Septic shock and cancer occur routinely in intensive care unit patients. Our aim was to use the French national hospitalization database to overcome the limitations of the small cohorts used in previous studies that examined the 90-day mortality rate of patients with septic shock and either solid or hematological cancers. We performed a retrospective cohort study using data from the French national hospitalization database regarding adult patients with septic shock from 2017 to 2018. The primary outcomes were the hospital mortality rate at 90 days in patients with solid cancer and hematological cancer. Secondary outcomes were the risk factors associated with mortality in our cohort. Associations between 90-day mortality and cancer have been estimated by multivariable analysis. Septic shock was found in 77,888 patients, including 19,329 patients with solid cancer, 6,498 with hematological cancer, and 52,061 noncancer patients. The 90-day mortality rate was 44.3 %, 53.7%, and 59.1% for noncancer patients, solid cancer patients and hematological cancer patients, respectively. An association was found between 90-day mortality and solid cancer (adjusted hazard ratio 1.55 [1.51-1.59]) or hematological cancer (1.59 [1.53-1.65]) as compared with noncancer patients. Risk factors for 90-day mortality included both hematological and solid cancers. In septic shock patients, solid cancer and hematological cancer were associated with increased 90-day mortality compared with noncancer patients. Future investigations are required to assess the interplay between cancer and septic shock. National Commission for Data Protection (CNIL) under number F20220318151239. Weniger anzeigen

The optimal duration of antibiotic treatment in patients with bacteremia is a matter of ongoing debate. We conducted a meta-analysis of randomized controlled trials that compared 7 days with 14 days of antimicrobial treatment in adults with bacteremia. The systematic search included trials published until December 2024. Efficacy outcomes included 90-day all-cause mortality, recurrence of bacteremia and mean length of hospital stay. Safety outcomes included the total number of adverse events, Clostridioides difficile infections, diarrhea, acute kidney injury, rash or emergence of antibiotic resistance. The final analysis included four randomized controlled trials with a total of 4790 participants. Death by day 90 occurred in 321 (13.3%) of 2406 patients receiving antibiotic treatment for 7 days and 342 (14.3%) of 2384 patients receiving antibiotic treatment for 14 days (RR 0.93 [95% CI, 0.81 to 1.07)]; p = 0.30; prediction interval 0.74 to 1.17). The mean hospital stay did not differ significantly (mean difference - 0.18 days [95% CI, -1.03 to 0.67]; p = 0.69; prediction interval - 2.57 to 2.22). Recurrence of bacteremia was similar between antibiotic treatment for 7 days (64 [2.7%] of 2406) and antibiotic treatment for 14 days (56 [2.3%] of 2384) (RR 1.14 [95% CI, 0.80 to 1.63)]; p = 0.47; prediction interval 0.64 to 2.03). Safety outcomes, including the total number of adverse events, Clostridioides difficile infections, diarrhea, acute kidney injury, rash, and antibiotic resistance, were similar between groups. This meta-analysis suggests that 7-day and 14-day antimicrobial treatment is associated with a similar efficacy and safety profile in patients with bacteremia. Weniger anzeigen

