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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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AbstractAbstract 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.
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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AbstractAbstract 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.
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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AbstractAbstract PDFSupplementary 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
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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AbstractAbstract PDFSupplementary 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.

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  • 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
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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AbstractAbstract 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

Citations to this article as recorded by  
  • 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
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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AbstractAbstract 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

Citations to this article as recorded by  
  • 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
  • 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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AbstractAbstract PDFSupplementary Material
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

Citations to this article as recorded by  
  • 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
  • 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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AbstractAbstract 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.

Citations

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  • Inhibition of Pyruvate Dehydrogenase Kinase 4 Attenuates Myocardial and Mitochondrial Injury in Sepsis-Induced Cardiomyopathy
    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
  • Meta-Analysis of Initial Natriuretic Peptides in the Setting of Sepsis-Induced Myocardial Dysfunction
    Boyong He, Xin Wang, Liguo Shi, Hongbin Cheng, Luyi Zhao
    Biomarkers in Medicine.2024; 18(4): 145.     CrossRef
  • Therapeutic Dilemmas in Mixed Septic-Cardiogenic Shock
    Daniela Urina Jassir, Antoine H. Chaanine, Sapna Desai, Indranee Rajapreyar, Thierry H. Le Jemtel
    The American Journal of Medicine.2023; 136(1): 27.     CrossRef
  • A case of sepsis‐induced cardiomyopathy successfully treated with venoarterial extracorporeal membrane oxygenation
    Keigo Sato, Akihiro Naito, Taichi Shiratori, Masahiro Yamamoto, Kenichi Shimane, Manabu Mikami, Mariko Senda, Haruki Kume, Motofumi Suzuki
    IJU Case Reports.2023; 6(1): 26.     CrossRef
  • RNF20 deletion causes inflammation in model of sepsis through the NLRP3 activation
    Anlong Qi, Yancun Liu, Jianhua Zhai, Yongtao Wang, Wang Li, Tong Wang, Yanfen Chai
    Immunopharmacology and Immunotoxicology.2023; 45(4): 469.     CrossRef
  • S100a8/a9 contributes to sepsis-induced cardiomyopathy by activating ERK1/2-Drp1-mediated mitochondrial fission and respiratory dysfunction
    Feng Wu, Yan-Ting Zhang, Fei Teng, Hui-Hua Li, Shu-Bin Guo
