scholarly journals Peroxynitrite decomposition catalyst reduces vasopressin requirement in ovine MRSA sepsis

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Osamu Fujiwara ◽  
Satoshi Fukuda ◽  
Ernesto Lopez ◽  
Yaping Zeng ◽  
Yosuke Niimi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Fluid Resuscitation ◽  
Conscious State ◽  
Smoke Inhalation ◽  
Post Injury ◽  
Adjunct Treatment ◽  
Aggressive Fluid Resuscitation ◽  
Severe Hypotension ◽  
Bolus Intravenous Injection

Abstract Background Sepsis is one of the most frequent causes of death in the intensive care unit. Host vascular hypo-responsiveness to vasopressors during septic shock is one of the challenging problems. This study tested the hypothesis that adjunct therapy with peroxynitrite decomposition catalyst (WW-85) would reduce arginine vasopressin (AVP) requirements during sepsis resuscitation, using ovine sepsis model. Methods Thirteen adult female Merino sheep, previously instrumented with multiple vascular catheters, were subjected to “two-hit” (cotton smoke inhalation and intrapulmonary instillation of live methicillin-resistant Staphylococcus aureus; 3.5 × 1011 colony-forming units) injury. Post injury, animals were awakened and randomly allocated to the following groups: (1) AVP: injured, fluid resuscitated, and titrated with AVP, n = 6 or (2) WW-85 + AVP: injured, fluid resuscitated, treated with WW-85, and titrated with AVP, n = 7. One-hour post injury, a bolus intravenous injection of WW-85 (0.1 mg/kg) was followed by a 23-h continuous infusion (0.02 mg/kg/h). Titration of AVP started at a dose of 0.01 unit/min, when mean arterial pressure (MAP) decreased by 10 mmHg from baseline, despite aggressive fluid resuscitation, and the rate was further adjusted to maintain MAP. After the injury, all animals were placed on a mechanical ventilator and monitored in the conscious state for 24 h. Results The injury induced severe hypotension refractory to aggressive fluid resuscitation. High doses of AVP were required to partially attenuate the sepsis-induced hypotension. However, the cumulative AVP requirement was significantly reduced by adjunct treatment with WW-85 at 17–24 h after the injury (p < 0.05). Total AVP dose and the highest AVP rate were significantly lower in the WW-85 + AVP group compared to the AVP group (p = 0.02 and 0.04, respectively). Treatment with WW-85 had no adverse effects. In addition, the in vitro effects of AVP on isolated artery diameter changes were abolished with peroxynitrite co-incubation. Conclusions The modulation of reactive nitrogen species, such as peroxynitrite, may be considered as a novel adjunct treatment option for septic shock associated with vascular hypo-responsiveness to vasopressors.

scholarly journals A case report of streptococcal toxic shock syndrome caused by Streptococcus mitis in a healthy adult

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiang Chen ◽  
Ying Ying Gong ◽  
Li Zhang
Keyword(s):  
Septic Shock ◽  
Mortality Rate ◽  
Fluid Resuscitation ◽  
Toxic Shock Syndrome ◽  
Group A Streptococcus ◽  
Vital Signs ◽  
Streptococcal Toxic Shock Syndrome ◽  
Toxic Shock ◽  
Streptococcus Mitis ◽  
Aggressive Fluid Resuscitation

Abstract Background Streptococcal toxic shock syndrome (STSS) is an acute, multisystem and toxin-mediated disease that usually causes shock and multiple organ failure in the early stages of its clinical course. It is associated with a substantial increase in mortality rate. The disease has been associated with invasive group A Streptococcus and is rarely caused by Streptococcus mitis (S. mitis). In healthy adults, S. mitis is closely related to endocarditis but rarely related to STSS. Case presentation We report a case of STSS caused by S. mitis in a healthy 45-year-old woman. She presented with fever 14 h after surgery and with hypotension 24 h later, and she subsequently suffered from septic shock, low albumin, dysfunction of coagulation, acute kidney dysfunction, respiratory alkalosis and metabolic acidosis, acute respiratory distress syndrome and cellulitis of the incision. The diagnosis was obtained through clinical manifestation and blood culture examination. The patient was treated with aggressive fluid resuscitation, adequate antibiotics for a total of 4 weeks, respiratory support, and surgical debridement and drainage of the incision. She was discharged after her vital signs returned to normal and the incision healed on day 40 after surgery. Conclusions The diagnosis of STSS is often delayed or missed, which leads to a high mortality rate. It is possible to cure patients if the disease can be identified early and treated with aggressive fluid resuscitation, adequate antibiotics and control of the source of infection. Clinicians should consider the disease in the differential diagnosis of septic shock to prevent death.

