Association of frailty with days alive at home in critically ill patients undergoing emergency general surgery: a population-based cohort study.

BACKGROUND: Frailty is an established risk factor for morbidity and mortality in older patients undergoing surgery. In people with critical illness before surgery, few data describe patient-centred outcomes. Our objective was to estimate the association of frailty with postoperative days alive at home in older critically ill patients requiring emergency general surgery. METHODS: A retrospective population-based cohort study was conducted using linked administrative health data in Ontario, Canada from 2009 to 2019. All individuals aged ≥66 yr with an ICU admission before emergency general surgery were included. We compared the count of days alive at home at 30 and 365 days after surgery based on frailty status using a validated, multidimensional index. Unadjusted and multilevel, multivariable adjusted effect estimates were calculated. A sensitivity analysis based on early recovery category was performed. RESULTS: We identified 7003 eligible patients; 2063 (29.5%) lived with frailty. At 30 days, mean days alive at home with frailty were 4.5 (standard deviation 8.2) and 7.6 (standard deviation 10.2) in those without frailty. In adjusted analysis, frailty was associated with fewer days alive at home at 30 (ratio of means [RoM] 0.68; 95% confidence interval [CI]: 0.60-0.78; P<0.001) and 365 days (RoM 0.72; 95% CI: 0.64-0.82; P<0.001). Individuals with frailty had a higher probability of poor recovery status, with effects increasing across the first postoperative month. CONCLUSIONS: In patients with critical illness requiring emergency general surgery, frailty is associated with fewer days alive at home. This information should be discussed with critically ill patients before emergent surgical intervention to better inform decision-making.

Association of frailty with days alive at home after cardiac surgery: a population-based cohort study.

BACKGROUND: Frailty is a geriatric syndrome that leaves people vulnerable to adverse outcomes. In cardiac surgery, minimal data describe associations between frailty and patient-centred outcomes. Our objective was to estimate the association between frailty and days alive at home after cardiac surgery. METHODS: We conducted a population-based cohort study using linked health administrative data in the Canadian province of Ontario. All individuals >65 yr at the time of cardiac surgery were assigned a frailty score using a validated frailty index. Days alive and at home in the 30 and 365 days after surgery were calculated. The unadjusted and adjusted associations between frailty and days alive at home were calculated. RESULTS: We identified 61 389 patients from 2009 to 2015. Frailty was associated with reduced days at home within 30 days (adjusted ratio of means for every 10% increase in frailty=0.79; 95% confidence interval [CI], 0.78-0.81; P<0.0001) and 365 days (adjusted ratio of means for every 10% increase in frailty=0.92; 95% CI, 0.91-0.93; P<0.0001) of surgery. Results were consistent in sensitivity analyses (5.0 fewer days alive at home [95% CI, 4.8-5.2] within 30 days and 9.0 fewer days alive at home [95% CI, 8.7-9.2] within 365 days after surgery). CONCLUSION: Frailty is associated with a reduction in days alive at home after major cardiac surgery. This information should be considered in prognostic discussions before surgery and in care planning for vulnerable older patient groups. Days alive at home may be a useful outcome for routine measurement in quality, reporting, and studies using routinely collected data.

Predicting 1-Year Mortality After Cardiac Surgery Complicated by Prolonged Critical Illness: Derivation and Validation of a Population-Based Risk Model.

