The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial

The Effect of IV Amino Acid Supplementation on Mortality in ICU Patients May Be Dependent on Kidney Function: Post Hoc Subgroup Analyses of a Multicenter Randomized Trial

by Zhu, Ran; Allingstrup, Matilde J.; Perner, Anders; Doig, Gordon S.; for the Nephro-Protective Trial Investigators Group  

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1293–1301

Objectives: We investigated whether preexisting kidney function determines if ICU patients may benefit from increased (2.0 g/kg/d) protein intake. Design: Post hoc, hypothesis-generating, subgroup analysis of a multicenter, phase 2, randomized clinical trial. All analyses were conducted by intention to treat and maintained group allocation. Ninety-day mortality was the primary outcome. Setting: ICUs of 16 hospitals throughout Australia and New Zealand. Patients: Adult critically ill patients expected to remain in the study ICU for longer than 2 days. Interventions: Random allocation to receive a daily supplement of up to 100 g of IV amino acids to achieve a total protein intake of 2.0 g/kg/d or standard nutrition care. Measurements and Main Results: A total of 474 patients were randomized: 235 to standard care and 239 to IV amino acid supplementation. There was a statistically significant interaction between baseline kidney function and supplementation with study amino acids (p value for interaction = 0.026). Within the subgroup of patients with normal kidney function at randomization, patients who were allocated to receive the study amino acid supplement were less likely to die before study day 90 (covariate-adjusted risk difference, –7.9%; 95% CI, –15.1 to –0.7; p = 0.034). Furthermore, amino acid supplementation significantly increased estimated glomerular filtration rate in these patients (repeated-measures treatment × time interaction p = 0.009). Within the subgroup of patients with baseline kidney dysfunction and/or risk of progression of acute kidney injury, a significant effect of the study intervention on mortality was not found (covariate-adjusted risk difference, –0.6%; 95% CI, –16.2 to 15.2; p = 0.95). Conclusions: In this post hoc, hypothesis-generating, subgroup analysis, we observed reduced mortality and improved estimated glomerular filtration rate in ICU patients with normal kidney function who were randomly allocated to receive increased protein intake (up to 2.0 g/kg/d). We strongly recommend confirmation of these results in trials with low risk of bias before this treatment is recommended for routine care.

What Matters Most When Considering Noninvasive Ventilation for Patients With Do-Not-Intubate or Comfort-Measures-Only Orders?*

Esbensen, Kari L., MD, PhD

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1367–1370

Utilizing noninvasive ventilation (NIV) for patients with do-not-intubate (DNI) or comfort-measures-only (CMO) orders remains controversial, despite decades of debate over this issue (1). Some argue that the use of NIV in these patients provides improved chances for survival and achieves important aims, such as improving patient comfort or providing additional time for patients to interact with loved ones or to fulfill meaningful end-of-life tasks (2, 3). Others claim that implementing NIV in this setting is more likely to produce harm than benefit, constitutes an unjust use of limited healthcare resources, and merely prolongs the dying process (4, 5). However, neither proponents nor opponents of NIV in this setting have had sufficient evidence to support their viewpoints, so the controversy has remained largely unresolved.

In this issue of Critical Care Medicine, Wilson et al (⁶) provide the first systematic review and meta-analysis exploring the outcomes of NIV in patients with acute respiratory failure (ARF) who have DNI or CMO orders. Among patients with DNI orders (2,020 patients, 27 studies), they assessed pooled survival rates to hospital discharge (56%) and at 1 year (32%). Hospital survival rates were highest among patients with chronic obstructive pulmonary disease and pulmonary edema (68%) but much lower for patients with active malignancy (37%). Importantly, they found that survival was comparable regardless of whether patients received NIV in the ICU or in a “well-equipped” hospital ward. Patients generally tolerated NIV well, and those who survived returned to their baseline quality of life (QOL) within 3 months following discharge…

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients*

Near-Continuous Glucose Monitoring Makes Glycemic Control Safer in ICU Patients*

 by Preiser, Jean-Charles; Lheureux, Olivier; Thooft, Aurelie; Brimioulle, Serge; Goldstein, Jacques; Vincent, Jean-Louis  

