Sepsis Resuscitation Research Articles

The Universal Vital Assessment (UVA) score at 6 hours post-resuscitation predicts mortality in hospitalized adults with severe sepsis in Mbarara, Uganda.

Sepsis is the leading cause of global death with the highest burden found in sub-Saharan Africa (sSA). The Universal Vital Assessment (UVA) score is a validated resource-appropriate clinical tool to identify hospitalized patients in sSA who are at risk of in-hospital mortality. Whether a decrease in the UVA score over 6 hours of resuscitation from sepsis is associated with improved outcomes is unknown. We aimed to determine (1) the association between 6-hour UVA score and in-hospital mortality, and (2) if a decrease in UVA score from admission to 6 hours was associated with improved in-hospital mortality. We analyzed data from participants with severe sepsis aged ≥14 years enrolled at the Mbarara Regional Referral Hospital in Uganda from October 2014 through May 2015. Among 197 participants, the median (interquartile range) age was 34 (27-47) years, 99 (50%) were female and 116 (59%) were living with HIV. At 6 hours, of the 65 participants in the high-risk group, 28 (43%) died compared to 28 (30%) of 94 in the medium-risk group (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.29,1.08, p = 0.086) and 3 (9%) of 33 in the low-risk group (OR 0.13, 95% CI 0.03, 0.42, p = 0.002). In a univariate analysis of the 85 participants who improved their UVA risk group at 6 hours, 20 (23%) died compared to 39 (36%) of 107 participants who did not improve (OR 0.54, 95% CI 0.27-1.06, p = 0.055). In the multivariable analysis, the UVA score at 6 hours (adjusted OR [aOR] 1.26, 95%CI 1.10-1.45, p<0.001) was associated with in-hospital mortality. When adjusted for age and sex, improvement in the UVA risk group over 6 hours was associated with a non-statistically significant 43% decrease in odds of mortality (aOR 0.57, 95%CI 0.29-1.07, p = 0.08). Targeting a decrease in UVA score over 6 hours from admission may be a useful clinical endpoint for sepsis resuscitation in sSA, but this would need to be proven in a clinical trial.

Volume therapy: which preparation for which situation?

The most commonly used fluids for volume therapy are crystalloids and colloids. Crystalloids comprise 0.9% sodium chloride and balanced crystalloids (BC). Colloids can be divided into artificial colloids and human albumin (anatural colloid). Large studies show advantages for BC over 0.9% NaCl with respect to renal endpoints, probably due to the unphysiologically high chloride content of 0.9% NaCl. However, other studies, such as the BaSICS and PLUS trials, showed no significant differences in mortality in aheterogeneous population. Despite this, meta-analyses suggest advantages for BC. Therefore, BC should be preferred, especially in patients at increased risk of acute kidney injury, with acidemia and/or hyperchloremia. Except for specific indications (e.g., in patients with cirrhosis, sepsis resuscitation after initial volume therapy with BC), albumin should not be used. There is clear evidence of harm from hydroxyethyl starch in intensive care patients.

The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) Trial

Intravenous fluids are an essential part of treatment in sepsis, but there remains clinical equipoise on which type of crystalloid fluids to use in sepsis. A previously reported sepsis subphenotype (ie, group D) has demonstrated a substantial mortality benefit from balanced crystalloids compared with normal saline. To test the hypothesis that targeting balanced crystalloids to patients with group D sepsis through an electronic health record (EHR) alert will reduce 30-day inpatient mortality. The Precision Resuscitation With Crystalloids in Sepsis (PRECISE) trial is a parallel-group, multihospital, single-blind, pragmatic randomized clinical trial to be conducted at 6 hospitals in the Emory Healthcare system. Patients with suspicion of group D infection in whom a clinician initiates an order for normal saline in the emergency department (ED) or intensive care unit (ICU) will be randomized to usual care and intervention arms. An EHR alert that appears in the ED and ICUs to nudge clinicians to use balanced crystalloids instead of normal saline. The primary outcome is 30-day inpatient mortality. Secondary outcomes are ICU admission, in-hospital mortality, receipt of vasoactive drugs, receipt of new kidney replacement therapy, and receipt of mechanical ventilation (vasoactive drugs, kidney replacement therapy, and mechanical ventilation are counted if they occur after randomization and within the 30-day study period). Intention-to-treat analysis will be conducted. The PRECISE trial may be one of the first precision medicine trials of crystalloid fluids in sepsis. Using routine vital signs (temperature, heart rate, respiratory rate, and blood pressure), available even in low-resource settings, a validated machine learning algorithm will prospectively identify and enroll patients with group D sepsis who may have a substantial mortality reduction from used of balanced crystalloids compared with normal saline. On finalizing participant enrollment and analyzing the data, the study's findings will be shared with the public through publication in a peer-reviewed journal. With use of a validated machine learning algorithm, precision resuscitation in sepsis could fundamentally redefine international standards for intravenous fluid resuscitation. ClinicalTrials.gov Identifier: NCT06253585.

