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Breast Surgery

Friday 16 September 2016

Metabolite Profiles in Sepsis: Developing Prognostic Tools Based on the Type of Infection

Metabolite Profiles in Sepsis: Developing Prognostic Tools Based on the Type of Infection

Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1649–1662

 Neugebauer, S et al.

Objectives: Currently used biomarkers insufficiently discriminate between patients with systemic inflammatory response syndrome of non-infectious origin and sepsis. The aim of this study was to identify surrogate markers that distinguish between systemic inflammatory response syndrome and sepsis as well as the underlying type of infection by targeted metabolomics. Design: Retrospective analysis. Settings: Six sites of the Hellenic Sepsis Study Group and at Jena University Hospital. Patients: A total of 406 patients were analyzed: 66 fulfilling criteria for diagnosis of systemic inflammatory response syndrome, 100 for community-acquired pneumonia, 112 for urinary tract infection, 83 for intra-abdominal infection and 45 for bloodstream infection. Patients were divided into test cohort (n = 268) and confirmation cohort (n = 138). Interventions: A total of 186 metabolites were determined by liquid chromatography tandem mass spectrometry. Measurements and Main Results: Serum concentrations of most acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to systemic inflammatory response syndrome. A regression model combining the sphingolipid SM C22:3 and the glycerophospholipid lysoPCaC24:0 was discovered for sepsis diagnosis with a sensitivity of 84.1% and specificity of 85.7%. Furthermore, specific metabolites could be used for the discrimination of different types of infection. The glycerophospholipid lysoPCaC26:1 identified patients with community-acquired pneumonia in sepsis or severe sepsis/septic shock. Within severe sepsis/septic shock, patients with bloodstream infection could be discriminated by a decrease of acetylornithine. Changes of metabolites between sepsis and severe sepsis/septic shock also varied according to the underlying type of infection, showing that putrescine, lysoPCaC18:0 and SM C16:1 are associated with unfavorable outcome in community-acquired pneumonia, intra-abdominal infections and bloodstream infections, respectively. Conclusions: Using a metabolomics approach, single metabolites are identified that allow a good, albeit at about 14% false positive rate of sepsis diagnosis. Additionally, metabolites might be also useful for differentiation and prognosis according to the type of underlying infection. However, confirmation of the findings in ongoing studies is mandatory before they can be applied in the development of novel diagnostic tools for the management of sepsis.

Implementing a pressure ulcer prevention bundle in an adult intensive care

Implementing a pressure ulcer prevention bundle in an adult intensive care

Intensive and Critical care Nursing Article in Press

Tayyib N,  Coyer F, LewisP A

The incidence of pressure ulcers (PUs) in intensive care units (ICUs) is high and numerous strategies have been implemented to address this issue. One approach is the use of a PU prevention bundle. However, to ensure success care bundle implementation requires monitoring to evaluate the care bundle compliance rate, and to evaluate the effectiveness of implementation strategies in facilitating practice change.

Liberal Glycemic Control in Critically Ill Patients With Type 2 Diabetes: An Exploratory Study

Liberal Glycemic Control in Critically Ill Patients With Type 2 Diabetes: An Exploratory Study

Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1695–1703

Kar, Palash

Objectives: The optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a “ liberal” approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe. Design: Prospective, open-label, sequential-period exploratory study. Setting: Medical-surgical ICU. Patients: During sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission). Intervention: During the “standard care” period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the “liberal” period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L. Measurements and Main Results: Time-weighted mean glucose concentrations and the number and duration of moderate (< 4.0 mmol/L) and severe (≤ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TWglucoseday 0–7, standard care: 9.3 [1.8] vs liberal: 10.3 [2.1] mmol/L; p = 0.02) and nadir blood glucose (4.4 [1.5] vs 5.5 [1.6] mmol/L; p < 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19–1.13]; p = 0.09). Ten patients (19%) during the standard period and one patient (3%) during the liberal period had recurrent episodes of moderate-severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%]; p < 0.01). Biomarker data and clinical outcomes were similar. Conclusions: In critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia.

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival

Cerebral Oximetry During Cardiac Arrest: A Multicenter Study of Neurologic Outcomes and Survival
Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1663–1674

 Parnia, Sam et alObjectives: Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. Design: Multicenter prospective study of in-hospital cardiac arrest. Setting: Five medical centers in the United States and the United Kingdom. Patients: Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1–2. Interventions: Cerebral oximetry monitoring. Measurements and Main Results: Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1–2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1–2 versus cerebral performance category 3–5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69–0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94–100) and 100% negative predictive value (95% CI, 79–100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95–100) and 93% positive predictive value (95% CI, 66–100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1–2 (area under the curve, 0.79; 95% CI, 0.70–0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46–95), 72% specificity (95% CI, 65–79), and 98% negative predictive value (95% CI, 93–100) for cerebral performance category 1–2. Conclusions: Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes.