OBJECTIVES: Patients experiencing prolonged critical illness after cardiac surgery represent a resource- intensive group with a high risk of mortality. The authors sought to derive and validate a multivariate model that accurately predicts 1-year mortality in people who have been critically ill for at least 1 week after cardiac surgery. DESIGN: This was a retrospective population-based cohort study using linked administrative data. SETTING: Eleven hospitals providing cardiac surgical care in the Canadian province of Ontario. PARTICIPANTS: All adult patients aged ≥18 years undergoing 1 of the 5 most common major cardiac surgical procedures between April 1, 2009, and March 31, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors' primary exposure was presence in an intensive care unit on the seventh postoperative day (POD7) and the primary outcome was all-cause mortality occurring after POD7 and within 1 year from the date of surgery. Candidate predictors included patient demographics, surgical details, preoperative medical conditions, postoperative status, and life supportive therapies utilized on POD7. Descriptive statistics were used to compare predictor variables between participants who did or did not die in the year after surgery. The prediction model was derived in the full data set using logistic regression and the prespecified set of predictor variables. A total of 2,031 individuals remained in an intensive care unit on POD7 (4.8% of all cardiac surgery patients). Five hundred twenty-one people died (25.6%) in the year after surgery; 353 died before hospital discharge (17.3% of total cohort, 67.8% of deaths). Requirement for multiple vasoactive or inotropic medications was the strongest predictor of mortality, followed by need for invasive ventilation, 3 or more preoperative comorbidities, need for a single inotropic or vasoactive medication, and requirement for dialysis before surgery. The derivation area under the curve was 0.80, and the model was well- calibrated with a Hosmer-Lemeshow p value of 0.5 and good calibration across risk deciles. CONCLUSIONS: A prespecified multivariate model using clinically relevant, routinely available variables was able to accurately predict death among those with prolonged critical illness after cardiac surgery.

Survival, Quality of Life, and Functional Status Following Prolonged ICU Stay in Cardiac Surgical Patients: A Systematic Review.

OBJECTIVES: Compared with noncardiac critical illness, critically ill postoperative cardiac surgical patients have different underlying pathophysiologies, are exposed to different processes of care, and thus may experience different outcome trajectories. Our objective was to systematically review the outcomes of cardiac surgical patients requiring prolonged intensive care with respect to survival, residential status, functional recovery, and quality of life in both hospital and long-term follow-up. DATA SOURCES: MEDLINE, Embase, CINAHL, Web of Science, and Dissertations and Theses Global up to July 21, 2017. STUDY SELECTION: Studies were included if they assessed hospital or long-term survival and/or patient-centered outcomes in adult patients with prolonged ICU stays following major cardiac surgery. After screening 10,159 citations, 114 articles were reviewed in full; a final 34 articles met criteria for data extraction. DATA EXTRACTION: Two reviewers independently extracted data and assessed risk of bias using the National Institutes of Health Quality Assessment Tool for Observational Studies. Extracted data included the used definition of prolonged ICU stay, number and characteristics of prolonged ICU stay patients, and any comparator short stay group, length of follow-up, hospital and long-term survival, residential status, patient-centered outcome measure used, and relevant score. DATA SYNTHESIS: The definition of prolonged ICU stay varied from 2 days to greater than 14 days. Twenty-eight studies observed greater in-hospital mortality among all levels of prolonged ICU stay. Twenty-five studies observed greater long-term mortality among all levels of prolonged ICU stay. Multiple tools were used to assess patient-centered outcomes. Long-term health-related quality of life and function was equivalent or worse with prolonged ICU stay. CONCLUSIONS: We found consistent evidence that patients with increases in ICU length of stay beyond 48 hours have significantly increasing risk of hospital and long-term mortality. The significant heterogeneity in exposure and outcome definitions leave us unable to precisely quantify the risk of prolonged ICU stay on mortality and patient-centered outcomes.

External Validation and Updating of the Cardiac Surgery Score for Prediction of Mortality in a Cardiac Surgery Intensive Care Unit.

