Is high-frequency oscillatory ventilation more effective and safer than conventional protective ventilation in adult acute respiratory distress syndrome patients? A meta-analysis of randomized controlled trials

Introduction

Comprehensively evaluating the efficacy and safety of high-frequency oscillatory ventilation (HFOV) is important to allow clinicians who are using or considering this intervention to make appropriate decisions.

Methods

To find randomized controlled trials (RCTs) comparing HFOV with conventional mechanical ventilation (CMV) as an initial treatment for adult ARDS patients, we searched electronic databases (including PubMed, MedLine, Springer Link, Elsevier Science Direct, ISI web of knowledge, and EMBASE) with the following terms: “acute respiratory distress syndrome”, “acute lung injury”, and “high frequency oscillation ventilation”. Additional sources included reference lists from the identified primary studies and relevant meta-analyses. Two investigators independently screened articles and extracted data. Meta-analysis was conducted using random-effects models.

Results

We included 6 RCTs with a total of 1,608 patients in this meta-analysis. Compared with CMV, HFOV did not significantly reduce the mortality at 30 or 28 days. The pooled relative risk (RR) was 1.051 (95% confidence interval (CI) 0.813 to 1.358). ICU mortality was also not significantly reduced in HFOV group, with a pooled RR of 1.218 (95% CI 0.925 to 1.604). The pooled effect sizes of HFOV for oxygenation failure, ventilation failure and duration of mechanical ventilation were 0.557 (95% CI 0.351 to 0.884), 0.892 (95% CI 0.435 to 1.829) and 0.079 (95% CI −0.045 to 0.203), respectively. The risk of barotrauma and hypotension were similar between the CMV group and HFOV group, with a RR of 1.205 (95% CI 0.834 to 1.742) and a RR of 1.326 (95% CI 0.271 to 6.476), respectively.

Conclusions

Although HFOV seems not to increase the risk of barotrauma or hypotension, and reduces the risk of oxygenation failure, it does not improve survival in adult acute respiratory distress syndrome patients.     

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.     

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.     

Optimal dosing of antibiotics in critically ill patients by using continuous/extended infusions: a systematic review and meta-analysis

Introduction

The aim of this study was to determine whether using pharmacodynamic-based dosing of antimicrobials, such as extended/continuous infusions, in critically ill patients is associated with improved outcomes as compared with traditional dosing methods.

Methods

We searched Medline, HealthStar, EMBASE, Cochrane Clinical Trial Registry, and CINAHL from inception to September 2013 without language restrictions for studies comparing the use of extended/continuous infusions with traditional dosing. Two authors independently selected studies, extracted data on methodology and outcomes, and performed quality assessment. Meta-analyses were performed by using random-effects models.

Results

Of 1,319 citations, 13 randomized controlled trials (RCTs) (n = 782 patients) and 13 cohort studies (n = 2,117 patients) met the inclusion criteria. Compared with traditional non-pharmacodynamic-based dosing, RCTs of continuous/extended infusions significantly reduced clinical failure rates (relative risk (RR) 0.68; 95% confidence interval (CI) 0.49 to 0.94, P = 0.02) and intensive care unit length of stay (mean difference, −1.5; 95% CI, −2.8 to −0.2 days, P = 0.02), but not mortality (RR, 0.87; 95% CI, 0.64 to 1.19; P = 0.38). No significant between-trial heterogeneity was found for these analyses (I² = 0). Reduced mortality rates almost achieved statistical significance when the results of all included studies (RCTs and cohort studies) were pooled (RR, 0.83; 95% CI, 0.69 to 1.00; P = 0.054).

Conclusions

Pooled results from small RCTs suggest reduced clinical failure rates and intensive care unit length-of-stay when using continuous/extended infusions of antibiotics in critically ill patients. Reduced mortality rates almost achieved statistical significance when the results of RCTs were combined with cohort studies. These results support the conduct of adequately powered RCTs to define better the utility of continuous/extended infusions in the era of antibiotic resistance.     

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 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.     

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.     

Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

Introduction

Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV).

Methods

A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality.

Results

A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO₂/FiO₂ ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality.

Conclusions

Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients.     

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.     

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     

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.     

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.     

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.     

Early fluid loading in acute respiratory distress syndrome with septic shock deteriorates lung aeration without impairing arterial oxygenation: a lung ultrasound observational study

Introduction

The study was designed to assess the impact of fluid loading on lung aeration, oxygenation and hemodynamics in patients with septic shock and acute respiratory distress syndrome (ARDS).

Methods

During a 1-year period, a prospective observational study was performed in 32 patients with septic shock and ARDS. Cardiorespiratory parameters were measured using Swan Ganz (n = 29) or PiCCO catheters (n = 3). Lung aeration and regional pulmonary blood flows were measured using bedside transthoracic ultrasound. Measurements were performed before (T0), at the end of volume expansion (T1) and 40 minutes later (T2), consisting of 1-L of saline over 30 minutes during the first 48 h following onset of septic shock and ARDS.

