Therapy For Septic Shock Research Articles

P-1516. Addition of Single-Dose Aminoglycosides to Empiric Beta-Lactam Therapy in Septic Shock in a Setting with High Antimicrobial Resistance Rates

Abstract Background At the Detroit Medical Center (DMC), the addition of an aminoglycoside (AMG) to β-lactam therapy is recommended in patients with septic shock due to high resistance rates; however, studies assessing the benefit of such combinations have yielded conflicting results. The objective of this study is to compare the outcomes of patients with septic shock who receive empiric β-lactam therapy with and without an AMG.Figure 1.Mortality Outcomes Methods This is a retrospective cohort study from 5/2021 to 7/2023. Patients were included if they met the following: 2 of 4 SIRS criteria, received vasopressors, serum lactate > 2 mmol/L, and appropriate empiric antimicrobial therapy within 24 hrs of admission . Patients who received an AMG within 24 hrs of admission were included in the AMG cohort, and those who did not were included in the control group. Key exclusion criteria were COVID-19, burn injury, and transfer to hospice care within 4 days of admission. The primary outcome was all-cause mortality at 7 days ; secondary outcomes included 30-day mortality, vasopressor-free days by day 7, ventilator-free days by day 28, and nephrotoxicity by day 7.Table 1.Patient and treatment characteristics Results Seventy-six patients were included (AMG=38; Control=38). The most common source of infection in AMG and control groups was pulmonary (44% vs. 31%, p=0.18). More AMG patients had a presumed SSTI source (17% vs. 0.0%, p=0.0049) patients, positive blood culture (79% vs. 26%, p< 0.0001), prior history of MDRO pathogen (22% vs. 0.0%, p=0.003), and received meropenem as initial empiric therapy (40% vs. 3%, p< 0.0001). APACHE II scores were similar (30 vs. 28, p=0.09). Time to appropriate antibiotic therapy was 4.8 hrs in the AMG group vs. 6.4 hrs in the control group, p=0.81. There were no differences in 7-day mortality (47% vs. 40%, p=0.49), 30-day mortality (63% vs. 53%, p=0.3527), vasopressor-free days by day 7 (2 vs. 2, p=0.08), or ventilator-free days by day 28 (2.5 vs. 8.5, p=0.31). There were also no differences in nephrotoxicity by day 7 (50% vs. 67%, p=0.23).Table 1.Patient and treatment characteristics, continued Conclusion Further evaluations should be conducted to determine whether an AMG in combination with β-lactams should be used in patients with septic shock.Table 2.Other clinical outcomes Disclosures All Authors: No reported disclosures

Personalized Adjunctive Hemoperfusion Therapy for Refractory Septic Shock Caused by Vibrio Cholerae in Thalassemia Patient

This case report describes a patient with Beta-thalassemia/hemoglobin E that developed Vibrio cholerae septicemia, leading to refractory septic shock with a maximum norepinephrine equivalent dose of 1.84 µg/kg/min and multi-organ failure. As the patient remained in refractory shock despite receiving proper antibiotics and organ support for 48 hours, adjunctive therapy including, HA330 hemoperfusion, was initiated. Shock reversal and significant reduction of inflammatory cytokines were achieved after two intervention sessions. The patient was discharged home, despite an initial predicted mortality rate of 85% based on Acute Physiology and Chronic Health Evaluation II (APACHE II).

Heterogeneity in the Effect of Early Goal-Directed Therapy for Septic Shock: A Secondary Analysis of Two Multicenter International Trials.

