The impact of hydroxyethyl starches in cardiac surgery: a meta-analysis

Introduction

Recent studies in septic patients showed that adverse effects of hydroxyethyl starches (HESs) possibly outweigh their benefits in severely impaired physiological haemostasis. It remains unclear whether this also applies to patient populations that are less vulnerable. In this meta-analysis, we evaluated the impact of various HES generations on safety and efficacy endpoints in patients undergoing cardiac surgery.

Methods

We searched the PubMed, Embase and Cochrane Central Register of Controlled Trials databases for randomised controlled trials (RCTs) in the English or German language comparing the use of HES to any other colloid or crystalloid during open heart surgery.

Results

Blood loss and transfusion requirements were higher for older starches with mean molecular weights more than 200 kDa compared to other volume substitutes. In contrast, this effect was not observed with latest-generation tetrastarches (130/0.4), which performed even better when compared to albumin (blood loss of tetrastarch versus albumin: standardised mean difference (SMD), −0.34; 95% CI, −0.63, −0.05; P = 0.02; versus gelatin: SMD, −0.06; 95% CI, −0.20, 0.08; P = 0.39; versus crystalloids: SMD, −0.05; 95% CI, −0.20, 0.10; P = 0.54). Similar results were found for transfusion needs. Lengths of stay in the intensive care unit or hospital were significantly shorter with tetrastarches compared to gelatin (intensive care unit: SMD, −0.10; 95% CI, −0.15, −0.05; P = 0.0002) and crystalloids (hospital: SMD, −0.52; 95% CI, −0.90, −0.14; P = 0.007).

Conclusions

In this meta-analysis of RCTs, we could not identify safety issues with tetrastarches compared with other colloid or crystalloid solutions in terms of blood loss, transfusion requirements or hospital length of stay in patients undergoing cardiac surgery. The safety data on coagulation with older starches raise some issues that need to be addressed in future trials.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0656-0) contains supplementary material, which is available to authorized users.     

Efficacy of ultrasound-guided radial artery catheterization: a systematic review and meta-analysis of randomized controlled trials

Introduction

Ultrasound guidance has emerged as an adjunct for central vein catheterization in both adults and children. However, the use of ultrasound guidance for radial arterial catheterization has not been well established. We conducted a systematic review and meta-analysis to evaluate the efficacy of ultrasound guidance for radial artery catheterization.

Methods

PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched. Randomized controlled trials (RCTs) comparing ultrasound guidance with other techniques (palpation or Doppler) in adult or pediatric patients requiring radial artery catheterization were included. The primary outcome was first-attempt success.

Results

Seven RCTs enrolling 546 patients met the inclusion criteria, and all the selected trials were considered as at high risk of bias. Ultrasound-guided radial artery catheterization was associated with an increased first-attempt success (relative risk (RR) 1.55, 95% confidence interval (CI) 1.02 to 2.35). There was significant heterogeneity among the studies (I² = 74%). Ultrasound-guided radial artery catheterization in small children and infants also provided an increased chance for first-attempt success (RR 1.94, 95% CI 1.31 to 2.88). Ultrasound guidance further significantly reduced mean attempts to success (weighted mean difference (WMD) −1.13, 95% CI −1.58 to −0.69), mean time to success (WMD −72.97 seconds, 95% CI −134.41 to −11.52), and incidence of the complication of hematoma (RR 0.17, 95% CI 0.07 to 0.41).

Conclusions

Ultrasound guidance is an effective and safe technique for radial artery catheterization, even in small children and infants. However, the results should be interpreted cautiously due to the heterogeneity among the studies.     

Sodium bicarbonate in the prevention of cardiac surgery-associated acute kidney injury: a systematic review and meta-analysis

Introduction

Sodium bicarbonate (SBIC) was reported to be a promising approach to prevent cardiac surgery-associated acute kidney injury (CSA-AKI). However, the results remain controversial. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SBIC on the prevention of CSA-AKI in adult patients undergoing cardiac surgery.

Methods

PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) assessing the effect of SBIC versus placebo on the prevention of CSA-AKI in adult patients undergoing cardiac surgery were included. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. The primary outcome was the incidence of CSA-AKI. Meta-analysis was performed using random-effects models.

