- Email: [email protected]
Lower Extremity Ischemia after Abdominal Aortic Aneurysm Repair
Lower Extremity Ischemia after Abdominal Aortic Aneurysm Repair Christian-Alexander Behrendt,1 Anand Dayama,2 Eike Sebastian Debus,1 Franziska Heidemann,1 Nathaniel M. Matolo,2 Tilo K€olbel,1 and Nikolaos Tsilimparis,1 Hamburg, Germany and French Camp, California
Background: Treatment reality of abdominal aortic aneurysm (AAA) is changing. Up to date, approximately 65% of intact AAA and 30% of ruptured AAA are treated endovascularly. As most comparative studies focus upon mortality and few major complications, some outcomes as lower extremity ischemia (LEI) after invasive AAA repair are often underreported. However, there is evidence for a worse outcome of patients suffering from this kind of complication. Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) vascular surgery targeted module from 2011 to 2014, we identified all patients undergoing endovascular aortic repair (EVAR) and open aortic repair (OAR) for AAA to illuminate the incidence and outcome of LEI after AAA repair. Results: In total, 185 patients (1.9%) developed LEI after AAA repair. 1.6% of all patients showed LEI after treatment of asymptomatic or symptomatic intact AAA, compared with 4.8% of ruptured AAA repair (P < 0.001). Operation time, male gender, current smoking, and increased creatinine levels (>1.5 mg/dL) were associated with an increased likelihood of exhibiting LEI. No statistically significant differences between EVAR versus OAR were noted in the multivariate model. If LEI occurred, length of hospital stay (6 vs. 2 days, P < 0.001) and mortality (20.5 vs. 4.6%, P < 0.001) was significantly higher as compared with the patients without LEI. Furthermore, 30-day mortality and most major complications were more common if LEI occurred. Conclusions: In this specialized analysis regarding LEI after AAA repair up to 2% develop this severe ischemic complication. Since the occurrence of LEI is associated with significantly worse outcome, future research and strategies to avoid this complication is needed.
INTRODUCTION Invasive treatment of intact abdominal aortic aneurysm (iAAA) and ruptured abdominal aortic
Conflict of interest: The authors have no conflicts of interest to disclose. 1
Department of Vascular Medicine, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2
San Joaquin General Hospital, French Camp, CA.
Correspondence to: Christian-Alexander Behrendt, MD, Dr. med., Department of Vascular Medicine, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; E-mail: [email protected] Ann Vasc Surg 2017; 45: 206–212 http://dx.doi.org/10.1016/j.avsg.2017.05.037 Ó 2017 Elsevier Inc. All rights reserved. Manuscript received: March 25, 2017; manuscript accepted: May 29, 2017; published online: 7 June 2017
206
aneurysm (rAAA) has remarkably changed over the past decade. Since findings from various randomized controlled trials reported statistically significant lower short-term mortality after endovascular aortic repair (EVAR) compared with conventional open aortic repair (OAR), the number of EVAR procedures increased continuously. Up to date, EVAR is used in approximately 65% of all intact and in 30% of all rupture AAA repairs.1 As most comparative studies focus on major outcome parameters like mortality rates, some outcomes are underreported in the existing literature. Acute lower extremity ischemia (LEI) is a serious complication after AAA repair and remains one of the most challenging emergencies in vascular surgery. LEI after AAA repair is a rare complication with reported frequencies of less than 2%, but it could be associated with worse overall outcome. The aim of this study
Volume 45, November 2017
was to describe the incidence and outcome of LEI after either open or endovascular AAA repair.
METHODS Study Design This study was a retrospective analysis of preoperative and postoperative variables as recorded by the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) national database. Using the NSQIP vascular surgery targeted module from 2011 to 2014, we identified all patients undergoing EVAR and OAR for abdominal aortic aneurysms. The NSQIP vascular surgery targeted module is an extension of the original NSQIP with approximately 75 participating hospitals in the AAA module as of 2014. It is a multi-institutional collaboration that continues to collect all the preoperative, intraoperative, and 30-day outcomes that were contained in the original NSQIP as well as further clinical detail selected by vascular surgeons in an effort to better risk adjust and determine best practices. Trained clinical nurse reviewers complete all data collection. Additional information on the NSQIP is available at www.facs.org/qualityprograms/acs-nsqip. For a retrospective analysis of anonymized registry data, no local ethic committee approval was required.
Variables Preoperative demographic and clinical variables included age, gender, ethnicity, presence of diabetes, current smoking, hypertension, obesity (defined as body mass index > 30 kg/m2), congestive heart failure (CHF), dialysis dependence, renal function (creatinine level), chronic obstructive pulmonary disease (COPD), American Society of Anaesthesiologists physical status classification, maximum aneurysm diameter, proximal aneurysm extent, aneurysm state (intact versus ruptured versus symptomatic), and dependent functional status. Postoperative outcomes included mortality at 30 days, acute LEI requiring intervention, myocardial infarction (MI), pulmonary complications (pneumonia and unplanned reintubation), sepsis, acute postoperative renal failure, change in renal function (progressive renal insufficiency), return to the operating room, wound infection, pulmonary embolism, ischemic colitis, and postoperative bleeding requiring transfusion. Length of hospital stay (LOS) and length of intensive care unit stay was measured in days. Manufacturer and type of
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main body device was collected for endovascular AAA repair. Acute LEI was defined by clinical symptoms as new (following AAA repair) ischemic rest pain (severe, unrelenting pain aggravated by elevation) or gangrene (marked skin discoloration and disruption indicative of death and decay of tissues in the extremities) requiring an intervention.
