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Cureus Jun 2022Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to... (Review)
Review
Eculizumab, first-line therapy for paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), has infectious side effects in addition to its therapeutic benefits. This study aims to discuss the mechanism of development of infections, prevention, and timely treatment to prevent complications such as septic shock and mortality. The study was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist and reporting guidelines for systematic review. Inclusion and exclusion criteria were determined. A total of 10 research papers were extracted after exploring Pubmed and Google Scholar from 2001 to 2021. The New Castle Ottawa Questionnaire for non-randomized clinical trials and the National Institutes of Health (NIH) quality assessment tool for case reports and case series were used to assess the risk of bias. The studies included in this systematic review describe infections with , , unusual species, , and . The main goal of this review is to impress upon the seriousness of the infectious complications associated with eculizumab. Health care providers should maintain a high index of suspicion for early identification and treatment.
PubMed: 35784997
DOI: 10.7759/cureus.25640 -
Critical Care Medicine Dec 2023This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to conduct a comprehensive and updated systematic review with network meta-analysis (NMA) to assess the outcome benefits of various blood purification modalities for adult patients with severe infection or sepsis.
DATA SOURCES
We conducted a search of PubMed, MEDLINE, clinical trial registries, Cochrane Library, and Embase databases with no language restrictions.
STUDY SELECTION
Only randomized controlled trials (RCTs) were selected.
DATA EXTRACTION
The primary outcome was overall mortality. The secondary outcomes were the length of mechanical ventilation (MV) days and ICU stay, incidence of acute kidney injury (AKI), and kidney replacement therapy requirement.
DATA SYNTHESIS
We included a total of 60 RCTs with 4,595 participants, comparing 16 blood purification modalities with 17 interventions. Polymyxin-B hemoperfusion (relative risk [RR]: 0.70; 95% CI, 0.57-0.86) and plasma exchange (RR: 0.61; 95% CI, 0.42-0.91) were associated with low mortality (very low and low certainty of evidence, respectively). Because of the presence of high clinical heterogeneity and intransitivity, the potential benefit of polymyxin-B hemoperfusion remained inconclusive. The analysis of secondary outcomes was limited by the scarcity of available studies. HA330 with high-volume continuous venovenous hemofiltration (CVVH), HA330, and standard-volume CVVH were associated with shorter ICU stay. HA330 with high-volume CVVH, HA330, and standard-volume CVVH were beneficial in reducing MV days. None of the interventions showed a significant reduction in the incidence of AKI or the need for kidney replacement therapy.
CONCLUSIONS
Our NMA suggests that plasma exchange and polymyxin-B hemoperfusion may provide potential benefits for adult patients with severe infection or sepsis/septic shock when compared with standard care alone, but most comparisons were based on low or very low certainty evidence. The therapeutic effect of polymyxin-B hemoperfusion remains uncertain. Further RCTs are required to identify the specific patient population that may benefit from extracorporeal blood purification.
Topics: Adult; Humans; Shock, Septic; Network Meta-Analysis; Randomized Controlled Trials as Topic; Sepsis; Polymyxin B; Acute Kidney Injury
PubMed: 37470680
DOI: 10.1097/CCM.0000000000005991 -
Shock (Augusta, Ga.) Nov 2023Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour's vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Norepinephrine; Cohort Studies; Renal Replacement Therapy
PubMed: 37695641
DOI: 10.1097/SHK.0000000000002214 -
Journal of Critical Care Jun 2023We reviewed the different studies using the terms "refractory septic shock" and/or "catecholamine resistance" and/or "high dose norepinephrine" so as to highlight the...
BACKGROUND
We reviewed the different studies using the terms "refractory septic shock" and/or "catecholamine resistance" and/or "high dose norepinephrine" so as to highlight the heterogeneity of the definitions used by authors addressing such concepts.
METHOD
A systematic review was conducted assessing the papers reporting data on refractory septic shock. We used keywords as exact phrases and subject headings according to database syntax.
RESULTS
Of 276 papers initially reviewed, we included 8 studies - 3 randomized controlled trials, 3 prospective studies and 2 retrospective studies, representing a total of 562 patients with septic shock. Catecholamine resistance was generally defined as "a decreased vascular responsiveness to catecholamine independently of the administered norepinephrine dose". Refractory septic shock was broadly defined as "a clinical condition characterized by persistent hyperdynamic shock even though adequate fluid resuscitation (individualized doses) and high doses of norepinephrine (≥ 1 μg/kg/min)". Reported "high doses" of norepinephrine were often ≥1 μg/kg/min. However, wide variability was found throughout the literature on the use of these terms.