Results

Five RCTs involving 1079 patients were included in the meta-analysis. Overall, compared with placebo, SBIC was not associated with a reduced risk of CSA-AKI (relative risk [RR] 0.99; 95% confidence interval [CI] 0.78 to 1.24; P = 0.911). SBIC failed to alter the clinical outcomes of hospital length of stay (weighted mean difference [WMD] 0.23 days; 95%CI −0.88 to 1.33 days; P = 0.688), renal replacement therapy (RR 0.94; 95%CI 0.49 to 1.82; P = 0.861), hospital mortality (RR 1.37; 95%CI 0.46 to 4.13; P = 0.572), postoperative atrial fibrillation (RR 1.02; 95%CI 0.65 to 1.61; P = 0.915). However, SBIC was associated with significant increased risks in longer duration of ventilation (WMD 0.64 hours; 95%CI 0.16 to 1.11 hours; P = 0.008), longer ICU length of stay (WMD 2.06 days; 95%CI 0.54 to 3.58 days; P = 0.008), and increased incidence of alkalemia (RR 2.21; 95%CI 1.42 to 3.42; P <0.001).

Conclusions

SBIC could not reduce the incidence of CSA-AKI. Contrarily, SBIC prolongs the duration of ventilation and ICU length of stay, and increases the risk of alkalemia. Thus, SBIC should not be recommended for the prevention of CSA-AKI and perioperative SBIC infusion should be administrated with caution.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0517-x) contains supplementary material, which is available to authorized users.     

Albumin versus crystalloid solutions in patients with the acute respiratory distress syndrome: a systematic review and meta-analysis

Introduction

In patients with acute respiratory distress syndrome (ARDS) fluid therapy might be necessary. The aim of this systematic review and meta-analysis is to determine the effects of colloid therapy compared to crystalloids on mortality and oxygenation in adults with ARDS.

Methods

Randomized controlled trials (RCTs) were identified through a systematic literature search of MEDLINE, EMBASE, CENTRAL and LILACS. Articles published up to 15^th February 2013 were independently screened, abstracted, and assessed (Cochrane Risk of Bias Tool) to provide evidence-based therapy recommendations. RCTs were eligible if they compared colloid versus crystalloid therapy on lung function, inflammation, damage or mortality in adults with ARDS. Primary outcome parameters were respiratory mechanics, gas exchange lung inflammation and damage as well as hospital mortality. Kidney function, need for renal replacement therapy, hemodynamic stabilization and intensive care unit (ICU) length of stay served as secondary outcomes.

Results

A total of 3 RCTs out of 4130 potential trials found in the databases were selected for qualitative and quantitative analysis totaling 206 patients who received either albumin or saline. Overall risk of bias was unclear to high in the identified trials. Calculated pooled risk of death was not statistically significant (albumin 34 of 100 (34.0%) versus 40 of 104 (38.5%), relative risk (RR) = 0.89, 95% confidence interval (CI) 0.62 to 1.28, P = 0.539). Weighted mean difference (WMD) in PaO₂/FiO₂ (mmHg) improved in the first 48 hours (WMD = 62, 95% CI 47 to 77, P <0.001, I² = 0%) after therapy start and remained stable after 7 days (WMD = 20, 95% CI 4 to 36, P = 0.017, I² = 0%).

Conclusions

There is a high need for RCTs investigating the effects of colloids in ARDS patients. Based on the findings of this review, colloid therapy with albumin improved oxygenation but did not affect mortality.     

Parenteral glutamine supplementation in critical illness: a systematic review

Introduction

The potential benefit of parenteral glutamine (GLN) supplementation has been one of the most commonly studied nutritional interventions in the critical care setting. The aim of this systematic review was to incorporate recent trials of traditional parenteral GLN supplementation in critical illness with previously existing data.

Methods

All randomized controlled trials of parenterally administered GLN in critically ill patients conducted from 1997 to 2013 were identified. Studies of enteral GLN only or combined enteral/parenteral GLN were excluded. Methodological quality of studies was scored and data was abstracted by independent reviewers.

Results

A total of 26 studies involving 2,484 patients examining only parenteral GLN supplementation of nutrition support were identified in ICU patients. Parenteral GLN supplementation was associated with a trend towards a reduction of overall mortality (relative risk (RR) 0.88, 95% confidence interval (CI) 0.75, 1.03, P = 0.10) and a significant reduction in hospital mortality (RR 0.68, 95% CI 0.51, 0.90, P = 0.008). In addition, parenteral GLN was associated with a strong trend towards a reduction in infectious complications (RR 0.86, 95% CI 0.73, 1.02, P = 0.09) and ICU length of stay (LOS) (WMD –1.91, (95% CI -4.10, 0.28, P = 0.09) and significant reduction in hospital LOS (WMD -2.56, 95% CI -4.71, -0.42, P = 0.02). In the subset of studies examining patients receiving parenteral nutrition (PN), parenteral GLN supplementation was associated with a trend towards reduced overall mortality (RR 0.84, 95% CI 0.71, 1.01, P = 0.07).