Fluid bolus in suspected Sepsis patients with Hyperlactatemia (FISH): Study protocol for an open-labeled, randomized controlled trial

Background: The adequate preload was the goal of hemodynamic optimization for sepsis resuscitation. The fluid strategy in the early phase of sepsis is unclear. Objective: To investigate the efficacy of a fluid bolus to prevent new-onset hypotension in suspected sepsis patients with hyperlactatemia (Point-of-care serum lactate 2-4 mmol/L). Methods: The Fluid Bolus in Suspected Sepsis Patients with Hyperlactatemia Trial (FISH) is a single-center, open-label randomized controlled trial. Participants will be patients suspected of having sepsis with hyperlactatemia (Point-of-care serum lactate 2-4 mmol/L) in the emergency department of Srinagarind Hospital, Thailand. Eligible patients will be randomized (1:1) to one of the study arms using block randomization. They will be placed in either the fluid bolus group (intervention, 30 mL/kg within 3 hours) or the standard care group (control). The primary outcome is new-onset hypotension within 24 hours after randomization. Secondary outcomes include lactate clearance, ∆SOFA at 72-hours, organ failure, and support ‘free days’ to day 28, 28-day mortality. Hypothesis: We hypothesize that a fluid bolus will prevent new-onset hypotension in suspected sepsis patients with hyperlactatemia (point-of-care serum lactate 2-4 mmol/L). Discussion: The optimal strategy for intravenous fluid therapy in a patient suspected of sepsis with hyperlactatemia is unknown. This is the first randomized trial examining fluid strategy in the early phase of sepsis with mild hyperlactatemia. Trial registration: TCTR20230502003

Myocardial strain is regulated by cardiac preload in the early stage of sepsis

BackgroundOwing to a lack of data, this study aimed to explore the effect of cardiac preload on myocardial strain in patients with sepsis.MethodsA total of 70 patients with sepsis in intensive care unit (ICU) of a tertiary teaching hospital in China from January 2018 to July 2019 and underwent transthoracic echocardiography were enrolled. Echocardiographic data were recorded at ICU admission and 24 h later. Patients were assigned to low left ventricular end-diastolic volume index (LVEDVI) and normal LVEDVI groups. We assessed the impact of preload on myocardial strain between the groups and analyzed the correlation of echocardiographic parameters under different preload conditions.ResultsThirty-seven patients (53%) had a low LVEDVI and 33 (47%) a normal LVEDVI. Those in the low LVEDVI group had a faster heart rate (121.7 vs. 95.3, p < 0.001) and required a greater degree of fluid infusion (3.67 L vs. 2.62 L, P = 0.019). The left ventricular global strain (LVGLS) (-8.60% vs. -10.80%, p = 0.001), left ventricular global circumferential strain (LVGCS) (-13.83% vs. -18.26%, p = 0.006), and right ventricular global longitudinal strain (RVGLS) (-6.9% vs. -10.60%, p = 0.001) showed significant improvements in the low LVEDVI group after fluid resuscitation. However, fluid resuscitation resulted in a significantly increased cardiac afterload value (1172.00 vs. 1487.00, p = 0.009) only in the normal LVEDVI group. Multivariate backward linear regression showed that LVEDVI changes were independently associated with myocardial strain-related improvements during fluid resuscitation. The baseline LVEDVI was significantly negatively correlated with the LVGLS and RVGLS (r = -0.44 and − 0.39, respectively) but not LVGCS. LVEDVI increases during fluid resuscitation were associated with improvements in the myocardial strain degree.ConclusionsMyocardial strain alterations were significantly influenced by the cardiac preload during fluid resuscitation in sepsis.

