Key Advances in the Treatment of the Critically Ill

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Intensive Care".

Deadline for manuscript submissions: closed (16 July 2023) | Viewed by 38339

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Guest Editor
First Department of Intensive Care Medicine, National and Kapodistrian University of Athens, Evaggelismos General Hospital, 10675 Athens, Greece
Interests: cardiac arrest; postcardiac arrest syndrome; mechanical ventilation; ethics of end-of-life decisions; hospital-acquired infections; airway management
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Special Issue Information

Dear Colleagues,

It is my pleasure to invite you and members of your research group to submit an article for a Special Issue entitled “Key Advances in the Treatment of the Critically Ill”.

Intensive Care Medicine (ICM) aims to address organ-system failures in the context of an extremely broad variety of acute and severe disease states and coexisting comorbid conditions. Accordingly, survival without severe disability may vary from <10% to >90%. Despite intense randomized controlled clinical research for several decades, only a handful of key interventions have been shown to improve patient outcomes. Examples include lung-protective mechanical ventilation and prone positioning in acute respiratory failure, targeted temperature management, amiodarone, and the vasopressin-steroids-epinephrine combination in cardiac arrest, tranexamic acid in trauma (including head injury), and early antibiotics in sepsis/septic shock. The severe acute respiratory syndrome coronavirus-2 pandemic has prompted urgent and intensified research on the development of effective treatments such as the messenger RNA-based vaccines, the monoclonal antibodies, certain immunomodulating interventions, and the recently authorized coronavirus disease-19 pills. Lastly, extracorporeal membrane oxygenation still constitutes a potentially promising intervention for selected patients with treatment-refractory respiratory and/or circulatory failure. Notably, the rapid evolution of evidence-based ethics of end-of-life decisions seems to increasingly augment the consistency between therapeutic interventions and patient/family values, goals and preferences. We do encourage submissions of reviews and original articles related to any of the aforementioned hot topics of ICM.

Prof. Dr. Spyros D. Mentzelopoulos
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • respiration, artificial
  • prone position
  • respiratory distress syndrome
  • respiratory insufficiency
  • heart arrest
  • hypothermia, induced
  • amiodarone
  • vasopressins
  • steroids
  • epinephrine
  • multiple trauma
  • wounds and injuries
  • tranexamic acid
  • sepsis
  • anti-bacterial agents
  • COVID-19
  • COVID-19 Vaccines
  • COVID-19 breakthrough infections
  • COVID-19 drug treatment
  • extracorporeal membrane oxygenation
  • ethics
  • death
  • decision making, shared

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Published Papers (19 papers)

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Editorial

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5 pages, 226 KiB  
Editorial
Key Advances in Intensive Care and the Coronavirus Disease-19 Research and Practice Boost
by Spyros D. Mentzelopoulos and George Adamos
J. Clin. Med. 2022, 11(12), 3370; https://doi.org/10.3390/jcm11123370 - 12 Jun 2022
Viewed by 1192
Abstract
Components of intensive care include resuscitation, cardiorespiratory stabilization, reversal of organ/system dysfunction or failure, treatment of the underlying pathology, weaning from external support of vital organs, and supportive interventions (e [...] Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)

Research

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13 pages, 1387 KiB  
Article
Norwegian Version of the Chelsea Critical Care Physical Assessment Tool (CPAx-NOR): Translation, Face Validity, Cross-Cultural Adaptation and Inter-Rater Reliability
by Charlotte Marie Schanke, Anne Kristine Brekka, Stein Arne Rimehaug, Mari Klokkerud and Tiina Maarit Andersen
J. Clin. Med. 2023, 12(15), 5033; https://doi.org/10.3390/jcm12155033 - 31 Jul 2023
Viewed by 1769
Abstract
Background: Assessment of physical and respiratory function in the intensive care unit (ICU) is useful for developing an individualized treatment plan and evaluating patient progress. There is a need for measurement tools that are culturally adapted, reliable and easy to use. The Chelsea [...] Read more.
