Acute and Critical Care

Original Article

Basic science and research
Impact of tadalafil on cardiovascular and organ dysfunction induced by experimental sepsis: Marcelo Almeida Nakashima, Gabrielle Delfrate, Lucas Braga Albino, Gustavo Ferreira Alves, Junior Garcia Oliveira, Daniel Fernandes; Acute Crit Care. 2025;40(1):46-58. Published online February 12, 2025; DOI: https://doi.org/10.4266/acc.002904

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Abstract PDF: Background
Sepsis is a life-threatening condition that affects the cardiovascular and renal systems. Severe hypotension during sepsis compromises tissue perfusion, which can lead to multiple organ dysfunction and death. Phosphodiesterase 5 (PDE5) degrades intracellular cyclic guanosine monophosphate (cGMP) levels which promotes vasodilatation in specific sites. Our previous studies show that inhibiting cGMP production in early sepsis increases mortality, implying a protective role for cGMP production. Then, we hypothesized that cGMP increased by tadalafil (PDE5 inhibitor) could improve microcirculation and prevent sepsis-induced organ dysfunction.
Methods
Rats were submitted to cecal ligation and puncture (CLP) sepsis model and treated with tadalafil (2 mg/kg, s.c.) 8 hours after the procedure. Hemodynamic, inflammatory and biochemical assessments were performed 24 hours after sepsis induction. Moreover, the effect of tadalafil on the survival of septic rats was evaluated for 5 days.
Results
Tadalafil treatment improves basal renal blood flow during sepsis and preserves it during noradrenaline infusion. Sepsis induces hypotension, impaired response to noradrenaline, and increased cardiac and renal neutrophil infiltration, in addition to increased levels of plasma nitric oxide and lactate. None of these dysfunctions were changed by tadalafil. Additionally, tadalafil treatment did not increase the survival rate of septic rats.
Conclusions
Tadalafil improved microcirculation of septic animals; however, no beneficial effects were observed on macrocirculation and inflammation parameters. Then, the potential benefit of tadalafil in the prognosis of sepsis should be evaluated within a therapeutic strategy covering all sepsis injury mechanisms.

Guideline

Meta-analysis
Early management of adult sepsis and septic shock: Korean clinical practice guidelines: Chul Park, Nam Su Ku, Dae Won Park, Joo Hyun Park, Tae Sun Ha, Do Wan Kim, So Young Park, Youjin Chang, Kwang Wook Jo, Moon Seong Baek, Yijun Seo, Tae Gun Shin, Gina Yu, Jongmin Lee, Yong Jun Choi, Ji Young Jang, Yun Tae Jung, Inseok Jeong, Hwa Jin Cho, Ala Woo, Sua Kim, Dae-Hwan Bae, Sung Wook Kang, Sun Hyo Park, Gee Young Suh, Sunghoon Park; Acute Crit Care. 2024;39(4):445-472. Published online November 18, 2024; DOI: https://doi.org/10.4266/acc.2024.00920

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Background
Despite recent advances and global improvements in sepsis recognition and supportive care, mortality rates remain high, and adherence to sepsis bundle components in Korea is low. To address this, the Korean Sepsis Alliance, affiliated with the Korean Society of Critical Care Medicine, developed the first sepsis treatment guidelines for Korea based on a comprehensive systematic review and meta-analysis.
Methods
A de novo method was used to develop the guidelines. Methodologies included determining key questions, conducting a literature search and selection, assessing the risk of bias, synthesizing evidence, and developing recommendations. The certainty of evidence and the strength of recommendations were determined using the Grading of Recommendations, Assessment, Development, and Evaluations approach. Draft recommendations underwent internal and external review processes and public hearings. The development of these guidelines was supported by a research grant from the Korean Disease Control and Prevention Agency.
Results
In these guidelines, we focused on early treatments for adult patients with sepsis and septic shock. Through the guideline development process, 12 key questions and their respective recommendations were formulated. These include lactate measurement, fluid therapies, target blood pressure, antibiotic administration, use of vasopressors and dobutamine, extracorporeal membrane oxygenation, and echocardiography.
Conclusions
These guidelines aim to support medical professionals in making appropriate decisions about treating adult sepsis and septic shock. We hope these guidelines will increase awareness of sepsis and reduce its mortality rate.

Citations

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Comparison between norepinephrine plus epinephrine and norepinephrine plus vasopressin after return of spontaneous circulation in patients with out-of-hospital cardiac arrest
Sejoong Ahn, Bo-Yeong Jin, Sukyo Lee, Jong-Hak Park, Hanjin Cho, Sungwoo Moon, Sang Kuk Han, Phil Cho Choi, Young Hwan Lee, Sang O. Park, Jong Seok Lee, Ki Young Jeong, Sung Hyuk Choi, Young Hoon Yoon, Su Jin Kim, Kap Su Han, Min Seob Sim, Gun Tak Lee, Yo
Scientific Reports.2025;[Epub] CrossRef

Original Article

Epidemiology
Pediatric septic shock estimation using deep learning and electronic medical records: Ji Weon Lee, Bongjin Lee, June Dong Park; Acute Crit Care. 2024;39(3):400-407. Published online August 1, 2024; DOI: https://doi.org/10.4266/acc.2024.00031