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1224–1229

Objectives: Tight glycemic control using intermittent blood glucose measurements is associated with a risk of hypoglycemia. Glucose concentrations can now be measured near continuously (every 5–15 min). We assessed the quality and safety of glycemic control guided by a near-continuous glucose monitoring system in ICU patients. Design: Prospective, cluster-randomized, crossover study. Setting: Thirty-five–bed medico-surgical department of intensive care with four separate ICUs. Patients: Adult patients admitted to the department and expected to stay for at least 3 days were considered for inclusion if they had persistent hyperglycemia (blood glucose > 150 mg/dL) up to 6 hours after admission and/or were receiving insulin therapy. Interventions: A peripheral venous catheter was inserted in all patients and connected to a continuous glucose monitoring sensor (GlucoClear; Edwards Lifesciences, Irvine, CA). The four ICUs were randomized in pairs in a crossover design to glycemic control using unblinded or blinded continuous glucose monitoring monitors. The insulin infusion rate was adjusted to keep blood glucose between 90 and 150 mg/dL using the blood glucose values displayed on the continuous glucose monitor (continuous glucose monitoring group—unblinded units) or according to intermittent blood glucose readings (intermittent glucose monitoring group—blinded units). Measurements and Main Results: The quality and safety of glycemic control were assessed using the proportion of time in range, the frequency of blood glucose less than 70 mg/dL, and the time spent with blood glucose less than 70 mg/dL (TB70), using blood glucose values measured by the continuous glucose monitoring device. Seventy-seven patients were enrolled: 39 in the continuous glucose monitoring group and 38 in the intermittent glucose monitoring group. A total of 43,107 blood glucose values were recorded. The time in range was similar in the two groups. The incidence of hypoglycemia (8/39 [20.5%] vs 15/38 [39.5%]) and the TB70 (0.4% ± 0.9% vs 1.6% ± 3.4%; p < 0.05) was lower in the continuous glucose monitoring than in the intermittent glucose monitoring group. Conclusions: Use of a continuous glucose monitoring–based strategy decreased the incidence and severity of hypoglycemia, thus improving the safety of glycemic control.

Surviving Sepsis Campaign: Research Priorities for Sepsis and Septic Shock

Surviving Sepsis Campaign: Research Priorities for Sepsis and Septic Shock

 by Coopersmith, Craig M.; De Backer, Daniel; Deutschman, Clifford S.; Ferrer, Ricard; Lat, Ishaq; Machado, Flavia R.; Martin, Greg S.; Martin-Loeches, Ignacio; Nunnally, Mark E.; Antonelli, Massimo; Evans, Laura E.; Hellman, Judith; Jog, Sameer; Kesecioglu, Jozef; Levy, Mitchell M.; Rhodes, Andrew  

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1334–1356

Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock. Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations. Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (Supplemental Table 1, Supplemental Digital Content 2, http://links.lww.com/CCM/D636) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results: The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: 1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; 2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; 3) should rapid diagnostic tests be implemented in clinical practice?; 4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; 5) what are the predictors of sepsis long-term morbidity and mortality?; and 6) what information identifies organ dysfunction? Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

Noninvasive Ventilation in Patients With Do-Not-Intubate and Comfort-Measures-Only Orders: A Systematic Review and Meta-Analysis*

Noninvasive Ventilation in Patients With Do-Not-Intubate and Comfort-Measures-Only Orders: A Systematic Review and Meta-Analysis*

by Wilson, Michael E.; Majzoub, Abdul M.; Dobler, Claudia C.; Curtis, J. Randall; Nayfeh, Tarek; Thorsteinsdottir, Bjorg; Barwise, Amelia K.; Tilburt, Jon C.; Gajic, Ognjen; Montori, Victor M.; Murad, M. Hassan  