Background: Assessment of physical and respiratory function in the intensive care unit (ICU) is useful for developing an individualized treatment plan and evaluating patient progress. There is a need for measurement tools that are culturally adapted, reliable and easy to use. The Chelsea Critical Care Physical Assessment Tool (CPAx) is a valid measurement tool with strong psychometric properties for the intensive care population. This study aims to translate, adapt and test face validity and inter-rater reliability of the Norwegian version of CPAx (CPAx-NOR) for use in critically ill adult patients receiving prolonged mechanical ventilation. Method: CPAx-NOR was forward backward translated, culturally adapted and tested by experts and patients for face validity. Thereafter tested by 10 physiotherapists in five hospitals for inter-rater reliability. Results: The experts and pilot testers reached consensus on the translation and face validity. Patients were tested at time point A (n = 57) and at time point B (n = 53). The reliability of CPAx-NOR at “A” was 0.990 (0.983–0.994) and at “B” 0.994 (0.990–0.997). Based on A+B combined and adjusted, the ICC was 0.990 (95% CI 0.996–0.998). Standard error of measurement (SEM) was 0.68 and the minimal detectable change (MDC) was 1.89. The Bland–Altman plot showed low bias and no sign of heteroscedasticity. CPAx-NOR changed with a mean score of 14.9, and showed a moderate floor effect at the start of physiotherapy and low ceiling effects at discharge. Conclusion: CPAx-NOR demonstrated good face validity and excellent inter-rater reliability. It can be used as an assessment tool for physical function in critically ill adults receiving prolonged mechanical ventilation in Norway. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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9 pages, 428 KiB  
Article
Prone Position Ventilation in Severe ARDS due to COVID-19: Comparison between Prolonged and Intermittent Strategies
by George Karlis, Despina Markantonaki, Sotirios Kakavas, Dimitra Bakali, Georgia Katsagani, Theodora Katsarou, Christos Kyritsis, Vasiliki Karaouli, Paraskevi Athanasiou and Mary Daganou
J. Clin. Med. 2023, 12(10), 3526; https://doi.org/10.3390/jcm12103526 - 17 May 2023
Cited by 4 | Viewed by 1392
Abstract
Ventilation in a prone position (PP) for 12 to 16 h per day improves survival in ARDS. However, the optimal duration of the intervention is unknown. We performed a prospective observational study to compare the efficacy and safety of a prolonged PP protocol [...] Read more.
Ventilation in a prone position (PP) for 12 to 16 h per day improves survival in ARDS. However, the optimal duration of the intervention is unknown. We performed a prospective observational study to compare the efficacy and safety of a prolonged PP protocol with conventional prone ventilation in COVID-19-associated ARDS. Prone position was undertaken if P/F < 150 with FiO2 > 0.6 and PEEP > 10 cm H2O. Oxygenation parameters and respiratory mechanics were recorded before the first PP cycle, at the end of the PP cycle and 4 h after supination. We included 63 consecutive intubated patients with a mean age of 63.5 years. Of them, 37 (58.7%) underwent prolonged prone position (PPP group) and 26 (41.3%) standard prone position (SPP group). The median cycle duration for the SPP group was 20 h and for the PPP group 46 h (p < 0.001). No significant differences in oxygenation, respiratory mechanics, number of PP cycles and rate of complications were observed between groups. The 28-day survival was 78.4% in the PPP group versus 65.4% in the SPP group (p = 0.253). Extending the duration of PP was as safe and efficacious as conventional PP, but did not confer any survival benefit in a cohort of patients with severe ARDS due to COVID-19. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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6 pages, 560 KiB  
Communication
Early Patient-Triggered Pressure Support Breathing in Mechanically Ventilated Patients with COVID-19 May Be Associated with Lower Rates of Acute Kidney Injury
by Mark E. Seubert and Marco Goeijenbier
J. Clin. Med. 2023, 12(5), 1859; https://doi.org/10.3390/jcm12051859 - 26 Feb 2023
Cited by 1 | Viewed by 1475
Abstract
Background: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential [...] Read more.
Background: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential benefits such as conserving diaphragmatic motility, sidestepping the negative consequences of the longer usage of neuromuscular blockers, and limiting the occurrence of ventilator-induced lung injury (VILI). Methods: In this retrospective cohort study of mechanically ventilated and confirmed non-hyperdynamic SARS-CoV-2 patients, we studied the relation between the occurrence of kidney injury and the decreased ratio of support to controlled ventilation. Results: Total AKI incidence in this cohort was low (5/41). In total, 16 of 41 patients underwent patient-triggered pressure support breathing at least 80% of the time. In this group we observed a lower percentage of AKI (0/16 vs. 5/25), determined as a creatinine level above 177 µmol/L in the first 200 h. There was a negative correlation between time spent on support ventilation and peak creatinine levels (r = −0.35 (−0.6–0.1)). The group predominantly on control ventilation showed significantly higher disease severity scores. Conclusions: Early patient-triggered ventilation in patients with COVID-19 may be associated with lower rates of acute kidney injury. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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12 pages, 841 KiB  
Article
Admission Lactate Concentration, Base Excess, and Alactic Base Excess Predict the 28-Day Inward Mortality in Shock Patients
by Piotr Smuszkiewicz, Natalia Jawień, Jakub Szrama, Marta Lubarska, Krzysztof Kusza and Przemysław Guzik
J. Clin. Med. 2022, 11(20), 6125; https://doi.org/10.3390/jcm11206125 - 18 Oct 2022
Cited by 4 | Viewed by 1889
Abstract
Base excess (BE) and lactate concentration may predict mortality in critically ill patients. However, the predictive values of alactic BE (aBE; the sum of BE and lactate), or a combination of BE and lactate are unknown. The study aimed to investigate whether BE, [...] Read more.