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Abstract PDF

Background
Diagnosing pediatric septic shock is difficult due to the complex and often impractical traditional criteria, such as systemic inflammatory response syndrome (SIRS), which result in delays and higher risks. This study aims to develop a deep learning-based model using SIRS data for early diagnosis in pediatric septic shock cases.
Methods
The study analyzed data from pediatric patients (<18 years old) admitted to a tertiary hospital from January 2010 to July 2023. Vital signs, lab tests, and clinical information were collected. Septic shock cases were identified using SIRS criteria and inotrope use. A deep learning model was trained and evaluated using the area under the receiver operating characteristics curve (AUROC) and area under the precision-recall curve (AUPRC). Variable contributions were analyzed using the Shapley additive explanation value.
Results
The analysis, involving 9,616,115 measurements, identified 34,696 septic shock cases (0.4%). Oxygen supply was crucial for 41.5% of the control group and 20.8% of the septic shock group. The final model showed strong performance, with an AUROC of 0.927 and AUPRC of 0.879. Key influencers were age, oxygen supply, sex, and partial pressure of carbon dioxide, while body temperature had minimal impact on estimation.
Conclusions
The proposed deep learning model simplifies early septic shock diagnosis in pediatric patients, reducing the diagnostic workload. Its high accuracy allows timely treatment, but external validation through prospective studies is needed.

Citations

Citations to this article as recorded by

Aligning prediction models with clinical information needs: infant sepsis case study
Lusha Cao, Aaron J Masino, Mary Catherine Harris, Lyle H Ungar, Gerald Shaeffer, Alexander Fidel, Elease McLaurin, Lakshmi Srinivasan, Dean J Karavite, Robert W Grundmeier
JAMIA Open.2025;[Epub] CrossRef

Review Article

Basic science and research
Sex or gender differences in treatment outcomes of sepsis and septic shock: Seung Yeon Min, Ho Jin Yong, Dohhyung Kim; Acute Crit Care. 2024;39(2):207-213. Published online May 24, 2024; DOI: https://doi.org/10.4266/acc.2024.00591

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Abstract PDF

Gender disparities in intensive care unit (ICU) treatment approaches and outcomes are evident. However, clinicians often pay little attention to the importance of biological sex and sociocultural gender in their treatment courses. Previous studies have reported that differences between sexes or genders can significantly affect the manifestation of diseases, diagnosis, clinicians' treatment decisions, scope of treatment, and treatment outcomes in the intensive care field. In addition, numerous reports have suggested that immunomodulatory effects of sex hormones and differences in gene expression from X chromosomes between genders might play a significant role in treatment outcomes of various diseases. However, results from clinical studies are conflicting. Recently, the need for customized treatment based on physical, physiological, and genetic differences between females and males and sociocultural characteristics of society have been increasingly emphasized. However, interest in and research into this field are remarkably lacking in Asian countries, including South Korea. Through this review, we hope to enhance our awareness of the importance of sex and gender in intensive care treatment and research by briefly summarizing several principal issues, mainly focusing on sex and sex hormone-based outcomes in patients admitted to the ICU with sepsis and septic shock.

Citations

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Clinical predictors of hospital-acquired bloodstream infections: A healthcare system analysis
Harjinder Singh, Radhika Sheth, Mehakmeet Bhatia, Abdullah Muhammad, Candi Bachour, David Metcalf, Vivek Kak
Spartan Medical Research Journal.2024;[Epub] CrossRef
Impact of metabolic syndrome on cardiovascular, inflammatory and hematological parameters in female mice subjected to severe sepsis
Leonardo Berto-Pereira, Raquel Pires Nakama, Lucas Felipe dos Santos, Aparecida Donizette Malvezi, Isabella Ramos Trevizani Thihara, Lucas Sobral de Rossi, Fabricio Seidy Ribeiro Inoue, Wander Rogério Pavanelli, Priscila Cassolla, Phileno Pinge-Filho, Mar
Biochemical and Biophysical Research Communications.2024; 739: 150966. CrossRef

Original Articles

Pulmonary
Are sodium-glucose co-transporter-2 inhibitors associated with improved outcomes in diabetic patients admitted to intensive care units with septic shock?: Nikita Ashcherkin, Abdelmohaymin A. Abdalla, Simran Gupta, Shubhang Bhatt, Claire I. Yee, Rodrigo Cartin-Ceba; Acute Crit Care. 2024;39(2):251-256. Published online May 14, 2024; DOI: https://doi.org/10.4266/acc.2023.01046

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Abstract PDF

Background
Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce organ dysfunction in renal and cardiovascular disease. There are limited data on the role of SGLT2i in acute organ dysfunction. We conducted a study to assess the effect of SGLT2i taken prior to intensive care unit (ICU) admission in diabetic patients admitted with septic shock.
Methods
This retrospective cohort study used electronic medical records and included diabetic patients admitted to the ICU with septic shock. We compared diabetic patients on SGLT2i to those who were not on SGLT2i prior to admission. The primary outcome was in-hospital mortality, and secondary outcomes included hospital and ICU length of stay, use of renal replacement therapy, and 28- and 90-day mortality.
Results
A total of 98 diabetic patients was included in the study, 36 in the SGLT2i group and 62 in the non-SGLT2i group. The Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation III scores were similar in the groups. Inpatient mortality was significantly lower in the SGLT2i group (5.6% vs. 27.4%, P=0.008). There was no significant difference in secondary outcomes.
Conclusions
Our study found that diabetic patients on SGLT2i prior to hospitalization who were admitted to the ICU with septic shock had lower inpatient mortality compared to patients not on SGLT2i.

