Resuscitation Of Septic Shock Research Articles

Balanced crystalloid versus saline for resuscitation in pediatric septic shock: a systematic review and meta-analysis

BackgroundFluid resuscitation is a cornerstone of septic shock management in pediatric patients, with normal saline (NS) being the traditional choice. However, balanced solutions (BS) have gained attention due to their potential to mitigate acid-base and electrolyte disturbances. Despite this, the optimal choice between BS and NS for pediatric sepsis remains unclear. Therefore, we aimed to conduct a meta-analysis comparing the clinical outcomes of BS versus NS in pediatric patients with sepsis.MethodsWe systematically searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials, along with reference lists of retrieved publications, for studies comparing clinical outcomes in pediatric patients with sepsis treated with BS versus NS. Our outcomes of interest included acute kidney injury (AKI), hospital mortality, hospital length of stay, pediatric intensive care unit (PICU) length of stay, need for renal replacement therapy, hyperchloremia and mechanical ventilation. We performed statistical analysis using Review Manager Web 8.0.0 and Rstudio.ResultsWe included 12,231 patients from 8 studies, of which 4 were randomized clinical trials (RCTs). BS was used to treat septic shock in 2,460 (20.1%) patients. The mean age was 5.98 ± 3.08 years, with 43.82% female patients. Follow-up ranged from 3 to 90 days. We found no statistically significant difference between groups in AKI, hospital mortality, mechanical ventilation, need for renal replacement therapy, and PICU length of stay. Hospital length of stay in days was significantly longer with BS compared to NS (MD 3.38; 95% CI 1.13 to 5.64; p = 0.003; I² = 0%) and the occurrence of hyperchloremia was lower in the BS compared to NS (RR 0.70; 95% CI 0.59 to 0.82; p = 0.0001; I² = 0%). In a subgroup analysis of RCTs only, AKI occurrence was not significantly different between BS and NS groups (RR 0.81; 95% CI 0.48 to 1.38; p = 0.44; I² = 18%). However, the need for renal replacement therapy was significantly less frequent in patients treated with BS compared to NS (RR 0.58; 95% CI 0.39 to 0.87; p = 0.008; I² = 0%).ConclusionIn pediatric septic shock patients, treatment with balanced solutions (BS) was associated with a lower need for renal replacement therapy and a reduced occurrence of hyperchloremia. However, hospital length of stay was longer in patients treated with BS compared to those receiving normal saline (NS). These results underscore the complexity of fluid management in pediatric septic shock and emphasize the need for further research.

Statistical analysis plan for hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock: the ANDROMEDA-SHOCK-2 randomized clinical trial.

ANDROMEDA-SHOCK 2 is an international, multicenter, randomized controlled trial comparing hemodynamic phenotype-based, capillary refill time-targeted resuscitation in early septic shock to standard care resuscitation to test the hypothesis that the former is associated with lower morbidity and mortality in terms of hierarchal analysis of outcomes. To report the statistical plan for the ANDROMEDA--SHOCK 2 randomized clinical trial. We briefly describe the trial design, patients, methods of randomization, interventions, outcomes, and sample size. We portray our planned statistical analysis for the hierarchical primary outcome using the stratified win ratio method, as well as the planned analysis for the secondary and tertiary outcomes. We also describe the subgroup and sensitivity analyses. Finally, we provide details for presenting our results, including mock tables, baseline characteristics, and the effects of treatments on outcomes. According to best trial practices, we report our statistical analysis plan and data management plan prior to locking the database and initiating the analyses. We anticipate that this practice will prevent analysis bias and improve the utility of the study's reported results.

Resuscitation in Paediatric Septic Shock Using Vitamin C and Hydrocortisone (RESPOND): The RESPOND Randomized Controlled Trial Protocol.

