A risk-adjusted analysis of mortality and severe morbidity in patients with ruptured abdominal aortic aneurysm from February 1994 till February 2010 in the OLVG, Amsterdam Master program medical science, scientific rotation University of Groningen, the Netherlands O.N.H. Kahmann Onze Lieve Vrouwe Gasthuis, Amsterdam Department of vascular surgery 03/03/2010 - 21/07/2010 Supervised by: Dr. A.C. Vahl, vascular surgeon OLVG, clinical epidemiologist Dr. J.J.A.M. van den Dungen, vascular surgeon UMCG ABSTRACT Background. A ruptured abdominal aortic aneurysm (RAAA) is a life-threatening disorder. It is associated with a risk of death approaching 80-90%, including operative therapy. Despite improved perioperative care, the operative mortality rate (40-50%) has not changed during recent decades. Given the preoperative variability in presentation of patients, it is difficult to compare postoperative outcomes. The purpose of the present study was to make a retrospective risk-adjusted analysis of the outcomes of RAAA during a 16-year period in the Onze Lieve Vrouwe Gasthuis in Amsterdam. Methods. Over a 16-year period (February 1994 to February 2010) 206 patients underwent conventional open surgery or endovascular repair for RAAA. Through a retrospective review of the patient’s hospital charts, data were collected to determine the actual mortality and severe morbidity. These findings were compared with the preoperative risk assessment according to the V-POSSUM (Vascular – Physiological and Operative Severity Score for enUmeration of Mortality and morbidity) method and the GAS (Glasgow Aneurysm Score). Results. The 30-day mortality rate was 45/206 (22%) in the whole cohort, 41/179 (23%, 95% Confidence Interval (CI) 17-30) after open repair and 4/27 (15%, 95% CI 6-32) after emergency EndoVascular Aneurysm Repair (eEVAR). The patient population did not significantly change over time according to age, gender, GAS and VPOSSUM. Neither did the 30-day mortality rate. 54 patients (26%) required intensive care treatment for more than 5 days and 72 (35%) had one or more major complications. The mean GAS in patients who did not survive RAAA repair was 102 (± SD 11), compared to 89 (± SD 15) among patients who survived (P<0.001). The GAS appeared to be a reasonable predictor of postoperative outcome for both open and endovascular RAAA repair, with an AUC (Area Under the Curve) of 0.73 (± SD 0.04; 95% CI 0.65-0.80; P<0.001) . The mean V-POSSUM among patients who died was 73 (± SD 21), compared with 54 (± SD 28) among survivors (P<0.001). The V-POSSUM predicted mortality was less accurate: AUC 0.69 (± SD 0.05; 95% CI 0.60-0.77; P<0.001). The only preoperative variables independently predicting 30-day mortality, were age (P=0.006) and lowest preoperative systolic blood pressure (P=0.032). Conclusion. In this study the 30-day mortality rate after RAAA repair was low (22%). It did not change significantly over the past 16 years. A noticeable trend was that the introduction of a less invasive operation technique (eEVAR) resulted in a lower amount of severe postoperative complications. The GAS appeared to be a reasonable predictor for outcome after both open and endovascular RAAA repair. The V-POSSUM scoring method had limited predictive value and overestimated preoperative risk. The preoperative measures for risk assessment we used, did not identify the high risk patients at an individual level. Therefore it appears that V2 POSSUM and GAS do not aid in determining whether or not an attempted operation is appropriate. Nevertheless these methods can be used in surgical audit or for interhospital comparisons. 3 INDEX Abstract 2 I. Introducion Epidemiology Etiology Symptoms Risk of rupture Treatment Predictors for outcome Measures predicting outcome Aim 5 5 6 6 7 7 8 9 II. Patients and methods Study population Study method Data collection and definitions Outcome measures Statistical analyses 10 10 10 11 11 III. Results 12 IV. Discussion 17 V. Conclusion 21 VI. Samenvatting 22 VII. References 24 4 I. INTRODUCTION Epidemiology All reported incidences of RAAA vary due to variability in data retrieval methods, sample selection, sex, age, and autopsy rate. The incidence of RAAA is approximately 6.0/100,000 per year and has not changed over recent decades.(1-3) The incidence rate of RAAA between men and women is about 3:1.(1;2;4) Gender related differences in AAA development seems to be caused by an estrogen mediated reduction in proteases derived from macrophages. These proteases are causing extracellular matrix breakdown, leading to aneurysm formation.(5;6) Using the same diameter (≥ 3 cm) in defining AAA, most prevalence studies underestimate AAA incidence in women, not taking into account gender associated differences in normal aortic diameter.(7) Despite advances in surgical health care and in perioperative intensive care, RAAA remains a life-threatening condition with an estimated overall mortality of 80-90%. More than 50% of patients die before reaching hospital or without operation.(1;2) A graduate reduction of mortality after RAAA repair is seen in a meta-analysis over a 50-year period.