Constrained Functional Connectivity Dynamics in Pediatric Surgical Patients Undergoing General Anesthesia.

BACKGROUND: Functional connectivity in cortical networks is thought to be important for consciousness and can be disrupted during the anesthetized state. Recent work in adults has revealed dynamic connectivity patterns during stable general anesthesia, but whether similar connectivity state transitions occur in the developing brain remains undetermined. The hypothesis was that anesthetic-induced unconsciousness is associated with disruption of functional connectivity in the developing brain and that, as in adults, there are dynamic shifts in connectivity patterns during the stable maintenance phase of general anesthesia. METHODS: This was a preplanned analysis of a previously reported single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists status I or II) children aged 8 to 16 yr undergoing surgery with general anesthesia (n = 50) at Michigan Medicine. Whole-scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Functional connectivity was measured using a weighted phase lag index, and discrete connectivity states were classified using cluster analysis. RESULTS: Changes in functional connectivity were associated with anesthetic state transitions across multiple regions and frequency bands. An increase in prefrontal-frontal alpha (median [25th, 75th]; baseline, 0.070 [0.049, 0.101] vs. maintenance 0.474 [0.286, 0.606]; P < 0.001) and theta connectivity (0.038 [0.029, 0.048] vs. 0.399 [0.254, 0.488]; P < 0.001), and decrease in parietal-occipital alpha connectivity (0.171 [0.145, 0.243] vs. 0.089 [0.055, 0.132]; P < 0.001) were among those with the greatest effect size. Contrary to the hypothesis, connectivity patterns during the maintenance phase of general anesthesia were dominated by stable theta and alpha prefrontal-frontal and alpha frontal-parietal connectivity and exhibited high between-cluster similarity (r = 0.75 to 0.87). CONCLUSIONS: Changes in functional connectivity are associated with anesthetic state transitions but, unlike in adults, connectivity patterns are constrained during general anesthesia in late childhood and early adolescence.

Use of the Change in Weaning Parameters as a Predictor of Successful Re-Extubation.

OBJECTIVE: Weaning parameters are well studied in patients undergoing first time extubation. Fewer data exists to guide re-extubation of patients who failed their first extubation attempt. It is reasonable to postulate that improved weaning parameters between the first and second extubation attempt would lead to improved rates of re-extubation success. To investigate, we studied a cohort of patients who failed their first extubation attempt and underwent a second attempt at extubation. We hypothesized that improvement in weaning parameters between the first and the second extubation attempt is associated with successful reextubation. INTERVENTIONS: Rapid shallow breathing index (RSBI), maximum inspiratory pressure (MIP), vital capacity (VC), and the blood partial pressure of CO2 (PaCO2) were measured and recorded in the medical record prior to extubation along with demographic information. We examined the relationship between the change in extubation and re-extubation weaning parameters and re-extubation success. MEASUREMENTS AND MAIN RESULTS: A total of 1283 adult patients were included. All weaning parameters obtained prior to re-extubation differed between those who were successful and those who required a second reintubation. Those with reextubation success had slightly lower PaCO2 values (39.5 ± 7.4 mmHg vs. 41.6 ± 9.1 mmHg, p = 0.0045) and about 13% higher vital capacity volumes (1021 ± 410 mL vs. 907 ± 396 mL, p = 0.0093). Lower values for RSBI (53 ± 32 breaths/min/L vs. 69 ± 42 breaths/min/L, p < 0.001) and MIP (-41 ± 12 cmH2O vs. -38 ± 13 cm H2O), p = 0.0225) were seen in those with re-extubation success. Multivariable logistical regression demonstrates lack of independent associated between the change in parameters between the 2 attempts and re-extubation success. CONCLUSIONS: The relationship between the changes in extubation parameters through successive attempts is driven primarily by the value obtained immediately prior to re-extubation. These findings do not support waiting for an improvement in extubation parameters to extubate patients who failed a first attempt at extubation if extubation parameters are compatible with success.