Pediatric sepsis results in significant morbidity and mortality worldwide. There is an urgent need to investigate adjunctive therapies that can be administered early. We hypothesize that using vitamin C combined with hydrocortisone increases survival free of inotropes/vasopressors support until day 7 compared with standard care. Here we describe the Resuscitation in Paediatric Septic Shock using Vitamin C and Hydrocortisone (RESPOND) trial protocol, which aims to address this hypothesis. Randomized, open label, controlled, parallel-group, three-arm trial with integrated economic evaluation. Nine Australia and New Zealand PICUs, with interest from additional international sites. Children between 7 days and younger than 18 years old who are treated for suspected or confirmed sepsis and receiving inotropes/vasopressors for greater than 1 hour. IV vitamin C (100 mg/kg [maximum 5 g] every 6 hr) and hydrocortisone (1 mg/kg [maximum 50 mg] every 6 hr), or IV hydrocortisone alone (1 mg/kg [maximum 50 mg] every 6 hr) or standard care. Three hundred eighty-four children will be randomly assigned to receive the interventions, or standard care in a 1:1:1 ratio with stratification by steroid administration pre-randomization and hospital site. The primary outcome is time alive and free of inotropes/vasopressors, censored at 7 days. Secondary outcomes include 28-day mortality, survival free of organ support, PICU length of stay, quality of life, functional status and neurodevelopmental vulnerability at 6 months post-enrollment, and hospitalization-related costs. Statistical analysis will be based on an intention-to-treat principle. The study has ethical approval (HREC/20/QCHQ/69922, dated December 21, 2020), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12621000247875), commenced recruitment on December 8, 2021, and is expected to finish recruitment by mid-2026. Dissemination of the results will occur through publication in peer-reviewed journals, presentations at international conferences, and additional consumer-informed pathways.

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.

The Sublingual Microcirculation in Critically Ill Children with Septic Shock Undergoing Hemoadsorption: A Pilot Study.

Background: The importance of perfusion-guided resuscitation in septic shock has recently emerged. We explored whether the use of hemoadsorption led to a potential beneficial role in microvascular alterations in this clinical setting. Methods: A pre-planned secondary analysis of a Phase-II interventional single-arm pilot study (NCT05658588) was carried out, where 17 consecutive septic shock children admitted into PICU were treated with continuous renal replacement therapy (CRRT) and CytoSorb. Thirteen patients were eligible to be investigated with sublingual microcirculation at baseline, 24, 48, 72 and 96 h from the onset of blood purification. Patients achieving a microvascular flow index (MFI) ≥ 2.5 and/or proportion of perfused vessels (PPV) exceeding 90% by 96 h were defined as responders. Results: In 10/13 (77%), there was a significant improvement in MFIs (p = 0.01) and PPVs% (p = 0.04) between baseline and 24 h from the end of treatment. Eight patients displayed a high heterogenicity index (HI > 0.5) during blood purification and among these, five showed an improvement by the end of treatment (HI < 0.5). Conclusions: In this pilot study, we have found a potential association between CytoSorb hemoadsorption and a microcirculation improvement in pediatric patients with septic shock, particularly when this observation has been associated with hemodynamic improvement.

Statistical analysis plan for the SQUEEZE trial: A trial to determine whether septic shock reversal is quicker in pediatric patients randomized to an early goal-directed fluid-sparing strategy vs. usual care (SQUEEZE)

