Small bowel feeding and risk of pneumonia in adult critically ill patients: a systematic review and meta-analysis of randomized trials

Introduction

This systematic review and meta-analysis aimed to evaluate the effect of small bowel feeding compared with gastric feeding on the frequency of pneumonia and other patient-important outcomes in critically ill patients.

Methods

We searched EMBASE, MEDLINE, clinicaltrials.gov and personal files from 1980 to Dec 2012, and conferences and proceedings from 1993 to Dec 2012 for randomized trials of adult critically ill patients in the intensive care unit (ICU) comparing small bowel feeding to gastric feeding, and evaluating risk of pneumonia, mortality, length of ICU stay, achievement of caloric requirements, duration of mechanical ventilation, vomiting, and aspiration. Independently, in duplicate, we abstracted trial characteristics, outcomes and risk of bias.

Results

We included 19 trials with 1394 patients. Small bowel feeding compared to gastric feeding was associated with reduced risk of pneumonia (risk ratio [RR] 0.70; 95% CI, 0.55, 0.90; P = 0.004; I² = 0%) and ventilator-associated pneumonia (RR 0.68; 95% CI 0.53, 0.89; P = 0.005; I² = 0%), with no difference in mortality (RR 1.08; 95% CI 0.90, 1.29; P = 0.43; I² = 0%), length of ICU stay (WMD -0.57; 95%CI -1.79, 0.66; P = 0.37; I² = 0%), duration of mechanical ventilation (WMD -1.01; 95%CI -3.37, 1.35; P = 0.40; I² = 17%), gastrointestinal bleeding (RR 0.89; 95% CI 0.56, 1.42; P = 0.64; I² = 0%), aspiration (RR 0.92; 95% CI 0.52, 1.65; P = 0.79; I² = 0%), and vomiting (RR 0.91; 95% CI 0.53, 1.54; P = 0.72; I² = 57%). The overall quality of evidence was low for pneumonia outcome.

Conclusions

Small bowel feeding, in comparison with gastric feeding, reduces the risk of pneumonia in critically ill patients without affecting mortality, length of ICU stay or duration of mechanical ventilation. These observations are limited by variation in pneumonia definition, imprecision, risk of bias and small sample size of individual trials.     

Comparative effects on glucose absorption of intragastric and post-pyloric nutrient delivery in the critically ill

Introduction

Studies in the critically ill that evaluate intragastric and post-pyloric delivery of nutrient have yielded conflicting data. A limitation of these studies is that the influence in the route of feeding on glucose absorption and glycaemia has not been determined.

Methods

In 68 mechanically ventilated critically ill patients, liquid nutrient (100 ml; 1 kcal/ml containing 3 g of 3-O-Methyl-D-glucopyranose (3-OMG), as a marker of glucose absorption), was infused into either the stomach (n = 24) or small intestine (n = 44) over six minutes. Blood glucose and serum 3-OMG concentrations were measured at regular intervals for 240 minutes and the area under the curves (AUCs) calculated for ''early'' (AUC₆₀) and ''overall'' (AUC₂₄₀) time periods. Data are presented as mean (95% confidence intervals).

Results

Glucose absorption was initially more rapid following post-pyloric, when compared with intragastric, feeding (3-OMG AUC₆₀: intragastric 7.3 (4.3, 10.2) vs. post-pyloric 12.5 (10.1, 14.8) mmol/l.min; P = 0.008); however, ''overall'' glucose absorption was similar (AUC₂₄₀: 49.1 (34.8, 63.5) vs. 56.6 (48.9, 64.3) mmol/l.min; P = 0.31). Post-pyloric administration of nutrients was also associated with greater increases in blood glucose concentrations in the ''early'' period (AUC₆₀: 472 (425, 519) vs. 534 (501, 569) mmol/l.min; P = 0.03), but ''overall'' glycaemia was also similar (AUC₂₄₀: 1,875 (1,674, 2,075) vs. 1,898 (1,755, 2,041) mmol/l.min; P = 0.85).

