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1.  Non-invasive cardiac stress testing before elective major non-cardiac surgery: population based cohort study 
Objective To determine the association of non-invasive cardiac stress testing before elective intermediate to high risk non-cardiac surgery with survival and hospital stay.
Design Population based retrospective cohort study.
Setting Acute care hospitals in Ontario, Canada, between 1 April 1994 and 31 March 2004.
Participants Patients aged 40 years or older who underwent specific elective intermediate to high risk non-cardiac surgical procedures.
Interventions Non-invasive cardiac stress testing performed within six months before surgery.
Main outcome measures Postoperative one year survival and length of stay in hospital.
Results Of the 271 082 patients in the entire cohort, 23 991 (8.9%) underwent stress testing. After propensity score methods were used to reduce important differences between patients who did or did not undergo preoperative stress testing and assemble a matched cohort (n=46 120), testing was associated with improved one year survival (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.99; P=0.03) and reduced mean hospital stay (difference −0.24 days, 95% CI −0.07 to −0.43; P<0.001). In an analysis of subgroups defined by Revised Cardiac Risk Index (RCRI) class, testing was associated with harm in low risk patients (RCRI 0 points: HR 1.35, 95% CI 1.05 to 1.74), but with benefit in patients who were at intermediate risk (RCRI 1-2 points: 0.92, 95% CI 0.85 to 0.99) or high risk (RCRI 3-6 points: 0.80, 95% CI 0.67 to 0.97).
Conclusions Preoperative non-invasive cardiac stress testing is associated with improved one year survival and length of hospital stay in patients undergoing elective intermediate to high risk non-cardiac surgery. These benefits principally apply to patients with risk factors for perioperative cardiac complications.
PMCID: PMC2813428  PMID: 20110306
2.  Does the revised cardiac risk index predict cardiac complications following elective lung resection? 
Revised Cardiac Risk Index (RCRI) score and Thoracic Revised Cardiac Risk Index (ThRCRI) score were developed to predict the risks of postoperative major cardiac complications in generic surgical population and thoracic surgery respectively. This study aims to determine the accuracy of these scores in predicting the risk of developing cardiac complications including atrial arrhythmias after lung resection surgery in adults.
We studied 703 patients undergoing lung resection surgery in a tertiary thoracic surgery centre. Observed outcome measures of postoperative cardiac morbidity and mortality were compared against those predicted by risk.
Postoperative major cardiac complications and supraventricular arrhythmias occurred in 4.8% of patients. Both index scores had poor discriminative ability for predicting postoperative cardiac complications with an area under receiver operating characteristic (ROC) curve of 0.59 (95% CI 0.51-0.67) for the RCRI score and 0.57 (95% CI 0.49-0.66) for the ThRCRI score.
In our cohort, RCRI and ThRCRI scores failed to accurately predict the risk of cardiac complications in patients undergoing elective resection of lung cancer. The British Thoracic Society (BTS) recommendation to seek a cardiology referral for all asymptomatic pre-operative lung resection patients with > 3 RCRI risk factors is thus unlikely to be of clinical benefit.
PMCID: PMC3879030  PMID: 24289748
Risk factors; Lung; Surgery; Complications; Cardiac arrhythmia
3.  Preoperative NT-proBNP and CRP predict perioperative major cardiovascular events in non-cardiac surgery 
Heart  2009;96(1):56-62.
To investigate whether simple and non-invasive measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) and/or C-reactive protein (CRP) can predict perioperative major cardiovascular event (PMCE).
Prospective, single-centre, cohort study.
A 1900-bed tertiary-care university hospital in Seoul, Korea
Design and patients:
The predictive power of NT-proBNP, CRP and Revised Cardiac Risk Index (RCRI) for the risk of PMCE (myocardial infarction, pulmonary oedema or cardiovascular death) were evaluated from a prospective cohort of 2054 elective major non-cardiac surgery patients. Optimal cut-off values were derived from receiver operating characteristic curve (ROC) analysis.
Main outcome measurement:
PMCE (myocardial infarction, pulmonary oedema or cardiovascular death) within postoperative 30 days.
PMCE developed in a total of 290 patients (14.1%). Each increasing quartile of NT-proBNP or CRP level was associated with a greater risk of PMCE after adjustment for traditional clinical risk factors. The relative risk (RR) of highest versus lowest quartile was 5.2 for NT-proBNP (p<0.001) and 3.7 for CRP (p<0.001). Both NT-proBNP (cut-off  = 301 ng/l) and CRP (cut-off  = 3.4 mg/l) predicted PMCE better than RCRI (cut-off  = 2) by ROC analysis (p<0.001). Moreover, the predictive power of RCRI (adjusted RR  = 1.5) could be improved significantly by addition of CRP and NT-proBNP to RCRI (adjusted RR 4.6) (p<0.001).
High preoperative NT-proBNP or CRP is a strong and independent predictor of perioperative major cardiovascular event in non-cardiac surgery. The predictive power of current clinical risk evaluation system would be strengthened by these biomarkers.
PMCID: PMC2791233  PMID: 19861299
4.  Plasma N-Terminal Pro-B-Type Natriuretic Peptide Is Predictive of Perioperative Cardiac Events in Patients Undergoing Vascular Surgery 
Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery.
Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (≥ 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI.
A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NT-proBNP level of > 302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p < 0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI.
Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.
PMCID: PMC3443723  PMID: 23019395
Pro-B-type natriuretic peptide; Vascular surgical procedures; Postoperative complications
5.  A look into Lee's score: peri-operative cardiovascular risk assessment in non-cardiac surgeries—usefulness of revised cardiac risk index 
Indian Heart Journal  2012;64(2):134-138.
