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Annals of Laboratory Medicine Jun 2024Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic...
Diagnostic Accuracy of Plasma Renin and Renin Activity in Predicting Mortality and Kidney Outcomes in Patients With Septic Shock and Hypoperfusion or Hypotension: A Multicenter, Prospective, Observational Study.
BACKGROUND
Lactate is a commonly used biomarker for sepsis, although it has limitations in certain cases, suggesting the need for novel biomarkers. We evaluated the diagnostic accuracy of plasma renin concentration and renin activity for mortality and kidney outcomes in patients with sepsis with hypoperfusion or hypotension.
METHODS
This was a multicenter, prospective, observational study of 117 patients with septic shock treated at three tertiary emergency departments between September 2021 and October 2022. The accuracy of renin activity, renin, and lactate concentrations in predicting 28-day mortality, acute kidney injury (AKI), and renal replacement requirement was assessed using the area under the ROC curve (AUC) analysis.
RESULTS
The AUCs of initial renin activity, renin, and lactate concentrations for predicting 28-day mortality were 0.66 (95% confidence interval [CI], 0.55-0.77), 0.63 (95% CI, 0.52-0.75), and 0.65 (95% CI, 0.53-0.77), respectively, and those at 24 hrs were 0.74 (95% CI, 0.62-0.86), 0.70 (95% CI, 0.56-0.83), and 0.67 (95% CI, 0.54-0.79). Renin concentrations and renin activity outperformed initial lactate concentrations in predicting AKI within 14 days. The AUCs of renin and lactate concentrations were 0.71 (95% CI, 0.61-0.80) and 0.57 (95% CI, 0.46-0.67), respectively (=0.030). The AUC of renin activity (0.70; 95% CI, 0.60-0.80) was also higher than that of lactate concentration (=0.044).
CONCLUSIONS
Renin concentration and renin activity show comparable performance to lactate concentration in predicting 28-day mortality in patients with septic shock but superior performance in predicting AKI.
PubMed: 38910340
DOI: 10.3343/alm.2023.0425 -
Medicina Intensiva Jun 2024Central venous-arterial PCO to arterial-central venous O content ratio (PCO/CO) is commonly used as a surrogate for respiratory quotient (RQ) and tissue oxygenation....
Lack of correlation between central venous minus arterial PCO to arterial minus central venous O content ratio and respiratory quotient in patients with septic shock: A prospective observational study.
OBJECTIVE
Central venous-arterial PCO to arterial-central venous O content ratio (PCO/CO) is commonly used as a surrogate for respiratory quotient (RQ) and tissue oxygenation. Although PCO/CO might be associated with hyperlactatemia and outcome, neither the interchangeability with RQ nor the correlation with conclusive variables of anaerobic metabolism has never been demonstrated in septic shock. Our goal was to compare PCO/CO and RQ in patients with septic shock.
DESIGN
Prospective, observational study.
SETTING
Two adult ICUs.
PATIENTS
Forty-seven patients with septic shock on mechanical ventilation with stable respiratory settings and vasopressor dose after initial resuscitation.
INTERVENTIONS
None.
MAIN VARIABLES OF INTEREST
We measured arterial and central venous gases, Hb, and OHb. PCO/CO and the ratio of central venous-arterial CO content to arterial-central venous O content (CCO/CO) were calculated. RQ was determined by indirect calorimetry.
RESULTS
PCO/CO and CCO/CO were not correlated with RQ (R = 0.01, P = 0.50 and R = 0.01, P = 0.58, respectively), showing large bias and wide 95 % limits of agreement with RQ (1.09, -1.10-3.27 and 0.42, -1.53-2.37). A multiple linear regression model showed Hb, and central venous PCO and OHb, but not RQ, as PCO/CO determinants (R = 0.36, P = 0.0007).
CONCLUSIONS
In patients with septic shock, PCO/CO did not correlate with RQ and was mainly determined by factors that modify the dissociation of CO from Hb. PCO/CO seems to be a poor surrogate for RQ; therefore, its values should be interpreted with caution.
PubMed: 38909012
DOI: 10.1016/j.medine.2024.06.005 -
International Journal of Antimicrobial... Jun 2024The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in...
BACKGROUND
The role of intravenous fosfomycin (iv-FOS), as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI), needs to be evaluated in clinical practice as in vitro data show a potential efficacy.
METHODS
All consecutive patients with a GNB-BSI from January 1, 2021, to April 1, 2023, were included. Primary outcome was 30-day mortality. A Cox- regression analysis was used to identify predictors of mortality. Moreover, an inverse-probability of treatment-weighting (IPTW) analysis was also performed.