(8) Mortality rate in patients reaching the hospital alive, remains as high as 48%; multi organ failure being the predominant cause.(9) A meta-analysis of articles published between 1991 and 2006 showed a constant inhospital mortality rate of 48.5%.(10) According to the authors this lack of improvement is caused by the increased age of patients undergoing RAAA repair. In the Netherlands Visser et al. found an in-hospital mortality rate of 41% that did not change in a 10-year period (1991-2000).(11) They found age and hospital type to be the most significant predictors of mortality. Highest mortality rates were found in University hospitals and lowest in the smaller hospitals (0-399 beds). In industrialized countries RAAAs cause 1 to 2% of all deaths.(12;13) Age being one of the main risk factors in developing AAAs, the number of RAAAs will increase because of the proportional rise in the ageing population. Etiology The normal aortic diameter is approximately 2.0 cm, with a range of 1.4 to 3.0 cm. An AAA is most commonly described as an abdominal aortic measuring 3.0 cm or more in diameter.(14) The underlying cause of developing an AAA is often uncertain. There is considerable evidence for genetic predisposition.(5;15) The role of atherosclerotic disease in causing AAA is questionable.(5;6) Histologicaly, there is a destruction of elastin and collagen in the tunica media and the tunica adventitia of the arterial wall. The medial wall is characterized by smooth muscle cell loss and 5 there is infiltration of lymphocytes and macrophages. Inflammation and proteases play an important role in this process.(5;6;16) Symptoms AAAs expand at a variable rate and are usually asymptomatic. When the strength of the aortic wall is insufficient to sustain the intraluminal pressure, the aneurysm ruptures. One of the symptoms is pain in abdomen and back, possibly radiating to the groin and legs. Other symptoms are nausea, vomiting, pallor, sweating, tachycardia and hypotension.(1) Immediate surgical treatment is the only way to save the life of a patient with RAAA. Only when the rupture is contained, symptoms can be less acute or even missing. Operative treatment can then be performed with a delay of some days or even weeks.(17) Risk of rupture 13% of all AAAs will eventually rupture.(1) Several studies evaluated the factors that may contribute to AAA rupture. The maximum diameter of an AAA is an important predictor of rupture, with risk increasing markedly at diameters more than 5.5 cm (Figure I).(18) Figure I Risk of rupture through time according to initial diameter While male sex is a risk factor for developing an AAA, female gender is considered to be a risk factor associated with rupture.(5) This can simply be explained by the difference in normal aortic diameter, which is smaller in women than in men. Therefore an increased aortic diameter reflects a greater degree of dilatation in women than in men. Nevertheless, for both genders the current threshold for elective repair is similar. A lower threshold for women with AAA should be considered.(7) 6 Besides aneurysm diameter and gender, aneurysm growth rate and biomechanical factors are other important factors associated with a higher risk of rupture.(5;18;19) Other factors increasing the risk of rupture are continued smoking, uncontrolled hypertension and increased wall stress.(20) Treatment When the risk for aneurysm rupture is clearly higher than the expected operative mortality, elective surgery is indicated. Open surgery used to be the standard procedure for ruptured or intact AAA repair. The first successful elective AAA repair occurred in 1952.(21) In 1991 Parodi and Volodos published their first results after introduction of a new technique for elective AAA surgery: endovascular aneurysm repair (EVAR).(22;23) This treatment was used as a less invasive alternative technique and appeared to be suitable for both elective and emergency repair. Through the femoral arteries, under fluoroscopic guidance, an endograft is placed to act as a false lumen excluding the aneurysm lumen. The first report of emergency endovascular repair of a RAAA (eEVAR) was published in 1994.(24) Not all patients with a RAAA are suitable for eEVAR. Based on the dimensions of the endovascular graft, the infrarenal aortic neck and both iliac arteries must have a sufficient length and diameter. To evaluate the possibility of endovascular repair a CT angiography must be performed. In the OLVG the first eEVAR took place in October 1999. Since 2004 the OLVG is one of the three hospitals in Amsterdam participating in the Amsterdam Acute Endovascular Treatment to Improve Outcome of Ruptured Aortoiliac Aneurysm trial (AJAX trial). This trial is aiming to study the combined outcome of conventional emergency surgery versus endovascular treatment for RAAA. All patients with a suspected RAAA are transported to the trial centre on duty. CT-angiography is performed to prove anatomical suitability. If patients are unfit for eEVAR because of unfavourable anatomy or if they are in an unstable condition before or during CTscanning, immediate open surgery is performed. All other patients are randomized. Outcomes of all patients are recorded and compared.