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Journal of Intensive Care Medicine Sep 2023The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal... (Meta-Analysis)
Meta-Analysis
The initial hemodynamic goal during septic shock resuscitation is to achieve a mean arterial pressure (MAP) above 65 mm Hg, although this does not assure a normal tissue perfusion. Capillary refill time (CRT), a marker of skin blood flow, has been validated as a marker of the reperfusion process. The aim of the study was to explore the relationship between MAP and CRT in patients in septic shock. We systematically reviewed studies which reported CRT and MAP in septic shock patients. Authors of eligible studies were asked to provide necessary data for performing a meta-correlation of Spearman's rank correlation coefficients. Subgroup analyses were performed, including studies of good quality and studies with higher/lower norepinephrine doses. We identified 10 studies, comprising 917 patients. There were 5 studies considered to be of good quality. A meta-correlation showed a statistically significant but poor negative correlation between MAP and CRT ( = -0.158, range -0.221 to -0.093, < .001, I2 = 0.0%). Subgroup analysis of best-quality studies gave similar results ( = -0.201, range -0.282 to -0.116, < .001, I2 = 0.0%). In subanalysis concerning norepinephrine doses, no significant correlations were found. In patients with septic shock, there is poor inverse correlation between MAP and CRT. MAP > 65 mm Hg does not guarantee normalization of CRT. PROSPERO: CRD42022355996. Registered on 5 September 2022.
Topics: Humans; Shock, Septic; Arterial Pressure; Hemodynamics; Norepinephrine; Resuscitation
PubMed: 37042043
DOI: 10.1177/08850666231168038 -
Current Medicinal Chemistry Jan 2024This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes...
BACKGROUND
This systematic review and meta-analysis aimed to determine whether the combination of hydrocortisone, vitamin C (ascorbic acid), and thiamine (HAT therapy) diminishes the mortality and is effective in expediting the resolution of sepsis and septic shock or not.
METHODS
The following databases of PubMed, Scopus, ISI Web of Science, and Google Scholar were explored until March 2021 for all existing literature related to this field. An automatic alert for all databases was also activated to update our search. Meta-analysis was performed on clinical trials and cohorts separately as well as on all the pooled populations.
RESULTS
This study evaluated nine clinical trials (1358 participants) and nine cohorts (339,437 participants) and is the most comprehensive systematic review in this field. The results of our meta-analysis demonstrated a significant difference in the reduction of Sepsis-Related Organ Failure Assessment (SOFA) score changes (Δ-SOFA) over 72 h (Standard Mean Difference (SMD) = -0.429; 95% CI: -0.737, 0.120; P = 0.006), duration of vasopressor (VP) (SMD = -0.373; 95% CI: -0.619, -0.128; P = 0.003), and procalcitonin (PCT) clearance (SMD = 0.496; 95% CI: 0.061, 0.931%; P = 0.026). Considering the results of cohorts, HAT therapy was effective in the survival of intensive care units (ICUs) patients (OR = 0.641; 95% CI: 0.423-0.970, P = 0.035). However, no significant difference was observed between the intervention and control groups in hospital mortality (Odds Ratio (OR) = 0.811, 95% CI: 0.544-1.209, P = 0.304), 28- to 30-day mortality (OR = 1.000; 95% CI: 0.782-1.279, P = 0.998), new onset acute kidney injury requiring renal replacement therapy ((OR = 0.856, 95% CI: 0.526, 1.391; P = 0.529), in-hospital length of stay (LOS) (SMD = 0.090; 95% CI: -0.036, 0.216 days; P = 0.162), LOS in ICU (SMD = 0.016, 95% CI: -0.138, 0.170 days; P = 0.838), and mechanical ventilation-free days (SMD = 0.004; 95% CI: -0.154, 0.163 days; P = 0.956).
