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Breast Surgery

Tuesday, 14 August 2018

Blue Light Enhances Bacterial Clearance and Reduces Organ Injury During Sepsis*

by Lewis, Anthony J.; Zhang, Xianghong; Griepentrog, John E.; Yuan, Du; Collage, Richard D.; Waltz, Paul K.; Angus, Derek C.; Zuckerbraun, Brian S.; Rosengart, Matthew R.  

Objectives: The physiology of nearly all mammalian organisms are entrained by light and exhibit circadian rhythm. The data derived from animal studies show that light influences immunity, and these neurophysiologic pathways are maximally entrained by the blue spectrum. Here, we hypothesize that bright blue light reduces acute kidney injury by comparison with either bright red or standard, white fluorescent light in mice subjected to sepsis. To further translational relevance, we performed a pilot clinical trial of blue light therapy in human subjects with appendicitis. Design: Laboratory animal research, pilot human feasibility trial. Setting: University basic science laboratory and tertiary care hospital. Subjects: Male C57BL/6J mice, adult (> 17 yr) patients with acute appendicitis. Interventions: Mice underwent cecal ligation and puncture and were randomly assigned to a 24-hour photoperiod of bright blue, bright red, or ambient white fluorescent light. Subjects with appendicitis were randomized to receive postoperatively standard care or standard care plus high-illuminance blue light. Measurements and Main Results: Exposure to bright blue light enhanced bacterial clearance from the peritoneum, reduced bacteremia and systemic inflammation, and attenuated the degree of acute kidney injury. The mechanism involved an elevation in cholinergic tone that augmented tissue expression of the nuclear orphan receptor REV-ERBα and occurred independent of alterations in melatonin or corticosterone concentrations. Clinically, exposure to blue light after appendectomy was feasible and reduced serum interleukin-6 and interleukin-10 concentrations. Conclusions: Modifying the spectrum of light may offer therapeutic utility in sepsis.

Effect of Body Temperature on Cerebral Autoregulation in Acutely Comatose Neurocritically Ill Patients

by Adatia, Krishma; Geocadin, Romergryko G.; Healy, Ryan; Ziai, Wendy; Ponce-Mejia, Luciano; Anderson-White, Mirinda; Shah, Dhaval; Radzik, Batya R.; Palmisano, Caitlin; Hogue, Charles W.; Brown, Charles; Rivera-Lara, Lucia

Objectives: Impaired cerebral autoregulation following neurologic injury is a predictor of poor clinical outcome. We aimed to assess the relationship between body temperature and cerebral autoregulation in comatose patients. Design: Retrospective analysis of prospectively collected data. Setting: Neurocritical care unit of the Johns Hopkins Hospital. Patients: Eighty-five acutely comatose patients (Glasgow Coma Scale score of ≤ 8) admitted between 2013 and 2017. Interventions: None. Measurement and Main Results: Cerebral autoregulation was monitored using multimodal monitoring with near-infrared spectroscopy–derived cerebral oximetry index. Cerebral oximetry index was calculated as a Pearson correlation coefficient between low-frequency changes in regional cerebral oxygenation saturation and mean arterial pressure. Patients were initially analyzed together, then stratified by temperature pattern over the monitoring period: no change (< 1°C difference between highest and lowest temperatures; n = 11), increasing (≥ 1°C; n = 9), decreasing (≥ 1°C; n = 9), and fluctuating (≥ 1°C difference but no sustained direction of change; n = 56). Mixed random effects models with random intercept and multivariable logistic regression analysis were used to assess the association between hourly temperature and cerebral oximetry index, as well as between temperature and clinical outcomes. Cerebral oximetry index showed a positive linear relationship with temperature (β = 0.04 ± 0.10; p = 0.29). In patients where a continual increase or decrease in temperature was seen during the monitoring period, every 1°C change in temperature resulted in a cerebral oximetry index change in the same direction by 0.04 ± 0.01 (p < 0.001) and 0.02 ± 0.01 (p = 0.12), respectively, after adjusting for PaCO2, hemoglobin, mean arterial pressure, vasopressor and sedation use, and temperature probe location. There was no significant difference in mortality or poor outcome (modified Rankin Scale score of 4–6) between temperature pattern groups at discharge, 3, or 6 months. Conclusions: In acute coma patients, increasing body temperature is associated with worsening cerebral autoregulation as measured by cerebral oximetry index. More studies are needed to clarify the impact of increasing temperature on cerebral autoregulation in patients with acute brain injury.

Long-Term Survival of Young Patients Surviving ICU Admission With Severe Sepsis*

by Abu-Kaf, Heba; Mizrakli, Yuval; Novack, Victor; Dreiher, Jacob  

Objectives: Sepsis remains a disease with a high mortality rate. The study goal was to assess long-term survival of severe sepsis in young patients. Design: Retrospective cohort study. Setting: Patients admitted with sepsis to ICUs in seven tertiary hospitals between 2003 and 2011. Patients: A total of 409 patients less than 45 years who survived to hospital discharge were age and sex matched with 818 patients with infectious disease without sepsis selected from internal medicine or surgical department admissions. Interventions: None. Measurements and Main Results: The median age in sepsis patients and the comparison group was 31 and 32 years, respectively. The proportions of patients surviving after hospital discharge were significantly lower in the sepsis group compared with the control group; among survivors, 6-month, 1-year, and 3-year mortality rates were 0.7% versus 0%, 4.5% versus 0.7%, 7.9% versus 1.2%, and 10.8% versus 1.8%, respectively (p < 0.001 for all). In a multivariate Cox proportional hazards regression model, sepsis was associated with an increased risk of mortality (hazard ratio, 3.79; 95% CI, 2.27–6.32), while controlling for age, Charlson Comorbidity Index, history of stroke, and congestive heart failure. Past the 24-month landmark, sepsis was not found to be an independent risk for mortality (hazard ratio, 1.79; 95% CI, 0.67–4.79). Based on cause of death analysis, chronic underlying comorbidities might explain the excess mortality in patients with sepsis. Conclusions: Young patients experiencing an episode of severe sepsis continue to be at higher risk of long-term mortality. The highest mortality rates were observed during the first 24 months following discharge.

Mortality Measures to Profile Hospital Performance for Patients With Septic Shock*

 by Walkey, Allan J.; Shieh, Meng-Shiou; Liu, Vincent X.; Lindenauer, Peter K.

Objectives: Sepsis care is becoming a more common target for hospital performance measurement, but few studies have evaluated the acceptability of sepsis or septic shock mortality as a potential performance measure. In the absence of a gold standard to identify septic shock in claims data, we assessed agreement and stability of hospital mortality performance under different case definitions. Design: Retrospective cohort study. Setting: U.S. acute care hospitals. Patients: Hospitalized with septic shock at admission, identified by either implicit diagnosis criteria (charges for antibiotics, cultures, and vasopressors) or by explicit International Classification of Diseases, 9th revision, codes. Interventions: None. Measurements and Main Results: We used hierarchical logistic regression models to determine hospital risk–standardized mortality rates and hospital performance outliers. We assessed agreement in hospital mortality rankings when septic shock cases were identified by either explicit International Classification of Diseases, 9th revision, codes or implicit diagnosis criteria. Kappa statistics and intraclass correlation coefficients were used to assess agreement in hospital risk–standardized mortality and hospital outlier status, respectively. Fifty-six thousand six-hundred seventy-three patients in 308 hospitals fulfilled at least one case definition for septic shock, whereas 19,136 (33.8%) met both the explicit International Classification of Diseases, 9th revision, and implicit septic shock definition. Hospitals varied widely in risk-standardized septic shock mortality (interquartile range of implicit diagnosis mortality: 25.4–33.5%; International Classification of Diseases, 9th revision, diagnosis: 30.2–38.0%). The median absolute difference in hospital ranking between septic shock cohorts defined by International Classification of Diseases, 9th revision, versus implicit criteria was 37 places (interquartile range, 16–70), with an intraclass correlation coefficient of 0.72, p value of less than 0.001; agreement between case definitions for identification of outlier hospitals was moderate (kappa, 0.44 [95% CI, 0.30–0.58]). Conclusions: Risk-standardized septic shock mortality rates varied considerably between hospitals, suggesting that septic shock is an important performance target. However, efforts to profile hospital performance were sensitive to septic shock case definitions, suggesting that septic shock mortality is not currently ready for widespread use as a hospital quality measure.

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  

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?*

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*

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

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

 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  

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*

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  

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*

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

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.