Independent Preoperative Predictors of Outcomes in Orthopedic and Vascular Surgery O A
Transcription
Independent Preoperative Predictors of Outcomes in Orthopedic and Vascular Surgery O A
ORIGINAL ARTICLE Independent Preoperative Predictors of Outcomes in Orthopedic and Vascular Surgery The Influence of Time Interval Between an Acute Coronary Syndrome or Stroke and the Operation Robert D. Sanders, FRCA,∗ Alex Bottle, PhD,† Simon S. Jameson, MRCS,‡ Abdul Mozid, MRCP,§ Paul Aylin, FFPHM,† Lliam Edger, FRCA,|| Daqing Ma, MD, PhD,∗ Mike R. Reed, FRCS,‡ Matthew Walters, FRCP,¶ Kennedy R. Lees, FRCP,¶ and Mervyn Maze, FRCP, FRCA, FMedSci# Objective: To identify independent preoperative predictors of outcome for total hip or knee replacement (THKR) and abdominal aortic aneurysm (AAA) repair, including the importance of the time interval between an acute coronary syndrome (ACS) or stroke and surgery. Background: Present guidelines do not advocate a prolonged delay after ACS though recent data suggest delaying operations by 8 weeks. There is a lack of data on when to schedule surgery following stroke. Methods: The Hospital Episode Statistics database was analyzed for elective admissions for THKR and AAA surgery between 2006–2007 and 2009–2010. Patient factors influencing mortality, length of stay, and readmission rates were identified by logistic regression. Results: A total of 414,985 THKRs (mortality: 0.2%) and 14,524 AAA repairs (mortality: 3.5%) were included. Heart failure, renal failure, liver disease, peripheral vascular disease, and non-atrial fibrillation arrhythmia increased the odds of mortality for both surgeries. Among other factors, previous ACS and stroke predicted mortality after THKR but not AAA surgery. Compared with more delayed surgery, THKR surgery performed within 6 months of an ACS (odds ratio [OR]: 3.81; 95% confidence interval [CI]: 1.55–9.34), but From the ∗ Magill Department of Anaesthetics, Intensive Care and Pain Medicine, Imperial College London, Chelsea and Westminster Hospital, London; †School of Public Health, Imperial College London; ‡Department of Orthopaedics, Northumbria NHS Foundation Trust, Woodhorne Lane, Ashington, UK; §Department of Cardiology, The London Chest Hospital, London; ||Department of Anaesthetics and Intensive Care Medicine, Central Middlesex Hospital, London; ¶Institute of Cardiovascular and Medical Sciences, University of Glasgow, Lanarkshire, UK; and #Department of Anesthesia and Perioperative Care, University of California San Francisco. Disclosure: No conflict of interest is reported by the authors. All authors have completed the Unified Competing Interest form at http://www.icmje.org/coi disclosure.pdf (available on request from the corresponding author) and declare: no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, no other relationships or activities that could appear to have influenced the submitted work. This work was funded by an AAGBI/Anaesthesia Department Project Grant administered by the National Institute of Academic Anaesthesia and awarded to Dr Sanders. The Dr Foster Unit at Imperial is largely funded via a research grant by Dr Foster Intelligence, an independent health care information company and joint venture with the NHS Information Centre. The Dr Foster Unit is affiliated with the Centre for Patient Safety and Service Quality at Imperial College Healthcare NHS Trust that is funded by the National Institute of Health Research. The Department of Primary Care and Public Health is grateful for support from the NIHR Biomedical Research Centre funding scheme. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.annalsofsurgery.com). Reprints: Robert D. Sanders, FRCA, Magill Department of Anaesthetics, Intensive Care and Pain Medicine, Imperial College London, Chelsea and Westminster Hospital, 369 Fulham Road, London, SW10 9NH, UK. E-mail: [email protected]. C 2012 by Lippincott Williams & Wilkins Copyright ISSN: 0003-4932/12/25505-0901 DOI: 10.1097/SLA.0b013e31824c438d Annals of Surgery r Volume 255, Number 5, May 2012 not stroke, increased the odds of mortality. The effect of ACS persisted up to 12 months (OR: 1.99; 95% CI: 1.02–3.88) and was not altered by exclusion of patients who received percutaneous coronary intervention or coronary artery bypass grafting for treatment of their ACS. Conclusions: Previous stroke and ACS increased the odds of perioperative mortality from THKR but not AAA surgery; THKR surgery conducted up to 12 months after an ACS was associated with increased mortality. (Ann Surg 2012;255:901–907) D etermining the appropriateness and timing of surgery is dependent on many factors; however, perioperative risk is the most important. Timing of elective surgery after vascular