BackgroundThe SQUEEZE trial is a multicentred randomized controlled trial which seeks to determine the optimal approach to fluid resuscitation in paediatric septic shock. SQUEEZE also includes a nested translational study, SQUEEZE-D, investigating the value of plasma cell-free DNA for prediction of clinical outcomes. ObjectiveTo present a pre-specified statistical analysis plan (SAP) for the SQUEEZE trial prior to finalizing the trial data set and prior to commencing data analysis. DesignSQUEEZE is a pragmatic, two-arm, open-label, prospective multicentre randomized controlled trial. SettingCanadian paediatric tertiary care centres. ParticipantsPaediatric patients with suspected sepsis and persistent signs of shock in need of ongoing resuscitation. Sample size target: 400 participants. InterventionsThe trial is designed to compare a fluid-sparing resuscitation strategy to usual care. Main outcome measuresThe primary outcome for the SQUEEZE trial is the time to shock reversal (in hours). The primary outcome analysis will assess the difference in time to shock reversal between the intervention and control groups, reported as point estimate with 95% confidence intervals. The statistical test for the primary analysis will be a two-sided t-test. Secondary outcome measures include clinical outcomes and adverse events including measures of organ dysfunction and mortality outcomes. ResultsThe SAP presented here is reflective of and where necessary clarifies in detail the analysis plan as presented in the trial protocol. The SAP includes a mock CONSORT diagram, figures and tables. Data collection methods are summarized, primary and secondary outcomes are defined, and outcome analyses are described. ConclusionsWe have developed a statistical analysis plan for the SQUEEZE Trial for transparency and to align with best practices. Analysis of SQUEEZE Trial data will adhere to the SAP to reduce the risk of bias. RegistrationClinicalTrials.gov identifiers: Definitive trial NCT03080038; Registered Feb 28, 2017. Pilot Trial NCT 01973907; Registered Oct 27, 2013.

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.

Early intravenous hydrocortisone in sepsis: A randomized control trial (Protocol)

Background: The evidence of the appropriate timing of hydrocortisone is still weak and controversial. Observational studies showed a trend towards greater benefits when hydrocortisone was given earlier in the course of septic shock resuscitation. This study evaluates the effects of early intravenous low-dose hydrocortisone administered at the beginning of the onset of sepsis-induced hypotension compared with standard care. Methods: This study is a single-center, parallel-group, double-blinded, randomized control trial, conducted in a non-trauma emergency department. Adult patients with sepsis-induced hypotension will be included. Patients will be randomly assigned in a 1:1 ratio to receive early intravenous low-dose hydrocortisone or standard care. Blood inflammatory biomarkers at baseline will be collected. The primary outcome is 28-day mortality. Resuscitation-related secondary outcomes and safety outcomes will also be observed. Outcomes will be compared between groups. Subgroup analyses considering inflammatory biomarker levels will also be performed to evaluate the effect of early intravenous hydrocortisone, especially in patients with hyperinflammation. Hypothesis: We hypothesize that early intravenous low-dose hydrocortisone administration in patients with sepsis-induced hypotension would result in less mortality and improve resuscitation outcomes, especially in subgroup of patients with hyperinflammation. Ethics and dissemination: The study protocol was approved by the Siriraj Institutional Review Board with the certificate of approval number Si 917/2023. Trial registration: Clinicaltrial.gov NCT06217939

Albumin: a comprehensive review and practical guideline for clinical use.

Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin.

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

BackgroundSeveral 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.MethodsThirty-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).ResultsCRT 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.ConclusionsOur 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.

The Effect of Albumin Replacement on Vasopressor Duration in Septic Shock in Patients With Hypoalbuminemia.

The use of albumin resuscitation in septic shock is only recommended in patients who have received large volumes of crystalloid resuscitation regardless of serum albumin concentration. The role of albumin is still largely debated and evidence to support its use still lacking. The objective of this study was to evaluate whether albumin replacement increases the number of vasopressor-free days in patients with septic shock and hypoalbuminemia. A retrospective analysis was conducted to assess the effect of albumin replacement in septic shock. Hypoalbuminemic patients with septic shock who received albumin were retrospectively compared with a cohort who did not. The primary outcome was number of vasopressor-free days at day 14 from shock presentation, which was analyzed using an adjusted linear regression model to adjust for confounders. There was no difference in vasopressor-free days at day 14 in patients who received albumin versus those who did not, after adjusting for confounders of exposure (0.50, 95% CI = -0.97 to 1.97; P = 0.502). There also was no difference in secondary outcomes except for need for invasive mechanical ventilation (MV), which was significantly lower in patients who received albumin (61 [54.4%] vs 88 [67.7%]; P = 0.035). We observed no difference in vasopressor-free days at day 14 in patients with hypoalbuminemia who received albumin compared with those who did not. However, patients who received albumin required significantly less MV although further studies are warranted to assess this effect.

