Sources of Heterogeneity in Trials Reporting Hydroxyethyl Starch 130/0.4 or 0.42 Associated Excess Mortality in Septic Patients： A Systematic Review and Meta-regression

Background： This meta-analysis was to determine the association of the cumulative dose of 130/0.4 or 0.42 （hydroxyethyl starch [HES] 130/0.4＊） or delta daily fluid balance （i.e., daily fluid balance in HES group over or below control group） with the heterogeneity of risk ratio （RR） for mortality in randomized control trials （RCTs）. Methods： Three databases （PubMed, EMBASE, Cochrane） were searched to identify prospective RCTs reporting mortality in adult patients with sepsis to compare HES 130/0.4＊ with crystalloids or albumin. Meta-analysis was performed using random effects. Sensitivity and meta-regression analyses were used to examine the heterogeneity sources of RR for mortality, Results： A total number of 4408 patients from 11 RCTs were included. The pooled RR showed no significant difference for overall mortality in patients with administration of liES130/0.4＂ compared with treatment of control fluids （RR： 1.02, 95% confidence interval： 0.9-1.17; P = 0.73）. Heterogeneity was moderate across recruited trials （l^2 = 34%, P = 0.13）. But, a significant variation was demonstrated in subgroup with crystalloids as control fluids （l^2 = 42%, P 〈 0.1）. Sensitivity analysis revealed that trials with high risk of bias did not significantly impact the pooled estimates for mortality. Meta-regression analysis also did not determine a dose-effect relationship of HES 130/0.4＊ with mortality （P - 0.298）, but suggested daily delta fluid balance being likely associated with mortality in septic patients receiving HES130/130/0.4＊ （P = 0.079）.Conclusions： Inappropriate daily positive fluid balance was likely an important source of heterogeneity in these trials reporting HES 130/0.4＊ associated with excess mortality in septic patients.

Normal saline for intravenous fluid therapy in critically ill patients

The efficacy and safety of normal saline （HS） for fluid therapy in critically ill patients remain controversy. In this review, we summarized the evidence of randomized controlled trials （RCTs） which compared NS with other solutions in critically ill patients. The results showed that when compared with 6% hydrox- yethyl starch （HES）, NS may reduce the onset of acute kidney injury （AKI）. However, there is no significant different in mortality and incidence of AKl when compared with 10% HES, albumin and buffered crystalloid solution. Therefore, it is important to prescribe intravenous fluid for patients according to their individual condition.

Extensive Variability in Vasoactive Agent Therapy： A Nationwide Survey in Chinese Intensive Care Units

Background： Inconsistencies in the use of the vasoactive agent therapy to treat shock are found in previous studies. A descriptive study was proposed to investigate current use of vasoactive agents for patients with shock in Chinese intensive care settings. Methods： A nationwide survey of physicians was conducted from August 17 to December 30, 2012. Physicians were asked to complete a questionnaire which focused on the selection of vasoactive agents, management in the use ofvasopressor/inotropic therapy, monitoring protocols when using these agents, and demographic characteristics. Results： The response rate was 65.1% with physicians returning 586 valid questionnaires. Norepinephrine was the first choice of a vasopressor used to treat septic shock by 70.8% of respondents; 73.4% of respondents favored dopamine for hypovolemic shock： and 68.3% of respondents preferred dopamine for cardiogenic shock. Dobutamine was selected by 84.1%, 64.5%, and 60.6% , of respondents for septic, hypovolemic, and cardiogenic shock, respectively. Vasodilator agents were prescribed by physicians in the management of cardiogenic shock （67.1%） rather than for septic （32.3%） and hypovolemic shock （6.5%）. A significant number of physicians working in teaching hospitals were using vasoactive agents in an appropriate manner when compared to physicians in nonteaching hospitals. Conclusions： Vasoactive agent use for treatment of shock is inconsistent according to self-report by Chinese intensive care physicians： however, the variation in use depends upon the form of shock being treated and the type of hospital： thus, corresponding educational programs about vasoactive agent use for shock management should be considered.

Association between anemia and ICU outcomes

To the Editor:Anemia is a common finding among patients admitted to intensive care units(ICUs),nearly 60%of ICU patients had serum hemoglobin levels<12 g/dL at baseline,30%of whom had serum hemoglobin levels<9 g/dL,over 95%of critically ill patients were anemic within 3 days of ICU admission.[1]Moreover,anemia may be aggravated or newly developed in critically ill patients during their ICU stay.

Early fluid loading for septic patients： Any safety limit needed？

Early adequate fluid loading was the corner stone of hemodynamic optimization for sepsis and septic shock. Meanwhile, recent recommended protocol for fluid resuscitation was increasingly debated on hemodynamic stability vs risk of overloading. In recent publications, it was found that a priority was often given to hemodynamic stability rather than organ function alternation in the early fluid resusci- tation of sepsis. However, no safety limits were used at all in most of these reports. In this article, the rationality and safety of early aggressive fluid loading for septic patients were discussed. It was concluded that early aggressive fluid loading improved hemodynamics transitorily, but was probably traded off with a follow-up organ function impairment, such as worsening oxygenation by reduction of lung aeration, in a part of septic patients at least. Thus, a safeguard is needed against unnecessary excessive fluids in early aggressive fluid loading for set）tic patients.

Incomparable Subsequent Effects between Study and Control Fluids Might Cause Questionable Results in Randomized Controlled Trials

Dr. Wiedermann commented on our systematic review and meta-regression tbr the sources of heterogeneity in trials reporting H ES 130/0.4 or 0.42 associated excess mortality in septic patients that the pooled analysis of mortality, which showed neither benefit nor harm, might be influenced by trials of low-quality. Statistically, we agree with this conclusion if two of the recruited trials judged as the intermediate risk of bias are precluded.