events such as acute coronary syndrome (ACS) or stroke poses an interesting problem. Thirty years ago, Goldman et al1 observed that surgery conducted within 6 months of myocardial infarction was associated with increased perioperative cardiac risk. Further studies have attempted to clarify the relationship between timing of surgery relative to myocardial infarction and perioperative risk; however, these studies have either been underpowered to detect temporal effects2 or have studied a heterogeneous group of scheduled and unscheduled procedures with limited adjustment for other prognostic variables.3 Focus specifically on elective operations is of particular importance, as there is the opportunity to delay surgery. Current guidelines state that surgery should be delayed 4 to 6 weeks after at ACS,4 largely dismissing the data given by Goldman et al because of changing diagnostic criteria for management of and outcomes after coronary events over the 30-year period. We sought contemporary evidence to substantiate whether there is a more prolonged phase (as suggested by Goldman et al1 and recently by Livhits et al3 ) after an ACS during which elective surgery is a high risk. The effect of recent stroke on perioperative risk has been less studied and remains unclear, hence a paucity of information is available to guide clinicians when deciding on the timing of elective surgery after major vascular events. We aimed to clarify these important questions by using a large registry of routinely collected clinical data to study the influence of recent ACS and stroke on perioperative risk in patients undergoing a series of common, elective surgical procedures. METHODS Following local research ethics committee and Section 251 (formerly Section 60) National Information Governance Board for Health and Social Care approval, we extracted all nonduplicate elective (planned) admissions in England and Wales for the financial years April 1, 2006, to March 31, 2010, with valid age, sex, length of stay (LOS), and patient ID from the Hospital Episode Statistics database. This is an administrative database covering all admissions to NHS (public) hospitals in England, including private patients treated in www.annalsofsurgery.com | 901 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Annals of Surgery r Volume 255, Number 5, May 2012 Sanders et al these hospitals. Diagnostic information is coded using the International Classification of Diseases, system version 10 (ICD-10); the 13 secondary diagnoses record comorbidities and complications. Its 12 procedure fields use the classification of interventions and procedures of the Office of Population Censuses and Surveys (OPCS), unique to the UK.5 Admissions (“spells”) ending in transfer to another hospital were linked together to form “superspells” (we will refer to the continuous inpatient period, including any transfers, as one admission). The principal procedure of interest in this study was a total hip replacement [OPCS codes W371, W381, and W391; resurfacing (W581 with accompanying Z843) procedures were also included], total knee replacement (W401, W411 and W421), or abdominal aortic aneurysm (AAA) repair (L183–6, L193–6, L203–6, L213–6, L271–2, L275–6, L281–2, L285–6). The first operation per patient was selected and the rest discarded because the postoperative risk may be higher for reoperations. We hypothesized that preoperative factors would differentially influence intermediate- and high-risk surgery2,4,6 and hence clinicians should judge a procedure-specific risk.4 For intermediate risk surgery, we selected elective total hip or knee replacements (THKRs). Preliminary analysis suggested that the population of patients undergoing these procedures had similar demographics and incurred similar perioperative mortality, supporting their grouping. For high-risk surgery, elective AAA repair was selected. Preoperative “Vascular events,” including stroke, myocardial infarction, and unstable angina, were defined as conditions necessitating hospital admission and therefore generating a primary diagnosis code with known timing. We therefore looked retrospectively for admissions within the previous 10 years with the primary diagnosis of stroke (I61–I64 or I66), myocardial infarction (I21, I22), and unstable angina (I200) before their index procedure until 1996. We looked in every spell in the preoperative admissions in case the stroke, myocardial infarction, or unstable angina occurred after transfer (ie, was in spell >1). The time in days from the stroke, myocardial infarction, or unstable angina admission to the index operation was noted. If a patient had more than 1 “vascular event,” then the date of the most recent was noted. Comorbidities