Conclusions

In the critically ill, glucose absorption was similar whether nutrient was administered via a gastric or post-pyloric catheter. These data may have implications for the perceived benefit of post-pyloric feeding on nutritional outcomes and warrant further investigation.     

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.     

Neuromuscular blocking agents in acute respiratory distress syndrome: a systematic review and meta-analysis of randomized controlled trials

Introduction

Randomized trials investigating neuromuscular blocking agents in adult acute respiratory distress syndrome (ARDS) have been inconclusive about effects on mortality, which is very high in this population. Uncertainty also exists about the associated risk of ICU-acquired weakness.

Methods

We conducted a systematic review and meta-analysis. We searched the Cochrane (Central) database, MEDLINE, EMBASE, ACP Journal Club, and clinical trial registries for randomized trials investigating survival effects of neuromuscular blocking agents in adults with ARDS. Two independent reviewers abstracted data and assessed methodologic quality. Primary study investigators provided additional unpublished data.

Results

Three trials (431 patients; 20 centers; all from the same research group in France) met inclusion criteria for this review. All trials assessed 48-hour infusions of cisatracurium besylate. Short-term infusion of cisatracurium besylate was associated with lower hospital mortality (RR, 0.72; 95% CI, 0.58 to 0.91; P = 0.005; I² = 0). This finding was robust on sensitivity analyses. Neuromuscular blockade was also associated with lower risk of barotrauma (RR, 0.43; 95% CI, 0.20 to 0.90; P = 0.02; I² = 0), but had no effect on the duration of mechanical ventilation among survivors (MD, 0.25 days; 95% CI, 5.48 to 5.99; P = 0.93; I² = 49%), or the risk of ICU-acquired weakness (RR, 1.08; 95% CI, 0.83 to 1.41; P = 0.57; I² = 0). Primary studies lacked protracted measurements of weakness.

Conclusions

Short-term infusion of cisatracurium besylate reduces hospital mortality and barotrauma and does not appear to increase ICU-acquired weakness for critically ill adults with ARDS.     

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.     

Critical illness induces nutrient-independent adipogenesis and accumulation of alternatively activated tissue macrophages

Introduction

We previously reported that in artificially-fed critically ill patients, adipose tissue reveals an increase in small adipocytes and accumulation of M2-macrophages. We hypothesized that nutrient-independent factors of critical illness explain these findings, and that the M2-macrophage accumulation may not be limited to adipose tissue.

Methods

In a long-term cecal ligation and puncture (CLP) mouse model of sepsis, we compared the effect of parenteral nutrition (CLP-fed, n = 13) with nutrient restriction (CLP-restricted, n = 11) on body composition, adipocyte size and macrophage accumulation in adipose tissue, liver and lungs. Fed healthy mice (n = 11) were studied as controls. In a human study, in vivo adipose tissue biopsies were studied from ICU patients (n = 40) enrolled in a randomized control trial which compared early initiation of parenteral nutrition (PN) versus tolerating nutrient restriction during the first week of ICU stay. Adipose tissue morphology was compared with healthy human controls (n = 13).

Results

Irrespective of nutritional intake, critically ill mice lost weight, fat and fat-free mass. Adipocyte number, proliferation marker Proliferating Cell Nuclear Antigen (PCNA) and adipogenic markers PPARγ and CCAAT/enhancer binding protein-β (C/EBPβ) increased with illness, irrespective of nutritional intake. M2-macrophage accumulation was observed in adipose tissue, liver and lungs of critically ill mice. Macrophage M2-markers correlated with CCL2 expression. In adipose tissue biopsies of critically ill patients, increased adipogenic markers and M2 macrophage accumulation were present irrespective of nutritional intake.

Conclusions

Adipogenesis and accumulation of tissue M2-macrophages are hallmarks of prolonged critical illness, irrespective of nutritional management. During critical illness, M2-macrophages accumulate not only in adipose tissue, but also in the liver and lungs.     