(25) First results are expected late 2010. Predictors for outcome Most vascular surgeons practice a selective policy of operative intervention for patients with RAAA. Determining whether or not an attempted operation is appropriate, is largely a subjective decision. The evidence on which to base operative selection remains uncertain.(26) In previous studies several factors have been mentioned as possible predictors for outcome after RAAA repair. Higher age was associated with a higher mortality rate.(3;11;27;28) Co-morbidity (COPD, cerebrovascular disease, renal insufficiency, coronary heart disease), along with advanced age, affected mortality after RAAA.(28) In contrast, other studies 7 suggested there is no association between preoperative co-morbidity and outcome.(29;30) Gender did not seem to affect postoperative mortality.(11;28) Measures predicting outcome Many previous studies reported the outcomes after RAAA repair. These mortality rates have varied depending on the patient’s clinical condition at presentation. Crude numbers of mortality and morbidity alone are insufficient to reflect the quality of care. Appropriate risk adjusted analysis of patients with RAAA would support comparative audit between different institutions and surgeons, allowing better evaluation of RAAA repair.(31;32) In addition to surgical audit, risk stratification can be useful in preoperative decision-making. Several scoring systems were developed to estimate preoperative risk. The POSSUM scoring system and the Glasgow Aneurysm Scale are two such statistical models. POSSUM scoring system. The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) is a method that is developed for standardizing patient data and for comparative audit in series of surgical patients.(33) It was described and prospectively validated by Copeland et al. in 1991.(34) The original POSSUM scoring system was designed for a broad range of general surgery patients. A special method was developed for patients undergoing vascular surgery, the V-POSSUM, using the same variables in an other equation.(35) The V-POSSUM data set consists of 12 preoperative variables (age, cardiac signs, respiratory signs, systolic blood pressure, pulse rate, Glasgow coma scale, serum urea, serum sodium, serum potassium, hemoglobin level, white blood cell count, electrocardiogram) and 6 intra-operative variables (grade of operation, number of procedures, total blood loss, peritoneal soiling, presence of malignancy, timing of operation). The combined physiologic scores and operative scores are used to generate risk equations by logistic regression analyses that convert the data into a predicted percentage mortality. GAS scoring system. The Glasgow Aneurysm Score is a preoperative scoring system, established in 1994, for predicting outcome after open repair of intact or ruptured AAA. The preoperative score is calculated using the following formula: Risk score = age in years + 17 points for shock + 7 points for myocardial disease + 10 points for cerebrovascular disease + 14 points for renal insufficiency.(28) ‘Shock’ is based on the clinical information of hypotension, tachycardia, pallor and sweating. Myocardial disease refers to previous myocardial infarction and/or ongoing angina pectoris. Cerebrovascular disease refers to all grades of stroke, including transient ischemic attacks. Renal insufficiency includes a history of acute and chronic renal failure, and/or a serum urea level > 20 µmol/l and or serum creatinine level > 150 µmol/l at presentation. A preoperative score < 70 is associated with a low risk of 8 mortality after RAAA repair. A high risk of mortality is seen in patients with a GAS > 85. A GAS > 95 correlated with a mortality rate of 80 % in a group of 92 patients.(36) Aim The main purpose of this study was to make an analysis of mortality and severe morbidity in patients with RAAA in the OLVG from February 1994 till February 2010, adjusted for the variability in preoperative risk using the V-POSSUM and the GAS scoring systems. Main interests were changes of patient population and postoperative outcome over the years, investigating the effect of the introduction of eEVAR and the AJAX trial. The second aim was to evaluate independent preoperative variables which influence the outcome after RAAA repair. 9 II. PATIENTS AND METHODS Study population All consecutive patients who underwent RAAA repair in the Onze Lieve Vrouwe Gasthuis in Amsterdam between February 1994 and February 2010 were included in this survey. Patients were included if they underwent either open surgery or endovascular repair. RAAA was defined as blood outside the aortic wall and was determined by preoperative ultrasound or computed tomography (CT) or intraoperative findings. Intra-operative deaths were also included for analysis. The patients who died on their way to the hospital and the patients who did not survive the transport to the operation room were excluded. Study method Through a retrospective review of the patients’ hospital charts, data were collected to determine the actual mortality and severe morbidity. These findings were compared with the predicted mortality