The optimal approach for resuscitation in septic shock remains unclear despite multiple randomized controlled trials (RCTs). Our objective was to investigate whether previously uncharacterized variation across individuals in their response to resuscitation strategies may contribute to conflicting average treatment effects in prior RCTs. We randomly split study sites from the Australian Resuscitation of Sepsis Evaluation (ARISE) and Protocolized Care for Early Septic Shock (ProCESS) trials into derivation and validation cohorts. We trained machine learning models to predict individual absolute risk differences (iARDs) in 90-day mortality in derivation cohorts and tested for heterogeneity of treatment effect (HTE) in validation cohorts and swapped these cohorts in sensitivity analyses. We fit the best-performing model in a combined dataset to explore roles of patient characteristics and individual components of early goal-directed therapy (EGDT) to determine treatment responses. Eighty-one sites in Australia, New Zealand, Hong Kong, Finland, Republic of Ireland, and the United States. Adult patients presenting to the emergency department with severe sepsis or septic shock. EGDT vs. usual care. A local-linear random forest model performed best in predicting iARDs. In the validation cohort, HTE was confirmed, evidenced by an interaction between iARD prediction and treatment (p < 0.001). When patients were grouped based on predicted iARDs, treatment response increased from the lowest to the highest quintiles (absolute risk difference [95% CI], -8% [-19% to 4%] and relative risk reduction, 1.34 [0.89-2.01] in quintile 1 suggesting harm from EGDT, and 12% [1-23%] and 0.64 [0.42-0.96] in quintile 5 suggesting benefit). Sensitivity analyses showed similar findings. Pre-intervention albumin contributed the most to HTE. Analyses of individual EGDT components were inconclusive. Treatment response to EGDT varied across patients in two multicenter RCTs with large benefits for some patients while others were harmed. Patient characteristics, including albumin, were most important in identifying HTE.

A pilot randomized controlled trial comparing noradrenaline and adrenaline as a first-line vasopressor for fluid-refractory septic shock in neonates.

Limited data exists on noradrenaline therapy in neonatal septic shock. We compared the efficacy of noradrenaline with adrenaline in neonatal septic shock. This single center, open label, pilot randomized controlled trial included neonates with clinical evidence of sepsis and shock. Primary outcomes were: 1) resolution of shock one hour after treatment, and 2) mortality during hospital stay. Secondary outcomes included: need for additional vasopressors; hemodynamic stability without further administration of vasopressors for ≥2 h; changes in blood pressure and heart rate after 1 h of vasopressor treatment; and morbidities during the hospital stay. Of 65 eligible neonates, 42 were randomized (21 each in adrenaline and noradrenaline treatment arms) between August 2020 and January 2022, at level III neonatal intensive care unit (NICU) of Bharati Vidyapeeth Deemed University Medical College and Hospital (BVDUMCH). The mean (SD) gestational age and mean (SD) birth weight were 36.1(4.2) weeks and 1.8 (0.2) kilograms birth weight for noradrenaline and 36.9 (4.1) weeks and 1.7 (0.7) kilograms for adrenaline. Shock resolved within 1 h of vasopressor therapy in 76.2% neonates in the noradrenaline arm and 61.9% in adrenaline arm (p value-0.53). Mortality during hospital stay was 28.6% (6/21) in noradrenaline group and 33.3% (7/21) in adrenaline group (p value- 0.58). Additional vasopressors were required in 23.8% neonates of the noradrenaline group compared to 38.1% neonates in adrenaline arm (p value-0.53). Median (SD) duration of intensive care stay was 6 (SD) days in the noradrenaline group and 10 (SD) days in the adrenaline group (p value-0.045). Among neonates with septic shock, the efficacy of noradrenaline was comparable to adrenaline in resolving septic shock after one hour of infusion and on the mortality during hospital stay. https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=NDI2NTc=&Enc=&userName=noradrenaline, Clinical Trials Registry - India with identifier CTRI/2020/08/027185 (17/08/2020).

Use of Venous to Arterial Carbon Dioxide Tension Difference to Guide Resuscitation Therapy in Septic Shock

