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Purpose The difference between arterial and end-tidal partial pressure of carbon dioxide (ΔCO2) is a measure of alveolar dead space, commonly evaluated intraoperatively. Given its relationship to ventilation and perfusion, ΔCO2 may provide prognostic information and guide clinical decisions. We hypothesized that higher ΔCO2 values are associated with occurrence of a composite outcome of re-intubation, postoperative mechanical ventilation, or 30-day mortality in patients undergoing non-cardiac surgery. Methods We conducted a historical cohort study of adult patients undergoing non-cardiac surgery with an arterial line at a single tertiary care medical centre. The composite outcome, identified from electronic health records, was re-intubation, postoperative mechanical ventilation, or 30-day mortality. Student’s t test and Chi-squared test were used for univariable analysis. Logistic regression was used for multivariable analysis of the relationship of ΔCO2 with the composite outcome. Results A total of 19,425 patients were included in the final study population. Univariable analysis showed an association between higher mean (standard deviation [SD]) intraoperative ΔCO2 values and the composite outcome (6.1 [5.3] vs 5.7 [4.5] mm Hg; P = 0.002). After adjusting for baseline subject characteristics, every 5-mm Hg increase in the ΔCO2 was associated with a nearly 20% increased odds of the composite outcome (odds ratio, 1.20; 95% confidence interval, 1.12 to 1.28; P < 0.001). Conclusions In this patient population, increased intraoperative ΔCO2 was associated with an increased odds of the composite outcome of postoperative mechanical ventilation, re-intubation, or 30-day mortality that was independent of its relationship with pre-existing pulmonary disease. Future studies are needed to determine if ΔCO2 can be used to guide patient management and improve patient outcomes.

OBJECTIVE: Despite advances in echocardiography and hemodynamic monitoring, limited progress has been made to effectively quantify left ventricular function during cardiac surgery. Traditional measures including left ventricular ejection fraction (LVEF) and cardiac index remain dependent on loading conditions; more complex measures remain impractical in a dynamic surgical setting. However, the Smith-Madigan Inotropy Index (SMII) and potential-to-kinetic energy ratio (PKR) offer promise as measures calculable during cardiac surgery and potentially predictive of outcomes. Using echocardiographic and hemodynamic monitoring data, we aimed to calculate SMII and PKR values after cardiopulmonary bypass, and understand associations with postoperative outcomes, adjusting for previously identified risk factors. DESIGN: Observational cohort study. SETTING: Tertiary care academic hospital. PATIENTS: 189 elective adult cardiac surgical procedures from 2015 to 2016. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was postoperative mortality or organ system complication (stroke, prolonged ventilation, reintubation, cardiac arrest, acute kidney injury, new-onset atrial fibrillation). After adjustment, SMII

Background Heart failure with reduced ejection fraction (HFrEF) is a condition imposing significant health care burden. Given its syndromic nature and often insidious onset, the diagnosis may not be made until clinical manifestations prompt further evaluation. Detecting HFrEF in precursor stages could allow for early initiation of treatments to modify disease progression. Granular data collected during the perioperative period may represent an underutilized method for improving the diagnosis of HFrEF. We hypothesized that patients ultimately diagnosed with HFrEF following surgery can be identified via machine-learning approaches using pre- and intraoperative data. Methods Perioperative data were reviewed from adult patients undergoing general anesthesia for major surgical procedures at an academic quaternary care center between 2010 and 2016. Patients with known HFrEF, heart failure with preserved ejection fraction, preoperative critical illness, or undergoing cardiac, cardiology, or electrophysiologic procedures were excluded. Patients were classified as healthy controls or undiagnosed HFrEF. Undiagnosed HFrEF was defined as lacking a HFrEF diagnosis preoperatively but establishing a diagnosis within 730 days postoperatively. Undiagnosed HFrEF patients were adjudicated by expert clinician review, excluding cases for which HFrEF was secondary to a perioperative triggering event, or any event not associated with HFrEF natural disease progression. Machine-learning models, including L1 regularized logistic regression, random forest, and extreme gradient boosting were developed to detect undiagnosed HFrEF, using perioperative data including 628 preoperative and 1195 intraoperative features. Training/validation and test datasets were used with parameter tuning. Test set model performance was evaluated using area under the receiver operating characteristic curve (AUROC), positive predictive value, and other standard metrics. Results Among 67,697 cases analyzed, 279 (0.41%) patients had undiagnosed HFrEF. The AUROC for the logistic regression model was 0.869 (95% confidence interval, 0.829-0.911), 0.872 (0.836-0.909) for the random forest model, and 0.873 (0.833-0.913) for the extreme gradient boosting model. The corresponding positive predictive values were 1.69% (1.06%-2.32%), 1.42% (0.85%-1.98%), and 1.78% (1.15%-2.40%), respectively. Conclusions Machine-learning models leveraging perioperative data can detect undiagnosed HFrEF with good performance. However, the low prevalence of the disease results in a low positive predictive value, and for clinically meaningful sensitivity thresholds to be actionable, confirmatory testing with high specificity (eg, echocardiography or cardiac biomarkers) would be required following model detection. Future studies are necessary to externally validate algorithm performance at additional centers and explore the feasibility of embedding algorithms into the perioperative electronic health record for clinician use in real time.