The optimal timing for initiating norepinephrine in septic shock is debated. This updated systematic review and meta-analysis aimed to evaluate the impact of early versus delayed norepinephrine initiation on mortality and clinical outcomes in adults with septic shock. A systematic search in Pubmed, EMbase and the Cochrane Library to identify eligible randomized controlled trials, propensity score matching (PSM) and observational studies that compare early norepinephrine initiation with non-early norepinephrine initiation in patients with acute circulatory failure. The primary outcome was mortality in intensive care unit. Secondary outcomes included intensive care unit length of stay, fluid volume received at 6 h, norepinephrine dose, mechanical ventilation-free days, renal replacement therapy free days, and time to achieve a targeted mean arterial pressure (MAP). Meta-analysis and subgroup analysis were conducted to calculate odds ratio (OR) or mean difference with 95% confidence interval (95%CI) using random-effect model. Trial sequential analysis was conducted to evaluate the conclusiveness of evidence. Ten studies (two RCT, three PSM and five observational studies) involving 4767 patients were included. Early norepinephrine significantly reduced mortality in RCT (OR 0.49, 95%CI 0.25-0.96; I = 45%, p = 0.04), pooled RCT and PSM (OR 0.65, 95%CI 0.42-0.99; I = 74%, p = 0.05), and observational studies (OR 0.71, 95%CI 0.54-0.94; I = 66%). The trial sequential analysis indicated more data are needed. Subgroup analyses showed reduced mortality with early norepinephrine when lactate was ≤ 3mmol/L and administered within 1 h. Secondary outcomes showed a reduced fluid volume at 6h (RCT + PSM: mean difference -502 mL, 95%CI -899 to -106; I = 91%, p = 0.01), faster MAP target achievement (RCT + PSM: mean difference -1.30h, 95%CI -1.75 to -0.85; I = 0%, p < 0.01), more mechanical ventilation-free days (RCT + PSM: mean difference 3.99 days, 95%CI 2.42-5.57; I = 32%, p < 0.01) and smaller cumulative norepinephrine dose (Observational: mean difference -3.44 mcg/kg, 95%CI -6.13 to -0.76; I = 0%, p = 0.01) in the early initiation group compare to the non-early initiation group. Early norepinephrine introduction in septic shock is associated with reduced mortality, decreased fluid volume administered at 6 h, faster time to achieve MAP target and more mechanical ventilation-free days. However, the trial sequential analysis indicates that further RCT are still needed to confirm these findings. Weniger anzeigen

Sepsis is the leading cause of inpatient mortality in the United States. The optimal timing and volume of fluid resuscitation for septic shock remain a topic of debate. This study evaluated the effect of time to completion of at least 30 mL/kg of fluid and the impact of smaller fluid volumes on hospital outcomes among patients with septic shock. Retrospective cohort study in a large community healthcare system (310,000 annual emergency visits) of all adults (age ≥ 18 yr) admitted from January 2017 to December 2022 with an International Classification of Diseases, 10th Revision diagnosis of sepsis and an initial emergency department (ED) systolic blood pressure (SBP) less than 90 mm Hg, mean arterial blood pressure less than 65 mm Hg, and/or lactate greater than or equal to 4 mmol/L. The main outcomes include hospital mortality, ICU admission, mechanical ventilation, and vasopressor use. The relationship between time to completion of 30 mL/kg and the main outcomes was assessed using generalized linear models. Among the 1602 patients who met inclusion criteria, 1190 (74.3%) received at least 30 mL/kg of fluid after ED arrival. The overall mortality rate was 24.2%, with 28.7% requiring mechanical ventilation and 64.3% requiring vasopressors. Receipt of at least 30 mL/kg between 2 and 3 hours from the time of initial ED SBP (time zero) was associated with lower odds of mortality (odds ratio [OR], 0.61; 95% CI, 0.39-0.97; p = 0.04) and mechanical ventilation use (OR, 0.43; 95% CI, 0.29-0.65; p < 0.01) compared with other intervals. Compared with receiving 30 mL/kg or greater, receiving at least 20 but less than 30 mL/kg within the first hour was associated with the lowest odds of mortality (OR, 0.33; 95% CI, 0.11-0.97; p = 0.04). Our findings show that receipt of 30 mL/kg of fluid within 3 hours is associated with reduced mortality and the need for mechanical ventilation among patients with septic shock. These results support the current Surviving Sepsis Campaign fluid recommendations. Weniger anzeigen