CONCLUSION
Supplementation of septic and septic shock patients with HAT therapy has significant beneficial effects on SOFA score over 72 hours, duration of exogenous vasopressor infusion and procalcitonin clearance. Considering the results of cohort studies, supplementation with HAT is efficacious in reducing ICU mortality.
PubMed: 38265393
DOI: 10.2174/0109298673245464231121094448 -
BMC Infectious Diseases Dec 2023Lymphopenia is defined as a decrease below normal value (often 1.0 x 10 cells/L) of blood circulating lymphocyte count. In the general population, lymphopenia is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Lymphopenia is defined as a decrease below normal value (often 1.0 x 10 cells/L) of blood circulating lymphocyte count. In the general population, lymphopenia is associated with an increased risk of hospitalisation secondary to infection, independent of traditional clinical risk factors. In hospital, lymphopenia is associated with increased risk of healthcare-associated infection and mortality. By summarising lymphopenia's prevalence and impact on clinical outcomes, we can identify an at-risk population and inform future studies of immune dysfunction following severe illness.
METHODS
Peer-reviewed search strategy was performed on three databases. Primary objective was to summarise the pooled prevalence of lymphopenia. Primary outcome was infection including pre-existing lymphopenia as a risk factor for admission with infection and as an in-hospital risk factor for healthcare-associated infection. Secondary outcomes were length of stay and mortality. Mortality data extracted included in-hospital, 28/30-day ('early'), and 90-day/1-year ('late') mortality. Meta-analysis was carried out using random-effects models for each outcome measure. Heterogeneity was assessed using I statistic. Joanna Briggs Institute checklist for cohort studies was used to assess risk of bias. The protocol was published on PROSPERO.
RESULTS
Fifteen observational studies were included. The pooled prevalence of lymphopenia in all-cause hospitalisations was 38% (CI 0.34-0.42, I= 97%, p< 0.01). Lymphopenia was not associated with an infection diagnosis at hospital admission and healthcare associated infection (RR 1.03; 95% CI 0.26-3.99, p=0.97, I = 55% and RR 1.31; 95% CI 0.78-2.20, p=0.31, I=97%, respectively), but was associated with septic shock (RR 2.72; 95% CI 1.02-7.21, p=0.04, I =98%). Lymphopenia was associated with higher in-hospital mortality and higher 'early' mortality rates (RR 2.44; 95% CI 1.71-3.47, p < 0.00001, I = 89% and RR 2.05; 95% CI 1.64-2.56, p < 0.00001, I = 29%, respectively). Lymphopenia was associated with higher 'late' mortality (RR 1.59; 1.33-1.90, p < 0.00001, I = 0%).
CONCLUSIONS
This meta-analysis demonstrates the high prevalence of lymphopenia across all-cause hospitalisations and associated increased risk of septic shock, early and late mortality. Lymphopenia is a readily available marker that may identify immune dysfunctional patients. Greater understanding of immune trajectories following survival may provide insights into longer-term poor clinical outcomes.
Topics: Humans; Prevalence; Shock, Septic; Hospitalization; Outcome Assessment, Health Care; Lymphopenia
PubMed: 38042792
DOI: 10.1186/s12879-023-08845-1 -
International Journal of Surgery... Apr 2024Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis syndromes are a major burden in the ICU with very high mortality. Vasopressin and copeptin are released in response to hypovolemia and have shown potential significance in diagnosing sepsis.
OBJECTIVE
To investigate the levels of copeptin in patients with sepsis syndromes and evaluate its relation with patient prognosis and mortality.
METHODS
Four databases were searched for literature published from inception to the 8th of November 2022. Original research articles where copeptin was measured in sepsis patients and compared with controls were included. Data extraction and synthesis: study characteristics, levels of copeptin in the participants, and copeptin assay description were extracted. Levels of copeptin in patients were pooled and compared with controls in terms of the standard mean difference (SMD) generated using a random-effects model.