Predicting Performance Status 1 Year After Critical Illness in Patients 80 Years or Older: Development of a Multivariable Clinical Prediction Model

Predicting Performance Status 1 Year After Critical Illness in Patients 80 Years or Older: Development of a Multivariable Clinical Prediction Model


Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1718–1726

Heyland, Daren K et al

Objective: We sought to develop and internally validate a clinical prediction model to estimate the outcome of very elderly patients 12 months after being admitted to the ICU. Design: Prospective, longitudinal cohort study. Setting: Twenty-two Canadian ICUs. Patients: We recruited 527 patients 80 years or older who had a medical or urgent surgical diagnosis and were admitted to an ICU for at least 24 hours. Measurements and Main Results: At baseline, we completed a comprehensive geriatric assessment of enrolled patients; survival and functional status was determined 12 months later. We defined recovery from critical illness as Palliative Performance Scale score of greater than or equal to 60. We used logistic regression analysis to examine factors associated with this outcome. Of the 434 patients (82%) whose Palliative Performance Scale was known at 12 months, 50% had died and 29% (126/434) had a score of greater than or equal to 60. In the multivariable model, we found that being married, having a primary diagnosis of emergency coronary artery bypass grafting or valve replacement, and higher baseline Palliative Performance Scale were independently predictive of a 12-month Palliative Performance Scale score of greater than or equal to 60. Male sex, primary diagnosis of stroke, and higher Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity index, or clinical frailty scale were independently predictive of Palliative Performance Scale score of less than 60. Conclusion: Approximately one-quarter of very old ICU patients achieve a reasonable level of function 1 year after admission. This prediction model applied to individual patients may be helpful in decision making about the utility of life support for very elderly patients who are admitted to the ICU.

Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation

Signatures of Subacute Potentially Catastrophic Illness in the ICU: Model Development and Validation

Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1639–1648

Moss, Travis J.


Objectives: Patients in ICUs are susceptible to subacute potentially catastrophic illnesses such as respiratory failure, sepsis, and hemorrhage that present as severe derangements of vital signs. More subtle physiologic signatures may be present before clinical deterioration, when treatment might be more effective. We performed multivariate statistical analyses of bedside physiologic monitoring data to identify such early subclinical signatures of incipient life-threatening illness. Design: We report a study of model development and validation of a retrospective observational cohort using resampling (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis type 1b internal validation) and a study of model validation using separate data (type 2b internal/external validation). Setting: University of Virginia Health System (Charlottesville), a tertiary-care, academic medical center. Patients: Critically ill patients consecutively admitted between January 2009 and June 2015 to either the neonatal, surgical/trauma/burn, or medical ICUs with available physiologic monitoring data. Interventions: None. Measurements and Main Results: We analyzed 146 patient-years of vital sign and electrocardiography waveform time series from the bedside monitors of 9,232 ICU admissions. Calculations from 30-minute windows of the physiologic monitoring data were made every 15 minutes. Clinicians identified 1,206 episodes of respiratory failure leading to urgent unplanned intubation, sepsis, or hemorrhage leading to multi-unit transfusions from systematic individual chart reviews. Multivariate models to predict events up to 24 hours prior had internally validated C-statistics of 0.61–0.88. In adults, physiologic signatures of respiratory failure and hemorrhage were distinct from each other but externally consistent across ICUs. Sepsis, on the other hand, demonstrated less distinct and inconsistent signatures. Physiologic signatures of all neonatal illnesses were similar. Conclusions: Subacute potentially catastrophic illnesses in three diverse ICU populations have physiologic signatures that are detectable in the hours preceding clinical detection and intervention. Detection of such signatures can draw attention to patients at highest risk, potentially enabling earlier intervention and better outcomes.

Incidence and Etiology of Potentially Preventable ICU Readmissions

Incidence and Etiology of Potentially Preventable ICU Readmissions

Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1704–1709


 Al-Jaghbeer, Mohammed J

Objectives: The rate of unplanned ICU readmissions is often considered a measure of hospital performance. However, the degree to which these readmissions are preventable and the causes of preventable readmissions are unknown, creating uncertainty about the feasibility and value of reducing ICU readmission rates. To inform this issue, we sought to determine the frequency and underlying causes of potentially preventable ICU readmissions. Design: Retrospective cohort study. Setting: Urban, academic medical center in the mid-Atlantic United States. Patients: Adult patients discharged alive from their first ICU admission with an unplanned readmission within 48 hours of discharge. Measurements and Main Results: Each patient’s medical chart was reviewed by two independent investigators who rated each readmission’s preventability according to standardized scale and assessed the etiology of both preventable and nonpreventable readmissions. We assessed concordance between raters using the κ statistic and resolved disagreements through iterative discussion. Of 136 readmissions in the final analysis, 16 (11.8%; 95% CI, 6.9–18.4) were considered preventable and 120 (88.2%; 95% CI, 81.5–93.1) were considered nonpreventable. Of nonpreventable readmissions, 67 were due to a new clinical problem and 53 were due to an existing clinical problem. Among preventable readmissions, six were attributable to system errors, six were attributable to management errors, two were attributable to procedural events, one was attributable to a diagnostic error, and one was attributable to a medication error. Compared to nonpreventable readmissions, preventable readmissions tended to have shorter index ICU lengths of stay (2 vs 3 d; p = 0.05) and a shorter duration of time on the ward prior to readmission (16.6 vs 23.6 hr; p = 0.05). Conclusions: The majority of early ICU readmissions are nonpreventable, raising important concerns about ICU readmission rates as a measure of hospital performance.