not meeting the criteria for a “vascular event,” such as diabetes mellitus, liver disease, or renal failure, were identified from the secondary diagnosis codes on admission for the surgical procedure (supplementary Table 1, available at http://links.lww.com/ SLA/A231). Age was analyzed as a continuous variable (“risk per additional single year”), though in Table 1 a threshold is displayed for illustrative purposes. The reference gender was male. We derived a set of comorbidity variables representing risk factors for postoperative death using an ICD-10 version of the Charlson comorbidity index7 and other risk indices2,8,9 as a starting point and augmenting their components where necessary. However, rather than using the Charlson comorbidity index to adjust for perioperative risk, we adjusted for the impact of each preoperative factor by logistic regression to assign appropriate weights to the comorbidities in our study population. Our primary endpoint was the adjusted odds ratio (OR) of perioperative mortality (defined as inpatient death within 30 days of surgery); secondary endpoints were 2 surrogates of perioperative morbidity: prolonged LOS (above the national upper quartile for the 4 years of index procedures combined: 12 days for AAA repair and 7 days for THR and TKR) and emergency (unplanned) readmission for any reason within 28 days of discharge. We then grouped myocardial infarction and unstable angina to form ACS and analyzed how the preoperative timing of ACS or stroke influenced perioperative outcomes. Patients with a defined preoperative event were extracted and grouped according to the preoperative event type (stroke or ACS). Each cohort (based on the defined preoperative event) was then analyzed to define the adjusted risk imposed by the timing of the condition preoperatively using the outcomes mentioned earlier. The ACS group was analyzed with and without exclusion of all percutaneous coronary intervention (PCI) for treatment of the ACS (OPCS codes K49, K50, K75), PCI and/or coronary TABLE 1. Patient Demographics for THKR and AAA Surgery THKR Absent Operation Risk Factor Age (>70 years) Male Hypertension Atrial fibrillation Non-AF arrhythmia Valvular heart disease Heart failure Respiratory disease Diabetes mellitus Renal failure Cancer Liver disease Peripheral vascular disease Stroke Stable angina Myocardial infarction Unstable angina ACS AAA Present Case Total (%) Mortality Rate: Number (%) 216740 (52.2) 243598 (58.7) 250605 (60.4) 396084 (95.4) 412746 (99.5) 411977 (99.3) 411852 (99.2) 374278 (90.2) 377354 (90.9) 411340 (99.1) 411647 (99.2) 414128 (99.8) 412045 (99.3) 411924 (99.3) 414881 (99.8) 408525 (98.4) 409494 (98.7) 403753 (97.3) 122 (0.1) 374 (0.2) 388 (0.2) 679 (0.2) 802 (0.2) 796 (0.2) 689 (0.2) 699 (0.2) 698 (0.2) 673 (0.2) 800 (0.2) 810 (0.2) 798 (0.2) 811(0.2) 829 (0.2) 791 (0.2) 792 (0.2) 761 (0.2) Absent Case Total (%) Mortality Rate: Number (%) 198245 (47.8) 171387 (41.3) 164380 (39.6) 18901 (4.6) 2239 (0.5) 3008 (0.7) 3133 (0.8) 40707 (9.8) 37631 (9.1) 3645 (0.9) 3338 (0.8) 857 (0.2) 2940 (0.7) 3061 (0.7) 104 (0.0) 6460 (1.6) 5491 (1.3) 11232 (2.7) 707 (0.4) 455 (0.3) 441 (0.3) 150 (0.8) 27 (1.2) 33 (1.1) 140 (4.5) 130 (0.3) 131 (0.3) 156 (4.3) 29 (0.9) 19 (2.2) 31 (1.1) 18 (0.6) 0 (0.0) 38 (0.6) 37 (0.7) 68 (0.6) Present Case Total (%) Mortality Rate: Number (%) Case Total (%) Mortality Rate: Number (%) 4862 (33.5) 2043 (14.1) 6554 (45.1) 12789 (88.1) 14348 (98.8) 14274 (98.3) 14030 (96.6) 12298 (84.7) 12873 (88.6) 13791 (9.5) 13867 (95.5) 14413 (99.2) 13017 (89.6) 14228 (98.0) 14520 (100.0) 13699 (94.3) 13976 (96.2) 13255 (91.3) 114 (2.3) 84 (4.1) 225 (3.4) 412 (3.2) 498 (3.5) 497 (3.5) 435 (3.1) 416 (3.4) 453 (3.5) 384 (2.8) 482 (3.5) 489 (3.4) 406 (3.1) 495 (3.5) 511 (3.5) 484 (3.5) 488 (3.5) 464 (3.5) 9662 (66.5) 12481 (85.9) 7970 (54.9) 1735 (11.9) 176 (1.2) 250 (1.7) 494 (3.4) 2226 (15.3) 1651 (11.4) 733 (5.0) 657 (4.5) 111 (0.8) 1507 (10.4) 296 (2.0) 4 (0.0) 825 (5.7) 548 (3.8) 1269 (8.7) 397 (4.1) 427 (3.4) 286 (3.6) 99 (5.7) 13 (7.4) 14 (5.6) 76 (15.4) 95 (4.3) 58 (3.5) 127 (17.3) 29 (4.4) 22 (19.8) 105 (7.0) 16 (5.4) 0 (0.0) 27 (3.3) 23 (4.2) 47 (3.7) ACS indicates acute coronary syndrome. 