Critical Care Medicine: August 2018 - Volume 46 - Issue 8 - p 1209–1216

Objectives: To assess the effectiveness of noninvasive ventilation in patients with acute respiratory failure and do-not-intubate or comfort-measures-only orders. Data Sources: MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science from inception to January 1, 2017. Study Selection: Studies of all design types that enrolled patients in the ICU or hospital ward who received noninvasive ventilation and had preset do-not-intubate or comfort-measures-only orders. Data Extraction: Data abstraction followed Meta-analysis of Observational Studies in Epidemiology guidelines. Data quality was assessed using a modified Newcastle-Ottawa Scale. Data Synthesis: Twenty-seven studies evaluating 2,020 patients with do-not-intubate orders and three studies evaluating 200 patients with comfort-measures-only orders were included. In patients with do-not-intubate orders, the pooled survival was 56% (95% CI, 49–64%) at hospital discharge and 32% (95% CI, 21–45%) at 1 year. Hospital survival was 68% for chronic obstructive pulmonary disease, 68% for pulmonary edema, 41% for pneumonia, and 37% for patients with malignancy. Survival was comparable for patients treated in a hospital ward versus an ICU. Quality of life of survivors was not reduced compared with baseline, although few studies evaluated this. No studies evaluated quality of dying in nonsurvivors. In patients with comfort-measures-only orders, a single study showed that noninvasive ventilation was associated with mild reductions in dyspnea and opioid requirements. Conclusions: A large proportion of patients with do-not-intubate orders who received noninvasive ventilation survived to hospital discharge and at 1 year, with limited data showing no decrease in quality of life in survivors. Provision of noninvasive ventilation in a well-equipped hospital ward may be a viable alternative to the ICU for selected patients. Crucial questions regarding quality of life in survivors, quality of death in nonsurvivors, and the impact of noninvasive ventilation in patients with comfort-measures-only orders remain largely unanswered.

Inclusion of Unstructured Clinical Text Improves Early Prediction of Death or Prolonged ICU Stay*

Inclusion of Unstructured Clinical Text Improves Early Prediction of Death or Prolonged ICU Stay*

by Weissman, Gary E.; Hubbard, Rebecca A.; Ungar, Lyle H.; Harhay, Michael O.; Greene, Casey S.; Himes, Blanca E.; Halpern, Scott D.  

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1125–1132

Objectives: Early prediction of undesired outcomes among newly hospitalized patients could improve patient triage and prompt conversations about patients’ goals of care. We evaluated the performance of logistic regression, gradient boosting machine, random forest, and elastic net regression models, with and without unstructured clinical text data, to predict a binary composite outcome of in-hospital death or ICU length of stay greater than or equal to 7 days using data from the first 48 hours of hospitalization. Design: Retrospective cohort study with split sampling for model training and testing. Setting: A single urban academic hospital. Patients: All hospitalized patients who required ICU care at the Beth Israel Deaconess Medical Center in Boston, MA, from 2001 to 2012. Interventions: None. Measurements and Main Results: Among eligible 25,947 hospital admissions, we observed 5,504 (21.2%) in which patients died or had ICU length of stay greater than or equal to 7 days. The gradient boosting machine model had the highest discrimination without (area under the receiver operating characteristic curve, 0.83; 95% CI, 0.81–0.84) and with (area under the receiver operating characteristic curve, 0.89; 95% CI, 0.88–0.90) text-derived variables. Both gradient boosting machines and random forests outperformed logistic regression without text data (p < 0.001), whereas all models outperformed logistic regression with text data (p < 0.02). The inclusion of text data increased the discrimination of all four model types (p < 0.001). Among those models using text data, the increasing presence of terms “intubated” and “poor prognosis” were positively associated with mortality and ICU length of stay, whereas the term “extubated” was inversely associated with them. Conclusions: Variables extracted from unstructured clinical text from the first 48 hours of hospital admission using natural language processing techniques significantly improved the abilities of logistic regression and other machine learning models to predict which patients died or had long ICU stays. Learning health systems may adapt such models using open-source approaches to capture local variation in care patterns.

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model*

The Development of a Machine Learning Inpatient Acute Kidney Injury Prediction Model*

 by Koyner, Jay L.; Carey, Kyle A.; Edelson, Dana P.; Churpek, Matthew M.