Conclusions

Parenteral GLN supplementation given in conjunction with nutrition support continues to be associated with a significant reduction in hospital mortality and hospital LOS. Parenteral GLN supplementation as a component of nutrition support should continue to be considered to improve outcomes in critically ill patients.     

Percutaneous and surgical tracheostomy in critically ill adult patients: a meta-analysis

Introduction

The aim of this study was to conduct a meta-analysis to determine whether percutaneous tracheostomy (PT) techniques are advantageous over surgical tracheostomy (ST), and if one PT technique is superior to the others.

Methods

Computerized databases (1966 to 2013) were searched for randomized controlled trials (RCTs) reporting complications as predefined endpoints and comparing PT and ST and among the different PT techniques in mechanically ventilated adult critically ill patients. Odds ratios (OR) and mean differences (MD) with 95% confidence interval (CI), and I² values were estimated.

Results

Fourteen RCTs tested PT techniques versus ST in 973 patients. PT techniques were performed faster (MD, −13.06 minutes (95% CI, −19.37 to −6.76 (P <0.0001)); I² = 97% (P <0.00001)) and reduced odds for stoma inflammation (OR, 0.38 (95% CI, 0.19 to 0.76 (P = 0.006)); I² = 2% (P = 0.36)), and infection (OR, 0.22 (95% CI, 0.11 to 0.41 (P <0.00001)); I² = 0% (P = 0.54)), but increased odds for procedural technical difficulties (OR, 4.58 (95% CI, 2.21 to 9.47 (P <0.0001)); I² = 0% (P = 0.63)). PT techniques reduced odds for postprocedural major bleeding (OR, 0.39 (95% CI, 0.15 to 0.97 (P = 0.04)); I² = 0% (P = 0.69)), but not when a single RCT using translaryngeal tracheostomy was excluded (OR, 0.58 (95% CI, 0.21 to 1.63 (P = 0.30)); I² = 0% (P = 0.89)). Eight RCTs compared different PT techniques in 700 patients. Multiple (MDT) and single step (SSDT) dilatator techniques are associated with the lowest odds for difficult dilatation or cannula insertion (OR, 0.30 (95% CI, 0.12 to 0.80 (P = 0.02)); I² = 56% (P = 0.03)) and major intraprocedural bleeding (OR, 0.29 (95% CI, 0.10 to 0.85 (P = 0.02)); I² = 0% (P = 0.72)), compared to the guide wire dilatation forceps technique.

Conclusion

In critically ill adult patients, PT techniques can be performed faster and reduce stoma inflammation and infection but are associated with increased technical difficulties when compared to ST. Among PT techniques, MDT and SSDT were associated with the lowest intraprocedural risks and seem to be preferable.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0544-7) contains supplementary material, which is available to authorized users.     

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Introduction

Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP.

Methods

Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration.

Results

A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥10 cmH₂O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04).

Conclusions

PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.     

The effect of glutamine therapy on outcomes in critically ill patients: a meta-analysis of randomized controlled trials

Introduction

Glutamine supplementation is supposed to reduce mortality and nosocomial infections in critically ill patients. However, the recently published reducing deaths due to oxidative stress (REDOX) trials did not provide evidence supporting this. This study investigated the impact of glutamine-supplemented nutrition on the outcomes of critically ill patients using a meta-analysis.

Methods

We searched for and gathered data from the Cochrane Central Register of Controlled Trials, MEDLINE, Elsevier, Web of Science and ClinicalTrials.gov databases reporting the effects of glutamine supplementation on outcomes in critically ill patients. We produced subgroup analyses of the trials according to specific patient populations, modes of nutrition and glutamine dosages.

