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Clinics (Sao Paulo, Brazil) 2022Sepsis and septic shock are severe and difficult-to-treat conditions with high lethality. There is interest in identifying new adjunct therapies that are effective in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sepsis and septic shock are severe and difficult-to-treat conditions with high lethality. There is interest in identifying new adjunct therapies that are effective in reducing mortality. In this context, L-carnitine has been investigated in trials as a potentially beneficial drug. Therefore, the aim of this systematic review was to assess the clinical evidence to support the use of L-carnitine in septic shock patients to reduce the risk of mortality. The objective of this review was to evaluate the effect of L-carnitine compared to placebo or Usual Care (UC) on the mortality rate in hospitalized adult septic shock patients.
METHODS
The authors exclusively included randomized clinical trials that compared the use of L-carnitine versus placebo in adult (> 18 years old) septic shock patients. The outcome was a mortality rate of 28 days. This systematic review and meta-analysis were performed following the PRISMA guidelines and registered in PROSPERO with the ID CRD42020180499.
RESULTS
Following the initial search, 4007 citations were identified, with 2701 remaining after duplicate removal. Eight citations were selected for body text reading, and two were selected for inclusion. The studies enrolled 275 patients, with 186 in the carnitine arm and 89 in the placebo arm. The effect of L-carnitine uses in septic shock patients showed a difference risk of -0.03 (95% Confidence Interval: -0.15-0.10, I = 77%, p = 0.69) compared to placebo/in mortality rate with low quality of evidence.
CONCLUSIONS
There is low-quality evidence that the use of L-carnitine has no significant effect on reducing 28-day mortality in septic shock patients.
Topics: Adult; Humans; Adolescent; Shock, Septic; Carnitine; Sepsis; Dietary Supplements
PubMed: 36327640
DOI: 10.1016/j.clinsp.2022.100124 -
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 -
Journal of Critical Care Apr 2019Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic... (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
Guidelines recommend crystalloids for fluid resuscitation in sepsis/shock and switching to albumin in cases where crystalloids are insufficient. We evaluated hemodynamic response to crystalloids/colloids in critically ill adults.
MATERIALS AND METHODS
The primary research question was: "Are crystalloids sufficient for volume replacement in severe indications (intensive care unit [ICU]/critical illness)?" Randomized, controlled trials (RCTs) were identified using PubMed and EMBASE, and screened against predefined inclusion/exclusion criteria. Meta-analyses were performed on extracted data.
RESULTS
Fifty-five RCTs (N = 27,036 patients) were eligible. Central venous pressure was significantly lower with crystalloids than with albumin, hydroxyethyl starch (HES), or gelatin (all p < .001). Mean arterial pressure was significantly lower with crystalloids vs. albumin (mean difference [MD]: -3.5 mm Hg; p = .03) or gelatin (MD: -9.2 mm Hg; p = .02). Significantly higher volumes of crystalloids were administered vs. HES (MD: +1775 mL); volume administered was numerically higher vs. albumin (MD: +1985 mL). Compared with the albumin group, cardiac index was significantly lower in the crystalloid group (MD: -0.6 L/min/m, p < .001). All mortality and 90-day mortality were significantly lower for crystalloids compared with HES (relative risk 0.91; p = .009 and 0.9; p = .005, respectively).
CONCLUSIONS
Crystalloids were less efficient than colloids at stabilizing resuscitation endpoints; guidance on when to switch is urgently required.
Topics: Albumins; Central Venous Pressure; Colloids; Critical Care; Critical Illness; Crystalloid Solutions; Fluid Therapy; Gelatin; Hemodynamics; Humans; Hydroxyethyl Starch Derivatives; Intensive Care Units; Isotonic Solutions; Resuscitation; Shock, Septic
PubMed: 30540968
DOI: 10.1016/j.jcrc.2018.11.031 -
BMC Nephrology Jul 2020Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Due to the high incidence and mortality of sepsis-associated acute kidney injury, a significant number of studies have explored the causes of sepsis-associated acute kidney injury (AKI). However, the opinions on relevant predictive risk factors remain inconclusive. This study aimed to provide a systematic review and meta-analysis to determine the predisposing factors for sepsis-associated AKI.
METHOD
A systematic literature search was performed in the Medline, Embase, Cochrane Library, PubMed, and Web of Science, databases, with an end-date of 25th May 2019. Valid data were retrieved in compliance with specific inclusion and exclusion criteria.