Citations

Citations to this article as recorded by

Melioidosis in people living with diabetes; clinical presentation, clinical course and implications for patient management
Laura Prideaux, Megan Sandeman, Hayley Stratton, Anthony D Kelleher, Simon Smith, Josh Hanson
Acta Tropica.2025; 263: 107559. CrossRef

Immunology
Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea: Seung-Hun You, Oh Joo Kweon, Sun-Young Jung, Moon Seong Baek, Won-Young Kim; Acute Crit Care. 2023;38(3):286-297. Published online August 21, 2023; DOI: https://doi.org/10.4266/acc.2023.00507

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Abstract PDF Supplementary Material

Background
Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine.
Methods
This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1–2, 3–4, and 6–8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups.
Results
The median age was 78 years (interquartile range, 70–84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: –0.09±0.16 μg/kg/min vs. –0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. –4±3, P=0.002) between days 1 and 4.
Conclusions
There may be different subphenotypes in septic patients receiving the vitamin C protocol.

Citations

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Micronutrients as therapy in critical illness
Christian Stoppe, Ellen Dresen, Angelique de Man
Current Opinion in Critical Care.2024; 30(2): 178. CrossRef
Novel cortisol trajectory sub-phenotypes in sepsis
Fei Leng, Zhunyong Gu, Simeng Pan, Shilong Lin, Xu Wang, Ming Zhong, Jieqiong Song
Critical Care.2024;[Epub] CrossRef

Infection
The prognostic impact of rheumatoid arthritis in sepsis: a population-based analysis: Lavi Oud, John Garza; Acute Crit Care. 2022;37(4):533-542. Published online October 6, 2022; DOI: https://doi.org/10.4266/acc.2022.00787

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Abstract PDF Supplementary Material

Background
Rheumatoid arthritis (RA) is associated with increased risk of sepsis and higher infection-related mortality compared to the general population. However, the evidence on the prognostic impact of RA in sepsis has been inconclusive. We aimed to estimate the population-level association of RA with short-term mortality in sepsis.
Methods
We used statewide data to identify hospitalizations aged ≥18 years in Texas with sepsis, with and without RA during 2014–2017. Hierarchical logistic models with propensity adjustment (primary model), propensity score matching, and multivariable logistic regression without propensity adjustment were used to estimate the association of RA with short-term mortality among sepsis hospitalizations.
Results
Among 283,025 sepsis hospitalizations, 7,689 (2.7%) had RA. Compared to sepsis hospitalizations without RA, those with RA were older (aged ≥65 years, 63.9% vs. 56.4%) and had higher burden of comorbidities (mean Deyo comorbidity index, 3.2 vs. 2.7). Short-term mortality of sepsis hospitalizations with and without RA was 26.8% vs. 31.4%. Following adjustment for confounders, short-term mortality was lower among RA patients (adjusted odds ratio [aOR], 0.910; 95% confidence interval [CI], 0.856–0.967), with similar findings on alternative models. On sensitivity analyses, short-term mortality was lower in RA patients among sepsis hospitalizations aged ≥65 years and those with septic shock, but not among those admitted to intensive care unit (ICU; aOR, 0.990; 95% CI, 0.909–1.079).
Conclusions
RA was associated, unexpectedly, with lower short-term mortality in septic patients. However, this “protective” association was driven by those patients without ICU admission. Further studies are warranted to confirm these findings and to examine the underlying mechanisms.

Citations

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Decreased in-hospital mortality in shock patients with rheumatoid arthritis compared to those without: a retrospective analysis of a critical care database
Jin Wan, Xiaoyu Cao, Yaran Yang
Clinical Rheumatology.2025; 44(2): 615. CrossRef
LGR4 (GPR48): The Emerging Inter-Bridge in Osteoimmunology
Wonbong Lim
Biomedicines.2025; 13(3): 607. CrossRef
Genetic associations between autoimmune diseases and the risks of severe sepsis and 28-day mortality: a two-sample Mendelian randomization study
Xin Tie, Yanjie Zhao, Jing Su, Xing Liu, Tongjuan Zou, Wanhong Yin
Frontiers in Medicine.2024;[Epub] CrossRef
Evolving Paradigms in Sepsis Management: A Narrative Review
Min-Ji Kim, Eun-Joo Choi, Eun-Jung Choi
Cells.2024; 13(14): 1172. CrossRef

Infection
Validation of presepsin measurement for mortality prediction of sepsis: a preliminary study: Seung Min Baik, Jin Park, Tae Yoon Kim, Se Hong Choi, Kyung Sook Hong; Acute Crit Care. 2022;37(4):527-532. Published online August 19, 2022; DOI: https://doi.org/10.4266/acc.2022.00150