Immunonutrition in critical illness: still fishing for the truth

Citation

Marik PE, Zaloga GP. Immunonutrition in critically ill patients: a systematic review and analysis of the literature. Intensive Care Med 2008;34:1980–1990 [1].

Background

The role of immuno-modulating diets (IMD''s) in critically ill patients is controversial.

Methods

Objective

The goal of this meta-analysis was to determine the impact of IMD''s on hospital mortality, nosocomial infections and length of stay (LOS) in critically ill patients. Outcome was stratified according to type of IMD and patient setting.

Data Sources

MEDLINE, Embase, Cochrane Register of Controlled Trials.

Study Selection

RCT''s that compared the outcome of critically ill patients randomized to an IMD or a control diet.

Data Synthesis

Twenty-four studies (with a total of 3013 patients) were included in the meta-analysis; 12 studies included ICU patients, 5 burn patients and 7 trauma patients. Four of the studies used formulas supplemented with arginine, two with arginine and glutamine, nine with arginine and fish oil (FO), two with arginine, glutamine and FO, six with glutamine alone and three studies used a formula supplemented with FO alone. Overall IMD''s had no effect on mortality or LOS, but reduced the number of infections (OR 0.63; 95% CI 0.47–0.86, P = 0.004, I² = 49%). Mortality, infections and LOS were significantly lower only in the ICU patients receiving the FO IMD (OR 0.42, 95% CI 0.26–0.68; OR 0.45, 95% CI 0.25–0.79 and WMD -6.28 days, 95% CI -9.92 to -2.64, respectively).

Conclusion

An IMD supplemented with FO improved the outcome of medical ICU patients (with SIRS/sepsis/ARDS). IMD''s supplemented with arginine with/without additional glutamine or FO do not appear to offer an advantage over standard enteral formulas in ICU, trauma and burn patients.     

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.     

Liver transplantation in the critically ill: a multicenter Canadian retrospective cohort study

Introduction

Critically ill cirrhosis patients awaiting liver transplantation (LT) often receive prioritization for organ allocation. Identification of patients most likely to benefit is essential. The purpose of this study was to examine whether the Sequential Organ Failure Assessment (SOFA) score can predict 90-day mortality in critically ill recipients of LT and whether it can predict receipt of LT among critically ill cirrhosis listed awaiting LT.

Methods

We performed a multicenter retrospective cohort study consisting of two datasets: (a) all critically-ill cirrhosis patients requiring intensive care unit (ICU) admission before LT at five transplant centers in Canada from 2000 through 2009 (one site, 1990 through 2009), and (b) critically ill cirrhosis patients receiving LT from ICU (n = 115) and those listed but not receiving LT before death (n = 106) from two centers where complete data were available.

Results

In the first dataset, 198 critically ill cirrhosis patients receiving LT (mean (SD) age 53 (10) years, 66% male, median (IQR) model for end-stage liver disease (MELD) 34 (26-39)) were included. Mean (SD) SOFA scores at ICU admission, at 48 hours, and at LT were 12.5 (4), 13.0 (5), and 14.0 (4). Survival at 90 days was 84% (n = 166). In multivariable analysis, only older age was independently associated with reduced 90-day survival (odds ratio (OR), 1.07; 95% CI, 1.01 to 1.14; P = 0.013). SOFA score did not predict 90-day mortality at any time. In the second dataset, 47.9% (n = 106) of cirrhosis patients listed for LT died in the ICU waiting for LT. In multivariable analysis, higher SOFA at 48 hours after admission was independently associated with lower probability of receiving LT (OR, 0.89; 95% CI, 0.82 to 0.97; P = 0.006). When including serum lactate and SOFA at 48 hours in the final model, elevated lactate (at 48 hours) was also significantly associated with lower likelihood of receiving LT (0.32; 0.17 to 0.61; P = 0.001).