902 | www.annalsofsurgery.com C 2012 Lippincott Williams & Wilkins Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Annals of Surgery r Volume 255, Number 5, May 2012 artery bypass grafting (CABG) (OPCS codes K49, K50, K75, K40– 46), and PCI with coronary stent placement (OPCS code K75). STATISTICAL ANALYSIS Logistic regression models were fitted for mortality with the following patient factors: age, sex, Carstairs deprivation populationweighted fifth (the population divided into 20 percentiles),10 comorbidity and a “time” flag for previous stroke, unstable angina or myocardial infarction. Unstable angina and myocardial infarction were also grouped to form ACS. Other comorbidities, which were derived using the secondary diagnoses in the index admission, were included as indicator variables if they were recorded in at least 30 patients and sometimes had to be dropped even with less than 30 to enable the model to converge. To avoid the problems of stepwise model selection procedures, we retained all candidate variables even if not significant and only removed them because of nonconvergence. To elicit any possible effect of the timing of the stroke and ACS, we identified only those patients with a prior event (in the previous 10 years) and fitted the lag time as a continuous variable. We also looked for a nonlinear effect by categorizing the lag. To identify a clinically important “window” during which surgery should be avoided, we set thresholds of 6 (based on previous studies1–3 ) and 12 months (based on advised termination of dual antiplatelet therapy for ACS11 ) to the index surgical procedure. We tried fitting 2-level models to account for the clustering of patients within hospitals but found minimal clustering and therefore present the results from the single-level regression models. All analyses were performed using SAS v9.2 (SAS Institute Inc, Cary, NC). Data are tabulated and reported as adjusted ORs. Where of interest data are presented as “number needed to harm” (NNH) that is the inverse of the attributable risk (risk in the people exposed minus the risk in the people not exposed). In this context, exposure refers to previous ACS. The data are presented in accordance with STROBE (STrengthening Reporting of Observational studies in Epidemiology) guidance. RESULTS Cohort Demographics A total of 414,985 THKRs and 14,524 AAA repairs were performed between 2006–2007 and 2009–2010. Summary data are available in Table 1. Mortality was 0.2% for THKR with 829 deaths (0.21% for total hip replacement with 401 deaths and 0.19% for total knee replacement with 428 deaths) and 3.5% for AAA repair with 511 deaths. For THKR, there were 431 causes for readmission (3-character ICD-10 codes); 38.9% were attributable to surgical reasons and 11.1% were for cardiovascular causes (ACS 1.3% and stroke 0.5%). For AAA surgery, there were 185 causes of readmission; 34.9% of readmissions were for surgical reasons while 14.6% were secondary to cardiovascular disorders (ACS 3.9% and stroke 1.0%). Perioperative Risk Factors Heart failure, liver failure and renal failure, peripheral vascular disease, and non-atrial fibrillation arrhythmia were common factors that increased the odds of perioperative death, prolonged LOS, and readmission for both THKR and AAA surgery (Table 2). For THKR, but not AAA surgery, the odds of perioperative mortality were increased by ACS and stroke, as well as diabetes mellitus, hypertension, atrial fibrillation, valvular heart disease, cancer, and respiratory disease (Table 2). Similar factors, and also age, affected risk of prolonged LOS and readmission rates from THKR (Table 2). In addition to the common factors, perioperative mortality after AAA repair was predicted by increased age (Table 2). Although mortality after AAA repair was not affected by prior ACS or stroke, the odds of pro C 2012 Lippincott Williams & Wilkins Timing Surgery Postvascular Event longed LOS were increased by previous stroke, whereas the odds of readmission were affected by ACS (Table 2). Perioperative Risk Imposed by the Timing of Prior ACS and Stroke We analyzed the effect of timing of ACS or stroke for either type of surgery based on continuous methods but did not find a linear relationship between the timing of vascular event and perioperative mortality, prolonged LOS, and readmission rates. Analysis by dichotomous methods revealed that in patients undergoing THKR, ACS 6 months before an operation increased the risk of perioperative mortality (Table 3). This effect persisted even after removing all patients who had a PCI (OR: 3.14, P = 0.032), PCI and/or CABG (OR: 3.35, P = 0.024), or just those with coronary stent placement (OR: 4.1, P = 0.003) for treatment of their ACS. If the threshold was reset at 12 months [11 of 967 (1.13%) patients died], recent ACS still increased the odds of perioperative death. Removal of all patients who had PCI (OR: 2.02, P = 0.056), PCI and/or CABG (OR: 1.6, P = 0.255), or just a coronary stent (OR: 2.20, P = 0.022) as treatment of their ACS did little to affect the point estimate of the results. To quantify the effect of prior ACS on postoperative mortality, we calculated the NNH. Overall prior ACS exerted a modest effect on mortality from THKR (NNH 1:700); however, if