Patients and Cohorts In total, 9,537 patients with repair of intact (iAAA) or ruptured (rAAA) repairs collected between January 2011 and December 2014 were included. REF: www.facs.org/quality-programs/acs-nsqip.
Statistical Analysis Data are presented either with mean and standard deviation or with median and interquartile range for continuous variables based on distribution. Proportions are reported by percentages and 95% confidence interval. Tests of normality were conducted by Kolmogorov-Smirnov test. Linearity of the continuous variables with respect to the logit of the dependent variable was assessed via the BoxTidwell procedure with Bonferroni correction. Mann-Whitney U Test and Kruskal-Wallis H test were used for comparison of nonnormally distributed data. Student’s t tests were used for comparison of normally distributed data. Rates and univariate differences were compared with Pearson’s chisquared test and Fisher’s exact test, depending on the sample size. Binomial logistic regression model was used to estimate odds ratios for different predictors of LEI. The assumption of proportional odds was tested by a full likelihood ratio test. The models were tested for goodness of fit and ability to predict outcome (Hosmer-Lemeshow statistic and Nagelkerkes R-square). A P value of < 0.05 was regarded as statistically significant. Statistical analyses were performed with IBM SPSS Statistics software version 23.0 (IBM, Armonk, NY).
RESULTS Patients and Procedures A total of 9,537 patients were identified, 7,648 treated for asymptomatic iAAA (81.6%), 738 for symptomatic iAAA (7.9%), and 991 for ruptured AAA (10.6%; Fig. 1).
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Fig. 1. Flow chart. 9,537 patients were submitted for the time period from 2011 to 2014.
Postoperative Acute Lower Extremity Ischemia In total, 185 patients (1.9%) developed an LEI after AAA repair. More than 75% (n ¼ 138) of all counted incidences occurred within the first 48 hours after surgery (Fig. 2). 1.6% of all patients showed LEI after treatment of asymptomatic or symptomatic intact AAA, compared with 4.8% of ruptured AAA repair (P < 0.001). Patients with LEI had longer median operative time (193 vs. 148 min, P < 0.001) and higher preoperative creatinine levels (1.34 vs. 1.18 mg/dL, P ¼ 0.018) as compared with patients without this complication. Important baseline characteristics of the analyzed cohort are shown in Table I.
Outcome following Acute Lower Extremity Ischemia Most relevant outcome parameters by occurrence of LEI are shown in Table II. In total, 30-day mortality following AAA repair was higher if LEI occurred (20.5 vs. 4.6%, P < 0.001). This difference appeared both after intact (2.1 vs. 14.6%, P < 0.001) and ruptured (27.4 vs. 37.5%, P < 0.138) AAA repair (Table III). LOS was significantly longer if LEI occurred (median 4 vs. 2 days after EVAR and 10 vs. 8 days after OAR). Regarding most important complications, occurrence of LEI was associated with statistically significantly worse outcome. Major adverse events such as MI and ischemic colitis but
also minor complications were more common in LEI patients (Table II). The incidence of LEI after EVAR with the different commercially available endografts is reported in Table IV. Predictors on Acute Lower Extremity Ischemia A logistic regression was performed to ascertain the effects of aneurysm status, endovascular approach, male gender, operation time, aneurysm diameter, involvement of renal arteries, and other predictors on the likelihood that patients develop LEI after AAA repair. Of the 13 predictor variables only 5 were statistically significant: ruptured aneurysm, operation time, male gender, current smoking, and creatinine level >1.5 mg/dL (Table V). Ruptured AAA had 2.2 times higher odds to exhibit LEI than nonruptured AAA. Increasing operation time was associated with an increased likelihood of exhibiting LEI.
DISCUSSION This study is the first specialized analysis of LEI occurring after AAA repair in a large multicentric registry using the database of the American College of Surgeons NSQIP. Statistically significant differences were demonstrated between the group of patients suffering from postoperative LEI and the group without. Ruptured AAA
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Fig. 2. Incidence of lower extremity ischemia (LEI, orange) by days after surgery.
Table I. Baseline characteristics by occurrence of lower extremity ischemia. Values reported in % unless otherwise indicated Variable
Patients with lower extremity ischemia
No lower extremity ischemia
No. Male gender Age, years, mean (SD) Octogenarians White Diabetes Current smoker Obesity (BMI > 30) Dyspnea at rest or exertion History of severe COPD History of CHF Dependent functional status ASA class > 3 Creatinine mg/dL, mean (SD) Creatinine > 1.5 mg/dL Acute renal failure preoperatively On dialysis preoperatively Steroid use for chronic condition Ruptured Not infrarenal EVAR Total operation time, minutes, mean (SD) Total operation time, minutes, median (IQR) Aneurysm diameter, cm, mean (SD) Aneurysm diameter, cm, median (IQR)
185 70.8 72.6 (9.1) 24.2 91.3 12.4 43.2 29.3 17.3 22.2 3.8 6.0 96.8 1.34 (0.82) 22.2 1.1 3.2 6.5 25.9 23.1 62.2 233 (143.2) 193 (115e301) 6.52 (2.12) 5.7 (5.1e8.0)
9,352 79.5 73.0 (8.8) 25.2 91.8 14.9 33.6 31.3 16.5 18.6 1.7 3.0 94.6 1.18 (0.69) 14.5 0.4 1.4 4.6 10.1 18.5 77.3 172 (96.4) 148 (107e210) 6.02 (1.78) 5.6 (5.1e6.5)
P value
0.006 0.625 0.796 0.772 0.404 0.007 0.674 0.764 0.217 0.044 0.026 0.247 0.018 0.006 0.182 0.045 0.212 <0.001 0.138 <0.001 <0.001 <0.001 0.012
Significant P values are marked bold. ASA, American Society of Anesthesiologists risk classification; BMI, body mass index; IQR, interquartile range; SD, standard deviation.