OBJECTIVE: To externally validate the predictive performance of the logistic and additive Cardiac Surgery Score (CASUS), a postoperative severity of illness score designed specifically for prediction of mortality in the cardiac surgery intensive care unit. DESIGN: A retrospective analysis of prospectively collected data between July 1, 2012, and September 30, 2015. SETTING: Single university cardiac surgery intensive care unit in Canada. PARTICIPANTS: Consecutive adult patients (n = 4,519) admitted to the intensive care unit after cardiac surgery. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The mortality predicted by logistic CASUS was calculated for each patient on admission day 0 and postoperative days 2, 4, 7, and 10 using the original model equation. The mortality predicted by additive CASUS was determined on each day with separate logistic regression models, using the total score as a single variable. The observed mortality was 1.8%. Logistic CASUS overestimated mortality by 78%, 59%, 51%, 52%, and 29% on days 0, 2, 4, 7, and 10, respectively. After model updating with logistic calibration, logistic CASUS consistently provided estimates of death comparable with the observed mortality, as determined with the Hosmer-Lemeshow goodness-of-fit test. The stability of those estimates was confirmed by bootstrapping. Similar calibration results were obtained with additive CASUS. Logistic and additive CASUS had good discrimination with areas under the receiver operating characteristic curve greater than 0.7 on each study day. CONCLUSIONS: Recalibrated logistic CASUS reliably predicts mortality in the intensive care unit after cardiac surgery. Logistic regression models derived from additive CASUS perform as well as logistic CASUS.

Long-term survival and resource use in critically ill cardiac surgery patients: a population-based study.

PURPOSE: Most cardiac surgery patients recover well; a substantial minority become critically ill after surgery. The epidemiology of critical illness after cardiac surgery is poorly described. We measured the association of prolonged critical illness with long-term survival and resource use after cardiac surgery. METHODS: This was a historical population-based cohort study in Ontario, Canada (2002-2013), of adult cardiac surgery patients. Validated methods were used to measure postoperative intensive care unit (ICU) length of stay (LOS). We categorized patients into short (0-2 day), moderate (3-9 day), and long (10+ day) ICU LOS groups. The adjusted associations of ICU LOS with one-year survival (primary outcome) and costs, hospital readmissions, and institutional discharge were measured using multilevel, multivariable regression. Pre-specified sensitivity analyses were performed. RESULTS: We included 111,740 patients having their first cardiac surgery during the study period who survived ≥ ten postoperative days. Most patients had a short ICU LOS (75.9%); 20.9% and 3.3% had moderate or long ICU LOS, respectively. The short-stay one-year mortality rate was 2.1%. Longer ICU LOS was independently associated with decreased one-year survival (moderate LOS: hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.6 to 1.94; long LOS: HR, 8.66; 95% CI, 7.93 to 9.44). Sensitivity analyses supported the findings of the primary analysis. Secondary outcomes were independently associated with longer ICU LOS. Long ICU LOS patients occupied 30% of all ICU bed days, and 55% died or were discharged to an institution. CONCLUSION: Prolonged ICU LOS after cardiac surgery is associated with decreased 1-year survival and increased healthcare resource use.

Role of nutrition support in adult cardiac surgery: a consensus statement from an International Multidisciplinary Expert Group on Nutrition in Cardiac Surgery.

Nutrition support is a necessary therapy for critically ill cardiac surgery patients. However, conclusive evidence for this population, consisting of well-conducted clinical trials is lacking. To clarify optimal strategies to improve outcomes, an international multidisciplinary group of 25 experts from different clinical specialties from Germany, Canada, Greece, USA and Russia discussed potential approaches to identify patients who may benefit from nutrition support, when best to initiate nutrition support, and the potential use of pharmaco-nutrition to modulate the inflammatory response to cardiopulmonary bypass. Despite conspicuous knowledge and evidence gaps, a rational nutritional support therapy is presented to benefit patients undergoing cardiac surgery.

Evaluation of Persistent Organ Dysfunction Plus Death As a Novel Composite Outcome in Cardiac Surgical Patients.