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1070–1077

Objectives: To develop an acute kidney injury risk prediction model using electronic health record data for longitudinal use in hospitalized patients. Design: Observational cohort study. Setting: Tertiary, urban, academic medical center from November 2008 to January 2016. Patients: All adult inpatients without pre-existing renal failure at admission, defined as first serum creatinine greater than or equal to 3.0 mg/dL, International Classification of Diseases, 9th Edition, code for chronic kidney disease stage 4 or higher or having received renal replacement therapy within 48 hours of first serum creatinine measurement. Interventions: None. Measurements and Main Results: Demographics, vital signs, diagnostics, and interventions were used in a Gradient Boosting Machine algorithm to predict serum creatinine–based Kidney Disease Improving Global Outcomes stage 2 acute kidney injury, with 60% of the data used for derivation and 40% for validation. Area under the receiver operator characteristic curve (AUC) was calculated in the validation cohort, and subgroup analyses were conducted across admission serum creatinine, acute kidney injury severity, and hospital location. Among the 121,158 included patients, 17,482 (14.4%) developed any Kidney Disease Improving Global Outcomes acute kidney injury, with 4,251 (3.5%) developing stage 2. The AUC (95% CI) was 0.90 (0.90–0.90) for predicting stage 2 acute kidney injury within 24 hours and 0.87 (0.87–0.87) within 48 hours. The AUC was 0.96 (0.96–0.96) for receipt of renal replacement therapy (n = 821) in the next 48 hours. Accuracy was similar across hospital settings (ICU, wards, and emergency department) and admitting serum creatinine groupings. At a probability threshold of greater than or equal to 0.022, the algorithm had a sensitivity of 84% and a specificity of 85% for stage 2 acute kidney injury and predicted the development of stage 2 a median of 41 hours (interquartile range, 12–141 hr) prior to the development of stage 2 acute kidney injury. Conclusions: Readily available electronic health record data can be used to predict impending acute kidney injury prior to changes in serum creatinine with excellent accuracy across different patient locations and admission serum creatinine. Real-time use of this model would allow early interventions for those at high risk of acute kidney injury.

Increased Heat Generation in Postcardiac Arrest Patients During Targeted Temperature Management Is Associated With Better Outcomes*

Increased Heat Generation in Postcardiac Arrest Patients During Targeted Temperature Management Is Associated With Better Outcomes*

by Uber, Amy J.; Perman, Sarah M.; Cocchi, Michael N.; Patel, Parth V.; Ganley, Sarah E.; Portmann, Jocelyn M.; Donnino, Michael W.; Grossestreuer, Anne V

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1133–1138

Objectives: Assess if amount of heat generated by postcardiac arrest patients to reach target temperature (Ttarget) during targeted temperature management is associated with outcomes by serving as a proxy for thermoregulatory ability, and whether it modifies the relationship between time to Ttarget and outcomes. Design: Retrospective cohort study. Setting: Urban tertiary-care hospital. Patients: Successfully resuscitated targeted temperature management–treated adult postarrest patients between 2008 and 2015 with serial temperature data and Ttarget less than or equal to 34°C. Interventions: None. Measurements and Main Results: Time to Ttarget was defined as time from targeted temperature management initiation to first recorded patient temperature less than or equal to 34°C. Patient heat generation (“heat units”) was calculated as inverse of average water temperature × hours between initiation and Ttarget × 100. Primary outcome was neurologic status measured by Cerebral Performance Category score; secondary outcome was survival, both at hospital discharge. Univariate analyses were performed using Wilcoxon rank-sum tests; multivariate analyses used logistic regression. Of 203 patients included, those with Cerebral Performance Category score 3–5 generated less heat before reaching Ttarget (median, 8.1 heat units [interquartile range, 3.6–21.6 heat units] vs median, 20.0 heat units [interquartile range, 9.0–33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.3 hr [interquartile range, 1.5–4.0 hr] vs median, 3.6 hr [interquartile range, 2.0–5.0 hr]; p = 0.01) than patients with Cerebral Performance Category score 1–2. Nonsurvivors generated less heat than survivors (median, 8.1 heat units [interquartile range, 3.6–20.8 heat units] vs median, 19.0 heat units [interquartile range, 6.5–33.5 heat units]; p = 0.001) and reached Ttarget quicker (median, 2.2 hr [interquartile range, 1.5–3.8 hr] vs median, 3.6 hr [interquartile range, 2.0–5.0 hr]; p = 0.01). Controlling for average water temperature between initiation and Ttarget, the relationship between outcomes and time to Ttarget was no longer significant. Controlling for location, witnessed arrest, age, initial rhythm, and neuromuscular blockade use, increased heat generation was associated with better neurologic (adjusted odds ratio, 1.01 [95% CI, 1.00–1.03]; p = 0.039) and survival (adjusted odds ratio, 1.01 [95% CI, 1.00–1.03]; p = 0.045) outcomes. Conclusions: Increased heat generation during targeted temperature management initiation is associated with better outcomes at hospital discharge and may affect the relationship between time to Ttarget and outcomes.