surgery was conducted within 6 months (NNH 1:64) or 12 months (NNH 1:183) of an ACS, the risk was augmented. Patients who had an ACS in the 6 months before AAA repair had a non-significantly increased odds of prolonged LOS (P = 0.08) and readmission (P = 0.25) suggesting that this may increase the odds of perioperative morbidity, but there was no discernable effect on perioperative mortality (Table 3). ACS within the 12 months before AAA repair was associated with a significantly higher postoperative readmission rate, supporting an effect on morbidity (Table 3). Stroke in the 6 months before THKR or AAA surgery did not influence mortality, LOS, or readmission rates (Table 4). DISCUSSION The common perioperative risk factors for THKR and AAA surgery include heart, renal, and liver failure; non-atrial fibrillation arrhythmia; and peripheral vascular disease. Some factors, such as preoperative ACS and stroke, relate in a more procedure-specific manner only affecting mortality from THKR surgery. Furthermore, for THKR surgery, the timing of ACS influences the odds of perioperative death; thresholds of 6 and 12 months showed a prolonged increase in risk after an ACS. This effect persisted even after removal of patients whose ACS treatment involved placing a coronary stent or any PCI or any PCI and/or CABG. Although previous ACS and stroke did not predict mortality from AAA repair, they influenced perioperative morbidity. In particular, patients undergoing AAA repair within 12 months of an ACS were at an increased risk of emergency readmission to hospital (Table 3). COMMON PERIOPERATIVE RISK FACTORS The common factors that influenced perioperative mortality are consistent with current knowledge1,2,8 though liver disease, a potent contributor to perioperative mortality,9,12 has been excluded from recent perioperative risk scoring systems.1,2,8 Although liver disease only affected 0.8% patients for AAA surgery and 0.3% for THKR (Table 1), it is important to identify these individuals as high risk to allow provision of suitable perioperative care. PERIOPERATIVE RISK FACTORS FOR AAA SURGERY Our data for AAA repair are consistent with the suboptimal predictive value of the revised cardiac risk index for predicting outcomes www.annalsofsurgery.com | 903 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. 904 | www.annalsofsurgery.com 2.50 (2.31–2.71) 1.44 (1.40–1.47) 2.14 (1.98–2.31) 1.73 (1.14–2.63) 1.38 (1.31–1.46) 1.60 (1.51–1.70) 1.54 (1.47–1.60) <0.001 <0.001 0.002 <0.001 <0.001 <0.001 <0.001 0.043 0.040 <0.001 <0.001 6.79 (5.48–8.42) 1.41 (1.16–1.71) 1.37 (1.13–1.67) 8.89 (7.29–10.85) 2.43 (1.65–3.58) 8.34 (4.77–14.56) 2.18 (1.48–3.2) 1.64 (1.02–2.65) 1.44 (1.02–2.05) 1.93 (1.36–2.75) 1.73 (1.33–2.25) 1.58 (1.54–1.62) 3.40 (3.16–3.65) 1.67 (1.55–1.80) 2.32 (2.01–2.69) 1.52 (1.40–1.64) 1.57 (1.45–1.69) 0.002 1.84 (1.26–2.69) 0.85 (0.85–0.86) 1.32 (1.29–1.34) 1.13 (1.11–1.14) 2.35 (2.28–2.43) 1.60 (1.46–1.76) OR (95% CI) 0.259 <0.001 0.027 <0.001 <0.001 P LOS THKR 0.95 (0.87–1.04) 0.58 (0.50–0.67) 1.18 (1.02–1.36) 1.54 (1.26–1.87) 3.44 (2.29–5.16) OR (95% CI) AF indicates atrial fibrillation. Age Sex Hypertension Atrial fibrillation Non-AF arrhythmia Valvular heart disease Heart failure Respiratory Disease Diabetes mellitus Renal failure Cancer Liver disease Peripheral vascular disease Stroke Stable angina Myocardial infarction Unstable angina ACS Operation Risk Factor Mortality 1.61 (1.48–1.76) 1.48 (1.38–1.58) 1.52 (1.35–1.71) 1.19 (0.58–2.46) 1.28 (1.17–1.40) <0.001 0.011 <0.001 <0.001 <0.001 1.16 (1.11–1.20) 1.22 (1.08–1.37) 1.28 (1.13–1.45) 1.65 (1.31–2.09) 1.35 (1.19–1.53) <0.001 <0.001 <0.001 <0.001 <0.001 1.07 (0.93–1.23) <0.001 1.23 (1.09–1.39) 1.33 (1.28–1.38) 0.95 (0.94–0.96) 0.83 (0.81–0.85) 1.04 (1.01–1.07) 1.21 (1.15–1.28) 1.32 (1.13–1.53) <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 OR (95% CI) P P <0.001 <0.001 <0.001 0.638 <0.001 <0.001 0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.323 <0.001 <0.001 0.005 <0.001 <0.001 Readmission TABLE 2. Effect of Preoperative Risk Factors on Outcomes From THKR and AAA Surgery 1.22 (0.78–1.91) 0.98 (0.71–1.34) 1.52 (0.90–2.58) 0.82 (0.50–1.24) 1.00 (0.75–1.33) 5.43 (4.31–6.83) 1.12 (0.75–1.67) 5.69 (3.32–9.73) 2.13 (1.68–2.69) 3.54 (2.65–4.73) 1.15 (0.91–1.46) 0.96 (0.54–1.73) 1.05 (1.03–1.06) 1.05 (0.81–1.35) 1.04 (0.87–1.26) 1.20 (0.94–1.53) 2.02 (1.11–3.7) OR (95% CI) Mortality 0.376 0.878 0.118 0.348 0.993 <0.001 0.592 <0.001 <0.001 <0.001 0.249 0.894 <0.001 0.720 0.656 0.143 0.022 P AAA 1.05 (0.85–1.30) 0.97 (0.84–1.12) 1.37 (1.05–1.78) 0.96 (0.80–1.15) 1.01 (0.88–1.14) 3.26 (2.79–3.81) 1.07 (0.88–1.30) 1.62 (1.06–2.46) 1.75 (1.55–1.97) 1.78 (1.46–2.16) 1.19 (1.06–1.32) 1.08 (0.80–1.44) 1.02 (1.02–1.03) 1.80 (1.61–2.00) 1.11 (1.02–1.21) 1.80 (1.61–2.02) 2.21 (1.61–3.03) OR (95% CI) LOS 0.660 0.682 0.021 0.639 0.932 <0.001 0.496 0.025 <0.001 <0.001 0.002 0.629 <0.001 <0.001 0.013 <0.001 <0.001 P 1.35 (1.03–1.76) 1.28 (1.07–1.54) 0.89 (0.59–1.34) 3.55 (0.37–34.52) 1.12 (0.89–1.40) 1.04 (0.87–1.24) 1.17 (0.90–1.52) 1.07 (0.82–1.39) 1.06 (0.53–2.12) 1.25 (1.05–1.49) 1.47 (1.11–1.94) 1.32 (1.14–1.52) 1.47 (1.02–2.12) 0.93 (0.87–0.99) 1.09 (0.93–1.27) 1.17 (1.04–1.31) 1.36 (1.15–1.59) 0.95 (0.57–1.58) OR (95% CI) P 0.027 0.008 0.583 0.275 0.352 0.670 0.238 0.624 0.876 0.011 0.006 <0.001 0.039 0.026 0.311 0.007 <0.001 0.835 Readmission Sanders et al Annals of Surgery r Volume 255, Number 5, May 2012 C 2012 Lippincott Williams & Wilkins Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. C 2012 Lippincott Williams & Wilkins 0.780 0.003 0.045 3.81 (1.55–9.34) 1.99 (1.02–3.88) P 1 (0.99–1.01) OR (95% CI) 1.18 (1.02–1.35) 1.22 (0.93–1.59) 1 (1–1) OR (95% CI) LOS THKR 0.024 1.21 (0.98–1.49) 1.28 (0.87–1.89) 1 (1–1) <0.001 0.152 OR (95% CI) P Readmission 0.082 0.207 0.032 P 1.18 (0.54–2.61) 0.85 (0.26–2.84) 1 (0.99–1.01) OR (95% CI) Mortality Timing of operation after stroke: continuous Timing of operation after stroke: 6-month threshold Operation Risk Factor 0.197 0.900 0.87 (0.1–7.57) P 1.01 (1–1.02) OR (95% CI) Mortality 1.35 (0.91–1.99) 1 (1–1) OR (95% CI) LOS THKR 0.133 0.290 P 0.86 (0.46–1.63) 1 (0.99–1) OR (95% CI) Readmission 0.647 0.315 P 0.59 (0.07–4.75) 1 (0.98–1.01) OR (95% CI) Mortality TABLE 4. The Effect of the Timing of Surgery After Stroke on Outcomes From THKR and AAA Surgery Timing of operation after ACS: continuous Timing of operation after ACS: 6-month threshold Timing of operation after ACS: 12-month threshold Operation Risk Factor Mortality TABLE 3. The Effect of Timing of ACS on Outcomes From THKR and AAA Surgery 0.617 0.789 P 0.675 0.800 0.679 P 0.69 (0.28–1.68) 1 (1–1.01) OR (95% CI) LOS AAA 1.05 (0.73–1.51) 1.52 (0.95–2.43) 1 (1–1.01) OR (95% CI) LOS AAA 0.411 0.301 P 0.804 0.083 0.132 P 0.62 (0.13–2.97) 1 (0.99–1.01) OR (95% CI) Readmission 2.07 (1.37–3.13) 1.41 (0.79–2.54) 0.99 (0.99–1) OR (95% CI) Readmission 0.554 0.914 P 0.001 0.250 0.017 P Annals of Surgery r Volume 255, Number 5, May 2012 Timing Surgery Postvascular Event www.annalsofsurgery.com | 905 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Annals of Surgery r Volume 255, Number 5, May 2012 Sanders et al from vascular surgery or for predicting perioperative mortality.2,13 Indeed, we have found that neither previous stroke nor ACS increases the risk of perioperative mortality from AAA surgery though the wide confidence intervals (CIs) for stroke suggest we should be cautious in suggesting that all strokes do not influence outcome. The lack of influence of previous ACS on perioperative mortality is consistent with the lack of benefit accrued by cardiac revascularization before AAA surgery.14,15 We suspect that the lack of effect of previous stroke and ACS on mortality may be related to the widespread vascular disease in this patient cohort (so individual end-organ insults are not necessarily discriminative in this population) and the high-risk nature of the surgery involved. Given the limitations of the patient history in this population, risk stratification of patients undergoing AAA surgery may be enhanced by additional preoperative biomarker monitoring such as measurement of preoperative brain natriuretic peptide.16 There are significant differences between the risk factors we identified and the customized probability model (CPM) for predicting perioperative mortality from all vascular surgery. Unlike the CPM, we found age to be predictive of mortality for AAA repair but did not find respiratory disease to increase the odds of death.8 As the CPM, by definition includes many types of vascular surgery, it may not be sufficient for judging a procedure-specific risk for AAA repair. Indeed our study highlights a problem with extrapolating findings from one procedure to another and argues that risk prediction models should be procedure specific. PERIOPERATIVE RISK FACTORS FOR THKR SURGERY Many more preoperative factors influenced perioperative outcome in THKR than AAA surgery. It is of interest that age did not predict perioperative mortality from THKR surgery; this is important as greater numbers of elderly patients are presenting for orthopedic surgery. Nonetheless, age did influence perioperative morbidity in this surgical cohort indicating these patients still require judicious perioperative care. Many vascular risk factors (prior stroke and ACS, diabetes mellitus, hypertension, and heart and renal failure) proved discriminative to predict perioperative