Background The variable presentations and different phenotypes of sepsis suggest that risk of sepsis comes from many genes each having a small effect. The cumulative effect can be used to create individual risk profile. The purpose of this study was to create a polygenic risk score and determine the genetic variants associated with sepsis. Methods We sequenced ~14 million single nucleotide polymorphisms with a minimac imputation quality R2>0.3 and minor allele frequency >10−6 in patients with Sepsis-2 or Sepsis-3. Genome-wide association was performed using Firth bias-corrected logistic regression. Semi-parsimonious logistic regression was used to create polygenic risk scores and reduced regression to determine the genetic variants independently associated with sepsis. Findings 2261 patients had sepsis and 13,068 control patients did not. The polygenic risk scores had good discrimination: c-statistic = 0.752 ± 0.005 for Sepsis-2 and 0.752 ± 0.007 for Sepsis-3. We found 772 genetic variants associated with Sepsis-2 and 442 with Sepsis-3, p Conclusions Sepsis-2 and Sepsis-3 have both separate and shared genetic variants. Most genetic variants have small effects sizes, but cumulatively, the polygenic risk scores have good discrimination.

The primary objective of this study was to compare the characteristics of culture-positive and culture-negative status in septic patients. We also determined whether culture status is associated with mortality and whether unique variables are associated with mortality in culture-positive and culture-negative patients separately.Utilizing patient records from intensive care units, emergency department, and general care wards in a large academic medical center, we identified adult patients with suspected infection and ≥2 systemic inflammatory response syndrome criteria between January 1, 2007, and May 31, 2014. We compared the characteristics between culture-positive and culture-negative patients and used binary logistic regression to identify variables independently associated with culture status and mortality. We also did sensitivity analyses using patients with Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria for sepsis.The study population included 9288 culture-negative patients (89%) and 1105 culture-positive patients (11%). Culture-negative patients received more antibiotics during the 48 hours preceding diagnosis but otherwise demonstrated similar characteristics as culture-positive patients. After adjusting for illness severity, a positive culture was not independently associated with mortality (odds ratio = 1.01 [95% CI, 0.81-1.26]; P = .945). The models predicting mortality separately in culture-negative and culture-positive patients demonstrated very good and excellent discrimination (C-statistic ± SD, 0.87 ± 0.01 and 0.92 ± 0.01), respectively. In the sensitivity analyses using patients with sepsis by Sequential Organ Failure Assessment and quick Sequential Organ Failure Assessment criteria, after adjustments for illness severity, positive cultures were still not associated with mortality (odds ratio = 1.13 [95% CI, 0.86-1.43]; P = .303; and odds ratio = 1.05 [95% CI, 0.83-1.33]; P = .665), respectively. In all models, physiological derangements were associated with mortality.While culture status is important for tailoring antibiotics, culture-negative and culture-positive patients with sepsis demonstrate similar characteristics and, after adjusting for severity of illness, similar mortality. The most important factor associated with negative cultures is receipt of antibiotics during the preceding 48 hours. The risk of death in patients suspected of having an infection is most associated with severity of illness. This is aligned with the Sepsis-3 definition using Sequential Organ Failure Assessment score to better identify those suspected of infection at highest risk of a poor outcome.

Purpose To determine if earlier initiation of renal replacement therapy (RRT) is associated with improved survival in patients with severe acute kidney injury. Methods We performed a retrospective case–control study of propensity-matched groups with multivariable logistic regression using Akaike Information Criteria to adjust for non-matched variables in a surgical ICU in a tertiary care hospital. Results We matched 169 of 205 (82%) patients with new initiation of RRT (EARLY group) to 169 similar patients who did not initiate RRT on that day (DEFERRED group). Eighteen (11%) of DEFERRED eventually received RRT before discharge. By univariate analysis, ICU mortality was higher in EARLY (n = 60 (36%) vs. n = 23 (14%), p Conclusions While ICU mortality was increased in the EARLY group, there was no difference in hospital mortality between EARLY and DEFERRED groups.