Defining Futile and Potentially Inappropriate Interventions: A Policy Statement From the Society of Critical Care Medicine Ethics Committee

Defining Futile and Potentially Inappropriate Interventions: A Policy Statement From the Society of Critical Care Medicine Ethics Committee

Critical Care Medicine:
September 2016 - Volume 44 - Issue 9 - p 1769–1774

Kon, Alexander A et al

Objectives: The Society of Critical Care Medicine and four other major critical care organizations have endorsed a seven-step process to resolve disagreements about potentially inappropriate treatments. The multiorganization statement (entitled: An official ATS/AACN/ACCP/ESICM/SCCM Policy Statement: Responding to Requests for Potentially Inappropriate Treatments in Intensive Care Units) provides examples of potentially inappropriate treatments; however, no clear definition is provided. This statement was developed to provide a clear definition of inappropriate interventions in the ICU environment. Design: A subcommittee of the Society of Critical Care Medicine Ethics Committee performed a systematic review of empirical research published in peer-reviewed journals as well as professional organization position statements to generate recommendations. Recommendations approved by consensus of the full Society of Critical Care Medicine Ethics Committees and the Society of Critical Care Medicine Council were included in the statement. Measurements and Main Results: ICU interventions should generally be considered inappropriate when there is no reasonable expectation that the patient will improve sufficiently to survive outside the acute care setting, or when there is no reasonable expectation that the patient’s neurologic function will improve sufficiently to allow the patient to perceive the benefits of treatment. This definition should not be considered exhaustive; there will be cases in which life-prolonging interventions may reasonably be considered inappropriate even when the patient would survive outside the acute care setting with sufficient cognitive ability to perceive the benefits of treatment. When patients or surrogate decision makers demand interventions that the clinician believes are potentially inappropriate, the seven-step process presented in the multiorganization statement should be followed. Clinicians should recognize the limits of prognostication when evaluating potential neurologic outcome and terminal cases. At times, it may be appropriate to provide time-limited ICU interventions to patients if doing so furthers the patient’s reasonable goals of care. If the patient is experiencing pain or suffering, treatment to relieve pain and suffering is always appropriate. Conclusions: The Society of Critical Care Medicine supports the seven-step process presented in the multiorganization statement. This statement provides added guidance to clinicians in the ICU environment.

Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure

Spontaneous Effort During Mechanical Ventilation: Maximal Injury With Less Positive End-Expiratory Pressure

Critical Care Medicine:
August 2016 - Volume 44 - Issue 8 - p e678–e688

Yoshida T  et al
Objectives: We recently described how spontaneous effort during mechanical ventilation can cause “pendelluft,” that is, displacement of gas from nondependent (more recruited) lung to dependent (less recruited) lung during early inspiration. Such transfer depends on the coexistence of more recruited (source) liquid-like lung regions together with less recruited (target) solid-like lung regions. Pendelluft may improve gas exchange, but because of tidal recruitment, it may also contribute to injury. We hypothesize that higher positive end-expiratory pressure levels decrease the propensity to pendelluft and that with lower positive end-expiratory pressure levels, pendelluft is associated with improved gas exchange but increased tidal recruitment. Design: Crossover design. Setting: University animal research laboratory. Subjects: Anesthetized landrace pigs. Interventions: Surfactant depletion was achieved by saline lavage in anesthetized pigs, and ventilator-induced lung injury was produced by ventilation with high tidal volume and low positive end-expiratory pressure. Ventilation was continued in each of four conditions: positive end-expiratory pressure (low or optimized positive end-expiratory pressure after recruitment) and spontaneous breathing (present or absent). Tidal recruitment was assessed using dynamic CT and regional ventilation/perfusion using electric impedance tomography. Esophageal pressure was measured using an esophageal balloon manometer. Measurements and Results: Among the four conditions, spontaneous breathing at low positive end-expiratory pressure not only caused the largest degree of pendelluft, which was associated with improved ventilation/perfusion matching and oxygenation, but also generated the greatest tidal recruitment. At low positive end-expiratory pressure, paralysis worsened oxygenation but reduced tidal recruitment. Optimized positive end-expiratory pressure decreased the magnitude of spontaneous efforts (measured by esophageal pressure) despite using less sedation, from –5.6 ± 1.3 to –2.0 ± 0.7 cm H2O, while concomitantly reducing pendelluft and tidal recruitment. No pendelluft was observed in the absence of spontaneous effort. Conclusions: Spontaneous effort at low positive end-expiratory pressure improved oxygenation but promoted tidal recruitment associated with pendelluft. Optimized positive end-expiratory pressure (set after lung recruitment) may reverse the harmful effects of spontaneous breathing by reducing inspiratory effort, pendelluft, and tidal recruitment.