Resuscitating the macro- vs. microcirculation in septic shock.

This review summarizes current literature about the relationships between macro and microcirculation and their practical clinical implications in children with septic shock. Current evidence from experimental and clinical observational studies in children and adults with septic shock reveals that the response to treatment and resuscitation is widely variable. Furthermore, there is a loss of hemodynamic coherence, as resuscitation-induced improvement in macrocirculation (systemic hemodynamic parameters) does not necessarily result in a parallel improvement in the microcirculation. Therefore, patient-tailored monitoring is essential in order to adjust treatment requirements during resuscitation in septic shock. Optimal monitoring must integrate macrocirculation (heart rate, blood pressure, cardiac output, and ultrasound images), microcirculation (videomicroscopy parameters and capillary refill time) and cellular metabolism (lactic acid, central venous blood oxygen saturation, and difference of central venous to arterial carbon dioxide partial pressure). There is a dire need for high-quality studies to assess the relationships between macrocirculation, microcirculation and tissue metabolism in children with septic shock. The development of reliable and readily available microcirculation and tissue perfusion biomarkers (other than lactic acid) is also necessary to improve monitoring and treatment adjustment in such patients.

Assessment of Outcomes in Patients with Heart Failure and End-Stage Kidney Disease after Fluid Resuscitation for Sepsis and Septic Shock

BackgroundSepsis fluid resuscitation is controversial, especially for patients with volume overload risk. The Surviving Sepsis Campaign recommends a 30-mL/kg crystalloid fluid bolus for patients with sepsis-induced hypoperfusion. Criticism of this approach includes excessive fluid resuscitation in certain patients. ObjectiveThe aim of this study was to assess the efficacy and safety of guideline-concordant fluid resuscitation in patients with sepsis and heart failure (HF) or end-stage kidney disease (ESKD). MethodsA retrospective cohort study was conducted in patients with sepsis who qualified for guideline-directed fluid resuscitation and concomitant HF or ESKD. Those receiving crystalloid fluid boluses of at least 30 mL/kg within 3 h of sepsis diagnosis were placed in the concordant group and all others in the nonconcordant group. The primary outcome was in-hospital mortality. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS); vasoactive medications and net volume over 24 h; new mechanical ventilation, new or increased volume removal, and acute kidney injury within 48 h; and shock-free survival at 7 days. ResultsOne hundred twenty-five patients were included in each group. In-hospital mortality was 34.4% in the concordant group and 44.8% in the nonconcordant group (p = 0.1205). The concordant group had a shorter ICU LOS (7.6 vs. 10.5 days; p = 0.0214) and hospital LOS (12.9 vs. 18.3 days; p = 0.0163), but increased new mechanical ventilation (37.6 vs. 20.8%; p = 0.0052). No differences in other outcomes were observed. ConclusionsReceipt of a 30-mL/kg fluid bolus did not affect outcomes in a cohort of patients with mixed types of HF and sepsis-induced hypoperfusion.

Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation.This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Focused Cardiac Ultrasound Findings of Fluid Tolerance and Fluid Resuscitation in Septic Shock.

