2.1

Patients

This study was approved by the Institutional Review Board of Medstar Research Institute. All of our cardiac surgery patients were asked to give written informed consent for clinical record research review. Due to the retrospective nature of the study, the requirement for informed consent was waived.

From November 21, 2005, to June 9, 2006, 632 adult patients underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Washington Hospital Center. Of those, 334 patients underwent on-pump isolated CABG and 295 patients had open-heart surgery (OOHS); three patients with endocarditis underwent valve surgery were excluded from this study. Patient baseline demographics, procedure data and perioperative outcomes were recorded and entered concurrently into the computerized database of cardiac surgery by a data-coordinating center. All data were defined according to the Society of Thoracic Surgeons national database (Version 2.52). Guidelines and definitions are available at http://www.sts.org/sections/stsnationaldatabase/datamanagers . All adverse clinical events were source documented. Patients were contacted by telephone 30 days after hospital discharge as part of the routine clinical follow-up.

2.2

Postoperative treatments and data collection

Patients who underwent CABG procedure received a Swan-Ganz catheter if ejection fraction was less than 40%. All valve procedures received a Swan-Ganz catheter. For patients without Swan-Ganz catheter insertion in the operating room (OR) and when a mean arterial blood pressure (MAP) of 70 mmHg could not be maintained after separation from CPB and in the intensive care unit (ICU) despite fluid administration, Swan-Ganz catheter monitoring was initiated. Vasoactive agents were titrated according to the MAP, CO and SVR. The following hemodynamic variables were recorded: mean pulmonary arterial pressure (MAP), central venous pressure (CVP), pulmonary artery occlusion pressure, and CO. Systemic vascular resistance index (SVRI) and cardiac index (CI) were calculated.

2.3

PVS definition

In accordance with previous studies , PVS was defined as a MAP ≤70 mmHg, SVRI ≤1400 dynes-s cm ⁻⁵ m ⁻² , CI ≥2.5 min ⁻¹ m ⁻² , and CVP ≥10 mmHg. Only patients who met these criteria within 24 h after surgery and required vasopressor support with norepinephrine and/or vasopressin were included. Every patient, if not contradicted, received 2 g of magnesium perioperatively on a regular basis. No other vasodilators drugs were administered routinely. We excluded patients who received inotropic agents including epinephrine, dopamine, milrinone, or dobutamine within 24 h postoperatively from the PVS group; we also excluded patients who received intraoperative and/or postoperative intra-aortic balloon pump from the PVS group; these were patients with unstable postoperative haemodynamics which are highly correlated with compromised cardiac function. Three patients with preoperative endocarditis or other severe infections (e.g., pneumonia or intraabdominal abscess) were excluded from this study.

2.4

Anesthesia, surgery and CPB

Preoperative cardiac medications, including nitrates, β-blockers, calcium-channel blockers, and angiotensin-converting enzyme (ACE) inhibitors were administered until surgery. Primary anesthesia consisted of low-intermediate dose fentanyl (8 μg/kg), etomidate (1–2 mg/kg), and isoflurane to end-tidal concentration of 0.5–1 minimum alveolar concentration. Nondepolarizing muscle relaxant (pancuronium bromide 0.15/kg) was used to facilitate endotracheal intubation. CPB was conducted by a 2.4 L min m ⁻² flow (nonpulsatile pump) under moderate systemic hypothermia (30–34°C). Perfusion pressure was maintained at 60–80 mmHg. Myocardial protection was achieved through repetitive doses of antegrade or retrograde cold blood (4:1) cardioplegia at 20-minute intervals; hemoglobin (Hgb) was maintained at >7g/dl. All patients were operated on through a median sternotomy. Protamine was administered at the end of the operation to fully reverse the heparin effect. Aprotinin was not used. The same anesthesiologists and cardiac surgeons remained throughout the study period.

2.5

Data analysis

Patients who were diagnosed with PVS were compared with those without the PVS. The demographic, perioperative risk factors of PVS, and clinical outcomes between the two groups were compared. Data are expressed as percentages, mean value ± S.D., or median (25 ^th –75 ^th percentile). Differences between groups were compared using Student’s t test for normally distributed continuous variables and Wilcoxon rank-sum test for nonnormal distributed variables. Categorical variables were displayed as frequencies and percentages and were compared via a chi-square test of general association or via Fisher’s exact test for expected cell counts <5.

Initially, a multivariate logistic regression model was constructed to identify the independent predictors of PVS. The stepwise logistic regression method was used in the selection process of variables to be included in the final logistic model. Variables that met a significance level of 0.15 in the univariate analysis or those previously reported as important determinant of the outcome of interest were included in the multiple logistic regression model. Model fit was evaluated using the Hosmer and Lemeshow goodness-of-fit statistic, as well as residual diagnostics (deviance and df Betas) analysis. The c -statistic was reported as a measure of predictive power. The OR was used as a measure of the relative risk.

Additionally, six multivariate logistic models were established to assess the impact of PVS on major clinical complications, including operative mortality, postoperative ventilation hours, ICU stay, length of hospital stay, perioperative stroke, and myocardial infarction. Covariates selected for adjustment in these models included age, gender, hypertension, diabetes, chronic heart failure, procedures, ejection fraction and preoperative administration of beta-blockers, ACE inhibitors, lipid-lowering drugs, calcium-channel blockers. Perfusion variables of perfusion-time, cross-clamp time, lowest core temperature, and final Hgb were also included. All statistical analysis was performed with SAS for Windows Version 9.1 (SAS Institute, Cary, NC, USA). P ≤.05 was considered significant.