scholarly journals Effects of capillary refill time-vs. lactate-targeted fluid resuscitation on regional, microcirculatory and hypoxia-related perfusion parameters in septic shock: a randomized controlled trial

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ricardo Castro ◽  
Eduardo Kattan ◽  
Giorgio Ferri ◽  
Ronald Pairumani ◽  
Emilio Daniel Valenzuela ◽  
...  
Keyword(s):  
Septic Shock ◽  
Randomized Controlled Trial ◽  
Fluid Resuscitation ◽  
Controlled Trial ◽  
Tissue Perfusion ◽  
Capillary Refill Time ◽  
Capillary Refill ◽  
Randomized Controlled ◽  
Microcirculatory Flow ◽  
The Impact

Abstract Background Persistent hyperlactatemia has been considered as a signal of tissue hypoperfusion in septic shock patients, but multiple non-hypoperfusion-related pathogenic mechanisms could be involved. Therefore, pursuing lactate normalization may lead to the risk of fluid overload. Peripheral perfusion, assessed by the capillary refill time (CRT), could be an effective alternative resuscitation target as recently demonstrated by the ANDROMEDA-SHOCK trial. We designed the present randomized controlled trial to address the impact of a CRT-targeted (CRT-T) vs. a lactate-targeted (LAC-T) fluid resuscitation strategy on fluid balances within 24 h of septic shock diagnosis. In addition, we compared the effects of both strategies on organ dysfunction, regional and microcirculatory flow, and tissue hypoxia surrogates. Results Forty-two fluid-responsive septic shock patients were randomized into CRT-T or LAC-T groups. Fluids were administered until target achievement during the 6 h intervention period, or until safety criteria were met. CRT-T was aimed at CRT normalization (≤ 3 s), whereas in LAC-T the goal was lactate normalization (≤ 2 mmol/L) or a 20% decrease every 2 h. Multimodal perfusion monitoring included sublingual microcirculatory assessment; plasma-disappearance rate of indocyanine green; muscle oxygen saturation; central venous-arterial pCO2 gradient/ arterial-venous O2 content difference ratio; and lactate/pyruvate ratio. There was no difference between CRT-T vs. LAC-T in 6 h-fluid boluses (875 [375–2625] vs. 1500 [1000–2000], p = 0.3), or balances (982[249–2833] vs. 15,800 [740–6587, p = 0.2]). CRT-T was associated with a higher achievement of the predefined perfusion target (62 vs. 24, p = 0.03). No significant differences in perfusion-related variables or hypoxia surrogates were observed. Conclusions CRT-targeted fluid resuscitation was not superior to a lactate-targeted one on fluid administration or balances. However, it was associated with comparable effects on regional and microcirculatory flow parameters and hypoxia surrogates, and a faster achievement of the predefined resuscitation target. Our data suggest that stopping fluids in patients with CRT ≤ 3 s appears as safe in terms of tissue perfusion. Clinical Trials: ClinicalTrials.gov Identifier: NCT03762005 (Retrospectively registered on December 3rd 2018)

scholarly journals Polymerized albumin restores impaired hemodynamics in endotoxemia and polymicrobial sepsis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donald A. Belcher ◽  
Alexander T. Williams ◽  
Andre F. Palmer ◽  
Pedro Cabrales
Keyword(s):  
Septic Shock ◽  
Immune Response ◽  
Fluid Resuscitation ◽  
Cecal Ligation ◽  
Vascular Wall ◽  
Polymicrobial Sepsis ◽  
Vascular Integrity ◽  
Fluid Extravasation ◽  
Inflammatory Immune Response ◽  
Polymerized Human Serum Albumin