The gastro-renal effects of intra-abdominal hypertension: Implications for critical care nurses

The gastro-renal effects of intra-abdominal hypertension: Implications for critical care nurses

by Sherree Gray, Martin Christensen, Judy Craft  

Intensive and Critical Care Nursing

Intra-abdominal hypertension is classified as either primary or secondary – primary occurs due to intra-abdominal or retro-peritoneal pathophysiology, whereas secondary results in alterations in capillary fluid dynamics due to factors, such as massive fluid resuscitation and generalised inflammation. The renal and gastro-intestinal effects occur early in the progression of intra-abdominal hypertension, and may lead to poor patient outcomes if not identified. As a direct response to intra-abdominal hypertension, renal function is reduced with remarkable impairment from pressures of around 10 mmHg, oliguria developing at 15 mmHg and anuria developing at 30 mmHg.

Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis*

Combined Biomarkers Predict Acute Mortality Among Critically Ill Patients With Suspected Sepsis*

by Kelly, Brendan J.; Lautenbach, Ebbing; Nachamkin, Irving; Coffin, Susan E.; Gerber, Jeffrey S.; Fuchs, Barry D.; Garrigan, Charles; Han, Xiaoyan; Bilker, Warren B.; Wise, Jacqueleen; Tolomeo, Pam; Han, Jennifer H.; for the Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program  

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1106–1113

Objectives: Sepsis is associated with high early and total in-hospital mortality. Despite recent revisions in the diagnostic criteria for sepsis that sought to improve predictive validity for mortality, it remains difficult to identify patients at greatest risk of death. We compared the utility of nine biomarkers to predict mortality in subjects with clinically suspected bacterial sepsis. Design: Cohort study. Setting: The medical and surgical ICUs at an academic medical center. Subjects: We enrolled 139 subjects who met two or more systemic inflammatory response syndrome (systemic inflammatory response syndrome) criteria and received new broad-spectrum antibacterial therapy. Interventions: We assayed nine biomarkers (α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, procalcitonin, serum amyloid A, serum amyloid P, and tissue plasminogen activator) at onset of suspected sepsis and 24, 48, and 72 hours thereafter. We compared biomarkers between groups based on both 14-day and total in-hospital mortality and evaluated the predictive validity of single and paired biomarkers via area under the receiver operating characteristic curve. Measurements and Main Results: Fourteen-day mortality was 12.9%, and total in-hospital mortality was 29.5%. Serum amyloid P was significantly lower (4/4 timepoints) and tissue plasminogen activator significantly higher (3/4 timepoints) in the 14-day mortality group, and the same pattern held for total in-hospital mortality (Wilcoxon p ≤ 0.046 for all timepoints). Serum amyloid P and tissue plasminogen activator demonstrated the best individual predictive performance for mortality, and combinations of biomarkers including serum amyloid P and tissue plasminogen activator achieved greater predictive performance (area under the receiver operating characteristic curve > 0.76 for 14-d and 0.74 for total mortality). Conclusions: Combined biomarkers predict risk for 14-day and total mortality among subjects with suspected sepsis. Serum amyloid P and tissue plasminogen activator demonstrated the best discriminatory ability in this cohort.