Results

Among 823 related articles, eighteen Randomized Controlled Trials (RCTs) met all inclusion criteria. Mortality events among 3,383 patients were reported in 17 RCTs. Mortality showed no significant difference between glutamine group and control group. In the high dosage subgroup (above 0.5 g/kg/d), the mortality rate in the glutamine group was significantly higher than that of the control group (relative risk (RR) 1.18; 95% confidence interval (CI), 1.02 to 1.38; P = 0.03). In 15 trials, which included a total of 2,862 patients, glutamine supplementation reportedly affected the incidence of nosocomial infections in the critically ill patients observed. The incidence of nosocomial infections in the glutamine group was significantly lower than that of the control group (RR 0.85; 95% CI, 0.74 to 0.97; P = 0.02). In the surgical ICU subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.70; 95% CI, 0.52 to 0.94; P = 0.04). In the parental nutrition subgroup, glutamine supplementation statistically reduced the rate of nosocomial infections (RR 0.83; 95% CI, 0.70 to 0.98; P = 0.03). The length of hospital stay was reported in 14 trials, in which a total of 2,777 patients were enrolled; however, the patient length of stay was not affected by glutamine supplementation.

Conclusions

Glutamine supplementation conferred no overall mortality and length of hospital stay benefit in critically ill patients. However, this therapy reduced nosocomial infections among critically ill patients, which differed according to patient populations, modes of nutrition and glutamine dosages.     

Vitamin D deficiency as a risk factor for infection,sepsis and mortality in the critically ill: systematic review and meta-analysis

Introduction

In Europe, vitamin D deficiency is highly prevalent varying between 40% and 60% in the healthy general adult population. The consequences of vitamin D deficiency for sepsis and outcome in critically ill patients remain controversial. We therefore systematically reviewed observational cohort studies on vitamin D deficiency in the intensive care unit.

Methods

Fourteen observational reports published from January 2000 to March 2014, retrieved from Pubmed and Embase, involving 9,715 critically ill patients and serum 25-hydroxyvitamin D₃ (25 (OH)-D) concentrations, were meta-analysed.

Results

Levels of 25 (OH)-D less than 50 nmol/L were associated with increased rates of infection (risk ratio (RR) 1.49, 95% (confidence interval (CI) 1.12 to 1.99), P = 0.007), sepsis (RR 1.46, 95% (CI 1.27 to 1.68), P <0.001), 30-day mortality (RR 1.42, 95% (CI 1.00 to 2.02), P = 0.05), and in-hospital mortality (RR 1.79, 95% (CI 1.49 to 2.16), P <0.001). In a subgroup analysis of adjusted data including vitamin D deficiency as a risk factor for 30-day mortality the pooled RR was 1.76 (95% CI 1.37 to 2.26, P <0.001).

Conclusions

This meta-analysis suggests that vitamin D deficiency increases susceptibility for severe infections and mortality of the critically ill.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0660-4) contains supplementary material, which is available to authorized users.     

Exploring the heterogeneity of effects of corticosteroids on acute respiratory distress syndrome: a systematic review and meta-analysis

Introduction

The effectiveness of corticosteroid therapy on the mortality of acute respiratory distress syndrome (ARDS) remains under debate. We aimed to explore the grounds for the inconsistent results in previous studies and update the evidence.

Methods

We searched MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science up to December 2013. Eligible studies included randomized clinical trials (RCTs) and cohort studies that reported mortality and that had corticosteroid nonusers for comparison. The effect of corticosteroids on ARDS mortality was assessed by relative risk (RR) and risk difference (RD) for ICU, hospital, and 60-day mortality using a random-effects model.

Results

Eight RCTs and 10 cohort studies were included for analysis. In RCTs, corticosteroids had a possible but statistically insignificant effect on ICU mortality (RD, −0.28; 95% confidence interval (CI), −0.53 to −0.03 and RR, 0.55; 95% CI, 0.24 to 1.25) but no effect on 60-day mortality (RD, −0.01; 95% CI, −0.12 to 0.10 and RR, 0.97; 95% CI, 0.75 to 1.26). In cohort studies, corticosteroids had no effect on ICU mortality (RR, 1.05; 95% CI, 0.74 to 1.49) but non-significantly increased 60-day mortality (RR, 1.30; 95% CI, 0.96 to 1.78). In the subgroup analysis by ARDS etiology, corticosteroids significantly increased mortality in influenza-related ARDS (three cohort studies, RR, 2.45, 95% CI, 1.40 to 4.27).

Conclusions

The effects of corticosteroids on the mortality of ARDS differed by duration of outcome measures and etiologies. Corticosteroids did not improve longer-term outcomes and may cause harm in certain subgroups. Current data do not support routine use of corticosteroids in ARDS. More clinical trials are needed to specify the favorable and unfavorable subgroups for corticosteroid therapy.     