Base excess (BE) and lactate concentration may predict mortality in critically ill patients. However, the predictive values of alactic BE (aBE; the sum of BE and lactate), or a combination of BE and lactate are unknown. The study aimed to investigate whether BE, lactate, and aBE measured on admission to ICU may predict the 28-day mortality for patients undergoing any form of shock. In 143 consecutive adults, arterial BE, lactate, and aBE were measured upon ICU admission. Receiver Operating Curve (ROC) characteristics and Cox proportional hazard regression models (adjusted to age, gender, forms of shock, and presence of severe renal failure) were then used to investigate any association between these parameters and 28-day mortality. aBE < −3.63 mmol/L was found to be associated with a hazard ratio of 3.19 (HR; 95% confidence interval (CI): 1.62–6.27) for mortality. Risk of death was higher for BE < −9.5 mmol/L (HR: 4.22; 95% CI: 2.21–8.05), particularly at lactate concentrations > 4.5 mmol/L (HR: 4.62; 95% CI: 2.56–8.33). A 15.71% mortality rate was found for the combined condition of BE > cut-off and lactate < cut-off. When BE was below but lactate above their respective cut-offs, the mortality rate increased to 78.91%. The Cox regression model demonstrated that the predictive values of BE and lactate were mutually independent and additive. The 28-day mortality in shock patients admitted to ICU can be predicted by aBE, but BE and lactate deliver greater prognostic value, particularly when combined. The clinical value of our findings deserves further prospective evaluation. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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11 pages, 403 KiB  
Article
Left Ventricular Diastolic Dysfunction in ARDS Patients
by Paolo Formenti, Silvia Coppola, Laura Massironi, Giacomo Annibali, Francesco Mazza, Lisa Gilardi, Tommaso Pozzi and Davide Chiumello
J. Clin. Med. 2022, 11(20), 5998; https://doi.org/10.3390/jcm11205998 - 11 Oct 2022
Cited by 2 | Viewed by 1163
Abstract
Background: The aim of this study was to evaluate the possible presence of diastolic dysfunction and its possible effects in terms of respiratory mechanics, gas exchange and lung recruitability in mechanically ventilated ARDS. Methods: Consecutive patients admitted in intensive care unit (ICU) with [...] Read more.
Background: The aim of this study was to evaluate the possible presence of diastolic dysfunction and its possible effects in terms of respiratory mechanics, gas exchange and lung recruitability in mechanically ventilated ARDS. Methods: Consecutive patients admitted in intensive care unit (ICU) with ARDS were enrolled. Echocardiographic evaluation was acquired at clinical PEEP level. Lung CT-scan was performed at 5 and 45 cmH2O. In the study, 2 levels of PEEP (5 and 15 cmH2O) were randomly applied. Results: A total of 30 patients were enrolled with a mean PaO2/FiO2 and a median PEEP of 137 ± 52 and 10 [9–10] cmH2O, respectively. Of those, 9 patients (30%) had a diastolic dysfunction of grade 1, 2 and 3 in 33%, 45% and 22%, respectively, without any difference in gas exchange and respiratory mechanics. The total lung weight was significantly higher in patients with diastolic dysfunction (1669 [1354–1909] versus 1554 [1146–1942] g) but the lung recruitability was similar between groups (33.3 [27.3–41.4] versus 30.6 [20.0–38.8] %). Left ventricular ejection fraction (57 [39–62] versus 60 [57–60]%) and TAPSE (20.0 [17.0–24.0] versus 24.0 [20.0–27.0] mL) were similar between the two groups. The response to changes of PEEP from 5 to 15 cmH2O in terms of oxygenation and respiratory mechanics was not affected by the presence of diastolic dysfunction. Conclusions: ARDS patients with left ventricular diastolic dysfunction presented a higher amount of lung edema and worse outcome. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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10 pages, 1014 KiB  
Article
Increased Respiratory Drive after Prolonged Isoflurane Sedation: A Retrospective Cohort Study
by Lukas Martin Müller-Wirtz, Dustin Grimm, Frederic Walter Albrecht, Tobias Fink, Thomas Volk and Andreas Meiser
J. Clin. Med. 2022, 11(18), 5422; https://doi.org/10.3390/jcm11185422 - 15 Sep 2022
Cited by 1 | Viewed by 1364
Abstract
Low-dose isoflurane stimulates spontaneous breathing. We, therefore, tested the hypothesis that isoflurane compared to propofol sedation for at least 48 h is associated with increased respiratory drive in intensive care patients after sedation stop. All patients in our intensive care unit receiving at [...] Read more.