The compliance of sepsis resuscitation care bundle in patients diagnosed with septic shock or sepsis to the International Surviving Sepsis Campaign among patients admitted to a tertiary and teaching hospital, Ethiopia: A 1-year prospective observational study

BackgroundHigh rates of morbidity and mortality would be seen in patients suffering from sepsis and/or septic shock. It has been hypothesised that the Surviving Sepsis Campaign will reduce the morbidity and mortality of individuals who are diagnosed with septic shock and/or sepsis. Improving the surviving sepsis campaign's execution is necessary to reduce these deleterious occurrences. There is currently a lack of local data regarding the management in accordance with the guidelines in the Surviving Sepsis Campaign.Therefore, this study aimed to assess the compliance rate of sepsis resuscitation care bundle in patients diagnosed with septic shock and/or sepsis to the International Surviving Sepsis Campaign among patients admitted to a tertiary and teaching hospital, Ethiopia. MethodsHospital based, prospective observational study was conducted from January 1/2023 to December 31, 2023. Consecutive sampling technique was employed to select study participants for a period of one year and the smaple size was found to be 88 participants. A prepared checklist with standards taken from the International Surviving Sepsis Campaign was used to collect the data. Data were collected through direct-observation, interviewing the responsible physician who made the sepsis and/or septic shock diagnosis, and reviewing patient charts. Data were entered and analysed with statistical package for social sciences (SPSS) version-25. ResultsIn treating patients diagnosed with septic shock and/or sepsis, the total compliance rate with the International Surviving Sepsis Campaign's (ISSC) sepsis resuscitation care bundle was 38 %. In the initial one-hour care bundle, 100 % of patients received the RECOMMENDED initial fluid resuscitation, 64 (72.7 %) of patients received broad spectrum antibiotics, 12 (14 %) of patients had blood culture before antibiotics. ConclusionsThis study concluded that sepsis resuscitation care bundle practice was subpar. Therefore, we recommend that educational training, increased awareness, and sharing the current and existing evidences are an important measures to improve the utility of the recommendations of the International Surviving Sepsis Campaign's (ISSC). After the sepsis treatment bundle has been fully implemented, a re-evaluation will take place in the summer of 2025.

Fluid management for sepsis-induced hypotension in patients with advanced chronic kidney disease: a secondary analysis of the CLOVERS trial

BackgroundEarly fluid management in patients with advanced chronic kidney disease (CKD) and sepsis-induced hypotension is challenging with limited evidence to support treatment recommendations. We aimed to compare an early restrictive versus liberal fluid management for sepsis-induced hypotension in patients with advanced CKD.MethodsThis post-hoc analysis included patients with advanced CKD (eGFR of less than 30 mL/min/1.73 m2 or history of end-stage renal disease on chronic dialysis) from the crystalloid liberal or vasopressor early resuscitation in sepsis (CLOVERS) trial. The primary endpoint was death from any cause before discharge home by day 90.ResultsOf 1563 participants enrolled in the CLOVERS trial, 196 participants had advanced CKD (45% on chronic dialysis), with 92 participants randomly assigned to the restrictive treatment group and 104 assigned to the liberal fluid group. Death from any cause before discharge home by day 90 occurred significantly less often in the restrictive fluid group compared with the liberal fluid group (20 [21.7%] vs. 41 [39.4%], HR 0.5, 95% CI 0.29–0.85). Participants in the restrictive fluid group had more vasopressor-free days (19.7 ± 10.4 days vs. 15.4 ± 12.6 days; mean difference 4.3 days, 95% CI, 1.0–7.5) and ventilator-free days by day 28 (21.0 ± 11.8 vs. 16.5 ± 13.6 days; mean difference 4.5 days, 95% CI, 0.9–8.1).ConclusionsIn patients with advanced CKD and sepsis-induced hypotension, an early restrictive fluid strategy, prioritizing vasopressor use, was associated with a lower risk of death from any cause before discharge home by day 90 as compared with an early liberal fluid strategy.Trial RegistrationNCT03434028 (2018-02-09), BioLINCC 14149.

Relationship Between Fluid Administration During the First Three Hours of Sepsis Resuscitation and Mortality: A Multicenter Observational Study.