Conclusions

SOFA appears poor at predicting 90-day survival in critically ill cirrhosis patients after LT, but higher SOFA score and elevated lactate 48 hours after ICU admission are associated with a lower probability receiving LT. Older critically ill cirrhosis patients (older than 60) receiving LT have worse 90-day survival and should be considered for LT with caution.     

Glycemic variability and glucose complexity in critically ill patients: a retrospective analysis of continuous glucose monitoring data

Introduction

Glycemic variability as a marker of endogenous and exogenous factors, and glucose complexity as a marker of endogenous glucose regulation are independent predictors of mortality in critically ill patients. We evaluated the impact of real time continuous glucose monitoring (CGM) on glycemic variability in critically ill patients on intensive insulin therapy (IIT), and investigated glucose complexity - calculated using detrended fluctuation analysis (DFA) - in ICU survivors and non-survivors.

Methods

Retrospective analysis were conducted of two prospective, randomized, controlled trials in which 174 critically ill patients either received IIT according to a real-time CGM system (n = 63) or according to an algorithm (n = 111) guided by selective arterial blood glucose measurements with simultaneously blinded CGM for 72 hours. Standard deviation, glucose lability index and mean daily delta glucose as markers of glycemic variability, as well as glucose complexity and mean glucose were calculated.

Results

Glycemic variability measures were comparable between the real time CGM group (n = 63) and the controls (n = 111). Glucose complexity was significantly lower (higher DFA) in ICU non-survivors (n = 36) compared to survivors (n = 138) (DFA: 1.61 (1.46 to 1.68) versus 1.52 (1.44 to 1.58); P = 0.003). Diabetes mellitus was significantly associated with a loss of complexity (diabetic (n = 33) versus non-diabetic patients (n = 141) (DFA: 1.58 (1.48 to 1.65) versus 1.53 (1.44 to 1.59); P = 0.01).

Conclusions

IIT guided by real time CGM did not result in significantly reduced glycemic variability. Loss of glucose complexity was significantly associated with mortality and with the presence of diabetes mellitus.     

Nasogastric or nasojejunal feeding in predicted severe acute pancreatitis: a meta-analysis

Introduction

Enteral feeding can be given either through the nasogastric or the nasojejunal route. Studies have shown that nasojejunal tube placement is cumbersome and that nasogastric feeding is an effective means of providing enteral nutrition. However, the concern that nasogastric feeding increases the chance of aspiration pneumonitis and exacerbates acute pancreatitis by stimulating pancreatic secretion has prevented it being established as a standard of care. We aimed to evaluate the differences in safety and tolerance between nasogastric and nasojejunal feeding by assessing the impact of the two approaches on the incidence of mortality, tracheal aspiration, diarrhea, exacerbation of pain, and meeting the energy balance in patients with severe acute pancreatitis.

Method

We searched the electronic databases of the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. We included prospective randomized controlled trials comparing nasogastric and nasojejunal feeding in patients with predicted severe acute pancreatitis. Two reviewers assessed the quality of each study and collected data independently. Disagreements were resolved by discussion among the two reviewers and any of the other authors of the paper. We performed a meta-analysis and reported summary estimates of outcomes as Risk Ratio (RR) with 95% confidence intervals (CIs).

Results

We included three randomized controlled trials involving a total of 157 patients. The demographics of the patients in the nasogastric and nasojejunal feeding groups were comparable. There were no significant differences in the incidence of mortality (RR = 0.69, 95% CI: 0.37 to 1.29, P = 0.25); tracheal aspiration (RR = 0.46, 95% CI: 0.14 to 1.53, P = 0.20); diarrhea (RR = 1.43, 95% CI: 0.59 to 3.45, P = 0.43); exacerbation of pain (RR = 0.94, 95% CI: 0.32 to 2.70, P = 0.90); and meeting energy balance (RR = 1.00, 95% CI: 0.92 to 1.09, P = 0.97) between the two groups. Nasogastric feeding was not inferior to nasojejunal feeding.