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Abstract PDF

Background
Sepsis and septic shock remain the leading causes of death in critically ill patients worldwide. Various biomarkers are available to determine the prognosis and therapeutic effects of sepsis. In this study, we investigated the effectiveness of presepsin as a sepsis biomarker.
Methods
Patients admitted to the intensive care unit with major or minor diagnosis of sepsis were categorized into survival and non-survival groups. The white blood cell count and serum C-reactive protein, procalcitonin, and presepsin levels were measured in all patients.
Results
The study included 40 patients (survival group, 32; non-survival group, 8; mortality rate, 20%). The maximum serum presepsin levels measured during intensive care unit admission were significantly higher in the non-survival group (median [interquartile range]: 4,205.5 pg/ml [1,155.8–10,094.0] vs. 741.5 pg/ml [520.0–1,317.5], P<0.05). No statistically significant intergroup differences were observed in the maximum, minimum, and mean values of the white blood cell count, as well as serum C-reactive protein, and procalcitonin levels. Based on the receiver operating characteristic curve, the area under the curve for presepsin as a predictor of sepsis mortality was 0.764. At a cut-off value of 1,898.5 pg/ml, the sensitivity and specificity of presepsin for prediction of sepsis-induced mortality were 75.0% and 87.5%, respectively.
Conclusions
Early diagnosis of sepsis and prediction of sepsis-induced mortality are important for prompt initiation of treatment. Presepsin may serve as an effective biomarker for prediction of sepsis-induced mortality and for evaluation of treatment effectiveness.

Citations

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The Potential Role of Presepsin in Predicting Severe Infection in Patients with Diabetic Foot Ulcers
Eun Yeong Ha, Il Rae Park, Seung Min Chung, Young Nam Roh, Chul Hyun Park, Tae-Gon Kim, Woong Kim, Jun Sung Moon
Journal of Clinical Medicine.2024; 13(8): 2311. CrossRef
Combined estimation of presepsin and gelsolin might improve the diagnostic validity of clinical scoring to predict and stratify sepsis in non-sepsis surgical ICU patient
Hany A. Shehab, Ahmed M Eid, Yehya Shahin Dabour
Egyptian Journal of Anaesthesia.2024; 40(1): 262. CrossRef
Impact of nutrition‐related laboratory tests on mortality of patients who are critically ill using artificial intelligence: A focus on trace elements, vitamins, and cholesterol
Dong Jin Park, Seung Min Baik, Hanyoung Lee, Hoonsung Park, Jae‐Myeong Lee
Nutrition in Clinical Practice.2024;[Epub] CrossRef

Infection
Incidence and risk factors associated with early death in patients with emergency department septic shock: Matthew S. Reaven, Nigel L. Rozario, Maggie S. J. McCarter, Alan C. Heffner; Acute Crit Care. 2022;37(2):193-201. Published online February 11, 2022; DOI: https://doi.org/10.4266/acc.2021.00857

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Abstract PDF

Background
Limited research has explored early mortality among patients presenting with septic shock. The objective of this study was to determine the incidence and factors associated with early death following emergency department (ED) presentation of septic shock.
Methods
A prospective registry of patients enrolled in an ED septic shock clinical pathway was used to identify patients. Patients were compared across demographic, comorbid, clinical, and treatment variables by death within 72 hours of ED presentation.
Results
Among the sample of 2,414 patients, overall hospital mortality was 20.6%. Among patients who died in the hospital, mean and median time from ED presentation to death were 4.96 days and 2.28 days, respectively. Death at 24, 48, and 72 hours occurred in 5.5%, 9.5%, and 11.5% of patients, respectively. Multivariate regression analysis demonstrated that the following factors were independently associated with early mortality: age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.03–1.05), malignancy (OR, 1.53; 95% CI, 1.11–2.11), pneumonia (OR, 1.39; 95% CI, 1.02–1.88), urinary tract infection (OR, 0.63; 95% CI, 0.44–0.89), first shock index (OR, 1.85; 95% CI, 1.27–2.70), early vasopressor use (OR, 2.16; 95% CI, 1.60–2.92), initial international normalized ratio (OR, 1.14; 95% CI, 1.07–1.27), initial albumin (OR, 0.55; 95% CI, 0.44–0.69), and first serum lactate (OR, 1.21; 95% CI, 1.16–1.26).
Conclusions
Adult septic shock patients experience a high rate of early mortality within 72 hours of ED arrival. Recognizable clinical factors may aid the identification of patients at risk of early death.

Citations

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Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study
Sang Won Park, Na Young Yeo, Seonguk Kang, Taejun Ha, Tae-Hoon Kim, DooHee Lee, Dowon Kim, Seheon Choi, Minkyu Kim, DongHoon Lee, DoHyeon Kim, Woo Jin Kim, Seung-Joon Lee, Yeon-Jeong Heo, Da Hye Moon, Seon-Sook Han, Yoon Kim, Hyun-Soo Choi, Dong Kyu Oh, S
Journal of Korean Medical Science.2024;[Epub] CrossRef
Predicting sepsis at emergency department triage: Implementing clinical and laboratory markers within the first nursing assessment to enhance diagnostic accuracy
Ugo Giulio Sisto, Stefano Di Bella, Elisa Porta, Giorgia Franzoi, Franco Cominotto, Elena Guzzardi, Nicola Artusi, Caterina Anna Giudice, Eugenia Dal Bo, Nicholas Collot, Francesca Sirianni, Savino Russo, Gianfranco Sanson
Journal of Nursing Scholarship.2024; 56(6): 757. CrossRef
Comparison of Early and Late Norepinephrine Administration in Patients With Septic Shock
Chiwon Ahn, Gina Yu, Tae Gun Shin, Youngsuk Cho, Sunghoon Park, Gee Young Suh
CHEST.2024; 166(6): 1417. CrossRef
Red cell distribution width and in‐hospital mortality in septic shock: A public database research
Qiong Ding, Yingjie Su, Changluo Li, Ning Ding
International Journal of Laboratory Hematology.2022; 44(5): 861. CrossRef