The revised cardiac risk index (RCRI/Lee's score) was designed for peri-operative risk assessment before elective major non-cardiac surgeries. Through this article, we report the usefulness of RCRI in our daily practice, while evaluating patients undergoing surgeries of varying risk.
Only referred patients, aged ≥ 40 years, were included. Risk stratification was done using RCRI scoring system. Patients were categorised into 4 classes depending on 0, 1, 2, and ≥3 risk predictors (risk predictors were high-risk surgery, history of ischaemic heart disease (IHD), diabetes on insulin, history of stroke (cerebrovascular accident [CVA]), history of congestive heart failure (CHF) and serum creatinine of >2 mg%). Electrocardiograms (ECG) were done in all patients, while troponin I in intermediate and high-risk patients, and in others if symptomatic. Perioperative cardiovascular events were managed appropriately.
Of the 920 patients included, only 853 patients were analysed as 67 patients were not operated upon. The mean age was 59 ± 11years and 46% of the patients were women. Two hundred and ninety-two underwent high-risk surgeries, 97 patients had history of IHD, 89 had history of CHF, 36 gave history of CVA, 269 patients were diabetics on insulin and 68 had serum creatinine >2 mg%. Number of patients in Lee's classes I, II, III, and IV were 311, 347, 150, and 52, respectively. 26 out of 853 patients had peri-operative events. Of the six variables in RCRI, only history of IHD was an independent predictor of events. Event rates increased as the RCRI class increased, i.e. 1.7%, 2.0%, 6.7%, and 7.7% for classes I–IV, respectively. Age >70 years, poor general medical condition, emergency surgery and left bundle branch block (LBBB) on ECG, were significantly associated with peri-operative events.
The RCRI is a useful tool in pre-operative risk stratification. It should perhaps be further updated to improve its predictive accuracy.
PMCID: PMC3860848  PMID: 22572486
Non-cardiac surgeries; Peri-operative evaluation; Revised cardiac risk index
6.  Prediction of early postoperative major cardiac events after elective orthopedic surgery: the role of B-type natriuretic peptide, the revised cardiac risk index, and ASA class 
BMC Anesthesiology  2014;14:20.
The aim of this study was to evaluate pre- and post-operative brain natriuretic peptide (BNP) levels and compare the power of this test in predicting in-hospital major adverse cardiac events (MACE: atrial fibrillation, flutter, acute heart failure or non-fatal/fatal myocardial infarction) in patients undergoing elective prosthesis orthopedic surgery to that of the Revised Cardiac Risk Index (RCRI) and American Society of Anesthesiology (ASA) class, the most useful scores identified to date.
The study was an observational study of consecutive patients undergoing elective prosthesis orthopedic surgery. Surgical risk was established using RCRI score and ASA class criteria. Venous blood was sampled before surgery and on postoperative day 1 for the measurement of BNP. The intraoperative data collected included details of the surgery and anesthesia and any MACE experienced up until hospital discharge.
MACE occurred in 14 of the 227 patients treated (6.2%). Age was statistical associated with MACE (p < 0.004). Preoperative BNP levels were higher (p < 0.0007) in patients who experienced MACE than in event-free patients (median values: 92 and 35 pg/mL, respectively). Postoperative BNP levels were also greater (p < 0.0001) in patients sustaining MACE than in event-free patients (median values: 165 and 45 pg/mL, respectively). ROC curve analysis demonstrated that for a cut-off point ≥ 39 pg/mL, the area under the curve for preoperative BNP was equal to 0.77, while a postoperative BNP cut-off point ≥ 69 pg/mL gave an AUC of 0.82.
Both pre- and post-operative BNP concentrations are predictors of MACE in patients undergoing elective prosthesis orthopedic surgery.
PMCID: PMC3998048  PMID: 24655733
Brain natriuretic peptide; Orthopedic surgery; Preoperative care
7.  Determinants of postoperative acute kidney injury 
Critical Care  2009;13(3):R79.
Development of acute kidney injury (AKI) during the perioperative period is associated with increases in morbidity and mortality. Our aim was to evaluate the incidence and determinants of postoperative AKI after major noncardiac surgery in patients with previously normal renal function.
This retrospective cohort study was carried out in the multidisciplinary Post-Anaesthesia Care Unit (PACU) with five intensive care beds. The study population consisted of 1166 patients with no previous renal insufficiency who were admitted to these intensive care unit (ICU) beds over 2 years. After admission patients were followed for the development of AKI, defined as proposed by The Acute Kidney Injury Network (increment of serum creatinine [greater than or equal to] 0.3 mg/dL or 50% from baseline within 48 hours or urine output < 0.5 mL/kg/hr for > 6 hours despite fluid resuscitation when applicable). Patient preoperative characteristics, intraoperative management and outcome were evaluated for associations with acute kidney injury using an univariate and multiple logistic regression model.
A total of 1597 patients were admitted to the PACU and of these, 1166 met the inclusion criteria. Eighty-seven patients (7.5%) met AKI criteria. Univariate analysis identified age, American Society of Anesthesiologists (ASA) physical status, emergency surgery, high risk surgery, ischemic heart disease, congestive heart disease and Revised Cardiac Risk Index (RCRI) score as independent preoperative determinants for AKI in the postoperative period. Multivariate analysis identified ASA physical status, RCRI score, high risk surgery and congestive heart disease as preoperative determinants for AKI in the postoperative period. Patients that developed AKI had higher Simplified Acute Physiology Score (SAPS) II and Acute Physiology and Chronic Health Evaluation (APACHE) II, higher PACU length of stay (LOS), higher PACU mortality, higher hospital mortality and higher mortality at 6 months follow-up. AKI was an independent risk factor for hospital mortality (OR 3.12, 95% CI 1.41 to 6.93, P = 0.005).