Efficacy and adverse events of high-frequency oscillatory ventilation in adult patients with acute respiratory distress syndrome: a meta-analysis

Introduction

Theoretically, high-frequency oscillatory ventilation (HFOV) achieves all goals of a lung-protective ventilatory mode and seems ideal for the treatment of adult patients with acute respiratory distress syndrome (ARDS). However, its effects on mortality and adverse clinical outcomes remain uncertain given the paucity of high-quality studies in this area. This meta-analysis was performed to evaluate the efficacy and adverse events of HFOV in adults with ARDS.

Methods

We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials through February 2014 to retrieve randomized controlled trials of HFOV in adult ARDS patients. Two independent reviewers extracted data on study methods, clinical and physiological outcomes and adverse events. The primary outcome was 30-day or hospital mortality. Risk of bias was evaluated with the Cochrane Collaboration’s tool. Mortality, oxygenation and adverse effects of HFOV were compared to those of conventional mechanical ventilation. A random-effects model was applied for meta-analysis.

Results

A total of five trials randomly assigning 1,580 patients met inclusion criteria. Pooled data showed that HFOV significantly improved oxygenation on day one of therapy (four studies; 24% higher; 95% confidence interval (CI) 11 to 40%; P <0.01). However, HFOV did not reduce mortality risk (five studies; risk ratio (RR) 1.04; 95% CI 0.83 to 1.31; P = 0.71) and two early terminated studies suggested a harmful effect of HFOV in ARDS (two studies; RR 1.33; 95% CI 1.09 to 1.62; P <0.01). Safety profiles showed that HFOV was associated with a trend toward increased risk of barotrauma (five studies; RR 1.19; 95% CI 0.83 to 1.72; P = 0.34) and unfavorable hemodynamics (five studies; RR 1.16; 95% CI 0.97 to 1.39; P = 0.12).

Conclusions

HFOV improved oxygenation in adult patients with ARDS; however, it did not confer a survival benefit and might cause harm in the era of lung-protective ventilation strategy. The evidence suggests that HFOV should not be a routine practice in ARDS and further studies specifically selecting patients for this ventilator mode should be pursued.     

The effect of goal-directed therapy on mortality in patients with sepsis - earlier is better: a meta-analysis of randomized controlled trials

Introduction

The Surviving Sepsis Campaign guidelines recommend goal-directed therapy (GDT) for the early resuscitation of patients with sepsis. However, the findings of the ProCESS (Protocolized Care for Early Septic Shock) trial showed no benefit from GDT for reducing mortality rates in early septic shock. We performed a meta-analysis to integrate these findings with existing literature on this topic and evaluate the effect of GDT on mortality due to sepsis.

Methods

We searched the PubMed, Embase and CENTRAL (Cochrane Central Register of Controlled Trials) databases and reference lists of extracted articles. Randomized controlled trials comparing GDT with standard therapy or usual care in patients with sepsis were included. The prespecified primary outcome was overall mortality.

Results

In total, 13 trials involving 2,525 adult patients were included. GDT significantly reduced overall mortality in the random-effects model (relative risk (RR), 0.83; 95% confidence interval (CI), 0.71 to 0.96; P =0.01; I² = 56%). Predefined subgroup analysis according to the timing of GDT for resuscitation suggested that a mortality benefit was seen only in the subgroup of early GDT within the first 6 hours (seven trials; RR, 0.77; 95% CI, 0.67 to 0.89; P =0.0004; I² = 40%), but not in the subgroup with late or unclear timing of GDT (six trials; RR, 0.92; 95% CI, 0.69 to 1.24; P =0.59; I² = 56%). GDT was significantly associated with the use of dobutamine (five trials; RR, 2.71; 95% CI, 1.20 to 6.10; P =0.02).

Conclusions

The results of the present meta-analysis suggest that GDT significantly reduces overall mortality in patients with sepsis, especially when initiated early. However, owing to the variable quality of the studies, strong and definitive recommendations cannot be made.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0570-5) contains supplementary material, which is available to authorized users.     

Use of probiotics in the treatment of severe acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials

Introduction

Necrotic tissue infection can worsen the prognosis of severe acute pancreatitis (SAP), and probiotics have been shown to be beneficial in reducing the infection rate in animal experiments and primary clinical trials. However, the results of multicenter randomized clinical trials have been contradictory. Our aim in this study was to systematically review and quantitatively analyze all randomized controlled trials with regard to important outcomes in patients with predicted SAP who received probiotics.

