Increased muscle-to-serum lactate gradient predicts progression towards septic shock in septic patients

Purpose  

During septic shock, muscle produces lactate and pyruvate by way of an exaggerated Na⁺, K⁺-ATPase-stimulated aerobic glycolysis associated with epinephrine stimulation. We hypothesized that patients with sepsis without shock and increased epinephrine levels or an increased muscle-to-serum lactate gradient are likely to evolve towards septic shock. Thus, in sepsis patients, we investigated (1) whether muscle produces lactate and pyruvate, and (2) whether muscle lactate production is linked to epinephrine levels and the severity of the patient's condition.     

Restoring arterial pressure with norepinephrine improves muscle tissue oxygenation assessed by near-infrared spectroscopy in severely hypotensive septic patients

Purpose  

To examine the consequences of administration of norepinephrine on muscle tissue oxygenation in severely hypotensive septic shock patients.     

Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury

Purpose

To study the impact of inflammation/sepsis on the concentrations of neutrophil gelatinase-associated lipocalin (NGAL) in plasma and urine in adult intensive care unit (ICU) patients and to estimate the predictive properties of NGAL in plasma and urine for early detection of acute kidney injury (AKI) in patients with septic shock.

Methods

Sixty-five patients admitted to the general ICU at the Karolinska University Hospital Solna, Sweden, with normal plasma creatinine were assessed for eligibility. Twenty-seven patients with systemic inflammatory response syndrome (SIRS), severe sepsis, or septic shock without AKI and 18 patients with septic shock and concomitant AKI were included in the final analysis. Plasma and urine were analyzed twice daily for plasma NGAL (pNGAL), C-reactive protein (CRP), procalcitonin, myeloperoxidase, plasma cystatin C, plasma creatinine, urine NGAL (uNGAL), urine cystatin C, and urine α1-microglobulin.

Results

Of the 45 patients, 40 had elevated peak levels of pNGAL. Peak levels of pNGAL were not significantly different between septic shock patients with and without AKI. Peak levels of uNGAL were below the upper reference limit in all but four patients without AKI. uNGAL was a good predictor (area under ROC 0.86) whereas pNGAL was a poor predictor (area under ROC 0.67) for AKI within the next 12 h in patients with septic shock.

Conclusions

pNGAL is raised in patients with SIRS, severe sepsis, and septic shock and should be used with caution as a marker of AKI in ICU patients with septic shock. uNGAL is more useful in predicting AKI as the levels are not elevated in septic patients without AKI.     

Heat stress is associated with decreased lactic acidemia in rat sepsis

Background  

Elevated plasma lactate has been shown to correlate with mortality in patients with septic shock. Heat stress prior to sepsis has resulted in reduction in acute lung injury and mortality. We investigated whether heat stress resulted in decreased plasma lactate concentration and protected the lung by decreasing the inflammatory response to sepsis.     

Luminal concentrations of L- and D-lactate in the rectum may relate to severity of disease and outcome in septic patients

Introduction  

Little is known about the condition of the large bowel in patients with sepsis. We have previously demonstrated increased concentrations of L-lactate in the rectal lumen in patients with abdominal septic shock. The present study was undertaken to assess the concentrations of L- and D-lactate in rectal lumen and plasma in septic patients including the possible relation to site of infection, severity of disease, and outcome.     

Increased MerTK expression in circulating innate immune cells of patients with septic shock

Purpose

A new pathway of three protein tyrosine kinase receptors, namely, the TAM receptor family [Tyro-3, Axl and Mer tyrosine kinase (MerTK)], has recently been described to negatively control immune responses. The objective of this prospective, observational, clinical study was to investigate the expression patterns of TAM receptors in circulating white blood cells collected from patients with septic shock.

Methods

The expression of TAM receptors was measured by flow cytometry in circulating leukocytes from patients with septic shock sampled on days (D) 1–2 (n = 47) and D3–4 (n = 37) after the onset of shock, severe trauma patients at D1–2 after trauma (n = 51) and healthy individuals (n = 23).

