Efficacy of dietary supplements on mortality and clinical outcomes in adults with sepsis and septic shock: A systematic review and network meta-analysis.

AIM: The aim of this network meta-analysis (NMA) was to investigate the effects of different dietary supplements on the mortality and clinical status of adults with sepsis. METHODS: We searched PubMed, EMBASE, and the Cochrane Library Central Register of Controlled Trials until February 2023. The inclusion criteria were: 1) randomized controlled trials (RCT)s; 2) adults suffering sepsis or septic shock; 3) evaluation of short- or long-mortality; and 4) publications between 1994 and 2023. The general information of studies and details of interventions were extracted. The primary outcome was short-term mortality (<90 days), and the secondary outcomes were long-term mortality (≥90 days), length of ICU and hospital stays, and duration of mechanical ventilation (MV). The risk of bias of RCTs was assessed using the Cochrane risk of bias tool 2 (ROB2). A random effect NMA was performed to rank the effect of each intervention using a frequentist approach. RESULTS: Finally, 56 RCTs with 5957 participants met the criteria. Approximately, one-third of RCTs were low risk of bias. NMA analysis revealed that there was no treatment more effective in short- or long-term mortality than control or other interventions, except for magnesium (RR: 0.33, 95% CI: 0.14, 0.79; GRADE = low) and vitamin C (RR: 0.81, 95% CI: 0.67, 0.99; low certainty evidence), which had beneficial effects on short-term mortality. Moreover, eicosapentaenoic acid, gamma-linolenic acid, and antioxidants (EPA + GLA + AOs) combination was the most effective, and magnesium, vitamin D and vitamin C were the other effective approaches in terms of duration of MV, and ICU length of stay. There was no beneficial dietary supplement for hospital stay in these patients. CONCLUSIONS: In septic patients, none of the dietary supplements had a substantial effect on mortality except for magnesium and vitamin C, which were linked to lower short-term mortality with low certainty of evidence. Further investigation into high-quality studies with the use of dietary supplements for sepsis should be highly discouraged.

Ineffectiveness of hemoadsorption in large animals with abdominal sepsis: a randomized controlled porcine study.

OBJECTIVES: The use of hemoadsorption (HA) has become popular in the treatment of vasoplegic states associated with massive cytokine release, including septic shock. However, this approach does not seem to be based on robust evidence, and it does not follow international guidelines. To understand the pathophysiological rationale and timing of HA, we conducted a large animal septic shock experiment. DESIGN: Prospective randomized large-animal peritoneal septic shock experiment. SETTING: Laboratory investigation. SUBJECTS: Twenty-six anesthetized, mechanically ventilated, and instrumented pigs randomly assigned into (1) sham-operated group with HA (SHAM, n = 5); (2) sepsis animals without HA (SEPSIS, n = 5); (3) sepsis group with HA at norepinephrine initiation (EARLY, n = 8); and (4) sepsis group with HA initiated at norepinephrine rate reaching 0.5 µg/kg/min (LATE, n = 8). INTERVENTIONS: Peritoneal sepsis was induced by cultivated autologous feces inoculation. A CytoSorb cartridge (200 g) with a blood flow rate of 200 mL/min and heparin anticoagulation was used to perform HA. The animals received sedation and intensive organ support up to 48 h or until they experienced cardiovascular collapse. MEASUREMENTS AND MAIN RESULTS: Systemic hemodynamics, multiple-organ functions, and immune-inflammatory response were measured at predefined periods. The HA treatment was not associated with any measurable benefit in terms of systemic hemodynamics and organ support. The systemic inflammatory markers were unaffected by any of the treatment timings. In contrast, the HA resulted in higher vasopressor load and decreased 36-h survival (5 animals in SHAM (100%), 4 (80%) in SEPSIS, 4 (57%) in EARLY, and 2 (25%) in LATE; p = 0.041). The HA exposure in healthy animals was associated with hemodynamic deterioration, systemic inflammatory response, and cytopenia. CONCLUSIONS: In this large-animal-controlled fulminant sepsis study, the HA was unable to counteract the disease progression in the early or advanced septic shock phase. However, findings from the HA-exposed sham animals suggest potential safety concerns.