Methods

A systematic literature search of the PubMed, Embase and Cochrane Library databases was conducted using specific search terms. Eligible studies were randomized controlled trials that compared the effects of probiotic with placebo treatment in patients with predicted SAP. Mean difference (MD), risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel fixed- and random-effects models. A meta-analysis on the use of probiotics in the treatment of critically ill patients was also performed to serve as a reference.

Results

In this study, 6 trials comprising an aggregate total of 536 patients were analyzed. Significant heterogeneities were observed in the type, dose, treatment duration and clinical effects of probiotics in these trials. Systematic analysis showed that probiotics did not significantly affect the pancreatic infection rate (RR = 1.19, 95% CI = 0.74 to 1.93; P = 0.47), total infections (RR = 1.09, 95% CI = 0.80 to 1.48; P = 0.57), operation rate (RR = 1.42, 95% CI = 0.43 to 3.47; P = 0.71), length of hospital stay (MD = 2.45, 95% CI = −2.71 to 7.60; P = 0.35) or mortality (RR = 0.72, 95% CI = 0.42 to 1.45; P = 0.25).

Conclusions

Probiotics showed neither beneficial nor adverse effects on the clinical outcomes of patients with predicted SAP. However, significant heterogeneity was noted between the trials reviewed with regard to the type, dose and treatment duration of probiotics, which may have contributed to the heterogeneity of the clinical outcomes. The current data are not sufficient to draw a conclusion regarding the effects of probiotics on patients with predicted SAP. Carefully designed clinical trials are needed to validate the effects of particular probiotics given at specific dosages and for specific treatment durations.     

Early fluid resuscitation with hydroxyethyl starch 130/0.4 (6%) in severe burn injury: a randomized,controlled, double-blind clinical trial

Introduction

There are limited data on the efficacy of early fluid resuscitation with third-generation hydroxyethyl starch (HES 130) in burn injury. Adverse effects of HES on survival and organ function have been reported.

Methods

In this randomized, controlled, double-blind trial, 48 patients with severe burn injury were assigned to receive either lactated Ringer’s solution plus 6% HES 130/0.4 in a ratio of 2:1 or lactated Ringer’s solution with no colloid supplement for the first 72 hours. Primary outcome parameter was the group difference of administered total fluid from intensive care unit (ICU) admission up to day 3. Secondary outcomes included kidney and lung injury and failure, length of stay, and mortality.

Results

Three-day totals of administered resuscitation fluid (medians) were 21,190 mL in the lactated Ringer’s group and 19,535 mL in the HES group (HES: −1,213 mL; P = 0.39). Creatinine levels from day 1 to 3 (HES: +0.4 μmol/L; 95% confidence interval (CI) −18.7 to 19.5; P = 0.97) and urinary outputs from day 1 to 3 (HES: −58 mL; 95% CI −400 to 283; P = 0.90) were not different. Six patients in each group developed acute respiratory distress syndrome (ARDS) (risk ratio 0.96; 95% CI 0.35 to 2.64; P = 0.95). Length of ICU stay (HES vs. lactated Ringer’s: 28 vs. 24 days; P = 0.80) and length of hospital stay (31 vs. 29 days; P = 0.57) were similar. Twenty-eight-day mortality was 4 patients in each group (risk ratio 0.96; 95% CI 0.27 to 4.45; P = 0.95), and in-hospital mortality was 8 in the HES group vs. 5 patients in the lactated Ringer’s group (hazard ratio 1.86; 95% CI 0.56 to 6.19; P = 0.31).

Conclusions

There was no evidence that early fluid resuscitation with balanced HES 130/0.4 (6%) in addition to lactated Ringer’s solution would lead to a volume-sparing effect in severe burn injury. Together with the findings that early renal function, incidence of ARDS, length of stay, and mortality were not negatively influenced by HES in this setting, balanced HES 130/0.4 (6%) plus lactated Ringer’s solution could not be considered superior to lactated Ringer’s solution alone.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01012648","term_id":"NCT01012648"}}NCT01012648     

Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study

Introduction

The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response.

Methods

The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC_0–24/MIC ratio) >400 (assuming MIC ≤1 mg/L).

Results

Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC_0–24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC_0–24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a C_min ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5).

Conclusions

This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure.     

Proton pump inhibitors increase the risk for hospital-acquired Clostridium difficile infection in critically ill patients

Introduction

Proton pump inhibitors (PPI) have been linked to Clostridium difficile infection (CDI) but there are few data specific to ICU patients. We evaluated duration of PPI exposure as a potential risk factor for hospital-acquired CDI in the ICU.

