46-0.67]) and Group 2 consisted of patients with low EA (n = 62, EA = 0.27 EAU [0.17-0.36]). Acute Physiology And Chronic Health Evaluation II (APACHE II) score and SOFA score were similar in both groups (APACHE II = 23 [16-29] and 19 [16-25]; Sequential Organ Failure Assessment [SOFA] = 10 [7-13] and 11 [8-12] in Groups 1 and 2, respectively) (nonsignificant). The PCT level was 6 times higher in Group 1 than in Group 2 (19.6 ng/mL vs. 3.1 ng/mL, P < 0.001). There was a strong correlation between EA and serum PCT (P < 0.001, R = 0.5). The presence of endotoxemia on admission to the ICU was associated with an increased mortality rate: 52% in the group of patients with endotoxemia and 25% in the group without endotoxemia. EA in survivors was 0.39 EAU (0.26-0.57) and 0.53 EAU (0.4-0.61) in nonsurvivors (P = 0.004). The median PCT level in survivors was 6.7 ng/mL (2.3-28.0), compared with 16.7 ng/mL (5.3-31.0) in nonsurvivors (P = 0.04).This observational study revealed that endotoxemia in patients with septic shock on admission to the ICU was frequently found and was associated with an elevated PCT level and a high mortality rate. Endotoxemia was a common occurrence in patients with septic shock, regardless of the infecting microorganism.

Endotoxin Elimination in Patients with Septic Shock: An Observation Study.

To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66-0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43-0.77), (p = 0.005); MAP increased from 69 (62-80) to 80 mm Hg (68-88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15-0.80) to 0.1 µg/kg/min (0.00-0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9-15) to 9 (7-14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA -2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.

Advanced therapeutic methods for the treatment of meningococcal septic shock - case report.

BACKGROUND: Meningitis caused by Neisseria meningitidis is primarily a disease of children and young adults. If septic shock complicates the course of meningitis, it must be treated in the intensive care unit. CASE REPORT: An 18 year-old man with symptoms of meningococcal meningitis and clinical features of septic shock was admitted to the ICU. Tachycardia (heart rate 140 min⁻¹) required vasopressor to maintain blood pressure (noradrenalin 1 µg kg⁻¹ min⁻¹) on admission. Respiratory failure developed (respiratory rate of 40 min⁻¹, SaO2 79%, PaO2/FiO2 ratio = 55) and mechanical ventilatory support was used. The presence of Neisseria meningitidis was confirmed by a rapid latex agglutination test. Cefotaxime with vancomycin was administered on day one, and vancomycin was replaced by meropenem on day two. Additionally to the standard treatment of septic shock and multiorgan failure, haemoperfusion with LPS adsorber was performed to eliminate endotoxins from the bloodstream, and drotrecogin alfa was administered. Haemoperfusion was performed twice for sessions of two hours, and blood endotoxin activity decreased from 0.75 EAU to 0.4 EAU after 48 hours. The patient was admitted with signs of acute kidney injury and required continuous renal replacement therapy (Ca-Ca CVVHD, CVVHDF). CONCLUSIONS: Rapid pathogen identification, adequate antimicrobial therapy and endotoxin elimination from the bloodstream improved the haemodynamic and respiratory parameters of the patient. The application of routine plus non-standard methods of treatment of septic shock prevented the progression of the biological cascade in sepsis, and improved the patient's clinical condition.

[Severe acute respiratory distress syndrome complicating type A (H1N1) influenza treated with extracorporeal CO2 removal]. / Zespól ostrej niewydolnosci oddechowej w przebiegu grypy AH1N1 leczony skutecznie pozaustrojowa eliminacja CO2 .

BACKGROUND: The influenza pandemic of 2009 was reported to be frequently associated with pulmonary complications, including ARDS. We report the case of a morbidly obese, 37-year-old, AH1N1-infected woman, who was admitted to a regional hospital because of rapidly progressing respiratory failure. She was treated successfully with high frequency oscillatory ventilation (HFOV) and low-flow extracorporeal CO2 removal. CASE REPORT: The patient was admitted to a regional hospital because of severe viral infection, diabetes and hypertension that developed during pregnancy. On admission, she was deeply unconscious (GCS 5), hypotonic and anuric. Conventional ventilation, veno-venous haemofiltration, antibiotics and antiviral therapy (oseltamivir) did not improve the patient's condition, and she was transferred to a tertiary referral centre. Immediately before the transfer, she suffered two cardiac arrest episodes. They were successfully reversed. On admission, the patient was hypercapnic (PaCO2 150 mm Hg/20 kPa), acidotic (pH 6.92) and hyperkinetic (HR 120 min-1, CO 12.7 L min-1). Total lung compliance was 21 mL cm H2O-1, and SAP/DAP was 63/39 mm Hg). The PaO2/FIO2 index was 85. HFOV was instituted for 48 h, resulting in a marked improvement in gas exchange, however any manipulations caused immediate deterioration in the patient's condition. Extracorporeal CO2 removal was commenced and continued for 120 h, resulting in gradual improvement and eventual weaning from artificial ventilation after 17 days. Further treatment was complicated by septic shock due to Pseudomonas aeruginosa infection of the vagina, treated with piperacillin/tazobactam. The patient eventually recovered and returned to her regional hospital after 24 days. DISCUSSION: During the 2009 pandemic, a high number of pulmonary complications were observed all over the world. Viral infections are especially difficult to treat and the CESAR study indicated that the use of ECMO or extracorporeal CO2 removal devices may result in a lower mortality when compared with standard therapy. We conclude that the use of a simple CO2 removal device can be beneficial in complicated cases of AH1N1 influenza.

[In-hospital medical emergency teams]. / Szpitalne systemy ratunkowe.

A growing number of very sick and hospital-dependent patients in an ageing population, together with a chronic lack of intensive care beds, has resulted in a significant impairment in hospital care. Acute, life-threatening symptoms are frequently missed, leading to increased mortality and morbidity. Many projects have been introduced to improve the situation; among them, the creation of early warning scoring and trigger systems, and organisation of in-hospital medical response and critical care teams. The aim of this review is to discuss the development and implementation of such systems in different countries. Organisational aspects as well as the main differences between medical emergency teams and intensive care outreach services, are presented. During the development and organisation phase, all plans have to be assessed against specific local needs and requirements. The effects of the introduction of outreach systems and medical emergency teams on hospital morbidity, mortality and treatment outcome, are briefly analyzed.