Bench-to-bedside review: Amelioration of acute renal impairment using ethyl pyruvate

Inflammation and oxidative stress cause renal impairment. Renal failure exacerbates the effect of oxidative stress on many organ systems. Antioxidants can prevent or treat renal failure in various experimental models and clinical situations. Pyruvate is an endogenous antioxidant with beneficial effects in animal models of oxidative stress. Because sodium pyruvate rapidly degrades in solution, a simple derivative of pyruvic acid, namely ethyl pyruvate, has been investigated as a therapeutic agent in preclinical studies. Ethyl pyruvate reduces organ system damage in ischaemia/reperfusion injury and haemorrhagic and endotoxic shock, at least in part through its antioxidant action. In addition, ethyl pyruvate appears to have direct beneficial effects on cytokine expression and proinflammatory gene regulation. The effect is long lasting and, importantly, even when it is administered after the onset of inflammation it can ameliorate organ damage and improve survival. Ethyl pyruvate is a widely used as a food additive and was shown to be safe in phase I clinical trials. We suggest ethyl pyruvate warrants further evaluation in the management of acute renal impairment

The pursuit of a high central venous oxygen saturation in sepsis: growing concerns

In this issue of Critical Care, Dutch investigators report that, in a cohort of patients with sepsis/septic shock admitted to three different intensive care units (ICUs), low central venous oxygen saturation (ScvO2) was uncommon at the time of ICU admission, and hospital mortality was <30%. Their findings, taken together with those of recent reports from Australia and New Zealand (ANZ), raise serious concerns about the utility of early goal directed therapy (EGDT) outside the context of the original trial. Despite inclusion of EGDT into the Surviving Sepsis Guidelines, in response to growing uncertainty, ANZ and US investigators will soon begin randomization of patients into two large multicentre trials comparing EGDT to standard therapy. Until such studies are completed, basing international treatment guidelines on a single centre study performed in what may turn out to be a highly atypical environment would seem premature

The impact of advance care planning on end of life care in elderly patients: randomised controlled trial

Objective To investigate the impact of advance care planning on end of life care in elderly patients

Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients

Background: Sedative agents may variably impact the stress response. Dexmedetomidine is a sympatholytic alpha2-adrenergic agonist mainly used as a second-line sedative agent in mechanically ventilated patients. We hypothesised that early sedation with dexmedetomidine as the primary agent would result in a reduced stress response compared to usual sedatives in critically ill ventilated adults. Methods: This was a prospective sub-study nested within a multi-centre randomised controlled trial of early sedation with dexmedetomidine versus usual care. The primary outcome was the mean group differences in plasma levels of stress response biomarkers measured over 5 days following randomisation. Other hormonal, biological and physiological parameters were collected. Subgroup analyses were planned for patients with proven or suspected sepsis. Results: One hundred and three patients were included in the final analysis. Baseline illness severity (APACHE II score), the proportion of patients receiving propofol and the median dose of propofol received were comparable between groups. More of the usual-care patients received midazolam (57.7% vs 33.3%; p = 0.01) and at higher dose (median (95% interquartile range) 0.46 [0.20–0.93] vs 0.14 [0.08–0.38] mg/kg/day; p < 0.01). The geometric mean (95% CI) plasma level of the stress hormones, adrenaline (0.32 [0.26–0.4] vs 0.38 [0.31–0.48]), noradrenaline (4.27 [3.12–5.85] vs 6.2 [4.6–8.5]), adrenocorticotropic hormone (17.1 [15.1–19.5] vs 18.1 [15.9–20.5]) and cortisol (515 [409–648] vs 618 [491–776)] did not differ between dexmedetomidine and usual-care groups, respectively. There were no significant differences in any other assayed biomarkers or physiological parameters Sensitivity analyses showed no effect of age or sepsis. Conclusions: Early sedation with dexmedetomidine as the primary sedative agent in mechanically ventilated critically ill adults resulted in comparable changes in physiological and blood-borne parameters associated with the stress-response as with usual-care sedation

Dynamic lactate indices as predictors of outcome in critically ill patients

INTRODUCTION: Dynamic changes in lactate concentrations in the critically ill may predict patient outcome more accurately than static indices. We aimed to compare the predictive value of dynamic indices of lactatemia in the first 24 hours of intensive care unit (ICU) admission with the value of more commonly used static indices. METHODS: This was a retrospective observational study of a prospectively obtained intensive care database of 5,041 consecutive critically ill patients from four Australian university hospitals. We assessed the relationship between dynamic lactate values collected in the first 24 hours of ICU admission and both ICU and hospital mortality. RESULTS: We obtained 36,673 lactate measurements in 5,041 patients in the first 24 hours of ICU admission. Both the time weighted average lactate (LACTW₂₄) and the change in lactate (LACΔ₂₄) over the first 24 hours were independently predictive of hospital mortality with both relationships appearing to be linear in nature. For every one unit increase in LACTW₂₄ and LACΔ₂₄ the risk of hospital death increased by 37% (OR 1.37, 1.29 to 1.45; P < 0.0001) and by 15% (OR 1.15, 1.10 to 1.20; P < 0.0001) respectively. Such dynamic indices, when combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, improved overall outcome prediction (P < 0.0001) achieving almost 90% accuracy. When all lactate measures in the first 24 hours were considered, the combination of LACTW₂₄ and LACΔ₂₄ significantly outperformed (P < 0.0001) static indices of lactate concentration, such as admission lactate, maximum lactate and minimum lactate. CONCLUSIONS: In the first 24 hours following ICU admission, dynamic indices of hyperlactatemia have significant independent predictive value, improve the performance of illness severity score-based outcome predictions and are superior to simple static indices of lactate concentration