2.1

Patients

This study was approved by the Institutional Review Board of Medstar Research Institute. All of our cardiac surgery patients were asked to give written informed consent for clinical record research review. Due to the retrospective nature of the study, the requirement for informed consent was waived.

From November 21, 2005, to June 9, 2006, 632 adult patients underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Washington Hospital Center. Of those, 334 patients underwent on-pump isolated CABG and 295 patients had open-heart surgery (OOHS); three patients with endocarditis underwent valve surgery were excluded from this study. Patient baseline demographics, procedure data and perioperative outcomes were recorded and entered concurrently into the computerized database of cardiac surgery by a data-coordinating center. All data were defined according to the Society of Thoracic Surgeons national database (Version 2.52). Guidelines and definitions are available at http://www.sts.org/sections/stsnationaldatabase/datamanagers . All adverse clinical events were source documented. Patients were contacted by telephone 30 days after hospital discharge as part of the routine clinical follow-up.

2.2

Postoperative treatments and data collection

Patients who underwent CABG procedure received a Swan-Ganz catheter if ejection fraction was less than 40%. All valve procedures received a Swan-Ganz catheter. For patients without Swan-Ganz catheter insertion in the operating room (OR) and when a mean arterial blood pressure (MAP) of 70 mmHg could not be maintained after separation from CPB and in the intensive care unit (ICU) despite fluid administration, Swan-Ganz catheter monitoring was initiated. Vasoactive agents were titrated according to the MAP, CO and SVR. The following hemodynamic variables were recorded: mean pulmonary arterial pressure (MAP), central venous pressure (CVP), pulmonary artery occlusion pressure, and CO. Systemic vascular resistance index (SVRI) and cardiac index (CI) were calculated.

2.3

PVS definition

In accordance with previous studies , PVS was defined as a MAP ≤70 mmHg, SVRI ≤1400 dynes-s cm ⁻⁵ m ⁻² , CI ≥2.5 min ⁻¹ m ⁻² , and CVP ≥10 mmHg. Only patients who met these criteria within 24 h after surgery and required vasopressor support with norepinephrine and/or vasopressin were included. Every patient, if not contradicted, received 2 g of magnesium perioperatively on a regular basis. No other vasodilators drugs were administered routinely. We excluded patients who received inotropic agents including epinephrine, dopamine, milrinone, or dobutamine within 24 h postoperatively from the PVS group; we also excluded patients who received intraoperative and/or postoperative intra-aortic balloon pump from the PVS group; these were patients with unstable postoperative haemodynamics which are highly correlated with compromised cardiac function. Three patients with preoperative endocarditis or other severe infections (e.g., pneumonia or intraabdominal abscess) were excluded from this study.

2.4

Anesthesia, surgery and CPB

Preoperative cardiac medications, including nitrates, β-blockers, calcium-channel blockers, and angiotensin-converting enzyme (ACE) inhibitors were administered until surgery. Primary anesthesia consisted of low-intermediate dose fentanyl (8 μg/kg), etomidate (1–2 mg/kg), and isoflurane to end-tidal concentration of 0.5–1 minimum alveolar concentration. Nondepolarizing muscle relaxant (pancuronium bromide 0.15/kg) was used to facilitate endotracheal intubation. CPB was conducted by a 2.4 L min m ⁻² flow (nonpulsatile pump) under moderate systemic hypothermia (30–34°C). Perfusion pressure was maintained at 60–80 mmHg. Myocardial protection was achieved through repetitive doses of antegrade or retrograde cold blood (4:1) cardioplegia at 20-minute intervals; hemoglobin (Hgb) was maintained at >7g/dl. All patients were operated on through a median sternotomy. Protamine was administered at the end of the operation to fully reverse the heparin effect. Aprotinin was not used. The same anesthesiologists and cardiac surgeons remained throughout the study period.

2.5

Data analysis

Patients who were diagnosed with PVS were compared with those without the PVS. The demographic, perioperative risk factors of PVS, and clinical outcomes between the two groups were compared. Data are expressed as percentages, mean value ± S.D., or median (25 ^th –75 ^th percentile). Differences between groups were compared using Student’s t test for normally distributed continuous variables and Wilcoxon rank-sum test for nonnormal distributed variables. Categorical variables were displayed as frequencies and percentages and were compared via a chi-square test of general association or via Fisher’s exact test for expected cell counts <5.

Initially, a multivariate logistic regression model was constructed to identify the independent predictors of PVS. The stepwise logistic regression method was used in the selection process of variables to be included in the final logistic model. Variables that met a significance level of 0.15 in the univariate analysis or those previously reported as important determinant of the outcome of interest were included in the multiple logistic regression model. Model fit was evaluated using the Hosmer and Lemeshow goodness-of-fit statistic, as well as residual diagnostics (deviance and df Betas) analysis. The c -statistic was reported as a measure of predictive power. The OR was used as a measure of the relative risk.

Additionally, six multivariate logistic models were established to assess the impact of PVS on major clinical complications, including operative mortality, postoperative ventilation hours, ICU stay, length of hospital stay, perioperative stroke, and myocardial infarction. Covariates selected for adjustment in these models included age, gender, hypertension, diabetes, chronic heart failure, procedures, ejection fraction and preoperative administration of beta-blockers, ACE inhibitors, lipid-lowering drugs, calcium-channel blockers. Perfusion variables of perfusion-time, cross-clamp time, lowest core temperature, and final Hgb were also included. All statistical analysis was performed with SAS for Windows Version 9.1 (SAS Institute, Cary, NC, USA). P ≤.05 was considered significant.