The Centers for Medicare & Medicaid Services (CMS) Severe Sepsis and Septic Shock Management Bundle (SEP-1) is now included in the Hospital Value-Based Purchasing (VBP) Program. To assess the evidence supporting SEP-1 compliance or SEP-1 implementation in improving sepsis mortality. PubMed, Web of Science, EMBASE, CINAHL Complete, and Cochrane Library from inception to 26 November 2024. Studies of adults with sepsis that included 3- or 6-hour sepsis bundles defined by SEP-1 specifications. Article screening, full-text review, data extraction, and risk-of-bias assessment were independently performed by 2 authors. Level of evidence was determined using GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria and National Quality Forum criteria. A total of 4403 unique references were screened, and 17 studies were included. Twelve studies assessed the relationship between SEP-1 compliance and mortality; 5 showed statistically significant benefit, whereas 7 did not. Among studies showing benefit, 1 did not adjust for confounders, 1 found benefit only among patients with severe sepsis, 1 included only patients with septic shock, and 1 included only Medicare beneficiaries. Five studies assessed the relationship between SEP-1 implementation and sepsis mortality; only 1 showed significant benefit, but it did not adjust for mortality trends before SEP-1 implementation. All 17 studies were observational, and none had low risk of bias. The conclusions are limited by the underlying quality of the available studies, as all were observational. Because there was considerable methodologic heterogeneity among the included studies, a meta-analysis was not performed as the results could have been misleading. This review found no moderate- or high-level evidence to support that compliance with or implementation of SEP-1 was associated with sepsis mortality. CMS should reconsider the addition of SEP-1 to the Hospital VBP Program. None. (PROSPERO: CRD42023482787). Weniger anzeigen

The Centers for Medicare & Medicaid Services Severe Sepsis and Septic Shock Management Bundle (SEP-1) is supported by observational studies that report SEP-1 compliance is associated with lower mortality. Most studies, however, adjusted for limited confounders and provided little insight into why bundle-compliant care was not provided. To identify the clinical factors that complicate the diagnosis and management of sepsis and assess their association with SEP-1 compliance and mortality. This retrospective cohort study was conducted among 590 adults with sepsis in the emergency department of 4 academic hospitals from January 1, 2019, to December 31, 2022. Patients‘ medical records were reviewed between September 2022 and December 2023. Study outcomes were (1) characteristics of patients who received SEP-1-compliant care vs characteristics of patients who received noncompliant care and (2) association between SEP-1 compliance and hospital mortality using multivariable models to adjust for successively more potential confounders (first demographics and comorbidities, then infection source, then severity of illness, and then clinical markers of complexity). Of 590 patients with sepsis (median age, 65 years [IQR, 53-77 years]; 329 men [55.8%]), 335 (56.8%) received SEP-1-compliant care, and 225 (43.2%) received noncompliant care. Compared with patients in the compliant group, patients in the noncompliant group were more likely to be 65 years or older (142 [55.7%] vs 158 [47.2%]; odds ratio [OR], 1.41 [95% CI, 1.01-1.95]), to have multiple comorbidities (Elixhauser score >20: 99 [38.8%] vs 99 [29.6%]; OR, 1.51 [95% CI, 1.07-2.13]), and to have a higher incidence of septic shock (107 [42.0%] vs 107 [31.9%]; OR, 1.54 [95% CI, 1.10-2.16]), kidney dysfunction (87 [34.1%] vs 80 [23.9%]; OR, 1.65 [95% CI, 1.15-2.37]), and thrombocytopenia (43 [16.9%] vs 37 [11.0%]; OR, 1.16 [95% CI, 1.02-2.62]) on presentation. Compared with patients in the compliant group, those in the noncompliant group also had more nonfebrile presentations (136 [53.3%] vs 121 [36.1%]; OR, 2.02 [95% CI, 1.45-2.82]), impaired mental status (92 [36.1%] vs 94 [28.1%]; OR, 1.45 [95% CI, 1.02-2.05]), need for bedside procedures (57 [22.4%] vs 41 [12.2%]; OR, 2.06 [95% CI, 1.33-3.21]), acute concurrent noninfectious illnesses (140 [54.9%] vs 151 [45.1%]; OR, 1.48 [95% CI, 1.07-2.06]), and noninfectious illness as the primary factor associated with their presentation (84 [32.9%] vs 71 [21.2%]; OR, 1.82 [95% CI, 1.08-3.08]). SEP-1 compliance was associated with lower crude mortality rates compared with noncompliance (40 [11.9%] vs 41 [16.1%]; unadjusted OR, 0.60 [95% CI, 0.37-0.98]), but there was no statistically significant difference between groups after successively adjusting for demographics and comorbidities (adjusted OR [AOR], 0.71 [95% CI, 0.42-1.18]), infection source (AOR, 0.71 [95% CI, 0.43-1.20]), severity of illness (AOR, 0.86 [95% CI, 0.50-1.49]), and clinical markers of complexity (AOR, 1.08 [95% CI, 0.61-1.91]). In this cohort study of adults with sepsis, complex clinical presentations were more common among patients whose treatment was noncompliant with SEP-1. These nuances are poorly captured in most observational studies but confound the association between SEP-1 compliance and mortality. Weniger anzeigen

