Outcome In Septic Shock Research Articles

The effect of GM-CSF and predictors of treatment outcome in pediatric septic shock patients

BackgroundPediatric septic shock is a critical condition associated with high mortality rates, largely due to sepsis-induced immunosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been explored as a therapeutic intervention to counteract this immunosuppression. Despite its potential, the efficacy of GM-CSF in pediatric septic shock has not been clearly established. This study aims to investigate the impact of GM-CSF administration on survival rates and to identify key predictors of treatment outcomes in pediatric septic shock patients.MethodsWe conducted a retrospective cohort study at the Pediatric Intensive Care Unit (PICU) of Children’s Hospital of Fudan University, Shanghai, from January 1, 2019, to December 31, 2023. The study included pediatric patients diagnosed with septic shock, analyzing their demographic data, GM-CSF and adjunctive therapies, laboratory results, and clinical outcomes. We employed univariate and multivariate logistic regression models to assess the influence of GM-CSF on 28-day mortality and identify significant predictors of treatment outcomes.ResultsThe study included 200 pediatric patients, with 66 receiving GM-CSF treatment and 134 not treated with GM-CSF. The initial comparison showed a higher 28-day mortality in the GM-CSF group (59.1%) compared to the non-GM-CSF group (35.1%, P = 0.001). Notably, after adjustment for confounding factors, multivariate analysis revealed that the effect of GM-CSF treatment on 28-day mortality among pediatric septic shock patients did not reach statistical significance, with an odds ratio (OR) of 0.472 and a 95% confidence interval (CI) ranging from 0.153 to 1.457 (P = 0.192). However, the analysis indicated a potential trend suggesting that GM-CSF treatment may contribute to a reduction in 28-day mortality. In addition, significant predictors of treatment outcomes included hematopoietic stem cell transplantation (HSCT), lactic acid (LAC) levels, hospital-acquired septic shock (HASS), red blood cell (RBC) count, and platelet (PLT) count.ConclusionsGM-CSF treatment may benefit pediatric septic shock patients, especially those with higher lactic acid, and lower RBC and platelet counts. These factors, which are significant predictors of outcomes, should be monitored during therapy.

Evaluating shock index as a prognostic tool in septic shock patients

Background: Septic shock is a leading cause of morbidity and mortality in children worldwide. The shock index (SI), defined as a quotient obtained by dividing the heart rate (HR) with systolic blood pressure (SBP), is a potential tool that may aid in early prognostication of outcomes in paediatric septic shock, though data on its utility remains limited. Methods: A hospital-based cross-sectional study was conducted in the paediatric intensive care unit (PICU) at Navodaya Medical College, Raichur, over one year. A total of 100 children aged 1 month to 12 years with septic shock were included. SI values were calculated and analysed for their association with inotrope requirement, multiple organ dysfunction syndrome (MODS), length of PICU stay, and outcomes. Children with cardiogenic, hypovolemic, or obstructive shock and those previously treated at other centres were excluded. Results: Out of 100 children with septic shock, 76 survived and 24 died, with a mortality rate of 24%. Elevated SI values (>1.2) were seen in 78%, correlating with disease severity. Survivors had a mean SI of 0.9±0.1, while non-survivors had 1.3±0.2 (p<0.05). Among elevated SI cases, 64% required inotropes, and 42% developed MODS compared to 8% with normal SI (p<0.01). The average PICU stay was longer for elevated SI cases (7±3 days versus 4±1 days). Persistently high SI values predicted poor outcomes and mortality. Conclusions: Elevated SI can be a valuable non-invasive parameter that aids health care professionals in triaging sick children in a limited resource setting, allowing for timely referral to higher centres. Continuous monitoring of SI trends alongside HR and SBP can aid in early identification of high-risk patients, enabling timely and targeted interventions.

Impact of early goal-directed therapy on outcomes in adult septic shock: a systematic review