yielded by two different outcome predicting scoring systems: The V-POSSUM method and the Glasgow Aneurysm Scale. Data collection and definitions Retrospectively collected data included: patient characteristics (i.e. gender, age, known cardiac and respiratory co-morbidity, history of cerebrovascular disease and renal insufficiency), patients hemodynamic condition upon arrival at the emergency room (i.e. highest and lowest systolic blood pressure and pulse rate), other clinical signs of shock at presentation (i.e. pallor, sweating), preoperative V-POSSUM variables (i.e. Glasgow coma scale, serum urea, serum sodium, serum potassium, hemoglobin level, white blood cell count, electrocardiogram), use of CT-scan for diagnosis, morphology of the AAAA (suprarenal, juxtarenal or infrarenal), time to treatment, which mode of repair was performed (open surgery or eEVAR) and 6 intra-operative V-POSSUM variables (grade of operation, number of procedures, total blood loss, peritoneal soiling, presence of malignancy, timing of operation). Postoperative data include: days in hospital, days on intensive care unit, minor morbidity (pneumonia, urinary tract infection, conservatively treated wound infection, temporary kidney insufficiency) severe morbidity (myocardial infarction, stroke, graft thrombosis, permanent kidney insufficiency, major amputation, bowel ischemia, spinal cord ischemia, prothesis infection, inevitable re-operation and the reason for re-operation) and 30-day mortality (intra-operative mortality and death ≤ 30 days after operation). If there were missing data regarding medical history, the risk factor was assumed not to be present. 10 Outcome measures The V-POSSUM score and the Glasgow Aneurysm Score were retrospectively calculated. Preoperative scores were related to postoperative outcome. Statistical Analyses Results were tabulated and analysed using SPSS Statistics for Windows version 17.0 (SPSS Inc, Chicago, Il). Patient demographics and continuous variables were summarised using measures of central tendency (i.e. mean) and dispersion (i.e. standard deviation). Categorical data were summarised using number and percentage. To assess the distribution of continuous variables in different subgroups we used the Student’s t-test. Chi-square and Fisher’s exact test were used for univariate analysis in categorical data. The discriminative ability of the preoperative risk assessments (GAS and POSSUM score) was evaluated by using receiver operating characteristics (ROC) curves. If the area under the ROC curve (AUC) is 0.5 there is no discriminative ability. The better the discriminative ability, the closer the AUC gets to 1.0. AUC values >0.8 represent good discriminative ability, whereas values of 0.7–0.8 represent reasonable discrimination. Preoperative variables with P<0.05 at univariate analysis were included for a multivariate analysis. We used the logistic regression with backward stepwise selection to evaluate the factors affecting the 30-day mortality. A P<0.05 was considered statistically significant. 11 III. RESULTS Patient population. Between February 1994 and February 2010, a total of 206 patients underwent RAAA repair. This study cohort with a mean age of 74 (± SD 8) consisted of 174 males (84.5%). 179 patients underwent open repair and 27 underwent emergency endovascular repair. The patient demographics and characteristics are listed in Table I. Mean V-POSSUM score is lower (P<0.001) in the eEVAR group as favourable operative factors (i.e. blood loss, peritoneal contamination) are taken into account. All patients with an altered Glasgow Coma Scale (i.e. <15) were in the open surgery group, because further preoperative CT imaging and thus eEVAR were impossible. Taking into account the endovascular group was small (13% of the whole cohort), there were no other statistically significant differences between both groups. Table I Patient demographics and characteristics Whole cohort (n = 206) Male Open surgery (n = 179) eEVAR (n = 27) 174 (85) 151 (84) 23 (85) Mean age 74 (8) 74 (8) 75 (8) CVA/TIA 34 (17) 28 (16) 6 (21) Renal insufficiency 42 (20) 36 (20) 6 (21) Cardiac co-morbidity 73 (35) 63 (35) 10 (36) Respiratory co-morbidity 44 (22) 38 (22) 6 (21) Mean systolic blood pressure 98 (45) 96 (45) 110 (45) Abnormal ECG 65 (32) 56 (31) 9 (32) Mean heart rate 87 (22) 87 (22) 87 (21) Altered GCS (i.e. <15) 13 (7) 13 (8) 0 (0) Shock 133 (65) 120 (67) 14 (50) Cardiac arrest 30 (15) 27 (15) 3 (11) Mean hemoglobin 7,1 (2) 7,1 (2) 7,2 (1) Mean white cell count 12,9 (6) 13 (5) 12,4 (6) Mean serum sodium 139 (4) 139 (4) 138 (3) 4 (1) 4 (1) 3,9 (1) Mean serum urea 8,5 (4) 8,5 (4) 8,8 (4) Mean serum creatinine 118 (43) 118 (42) 117 (49) Mean GAS 92 (15) 92 (15) 91 (17) Mean V-POSSUM mortality rate 58 (28) 62 (26) 32 (24) Length of stay (days) 19 (12) 20 (13) 14 (10) Observed 30-day mortality 45 (22) 41 (23) 4 (15) Mean serum potassium All variables are in no (%) or mean (+-SD) where appropriate. 12 Mortality. The 30-day mortality rate was 45/206 (22%) in the whole cohort, 41/179 (23%; 95% Confidence Interval (CI) 17-30) after open repair and 4/27 (15%: 95% CI 632) after eEVAR (P=0.34). Intra-operative death occurred in 19 patients (42% of 45 patients not surviving RAAA repair). The mean survival period of the 26 patients who died in the 30-day postoperative period was 7 days. Complications. 