Acute and Critical Care

Original Articles

Surgery
Biomarkers to predict mortality in patients with Fournier’s gangrene admitted to the intensive care unit after surgery in South Korea: In Sik Shin, Seong Chan Gong, Sanghyun An, Kwangmin Kim; Acute Crit Care. 2023;38(4):452-459. Published online November 21, 2023; DOI: https://doi.org/10.4266/acc.2023.00766

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Background
The use of biomarkers to predict patient outcomes may be crucial for patients admitted to the intensive care unit (ICU) following surgery because biomarkers guide clinicians in tailoring treatment plans accordingly. Therefore, we aimed to identify potential biomarkers to predict the prognosis of patients with Fournier’s gangrene (FG) admitted to the ICU after surgery.
Methods
We enrolled patients with FG admitted to our Hospital between January 2013 and December 2022. We retrospectively analyzed patient characteristics, factors related to management, scores known to be associated with the prognosis of FG, and laboratory data.
Results
The study population included 28 survivors and 13 nonsurvivors. The initial serum lactate level taken in the emergency department; white blood cell, neutrophil, and platelet counts; delta neutrophil index and international normalized ratio; albumin, glucose, HCO3, and postoperative lactate levels; and the laboratory risk indicator for necrotizing fasciitis differed between survivors and nonsurvivors. Postoperative lactate and initial albumin levels were independent predictors of mortality in patients with FG. In the receiver operating characteristic curve analysis, the postoperative lactate level was the best indicator of mortality (area under the curve, 0.877; 95% confidence interval, 0.711–1.000). The optimal cutoff postoperative lactate level for predicting mortality was 3.0 mmol/L (sensitivity, 80.0%; specificity, 95.0%).
Conclusions
Postoperative lactate and initial albumin levels could be potential predictors of mortality in patients with FG admitted to the ICU after surgery, and the optimal cutoff postoperative lactate and initial albumin levels to predict mortality were 3.0 mmol/L and 3.05 g/dl, respectively. Large-scale multicenter prospective studies are required to confirm our results.

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Risk Factors for Mortality Among Patients With Fournier Gangrene: A Systematic Review
Pavan Shet, Ashmit Daiyan Mustafa, Karan Varshney, Lavina Rao, Sameen Sawdagar, Florence McLennan, Siraaj Ansari, Darshan Shet, Niveshan Sivathamboo, Sian Campbell
Surgical Infections.2024; 25(4): 261. CrossRef

Cardiology
Predictors and outcomes of sepsis-induced cardiomyopathy in critically ill patients: Myung Jin Song, Sang Hoon Lee, Ah Young Leem, Song Yee Kim, Kyung Soo Chung, Eun Young Kim, Ji Ye Jung, Young Ae Kang, Young Sam Kim, Joon Chang, Moo Suk Park; Acute Crit Care. 2020;35(2):67-76. Published online May 15, 2020; DOI: https://doi.org/10.4266/acc.2020.00024

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Abstract PDF

Background
Sepsis-induced cardiomyopathy (SIC) occurs frequently in critically ill patients, but the clinical features and prognostic impact of SIC on sepsis outcome remain controversial. Here, we investigated the predictors and outcomes of SIC.
Methods
Patients admitted to a single medical intensive care unit from June 2016 to September 2017 were retrospectively reviewed. SIC was diagnosed by ejection fraction (EF) <50% and ≥10% decrease in baseline EF that recovered within 2 weeks.
Results
In total, 342 patients with sepsis met the inclusion criteria, and 49 patients (14.3%) were diagnosed with SIC; the latter were compared with 259 patients whose EF was not deteriorated by sepsis (non-SIC). Low systolic blood pressure and increased left ventricular end-diastolic diameter (LVEDD) were identified as predictors of SIC. SIC and non-SIC patients did not differ significantly in terms of 28-day all-cause mortality (24.5% vs. 26.3%, P=0.936). Acute Physiology and Chronic Health Evaluation II (APACHE II; hazard ratio [HR], 1.10; 95% confidential interval [CI], 1.02 to 1.18; P=0.009) and delta neutrophil index (DNI; HR, 1.02; 95% CI, 1.00 to 1.08; P=0.026) were independent risk factors for 28-day mortality with SIC. DNI, APACHE II, and lactate were identified as risk factors for 28-day mortality in sepsis patients as a whole.
Conclusions
SIC was not associated with increased mortality compared to non-SIC. Low systolic blood pressure and increased LVEDD were predictors of SIC. High APACHE II score and elevated DNI, which reflect sepsis severity, predict 28-day all-cause mortality.