Results

Lung ultrasound score increased by 23% at T2, from 13 at baseline to 16 (P < 0.001). Cardiac index and cardiac filling pressures increased significantly at T1 (P < 0.001) and returned to control values at T2. The increase in lung ultrasound score was statistically correlated with fluid loading-induced increase in cardiac index and was not associated with increase in pulmonary shunt or regional pulmonary blood flow. At T1, PaO₂/FiO₂ significantly increased (P < 0.005) from 144 (123 to 198) to 165 (128 to 226) and returned to control values at T2, whereas lung ultrasound score continued to increase.

Conclusions

Early fluid loading transitorily improves hemodynamics and oxygenation and worsens lung aeration. Aeration changes can be detected at the bedside by transthoracic lung ultrasound, which may serve as a safeguard against excessive fluid loading.     

Non-invasive ventilation for acute hypoxemic respiratory failure: intubation rate and risk factors

Introduction

We assessed rates and predictive factors of non-invasive ventilation (NIV) failure in patients admitted to the intensive care unit (ICU) for non-hypercapnic acute hypoxemic respiratory failure (AHRF).

Methods

This is an observational cohort study using data prospectively collected over a three-year period in a medical ICU of a university hospital.

Results

Among 113 patients receiving NIV for AHRF, 82 had acute respiratory distress syndrome (ARDS) and 31 had non-ARDS. Intubation rates significantly differed between ARDS and non-ARDS patients (61% versus 35%, P = 0.015) and according to clinical severity of ARDS: 31% in mild, 62% in moderate, and 84% in severe ARDS (P = 0.0016). In-ICU mortality rates were 13% in non-ARDS, and, respectively, 19%, 32% and 32% in mild, moderate and severe ARDS (P = 0.22). Among patients with moderate ARDS, NIV failure was lower among those having a PaO₂/FiO₂ >150 mmHg (45% vs. 74%, p = 0.04). NIV failure was associated with active cancer, shock, moderate/severe ARDS, lower Glasgow coma score and lower positive end-expiratory pressure level at NIV initiation. Among intubated patients, ICU mortality rate was 46% overall and did not differ according to the time to intubation.

Conclusions

With intubation rates below 35% in non-ARDS and mild ARDS, NIV stands as the first-line approach; NIV may be attempted in ARDS patients with a PaO₂/FiO₂ > 150. By contrast, 84% of severe ARDS required intubation and NIV did not appear beneficial in this subset of patients. However, the time to intubation had no influence on mortality.     

Body temperature affects cerebral hemodynamics in acutely brain injured patients: an observational transcranial color-coded duplex sonography study

Introduction

Temperature changes are common in patients in a neurosurgical intensive care unit (NICU): fever is frequent among severe cases and hypothermia is used after cardiac arrest and is currently being tested in clinical trials to lower intracranial pressure (ICP). This study investigated cerebral hemodynamics when body temperature varies in acute brain injured patients.

Methods

We enrolled 26 patients, 14 with acute brain injury who developed fever and were given antipyretic therapy (defervescence group) and 12 who underwent an intracranial neurosurgical procedure and developed hypothermia in the operating room; once admitted to the NICU, still under anesthesia, they were re-warmed before waking (re-warming group). We measured cerebral blood flow velocity (CBF-V) and pulsatility index (PI) at the middle cerebral artery using transcranial color-coded duplex sonography (TCCDS).

Results

In the defervescence group mean CBF-V decreased from 75 ± 26 (95% CI 65 to 85) to 70 ± 22 cm/s (95% CI 61 to 79) (P = 0.04); the PI also fell, from 1.36 ± 0.33 (95% CI 1.23 to 1.50) to 1.16 ± 0.26 (95% CI 1.05 to 1.26) (P = 0.0005). In the subset of patients with ICP monitoring, ICP dropped from 16 ± 8 to 12 ± 6 mmHg (P = 0.003). In the re-warming group mean CBF-V increased from 36 ± 10 (95% CI 31 to 41) to 39 ± 13 (95% CI 33 to 45) cm/s (P = 0.04); the PI rose from 0.98 ± 0.14 (95% CI 0.91 to 1.04) to 1.09 ± 0.22 (95% CI 0.98 to 1.19) (P = 0.02).

Conclusions

Body temperature affects cerebral hemodynamics as evaluated by TCCDS; when temperature rises, CBF-V increases in parallel, and viceversa when temperature decreases. When cerebral compliance is reduced and compensation mechanisms are exhausted, even modest temperature changes can greatly affect ICP.     

Chloride-liberal fluids are associated with acute kidney injury after liver transplantation

Introduction

Acute kidney injury (AKI) occurs frequently after liver transplantation and is associated with significant morbidity and mortality. Recent evidence has linked the predominant usage of ‘chloride-liberal’ intravenous fluids, such as 0.9% saline to the development of renal dysfunction in general critically ill patients. We compared the effects of perioperative fluid types on AKI in liver transplant recipients.