54 patients (26%) required intensive care treatment for more than 5 days and 72 (35%) had one or more major complications (myocardial infarction, stroke, graft thrombosis, permanent kidney insufficiency, major amputation, bowel ischemia, prosthesis infection, inevitable re-operation). Details of postoperative major and minor complications are listed in Table II. Especially infections and severe renal failure were seen more often after open surgery. There were more major complications after open surgery, although not statistically significant (P=0.055). Table II Postoperative complications Whole cohort (n = 206) N (%) Open surgery (n = 179) N (%) eEVAR (n = 27) N (%) Infections Pneumonia 32 (16) 27 (15) 4 (15) Urinary tract infection 17 (8) 17 (10) 0 (0) Wound infection 14 (7) 14 (8) 0 (0) Sepsis 13 (6) 12 (7) 1 (4) Intra-abdominal abces 11 (5) 11 (6) 0 (0) CVC infection 5 (2) 5 (3) 0 (0) Prothesis infection 4 (2) 4 (2) 0 (0) Renal failure not requiring dialyis 32 (16) 25 (14) 7 (26) Renal failure requiring temporary dialyis 21 (10) 21 (12) 0 (0) Renal failure requiring permanent dialyis 5 (2) 5 (3) 0 (0) Bleeding 23 (11) 22 (12) 1 (4) Intestinal ischemia 20 (10) 18 (10) 2 (7) Second look 15 (7) 14 (8) 1 (4) Lower limb ischemia 13 (6) 12 (7) 1 (4) Abces 12 (6) 12 (7) 0 (0) 8 (4) 7 (4) 1 (4) 54 (26) 48 (27) 6 (22) Re-operation Wound dehiscence >5 Days intensive care treatment CVA 1 (1) 1 (1) 0 (0) Myocardial infarction 12 (6) 10 (6) 2 (7) ≥1 Major complication 72 (35) 67 (38) 5 (18) 13 GAS. The mean GAS in the group of patients who did not survive RAAA repair was 102 (± SD 11), compared to 89 (± SD 15) among patients who survived (P<0.001). In Figure III mean postoperative mortality rate is shown for different quartiles of the GAS. All patients with a GAS <85 survived. 8 of 18 patients (44%) with the highest GAS (>115) died. Figure III Mean 30-day mortality rates (%) among quartiles of the Glasgow Aneurysm Score and the V-POSSUM calculated mortality risk V-POSSUM. The mean V-POSSUM among patients who died was 73 (+/- SD 21), compared with 54 (+/- SD 28) among survivors (P<0.001). The mean 30-day postoperative mortality rate is shown for different quartiles of the V-POSSUM score in Figure III. Only one person (2.6%) died in the lowest risk group (0-25%). 48 of 72 of the patients in the highest risk group (predicted mortality of 75-100%) survived (66.7%). The observed-to-expected (O:E) ratios were calculated for each quartile (Table III). The overall O:E ratio was 0.38. This reflects the high number of predicted deaths (120) compared to the number of actual deaths (45). In each group there was a difference between observed and predicted mortality which was most obvious in the low risk group (O:E ratio 0.17). The V-POSSUM over-predicted risk in all quartiles. Table III V-POSSUM predicted mortality compared with actual 30-day mortality Score Number of patients Actual deaths (%) Mean predicted mortality risk 0-25% 39 1 (3) 15.9 25-50% 36 4 (11) 37.6 50-75% 59 16 (27) 75-100% 72 24 Total 206 45 Predicted deaths O:E ratio (6) 6 0.17 (7) 14 0.29 62.3 (7) 37 0.43 (33) 88.0 (7) 63 0.38 (22) 58.2 (28) 120 0.38 14 (SD) Receiver operating characteristics curve. The ROC curve was plotted to analyze the relationship between the preoperative risk measures and the 30-day mortality (Figure IV). The AUC of the GAS was 0.73 (SD 0.04; 95% CI 0.65-0.80; P<0.001). This represented a reasonable discrimination of the preoperative risk assessment by the GAS. The AUC of the V-POSSUM predicted mortality was 0.69 (SD 0.05; 95% CI 0.600.77; P<0.001) representing a less favourable discriminative ability of the predicted mortality by the V-POSSUM scoring method. Figure IV The ROC curve of the Glasgow Aneurysm Score (AUC 0.73; SD 0.04; 95% CI 0.65-0.80; P<0.001) and of the V-POSSUM predicted mortality (AUC 0.69; SD 0.05; 95% CI 0.60-0.77; P<0.001) Predicting risk. Predictors of 30-day mortality are listed in Table IV. The only preoperative variables that were independent predictors for 30-day mortality were age (P=0.006) and lowest preoperative systolic blood pressure (P=0.032). Table IV Preoperative variables associated with 30-day mortality Variables Univariate analysis Multivariate analysis Age P = 0.002 P = 0.006 Cardiac comorbidity P = 0.001 Cerebrovascular comorbidity P < 0.0001 Renal comorbidity P < 0.0001 Lowest systolic blood pressure P = 0.021 Shock P < 0.0001 Cardiac arrest P < 0.0001 Hemoglobin concentration P = 0.003 Creatinine concentration P = 0.002 Ureum concentration P = 0.043 15 P = 0.032 16 years of RAAA repair. The number of procedures performed each year increased significantly over the past 16 years (Figure V). In 2010 three patients underwent RAAA repair in the period until February. This was when data collection was aborted. Figure V Number of procedures over the years, split by way of repair To evaluate preoperative variables and postoperative outcome in time, patients were subdivided into two groups. The first group were treated before the start of the AJAX trial (1994-2003), the second group during the AJAX trial (2004-2010). The patient population, divided into two time groups, did not significantly change over time, according to age, gender, GAS and V-POSSUM. Neither did the 30-day mortality (Table V). Table V Characteristics of the patient population, split in three time groups. 