Results

On D1–2 after injury, MerTK was overexpressed in monocytes and neutrophils collected from patients with septic shock in comparison with those collected from healthy volunteers and trauma patients. This phenomenon was also observed for mRNA. Conversely, the expression of Tyro-3 and Axl was higher in monocytes from trauma patients versus healthy volunteers or those in septic shock. MerTK expression between D1–2 and D3–4 remained elevated in patients suffering from septic shock who died or developed an intensive care unit-acquired infection, whereas it decreased in patients who recovered uneventfully. This in vivo observed expression pattern was reproduced ex vivo after the incubation of healthy volunteer cells with plasma from septic shock or trauma patients.

Conclusions

MerTK expression in circulating innate immune cells is increased in patients with septic shock in comparison with healthy volunteers and trauma patients. Persistent MerTK overexpression after septic shock is associated with adverse outcome. The role of this family of receptors in the pathophysiology of injury-induced immune dysfunctions deserves to be specifically investigated.     

Clinical relevance of the severe abnormalities of the T cell compartment in septic shock patients

Introduction  

Given the pivotal role of T lymphocytes in the immune system, patients with septic shock may show T cell abnormalities. We have characterised the T cell compartment in septic shock and assess its clinical implications.     

Coenzyme Q10 levels are low and may be associated with the inflammatory cascade in septic shock

Introduction  

Mitochondrial dysfunction is associated with increased mortality in septic shock. Coenzyme Q10 (CoQ10) is a key cofactor in the mitochondrial respiratory chain, but whether CoQ10 is depleted in septic shock remains unknown. Moreover, statin therapy may decrease CoQ10 levels, but whether this occurs acutely remains unknown. We measured CoQ10 levels in septic shock patients enrolled in a randomized trial of simvastatin versus placebo.     

Early initiation of low-dose corticosteroid therapy in the management of septic shock: a retrospective observational study

Introduction  

The use of low-dose steroid therapy in the management of septic shock has been extensively studied. However, the association between the timing of low-dose steroid therapy and the outcome has not been evaluated. Therefore, we evaluated whether early initiation of low-dose steroid therapy is associated with mortality in patients with septic shock.     

Effects on management and outcome of severe sepsis and septic shock patients admitted to the intensive care unit after implementation of a sepsis program: a pilot study

Introduction  

The application in clinical practice of evidence-based guidelines for the management of patients with severe sepsis/septic shock is still poor in the emergency department, while little data are available for patients admitted to the intensive care unit (ICU). The aim of this study was to evaluate the effect of an in-hospital sepsis program on the adherence to evidence-based guidelines and outcome of patients with severe sepsis/septic shock admitted to the ICU.     

Pharmacokinetics of epinephrine in patients with septic shock: modelization and interaction with endogenous neurohormonal status

Introduction  

In septic patients, an unpredictable response to epinephrine may be due to pharmacodynamic factors or to non-linear pharmacokinetics. The purpose of this study was to investigate the pharmacokinetics of epinephrine and its determinants in patients with septic shock.     

Dopexamine and norepinephrine versus epinephrine on gastric perfusion in patients with septic shock: a randomized study [NCT00134212]

Introduction  

Microcirculatory blood flow, and notably gut perfusion, is important in the development of multiple organ failure in septic shock. We compared the effects of dopexamine and norepinephrine (noradrenaline) with those of epinephrine (adrenaline) on gastric mucosal blood flow (GMBF) in patients with septic shock. The effects of these drugs on oxidative stress were also assessed.     

Masseter muscle oxygen saturation is associated with central venous oxygen saturation in patients with severe sepsis

Objective  

This monocentric prospective study was conducted to determine if tissue oxygen saturation measured non invasively over masseter muscle site (Masseter-StO2) can predict the central venous oxygen saturation (ScvO2) level in severe sepsis and septic shock.     