DISCUSSION
Marked inconsistencies were identified in the usage of the terms for refractory septic shock. There is a pressing need to determine consensus definitions so as to establish a common language in the medical literature and to harmonize future studies.
Topics: Humans; Shock, Septic; Retrospective Studies; Prospective Studies; Norepinephrine; Fluid Therapy; Vasoconstrictor Agents
PubMed: 36706554
DOI: 10.1016/j.jcrc.2023.154258 -
Critical Care (London, England) Aug 2018The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis... (Meta-Analysis)
Meta-Analysis
Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in intensive care unit patients with infection and sepsis patients: a patient-level meta-analysis of randomized trials.
BACKGROUND
The clinical utility of serum procalcitonin levels in guiding antibiotic treatment decisions in patients with sepsis remains unclear. This patient-level meta-analysis based on 11 randomized trials investigates the impact of procalcitonin-guided antibiotic therapy on mortality in intensive care unit (ICU) patients with infection, both overall and stratified according to sepsis definition, severity, and type of infection.
METHODS
For this meta-analysis focusing on procalcitonin-guided antibiotic management in critically ill patients with sepsis of any type, in February 2018 we updated the database of a previous individual patient data meta-analysis which was limited to patients with respiratory infections only. We used individual patient data from 11 trials that randomly assigned patients to receive antibiotics based on procalcitonin levels (the "procalcitonin-guided" group) or the current standard of care (the "controls"). The primary endpoint was mortality within 30 days. Secondary endpoints were duration of antibiotic treatment and length of stay.
RESULTS
Mortality in the 2252 procalcitonin-guided patients was significantly lower compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on mortality persisted in a subgroup of patients meeting the sepsis 3 definition and based on the severity of sepsis (assessed on the basis of the Sequential Organ Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and need for vasopressor or ventilatory support) and on the type of infection (respiratory, urinary tract, abdominal, skin, or central nervous system), with interaction for each analysis being > 0.05. Procalcitonin guidance also facilitated earlier discontinuation of antibiotics, with a reduction in treatment duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to -0.66; p < 0.001).
CONCLUSION
Procalcitonin-guided antibiotic treatment in ICU patients with infection and sepsis patients results in improved survival and lower antibiotic treatment duration.
Topics: Anti-Bacterial Agents; Biomarkers; Humans; Intensive Care Units; Length of Stay; Organ Dysfunction Scores; Patient Outcome Assessment; Procalcitonin; Randomized Controlled Trials as Topic; Sepsis
PubMed: 30111341
DOI: 10.1186/s13054-018-2125-7 -
The Cochrane Database of Systematic... Jan 2017Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU), despite advances in the treatment of patients with severe sepsis and septic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Severe sepsis and septic shock are leading causes of death in the intensive care unit (ICU), despite advances in the treatment of patients with severe sepsis and septic shock, including early recognition, appropriate treatment with antibiotics and support of organs that may have been affected by the illness. High-volume haemofiltration (HVHF) is a blood purification technique that may improve outcomes in severe sepsis or septic shock. The technique of HVHF has evolved from renal replacement therapies used in the ICU to treat critically ill patients with acute kidney injury (AKI). This review was first published in 2013 and was updated in 2016.
OBJECTIVES
To investigate whether HVHF improves outcomes in critically ill adults admitted to the intensive care unit with severe sepsis or septic shock. The primary outcome of this systematic review is patient mortality; secondary outcomes include duration of stay, severity of organ dysfunction and adverse events.
SEARCH METHODS
For this updated version, we extended searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American Caribbean Health Sciences Literature (LILACS), Web of Science and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to 31 December 2015. The original search was performed in 2011. We also searched trials registers.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus standard or usual dialysis therapy, as well as RCTs and quasi-randomized trials comparing HVHF or high-volume haemodiafiltration versus no similar dialysis therapy. These studies involved adults treated in critical care units.
DATA COLLECTION AND ANALYSIS
Three review authors independently extracted data and assessed trial quality. We sought additional information from trialists as required.