Low-dose isoflurane stimulates spontaneous breathing. We, therefore, tested the hypothesis that isoflurane compared to propofol sedation for at least 48 h is associated with increased respiratory drive in intensive care patients after sedation stop. All patients in our intensive care unit receiving at least 48 h of isoflurane or propofol sedation in 2019 were included. The primary outcome was increased respiratory drive over 72 h after sedation stop, defined as an arterial carbon dioxide pressure below 35 mmHg and a base excess more than −2 mmol/L. Secondary outcomes were acid–base balance and ventilatory parameters. We analyzed 64 patients, 23 patients sedated with isoflurane and 41 patients sedated with propofol. Patients sedated with isoflurane were about three times as likely to show increased respiratory drive after sedation stop than those sedated with propofol: adjusted risk ratio [95% confidence interval]: 2.9 [1.3, 6.5], p = 0.010. After sedation stop, tidal volumes were significantly greater and arterial carbon dioxide partial pressures were significantly lower, while respiratory rates did not differ in isoflurane versus propofol-sedated patients. In conclusion, prolonged isoflurane use in intensive care patients is associated with increased respiratory drive after sedation stop. Beneficial effects of isoflurane sedation on respiratory drive may, thus, extend beyond the actual period of sedation. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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11 pages, 1237 KiB  
Article
The Potential Impact of Heparanase Activity and Endothelial Damage in COVID-19 Disease
by Elisabeth Zechendorf, Katharina Schröder, Lara Stiehler, Nadine Frank, Christian Beckers, Sandra Kraemer, Michael Dreher, Alexander Kersten, Christoph Thiemermann, Gernot Marx, Tim-Philipp Simon and Lukas Martin
J. Clin. Med. 2022, 11(18), 5261; https://doi.org/10.3390/jcm11185261 - 06 Sep 2022
Cited by 3 | Viewed by 1263
Abstract
SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can [...] Read more.
SARS-CoV-2 was first detected in 2019 in Wuhan, China. It has been found to be the most pathogenic virus among coronaviruses and is associated with endothelial damage resulting in respiratory failure. Determine whether heparanase and heparan sulfate fragments, biomarkers of endothelial function, can assist in the risk stratification and clinical management of critically ill COVID-19 patients admitted to the intensive care unit. We investigated 53 critically ill patients with severe COVID-19 admitted between March and April 2020 to the University Hospital RWTH Aachen. Heparanase activity and serum levels of both heparanase and heparan sulfate were measured on day one (day of diagnosis) and day three in patients with COVID-19. The patients were classified into four groups according to the severity of ARDS. When compared to baseline data (day one), heparanase activity increased and the heparan sulfate serum levels decreased with increasing severity of ARDS. The heparanase activity significantly correlated with the lactate concentration on day one (r = 0.34, p = 0.024) and on day three (r = 0.43, p = 0.006). Heparanase activity and heparan sulfate levels correlate with COVID-19 disease severity and outcome. Both biomarkers might be helpful in predicting clinical course and outcomes in COVID-19 patients. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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17 pages, 1316 KiB  
Article
Evolution of European Resuscitation and End-of-Life Practices from 2015 to 2019: A Survey-Based Comparative Evaluation
by Spyros D. Mentzelopoulos, Keith Couper, Violetta Raffay, Jana Djakow and Leo Bossaert
J. Clin. Med. 2022, 11(14), 4005; https://doi.org/10.3390/jcm11144005 - 11 Jul 2022
Cited by 1 | Viewed by 1267
Abstract
Background: In concordance with the results of large, observational studies, a 2015 European survey suggested variation in resuscitation/end-of-life practices and emergency care organization across 31 countries. The current survey-based study aimed to comparatively assess the evolution of practices from 2015 to 2019, especially [...] Read more.