Identification of intraoperative management strategies that have a differential effect on patients with reduced left ventricular ejection fraction: a retrospective cohort study.

BACKGROUND: There are few data to guide the intraoperative management of patients with reduced left ventricular ejection fraction (LVEF). This study aimed to describe how patients with reduced LVEF are managed differently and to identify and treatments had a different risk profile in this population. METHODS: We performed a retrospective cohort study of adult patients who underwent general anesthesia for non-cardiac surgery. The effect of anesthesia medications and fluid balance was compared between those with and without a reduced preoperative LVEF. The primary outcome was a composite of acute kidney injury, myocardial injury, pulmonary complications, and 30-day mortality. Multivariable logistic regression was used to adjust for confounders. Treatments that affected patients with reduced LVEF differently were defined as those associated with the primary outcome that also had a significant interaction with LVEF. RESULTS: A total of 9420 patients were included. Patients with reduced LVEF tended to have a less positive fluid balance. Etomidate, calcium, and phenylephrine were use more frequently, while propofol and remifentanil were used less frequently. Remifentanil affected patients with reduced LVEF differently than those without (interaction term OR 2.71, 95% CI 1.30-5.68, p = 0.008). While the use of remifentanil was associated with fewer complications in patients with normal systolic function (OR 0.54, 95% CI 0.42-0.68, p < 0.001), it was associated with an increase in complications in patients with reduced LVEF (OR = 3.13, 95% CI 3.06-5.98, p = 0.026). CONCLUSIONS: Patients with a reduced preoperative LVEF are treated differently than those with a normal LVEF when undergoing non-cardiac surgery. An association was found between the use of remifentanil and an increase in postoperative adverse events that was unique to this population. Future research is needed to determine if this relationship is secondary to the medication itself or reflects a difference in how remifentanil is used in patients with reduced LVEF.

Neurophysiologic Complexity in Children Increases with Developmental Age and Is Reduced by General Anesthesia.

BACKGROUND: Neurophysiologic complexity in the cortex has been shown to reflect changes in the level of consciousness in adults but remains incompletely understood in the developing brain. This study aimed to address changes in cortical complexity related to age and anesthetic state transitions. This study tested the hypotheses that cortical complexity would (1) increase with developmental age and (2) decrease during general anesthesia. METHODS: This was a single-center, prospective, cross-sectional study of healthy (American Society of Anesthesiologists physical status I or II) children (n = 50) of age 8 to 16 undergoing surgery with general anesthesia at Michigan Medicine. This age range was chosen because it reflects a period of substantial brain network maturation. Whole scalp (16-channel), wireless electroencephalographic data were collected from the preoperative period through the recovery of consciousness. Cortical complexity was measured using the Lempel-Ziv algorithm and analyzed during the baseline, premedication, maintenance of general anesthesia, and clinical recovery periods. The effect of spectral power on Lempel-Ziv complexity was analyzed by comparing the original complexity value with those of surrogate time series generated through phase randomization that preserves power spectrum. RESULTS: Baseline spatiotemporal Lempel-Ziv complexity increased with age (yr; slope [95% CI], 0.010 [0.004, 0.016]; P < 0.001); when normalized to account for spectral power, there was no significant age effect on cortical complexity (0.001 [-0.004, 0.005]; P = 0.737). General anesthesia was associated with a significant decrease in spatiotemporal complexity (median [25th, 75th]; baseline, 0.660 [0.620, 0.690] vs. maintenance, 0.459 [0.402, 0.527]; P < 0.001), and spatiotemporal complexity exceeded baseline levels during postoperative recovery (0.704 [0.642, 0.745]; P = 0.009). When normalized, there was a similar reduction in complexity during general anesthesia (baseline, 0.913 [0.887, 0.923] vs. maintenance 0.851 [0.823, 0.877]; P < 0.001), but complexity remained significantly reduced during recovery (0.873 [0.840, 0.902], P < 0.001). CONCLUSIONS: Cortical complexity increased with developmental age and decreased during general anesthesia. This association remained significant when controlling for spectral changes during anesthetic-induced perturbations in consciousness but not with developmental age.