Objectives Patients with coronavirus disease 19 ( COVID-19 ) are at high risk for fibrin-based occlusion of vascular beds of all sizes. Considering endothelial cell activation has regularly been described as part of the COVID-19 thrombo-inflammatory storm, we aimed to find upstream mediators of this activation. Methods Cultured endothelial cells were exposed to sera or plasma from 244 patients hospitalized with COVID-19 or plasma from 100 patients in the intensive care unit with sepsis. Cell adhesion molecules E-selectin, VCAM-1, and ICAM-1 were detected by in-cell ELISA. Soluble E-selectin was measured in serum. Results As compared with healthy controls, sera and plasma from patients with COVID-19, and to a lesser extent plasma from patients with sepsis, increased expression of E-selectin, VCAM-1, and ICAM-1 on cultured endothelial cells. We found modest correlations between serum neutrophil extracellular trap (NET) remnants and upregulation of cell adhesion molecules on endothelial cells. A stronger marker of the ability of COVID-19 serum to activate endothelial cells was the presence of circulating antiphospholipid antibodies, specifically anticardiolipin IgG and IgM and anti-phosphatidlyserine/prothrombin (anti-PS/PT) IgG and IgM. Depletion of total IgG from anticardiolipin-positive and anti-PS/PT-positive samples markedly restrained upregulation of E-selectin, VCAM-1, and ICAM-1. At the same time, supplementation of control serum with patient IgG was sufficient to trigger endothelial cell activation. Conclusions These data are the first to suggest that some patients with COVID-19 have potentially diverse antibodies that drive endothelial cell activation in COVID-19. The data also add important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19. KEY MESSAGES What is already known about this subject?: Patients with COVID-19 are at high risk for fibrin-based occlusion of vascular beds of all sizes.Endothelial cell activation has regularly been described as part of the COVID-19 thrombo-inflammatory storm.What does this study add?: The presence of circulating antiphospholipid antibodies may be a predictor of the ability of a patient’s total antibody profile to activate endothelial cells.Purified COVID-19 IgG with high levels of anticardiolipin and anti-PS/PT activity trigger a pro-adhesive phenotype in endothelial cells.How might this impact on clinical practice or future developments?: Patients might be screened for antiphospholipid antibodies to evaluate their risk of having an antibody profile likely to activate endothelial cells.Patients with high antiphospholipid antibody titers might benefit from treatments used in traditional cases of severe APS such as therapeutic anticoagulation, corticosteroids, and plasmapheresis.

OBJECTIVES: Recently, the definition of sepsis has changed from a physiologic derangement (Sepsis-1 and -2) to organ dysfunction (Sepsis-3) based. We sought to determine the concordance between the different sepsis phenotypes and how that affected mortality. DESIGN: Retrospective, multicenter study. SETTING: Three academic medical centers. PATIENTS: 29,459 patients who had suspected infection, defined as obtaining blood cultures and receiving antibiotics: 18,183 (62%) had either Sepsis-2 or Sepsis-3. MEASUREMENTS AND MAIN RESULTS: Kappa was used to show agreement between phenotypes. Conditional logistic regression was used to create models of associations between factors and phenotypes and between factors and mortality. About 12,981 patients had Sepsis-2; 12,043 had Sepsis-3; and 6,841 patients had both Sepsis-2 and Sepsis-3. Fifty-three percent of Sepsis-2 patients also had Sepsis-3, whereas 57% of Sepsis-3 patients also had Sepsis-2. Agreement between the two phenotypes was poor: kappa = 0.213±0.006. Mortality was 6% in patients with only Sepsis-2, 10% with only Sepsis-3, and 18% in patients who had both phenotypes. Combining the variables in Sepsis-2 and Sepsis-3 improved the discrimination (C-statistic = 0.742±0.005, p < 0.001) of mortality. CONCLUSIONS: We found that Sepsis-2 and Sepsis-3-based sepsis diagnoses represent separate phenotypes with poor agreement. Patients who have both phenotypes are at increased risk of mortality compared with having either phenotype alone. Inclusion of both systemic inflammatory response syndrome and Sequential Organ Failure Assessment criteria in the same model improves the discrimination of mortality.

Background The use of extracorporeal life support ( ECLS ) has expanded to include unique populations such as peripartum women. This systematic review aims to (1) quantify the number of cases and indications for ECLS in women during the peripartum period reported in the literature and (2) report maternal and fetal complications and outcomes associated with peripartum ECLS . Methods and Results This review was registered in PROSPERO ( CRD 42018108142). MEDLINE , Embase, and CINAHL were searched for case reports, case series, and studies reporting cases of ECLS during the peripartum period that reported one or more of the following outcomes: maternal survival, maternal complications, fetal survival, and/or fetal complications. Qualitative assessment of 221 publications evaluated the number of cases, clinical details, and maternal and fetal outcomes of ECLS during the peripartum period. There were 358 women included and 68 reported fetal outcomes in cases where the mother was pregnant at the time of cannulation. The aggregate maternal survival at 30 days was 270 (75.4%) and at 1 year was 266 (74.3%); fetal survival was 44 (64.7%). The most common indications for ECLS overall in pregnancy included acute respiratory distress syndrome 177 (49.4%), cardiac failure 67 (18.7%), and cardiac arrest 57 (15.9%). The most common maternal complications included mild to moderate bleeding 66 (18.4%), severe bleeding requiring surgical intervention 48 (13.4%), and intracranial neurologic morbidity 19 (5.3%). The most commonly reported fetal complications included preterm delivery 33 (48.5%) and neonatal intensive care unit admission 19 (27.9%). Conclusions Reported rates of survival in ECLS in pregnant and postpartum women are high and major complications relatively low.

