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BMC Anesthesiology Aug 2023Sepsis and septic shock are disorders of tissue perfusion and microcirculation associated with increased mortality. The role of biomarkers such as proadrenomedullin...
INTRODUCTION
Sepsis and septic shock are disorders of tissue perfusion and microcirculation associated with increased mortality. The role of biomarkers such as proadrenomedullin (PRO-ADM), interleukin 6 (IL-6) and neutrophil CD64 (CD64) in the diagnosis and prognosis of septic shock has been studied.
METHODS
GCS, SOFA score, APACHE 2 score, lactate, CRP, procalcitonin, PRO-ADM, IL-6, CD64 level and 28-day mortality were evaluated in patients with septic shock followed-up in the intensive care unit of Marmara University Hospital between July 2021 and December 2021. The study was planned as prospective, non-drug clinical research Committee.
RESULTS
There were no statistically significant differences between patient groups in gender, BMI, and presence of comorbidities (p > 0.05). The alive patient group had significantly higher GCS values and lower SOFA, APACHE 2, lactate and CD64 values than the dead patient group (p < 0.01). The cut-off values of laboratory parameters were determined using ROC analysis to predict mortality, SOFA and CD64 had high AUC. This is also a good indicator for mortality.The multivariate logistic regression model was estimated using the backward selection method. The mortality of ICU patients was predicted by a SOFA-value ≥ 12 (OR (95%CI) = 56.13 (5.44-578.64)), CD64 value ≥ 28.54 (OR (95% CI) = 23.78 (2.61-216.85)), and ADM-value ≥ 86.79 (OR (95% CI) = 15.86 (1.02-246.49)) (p < 0.05) .
CONCLUSION
In conclusion, serum CD64 level, PRO-ADM level, and SOFA score proved to be effective parameters for predicting prognosis and mortality in septic shock. However, IL-6 proved to be a weak biomarker and failed to predict mortality. CD64, which is easier and more practical to use, can be used instead of the SOFA score.
Topics: Humans; Interleukin-6; Shock, Septic; Prospective Studies; Prognosis; Lactic Acid
PubMed: 37592204
DOI: 10.1186/s12871-023-02237-3 -
Intensive Care Medicine Apr 2024
Topics: Humans; Shock, Septic; Hemodynamics; Skin
PubMed: 38498167
DOI: 10.1007/s00134-024-07361-3 -
Critical Care (London, England) Nov 2023Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume...
BACKGROUND
Capillary refill time (CRT) has been suggested as a variable to follow during the course of septic shock. We systematically investigated the effects on CRT of volume expansion and norepinephrine.
METHODS
In 69 septic shock patients, we recorded mean arterial pressure (MAP), cardiac index (CI), and 5 consecutive CRT measurements (video method, standardized pressure applied on the fingertip) before and after a 500-mL saline infusion in 33 patients and before and after an increase of the norepinephrine dose in 36 different patients. Fluid responders were defined by an increase in CI ≥ 15%, and norepinephrine responders by an increase in MAP ≥ 15%.
RESULTS
The least significant change of CRT was 23%, so that changes in CRT were considered significant if larger than 23%. With volume expansion, CRT remained unchanged on average in patients with baseline CRT < 3 s (n = 7) and in all but one patient with baseline CRT ≥ 3 s in whom fluid increased CI < 15% (n = 13 "fluid non-responders"). In fluid responders with baseline CRT ≥ 3 s (n = 13), CRT decreased in 8 patients and remained unchanged in the others, exhibiting a dissociation between CI and CRT responses. The proportion of patients included > 24 h after starting norepinephrine was higher in patients with such a dissociation than in the other ones (60% vs. 0%, respectively). Norepinephrine did not change CRT significantly (except in one patient) if baseline CRT was ≥ 3 s and the increase in MAP < 15% (n = 6). In norepinephrine responders with prolonged baseline CRT (n = 11), it increased in 4 patients and remained unchanged in the other ones, which exhibited a dissociation between MAP and CRT responses.
CONCLUSIONS
In septic shock patients with prolonged CRT, CRT very rarely improves with treatment when volume expansion increases cardiac output < 15% and increasing norepinephrine increases MAP < 15%. When the effects of fluid infusion on cardiac output and of norepinephrine on MAP are significant, the response of CRT is variable, as it decreases in some patients and remains stable in others which exhibit a dissociation between changes in macrohemodynamic variables and in CRT. In this regard, CRT behaves as a marker of microcirculation.