Ventilator Bundle and Its Effects on Mortality Among ICU Patients: A Meta-Analysis*

Ventilator Bundle and Its Effects on Mortality Among ICU Patients: A Meta-Analysis*

by Pileggi, Claudia; Mascaro, Valentina; Bianco, Aida; Nobile, Carmelo G. A.; Pavia, Maria  

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1167–1174

Objectives: To assess the effectiveness of the ventilator bundle in the reduction of mortality in ICU patients. Data Sources: PubMed, Scopus, Web of Science, Cochrane Library for studies published until June 2017. Study Selection: Included studies: randomized controlled trials or any kind of nonrandomized intervention studies, made reference to a ventilator bundle approach, assessed mortality in ICU-ventilated adult patients. Data Extraction: Items extracted: study characteristics, description of the bundle approach, number of patients in the comparison groups, hospital/ICU mortality, ventilator-associated pneumonia–related mortality, assessment of compliance to ventilator bundle and its score. Data Synthesis: Thirteen articles were included. The implementation of a ventilator bundle significantly reduced mortality (odds ratio, 0.90; 95% CI, 0.84–0.97), with a stronger effect with a restriction to studies that reported mortality in ventilator-associated pneumonia patients (odds ratio, 0.71; 95% CI, 0.52–0.97), to studies that provided active educational activities was analyzed (odds ratio, 0.88; 95% CI, 0.78–0.99), and when the role of care procedures within the bundle (odds ratio, 0.87; 95% CI, 0.77–0.99). No survival benefit was associated with compliance to ventilator bundles. However, these results may have been confounded by the differential implementation of evidence-based procedures at baseline, which showed improved survival in the study subgroup that did not report implementation of these procedures at baseline (odds ratio, 0.82; 95% CI, 0.70–0.96). Conclusions: Simple interventions in common clinical practice applied in a coordinated way as a part of a bundle care are effective in reducing mortality in ventilated ICU patients. More prospective controlled studies are needed to define the effect of ventilator bundles on survival outcomes.

Early Enteral Nutrition Provided Within 24 Hours of ICU Admission: A Meta-Analysis of Randomized Controlled Trials*

Early Enteral NutritionProvided Within 24 Hours of ICU Admission: A Meta-Analysis of RandomizedControlled Trials*

 by Tian, Feng; Heighes, Philippa T.; Allingstrup, Matilde J.; Doig, Gordon S.  

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1049–1056

Objectives: To identify, appraise, and synthesize the most current evidence to determine whether early enteral nutrition alters patient outcomes from critical illness. Data Sources: Medline and Embase were searched. The close out date was November 20, 2017. Study Selection: Early enteral nutrition was defined as a standard formula commenced within 24 hours of ICU admission. Comparators included any form of nutrition support “except” early enteral nutrition. Only randomized controlled trials conducted in adult patients requiring treatment in an ICU were eligible for inclusion. Data Extraction: The primary outcome was mortality. Secondary outcomes included pneumonia, duration of mechanical ventilation, and ICU and hospital stay. Data Synthesis: Six-hundred ninety-nine full-text articles were retrieved and screened. Sixteen randomized controlled trials enrolling 3,225 critically ill participants were included. Compared with all other types of nutrition support, commencing enteral nutrition within 24 hours of ICU admission did not result in a reduction in mortality (odds ratio, 1.01; 95% CI, 0.86–1.18; p = 0.91; I2 = 32%). However, there was a differential treatment effect between a priori identified subgroups (p = 0.032): early enteral nutrition reduced mortality compared with delayed enteral intake (odds ratio, 0.45; 95% CI, 0.21–0.95; p = 0.038; I2 = 0%), whereas a mortality difference was not detected between early enteral nutrition and parenteral nutrition (odds ratio, 1.04; 95% CI, 0.89–1.22; p = 0.58; I2 = 30%). Overall, patients who were randomized to receive early enteral nutrition were less likely to develop pneumonia (odds ratio, 0.75; 95% CI, 0.60–0.94; p = 0.012; I2 = 48%). Conclusions: Overall, there was no difference between early enteral nutrition and all other forms of nutrition support. A priori planned subgroup analysis revealed early enteral nutrition reduced mortality and pneumonia compared with delayed enteral intake; however, there were no clear clinical advantages of early enteral nutrition over parenteral nutrition.

Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial*

Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial*

 by Nishikimi, Mitsuaki; Numaguchi, Atsushi; Takahashi, Kunihiko; Miyagawa, Yasuhiro; Matsui, Kota; Higashi, Michiko; Makishi, Go; Matsui, Shigeyuki; Matsuda, Naoyuki  / 

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1099–1105

Objectives: Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients. Design: A single-center, triple-blinded, randomized placebo-controlled trial. Setting: ICU of an academic hospital. Patients: Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission. Interventions: The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU. Measurements and Main Results: A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings. Conclusions: Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly.

What Faces Reveal: A Novel Method to Identify Patients at Risk of Deterioration Using Facial Expressions*

What Faces Reveal: A NovelMethod to Identify Patients at Risk of Deterioration Using Facial Expressions*

by Madrigal-Garcia, Maria Isabel; Rodrigues, Marcos; Shenfield, Alex; Singer, Mervyn; Moreno-Cuesta, Jeronimo  

Critical Care Medicine: July 2018 - Volume 46 - Issue 7 - p 1057–1062

Objectives: To identify facial expressions occurring in patients at risk of deterioration in hospital wards. Design: Prospective observational feasibility study. Setting: General ward patients in a London Community Hospital, United Kingdom. Patients: Thirty-four patients at risk of clinical deterioration. Interventions: A 5-minute video (25 frames/s; 7,500 images) was recorded, encrypted, and subsequently analyzed for action units by a trained facial action coding system psychologist blinded to outcome. Measurements and Main Results: Action units of the upper face, head position, eyes position, lips and jaw position, and lower face were analyzed in conjunction with clinical measures collected within the National Early Warning Score. The most frequently detected action units were action unit 43 (73%) for upper face, action unit 51 (11.7%) for head position, action unit 62 (5.8%) for eyes position, action unit 25 (44.1%) for lips and jaw, and action unit 15 (67.6%) for lower face. The presence of certain combined face displays was increased in patients requiring admission to intensive care, namely, action units 43 + 15 + 25 (face display 1, p < 0.013), action units 43 + 15 + 51/52 (face display 2, p < 0.003), and action units 43 + 15 + 51 + 25 (face display 3, p < 0.002). Having face display 1, face display 2, and face display 3 increased the risk of being admitted to intensive care eight-fold, 18-fold, and as a sure event, respectively. A logistic regression model with face display 1, face display 2, face display 3, and National Early Warning Score as independent covariates described admission to intensive care with an average concordance statistic (C-index) of 0.71 (p = 0.009). Conclusions: Patterned facial expressions can be identified in deteriorating general ward patients. This tool may potentially augment risk prediction of current scoring systems.

Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury

Revisited: A Systematic Review of TherapeuticHypothermia for Adult Patients Following Traumatic Brain Injury

by Watson, Hannah I.; Shepherd, Andrew A.; Rhodes, Jonathan K. J.; Andrews, Peter J. D. 

Objectives: Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia. Data Sources: The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE. Study Selection: Only foreign articles published in the English language were included. Only articles that were randomized controlled trials investigating adult traumatic brain injury sustained following an acute, closed head injury were included. Two authors independently assessed at each stage. Data Extraction: Quality was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias. All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs. p value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using RevMan 5 (Cochrane Collaboration, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Data Synthesis: Twenty-two studies with 2,346 patients are included. Randomized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04–1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group (risk ratio, 0.70; 95% CI, 0.60–0.82; p < 0.00001). Conclusions: Overall, this review is in-keeping with the conclusions published by the most recent randomized controlled trials. High-quality studies show no significant difference in mortality, poor outcomes, or new pneumonia. In addition, this review shows a place for fever control in the management of traumatic brain injury.