Purpose. To determine if left ventricular or inferior vena cava (IVC) measurements are easier to obtain on point-of-care ultrasound by anesthesiologists in preoperative patients, and to assess the relationship between preoperative cardiac dimensions and hypotension with the induction of general anesthesia. Methods. This prospective observational study was conducted at a large academic medical center. Sixty-three patients undergoing noncardiac surgeries under general anesthesia were enrolled. Ultrasound examinations were performed by anesthesiologists in the preoperative area. To ensure that hypotension represented both a relative and absolute decrease in blood pressure, both a mean arterial pressure (MAP) 30% from preoperative value defined this outcome. Results. Left ventricular measurements were more likely to be acquired than IVC measurements (97% vs. 79%). Subjects without adequate images to assess IVC collapsibility tended to have a higher body mass index (33.6 ± 5.5 vs. 28.5 ± 4.5, p = 0.001 ). While high left ventricular end-diastolic diameter values were associated with a decreased odds of MAP p = 0.023 ) or a MAP decrease of >30% from baseline alone (OR: 0.25, 95% CI: 0.07–0.83, p = 0.023 ), the primary endpoint of both relative and absolute hypotension was not associated with preoperative left ventricular dimensions. Conclusions. Preoperative cardiac ultrasound may be a more reliable way for anesthesiologists to assess patients’ volume status compared to ultrasound of the IVC, particularly for patients with a higher body mass index.

Attributing causes of postoperative mortality is challenging, as death may be multifactorial. A better understanding of complications that occur in patients who die is important, as it allows clinicians to focus on the most impactful complications. We sought to determine the postoperative complications with the strongest independent association with 30-day mortality.Data were obtained from the 2012-2013 National Surgical Quality Improvement Program Participant Use Data Files. All inpatient or admit day of surgery cases were eligible for inclusion in this study. A multivariable least absolute shrinkage and selection operator regression analysis was used to adjust for patient pre- and intraoperative risk factors for mortality. Attributable mortality was calculated using the population attributable fraction method: the ratio between the odds ratio for mortality and a given complication in the population. Patients were separated into 10 age groups to facilitate analysis of age-related differences in mortality.A total of 1,195,825 patients were analyzed, and 9255 deceased within 30 days (0.77%). A complication independently associated with attributable mortality was found in 1887 cases (20%). The most common causes of attributable mortality (attributable deaths per million patients) were bleeding (n = 368), respiratory failure (n = 358), septic shock (n = 170), and renal failure (n = 88). Some complications, such as urinary tract infection and pneumonia, were associated with attributable mortality only in older patients.Additional resources should be focused on complications associated with the largest attributable mortality, such as respiratory failure and infections. This is particularly important for complications disproportionately impacting younger patients, given their longer life expectancy.

Point-of-care transthoracic echocardiography is increasingly being utilized by the intensive care physicians in the management of hemodynamically unstable patients. However, its use in the management of critically ill patients requiring cardiopulmonary mechanical device support remains to be well described. In this case series, we present two case reports where point-of-care echocardiography was successfully used by the intensive care team in diagnosing and managing problems related to cardiopulmonary assist device malposition. Electronic supplementary material The online version of this article (10.1186/s13089-017-0080-1) contains supplementary material, which is available to authorized users.

Background We currently have an incomplete understanding of which postoperative complications after coronary artery bypass grafting (CABG) are associated with long-term death. The purpose of this study was to find the associations between complications and attributable death. Methods Prospectively collected data on patient characteristics, risk factors, and complications of patients undergoing isolated CABG with 20-year follow-up were analyzed with a Cox regression model to calculate the overall hazard of dying associated with each postoperative complication. An individual's age and hazard of dying from each complication were then used to calculate years of life lost to each complication. Results The postoperative mortality rate was 0.79% (69 of 8,773) at 30 days, 2.85% (250 of 8,773) at 180 days, and 6.38% (560 of 8,773) at 2 years. At a median follow-up of 9.8 years, 1,891 patients (21.6%) had died. Postoperative complications occurred in 3,438 patients (39.2%). Cardiac arrest (hazard ratio, 2.153), reoperation (hazard ratio, 1.679), and new dialysis (hazard ratio, 1.64) were the complications with the greatest hazard of death. After adjusting for complication incidence and patient age, cardiac arrest (703 years), reoperation (544 years), atrial fibrillation (470 years), and prolonged mechanical ventilation (371 years) were associated with the greatest number of years of life lost. Conclusions Acute cardiac arrest, reoperation for other cardiac reasons, new dialysis, atrial fibrillation, and prolonged mechanical ventilation are associated with the largest increase in attributable deaths. Prevention and treatment of these complications may improve mortality rates after cardiac operations.