Reduced Echocardiographic Inotropy Index after Cardiopulmonary Bypass Is Associated With Complications After Cardiac Surgery: An Institutional Outcomes Study.

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, the authors 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: The study comprised 189 elective adult cardiac surgical procedures from 2015-2016. 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 <0.83 W/m2 independently predicted the primary outcome (adjusted odds ratio 2.19, 95% confidence interval 1.08-4.42); whereas PKR, LVEF, and cardiac index demonstrated no associations. When SMII and PKR were incorporated into a EuroSCORE II risk model, predictive performance improved (net reclassification index improvement 0.457; p = 0.001); whereas a model incorporating LVEF and cardiac index demonstrated no improvement (0.130; p = 0.318). CONCLUSION: The present study demonstrated that SMII, but not PKR, as a measure of cardiac function was associated with major complications. The study's data may guide investigations of more suitable perioperative goal-directed therapies to reduce complications after cardiac surgery.

Association of Intraoperative Ventilator Management With Postoperative Oxygenation, Pulmonary Complications, and Mortality.

BACKGROUND: "Lung-protective ventilation" describes a ventilation strategy involving low tidal volumes (VTs) and/or low driving pressure/plateau pressure and has been associated with improved outcomes after mechanical ventilation. We evaluated the association between intraoperative ventilation parameters (including positive end-expiratory pressure [PEEP], driving pressure, and VT) and 3 postoperative outcomes: (1) PaO2/fractional inspired oxygen tension (FIO2), (2) postoperative pulmonary complications, and (3) 30-day mortality. METHODS: We retrospectively analyzed adult patients who underwent major noncardiac surgery and remained intubated postoperatively from 2006 to 2015 at a single US center. Using multivariable regressions, we studied associations between intraoperative ventilator settings and lowest postoperative PaO2/FIO2 while intubated, pulmonary complications identified from discharge diagnoses, and in-hospital 30-day mortality. RESULTS: Among a cohort of 2096 cases, the median PEEP was 5 cm H2O (interquartile range = 4-6), median delivered VT was 520 mL (interquartile range = 460-580), and median driving pressure was 15 cm H2O (13-19). After multivariable adjustment, intraoperative median PEEP (linear regression estimate [B] = -6.04; 95% CI, -8.22 to -3.87; P < .001), median FIO2 (B = -0.30; 95% CI, -0.50 to -0.10; P = .003), and hours with driving pressure >16 cm H2O (B = -5.40; 95% CI, -7.2 to -4.2; P < .001) were associated with decreased postoperative PaO2/FIO2. Higher postoperative PaO2/FIO2 ratios were associated with a decreased risk of pulmonary complications (adjusted odds ratio for each 100 mm Hg = 0.495; 95% CI, 0.331-0.740; P = .001, model C-statistic of 0.852) and mortality (adjusted odds ratio = 0.495; 95% CI, 0.366-0.606; P < .001, model C-statistic of 0.820). Intraoperative time with VT >500 mL was also associated with an increased likelihood of developing a postoperative pulmonary complication (adjusted odds ratio = 1.06/hour; 95% CI, 1.00-1.20; P = .042). CONCLUSIONS: In patients requiring postoperative intubation after noncardiac surgery, increased median FIO2, increased median PEEP, and increased time duration with elevated driving pressure predict lower postoperative PaO2/FIO2. Intraoperative duration of VT >500 mL was independently associated with increased postoperative pulmonary complications. Lower postoperative PaO2/FIO2 ratios were independently associated with pulmonary complications and mortality. Our findings suggest that postoperative PaO2/FIO2 may be a potential target for future prospective trials investigating the impact of specific ventilation strategies for reducing ventilator-induced pulmonary injury.

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study.

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.