mortality for THKR, consistent with the revised cardiac risk index (that was devised on the basis of large orthopedic population2 ). In addition to the common factors and vascular risk factors, cancer and respiratory disease were important predictors of perioperative mortality. Cancer may indicate general frailty, poor nutritional status, or vulnerability to postoperative complications such as infection or thromboembolism. It is important that respiratory disease has been isolated as an important factor for THKR surgery. In these patients, regional rather than general anesthetic techniques may prove beneficial as it is associated with reduced respiratory complications after surgery.17 TIMING OF ELECTIVE SURGERY AFTER ACSs AND STROKE Although we did not find that the timing of prior ACS influenced outcomes when analyzed as a continuous variable, our data based on thresholds of 6 and 12 months show that ACS induces a long-term increase in perioperative risk for THKR. We suggest that surgery should be avoided for 6 months after an ACS and considered high risk up to 12 months. For surgery conducted within 6 months of a prior ACS, one might expect one additional perioperative death in every 64 procedures. If surgery was conducted within 12 months, one additional death may occur in every 183 procedures. Thus, while prior ACS itself is a modest risk factor for mortality, the timing of the procedure plays an important role in exaggerating the mortality risk. Furthermore, we have shown this effect persists even when all patients 906 | www.annalsofsurgery.com having PCI or PCI and/or CABG or just those with coronary stents are excluded. Current guidelines suggest that surgery be delayed for 2 weeks after angioplasty, 6 weeks after bare metal stent placement, or 12 months after drug eluting stent placement.4 Our data suggest that there is a pervasive prolonged risk after ACS for THKR surgery regardless of whether coronary intervention is performed. Indeed, even when all patients who had PCI and/or CABG were excluded from the analysis, THKR operation within 6 months of an ACS was associated with increased risk. Although exclusion of patients who had a PCI and/or CABG only slightly reduced, the point estimate of harm at 12 months statistical significance was lost. It is likely that exclusion of the subjects reduced statistical power to identify the effect. In sum, our observations support further investigation of the hypothesis that patients with ACS should, wherever possible, have elective surgery deferred for longer than is currently the case. This strategy could be expected to reduce complications resulting from the ACS (by allowing uninterrupted 12-month antiplatelet therapy as recommended by current guidelines9,18 ) and perioperative complications, particularly bleeding risk from aggressive antithrombotic strategies,19 or increased risk of thrombotic events if dual therapy is stopped.19 Unfortunately, data on the use of antiplatelet agents were not available for use in our analysis. Elective AAA surgery conducted within 12 months of an ACS was associated with increased odds of readmission but not death. We speculate that this disparity may relate to the extent and severity of vascular disease in this patient cohort as opposed to the orthopedic population. Nonetheless, AAA repair conducted within a year of an ACS should be considered higher risk based on the increased risk of morbidity. After AAA surgery, cardiovascular causes account for 14.6% of readmissions, and specifically ACS accounts for 3.9% of readmissions; therefore, it is certainly plausible that timing of ACS may influence readmission rate. Our findings are in agreement with Livhits et al’s recent study that, despite showing increased perioperative risk (in mixed surgeries) for up to 1 year after myocardial infarction, recommended that surgery should be delayed for 2 months;3 we consider this recommendation too permissive given the increased risk imparted by performing the surgery too soon after an ACS. Unfortunately, extrapolation of their findings to specific operations is difficult given the inclusion of both elective and unscheduled procedures. Furthermore, Livhits et al’s use of controls that never experienced a myocardial infarction likely exaggerates the impact of the timing of myocardial infarction and their limited adjustment for other patient variables (by use of Charlson comorbidity index rather than weighting each condition accordingly) reduces confidence in their findings.3 Despite these limitations, their data supports our proposal that surgery should be delayed beyond the currently recommended period of 4 to 6 weeks after an ACS. Beyond delaying surgery, we must focus preoperative