repair showed 2.2 times higher odds than nonruptured AAA. Furthermore, operation time, male gender, current smoking, and increased creatinine levels (<1.5 mg/dL) were associated with an increased likelihood of exhibiting LEI. However, no association could be found for
endovascular approach, COPD, or exacerbation of CHF (Table I). The majority (75.8%) of all incidences occurred within the first 2 days after surgery (median 1 day). Occurrence of LEI was associated with significantly higher 30-day-mortality after intact (2.1 vs. 14.6%, P < 0.001) and
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Table II. Relevant outcome parameters by occurrence of lower extremity ischemia versus no lower extremity ischemia. Values reported in % unless otherwise indicated Variable
No. Mortality within 30 days Myocardial infarction Pneumonia Sepsis Unplanned reintubation Acute postoperative renal failure Progressive renal insufficiency Superficial surgical site infection Open wound infection Pulmonary embolism Ischemic colitis Postoperative bleeding/transfusions Ventilation > 48 hours Return to OR At least one unplanned reoperation If endovascular aortic repair (EVAR): length of hospital stay, days (IQR) If open aortic repair (OAR): length of hospital stay, days (IQR)
No lower extremity ischemia
Occurrence of lower extremity ischemia
P value
9,352 4.6 2.1 3.2 1.5 3.5 2.4 1.2 1.2 1.1 0.4 1.8 28.1 5.5 5.6 5.0 2 (1e4)
185 20.5 8.1 8.6 4.3 9.2 16.2 2.7 5.4 2.2
<0.001 <0.001 <0.001 0.008 <0.001 <0.001 0.073 <0.001 0.165
15.1 50.8 28.1 68.6 61.6 4 (2e8)
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001
8 (6e12)
10 (6e24)
<0.001
Significant P values are marked bold. IQR, interquartile range; OR, operating room.
Table III. In-hospital mortality by occurrence of lower extremity ischemia (LEI) and ruptured versus nonruptured abdominal aortic aneurysm (AAA). Values reported in total numbers (n/N ) and percentage
Table IV. Distribution of main body devices for endovascular AAA repair and incidence of Lower extremity ischemia (LEI) for each specific device. Values reported in % refer to the percentage of LEI within each endograft category
In-hospital mortality
Main body device
N
LEI, n (%)
Gore Excluder Medtronic Endurant Cook Zenith Endologix Powerlink Cook Zenith Fenestrated Trivascular Ovation Cook Zenith Renu Other or not documented
2,359 2,013 1,411 539 168 111 95 531
27 40 18 10 2 3 1 14
Occurrence of LEI No LEI P values
Intact AAA
20/137 (14.6%) 174/8,409 (2.1%) <0.001
Ruptured AAA
18/48 (37.5%) 258/943 (27.4%) 0.138
Bold values are statistically significant.
ruptured (27.4 vs. 37.5%, P < 0.001) AAA repair (Table III). Interpretation of the presented results is challenging, since LEI after AAA repair has not been previously specifically reported. In general, ischemic complications after EVAR and odds ratio (OR) may be caused by limb occlusion, access injury, or thromboembolism. Previous studies using the NSQIP database to illuminate 30-day outcome after AAA repair in general have been reporting LEI rates of 1.4% for intact versus 5.1% for ruptured AAA.2 Maldonado et al.3 retrospectively reviewed all EVAR procedures at their institution between
(1.1) (1.9) (1.3) (1.8) (1.2) (2.6) (1.0) (2.6)
1993 and 2005 (n ¼ 430), most of the cases were asymptomatic. Among the 430 patients, 15 early (<30 days postoperative) limb ischemia occurred (3.5%). Ischemic complications have significantly decreased over time as the issue of limb occlusions was acknowledged, and new generation stent grafts are typically manufactured with flexible and kinkresistant limbs. Cochennec et al. published their single-center experience with limb graft occlusion following EVAR, including data from 460 AAA repairs between 1995 and 2005. They reported a total proportion of 7.2% occluded limbs leading to an
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Table V. Predictors of lower extremity ischemia after AAA repair Covariate
OR
95% CI
P value
Ruptured EVAR (versus open) Total operation time (increase by 1 hour) Aneurysm diameter (increase by 1 cm) ASA class > 3 Age increase (by 1 year) Male gender Current smoker History of severe COPD History of CHF exacerbation Dependent functional status Creatinine > 1.5 mg/dL Involvement of renal arteries
2.187 0.893 1.259 1.041 1.658 1.004 0.624 1.436 1.029 1.593 1.591 1.515 0.846
1.430e3.344 0.596e1.336 1.169e1.355 0.979e1.108 0.606e4.537 0.984e1.025 0.431e0.902 1.007e2.049 0.694e1.526 0.633e4.008 0.802e3.155 1.016e2.260 0.555e1.288
<0.001 0.581 <0.001 0.201 0.325 0.673 0.012 0.046 0.886 0.323 0.184 0.042 0.434
Logistic regression model. Dependent variable: lower extremity ischemia within 30 days. Hosmer and Lemeshow ¼ 0.686. Significant P values are marked bold. ASA, American Society of Anesthesiologists risk classification; CI, confidence interval.
