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.     

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.     

Coefficient of glucose variation is independently associated with mortality in critically ill patients receiving intravenous insulin

Introduction

Both patient- and context-specific factors may explain the conflicting evidence regarding glucose control in critically ill patients. Blood glucose variability appears to correlate with mortality, but this variability may be an indicator of disease severity, rather than an independent predictor of mortality. We assessed blood glucose coefficient of variation as an independent predictor of mortality in the critically ill.

Methods

We used eProtocol-Insulin, an electronic protocol for managing intravenous insulin with explicit rules, high clinician compliance, and reproducibility. We studied critically ill patients from eight hospitals, excluding patients with diabetic ketoacidosis and patients supported with eProtocol-insulin for < 24 hours or with < 10 glucose measurements. Our primary clinical outcome was 30-day all-cause mortality. We performed multivariable logistic regression, with covariates of age, gender, glucose coefficient of variation (standard deviation/mean), Charlson comorbidity score, acute physiology score, presence of diabetes, and occurrence of hypoglycemia < 60 mg/dL.

Results

We studied 6101 critically ill adults. Coefficient of variation was independently associated with 30-day mortality (odds ratio 1.23 for every 10% increase, P < 0.001), even after adjustment for hypoglycemia, age, disease severity, and comorbidities. The association was higher in non-diabetics (OR = 1.37, P < 0.001) than in diabetics (OR 1.15, P = 0.001).

Conclusions

Blood glucose variability is associated with mortality and is independent of hypoglycemia, disease severity, and comorbidities. Future studies should evaluate blood glucose variability.     

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.     

Pro-adrenomedullin,pro-endothelin-1, procalcitonin,C-reactive protein and mortality risk in critically ill children: a prospective study

Introduction

We tested the hypothesis that higher mid-regional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations would be associated with increased prediction of mortality risk scores.

Methods

Prospective observational study set in two pediatric intensive care units (PICUs). Two-hundred-thirty-eight patients were included. MR-proADM, CT-proET-1, PCT and CRP levels were compared between children with PRISM III and PIM 2 > p75 (Group A; n = 33) and the rest (Group B; n = 205).

Results

Median (range) MR-proADM levels were 1.39 nmol/L (0.52–12.67) in group A versus 0.54 (0.15–3.85) in group B (P < 0.001). CT-proET-1 levels were 172 pmol/L (27–500) versus 58 (4–447) (P < 0.001). PCT levels were 7.77 ng/mL (0.34–552.00) versus 0.28 (0.02–107.00) (P < 0.001). CRP levels were 6.23 mg/dL (0.08-28.25) versus 1.30 mg/dL (0.00-42.09) (P = 0.210). The area under the ROC curve (AUC) for the differentiation of group A and B was 0.87 (95% CI:0.81–0.821) for MR-proADM, 0.86 (95% CI:0.79–0.92) for CT-proET-1 and 0.84 (95% CI:0.74–0.94) for PCT. A MR-proADM > 0.79 nmol/L had 93% sensitivity and 76% specificity to differentiate groups, whereas a CT-proET-1 > 123 pmol/L had 77% sensitivity and 84% specificity, and a PCT concentration > 2.05 ng/mL had 80% sensitivity and specificity.

Conclusions

In critically ill children, high levels of MR-proADM, CT-proET-1 and PCT were associated with increased prediction of mortality risk scores. MR-proADM, CT-proET-1 and PCT concentrations higher than 0.80 nmol/L, 123 pmol/L and 2 ng/mL, respectively, could be used by clinicians to identify critically ill children at higher prediction of risk death scores.     

Inflammation biomarkers and delirium in critically ill patients

Introduction

Delirium is a common occurrence in critically ill patients and is associated with an increase in morbidity and mortality. Septic patients with delirium may differ from a general critically ill population. The aim of this investigation was to study the relationship between systemic inflammation and the development of delirium in septic and non-septic critically ill patients.