Septic shock is a critical form of sepsis, a life-threatening illness marked by organ failure due to an aberrant immunological response from the host. This condition frequently leads to multiple organ dysfunction syndrome, primarily caused by microbial imbalance. As septic shock poses significant challenges requiring immediate medical intervention to prevent organ failure and reduce mortality, research into its management is crucial. The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify relevant literature on EGDT's effects. Searches were conducted in PubMed, Web of Science, Cochrane Library, and EBSCOHost databases. Data were analyzed with RevMan software, and the Newcastle-Ottawa Quality Assessment Scale along with Cochrane's Risk of Bias tool were used to evaluate the quality of included studies. Studies were classified as having a high (0–3), moderate (4–6), or low (7–9) risk of bias. Results showed no significant differences in Sequential Organ Failure Assessment (SOFA) scores. Although EGDT reduced mortality rates, it did not demonstrate significant improvements in outcomes compared to standard treatment. The findings suggested that non-invasive, protocolized treatments might improve hemodynamics and mortality. The review indicated that advancements in standard sepsis management might have reduced the relative benefits of EGDT. Future research should focus on identifying patient subgroups that benefit most from EGDT, refining resuscitation techniques, and exploring less invasive approaches. Research into biomarkers and advanced monitoring technologies might provide deeper insights into patient responses, enabling more tailored and effective interventions.

Epidemiology and outcomes of septic shock in Thai children: a nationwide retrospective study from 2015 to 2022

BackgroundPaediatric septic shock is a formidable challenge worldwide that significantly impacts health care systems. This nationwide retrospective study analyses the prevalence and mortality rates of paediatric septic shock across Thailand from 2015 to 2022, focusing on hospital burdens, including mechanical ventilation and renal replacement therapy.MethodsThe study included paediatric patients ranging from infants to individuals under 18 years of age who were admitted to hospitals due to septic shock across Thailand. Data were retrospectively gathered from the Thai National Health Security Office for the years 2015–2022. The data included demographic data, clinical outcomes, and hospital burden indicators such as mechanical ventilation and renal replacement therapy.ResultsFrom 2015 to 2022, there were 30,718 paediatric admissions for septic shock, with a peak in 2019. The highest incidence was observed in infants, accounting for 44.7% of the cases. The prevalence rate increased from 190 per 100,000 population in 2015 to a peak of 280 per 100,000 population in 2020. Mortality rates decreased from 30.7% in 2015 to 20.2% in 2022, with a peak of 40.5% observed in the central region in 2015. The study highlighted a substantial health care burden, with 34.9% of patients requiring prolonged mechanical ventilation and 23.4% needing renal replacement therapy.ConclusionsDespite a decrease in mortality, paediatric septic shock remains a significant burden on the health care system in Thailand. Urgent improvements in resources and adherence to clinical guidelines, especially in under-resourced areas, are necessary. Addressing disparities in mortality and resource usage across hospital levels is vital for improving outcomes and reducing the health care burden of paediatric patients with septic shock.

The association between integrating echocardiography use in the management of septic shock patients and outcomes in the intensive care unit: a systematic review and meta-analysis.

Septic shock in critically ill patients can increases morbidity and mortality. We aimed to study the effect on outcomes when integrating point of care (POC) echocardiography in the management of septic shock patients in the Intensive Care Unit (ICU) who are being treated according to the Surviving Sepsis Campaign (SSC) guidelines. An electronic search of MEDLINE through PubMed, clinical trials.gov and google scholar was conducted for the period from January 1990-January 2024 to identify studies of septic shock adult and pediatric patients in the ICU managed according to SSC guidelines with or without POC echocardiography. Three reviewers extracted data independent of each other. Cochrane collaboration tool was used for bias assessment. Random effect meta-analysis used to pool data. A total of 1701 articles identified. Seven studies included in the final report with a total of 3885 patients. POC echocardiography guided septic shock management was associated with lower in-hospital and 28-day mortality (sOR = 0.82 [95%CI: 0.71-0.95], p = 0.01), more frequent initiation of inotropic support (sOR = 2.42 [95%CI 1.92-3.03], p < 0.0001) and shorter time to achieve lactate clearance (SMD = - 0.87h [95%CI - 1.23h to - 0.51h], p < 0.0001). Summary estimates did not achieve significance for effect of POC echocardiography on 24-h fluid intake (SMD = - 2.11ml [95%CI - 5.93ml to 1.72ml], p = 0.28) on mechanical ventilation-free days (SMD = 0.03days [95%CI - 0.04 to 0.10], p = 0.94). Shock reversal time analysis was less meaningful due to the small number of studies reporting outcome. POC echocardiography guided management in septic shock patients in the ICU can lead to a decrease in mortality, increase in initiation of inotropic support, and a decrease in lactate clearance time. Larger cohort studies and data collection and analysis are needed for further understanding and optimizing standardization of protocols for POC echocardiography use in septic shock patients in the ICU.

Impact of different blood pressure targets on cerebral hemodynamics in septic shock: A prospective pilot study protocol-SEPSIS-BRAIN.