Infection
Serum lactate levels in cirrhosis and non-cirrhosis patients with septic shock: Surat Tongyoo, Kamonlawat Sutthipool, Tanuwong Viarasilpa, Chairat Permpikul; Acute Crit Care. 2022;37(1):108-117. Published online November 26, 2021; DOI: https://doi.org/10.4266/acc.2021.00332

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Background
In septic shock patients with cirrhosis, impaired liver function might decrease lactate elimination and produce a higher lactate level. This study investigated differences in initial lactate, lactate clearance, and lactate utility between cirrhotic and non-cirrhotic septic shock patients.
Methods
This is a retrospective cohort study conducted at a referral, university-affiliated medical center. We enrolled adults admitted during 2012–2018 who satisfied the septic shock diagnostic criteria of the Surviving Sepsis Campaign: 2012. Patients previously diagnosed with cirrhosis by an imaging modality were classified into the cirrhosis group. The initial lactate levels and levels 6 hours after resuscitation were measured and used to calculate lactate clearance. We compared initial lactate, lactate at 6 hours, and lactate clearance between the cirrhosis and non-cirrhosis groups. The primary outcome was in-hospital mortality.
Results
Overall 777 patients were enrolled, of whom 91 had previously been diagnosed with cirrhosis. Initial lactate and lactate at 6 hours were both significantly higher in cirrhosis patients, but there was no difference between the groups in lactate clearance. A receiver operating characteristic curve analysis for predictors of in-hospital mortality revealed cut-off values for initial lactate, lactate at 6 hours, and lactate clearance of >4 mmol/L, >2 mmol/L, and <10%, respectively, among non-cirrhosis patients. Among patients with cirrhosis, the cut-off values predicting in-hospital mortality were >5 mmol/L, >5 mmol/L, and <20%, respectively. Neither lactate level nor lactate clearance was an independent risk factor for in-hospital mortality among cirrhotic and non-cirrhotic septic shock patients.
Conclusions
The initial lactate level and lactate at 6 hours were significantly higher in cirrhosis patients than in non-cirrhosis patients.

Citations

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Comparison between traditional logistic regression and machine learning for predicting mortality in adult sepsis patients
Hongsheng Wu, Biling Liao, Tengfei Ji, Keqiang Ma, Yumei Luo, Shengmin Zhang
Frontiers in Medicine.2025;[Epub] CrossRef
Serum lactate and mean arterial pressure thresholds in patients with cirrhosis and septic shock
Thomas N. Smith, Chansong Choi, Puru Rattan, Laura Piccolo Serafim, Blake A. Kassmeyer, Ryan J. Lennon, Ognjen Gajic, Jody C. Olson, Patrick S. Kamath, Alice Gallo De Moraes, Douglas A. Simonetto
Hepatology Communications.2024;[Epub] CrossRef
Review article: Evaluation and care of the critically ill patient with cirrhosis
Iva Kosuta, Madhumita Premkumar, K. Rajender Reddy
Alimentary Pharmacology & Therapeutics.2024; 59(12): 1489. CrossRef
Diagnostic Value of Endotoxin Activity for Acute Postoperative Complications: A Study in Major Abdominal Surgery Patients
Hye Sung Kim, Gyeo Ra Lee, Eun Young Kim
Biomedicines.2024; 12(12): 2701. CrossRef
Norepinephrine dose, lactate or heart rate: what impacts prognosis in sepsis and septic shock? Results from a prospective, monocentric registry
Tobias Schupp, Kathrin Weidner, Jonas Rusnak, Schanas Jawhar, Jan Forner, Floriana Dulatahu, Lea Marie Brück, Ursula Hoffmann, Thomas Bertsch, Ibrahim Akin, Michael Behnes
Current Medical Research and Opinion.2023; 39(5): 647. CrossRef
Intensive care management of acute-on-chronic liver failure
Giovanni Perricone, Thierry Artzner, Eleonora De Martin, Rajiv Jalan, Julia Wendon, Marco Carbone
Intensive Care Medicine.2023; 49(8): 903. CrossRef

Infection
Sepsis-induced cardiomyopathy is associated with higher mortality rates in patients with sepsis: Balaram Krishna J Hanumanthu, Anika Sasidharan Nair, Adarsh Katamreddy, Jason S Gilbert, Jee Young You, Obiageli Lynda Offor, Ankit Kushwaha, Ankita Krishnan, Marzio Napolitano, Leonidas Palaidimos, Joaquin Morante, Seema S. Tekwani, Suchita Mehta, Aanchal Gupta, Harmeen Goraya, Mengyang Sun, Robert T. Faillace, Perminder Gulani; Acute Crit Care. 2021;36(3):215-222. Published online July 26, 2021; DOI: https://doi.org/10.4266/acc.2021.00234