Background Acute kidney injury can be defined by a fall in urine output, and urine output criteria may be more sensitive in identifying acute kidney injury than traditional serum creatinine criteria. However, as pointed out in the Kidney Disease Improving Global Outcome guidelines, the association of urine output with subsequent creatinine elevations and death is poorly characterized. The purpose of this study was to determine what degrees of reduced urine output are associated with subsequent creatinine elevation and death. Methods This was a retrospective cohort study of adult patients (age ≥18 years) cared for in a cardiovascular intensive care unit after undergoing cardiac operations in a tertiary care university medical center. All adult patients who underwent cardiac operations and were not receiving dialysis preoperatively were studied. The development of acute kidney injury was defined as an increase in creatinine of more than 0.3 mg/dL or by more than 50% above baseline by postoperative day 3. Results Acute kidney injury developed in 1,061 of 4,195 patients (25%). Urine output had moderate discrimination in predicting subsequent acute kidney injury (C statistic = .637 ± .054). Lower urine output and longer duration of low urine output were associated with greater odds of developing acute kidney injury and death. Conclusions We found that there is similar accuracy in using urine output corrected for actual, ideal, or adjusted weight to discriminate future acute kidney injury by creatinine elevation and recommend using actual weight for its simplicity. We also found that low urine output is associated with subsequent acute kidney injury and that the association is greater for lower urine output and for low urine output of longer durations. Low urine output ( –1 · h –1 ), even in the absence of acute kidney injury by creatinine elevation, is independently associated with mortality.

Given the significant morbidity and mortality of maternal sepsis, early identification is key to improve outcomes. This study aims to evaluate the performance characteristics of the systemic inflammatory response syndrome (SIRS), quick Sequential [Sepsis-related] Organ Failure Assessment (qSOFA), and maternal early warning (MEW) criteria for identifying cases of impending sepsis in parturients. The secondary objective of this study is to identify etiologies and risk factors for maternal sepsis and to assess timing of antibiotics in patients diagnosed with sepsis.Validated maternal sepsis cases during the delivery hospitalization from 1995 to 2012 were retrospectively identified at 7 academic medical centers in the United States and Israel. Control patients were matched by date of delivery in a 1:4 ratio. The sensitivity and specificity of SIRS, qSOFA, and MEW criteria for identifying sepsis were calculated. Data including potential risk factors, vital signs, laboratory values, and clinical management were collected for cases and controls.Eighty-two sepsis cases during the delivery hospitalization were identified and matched to 328 controls. The most common causes of sepsis were the following: chorioamnionitis 20 (24.4%), endometritis 19 (23.2%), and pneumonia 9 (11.0%). Escherichia coli 12 (14.6%), other Gram-negative rods 8 (9.8%), and group A Streptococcus 6 (7.3%) were the most commonly found pathogens. The sensitivities and specificities for meeting criteria for screening tools were as follows: (1) SIRS (0.93, 0.63); (2) qSOFA (0.50, 0.95); and (3) MEW criteria for identifying sepsis (0.82, 0.87). Of 82 women with sepsis, 10 (12.2%) died. The mortality rate for those who received antibiotics within 1 hour of diagnosis was 8.3%. The mortality rate was 20% for the patients who received antibiotics after1 hour.Chorioamnionitis and endometritis were the most common causes of sepsis, together accounting for about half of cases. Notable differences were observed in the sensitivity and specificity of sepsis screening tools with the highest to lowest sensitivity being SIRS, MEW, and qSOFA criteria, and the highest to lowest specificity being qSOFA, MEW, and SIRS. Mortality was doubled in the cohort of patients who received antibiotics after1 hour. Clinicians need to be vigilant to identify cases of peripartum sepsis early in its course and prioritize timely antibiotic therapy.

Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Compared with historic ventilation strategies, modern lung-protective ventilation includes lower tidal volumes (VT), lower driving pressures, and application of positive end-expiratory pressure (PEEP). The contributions of each component to an overall intraoperative protective ventilation strategy aimed at reducing postoperative pulmonary complications have neither been adequately resolved, nor comprehensively evaluated within an adult cardiac surgical population. The authors hypothesized that a bundled intraoperative protective ventilation strategy was independently associated with decreased odds of pulmonary complications after cardiac surgery. Methods In this observational cohort study, the authors reviewed nonemergent cardiac surgical procedures using cardiopulmonary bypass at a tertiary care academic medical center from 2006 to 2017. The authors tested associations between bundled or component intraoperative protective ventilation strategies (VT below 8 ml/kg ideal body weight, modified driving pressure [peak inspiratory pressure − PEEP] below 16 cm H2O, and PEEP greater than or equal to 5 cm H2O) and postoperative outcomes, adjusting for previously identified risk factors. The primary outcome was a composite pulmonary complication; secondary outcomes included individual pulmonary complications, postoperative mortality, as well as durations of mechanical ventilation, intensive care unit stay, and hospital stay. Results Among 4,694 cases reviewed, 513 (10.9%) experienced pulmonary complications. After adjustment, an intraoperative lung-protective ventilation bundle was associated with decreased pulmonary complications (adjusted odds ratio, 0.56; 95% CI, 0.42–0.75). Via a sensitivity analysis, modified driving pressure below 16 cm H2O was independently associated with decreased pulmonary complications (adjusted odds ratio, 0.51; 95% CI, 0.39–0.66), but VT below 8 ml/kg and PEEP greater than or equal to 5 cm H2O were not. Conclusions The authors identified an intraoperative lung-protective ventilation bundle as independently associated with reduced pulmonary complications after cardiac surgery. The findings offer insight into components of protective ventilation associated with adverse outcomes and may serve as targets for future prospective interventional studies investigating the impact of specific protective ventilation strategies on postoperative outcomes after cardiac surgery.

