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Journal of the American Heart... Aug 2023Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process... (Review)
Review
Cardiogenic shock is characterized by tissue hypoxia caused by circulatory failure arising from inadequate cardiac output. In addition to treating the pathologic process causing impaired cardiac function, prompt hemodynamic support is essential to reduce the risk of developing multiorgan dysfunction and to preserve cellular metabolism. Pharmacologic therapy with the use of vasopressors and inotropes is a key component of this treatment strategy, improving perfusion by increasing cardiac output, altering systemic vascular resistance, or both, while allowing time and hemodynamic stability to treat the underlying disease process implicated in the development of cardiogenic shock. Despite the use of mechanical circulatory support recently garnering significant interest, pharmacologic hemodynamic support remains a cornerstone of cardiogenic shock management, with over 90% of patients receiving at least 1 vasoactive agent. This review aims to describe the pharmacology and hemodynamic effects of current pharmacotherapies and provide a practical approach to their use, while highlighting important future research directions.
Topics: Humans; Shock, Cardiogenic; Vasoconstrictor Agents; Hemodynamics; Vascular Resistance; Perfusion
PubMed: 37489740
DOI: 10.1161/JAHA.123.029787 -
Medizinische Klinik, Intensivmedizin... Dec 2023The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult... (Review)
Review
The Surviving Sepsis Campaign (SSC) International Guidelines for the Management of Sepsis and Septic Shock provide recommendations on the care of hospitalized adult patients with (or at risk for) sepsis. This review discusses what is new or different in the 2021 SSC adult sepsis guidelines compared to 2016. The guidelines include new weak recommendations for use of balanced fluid over saline 0.9%, use of intravenous corticosteroids for septic shock when there is ongoing vasopressor requirement, and peripheral initiation of intravenous vasopressors over delaying initiation in order to obtain central venous access. As before, there is a strong recommendation to initiate antimicrobials within 1 h of sepsis and septic shock, but there are now additional recommendations when the diagnosis is uncertain. The recommendation for initial fluid resuscitation in septic shock of 30 mL/kg crystalloid has been downgraded from strong to weak. Finally, there are 12 new recommendations addressing long-term outcomes from sepsis, including strong recommendations to screen for economic and social support and to make referrals for follow-up where available; use shared decision-making in post-intensive care unit (ICU) and hospital discharge planning; reconcile medications at both ICU and hospital discharge; provide information about sepsis and its sequelae in written and verbal hospital discharge summary; and to provide assessment and follow-up for physical, cognitive, and emotional problems after hospital discharge.
Topics: Adult; Humans; Shock, Septic; Sepsis; Intensive Care Units; Fluid Therapy; Vasoconstrictor Agents
PubMed: 37286842
DOI: 10.1007/s00063-023-01028-5 -
Critical Care (London, England) Oct 2023Septic shock can be caused by a variety of mechanisms including direct effects of bacterial toxins such as endotoxin. Annually, approximately 5-7 million patients... (Review)
Review
Septic shock can be caused by a variety of mechanisms including direct effects of bacterial toxins such as endotoxin. Annually, approximately 5-7 million patients worldwide develop sepsis with very high endotoxin activity in the blood and more than half die. The term endotoxic septic shock has been used for these patients but it is important to emphasize that endotoxin may be a factor in all forms of septic shock including non-bacterial etiologies like COVID-19 since translocation of bacterial products is a common feature of septic shock. A pattern of organ failure including hepatic dysfunction, acute kidney injury and various forms of endothelial dysfunction ranging from disseminated intravascular coagulation to thrombotic microangiopathy characterize endotoxic septic shock. However, while characteristic, the clinical phenotype is not unique to patients with high endotoxin, and the diagnosis relies on the measurement of endotoxin activity in addition to clinical assessment. Therapies for endotoxic septic shock are limited with immune modulating therapies under investigation and extracorporeal blood purification still controversial in many parts of the world.
Topics: Humans; Shock, Septic; Endotoxins; COVID-19; Sepsis
PubMed: 37858258
DOI: 10.1186/s13054-023-04690-5 -
Rheumatic Diseases Clinics of North... Aug 2023Multisystem inflammatory syndrome in children (MIS-C) is a delayed postinflammatory disorder associated with the previous infection with severe acute respiratory... (Review)
Review
Multisystem inflammatory syndrome in children (MIS-C) is a delayed postinflammatory disorder associated with the previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initially, MIS-C was described as highly similar to Kawasaki disease (KD), a pediatric febrile systemic vasculitis that can lead to the development of coronary artery aneurysms (CAAs). While KD and MIS-C are both inflammatory disorders, the 2 entities differ in their epidemiological, clinical, immunological, and pathological features. MIS-C clinical and laboratory characteristics are more closely related to toxic shock syndrome (TSS) than KD, which informs the understanding of pathogenesis and potential therapeutic approaches.