Abstract Background Early recognition and correction of tissue hypoperfusion is a cornerstone in the management of septic shock patients. The venous to arterial carbon dioxide tension difference, which is a marker of the adequacy of cardiac output to global metabolic demand, is a helpful additional means to detect patients who stay under resuscitation after optimization of o2 derived parameters. In this regard, its monitoring should help the clinicians for the decision of giving therapy targeting at increasing cardiac output. Aim of the Work Venous To arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock. Patients and Methods This study was a prospective, cross sectional study done on patients recruited from Respiratory ICU at Ain Shams University Results The P(v-a)CO2/C(a-v)O2 ratio might provide additional information for assessments of oxygen debt, it may become a specific end point for resuscitation. However, the P(v-a)CO2/C(a-v)O2 ratio depends on complex interactions between the central venous oxygen saturation (Scvo2), P(v-a)CO2, hemoglobin concentration (Hb), arterial oxygen saturation (Sao2), and arterial oxygen tension (Pao2). Thus, many factors can influence the calculation of the P(v-a)CO2/C(a-v)O2 ratio in real clinical practice. The value of the P(v-a)CO2/C(a-v)O2 ratio remains controversial. Conclusion In the presence of a normal/high ScvO2 (≥ 70%), an elevated ΔPCO2 still suggests that rising cardiac output can be indicated with the purpose of reducing global tissue hypoxia. However, if both ScvO2 and ΔPCO2 are normal in a state of global anaerobic metabolism, manipulating the microcirculation will probably be ineffective to reduce oxygen deficit.

Oxiris Membrane Performance in Patients with Septic Shock and Continuous Kidney Replacement Therapy Requirement: A Randomized Controlled Trial

Oxiris Membrane Performance in Patients with Septic Shock and Continuous Kidney Replacement Therapy Requirement: A Randomized Controlled Trial

Efficacy of methylene blue in refractory septic shock: study protocol for a multicenter, randomized, placebo-controlled trial

BackgroundSeptic shock is now the leading cause of mortality in intensive care units (ICUs). Refractory septic shock requires high doses of vasopressors. Some previous studies have revealed that methylene blue could improve hypotension status and help reduce the dosage of catecholamines. This study aims to investigate the clinical effect of methylene blue in septic shock and explore whether it can increase arterial pressure and reduce the usage of vasopressors.MethodsThis study is a multicenter, randomized, placebo-controlled trial planning to include 100 refractory septic shock patients. The protocol is to administer a bolus of 2 mg/kg methylene blue intravenously followed by a continuous infusion of 0.5 mg/kg/h for 48 h. The primary outcome is the total dose of vasopressor required in refractory septic shock in the first 48 h. Secondary outcomes include other hemodynamic parameters, oxygen metabolism indexes, tissue perfusion indexes, major organ function indexes, and certain plasma cytokines and other factors.DiscussionThis protocol aims to evaluate the safety and efficacy of methylene blue as adjuvant therapy for refractory septic shock. The main outcome measure will be vasopressor requirements and hemodynamic parameters. Additionally, bedside ultrasonography, blood gases, and cytokines will be assessed to evaluate perfusion, respiratory, and metabolic effects. The results are intended to provide evidence on the safety and efficacy of methylene blue in refractory septic shock, guiding clinical decision-making.Trial registrationThis clinical trial has been registered at ChiCTR (https://www.chictr.org.cn/) on March 16, 2023. ChiCTR registration number: ChiCTR2300069430.

Veno-Venous Extracorporeal Membrane Oxygenation in COVID-19-Associated ARDS: Predictors of Mortality

The aim of the study was to identify factors associated with hospital mortality in patients with COVID-19associated acute respiratory distress syndrome (ARDS) receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO).Materials and methods. The retrospective study included data from the medical records of 123 patients treated in the intensive care unit (ICU) № 7 of the City Clinical Hospital № 52 of Moscow Department of Health. ECMO was initiated in all patients for respiratory indications according to current recommendations. A number of factors potentially associated with mortality were systematized and analyzed. Statistical processing to identify predictors of death included univariate analysis and calculation of odds ratio (OR), ROC analysis with calculation of area under the ROC curve (AUROC).Results. The resulting mortality rate was 87% (107/123), 11% (14/107) of all deaths occurred after weaning from ECMO. High VV-ECMO flow, delayed initiation of mechanical ventilation and ECMO therapy, and low pH at the time of ECMO initiation were identified as independent predictors of death in the study group. Low median albumin concentration and prolonged use of vasopressors were identified as predictors of death within 28 days of initiation of VV-ECMO. Development of acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT), septic shock and its recurrences, and the use of extracorporeal blood purification therapy for septic shock were found to be predictors of death during VV-ECMO therapy.Conclusion. High-flow VV-ECMO regimen, delayed initiation of mechanical ventilation and ECMO support, hypoalbuminemia, prolonged need for norepinephrine infusion, development of AKI requiring CRRT, septic shock occurrence and the number of its recurrences requiring extracorporeal blood purification therapy during VV-ECMO support were identified as predictors of death in patients with COVID-19-associated ARDS after initiation of VV-ECMO therapy.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Veno-Arterial Extracorporeal Membrane Oxygenation in the Rat.