Purpose To determine if baseline lipid levels contribute to the relationship between lipid levels during sepsis and outcomes. Materials and methods We conducted a retrospective cohort study at a tertiary-care academic medical center. Multivariable logistic regression models were used to adjust for confounders. Both Systemic Inflammatory Response Syndrome (SIRS) and Sequential Organ Failure Assessment (SOFA) score-based definitions of sepsis were analyzed. Measurements and main results After adjusting for patient characteristics and severity of illness, baseline values for both low density lipoprotein (LDL) cholesterol and triglycerides were associated with mortality (LDL cholesterol odds ratio [OR] 0.44, 95% confidence interval [CI] 0.23–0.84, p = .013; triglyceride OR 0.54, 95% CI 0.37–0.78, p = .001) using a SIRS based definition of sepsis. An interaction existed between these two variables, which resulted in increased mortality with higher baseline low density lipoprotein (LDL) cholesterol values for individuals with triglycerides below 208 mg/dL and the opposite direction of association above this level (interaction OR 1.48, 95% CI 1.02–2.16, p = .039). When using a SOFA score-based definition, only triglycerides remained associated with the mortality (OR 0.55, 95% CI 0.35–0.86, p = .008). Conclusions Baseline lipid values, particularly triglyceride concentrations, are associated with hospital mortality in septic patients.

BACKGROUND: Even small elevations in preoperative troponin levels have been shown to be associated with adverse outcomes. However, there are currently limited data on the relationship between troponin increase and timing of surgery. METHODS: We performed a single-institution, retrospective cohort study of 6030 individuals with a troponin measurement made during the 30 days preceding a noncardiac surgical procedure. Subjects with detectable troponin levels were separated into terciles based on both the magnitude of the value and the time elapsed between this value and the surgery. For those undergoing nonemergent procedures, these 9 cohorts were compared with the group of individuals with undetectable preoperative troponin levels using bivariable and multivariable logistic regression. RESULTS: Thirty-day mortality was 4.7% in the group with undetectable troponin levels and increased with higher concentrations, with rates of 8.9%, 12.7%, and 12.7% in the low, medium, and high tercile groups, respectively. Unadjusted risk of 30-day mortality was highest in those with the highest troponin levels and shortest duration between the measurement and surgery (odds ratio, 4.497; 95% confidence interval, 2.058–9.825). After adjusting for subject characteristics, troponin remained associated with 30-day mortality in several groups, including individuals with troponin levels in the normal range. CONCLUSIONS: Higher levels of preoperative cardiac troponin I were associated with higher postoperative mortality, and longer time to surgery appeared to reduce this risk for individuals with mild preoperative troponin elevations. Prospective studies are needed to determine whether delaying surgery in patients with elevated preoperative troponin levels improves postoperative outcomes.

When adding new markers to existing prediction models, it is necessary to evaluate the models to determine whether the additional markers are useful. The net reclassification improvement (NRI) has gained popularity in this role because of its simplicity, ease of estimation, and understandability. Although the NRI provides a single-number summary describing the improvement new markers bring to a model, it also has several potential disadvantages. Any improved classification by the new model is weighted equally, regardless of the direction of reclassification. In prediction models that already identify the high- and low-risk groups well, a positive NRI may not mean better classification of those with medium risk, where it could make the most difference. Also, overfitting, or otherwise misspecified training models, produce overly positive NRI results. Because of the unaccounted for uncertainty in the model coefficient estimation, investigators should rely on bootstrapped confidence intervals rather than on tests of significance. Keeping in mind the limitations and drawbacks, the NRI can be helpful when used correctly.

BACKGROUND Intraoperative electrocardiographic monitoring is considered a standard of care. However, there are no evidence-based algorithms for using intraoperative ST segment data to identify patients at high risk for adverse perioperative cardiac events. Therefore, we performed an exploratory study of statistical measures summarizing intraoperative ST segment values determine whether the variability of these measurements was associated with adverse postoperative events. We hypothesized that elevation, depression, and variability of ST segments captured in an anesthesia information management system are associated with postoperative serum troponin elevation. METHODS We conducted a single-institution, retrospective study of intraoperative automated ST segment measurements from leads I, II, and III, which were recorded in the electronic anesthesia record of adult patients undergoing noncardiac surgery. The maximum, minimum, mean, and SD of ST segment values were entered into logistic regression models to find independent associations with myocardial injury, defined as an elevated serum troponin concentration during the 7 days after surgery. Performance of these models was assessed by measuring the area under the receiver operator characteristic curve. The net reclassification improvement was calculated to quantify the amount of information that the ST segment values analysis added regarding the ability to predict postoperative troponin elevation. RESULTS Of 81,011 subjects, 4504 (5.6%) had postoperative myocardial injury. After adjusting for patient characteristics, the ST segment maximal depression (e.g., lead I: odds ratio [OR], 1.66; 95% confidence interval [CI], 1.26-2.19; P = 0.0004), maximal elevation (e.g., lead I: OR, 1.70; 95% CI, 1.34-2.17; P < 0.0001), and SD (e.g., lead I: OR, 0.16; 95% CI, 0.06-0.42; P = 0.0002) were found to have statistically significant associations with myocardial injury. Increased SD was associated with decreased risk when accounting for the maximal amount of ST segment depression and elevation and for patient characteristics. The ST segment summary statistics model had fair discrimination, with an area under the receiver operator characteristic curve of 0.71 (95% CI, 0.68-0.73). Addition of ST segment data produced a net reclassification improvement of 0.0345 (95% CI, 0.00016-0.0591; P = 0.0474). CONCLUSIONS Analysis of automated ST segment values obtained during anesthesia may be useful for improving the prediction of postoperative troponin elevation.