acute ischemia in 33%, rest pain in 27%, and claudication in 30%. The authors concluded that acute graft limb occlusion was not a rare event after EVAR.4 A recent study of the Vascular Study Group of New England primarily investigated bowel ischemia as rare complication after AAA repairs conducted from 2003 to 2014. LEI was reported in 1.3% of all intact and 7.0% of all ruptured AAA repairs.5 Carroccio et al. examined 351 patients treated with different EVAR devices for AAA and found a total of 26 thromboses of 702 limbs (3.7%) during a 4-year follow-up. 50% (n ¼ 13) of all limb thromboses occurred with the 30-day postoperative period, of whom 8 patients presented with mild to moderate claudication, 7 patients with a severe claudication as well as 2 patients with paresthesia and rest pain.6 Faure et al. prospectively included 1,143 patients into the Endurant Stent Graft Natural Selection Global Postmarket Registry and found a total of 42 graft limb occlusions in 39 patients (3.4% of the patients) during a 2-year follow-up period. Thirteen of the 42 occlusions (31%) occurring within the 30 days after operation.7 Ali et al. investigated the in-hospital morbidity after EVAR and OR in ruptured AAA using Vascular Quality Initiative data. Among the 514 patients treated with EVAR and 651 patients treated with OR, a significantly lower incidence of LEI could be shown in the EVAR group (EVAR 2.7% vs. OR 8.1%; P < 0.0001).8 Nedeau et al. retrospectively analyzed 74 patients with infrarenal rAAA (n ¼ 19 EVAR and n ¼ 55 OR) and found 5.3% acute limb ischemia in the EVAR, and 5.5% in the OR group respectively.9
Considering the latest reported 1-year outcome from the Immediate Management of Patients with Rupture: Open Versus Endovascular Repair randomized trial comparing endovascular versus open repair strategies for ruptured AAA, 43 (7.0%) reinterventions within 1 year were due to limb ischemia (24 after EVAR vs. 19 after OAR). The majority (93%) occurred within the first 30 days after surgery.10 Compared with the abovementioned studies, the proportion of LEI in the present study appear slightly lower. 1.6% of all intact and 4.8% of all ruptured AAA showed LEI within 30 days. But consistent to previously reported data, the majority of LEI occurred within the first day up to 30 days after surgery. Some limitations of this study must be highlighted while interpreting and comparing these results. First, there is no valid information collected about preexistent peripheral artery disease (PAD) in these patients. This might bias some of the interpretations, namely differences in incidence of LEI and outcomes like premature death. However, all registries struggle with various definitions of PAD. Furthermore, as this covariate is common among AAA patients, problems with validity would also appear if this variable would be available. Second, the event rates for the outcomes were relatively small. This might lower the validity of several statistical methods (especially asymptotic methods as logistic regression) and the generalizability of our findings. Since this study reflects real-world data, no prestudy power analysis could be conducted.
212 Behrendt et al.
Interestingly, although the cause of peripheral ischemic complications is different between EVAR and OAR, the total number of ischemic events is not significantly different between the 2 groups. Nevertheless, dependent on the analyzed cohort, up to 2% develop an acute LEI after AAA repair.
CONCLUSION LEI following AAA repair is a major complication negatively affecting overall outcome. This retrospective study utilizing a large multicentric registry demonstrates that 30-day-mortality and rate of several major complications was higher if LEI occurred. Nevertheless, evidence regarding this complication is lacking. This study also indicates that there is a need of further studies targeting this complication.
Ethical approval: Several Review Boards determined that using the NSQIP database is not human subject research because completely deidentified data was used. Thus, patient informed consent was not obtained for this study. This article does not contain any studies with human participants performed by any of the authors. REFERENCES 1. Beck AW, Sedrakyan A, Mao J, et al., International Consortium of Vascular R. Variations in Abdominal Aortic Aneu-
Annals of Vascular Surgery
2.
3.
4.
5.
6.
7.
8.
9.
10.
rysm Care: A Report from the International Consortium of Vascular Registries. Circulation 2016;134:1948e58. Soden PA, Zettervall SL, Ultee KH, et al. Outcomes for symptomatic abdominal aortic aneurysms in the American College of Surgeons National Surgical Quality Improvement Program. J Vasc Surg 2016;64:297e305. Maldonado TS, Rockman CB, Riles E, et al. Ischemic complications after endovascular abdominal aortic aneurysm repair. J Vasc Surg 2004;40:703e9. discussion 709-710. Cochennec F, Becquemin JP, Desgranges P, et al. Limb graft occlusion following EVAR: clinical pattern, outcomes and predictive factors of occurrence. Eur J Vasc Endovasc Surg 2007;34:59e65. Ultee KH, Zettervall SL, Soden PA, et al., Vascular Study Group of New E. Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair. J Vasc Surg 2016;64:1384e91. Carroccio A, Faries PL, Morrissey NJ, et al. Predicting iliac limb occlusions after bifurcated aortic stent grafting: anatomic and device-related causes. J Vasc Surg 2002;36: 679e84. Faure EM, Becquemin JP, Cochennec F, collaborators E. Predictive factors for limb occlusions after endovascular aneurysm repair. J Vasc Surg 2015;61:1138e1145.e2. Ali MM, Flahive J, Schanzer A, et al. In patients stratified by preoperative risk, endovascular repair of ruptured abdominal aortic aneurysms has a lower in-hospital mortality and morbidity than open repair. J Vasc Surg 2015;61: 1399e407. Nedeau AE, Pomposelli FB, Hamdan AD, et al. Endovascular vs open repair for ruptured abdominal aortic aneurysm. J Vasc Surg 2012;56:15e20. Investigators IT. Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial. Eur Heart J 2015;36: 2061e9.