Background Timely and effective fluid resuscitation is vital for stabilizing sepsis while avoiding volume overload. We aimed to assess how the administration of a 30 mL/kg bolus fluid affects patients with sepsis within three hours of clinical outcomes. Methods This multicenter observational study included adult patients diagnosed with sepsis in 17 intensive care units at tertiary hospitals in Japan between July 2019 and August 2020. The clinical outcomes of patients with sepsis who received ≥30 mL/kg bolus fluid within three hours (30 × 3 group) were compared with those who received <30 mL/kg fluid (non-30 × 3 group). Results Of 172 eligible patients, 74 (43.0%) belonged to the 30 × 3 group, and 98 (57.0%) belonged to the non-30 × 3 group. The median Sequential Organ Failure Assessment score was 9 (interquartile range (Q1-Q3): 7-11) in the 30 × 3 group and 7 (Q1-Q3: 4-9) in the non-30 × 3 group (P < 0.01). The 28-day mortality rate was 29.7% in the 30 × 3 group and 12.2% in the non-30 × 3 group (P < 0.01). However, the adjusted odds ratio by the inverse probability of treatment weighting analysis with propensity score for the 28-day mortality rate of the 30 × 3 group compared with that in the non-30 × 3 group was 2.17 (95% confidence interval: 0.85-5.54). Among the propensity score-matched patients, the 28-day mortality rate was 30% in the 30 × 3 (n = 70) and non-30 × 3 (n = 95) groups, respectively (P = 0.72). Conclusions Patients with sepsis who received the 30 mL/kg bolus fluid within three hours experienced more severe clinical outcomes. However, it was not associated with the increased odds of the 28-day mortality.

Albumin Versus Balanced Crystalloid for the Early Resuscitation of Sepsis: An Open Parallel-Group Randomized Feasibility Trial- The ABC-Sepsis Trial.

International guidelines recommend IV crystalloid as the primary fluid for sepsis resuscitation, with 5% human albumin solution (HAS) as the second line. However, it is unclear which fluid has superior clinical effectiveness. We conducted a trial to assess the feasibility of delivering a randomized controlled trial comparing balanced crystalloid against 5% HAS as sole early resuscitation fluid in patients with sepsis presenting to hospital. Multicenter, open, parallel-group randomized feasibility trial. Emergency departments (EDs) in 15 U.K. National Health Service (NHS) hospitals. Adult patients with sepsis and a National Early Warning Score 2 greater than or equal to five requiring IV fluids withing one hour of randomization. IV fluid resuscitation with balanced crystalloid or 5% HAS for the first 6 hours following randomization. Primary feasibility outcomes were recruitment rate and 30-day mortality. We successfully recruited 301 participants over 12 months. Mean ( sd ) age was 69 years (± 16 yr), and 151 (50%) were male. From 1303 participants screened; 502 participants were potentially eligible and 300 randomized to receive trial intervention with greater than 95% of participants receiving the intervention. The median number of participants per site was 19 (range, 1-63). Thirty-day mortality was 17.9% ( n = 53). Thirty-one participants died (21.1%) within 30 days in the 5% HAS arm, compared with 22 participants (14.8%) in the crystalloid arm (adjusted odds ratio, 1.50; 95% CIs, 0.84-2.83). Our results suggest it is feasible to recruit critically ill patients to a fluid resuscitation trial in U.K. EDs using 5% HAS as a primary resuscitation fluid. There was lower mortality in the balanced crystalloid arm. Given these findings, a definitive trial is likely to be deliverable, but the point estimates suggest such a trial would be unlikely to demonstrate a significant benefit from using 5% HAS as a primary resuscitation fluid in sepsis.

Use of digital technologies for staff education and training programmes on newborn resuscitation and complication management: a scoping review

BackgroundPoor-quality care is linked to higher rates of neonatal mortality in low-income and middle-income countries (LMICs). Limited educational and upskilling opportunities for healthcare professionals, particularly those who work in remote...