Methods

This retrospective, case-control study was conducted using the Multiparameter Intelligent Monitoring in Intensive Care II database, a large publically available database of more than 35,000 ICU patients. Adult patients with CDI were identified using the ICD-9 code for Clostridium difficile listed as a secondary diagnosis. To be included, patients had to be present in an ICU for ≥48 hours prior to Clostridium difficile acquisition. These patients were then matched to patients without CDI using the ICD-9 primary diagnosis, age (+/−5 years) and SOFA score (+/−1). Successfully matched patients were reviewed for PPI exposure and other potential confounding variables for CDI. PPI exposure was characterized as short (<2 days) or long (≥2 days). Multivariate modeling was performed to identify independent risk factors for CDI.

Results

There were 408 patients evaluated and 81% received a PPI. The percentage of patients who had a long exposure to PPIs was 83% in the CDI group compared to 73% with controls (P = 0.012). Upon inclusion of the following variables into a multivariate analysis (long PPI exposure, histamine-2-receptor antagonist administration, antibiotic administration, immunosuppression and study duration), long PPI exposure (odds ratio (OR) (95% confidence interval (CI) = 2.03 (1.23 to 3.36), P = 0.006) and antibiotic use (OR (95% CI) = 2.52 (1.23 to 5.18), P = 0.012) were identified as independent predictors of CDI.

Conclusions

Proton pump inhibitors are independent risk factors for the development of CDI in ICU patients. This risk is particularly exposed after two or more days of therapy.     

Continuous venovenous hemofiltration versus extended daily hemofiltration in patients with septic acute kidney injury: a retrospective cohort study

Introduction

Whether continuous venovenous hemofiltration (CVVHF) is superior to extended daily hemofiltration (EDHF) for the treatment of septic AKI is unknown. We compared the effect of CVVHF (greater than 72 hours) with EDHF (8 to 12 hours daily) on renal recovery and mortality in patients with severe sepsis or septic shock and concurrent acute kidney injury (AKI).

Methods

A retrospective analysis of 145 septic AKI patients who underwent renal replacement therapy (RRT) between July 2009 and May 2013 was performed. These patients were treated by CVVHF or EDHF with the same polyacrylonitrile membrane and bicarbonate-based buffer. The primary outcomes measured were occurrence of renal recovery and all-cause mortality by 60 days.

Results

Sixty-five and eighty patients were treated with CVVHF and EDHF, respectively. Patients in the CVVHF group had significantly higher recovery of renal function (50.77% of CVVHF group versus 32.50% in the EDHF group, P = 0.026). Median time to renal recovery was 17.26 days for CVVHF patients and 25.46 days for EDHF patients (P = 0.039). Sixty-day all-cause mortality was similar between CVVHF and EDHF groups (44.62%, and 46.25%, respectively; P = 0.844). 55.38% of patients on CVVHF and 28.75% on EDHF developed hypophosphatemia (P = 0.001). The other adverse events related to RRT did not differ between groups. On multivariate analysis, including physiologically clinical relevant variables, CVVHF therapy was significantly associated with recovery of renal function (HR 3.74; 95% CI 1.82 to 7.68; P < 0.001), but not with mortality (HR 0.69; 95% CI 0.34 to 1.41; P = 0.312).

Conclusions

Patients undergoing CVVHF therapy had significantly improved renal recovery independent of clinically relevant variables. The patients with septic AKI had similar 60-day all-cause mortality rates, regardless of type of RRT.     

Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis

Introduction

The aim of this study was to conduct a systematic review and meta-analysis for determining the effects of prehospital adrenaline administration on return of spontaneous circulation, hospital admission, survival to discharge and discharge with cerebral performance category 1 or 2 in out-of-hospital cardiac arrest patients.

Methods

MEDLINE and Scopus databases were searched to identify studies reported to March 2014. Study selection and data extraction were independently completed by two reviewers (PA and SR). The baseline characteristics of each study and number of events were extracted. Risk ratios (RR) and 95% confidence interval (CI) were estimated. Heterogeneity and publication bias were also explored.

