- Email: [email protected]
Risk Factors for Complications after Peripheral Vascular Surgery in 3,202 Patient Procedures
Accepted Manuscript Risk factors for complications after peripheral vascular surgery in 3202 patient procedures Mette Kehlet, MD, Ph.d, Leif Panduro Jensen, MD, Torben V. Schroeder, MD, DMSc PII:
S0890-5096(16)30423-X
DOI:
10.1016/j.avsg.2016.02.028
Reference:
AVSG 2845
To appear in:
Annals of Vascular Surgery
Received Date: 7 August 2015 Revised Date:
20 January 2016
Accepted Date: 17 February 2016
Please cite this article as: Kehlet M, Jensen LP, Schroeder TV, Risk factors for complications after peripheral vascular surgery in 3202 patient procedures, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2016.02.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Risk factors for complications after peripheral vascular surgery in 3202 patient procedures.
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1) Vascular Clinic, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark 2) Centre for Clinical Education, Capital Region, Blegdamsvej 9, 2100 Copenhagen, Denmark E-mail:[email protected] 3) Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark 4) Finsen Centre, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark Email: [email protected]
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Mette Kehlet, MD, Ph.d (1, 3), Leif Panduro Jensen, MD (4) & Torben V Schroeder, MD, DMSc (1,2,3)
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Corresponding author:
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Mette Kehlet
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Department for Vascular Surgery, RK 3111
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Rigshospitalet
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Blegdamsvej 9
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2100 Copenhagen
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Denmark
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E-mail: [email protected]
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Acknowledgements
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We are grateful to Nikolaj Eldrup for his continuous work with the national Danish vascular registry -Karbase, and for providing data on numerous occasions.
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Conflict of interest
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The authors declare no conflict of interest.
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Abstract
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Background: Complications after open vascular surgery is a major health challenge
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for the health care system and the patients. Infrainguinal vascular surgery is often
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perceived as less risky than aortic surgery and the aim of this study was to identify
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which risk factors correlated with postoperative complications after open vascular
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surgery for infrainguinal occlusive disease in an 8-year cohort using the Danish
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National Vascular Registry –Karbase, which gathers information on all vascular
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procedures in Denmark.
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Methods: A retrospective cohort study. The Karbase was searched for the pre-
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defined procedures from January 1, 2005 through December 31, 2012 at our two
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vascular departments. Both elective and urgent surgery was included.
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Complications were defined as: wound-, surgical- or general complication
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according to Karbase.
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Results: 3202 procedures were identified. Median age was 70 years and 21% were
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octogenarians. 60% were male. There was an overall complication rate of 30%,
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with 19% being wound complications, 6% surgical and 10% general
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complications. The greatest risk factors for developing a complication were high
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age, cardiac and renal disease, high ASA-score and general anesthetics. The 30-day
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mortality was 5% (1% for claudicants and 8% for acute ischemia) and the 30-day
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amputation rate was 7% (0.5% for claudicants and 21% for gangrene)
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Conclusion: There is a high risk of complications in peripheral vascular surgery.
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Risk factors are modifiable or non-modifiable. It is important to identify the risk
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factors and treat and optimize the patient cardiac and renal status prior to surgery
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if time allows, and also to perform surgery in local or regional anesthesia
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whenever possible, to reduce the risk of postoperative complications.
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Keywords: Postoperative complications; Peripheral vascular surgery; Risk
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reduction; Danish National Vascular Registry; Karbase.
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Introduction
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Complications after surgery is a major health challenge, both financially for the
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health care system and mentally, physically and emotionally for the patients. All
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surgical procedures carry the risk of postoperative complications, increasing the
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length of hospital stay, re-operations and risk of death.
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Though huge improvements have been achieved in surgical practices, anaesthesia
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and postoperative management, vascular surgery is still burdened with a high rate
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of complications[1-3]. Vascular patients often have comorbidities, and are thereby
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at a higher risk of developing postoperative complications. The increasing use of
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endovascular procedures has reduced this risk[4,5], but a substantial number of
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patients are not eligible for minimally invasive procedures. Among open vascular
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surgery, infrainguinal procedures are perceived as less demanding to the patient
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and therefore often considered associated with fewer serious complications than
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aortic surgery. But there is also a tendency to offer peripheral surgery to less fit
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patients.
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One could therefore ask the question whether surgery to the peripheral arteries
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gives fewer complications and which risk factors influence the occurrence of
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complications. Identifying risk factors for postoperative complications in specific
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patient populations is important to balance the potential risks and benefits of
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surgical interventions offered to individual patients. For the physician advising the
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vascular patient prior to surgery, it is also important knowledge. Several risk
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factors may be modified pre-operatively in order to reduce the risks of
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postoperative complications. Among others, cessation of drinking and smoking has
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been shown to reduce the incidence of postoperative complications though there is
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no consensus on the optimal duration of abstinence[6-9].
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This study aimed at identifying risk factors correlated with postoperative
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complications occurring after open infrainguinal vascular surgery in an 8-year
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cohort.
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10 Materials
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This is a retrospective cohort study using patient data extracted from the Danish
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National Vascular Registry, Karbase, which is a validated database of prospectively
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collected data of surgical procedures from all vascular departments in
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Denmark[10,11]. Inclusion criteria were patients, aged 35-99 years, operated on
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for vascular occlusive disease in the eight-year period between January 1, 2005
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through December 31, 2012 at the Vascular Department, Gentofte Hospital and
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Rigshospitalet, Denmark. The hospitals serve as primary referral hospitals in
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vascular surgery for the Capital Region of Denmark (1.6 million inhabitants) as
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well as tertiary referral hospitals from Region Sjaelland (another 0.8 million
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inhabitants). Elective as well as acutely admitted patients were included. Only
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patients who underwent open surgery for infrainguinal occlusive arterial disease
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were included. Thus patients who had thrombolysis or percutaneous transluminal
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angioplasty (PTA) with or without stenting were not included.