Simulation training on respectful emergency obstetric and neonatal care in north-western Madagascar: a mixed-methods evaluation of an innovative training program

BackgroundThe rates of maternal and neonatal deaths in Madagascar are among the highest in the world. In response to a request for additional training from obstetrical care providers at the Ambanja district hospital in north-eastern Madagascar, a partnership of institutions in Switzerland and Madagascar conducted innovative training on respectful emergency obstetric and newborn care using e-learning and simulation methodologies. The training focused on six topics: pre-eclampsia, physiological childbirth, obstetric maneuvers, postpartum hemorrhage, maternal sepsis, and newborn resuscitation. Cross-cutting themes were interprofessional communication and respectful patient care. Ten experienced trainers participated in an e-training-of-trainers course conducted by the Swiss partners. The newly-trained trainers and Swiss partners then jointly conducted the hybrid remote/in-person training for 11 obstetrical care providers in Ambanja.MethodsA mixed methods evaluation was conducted of the impact of the training on participants’ knowledge and practices. Trainees’ knowledge was tested before, immediately after, and 6 months after the training. Focus group discussions were conducted to elicit participants’ opinions about the training, including the content and pedagogical methods.ResultsTrainees’ knowledge of the six topics was higher at 6 months (with an average of 71% correct answers) compared to before the training (62%), although it was even higher (83%) immediately after the training. During the focus group discussions, participants highlighted their positive impressions of the training, including its impact on their sense of professional effectiveness. They reported that their interprofessional relationships and focus on respectful care had improved. Simulation, which was a new methodology for the participants native to Madagascar, was appreciated for its engaging and active format, and they enjoyed the hybrid delivery of the training. Participants (including the trainers) expressed a desire for follow-up engagement, including additional training, and improved access to more equipment.ConclusionThe evaluation showed improvements in trainees’ knowledge and capacity to provide respectful emergency care to pregnant women and newborns across all training topics. The hybrid simulation-based training method elicited strong enthusiasm. Significant opportunity exists to expand the use of hybrid onsite/remote simulation-based training to improve obstetrical care and health outcomes for women and newborns in Madagascar and elsewhere.

Can Machine Learning Personalize Cardiovascular Therapy in Sepsis?

Large randomized trials in sepsis have generally failed to find effective novel treatments. This is increasingly attributed to patient heterogeneity, including heterogeneous cardiovascular changes in septic shock. We discuss the potential for machine learning systems to personalize cardiovascular resuscitation in sepsis. While the literature is replete with proofs of concept, the technological readiness of current systems is low, with a paucity of clinical trials and proven patient benefit. Systems may be vulnerable to confounding and poor generalization to new patient populations or contemporary patterns of care. Typical electronic health records do not capture rich enough data, at sufficient temporal resolution, to produce systems that make actionable treatment suggestions. To resolve these issues, we recommend a simultaneous focus on technical challenges and removing barriers to translation. This will involve improving data quality, adopting causally grounded models, prioritizing safety assessment and integration into healthcare workflows, conducting randomized clinical trials and aligning with regulatory requirements.

Current diagnosis and management of necrotizing soft tissue infections: What you need to know.

Necrotizing soft tissue infections are rare bacterial infections of the skin and soft tissues with a high morbidity and mortality rate, requiring prompt diagnosis and surgical intervention. These represent a spectrum of disease resulting in tissue necrosis that is rapidly progressive; however, they remain a diagnostic challenge because the average surgeon or emergency medicine provider may only see one or two over the course of their career. Diagnosis is largely clinical and based on subtle physical examination findings, physiologic instability, and laboratory derangements. Aids to diagnosis such as scoring systems and cross-sectional imaging may be used; however, the findings are not specific, so management should not be based on these alone. The most common cause of necrotizing soft tissue infection is polymicrobial infection; however, specific bacteria such as clostridial species, group A streptococcal, methicillin resistant Staphylococcus aureus , and aquatic bacteria may also be causative. Initial management includes broad spectrum antibiotics, fluid resuscitation for severe sepsis, and early aggressive surgical debridement. Often, these patients require multiple operative debridement to achieve source control, and a low threshold for repeat debridement should be maintained because these infections can progress rapidly. Once source control is achieved, patients may be left with extensive wounds requiring multidisciplinary care and wound management. Necrotizing infections have long been viewed based on mortality outcomes alone because of their rarity and severity. Over recent years, more reports have shown a decrease in the mortality rates from those previously reported, allowing for a focus on methods to improve morbidity of these infections.

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.