Conclusions

Nasogastric feeding is safe and well tolerated compared with nasojejunal feeding. Study limitations included a small total sample size among others. More high-quality large-scale randomized controlled trials are needed to validate the use of nasogastric feeding instead of nasojejunal feeding.     

Augmented renal clearance in septic and traumatized patients with normal plasma creatinine concentrations: identifying at-risk patients

Introduction

Improved methods to optimize drug dosing in the critically ill are urgently needed. Traditional prescribing culture involves recognition of factors that mandate dose reduction (such as renal impairment), although optimizing drug exposure, through more frequent or augmented dosing, represents an evolving strategy. Elevated creatinine clearance (CL_CR) has been associated with sub-therapeutic antibacterial concentrations in the critically ill, a concept termed augmented renal clearance (ARC). We aimed to determine the prevalence of ARC in a cohort of septic and traumatized critically ill patients, while also examining demographic, physiological and illness severity characteristics that may help identify this phenomenon.

Methods

This prospective observational study was performed in a 30-bed tertiary level, university affiliated, adult intensive care unit. Consecutive traumatized and septic critically ill patients, receiving antibacterial therapy, with a plasma creatinine concentration ≤110 μmol/L, were eligible for enrolment. Pulse contour analysis (Vigileo / Flo Trac^® system, Edwards Lifesciences, Irvine, CA, USA), was used to provide continuous cardiac index (CI) assessment over a single six-hour dosing interval. Urinary CL_CR measures were obtained concurrently.

Results

Seventy-one patients contributed data (sepsis n = 43, multi-trauma n = 28). Overall, 57.7% of the cohort manifested ARC, although there was a greater prevalence in trauma (85.7% versus 39.5%, P <0.001). In all patients, a weak correlation was noted between CI and CL_CR (r = 0.346, P = 0.003). This was mostly driven by septic patients (r = 0.508, P = 0.001), as no correlation (r = -0.012, P = 0.951) was identified in trauma. Those manifesting ARC were younger (P <0.001), male (P = 0.012), with lower acute physiology and chronic health evaluation (APACHE) II (P= 0.008) and modified sequential organ failure assessment (SOFA) scores (P = 0.013), and higher cardiac indices (P = 0.013). In multivariate analysis, age ≤50 years, trauma, and a modified SOFA score ≤4, were identified as significant risk factors. These had greater utility in predicting ARC, compared with CI assessment alone.

Conclusions

Diagnosis, illness severity and age, are likely to significantly influence renal drug elimination in the critically ill, and must be regularly considered in future study design and daily prescribing practice.See related commentary by De Waele and Carlier, http://ccforum.com/content/17/2/130     

Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation

Introduction

Glutamine rate of appearance (R_a) may be used as an estimate of endogenous glutamine production. Recently a technique employing a bolus injection of isotopically labeled glutamine was introduced, with the potential to allow for multiple assessments of the glutamine R_a over time in critically ill patients, who may not be as metabolically stable as healthy individuals. Here the technique was used to evaluate the endogenous glutamine production in critically ill patients in the fed state with and without exogenous glutamine supplementation intravenously.

Methods

Mechanically ventilated patients (n = 11) in the intensive care unit (ICU) were studied on two consecutive days during continuous parenteral feeding. To allow the patients to be used as their own controls, they were randomized for the reference measurement during basal feeding without supplementation, before or after the supplementation period. Glutamine R_a was determined by a bolus injection of ¹³C-glutamine followed by a period of frequent sampling to establish the decay-curve for the glutamine tracer. Exogenous glutamine supplementation was given by intravenous infusion of a glutamine containing dipeptide, L-alanyl-L-glutamine, 0.28 g/kg during 20 hours.

Results

A 14% increase of endogenous glutamine R_a was seen at the end of the intravenous supplementation period as compared to the basal measurements (P = 0.009).