Septic shock, a life-threatening condition, can result in cerebral dysfunction and heightened mortality rates. In these patients, disturbances in cerebral hemodynamics, as reflected by impairment of myogenic cerebral autoregulation (CA), metabolic regulation, expressed by critical closing pressure (CrCP) and reductions in intracranial compliance (ICC), can adversely impact septic shock outcomes. The general recommendation is to maintain a target mean arterial pressure (MAP) of 65 mmHg but the effect of different MAP targets on cerebral hemodynamics in these patients is not clear and optimal targets might be dependent on the status of CA. This protocol aims to assess the cerebral hemodynamics profile at different pressure targets in septic shock patients. Prospective, non-randomized, single-center trial, which will study cerebral hemodynamics in patients with septic shock within 48 hours of its onset. Patients will be studied at their baseline MAP and at three MAP targets (T1: 65, T2: 75, T3: 85 mmHg). Cerebral hemodynamics will be assessed by transcranial Doppler (TCD) and a skull micro-deformation sensor (B4C). Dynamic CA will be expressed by the autoregulation index (ARI), calculated by transfer function analysis, using fluctuations of MAP as input and corresponding oscillations in cerebral blood velocity (CBv). The instantaneous relationship between arterial blood pressure and CBv will be used to estimate CrCP and resistance-area product (RAP) for each cardiac cycle using the first harmonic method. The B4C will access ICC by intracranial pressure waveforms (P2/P1). The primary aim is to assess cerebral hemodynamics (ARI, CrCP, RAP, and P2/P1) at different targets of MAP in septic shock patients. Our secondary objective is to assess cerebral hemodynamics at 65mmHg (target recommended by guidelines). In addition, we will assess the correlation between markers of organ dysfunction (such as lactate levels, vasoactive drugs usage, SOFA score, and delirium) and CA. The results of this study may help to understand the effect of the recommended MAP and variations in blood pressure in patients with septic shock and impaired CA and ICC. Furthermore, the results can assist large trials in establishing new hypotheses about neurological management in this group of patients. Approval was obtained from the local Ethics Committee (28134720.1.0000.0048). It is anticipated that the results of this study will be presented at national and international conferences and will be published in peer-reviewed journals in 2024 and 2025. Trial registration number: NCT05833607. https://clinicaltrials.gov/study/NCT05833607.

Changes in the ratio of neutrophils to albumin depending on the severity of abdominal sepsis in patients with benign and malignant non-traumatic perforation of the left colon

Background. According to the Third International Consensus (Sepsis-3), sepsis is defined as a life-threatening organ dysfunction caused by an uncontrolled response of the affected organism to a new infection, and septic shock as a sepsis-related condition characterized by the development of circulatory failure accompanied by arterial hypotension, with lactatemia and requiring maintenance of blood pressure with vasopressors. Despite progress in diagnosing and treating sepsis in patients with intra-abdominal infections, it continues to be the leading cause of mortality among patients in emergency departments worldwide. Purpose – the objective of this study was to ascertain the capacity of the neutrophilto-albumin ratio (NAR) before surgery to predict the severity of abdominal sepsis and 30-day mortality in patients with benign and malignant non-traumatic perforation left side of the colon. Methods. This was a retrospective, cross-sectional study that analyzed 117 patients of different age groups with sepsis caused by colon perforation who were hospitalized and operated on from January 2014 to March 2024. To evaluate the diagnostic value of INA in predicting sepsis severity and 30-day mortality, we analyzed the biomarker’s ROC curves, including the determination of optimal cut-off thresholds and associated specificity and sensitivity. The association of INA, sepsis severity, and perforation type with 30-day mortality was investigated using survival analysis, including the comparison of Kaplan–Meier curves and the development and analysis of Cox proportional hazards regression models. Comparisons between groups of study patients concerning quantitative characteristics were conducted, with the presence of septic shock and treatment outcome serving as the independent variables. This was done using nonparametric criteria for independent measurements, specifically the Kruskal–Wallis and Mann–Whitney tests. The statistical significance of the relationships between the qualitative indicators of the study was assessed based on the χ2 criterion and the odds ratio. Results. The results demonstrated that the INR has a high prognostic value in determining the severity of sepsis. This was evidenced by a high value of the area under the ROC curve (AUC = 0.948, p = 2, 309×10–41 &lt; 0.05, 95% CI = 0.882–1.013). It has been demonstrated that the development of septic shock can be predicted by a preoperative INA value not exceeding 22.1, with the highest possible specificity (93.4%) and sensitivity (92.3%). The INA was also found to be an effective predictor of 30-day mortality in our data. The optimal INA threshold for mortality prediction was 23.8, with a specificity of 77.1 and sensitivity of 78.7% (AUC = 0.862, p = 6,072 ×10–28 &lt; 0.05, 95% CI = 0.786-0.919). Furthermore, no statistically significant association was observed between the type of perforation and patient outcomes (χ2 = 0.00493, p = 0.944, p &gt; 0.05). However, our study did confirm higher 30-day mortality in patients with colonic perforation in the presence of septic shock compared to patients with sepsis. Conclusions. The neutrophil-to-albumin ratio has been identified as an accurate and reliable biomarker for predicting the severity of abdominal sepsis. The biomarker demonstrated a specificity of 93.4%, a sensitivity of 92.3%, and a cut-off value of 22.1 for stratifying patients with septic shock. Furthermore, this biomarker was identified as an important predictor of 30-day mortality in both types of perforation, with an area under the ROC curve (AUC) of 0.862. Nevertheless, the value of this indicator for predicting mortality was somewhat lower than for determining septic shock. Furthermore, the results of the Cox regression analysis indicated that the impact of IA on survival was more pronounced in patients with malignant colon perforation. In patients with benign colon perforation, the model demonstrated a satisfactory fit to the input data. The presence or absence of septic shock did not influence the survival of patients in this category. The findings of the study indicated a significant correlation between INA and sepsis severity, suggesting that this indicator may serve as a straightforward prognostic tool for determining the severity of sepsis before surgery. Ultimately, the stratification of patients according to the severity of sepsis before surgery may lead to improved clinical outcomes for these patients.