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Abstract PDF

Background
Patients with sepsis are at risk for developing sepsis-induced cardiomyopathy (SIC). Previous studies offer inconsistent results regarding the association of SIC and mortality. This study sought to assess whether SIC is linked to mortality in patients with sepsis and to evaluate predictors of the development of SIC.
Methods
In this retrospective study, patients admitted to the medical intensive care unit with a diagnosis of sepsis in the absence of acute coronary syndrome were included. SIC was identified using transthoracic echo and was defined by a new onset decline in left ventricular ejection fraction (LVEF) ≤50%, or ≥10% decline in LVEF compared to baseline in patients with a history of heart failure with reduced ejection fraction. Multivariable logistic regression analysis was performed using the R software program.
Results
Of the 359 patients in the final analysis, 19 (5.3%) had SIC. Eight (42.1%) of the 19 patients in the SIC group and 60 (17.6%) of the 340 patients in the non-SIC group died during hospitalization. SIC was associated with an increased risk for all-cause in-hospital mortality (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.15–18.69; P=0.03). Independent predictors for the development of SIC were albumin level (OR, 0.47; 95% CI, 0.23–0.93; P=0.03) and culture positivity (OR, 8.47; 95% CI, 2.24–55.61; P=0.006). Concomitant right ventricular hypokinesis was noted in 13 (68.4%) of the 19 SIC patients.
Conclusions
SIC was associated with an increased risk for all-cause in-hospital mortality. Low albumin level and culture positivity were independent predictors of SIC.

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Decreased left ventricular ejection fraction is associated with increased mortality in sepsis: A retrospective cohort study
August A. Longino, Jacqueline A. Urban, Katharine C. Martin, Katarina R. Leyba, Theresa N. Thai, Ivor S. Douglas, David S. Raymer
European Journal of Heart Failure.2025; 27(1): 174. CrossRef
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George E. Zakynthinos, Grigorios Giamouzis, Andrew Xanthopoulos, Evangelos Oikonomou, Konstantinos Kalogeras, Nikitas Karavidas, Ilias E. Dimeas, Ioannis Gialamas, Maria Ioanna Gounaridi, Gerasimos Siasos, Manolis Vavuranakis, Epaminondas Zakynthinos, Vas
Journal of Clinical Medicine.2025; 14(3): 986. CrossRef
Neutrophil-derived exosomal S100A8 aggravates lung injury in sepsis by inducing pyroptosis
Xinxin Li, Wei Zhou, Liangliang Zhou, Yingbin Li, Xufeng Wu, Jianjun Chen
Molecular Immunology.2025; 181: 29. CrossRef
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Rui Liu, Lina Jia, Lin Yu, Detian Lai, Qingzhu Li, Bingyu Zhang, Enwei Guo, Kailiang Xu, Qiancheng Luo
Frontiers in Immunology.2025;[Epub] CrossRef
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Tangtian Chen, Liang Ye, Jing Zhu, Bin Tan, Qin Yi, Yanting Sun, Qiumin Xie, Han Xiang, Rui Wang, Jie Tian, Hao Xu
The Journal of Infectious Diseases.2024; 229(4): 1178. CrossRef
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Ulrich Gergs, Tina Jahn, Nico Schulz, Claudia Großmann, Uwe Rueckschloss, Uta Demus, Igor B. Buchwalow, Joachim Neumann
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SSRN Electronic Journal .2022;[Epub] CrossRef

Review Articles

Meta-analysis
The efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis: Manoj Kumar Reddy Somagutta, Maria Kezia Lourdes Pormento, Muhammad Adnan Khan, Alaa Hamdan, Namrata Hange, Manish KC, Sukrut Pagad, Molly Sanjay Jain, Sivasthikka Lingarajah, Vishal Sharma, Jaspreet Kaur, Bernard Emuze, Erkan Batti, Obumneme Jude Iloeje; Acute Crit Care. 2021;36(3):185-200. Published online June 30, 2021; DOI: https://doi.org/10.4266/acc.2021.00108

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Abstract PDF Supplementary Material

Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis. Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis. Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P=0.92; I²=0%); intensive care unit (ICU) mortality (RR, 0.77; P=0.20; I²=58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I² =37%) or hospital length of stay (WMD: 0.57; P=0.49; I²=17%), and renal replacement therapy (RR, 0.64; P=0.44; I²=39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, –0.72; P=0.01; I²=32%). However, a significant effect was noted for the duration of vasopressor use (WMD, –25.49; P<0.001; I²=46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration. HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.