MAIN RESULTS
We included four randomized trials involving 200 participants. Owing to small numbers of studies and participants, it was not possible to combine data for all outcomes. Two trials reported 28-day mortality, and one trial reported hospital mortality; in the third trial, the number of deaths stated did not match the quoted mortality rates. The pooled risk ratio (95% confidence interval) for 28-day mortality associated with HVHF was 0.89 (0.60 to 1.32, two trials, 146 participants, low-quality evidence). One study (137 participants, low-quality evidence) reported length of stay in the ICU. Two trials (170 participants, low-quality evidence) reported organ dysfunction, but we could not pool results owing to reporting differences. Three studies (189 participants, low-quality evidence) reported on haemodynamic changes, but we could not pool results owing to reporting differences. Investigators reported no adverse events. Overall, the included studies had low risk of bias.
AUTHORS' CONCLUSIONS
Investigators reported no adverse effects of HVHF (low-quality evidence). The results of this meta-analysis show that very few studies have been conducted to investigate the use of HVHF in critically ill patients with severe sepsis or septic shock (four studies, 201 participants, low-quality evidence). Researchers should consider additional randomized controlled trials that are large and multi-centred and have clinically relevant outcome measures. The cost-effectiveness of HVHF should also be studied. .
Topics: Adult; Critical Illness; Hemodiafiltration; Hemofiltration; Hospital Mortality; Humans; Intensive Care Units; Organ Dysfunction Scores; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic; Time Factors
PubMed: 28141912
DOI: 10.1002/14651858.CD008075.pub3 -
Emerging Microbes & Infections Dec 2023Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from... (Meta-Analysis)
Meta-Analysis Review
Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE) bacteremia can have poor clinical outcomes. Thus, determining the predictors of mortality from ESBL-PE bacteremia is very important. The present systematic review and meta-analysis aimed to evaluate studies to determine predictors associated with ESBL-PE bacteremia mortality. We searched PubMed and Cochrane Library databases for all relevant publications from January 2000 to August 2022. The outcome measure was mortality rate. In this systematic review of 22 observational studies, 4607 patients with ESBL-PE bacteremia were evaluated, of whom 976 (21.2%) died. The meta-analysis showed that prior antimicrobial therapy (RR, 2.89; 95% CI, 1.22-6.85), neutropenia (RR, 5.58; 95% CI, 2.03-15.35), nosocomial infection (RR, 2.46; 95% CI, 1.22-4.95), rapidly fatal underlying disease (RR, 4.21; 95% CI, 2.19-8.08), respiratory tract infection (RR, 2.12; 95% CI, 1.33-3.36), Pitt bacteremia score (PBS) (per1) (RR, 1.35; 95% CI, 1.18-1.53), PBS ≥ 4 (RR, 4.02; 95% CI, 2.77-5.85), severe sepsis (RR, 11.74; 95% CI, 4.68-29.43), and severe sepsis or septic shock (RR, 4.19; 95% CI, 2.83-6.18) were found to be mortality predictors. Moreover, urinary tract infection (RR, 0.15; 95% CI, 0.04-0.57) and appropriate empirical therapy (RR, 0.39; 95% CI, 0.18-0.82) were found to be a protective factor against mortality. Patients with ESBL-PE bacteremia who have the aforementioned require prudent management for improved outcomes. This research will lead to better management and improvement of clinical outcomes of patients with bacteremia caused by ESBL-PE.
Topics: Humans; Enterobacteriaceae Infections; Enterobacteriaceae; Bacteremia; Sepsis; beta-Lactamases; Anti-Bacterial Agents; Retrospective Studies; Treatment Outcome
PubMed: 37219067
DOI: 10.1080/22221751.2023.2217951 -
Journal of Anesthesia, Analgesia and... Jul 2022Carbapenem-resistant Gram-negative bacteria are frequent causes of sepsis and septic shock in intensive care unit (ICU) and thus considered a public health threat. Until... (Review)
Review
Carbapenem-resistant Gram-negative bacteria are frequent causes of sepsis and septic shock in intensive care unit (ICU) and thus considered a public health threat. Until now, the best available therapies consist of combinations of preexisting or new antibiotics with β-lactamase inhibitors (either new or preexisting). Several mechanisms of resistance, especially those mediated by metallo-β-lactamases (MBL), are responsible for the inefficacy of these treatments, leaving an unmet medical need. Intravenous cefiderocol has been recently approved by the American Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of complicated urinary tract infections and nosocomial pneumonia due to Gram-negative, when limited therapeutical options are available. In addition, its ability to hijack bacterial iron uptake mechanisms makes cefiderocol stable against the whole Ambler β-lactamase inhibitors and increases the in vitro efficacy against Gram-negative pathogens (e.g., Enterobacterales spp., Pseudomonas aeruginosa, and Acinetobacter baumannii). Trials have already demonstrated their non-inferiority to comparators. In 2021, ESCMID guidelines released a conditional recommendation supporting the use of cefiderocol against metallo-β-lactamase-producing Enterobacterales and against Acinetobacter baumannii. This review provides the opinion of experts about the general management of empiric treatment of patients with sepsis and septic shock in the intensive care unit and detects the proper place in therapy of cefiderocol considering recent evidence sought through a systematic search.