Background: Treatment reality of abdominal aortic aneurysm (AAA) is changing. Up to date, approximately 65% of intact AAA and 30% of ruptured AAA are treated endovascularly. As most comparative studies focus upon mortality and few major complications, some outcomes as lower extremity ischemia (LEI) after invasive AAA repair are often underreported. However, there is evidence for a worse outcome of patients suffering from this kind of complication. Methods: Using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) vascular surgery targeted module from 2011 to 2014, we identified all patients undergoing endovascular aortic repair (EVAR) and open aortic repair (OAR) for AAA to illuminate the incidence and outcome of LEI after AAA repair. Results: In total, 185 patients (1.9%) developed LEI after AAA repair. 1.6% of all patients showed LEI after treatment of asymptomatic or symptomatic intact AAA, compared with 4.8% of ruptured AAA repair (P < 0.001). Operation time, male gender, current smoking, and increased creatinine levels (>1.5 mg/dL) were associated with an increased likelihood of exhibiting LEI. No statistically significant differences between EVAR versus OAR were noted in the multivariate model. If LEI occurred, length of hospital stay (6 vs. 2 days, P < 0.001) and mortality (20.5 vs. 4.6%, P < 0.001) was significantly higher as compared with the patients without LEI. Furthermore, 30-day mortality and most major complications were more common if LEI occurred. Conclusions: In this specialized analysis regarding LEI after AAA repair up to 2% develop this severe ischemic complication. Since the occurrence of LEI is associated with significantly worse outcome, future research and strategies to avoid this complication is needed.
INTRODUCTION Invasive treatment of intact abdominal aortic aneurysm (iAAA) and ruptured abdominal aortic
Conflict of interest: The authors have no conflicts of interest to disclose. 1
Department of Vascular Medicine, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2
San Joaquin General Hospital, French Camp, CA.
Correspondence to: Christian-Alexander Behrendt, MD, Dr. med., Department of Vascular Medicine, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; E-mail: [email protected] Ann Vasc Surg 2017; 45: 206–212 http://dx.doi.org/10.1016/j.avsg.2017.05.037 Ó 2017 Elsevier Inc. All rights reserved. Manuscript received: March 25, 2017; manuscript accepted: May 29, 2017; published online: 7 June 2017
206
aneurysm (rAAA) has remarkably changed over the past decade. Since findings from various randomized controlled trials reported statistically significant lower short-term mortality after endovascular aortic repair (EVAR) compared with conventional open aortic repair (OAR), the number of EVAR procedures increased continuously. Up to date, EVAR is used in approximately 65% of all intact and in 30% of all rupture AAA repairs.1 As most comparative studies focus on major outcome parameters like mortality rates, some outcomes are underreported in the existing literature. Acute lower extremity ischemia (LEI) is a serious complication after AAA repair and remains one of the most challenging emergencies in vascular surgery. LEI after AAA repair is a rare complication with reported frequencies of less than 2%, but it could be associated with worse overall outcome. The aim of this study
Volume 45, November 2017
was to describe the incidence and outcome of LEI after either open or endovascular AAA repair.
METHODS Study Design This study was a retrospective analysis of preoperative and postoperative variables as recorded by the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) national database. Using the NSQIP vascular surgery targeted module from 2011 to 2014, we identified all patients undergoing EVAR and OAR for abdominal aortic aneurysms. The NSQIP vascular surgery targeted module is an extension of the original NSQIP with approximately 75 participating hospitals in the AAA module as of 2014. It is a multi-institutional collaboration that continues to collect all the preoperative, intraoperative, and 30-day outcomes that were contained in the original NSQIP as well as further clinical detail selected by vascular surgeons in an effort to better risk adjust and determine best practices. Trained clinical nurse reviewers complete all data collection. Additional information on the NSQIP is available at www.facs.org/qualityprograms/acs-nsqip. For a retrospective analysis of anonymized registry data, no local ethic committee approval was required.
Variables Preoperative demographic and clinical variables included age, gender, ethnicity, presence of diabetes, current smoking, hypertension, obesity (defined as body mass index > 30 kg/m2), congestive heart failure (CHF), dialysis dependence, renal function (creatinine level), chronic obstructive pulmonary disease (COPD), American Society of Anaesthesiologists physical status classification, maximum aneurysm diameter, proximal aneurysm extent, aneurysm state (intact versus ruptured versus symptomatic), and dependent functional status. Postoperative outcomes included mortality at 30 days, acute LEI requiring intervention, myocardial infarction (MI), pulmonary complications (pneumonia and unplanned reintubation), sepsis, acute postoperative renal failure, change in renal function (progressive renal insufficiency), return to the operating room, wound infection, pulmonary embolism, ischemic colitis, and postoperative bleeding requiring transfusion. Length of hospital stay (LOS) and length of intensive care unit stay was measured in days. Manufacturer and type of
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main body device was collected for endovascular AAA repair. Acute LEI was defined by clinical symptoms as new (following AAA repair) ischemic rest pain (severe, unrelenting pain aggravated by elevation) or gangrene (marked skin discoloration and disruption indicative of death and decay of tissues in the extremities) requiring an intervention.
Patients and Cohorts In total, 9,537 patients with repair of intact (iAAA) or ruptured (rAAA) repairs collected between January 2011 and December 2014 were included. REF: www.facs.org/quality-programs/acs-nsqip.