TRIAL REGISTRATION
ClinicalTrial.gov (NCT04870892). Registered January15, 2021. Ethics committee approval CE SRLF 21-25.
Topics: Humans; Cardiac Output; Hemodynamics; Microcirculation; Norepinephrine; Shock, Septic
PubMed: 37932812
DOI: 10.1186/s13054-023-04714-0 -
Journal of Intensive Care Medicine Oct 2023Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. We examined the correlation between bioimpedance and... (Observational Study)
Observational Study
Bioimpedance may be a useful tool to guide fluid treatment and avoid organ dysfunction related to fluid overload. We examined the correlation between bioimpedance and organ dysfunction in patients with septic shock. Prospective observational study of adult intensive care unit patients fulfilling the sepsis-3 criteria. Bioimpedance was measured using a body composition monitor (BCM) and BioScan Touch i8 (MBS). We measured impedance at inclusion and after 24 h and reported the impedance, change in impedance, bioimpedance-derived fluid balance, and changes in bioimpedance-derived fluid balance. Organ markers on respiratory, circulatory, and kidney function and overall disease severity were ascertained on days 1-7. The effect of bioimpedance on the change in organ function was assessed by mixed effects linear models. We considered < .01 as significant. Forty-nine patients were included. None of the single baseline measurements or derived fluid balances were associated with the course of organ dysfunction. Changes in impedance were associated with the course of overall disease severity ( < .001; with MBS), and with changes in noradrenaline dose ( < .001; with MBS) and fluid balance ( < .001; with BCM). The changes in bioimpedance-derived fluid balance were associated with changes in noradrenaline dose ( < .001; with BCM), cumulative fluid balances ( < .001; with MBS), and lactate concentrations ( < .001; with BCM). Changes in bioimpedance were correlated with the duration of overall organ failure, circulatory failure, and fluid status. Single measurements of bioimpedance were not associated with any changes in organ dysfunction.
Topics: Adult; Humans; Shock, Septic; Multiple Organ Failure; Body Composition; Water-Electrolyte Imbalance; Norepinephrine
PubMed: 37186782
DOI: 10.1177/08850666231175819 -
BMC Anesthesiology Sep 2023Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of high-dose intravenous ascorbic acid on microcirculation and endothelial glycocalyx during sepsis and septic shock: a double-blind, randomized, placebo-controlled study.
Previous studies indicate supplemental vitamin C improves microcirculation and reduces glycocalyx shedding in septic animals. Our randomized, double-blind, placebo-controlled trial aimed to investigate whether a high dose of intravenous ascorbic acid (AA) might improve microcirculation and affect glycocalyx in septic patients. In our study, 23 septic patients were supplemented with a high dose (50 mg/kg every 6 h) of intravenous AA or placebo for 96 h. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field (IDF) video microscope. A sidestream dark field video microscope (SDF), connected to the GlycoCheck software (GlycoCheck ICU®; Maastricht University Medical Center, Maastricht, the Netherlands), was employed to observe glycocalyx. We found a significantly higher proportion of perfused small vessels (PPV) 6 h after the beginning of the trial in the experimental group compared with placebo. As an indicator of glycocalyx thickness, the perfused boundary region was lower in capillaries of the 5-9 μm diameter in the AA group than placebo after the first dose of AA. Our data suggest that high-dose parenteral AA tends to improve microcirculation and glycocalyx in the early period of septic shock. The study was retrospectively registered in the clinicaltrials.gov database on 26/02/2021 (registration number NCT04773717).
Topics: Ascorbic Acid; Glycocalyx; Microcirculation; Sepsis; Shock, Septic; Humans
PubMed: 37700249
DOI: 10.1186/s12871-023-02265-z -
The Lancet. Respiratory Medicine May 2024Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Glucocorticoids probably improve outcomes in patients hospitalised for community acquired pneumonia (CAP). In this a priori planned exploratory subgroup analysis of the phase 3 randomised controlled Activated Protein C and Corticosteroids for Human Septic Shock (APROCCHSS) trial, we aimed to investigate responses to hydrocortisone plus fludrocortisone between CAP and non-CAP related septic shock.