The Management and Outcomes of Septic Shock Among Surgical Patients at the Jimma University Medical Center, Jimma, Ethiopia: A Prospective Study.

Background and objective Sepsis and septic shock are major healthcare issues in surgical patients admitted to the surgery ward or ICU, affecting millions of people worldwide annually, with a mortality rate between one in three and one in six of those affected.The incidence and mortality of sepsis vary greatly by region, with the highest prevalence in Sub-Saharan Africa, Oceania, South Asia, East Asia, and Southeast Asia. Of all sepsis cases in 2017, 33.1 million people suffered from ill health due to underlying infectious diseases, and 15.8 million suffered from underlying injuries or non-communicable diseases. Methods This prospective observational study was conducted at the Jimma University Medical Centre (JUMC) in Jimma town in southwest Ethiopia, from April 2023 to October 2023. Allsurgical patients aged ≥15 years who presented with or developed septic shock at the Jimma University Medical Centre were included. Results The study involved a total of 61 patients. The median age of the patients was 45 years [interquartile range (IQR): 40-60years], and 77% (n=47) of the patients were male. The most frequent source of infection in this study was community-acquired infection (83.3%, n=49). The most common focus of sepsis was the intra-abdominal infection of the digestive system (82%, n=50). Lactate level testing and blood cultures before administering antibiotics were not done for all septic shock patients. Source control surgery was performed in 52.5% (n=32) of patients after developing septic shock, and 84.4% (n=27) of surgeries were performed within 24 hours. The 30-day mortality rate was 80.3%, with an ICU mortality rate of 78.94%. The median length of stay in the ICU was three days (IQR: 1-5 days), and the median length of hospital stay was six days (IQR: 2-15 days). Conclusions The mortality rate in our cohort washigher compared to that in studies from high-income and low-income countries. There was poor adherence and compliance with the Surviving Sepsis Campaign (SSC) (the one-hour bundle) guidelines. The length of stay in hospitals and ICUs was lower compared to studies from high-income countries due to the high early mortality rates.

Antibiotic dose optimisation in the critically ill: targets, evidence and future strategies.

To highlight the recent evidence for antibiotic pharmacokinetics and pharmacodynamics (PK/PD) in enhancing patient outcomes in sepsis and septic shock. We also summarise the limitations of available data and describe future directions for research to support translation of antibiotic dose optimisation to the clinical setting. Sepsis and septic shock are associated with poor outcomes and require antibiotic dose optimisation, mostly due to significantly altered pharmacokinetics. Many studies, including some randomised controlled trials have been conducted to measure the clinical outcome effects of antibiotic dose optimisation interventions including use of therapeutic drug monitoring. Current data support antibiotic dose optimisation for the critically ill. Further investigation is required to evolve more timely and robust precision antibiotic dose optimisation approaches, and to clearly quantify whether any clinical and health-economic benefits support expanded use of this treatment intervention. Antibiotic dose optimisation appears to improve outcomes in critically ill patients with sepsis and septic shock, however further research is required to quantify the level of benefit and develop a stronger knowledge of the role of new technologies to facilitate optimised dosing.