This study shows that age, emergency and high risk surgery, ischemic heart disease, congestive heart disease, ASA physical status and RCRI score were considered risk factors for the development of AKI, in patients needing intensive care after surgery. AKI has serious impact on PACU length of stay and mortality. AKI was an independent risk factor for hospital mortality.
PMCID: PMC2717442  PMID: 19463152
8.  An international prospective cohort study evaluating major vascular complications among patients undergoing noncardiac surgery: the VISION Pilot Study 
Open Medicine  2011;5(4):e193-e200.
Among patients undergoing noncardiac surgery, our objectives were to: (1) determine the feasibility of undertaking a large international cohort study; (2) estimate the current incidence of major perioperative vascular events; (3) compare the observed event rates to the expected event rates according to the Revised Cardiac Risk Index (RCRI); and (4) provide an estimate of the proportion of myocardial infarctions without ischemic symptoms that may go undetected without perioperative troponin monitoring.
An international prospective cohort pilot study.
Patients undergoing noncardiac surgery who were > 45 years of age, receiving a general or regional anesthetic, and requiring hospital admission.
Patients had a Roche fourth-generation Elecsys troponin T measurement collected 6 to 12 hours postoperatively and on the first, second, and third days after surgery. Our primary outcome was major vascular events (a composite of vascular death [i.e., death from vascular causes], nonfatal myocardial infarction, nonfatal cardiac arrest, and nonfatal stroke) at 30 days after surgery. Our definition for perioperative myocardial infarction included: (1) an elevated troponin T measurement with at least one of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic electrocardiogram changes, coronary artery intervention, or cardiac imaging evidence of myocardial infarction; or (2) autopsy findings of acute or healing myocardial infarction.
We recruited 432 patients across 5 hospitals in Canada, China, Italy, Colombia, and Brazil. During the first 30 days after surgery, 6.3% (99% confidence interval 3.9–10.0) of the patients suffered a major vascular event (10 vascular deaths, 16 nonfatal myocardial infarctions, and 1 nonfatal stroke). The observed event rate was increased 6-fold compared with the event rate expected from the RCRI. Of the 18 patients who suffered a myocardial infarction, 12 (66.7%) had no ischemic symptoms to suggest myocardial infarction.
This study suggests that major perioperative vascular events are common, that the RCRI underestimates risk, and that monitoring troponins after surgery can assist physicians to avoid missing myocardial infarction. These results underscore the need for a large international prospective cohort study.
PMCID: PMC3345376  PMID: 22567075
9.  Quality of life after carotid endarterectomy 
Most studies documenting beneficial outcomes after carotid endarterectomy (CE) are limited to mortality and morbidity rates, costs, and length of hospital stay (LOS). Few have examined the dependency of patients and how they perceive their own health changes after surgery. The aim of the present study was to evaluate quality of life and independence in activities of daily living (ADL) and to study its determinants.
Sixty-three patients admitted in the Post Anaesthesia Care Unit (PACU) after CE were eligible for this 14-month follow-up study. Patients were contacted 6 months after discharge to complete a Short Form-36 questionnaire (SF-36) and to have their dependency in ADL evaluated.
Among 59 hospital survivors at 6 months follow-up, 43 completed the questionnaires. Sixty-three percent reported that their general level of health was better on the day they answered the questionnaire than 12 months earlier. Patients had worse SF-36 scores for all domains except bodily pain than a general urban population, and comparison with a group of patients 6 months after surgical ICU discharge showed no differences. Six months after PACU discharge, the Lawton Instrumental Activities of ADL Scale and the Katz Index of ADL demonstrated higher dependency scores (5.9 ± 2.2 versus 4.3 ± 2.4 and 0.3 ± 0.8 versus 0.6 ± 0.9, p < 0.001 and p = 0.047). Sixty-five percent and 33% were dependent in at least one activity in instrumental and personal ADL, respectively. Patients dependent in at least one ADL task had higher Revised Cardiac Risk Index (RCRI) scores (1.0 versus 1.5, p = 0.017). After controlling for multiple comparisons, no significant differences were found.
Patients undergoing CE have improved self-perception of quality of life despite being more dependent. Almost all their scores are worse than those in an urban population. We could identify no predictors of greater dependency in ADL tasks six months after PACU discharge.
PMCID: PMC2600818  PMID: 19021913
10.  Comparison of Transthoracic Echocardiography With N-Terminal Pro-Brain Natriuretic Peptide as a Tool for Risk Stratification of Patients Undergoing Major Noncardiac Surgery 
Korean Circulation Journal  2011;41(9):505-511.
Background and Objectives
The role of preoperative transthoracic echocardiography (TTE) for the risk stratification has not been well investigated yet. We compared the predictive power of TTE with N-terminal pro-brain natriuretic peptide (NT-proBNP), a representative biomarker that predicts perioperative cardiovascular risk, and investigated whether these tests have incremental value to the clinically determined risk.
Subjects and Methods
We evaluated the Revised Cardiac Risk Index (RCRI), TTE, and NT-proBNP in 1,923 noncardiac surgery cases. The primary endpoint was a perioperative major cardiovascular event (PMCE), which was defined by any single or combined event of secondary endpoints including myocardial infarction, development of pulmonary edema, or primary cardiovascular death within 30 days after surgery.
All echocardiographic parameters including left ventricular ejection fraction, regional wall motion score index, and transmitral early diastolic velocity/tissue Doppler mitral annular early diastolic velocity (E/E') were predictive of PMCE (c-statistics=0.579±0.019 to 0.589±0.015), but none of these parameters were better than the clinically determined RCRI (c-statistics=0.594±0.019) and were inferior to NT-proBNP (c-statistics=0.748±0.019, p<0.001). The predictive power of RCRI {adjusted relative risk (RR)=1.4} could be improved by addition of echocardiographic parameters (adjusted RR=1.8, p<0.001), but not to that extent as by addition of NT-proBNP to RCRI (adjusted RR=3.7, p<0.001).