RESULT
Forty-seven observational studies were included for analysis, achieving a cumulative patient number of 55,911. The highest incidence of AKI was caused by septic shock. Thirty-one potential risk factors were included in the meta-analysis. Analysis showed that 20 factors were statistically significant. The odds ratio (OR) and 95% confidence interval (CI), as well as the prevalence of the most frequently-seen predisposing factors for sepsis-associated AKI, were as follows: septic shock [2.88 (2.36-3.52), 60.47%], hypertension [1.43 (1.20-1.70), 38.39%], diabetes mellitus [1.59 (1.47-1.71), 27.57%], abdominal infection [1.44 (1.32-1.58), 30.87%], the administration of vasopressors [2.95 (1.67-5.22), 64.61%], the administration of vasoactive drugs [3.85 (1.89-7.87), 63.22%], mechanical ventilation [1.64 (1.24-2.16), 68.00%], positive results from blood culture [1.60 (1.35-1.89), 41.19%], and a history of smoking [1.60 (1.09-2.36), 43.09%]. Other risk factors included cardiovascular diseases, coronary artery diseases, liver diseases, unknown infections, the administration of diuretics and ACEI/ARB, the infection caused by gram-negative bacteria, and organ transplantation.
CONCLUSION
Risk factors of S-AKI arise from a wide range of sources, making it difficult to predict and prevent this condition. Comorbidities, and certain drugs, are the main risk factors for S-AKI. Our review can provide guidance on the application of interventions to reduce the risks associated with sepsis-associated acute kidney injury and can also be used to tailor patient-specific treatment plans and management strategies in clinical practice.
Topics: Acute Kidney Injury; Bacteremia; Blood Culture; Diabetes Mellitus; Humans; Hypertension; Intraabdominal Infections; Respiration, Artificial; Risk Factors; Sepsis; Shock, Septic; Smoking; Vasoconstrictor Agents
PubMed: 32736541
DOI: 10.1186/s12882-020-01974-8 -
Frontiers in Pharmacology 2019The meta-analysis aims to evaluate the efficacy and safety of terlipressin compared with norepinephrine for septic shock. The relevant studies from MEDLINE, Cochrane...
The meta-analysis aims to evaluate the efficacy and safety of terlipressin compared with norepinephrine for septic shock. The relevant studies from MEDLINE, Cochrane Library, Embase were searched by two independent investigators. A variety of keywords were used to search the studies. Stata software (version 11.0, Stata Corp LP, College Station, TX, USA) was used for statistical analysis. A total of six studies were identified and incorporated into the meta-analysis. The results showed that there was no difference for 28-day mortality (RR = 0.99, 95% CI = [0.85,1.15], P = 0.849), AE (RR = 2.54, 95% CI = [0.58,11.08], P = 0.214), and MAP (SMD = -0.10, 95% CI = [-0.35,0.14], P = 0.405), OI, urinary output, Scr, total bilirubin, ALT, and AST between TP group and NE group. While TP could decrease HR at 24 and 48 h compared with NE. Current results suggest that terlipressin showed no added survival benefit for septic shock when compared with norepinephrine, while terlipressin could decrease heart rate in the late phase of septic shock compared with norepinephrine without further liver and kidney injury. PROSPERO (ID: CRD42019128743). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019128743.
PubMed: 31920672
DOI: 10.3389/fphar.2019.01492 -
European Journal of Internal Medicine Mar 2023To evaluate the impact of active fluid de-resuscitation on mortality in critically ill patients with septic shock. (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the impact of active fluid de-resuscitation on mortality in critically ill patients with septic shock.
METHODS
A systematic search was performed on PubMed, EmBase, and the Cochrane Library databases. Trials investigating active fluid de-resuscitation and reporting data on mortality in patients with septic shock were eligible. The primary objective was the impact of active de-resuscitation in patients with septic shock on short-term mortality. Secondary outcomes were whether de-resuscitation lead to a fluid separation, and the impact of de-resuscitation on patient-centred outcomes.
RESULTS
Thirteen trials (8,030 patients) were included in the systematic review, whereof 5 randomised-controlled trials (RCTs) were included in the meta-analysis. None of the RCTs showed a reduction in mortality with active de-resuscitation measures (relative risk (RR) 1.12 [95%-CI 0.84 - 1.48]). Fluid separation was achieved by two RCTs. Evidence from non-randomised trials suggests a mortality benefit with de-resuscitation strategies and indicates a trend towards a more negative fluid balance. Patient-centred outcomes were not influenced in the RCTs, and only one non-randomised trial revealed an impact on the duration of mechanical ventilation and renal replacement requirement (RRT).