Cardiac index and heart rate as prognostic indicators for mortality in septic shock: A retrospective cohort study from the MIMIC-IV database.

Background: Septic shock is a life-threatening condition that can lead to organ dysfunction and death. In the ICU, monitoring of cardiac index (CI) and heart rate (HR) is commonly used to guide management and predict outcomes in septic shock patients. However, there is a lack of research on the association between CI and HR and the risk of mortality in this patient population. Therefore, the aim of this study was to investigate the relationship between different levels of CI and HR and mortality in septic shock patients. Methods: Data analysis was obtained from the MIMIC-IV version 2.0 database. Sepsis and septic shock were primarily defined by sepsis-3, the third international consensus on sepsis and septic shock. CI was computed using cardiac output (CO) and body surface area (BSA). To evaluate the incidence of CI with respect to each endpoint (7-, 14-, 21-, and 28-day mortality), a restricted cubic spline curve function (RCS) was used. The optimal cutoff value for predicted mortality was determined using the Youden index. Analyses of KM curves, cox regression, and logistic regression were conducted separately to determine the relationship between various CI and HR and 28-day mortality. Results: This study included 1498 patients with septic shock. A U-shaped relationship between CI levels and risk of mortality in septic shock was found by RCS analysis (p < 0.001). CI levels within the intermediate range of 1.85-2.8 L/min/m2 were associated with a mortality hazard ratio (HR) < 1. In contrast, low CI (HR = 1.87 95% CI: 1.01-3.49) and high CI (HR = 1.93 95% CI: 1.26-2.97) had a significantly increased risk of mortality. The AUC for heart rate prediction of mortality by Youden index analysis was 0.70 95%CI:0.64-0.76 with a cut-off value of 93.63 bpm. According to the characteristics of HR and CI, patients were divided into six subgroups HR↓+CI intermediate group (n = 772), HR↓+CI↓ group (n = 126), HR↓+CI↑ group (n = 294), HR↑+CI intermediate group (n = 132), HR↑+CI↓ group (n = 24), and HR↑+CI↑ group (n = 150). The KM curves, COX regression, and logistic regression analysis showed that the survival rates the of HR↓+CI intermediate group, HR↓+CI↓ group, and HR↓+CI↑ were higher than the other groups. The risk factors of HR↑+CI intermediate group, HR↑+CI↓, and HR↑+CI↑ with ICU 28-day mortality were HR = 2.91 (95% CI: 1.39-5.97), HR = 3.67 (95% CI: 1.39-11.63), and HR = 5.77 (95% CI: 2.98-11.28), respectively. Conclusion: Our retrospective study shows that monitoring cardiac index and heart rate in patients with septic shock may help predict the organismal response and hemodynamic consequences, as well as the prognosis. Thus, healthcare providers should carefully monitor changes in these parameters in septic shock patients transferred to the ICU for treatment.

Integrated Analysis Identified TGFBI as a Biomarker of Disease Severity and Prognosis Correlated with Immune Infiltrates in Patients with Sepsis.

Background: Sepsis is a major contributor to morbidity and mortality among hospitalized patients. This study aims to identify markers associated with the severity and prognosis of sepsis, providing new approaches for its management and treatment. Methods: Data were mined from the Gene Expression Omnibus (GEO) databases and were analyzed by multiple statistical methods like the Spearman correlation coefficient, Kaplan-Meier analysis, Cox regression analysis, and functional enrichment analysis. Candidate indicator' associations with immune infiltration and roles in sepsis development were evaluated. Additionally, we employed techniques such as flow cytometry and neutral red staining to evaluate its impact on macrophage functions like polarization and phagocytosis. Results: Twenty-eight genes were identified as being closely linked to the severity of sepsis, among which transforming growth factor beta induced (TGFBI) emerged as a distinct marker for predicting clinical outcomes. Notably, reductions in TGFBI expression during sepsis correlate with poor prognosis and rapid disease progression. Elevated expression of TGFBI has been observed to mitigate abnormalities in sepsis-related immune cell infiltration that are critical to the pathogenesis and prognosis of the disease, including but not limited to type 17 T helper cells and activated CD8 T cells. Moreover, the protein-protein interaction network revealed the top ten genes that interact with TGFBI, showing significant involvement in the regulation of the actin cytoskeleton, extracellular matrix-receptor interactions, and phagosomes. These are pivotal elements in the formation of phagocytic cups by macrophages, squaring the findings of the Human Protein Atlas. Additionally, we discovered that TGFBI expression was significantly higher in M2-like macrophages, and its upregulation was found to inhibit lipopolysaccharide-induced polarization and phagocytosis in M1-like macrophages, thereby playing a role in preventing the onset of inflammation. Conclusion: TGFBI warrants additional exploration as a promising biomarker for assessing illness severity and prognosis in patients with sepsis, considering its significant association with immunological and inflammatory responses in this condition.