RESULTS
Fifteen studies met the selection criteria. Copeptin levels were significantly higher in patients with sepsis, severe sepsis, and septic shock as compared to controls [(SMD: 1.49, 95% CI: 0.81-2.16, P<0.0001), (SMD: 1.94, 95% CI: 0.34-3.54, P=0.02), and (SMD: 2.17, 95% CI: 0.68-3.66, P=0.004), respectively]. The highest copeptin levels were noted in septic shock patients. The admission copeptin levels were significantly lower in survivors as compared to nonsurvivors (SMD: -1.73; 95% CI: -2.41 to -1.06, P<0.001).
CONCLUSION AND RELEVANCE
Copeptin was significantly elevated in sepsis, severe sepsis, and septic shock. Survivors had a significantly lower copeptin during admission. Copeptin offered an excellent predictability to predict 1-month mortality. Measuring the copeptin in sepsis patients can aid treating physicians to foresee patients' prognosis.
Topics: Humans; Glycopeptides; Prognosis; Sepsis; Biomarkers
PubMed: 38668663
DOI: 10.1097/JS9.0000000000001069 -
Journal of the American College of... Aug 2023Sepsis is a life-threatening medical emergency and a leading cause of morbidity and mortality worldwide. Reductions in time to antibiotics in patients presenting with...
INTRODUCTION
Sepsis is a life-threatening medical emergency and a leading cause of morbidity and mortality worldwide. Reductions in time to antibiotics in patients presenting with sepsis or septic shock are associated with reduced mortality, and Surviving Sepsis Campaign guidelines recommend antibiotics within one hour of recognition. Pharmacists are well-equipped to help navigate the therapeutic and operational challenges associated with achieving this goal.
OBJECTIVES
To assess the association of pharmacist involvement in sepsis response with time to antibiotics in hospitalized patients with sepsis and septic shock.
METHODS
A systematic review of the following databases was conducted: PubMed/MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. Studies must have included a designated role of an individual pharmacist in the management of sepsis or septic shock and not be considered an operational change. The primary outcome of interest was time to antibiotic administration, with secondary outcomes including intensive care unit (ICU) and hospital length of stay as well as in-hospital mortality.
RESULTS
We identified 10 studies including 1772 patients with sepsis or septic shock that evaluated a sepsis response in which a pharmacist was included. Studies included patients in the ICU, emergency department, and hospital ward setting. Seven studies demonstrated a significant reduction in time to antibiotics, with two other studies supporting this conclusion in extrapolation or sensitivity analysis. There was not a consistent reduction in ICU or hospital length of stay nor in-hospital mortality between those interventions involving a pharmacist compared with their defined control groups.
CONCLUSION
Pharmacist involvement in sepsis response, often as part of a multi-professional team-based approach to sepsis care, is associated with a reduced time to antibiotic administration for hospitalized patients with sepsis or septic shock.
PubMed: 37608990
DOI: 10.1002/jac5.1723 -
Phytotherapy Research : PTR Sep 2023Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading... (Review)
Review
Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading pathogenesis. Resveratrol (3,5,4'-trihydroxytrans-stilbene), is a phenolic and non-flavonoid compound naturally produced by some plants and fruits. The object of the current study is to systematically review the impacts of resveratrol and its mechanisms of function in the management of sepsis and its related complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (PROSPERO: CRD42021289357). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Study criteria were met by 72 out of 1415 articles screened. The results of this systematic review depict that resveratrol can reduces the complications of sepsis by affecting inflammatory pathways, oxidative stress, and modulating immune responses. Future human randomized clinical trials are necessary due to the promising therapeutic effects of resveratrol on sepsis complications and the lack of clinical trials in this regard.
Topics: Humans; Antioxidants; Oxidative Stress; Resveratrol; Sepsis
PubMed: 37405908
DOI: 10.1002/ptr.7917 -
Prognostic value of capillary refill time in adult patients: a systematic review with meta-analysis.Critical Care (London, England) Dec 2023Acute circulatory failure leads to tissue hypoperfusion. Capillary refill time (CRT) has been widely studied, but its predictive value remains debated. We conducted a... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Acute circulatory failure leads to tissue hypoperfusion. Capillary refill time (CRT) has been widely studied, but its predictive value remains debated. We conducted a meta-analysis to assess the ability of CRT to predict death or adverse events in a context at risk or confirmed acute circulatory failure in adults.