CONCLUSION
We found no evidence for superiority of active fluid de-resuscitation compared to usual care regarding mortality, fluid balance or patient-centred outcomes in patients with septic shock. Current evidence is limited by the lack of high-quality RCTs in patients with septic shock, the small sample sizes and the heterogeneity of the applied de-resuscitation techniques. In addition, validity of the majority of RCTs is compromised by their inability to achieve fluid separation.
Topics: Humans; Shock, Septic; Critical Illness; Resuscitation; Fluid Therapy; Respiration, Artificial
PubMed: 36635127
DOI: 10.1016/j.ejim.2023.01.009 -
Journal of Anesthesia, Analgesia and... May 2023In septic patients, hyperoxia may help with its bactericidal effects, but it may cause systemic impairments. The role of hyperoxia and the appropriate oxygen target in... (Review)
Review
BACKGROUND
In septic patients, hyperoxia may help with its bactericidal effects, but it may cause systemic impairments. The role of hyperoxia and the appropriate oxygen target in these patients is unknown. The aim of this systematic review was to summarize the available literature.
METHODS
We conducted a systematic search screening PubMed and Cochrane Library. Studies on adult patients with sepsis or septic shock and admitted to ICU addressing the topic of hyperoxia were included and described.
RESULTS
We included 12 studies, for a total of 15.782 included patients. Five studies were randomized controlled trials (RCTs) or analyses from RCTs, three were prospective observational studies, and four were retrospective observational studies. The definition of hyperoxia was heterogeneous across the included studies. Mortality was the most frequent outcome: six studies showed an increased rate or risk of mortality with hyperoxia, three found no differences, and one a protective effect of hyperoxia. At the critical appraisal assessment stage, no major methodological flaws were detected, except for a single-center, pilot study, with a lack of adjustment for confounders and imbalance between the groups.
CONCLUSION
The optimum range of oxygen level able to minimize risks and provide benefits in patients with sepsis or septic shock seems still unknown. Clinical equipoise between hyperoxia and normoxia is uncertain as conflicting evidence exists. Further studies should aim at identifying the best range of oxygenation and its optimal duration, investigating how effects of different levels of oxygen may vary according to identified pathogens, source of infection, and prescribed antibiotics in critically ill patients with sepsis and septic shock.
PubMed: 37386595
DOI: 10.1186/s44158-023-00096-5 -
Current Medical Research and Opinion 2015Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with... (Review)
Review
OBJECTIVE
Recent growing evidence suggests that beta-blocker treatment could improve cardiovascular dynamics and possibly the outcome of patients admitted to intensive care with severe sepsis or septic shock.
DESIGN
Systematic review.
DATA SOURCES
MEDLINE and EMBASE healthcare databases.
REVIEW METHODS
To investigate this topic, we conducted a systematic review of the above databases up to 31 May 2015. Due to the clinical novelty of the subject, we also included non-randomized clinical studies. We focused on the impact of beta-blocker treatment on mortality, also investigating its effects on cardiovascular, immune and metabolic function. Evidence from experimental studies was reviewed as well.
RESULTS
From the initial search we selected 10 relevant clinical studies. Five prospective studies (two randomized) assessed the hemodynamic effects of the beta1-blocker esmolol. Heart rate decreased significantly in all, but the impact on other parameters differed. The imbalance between prospective studies' size (10 to 144 patients) and the differences in their design disfavor a meta-analysis. One retrospective study showed improved hemodynamics combining metoprolol and milrinone in septic patients, and another retrospective study found no association between beta-blocker administration and mortality. We also found three case series. Twenty-one experimental studies evaluated the hemodynamic, immune and/or metabolic effects of selective and/or non-selective beta-blockers in animal models of sepsis (dogs, mice, pigs, rats, sheep), yielding conflicting results.
CONCLUSIONS
Whilst there is not enough prospective data to conduct a meta-analysis, the available clinical data are promising. We discuss the ability of beta blockade to modulate sepsis-induced alterations at cardiovascular, metabolic, immunologic and coagulation levels.
Topics: Adrenergic beta-Antagonists; Animals; Heart Rate; Hemodynamics; Humans; Metoprolol; Propanolamines; Sepsis; Shock, Septic
PubMed: 26121122
DOI: 10.1185/03007995.2015.1062357 -
Intensive Care Medicine Jun 2019We performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and... (Meta-Analysis)
Meta-Analysis
PURPOSE
We performed an individual patient data meta-analysis to investigate the possible benefits and harms of vasopressin therapy in adults with septic shock both overall and in pre-defined subgroups.