Research progress of diagnostic and therapeutic value of carbon dioxide-derived indicators in patients with sepsis

Effectively assessing oxygen delivery and demand is one of the key targets for fluid resuscitation in sepsis. Clinical signs and symptoms, blood lactic acid levels, and mixed venous oxygen saturation (SvO2) or central venous oxygen saturation (ScvO2) all have their limitations. In recent years, these limitations have been overcome through the use of derived indicators from carbon dioxide (CO2) such as mixed veno-arterial carbon dioxide partial pressure difference (Pv-aCO2, PCO2 gap, or ΔPCO2), the ratio of mixed veno-arterial carbon dioxide partial pressure difference to arterial-mixed venous oxygen content difference (Pv-aCO2/Ca-vO2). Pv-aCO2, PCO2 gap or ΔPCO2 is not a purely anaerobic metabolism indicator as it is influenced by oxygen consumption. However, it reliably indicates whether blood flow is sufficient to carry CO2 from peripheral tissues to the lungs for clearance, thus reflecting the adequacy of cardiac output and metabolism. The Pv-aCO2/Ca-vO2 may serve as a marker of hypoxia. SvO2 and ScvO2 represent venous oxygen saturation, reflecting tissue oxygen utilization. When oxygen delivery decreases but tissues still require more oxygen, oxygen extraction rate usually increases to meet tissue demands, resulting in decreased SvO2 and ScvO2. But in some cases, even if the oxygen delivery rate and tissue utilization rate of oxygen are reduced, it may still lead to a decrease in SvO2 and ScvO2. Sepsis is a classic example where tissue oxygen utilization decreases due to factors such as microcirculatory dysfunction, even when oxygen delivery is sufficient, leading to decrease in SvO2 and ScvO2. Additionally, the solubility of CO2 in plasma is approximately 20 times that of oxygen. Therefore, during sepsis or septic shock, derived variables of CO2 may serve as sensitive markers for monitoring tissue perfusion and microcirculatory hemodynamics. Its main advantage over blood lactic acid is its ability to rapidly change and provide real-time monitoring of tissue hypoxia. This review aims to demonstrate the principles of CO2-derived variables in sepsis, assess the available techniques for evaluating CO2-derived variables during the sepsis process, and discuss their clinical relevance.

Positive fluid balance and poor outcomes after initial intensive care unit admission in sepsis resuscitation: a retrospective study.

Fluid resuscitation of patients with sepsis is crucial. This study explored the role of fluid balance in the early resuscitation of sepsis patients in the intensive care unit (ICU). A retrospective study of patients with sepsis using the Peking Union Medical College Hospital Intensive Care Medical Information System and Database from January 2014 to June 2020 was performed. Based on the survival status on day 28, the training cohort was divided into an alive group (n = 1,803) and a deceased group (n = 429). Univariate and multivariate analyses were used to identify risk factors, and the integrated learning XGBoost algorithm was used to construct a model for predicting outcomes. ROC and Kaplan-Meier survival curves were used to evaluate the effectiveness of the model. A verification cohort (n = 433) was used to verify the model. Univariate analysis showed that fluid balance is an important covariate. Based on the scatterplot distribution, a significant difference in mortality was determined between groups stratified with a balance of 1000 ml. There were associations in the multivariate analysis between poor outcomes and sex, PO2/FiO2, serum creatinine, FiO2, platelets, respiratory rate, SPO2, temperature, and total fluid volume (1000 ml). Among these variables, total fluid balance (1000 ml) had an OR of 1.98 (CI: 1.41-2.77, p < 0.001). Therefore, the model was built with these nine factors using XGBoost. Cross validation was used to verify generalizability. This model performed better than the SOFA and APACHE II models. The result was well verified in the verification cohort. A causal forest model suggested that patients with hypoxemia may suffer from positive fluid balance. Sepsis fluid resuscitation in the ICU should be a targeted and goal-oriented treatment. A new prognostic prediction model was constructed and indicated that a 6-hour positive fluid balance after ICU initial admission is a risk factor for poor outcomes in sepsis patients. A 6-hour fluid balance above 1000 ml should be performed with caution.

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.

