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.
Background Candidemia is associated with markedly high intensive care unit (ICU) mortality rates. Although the Impact of Early Enteral vs. Parenteral Nutrition on Mortality in Patients Requiring Mechanical Ventilation and Catecholamines (NUTRIREA-2) trial indicated that early enteral nutrition (EN) did not reduce 28-day mortality rates among critically ill patients with shock, the European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend avoiding EN in cases of uncontrolled shock. Whether increased caloric intake from EN positively impacts clinical outcomes in patients with candidemia and shock remains unclear.
Methods We retrospectively collected data from a tertiary medical center between January 2015 and December 2018. We enrolled patients who developed shock within the first 7 days following ICU admission and received a diagnosis of candidemia during their ICU stay. Patients with an ICU stay shorter than 48 hours were excluded.
Results The study included 106 patients, among whom the hospital mortality rate was 77.4% (82 patients). The median age of the patients was 71 years, and the median Acute Physiology and Chronic Health Evaluation II score was 29. The Cox regression model revealed that a higher 7-day average caloric intake through EN (hazard ratio, 0.61; 95% CI, 0.44–0.83) was significantly associated with lower hospital mortality rates. Our findings suggest EN as the preferred feeding route for critically ill patients with shock.
Conclusions Increased caloric intake through EN may be associated with lower hospital mortality rates in patients with candidemia and shock.
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
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.
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is widely used to treat medically refractory cardiogenic shock and cardiac arrest, and its usage has increased exponentially over time. Although VA-ECMO has many advantages over other mechanical circulatory supports, it has the unavoidable disadvantage of increasing retrograde arterial flow in the afterload, which causes left ventricular (LV) overload and can lead to undesirable consequences during VA-ECMO treatment. Weak or no antegrade flow without sufficient opening of the aortic valve increases the LV end-diastolic pressure, and that can cause refractory pulmonary edema, blood stagnation, thrombosis, and refractory ventricular arrhythmia. This hemodynamic change is also related to an increase in myocardial energy consumption and poor recovery, making LV unloading an essential management issue during VA-ECMO treatment. The principal factors in effective LV unloading are its timing, indications, and modalities. In this article, we review why LV unloading is required, when it is indicated, and how it can be achieved.
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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.
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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.
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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.
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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.
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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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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.
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Background Some variables of the Sequential Organ Failure Assessment (SOFA) score are not routinely measured in sepsis patients, especially in countries with limited resources. Therefore, this study was conducted to evaluate the accuracy of the modified SOFA (mSOFA) and compared its ability to predict mortality in sepsis patients to that of the original SOFA score.
Methods Sepsis patients admitted to the medical intensive care unit of Songklanagarind Hospital between 2011 and 2018 were retrospectively analyzed. The primary outcome was all-cause in-hospital mortality.
Results A total of 1,522 sepsis patients were enrolled. The mean SOFA and mSOFA scores were 9.7±4.3 and 8.8±3.9, respectively. The discrimination of the mSOFA score was significantly higher than that of the SOFA score for all-cause in-hospital mortality (area under the receiver operating characteristic curve, 0.891 [95% confidence interval, 0.875–0.907] vs. 0.879 [0.862–0.896]; P<0.001), all-cause intensive care unit (ICU) mortality (0.880 [0.863–0.898] vs. 0.871 [0.853–0.889], P=0.01) and all-cause 28-day mortality (0.887 [0.871–0.904] vs. 0.874 [0.856–0.892], P<0.001). The ability of mSOFA score to predict all-cause in-hospital and 28-day mortality was higher than that of the SOFA score within the subgroups of sepsis according to age, sepsis severity and serum lactate levels. The mSOFA score was demonstrated to have a performance similar to the original SOFA score regarding the prediction of mortality in sepsis patients with cirrhosis or hepatic dysfunction.
Conclusions The mSOFA score was a good alternative to the original SOFA core in predicting mortality among sepsis patients admitted to the ICU.
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Acute Crit Care. 2024;39(1):194-198. Published online May 11, 2022
The main mechanism of Takotsubo cardiomyopathy (TCM) is catecholamine-induced acute myocardial stunning. Pheochromocytoma, a catecholamine-secreting tumor, can cause several cardiovascular complications, including hypertensive crisis, myocardial infarction, toxic myocarditis, and TCM. A 29-year-old woman presented to our hospital with general weakness, vomiting, dyspnea, and chest pain. The patient was nullipara, 28 weeks’ gestation, and had a cachexic morphology. Her cardiac enzyme levels were elevated and bedside echocardiography showed apical akinesia, suggesting TCM. The next day, she could not feel the fetal movement, and an emergency cesarean section was performed. After delivery, the patient experienced cardiac arrest and was transferred to the intensive care unit for cardiopulmonary resuscitation (CPR). Spontaneous circulation returned after 28 minutes of CPR, but cardiogenic shock continued, and extracorporeal membrane oxygenation (ECMO) was initiated. On the third day of ECMO maintenance, left ventricular ejection fraction improved and blood pressure stabilized. On the eighth day after ECMO insertion, it was removed. However, complications of the left leg vessels occurred, and several surgeries and interventions were performed. A left adrenal gland mass was found on computed tomography and was removed while repairing the leg vessels. Pheochromocytoma was diagnosed and left adrenalectomy was performed.
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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.
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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.
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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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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
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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
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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
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