    International Immunopharmacology.2023; 115: 109716.     CrossRef
  • Ultrasound in Sepsis and Septic Shock—From Diagnosis to Treatment
    Gianluca Tullo, Marcello Candelli, Irene Gasparrini, Sara Micci, Francesco Franceschi
    Journal of Clinical Medicine.2023; 12(3): 1185.     CrossRef
  • A novel signature combing cuproptosis- and ferroptosis-related genes in sepsis-induced cardiomyopathy
    Juanjuan Song, Kairui Ren, Dexin Zhang, Xinpeng Lv, Lin Sun, Ying Deng, Huadong Zhu
    Frontiers in Genetics.2023;[Epub]     CrossRef
  • Prevalence and Prognosis of Sepsis-Induced Cardiomyopathy: A Systematic Review and Meta-Analysis
    Daisuke Hasegawa, Yoshiko Ishisaka, Tetsuro Maeda, Narut Prasitlumkum, Kazuki Nishida, Siddharth Dugar, Ryota Sato
    Journal of Intensive Care Medicine.2023; 38(9): 797.     CrossRef
  • Sepsis-Induced myocardial dysfunction: heterogeneity of functional effects and clinical significance
    Tatyana Shvilkina, Nathan Shapiro
    Frontiers in Cardiovascular Medicine.2023;[Epub]     CrossRef
  • Research Progress on the Mechanism and Management of Septic Cardiomyopathy: A Comprehensive Review
    Xue-Bin Pei, Bo Liu, Maciej Dyrbuś
    Emergency Medicine International.2023; 2023: 1.     CrossRef
  • Protein Phosphatase 2A Improves Cardiac Functional Response to Ischemia and Sepsis
    Ulrich Gergs, Tina Jahn, Nico Schulz, Claudia Großmann, Uwe Rueckschloss, Uta Demus, Igor B. Buchwalow, Joachim Neumann
    International Journal of Molecular Sciences.2022; 23(9): 4688.     CrossRef
  • Feasibility and discriminatory value of tissue motion annular displacement in sepsis-induced cardiomyopathy: a single-center retrospective observational study
    Jieqiong Song, Yao Yao, Shilong Lin, Yizhou He, Duming Zhu, Ming Zhong
    Critical Care.2022;[Epub]     CrossRef
  • Sepsis-Induced Cardiomyopathy Reviewed: The Case for Early Consideration of Mechanical Support
    Daniel L. Plack, Olivier Royer, Etienne J. Couture, Christoph G.S. Nabzdyk
    Journal of Cardiothoracic and Vascular Anesthesia.2022; 36(10): 3916.     CrossRef
  • Association of sepsis-induced cardiomyopathy and mortality: a systematic review and meta-analysis
    Yu-Min Lin, Mei-Chuan Lee, Han Siong Toh, Wei-Ting Chang, Sih-Yao Chen, Fang-Hsiu Kuo, Hsin-Ju Tang, Yi-Ming Hua, Dongmei Wei, Jesus Melgarejo, Zhen-Yu Zhang, Chia-Te Liao
    Annals of Intensive Care.2022;[Epub]     CrossRef
  • Association of Sepsis-Induced Cardiomyopathy and Mortality: A Systematic Review and Meta-Analysis
    Yu-Min Lin, Mei-Chuan Lee, Han Siong Toh, Wei-Ting Chang, Sih-Yao Chen, Fang-Hsiu Kuo, Hsin-Ju Tang, Yi-Ming Hua, Dongmei Wei, Jesus Melgarejo, Zhen-Yu Zhang, Chia-Te Liao
    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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AbstractAbstract PDFSupplementary 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
  • Role of high dose vitamin C in management of hospitalised COVID-19 patients: A minireview
    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
    World Journal of Critical Care Medicine.2022; 11(6): 349.     CrossRef
  • 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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    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
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AbstractAbstract 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.