Statistical Analysis Data are presented either with mean and standard deviation or with median and interquartile range for continuous variables based on distribution. Proportions are reported by percentages and 95% confidence interval. Tests of normality were conducted by Kolmogorov-Smirnov test. Linearity of the continuous variables with respect to the logit of the dependent variable was assessed via the BoxTidwell procedure with Bonferroni correction. Mann-Whitney U Test and Kruskal-Wallis H test were used for comparison of nonnormally distributed data. Student’s t tests were used for comparison of normally distributed data. Rates and univariate differences were compared with Pearson’s chisquared test and Fisher’s exact test, depending on the sample size. Binomial logistic regression model was used to estimate odds ratios for different predictors of LEI. The assumption of proportional odds was tested by a full likelihood ratio test. The models were tested for goodness of fit and ability to predict outcome (Hosmer-Lemeshow statistic and Nagelkerkes R-square). A P value of < 0.05 was regarded as statistically significant. Statistical analyses were performed with IBM SPSS Statistics software version 23.0 (IBM, Armonk, NY).
RESULTS Patients and Procedures A total of 9,537 patients were identified, 7,648 treated for asymptomatic iAAA (81.6%), 738 for symptomatic iAAA (7.9%), and 991 for ruptured AAA (10.6%; Fig. 1).
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Fig. 1. Flow chart. 9,537 patients were submitted for the time period from 2011 to 2014.
Postoperative Acute Lower Extremity Ischemia In total, 185 patients (1.9%) developed an LEI after AAA repair. More than 75% (n ¼ 138) of all counted incidences occurred within the first 48 hours after surgery (Fig. 2). 1.6% of all patients showed LEI after treatment of asymptomatic or symptomatic intact AAA, compared with 4.8% of ruptured AAA repair (P < 0.001). Patients with LEI had longer median operative time (193 vs. 148 min, P < 0.001) and higher preoperative creatinine levels (1.34 vs. 1.18 mg/dL, P ¼ 0.018) as compared with patients without this complication. Important baseline characteristics of the analyzed cohort are shown in Table I.
Outcome following Acute Lower Extremity Ischemia Most relevant outcome parameters by occurrence of LEI are shown in Table II. In total, 30-day mortality following AAA repair was higher if LEI occurred (20.5 vs. 4.6%, P < 0.001). This difference appeared both after intact (2.1 vs. 14.6%, P < 0.001) and ruptured (27.4 vs. 37.5%, P < 0.138) AAA repair (Table III). LOS was significantly longer if LEI occurred (median 4 vs. 2 days after EVAR and 10 vs. 8 days after OAR). Regarding most important complications, occurrence of LEI was associated with statistically significantly worse outcome. Major adverse events such as MI and ischemic colitis but
also minor complications were more common in LEI patients (Table II). The incidence of LEI after EVAR with the different commercially available endografts is reported in Table IV. Predictors on Acute Lower Extremity Ischemia A logistic regression was performed to ascertain the effects of aneurysm status, endovascular approach, male gender, operation time, aneurysm diameter, involvement of renal arteries, and other predictors on the likelihood that patients develop LEI after AAA repair. Of the 13 predictor variables only 5 were statistically significant: ruptured aneurysm, operation time, male gender, current smoking, and creatinine level >1.5 mg/dL (Table V). Ruptured AAA had 2.2 times higher odds to exhibit LEI than nonruptured AAA. Increasing operation time was associated with an increased likelihood of exhibiting LEI.
DISCUSSION This study is the first specialized analysis of LEI occurring after AAA repair in a large multicentric registry using the database of the American College of Surgeons NSQIP. Statistically significant differences were demonstrated between the group of patients suffering from postoperative LEI and the group without. Ruptured AAA
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Fig. 2. Incidence of lower extremity ischemia (LEI, orange) by days after surgery.
Table I. Baseline characteristics by occurrence of lower extremity ischemia. Values reported in % unless otherwise indicated Variable
Patients with lower extremity ischemia
No lower extremity ischemia
No. Male gender Age, years, mean (SD) Octogenarians White Diabetes Current smoker Obesity (BMI > 30) Dyspnea at rest or exertion History of severe COPD History of CHF Dependent functional status ASA class > 3 Creatinine mg/dL, mean (SD) Creatinine > 1.5 mg/dL Acute renal failure preoperatively On dialysis preoperatively Steroid use for chronic condition Ruptured Not infrarenal EVAR Total operation time, minutes, mean (SD) Total operation time, minutes, median (IQR) Aneurysm diameter, cm, mean (SD) Aneurysm diameter, cm, median (IQR)
185 70.8 72.6 (9.1) 24.2 91.3 12.4 43.2 29.3 17.3 22.2 3.8 6.0 96.8 1.34 (0.82) 22.2 1.1 3.2 6.5 25.9 23.1 62.2 233 (143.2) 193 (115e301) 6.52 (2.12) 5.7 (5.1e8.0)
9,352 79.5 73.0 (8.8) 25.2 91.8 14.9 33.6 31.3 16.5 18.6 1.7 3.0 94.6 1.18 (0.69) 14.5 0.4 1.4 4.6 10.1 18.5 77.3 172 (96.4) 148 (107e210) 6.02 (1.78) 5.6 (5.1e6.5)
P value
0.006 0.625 0.796 0.772 0.404 0.007 0.674 0.764 0.217 0.044 0.026 0.247 0.018 0.006 0.182 0.045 0.212 <0.001 0.138 <0.001 <0.001 <0.001 0.012
Significant P values are marked bold. ASA, American Society of Anesthesiologists risk classification; BMI, body mass index; IQR, interquartile range; SD, standard deviation.