Methods

We performed a prospective cohort study in a 20-bed mixed intensive care unit (ICU) including 78 (delirium = 31; non-delirium = 47) consecutive patients admitted for more than 24 hours. At enrollment, patients were allocated to septic or non-septic groups according to internationally agreed criteria. Delirium was diagnosed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) during the first 72 hours of ICU admission. Blood samples were collected within 12 hours of enrollment for determination of tumor necrosis factor (TNF)-α, soluble TNF Receptor (STNFR)-1 and -2, interleukin (IL)-1β, IL-6, IL-10 and adiponectin.

Results

Out of all analyzed biomarkers, only STNFR1 (P = 0.003), STNFR2 (P = 0.005), adiponectin (P = 0.005) and IL-1β (P < 0.001) levels were higher in delirium patients. Adjusting for sepsis and sedation, these biomarkers were also independently associated with delirium occurrence. However, none of them were significant influenced by sepsis.

Conclusions

STNFR1, STNFR2, adiponectin and IL-1β were associated with delirium. Sepsis did not modify the relationship between the biomarkers and delirium occurrence.     

Are Growing Pains Related to Vitamin D Deficiency? Efficacy of Vitamin D Therapy for Resolution of Symptoms

Objectives

The aim of this study was to investigate the 25-hydroxyvitamin D [25(OH)D] status of children with growing pains and to evaluate the efficacy of vitamin D treatment on the resolution of pain symptoms.

Subjects and Methods

One hundred and twenty children with growing pains were included in a prospective cohort study. Serum 25(OH)D and bone mineral levels were measured in all subjects at the time of enrollment. The pain intensity of those with vitamin D deficiency was measured using a pain visual analog scale (VAS). After a single oral dose of vitamin D, the pain intensity was remeasured by means of the VAS at 3 months. The 25(OH)D levels and VAS scores before and after oral vitamin D administration were compared by means of a paired Student''s t test.

Results

In the 120 children with growing pains, vitamin D insufficiency was noted in 104 (86.6%). Following vitamin D supplementation, the mean 25(OH)D levels increased from 13.4 ± 7.2 to 44.5 ± 16.4 ng/ml, the mean pain VAS score decreased from 6.8 ± 1.9 to 2.9 ± 2.5 cm (a mean reduction of −3.8 ± 2.1, p < 0.001) and the difference was statistically significant.

Conclusion

Supplementation with oral vitamin D resulted in a significant reduction in pain intensity among these children with growing pains who had hypovitaminosis D.Key Words: Growing pains, Vitamin D, Visual analog scale, Children     

Low skeletal muscle area is a risk factor for mortality in mechanically ventilated critically ill patients

Introduction

Higher body mass index (BMI) is associated with lower mortality in mechanically ventilated critically ill patients. However, it is yet unclear which body component is responsible for this relationship.

Methods

This retrospective analysis in 240 mechanically ventilated critically ill patients included adult patients in whom a computed tomography (CT) scan of the abdomen was made on clinical indication between 1 day before and 4 days after admission to the intensive care unit. CT scans were analyzed at the L3 level for skeletal muscle area, expressed as square centimeters. Cutoff values were defined by receiver operating characteristic (ROC) curve analysis: 110 cm² for females and 170 cm² for males. Backward stepwise regression analysis was used to evaluate low-muscle area in relation to hospital mortality, with low-muscle area, sex, BMI, Acute Physiologic and Chronic Health Evaluation (APACHE) II score, and diagnosis category as independent variables.

Results

This study included 240 patients, 94 female and 146 male patients. Mean age was 57 years; mean BMI, 25.6 kg/m². Muscle area for females was significantly lower than that for males (102 ± 23 cm² versus 158 ± 33 cm²; P < 0.001). Low-muscle area was observed in 63% of patients for both females and males. Mortality was 29%, significantly higher in females than in males (37% versus 23%; P = 0.028). Low-muscle area was associated with higher mortality compared with normal-muscle area in females (47.5% versus 20%; P = 0.008) and in males (32.3% versus 7.5%; P < 0.001). Independent predictive factors for mortality were low-muscle area, sex, and APACHE II score, whereas BMI and admission diagnosis were not. Odds ratio for low-muscle area was 4.3 (95% confidence interval, 2.0 to 9.0, P < 0.001). When applying sex-specific cutoffs to all patients, muscle mass appeared as primary predictor, not sex.