Conclusions

The bolus injection technique to measure glutamine R_a to estimate the endogenous production of glutamine in critically ill patients was demonstrated to be useful for repetitive measurements. The hypothesized attenuation of endogenous glutamine production during L-alanyl-L-glutamine infusion given as a part of full nutrition was not seen.     

Whole body protein kinetics during hypocaloric and normocaloric feeding in critically ill patients

Introduction

Optimal feeding of critically ill patients in the ICU is controversial. Existing guidelines rest on rather weak evidence. Whole body protein kinetics may be an attractive technique for assessing optimal protein intake. In this study, critically ill patients were investigated during hypocaloric and normocaloric IV nutrition.

Methods

Neurosurgical patients on mechanical ventilation (n = 16) were studied during a 48-hour period. In random order 50% and 100% of measured energy expenditure was given as IV nutrition during 24 hours, corresponding to hypocaloric and normocaloric nutrition, respectively. At the end of each period, whole body protein turnover was measured using d5-phenylalanine and 13C-leucine tracers.

Results

The phenylalanine tracer indicated that whole-body protein synthesis was lower during hypocaloric feeding, while whole-body protein degradation and amino acid oxidation were unaltered, which resulted in a more negative protein balance, namely −1.9 ± 2.1 versus −0.7 ± 1.3 mg phenylalanine/kg/h (P = 0.014). The leucine tracer indicated that whole body protein synthesis and degradation and amino acid oxidation were unaltered, but the protein balance was negative during hypocaloric feeding, namely −0.3 ± 0.5 versus 0.6 ± 0.5 mg leucine/kg/h (P < 0.001).

Conclusion

In the patient group studied, hypocaloric feeding was associated with a more negative protein balance, but the amino acid oxidation was not different. The protein kinetics measurements and the study’s investigational protocol were useful for assessing the efficacy of nutrition support on protein metabolism in critically ill patients.     

Early high protein intake is associated with low mortality and energy overfeeding with high mortality in non-septic mechanically ventilated critically ill patients

Introduction

Early protein and energy feeding in critically ill patients is heavily debated and early protein feeding hardly studied.

Methods

A prospective database with mixed medical-surgical critically ill patients with prolonged mechanical ventilation (>72 hours) and measured energy expenditure was used in this study. Logistic regression analysis was used to analyse the relation between admission day-4 protein intake group (with cutoffs 0.8, 1.0, and 1.2 g/kg), energy overfeeding (ratio energy intake/measured energy expenditure > 1.1), and admission diagnosis of sepsis with hospital mortality after adjustment for APACHE II (Acute Physiology and Chronic Health Evaluation II) score.

Results

A total of 843 patients were included. Of these, 117 had sepsis. Of the 736 non-septic patients 307 were overfed. Mean day-4 protein intake was 1.0 g/kg pre-admission weight per day and hospital mortality was 36%. In the total cohort, day-4 protein intake group (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.73 to 0.99; P = 0.047), energy overfeeding (OR 1.62; 95%CI 1.07 to 2.44; P = 0.022), and sepsis (OR 1.77; 95%CI 1.18 to 2.65; P = 0.005) were independent risk factors for mortality besides APACHE II score. In patients with sepsis or energy overfeeding, day-4 protein intake was not associated with mortality. For non-septic, non-overfed patients (n = 419), mortality decreased with higher protein intake group: 37% for <0.8 g/kg, 35% for 0.8 to 1.0 g/kg, 27% for 1.0 to 1.2 g/kg, and 19% for ≥1.2 g/kg (P = 0.033). For these, a protein intake level of ≥1.2 g/kg was significantly associated with lower mortality (OR 0.42, 95%CI 0.21 to 0.83, P = 0.013).

Conclusions

In non-septic critically ill patients, early high protein intake was associated with lower mortality and early energy overfeeding with higher mortality. In septic patients early high protein intake had no beneficial effect on mortality.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0701-z) contains supplementary material, which is available to authorized users.     