The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. Significance Statement In the quest to combat antibiotic-resistant bacterial infections and sepsis, an innovative approach has emerged in which nanoscale particles are enveloped in natural cell membranes purified from human blood cells. Since this technology shows the ability to (a) neutralize bacterial toxins that injure host cells and (b) quell the exaggerated septic inflammation that leads to deadly organ system failure, these novel nanomedicines may represent a versatile strategy to complement antibiotics and vaccines in the ongoing battle against infectious diseases.

Septic Shock After Endoscopic Sleeve Gastroplasty: A Post-procedural Complication?

BACKGROUND: ESG is a safe and effective technique in the obesity management, usually indicated in class I and II obesity. It is also an acceptable treatment in patients with class III obesity who have high surgical risk or refuse surgery. This procedure results in a significant weight loss and important improvement in metabolic comorbidities. Nevertheless, there are several procedure-related complications. Few cases of gastric perforation following ESG have been reported. We present a case of septic shock after ESG with preoperative diagnostic uncertainties. METHODS: We present the case of a 54-year-old male with a BMI of 43.6 kg/m2 who underwent ESG 7 days before in an external center. The patient came to the emergency department presenting abdominal pain, nausea, and vomiting since the day after the procedure. Physical examination revealed hemodynamic instability, altered level of consciousness, diffuse abdominal pain, and a painful umbilical lump due to a complicated umbilical hernia. Emergent surgery was decided after preoperative assessment. RESULTS: Intraoperative gastroscopy was performed, viewing a gastric ischemic ulcer covered with fibrin and a mucosal defect and suspecting a covered gastric perforation. Firstly, we performed an open approach to the complicated umbilical hernia. Subsequently, an exploratory laparoscopy was performed through the hernial ring, where a fibrin-covered area was evidenced in the anterior face of the gastric body, adhered to the round ligament by a transmural suture of the ESG. Additionally, multiple transmural sutures were observed adhered to the greater omentum and lesser sac and an intramural hematoma in the greater gastric curvature. No intra-abdominal free fluid was evidenced. A laparoscopic barbed suture of the area covered with fibrin was performed, after its release from the round ligament. The adhesions of the sutures and metallic material from the ESG were released. Finally, two abdominal drains were placed in the anterior and posterior gastric face. The patient presented superficial incisional surgical site infection and was discharged 6 days after laparoscopic surgery. CONCLUSIONS: ESG is a novel procedure, which has proven to be an effective alternative in the treatment of obesity. However, this technique may have major complications that can require urgent surgery.

Exploring the Efficacy of Midodrine for Tapering Off Vasopressors.

Sepsis and septic shock represent critical conditions, often necessitating vasopressor support in the intensive care unit (ICU). Midodrine, an oral vasopressor, has gathered attention as a potential adjunct to vasopressor therapy, aiming to facilitate weaning and improve clinical outcomes. However, the efficacy of midodrine remains questionable, with conflicting evidence from clinical trials and meta-analyses. This article provides a comprehensive review of the literature on midodrine's role in ICU settings by gathering evidence from multicenter trials, retrospective studies, and meta-analyses. While some studies suggest a limited benefit of midodrine in expediting vasopressor weaning and reducing ICU/hospital stays, others report potential advantages, particularly in reducing mortality rates among septic shock patients. Ongoing efforts aim to address knowledge gaps surrounding midodrine's efficacy and safety.