Results

In total 15 studies were eligible and included in the study. Of 13 adult observational studies, four to eight studies were pooled for each outcome. These yielded a total sample size that ranged from 2,381 to 421,459. A random effects model suggested that patients receiving prehospital adrenaline were 2.89 times (95% CI: 2.36, 3.54) more likely to achieve prehospital return of spontaneous circulation than those not administered adrenaline. However, there were no significant effects on overall return of spontaneous circulation (RR = 0.93, 95% CI: 0.5, 1.74), admission (RR = 1.05, 95% CI: 0.80, 1.38) and survival to discharge (RR = 0.69, 95% CI: 0.48, 1.00).

Conclusions

Prehospital adrenaline administration may increase prehospital return of spontaneous circulation, but it does not improve overall rates of return of spontaneous circulation, hospital admission and survival to discharge.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0463-7) contains supplementary material, which is available to authorized users.     

Single bolus versus split dose gadolinium administration in extra-cellular volume calculation at 3 Tesla

Background

Diffuse myocardial fibrosis may be quantified with cardiovascular magnetic resonance (CMR) by calculating extra-cellular volume (ECV) from native and post-contrast T1 values. Accurate ECV calculation is dependent upon the contrast agent having reached equilibrium within tissue compartments. Previous studies have used infusion or single bolus injections of contrast to calculate ECV. In clinical practice however, split dose contrast injection is commonly used as part of stress/rest perfusion studies. In this study we sought to assess the effects of split dose versus single bolus contrast administration on ECV calculation.

Methods

Ten healthy volunteers and five patients ( 4 ischaemic heart disease, 1 hypertrophic cardiomyopathy) were studied on a 3.0 Tesla (Philips Achieva TX) MR system and underwent two (patients) or three (volunteers) separate CMR studies over a mean of 12 and 30 days respectively. Volunteers underwent one single bolus contrast study (Gadovist 0.15mmol/kg). In two further studies, contrast was given in two boluses (0.075mmol/kg per bolus) as part of a clinical adenosine stress/rest perfusion protocol, boluses were separated by 12 minutes. Patients underwent one bolus and one stress perfusion study only. T1 maps were acquired pre contrast and 15 minutes following the single bolus or second contrast injection.

Results

ECV agreed between bolus and split dose contrast administration (coefficient of variability 5.04%, bias 0.009, 95% CI −3.754 to 3.772, r² = 0.973, p = 0.001)). Inter-study agreement with split dose administration was good (coefficient of variability, 5.67%, bias −0.018, 95% CI −4.045 to 4.009, r² = 0.766, p > 0.001).

Conclusion

ECV quantification using split dose contrast administration is reproducible and agrees well with previously validated methods in healthy volunteers, as well as abnormal and remote myocardium in patients. This suggests that clinical perfusion CMR studies may incorporate assessment of tissue composition by ECV based on T1 mapping.     

VALIDATION OF TWO CLINICAL MEASURES OF CORE STABILITY

Background

Emerging evidence suggests poor core stability is a risk factor for low back and lower extremity injuries in athletes. Recently the trunk stability test (TST) and unilateral hip bridge endurance test (UHBE) were developed to clinically assess core stability. Although these and other clinical tests of core stability exist, how well they assess core stability when compared to biomechanical measures of isolated core stability has not been thoroughly evaluated.

Purpose/Hypothesis

The purposes of this study were to 1) determine concurrent validity of two novel clinical core stability assessments (TST and UHBE), and 2) assess relationships between these assessments and the trunk endurance and Y-Balance tests. The authors’ hypothesized that the TST and UHBE would be highly correlated to the lab-based biomechanical measure of isolated core stability. Also, the TST and UHBE would be moderately correlated with each other, but not with the trunk extensor endurance and Y-Balance.

Study Design

Cross-Sectional design

Methods

Twenty healthy active individuals completed the TST (recorded number of errors), UHBE (s), trunk extensor endurance (s), Y-Balance (% leg length) test (YBT), and biomechanical test of core stability.

Results

Correlational analyses revealed a small, non-significant association between TST and biomechanical measures (r_s = 0.2 – 0.22), while a moderate, significant relationship existed between UHBE and biomechanical measures (r_s = −0.49 to −0.56, p < 0.05). There was little to no relationship between TST and UHBE (r = −0.07 to – 0.21), or TST and extensor endurance (r = −0.18 to −0.24). A moderate, significant association existed between TST and two reach directions of the YBT (r = −0.41 to −0.43, p < 0.05).

Conclusions

Study data support the utility of UHBE as a clinical measure of core stability. The poor relationship between the TST and biomechanical measures, combined with observation of most control faults occurring in the lower extremity (LE) suggest the TST may not be an appropriate clinical test of core stability.

Levels of Evidence

Level 3