METHOD
MEDLINE, EMBASE, and Google scholar databases were screened for relevant studies. The pooled area under the ROC curve (AUC ROC), sensitivity, specificity, threshold, and diagnostic odds ratio using a random-effects model were determined. The primary analysis was the ability of abnormal CRT to predict death in patients with acute circulatory failure. Secondary analysis included the ability of CRT to predict death or adverse events in patients at risk or with confirmed acute circulatory failure, the comparison with lactate, and the identification of explanatory factors associated with better accuracy.
RESULTS
A total of 60,656 patients in 23 studies were included. Concerning the primary analysis, the pooled AUC ROC of 13 studies was 0.66 (95%CI [0.59; 0.76]), and pooled sensitivity was 54% (95%CI [43; 64]). The pooled specificity was 72% (95%CI [55; 84]). The pooled diagnostic odds ratio was 3.4 (95%CI [1.4; 8.3]). Concerning the secondary analysis, the pooled AUC ROC of 23 studies was 0.69 (95%CI [0.65; 0.74]). The prognostic value of CRT compared to lactate was not significantly different. High-quality CRT was associated with a greater accuracy.
CONCLUSION
CRT poorly predicted death and adverse events in patients at risk or established acute circulatory failure. Its accuracy is greater when high-quality CRT measurement is performed.
Topics: Humans; Adult; Prognosis; Hemodynamics; Shock; Odds Ratio
PubMed: 38042855
DOI: 10.1186/s13054-023-04751-9 -
Critical Care (London, England) Jan 2024The impact of therapeutic plasma exchange (TPE) on short-term mortality in adult patients with sepsis-induced organ dysfunction remains uncertain. The objective of the... (Meta-Analysis)
Meta-Analysis Review
Influence of therapeutic plasma exchange treatment on short-term mortality of critically ill adult patients with sepsis-induced organ dysfunction: a systematic review and meta-analysis.
INTRODUCTION
The impact of therapeutic plasma exchange (TPE) on short-term mortality in adult patients with sepsis-induced organ dysfunction remains uncertain. The objective of the study is to assess the effect of adjunct TPE in this setting through a comprehensive literature review.
METHODS
The National Library of Medicine's Medline, Ovid (Embase), the Cochrane Library database and clinicaltrial.gov from January 01, 1966, until October 01, 2022, were searched for terms: therapeutic plasma exchange, plasmapheresis, sepsis, and septic shock. We reviewed, selected and extracted data from relevant randomized clinical trials (RCTs) and matched cohort studies (MCSs) comparing short-term mortality in critically ill adult septic patients treated with standard therapy versus those receiving adjunct TPE. Risk of bias was assessed in the RCTs using Cochrane Collaboration tool and in MCSs using ROBINS-I tool. Summary statistics, risk ratios (RRs), and confidence intervals (CIs) were calculated using random effects model.
RESULTS
This systematic review included 937 adult critically ill septic patients from five RCTs (n = 367) and fifteen MCSs (n = 570). Of these total, 543 received treatment with TPE in addition to standard care. The meta-analysis includes all five RCTs and only six MCSs (n = 627). The adjunct TPE treatment (n = 300) showed a significant reduction in short-term mortality (RR 0.59, 95% CI 0.47-0.74, I2 3%) compared to standard therapy alone (n = 327). The systematic review of all 20 trials revealed that adding TPE to the standard therapy of critically ill septic patients resulted in faster clinical and/or laboratory recovery.