repair showed 2.2 times higher odds than nonruptured AAA. Furthermore, operation time, male gender, current smoking, and increased creatinine levels (<1.5 mg/dL) were associated with an increased likelihood of exhibiting LEI. However, no association could be found for
endovascular approach, COPD, or exacerbation of CHF (Table I). The majority (75.8%) of all incidences occurred within the first 2 days after surgery (median 1 day). Occurrence of LEI was associated with significantly higher 30-day-mortality after intact (2.1 vs. 14.6%, P < 0.001) and
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Table II. Relevant outcome parameters by occurrence of lower extremity ischemia versus no lower extremity ischemia. Values reported in % unless otherwise indicated Variable
No. Mortality within 30 days Myocardial infarction Pneumonia Sepsis Unplanned reintubation Acute postoperative renal failure Progressive renal insufficiency Superficial surgical site infection Open wound infection Pulmonary embolism Ischemic colitis Postoperative bleeding/transfusions Ventilation > 48 hours Return to OR At least one unplanned reoperation If endovascular aortic repair (EVAR): length of hospital stay, days (IQR) If open aortic repair (OAR): length of hospital stay, days (IQR)
No lower extremity ischemia
Occurrence of lower extremity ischemia
P value
9,352 4.6 2.1 3.2 1.5 3.5 2.4 1.2 1.2 1.1 0.4 1.8 28.1 5.5 5.6 5.0 2 (1e4)
185 20.5 8.1 8.6 4.3 9.2 16.2 2.7 5.4 2.2
<0.001 <0.001 <0.001 0.008 <0.001 <0.001 0.073 <0.001 0.165
15.1 50.8 28.1 68.6 61.6 4 (2e8)
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001
8 (6e12)
10 (6e24)
<0.001
Significant P values are marked bold. IQR, interquartile range; OR, operating room.
Table III. In-hospital mortality by occurrence of lower extremity ischemia (LEI) and ruptured versus nonruptured abdominal aortic aneurysm (AAA). Values reported in total numbers (n/N ) and percentage
Table IV. Distribution of main body devices for endovascular AAA repair and incidence of Lower extremity ischemia (LEI) for each specific device. Values reported in % refer to the percentage of LEI within each endograft category
In-hospital mortality
Main body device
N
LEI, n (%)
Gore Excluder Medtronic Endurant Cook Zenith Endologix Powerlink Cook Zenith Fenestrated Trivascular Ovation Cook Zenith Renu Other or not documented
2,359 2,013 1,411 539 168 111 95 531
27 40 18 10 2 3 1 14
Occurrence of LEI No LEI P values
Intact AAA
20/137 (14.6%) 174/8,409 (2.1%) <0.001
Ruptured AAA
18/48 (37.5%) 258/943 (27.4%) 0.138
Bold values are statistically significant.
ruptured (27.4 vs. 37.5%, P < 0.001) AAA repair (Table III). Interpretation of the presented results is challenging, since LEI after AAA repair has not been previously specifically reported. In general, ischemic complications after EVAR and odds ratio (OR) may be caused by limb occlusion, access injury, or thromboembolism. Previous studies using the NSQIP database to illuminate 30-day outcome after AAA repair in general have been reporting LEI rates of 1.4% for intact versus 5.1% for ruptured AAA.2 Maldonado et al.3 retrospectively reviewed all EVAR procedures at their institution between
(1.1) (1.9) (1.3) (1.8) (1.2) (2.6) (1.0) (2.6)
1993 and 2005 (n ¼ 430), most of the cases were asymptomatic. Among the 430 patients, 15 early (<30 days postoperative) limb ischemia occurred (3.5%). Ischemic complications have significantly decreased over time as the issue of limb occlusions was acknowledged, and new generation stent grafts are typically manufactured with flexible and kinkresistant limbs. Cochennec et al. published their single-center experience with limb graft occlusion following EVAR, including data from 460 AAA repairs between 1995 and 2005. They reported a total proportion of 7.2% occluded limbs leading to an
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Table V. Predictors of lower extremity ischemia after AAA repair Covariate
OR
95% CI
P value
Ruptured EVAR (versus open) Total operation time (increase by 1 hour) Aneurysm diameter (increase by 1 cm) ASA class > 3 Age increase (by 1 year) Male gender Current smoker History of severe COPD History of CHF exacerbation Dependent functional status Creatinine > 1.5 mg/dL Involvement of renal arteries
2.187 0.893 1.259 1.041 1.658 1.004 0.624 1.436 1.029 1.593 1.591 1.515 0.846
1.430e3.344 0.596e1.336 1.169e1.355 0.979e1.108 0.606e4.537 0.984e1.025 0.431e0.902 1.007e2.049 0.694e1.526 0.633e4.008 0.802e3.155 1.016e2.260 0.555e1.288
<0.001 0.581 <0.001 0.201 0.325 0.673 0.012 0.046 0.886 0.323 0.184 0.042 0.434
Logistic regression model. Dependent variable: lower extremity ischemia within 30 days. Hosmer and Lemeshow ¼ 0.686. Significant P values are marked bold. ASA, American Society of Anesthesiologists risk classification; CI, confidence interval.