Complications Associated With Mortality in the National Surgical Quality Improvement Program Database.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

Complications, Risk Factors, and Staffing Patterns for Noncardiac Surgery in Patients with Left Ventricular Assist Devices.

BACKGROUND: Patients with left ventricular assist devices presenting for noncardiac surgery are increasingly commonplace; however, little is known about their outcomes. Accordingly, the authors sought to determine the frequency of complications, risk factors, and staffing patterns. METHODS: The authors performed a retrospective study at their academic tertiary care center, investigating all adult left ventricular assist device patients undergoing noncardiac surgery from 2006 to 2015. The authors described perioperative profiles of noncardiac surgery cases, including patient, left ventricular assist device, surgical case, and anesthetic characteristics, as well as staffing by cardiac/noncardiac anesthesiologists. Through univariate and multivariable analyses, the authors studied acute kidney injury as a primary outcome; secondary outcomes included elevated serum lactate dehydrogenase suggestive of left ventricular assist device thrombosis, intraoperative bleeding complication, and intraoperative hypotension. The authors additionally studied major perioperative complications and mortality. RESULTS: Two hundred and forty-six patients underwent 702 procedures. Of 607 index cases, 110 (18%) experienced postoperative acute kidney injury, and 16 (2.6%) had elevated lactate dehydrogenase. Of cases with complete blood pressure data, 176 (27%) experienced intraoperative hypotension. Bleeding complications occurred in 45 cases (6.4%). Thirteen (5.3%) patients died within 30 days of surgery. Independent risk factors associated with acute kidney injury included major surgical procedures (adjusted odds ratio, 4.4; 95% CI, 1.1 to 17.3; P = 0.03) and cases prompting invasive arterial line monitoring (adjusted odds ratio, 3.6; 95% CI, 1.3 to 10.3; P = 0.02) or preoperative fresh frozen plasma transfusion (adjusted odds ratio, 1.7; 95% CI, 1.1 to 2.8; P = 0.02). CONCLUSIONS: Intraoperative hypotension and acute kidney injury were the most common complications in left ventricular assist device patients presenting for noncardiac surgery; perioperative management remains a challenge.

Timing of Preoperative Troponin Elevations and Postoperative Mortality After Noncardiac Surgery.

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.

Net Reclassification Improvement.

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.

Variability of Automated Intraoperative ST Segment Values Predicts Postoperative Troponin Elevation.

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.

Regional versus general anesthesia in surgical patients with chronic obstructive pulmonary disease: does avoiding general anesthesia reduce the risk of postoperative complications?

BACKGROUND: Surgical patients with chronic obstructive pulmonary disease (COPD) are at increased risk of perioperative complications. In this study, we sought to quantify the benefit of avoiding general anesthesia in this patient population. METHODS: Data from the National Surgical Quality Improvement Program database (2005-2010) were used for this review. Patients who met the National Surgical Quality Improvement Program definition for COPD and underwent surgery under general, spinal, epidural, or peripheral nerve block anesthesia were included in this study. For each primary current procedural terminology code with ≥ 1 general and ≥ 1 regional (spinal, epidural, or peripheral nerve block) anesthetic, regional patients were propensity score--matched to general anesthetic patients. Propensity scoring was calculated using all available demographic and comorbidity data. This match yielded 2644 patients who received regional anesthesia and 2644 matched general anesthetic patients. These groups were compared for morbidity and mortality. RESULTS: Groups were well matched on demographics, comorbidities, and type of surgery. Compared with matched patients who received regional anesthesia, patients who received general anesthesia had a higher incidence of postoperative pneumonia (3.3% vs 2.3%, P = 0.0384, absolute difference with 95% confidence interval = 1.0% [0.09, 1.88]), prolonged ventilator dependence (2.1% vs 0.9%, P = 0.0008, difference = 1.2% [0.51, 1.84]), and unplanned postoperative intubation (2.6% vs 1.8%, P = 0.0487, difference = 0.8% [0.04, 1.62]). Composite morbidity was 15.4% in the general group versus 12.6% (P = 0.0038, difference = 2.8% [0.93, 4.67]). Composite morbidity not including pulmonary complications was 13.0% in the general group versus 11.1% (P = 0.0312, difference = 1.9% [0.21, 3.72]). Thirty-day mortality was similar (2.7% vs 3.0%, P = 0.6788, difference = 0.3% [-1.12, 0.67]). As a test for validity, we found a positive association between pulmonary end points because patients with 1 pulmonary complication were significantly more likely to have additional pulmonary complications. CONCLUSIONS: The use of regional anesthesia in patients with COPD is associated with lower incidences of composite morbidity, pneumonia, prolonged ventilator dependence, and unplanned postoperative intubation.