Despite significant efforts toward improving therapy for septic shock, mortality remains high. Applying veno-arterial (V-A) extracorporeal membrane oxygenation (ECMO) in this context remains controversial. Since the cannulation of the femoral artery for V-A ECMO return leads to lower body hyperoxia, this study investigated the impact of V-A ECMO therapy on the intestinal and hepatic microcirculation during septic shock in a rodent model. Thirty male Lewis rats were randomly assigned to receive V-A ECMO therapy with low (60 mL/kg/min) or high (90 mL/kg/min) blood flow or a sham procedure. Hemodynamic data were collected through a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by intravenous administration of lipopolysaccharide (1 mg/kg). The rats received lung-protective ventilation during V-A ECMO therapy. The hepatic and intestinal microcirculation was measured by micro-lightguide spectrophotometry after median laparotomy for two hours. Systemic and pulmonary inflammation was detected via enzyme-linked immunosorbent assays (ELISA) of the plasma and bronchoalveolar lavage (BAL), respectively, measuring tumor necrosis factor-alpha (TNF-α), interleukins 6 (IL-6) and 10 (IL-10), and C-X-C motif ligands 2 (CXCL2) and 5 (CXCL5). Oxygen saturation and relative hemoglobin concentration were reduced in the hepatic and intestinal microcirculation during V-A ECMO therapy, independent of the blood flow rate. Further, rats treated with V-A ECMO therapy also presented elevated systolic, diastolic, and mean arterial blood pressure and increased stroke volume, cardiac output, and left ventricular end-diastolic volume. However, left ventricular end-diastolic pressure was only elevated during high-flow V-A ECMO therapy. Blood gas analysis revealed a dilutional anemia during V-A ECMO therapy. ELISA analysis showed an elevated plasma CXCL2 concentration only during high-flow V-A ECMO therapy and elevated BAL CXCL2 and CXCL5 concentrations only during low-flow V-A ECMO therapy. Rats undergoing V-A ECMO therapy exhibited impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Increased pulmonary inflammation was detected only during low-flow V-A ECMO therapy in septic shock.

Acute kidney injury in Staphylococcus aureus bacteraemia: a recurrent events analysis

ObjectivesTo estimate risk factors for acute kidney injury (AKI) and the effect of AKI on mortality in Staphylococcus aureus bacteraemia, while taking into account recurrent AKI episodes, competing risks, time-varying variables, and time-varying effects. MethodsWe performed an unplanned analysis using data from a multicentre cohort study of patients with Staphylococcus aureus bacteraemia (SAB). The primary outcome was cumulative incidence of AKI, according to Kidney Disease Improving Global Outcomes definitions. ResultsWe included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (hazard ratio (HR) 1.013, 95% CI 1.001–1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01–1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28–2.42), septic shock (HR 3.28, 95% CI 2.31–4.66), persistent bacteraemia (HR 1.53, 95% CI 1.08–2.17), and vancomycin therapy (HR 1.80, 95% CI 1.05–3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin, and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91–6.23). DiscussionThe incidence of AKI in SAB is high and a substantial proportion of patients develop recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. The clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.

New Insights into Hepatic and Intestinal Microcirculation and Pulmonary Inflammation in a Model of Septic Shock and Venovenous Extracorporeal Membrane Oxygenation in the Rat.