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  • 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
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    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
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    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
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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
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AbstractAbstract 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 Articles
Pediatrics
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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AbstractAbstract 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.

Citations

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    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
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    Charlotte Berninghausen, Frank Schwab, Alexander Gropmann, Bernd A. Leidel, Rajan Somasundaram, Lydia Hottenbacher, Petra Gastmeier, Sonja Hansen
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    Joong-Yub Kim, Hong Yeul Lee, Jinwoo Lee, Dong Kyu Oh, Su Yeon Lee, Mi Hyeon Park, Chae-Man Lim, Sang-Min Lee
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    Rehab Salah Taha, Mohamed Elsayed Afandy, Abdelaziz Hamid Elbadawi, Mohamed Samir Abd El Ghafar
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    Hyung-Jun Kim, Dong Kyu Oh, Sung Yoon Lim, Young-Jae Cho, Sunghoon Park, Gee Young Suh, Chae-Man Lim, Yeon Joo Lee
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    Ji Hwan Kim, Yong Kyun Kim, Dong Kyu Oh, Kyeongman Jeon, Ryoung-Eun Ko, Gee Young Suh, Sung Yun Lim, Yeon Joo Lee, Young-Jae Cho, Mi-Hyeon Park, Sang-Bum Hong, Chae-Man Lim, Sunghoon Park
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    Myeong Namgung, Chiwon Ahn, Yeonkyung Park, Il-Youp Kwak, Jungguk Lee, Moonho Won
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    Se Hun Kim, Ki Hoon Kim
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    Tae Wan Kim, Se-Uk Lee, Boram Park, Kyeongman Jeon, Sunghoon Park, Gee Young Suh, Dong Kyu Oh, Soo Yeon Lee, Mi Hyeon Park, Haein Lee, Chae-man Lim, Ryoung-Eun Ko, Sang-Bum Hong, Suk-Kyung Hong, Yeon Joo Lee, Young-Jae Cho, Sung Yoon Lim, Jeongwon Heo, Ja
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    Yong Jun Choi, Jae Hwa Cho
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    Soo Jin Na, Dong Kyu Oh, Sunghoon Park, Yeon Joo Lee, Sang-Bum Hong, Mi-Hyun Park, Ryoung-Eun Ko, Chae-Man Lim, Kyeongman Jeon
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    Dong-gon Hyun, Su Yeon Lee, Jee Hwan Ahn, Jin Won Huh, Sang-Bum Hong, Younsuck Koh, Chae-Man Lim, Dong Kyu Oh, Gee Young Suh, Kyeongman Jeon, Ryoung-Eun Ko, Young-Jae Cho, Yeon Joo Lee, Sung Yoon Lim, Sunghoon Park, Jeongwon Heo, Jae-myeong Lee, Kyung Cha
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    L. I. Gomanova, A. Y. Brazhnikov
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    Mi-Hee Kim, Jung-Hyun Choi
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    Sunghoon Park, Kyeongman Jeon, Dong Kyu Oh, Eun Young Choi, Gil Myeong Seong, Jeongwon Heo, Youjin Chang, Won Gun Kwack, Byung Ju Kang, Won-Il Choi, Kyung Chan Kim, So Young Park, Yoon Mi Shin, Heung Bum Lee, So Hee Park, Seok Chan Kim, Sang Hyun Kwak, Ja
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Infection
Relationship between low hemoglobin levels and mortality in patients with septic shock
Sung Min Jung, Youn-Jung Kim, Seung Mok Ryoo, Won Young Kim
Acute Crit Care. 2019;34(2):141-147.   Published online May 31, 2019
DOI: https://doi.org/10.4266/acc.2019.00465
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AbstractAbstract PDFSupplementary Material
Background
Hemoglobin levels are a critical parameter for oxygen delivery in patients with shock. On comparing target hemoglobin levels upon transfusion initiation, the correlation between the severity of decrease in hemoglobin levels and patient outcomes remains unclear. We evaluated the association between initial hemoglobin levels and mortality in patients with septic shock treated with protocol-driven resuscitation bundle therapy at an emergency department.
Methods
Data of adult patients diagnosed with septic shock between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Patients were classified into four groups according to initial hemoglobin levels: ≥9.0 g/dl, 8.0−8.9 g/dl, 7.0−7.9 g/dl, and <7.0 g/dl. The primary endpoint was 90-day mortality.
Results
In total, 2,265 patients (male, 58.3%; median age, 70.0 years [interquartile range, 60 to 78 years]) with septic shock were included. For the four groups, 90-day mortality rates were as follows: 29.1%, 43.0%, 46.5%, and 46.9% for ≥9.0 g/dl (n=1,808), 8.0−8.9 g/dl (n=217), 7.0−7.9 g/dl (n=135), and <7.0 g/dl (n=105), respectively (P<0.001). Multivariate logistic regression showed that initial hemoglobin levels were an independent factor associated with 90-day mortality and mortality proportionally increased with decreasing hemoglobin levels (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.36 to 2.61 for 8.0−8.9 g/dl; OR, 1.97; 95% CI, 1.31 to 2.95 for 7.0–7.9 g/dl; and OR, 2.35; 95% CI, 1.52 to 3.63 for <7.0 g/dl).
Conclusions
Low hemoglobin levels (<9.0 g/dl) were observed in approximately 20% of patients with septic shock, and the severity of decrease in these levels correlated with mortality.