TTE was modestly predictive of perioperative cardiovascular events but was not superior to NT-proBNP. Moreover, it did not have incremental value to the clinically determined risk. The results of our study did not support the use of routine echocardiography before noncardiac surgery.
PMCID: PMC3193041  PMID: 22022325
Cardiovascular disease; Postoperative complications; Echocardiography; Natriuretic peptides
11.  B-type natriuretic peptide-guided therapy for perioperative medicine? 
Open Heart  2014;1(1):e000105.
The recent guideline from the European Society of Cardiology and European Society of Anesthesiology recommended the use of B-type natriuretic peptide (BNP) as preoperative testing for high-risk cardiac patients undergoing non-cardiac surgery. In this article, the potential benefits, risks and details for implementing BNP testing in perioperative medicine are discussed. Review of four related lines of research including the use of BNP test for preoperative prognosis, BNP test for screening asymptomatic heart failure, BNP as prognostic test in asymptomatic, non-heart failure patients and using BNP for detecting silent myocardial ischaemia showed converging cut-off levels of BNP for risk stratification. BNP has better OR and relative risk in comparison with Revised Cardiac Risk Index (RCRI) in predicting perioperative cardiac risk. BNP-guided therapy can be low risk based on current evidence on non-surgical patients, including treating asymptomatic patients without heart failure to prevent cardiovascular complications. At present, there is lack of direct evidence supporting perioperative BNP testing. Further research with randomised controlled trials is needed to confirm the benefit of BNP-guided management. Preoperative BNP testing may be considered in patients with RCRI above 0 undergoing intermediate or high-risk surgery. BNP-guided therapy is likely a beneficial addition to perioperative medicine. Its combination with β-blocker titration, RCRI and perioperative cardiovascular monitoring can be a major advance in reducing cardiac risk resulting in a dynamic, individualised optimisation process.
PMCID: PMC4189229  PMID: 25332815
12.  Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors. 
Annals of the Rheumatic Diseases  1989;48(6):488-495.
The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs.
PMCID: PMC1003793  PMID: 2662917
13.  Is Peri-Operative Isolated Systolic Hypertension (ISH) a Cardiac Risk Factor? 
Current Cardiology Reviews  2008;4(1):22-33.
We are presenting a review of Isolated Systolic Hypertension (ISH) as a cardiovascular risk factor with emphasis on the perioperative period.
Isolated systolic hypertension is associated with aging and is the most frequent subtype (65%) among patients with uncontrolled hypertension. ISH is strongly associated with increased risks of cardiac and cerebrovascular events exceeding those in comparably aged individuals with diastolic hypertension. Patients with ISH show an increase in left ventricular (LV) mass and an increase in the prevalence of left ventricular hypertrophy (LVH). These LV changes increase cardiovascular events and frequently lead to diastolic dysfunction (DD). Treatment to reduce elevated systolic blood pressure has been shown to reduce the risk of cardiovascular events.
In the perioperative setting, essential hypertension has not been found to be a significant risk factor for cardiac complications. Most of the studies were based on the definition of essential hypertension and underpowered in sample size. The significance of perioperative ISH, however, is not well studied, partly due to its recognition only fairly recently as a cardiovascular risk factor in the non-surgical setting, and partly due to the evolving definition of ISH.
Perioperative cardiac complications remain a significant problem to the healthcare system and to the patient. Although the incidence of perioperative cardiac complications is prominent in high-risk patients as defined by the Revised Cardiac Risk Index (RCRI), the bulk of the cardiac complications actually occur in low-risk group. Currently, little understanding exists on the occurrence of perioperative cardiac complications in low- risk patients. A factor such as ISH, with its known pathophysiological changes, is a potential perioperative risk factor.
We believe ISH is an under-recognized perioperative risk factor and deserves further studying. Our research group has recently been funded by the Heart Stroke Foundation (HSF) to examine ISH as a perioperative risk factor (PROMISE Study).
PMCID: PMC2774582  PMID: 19924274
Isolated systolic hypertension; cardiovascular risk factors; perioperative.
14.  Early postoperative statin therapy is associated with a lower incidence of acute kidney injury following cardiac surgery 
To test the hypothesis that perioperative statin use reduces acute kidney injury (AKI) following cardiac surgery
Retrospective analysis of prospectively collected data from an ongoing clinical trial
Quaternary-care university hospital
Three hundred twenty-four elective adult cardiac surgery patients
Measurements and Main Results
We assessed the association of preoperative statin use, early postoperative statin use, and acute statin withdrawal with the incidence of AKI. Early postoperative statin use was defined as statin treatment within the first postoperative day. Statin withdrawal was defined as discontinuation of preoperative statin treatment prior to surgery until at least postoperative day 2. Logistic regression and propensity score modeling were used to control for AKI risk factors. Sixty-eight of 324 patients (21.0%) developed AKI. AKI patients stayed in the hospital longer (P=0.03) and were more likely to develop pneumonia (P=0.002) or die (P=0.001). Higher body mass index (P=0.003), higher central venous pressure (P=0.03), and statin withdrawal (27.4 vs. 14.7%, P=0.046) were associated with a higher incidence of AKI, while early postoperative statin use was protective (12.5 vs. 23.8%, P=0.03). Preoperative statin use did not affect risk of AKI. In multivariate logistic regression, age (P=0.03), male gender (P=0.02), body mass index (P<0.001), and early postoperative statin use (OR 0.32, 95% CI 0.14–0.72, P=0.006) independently predicted AKI. Propensity score-adjusted risk assessment confirmed the association between early postoperative statin use and reduced AKI (OR 0.30, 95% CI 0.13–0.70, P=0.005).