METHODS
APROCCHSS was a randomised controlled trial that investigated the effects of hydrocortisone plus fludrocortisone, drotrecogin-alfa (activated), or both on mortality in septic shock in a two-by-two factorial design; after drotrecogin-alfa was withdrawn on October 2011, from the market, the trial continued on two parallel groups. It was conducted in 34 centres in France. In this subgroup study, patients with CAP were a preselected subgroup for an exploratory secondary analysis of the APROCCHSS trial of hydrocortisone plus fludrocortisone in septic shock. Adults with septic shock were randomised 1:1 to receive, in a double-blind manner, a 7-day treatment with daily administration of intravenous hydrocortisone 50 mg bolus every 6h and a tablet of 50 μg of fludrocortisone via the nasogastric tube, or their placebos. The primary outcome was 90-day all-cause mortality. Secondary outcomes included all-cause mortality at intensive care unit (ICU) and hospital discharge, 28-day and 180-day mortality, the number of days alive and free of vasopressors, mechanical ventilation, or organ failure, and ICU and hospital free-days to 90-days. Analysis was done in the intention-to-treat population. The trial was registered at ClinicalTrials.gov (NCT00625209).
FINDINGS
Of 1241 patients included in the APROCCHSS trial, CAP could not be ruled in or out in 31 patients, 562 had a diagnosis of CAP (279 in the placebo group and 283 in the corticosteroid group), and 648 patients did not have CAP (329 in the placebo group and 319 in the corticosteroid group). In patients with CAP, there were 109 (39%) deaths of 283 patients at day 90 with hydrocortisone plus fludrocortisone and 143 (51%) of 279 patients receiving placebo (odds ratio [OR] 0·60, 95% CI 0·43-0·83). In patients without CAP, there were 148 (46%) deaths of 319 patients at day 90 in the hydrocortisone and fludrocortisone group and 157 (48%) of 329 patients in the placebo group (OR 0·95, 95% CI 0·70-1·29). There was significant heterogeneity in corticosteroid effects on 90-day mortality across subgroups with CAP and without CAP (p=0·046 for both multiplicative and additive interaction tests; moderate credibility). Of 1241 patients included in the APROCCHSS trial, 648 (52%) had ARDS (328 in the placebo group and 320 in the corticosteroid group). There were 155 (48%) deaths of 320 patients at day 90 in the corticosteroid group and 186 (57%) of 328 patients in the placebo group. The OR for death at day 90 was 0·72 (95% CI 0·53-0·98) in patients with ARDS and 0·85 (0·61-1·20) in patients without ARDS (p=0·45 for multiplicative interaction and p=0·42 for additive interaction). The OR for observing at least one serious adverse event (corticosteroid group vs placebo) within 180 days post randomisation was 0·64 (95% CI 0·46-0·89) in the CAP subgroup and 1·02 (0·75-1·39) in the non-CAP subgroup (p=0·044 for multiplicative interaction and p=0·042 for additive interaction).
INTERPRETATION
In a pre-specified subgroup analysis of the APROCCHSS trial of patients with CAP and septic shock, hydrocortisone plus fludrocortisone reduced mortality as compared with placebo. Although a large proportion of patients with CAP also met criteria for ARDS, the subgroup analysis was underpowered to fully discriminate between ARDS and CAP modifying effects on mortality reduction with corticosteroids. There was no evidence of a significant treatment effect of corticosteroids in the non-CAP subgroup.
FUNDING
Programme Hospitalier de Recherche Clinique of the French Ministry of Health, by Programme d'Investissements d'Avenir, France 2030, and IAHU-ANR-0004.