Parsimonious Waveform-derived Features consisting of Pulse Arrival Time and Heart Rate Variability Predicts the Onset of Septic Shock.

Sepsis is a major public health emergency and one of the leading causes of morbidity and mortality in critically ill patients. For each hour treatment is delayed, shock-related mortality increases, so early diagnosis and intervention is of utmost importance. However, earlier recognition of shock requires active monitoring, which may be delayed due to subclinical manifestations of the disease at the early phase of onset. Machine learning systems can increase timely detection of shock onset by exploiting complex interactions among continuous physiological waveforms. We use a dataset consisting of high-resolution physiological waveforms from intensive care unit (ICU) of a tertiary hospital system. We investigate the use of mean arterial blood pressure (MAP), pulse arrival time (PAT), heart rate variability (HRV), and heart rate (HR) for the early prediction of shock onset. Using only five minutes of the aforementioned vital signals from 239 ICU patients, our developed models can accurately predict septic shock onset 6 to 36 hours prior to clinical recognition with area under the receiver operating characteristic (AUROC) of 0.84 and 0.8 respectively. This work lays foundations for a robust, efficient, accurate and early prediction of septic shock onset which may help clinicians in their decision-making processes. This study introduces machine learning models that provide fast and accurate predictions of septic shock onset times up to 36 hours in advance. BP, PAT and HR dynamics can independently predict septic shock onset with a look-back period of only 5 mins.

GSNOR negatively regulates the NLRP3 inflammasome via S-nitrosation of MAPK14.

Hyperactivation of the NLRP3 inflammasome has been implicated in the pathogenesis of numerous diseases. However, the precise molecular mechanisms that modulate the transcriptional regulation of NLRP3 remain largely unknown. In this study, we demonstrated that S-nitrosoglutathione reductase (GSNOR) deficiency in macrophages leads to significant increases in the Nlrp3 and Il-1ß expression levels and interleukin-1ß (IL-1ß) secretion in response to NLRP3 inflammasome stimulation. Furthermore, in vivo experiments utilizing Gsnor-/- mice revealed increased disease severity in both lipopolysaccharide (LPS)-induced septic shock and dextran sodium sulfate (DSS)-induced colitis models. Additionally, we showed that both LPS-induced septic shock and DSS-induced colitis were ameliorated in Gsnor-/- Nlrp3-/- double-knockout (DKO) mice. Mechanistically, GSNOR deficiency increases the S-nitrosation of mitogen-activated protein kinase 14 (MAPK14) at the Cys211 residue and augments MAPK14 kinase activity, thereby promoting Nlrp3 and Il-1ß transcription and stimulating NLRP3 inflammasome activity. Our findings suggested that GSNOR is a regulator of the NLRP3 inflammasome and that reducing the level of S-nitrosylated MAPK14 may constitute an effective strategy for alleviating diseases associated with NLRP3-mediated inflammation.

Nutritional Intake in Children with Septic Shock: A Retrospective Single-Center Study.

Nutritional practice in children with severe sepsis or septic shock remains poorly described. We aimed to describe nutrition received by children with severe sepsis or septic shock and explore the association of nutritional intake with clinical outcomes. This study was a retrospective study of children who required pediatric intensive care unit (PICU) admission from 2009 to 2016. Outcomes were mortality, ventilator-free days (VFDs), and PICU-free days (IFDs). A total of 74 patients with septic shock or severe sepsis were identified. Forty-one (55.4%) patients received enteral nutrition (EN) only, 6 (8.1%) patients received parental nutrition (PN) only, 15 (20.3%) patients received both EN and PN, and 12 (16.2%) patients received intravenous fluids alone. Eight of 74 (10.8%) and 4 of 74 (5.4%) had adequate energy and protein intake, respectively. Patients who received early EN had lower odds of 28-day mortality (adjusted hazard ratio [HR] = 0.09, 95% confidence interval [CI]: 0.02, 0.45, p = 0.03) more 28-day VFDs (adjusted ß-coefficient = 18.21 [95% CI: 11.11, 25.32], p < 0.001), and IFDs (adjusted ß-coefficient = 16.71 [95% CI: 9.86, 23.56], p < 0.001) than patients who did not receive EN. Late EN was also associated with lower odds of mortality, more VFDs, and IFDs compared with no EN (HR = 0.06, 95% CI: 0.02, 0.23; p < 0.001; adjusted ß coefficient = 15.66, 95% CI: 9.31, 22.02; p < 0.001; and 12.34 [95% CI: 6.22, 18.46], p < 0.001; respectively). Inadequate calories and protein were not associated with mortality. EN in children with septic shock or severe sepsis was associated with improved clinical outcomes. Future prospective studies are required to explore the impact of EN timing and optimal nutritional intake in these children.

Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Effects of IV fluid restriction according to site-specific intensity of standard fluid treatment-protocol.

BACKGROUND: Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site-specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics. METHODS: We will assess the effects of heterogeneity in treatment intensity across one primary (all-cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90 days. We will classify sites based on the site-specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24 h in the standard-fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup. DISCUSSION: This study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock. REGISTRATIONS: The European Clinical Trials Database (EudraCT): 2018-000404-42, ClinicalTrials. gov: NCT03668236.

Biomarkers and sepsis severity as predictors of mechanical ventilation and mortality in COVID-19.

Introduction: Patients with septic shock face an elevated risk of mortality compared to those with sepsis. Several biomarkers, including lactate dehydrogenase, albumin, and lactate/albumin (L/A), have been associated with increased mortality in COVID-19 patients. This study aims to assess the relationship between sepsis, septic shock, and mortality, as well as the need for mechanical ventilation in COVID-19 patients. Demographic, sepsis severity factors, and biomarkers are examined. Methods: A retrospective case series from June 2020 to March 2021 included 490 patients diagnosed with sepsis or septic shock secondary to SARS-CoV-2 pneumonia. Time-to-event analyses were conducted for mechanical ventilation and mortality. Statistical significance was set at p ≤ .0038. Serum lactate, albumin, lactate/albumin ratio, C-reactive protein, platelet levels, and three sepsis severity scales, (CCI, SOFA, APACHE IV) were assessed. Results: Sepsis was identified in 352 patients (71.8%), while 138 had septic shock. Patients with septic shock were more likely to require invasive ventilator support. Factors associated with a higher risk of intubation included higher APACHE IV scores, elevated serum albumin levels, and increased L/A ratio. L/A ratio and serum lactate levels demonstrated the best diagnostic accuracy for mechanical ventilation (AUC, 0.964 and 0.946, respectively), mortality (AUC, 0.926 and 0.887, respectively). Discussion: Increased C-reactive protein, combined with increased serum lactate and a high lactate/albumin ratio, may assist clinicians in identifying COVID-19 patients at risk of mechanical ventilation and mortality upon admission. Optimal cut-off values for lactate (1.45-1.65 mmol/L) and L/A ratio (0.413) can aid in prioritizing medical care for at risk COVID-19 patients.

Capillary refill time response to a fluid challenge or a vasopressor test: an observational, proof-of-concept study.