Treatment of critically ill patients with venovenous (V-V) extracorporeal membrane oxygenation (ECMO) has gained wide acceptance in the last few decades. However, the use of V-V ECMO in septic shock remains controversial. The effect of ECMO-induced inflammation on the microcirculation of the intestine, liver, and critically damaged lungs is unknown. Therefore, the aim of this study was to measure the hepatic and intestinal microcirculation and pulmonary inflammatory response in a model of V-V ECMO and septic shock in the rat. Twenty male Lewis rats were randomly assigned to receive V-V ECMO therapy or a sham procedure. Hemodynamic data were measured by a pressure-volume catheter in the left ventricle and a catheter in the lateral tail artery. Septic shock was induced by the intravenous infusion of lipopolysaccharide (1 mg/kg). During V-V ECMO therapy, rats received lung-protective ventilation. The hepatic and intestinal microcirculation was assessed by micro-lightguide spectrophotometry after median laparotomy for 2 h. Systemic and pulmonary inflammation was measured by enzyme-linked immunosorbent assays of plasma and bronchoalveolar lavage (BAL), respectively, which included tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-10, C-X-C motif ligand 2 (CXCL2), and CXCL5. Reduced oxygen saturation and relative hemoglobin concentration were measured in the hepatic and intestinal microcirculation during treatment with V-V ECMO. These animals also showed increased systolic, mean, and diastolic blood pressures. While no differences in left ventricular ejection fraction were observed, animals in the V-V ECMO group presented an increased heart rate, stroke volume, and cardiac output. Blood gas analysis showed dilutional anemia during V-V ECMO, whereas plasma analysis revealed a decreased concentration of IL-10 during V-V ECMO therapy, and BAL measurements showed increased concentrations of TNF-α, CXCL2, and CXCL5. Rats treated with V-V ECMO showed impaired microcirculation of the intestine and liver during septic shock despite increased blood pressure and cardiac output. Despite lung-protective ventilation, increased pulmonary inflammation was recognized during V-V ECMO therapy in septic shock.

ExtraCorporeal Membrane Oxygenation in the therapy for REfractory Septic shock with Cardiac function Under Estimated (ECMO-RESCUE): study protocol for a prospective, multicentre, non-randomised cohort study

IntroductionSevere septic cardiomyopathy (SCM) is one of the main causes of refractory septic shock (RSS), with a high mortality. The application of venoarterial extracorporeal membrane oxygenation (ECMO) to support the...

Combating bacterial resistance to Meropenem by infusion strategy applied to septic burn patients with vasopressor requirements or acute kidney injury to achieve the target

Introduction: Faced with the growing challenge to the use of antimicrobials for the adequate and effective therapy of nosocomial infections, international health agencies have reinforced that combating bacterial resistance and preventing the development of multidrug-resistant (MDR) strains are urgent, since a significant increase based on minimum inhibitory concentration (MIC) for therapeutic agents were reported by the committee of hospitals infection. Meropenem, a carbapenem agent, is widely prescribed for therapy of septic shock caused by susceptible Gram-negative bacteria. In general, the prolonged 3-hrs-infusion has been widely applied in these patients over the past 10 years providing coverage only against susceptible Gram-negative pathogens (MIC 2 mg/L), extended also to intermediate susceptible strains up to MIC 4 mg/L, according to Clinical Laboratory Standard Institute (CLSI database). However, new strategies have been recommended to combat the development of resistance to pathogens isolated from cultures to increase the coverage of this carbapenem agent up to MIC 8 mg/L, to avoid mutant selection with death in ICU. Subject: Clinical protocol was carried out to investigate the efficacy &amp; safety of meropenem at the dose regimen recommended 1g q8h by prolonged infusion, based on serum levels and on cultures monitoring of isolates. Aim of protocol was to assess pharmacodynamics (PD) based on changes of pharmacokinetics (PK), which could affect the coverage of meropenem in septic burns patients with increased or decreased renal function. Pharmacokinetic-pharmacodynamics (PK/PD) tools were applied to investigate efficacy &amp; safety. Methods-clinical protocol: Forty-eight major septic burn patients with high variability on renal function in ICU were included. Cultures were collected before meropenem therapy starts; all of them had nosocomial infection caused by Gram-negative pathogens isolated. Patients undergoing meropenem therapy at the initial stage of septic shock from day-0 to day-8 (D0-D8) and at the late stage of septic shock from day 8 to day 14 (D-8 to D-14) were investigated according to dose requirements based on creatinine clearance, drug serum levels (TDM), and coverage up to MIC 8 mg/L, dose dependent on renal function. Results: Coverage occurred for all patients of both groups after the extended infusion against susceptible Gram-negative strains up to MIC 2 mg/L (minimum inhibitory concentration), and up to MIC 4 mg/L, strains of intermediate susceptibility, according to Clinical Laboratory Standards Institute (CLSI, database) of our hospital. It was demonstrated in patients with renal function augmented by vasopressors, the superiority on coverage by trice that occurred in 24/27 patients (89%) after 4 hrs.-infusion at TDM3 against strains MIC 8 mg/L by comparison with coverage registered in 12/39 patients (30%) after 3 hrs.-infusion at TDM2. On the other hand, meropenem dose regimen must be adjusted to 1g q24h in patients with AKI to guarantee effectiveness &amp; safety in those patients. In addition, after continuous venovenous haemodialysis-filtration (CVVHDF) installed in those patients, meropenem PK/PD target was attained up to MIC 8 mg/L in patients with the empirical dose regimen recommended of 1g q8h, 3hrs.-infusion. Conclusion: Precision medicine guarantees meropenem serum levels combined with cultures monitoring; consequently, must be applied routinely to guarantee coverage against Gram-negative nosocomial pathogens susceptible including strains of intermediate susceptibility (MIC 4-8 mg/L) to avoid mutant selection. Therefore, effective, and safe antimicrobial therapy for patients in septic shock, combined with a continuous monitoring of inflammatory biomarkers, should guide clinical management to ensure cure with early ICU discharge.