Background It is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population. Methods Samples for this longitudinal observational cohort study were collected at multiple tertiary-care academic medical centers as part of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic assay was used to quantify the lipidome in plasma samples from 30 individuals. Samples from two different days were analyzed for each subject. After removing lipids with a coefficient of variation > 30%, differences between cohorts were identified using repeated measures analysis of variance. The false discovery rate was used to adjust for multiple comparisons. Relationships between significant compounds were explored using hierarchical clustering of the Pearson correlation coefficients and the magnitude of these relationships was described using receiver operating characteristic curves. Results The mass spectrometry assay reliably measured 359 lipids. After adjusting for multiple comparisons, 90 compounds differed between survivors and non-survivors. Survivors had higher levels for each of these lipids except for five membrane lipids. Glycerolipids, particularly those containing polyunsaturated fatty acid side-chains, represented many of the lipids with higher concentrations in survivors. The change in lipid concentration over time did not differ between survivors and non-survivors. Conclusions The concentration of multiple plasma lipids is associated with mortality in this group of critically ill patients with ARDS. Absolute lipid levels provided more information than the change in concentration over time. These findings support future research aimed at integrating lipidomics into critical care medicine. Electronic supplementary material The online version of this article (10.1186/s12931-018-0758-3) contains supplementary material, which is available to authorized users.

Heart failure (HF) is an important risk factor for perioperative morbidity and mortality. While these patients are at high risk for cardiac adverse events, there are few current data describing the types of noncardiac complications that occur in this population.We performed a multicenter cohort study of patients undergoing noncardiac surgery from 2005 to 2010 as part of the American College of Surgeons National Surgical Quality Improvement Program. A HF cohort (HF that is new or worsening within 30 days of surgery) was compared with a control cohort that was matched regarding other surgical risk factors.Five thousand ninety-four patients with worsening preoperative HF were compared with an otherwise similar cohort of patients without worsening preoperative HF. Worsening preoperative HF was associated with increased risk of 30-day all-cause mortality (relative risk [RR] 2.08; 95% confidence interval [CI], 1.75-2.46; P0.001) and increased risk of morbidity (any recorded postoperative complication) (RR 1.54; 95% CI, 1.40-1.69; P0.001). HF patients had increased risk of developing renal failure (RR 1.85; 95% CI, 1.37-2.49; P0.001), need for mechanical ventilation longer than 48 hours (RR 1.81; 95% CI, 1.52-2.15; P0.001), pneumonia (RR 1.73; 95% CI, 1.44-2.08; P0.001), cardiac arrest (RR 1.69; 95% CI, 1.29-2.21; P0.001), unplanned intubation (RR 1.68; 95% CI, 1.41-1.99; P0.001), renal insufficiency (RR 1.64; 95% CI, 1.10-2.44; P = 0.014), sepsis (RR 1.43, 95% CI, 1.24-1.64; P0.001), and urinary tract infection (RR 1.29; 95% CI, 1.06-1.58; P = 0.011). The incidence of myocardial infarction in the sample was similar between the 2 groups (RR 1.07; 95% CI, 0.75-1.52; P = 0.719).Worsening preoperative HF is associated with a significant increase in postoperative morbidity and mortality when controlling for other comorbidities. Although these likely have a multifactorial etiology, patients are much more likely to suffer from respiratory, renal, and infectious complications than cardiac complications.

Background— During exercise, the sympathetic nervous system is activated and blood pressure and heart rate increase. In heart failure (HF), the muscle metaboreceptor contribution to sympathetic outflow is attenuated and the mechanoreceptor contribution is accentuated. Previous studies suggest that (1) capsaicin stimulates muscle metabosensitive vanilloid receptor subtype 1 (VR1), inducing a neurally mediated pressor response, and (2) activation of ATP-sensitive P2X receptors enhances the pressor response seen when muscle mechanoreceptors are engaged by muscle stretch. Thus, we hypothesized that the pressor response to VR1 stimulation would be smaller and the sensitizing effects of P2X stimulation greater in rats with HF due to chronic myocardial infarction (MI) than in controls. Methods and Results— Eight to 14 weeks after coronary ligation, rats with infarcts >35% had an increased left ventricular end-diastolic pressure and a marked increase in heart weight. Capsaicin injected into the arterial supply of the hindlimb increased blood pressure by 39% (baseline, 93.9±9.5 mm Hg) in control animals but only by 8% (baseline, 94.8±10.1 mm Hg) in rats with large MIs ( P P Conclusions— Compared with control animals, cardiovascular responses to VR1 stimulation are blunted and P2X-mediated responses are augmented in rats with HF owing to large MIs.