Background: In concordance with the results of large, observational studies, a 2015 European survey suggested variation in resuscitation/end-of-life practices and emergency care organization across 31 countries. The current survey-based study aimed to comparatively assess the evolution of practices from 2015 to 2019, especially in countries with “low” (i.e., average or lower) 2015 questionnaire domain scores. Methods: The 2015 questionnaire with additional consensus-based questions was used. The 2019 questionnaire covered practices/decisions related to end-of-life care (domain A); determinants of access to resuscitation/post-resuscitation care (domain B); diagnosis of death/organ donation (domain C); and emergency care organization (domain D). Responses from 25 countries were analyzed. Positive or negative responses were graded by 1 or 0, respectively. Domain scores were calculated by summation of practice-specific response grades. Results: Domain A and B scores for 2015 and 2019 were similar. Domain C score decreased by 1 point [95% confidence interval (CI): 1–3; p = 0.02]. Domain D score increased by 2.6 points (95% CI: 0.2–5.0; p = 0.035); this improvement was driven by countries with “low” 2015 domain D scores. In countries with “low” 2015 domain A scores, domain A score increased by 5.5 points (95% CI: 0.4–10.6; p = 0.047). Conclusions: In 2019, improvements in emergency care organization and an increasing frequency of end-of-life practices were observed primarily in countries with previously “low” scores in the corresponding domains of the 2015 questionnaire. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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14 pages, 1467 KiB  
Article
Impaired Antibody Response Is Associated with Histone-Release, Organ Dysfunction and Mortality in Critically Ill COVID-19 Patients
by Rickard Lagedal, Oskar Eriksson, Anna Sörman, Joram B. Huckriede, Bjarne Kristensen, Stephanie Franzén, Anders Larsson, Anders Bergqvist, Kjell Alving, Anders Forslund, Barbro Persson, Kristina N. Ekdahl, Pablo Garcia de Frutos, Bo Nilsson, Gerry A. F. Nicolaes, Miklos Lipcsey, Michael Hultström and Robert Frithiof
J. Clin. Med. 2022, 11(12), 3419; https://doi.org/10.3390/jcm11123419 - 14 Jun 2022
Cited by 1 | Viewed by 2299
Abstract
Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 [...] Read more.
Purpose: the pathophysiologic mechanisms explaining differences in clinical outcomes following COVID-19 are not completely described. This study aims to investigate antibody responses in critically ill patients with COVID-19 in relation to inflammation, organ failure and 30-day survival. Methods: All patients with PCR-verified COVID-19 and gave consent, and who were admitted to a tertiary Intensive care unit (ICU) in Sweden during March–September 2020 were included. Demography, repeated blood samples and measures of organ function were collected. Analyses of anti-SARS-CoV-2 antibodies (IgM, IgA and IgG) in plasma were performed and correlated to patient outcome and biomarkers of inflammation and organ failure. Results: A total of 115 patients (median age 62 years, 77% male) were included prospectively. All patients developed severe respiratory dysfunction, and 59% were treated with invasive ventilation. Thirty-day mortality was 22.6% for all included patients. Patients negative for any anti-SARS-CoV-2 antibody in plasma during ICU admission had higher 30-day mortality compared to patients positive for antibodies. Patients positive for IgM had more ICU-, ventilator-, renal replacement therapy- and vasoactive medication-free days. IgA antibody concentrations correlated negatively with both SAPS3 and maximal SOFA-score and IgM-levels correlated negatively with SAPS3. Patients with antibody levels below the detection limit had higher plasma levels of extracellular histones on day 1 and elevated levels of kidney and cardiac biomarkers, but showed no signs of increased inflammation, complement activation or cytokine release. After adjusting for age, positive IgM and IgG antibodies were still associated with increased 30-day survival, with odds ratio (OR) 7.1 (1.5–34.4) and 4.2 (1.1–15.7), respectively. Conclusion: In patients with severe COVID-19 requiring intensive care, a poor antibody response is associated with organ failure, systemic histone release and increased 30-day mortality. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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13 pages, 949 KiB  
Article
Impact of Renal Replacement Therapy on Mortality and Renal Outcomes in Critically Ill Patients with Acute Kidney Injury: A Population-Based Cohort Study in Korea between 2008 and 2015
by Subin Hwang, Danbee Kang, Hyejeong Park, Youngha Kim, Eliseo Guallar, Junseok Jeon, Jung-Eun Lee, Wooseong Huh, Gee-Young Suh, Juhee Cho and Hye-Ryoun Jang
J. Clin. Med. 2022, 11(9), 2392; https://doi.org/10.3390/jcm11092392 - 24 Apr 2022
Viewed by 1698
Abstract
The outcomes depending on the type of renal replacement therapy (RRT) or pre-existing kidney disease in critically ill patients with acute kidney injury (AKI) have not been fully elucidated. All adult intensive care unit patients with AKI in Korea from 2008 to 2015 [...] Read more.