Impact of adding aspirin to beta-blocker and statin in high-risk patients undergoing major vascular surgery.

BACKGROUND: Beta-blockers (BB) and statins (S) independently have been shown to reduce perioperative mortality and myocardial infarction (MI) in patients undergoing vascular surgery. In this study we evaluated the benefits of adding aspirin (A) to BB and S (ABBS), with/without angiotensin-converting enzyme inhibitor (ACE-I) on postoperative outcome in high-risk patients undergoing major vascular surgery. METHODS: Analysis of consecutive patients undergoing elective vascular surgery at the University of Michigan Cardiovascular Center was performed. Univariate and multivariate analyses were done using cardiac risk index [Revised Cardiac Risk Index (RCRI), coronary artery disease (CAD), insulin-dependent diabetes mellitus (IDDM), cerebral vascular disease, renal dysfunction, congestive heart failure, and major surgery]; pulmonary disease; and A, BB, S (ABBS)±ACE-I use. Baseline clinical characteristics and medication were adjusted using propensity scores. Endpoints were bleeding, 30-day MI, stroke, and 12-month mortality. RESULTS: Between 2003 and 2010, 4,149 arterial procedures were performed, 819 of which were risk stratified as RCRI≥3. The incidence of MI was 3-fold lower (2.5% vs. 7.8%, OR 0.31, 95% CI 0.15-0.61, P=0.001) in ABBS±ACE-I (n=513) as compared with non-ABBS±ACE-I (n=306). The 12-month mortality was 8-fold lower in ABBS±ACE-I as compared non-ABBS±ACE-I (5.9% vs. 37.5%, HR 0.13, 95% CI 0.08-0.20, P<0.0001). After adjustment for the propensity to use various therapies, A (HR 0.35, 95% CI 0.24-0.53, P<0.0001), BB (HR 0.65, 95% CI 0.43-1.0, P=0.05), and S (HR 0.36, 95% CI 0.25-0.53, P<0.0001) remained associated with improved 12-month survival. ACE-I use (HR 0.80, 95% CI 0.54-1.19, P=0.27) was not predictive. Aspirin did not predict severe/moderate bleeding. CONCLUSIONS: In high-risk patients undergoing major vascular surgery, ABBS therapy has superior 30-day and 12-month risk reduction benefits for MI, stroke, and mortality as compared with A, BB, or S independently. ACE-I did not demonstrate additional risk-reduction benefits.

Preoperative Predictors of Severe Respiratory Events After Tonsillectomy: Consideration for Pediatric Intensive Care Admission.