Topics: Humans; Child; Mucocutaneous Lymph Node Syndrome; COVID-19; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 37331738
DOI: 10.1016/j.rdc.2023.03.002 -
Scandinavian Journal of Trauma,... Oct 2023Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used. The recently published UK-REBOA trial aimed to investigate patients suffering...
BACKGROUND
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is increasingly used. The recently published UK-REBOA trial aimed to investigate patients suffering haemorrhagic shock and randomized to standard care alone or REBOA as adjunct to standard care and concludes that REBOA may increase the mortality.
MAIN BODY
In this commentary we try to balance the discussion on use of REBOA and address limitations in the UK-REBOA trial that may have influenced the outcome of the study.
CONCLUSION
The situation is complex, and the patients are in extremis. In summary, we do not think this is the end of balloons.
Topics: Humans; Aorta; Balloon Occlusion; Endovascular Procedures; Resuscitation; Shock, Hemorrhagic; United Kingdom; Randomized Controlled Trials as Topic
PubMed: 37908007
DOI: 10.1186/s13049-023-01142-5 -
International Journal of Molecular... Nov 2023Endotoxin, also referred to as lipopolysaccharide (LPS), is a potent stimulator of the inflammatory cascade which may progress to sepsis and septic shock. The term... (Review)
Review
Endotoxin, also referred to as lipopolysaccharide (LPS), is a potent stimulator of the inflammatory cascade which may progress to sepsis and septic shock. The term endotoxic septic shock has been used for patients who have a clinical phenotype that is characterized by high endotoxin activity in addition to a high burden of organ failure; especially a pattern of organ failure including hepatic dysfunction, acute kidney injury, and various forms of endothelial dysfunction. Endotoxic septic shock has been a target for drug therapy for decades with no success. A likely barrier to their success was the inability to quantify endotoxin in the bloodstream. The Endotoxin Activity Assay (EAA) is positioned to change this landscape. In addition, medical devices using adsorptive technology in an extra-corporeal circulation has been shown to remove large quantities of endotoxin from the bloodstream. Focusing on the use of EAA to determine high concentrations of endotoxin will allow patients with endotoxic septic shock to be identified quickly and these patients may benefit most from removal of endotoxin using extracorporeal methods.
Topics: Humans; Shock, Septic; Sepsis; Endotoxins; Lipopolysaccharides
PubMed: 38003374
DOI: 10.3390/ijms242216185 -
BMJ Open Jul 2023Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes,...
INTRODUCTION
Venous congestion is a pathophysiological state where high venous pressures cause organ oedema and dysfunction. Venous congestion is associated with worse outcomes, particularly acute kidney injury (AKI), for critically ill patients. Venous congestion can be measured by Doppler ultrasound at the bedside through interrogation of the inferior vena cava (IVC), hepatic vein (HV), portal vein (PV) and intrarenal veins (IRV). The objective of this study is to quantify the association between Doppler identified venous congestion and the need for renal replacement therapy (RRT) or death for patients with septic shock.
METHODS AND ANALYSIS
This study is a prespecified substudy of the ANDROMEDA-SHOCK 2 (AS-2) randomised control trial (RCT) assessing haemodynamic resuscitation in septic shock and will enrol at least 350 patients across multiple sites. We will include adult patients within 4 hours of fulfilling septic shock definition according to Sepsis-3 consensus conference. Using Doppler ultrasound, physicians will interrogate the IVC, HV, PV and IRV 6-12 hours after randomisation. Study investigators will provide web-based educational sessions to ultrasound operators and adjudicate image acquisition and interpretation. The primary outcome will be RRT or death within 28 days of septic shock. We will assess the hazard of RRT or death as a function of venous congestion using a Cox proportional hazards model. Sub-distribution HRs will describe the hazard of RRT given the competing risk of death.
ETHICS AND DISSEMINATION
We obtained ethics approval for the AS-2 RCT, including this observational substudy, from local ethics boards at all participating sites. We will report the findings of this study through open-access publication, presentation at international conferences, a coordinated dissemination strategy by investigators through social media, and an open-access workshop series in multiple languages.
TRIAL REGISTRATION NUMBER
NCT05057611.
Topics: Adult; Humans; Cohort Studies; Hyperemia; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic; Ultrasonography, Doppler; Multicenter Studies as Topic
PubMed: 37487682
DOI: 10.1136/bmjopen-2023-074843 -
Theranostics 2023Sepsis is a potentially life-threatening condition caused by the body's response to a severe infection. Although the identification of multiple pathways involved in...