OBJECTIVES: Validated composite outcomes after complicated cardiac surgery are poorly established. Therefore, the authors evaluated a novel composite endpoint, persistent organ dysfunction (POD)+death, which is defined as any need for life-sustaining therapies or death at any time within 28 days from surgery. DESIGN: Secondary analysis extracted from a large-scale prospective randomized trial of critically ill cardiac surgery patients. SETTING: Multi-institutional, university hospitals. PARTICIPANTS: Ninety-five cardiac surgery patients with complicated postoperative courses. INTERVENTIONS: Cardiac surgery with cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: At 28 days following surgery, the prevalence of POD was 15%, and 23% of patients had died (POD+death = 38%). Patients alive with POD at day 28 exhibited a significantly higher extent of organ injury and longer ICU (33 v 7 days; p<0.001) and hospital lengths of stay (49 v 21 days; p<0.001) compared to patients without POD at day 28. At 3 and 6 months, quality-of-life scores (by Short Form 36 questionnaire) showed a significantly reduced rating for most components in patients with POD at day 28 compared to those without POD. The 6-month mortality rate was 21% among patients alive with POD at day 28 compared to 5% among patients alive without POD (p = 0.05). The calculated number of patients needed per arm to detect a 25% relative risk reduction for mortality alone was 762 compared to 386 per arm for POD+ death. CONCLUSIONS: POD+death at day 28 following cardiac surgery may be a valid composite endpoint and offers statistical efficiencies in terms of sample size calculations for cardiac surgical trials.

Impact of anesthetic handover on mortality and morbidity in cardiac surgery: a cohort study.

OBJECTIVE: Clinical handover is a critical moment in patient care. The authors tested the hypothesis that handover of anesthesia care is associated with increased mortality and morbidity in patients undergoing cardiac surgery. DESIGN: This was a single-center, retrospective cohort study of prospectively collected data. SETTING: The study was conducted in a quaternary care cardiac surgery center and university research hospital. PARTICIPANTS: All patients undergoing cardiac surgical procedures between April 1, 1999 and October 31, 2009 were included in the study. INTERVENTIONS: Propensity-score matching was used to adjust for differences between patients who received intraoperative handover of anesthesia care and those who did not, and in-hospital mortality and morbidity were compared using multivariate logistic modeling. MEASUREMENTS AND MAIN RESULTS: 14,421 patients met the inclusion criteria for this study; handover occurred in 966 cases (6.7%). After propensity-score matching, 7,137 patients were included for analysis. In-hospital mortality was 5.4% in the handover group and 4.0% in the non-handover group (match-adjusted odds ratio, 1.425; 95% confidence interval, 1.013-2.006; p = 0.0422); the incidence of major morbidity was 18.5% in the handover group and 15.6% in the non-handover group (match-adjusted odds ratio, 1.274; 95% confidence interval, 1.037-1.564; p = 0.0212). CONCLUSIONS: Handover of anesthetic care during cardiac surgery is associated with a 43% greater risk of in-hospital mortality and 27% greater risk of major morbidity. Further studies are required to explore this relationship and to systematically evaluate and improve the process of handover.

Impact of subglottic suctioning on the incidence of pneumonia after cardiac surgery: a retrospective observational study.

OBJECTIVE: Continuous aspiration of subglottic secretions (CASS) has been found to decrease the incidence of pneumonia in the general intensive care unit (ICU) population, but its benefit in cardiac surgery patients is unclear. The present study aimed to determine whether the routine use of CASS in cardiac surgical patients was associated with decreased pneumonia. DESIGN: A retrospective, single-center observational study. SETTING: The study was conducted in a quaternary care cardiac surgery center and university research hospital. PARTICIPANTS: 4,880 patients undergoing cardiac surgery were studied. INTERVENTIONS: The control group (no CASS) received a standard endotracheal tube and underwent surgery between April 1, 2007 and March 31, 2009. The intervention group (CASS) received a subglottic suctioning endotracheal tube and underwent surgery between June 1, 2009 and May 31, 2011. The primary outcome was the development of pneumonia, and the secondary outcomes were 30-day in-hospital mortality, ventilation time, need for tracheostomy, ICU length of stay (LOS), and hospital LOS. MEASUREMENTS AND MAIN RESULTS: The unadjusted incidence of pneumonia was 1.9% in the CASS group and 5.6% in the control group (p<0.0001). The CASS group also had lower 30-day in-hospital mortality (2.1% v 3.3%; p = 0.007), median ventilation time (8.42 v 7.3 hours; p<0.0001), and shorter median ICU LOS (1.77 v 1.17 days; p<0.0004) compared with the control group. Tracheostomy rates and median hospital LOS did not differ between groups. After adjusting using multivariable modeling, CASS remained an independent risk predictor for pneumonia (odds ratio [OR] 0.342, 95% confidence interval [CI] 0.239-0.490) and ICU LOS (OR 0.817, 95% CI 0.718-0.931). CONCLUSIONS: The universal implementation of CASS in a quaternary care cardiac surgical population was associated with a decreased incidence of pneumonia.