The outcomes depending on the type of renal replacement therapy (RRT) or pre-existing kidney disease in critically ill patients with acute kidney injury (AKI) have not been fully elucidated. All adult intensive care unit patients with AKI in Korea from 2008 to 2015 were screened. A total of 124,182 patients, including 21,165 patients with pre-existing kidney disease, were divided into three groups: control (no RRT), dialysis, and continuous RRT (CRRT). In-hospital mortality and progression to end-stage kidney disease (ESKD) were analyzed according to the presence of pre-existing kidney disease. The CRRT group had a higher risk of in-hospital mortality. Among the patients with pre-existing kidney disease, the dialysis group had a lower risk of in-hospital mortality compared to other groups. The risk of ESKD was higher in the dialysis and CRRT groups compared to the control group. In the CRRT group, the risk of ESKD was even higher in patients without pre-existing kidney disease. Although both dialysis and CRRT groups showed a higher incidence of ESKD, in-hospital mortality was lower in the dialysis group, especially in patients with pre-existing kidney disease. Our study supports that RRT and pre-existing kidney disease may be important prognostic factors for overall and renal outcomes in patients with AKI. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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Review

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11 pages, 538 KiB  
Review
The Role of the Intravenous IgA and IgM-Enriched Immunoglobulin Preparation in the Treatment of Sepsis and Septic Shock
by Giorgio Berlot, Silvia Zanchi, Edoardo Moro, Ariella Tomasini and Mattia Bixio
J. Clin. Med. 2023, 12(14), 4645; https://doi.org/10.3390/jcm12144645 - 12 Jul 2023
Cited by 3 | Viewed by 1368
Abstract
Polyclonal Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis and septic shock because the current guidelines recommend against their [...] Read more.
Polyclonal Intravenous Immunoglobulins (IvIg) are often administered to critically ill patients more as an act of faith than on the basis of relevant clinical studies. This particularly applies to the treatment of sepsis and septic shock because the current guidelines recommend against their use despite many investigations that have demonstrated their beneficial effects in different subsets of patients. The biology, mechanisms of action, and clinical experience related to the administration of IvIg are reviewed, which aim to give a more in-depth understanding of their properties in order to clarify their possible indications in sepsis and septic shock patients. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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31 pages, 930 KiB  
Review
General Critical Care, Temperature Control, and End-of-Life Decision Making in Patients Resuscitated from Cardiac Arrest
by Athanasios Chalkias, Georgios Adamos and Spyros D. Mentzelopoulos
J. Clin. Med. 2023, 12(12), 4118; https://doi.org/10.3390/jcm12124118 - 18 Jun 2023
Cited by 1 | Viewed by 2314
Abstract
Cardiac arrest affects millions of people per year worldwide. Although advances in cardiopulmonary resuscitation and intensive care have improved outcomes over time, neurologic impairment and multiple organ dysfunction continue to be associated with a high mortality rate. The pathophysiologic mechanisms underlying the post-resuscitation [...] Read more.
Cardiac arrest affects millions of people per year worldwide. Although advances in cardiopulmonary resuscitation and intensive care have improved outcomes over time, neurologic impairment and multiple organ dysfunction continue to be associated with a high mortality rate. The pathophysiologic mechanisms underlying the post-resuscitation disease are complex, and a coordinated, evidence-based approach to post-resuscitation care has significant potential to improve survival. Critical care management of patients resuscitated from cardiac arrest focuses on the identification and treatment of the underlying cause(s), hemodynamic and respiratory support, organ protection, and active temperature control. This review provides a state-of-the-art appraisal of critical care management of the post-cardiac arrest patient. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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12 pages, 561 KiB  
Review
The Techniques of Blood Purification in the Treatment of Sepsis and Other Hyperinflammatory Conditions
by Giorgio Berlot, Ariella Tomasini, Silvia Zanchi and Edoardo Moro
J. Clin. Med. 2023, 12(5), 1723; https://doi.org/10.3390/jcm12051723 - 21 Feb 2023
Cited by 3 | Viewed by 2666
Abstract
Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as [...] Read more.
Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as blood purification techniques. Their main categories include blood- and plasma processing procedures, which can run in a stand-alone mode or, more commonly, in association with a renal replacement treatment. The different techniques and principles of function, the clinical evidence derived from multiple clinical investigations, and the possible side effects are reviewed and discussed along with the persisting uncertainties about their precise role in the therapeutic armamentarium of these syndromes. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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22 pages, 849 KiB  
Review
COVID-19-Related ARDS: Key Mechanistic Features and Treatments
by John Selickman, Charikleia S. Vrettou, Spyros D. Mentzelopoulos and John J. Marini
J. Clin. Med. 2022, 11(16), 4896; https://doi.org/10.3390/jcm11164896 - 20 Aug 2022
Cited by 16 | Viewed by 2849
Abstract
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis [...] Read more.
Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome historically characterized by the presence of severe hypoxemia, high-permeability pulmonary edema manifesting as diffuse alveolar infiltrate on chest radiograph, and reduced compliance of the integrated respiratory system as a result of widespread compressive atelectasis and fluid-filled alveoli. Coronavirus disease 19 (COVID-19)-associated ARDS (C-ARDS) is a novel etiology caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that may present with distinct clinical features as a result of the viral pathobiology unique to SARS-CoV-2. In particular, severe injury to the pulmonary vascular endothelium, accompanied by the presence of diffuse microthrombi in the pulmonary microcirculation, can lead to a clinical presentation in which the severity of impaired gas exchange becomes uncoupled from lung capacity and respiratory mechanics. The purpose of this review is to highlight the key mechanistic features of C-ARDS and to discuss the implications these features have on its treatment. In some patients with C-ARDS, rigid adherence to guidelines derived from clinical trials in the pre-COVID era may not be appropriate. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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12 pages, 1382 KiB  
Review
Second- and Third-Tier Therapies for Severe Traumatic Brain Injury
by Charikleia S. Vrettou and Spyros D. Mentzelopoulos
J. Clin. Med. 2022, 11(16), 4790; https://doi.org/10.3390/jcm11164790 - 16 Aug 2022
Cited by 1 | Viewed by 6154
Abstract
Intracranial hypertension is a common finding in patients with severe traumatic brain injury. These patients need treatment in the intensive care unit, where intracranial pressure monitoring and, whenever possible, multimodal neuromonitoring can be applied. A three-tier approach is suggested in current recommendations, in [...] Read more.
Intracranial hypertension is a common finding in patients with severe traumatic brain injury. These patients need treatment in the intensive care unit, where intracranial pressure monitoring and, whenever possible, multimodal neuromonitoring can be applied. A three-tier approach is suggested in current recommendations, in which higher-tier therapies have more significant side effects. In this review, we explain the rationale for this approach, and analyze the benefits and risks of each therapeutic modality. Finally, we discuss, based on the most recent recommendations, how this approach can be adapted in low- and middle-income countries, where available resources are limited. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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22 pages, 740 KiB  
Review
Fungal Infections in Critically Ill COVID-19 Patients: Inevitabile Malum
by Nikoletta Rovina, Evangelia Koukaki, Vasiliki Romanou, Sevasti Ampelioti, Konstantinos Loverdos, Vasiliki Chantziara, Antonia Koutsoukou and George Dimopoulos
J. Clin. Med. 2022, 11(7), 2017; https://doi.org/10.3390/jcm11072017 - 04 Apr 2022
Cited by 8 | Viewed by 2323
Abstract
Patients with severe COVID-19 belong to a population at high risk of invasive fungal infections (IFIs), with a reported incidence of IFIs in critically ill COVID-19 patients ranging between 5% and 26.7%. Common factors in these patients, such as multiple organ failure, immunomodulating/immunocompromising [...] Read more.
Patients with severe COVID-19 belong to a population at high risk of invasive fungal infections (IFIs), with a reported incidence of IFIs in critically ill COVID-19 patients ranging between 5% and 26.7%. Common factors in these patients, such as multiple organ failure, immunomodulating/immunocompromising treatments, the longer time on mechanical ventilation, renal replacement therapy or extracorporeal membrane oxygenation, make them vulnerable candidates for fungal infections. In addition to that, SARS-CoV2 itself is associated with significant dysfunction in the patient’s immune system involving both innate and acquired immunity, with reduction in both CD4+ T and CD8+ T lymphocyte counts and cytokine storm. The emerging question is whether SARS-CoV-2 inherently predisposes critically ill patients to fungal infections or the immunosuppressive therapy constitutes the igniting factor for invasive mycoses. To approach the dilemma, one must consider the unique pathogenicity of SARS-CoV-2 with the deranged immune response it provokes, review the well-known effects of immunosuppressants and finally refer to current literature to probe possible causal relationships, synergistic effects or independent risk factors. In this review, we aimed to identify the prevalence, risk factors and mortality associated with IFIs in mechanically ventilated patients with COVID-19. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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9 pages, 2984 KiB  
Brief Report
A Trend towards Diaphragmatic Muscle Waste after Invasive Mechanical Ventilation in Multiple Trauma Patients—What to Expect?