Application of a combination of lactated Ringer's solution and ulinastatin for early resuscitation in sepsis

Purpose: To investigate the effect of early resuscitation using a combination of lactated Ringer's solution and ulinastatin on the survival rate of patients with sepsis.&#x0D; Methods: 82 patients with septic shock admitted to Xi'an People's Hospital, China from June 2017 to December 2020 were enrolled and randomly divided into control and study groups (n = 41 each). Patients in control group were given conventional fluid resuscitation and anti-infective therapy, while patients in study group were additionally given ulinastatin. Acute physiology and chronic health evaluation (APACHE II) score, sequential organ failure assessment (SOFA) score, and tissue perfusion were determined. Also, mechanical ventilation time, intensive care unit (ICU) stay time, and 28-day mortality rates were recorded.&#x0D; Results: Both groups presented no significant difference in clinical characteristics before treatment. After treatment, APACHE II score, SOFA score, and lactic acid level of the study group significantly decreased (p &lt; 0.05), and the patients’ condition improved. Moreover, inflammation-related indices, viz, procalcitonin (PCT), white blood cells (WBC), and C reactive protein (CRP) were significantly reduced in the study group (p &lt; 0.05). Renal function-related indices which include creatinine, and blood urea nitrogen (BUN) significantly decreased in study group (p &lt; 0.05). Mechanical ventilation time, and ICU stay time were significantly shortened (p &lt; 0.0001), while short-term survival rate significantly improved (p &lt; 0.05).&#x0D; Conclusion: Lactated Ringer's solution in combination with ulinastatin expedites tissue perfusion and recovery, suppresses inflammation, enhances renal function, and significantly enhances the survival rate of septic patients. These findings provide valuable information for exploring new therapeutic approaches to sepsis.

Cost-effectiveness of intravenous resuscitation fluids in sepsis patients: a patient-level data analysis in Jordan

Aim Albumin role as fluid resuscitation in sepsis remains understudied in low- and middle-income countries. This study aimed to evaluate the cost-effectiveness of intravenous (IV) Albumin compared to Crystalloids in sepsis patients using patient-level data in Jordan. Methods This was a retrospective cohort study of sepsis patients aged 18 or older admitted to intensive care units (ICU) at two major tertiary hospitals during the period 2018–2019. Patients information, type of IV fluid, and clinical outcomes were retrieved from medical records, and charges were retrieved from the billing system. A 90-day partitioned survival model with two health states (alive and dead) was constructed to estimate the survival of sepsis patients receiving either Albumin or Crystalloids as IV fluids for resuscitation. Overall survival was predicted by fitting a Weibull model on the patient-level data from the current study. To further validate the results, and to support the assessment of uncertainty, time-dependent transition probabilities of death at each cycle were estimated and used to construct a state-transition patient-level simulation model with 10,000 microsimulation trials. Adopting the healthcare system perspective, incremental cost-effectiveness ratios(ICERs) of Albumin versus Crystalloids were calculated in terms of the probability to be discharged alive from the ICU. Uncertainty was explored using probabilistic sensitivity analysis. Results In the partitioned survival model, Albumin was associated with an incremental cost of $1,007 per incremental1% in the probability of being discharged alive from the ICU. In the state-transition patient-level simulation model, ICER was $1,268 per incremental 1% in the probability of being discharged alive. Probabilistic sensitivity analysis showed that Albumin was favored at thresholds >$800 per incremental 1%in the probability of being discharged alive from the ICU. Conclusion IV Albumin use in sepsis patients might not be cost-effective from the healthcare perspective of Jordan. This has important implications for policymakers to readdress Albumin prescribing practice in sepsis patients.

Raise the Flag I: the impact of a sepsis quality improvement programme on delivery of a sepsis resuscitation bundle at a tertiary hospital in New Zealand.

To study changes in sepsis resuscitation practice at a tertiary hospital before and after the introduction of a quality improvement programme, and to identify variables associated with its delivery. "Raise the Flag", a quality sepsis programme, including the Sepsis Six, was launched in 2018. Adult patients with sepsis were sampled prior to the intervention and during two subsequent periods. Clinicians were more likely to deliver the resuscitation bundle in the post-implementation period (adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.27-3.79, p=0.005). This was not sustained at 18-30 months (aOR 1.22, 95% CI 0.89-1.66, p=0.21). After adjusting for potential confounders, each additional decade of patient age was associated with reduced odds of receiving the bundle (aOR 0.83, 95% CI 0.73-0.95, p=0.005). Admission to intensive care increased in the combined post-implementation periods (aOR 2.81, 95% CI 1.13-6.97, p=0.03). The odds of receiving a resuscitation bundle improved immediately following the launch of the Raise the Flag programme. Resuscitation practice differed based on patient age. Odds of admission to intensive care were increased.