Conclusions

Low skeletal muscle area, as assessed by CT scan during the early stage of critical illness, is a risk factor for mortality in mechanically ventilated critically ill patients, independent of sex and APACHE II score. Further analysis suggests muscle mass as primary predictor, not sex. BMI is not an independent predictor of mortality when muscle area is accounted for.     

Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study

Introduction

Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients.

Methods

In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry.

Results

A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC₂₄) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (C_min) < 0.13 to 14.49 mg/L, median 2.06 mg/L). Furthermore, potentially subtherapeutic linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC₂₄ < 200 mg*h/L and C_min < 2 mg/L) were observed for 63% and 50% of the patients, respectively. Finally, potentially toxic levels (defined as AUC₂₄ > 400 mg*h/L and C_min > 10 mg/L) were observed for 7 of the patients.

Conclusions

A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients.

Trial registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01793012","term_id":"NCT01793012"}}NCT01793012. Registered 24 January 2013.     

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.     

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.     

The plasma level and biomarker value of neutrophil gelatinase-associated lipocalin in critically ill patients with acute kidney injury are not affected by continuous venovenous hemofiltration and anticoagulation applied

Introduction

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury (AKI), and levels reflect severity of disease in critically ill patients. However, continuous venovenous hemofiltration (CVVH) may affect plasma levels by clearance or release of NGAL by activated neutrophils in the filter, dependent on the anticoagulation regimen applied. We therefore studied handling of NGAL by CVVH in patients with AKI.

Methods

Immediately before initiation of CVVH, prefilter blood was drawn. After 10, 60, 180, and 720 minutes of CVVH, samples were collected from pre- and postfilter (in- and outlet) blood and ultrafiltrate. CVVH with the following anticoagulation regimens was studied: no anticoagulation in case of a high bleeding tendency (n = 13), unfractionated heparin (n = 8), or trisodium citrate (n = 21). NGAL levels were determined with enzyme-linked immunosorbent assay (ELISA).

Results

Concentrations of NGAL at inlet and outlet were similar, and concentrations did not change over time in any of the anticoagulation groups; thus no net removal or production of NGAL occurred. Concentrations of NGAL at inlet correlated with disease severity at initiation of CVVH and at the end of a CVVH run. Concentrations of NGAL in the ultrafiltrate were lower with citrate-based CVVH (P = 0.03) and decreased over time, irrespective of anticoagulation administered (P < 0.001). The sieving coefficient and clearance of NGAL were low and decreased over time (P < 0.001).

Conclusions

The plasma level and biomarker value of NGAL in critically ill patients with AKI are not affected by CVVH, because clearance by the filter was low. Furthermore, no evidence exists for intrafilter release of NGAL by neutrophils, irrespective of the anticoagulation method applied.     

Guideline-concordant administration of prothrombin complex concentrate and vitamin K is associated with decreased mortality in patients with severe bleeding under vitamin K antagonist treatment (EPAHK study)

Introduction

In vitamin K antagonist (VKA)-treated patients with severe hemorrhage, guidelines recommend prompt VKA reversal with prothrombin complex concentrate (PCC) and vitamin K. The aim of this observational cohort study was to evaluate the impact of guideline concordant administration of PCC and vitamin K on seven-day mortality.

Methods

Data from consecutive patients treated with PCC were prospectively collected in 44 emergency departments. Type of hemorrhage, coagulation parameters, type of treatment and seven-day mortality mortality were recorded. Guideline-concordant administration of PCC and vitamin K (GC-PCC-K) were defined by at least 20 IU/kg factor IX equivalent PCC and at least 5 mg of vitamin K performed within a predefined time frame of eight hours after admission. Multivariate analysis was used to assess the effect of appropriate reversal on seven-day mortality in all patients and in those with intracranial hemorrhage (ICH).