OBJECTIVE: Few data are available to guide postadenotonsillectomy (AT) pediatric intensive care (PICU) admission. The aim of this study of children with a preoperative polysomnogram (PSG) was to assess whether preoperative information may predict severe respiratory events (SRE) after AT. STUDY DESIGN: Retrospective cohort study. SETTING: Single tertiary center. METHODS: Children aged 6 months to 17 years who underwent AT with preoperative polysomnography (2012-2018) were identified by billing codes. Data were extracted from medical records. SRE were defined as any 1 or more of desaturations <80% requiring intervention; newly initiated positive airway pressure; postoperative intubation; pneumonia/pneumonitis; respiratory code, cardiac arrest, or death. We hypothesized that SRE would be associated with age <24 months, major medical comorbidity, obesity (>95th percentile), apnea-hypopnea index (AHI) ≥ 30, and O2 nadir <70% on PSG. Analysis was performed with multivariable logistic regression. RESULTS: Of 1774 subjects, 28 (1.7%) experienced SRE. Compared to those without, children with SRE were on average younger (3 vs 5 years, p < .01) with a greater probability of medical comorbidities (59% vs 18%, p < .001). After adjustment for sex, black race, obesity, and age <24 months, children with major medical comorbidity were more likely than other children to have SRE (odds ratio [OR]: 14.2; 95% confidence interval [CI]: [5.7, 35.2]), as were children with AHI ≥ 30 (OR: 7.7 [3.0, 19.9]), or O2 nadir <70% (OR 6.1 [2.1, 17.9]). Age, obesity, sex, and black race did not independently predict SRE. CONCLUSION: PICU admission may be most prudent for children with complex medical co-morbidities, high AHI (>30), and/or low O2 nadir (<70%).

Intraoperative blood collection without fluid replacement for cardiac surgery - A retrospective analysis.

Background: Transfusion rates in cardiac surgery are high. Aim: To determine if intraoperative autologous blood removal without volume replacement is associated with fewer homologous blood transfusions without increasing acute kidney injury. Setting and Design: Retrospective, comparative study. Materials and Methods: Adult patients undergoing cardiac surgery, excluding those who underwent ventricular assist device surgery, heart transplants, or cardiac surgery without cardiopulmonary bypass were excluded, who had 1-3 units of intraoperative autologous blood removal were compared to patients without blood removal for determination of volume replacement, vasopressor support, acute kidney injury, and transfusions. Results: Autologous blood removal was associated with fewer patients receiving homologous transfusions: intraoperative red cell transfusions fell from 75% (Control) to 48% (1 unit removed), 40% (2 units), and 30% (3 units), P < 0.001. Total intraoperative and postoperative homologous RBC units transfused were lower in the blood removal groups: median (interquartile range) 3 (1, 6) in Control patients and 0 (0, 2), 0 (0, 2) and 0 (0, 1) in the 1, 2, and 3 units removed groups, P < 0.001. Similarly, plasma, platelet, and cryoprecipitate transfusions decreased. After adjustment for confounders, increased amounts of autologous blood removal were associated with increased intravenous fluids, only when 2 units were removed, and trivially increased vasopressor use. However, it was not associated with acidosis or acute kidney injury. Conclusions: Intraoperative autologous blood removal without volume replacement of 1-3 units for later autologous transfusion is associated with decreased homologous transfusions without acidosis or acute kidney injury.

Genetic variants associated with sepsis.

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<0.01. After multivariate adjustment, 100 variants on 85 genes were associated with Sepsis-2 and 69 variants in 54 genes with Sepsis-3. Twenty-five variants were present in both the Sepsis-2 and Sepsis-3 groups out of 32 genes that were present in both groups. The other 7 genes had different variants present. Most variants had small effect sizes. 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 effect of timing of initiation of renal replacement therapy on mortality: A retrospective case-control study.

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 < 0.001) as was hospital mortality (n = 73 (43%) vs. n = 44 (26%), p = 0.001). Of the 18 RRT patients in DEFERRED, 12 (67%) died in ICU and 13 (72%) in hospital. After propensity matching and logistic regression, we found that EARLY initiation of RRT was associated with a more than doubling of ICU mortality (aOR = 2.310, 95% confidence interval = 1.254-4.257, p = 0.007). However, after similar adjustment, there was no difference in hospital mortality (aOR = 1.283, 95% CI = 0.753-2.186, p = 0.360). CONCLUSIONS: While ICU mortality was increased in the EARLY group, there was no difference in hospital mortality between EARLY and DEFERRED groups.

Impact of the pre-illness lipid profile on sepsis mortality.

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.