Citations

Citations to this article as recorded by

Testosterone and soluble ST2 as mortality predictive biomarkers in male patients with sepsis-induced cardiomyopathy
Lu Wang, Wen Dai, Ruiyao Zhu, Tingting Long, Zhaocai Zhang, Zhenju Song, Sucheng Mu, Shasha Wang, Huijuan Wang, Jiaxi Lei, Jing Zhang, Wenfang Xia, Guang Li, Wenwei Gao, Handong Zou, Yan Li, Liying Zhan
Frontiers in Medicine.2024;[Epub] 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
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
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
Biomarkers to Predict Multiorgan Distress Syndrome and Acute Kidney Injury in Critically Ill Surgical Patients
In Sik Shin, Da Kyung Kim, Sanghyun An, Sung Chan Gong, Moo Hyun Kim, Md Habibur Rahman, Cheol-Su Kim, Joon Hyeong Sohn, Kwangmin Kim, Hoon Ryu
Medicina.2023; 59(12): 2054. CrossRef
Risk factors of postoperative septic cardiomyopathy in perioperative sepsis patients
Yuchang Xin, Ying Ge, Liuhui Chang, Yong Ni, Hairui Liu, Jiang Zhu
BMC Anesthesiology.2022;[Epub] CrossRef
Effect of milrinone versus placebo on hemodynamic in patients with septic shock: A randomize control trial
Suratee Chobngam, Surat Tongyoo
Clinical Critical 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
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
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, Aancha
Acute and Critical Care.2021; 36(3): 215. CrossRef
The Correlation Between Whole Blood Copper (Cu), Zinc (Zn) Levels and Cu/Zn Ratio and Sepsis-Induced Left Ventricular Systolic Dysfunction (SILVSD) in Patients with Septic Shock: A Single-Center Prospective Observational Study
Jian-Biao Meng, Ma-Hong Hu, Ming Zhang, Gong-Pai Hu, Wei Zhang, Shen-Jiang Hu
International Journal of General Medicine.2021; Volume 14: 7219. CrossRef

Infection
The Effects of Flecainide Acetate on Inflammatory-Immune Response in Lipopolysaccharide-Stimulated Neutrophils and on Mortality in Septic Rats: Shi Young Chung, Jinyoung Kim, Hong Bum Bae, Tran Duc Tin, Wan Ju, Sang Hyun Kwak; Acute Crit Care. 2018;33(1):34-41. Published online February 28, 2018; DOI: https://doi.org/10.4266/acc.2017.00577

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Abstract PDF

Background
Flecainide acetate is a drug used primarily for cardiac arrhythmia. Some studies also imply that flecainide acetate has the potential to regulate inflammatory-immune responses; however, its mechanism of action is contended. We determined the effects of flecainide acetate on lipopolysaccharide (LPS)-stimulated human neutrophils in vitro and on mortality in a septic rat model.
Methods
Neutrophils from human blood were cultured with varying concentrations of flecainide acetate (1 μM, 10 μM, or 100 μM) with or without LPS (100 ng/ml). To assess neutrophil activation, the protein levels of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 and IL-8 were measured after a 4-hour culture period. To assess the intracellular signaling pathways, the levels of phosphorylation of p38 mitogen-activated protein kinase (p38), extracellular signal-regulated kinase (ERK) 1/2, and c-Jun N-terminal kinase (JNK) were measured after a 30-minute culture period, and the nuclear translocation of nuclear factor (NF)-κB was measured after a 1-hour culture period. Additionally, the survival rate was investigated in a rat sepsis model.
Results
Flecainide acetate down-regulated the activation of proinflammatory cytokines, including TNF-α and IL-6 and IL-8, and intracellular signaling pathways including ERK 1/2 and NF-κB. Flecainide acetate also improved the survival rate in the rat sepsis model.
Conclusions
Collectively, these findings indicate that flecainide acetate can improve survival in a rat sepsis model by attenuating LPS-induced neutrophil responses. We therefore suggest that flecainide acetate plays an important role in modulating inflammatoryimmune responses.

Citations

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Protective Role of Astaxanthin in Regulating Lipopolysaccharide-Induced Inflammation and Apoptosis in Human Neutrophils
Seongheon Lee, Sung Kuk Son, Eunye Cho, Sungah Yoo, Eun-A Jang, Sang Hyun Kwak
Current Issues in Molecular Biology.2024; 46(8): 8567. CrossRef
Persistence is key: unresolved immune dysfunction is lethal in both COVID-19 and non-COVID-19 sepsis
Andy Y. An, Arjun Baghela, Peter Zhang, Reza Falsafi, Amy H. Lee, Uriel Trahtemberg, Andrew J. Baker, Claudia C. dos Santos, Robert E. W. Hancock
Frontiers in Immunology.2023;[Epub] CrossRef

Rebound Inflammation Associated with Rewarming from Hypothermia in an Endotoxin-Injured Lung: Chae Man Lim; Korean J Crit Care Med. 2013;28(2):80-85.; DOI: https://doi.org/10.4266/kjccm.2013.28.2.80