Microbeads: a novel multiparticulate drug delivery technology for increasing the solubility and dissolution of celecoxib.

The purpose of this study was to develop a novel multipaticulate drug delivery technology suitable for the delivery of pre-solubilized celecoxib to the gastrointestinal tract and more specifically to the colon. The solubility of celecoxib in a range of oils, surfactants and co-solvents was evaluated. Celecoxib was solubilized in mixtures of these vehicles to produce liquid formulations. The in vitro dissolution of these liquid formulations was assessed and the data obtained was used to design microbead formulations containing celecoxib dissolved within an emulsion/micellar solution core. Microbead formulations were optimized to increase drug loading, avoid precipitation and to achieve good in vitro dissolution performance. An optimized formulation with a celecoxib loading of 6% w/w was produced and yielded an in vitro dissolution result of 80% over 6 h. The structure of these microbead formulations was characterized using light microscopy to reveal a correlation between droplet size and dissolution performance.

The association between tracheostomy and sternal wound infection in postoperative cardiac surgery patients.

PURPOSE: To investigate whether tracheostomy increases the risk of sternal wound infection (SWI) post cardiac surgery. METHODS: All patients undergoing cardiac surgery via median sternotomy from September 1997 to October 2010 were included in this retrospective observational study. Primary exposure was tracheostomy performed during admission to the cardiac surgical intensive care unit. The primary outcome was SWI during hospital admission. Multivariable logistic regression was used to determine if tracheostomy was an independent predictor of SWI. Restriction and propensity score analyses were then used to assess if tracheostomy is a causal risk factor for SWI. RESULTS: Four hundred and eleven of 18,845 patients (2.2%) were treated with tracheostomy. Incidences of SWI in tracheostomy and non-tracheostomy groups were 19.5% (80/411) and 0.8% (154/18,434), respectively. Using multivariable logistic regression analysis, tracheostomy was found to be an independent predictor of SWI (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.9 to 4.2). In an analysis restricted to respiratory failure patients, tracheostomy was associated with sternal wound infection (OR 3.4; 95% CI 2.4 to 4.9). When the analysis was stratified by the risk of receiving tracheostomy as represented by propensity score (PS), 46 patients (12%) in the intermediate risk category (PS 0.2-0.4) had SWIs (adjusted OR 2.97; 95% CI 1.6 to 5.6), and 52 patients (14%) in the highest risk category (PS > 0.4) had SWIs (OR 1.52; 95% CI 0.85 to 2.87). DISCUSSION: Our single-centre observational study of cardiac surgery patients found tracheostomy to be an independent risk factor for SWI. Our analysis showed a robust association when restricted to patients with respiratory failure and after the population was stratified by the propensity to have a tracheostomy.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