acute ischemia in 33%, rest pain in 27%, and claudication in 30%. The authors concluded that acute graft limb occlusion was not a rare event after EVAR.4 A recent study of the Vascular Study Group of New England primarily investigated bowel ischemia as rare complication after AAA repairs conducted from 2003 to 2014. LEI was reported in 1.3% of all intact and 7.0% of all ruptured AAA repairs.5 Carroccio et al. examined 351 patients treated with different EVAR devices for AAA and found a total of 26 thromboses of 702 limbs (3.7%) during a 4-year follow-up. 50% (n ¼ 13) of all limb thromboses occurred with the 30-day postoperative period, of whom 8 patients presented with mild to moderate claudication, 7 patients with a severe claudication as well as 2 patients with paresthesia and rest pain.6 Faure et al. prospectively included 1,143 patients into the Endurant Stent Graft Natural Selection Global Postmarket Registry and found a total of 42 graft limb occlusions in 39 patients (3.4% of the patients) during a 2-year follow-up period. Thirteen of the 42 occlusions (31%) occurring within the 30 days after operation.7 Ali et al. investigated the in-hospital morbidity after EVAR and OR in ruptured AAA using Vascular Quality Initiative data. Among the 514 patients treated with EVAR and 651 patients treated with OR, a significantly lower incidence of LEI could be shown in the EVAR group (EVAR 2.7% vs. OR 8.1%; P < 0.0001).8 Nedeau et al. retrospectively analyzed 74 patients with infrarenal rAAA (n ¼ 19 EVAR and n ¼ 55 OR) and found 5.3% acute limb ischemia in the EVAR, and 5.5% in the OR group respectively.9
Considering the latest reported 1-year outcome from the Immediate Management of Patients with Rupture: Open Versus Endovascular Repair randomized trial comparing endovascular versus open repair strategies for ruptured AAA, 43 (7.0%) reinterventions within 1 year were due to limb ischemia (24 after EVAR vs. 19 after OAR). The majority (93%) occurred within the first 30 days after surgery.10 Compared with the abovementioned studies, the proportion of LEI in the present study appear slightly lower. 1.6% of all intact and 4.8% of all ruptured AAA showed LEI within 30 days. But consistent to previously reported data, the majority of LEI occurred within the first day up to 30 days after surgery. Some limitations of this study must be highlighted while interpreting and comparing these results. First, there is no valid information collected about preexistent peripheral artery disease (PAD) in these patients. This might bias some of the interpretations, namely differences in incidence of LEI and outcomes like premature death. However, all registries struggle with various definitions of PAD. Furthermore, as this covariate is common among AAA patients, problems with validity would also appear if this variable would be available. Second, the event rates for the outcomes were relatively small. This might lower the validity of several statistical methods (especially asymptotic methods as logistic regression) and the generalizability of our findings. Since this study reflects real-world data, no prestudy power analysis could be conducted.
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Interestingly, although the cause of peripheral ischemic complications is different between EVAR and OAR, the total number of ischemic events is not significantly different between the 2 groups. Nevertheless, dependent on the analyzed cohort, up to 2% develop an acute LEI after AAA repair.
CONCLUSION LEI following AAA repair is a major complication negatively affecting overall outcome. This retrospective study utilizing a large multicentric registry demonstrates that 30-day-mortality and rate of several major complications was higher if LEI occurred. Nevertheless, evidence regarding this complication is lacking. This study also indicates that there is a need of further studies targeting this complication.
Ethical approval: Several Review Boards determined that using the NSQIP database is not human subject research because completely deidentified data was used. Thus, patient informed consent was not obtained for this study. This article does not contain any studies with human participants performed by any of the authors. REFERENCES 1. Beck AW, Sedrakyan A, Mao J, et al., International Consortium of Vascular R. Variations in Abdominal Aortic Aneu-
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rysm Care: A Report from the International Consortium of Vascular Registries. Circulation 2016;134:1948e58. Soden PA, Zettervall SL, Ultee KH, et al. Outcomes for symptomatic abdominal aortic aneurysms in the American College of Surgeons National Surgical Quality Improvement Program. J Vasc Surg 2016;64:297e305. Maldonado TS, Rockman CB, Riles E, et al. Ischemic complications after endovascular abdominal aortic aneurysm repair. J Vasc Surg 2004;40:703e9. discussion 709-710. Cochennec F, Becquemin JP, Desgranges P, et al. Limb graft occlusion following EVAR: clinical pattern, outcomes and predictive factors of occurrence. Eur J Vasc Endovasc Surg 2007;34:59e65. Ultee KH, Zettervall SL, Soden PA, et al., Vascular Study Group of New E. Incidence of and risk factors for bowel ischemia after abdominal aortic aneurysm repair. J Vasc Surg 2016;64:1384e91. Carroccio A, Faries PL, Morrissey NJ, et al. Predicting iliac limb occlusions after bifurcated aortic stent grafting: anatomic and device-related causes. J Vasc Surg 2002;36: 679e84. Faure EM, Becquemin JP, Cochennec F, collaborators E. Predictive factors for limb occlusions after endovascular aneurysm repair. J Vasc Surg 2015;61:1138e1145.e2. Ali MM, Flahive J, Schanzer A, et al. In patients stratified by preoperative risk, endovascular repair of ruptured abdominal aortic aneurysms has a lower in-hospital mortality and morbidity than open repair. J Vasc Surg 2015;61: 1399e407. Nedeau AE, Pomposelli FB, Hamdan AD, et al. Endovascular vs open repair for ruptured abdominal aortic aneurysm. J Vasc Surg 2012;56:15e20. Investigators IT. Endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomized trial. Eur Heart J 2015;36: 2061e9.