Early postoperative statin use is associated with a lower incidence of AKI among both chronic statin users and statin-naïve cardiac surgery patients.
PMCID: PMC2992577  PMID: 20599398
acute kidney injury; acute renal failure; cardiac surgery; statin; oxidative stress; obesity
15.  Milrinone Use is Associated With Postoperative Atrial Fibrillation Following Cardiac Surgery 
Circulation  2008;118(16):1619-1625.
Postoperative atrial fibrillation (AF), a frequent complication following cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF.
Methods and Results
We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven (28.9%) patients developed AF a mean of 2.9±2.1 days after surgery. Patients who developed AF stayed in the hospital longer (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in non-users, P<0.001). Older age (63.4±10.7 versus 56.7±12.3 years, P<0.001), hypertension (P=0.04), lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02), right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure (PAP) (27.1±9.3 versus 21.8±7.5 mmHg, P=0.001) were also associated with postoperative AF. In multivariable logistic regression, age (P<0.001), ejection fraction (P=0.02), and milrinone use (odds ratio 4.86, 95% CI 2.31-10.25, P<0.001) independently predicted postoperative AF. When data only from patients with pulmonary artery catheters were analyzed and PAP was included in the model, age, milrinone use (odds ratio 4.45, 95% CI 2.01-9.84, P<0.001), and higher PAP (P=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF.
Milrinone use is an independent risk factor for postoperative AF following elective cardiac surgery.
PMCID: PMC2770257  PMID: 18824641
atrial fibrillation; surgery; inotropic agents
16.  The Waterlow score for risk assessment in surgical patients 
Perioperative scoring systems aim to predict outcome following surgery and are used in preoperative counselling to guide management and to facilitate internal or external audit. The Waterlow score is used prospectively in many UK hospitals to stratify the risk of decubitus ulcer development. The primary aim of this study was to assess the potential value of this existing scoring system in the prediction of mortality and morbidity in a general surgical and vascular cohort.
A total of 101 consecutive moderate to high risk emergency and elective surgical patients were identified through a single institution database. The preoperative Waterlow score and outcome data pertaining to that admission were collected. The discriminatory power of the Waterlow score was compared against that of the American Society of Anesthesiologists (ASA) grade and the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM).
The inpatient mortality rate was 17% and the 30-day morbidity rate was 29%. A statistically significant association was demonstrated between the preoperative Waterlow score and inpatient mortality (p<0.0001) and 30-day morbidity (p=0.0002). Using a threshold Waterlow score of 20 to dichotomise risk, accuracies of 0.84 and 0.76 for prediction of mortality and morbidity were demonstrated. In comparison with P-POSSUM, the preoperative Waterlow score performed well on receiver operating characteristic analysis. With respect to mortality, the area under the curve was 0.81 (0.80–0.85) and for morbidity it was 0.72 (0.69–0.76). The ASA grade achieved a similar level of discrimination.
The Waterlow score is collected routinely by nursing staff in many hospitals and might therefore be an attractive means of predicting postoperative morbidity and mortality. It might also function to stratify perioperative risk for comparison of surgical outcome data. A prospective study comparing these risk prediction scores is required to support these findings.
PMCID: PMC3964640  PMID: 23317729
General surgery; Risk assessment; Mortality; Morbidity
17.  Preoperative anemia increases postoperative morbidity in elective cranial neurosurgery 
Preoperative anemia may affect postoperative mortality and morbidity following elective cranial operations.
The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was used to identify elective cranial neurosurgical cases (2006-2012). Morbidity was defined as wound infection, systemic infection, cardiac, respiratory, renal, neurologic, and thromboembolic events, and unplanned returns to the operating room. For 30-day postoperative mortality and morbidity, adjusted odds ratios (ORs) were estimated with multivariable logistic regression.
Of 8015 patients who underwent elective cranial neurosurgery, 1710 patients (21.4%) were anemic. Anemic patients had an increased 30-day mortality of 4.1% versus 1.3% in non-anemic patients (P < 0.001) and an increased 30-day morbidity rate of 25.9% versus 14.14% in non-anemic patients (P < 0.001). The 30-day morbidity rates for all patients undergoing cranial procedures were stratified by diagnosis: 26.5% aneurysm, 24.7% sellar tumor, 19.7% extra-axial tumor, 14.8% intra-axial tumor, 14.4% arteriovenous malformation, and 5.6% pain. Following multivariable regression, the 30-day mortality in anemic patients was threefold higher than in non-anemic patients (4.1% vs 1.3%; OR = 2.77; 95% CI: 1.65-4.66). The odds of postoperative morbidity in anemic patients were significantly higher than in non-anemic patients (OR = 1.29; 95% CI: 1.03-1.61). There was a significant difference in postoperative morbidity event odds with a hematocrit level above (OR = 1.07; 95% CI: 0.78-1.48) and below (OR = 2.30; 95% CI: 1.55-3.42) 33% [hemoglobin (Hgb) 11 g/dl].
Preoperative anemia in elective cranial neurosurgery was independently associated with an increased risk of 30-day postoperative mortality and morbidity when compared to non-anemic patients. A hematocrit level below 33% (Hgb 11 g/dl) was associated with a significant increase in postoperative morbidity.
PMCID: PMC4235129  PMID: 25422784
Anemia; cranial; hematocrit; hemoglobin; National Surgical Quality Improvement Program; neurosurgery
18.  Plasma sRAGE enables prediction of acute lung injury after cardiac surgery in children 
Critical Care  2012;16(3):R91.