BACKGROUND: Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. METHODS: We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). RESULTS: Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. CONCLUSION: Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Evaluating the potential impact of an emergency department extracorporeal resuscitation (ECPR) program: a health records review.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation in refractory cardiac arrest (ECPR) is an emerging resuscitative therapy that has shown promising results for selected patients who may not otherwise survive. We sought to identify the characteristics of cardiac arrest patients presenting to our institution to begin assessing the feasibility of an ECPR program. METHODS: This retrospective health records review included patients aged 18-75 years old presenting to our academic teaching hospital campuses with refractory nontraumatic out-of-hospital or in-emergency department (ED) cardiac arrest over a 2-year period. Based on a scoping review of the literature, both "liberal" and "restrictive" ECPR criteria were defined and applied to our cohort. RESULTS: A total of 179 patients met inclusion criteria. Median age was 60 years, and patients were predominantly male (72.6%). The initial rhythm was ventricular tachycardia/ventricular fibrillation in 49.2%. The majority of arrests were witnessed (69.3%), with immediate bystander CPR performed on 53.1% and an additional 12% receiving CPR within 10 minutes of collapse. Median prehospital time was 40 minutes (interquartile range, 31-53.3). Two-thirds of patients (65.9%) were identified as having a reversible cause of arrest and favorable premorbid status was identified in nearly three quarters (74.3%). Our two sets of ECPR inclusion criteria revealed that 33 and 5 patients (liberal and restrictive criteria, respectively), would have been candidates for ECPR. CONCLUSION: At our institution, we estimate between 6% and 40% of ED refractory cardiac arrest patients would be candidates for ECPR. These findings suggest that the implementation of an ECPR program should be explored.

Multidisciplinary Code Shock Team in Cardiogenic Shock: A Canadian Centre Experience.

BACKGROUND: Cardiogenic shock (CS) is associated with high mortality. We report on a "Shock Team" approach of combined interdisciplinary expertise for decision making, expedited assessment, and treatment. METHODS: We reviewed 100 patients admitted in CS over 52 months. Patients managed under a Code Shock Team protocol (n = 64, treatment) from 2016 to 2019 were compared with standard care (n = 36, control) from 2015 to 2016. The cohort was predominantly male (78% treatment, 67% control) with a median age of 55 years (interquartile range [IQR], 43-64) for treatment vs 64 years (IQR, 48-69) for control (P = 0.01). New heart failure was more common in the treatment group: 61% vs 36%, P = 0.02. Acute myocardial infarction comprised 13% of patients in CS. There were no significant differences between treatment and control in markers of clinical acuity, including median left ventricular ejection fraction (18% vs 20%), prevalence of moderate-severe right ventricular dysfunction (64% vs 56%), median peak serum lactate (5.3 vs 4.7 mmol/L), acute kidney injury (70% vs 75%), or acute liver injury (50% vs 31%). Inotropes, dialysis, and invasive ventilation were required in 92%, 33%, and 66% of patients, respectively. Temporary mechanical circulatory support was used in 45% of treatment and 28% of control patients (P = 0.08). There were no significant differences in median hospital length of stay (17.5 days), 30-day survival (71%), or survival to hospital discharge (66%). Over 240 days (IQR, 14,847) of median follow-up, survival was 67% for treatment vs 42% for control (hazard ratio, 0.53; 95% confidence interval, 0.28-0.99; P = 0.03). CONCLUSION: A multidisciplinary Code Shock Team approach for CS is feasible and may be associated with improved long-term survival.