An observational prospective cross-sectional study on extravascular lung water by lung ultrasound as a guide to fluid resuscitation therapy in adult septic shock in tertiary care hospital in central India

Background Septic shock is a life-threatening condition characterized by systemic inflammation and organ dysfunction, with fluid resuscitation being a cornerstone of management. However, indiscriminate fluid administration can lead to fluid overload and worsen outcomes. Extravascular lung water (EVLW) estimation by lung ultrasound has emerged as a promising tool for guiding fluid therapy in septic shock, allowing clinicians to assess pulmonary edema and tailor resuscitation strategies accordingly. Methods This prospective observational study aims to evaluate the utility of EVLW estimation by lung ultrasound in guiding fluid resuscitation therapy in adult patients with septic shock admitted to a rural tertiary care teaching hospital. Eligible patients admitted to the intensive care unit (ICU) will undergo baseline demographic and clinical assessments, including lung ultrasound, to quantify EVLW using B-line analysis. Fluid resuscitation therapy will be initiated based on EVLW findings, with subsequent adjustments guided by repeat lung ultrasound examinations at 6, 12, 24, and 48 hours post-initiation. Outcome measures include changes in mean PaO2/FiO2 ratios, respiratory parameters, renal function, fluid balance, and mortality rates. Expected Outcome We anticipate that EVLW-guided fluid resuscitation therapy will lead to more precise and tailored management of septic shock, potentially reducing the incidence of fluid overload, ARDS, and renal dysfunction. By optimizing fluid management strategies based on individual patient characteristics and responses, we aim to improve clinical outcomes and enhance the delivery of care for patients with septic shock.

Clinical features and death risk factors of pneumocystis jirovecii pneumonia in kidney disease patients with immunosuppressive therapy