Acute lung injury (ALI) after cardiac surgery is associated with a high postoperative morbidity and mortality, but few predictors are known for the occurrence of the complication. This study evaluated whether elevated plasma levels of soluble receptor for advanced glycation end products (sRAGE) and S100A12 reflected impaired lung function in infants and young children after cardiac surgery necessitating cardiopulmonary bypass (CPB).
Consecutive children younger than 3 years after cardiac surgery were prospectively enrolled and assigned to ALI and non-ALI groups, according to the American-European Consensus Criteria. Plasma concentrations of sRAGE and S100A12 were measured at baseline, before, and immediately after CPB, as well as 1 hour, 12 hours, and 24 hours after operation.
Fifty-eight patients were enrolled and 16 (27.6%) developed postoperative ALI. Plasma sRAGE and S100A12 levels increased immediately after CPB and remained significantly higher in the ALI group even 24 hour after operation (P < 0.01). In addition, a one-way MANOVA revealed that the overall sRAGE and S100A12 levels were higher in the ALI group than in the non-ALI group immediately after CPB (P < 0.001). The multivariate logistic regression analysis showed that the plasma sRAGE level immediately after CPB was an independent predictor for postoperative ALI (OR, 1.088; 95% CI, 1.011 to 1.171; P = 0.025). Increased sRAGE and S100A12 levels immediately after CPB were significantly correlated with a lower PaO2/FiO2 ratio (P < 0.01) and higher radiographic lung-injury score (P < 0.01), as well as longer mechanical ventilation time (sRAGEN: r = 0.405; P = 0.002; S100A12N: r = 0.322; P = 0.014), longer surgical intensive care unit stay (sRAGEN: r = 0.421; P = 0.001; S100A12N: r = 0.365; P = 0.005) and hospital stay (sRAGEN: r = 0.329; P = 0.012; S100A12N: r = 0.471; P = 0.001).
Elevated sRAGE and S100A12 levels correlate with impaired lung function, and sRAGE is a useful early biomarker of ALI in infants and young children undergoing cardiac surgery.
PMCID: PMC3580637  PMID: 22616947
19.  Enhanced Recovery After Surgery (ERAS) Versus Conventional Postoperative Care in Colorectal Surgery 
Enhanced Recovery After Surgery (ERAS) programs are associated with reduced hospital morbidity and mortality. The aim of the present study was to evaluate whether the introduction of ERAS care improved the adverse events in colorectal surgery. In a cohort study, mortality, morbidity, and length of stay were compared between ERAS patients and carefully matched historical controls.
Patients were matched for their type of disease, the type of surgery, P-Possum (Portsmouth-Possum), CR-Possum (Colorectal-Possum) Physiological and Operative Score for Enumeration of Mortality and Morbidity (POSSUM), gender, and American Society of Anesthesiologists (ASA) grade. The primary outcome measures of this study were mortality and morbidity. Secondary outcome measures were fluid intake, length of hospital stay, the number of relaparotomies, and the number of readmissions within 30 days. Data on the ERAS patients were collected prospectively.
Sixty-one patients treated according to the ERAS program were compared with 122 patients who received conventional postoperative care. The two groups were comparable with respect to age, ASA grade, P-Possum (Portsmouth-Possum), CR-Possum (Colorectal-Possum) score, type of surgery, stoma formation, type of disease, and gender. Morbidity was lower in the ERAS group compared to the control group (14.8% versus 33.6% respectively; P = <0.01). Patients in the ERAS group received significantly less fluid and spent fewer days in the hospital (median 6 days, range 3–50 vs. median 9 days, range 3–138; P = 0.032). There was no difference between the ERAS and the control group for mortality (0% vs. 1.6%; P = 0.55) and readmission rate (3.3% vs. 1.6%; P = 0.60).
Enhanced Recovery After Surgery program reduces morbidity and the length of hospital stay for patients undergoing elective colonic or rectal surgery.
PMCID: PMC2793377  PMID: 19779947
Enhanced recovery; Colorectal surgery; Abdominal surgery; Fast track; Mortality; Morbidity
20.  Primary Payer Status is Significantly Associated with Postoperative Mortality, Morbidity, and Hospital Resource Utilization in Pediatric Surgical Patients within the United States 
Journal of pediatric surgery  2013;48(1):81-87.
Current healthcare reform efforts have highlighted the potential impact of insurance status on patient outcomes. The influence of primary payer status (PPS) within the pediatric surgical patient population remains unknown. The purpose of this study was to examine risk-adjusted associations between PPS and postoperative morbidity, mortality, and resource utilization in pediatric surgical patients within the United States.
A weighted total of 153,333 pediatric surgical patients were evaluated using the national Kids’ Inpatient Database (2003 and 2006): appendectomy, intussusception, decortication, pyloroplasty, congenital diaphragmatic hernia repair, and colonic resection for Hirschsprung’s disease. Patients were stratified according to PPS: Medicare (n=180), Medicaid (n=51, 862), uninsured (n=12,539), and private insurance (n=88,753). Multivariable hierarchical regression modeling was utilized to evaluate risk-adjusted associations between PPS and outcomes.
Overall median patient age was 12 years, operations were primarily non-elective (92.4%), and appendectomies accounted for the highest proportion of cases (81.3%). After adjustment for patient, hospital, and operation-related factors, PPS was independently associated with in-hospital death (p<0.0001) and postoperative complications (p<0.02), with increased risk for Medicaid and uninsured populations. Moreover, Medicaid PPS was also associated with greater adjusted lengths of stay and total hospital charges (p<0.001). Importantly, these results were dependent on operation type.