CONTEXTE: Le choc cardiogénique (CC) est associé à une mortalité élevée. Nous décrivons une approche où la prise de décision, l'évaluation rapide des cas et le traitement sont confiés à une « équipe de choc ¼ interdisciplinaire. MÉTHODOLOGIE: Nous avons examiné les cas de 100 patients hospitalisés en raison d'un CC sur une période de 52 mois. Les patients pris en charge par une équipe interdisciplinaire selon un protocole d'intervention déclenché par un code-choc (n = 64, groupe traité) de 2016 à 2019 ont été comparés à des patients ayant reçu des soins courants (n = 36, groupe témoin) de 2015 à 2016. Les patients de la cohorte étaient majoritairement de sexe masculin (78 % dans le groupe traité, 67 % dans le groupe témoin) et l'âge médian était de 55 ans (intervalle interquartile [IIQ] : 43-64) au sein du groupe traité par rapport à 64 ans (IIQ : 48-69) au sein du groupe témoin (p = 0,01). Les nouveaux cas d'insuffisance cardiaque étaient plus fréquents dans le groupe traité : 61 % vs 36 % (p = 0,02). Les patients hospitalisés en raison d'un CC avaient subi un infarctus aigu du myocarde dans 13 % des cas. Aucune différence significative n'a été relevée entre le groupe traité et le groupe témoin au chapitre des marqueurs d'acuité clinique, y compris la fraction médiane d'éjection ventriculaire gauche (18 % vs 20 %), la prévalence d'une dysfonction modérée ou sévère du ventricule droit (64 % vs 56 %), la concentration maximale médiane de lactate sérique (5,3 vs 4,7 mmol/l), l'insuffisance rénale aiguë (70 % vs 75 %) ou l'insuffisance hépatique aiguë (50 % vs 31 %). L'administration d'inotropes, la dialyse et la ventilation effractive ont été nécessaires chez 92 %, 33 % et 66 % des patients, respectivement. Une assistance circulatoire mécanique temporaire a été utilisée chez 45 % des patients du groupe traité et 28 % des patients du groupe témoin (p = 0,08). Aucune différence significative n'a été notée en ce qui concerne la durée médiane des hospitalisations (17,5 jours), la survie à 30 jours (71 %) ou la survie à la sortie de l'hôpital (66 %). Au cours d'une période de suivi médiane de 240 jours (IIQ : 14 847), le taux de survie était de 67 % dans le groupe traité vs 42 % dans le groupe témoin (rapport des risques instantanés : 0,53; intervalle de confiance à 95 % : 0,28-0,99; p = 0,03). CONCLUSION: Dans les cas de CC, l'intervention d'une équipe interdisciplinaire déclenchée par un code-choc est réalisable et pourrait être associée à une amélioration de la survie à long terme.

Prediction of Prolonged ICU Stay in Cardiac Surgery Patients as a Useful Method to Identify Nutrition Risk in Cardiac Surgery Patients: A Post Hoc Analysis of a Prospective Observational Study.

BACKGROUND: Cardiovascular surgery patients with a prolonged intensive care unit (ICU) stay may benefit most from early nutrition support. Using established scoring systems for nutrition assessment and operative risk stratification, we aimed to develop a model to predict a prolonged ICU stay ≥5 days in order to identify patients who will benefit from early nutrition interventions. METHODS: This is a retrospective analysis of a prospective observational study of patients undergoing elective valvular, coronary artery bypass grafting, or combined cardiac surgery. The nutrition risk was assessed by well-established screening tools. Patients' preoperative EuroSCORE (European System for Cardiac Operative Risk Evaluation), primary disease, and intraoperative cardiopulmonary bypass (CPB) time were included as independent variables in a multivariate logistic regression analysis to predict a prolonged ICU stay (>4 days). RESULTS: The number of cardiac surgery patients included was 1193. Multivariate analysis revealed that for prediction of ICU stay >4 days, both Nutritional Risk Screening 2002 (area under the curve (AUC): 0.716, P = .020) and Mini Nutritional Assessment (MNA) score (AUC: 0.715, P = .037) were significant, whereas for prediction of ICU stay >5 days, only the MNA score showed significant results (AUC: 0.762, P = .011). CONCLUSION: Present data provide first evidence about the combined use of EuroSCORE, primary disease, CPB time, and nutrition risk screening tools for prediction of prolonged ICU stay in cardiac surgery patients. If prospectively evaluated in adequately designed studies, this model may help to identify patients with prolonged ICU stay to initiate early postoperative nutrition therapy and thus, facilitate an enhanced recovery.

How detrimental is reexploration for bleeding after cardiac surgery?