Associations of tissue factor and tissue factor pathway inhibitor with organ dysfunctions in septic shock

Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002–0.005) vs. 0.006 (0.005–0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354–54023) vs. 28041 (21675–46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309–0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.

Loss-of-function/gain-of-function polymorphisms of the ATP sensitive P2X7R influence sepsis, septic shock, pneumonia, and survival outcomes.

Extracellular ATP (eATP) released from damaged cells activates the P2X7 receptor (P2X7R) ion channel on the surface of surrounding cells, resulting in calcium influx, potassium efflux and inflammasome activation. Inherited changes in the P2X7R gene (P2RX7) influence eATP induced responses. Single nucleotide polymorphisms (SNPs) of P2RX7 influence both function and signaling of the receptor, that in addition to ion flux includes pathogen control and immunity. Subjects (n = 105) were admitted to the ICU at the University Hospital Ulm, Germany between June 2018 and August 2019. Of these, subjects with a diagnosis of sepsis (n = 75), were also diagnosed with septic shock (n = 24), and/or pneumonia (n = 42). Subjects with pneumonia (n = 43) included those without sepsis (n = 1), sepsis without shock (n = 29) and pneumonia with septic shock (n = 13). Out of the 75 sepsis/septic shock patients, 33 patients were not diagnosed with pneumonia. Controls (n = 30) were recruited to the study from trauma patients and surgical patients without sepsis, septic shock, or pneumonia. SNP frequencies were determined for 16 P2RX7 SNPs known to affect P2X7R function, and association studies were performed between frequencies of these SNPs in sepsis, septic shock, and pneumonia compared to controls. The loss-of-function (LOF) SNP rs17525809 (T253C) was found more frequently in patients with septic shock, and non-septic trauma patients when compared to sepsis. The LOF SNP rs2230911 (C1096G) was found to be more frequent in patients with sepsis and septic shock than in non-septic trauma patients. The frequencies of these SNPs were even higher in sepsis and septic patients with pneumonia. The current study also confirmed a previous study by our group that showed a five SNP combination that included the GOF SNPs rs208294 (C489T) and rs2230912 (Q460R) that was designated #21211 was associated with increased odds of survival in severe sepsis. The results found an association between expression of LOF P2RX7 SNPs and presentation to the ICU with sepsis, and septic shock compared to control ICU patients. Furthermore, frequencies of LOF SNPs were found to be higher in sepsis patients with pneumonia compared to those without pneumonia. In addition, a five SNP GOF combination was associated with increased odds of survival in severe sepsis. These results suggest that P2RX7 is required to control infection in pneumonia and that inheritance of LOF variants increases the risk of sepsis when associated with pneumonia. This study confirms that P2RX7 genotyping in pneumonia may identify patients at risk of developing sepsis. The study also identifies P2X7R as a target in sepsis associated with an excessive immune response in subjects with GOF SNP combinations.

Association of chronic or acute systolic and diastolic heart failure with incidence rates of pneumonia, sepsis, and septic shock in patients with lung cancer.