Primary payer status is associated with risk-adjusted postoperative mortality, morbidity, and resource utilization among pediatric surgical patients. Uninsured patients are at increased risk for postoperative mortality while Medicaid patients accrue greater morbidity, hospital lengths of stay, and total charges. These results highlight a complex interaction between socioeconomic and patient-related factors, and primary payer status should be considered in the preoperative risk stratification of pediatric patients.
PMCID: PMC3921619  PMID: 23331797
Payer status; Pediatric surgery outcomes; Healthcare reform
21.  Risk adjustment is crucial in comparing outcomes of various surgical modalities in patients with ileal perforation 
Using crude mortality and morbidity rates for comparing outcomes can be misleading. The aim of the present study was to compare the outcome of various surgical modalities without and with risk adjustment using Physiologic and Operative Severity Scoring for the enUmeration of Mortality and morbidity (POSSUM) score in cases of ileal perforations.
Prospective study on 125 patients of ileal perforations. Resection anastamosis (Group I) was done in 38 patients, primary repair (Group II) in 42 patients and 45 patients had an ileostomy (Group III). The disease severity was assessed in all patients using POSSUM score. The odds of death without and with risk adjustment using POSSUM mortality score were calculated for all groups
Seventeen patients (14%) patients died and 99 (79%) developed postoperative complications. Using crude mortality rates Group I appeared to be the best treatment option with only 2 (5%) deaths followed by Group II with 5 (12%) deaths where as Group III had the worst outcome with 10 deaths (22%). However, Group III (ileostomy) patients had higher mean POSSUM mortality and morbidity score (55.55%, 91.33%) than Group I (28%, 75.26%) and Group II (27%, 73.59%). Taking Group I as the reference (odds ratio, OR1) odds of death were greatest in Group III (OR 5.14, p = 0.043) followed by Group II (OR 2.43, p = 0.306). With risk adjustment using POSSUM mortality score the odds of death decreased in Group III (OR 1.16 p = 0.875). For the whole group, there was a significant association between the POSSUM score and postoperative complications and deaths. Mean POSSUM mortality and morbidity score of those who died (63.40 vs.33.68, p = 0.001) and developed complications (66.32 vs.84.20, p = 0.001) was significantly higher. For every percent increase in severity score the risk of postoperative complications and death increased by 1.10 (p = 0.001) and1.06 (p = 0.001) respectively.
Despite ileostomy patients having highest crude mortality and complication rates, after risk adjustment it was equally safe. Severity of the disease rather than the surgical option had a significant impact on the outcome in patients with ileal perforations.
PMCID: PMC2614410  PMID: 19025633
22.  Evaluation of the POSSUM, P-POSSUM and E-PASS scores in the surgical treatment of hilar cholangiocarcinoma 
The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) model, its Portsmouth (P-POSSUM) modification and the Estimation of physiologic ability and surgical stress (E-PASS) are three surgical risk scoring systems used extensively to predict postoperative morbidity and mortality in general surgery. The aim was to undertake the first study of the predictive value of these models in patients undergoing surgical treatment of hilar cholangiocarcinoma.
A retrospective analysis was performed on data collected prospectively over a 10-year interval from January 2003 to December 2012. The morbidity and mortality risks were calculated using the POSSUM, P-POSSUM and E-PASS equations.
One hundred patients underwent surgical treatment of hilar cholangiocarcinoma. Complications were seen in 52 of 100 patients (52.0%). There were 10 postoperative in-hospital deaths (10.0%). Of 31 preoperative and intraoperative variables studied, operative type (P = 0.000), preoperative serum albumin (P = 0.003) and aspartate aminotransferase (P = 0.029) were found to be factors multivariate associated with postoperative complications. Intraoperative blood loss (P = 0.015), Bismuth-Corlette classification (P = 0.033) and preoperative hemoglobin (P = 0.041) were independent factors multivariate associated with in-hospital death. The POSSUM system predicted morbidity risk effectively with no significant lack of fit (P = 0.488) and an area under the ROC curve (AUC) of 0.843. POSSUM, P-POSSUM and E-PASS scores showed no significant lack of fit in calculating the mortality risk (P >0.05) and all yielded an AUC value exceeding 0.8. POSSUM had significantly more accuracy in predicting morbidity after major and major plus operations (O:E (observed/expected) ratio 0.98 and AUC 0.901) than after minor and moderate operations (O:E ratio 1.13 and AUC 0.759).
POSSUM, P-POSSUM and E-PASS scores effectively predict morbidity and mortality in surgical treatment of hilar cholangiocarcinoma. However, improvements are still needed in the future because none of these scoring systems yielded an AUC value exceeding 0.9 for operations with all different levels of severity. Only POSSUM had more accuracy in predicting postoperative morbidity after operations with higher severity.
Trial registration
This study was undertaken after obtaining approval from the ethics committee of School of Medicine, Shanghai Jiao Tong University with a trial registration number of http://09411960800.
PMCID: PMC4079624  PMID: 24961847
POSSUM; P-POSSUM; E-PASS; Morbidity; Mortality; Hilar cholangiocarcinoma
23.  Hemoglobin and B-type natriuretic peptide preoperative values but not inflammatory markers, are associated with postoperative morbidity in cardiac surgery: a prospective cohort analytic study 
Risk stratification in cardiac surgery significantly impacts outcome. This study seeks to define whether there is an independent association between the preoperative serum level of hemoglobin (Hb), leukocyte count (LEUCO), high sensitivity C-reactive protein (hsCRP), or B-type natriuretic peptide (BNP) and postoperative morbidity and mortality in cardiac surgery.
Prospective, analytic cohort study, with 554 adult patients undergoing cardiac surgery in a tertiary cardiovascular hospital and followed up for 12 months. The cohort was distributed according to preoperative values of Hb, LEUCO, hsCRP, and BNP in independent quintiles for each of these variables.
