This retrospective, observational, cohort study was conducted using the data obtained from Society of Thoracic Surgery (STS) database and institutional Anesthesia Information Management Systems (AIMS) database, after the Institutional Review Board approval (IRB, Beth Israel Deaconess Medical Centre, Boston, US, Protocol #2008P000478). Informed patient consent was waived by our IRB. This manuscript adheres to the applicable Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) standards for observational studies . Blood pressure data were collected from a total of 3,687 patients over 18 years of age who underwent cardiac surgery that required cardio-pulmonary bypass (CPB) from January 2008 to June 20143.
Perioperative management of the patient cohort analysed in this study was along the lines of the Institute protocol during the period of data acquisition. As the type of anesthetic regimen used is an important predictor for hypotension after induction , we have described our anesthesia technique. In brief, anesthesia induction typically included fentanyl, Propofol or etomidate tailored to the patient profile and rocuronium for neuro-muscular blockade. Isoflurane in 100% oxygen was used for maintenance, along with supplemental boluses of fentanyl. A non-pulsatile cardiopulmonary bypass was used with the flow titrated to maintain mean arterial pressure of 50-70 mmHg and a venous oxygen saturation greater than 60%. Alpha stat pH management was employed to manage blood gases. Temperature was maintained at 34°C in coronary artery bypass grafting (CABG) surgeries, 32°C in valve surgeries. All patients were shifted transferred to cardiovascular intensive care unit for postoperative care.
Invasive arterial blood pressure data including systolic and mean pressures during the pre-bypass, bypass and post-bypass phases of cardiac surgery were obtained from the hospital’s anesthesia information management systems (AIMS) (CompuRecord, Philips Healthcare, Andover, MA, USA) at a rate of one sample every 15 seconds. Given the lack of pulsatility, systolic blood pressure (SBP) was not measured during CPB. Mean arterial pressure (MAP) was recorded during all the three phases. Patient characteristics were obtained from the STS database. This database is a clinical outcomes registry that records the care of patients undergoing cardiac procedures at participating hospitals. Patient characteristics obtained from STS include, baseline demographic data, patient characteristics such as comorbidities, medications, intraoperative characteristics, STS risk scores for morbidity and mortality, STS Predicted risk scores for renal failure, and post-operative outcomes, namely, 30-day mortality and renal failure during hospital admission.
STS risk scores were computed for each patient undergoing cardiac surgery by institutional STS coordinators as a part of nationwide STS database. Data on mortality was gathered from this STS database. If a patient was discharged and sent home, the patient was given a 30-day appointment. Those who missed the 30-day appointment were given a call by the STS database coordinator to note the morbidity and mortality. State STS coordinators also run the Social Security Death Index to capture those who died within 30 days after cardiac surgery, and this information was sent to the individual hospital.
BP variability was calculated in terms of coefficient of variation (CV) and Poincaré plots. CV is defined as the standard deviation divided by mean. Poincaré plot is a quantitative, graphical tool that provides a visual representation of the non-linear aspects of a time series data sequence on a phase-space or Cartesian plane. It is a geometrical representation of a physiological signal’s time-series and provides qualitative visualization of its nonlinear dynamic changes. It is a scatter plot (AKA return map / phase delay map) where each data point on a time series ( is plotted against the next one ( [13,19]. It is a simple visual tool, the shape of which represents the variability of the time series .. The ellipse shape of the plot provides two standard descriptors SD1 and SD2 for quantifying the plot geometry . The line of identity is the 45° imaginary diagonal line on the elliptical Poincaré plot. SD1 is the minor semi-axis of the fitted ellipse and measures the dispersion of data perpendicular to the line of identity. SD2 is the major semi-axis of the fitted ellipse and measures the dispersion along the line of identity. SD1 represents short-term variability, and SD2 long-term variability .
Poincaré plots of SBP and MAP, measured every 15 seconds were constructed per patient using MATLAB (Natick, MA) by producing a scatter plot of each BP value against the next one. SD1, SD2 were obtained from the plot using the ellipse fitting technique. This was done specifically for each phase of surgery (pre-bypass, bypass and post-bypass). BPV data was merged with patient characteristics and outcome details obtained from the Society of Thoracic Surgeons National Adult Cardiac Surgery Database (STS).
Our primary outcomes were 30-day mortality and in-hospital renal failure that were defined based on STS version 2.61 definitions for postoperative outcomes. Renal failure was defined as having one or both of: 1) increase in serum creatinine level >2.0, and 2 x greater than baseline, 2) a new requirement for dialysis postoperatively. Mortality includes: 1) all deaths, regardless of cause, occurring during the hospitalization in which the operation was performed, even if after 30 days (including patients transferred to other acute care facilities); and (2) all deaths, regardless of cause, occurring after discharge from the hospital, but before the end of the thirtieth postoperative day. If a patient was discharged, they were given a 30-day appointment. Those who missed the 30-day appointment were contacted through phone by the STS database coordinator to note the morbidity and mortality. State STS coordinators also run the Social Security Death Index to capture those who died within 30 days after cardiac surgery, and this information was sent to the individual hospital.
Data is presented as median (interquartile range) or n (%) depending upon the variable. Chi-square, Fischer’s exact or Mann-Whitney U test were appropriately used to assess differences in baseline characteristics, surgical and blood pressure data between groups, stratified by mortality and renal failure. Normality of continuous variables was assessed using Shapiro-Wilk test. All analyses were conducted using IBM SPSS Statistics, Version 24.0 (Armonk, NY: IBM Corp.)
A goodness of fit for a multivariable binary logistic regression model (mortality vs. no mortality, renal failure vs. no renal failure) was tested using the Hosmer-Lemeshow test. The groups and contingency table used for Hosmer-Lemeshow test were presented in Supplementary Table 1. The concordance statistic (C-statistic) was calculated to quantify the predictive strength of this ‘baseline model’ which included patient characteristics from the STS database as independent variables. The same was performed on univariable models with CV, SD1 and SD2 respectively as the predictive variables. The final models included the STS variables along with the BPV parameters to test any improvement in performance over the baseline model. In brief, the multivariable model that explored predictive ability of STS risk index alone, was adjusted to age, surgery category, STS risk score, and intraoperative vasopressor dose. In models exploring the predictive ability of BP variability indices, it was adjusted to age, surgery category, STS risk score, and intraoperative vasopressor dose. Missing STS risk algorithm scores were imputed and assessed for inclusion in the model. We considered p <0.05 as statistically significant.
We included STS risk score as a variable in the models as they are used at the national level as a common metric for assessing center-to-center performance, patient counseling and clinical decision making. Moreover, it includes valuable information about patient demographics and surgical characteristics that could potentially affect the outcome after surgery and have been used as a variable in previous studies. Initial variables selection for the multivariate models were based on clinical judgement and statistical significance in univariate analysis. Further variable selection was performed in a hierarchical fashion using stepwise variable selection. Estimation was terminated at iteration number 7 because parameter estimates changed by less than .001.
No a priori power or sample size calculation was performed for the study. Given the exploratory nature of the BP data analysis, all patients who met entry criteria during the study period were included in the analysis.