Norepinephrine is the first-line vasopressor for patients with septic shock. When and whether a second agent, such as vasopressin, should be added is unknown. To derive and validate a reinforcement learning model to determine the optimal initiation rule for vasopressin in adult, critically ill patients receiving norepinephrine for septic shock. Reinforcement learning was used to generate the optimal rule for vasopressin initiation to improve short-term and hospital outcomes, using electronic health record data from 3608 patients who met the Sepsis-3 shock criteria at 5 California hospitals from 2012 to 2023. The rule was evaluated in 628 patients from the California dataset and 3 external datasets comprising 10 217 patients from 227 US hospitals, using weighted importance sampling and pooled logistic regression with inverse probability weighting. Clinical, laboratory, and treatment variables grouped hourly for 120 hours in the electronic health record. The primary outcome was in-hospital mortality. The derivation cohort (n = 3608) included 2075 men (57%) and had a median (IQR) age of 63 (56-70) years and Sequential Organ Failure Assessment (SOFA) score at shock onset of 5 (3-7 [range, 0-24, with higher scores associated with greater mortality]). The validation cohorts (n = 10 217) were 56% male (n = 5743) with a median (IQR) age of 67 (57-75) years and a SOFA score of 6 (4-9). In validation data, the model suggested vasopressin initiation in more patients (87% vs 31%), earlier relative to shock onset (median [IQR], 4 [1-8] vs 5 [1-14] hours), and at lower norepinephrine doses (median [IQR], 0.20 [0.08-0.45] vs 0.37 [0.17-0.69] µg/kg/min) compared with clinicians‘ actions. The rule was associated with a larger expected reward in validation data compared with clinician actions (weighted importance sampling difference, 31 [95% CI, 15-52]). The adjusted odds of hospital mortality were lower if vasopressin initiation was similar to the rule compared with different (odds ratio, 0.81 [95% CI, 0.73-0.91]), a finding consistent across external validation sets. In adult patients with septic shock receiving norepinephrine, the use of vasopressin was variable. A reinforcement learning model developed and validated in several observational datasets recommended more frequent and earlier use of vasopressin than average care patterns and was associated with reduced mortality. Weniger anzeigen

Gram-negative bloodstream infections are a common cause of hospitalization. A 2-week duration of antibiotic therapy has been commonly used, but shorter durations may have similar outcomes. To assess whether 7 days of antibiotic therapy was noninferior to 14 days. Starting with a 2022 individual patient data meta-analysis, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify additional eligible randomized clinical trials (RCTs) conducted from May 1, 2022, until November 30, 2024. RCTs involving primarily adults who were hospitalized at the time of Gram-negative bloodstream infection and were allocated to 7 or 14 days of antibiotic therapy. Studies were independently reviewed by 2 investigators. PRISMA guidelines were followed. Data were extracted by 2 investigators. Any unpublished data were obtained directly from study authors. Risk of bias and certainty of the evidence were assessed in duplicate using the Cochrane Risk of Bias Tool, version 2, and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled by separate random-effects meta-analyses for the intention-to-treat (ITT) and per-protocol (PP) populations. A noninformative prior probability was used for the effect, and an evidence-based weakly informative prior probability was used for heterogeneity. Risk ratios (RRs), 95% credible intervals (CrIs), and probability of noninferiority were calculated using a prespecified upper bound of 1.25 or less. Ninety-day all-cause mortality. Four eligible RCTs contributed 3729 patients in the ITT population (1912 women [51.3%]; median age range, 67-79 years) and 3126 in the PP population. In the ITT analysis, within 90 days, 226 patients (12.8%) receiving 7 days of antibiotics died compared with 253 (13.7%) receiving 14 days, corresponding to an RR for 90-day mortality of 0.91 (95% CrI, 0.69-1.22) and a 97.8% probability of noninferiority. In the PP analysis, the RR was 0.93 (95% CrI, 0.68-1.32), corresponding to a 95.1% probability of noninferiority. In this systematic review and meta-analysis of patients with Gram-negative bloodstream infections and adequate source control, 7 days of antibiotic therapy had a high probability of being noninferior to 14 days. These findings support a shorter duration of antibiotic therapy for appropriately selected patients like those in the included RCTs. Weniger anzeigen