After adjustment for all covariates, a significant association was found between elevated preoperative BNP and the occurrence of low postoperative cardiac output (OR 3.46, 95% CI 1.53–7.80, p = 0.003) or postoperative atrial fibrillation (OR 3.8, 95% CI 1.45–10.38). For the combined outcome (death/acute coronary syndrome/rehospitalization within 12 months), we observed an OR of 1.93 (95% CI 1.00–3.74). An interaction was found between BNP level and the presence or absence of diabetes mellitus. The OR for non-diabetics was 1.26 (95% CI 0.61–2.60) and for diabetics was 18.82 (95% CI 16.2–20.5). Preoperative Hb was also significantly and independently associated with the occurrence of postoperative low cardiac output (OR 0.33, 95% CI 0.13–0.81, p = 0.016). Both Hb and BNP were significantly associated with the lengths of intensive care unit and hospital stays and the number of transfused red blood cells (p < 0.002). Inflammatory markers, although associated with adverse outcomes, lost statistical significance when adjusted for covariates.
High preoperative BNP or low Hb shows an association of independent risk with postoperative outcomes, and their measurement could help to stratify surgical risk. The ability to predict the onset of atrial fibrillation or postoperative low cardiac output has important clinical implications. Our results open the possibility of designing studies that incorporate BNP measurement as a routine part of preoperative evaluation, and this strategy could improve upon the standard evaluation in terms of reducing adverse postoperative events.
PMCID: PMC3717010  PMID: 23829692
Cardiac surgery; Hemoglobin; Inotropic agents; Natriuretic peptides; Postoperative care
24.  Perioperative predictors of morbidity and mortality following cardiac surgery under cardiopulmonary bypass 
Saudi Journal of Anaesthesia  2012;6(3):242-247.
Prediction of outcome after cardiac surgery is difficult despite a number of models using pre-, intra- and post-operative factors. Ideally, risk factors operating in all three phases of the patients’ stay in the hospital should be incorporated into any outcome prediction model. The aim of the present study was to identify the perioperative risk factors associated with morbidity, mortality and length of stay in the recovery room (LOSR) and length of stay in the hospital (LOSH).
Eighty-eight adults of either sex, patients undergoing elective open cardiac surgery were studied prospectively. The ability of a number of pre-, intra- and post-operative factors to predict outcome in the form of mortality, immediate morbidity (LOSR) and intermediate morbidity (LOSH) was assessed.
Factors associated with higher mortality were preoperative prothrombin index (PTI), American Society of Anesthesiology-Physical Status (ASA-PS) grade, Cardiac Anaesthesia Risk Evaluation (CARE) score and New York Heart Association (NYHA) class, intraoperative duration of cardiopulmonary bypass (DCPB), number of inotropes used while coming off cardiopulmonary bypass and postoperatively, Acute Physiology and Chronic Health Evaluation (APACHE) II excluding the Glassgow Comma Scale (GCS) component and the number of inotropes used. Immediate morbidity was associated with preoperative PTI, inotrope usage intra- and post-operatively and the APACHE score. Intermediate morbidity was associated with DCPB and intra- and post-operative inotrope usage. Individual surgeon influenced the LOSR and the LOSH.
APACHE score, a general purpose severity of illness score, was relatively ineffective in the postoperative period because of sedation, neuromuscular blockade and elective ventilation used in a number of these patients. The preoperative and intraoperative factors like CARE, ASA-PS grade, NYHA, DCPB and number of inotropes used influencing morbidity and mortality are consistent with the literature, despite the small size of our sample.
PMCID: PMC3498662  PMID: 23162397
Cardiac surgery; outcome prediction; prognostication; risk stratification
25.  Significance of Preoperative Total Lymphocyte Count as a Prognostic Criterion in Adult Cardiac Surgery 
Evaluation of operational risk is a consequential goal in perioperative management of patients in cardiac surgery. Preoperative total lymphocyte count (PTLC) is a prognostic criterion of adverse major cardiovascular outcomes.
The purpose of this study was to investigate the prognostic value of PTLC as an independent predictor of postoperative morbidity and mortality in cardiac surgery.
Patients and Methods:
Of 1604 patients scheduled for cardiac surgery between September, 2012 and March, 2013, a total of 1171 consecutive patients underwent elective primary valvular heart surgery and coronary artery bypass grafting. The patients were divided to three groups according to their PTLCs. The baseline characteristics and postoperative mortality and morbidity of the patients as well as the intensive care unit (ICU) stay according to the PTLCs were recorded and analyzed. The only inclusion criterion was a preoperative complete blood count. Exclusion criteria included: ages under 18 or over 80 years old, emergency surgery, adult patients with congenital heart disease and previous open heart surgery, and patients with any bacterial or viral infection during two weeks before the surgery. Protocol of anesthetic medications was used in all the patients similarly and according to standard. All the patients were admitted to the ICU after the surgery.
A PTLC < 1500 cells/µL was associated with significantly high mortality and morbidity (P = 0.0001). In-hospital mortality and major composite morbidity were 9.65% and 28.4%, respectively. Low PTLC was associated with more frequent need for inotropic and intra-aortic balloon pump (IABP) support (P < 0.001), dialysis-dependent acute renal failure (P = 0.0001), postoperative superficial wound infections (P = 0.0001) and prolong ICU stay (P = 0.0001).
Our study results showed that low PTLC was an independent, valuable prognostic criterion, with high sensitivity and specificity for evaluation of postoperative morbidity and mortality in cardiac surgery.
PMCID: PMC4183084  PMID: 25289377
Total Lymphocyte Count; Cardiopulmonary Bypass; Mortality; Morbidity; Postoperative Complications

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