Compliance with the fluid bonus component of the SEP-1 (severe sepsis and septic shock management) bundle remains poor due to concerns for iatrogenic harm from fluid overload. We sought to assess whether patients who received focused cardiac ultrasound (FCU) and were found to be fluid tolerant (FT) were more likely to receive the recommended 30 mL/kg fluid bolus within 3 hours of sepsis identification. Retrospective, observational cohort study. University-affiliated, tertiary-care hospital in the United States. Emergency department patients presenting with septic shock from 2018 to 2021. The primary exposure was receipt of FCU with identification of fluid tolerance 3 hours from onset of septic shock. None. Two hundred ninety-two of 1,024 patients with septic shock received FCU within 3 hours of sepsis onset. One hundred seventy-seven were determined to be FT. One hundred fifteen patients were determined to have poor fluid tolerance (pFT). FT patients were more likely to reach the recommended 30 mL/kg fluid bolus amount compared with pFT (FT 52.0% vs. pFT 31.3%, risk difference: 20.7%, [95% CI, 9.4-31.9]). Patients who did not receive FCU met the bolus requirement 34.3% of the time. FT patients received more fluid within 3 hours (FT 2,271 mL vs. pFT 1,646 mL, mean difference 625 mL [95% CI, 330-919]). Multivariable logistic regression was used to estimate the association between fluid tolerance FCU findings and compliance with 30 mL/kg bolus after adjustment for patient characteristics and markers of hemodynamic instability. FT with associated with a higher likelihood of meeting bolus requirement (odds ratio 2.17 [1.52-3.12]). Patients found to be FT by FCU were more likely to receive the recommended 30 mL/kg bolus in the SEP-1 bundle when compared with patients found with pFT or those that did not receive FCU. There was no difference between groups in 28-day mortality, vasopressor requirement, or need for mechanical ventilation.

RESTRICTIVE FLUID RESUSCITATION IN SEPTIC SHOCK PATIENTS HAS LOWER MORTALITY AND ORGAN DYSFUNCTION RATES THAN STANDARD THERAPY.

Background : The influence of restrictive fluid resuscitation and the early administration of vasopressors on the clinical outcomes in patients with septic shock are not fully understood. The purpose of this study was to evaluate the effects of restrictive fluid management on mortality and organ dysfunction in patients with septic shock. Methods : This study included consecutive patients with septic shock in need of fluid resuscitation. Based on the fluid management provided in the initial resuscitation phase, a comparison was made between a restrictive group and a standard fluid management group. The primary outcome was in-hospital death, whereas secondary outcomes included organ dysfunction and other adverse events. Results : A total of 238 patients were included in this study. Restrictive fluid management was administered to 59.2% of patients, whereas 40.8% received standard fluid management. Restrictive resuscitation was associated with a lower in-hospital mortality rate (24.8% vs. 52.6%), as well as a shorter median intensive care unit stay (8.0 vs. 11.0 days). The restrictive strategy was associated with a significantly lower prevalence of new-onset acute kidney injury (25.5% vs. 51.5%) and a decrease in the incidence of renal replacement therapy (20.6% vs. 40.2%). The standard group had a higher risk of the need for mechanical ventilation and a significantly lower median number of days without a ventilator than the restrictive group. The median duration of vasopressor-free days in the restrictive group was significantly longer than that in the standard group (25.0 vs. 18.0). The administration rate of inotropes in the restrictive group was significantly lower than that in the standard group. A multivariate logistic regression model showed that restrictive fluid management (odds ratio [OR], 0.312; 95% confidence interval [CI], 0.098-0.994) and vasopressor-free days (OR, 0.807; 95% CI, 0.765-0.851) protect against in-hospital death, whereas Acute Physiology and Chronic Health Evaluation II scores (OR, 1.121; 95% CI, 1.018-1.234) were independent risk factors for in-hospital death. Conclusions : Restrictive fluid resuscitation and early vasopressor protocol in patients with septic shock are associated with better outcomes, indicating that this regimen is feasible and safe.

Should we initiate vasopressors earlier in patients with septic shock: A mini systemic review.

Septic shock treatment remains a major challenge for intensive care units, despite the recent prominent advances in both management and outcomes. Vasopressors serve as a cornerstone of septic shock therapy, but there is still controversy over the timing of administration. Specifically, it remains unclear whether vasopressors should be used early in the course of treatment. Here, we provide a systematic review of the literature on the timing of vasopressor administration. Research was systematically identified through PubMed, Embase and Cochrane searching according to PRISMA guidelines. Fourteen studies met the eligibility criteria and were included in the review. The pathophysiological basis for early vasopressor use was classified, with the exploration on indications for the early administration of mono-vasopressors or their combination with vasopressin or angiotensinII. We found that mortality was 28.1%-47.7% in the early vasopressors group, and 33.6%-54.5% in the control group. We also investigated the issue of vasopressor responsiveness. Furthermore, we acknowledged the subsequent challenge of administration of high-dose norepinephrine via peripheral veins with early vasopressor use. Based on the literature review, we propose a possible protocol for the early initiation of vasopressors in septic shock resuscitation.