CONCLUSIONS
Our comprehensive and up-to-date review demonstrates that adjunct TPE may provide potential survival benefits when compared to standard care for critically ill adult patients with sepsis-induced organ dysfunction. While results of this meta-analysis are encouraging, large well-designed randomized trials are required to identify the optimal patient population and TPE procedure characteristics prior to widespread adoption into practice.
Topics: Adult; Humans; Plasma Exchange; Critical Illness; Multiple Organ Failure; Sepsis; Shock, Septic
PubMed: 38178170
DOI: 10.1186/s13054-023-04795-x -
Acute Medicine & Surgery 2023To identify the most useful tissue perfusion parameter for initial resuscitation in sepsis/septic shock adults using a network meta-analysis.
AIM
To identify the most useful tissue perfusion parameter for initial resuscitation in sepsis/septic shock adults using a network meta-analysis.
METHODS
We searched major databases until December 2022 for randomized trials comparing four tissue perfusion parameters or against usual care. The primary outcome was short-term mortality up to 90 days. The Confidence in Network Meta-Analysis web application was used to assess the quality of evidence.
RESULTS
Seventeen trials were identified. Lactate-guided therapy (risk ratios, 0.59; 95% confidence intervals [0.45-0.76]; high certainty) and capillary refill time-guided therapy (risk ratios, 0.53; 95% confidence intervals [0.33-0.86]; high certainty) were significantly associated with lower short-term mortality compared with usual care, whereas central venous oxygen saturation-guided therapy (risk ratio, 1.50; 95% confidence intervals [1.16-1.94]; moderate certainty) increased the risk of short-term mortality compared with lactate-guided therapy.
CONCLUSIONS
Lactate or capillary refill time-guided initial resuscitation for sepsis/septic shock patients may decrease short-term mortality. More research is essential to personalize and optimize treatment strategies for septic shock resuscitation.
PubMed: 38148753
DOI: 10.1002/ams2.914 -
Panminerva Medica Mar 2024Sepsis-related mortality is decreasing over time after the introduction of "Surviving Sepsis Campaign" Guidelines in 2004. The last Guidelines version collects 93...
INTRODUCTION
Sepsis-related mortality is decreasing over time after the introduction of "Surviving Sepsis Campaign" Guidelines in 2004. The last Guidelines version collects 93 recommendations, but several interventions supported by randomized evidence of mortality reduction are not included.
EVIDENCE ACQUISITION
We performed a systematic review of all randomized controlled trials reporting a statistically significant mortality reduction in septic patients and compared the identified studies to the Surviving Sepsis Campaign Guidelines 2021 to highlight discrepancies.
EVIDENCE SYNTHESIS
We identified 83 randomized controlled trials (58 interventions) influencing mortality in sepsis. Only 9/58 of these interventions were included in the Guidelines: lactate measurement and lactate-guided hemodynamic management, procalcitonin-guided antibiotics discontinuation, balanced crystalloids as first choice fluids, albumin infusion, avoidance of starches, noradrenaline as first line vasopressor, vasopressin as an adjunctive vasopressor to noradrenaline, neuromuscular blocking agents in moderate-severe sepsis-associated acute respiratory distress syndrome, and corticosteroids use. Only 11/93 Guidelines recommendations were supported by randomized evidence with mortality difference. Five of the interventions with survival benefit in literature (vitamin C, terlipressin, polymyxin B, liberal transfusion strategy and immunoglobulins) were recommended to avoid in the Guidelines, while 44 interventions were not mentioned, including three interventions (esmolol, omega 3, and external warming) with at least two randomized controlled trials with a documented survival benefit.
CONCLUSIONS
Several discrepancies exist between the randomized controlled trials with mortality difference in septic patients and the latest Surviving Sepsis Campaign Guidelines. This systematic review can be of help for improving future guidelines and may guide research on specific promising topics.
Topics: Humans; Shock, Septic; Sepsis; Adrenal Cortex Hormones; Norepinephrine; Lactic Acid
PubMed: 38093626
DOI: 10.23736/S0031-0808.23.04986-8