Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis. (Ward)

Marik PE, Hooper MH. Normocaloric versus hypocaloric feeding on the outcomes of ICU patients: a systematic review and meta-analysis. Intensive Care Med. 2016 Mar; 42(3) :316-23.

INTRODUCTION: Current clinical practice guidelines recommend providing ICU patients a daily caloric intake estimated to match 80-100 % of energy expenditure (normocaloric goals). However, recent clinical trials of intentional hypocaloric feeding question this approach.

METHODS: We performed a systematic review and meta-analysis to compare the outcomes of ICU patients randomized to intentional hypocaloric or normocaloric goals. We included randomized controlled trials that enrolled ICU patients and compared intentional hypocaloric with normocaloric nutritional goals. We included studies that evaluated both trophic feeding as well as permissive underfeeding. Data sources included MEDLINE, Cochrane Register of Controlled Trials and citation review of relevant primary and review articles. The outcomes of interest included hospital acquired infection, hospital mortality, ICU length of stay (LOS) and ventilator-free days (VFDs).

RESULTS: Six studies which enrolled 2517 patients met our inclusion criteria. The mean age and body mass index (BMI) across the studies were 53 ± 5 years and 29.1 ± 1.5 kg/m(2), respectively. Two studies compared normocaloric feeding (77 % of goal) with trophic feeding (20 % of goal), while four studies compared normocaloric feeding (72 % of goal) with permissive underfeeding (49 % of goal). Overall, there was no significant difference in the risk of infectious complications (OR 1.03; 95 % CI 0.84-1.27, I (2) = 16 %), hospital mortality (OR 0.91; 95 % CI 0.75-1.11, I (2) = 8 %) or ICU LOS (mean difference 0.05 days; 95 % CI 1.33-1.44 days; I (2) = 37 %) between groups. VFDs were reported in three studies with no significant difference between the normocaloric and intentional hypocaloric groups (data not pooled).

CONCLUSION: This meta-analysis demonstrated no difference in the risk of acquired infections, hospital mortality, ICU length of stay or ventilator-free days between patients receiving intentional hypocaloric as compared to normocaloric nutritional goals.

Benzodiazepine-associated delirium in critically ill adults. (Betters)

Zaal IJ, et al. Benzodiazepine-associated delirium in critically ill adults. Intensive Care Med. 2015 Dec;41(12):2130-7.

PURPOSE: The association between benzodiazepine use and delirium risk in the ICU remains unclear. Prior investigations have failed to account for disease severity prior to delirium onset, competing events that may preclude delirium detection, other important delirium risk factors, and an adequate number of patients receiving continuous midazolam. The aim of this study was to address these limitations and evaluate the association between benzodiazepine exposure and ICU delirium occurrence.

METHODS: In a cohort of consecutive critically ill adults, daily mental status was classified as either awake without delirium, delirium, or coma. In a first-order Markov model, multinomial logistic regression analysis was used, which considered five possible outcomes the next day (i.e., awake without delirium, delirium, coma, ICU discharge, and death) and 16 delirium-related covariables, to quantify the association between benzodiazepine use and delirium occurrence the following day.

RESULTS: Among 1112 patients, 9867 daily transitions occurred. Benzodiazepine administration in an awake patient without delirium was associated with increased risk of delirium the next day [OR 1.04 (per 5 mg of midazolam equivalent administered) 95 % CI 1.02-1.05). When the method of benzodiazepine administration was incorporated in the model, the odds of transitioning to delirium was higher with benzodiazepines given continuously (OR 1.04, 95 % CI 1.03-1.06) compared to benzodiazepines given intermittently (OR 0.97, 95 % CI 0.88-1.05).

CONCLUSIONS: After addressing potential methodological limitations of prior studies, we confirm that benzodiazepine administration increases the risk for delirium in critically ill adults but this association seems to be limited to continuous infusion use only.

Thromboelastography in patients with severe sepsis: a prospective cohort study. (Grunwell)

Haase N, Ostrowski SR, Wetterslev J, et al. Thromboelastography in patients with severe sepsis: a prospective cohort study. Intensive Care Med. 2015 Jan;41(1):77-85.

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PURPOSE: To investigate the association between consecutively measured thromboelastographic (TEG) tracings and outcome in patients with severe sepsis.

METHODS: Multicentre prospective observational study in a subgroup of the Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial (NCT00962156) comparing hydroxyethyl starch (HES) 130/0.42 vs. Ringer’s acetate for fluid resuscitation in severe sepsis. TEG (standard and functional fibrinogen) was measured consecutively for 5 days, and clinical data including bleeding and death was retrieved from the trial database. Statistical analyses included Cox regression with time-dependent covariates and joint modelling techniques.

RESULTS: Of 267 eligible patients, we analysed 260 patients with TEG data. At 90 days, 68 (26 %) had bled and 139 (53 %) had died. For all TEG variables, hypocoagulability according to the reference range was significantly associated with increased risk of death. In a linear model, hazard ratios for death were 6.03 (95 % confidence interval, 1.64-22.17) for increased clot formation speed, 1.10 (1.04-1.16) for decreased angle, 1.09 (1.05-1.14) for decreased clot strength and 1.12 (1.06-1.18) for decreased fibrinogen contribution to clot strength (functional fibrinogen MA), showing that deterioration towards hypocoagulability in any TEG variable significantly increased the risk of death. Patients treated with HES had lower functional fibrinogen MA than those treated Ringer’s acetate, which significantly increased the risk of subsequent bleeding [HR 2.43 (1.16-5.07)] and possibly explained the excess bleeding with HES in the 6S trial.

CONCLUSIONS: In our cohort of patients with severe sepsis, progressive hypocoagulability defined by TEG variables was associated with increased risk of death and increased risk of bleeding.

Pulse oximetry vs. PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk. (Singh)

Khemani RG, Rubin S, Belani S, et al. Pulse oximetry vs. PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk. Intensive Care Med. 2015 Jan;41(1):94-102.

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PURPOSE: Requiring PaO2/FiO2 ratio (PF) to define ARDS may bias towards children with cardiovascular dysfunction and hypoxemia. We sought to evaluate (1) the Berlin definition of ARDS in children using PF; (2) the effect of substituting SpO2/FiO2(SF) ratio; (3) differences between patients with and without arterial blood gases; and (4) the ability of SpO2 and PaO2 indices to discriminate ICU mortality.

METHODS: Single center retrospective review (3/2009-4/2013) of mechanically ventilated (MV) children. Initial values for PF, SF, oxygenation index (OI), and oxygen saturation index (OSI) after intubation and average values on day 1 of MV were analyzed against ICU mortality, subgrouped by Berlin severity categories.

RESULTS: Of the 1,833 children included, 129 met Berlin PF ARDS criteria (33 % mortality); 312 met Berlin SF ARDS criteria (22 % mortality). Children with a PaO2 on day 1 of MV had higher mortality and severity of illness, were older, and had more vasoactive-inotropic infusions (p < 0.001). SF could be calculated for 1,201 children (AUC for ICU mortality 0.821), OSI for 1,034 (0.793), PF for 695 (0.706), and OI for 673 (0.739). Average SF on day 1 discriminated mortality better than PF (p = 0.003).

CONCLUSIONS: Berlin PF criteria for ARDS identified less than half of the children with ARDS, favoring those with cardiovascular dysfunction. SF or OSI discriminate ICU mortality as well as PF and OI, double the number of children available for risk stratification, and should be considered for severity of illness scores and included in a pediatric-specific definition of ARDS. Multicenter validation is required.