BACKGROUND: Several studies have validated capillary refill time (CRT) as a marker of tissue hypoperfusion, and recent guidelines recommend CRT monitoring during septic shock resuscitation. Therefore, it is relevant to further explore its kinetics of response to short-term hemodynamic interventions with fluids or vasopressors. A couple of previous studies explored the impact of a fluid bolus on CRT, but little is known about the impact of norepinephrine on CRT when aiming at a higher mean arterial pressure (MAP) target in septic shock. We designed this observational study to further evaluate the effect of a fluid challenge (FC) and a vasopressor test (VPT) on CRT in septic shock patients with abnormal CRT after initial resuscitation. Our purpose was to determine the effects of a FC in fluid-responsive patients, and of a VPT aimed at a higher MAP target in chronically hypertensive fluid-unresponsive patients on the direction and magnitude of CRT response. METHODS: Thirty-four septic shock patients were included. Fluid responsiveness was assessed at baseline, and a FC (500 ml/30 mins) was administered in 9 fluid-responsive patients. A VPT was performed in 25 patients by increasing norepinephrine dose to reach a MAP to 80-85 mmHg for 30 min. Patients shared a multimodal perfusion and hemodynamic monitoring protocol with assessments at at least two time-points (baseline, and at the end of interventions). RESULTS: CRT decreased significantly with both tests (from 5 [3.5-7.6] to 4 [2.4-5.1] sec, p = 0.008 after the FC; and from 4.0 [3.3-5.6] to 3 [2.6 -5] sec, p = 0.03 after the VPT. A CRT-response was observed in 7/9 patients after the FC, and in 14/25 pts after the VPT, but CRT deteriorated in 4 patients on this latter group, all of them receiving a concomitant low-dose vasopressin. CONCLUSIONS: Our findings support that fluid boluses may improve CRT or produce neutral effects in fluid-responsive septic shock patients with persistent hypoperfusion. Conversely, raising NE doses to target a higher MAP in previously hypertensive patients elicits a more heterogeneous response, improving CRT in the majority, but deteriorating skin perfusion in some patients, a fact that deserves further research.

Invasive group A streptococcal infection can be fatal to pregnant women in restricted medical resources remote areas-Emergent alert after COVID-19 pandemic.

Invasive group A streptococcal (iGAS) infection is a leading cause of maternal death. The increase in the number of patients with iGAS in Japan is markedly greater than before the coronavirus pandemic. We encountered a case of iGAS infection, on a remote island with restricted medical resources, in a third-trimester pregnant woman, resulting in both maternal and fetal death. A 34-year-old woman was admitted via a local general hospital with a high fever. Intrauterine fetal death disseminated intravascular coagulation, and septic shock were confirmed. Broad-spectrum antibiotics were started, and the patient was returned to the local general hospital. Eight hours after arrival, the patient died of circulatory and respiratory dysfunction complications. iGAS infections in remote areas may directly lead to life-threatening conditions and should be treated as an emergency, comparable to the serious conditions of placental abruption or placenta previa.

Pylephlebitis combined with septic shock secondary to acute nonperforated appendicitis: a case report.

Pylephlebitis, which is a type of septic thrombophlebitis of the portal vein, is a rare and life-threatening complication that commonly occurs following appendicitis. However, nonspecific abdominal complaints and fever can impede the diagnosis of pylephlebitis. Timely use of appropriate antibiotics and anticoagulants is paramount for treating this condition. We present a case of pylephlebitis and septic shock caused by acute nonperforated appendicitis. A 32-year-old man presented with migratory right lower abdominal pain. Blood cultures showed the presence of Escherichia coli. Blood test results showed increased bilirubin concentrations and coagulation factor abnormalities. A computed tomographic abdominal scan showed that the portal vein had a widened intrinsic diameter. After intensive care treatment with antibiotics, antishock therapy, anticoagulants, and other supportive treatments, the infection was monitored, the abdominal pain disappeared, and the jaundice subsided. Laparoscopic appendectomy was performed. Histopathology showed acute suppurative appendicitis, and no abnormalities were observed during the follow-up period after discharge. A multidisciplinary approach is mandatory for the decision-making process in the presence of pylephlebitis caused by appendicitis to obtain a correct diagnosis and prompt treatment. Similarly, the timing of appendectomy is important for minimizing intra- and postoperative complications.

A service evaluation of measuring fluid responsiveness in acutely unwell hypotensive patients outside of critical care.