optimization and vigilant perioperative care in a procedure-specific manner; the protective potential of statin,20 alpha-2 adrenergic agonist,21 and βblocker therapy22,23 needs evaluation in THKR surgery. We were surprised that the preoperative timing of stroke did not influence perioperative outcome in a similar manner to ACS. This may reflect the heterogeneity of stroke or that severe strokes rendered the patient unsuitable for surgery. The wide CIs for the 6month threshold for stroke before THKR suggest that the study may have been underpowered to address the timing of stroke. However, the results did not differ if a 12-month threshold was imposed or if the data were analyzed in a continuous manner (Table 4). However, timing is only one of many stroke-related factors that may influence perioperative outcomes. Indeed, “stroke” is a heterogeneous condition including both hemorrhagic and ischemic events that we were unable to divide into separate cohorts. C 2012 Lippincott Williams & Wilkins Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Annals of Surgery r Volume 255, Number 5, May 2012 Timing Surgery Postvascular Event STRENGTHS AND LIMITATIONS Hospital Episode Statistics is a large administrative data set that has shown good comparability with clinical risk prediction scores of perioperative mortality despite lacking much clinical information.24 The large sample size surveyed gives us power to address the effects of a diverse range of comorbidities and their timing (and avoiding the use of composite endpoints2 ) on the “hard” measures mortality and surrogates of morbidity (LOS and readmission). A further strength of our analysis is that we have not been constrained by focus on perioperative cardiac risk and therefore identified other influential variables beyond vascular risk factors, such as cancer and liver disease. Nonetheless, some variables, for example, stable angina, had to be dropped from the analysis because of limited patient numbers with that diagnosis. We focused on short-term endpoints (ie, those within 30 days of the operation), as it was our objective to study perioperative risk; however, we acknowledge that further analyses of longer term outcomes (such as 12 month mortality) are also warranted. The reliability of administrative data has been questioned. However, the accuracy of UK hospital administrative data was found to approximate 84% and 97% for diagnostic and operation codes, respectively, in a 2001 systematic review of coding accuracy.25 The coding is subject to annual inspection, and accuracy has improved since the introduction of Payment by Results system with its data assurance framework. For example, the average clinical coding error rate of 16.5% across primary and secondary diagnosis and procedure coding in 2007–2008 improved in 2008–2009 to 12.8% with a concomitant reduction in the variability across acute NHS Trusts in England.26 We have no reason to suspect that data inaccuracies are more likely to affect records for patients with prior vascular events than those without. CONCLUSIONS Although some common preoperative risk factors emerged in our analysis, preoperative predictors of perioperative mortality and surrogates of morbidity are procedure specific. Therefore, riskprediction systems should focus on specific procedures rather than including multiple different types of surgery. Furthermore, our data suggest that patients who have an ACS before elective THKR surgery should be considered higher risk within the first year of the event. ACKNOWLEDGMENTS R.D.S. and L.E. developed the initial question and performed the initial literature searches (with D.M. and M.M.). All authors contributed to study design (lead by A.B., P.A., and R.D.S.). Specifically K.R.L., M.W., and A.M. provided expert medical opinion and discussed methodology. S.S.J. and M.R. provided similar surgical input. A.B. analyzed the data. All authors contributed to data interpretation. R.D.S. and A.B. wrote the manuscript with input from all authors. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. REFERENCES 1. Goldman L, Caldera DL, Nussbaum SR, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med. 1977;297:845–850. 2. Lee TH, Marcantonio ER, Mangione CM, et al. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation. 1999;100:1043–1049. 3. Livhits M, Ko CY, Leonardi MJ, et al. 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Key messages from Year 2 of the national clinical coding audit programme. http://www.auditcommission.gov.uk/SiteCollectionDocuments/AuditCommissionReports/ NationalStudies/20090827pbrdataassuranceframework0809rep.pdf. Accessed February 2010. www.annalsofsurgery.com | 907 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.