Association of body temperature and antipyretic treatments with mortality of critically ill patients with and without sepsis: multi-centered prospective observational study

Introduction

Fever is frequently observed in critically ill patients. An independent association of fever with increased mortality has been observed in non-neurological critically ill patients with mixed febrile etiology. The association of fever and antipyretics with mortality, however, may be different between infective and non-infective illness.

Methods

We designed a prospective observational study to investigate the independent association of fever and the use of antipyretic treatments with mortality in critically ill patients with and without sepsis. We included 1,425 consecutive adult critically ill patients (without neurological injury) requiring > 48 hours intensive care admitted in 25 ICUs. We recorded four-hourly body temperature and all antipyretic treatments until ICU discharge or 28 days after ICU admission, whichever occurred first. For septic and non-septic patients, we separately assessed the association of maximum body temperature during ICU stay (MAX_ICU) and the use of antipyretic treatments with 28-day mortality.

Results

We recorded body temperature 63,441 times. Antipyretic treatment was given 4,863 times to 737 patients (51.7%). We found that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen independently increased 28-day mortality for septic patients (adjusted odds ratio: NSAIDs: 2.61, P = 0.028, acetaminophen: 2.05, P = 0.01), but not for non-septic patients (adjusted odds ratio: NSAIDs: 0.22, P = 0.15, acetaminophen: 0.58, P = 0.63). Application of physical cooling did not associate with mortality in either group. Relative to the reference range (MAX_ICU 36.5°C to 37.4°C), MAX_ICU ≥ 39.5°C increased risk of 28-day mortality in septic patients (adjusted odds ratio 8.14, P = 0.01), but not in non-septic patients (adjusted odds ratio 0.47, P = 0.11).

Conclusions

In non-septic patients, high fever (≥ 39.5°C) independently associated with mortality, without association of administration of NSAIDs or acetaminophen with mortality. In contrast, in septic patients, administration of NSAIDs or acetaminophen independently associated with 28-day mortality, without association of fever with mortality. These findings suggest that fever and antipyretics may have different biological or clinical or both implications for patients with and without sepsis.

Trial registration

ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00940654","term_id":"NCT00940654"}}NCT00940654     

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.     

Acute kidney injury in intensive care unit patients: a comparison between the RIFLE and the Acute Kidney Injury Network classifications

Introduction

Whether discernible advantages in terms of sensitivity and specificity exist with Acute Kidney Injury Network (AKIN) criteria versus Risk, Injury, Failure, Loss of Kidney Function, End-stage Kidney Disease (RIFLE) criteria is currently unknown. We evaluated the incidence of acute kidney injury and compared the ability of the maximum RIFLE and of the maximum AKIN within intensive care unit hospitalization in predicting inhospital mortality of critically ill patients.

Methods

Patients admitted to the Department of Intensive Medicine of our hospital between January 2003 and December 2006 were retrospectively evaluated. Chronic kidney disease patients undergoing dialysis or renal transplant patients were excluded from the analysis.

Results

In total, 662 patients (mean age, 58.6 ± 19.2 years; 392 males) were evaluated. AKIN criteria allowed the identification of more patients as having acute kidney injury (50.4% versus 43.8%, P = 0.018) and classified more patients with Stage 1 (risk in RIFLE) (21.1% versus 14.7%, P = 0.003), but no differences were observed for Stage 2 (injury in RIFLE) (10.1% versus 11%, P = 0.655) and for Stage 3 (failure in RIFLE) (19.2% versus 18.1%, P = 0.672). Mortality was significantly higher for acute kidney injury defined by any of the RIFLE criteria (41.3% versus 11%, P < 0.0001; odds ratio = 2.78, 95% confidence interval = 1.74 to 4.45, P < 0.0001) or of the AKIN criteria (39.8% versus 8.5%, P < 0.0001; odds ratio = 3.59, 95% confidence interval = 2.14 to 6.01, P < 0.0001). The area under the receiver operator characteristic curve for inhospital mortality was 0.733 for RIFLE criteria (P < 0.0001) and was 0.750 for AKIN criteria (P < 0.0001). There were no statistical differences in mortality by the acute kidney injury definition/classification criteria (P = 0.72).