RESULTS
Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson-comorbidity index of 5 (3-7). At GNB-BSI onset, median SOFA score was 5 (2-7), 122 (34%) presented with septic shock. Pathogens involved were principally K. pneumoniae (42%), E. coli (28%), and P. aeruginosa (17%); of them 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) gr/daily. Use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, p-value=0.147). However, at multivariable Cox-regression combination therapy with iv-FOS resulted protective for mortality (aHR=0.51, 95%CI=0.28-0.92), but not other combo-therapies (HR=0.69, 95%CI=0.44-1.16). This result was also confirmed at the IPTW-adjusted-Cox-model (aHR=0.52, 95%CI=0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA>6, PITT≥4) and when iv-FOS was initiated within 24 hours from GNB-BSI onset.
CONCLUSIONS
Fosfomycin in combination therapy for GNB-BSI may have a role to improve survival. These results justify the development of further clinical trials.
PubMed: 38906485
DOI: 10.1016/j.ijantimicag.2024.107247 -
PloS One 2024Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a...
INTRODUCTION
Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria to characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb).
METHODS
We examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L.
RESULTS
We identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,312 unique sepsis episodes, of which 30.2% met the criteria for septic shock. A total of 4,911/6,312 sepsis (77.8%) episodes occurred on ICU admission. Forty-seven percent of emergency medical admissions and 36.7% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.4%) than those without shock (11.4%).
CONCLUSIONS
We successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres.
Topics: Humans; Netherlands; Male; Female; Middle Aged; Sepsis; Aged; Intensive Care Units; Organ Dysfunction Scores; Adult; Hospital Mortality; Databases, Factual; Shock, Septic; Critical Care; Anti-Bacterial Agents
PubMed: 38905261
DOI: 10.1371/journal.pone.0304133 -
Critical Care Explorations Jul 2024Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.
DATA SOURCES
We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.
STUDY SELECTION
We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.
DATA EXTRACTION
Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
DATA SYNTHESIS
We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.
CONCLUSIONS
Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.
REGISTRATION
Center for Open Science (https://osf.io/hpy4j).
Topics: Methylene Blue; Humans; Shock, Septic; Randomized Controlled Trials as Topic; Length of Stay; Critical Illness
PubMed: 38904978
DOI: 10.1097/CCE.0000000000001110 -
Frontiers in Medicine 2024Assessing volume status in septic shock patients is crucial for tailored fluid resuscitation. Estimated plasma volume status (ePVS) has emerged as a simple and effective...
BACKGROUND
Assessing volume status in septic shock patients is crucial for tailored fluid resuscitation. Estimated plasma volume status (ePVS) has emerged as a simple and effective tool for evaluating patient volume status. However, the prognostic value of ePVS in septic shock patients remains underexplored.
METHODS
The study cohort consisted of septic shock patients admitted to the ICU, sourced from the MIMIC-IV database. Patients were categorized into two groups based on 28-day survival outcomes, and their baseline characteristics were compared. According to the ePVS (6.52 dL/g) with a hazard ratio of 1 in the restricted cubic spline (RCS) analysis, patients were further divided into high and low ePVS groups. A multivariable Cox regression model was utilized to evaluate the association between ePVS and 28-day mortality rate. The Kaplan-Meier survival curve was plotted, and all-cause mortality was compared between the high and low groups using the log-rank test.
RESULTS
A total of 7,607 septic shock patients were included in the study, among whom 2,144 (28.2%) died within 28 days. A J-shaped relationship was observed between ePVS at ICU admission and 28-day mortality, with an increase in mortality risk noted when ePVS exceeded 6.52 dL/g. The high ePVS group exhibited notably higher mortality rates compared to the low ePVS group (28-day mortality: 26.2% vs. 30.2%; 90-day mortality: 35% vs. 42.3%). After adjustment for confounding factors, ePVS greater than 6.52 dL/g independently correlated with an increased risk of 28-day mortality (HR: 1.20, 95% CI: 1.10-1.31, < 0.001) and 90-day mortality (HR: 1.25, 95% CI: 1.15-1.35, < 0.001). Kaplan-Meier curves demonstrated a heightened risk of mortality associated with ePVS values exceeding 6.52 dL/g.
CONCLUSION
A J-shaped association was observed between ePVS and 28-day mortality in septic shock patients, with higher ePVS levels associated with increased risk of mortality.
PubMed: 38903828
DOI: 10.3389/fmed.2024.1416396 -
Frontiers in Medicine 2024The benefit of temperature control in sepsis or septic shock is still under debate in the literature. We developed a national survey to assess the current state of...
The benefit of temperature control in sepsis or septic shock is still under debate in the literature. We developed a national survey to assess the current state of knowledge and the practical management of spontaneous septic hypothermia in French intensive care units. Out of more 764 intensivists who were contacted, 436 responded to the survey. The majority of doctors (52.4%) considered spontaneous septic hypothermia to be a frequently encountered situation in intensive care, and 62.1% were interested in this problem. Definition of spontaneous septic hypothermia among French intensivists was not consensual. More than half of the doctors questioned (57.1%) stated that they did not actively rewarm patients suffering from spontaneous septic hypothermia.