INTRODUCTION: Early recognition and prompt, appropriate management may reduce mortality in patients with sepsis. The Surviving Sepsis Campaign's guidelines suggest the use of dynamic measurements to guide fluid resuscitation in sepsis; although these methods are rarely employed to monitor cardiac output in response to fluid administration outside intensive care units. This service evaluation investigated the introduction of a nurse led protocolised goal-directed fluid management using a non-invasive cardiac output monitor to the standard assessment of hypotensive ward patients. METHODS: We introduced the use of a goal-directed fluid management protocol into our critical care outreach teams' standard clinical assessment. Forty-nine sequential patients before and thirty-nine after its introduction were included in the assessment. RESULTS: Patients in the post-intervention cohort received less fluid in the 6 h following outreach assessment (750mls vs 1200mls). There were no differences in clinical background or rates of renal replacement therapy, but rates of invasive and non-invasive ventilation were reduced (0% vs 31%). Although the groups were similar, the post-intervention patients had lower recorded blood pressures. CONCLUSION: IV fluid therapy in the patient with hypotension complicating sepsis can be challenging. Excessive IV fluid administration is commonplace and associated with harm, and the use of advanced non-invasive haemodynamic monitoring by trained nurses can provide objective evaluation of individualised response to treatment. Avoiding excessive IV fluid and earlier institution of appropriate vasopressor therapy may improve patient outcomes. IMPLICATIONS FOR CLINICAL PRACTICE: Adoption of dynamic measures of cardiac output outside of critical care by trained critical care nurses is feasible and may translate into improved patient outcomes. In hospitals with a nurse-led critical care outreach service, consideration should be given to such an approach.

Hemodynamic goals in sepsis and septic shock resuscitation: An umbrella review of systematic reviews and meta-analyses with trial sequential analysis.

OBJECTIVE: The objective of this study was to verify whether any parameter among those used as the target for haemodynamic optimisation (e.g., mean arterial pressure, central venous oxygen saturation, systolic or diastolic dysfunction, CO2 gap, lactates, right ventricular dysfunction, and PvaCO2/CavO2 ratio) is correlated with mortality in an undifferentiated population with sepsis or septic shock. METHODS: An umbrella review, searching MEDLINE, the Cochrane Database of Systematic Reviews, Health Technology Assessment Database, and the JBI Database of Systematic Reviews and Implementation Reports, was performed. We included systematic reviews and meta-analyses enrolling a population of unselected patients with sepsis or septic shock. The main outcome was mortality. Two authors conducted data extraction and risk-of-bias assessments independently. We used a random-effects model to pool binary and continuous data and summarised estimates of effect using equivalent odds ratios (eORs). We used the ROBIS tool to assess risk of bias and the assessment of multiple systematic reviews 2 score to assess global quality. DATA SYNTHESIS: 17 systematic reviews and meta-analyses (15 828 patients) were included in the quantitative analysis. Diastolic dysfunction (eOR: 1.42; 95% confidence interval [CI]: 1.14-1.76), PvaCO2/CavO2 ratio (eOR: 2.15; 95% CI: 1.37-3.37), and CO2 gap (eOR: 1.86; 95% CI: 1.07-3.25) showed a significant correlation with mortality. Lactates were the parameter with highest inconsistency (I2 = 92%). Central venous oxygen saturation and right ventricle dysfunction showed significant statistical excess test of significance (p-value = 0.009 and 0.005, respectively). None of the considered parameters showed statistically significant publication bias. CONCLUSIONS: According to this umbrella review, diastolic dysfunction is the haemodynamic variable that is most closely linked to the prognosis of septic patients. The PvaCO2/CavO2 ratio and the CO2gap are significantly related to the mortality of septic patients, but the poor quality of evidence or the low number of cases, studied so far, limit their clinical applicability. CLINICAL TRIAL REGISTRATION: PROSPERO: International prospective register of systematic reviews, 2023, CRD42023432813 (Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023432813).

A Guide to the Use of Vasopressors and Inotropes for Patients in Shock.

Shock is a life-threatening circulatory failure that results in inadequate tissue perfusion and oxygenation. Vasopressors and inotropes are vasoactive medications that are vital in increasing systemic vascular resistance and cardiac contractility, respectively, in patients presenting with shock. To be well versed in using these agents is an important skill to have in the critical care setting where patients can frequently exhibit symptoms of shock. In this review, we will discuss the pathophysiological mechanisms of shock and evaluate the current evidence behind the management of shock with an emphasis on vasopressors and inotropes.