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Infection
Application of Sepsis-3 Criteria to Korean Patients with Critical Illnesses
Jae Yeol Kim, Hwan Il Kim, Gee Young Suh, Sang Won Yoon, Tae-Yop Kim, Sang Haak Lee, Jae Young Moon, Jae-Young Kwon, Sungwon Na, Ho Geol Ryu, Jisook Park, Younsuck Koh
Acute Crit Care. 2019;34(1):30-37.   Published online January 29, 2019
DOI: https://doi.org/10.4266/acc.2018.00318
Correction in: Acute Crit Care 2019;34(2):172
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AbstractAbstract PDF
Background
The 2016 Society of Critical Care Medicine (SCCM)/European Society of Intensive Care Medicine (ESICM) task force for Sepsis-3 devised new definitions for sepsis, sepsis with organ dysfunction and septic shock. Although Sepsis-3 was data-driven, evidence-based approach, East Asian descents comprised minor portions of the project population. Methods: We selected Korean participants from the fever and antipyretics in critically ill patients evaluation (FACE) study, a joint study between Korea and Japan. We calculated the concordance rates for sepsis diagnosis between Sepsis-2 and Sepsis-3 criteria and evaluated mortality rates of sepsis, sepsis with organ dysfunction, and septic shock by Sepsis-3 criteria using the selected data. Results: Korean participants of the FACE study were 913 (383 with sepsis and 530 without sepsis by Sepsis-2 criteria). The concordance rate for sepsis diagnosis between Sepsis-2 and Sepsis-3 criteria was 55.4%. The intensive care unit (ICU) and 28-day mortality rates of sepsis, sepsis with organ dysfunction, and septic shock patients according to Sepsis-3 criteria were 26.2% and 31.0%, 27.5% and 32.5%, and 40.8% and 43.4%, respectively. The quick Sequential Organ Failure Assessment (qSOFA) was inferior not only to SOFA but also to systemic inflammatory response syndrome (SIRS) for predicting ICU and 28-day mortality. Conclusions: The concordance rates for sepsis diagnosis between Sepsis-2 and Sepsis-3 criteria were low. Mortality rate for septic shock in Koreans was consistent with estimates made by the 2016 SCCM/ESICM task force. SOFA and SIRS were better than qSOFA for predicting ICU and 28-day mortality in Korean ICU patients.

Citations

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  • HYPOTENSION AT THE TIME OF SEPSIS RECOGNITION IS NOT ASSOCIATED WITH INCREASED MORTALITY IN SEPSIS PATIENTS WITH NORMAL LACTATE LEVELS
    Ji Hwan Kim, Yong Kyun Kim, Dong Kyu Oh, Kyeongman Jeon, Ryoung-Eun Ko, Gee Young Suh, Sung Yun Lim, Yeon Joo Lee, Young-Jae Cho, Mi-Hyeon Park, Sang-Bum Hong, Chae-Man Lim, Sunghoon Park
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Case Report
Genetic
Lethal Hyperammonemia due to Ornithine Transcarbamylase Deficiency in a Patient with Severe Septic Shock
Ji An Hwang, Joo Han Song, Young Seok Lee, Kyung Soo Chung, Song Yee Kim, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Joon Chang, Moo Suk Park
Korean J Crit Care Med. 2016;31(2):140-145.   Published online May 31, 2016
DOI: https://doi.org/10.4266/kjccm.2016.31.2.140
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AbstractAbstract PDF
Severe hyperammonemia can occur as a result of inherited or acquired liver enzyme defects in the urea cycle, among which ornithine transcarbamylase deficiency (OTCD) is the most common form. We report a very rare case of a 45-year-old Korean male who was admitted to the intensive care unit (ICU) due to severe septic shock with acute respiratory failure caused by Pneumocystis jiroveci pneumonia. During his ICU stay with ventilator care, the patient suffered from marked hyperammonemia (>1,700 μg/dL) with abrupt mental change leading to life-threatening cerebral edema. Despite every effort including continuous renal replacement therapy and use of a molecular adsorbent recirculating system (extracorporeal liver support–albumin dialysis) to lower his serum ammonia level, the patient was not recovered. The lethal hyperammonemia in the patient was later proven to be a manifestation of acquired liver enzyme defect known as OTCD, which is triggered by serious catabolic conditions, such as severe septic shock with acute respiratory failure.

ACC : Acute and Critical Care