Results

Data from 822 VKA-treated patients with severe hemorrhage were collected over 14 months. Bleeding was gastrointestinal (32%), intracranial (32%), muscular (13%), and “other” (23%). In the whole cohort, seven-day mortality was 13% and 33% in patients with ICH. GC-PCC-K was performed in 38% of all patients and 44% of ICH patients. Multivariate analysis showed a two-fold decrease in seven-day mortality in patients with GC-PCC-K (odds ratio (OR) = 2.15 (1.20 to 3.88); P = 0.011); this mortality reduction was also observed when only ICH was considered (OR = 3.23 (1.53 to 6.79); P = 0.002).

Conclusions

Guideline-concordant VKA reversal with PCC and vitamin K within eight hours after admission was associated with a significant decrease in seven-day mortality.     

Sustained high serum malondialdehyde levels are associated with severity and mortality in septic patients

Introduction

There is a hyperoxidative state in sepsis. The objective of this study was to determine serum malondialdehyde (MDA) levels during the first week of follow up, whether such levels are associated with severity during the first week and whether non-surviving patients showed higher MDA levels than survivors during the first week.

Methods

We performed an observational, prospective, multicenter study in six Spanish Intensive Care Units. Serum levels of MDA were measured in 328 patients (215 survivors and 113 non-survivors) with severe sepsis at days one, four and eight of diagnosis, and in 100 healthy controls. The primary endpoint was 30-day mortality and the secondary endpoint was six -month mortality. The association between continuous variables was carried out using Spearman’s rank correlation coefficient. Cox regression analysis was applied to determine the independent contribution of serum MDA levels on the prediction of 30-day and 6-month mortality. Hazard ratio (HR) and 95% confidence intervals (CI) were calculated as measures of the clinical impact of the predictor variables.

Results

We found higher serum MDA in septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001) of diagnosis than in healthy controls. Serum MDA was lower in surviving than non-surviving septic patients at day one (p < 0.001), day four (p < 0.001) and day eight (p < 0.001). Serum MDA levels were positively correlated with lactic acid and SOFA during the first week. Finally, serum MDA levels were associated with 30-day mortality (HR = 1.05; 95% CI = 1.02-1.09; p = 0.005) and six-month mortality (hazard ratio (HR) = 1.05; 95% CI = 1.02-1.09; p = 0.003) after controlling for lactic acid levels, acute physiology and chronic health evaluation (APACHE)-II, diabetes mellitus, bloodstream infection and chronic renal failure.

Conclusions

To our knowledge, this is the largest series providing data on the oxidative state in septic patients to date. The novel finding is that high serum MDA levels sustained throughout the first week of follow up were associated with severity and mortality in septic patients.     

Introducing intravascular microdialysis for continuous lactate monitoring in patients undergoing cardiac surgery: a prospective observational study

Introduction

Lactate is a marker of hypoperfusion and may be used for risk assessment in critically ill patients. Although evidence suggests that repeated lactate measurements are of clinical interest, how and when lactate should be analyzed is controversial. Intravascular microdialysis provides a novel method for the continuous monitoring of lactate, which may be clinically beneficial in critically ill patients.

Methods

Circulating lactate levels were continuously monitored in 80 patients undergoing cardiac surgery using either a separate single-lumen microdialysis catheter or a triple-lumen central venous catheter with an integrated microdialysis function. The catheter was placed with the tip positioned in the superior vena cava. Arterial blood gas samples were taken every hour to obtain reference values, and the lactate levels were analyzed in a blood gas analyzer.

Results

A total of 1,601 paired microdialysis–arterial blood gas lactate samples were obtained. Bland-Altman analysis showed a bias (mean difference) ± limits of agreement (±1.96 SD) of 0.02 ± 0.42 mmol/L. The regression coefficient was 0.98 (P = 0.0001).