Activated protein C in septic shock: a propensity-matched analysis

Introduction  

The use of human recombinant activated protein C (rhAPC) for the treatment of severe sepsis remains controversial despite multiple reported trials. The efficacy of rhAPC remains a matter of dispute. We hypothesized that patients with septic shock who were treated with rhAPC had an improved in-hospital mortality compared to patients with septic shock with similar acuity who did not receive rhAPC.     

Rescue treatment with terlipressin in children with refractory septic shock: a clinical study

Introduction  

Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock.     

Clinical Factors and Outcomes of Dialysis-Dependent End-Stage Renal Disease Patients with Emergency Department Septic Shock

Background

Infection is the second leading cause of death in end-stage renal disease (ESRD) patients. Prior investigations of acute septic shock in this specific population are limited.

Beneficial effects of the heme oxygenase-1/carbon monoxide system in patients with severe sepsis/septic shock

Purpose

We evaluated the relations among the arterial carbon monoxide (CO) concentration, heme oxygenase (HO)-1 expression by monocytes, oxidative stress, plasma levels of cytokines and bilirubin, and the outcome of patients with severe sepsis or septic shock.

Methods

Thirty-six patients who fulfilled the criteria for severe sepsis or septic shock and 21 other patients without sepsis during their stay in the intensive care unit were studied. HO-1 protein expression by monocytes, arterial CO, oxidative stress, bilirubin, and cytokines were measured.

Results

Arterial blood CO, cytokine, and bilirubin levels, and monocyte HO-1 protein expression were higher in patients with severe sepsis/septic shock than in non-septic patients. Increased HO-1 expression was related to the arterial CO concentration and oxidative stress. There was a positive correlation between survival and increased HO-1 protein expression or a higher CO level.

Conclusions

Arterial CO and monocyte HO-1 protein expression were increased in critically ill patients, particularly those with severe sepsis or septic shock, suggesting that oxidative stress is closely related to HO-1 expression. The HO-1/CO system may play an important role in sepsis.     

Activation of factor VII-activating protease in human inflammation: a sensor for cell death

Introduction

Cell death is a central event in the pathogenesis of sepsis and is reflected by circulating nucleosomes. Circulating nucleosomes were suggested to play an important role in inflammation and were demonstrated to correlate with severity and outcome in sepsis patients. We recently showed that plasma can release nucleosomes from late apoptotic cells. Factor VII-activating protease (FSAP) was identified to be the plasma serine protease responsible for nucleosome release. The aim of this study was to investigate FSAP activation in patients suffering from various inflammatory diseases of increasing severity.

Methods

We developed ELISAs to measure FSAP-C1-inhibitor and FSAP-α₂-antiplasmin complexes in plasma. FSAP-inhibitor complexes were measured in the plasma of 20 adult patients undergoing transhiatal esophagectomy, 32 adult patients suffering from severe sepsis and 8 from septic shock and 38 children suffering from meningococcal sepsis.

Results

We demonstrate plasma FSAP to be activated upon contact with apoptotic and necrotic cells by an assay detecting complexes between FSAP and its target serpins α₂-antiplasmin and C1-inhibitor, respectively. By means of that assay we demonstrate FSAP activation in post-surgery patients, patients suffering from severe sepsis, septic shock and meningococcal sepsis. Levels of FSAP-inhibitor complexes correlate with nucleosome levels and correlate with severity and mortality in these patients.

Conclusions

These results suggest FSAP activation to be a sensor for cell death in the circulation and that FSAP activation in sepsis might be involved in nucleosome release, thereby contributing to lethality.     

Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients

Introduction  

Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients.     

Recommended β-lactam regimens are inadequate in septic patients treated with continuous renal replacement therapy

Introduction  

Sepsis is responsible for important alterations in the pharmacokinetics of antibiotics. Continuous renal replacement therapy (CRRT), which is commonly used in septic patients, may further contribute to pharmacokinetic changes. Current recommendations for antibiotic doses during CRRT combine data obtained from heterogeneous patient populations in which different CRRT devices and techniques have been used. We studied whether these recommendations met optimal pharmacokinetic criteria for broad-spectrum antibiotic levels in septic shock patients undergoing CRRT.