Topics: Humans; Hydrocortisone; Shock, Septic; Community-Acquired Infections; Male; Female; Fludrocortisone; Aged; Middle Aged; Pneumonia; Double-Blind Method; Drug Therapy, Combination; Anti-Inflammatory Agents; Treatment Outcome; Protein C
PubMed: 38310918
DOI: 10.1016/S2213-2600(23)00430-7 -
Die Anaesthesiologie Jan 2024The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing... (Review)
Review
The time to administration of broad-spectrum antibiotics and (secondarily) to the initiation of hemodynamic stabilization are the most important factors influencing survival of patients with sepsis and septic shock; however, the basic prerequisite for the initiation of an adequate treatment is that a suspected diagnosis of sepsis is made first. Therefore, the treatment of sepsis, even before it has begun, is an interdisciplinary and interprofessional task. This article provides an overview of the current state of the art in sepsis treatment and points towards new evidence that has the potential to change guideline recommendations in the coming years. In summary, the following points are critical: (1) sepsis must be diagnosed as soon as possible and the implementation of a source control intervention (in case of a controllable source) has to be implemented as soon as (logistically) possible. (2) In general, intravenous broad-spectrum antibiotics should be given within the first hour after diagnosis if sepsis or septic shock is suspected. In organ dysfunction without shock, where sepsis is a possible but unlikely cause, the results of focused advanced diagnostics should be awaited before a decision to give broad-spectrum antibiotics is made. If it is not clear within 3 h whether sepsis is the cause, broad-spectrum antibiotics should be given when in doubt. Administer beta-lactam antibiotics as a prolonged (or if therapeutic drug monitoring is available, continuous) infusion after an initial loading dose. (3) Combination treatment with two agents for one pathogen group should remain the exception (e.g. multidrug-resistant gram-negative pathogens). (4) In the case of doubt, the duration of anti-infective treatment should rather be shorter than longer. Procalcitonin can support the clinical decision to stop (not to start!) antibiotic treatment! (5) For fluid treatment, if hypoperfusion is present, the first (approximately) 2L (30 ml/kg BW) of crystalloid solution is usually safe and indicated. After that, the rule is: less is more! Any further fluid administration should be carefully weighed up with the help of dynamic parameters, the patient's clinical condition and echo(cardio)graphy.
Topics: Humans; Shock, Septic; Sepsis; Anti-Bacterial Agents; beta Lactam Antibiotics; Combined Modality Therapy
PubMed: 37950017
DOI: 10.1007/s00101-023-01354-5 -
Current Opinion in Critical Care Aug 2023Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the... (Review)
Review
PURPOSE OF REVIEW
Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults.
RECENT FINDINGS
Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality.
SUMMARY
The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.
Topics: Adult; Humans; Ascorbic Acid; Critical Illness; Vitamins; Shock, Septic; Antioxidants; Multicenter Studies as Topic
PubMed: 37306524
DOI: 10.1097/MCC.0000000000001054 -
ELife Feb 2024Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral...
Septic shock is characterized by an excessive inflammatory response depicted in a cytokine storm that results from invasive bacterial, fungi, protozoa, and viral infections. Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and proinflammatory cytokine production via caspase-11 and gasdermin D (GSDMD). Here, we show that NAD treatment protected mice toward bacterial and lipopolysaccharide (LPS)-induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD administration impeded systemic IL-1β and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-β/STAT-1 signaling machinery. More importantly, NAD administration not only improved casp-11 KO (knockout) survival but rendered wild type (WT) mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD blocking septic shock through a specific inhibition of the non-canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.
Topics: Animals; Mice; Cytokines; Interleukin-10; Inflammasomes; NAD; Shock, Septic; Macrophages
PubMed: 38372712
DOI: 10.7554/eLife.88686 -
Medicine Sep 2023The efficacy of dexmedetomidine was elusive for septic shock. This meta-analysis aimed to explore the efficacy of dexmedetomidine for septic shock. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The efficacy of dexmedetomidine was elusive for septic shock. This meta-analysis aimed to explore the efficacy of dexmedetomidine for septic shock.
METHODS
PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases have been searched through October 2022 and we included randomized controlled trials reporting the effect of dexmedetomidine in patients with septic shock.
RESULTS
Five randomized controlled trials were included in the meta-analysis. Compared with control group for septic shock, dexmedetomidine treatment was able to substantially decrease Sequential Organ Failure Assessment score (mean difference [MD] = -0.99; 95% confidence interval [CI] = -1.14 to -0.84; P < .00001) and duration of mechanical ventilation (MD = -0.90; 95% CI = -1.27 to -0.54; P < .00001), but showed no obvious influence on morality at 28 days (odds ratio = 0.79; 95% CI = 0.38 to 1.66; P = 054), hospital mortality (odds ratio = 0.66; 95% CI = 0.35 to 1.24; P = .20) or intensive care unit length of stay (MD = -1.47; 95% CI = -4.60 to 1.66; P = .36).
CONCLUSIONS
Dexmedetomidine administration may help treat patients with septic shock.
Topics: Humans; Dexmedetomidine; Shock, Septic; Randomized Controlled Trials as Topic; Control Groups; Databases, Factual
PubMed: 37657031
DOI: 10.1097/MD.0000000000034414