To investigate the clinical features and death risk factors of pneumocystis jirovecii pneumonia (PJP) in kidney disease patients with immunosuppressive patients. A Retrospective case series study was performed in 52 PJP patients with kidney disease who received immunosuppressive therapy in Nephrology or Respiratory department of Peking University First Hospital from January 1, 2006 to August 31, 2021. Patients were divided into survival group (36 cases) and death group (16 cases) according to their clinical outcomes. Univariate analysis was performed to compare the differences of clinical features between the two groups. Multivariate logistic regression model was used to analyze the death risk factors. The results showed that the median serum creatinine was 192.5 (109.8, 293.7) μmol/L, and the incidence of acute kidney injury was 63.5% (33/52). Univariate analysis showed that age (t=1.197,P=0.030), C-reactive protein level (t=2.378,P=0.022), time from onset to diagnosis (χ2=6.62,P=0.010), PJP severity (χ2=5.482,P=0.019), complicated with septic shock (χ2=3.997,P=0.046), mechanical ventilation (χ2=11.755,P=0.001), and blood purification therapy (χ2=4.748,P=0.029) were statistically significant. There were no statistically significant differences between the two groups in gender, duration and dosage of hormone therapy before PJP onset, intravenous methylprednisolone pulse therapy, immunosuppressant use, and serum creatinine level before and after hospitalization for anti-PJP treatment (all P>0.05). Multivariate analysis showed that the time from onset to diagnosis of PJP was >10 days (OR=40.945, 95%CI: 1.738-451.214; P=0.021) and severe PJP (OR=25.502, 95%CI: 1.426-74.806; P=0.028) was an independent death risk factor for kidney disease complicated with PJP of immunosuppressive therapy. In conclusion, the time from onset to diagnosis of PJP and PJP severity are independent death risk factors in patients with kidney disease complicated with PJP of immunosuppressive therapy. Close attention should be paid to oxygenation condition and early diagnosis can prevent the aggravation of PJP and improve the prognosis.

Comparative efficacy of antioxidant therapies for sepsis and septic shock in the intensive care unit: A frequentist network meta-analysis

BackgroundAntioxidant therapy is gaining traction in managing sepsis and septic shock, owing to its perceived positive impact on patient outcomes. This study sought to compare the efficacy of five antioxidant therapies (melatonin, vitamin C, vitamin E, selenium, and N-acetylcysteine, both individually and in combination with other compounds such as vitamin B1, hydrocortisone, propolis, and glutamine) in treating sepsis or septic shock in the intensive care unit (ICU). MethodsThe study involved randomized and multi-arm trials with sepsis or septic shock patients using melatonin, vitamin C, vitamin E, selenium, or N-acetylcysteine. Studies were sourced from PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and WHO - Clinical Trials Registry Platform for the frequentist network meta-analysis on 28-day mortality and Sequential Organ Failure Assessment (SOFA) scores. The risk of bias was assessed using the Physiotherapy Evidence Database scale. Therapies were compared directly and indirectly using R software. ResultsThe study of 56 trials involving 9,366 patients was included. Bias assessment revealed that 89.3 % of trials achieved excellent or good quality. Based on treatment ranking and pairwise comparisons, melatonin with propolis (SUCRA = 93.29 %) is effective in improving SOFA scores, statistically significant, with no publication bias (p= 0.73). High-dose vitamin C (SUCRA = 83.97 %), vitamin C with vitamin B1 (SUCRA = 78.72 %), and melatonin (SUCRA = 67.03 %) are potential therapies for organ dysfunction. Melatonin (SUCRA = 88.22 %) and high-dose vitamin C (SUCRA = 80.75 %) were the most effective in reducing 28-day mortality rates. However, analysis indicated that the results for 28-day mortality rates were not statistically significant. Also, these results contained publication bias (p= 0.02). ConclusionThe study offers fresh perspectives on antioxidant therapy treatments for sepsis or septic shock in ICU, emphasizing the combination of melatonin and propolis notably reduces SOFA scores for those patients.

Adjunctive immunotherapeutic agents in patients with sepsis and septic shock: a multidisciplinary consensus of 23