Citations

Citations to this article as recorded by

Effect of intravenous vitamin C on adult septic patients: a systematic review and meta-analysis
Huoyan Liang, Qingqing Mu, Wenju Sun, Liming Liu, Simin Qiu, Zili Xu, Yuqing Cui, Yan Yan, Tongwen Sun
Frontiers in Nutrition.2023;[Epub] CrossRef
Insights Into Thiamine Supplementation in Patients With Septic Shock
Nara Aline Costa, Amanda Gomes Pereira, Clara Sandra Araujo Sugizaki, Nayane Maria Vieira, Leonardo Rufino Garcia, Sérgio Alberto Rupp de Paiva, Leonardo Antonio Mamede Zornoff, Paula Schmidt Azevedo, Bertha Furlan Polegato, Marcos Ferreira Minicucci
Frontiers in Medicine.2022;[Epub] CrossRef
Vitamin C-induced Hemolysis: Meta-summary and Review of Literature
Deven Juneja, Ravi Jain
Indian Journal of Critical Care Medicine.2022; 26(2): 224. CrossRef
Is it time to reconsider the administration of thiamine alone or in combination with vitamin C in critically ill patients? A meta-analysis of clinical trial studies
Nafiseh Shokri-mashhadi, Ali Aliyari, Zahra Hajhashemy, Saeed Saadat, Mohammad Hossein Rouhani
Journal of Intensive Care.2022;[Epub] CrossRef
Parenteral Vitamin C in Patients with Severe Infection: A Systematic Review
Arnav Agarwal, John Basmaji, Shannon M. Fernando, Fang Zhou Ge, Yingqi Xiao, Haseeb Faisal, Kimia Honarmand, Mathieu Hylands, Vincent Lau, Kimberley Lewis, Rachel Couban, François Lamontagne, Neill K. J. Adhikari
NEJM Evidence.2022;[Epub] CrossRef
Unanswered questions on the use of hydrocortisone, ascorbic acid, and thiamine therapy in sepsis and septic shock
David Ragoonanan, Nicolas Tran, Veeshal Modi, Paige Morgan Nickelsen
American Journal of Health-System Pharmacy.2022; 79(19): 1626. CrossRef
Impacts of Corticosteroid Therapy at Acute Stage of Hospital-Onset Clostridioides difficile Infections
Ching-Chi Lee, Jen-Chieh Lee, Chun-Wei Chiu, Pei-Jane Tsai, Wen-Chien Ko, Yuan-Pin Hung
Infection and Drug Resistance.2022; Volume 15: 5387. CrossRef
The impact of vitamin C-containing treatment on the mortality of patients with sepsis: A systematic review and meta-analysis of randomized controlled trials
Ching-Yi Chen, Chien-Tung Chiu, Ho-Sheng Lee, Chih-Cheng Lai
Journal of Infection and Public Health.2022; 15(12): 1514. CrossRef
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Deven Juneja, Anish Gupta, Sahil Kataria, Omender Singh
World Journal of Virology.2022; 11(5): 300. CrossRef
Current role of high dose vitamin C in sepsis management: A concise review
Deven Juneja, Prashant Nasa, Ravi Jain
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HYDROCORTISONE, ASCORBIC ACID, AND THIAMINE THERAPY DECREASE RENAL OXIDATIVE STRESS AND ACUTE KIDNEY INJURY IN MURINE SEPSIS
John Kim, Allan Stolarski, Qiuyang Zhang, Katherine Wee, Daniel Remick
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Early administration of Vitamin C in patients with sepsis or septic shock in emergency departments: A multicenter, double blinded, randomized controlled trial: The C-EASIE trial protocol
Stefanie Vandervelden, Lina Wauters, Jan Breuls, Steffen Fieuws, Philippe Vanhove, Ives Hubloue, Magali Bartiaux, Jacques Creteur, François Stifkens, Koen Monsieurs, Didier Desruelles, Elisa Panada
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Hydrocortisone, ascorbic acid, and thiamine (HAT) for sepsis and septic shock: a meta-analysis with sequential trial analysis
Weilan Na, Huili Shen, Yichu Li, Dong Qu
Journal of Intensive Care.2021;[Epub] CrossRef

Infection
Up-to-date information on polymyxin B-immobilized fiber column direct hemoperfusion for septic shock: Chieko Mitaka, Makio Kusaoi, Izumi Kawagoe, Daizoh Satoh; Acute Crit Care. 2021;36(2):85-91. Published online April 4, 2021; DOI: https://doi.org/10.4266/acc.2021.00150

8,780 View
356 Download
5 Web of Science
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Abstract PDF

Endotoxin adsorption therapy by polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) has been used for the treatment of septic shock patients. Endotoxin, an outer membrane component of Gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin triggers a signaling cascade for leukocytes, macrophage, and endothelial cells to secrete various mediators including cytokines and nitric oxide, leading to septic shock and multiple organ dysfunction syndrome. PMX-DHP directly adsorbed not only endotoxin but also monocytes and anandamide. It reduced blood levels of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha and IL-17A, adhesion molecules, plasminogen activator inhibitor 1, and high mobility group box-1. As a result, PMX-DHP increased blood pressure and reduced the dose of vasoactive-inotropic agents. PMX-DHP improved monocyte human leukocyte antigen-DR expression in patients with severe sepsis and septic shock. A post hoc analysis of EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in Randomized Controlled Trial of Adults Treated for Endotoxemia and Septic Shock) trial has shown that PMX-DHP significantly reduced 28-day mortality compared with the control group in septic shock patients with endotoxin activity assay level between 0.60 and 0.89. Longer duration of PMX-DHP may be another strategy to bring out the beneficial effects of PMX-DHP. Further studies are needed to confirm the efficacy of PMX-DHP treatment for septic shock.