e24005 Background: Systolic heart failure (SHF) and diastolic heart failure (DHF) can lead to volume overload and cause pulmonary venous congestion and pulmonary edema. While an association between lung cancer (LC) and increased infection rates is well established, we investigated whether chronic SHF or DHF, as well as acute SHF or DHF in concomitance with LC, influenced the incidence of pneumonia (PNA), sepsis, and septic shock. Methods: A retrospective study was conducted by obtaining patients with LC by applying specific ICD 10 codes (C34.0 - C34.9 including all sub-codes) from the National Inpatient Sample 2019-2020. Among this cohort, patients with acute and chronic SHF or DHF were further identified by applying specific ICD 10 codes ((I50.1 - I50.4 including all sub-codes). Pneumonia, sepsis, and septic shock outcomes were compared between LC patients with each of these types of heart failures versus those without using multivariate regression analysis (MVRA), adjusting for demographic factors, hospital-specific characteristics, common comorbidities and alcohol, smoking, or substance use. Results: 802,230 patients were identified with LC. 48.7% were female. 77.9% were Caucasian, 12.8% were African American, 4.6% were Hispanic, and 3.5% belonged to other ethnicities. Patients with LC and chronic SHF (n = 25880) had no significant difference in rates of PNA [Adjusted (Ad) odds ratio (OR): 0.9, p = 0.13] and sepsis (Ad OR: 0.9, p = 0.59) but had higher rates of septic shock (Ad OR: 1.4, p &lt; 0.001) compared to those LC patients without any heart failure (HF). Patients with LC who had acute SHF (n = 22295) showed higher rates of PNA (Ad OR: 1.4, p &lt; 0.001), sepsis (Ad OR: 1.5, p &lt; 0.001), as well as septic shock (Ad OR: 1.6, p &lt; 0.001) versus those without any HF. Patients with LC and concurrent chronic DHF (n = 31580) had similar rates of PNA (Ad OR: 1, p = 0.64), sepsis (Ad OR: 1.1, p = 0.62) and septic shock (Ad OR: 1, p = 0.77) compared to LC patients without any HF. However, acute DHF (n = 24080) led to a higher incidence of PNA (Ad OR: 1,4, p &lt; 0.001) and sepsis (Ad OR: 1.2, p = 0.05) in patients with LC, but no difference in the incidence of septic shock (Ad OR: 0.8, p = 0.072). Conclusions: Chronic SHF led to an increased incidence of septic shock, whereas acute SHF was associated with accentuated rates of PNA, sepsis, and septic shock in patients with LC. Chronic DHF did not predict an increased risk of infections; however, acute DHF was associated with enhanced rates of PNA and sepsis. Future investigations may focus on the effect of SHF or DHF on outcomes beyond hospitalization in patients with LC and the subtypes of LC and infection risk. Based on this signal-finding analysis, it may be postulated that early inter-disciplinary collaboration between oncology and cardiology may be crucial in managing patients with heart failure and LC and potentially lead to better patient outcomes.

Sex or gender differences in treatment outcomes of sepsis and septic shock.

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.

Impact of timing of antimicrobial therapy on outcome and mortality in severe sepsis and septic shock

Even though new antimicrobial treatments have been available for over 60 years, the fatality rate from septic shock has not decreased. Evolutionary pressure on microbial pathogens has, as expected, led to selection towards resistant species as a consequence of the creation of ever more broad-spectrum and strong antimicrobials. The ineffectiveness of antibiotic treatment of septic shock un the decades that followed may have been a result of this phenomena. The treatment of septic shock has traditionally focused on resuscitative measures. The management of these serious illnesses has not prioritised the prompt provision of effective antibiotic treatment.

Sepsis and Septic Shock in Patients Undergoing Thyroidectomy: Incidence, Risk Factors, and Outcomes

IntroductionPostoperative sepsis represents a rare complication following thyroidectomy. We aimed to explore the incidence, risk factors, sources, and outcomes of postoperative sepsis and septic shock among adult patients undergoing thyroidectomy. MethodsData from the American College of Surgeons National Surgical Quality Improvement Program were used in this retrospective cohort study. Patients aged ≥18 y who underwent elective thyroidectomy between 2005 and 2019 were included. Multivariable binary logistic regression models were computed to explore risk factors and outcomes of 30-d sepsis and septic shock. ResultsAmong the 180,373 included patients, 0.1% developed sepsis or septic shock. Male gender, low body mass index, American Society of Anesthesiologists classes 3-5, functional dependence, smoking, diabetes mellitus, pulmonary disease, inpatient surgery, malignant indication, clean-contaminated wound classification, and operation time ≥150 min were significant risk factors for development of sepsis or septic shock. Common infectious sources of sepsis included surgical site infections (29.6%), pneumonia (18.6%), urinary tract infections (16.2%), and multiple infections (6.9%). Patients with postoperative sepsis or septic shock were significantly more likely to develop complications, including wound disruption, stroke, cardiac and renal complications, thromboembolism, prolonged length of stay, unplanned reoperation, and mortality. ConclusionsSepsis is rare following thyroidectomy. Our study provides insight into risk factors and procedural characteristics which may contribute to the development of postoperative sepsis or septic shock in this population.

Procalcitonin and C-Reactive Protein in Critically Ill Patients with Sepsis and Septic Shock Admitted in an ICU of a Tertiary Care Hospital in Bangladesh