Reflex cardiovascular responses to muscle contraction are mediated by mechanical and metabolic stimulation of thin muscle afferent fibers. Metabolic stimulants and receptors involved in responses are uncertain. Capsaicin depolarizes thin sensory afferent nerves that have vanilloid type 1 receptors (VR1). Among potential endogenous ligands of thin fibers, H+ has been suggested as a metabolite mediating the reflex muscle response as well as a potential stimulant of VR1. It has also been suggested that acid-sensing ion channels (ASIC) mediate H+, evoking afferent nerve excitation. We have examined the roles of VR1 and ASIC in mediating cardiovascular reflex responses to acid stimulation of muscle afferents in a rat model. In anesthetized rats, injections of capsaicin into the arterial blood supply of triceps surae muscles evoked a biphasic response ( n = 6). An initial fall in mean arterial pressure (from baseline of 95.8 ± 9.5 to 70.4 ± 4.5 mmHg, P < 0.05 vs. baseline) was followed by an increase (to 131.6 ± 11.3 mmHg, P < 0.05 vs. baseline). Anandamide (an endogenous substance that activates VR1) induced the same change in blood pressure as did capsaicin. The pressor (but not depressor) component of the response was blocked by capsazepine (a VR1 antagonist) and section of afferent nerves. In decerebrate rats ( n = 8), H+ evoked a pressor response that was not blocked by capsazepine but was attenuated by amiloride (an ASIC blocker). In rats ( n = 12) pretreated with resiniferatoxin to destroy muscle afferents containing VR1, capsaicin and H+ responses were blunted. We conclude that H+ stimulates ASIC, evoking the reflex response, and that ASIC are likely to be frequently found on afferents containing VR1. The data also suggest that VR1 and ASIC may play a role in processing of muscle afferent signals, evoking the muscle pressor reflex.

Background: Acute lung injury (ALI) is associated with high mortality. Low tidal volume (Vt) ventilation has been shown to reduce mortality in ALI patients in the intensive care unit. Anesthesiologists do not routinely provide lung-protective ventilation strategies to patients with ALI in the operating room. The authors hypothesized that an alert, recommending lung-protective ventilation regarding patients with potential ALI, would result in lower Vt administration. Methods: The authors conducted a randomized controlled trial on anesthesia providers caring for patients with potential ALI. Patients with an average or last collected ratio of partial pressure of arterial oxygen to inspired fraction of oxygen less than 300 were randomized to providers being sent an alert with a recommended Vt of 6 cc/kg predicted body weight or conventional care. Primary outcomes were Vt/kg predicted body weight administered to patients. Secondary outcomes included ventilator parameters, length of postoperative ventilation, and death. Results: The primary outcome was a clinically significant reduction in mean Vt from 508–458 cc (P = 0.033), with a reduction in Vt when measured in cc/kg predicted body weight from 8 to 7.2 cc/kg predicted body weight (P = 0.040). There were no statistically significant changes in other outcomes or adverse events associated with either arm. Conclusions: Automated alerts generated for patients at risk of having ALI resulted in a statistically significant reduction in Vt administered when compared with a control group. Further research is required to determine whether a reduction in Vt results in decreased mortality and/or postoperative duration of mechanical ventilation.

Background The incidence of acute lung injury (ALI) in hypoxic patients undergoing surgery is currently unknown. Previous studies have identified lung protective ventilation strategies that are beneficial in the treatment of ALI. The authors sought to determine the incidence and examine the use of lung protective ventilation strategies in patients receiving anesthetics with a known history of ALI. Methods The ventilation parameters that were used in all patients were reviewed, with an average preoperative PaO₂/Fio₂ [corrected] ratio of ≤ 300 between January 1, 2005 and July 1, 2009. This dataset was then merged with a dataset of patients screened for ALI. The median tidal volume, positive end-expiratory pressure, peak inspiratory pressures, fraction inhaled oxygen, oxygen saturation, and tidal volumes were compared between groups. Results A total of 1,286 patients met criteria for inclusion; 242 had a diagnosis of ALI preoperatively. Comparison of patients with ALI versus those without ALI found statistically yet clinically insignificant differences between the ventilation strategies between the groups in peak inspiratory pressures and positive end-expiratory pressure but no other category. The tidal volumes in cc/kg predicted body weight were approximately 8.7 in both groups. Peak inspiratory pressures were found to be 27.87 cm H₂O on average in the non-ALI group and 29.2 in the ALI group. Conclusion Similar ventilation strategies are used between patients with ALI and those without ALI. These findings suggest that anesthesiologists are not using lung protective ventilation strategies when ventilating patients with low PaO₂/Fio₂ [corrected] ratios and ALI, and instead are treating hypoxia and ALI with higher concentrations of oxygen and peak pressures.