Sepsis is a potentially life-threatening condition caused by the body's response to a severe infection. Although the identification of multiple pathways involved in inflammation, tissue damage and aberrant healing during sepsis, there remain unmet needs for the development of new therapeutic strategies essential to prevent the reoccurrence of infection and organ injuries. Expression of Suppressor of Fused (Sufu) was evaluated by qRT-PCR, western blotting, and immunofluorescence in murine lung and peritoneal macrophages. The significance of Sufu expression in prognosis was assessed by Kaplan-Meier survival analysis. The GFP-TRAF6-expressing stable cell line (GFP-TRAF6 Blue cells) were constructed to evaluate phase separation of TRAF6. Phase separation of TRAF6 and the roles of Sufu in repressing TRAF6 droplet aggregation were analyzed by co-immunoprecipitation, immunofluorescence, Native-PAGE, FRAP and assays using purified proteins. The effects of Sufu on sepsis-induced lung inflammation were evaluated by cell function assays, LPS-induced septic shock model and polymicrobial sepsis-CLP mice model. We found that Sufu expression is reduced in early response to lipopolysaccharide (LPS)-induced acute inflammation in murine lung and peritoneal macrophages. Deletion of Sufu aggravated LPS-induced and CLP (cecal ligation puncture)-induced lung injury and lethality in mice, and augmented LPS-induced proinflammatory gene expression in cultured macrophages. In addition, we identified the role of Sufu as a negative regulator of the Toll-Like Receptor (TLR)-triggered inflammatory response. We further demonstrated that Sufu directly interacts with TRAF6, thereby preventing oligomerization and autoubiquitination of TRAF6. Importantly, TRAF6 underwent phase separation during LPS-induced inflammation, which is essential for subsequent ubiquitination activation and NF-κB activity. Sufu inhibits the phase-separated TRAF6 droplet formation, preventing NF-κB activation upon LPS stimulation. In a septic shock model, TRAF6 depletion rescued the augmented inflammatory phenotype in mice with myeloid cell-specific deletion of Sufu. These findings implicated Sufu as an important inhibitor of TRAF6 in sepsis and suggest that therapeutics targeting Sufu-TRAF6 may greatly benefit the treatment of sepsis.
Topics: Mice; Animals; NF-kappa B; TNF Receptor-Associated Factor 6; Shock, Septic; Lipopolysaccharides; Inflammation; Pneumonia; Sepsis
PubMed: 37441604
DOI: 10.7150/thno.83676 -
EuroIntervention : Journal of EuroPCR... Aug 2023Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation. (Randomized Controlled Trial)
Randomized Controlled Trial
Venoarterial extracorporeal membrane oxygenation or standard care in patients with cardiogenic shock complicating acute myocardial infarction: the multicentre, randomised EURO SHOCK trial.
BACKGROUND
Cardiogenic shock (CGS) occurs in 10% of patients presenting with acute myocardial infarction (MI), with in-hospital mortality rates of 40-50% despite revascularisation.
AIMS
The EURO SHOCK trial aimed to determine if early use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) could improve outcomes in patients with persistent CGS following primary percutaneous coronary intervention (PPCI).
METHODS
This multicentre, pan-European trial randomised patients with persistent CGS 30 minutes after PPCI of the culprit lesion to receive either VA-ECMO or continue with standard therapy. The primary outcome measure was 30-day all-cause mortality in an intention-to-treat analysis. Secondary endpoints included 12-month all-cause mortality and 12-month composite of all-cause mortality or rehospitalisation due to heart failure.
RESULTS
Due to the impact of the COVID-19 pandemic, the trial was stopped before completion of recruitment, after randomisation of 35 patients (standard therapy n=18, VA-ECMO n=17). Thirty-day all-cause mortality occurred in 43.8% of patients randomised to VA-ECMO and in 61.1% of patients randomised to standard therapy (hazard ratio [HR] 0.56, 95% confidence interval [CI]: 0.21-1.45; p=0.22). One-year all-cause mortality was 51.8% in the VA-ECMO group and 81.5% in the standard therapy arm (HR 0.52, 95% CI: 0.21-1.26; p=0.14). Vascular and bleeding complications occurred more often in the VA-ECMO arm (21.4% vs 0% and 35.7% vs 5.6%, respectively).
CONCLUSIONS
Due to the limited number of patients recruited to the trial, no definite conclusions could be drawn from the available data. Our study demonstrates the feasibility of randomising patients with CGS complicating acute MI but also illustrates the challenges. We hope these data will inspire and inform the design of future large-scale trials.
Topics: Humans; Shock, Cardiogenic; Extracorporeal Membrane Oxygenation; Pandemics; COVID-19; Myocardial Infarction; Retrospective Studies
PubMed: 37334659
DOI: 10.4244/EIJ-D-23-00204 -
CMAJ : Canadian Medical Association... Nov 2023
Topics: Humans; Rifampin; Tuberculosis; Latent Tuberculosis; Patients; Shock
PubMed: 37931950
DOI: 10.1503/cmaj.230317-f