Background: Early intervention and predicting outcome has become a cornerstone in the treatment of sepsis as this may ensure the difference between survival and mortality. Both C-reactive protein and Procalcitonin have long been identified as good diagnostic markers of sepsis but their prognostic value is still a matter of debate. This study aims to find this particular point out. Objectives: Objective of this current study is to see the relationship of Procalcitonin and C-reactive protein respectively with the outcome of the patients with sepsis and septic shock and to compare their usefulness as predictors of outcome. Methods: This study was carried out in Intensive Care Unit of BIRDEM General Hospital, Shahbag, Dhaka for a period of one year. All consecutive patients with sepsis and septic shock were enrolled as study subjects during this period according to selection criteria. At the time of diagnosis that is at zero hour of development of sepsis or septic shock both C-reactive protein and Procalcitonin were measured and it was repeated at 24 hours. Data were collected in preformed data collection sheet and analyzed by the SPSS. Results: In this study, total 170 patients were enrolled as a case of sepsis or septic shock. The mean age was 59.5 ± 15.8 with a range between 20-96 years. Fifty seven (34%) patients had septic shock either during admission or during the first 24 hour of ICU stay and 46 (27.1%) patients did not survive their illness. The mean SOFA score was 6.30±2.18, mean duration of ICU stay 5.5.±2.98 days and mean MAP was 83.73±24.49 mmHg and 98 patients (57.65%) patients were ventilated during their admission. Diabetes mellitus had majority among co-morbidities with 147 (86.4%) patients having diabetes mellitus. Finally after calculating the cut off values from Youden’s index C-reactive protein was found to be more sensitive and Procalcitonin more specific as predictors of outcome. Conclusion: This study concludes that both Procalcitonin and C-reactive protein can individually predict outcome in sepsis and septic shock and one is not inferiorto the other.The dynamic changes of both these biomarkers over first 24 hours were also strongly associated with outcome. It was noted that while C-reactive protein was more sensitive, Procalcitonin was more specific. Bangladesh Crit Care J March 2024; 12 (1): 4-10

The scientific rationale and study protocol for the DPP3, Angiotensin II, and Renin Kinetics in Sepsis (DARK-Sepsis) randomized controlled trial: serum biomarkers to predict response to angiotensin II versus standard-of-care vasopressor therapy in the treatment of septic shock

BackgroundData to support the use of specific vasopressors in septic shock are limited. Since angiotensin II (AT2) was approved by the Food and Drug Administration in 2017, multiple mechanistically distinct vasopressors are available to treat septic shock, but minimal data exist regarding which patients are most likely to benefit from each agent. Renin and dipeptidyl peptidase 3 (DPP3) are components of the renin–angiotensin–aldosterone system which have been shown to outperform lactate in predicting sepsis prognosis, and preliminary data suggest they could prove useful as biomarkers to guide AT2 use in septic shock.MethodsThe DARK-Sepsis trial is an investigator-initiated industry-funded, open-label, single-center randomized controlled trial of the use of AT2 versus standard of care (SOC) vasopressor therapy in patients admitted to the intensive care unit (ICU) with vasodilatory shock requiring norepinephrine ≥ 0.1 mcg/kg/min. In both groups, a series of renin and DPP3 levels will be obtained over the first 24 h of treatment with AT2 or SOC. The primary study outcome will be the ability of these biomarkers to predict response to vasopressor therapy, as measured by change in total norepinephrine equivalent dose of vasopressors at 3 h post-drug initiation or the equivalent timepoint in the SOC arm. To determine if the ability to predict vasopressor response is specific to AT2 therapy, the primary analysis will be the ability of baseline renin and DPP3 levels to predict vasopressor response adjusted for treatment arm (AT2 versus control) and Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes will include rates of acute kidney injury, need for mechanical ventilation and kidney replacement therapy, lengths of stay in the ICU and hospital, ICU and hospital mortality, and rates of prespecified adverse events.DiscussionWith an armamentarium of mechanistically distinct vasopressor agents now available, sub-phenotyping patients using biomarkers has the potential to improve septic shock outcomes by enabling treatment of the correct patient with the correct vasopressor at the correct time. However, this approach requires validation in a large definitive multicenter trial. The data generated through the DARK-Sepsis study will prove crucial to the optimal design and patient enrichment of such a pivotal trial.Trial registrationClinicalTrials.gov NCT05824767. Registered on April 24, 2023.

Surviving Sepsis Campaign Research Priorities 2023.