1994-2003 (n=85) n/year 9 (3) Age 74 Male 70 GAS V-POSSUM Mortality 2004-2010 (n=121) 20 (3) (8) 74 (8) (83) 104 (86) 90 (15) 93 (16) 59 (29) 58 (27) 17 (20) 28 (23) All variables are in no (%) or mean (+-SD) where appropriate. 16 IV. DISCUSSION Mortality. The 30-day mortality rate in this study compared favourably to those mentioned in a recently published prospective multicentre trial in the Netherlands; 57/143 (40%) after open repair and 15/58 (26%) after eEVAR.(37) Veith et al. examined the collected data from 49 centres over the world and found an overall 30day mortality rate of 21% after eEVAR and 36% after open RAAA repair.(38) Collected data included details of 1037 patients treated by eEVAR and 763 patients who underwent open repair. The mean in-hospital mortality rates reported in previous studies and meta-analyses were 40-50%.(8;10) In our study 5 patients who survived the first 30 postoperative days, died in days or weeks after the first month, in hospital. Therefore the inhospital mortality rate in the OLVG was 50/206 (24%), which was still low compared to mortality rates in previous reports. Ouriel et al. correlated inter-hospital differences in mortality rates after RAAA repair with surgical experience, delay in treatment and differences in patient population.(39) Although reports on mortality rates in high and low volume centres remain contradicting, hospital volume might influence outcome after RAAA repair.(10;11;40;41) The OLVG is a referral hospital for elective and acute AAA repair with well developed emergency care, diagnostic facilities, preoperative care and postoperative intensive care. As can be seen in table V, patient population did not significantly change over time. This was in contrast with previous studies, which suggested the lack of improvement of RAAA repair is caused by the increased age of patients undergoing RAAA repair.(9;10) Mortality rates remained the same, which suggested a constant pre-, per-, and postoperative quality of care. As patients who were not operated were not included in this study, it was unclear which role preoperative selection plays in these postoperative outcomes in the OLVG. Mean age and mean preoperative scoring measures were comparable or even higher than scores mentioned in previous studies, suggesting the proportion of operated high-risk patients was comparable or even higher in the OLVG.(13;30;31;4244) For example, Harris et al. found an overall mortality of 46% and a V-POSSUM predicted mortality rate of 50%, compared to an overall mortality of 22% and a VPOSSUM of 58% in our study cohort.(30) However, further research into the group of non-operated patients is necessary to provide clarity on this subject. Open surgery vs. eEVAR. Veith et al., who examined the collected experience of eEVAR from 49 centres to clarify the controversial role of this treatment for RAAA, concluded that eEVAR was better than open repair, provided the patient had a favourable anatomy and that adequate logistics and skills were available and optimal techniques and strategies were employed.(38) In the present study, as can be seen in table 1, eEVAR was not significantly correlated with a lower mortality rate than open 17 RAAA repair (P=0.34). The small amount of patients who underwent eEVAR (n=27) may have contributed to a lack of significance in outcome differences. These differences might be explained by preoperative selection bias. Beacause of the fact eEVAR patients should be hemodynamically stable undergoing a preoperative CTscan, all critically ill and high risk patients were in the open repair group. High quality evidence to demonstrate superiority of eEVAR over open RAAA repair is lacking.(9) A randomized controlled trial, like the ongoing AJAX trial, will provide more insight into this topic, comparing both ways of RAAA repair. Complications. Despite being an important factor in surgical outcome, postoperative complications after RAAA repair were not often described in previously published reports. Compared with results of Leo et al., who published their complications after open RAAA repair in a group of 114 patients, complication rate in the present survey appeared to be high in all categories.