Methods

An observational analysis of liver transplant recipients over a 33-month period, between January 2010 and September 2013, was performed. Intensive care unit database and patient records were analyzed for determinants of early postoperative AKI. Univariate and multivariate regression analysis was carried out using a two-tailed P value less than 0.05 to establish significance. The institutional Research Ethics Committee approved the study methodology (RAC no. 2131 073).

Results

One hundred and fifty-eight liver transplants were performed, AKI developed in 57 (36.1%) patients: 39 (68.4%) fully recovered, 13 (22.8%) developed chronic renal failure and 10 (17.5%) required long-term hemodialysis. On univariate regression analysis, AKI was significantly associated with greater than 3,200 ml of chloride-liberal fluids infused within the first postoperative day (HR 5.9, 95% CI 2.64, 13.2, P <0.001), greater than 1,500 ml colloids received in the operating room (hazard ratio (HR) 1.97, 95% CI 1.01, 3.8, P = 0.046), vasopressor requirement for 48 hours posttransplant (HR 3.34, 95% CI 1.55, 7.21, P = 0.002), hyperchloremia at day 2 (HR 1.09, 95% CI 1.01, 1.18, P = 0.015) and preoperative model for end-stage liver disease (MELD) score (HR 1.08, 95% CI 1.03, 1.13, P <0.001).After stepwise multivariate regression, infusion of greater than 3,200 ml of chloride-liberal fluids (HR 6.25, 95% CI 2.69, 14.5, P <0.000) and preoperative MELD score (HR 1.08, 95% CI 1.02, 1.15, P = 0.004) remained significant predictors for AKI.

Conclusions

In a sample of liver transplant recipients, infusion of higher volumes of chloride-liberal fluids and preoperative status was associated with an increased risk for postoperative AKI.     

Association between vitamin D deficiency and mortality in critically ill adult patients: a meta-analysis of cohort studies

Introduction

Vitamin D deficiency is common in critically ill patients, and was reported to be associated with adverse outcomes. However, the effect of vitamin D deficiency on mortality in critically ill patients remains unclear.

Methods

We searched PubMed and EMBASE from the inception to July 2014 for cohort studies to assess the effect of vitamin D deficiency on the incidence of mortality in critically ill patients. Mortality-specific odds ratio (OR) with 95% confidence interval (CI) were pooled with a random- or fixed-effect models when appropriate.

Results

Seven cohort studies with a total of 4,204 participants including 1,679 cases of vitamin D deficiency were included in this meta-analysis. Vitamin D deficiency was significantly associated with an increased hospital mortality (OR 1.76; 95% CI, 1.38 to 2.24; P <0.001), with very low heterogeneity (I² = 2.3%; P = 0.402). The finding of increased hospital mortality in critically ill adult patients was consistently found in every stratum of our subgroup analyses.

Conclusions

This meta-analysis suggests that vitamin D deficiency is associated with increased incidence of hospital mortality in critically ill adult patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0684-9) contains supplementary material, which is available to authorized users.     

Decision support tool for differential diagnosis of Acute Respiratory Distress Syndrome (ARDS) vs Cardiogenic Pulmonary Edema (CPE): a prospective validation and meta-analysis

Introduction

We recently presented a prediction score providing decision support with the often-challenging early differential diagnosis of acute lung injury (ALI) vs cardiogenic pulmonary edema (CPE). To facilitate clinical adoption, our objective was to prospectively validate its performance in an independent cohort.

Methods

Over 9 months, adult patients consecutively admitted to any intensive care unit of a tertiary-care center developing acute pulmonary edema were identified in real-time using validated electronic surveillance. For eligible patients, predictors were abstracted from medical records within 48 hours of the alert. Post-hoc expert review blinded to the prediction score established gold standard diagnosis.

Results

Of 1,516 patients identified by electronic surveillance, data were abstracted for 249 patients (93% within 48 hours of disease onset), of which expert review (kappa 0.93) classified 72 as ALI, 73 as CPE and excluded 104 as “other”. With an area under the curve (AUC) of 0.81 (95% confidence interval =0.73 to 0.88) the prediction score showed similar discrimination as in prior cohorts (development AUC = 0.81, P = 0.91; retrospective validation AUC = 0.80, P = 0.92). Hosmer-Lemeshow test was significant (P = 0.01), but across eight previously defined score ranges probabilities of ALI vs CPE were the same as in the development cohort (P = 0.60). Results were the same when comparing acute respiratory distress syndrome (ARDS, Berlin definition) vs CPE.

Conclusion

The clinical prediction score reliably differentiates ARDS/ALI vs CPE. Pooled results provide precise estimates of the score’s performance which can be used to screen patient populations or to assess the probability of ALI/ARDS vs CPE in specific patients. The score may thus facilitate early inclusion into research studies and expedite prompt treatment.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0659-x) contains supplementary material, which is available to authorized users.