Citations

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TLR2 and NLRP3 Orchestrate Regulatory Roles in Escherichia coli Infection-Induced Septicemia in Mouse Models
Zhiguo Gong, Wei Mao, Jiamin Zhao, Peipei Ren, Zhuoya Yu, Yunjie Bai, Chao Wang, Yuze Liu, Shuang Feng, Surong Hasi
Journal of Innate Immunity.2024; 16(1): 513. CrossRef
Methods of Extracorporeal Hemocorrection in Sepsis (Review)
V. A. Kovzel, L. A. Davydova, A. V. Karzin, S. V. Tsarenko, V. Yu. Baturova, A. A. Polupan, A. I. Gutnikov
General Reanimatology.2023; 19(2): 68. CrossRef
Modifications of peripheral perfusion in patients with vasopressor-dependent septic shock treated with polymyxin B-direct hemoperfusion
Motohiro Sekino, Yu Murakami, Shuntaro Sato, Ryosuke Shintani, Shohei Kaneko, Naoya Iwasaki, Hiroshi Araki, Taiga Ichinomiya, Ushio Higashijima, Tetsuya Hara
Scientific Reports.2023;[Epub] CrossRef
Rhabdomyolysis secondary to hypervirulent Klebsiella pneumoniae infection: A case report
Naoko Niimi, Keiko Taga, Taiju Miyagami, Toshio Naito, Chieko Mitaka
Clinical Case Reports.2022;[Epub] CrossRef
Endotoxin Activity in Patients With Extracorporeal Membrane Oxygenation Life Support: An Observational Pilot Study
Chen-Tse Lee, Chih-Hsien Wang, Wing-Sum Chan, Yun-Yi Tsai, Tzu-Jung Wei, Chien-Heng Lai, Ming-Jiuh Wang, Yih-Sharng Chen, Yu-Chang Yeh
Frontiers in Medicine.2021;[Epub] CrossRef

Case Report

Gastroenterology
Circumferential esophageal perforation resulting in tension hydropneumothorax in a patient with septic shock: Saad Saffo, James Farrell, Anil Nagar; Acute Crit Care. 2021;36(3):264-268. Published online March 11, 2021; DOI: https://doi.org/10.4266/acc.2020.01067

10,101 View
151 Download
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Abstract PDF

Esophageal perforations occur traumatically or spontaneously and are typically associated with high mortality rates. Early recognition and prompt management are essential. We present the case of a 76-year-old man who was admitted to the medical intensive care unit with fulminant Clostridium difficile colitis, shock, and multi-organ failure. After an initial period of improvement, his condition rapidly deteriorated despite aggressive medical management, and he required mechanical ventilation. Radiography after endotracheal intubation showed interval development of pneumomediastinum and bilateral hydropneumothorax with tension physiology. Chest tube placement resulted in the drainage of multiple liters of dark fluid, and pleural fluid analysis was notable for polymicrobial empyemas. Despite the unusual presentation, esophageal perforation was suspected. Endoscopy ultimately confirmed circumferential separation of the distal esophagus from the stomach, and bedside endoscopic stenting was performed with transient improvement. Two weeks after admission, he developed mediastinitis complicated by recurrent respiratory failure and passed away. This report further characterizes our patient’s unique presentation and briefly highlights the clinical manifestations, management options, and outcomes of esophageal perforations.

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Current approach for Boerhaaves syndrome: A systematic review of case reports
Ippei Yamana, Takahisa Fujikawa, Yuichiro Kawamura, Suguru Hasegawa
World Journal of Meta-Analysis.2023; 11(4): 112. CrossRef

Original Article

Epidemiology
Characteristics, management and clinical outcomes of patients with sepsis: a multicenter cohort study in Korea: Kyeongman Jeon, Soo Jin Na, Dong Kyu Oh, Sunghoon Park, Eun Young Choi, Seok Chan Kim, Gil Myeong Seong, Jeongwon Heo, Youjin Chang, Won Gun Kwack, Byung Ju Kang, Won-Il Choi, Kyung Chan Kim, So Young Park, Sang Hyun Kwak, Yoon Mi Shin, Heung Bum Lee, So Hee Park, Jae Hwa Cho, Beongki Kim, Chae‐Man Lim; Acute Crit Care. 2019;34(3):179-191. Published online July 1, 2019; DOI: https://doi.org/10.4266/acc.2019.00514

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340 Download
27 Web of Science
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Abstract PDF

Background
Mortality rates associated with sepsis have increased progressively in Korea, but domestic epidemiologic data remain limited. The objective of this study was to investigate the characteristics, management and clinical outcomes of sepsis patients in Korea.
Methods
This study is a multicenter retrospective cohort study. A total of 64,021 adult patients who visited an emergency department (ED) within one of the 19 participating hospitals during a 1-month period were screened for eligibility. Among these, patients diagnosed with sepsis based on the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in the study.
Results
Using the Sepsis-3 criteria, 977 sepsis patients were identified, among which 36.5% presented with septic shock. The respiratory system (61.8%) was the most common site of infection. The pathogen involved was identified in 444 patients (45.5%) and multi-drug resistance (MDR) pathogens were isolated in 171 patients. Empiric antibiotic therapy was appropriate in 68.6% of patients, but the appropriateness was significantly reduced in infections associated with MDR pathogens as compared with non-MDR pathogens (58.8% vs. 76.0%, P<0.001). Hospital mortality was 43.2% and 18.5% in sepsis patients with and without shock, respectively. Of the 703 patients who survived to discharge, 61.5% were discharged to home and 38.6% were transferred to other hospitals or facilities.
Conclusions
This study found the prevalence of sepsis in adult patients visiting an ED in Korea was 1.5% (15.2/1,000 patients). Patients with sepsis, especially septic shock, had a high mortality and were often referred to step-down centers after acute and critical care.

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