(32) Their high mortality rate (45%) with a mean survival of 0.02 days after the operation, may contribute to a low complication rate; all patients who died in the first postoperative days were less susceptible to complications like pneumonia and sepsis. Although not statistically significant, there appeared to be a trend in complication rate, comparing open and endovascular repair, suggesting favourable outcome after endovascular repair (P=0.055). However, the small amount of endovascular patients and the above mentioned preoperative selection bias should be taken into account. The AJAX trial may provide clarity on this subject. Hospital volume. The number of procedures performed each year increased significantly over the past 15 years, with a mean of 9 procedures a year until 2003 and a mean amount of 20 procedures a year since 2004 (Figure V). This was when the smaller centres in the Amsterdam area started to refer their patients to one of the main centres on duty for the AJAX trial, explaining the increase of RAAA repair in the OLVG in this period. GAS. Several previous studies validated the GAS for RAAA repair. Results were inconsistent. Leo et al. found the GAS as a highly predictive risk-scoring method of postoperative death in open RAAA repair, in a retrospective study (AUC 0.91).(32) All patients with a GAS >100 died in this study. As mentioned before Samy et al., who designed the GAS, reported in a prospective evaluation of their scoring system 80% of patients with a GAS >95 did not survive open RAAA repair.(36) In Finland Korhonen et al. described a mortality rate of approximately 80% of patients with a GAS >98, with an AUC of 0.75.(43) More recently, Gatt et al. described a mortality rate of 74% of patients with a GAS >95.(13;43) Tambyraja et al. found the GAS as a poor predictor for postoperative death with their prospective data. 12 of 28 patients (43%) with a GAS >105 survived (AUC 0.61).(44) In the present study we found even higher survival rates in the high-risk group (GAS >105): 22 of 38 patients (58%) survived. The lower overall mortality rate may have contributed to the poor positive 18 predicting values, but lack of specificity in the preoperative test may be another cause. Nevertheless, the sensitivity was quite good: no patients in the lowest risk group (GAS <85) died. Overall the GAS appeared to have a reasonable discriminative ability with an AUC of 0.73 in the whole cohort. The AUC in the open repair group alone was also 0.73 (SD 0.07, P=0.02). Although the GAS was developed in a time open surgery was the standard procedure for RAAA repair, we found even better discriminative values when using outcomes of endovascular repair alone (AUC 0.88, SD 0.04, P<0.001). These results are in contradiction with the recently published findings of Visser et al. from a prospective multicentre study in the Netherlands, concluding that the discriminative ability of the GAS is limited.(37) The authors suggested this may be caused by the introduction of eEVAR and they updated the GAS by adding the type of procedure performed. Further investigation of (updated) preoperative scoring systems is needed to evaluate their validity in different procedures. V-POSSUM The V-POSSUM score was originally designed for standardizing patient data and for comparative audit in series of surgical patients.(33) It has never been recommended for outcome prediction.(44) In this retrospective study it appeared to be difficult to collect all 18 V-POSSUM variables, especially in the hemodynamically unstable patients who went to the operating room immediately and died during operation. In these high-risk patients, preoperative variables and risk factors were often missing. The V-POSSUM method scores missing data as normal. Therefore, using an incomplete database will lead to reduced V-POSSUM scores, especially in the critically ill patients. Nevertheless in the present study the V-POSSUM score overestimated preoperative risk in all quartiles (Table III). Furthermore, discriminative ability seamed to be limited with regards to an AUC of 0.69, which did not change analysing the different ways of repair separately. Tang et al. demonstrated the V-POSSUM method was not a valid tool for comparing outcome after elective and emergency open AAA repair, in their prospective study.(33) According to the authors predicted outcomes were easily influenced by missing data. Harris et al. found V-POSSUM scores that accurately predicted early mortality after RAAA repair.(30) These data were collected retrospectively and overall mortality (46%) was much higher. Predicting risk. As found in previous studies, we could not discover a direct association between preoperative co-morbidity and outcome.(29;30) Age and lowest preoperative systolic blood pressure appeared to be the only preoperative variables that were independent predictors for 30-day mortality. Nevertheless, the two oldest patients who were operated, both 90 years old, survived. Therefore we can conclude that age alone is no exclusion criteria for RAAA repair, neither is one of the other independent risk factors. Other factors, not taken into consideration in the present study, like terminal illness (e.g. cancer), may be more important in decision-making. 19 16 years of RAAA repair. Despite promising results of observational studies, there is lack of level one evidence demonstrating the advantages of eEVAR over open RAAA repair.