METHODS
Our pre-specified study protocol is published on PROSPERO, CRD42017071698. We identified randomised clinical trials up to January 2019 investigating vasopressin therapy versus any other vasoactive comparator in adults with septic shock. Individual patient data from each trial were compiled. Conventional two-stage meta-analyses were performed as well as one-stage regression models with single treatment covariate interactions for subgroup analyses.
RESULTS
Four trials were included with a total of 1453 patients. For the primary outcomes, there was no effect of vasopressin on 28-day mortality [relative risk (RR) 0.98, 95% CI 0.86-1.12] or serious adverse events (RR 1.02, 95% CI 0.82-1.26). Vasopressin led to more digital ischaemia [absolute risk difference (ARD) 1.7%, 95% CI 0.3%-3.2%] but fewer arrhythmias (ARD - 2.8%, 95% CI - 0.2% to - 5.3%). Mesenteric ischaemia and acute coronary syndrome events were similar between groups. Vasopressin reduced the requirement for renal replacement therapy (RRT) (RR 0.86, 95% CI 0.74-0.99), but this finding was not robust to sensitivity analyses. There were no statistically significant interactions in the pre-defined subgroups (baseline kidney injury severity, baseline lactate, baseline norepinephrine requirement and time to study inclusion).
CONCLUSIONS
Vasopressin therapy in septic shock had no effect on 28-day mortality although the confidence intervals are wide. It appears safe but with a different side effect profile from norepinephrine. The finding on reduced RRT should be interpreted cautiously. Future trials should focus on long-term outcomes in select patient groups as well as incorporating cost effectiveness analyses regarding possible reduced RRT use.
Topics: APACHE; Aged; Female; Humans; Length of Stay; Male; Middle Aged; Randomized Controlled Trials as Topic; Shock, Septic; Survivors; Vasoconstrictor Agents; Vasopressins
PubMed: 31062052
DOI: 10.1007/s00134-019-05620-2 -
Therapeutics and Clinical Risk... 2015Vasopressor agents are often prescribed in septic shock. However, their effects remain controversial. We conducted a systematic review and Bayesian network meta-analysis...
OBJECTIVE
Vasopressor agents are often prescribed in septic shock. However, their effects remain controversial. We conducted a systematic review and Bayesian network meta-analysis to compare the effects among different types of vasopressor agents.
DATA SOURCES
We searched for relevant studies in PubMed, Embase, and the Cochrane Library databases from database inception until December 2014.
STUDY SELECTION
Randomized controlled trials in adults with septic shock that evaluated different vasopressor agents were selected.
DATA EXTRACTION
Two authors independently selected studies and extracted data on study characteristics, methods, and outcomes.
DATA SYNTHESIS
Twenty-one trials (n=3,819) met inclusion criteria, which compared eleven vasopressor agents or vasopressor combinations (norepinephrine [NE], dopamine [DA], vasopressin [VP], epinephrine [EN], terlipressin [TP], phenylephrine [PE], TP+NE, TP + dobutamine [DB], NE+DB, NE+EN, and NE + dopexamine [DX]). Except for the superiority of NE over DA, the mortality of patients treated with any vasopressor agent or vasopressor combination was not significantly different. Compared to DA, NE was found to be associated with decreased cardiac adverse events, heart rate (standardized mean difference [SMD]: -2.10; 95% confidence interval [CI]: -3.95, -0.25; P=0.03), and cardiac index (SMD: -0.73; 95% CI: -1.14, -0.03; P=0.004) and increased systemic vascular resistance index (SVRI) (SMD: 1.03; 95% CI: 0.61, 1.45; P<0.0001). This Bayesian meta-analysis revealed a possible rank of probability of mortality among the eleven vasopressor agents or vasopressor combinations; from lowest to highest, they are NE+DB, EN, TP, NE+EN, TP+NE, VP, TP+DB, NE, PE, NE+DX, and DA.
CONCLUSION
In terms of survival, NE may be superior to DA. Otherwise, there is insufficient evidence to suggest that any other vasopressor agent or vasopressor combination is superior to another. When compared to DA, NE is associated with decreased heart rate, cardiac index, and cardiovascular adverse events, as well as increased SVRI. The effects of vasopressor agents or vasopressor combinations on mortality in patients with septic shock require further investigation.
PubMed: 26203253
DOI: 10.2147/TCRM.S80060