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.     

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.     

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.     

Concomitant arginine-vasopressin and hydrocortisone therapy in severe septic shock: association with mortality

Purpose  

To evaluate the association between concomitant arginine-vasopressin (AVP)/hydrocortisone therapy and mortality in severe septic shock patients.     

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.     

Relationship between alcohol use disorders,cortisol concentrations,and cytokine levels in patients with sepsis

Introduction  

Patients with alcohol use disorders (AUD) are at increased risk of developing sepsis and have higher mortality. AUD are associated with higher cortisol and anti-inflammatory cytokine profile. Higher cortisol increases risk of death in septic patients. The relationship between AUD and cortisol in septic patients is unknown. We aimed to study this relationship and postulated that AUD would be associated with higher cortisol and anti-inflammatory cytokine profile.     

Epinephrine: Is it really the black sheep of vasoactive agents?

Citation

Annane D, Vignon P, Renault A, Bollaert PE, Charpentier C, Martin C, Troche G, Ricard JD, Nitenberg G, Papazian L, Azoulay E, Bellissant E: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: a randomised trial. Lancet 370:676-684 [1].

Background

International guidelines for management of septic shock recommend that dopamine or norepinephrine are preferable to epinephrine. However, no large comparative trial has yet been done.

Methods

Objective

To compare the efficacy and safety of norepinephrine plus dobutamine (whenever needed) with those of epinephrine alone in septic shock.

Design

Prospective, multicenter, randomized, double-blind study.

Setting

19 participating intensive care units in France.

Subjects

330 adult patients with septic shock. Inclusion criteria were the presence for less than 7 days of: evidence of infection; at least 2 of the 4 criteria of systemic inflammatory response syndrome (SIRS); and at least two signs of tissue hypoperfusion or organ dysfunction. Additionally, subjects had to have had to meet the three following criteria for less than 24 hours: systolic blood pressure less than 90 mm Hg or mean BP less than 70 mm Hg; administration of fluid bolus of at least 1000 mL or capillary wedge pressure between 12 and 18 mm Hg; and need for more than 15 μg per kg bodyweight per min of dopamine or any dose of epinephrine or norepinephrine. Specific exclusion criteria were established to ensure other causes of shock were excluded.

Intervention

Participants were assigned to receive epinephrine (n = 161) or norepinephrine plus dobutamine (n = 169), which were titrated to maintain mean blood pressure at 70 mm Hg or more.

Outcomes

The primary outcome was 28-day all-cause mortality. The secondary outcomes were survival distribution from randomization to day 90; mortality rates at day 7, 14, at discharge from intensive care and from hospital, and at day 90; systemic hemodynamics; arterial pH and lactate; SOFA score; time to hemodynamic success and time to vaspressor withdrawal. Analyses were by intention to treat.

Results

There were no patients lost to follow-up; one patient withdrew consent after 3 days. At day 28, there were 64 (40%) deaths in the epinephrine group and 58 (34%) deaths in the norepinephrine plus dobutamine group (p = 0.31; relative risk 0.86, 95% CI 0.65-1.14). There was no significant difference between the two groups in mortality rates at discharge from intensive care (75 [47%] deaths vs. 75 [44%] deaths, p = 0.69), at hospital discharge (84 [52%] vs. 82 [49%], p = 0.51), and by day 90 (84 [52%] vs. 85 [50%], p = 0.73), time to hemodynamic success (log-rank p = 0.67), time to vasopressor withdrawal (log-rank p = 0.09), and time course of SOFA score. Rates of serious adverse events were also similar.

Conclusions

There is no evidence for a difference in efficacy and safety between epinephrine alone and norepinephrine plus dobutamine for the management of septic shock.

Trial Registration

(ClinicalTrials.gov number, NCT00148278).     

Pharmacokinetics of moxifloxacin in patients with severe sepsis or septic shock

Purpose  

To investigate the steady-state pharmacokinetics of moxifloxacin in critically ill patients after intravenous administration of the 400 mg fixed dose.     

Predictive value of procalcitonin decrease in patients with severe sepsis: a prospective observational study

Introduction  

This prospective study investigated the predictive value of procalcitonin (PCT) for survival in 242 adult patients with severe sepsis and septic shock treated in intensive care.     

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.     

C-reactive protein in critically ill cancer patients with sepsis: influence of neutropenia

Introduction  

Several biomarkers have been studied in febrile neutropenia. Our aim was to assess C-reactive protein (CRP) concentration in septic critically ill cancer patients and to compare those with and without neutropenia.     

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.     

Incidence and prognostic impact of new-onset atrial fibrillation in patients with septic shock: a prospective observational study

Introduction  

Since data regarding new-onset atrial fibrillation (AF) in septic shock patients are scarce, the purpose of the present study was to evaluate the incidence and prognostic impact of new-onset AF in this patient group.     

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.     

High central venous oxygen saturation in the latter stages of septic shock is associated with increased mortality

Introduction  

Current guidelines recommend maintaining central venous oxygen saturation (ScvO₂) higher than 70% in patients with severe sepsis and septic shock. As high levels of ScvO₂ may reflect an inadequate use of oxygen, our aim was to evaluate the relation between maximal ScvO₂ levels (ScvO_2max ) and survival among intensive care unit (ICU) patients with septic shock.     

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.     

Cardiac effects of induction agents in the septic rat heart

Introduction  

The current debate about the side effects of induction agents, e.g. possible adrenal suppression through etomidate, emphasizes the relevance of choosing the correct induction agent in septic patients. However, cardiovascular depression is still the most prominent adverse effect of these agents, and might be especially hazardous in septic patients presenting with a biventricular cardiac dysfunction - or so-called septic cardiomyopathy. Therefore, we tested the dose-response direct cardiac effects of clinically available induction agents in an isolated septic rat heart model.     

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.     

Plasma from septic shock patients induces loss of muscle protein

Introduction  

ICU-acquired muscle weakness commonly occurs in patients with septic shock and is associated with poor outcome. Although atrophy is known to be involved, it is unclear whether ligands in plasma from these patients are responsible for initiating degradation of muscle proteins. The aim of the present study was to investigate if plasma from septic shock patients induces skeletal muscle atrophy and to examine the time course of plasma-induced muscle atrophy during ICU stay.     

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.