OBJECTIVE: To establish the risk factors and impact of reexploration for bleeding in a large modern cardiac surgical cohort. METHODS: At a tertiary referral center, baseline, index procedural, reexploration, outcome, and readmission characteristics of 16,793 consecutive adult cardiac surgery patients were prospectively entered into dedicated clinical databases. Correlates of reexploration for bleeding, as well as its association with outcomes and readmission, were examined with multivariable regression models. RESULTS: The mean patient age was 65.9 ± 12.1 years, and 11,991 patients (71.4%) patients were male. Perioperative mortality was 2.8% (458 of 16,132) in those who did not undergo reexploration for bleeding and 12.0% (81 of 661) in those who underwent reexploration for bleeding, corresponding to an odds ratio of 3.4 ± 0.5 (P <.001) over other predictors of mortality, including Euroscore II. Mortality was highest in patients who underwent reexploration after the day of index surgery (odds ratio, 6.4 ± 1.1). Hospital stay was longer in patients who underwent reexploration for bleeding (median, 12 days, vs 7 days in patients who did not undergo reexploration; P <.001), to an extent beyond any other correlate. Reexploration for bleeding also was independently associated with new-onset postoperative atrial fibrillation, renal insufficiency, intensive care unit readmission, and wound infection. Risk factors for reexploration for bleeding were tricuspid valve repair, on-pump versus off-pump coronary artery bypass grafting, emergency status, cardiopulmonary bypass (CPB) duration, low body surface area, and lowest CPB hematocrit of <24%. CONCLUSIONS: Reexploration for bleeding is a lethal and morbid complication of cardiac surgery, with a detrimental effect that surpasses that of any other known potentially modifiable risk factor. All efforts should be made to minimize the incidence and burden of reexploration for bleeding, including further research on transfusion management during CPB.

In-vitro characterisation of a novel celecoxib microbead formulation for the treatment and prevention of colorectal cancer.

OBJECTIVES: Colorectal cancer (CRC) is a life-threatening disease that can develop as a consequence of a sustained chronic inflammatory pathology of the colon. Although not devoid of side effects, the anti-inflammatory drug celecoxib (CLX) has been shown to exert protective effects in CRC therapy. The purpose of this study was to develop and characterise a novel CLX microbead formulation suitable for use in the treatment and prevention of CRC, which has the potential to minimise the side effects associated with CLX. METHODS: The study involved the assessment of the effectiveness of CLX formulations in an in-vitro cell model (HT29 cells) and a comparison of these effects to that of the marketed CLX product, Celebrex. Liquid CLX formulations were developed as precursors to microbead formulations. The effect of liquid CLX formulations on HT29 cell viability (MTT and flow cytometry apoptotic assays) and motility (scratch wound assay) were assessed and compared with the effect of Celebrex. A correlation between the in-vitro dissolution performance of the formulations and the effect in the cell model was also explored. Liquid CLX formulations were translated into an optimised CLX microbead formulation, and a colonic targeted sustained release coat (Surelease) was applied to the beads with the aim of producing a formulation for a future in-vivo study to compare the effect of the coated CLX microbeads versus Celebrex in the attenuation of CRC tumours and inflammation in a CRC murine model. The production of CLX microbeads was scaled-up using vibrating-jet encapsulation technology to allow for the development of an optimised dissolution profile to enable colonic release. KEY FINDINGS: In-vitro cell viability and motility were shown to be significantly reduced after treatment with CLX liquid formulations relative to the control, whereas the results for treatment with Celebrex were comparable with the control. Dissolution experiments and correlation analysis demonstrated that the formulations that showed a greater extent of drug release had reduced cell viability and motility. The CLX liquid formulations were translated into colon-targeted CLX microbeads suitable for use in a future in-vivo mouse study. CONCLUSIONS: These results represent a significant step forward in the chemopreventative treatment of CRC using CLX, as the microbead formulation developed suggests the possibility of presenting CLX in a format that has the potential to minimise gastrointestinal and cardiovascular side effects.