(9) That is why, since 2004, the OLVG is one of the three hospitals in Amsterdam participating in the AJAX trial, evaluating the outcome of conventional open emergency surgery versus endovascular treatment for RAAA. Until February 2010, 40 patients were included in this trial at the OLVG. This number of patients was too small for conclusions to be drawn. In addition, as the trial was still going on and the patients were blinded, these patients were not analysed separately in this report. Nevertheless, we can conclude that despite considerable improvements in emergency care, diagnostic facilities and perioperative care and the introduction of a less invasive operation technique, 30-day mortality rate did not change significantly over the past 16 years of RAAA repair in the OLVG. We could not find a reasonable explanation for the lack of significant progress over the past 16 years. The mortality rate was already very low, due to excellent postoperative care. Further improvements may not be realistic. 20 V. CONCLUSION In this study the 30-day mortality rate after RAAA repair was low (22%). It did not change significantly over the past 16 years. A noticeable trend was that the introduction of a less invasive operation technique (eEVAR) resulted in a lower amount of severe postoperative complications. The patient population did not significantly change over time, according to age, gender, GAS and V-POSSUM. The GAS appeared to be a reasonable predictor for outcome after both open and endovascular repair. The V-POSSUM scoring method had limited predictive value and overestimated preoperative risk. The preoperative measures for risk assessment we used, did not identify the high risk patients at an individual level. Therefore it appears that V-POSSUM and GAS do not aid in determining whether or not an attempted operation is appropriate. Nevertheless these methods can be used in surgical audit or for inter-hospital comparisons. The only preoperative variables that were independent predictors for 30-day mortality appeared to be age and lowest preoperative systolic blood pressure. Age alone is no exclusion criteria for RAAA repair, neither is one of the other independent risk factors. Other factors, not taken into consideration in the present study, may be more important in decision-making. 21 VI. SAMENVATTING Achtergrond. Een ruptuur van een aneurysma aortae abdominalis (RAAA) is een levensbedreigende aandoening. Het is geassocieerd met een risico op overlijden van 80 tot 90%. Ondanks verbeterde perioperatieve zorg, is de operatieve sterfte niet veranderd in de afgelopen decennia (40-50%). Gezien de onderlinge preoperatieve verschillen binnen de patiëntenpopulatie, is het moeilijk om postoperatieve resultaten met elkaar te vergelijken. Het doel van deze studie was om een retrospectieve, risico gewogen analyse van de uitkomsten na RAAA operaties te maken, over een periode van 16 jaar in het Onze Lieve Vrouwe Gasthuis in Amsterdam. Methoden. Over een periode van 16 jaar (van februari 1994 tot februari 2010) ondergingen 206 patiënten een open buik operatie of een endovasculaire behandeling in verband met een RAAA. Door middel van een retrospectief statusonderzoek van de betreffende patiënten werden gegevens verzameld om de werkelijke sterfte en de ernstige morbiditeit vast te stellen. Deze bevindingen werden vergeleken met de preoperatieve risicobeoordeling volgens de V-POSSUM methode (Vascular – Physiological and Operative Severity Score for enUmeration of Mortality and morbidity) en de GAS (Glasgow Aneurysma Score). Resultaten. De 30-dagen mortaliteit bedroeg 45/206 (22%) in het gehele cohort, 41/179 (23%, 95% betrouwbaarheidinterval (BI) 17-30) na open chirurgische behandeling en 4 / 27 (15%, 95% BI 6-32) na eEVAR (emergency EndoVascular Aneurysm Repair). De patiëntenpopulatie liet geen significante verandering zien in de loop der tijd, gemeten naar leeftijd, geslacht, GAS en V-POSSUM. De 30-dagen mortaliteit bleef in de loop der jaren ook constant. De gemiddelde GAS bij patiënten die operatieve behandeling van RAAA niet overleefden was 102 (± SD 11), vergeleken met 89 (± SD 15) bij patiënten die wel overleefden (P<0.001). De GAS bleek een redelijke voorspeller van postoperatieve uitkomst voor zowel open als endovasculaire RAAA behandeling, met een AUC (Area Under the Curve) van 0.73 (± SD 0.04; 95% betrouwbaarheidsinterval 0.65-0.80; P<0.001). De V-POSSUM bleek minder nauwkeurig: AUC 0.69 (± SD 0.05; 95% BI 0.60-0.77; P<0.001). De enige onafhankelijke preoperatieve voorspellers van de 30-dagen mortaliteit, waren leeftijd (P=0.006) en de laagste preoperatieve systolische bloeddruk (P=0.032). Conclusie. In deze studie bleek de 30-dagen mortaliteit na behandeling van RAAA laag (22%). Ondanks de invoering van een minder invasieve operatietechniek (eEVAR), is de mortaliteit niet significant veranderd in afgelopen 16 jaar. Er leek wel een trend zichtbaar ten gunste van de endovasculaire procedure wat betreft de postoperatieve morbiditeit. De GAS bleek een redelijke voorspeller van de mortaliteit na zowel open als endovasculaire RAAA behandeling. De V-POSSUM scoringsmethode had beperkte voorspellende waarde en overschatte het 22 preoperatieve risico. De preoperatieve risico-evaluaties die werden gebruikt bleken ongeschikt om hoog risico patiënten op individueel niveau aan te wijzen. Daaruit blijkt dat de V-POSSUM en de GAS geen rol kunnen spelen in het oordeel om wel of niet te opereren. 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