AbstractFluid resuscitation following severe inflammation-induced hypoperfusion is critical for the restoration of hemodynamics and the prevention of multiorgan dysfunction syndrome during septic shock. Fluid resuscitation with commercially available crystalloid and colloid solutions only provides transient benefits, followed by fluid extravasation and tissue edema through the inflamed endothelium. The increased molecular weight (M.W.) of polymerized human serum albumin (PolyHSA) can limit fluid extravasation, leading to restoration of hemodynamics. In this prospective study, we evaluated how fluid resuscitation with PolyHSA impacts the hemodynamic and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model. Additionally, we evaluated fluid resuscitation with PolyHSA in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Resuscitation with PolyHSA attenuated the immune response and improved the maintenance of systemic hemodynamics and restoration of microcirculatory hemodynamics. This decrease in inflammatory immune response and maintenance of vascular wall shear stress likely contributes to the maintenance of vascular integrity following fluid resuscitation with PolyHSA. The sustained restoration of perfusion, decrease in pro-inflammatory immune response, and improved vascular integrity that results from the high M.W. of PolyHSA indicates that a PolyHSA based solution is a potential resuscitation fluid for endotoxic and septic shock.

Mortality Benefit From the Passive Leg Raise Maneuver in Guiding Resuscitation of Septic Shock Patients: A Systematic Review and Meta-Analysis of Randomized Trials

2021 ◽  
pp. 088506662110197
Author(s):  
Moosa Azadian ◽  
Suyee Win ◽  
Amir Abdipour ◽  
Carolyn Krystal Kim ◽  
H. Bryant Nguyen
Keyword(s):  
Systematic Review ◽  
Septic Shock ◽  
Fluid Resuscitation ◽  
Standard Care ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Time Interval ◽  
Eligibility Criteria ◽  
Significant Difference ◽  
Passive Leg Raise

Background: Fluid therapy plays a major role in the management of critically ill patients. Yet assessment of intravascular volume in these patients is challenging. Different invasive and non-invasive methods have been used with variable results. The passive leg raise (PLR) maneuver has been recommended by international guidelines as a means to determine appropriate fluid resuscitation. We performed this systematic review and meta-analysis to determine if using this method of volume assessment has an impact on mortality outcome in patients with septic shock. Methods: This study is a systematic review and meta-analysis. We searched available data in the MEDLINE, CINAHL, EMBASE, and CENTRAL databases from inception until October 2020 for prospective, randomized, controlled trials that compared PLR-guided fluid resuscitation to standard care in adult patients with septic shock. Our primary outcome was mortality at the longest duration of follow-up. Results: We screened 1,425 article titles and abstracts. Of the 23 full-text articles reviewed, 5 studies with 462 patients met our eligibility criteria. Odds ratios (ORs) and associated 95% confidence intervals (CIs) for mortality at the longest reported time interval were calculated for each study. Using random effects modeling, the pooled OR (95% CI) for mortality with a PLR-guided resuscitation strategy was 0.82 (0.52 -1.30). The included studies were not blinded and they ranged from having low to high risk of bias using the Cochrane Risk of Bias Tool. Conclusion: Our analysis showed there was no statistically significant difference in mortality among septic shock patients treated with PLR-guided resuscitation vs. those with standard care.

scholarly journals How much fluid resuscitation is optimal in septic shock?

Critical Care ◽  
2012 ◽  
Vol 16 (4) ◽  
pp. 146 ◽  
Author(s):  
James A Russell
Keyword(s):  
Septic Shock ◽  
Fluid Resuscitation

scholarly journals Multicountry survey of emergency and critical care medicine physicians’ fluid resuscitation practices for adult patients with early septic shock