PubMed: 37386663
DOI: 10.1186/s44158-022-00062-7 -
Clinical Chemistry and Laboratory... Apr 2024Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes.... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Sepsis is a life-threatening condition implicating an inadequate activation of the immune system. Platelets act as modulators and contributors to immune processes. Indeed, altered platelet turnover, thrombotic events, and changes in thrombopoietin levels in systemic inflammation have been reported, but thrombopoietin-levels in sepsis and septic-shock have not yet been systematically evaluated. We therefore performed a meta-analysis of thrombopoietin (TPO)-levels in patients with sepsis.
METHODS
Two independent reviewers screened records and full-text articles for inclusion. Scientific databases were searched for studies examining thrombopoietin levels in adult sepsis and septic-shock patients until August 1st 2022.
RESULTS
Of 95 items screened, six studies met the inclusion criteria, including 598 subjects. Both sepsis and severe sepsis were associated with increased levels of thrombopoietin (sepsis vs. control: standardized mean difference 3.06, 95 % CI 1.35-4.77; Z=3.50, p=0.0005) (sepsis vs. severe sepsis: standardized mean difference -1.67, 95 % CI -2.46 to -0.88; Z=4.14, p<0.0001). TPO-levels did not show significant differences between severe sepsis and septic shock patients but differed between sepsis and inflammation-associated non-septic controls. Overall, high heterogeneity and low sample size could be noted.
CONCLUSIONS
Concluding, increased levels of thrombopoietin appear to be present both in sepsis and severe sepsis with high heterogeneity but thrombopoietin does not allow to differentiate between severe sepsis and septic-shock. TPO may potentially serve to differentiate sepsis from non-septic trauma and/or tissue damage related (systemic) inflammation. Usage of different assays and high heterogeneity demand standardization of methods and further large multicenter trials.
Topics: Adult; Humans; Shock, Septic; Thrombopoietin; Sepsis
PubMed: 38037809
DOI: 10.1515/cclm-2023-0792 -
Intensive Care Medicine Dec 2016The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the... (Review)
Review
PURPOSE
The interpretation of septic shock trial data is profoundly affected by patients, control intervention, co-interventions and selected outcome measures. We evaluated the reporting of control groups in recent septic shock trials.
METHODS
We searched for original articles presenting randomized clinical trials (RCTs) in adult septic shock patients from 2006 to 2016. We included RCTs focusing on septic shock patients with at least two parallel groups and at least 50 patients in the control group. We selected and evaluated data items regarding patients, control group characteristics, and mortality outcomes, and calculated a data completeness score to provide an overall view of quality of reporting.
RESULTS
A total of 24 RCTs were included (mean n = 287 patients and 71 % of eligible patients were randomized). Of the 24 studies, 14 (58 %) presented baseline data on vasopressors and 58 % the proportion of patients with elevated lactate values. Five studies (21 %) provided data to estimate the proportion of septic shock patients fulfilling the Sepsis-3 definition. The mean data completeness score was 19 out of 36 (range 8-32). Of 18 predefined control group characteristics, a mean of 8 (range 2-17) were reported. Only 2 (8 %) trials provided adequate data to confirm that their control group treatment represented usual care.
CONCLUSIONS
Recent trials in septic shock provide inadequate data on the control group treatment and hemodynamic values. We propose a standardized trial dataset to be created and validated, comprising characteristics of patient population, interventions administered, hemodynamic values achieved, surrogate organ dysfunction, and mortality outcomes, to allow better analysis and interpretation of future trial results.
Topics: Biomedical Research; Control Groups; Humans; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Shock, Septic
PubMed: 27448676
DOI: 10.1007/s00134-016-4444-y