The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial.

BACKGROUND: Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI. METHODS: In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated. RESULTS: Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT. CONCLUSIONS: In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.

Novel Antimicrobial Agents for Gram-Negative Pathogens.

Gram-negative bacterial resistance to antimicrobials has had an exponential increase at a global level during the last decades and represent an everyday challenge, especially for the hospital practice of our era. Concerted efforts from the researchers and the industry have recently provided several novel promising antimicrobials, resilient to various bacterial resistance mechanisms. There are new antimicrobials that became commercially available during the last five years, namely, cefiderocol, imipenem-cilastatin-relebactam, eravacycline, omadacycline, and plazomicin. Furthermore, other agents are in advanced development, having reached phase 3 clinical trials, namely, aztreonam-avibactam, cefepime-enmetazobactam, cefepime-taniborbactam, cefepime-zidebactam, sulopenem, tebipenem, and benapenem. In this present review, we critically discuss the characteristics of the above-mentioned antimicrobials, their pharmacokinetic/pharmacodynamic properties and the current clinical data.

Variable cost of ICU care, a micro-costing analysis.

Intensive care unit (ICU) costs account for a great part of a hospital's expenses. The objective of the present study was to measure the patient-specific cost of ICU treatment, to identify the most important cost drivers in ICU and to examine the role of various contributing factors in cost configuration. A retrospective cost analysis of all ICU patients who were admitted during 2011 in a Greek General, seven-bed ICU and stayed for at least 24hours was performed, by applying bottom-up analysis. Data collected included demographics and the exact cost of every single material used for patients' care. Prices were yielded from the hospital's purchasing costs and from the national price list of the imaging and laboratory tests, which was provided by the Ministry of Health. A total of 138 patients were included. Variable cost per ICU day was €573.18. A substantial cost variation was found in the total costs obtained for individual patients (median: €3443, range: €243.70-€116,355). Medicines were responsible for more than half of the cost and antibiotics accounted for the largest part of it, followed by blood products and cardiovascular drugs. Medical cause of admission, severe illness and increased length of stay, mechanical ventilation and dialysis were the factors associated with cost escalation. ICU variable cost is patient-specific, varies according to each patient's needs and is influenced by several factors. The exact estimation of variable cost is a pre-requisite in order to control ICU expenses.

The immune response after stimulation with wall components of gram-positive bacteria and fungi.

Although several components of the microbial wall of gram-positive bacteria and fungi possess immunostimulatory properties, their pathogenetic role remains incompletely evaluated. The purpose of this study was to assess the basic immune status of patients susceptible to infections and their capability for cytokine production after stimulation with wall components of gram-positive bacteria and fungi. We measured serum cytokine levels as well as cytokine production after ex vivo lipoteichoic acid (LTA) and mannan stimulation of whole blood. The blood was taken from 10 healthy volunteers, 10 patients with end-stage renal disease (ESRD), 10 patients with diabetes mellitus (DM), and 10 patients on their 2nd day of stay in the Intensive Care Unit (ICU), who suffered from non septic systemic inflammatory response syndrome (SIRS) and had an APACHE II score ≥25. We used 1 µg/ml LTA and 100 µg/ml mannan for an incubation period of 8 h to stimulate 100 µl aliquots of whole blood. All patient groups had higher baseline values of TNF-α, IL-6, IL-1ß, and IL-10 compared to the control group, but only for ICU patients the difference was statistically significant. The ratio IL-10/IL-6 was found 0.33, 0.22, and 0.96 in healthy persons, ESRD, and DM patients respectively, and 1.32 in ICU patients. In all examined groups, the levels of cytokines significantly increased after stimulation by LTA and mannan, although in severely ill patients this change was considerably smaller, possibly reflecting a state of monocytes' depression and relative hyporesponsiveness. No significant differences between the LTA and the mannan stimulation were observed.

Role of new biomarkers: functional and structural damage.

Traditional diagnosis of acute kidney injury (AKI) depends on detection of oliguria and rise of serum creatinine level, which is an unreliable and delayed marker of kidney damage. Delayed diagnosis of AKI in the critically ill patient is related to increased morbidity and mortality, prolonged length of stay, and cost escalation. The discovery of a reliable biomarker for early diagnosis of AKI would be very helpful in facilitating early intervention, evaluating the effectiveness of therapy, and eventually reducing cost and improving outcome. Innovative technologies such as genomics and proteomics have contributed to the discovery of new biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (Cys C), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP). The current status of the most promising of these novel AKI biomarkers, including NGAL, Cys C, KIM-1, L-FABP, and IL-18, is reviewed.

Outcome of acute heroin overdose requiring intensive care unit admission.

BACKGROUND: Heroin use carries a large burden of morbidity and mortality. Heroin overdose and in particular events that need intensive care unit (ICU) admission have not been widely examined. The aim of this study was to describe the causes of ICU admission and the outcome of patients with a heroin overdose. METHODS: A retrospective chart review of all patients with a heroin overdose admitted to the ICU between 1987 and 2006 was conducted. RESULTS: Forty-two records were available for review. The average age of the patients was 28 years. In the field, 19 persons were found in coma Glasgow Coma Scale (GCS < 8) and respiratory depression and were treated with naloxone. The reasons for ICU admission included hypoxemia in 37 (88 percent), 28 of whom had acute lung injury (ALI) and nine aspiration pneumonia, shock in three (7.2 percent) and persistent mental compromise in two patients (4.8 percent). Intubation and mechanical ventilation (MV) were instituted in 37 patients. In 19 of the 37 patients, weaning and extubation became possible within the first 24 hours. Sixteen patients suffered complications and received MV for 5 +/- 2 days, with a mean length of ICU stay of 8 +/- 1 days, while two patients succumbed because of anoxemic encephalopathy and brain death. The complications observed were acute respiratory distress syndrome in eight patients, severe sepsis in four, catheter-related bacteremia in one, iatrogenic pneumothorax in one, and rhabdomyolysis in two, while four among them died due to severe sepsis. CONCLUSIONS: In our study, ALI and aspiration pneumonia were the most frequently observed respiratory complications after acute heroin overdose requiring intubation and ICU admission. Mortality rate was 14.2 percent and was attributed to septic complications and irreversible brain damage.