Conclusions

Central venous microdialysis is an accurate and reliable method for continuous blood lactate monitoring in patients undergoing cardiac surgery. The system may be useful for early lactate-guided therapy in critically ill patients.     

Systemic glucose variability predicts cerebral metabolic distress and mortality after subarachnoid hemorrhage: a retrospective observational study

Introduction

Cerebral glucose metabolism and energy production are affected by serum glucose levels. Systemic glucose variability has been shown to be associated with poor outcome in critically ill patients. The objective of this study was to assess whether glucose variability is associated with cerebral metabolic distress and outcome after subarachnoid hemorrhage.

Methods

A total of 28 consecutive comatose patients with subarachnoid hemorrhage, who underwent cerebral microdialysis and intracranial pressure monitoring, were studied. Metabolic distress was defined as lactate/pyruvate ratio (LPR) >40. The relationship between daily glucose variability, the development of cerebral metabolic distress and hospital outcome was analyzed using a multivariable general linear model with a logistic link function for dichotomized outcomes.

Results

Daily serum glucose variability was expressed as the standard deviation (SD) of all serum glucose measurements. General linear models were used to relate this predictor variable to cerebral metabolic distress and mortality at hospital discharge. A total of 3,139 neuromonitoring hours and 181 days were analyzed. After adjustment for Glasgow Coma Scale (GCS) scores and brain glucose, SD was independently associated with higher risk of cerebral metabolic distress (adjusted odds ratio = 1.5 (1.1 to 2.1), P = 0.02). Increased variability was also independently associated with in hospital mortality after adjusting for age, Hunt Hess, daily GCS and symptomatic vasospasm (P = 0.03).

Conclusions

Increased systemic glucose variability is associated with cerebral metabolic distress and increased hospital mortality. Therapeutic approaches that reduce glucose variability may impact on brain metabolism and outcome after subarachnoid hemorrhage.     

Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study,systematic review and individual patient data meta-analysis

Introduction

Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza.

Methods

Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search.

Results

PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder.

Conclusions

In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.     

Close to recommended caloric and protein intake by enteral nutrition is associated with better clinical outcome of critically ill septic patients: secondary analysis of a large international nutrition database

Introduction

Current international sepsis guidelines recommend low-dose enteral nutrition (EN) for the first week. This contradicts other nutrition guidelines for heterogenous groups of ICU patients. Data on the optimal dose of EN in septic patients are lacking. Our aim was to evaluate the effect of energy and protein amount given by EN on clinical outcomes in a large cohort of critically ill septic patients.

Methods

We conducted a secondary analysis of pooled data collected prospectively from international nutrition studies. Eligible patients had a diagnosis of sepsis and/or pneumonia and were admitted to the ICU for ≥3 days, mechanically ventilated within 48 hours of ICU admission and only receiving EN. Patients receiving parenteral nutrition were excluded. Data were collected from ICU admission up to a maximum of 12 days. Regression models were used to examine the impact of calorie and protein intake on 60-day mortality and ventilator-free days.

Results

Of the 13,630 patients included in the dataset, 2,270 met the study inclusion criteria. Patients received a mean amount of 1,057 kcal/d (14.5 kcal/kg/day) and 49 g protein/day (0.7 g/kg/d) by EN alone. Patients were mechanically ventilated for a median of 8.4 days and 60-day mortality was 30.5%. An increase of 1,000 kcal was associated with reduced 60-day mortality (odds ratio (OR) 0.61; 95% confidence interval (CI) 0.48 to 0.77, P <0.001) and more ventilator-free days (2.81 days, 95% CI 0.53 to 5.08, P = 0.02) as was an increase of 30 g protein per day (OR 0.76; 95% CI 0.65 to 0.87, P <0.001 and 1.92 days, 95% CI 0.58 to 3.27, P = 0.005, respectively).

Conclusions

In critically ill septic patients, a calorie and protein delivery closer to recommended amounts by EN in the early phase of ICU stay was associated with a more favorable outcome.     

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.