by Liliana Mirea, Cristian Cobilinschi, Raluca Ungureanu, Ana-Maria Cotae, Raluca Darie, Radu Tincu, Oana Avram, Sorin Constantinescu, Costin Minoiu, Alexandru Baetu and Ioana Marina Grintescu
J. Clin. Med. 2023, 12(9), 3338; https://doi.org/10.3390/jcm12093338 - 08 May 2023
Viewed by 1049
Abstract
Considering the prioritization of life-threatening injuries in trauma care, secondary dysfunctions such as ventilator-induced diaphragmatic dysfunction (VIDD) are often overlooked. VIDD is an entity induced by muscle inactivity during invasive mechanical ventilation, associated with a profound loss of diaphragm muscle mass. In order [...] Read more.
Considering the prioritization of life-threatening injuries in trauma care, secondary dysfunctions such as ventilator-induced diaphragmatic dysfunction (VIDD) are often overlooked. VIDD is an entity induced by muscle inactivity during invasive mechanical ventilation, associated with a profound loss of diaphragm muscle mass. In order to assess the incidence of VIDD in polytrauma patients, we performed an observational, retrospective, longitudinal study that included 24 polytraumatized patients. All included patients were mechanically ventilated for at least 48 h and underwent two chest CT scans during their ICU stay. Diaphragmatic thickness was measured by two independent radiologists on coronal and axial images at the level of celiac plexus. The thickness of the diaphragm was significantly decreased on both the left and right sides (left side: −0.82 mm axial p = 0.034; −0.79 mm coronal p = 0.05; right side: −0.94 mm axial p = 0.016; −0.91 coronal p = 0.013). In addition, we obtained a positive correlation between the number of days of mechanical ventilation and the difference between the two measurements of the diaphragm thickness on both sides (r =0.5; p = 0.02). There was no statistically significant correlation between the body mass indexes on admission, the use of vitamin C or N-acetyl cysteine, and the differences in diaphragmatic thickness. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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12 pages, 830 KiB  
Systematic Review
Proadrenomedullin in the Management of COVID-19 Critically Ill Patients in Intensive Care Unit: A Systematic Review and Meta-Analysis of Evidence and Uncertainties in Existing Literature
by Giorgia Montrucchio, Eleonora Balzani, Davide Lombardo, Alice Giaccone, Anna Vaninetti, Giulia D’Antonio, Francesca Rumbolo, Giulio Mengozzi and Luca Brazzi
J. Clin. Med. 2022, 11(15), 4543; https://doi.org/10.3390/jcm11154543 - 04 Aug 2022
Cited by 7 | Viewed by 1431
Abstract
Mid-regional proadrenomedullin (MR-proADM) is a new biomarker of endothelial damage and its clinical use is increasing in sepsis and respiratory infections and recently in SARS-CoV-2 infection. We conducted a systematic review and meta-analysis to clarify the use of MR-proADM in severe COVID-19 disease. [...] Read more.
Mid-regional proadrenomedullin (MR-proADM) is a new biomarker of endothelial damage and its clinical use is increasing in sepsis and respiratory infections and recently in SARS-CoV-2 infection. We conducted a systematic review and meta-analysis to clarify the use of MR-proADM in severe COVID-19 disease. After Pubmed, Embase, and Scopus search, registries, and gray literature, deduplication, and selection of full-texts, we found 21 studies addressing the use of proadrenomedullin in COVID-19. All the studies were published between 2020 and 2022 from European countries. A total of 9 studies enrolled Intensive Care Unit (ICU) patients, 4 were conducted in the Emergency Department, and 8 had mixed populations. Regarding the ICU critically ill patients, 4 studies evaluating survival as primary outcome were available, of which 3 reported completed data. Combining the selected studies in a meta-analysis, a total of 252 patients were enrolled; of these, 182 were survivors and 70 were non-survivors. At the admission to the ICU, the average MR-proADM level in survivor patients was 1.01 versus 1.64 in non-survivor patients. The mean differences of MR-proADM values in survivors vs. non-survivors was −0.96 (95% CI from −1.26, to −0.65). Test for overall effect: Z = 6.19 (p < 0.00001) and heterogeneity was I2 = 0%. MR-proADM ICU admission levels seem to predict mortality among the critical COVID-19 population. Further, prospective studies, focused on critically ill patients and investigating a reliable MR-proADM cut-off, are needed to provide adequate guidance to its use in severe COVID-19. Full article
(This article belongs to the Special Issue Key Advances in the Treatment of the Critically Ill)
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