To identify research priorities in the management, epidemiology, outcome, and pathophysiology of sepsis and septic shock. Shortly after publication of the most recent Surviving Sepsis Campaign Guidelines, the Surviving Sepsis Research Committee, a multiprofessional group of 16 international experts representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine, convened virtually and iteratively developed the article and recommendations, which represents an update from the 2018 Surviving Sepsis Campaign Research Priorities. Each task force member submitted five research questions on any sepsis-related subject. Committee members then independently ranked their top three priorities from the list generated. The highest rated clinical and basic science questions were developed into the current article. A total of 81 questions were submitted. After merging similar questions, there were 34 clinical and ten basic science research questions submitted for voting. The five top clinical priorities were as follows: 1) what is the best strategy for screening and identification of patients with sepsis, and can predictive modeling assist in real-time recognition of sepsis? 2) what causes organ injury and dysfunction in sepsis, how should it be defined, and how can it be detected? 3) how should fluid resuscitation be individualized initially and beyond? 4) what is the best vasopressor approach for treating the different phases of septic shock? and 5) can a personalized/precision medicine approach identify optimal therapies to improve patient outcomes? The five top basic science priorities were as follows: 1) How can we improve animal models so that they more closely resemble sepsis in humans? 2) What outcome variables maximize correlations between human sepsis and animal models and are therefore most appropriate to use in both? 3) How does sepsis affect the brain, and how do sepsis-induced brain alterations contribute to organ dysfunction? How does sepsis affect interactions between neural, endocrine, and immune systems? 4) How does the microbiome affect sepsis pathobiology? 5) How do genetics and epigenetics influence the development of sepsis, the course of sepsis and the response to treatments for sepsis? Knowledge advances in multiple clinical domains have been incorporated in progressive iterations of the Surviving Sepsis Campaign guidelines, allowing for evidence-based recommendations for short- and long-term management of sepsis. However, the strength of existing evidence is modest with significant knowledge gaps and mortality from sepsis remains high. The priorities identified represent a roadmap for research in sepsis and septic shock.

Neisseria meningitidis accumulate in large organs during meningococcal sepsis.

Neisseria meningitidis (Nm) is the cause of epidemic meningitis and fulminant meningococcal septicemia. The clinical presentations and outcome of meningococcal septic shock is closely related to the circulating levels of lipopolysaccharides (LPS) and of Neisseria meningitidis DNA (Nm DNA). We have previously explored the distribution of Nm DNA in tissues from large organs of patients dying of meningococcal septic shock and in a porcine meningococcal septic shock model. 1) To explore the feasibility of measuring LPS levels in tissues from the large organs in patients with meningococcal septic shock and in a porcine meningococcal septic shock model. 2) To evaluate the extent of contamination of non-specific LPS during the preparation of tissue samples. Plasma, serum, and fresh frozen (FF) tissue samples from the large organs of three patients with lethal meningococcal septic shock and two patients with lethal pneumococcal disease. Samples from a porcine meningococcal septic shock model were included. Frozen tissue samples were thawed, homogenized, and prepared for quantification of LPS by Pyrochrome® Limulus Amoebocyte Lysate (LAL) assay. N. meningitidis DNA and LPS was detected in FF tissue samples from large organs in all patients with meningococcal septic shock. The lungs are the organs with the highest LPS and Nm DNA concentration followed by the heart in two of the three meningococcal shock patients. Nm DNA was not detected in any plasma or tissue sample from patients with lethal pneumococcal infection. LPS was detected at a low level in all FF tissues from the two patients with lethal pneumococcal disease. The experimental porcine meningococcal septic shock model indicates that also in porcinis the highest LPS and Nm DNA concentration are detected in lungs tissue samples. The quantification analysis showed that the highest concentration of both Nm DNA and LPS are in the organs and not in the circulation of patients with lethal meningococcal septic shock. This was also shown in the experimental porcine meningococcal septic shock model. Our results suggest that LPS can be quantified in mammalian tissues by using the LAL assay.

Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study.

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock. The clinical findings for this study were already reported; MSC therapy was well-tolerated and safe in patients in this phase I clinical trial. In this exploratory metabolomics study, 9 out of 30 patients received an escalating dose of MSC treatment, while 21 patients were without MSC treatment. Serum metabolomics profiling was performed to detect and characterize metabolite changes due to MSC treatment and to help determine the sample size needed for a phase II clinical trial and to define a metabolomic response to MSC treatment. Serum metabolites were measured using 1H-NMR and HILIC-MS at times 0, 24 and 72 h after MSC infusion. The results demonstrated the significant impact of MSC treatment on serum metabolic changes in a dose- and time-dependent manner compared to non-MSC-treated septic shock patients. This study suggests that plasma metabolomics can be used to assess the response to MSC therapy and that treatment-related metabolomics effects can be used to help determine the sample size needed in a phase II trial. As this study was not powered to detect outcome, how the treatment-induced metabolomic changes described in this study of MSC-treated septic shock patients are related to outcomes of septic shock in the short and long term will need to be explored in a larger adequately powered phase II clinical trial.