Conclusions

Although AKIN criteria could improve the sensitivity of the acute kidney injury diagnosis, it does not seem to improve on the ability of the RIFLE criteria in predicting inhospital mortality of critically ill patients.     

Contrast-enhanced ultrasound to evaluate changes in renal cortical perfusion around cardiac surgery: a pilot study

Introduction

Contrast-enhanced ultrasound (CEUS) is a new technique that might enable portable and non-invasive organ perfusion quantification at the bedside. However, it has not yet been tested in critically ill patients. We sought to establish CEUS''s feasibility, safety, reproducibility and potential diagnostic value in the assessment of renal cortical perfusion in the peri-operative period in cardiac surgery patients.

Methods

We recruited twelve patients deemed at risk of acute kidney injury (AKI) planned for elective cardiac surgery. We performed renal CEUS with destruction-replenishment sequences before the operation, on ICU arrival and the day following the admission. Enhancement was obtained with Sonovue^® (Bracco, Milano, Italy) at an infusion rate of 1 ml/min. We collected hemodynamic parameters before, during and after contrast agent infusion. At each study time, we obtained five video sequences, which were analysed using dedicated software by two independent radiologists blinded to patient and time. The main output was a perfusion index (PI), corresponding to the ratio of relative blood volume (RBV) over mean transit time (mTT).

Results

All 36 renal CEUS studies, including 24 in the immediate post-operative period could be performed and were well tolerated. Correlation between readers for PI was excellent (R² = 0.96, P < 0.0001). Compared with baseline, there was no overall difference in median PI''s on ICU admission. However, the day after surgery, median PI''s had decreased by 50% (P < 0.01) (22% decrease in RBV (P = 0.09); 48% increase in mTT (P = 0.04), both suggestive of decreased perfusion). These differences persisted after correction for haemoglobin; vasopressors use and mean arterial pressure. Four patients developed AKI in the post-operative period.

Conclusions

CEUS appears feasible and well-tolerated in patients undergoing cardiac surgery even immediately after ICU admission. CEUS derived-parameters suggest a decrease in renal perfusion occurring within 24 hours of surgery.     

Continuous vs. intermittent hemodialysis: with which spin will my patient win?

Citation

Vinsonneau C, Camus C, Combes A, et al. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet 2006;368(9533):379–85 [1].

Background

Whether continuous renal replacement therapy is better than intermittent haemodialysis for the treatment of acute renal failure in critically ill patients is controversial.

Methods

Objective

To compare the effect of intermittent haemodialysis and continuous venovenous haemodiafiltration on survival rates in critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome.

Design

Prospective, randomized, controlled trial

Setting

21 medical or multidisciplinary intensive-care units from university or community hospitals in France between Oct 1, 1999 and March 3, 2003.

Subjects

360 critically ill patients with acute renal failure as part of multiple-organ dysfunction syndrome.

Intervention

Patients were randomized to intermittent haemodialysis (n = 184) or continuous venovenous haemodiafiltration (n = 175). Guidelines were provided to achieve optimum haemodynamic tolerance and effectiveness of solute removal in both groups. The two groups were treated with the same polymer membrane and bicarbonate-based buffer.

Measurements and main results

The primary endpoint was 60-day survival based on an intention-to-treat analysis. Rate of survival at 60-days did not differ between the groups (32% in the intermittent haemodialysis group versus 33% in the continuous renal replacement therapy group [95 % CI -8.8 to 11.1,]), or at any other time.

Conclusion

These data suggest that, provided strict guidelines to improve tolerance and metabolic control are used, almost all patients with acute renal failure as part of multiple-organ dysfunction syndrome can be treated with intermittent haemodialysis.