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Abstract PDF: BACKGROUND
Hypothermia is known to suppress inflammation in various experimental and clinical settings. We wanted to investigate how the suppressed inflammation by hypothermia is affected during rewarming.
METHODS
Mice were being assigned to normothermia (37degrees C) or hypothermia (32degrees C). After 30 minutes at the assigned temperature, lipopolysaccharide was administered intratracheally. The mice were then randomly grouped and subjected to 4 hours of normothermia (N), 24 hours of normothermia (NN), 4 hours of hypothermia (H), or 4 hours of hypothermia followed by normothermia for the next 20 hours (HN). In another experiment, other HN mice were treated with varying doses of anti-TNF-alpha or anti-IL-1beta antibodies (0, 6.25, 12.5, 25, and 50 microg/250 microl) immediately prior to rewarming.
RESULTS
The neutrophil counts of BAL fluid (x104/ml) were 23.0 +/- 13.1 in the N, 6.4 +/- 3.1 in the H (p = 0.002 vs N), 20.4 +/- 10.2 in the NN, and 49.7 +/- 21.0 in the HN (p = 0.005 vs H; p < 0.001 vs NN). Myeloperoxidase activity of the lung (unit/microg) was 6.7 +/- 2.9, 7.9 +/- 1.9, 17.8 +/- 4.0 (p < 0.001 vs N), and 12.9 +/- 5.9 (p = 0.034 vs H, p = 0.028 vs NN), respectively. Compared with control HN, total WBC and neutrophil counts of mice treated with anti-TNF-alpha antibody or anti-IL-1beta antibody prior to rewarming were lower at all tested doses. The combination of both anti-TNF-alpha or anti-IL-1beta antibodies was not increasingly reducing the neutrophilic sequestration.
CONCLUSIONS
Rewarming from induced hypothermia resulted in augmentation of neutrophilic sequestration of endotoxin-injured lung. Treatment with antibodies against TNF-alpha or IL-1beta prevented this rebound of neutrophilic infiltration.

Effect of the Neutrophil Elastase Inhibitor on Acute Lung Injury after Pulmonary Resection for Lung Cancer: A Preliminary Study: So Young Park, Sunghoon Park, Kyeongman Jeon, So Yeon Lim, Maeng Real Park, Sueah Kim, Jae Uk Song, Jhin Gook Kim, O Jung Kwon, Gee Young Suh; Korean J Crit Care Med. 2009;24(3):124-128.; DOI: https://doi.org/10.4266/kjccm.2009.24.3.124

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Abstract PDF: BACKGROUND
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the leading causes of death after lungresection. Neutrophil elastase is thought to be an important mediator in the pathogenesis of ALI. Sivelestat is a new neutrophil elastase inhibitor which may improve the outcome in patients with ALI/ARDS after lung resection. The objective of this study was to determine whether or not sivelestat can reduce mortality in patients with ALI after pulmonary resection for lung cancer.
METHODS
This study was a retrospective case-control study of twenty three patients who developed ALI/ARDS within seven days of lung resection for lung cancer. The control group (n = 12) received standard care, while the sivelestat group (n = 11) received a continuous infusion of sivelestat (0.2 mg/kg/hr) for seven days in addition to standard care.
RESULTS
There was no significant difference in the baseline characteristics between the control and sivelestat groups, except for heart rate. Six of twelve patients (50%) in the control group survived, while seven of twelve patients (64%) survived in the sivelestat group (p = 0.34). There was also no significant difference between the two groups in the progression to ARDS. In the sivelelestat group, survivors had lower APACHE II and SOFA scores than the patients in the control group.
CONCLUSIONS
There was no additional effect of a neutrophil elastase inhibitor in the treatment of ALI after pulmonary resection for lung cancer.

Influence of Collapse and Re-ventilation of Lung on the Development of Pulmonary Edema: Sang Hyun Kwak, Won Jong Jin, Hong Beom Bae, Seong Wook Jeong, Sung Su Chung, Chang Young Jeong; Korean J Crit Care Med. 2004;19(1):8-19.

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Abstract PDF: BACKGROUND
This study was to clarify the influence of collapse and re-ventilation of lung on the development of pulmonary edema in rabbit. METHODS: Animals were randomly assigned to one of three groups: Sham group receiving two lung ventilation (n=14), Collapse group receiving collapse of right lung (n=14), Reventilation group receiving collapse of right lung for 3 hours followed by reventilation of collapsed right lung for 3 hours (n=14). The lung of rabbits were ventilated with 50% oxygen through the tracheostomy. Right main bronchus was secured by thoracotomy in all animal. Collapse and reventilation were performed using by bulldog forcep. Mean arterial pressure, heart rate, arterial oxygen tension (PaO2), peripheral blood leukocyte and platelet counts were recorded at 0, 1, 2, 3, 4, 5 and 6 hour after the start of experiment. The wet to dry (W/D) weight ratio of lung, lung injury score and leukocyte counts, percentage of polymorphonuclear leukocyte (PMNL), concentration of albumin, and interleukin-8 (IL-8) in bronchoalveolar lavage fluid (BALF) were measured 6 hour after the start of experiment in both lung. RESULTS: W/D weight ratio of lung, lung injury score and leukocyte counts, percentage of PMNL, concentration of albumin and IL-8 in BALF were significantly increased in both lung of reventilation group. And the degree of increases is more significant in right than left lung. CONCLUSIONS: These findings suggest that reventilation of collapsed lung causes the bilateral pulmonary edema in rabbit mainly by activating neutrophil and IL-8 responses, which may play a central role in non cardiogenic pulmonary edema.

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