To determine the impact of short-acting beta-blocker therapy on outcomes in adult patients with septic shock. We searched MEDLINE, Embase, and unpublished sources from inception to April 19, 2024. We included randomized controlled trials (RCTs) that evaluated short-acting beta-blockers compared with usual care in patients with septic shock. We collected data regarding study and patient characteristics, beta-blocker administration, and clinical, hemodynamic, and biomarker outcomes. Twelve RCTs proved eligible (n = 1170 patients). Short-acting beta-blockers may reduce 28-day mortality (relative risk [RR], 0.76; 95% CI, 0.62-0.93; low certainty) and probably reduce new-onset tachyarrhythmias (RR, 0.37; 95% CI, 0.18-0.78; moderate certainty) but may increase the duration of vasopressors (mean difference [MD], 1.04 d; 95% CI, 0.37-1.72; low certainty). Furthermore, there is an uncertain effect as to whether short-acting beta blockers impact 90-day mortality (RR, 0.98; 95% CI, 0.73-1.31), ICU length of stay (MD, -0.75 d; 95% CI, -3.43 to 1.93 d), hospital length of stay (MD, 1.03 d; 95% CI, -1.92 to 3.98 d), duration of mechanical ventilation (MD, -0.10 d; 95% CI, -1.25 to 1.05 d) (all very low certainty), bradycardia episodes (RR, 3.14; 95% CI, 0.91-14.01), and hypotension episodes (RR, 4.74; 95% CI, 1.62-14.01) (all very low certainty). In patients with septic shock, short-acting beta-blockers may improve survival and reduce new-onset tachyarrhythmias. However, these findings were based on low certainty evidence and given ongoing concerns regarding adverse effects and the increase duration of vasopressor use, we need larger and more rigorous RCTs to evaluate this intervention. Weniger anzeigen

Fluid resuscitation is an important intervention in children with septic shock. The composition of resuscitation fluid is a matter of debate. Our aim was to study the effects of balanced salt solution (BSS) versus normal saline (NS) for resuscitation in pediatric septic shock. We searched MEDLINE, Embase, LILAC, Cochrane Collaboration, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform. Two independent authors screened title and abstracts and then full papers of included studies. Two authors extracted data from full papers independently. Random-effects model was used for analysis of RCTs. We used Cochrane’s risk of bias tool for assessing the quality of studies. Primary outcome was mortality and secondary outcomes were rates of acute kidney injury (AKI), need for renal replacement therapy (RRT), and adverse effects (hyperchloremia, metabolic acidosis, and fluid overload); and duration of PICU and hospital stay. Five RCTs with 992 children were included. Resuscitation with BSS versus NS was not associated with reduction in mortality (RR 0.82, 95% CI 0.45-1.50, p = 0.52; RCTs = 5); with similar results on sensitivity analysis (RR 0.76, 95% CI 0.41-1.41, p = 0.52; 4 RCTs = 4). However, resuscitation with BSS was associated with lower rates of AKI (sensitivity analysis RR 0.64, 95% CI 0.50-0.82, p = 0.0004; RCTs = 3); lesser need for RRT (RR 0.52, 95% CI 0.35-0.76, p = 0.0008; RCTs = 2); and lower rate of hyperchloremia (RR 0.74, 95% CI 0.62-0.87, p = 0.0002; RCTs = 3). The data is scant for other secondary outcomes (metabolic acidosis, fluid overload, and duration of PICU and hospital stay) to make any suggestions. The overall ‚risk of bias‘ was low and unclear in most domains. Use of BSS as resuscitation fluid in pediatric septic shock was not associated with reduction in mortality. However, BSS was associated with decreased risk of AKI, need of RRT and hyperchloremia. PROSPERO (CRD42022332208). Weniger anzeigen