PubMed: 38903822
DOI: 10.3389/fmed.2024.1393781 -
BioRxiv : the Preprint Server For... Feb 2024Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection...
BACKGROUND
Septic shock, in humans and in our well-established animal model, is associated with increases in biventricular end diastolic volume (EDV) and decreases in ejection fraction (EF). These abnormalities occur over 2 days and reverse within 10 days. Septic non-survivors do not develop an increase in EDV. The mechanism for this cardiac dysfunction and EDV differences is unknown.
METHODS
Purpose-bred beagles randomized to receive intrabronchial (n=27) or saline (n=6) were provided standard ICU care including sedation, mechanical ventilation, and fluid resuscitation to a pulmonary arterial occlusion pressure of over 10mmHg. No catecholamines were administered. Over 96h, cardiac magnetic resonance imaging, echocardiograms, and invasive hemodynamics were serially performed, and laboratory data was collected. Tissue was obtained at 66h from six septic animals.
RESULTS
From 0-96h after bacterial challenge, septic animals controls had significantly increased left ventricular wall edema (6%) and wall thinning with loss of mass (15%) which was more pronounced at 48h in non-survivors than survivors. On histology, edema was located predominantly in myocytes, the interstitium, and endothelial cells. Edema was associated with significantly worse biventricular function (lower EFs), ventricular-arterial coupling, and circumferential strain. In septic animals, from 0-24h, the EDV decreased from baseline and, despite cardiac filling pressures being similar, decreased significantly more in non-survivors. From 24-48h, all septic animals had increases in biventricular chamber sizes. Survivors biventricular EDVs were significantly greater than baseline and in non-survivors, where biventricular EDVs were not different from baseline. Preload, afterload, or HR differences did not explain these differential serial changes in chamber size.
CONCLUSION
Systolic and diastolic cardiac dysfunction during sepsis is associated with ventricular wall edema. Rather than differences in preload, afterload, or heart rate, structural alterations to the ventricular wall best account for the volume changes associated with outcome during sepsis. In non-survivors, from 0-24h, sepsis induces a more severe diastolic dysfunction, further decreasing chamber size. The loss of left ventricular mass with wall thinning in septic survivors may, in part explain, the EDV increases from 24-48h. However, these changes continued and even accelerated into the recovery phase consistent with a reparative process rather than ongoing injury.
PubMed: 38903100
DOI: 10.1101/2024.02.05.578971 -
BMC Emergency Medicine Jun 2024Sepsis is a leading cause of death and serious illness that requires early recognition and therapeutic management to improve survival. The quick-SOFA score helps in its...
BACKGROUND
Sepsis is a leading cause of death and serious illness that requires early recognition and therapeutic management to improve survival. The quick-SOFA score helps in its recognition, but its diagnostic performance is insufficient. To develop a score that can rapidly identify a community acquired septic situation at risk of clinical complications in patients consulting the emergency department (ED).
METHODS
We conducted a monocentric, prospective cohort study in the emergency department of a university hospital between March 2016 and August 2018 (NCT03280992). All patients admitted to the emergency department for a suspicion of a community-acquired infection were included. Predictor variables of progression to septic shock or death within the first 90 days were selected using backward stepwise multivariable logistic regression to develop a clinical score. Receiver operating characteristic (ROC) curves were constructed to determine the discriminating power of the area under the curve (AUC). We also determined the threshold of our score that optimized the performance required for a sepsis-worsening score. We have compared our score with the NEWS-2 and qSOFA scores.
RESULTS
Among the 21,826 patients admitted to the ED, 796 patients were suspected of having community-acquired infection and 461 met the sepsis criteria; therefore, these patients were included in the analysis. The median [interquartile range] age was 72 [54-84] years, 248 (54%) were males, and 244 (53%) had respiratory symptoms. The clinical score ranged from 0 to 90 and included 8 variables with an area under the ROC curve of 0.85 (confidence interval [CI] 95% 0.81-0.89). A cut-off of 26 yields a sensitivity of 88% (CI 95% 0.79-0.93), a specificity of 62% (CI 95% 57-67), and a negative predictive value of 95% (CI 95% 91-97). The area under the ROC curve for our score was 0.85 (95% CI, 0.81-0.89) versus 0.73 (95% CI, 0.68-0.78) for qSOFA and 0.66 (95% CI, 0.60-0.72) for NEWS-2.
CONCLUSIONS
Our study provides an accurate clinical score for identifying septic patients consulting the ED early at risk of worsening disease. This score could be implemented at admission.
Topics: Humans; Male; Prospective Studies; Emergency Service, Hospital; Female; Community-Acquired Infections; Sepsis; Middle Aged; Aged; ROC Curve; Aged, 80 and over; Organ Dysfunction Scores
PubMed: 38902668
DOI: 10.1186/s12873-024-01021-x -
Journal of Critical Care Jun 2024
PubMed: 38901070
DOI: 10.1016/j.jcrc.2024.154848