BMJ Open ◽  
2016 ◽  
Vol 6 (7) ◽  
pp. e010041 ◽  
Author(s):  
Lauralyn McIntyre ◽  
Brian H Rowe ◽  
Timothy S Walsh ◽  
Alasdair Gray ◽  
Yaseen Arabi ◽  
...  
Keyword(s):  
Septic Shock ◽  
Critical Care ◽  
Fluid Resuscitation ◽  
Adult Patients ◽  
Critical Care Medicine

scholarly journals Interaction of Antimicrobial Peptide Temporin L with Lipopolysaccharide In Vitro and in Experimental Rat Models of Septic Shock Caused by Gram-Negative Bacteria

2006 ◽  
Vol 50 (7) ◽  
pp. 2478-2486 ◽  
Author(s):  
Andrea Giacometti ◽  
Oscar Cirioni ◽  
Roberto Ghiselli ◽  
Federico Mocchegiani ◽  
Fiorenza Orlando ◽  
...  
Keyword(s):  
Septic Shock ◽  
Antimicrobial Peptide ◽  
Gram Negative Bacteria ◽  
Amphibian Skin ◽  
Necrosis Factor Alpha ◽  
Gram Negative ◽  
Rat Models ◽  
E Coli ◽  
Tnf Α

ABSTRACT Sepsis remains a major cause of morbidity and mortality in hospitalized patients, despite intense efforts to improve survival. The primary lead for septic shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of gram-negative bacteria. For these reasons, the quest for compounds with antiendotoxin properties is actively pursued. We investigated the efficacy of the amphibian skin antimicrobial peptide temporin L in binding Escherichia coli LPS in vitro and counteracting its effects in vivo. Temporin L strongly bound to purified E. coli LPS and lipid A in vitro, as proven by fluorescent displacement assay, and readily penetrated into E. coli LPS monolayers. Furthermore, the killing activity of temporin L against E. coli was progressively inhibited by increasing concentrations of LPS added to the medium, further confirming the peptide's affinity for endotoxin. Antimicrobial assays showed that temporin L interacted synergistically with the clinically used β-lactam antibiotics piperacillin and imipenem. Therefore, we characterized the activity of temporin L when combined with imipenem and piperacillin in the prevention of lethality in two rat models of septic shock, measuring bacterial growth in blood and intra-abdominal fluid, endotoxin and tumor necrosis factor alpha (TNF-α) concentrations in plasma, and lethality. With respect to controls and single-drug treatments, the simultaneous administration of temporin L and β-lactams produced the highest antimicrobial activities and the strongest reduction in plasma endotoxin and TNF-α levels, resulting in the highest survival rates.

scholarly journals Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1844
Author(s):  
Maria Luísa da Silveira Hahmeyer ◽  
José Eduardo da Silva-Santos
Keyword(s):  
Septic Shock ◽  
Actin Polymerization ◽  
Current Knowledge ◽  
Cecal Ligation ◽  
Experimental Models ◽  
Rho Proteins ◽  
Growing Cell ◽  
Sepsis And Septic Shock

Sepsis and septic shock are associated with acute and sustained impairment in the function of the cardiovascular system, kidneys, lungs, liver, and brain, among others. Despite the significant advances in prevention and treatment, sepsis and septic shock sepsis remain global health problems with elevated mortality rates. Rho proteins can interact with a considerable number of targets, directly affecting cellular contractility, actin filament assembly and growing, cell motility and migration, cytoskeleton rearrangement, and actin polymerization, physiological functions that are intensively impaired during inflammatory conditions, such as the one that occurs in sepsis. In the last few decades, Rho proteins and their downstream pathways have been investigated in sepsis-associated experimental models. The most frequently used experimental design included the exposure to bacterial lipopolysaccharide (LPS), in both in vitro and in vivo approaches, but experiments using the cecal ligation and puncture (CLP) model of sepsis have also been performed. The findings described in this review indicate that Rho proteins, mainly RhoA and Rac1, are associated with the development of crucial sepsis-associated dysfunction in different systems and cells, including the endothelium, vessels, and heart. Notably, the data found in the literature suggest that either the inhibition or activation of Rho proteins and associated pathways might be desirable in sepsis and septic shock, accordingly with the cellular system evaluated. This review included the main findings, relevance, and limitations of the current knowledge connecting Rho proteins and sepsis-associated experimental models.

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