BackgroundIn the last decades, several adjunctive treatments have been proposed to reduce mortality in septic shock patients. Unfortunately, mortality due to sepsis and septic shock remains elevated and NO trials evaluating adjunctive therapies were able to demonstrate any clear benefit. In light of the lack of evidence and conflicting results from previous studies, in this multidisciplinary consensus, the authors considered the rational, recent investigations and potential clinical benefits of targeted adjunctive therapies.MethodsA panel of multidisciplinary experts defined clinical phenotypes, treatments and outcomes of greater interest in the field of adjunctive therapies for sepsis and septic shock. After an extensive systematic literature review, the appropriateness of each treatment for each clinical phenotype was determined using the modified RAND/UCLA appropriateness method.ResultsThe consensus identified two distinct clinical phenotypes: patients with overwhelming shock and patients with immune paralysis. Six different adjunctive treatments were considered the most frequently used and promising: (i) corticosteroids, (ii) blood purification, (iii) immunoglobulins, (iv) granulocyte/monocyte colony-stimulating factor and (v) specific immune therapy (i.e. interferon-gamma, IL7 and AntiPD1). Agreement was achieved in 70% of the 25 clinical questions.ConclusionsAlthough clinical evidence is lacking, adjunctive therapies are often employed in the treatment of sepsis. To address this gap in knowledge, a panel of national experts has provided a structured consensus on the appropriate use of these treatments in clinical practice.

CO2 gap changes compared with cardiac output changes in response to intravenous volume expansion and/or vasopressor therapy in septic shock.

The difference in partial pressure of carbon dioxide (PCO2) between mixed or central venous blood and arterial blood, known as the ∆PCO2 or CO2 gap, has demonstrated a strong relationship with cardiac index during septic shock resuscitation. Early monitoring of the ∆PCO2 can help assess the cardiac output (CO) adequacy for tissue perfusion. To investigate the value of ∆PCO2 changes in early septic shock management compared with CO. This observational prospective study included 76 patients diagnosed with septic shock admitted to Cairo University Hospital's Critical Care Department between December 2020 and March 2022. Patients were categorised by initial resuscitation response, initial ∆PCO2 and 28-day mortality. The primary outcome was the relationship between the ∆PCO2 and CO changes before and after initial resuscitation, with secondary outcomes including ICU length of stay (LOS) and 28-day mortality. Peri-resuscitation ∆PCO2 changes predicted a ≥15% change in the cardiac index (CI) (area under the curve (AUC) 0.727; 95% CI 0.614 - 0.840) with 66.7% sensitivity and 62.8% specificity. The optimal ∆PCO2 change cut-off value was <-1.85, corresponding to a <-22% threshold for a 15% cardiac index increase. The PCO2 gap ratio (gap/gap ratio of T1- PCO2 gap to T0 -PCO2 gap) also predicted a ≥15% change in cardiac index (AUC 745; 95% CI 0.634 - 0.855) with 63.6% sensitivity and 79.1% specificity. The optimal CO2 gap/gap ratio cut-off value was <0.71. A significant difference in 28-day mortality was noted based on the gap/gap ratio. Peri-resuscitation ∆PCO2 and the gap/gap ratio are useful non-invasive bedside markers for predicting changes in CO and preload responsiveness. The current study provides an insight to the PCO2 gap changes during and after early resuscitation of septic shock patients, which correlate to cardiac output changes and might also serve as a fluid responsiveness indicator.

A Systematic Review and Meta-Analysis of the Timing of Vasopressor Therapy in Patients with Septic Shock: Assessing Clinical Outcomes and Implication

Background Septic shock, is associated with a high mortality rate and increased expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. There is still a controversy on when each vasopressor should be administered. Therefore, we conducted this review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated lower incidence of mortality and shorter duration to achieve target mean arterial pressure in the early vs. late epinephrine groups (OR:0.44; 95%CI: 0.35–0.55; p&lt;0.00001 and MD:-1.17; 95%CI:-2.00– -0.34; p=0.0006). However, the length of ICU stay didn’t differ between the early and late norepinephrine group (MD:0.55; 95%CI: -0.52–1.62; p=0.31). The subgroup analyses show that early vasopressin is associated with a decreased mortality than late administration (OR:0.60; 95%CI:0.41–0.90; p=0.01). Similarly, the pooled analysis has shown that early concomitant administration of vasopressin and norepinephrine is associated with a shorter duration to achieve target MAP than norepinephrine alone (MD:-3.15; 95%CI:-4.40– -1.90;p&lt;0.00001). Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.

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

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. 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. 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. The European Clinical Trials Database (EudraCT): 2018-000404-42, ClinicalTrials. gov: NCT03668236.