Subclinical cardiac dysfunction may impact on fluid and vasopressor administration during early resuscitation of septic shock

BackgroundAccording to the Surviving Sepsis Campaign (SSC) fluids and vasopressors are the mainstays of early resuscitation of septic shock while inotropes are indicated in case of tissue hypoperfusion refractory to fluids and vasopressors, suggesting severe cardiac dysfunction. However, septic cardiac disfunction encompasses a large spectrum of severities and may remain “subclinical” during early resuscitation. We hypothesized that “subclinical” cardiac dysfunction may nevertheless influence fluid and vasopressor administration during early resuscitation. We retrospectively reviewed prospectically collected data on fluids and vasoconstrictors administered outside the ICU in patients with septic shock resuscitated according to the SSC guidelines that had reached hemodynamic stability without the use of inotropes. All the patients were submitted to transpulmonary thermodilution (TPTD) hemodynamic monitoring at ICU entry. Subclinical cardiac dysfunction was defined as a TPTD-derived cardiac function index (CFI) ≤ 4.5 min−1.ResultsAt ICU admission, subclinical cardiac dysfunction was present in 17/40 patients (42%; CFI 3.6 ± 0.7 min−1 vs 6.6 ± 1.9 min−1; p < 0.01). Compared with patients with normal CFI, these patients had been resuscitate with more fluids (crystalloids 57 ± 10 vs 47 ± 9 ml/kg PBW; p < 0.01) and vasopressors (norepinephrine 0.65 ± 0.25 vs 0.43 ± 0.29 mcg/kg/min; p < 0.05). At ICU admission these patients had lower cardiac index (2.2 ± 0.6 vs 3.6 ± 0.9 L/min/m2, p < 0.01) and higher systemic vascular resistances (2721 ± 860 vs 1532 ± 480 dyn*s*cm−5/m2, p < 0.01).ConclusionsIn patients with septic shock resuscitated according to the SSC, we found that subclinical cardiac dysfunction may influence the approach to fluids and vasopressor administration during early resuscitation. Our data support the implementation of early, bedside assessment of cardiac function during early resuscitation of septic shock.

Use of Lactate Clearance as a Predictor of Mortality Rate after Initial Resuscitation in Patient with Severe Sepsis or Septic Shock

Abstract Background Early diagnosis of sepsis is the key for improving the survival. Culture is the diagnostic tool but the microbiological origin of infection is demonstrated in about 2/3rd of cases. Biomarkers have an important place in this process because they can indicate the presence or absence of sepsis and they are also important in evaluating the response to therapy and recovery from sepsis. Aim of the Work to find a correlation between the lactate clearance and mortality in patients with severe sepsis. Patients and Methods The study was conducted on 60 adult critically ill patients of both sexes with severe sepsis, who were admitted to the unit of Critical Care Unit in Ain Shams University Hospital. All participants were subjected to the following: detailed history, full laboratory and radiological investigations to diagnose sepsis including lactate level on presentation (0 hour), after 6 hours and after 24 hours, then lactate clearance is calculated and patients were divided to lactate clearance group and non-clearance group. Results The study showed that clearance patients significantly had lower mortality rate, SOFA score, vasopressor therapy duration, ventilation need and hospital stay days than the non-clearance patients. Conclusion Lactate is a good marker for predicting mortality and evaluating the initial resuscitation and management of severe sepsis and septic shock.

Doppler identified venous congestion in septic shock: protocol for an international, multi-centre prospective cohort study (Andromeda-VEXUS)

IntroductionVenous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill...