Determining predictors of underlying etiology and clinical deterioration in patients with physiologic instability in the emergency department

Thesis (M.A.)--Boston UniversityShock is a critical state defined by inadequate oxygen delivery to tissues. It is well known in the critical care community that early diagnosis and treatment of shock are crucial to improving patient outcomes. However, in many cases, when a state of circulatory shock has been reached, irreversible damage already occurred. In the present study, we broadened our patient cohort from those with shock to those with physiologic instability with the intent of finding predictive factors that allow us to recognize when a patient is at risk for deterioration or when it is already occurring. These patients included patients with pre-shock, shock, and other forms of dysfunction. The purpose of this study was to determine the predictors of underlying etiology of physiologic instability as well as the likelihood of clinical deterioration in these various states, using elements from the physical exam, history, laboratory values, and vital sign measurements. This study was a prospective observational study of patients, from November 15, 2012 to March 1, 2013, found to have physiologic instability in the emergency department at an urban, academic tertiary-care hospital with 55,000 annual visits. Physiologic instability was defined as any one of the following abnormalities: heart rate (HR) > 130, respiratory rate (RR>24), shock index (SI) > 1, systolic blood pressure (SBP) 4.0 mmol/L, for a time period of more than five minutes. We identified 540 patients, 74.8% of which were included. Data describing epidemiology, and elements from the patient history and physical exam were abstracted from physician charts and the final etiology of physiologic instability, defined as septic, cardiogenic, hypovolemic, hemorrhagic, or other, was adjudicated by a physician. Blood samples from a subset of our patient group were collected from the hospital hematology laboratory and sent to the Wyss Institute to be analyzed using a novel bacterial detection assay. All of the covariates that data was collected for were analyzed to determine their diagnostic and prognostic value. [TRUNCATED

The Royal Free Hospital score: a calibrated prognostic model for patients with cirrhosis admitted to intensive care unit. Comparison with current models and CLIF-SOFA score

Prognosis for patients with cirrhosis admitted to intensive care unit (ICU) is poor. ICU prognostic models are more accurate than liver-specific models. We identified predictors of mortality, developed a novel prognostic score (Royal Free Hospital (RFH) score), and tested it against established prognostic models and the yet unvalidated Chronic Liver Failure-Sequential Organ Failure Assessment (CLIF-SOFA) model

Outcomes of patients with acute respiratory failure on veno-venous extracorporeal membrane oxygenation requiring additional circulatory support by veno-venoarterial extracorporeal membrane oxygenation

ObjectiveVeno-venous (V-V) extracorporeal membrane oxygenation (ECMO) is increasingly used to support patients with severe acute respiratory distress syndrome (ARDS). In case of additional cardio-circulatory failure, some experienced centers upgrade the V-V ECMO with an additional arterial return cannula (termed V-VA ECMO). Here we analyzed short- and long-term outcome together with potential predictors of mortality.DesignMulticenter, retrospective analysis between January 2008 and September 2021.SettingThree tertiary care ECMO centers in Germany (Hannover, Bonn) and Switzerland (Zurich).PatientsSeventy-three V-V ECMO patients with ARDS and additional acute cardio-circulatory deterioration required an upgrade to V-VA ECMO were included in this study.Measurements and main resultsFifty-three patients required an upgrade from V-V to V-VA and 20 patients were directly triple cannulated. Median (Interquartile Range) age was 49 (28–57) years and SOFA score was 14 (12–17) at V-VA ECMO upgrade. Vasoactive-inotropic score decreased from 53 (12–123) at V-VA ECMO upgrade to 9 (3–37) after 24 h of V-VA ECMO support. Weaning from V-VA and V-V ECMO was successful in 47 (64%) and 40 (55%) patients, respectively. Duration of ECMO support was 12 (6–22) days and ICU length of stay was 32 (16–46) days. Overall ICU mortality was 48% and hospital mortality 51%. Two additional patients died after hospital discharge while the remaining patients survived up to two years (with six patients being lost to follow-up). The vast majority of patients was free from higher degree persistent organ dysfunction at follow-up. A SOFA score > 14 and higher lactate concentrations at the day of V-VA upgrade were independent predictors of mortality in the multivariate regression analysis.ConclusionIn this analysis, the use of V-VA ECMO in patients with ARDS and concomitant cardiocirculatory failure was associated with a hospital survival of about 50%, and most of these patients survived up to 2 years. A SOFA score > 14 and elevated lactate levels at the day of V-VA upgrade predict unfavorable outcome

Cumulative Prognostic Score Predicting Mortality in Patients Older Than 80 Years Admitted to the ICU.

OBJECTIVES: To develop a scoring system model that predicts mortality within 30 days of admission of patients older than 80 years admitted to intensive care units (ICUs). DESIGN: Prospective cohort study. SETTING: A total of 306 ICUs from 24 European countries. PARTICIPANTS: Older adults admitted to European ICUs (N = 3730; median age = 84 years [interquartile range = 81-87 y]; 51.8% male). MEASUREMENTS: Overall, 24 variables available during ICU admission were included as potential predictive variables. Multivariable logistic regression was used to identify independent predictors of 30-day mortality. Model sensitivity, specificity, and accuracy were evaluated with receiver operating characteristic curves. RESULTS: The 30-day-mortality was 1562 (41.9%). In multivariable analysis, these variables were selected as independent predictors of mortality: age, sex, ICU admission diagnosis, Clinical Frailty Scale, Sequential Organ Failure Score, invasive mechanical ventilation, and renal replacement therapy. The discrimination, accuracy, and calibration of the model were good: the area under the curve for a score of 10 or higher was .80, and the Brier score was .18. At a cut point of 10 or higher (75% of all patients), the model predicts 30-day mortality in 91.1% of all patients who die. CONCLUSION: A predictive model of cumulative events predicts 30-day mortality in patients older than 80 years admitted to ICUs. Future studies should include other potential predictor variables including functional status, presence of advance care plans, and assessment of each patient's decision-making capacity

Circulatory Failure and Outcome in Out-of-Hospital Cardiac Arrest

Circulatory failure is considered one of the entities of the post cardiac arrest syndrome contributing to poor outcome. It is reported at 15-70% of all patients successfully resuscitated from out-of-hospital cardiac arrest (OHCA). The pathophysiologic mechanism is attributed to limitation of cell metabolism due to inadequate supply of oxygen, caused by pump or conduction failure within the cardiovascular system. The term, however, remains poorly defined and no general consensus on definition exists. Due to the heterogeneity in definition and mechanism, the association with outcome for circulatory failure in cardiac arrest varies, and is partly conflicting. In this thesis we investigate four different surrogate measures of circulatory failure and their association with outcome after out-of-hospital cardiac arrest.Paper I: We conducted a post hoc analysis of adult, unconscious survivors of out-of-hospital included in the TTM- 1 trial, to investigate lactate, a marker of anaerobic metabolism, as a predictor of short-term survival. 877 patients had admission lactate sampled and were included in analyses. Lactate at admission and 12 hours were independently associated with 30-day survival in a model adjusted for known predictors of survival after out-of- hospital cardiac arrest. Estimations of area under the receiver operator curve indicate a poor precision for predicting short time survival, limiting the clinical utility for lactate metrics as a sole predictor of outcome.Paper II: Copeptin, physiologically associated with vasoregulatory status, was analyzed as a marker of severity of circulatory failure, in this post hoc analysis of 690 patients included in the TTM-1 biobank sub study. Copeptin measured at 24 hours was found to be independently associated with 30-day survival, circulatory etiology of death and cardiovascular deterioration.Paper III: In this retrospective registry study of 4004 adult, unconscious patients resuscitated from OHCA, a composite definition of circulatory shock (systolic blood pressure < 90 mmHg, or use of inotropes/vasoactive agents, or clinical signs of hypoperfusion), compared to no circulatory shock on admission was associated with worse odds of good neurological outcome at hospital discharge in an analysis adjusted for baseline comorbidity and predictors of outcome.Paper IV: Patients with moderate vasopressor support (defined as mean arterial pressure < 70 mmHg and/or adrenalin/noradrenaline dose ≤ 0.25 μg/kg/min) treated with target temperature management at 33oC had higher incidence of 6-month mortality compared to patients treated with normothermia, in a post hoc analysis of 1861 OHCA patients included in the TTM-2 trial. No difference in mortality was detected with temperature intervention in patients with no- or high vasopressor support. The increase in mortality seems to be driven by an increase in 30- day incidence of non-neurological death in patients treated at 33oC, compared to normothermia, in the moderate vasopressor support group, while no difference in etiology of death was detected for intervention in the no-, and high vasopressor support group.Conclusion: Circulatory failure after OHCA is associated with outcome, however, the mechanism is complex and probably contains multiple pathways

Identification of the severe sepsis patient at triage: a prospective analysis of the Australasian Triage Scale

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objective This study aims to investigate the accuracy and validity of the Australasian Triage Scale (ATS) as a tool to identify and manage in a timely manner the deteriorating patient with severe sepsis. Methods This was a prospective observational study conducted in five sites of adult patients. Keywords and physiological vital signs data from triage documentation were analysed for the ‘identified’ status compared with confirmed diagnosis of severe sepsis after admission to the intensive care unit. The primary outcome is the accuracy and validity of the ATS Triage scale categories to identify a prespecified severe sepsis population at triage. Secondary outcome measures included time compliance, antimicrobial administration and mortality prediction. Statistical analysis included parameters of diagnostic performance. Adjusted multivariate logistic regression analysis was applied to mortality prediction. Results Of 1022 patients meeting the criteria for severe sepsis, 995 were triaged through the emergency department, 164 with shock. Only 53% (n=534) were identified at triage. The overall sensitivity of the ATS to identify severe sepsis was 71%. ATS 3 was the most accurate (likelihood ratio positive, 2.45, positive predictive value 0.73) and ATS 2 the most valid (area under the curve 0.567) category. Identified cases were more likely to survive (OR 0.81, 95% CI 0.697 to 0.94, p4 (OR 1.63, 95% CI 1.10 to 2.89, p<0.001) and ATS 1 category (OR 1.55, 95% CI 1.09 to 2.35, p<0.005). Conclusions The ATS and its categories is a sensitive and moderately accurate and valid tool for identifying severe sepsis in a predetermined group, but lacks clinical efficacy and safety without further education or quality improvement strategies targeted to the identification of severe sepsis

Acute kidney injury after ascending aorta and aortic arch replacement surgery with moderate hypothermia, circulatory arrest and cardiopulmonary bypass

The correlation between deep hypothermic circulatory arrest (DHCA) and cardiopulmonary bypass (CPB) and their effect on renal function is still not clear enough. Renal failure after surgical replacement of ascending aorta in DHCA und CPB in patients due to aneurysm or calcification represents nowadays a major concern. This major study focused on the impact of DHCA and CPB on renal function in those patients. In the presented retrospective cohort study, the database for Kiel University clinic was searched for patients with aortic arch and aortic ascending replacement surgeries with HCA and CPB techniques. Between January 1, 2001, and December 31, 2017. 1359 patients were found in our database with different causes for those operations such as ascending aortic and aortic arch -aneurysm, -dissections or -calcifications, who were operated upon. The patient records were abstracted, and the data were entered into a database and then revised for accuracy by randomly checking chart data with data on the computer. Pre- and postoperative renal function are observed and documented. Acute kidney injury (AKI) was classified according to the current ‘Kidney Disease: Improving Global Outcomes’ (KDIGO} Guidelines. The potential correlation of the length of DHCA-CPBT and worsening renal function was evaluated using Spearman’s rank correlation. The data obtained from our analysis outlined the predictive role of longer moderate HCA and CPB times a for AKI. The complex multifactorial pathophysiology plays an underlying prognostic role regarding the outcome for this life-threatening complication and requires more focused clinical trials to illustrate the contradicting results from the previous analyses regarding the causing pathophysiology. In addition to that we found out that the incidence of AKI after ascending aorta and aortic arch replacement surgery using moderate HCA and CPB is approximately 15 %. And those patients with Postopertaitve AKI have an increase in the mortaliy rate by more than 6 times and 3 times longer ICU sta

Relationship between Pre-Implant Interleukin-6 Levels, Inflammatory Response, and Early Outcome in Patients Supported by Left Ventricular Assist Device: A Prospective Study

Purpose: The immune response is crucial in the development of multi-organ failure (MOF) and complications in end-stage heart failure patients supported by left ventricular assist device (LVAD). However, at pre-implant, the association between inflammatory state and post-LVAD outcome is not yet clarified. Aim of the study was to assess the relationship among preimplant levels of immune-related cytokines, postoperative inflammatory response and 3-month outcome in LVAD-patients. Methods: In 41 patients undergoing LVAD implantation, plasma levels of interleukin (IL)-6, IL-8, crucial for monocyte modulation, and urine neopterin/creatinine ratio (Neo/Cr), marker of monocyte activation, were assessed preoperatively, at 3 days, 1 and 4 weeks post-LVAD. MOF was evaluated by total sequential organ failure assessment (tSOFA) score. Intensive care unit (ICU)-death and/or post-LVAD tSOFA $11 was considered as main adverse outcome. Length of ICU-stay, 1 weektSOFA score, hospitalisation and 3-month survival were considered additional end-points. Results: During ICU-stay, 8 patients died of MOF, while 8 of the survivors experienced severe MOF with postoperative tSOFA score$11. Pre-implant level of IL-6 $ 8.3 pg/mL was identified as significant marker of discrimination between patients with or without adverse outcome (OR 6.642, 95% CI 1.201-36.509, p = 0.030). Patients were divided according to pre-implant IL-6 cutoff of 8.3 pg/ml in A [3.5 (1.2-6.1) pg/mL] and B [24.6 (16.4-38.0) pg/mL] groups. Among pre-implant variables, only white blood cells count was independently associated with pre-implant IL-6 levels higher than 8.3 pg/ml (OR 1.491, 95% CI 1.004-2.217, p = 0.048). The ICU-stay and hospitalisation resulted longer in B-group (p = 0.001 and p = 0.030, respectively). Postoperatively, 1 week-tSOFA score, IL-8 and Neo/Cr levels were higher in B-group. Conclusions: LVAD-candidates with elevated pre-implant levels of IL-6 are associated, after intervention, to higher release of monocyte activation related-markers, a clue for the development of MOF, longer clinical course and poor outcome

The Surviving Sepsis Campaign: research priorities for the administration, epidemiology, scoring and identification of sepsis

Epidemiologia; Disfunció d'òrgans; SèpsiaEpidemiology; Organ dysfunction; SepsisEpidemiología; Disfunción de órganos; SepsisObjective To identify priorities for administrative, epidemiologic and diagnostic research in sepsis. Design As a follow-up to a previous consensus statement about sepsis research, members of the Surviving Sepsis Campaign Research Committee, representing the European Society of Intensive Care Medicine and the Society of Critical Care Medicine addressed six questions regarding care delivery, epidemiology, organ dysfunction, screening, identification of septic shock, and information that can predict outcomes in sepsis. Methods Six questions from the Scoring/Identification and Administration sections of the original Research Priorities publication were explored in greater detail to better examine the knowledge gaps and rationales for questions that were previously identified through a consensus process. Results The document provides a framework for priorities in research to address the following questions: (1) What is the optimal model of delivering sepsis care?; (2) What is the epidemiology of sepsis susceptibility and response to treatment?; (3) What information identifies organ dysfunction?; (4) How can we screen for sepsis in various settings?; (5) How do we identify septic shock?; and (6) What in-hospital clinical information is associated with important outcomes in patients with sepsis? Conclusions There is substantial knowledge of sepsis epidemiology and ways to identify and treat sepsis patients, but many gaps remain. Areas of uncertainty identified in this manuscript can help prioritize initiatives to improve an understanding of individual patient and demographic heterogeneity with sepsis and septic shock, biomarkers and accurate patient identification, organ dysfunction, and ways to improve sepsis care.The authors volunteered their time to producing this manuscript and no funding was used to produce it