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6 Methods
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Demographic data such as age, gender and known co-morbidities were registered
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in the database at admission and urgency of surgical procedure, use of
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anaesthetics, surgical procedure etc. were registered postoperatively by the
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performing surgeon. Complications were registered in the database by a doctor
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from the department at discharge or 30 days after surgery at the first visit to the
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outpatient clinic. Mortality rates were obtained from the civil registration number
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registry[12], and amputation rates (below-knee, through-knee and femoral
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amputations) from the National Patient Registry (LPR)[13]. Using the unique civil
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registration numbers from our dataset when searching the LPR, the 30-day and
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12-months amputation rates could be determined. LPR data were merged with
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Karbase data to determine which limb was amputated and in doubt, the patients’
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medical records were manually searched for clarification.
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The dataset, patient characteristics and procedures performed are listed in table 1.
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The definitions from the Danish Vascular Registry - Karbase were used[14]. All
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variables were reduced to binary form. According to the Karbase, known cardiac or
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pulmonary disease is any form of medically or surgically treated heart or lung
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disease. Former cerebral event consists of previous TCI (transitory cerebral event)
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and stroke. We defined renal disease by plasma-creatinine levels in excess of 105
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µmol/l for men as well as for women. Smoking is in the Karbase defined as: Never
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smoker, former smoker (>3 months) and smoker. We compared former smoker
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with smoker in the analysis. Urgency of surgery is grouped in three: Acute
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(immediately), sub-acute (within a few days) or elective (>3 days after first clinical
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assessment) surgery. We combined acute and sub-acute surgery to urgent surgery.
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Similarly insulin and non-insulin dependent diabetes were pooled together. The
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American Society of Anaesthesiologists (ASA) score was re-grouped into two
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groups with the first two ASA groups (ASA I-II) as low ASA, and the three last
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groups (ASA III-V) as high ASA. BMI (Body Mass Index) was recorded as
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underweight when BMI was less than 18.5 in accordance with the Danish Health
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and Medicines Department[15]. Alcohol consumption was defined as >5 units a
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day. Alcohol consumption and smoking status were self-reported.
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In the Karbase, the most common perioperative complications are grouped in
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three: Wound complications, surgical complications and general complications
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(table 2).
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4 Statistics
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Statistical analysis was performed using SPSS version 19. Continuous variables
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were described as mean (SD) and categorical variables as absolute number
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(frequency). A univariate analysis was performed looking at frequencies of
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complications and risk factors individually. The predefined binary variables were
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assessed using the cross-table methods (chi2-test) with Fisher’s exact test (two
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sided) and the univariate odds ratio (OR) and 95% confidence interval (CI) for
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each variable is presented.
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To identify the relative impact of the independent risk factors for having a
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complication a logistic regression analysis was performed with the dependant
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binary variable ‘complication yes/no’ and by entering all the predictors, followed
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by the backward stepwise selection with an entry of 0,5 and removal 0.10. Missing
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data were excluded from the analysis, and are reported in table 3.
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Both the univariate and multivariate analysis were performed for each of the four
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pre-defined groups: Overall Complication, Wound Complication, Surgical
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Complication and General Complication (table 3). The predictors for mortality are
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shown in table 4 and here only the independent significant predictors, as found in
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the multivariate analysis, are listed.
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Results
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A total of 3202 patient procedures were identified in the Danish Vascular Database
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corresponding to the inclusion criteria of open infrainguinal vascular surgery.
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Indications for surgery were 675 (21%) with intermittent claudication, 645 (20%)
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with rest pain, 827 (26%) with ischemic ulcers, 374 (12%) with gangrene and 681
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(21%) with acute peripheral ischemia. Patient characteristics are listed in table 1
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and shows that the mean age was 70 years (SD ±11), 21% were octogenarians and
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40% were women.
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A total of 921 patients (30%) suffered one or more complications within 30 days of
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the surgical procedure. Of these 583 (19%) suffered wound complications, 193
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(6%) surgical complications and 320 (10%) experienced general complications. All
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the potential risk factors and their odds ratios from the univariate analysis are
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shown in table 3.
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Table 4 shows the multivariate analysis with the significant independent risk
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factors for having one or more overall complications to be: Age>80 years; OR 1.32
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(CI 1.03-1.69), having surgery in general anaesthetics; OR 1.50 (CI 1.20-1.86),
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pulmonary disease; OR 1.25 (CI 1.00-1.56) and being rated high ASA; OR 1.35 (CI
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1.11-1.62).
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The risk factors for being amongst one of the 583 patients with a wound
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complication were also age>80 years; OR 1.36 (CI 1.03-1.81), having surgery in
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general anaesthetics; OR 1.36 (CI 1.04-1.76) and being rated high ASA; OR 1.38; CI
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1.11-1.71). Surprisingly urgent surgery seemed to be less risky than elective
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surgery in terms of wound complications; OR 0.78 (CI 0.61-1.00).
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When looking at risk factors for surgical complications the only significant variable
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was renal disease; OR 1.66 (CI 1.16-2.37).
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The risk factors for developing a general medical complication were female
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gender; OR 1.55 (CI 1.15-2.06), having surgery in general anaesthetics; OR 1.69 (CI
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1.16-2.47), cardiac disease; OR 1.76 (CI 1.31-2.40), former cerebral event; OR 1.47
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(CI 1.00-2.15), renal disease; OR 2.22 (CI 1.65-3.00) and high ASA; OR 1.75 (CI
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1.29-2.39).
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The 30-day overall major amputation rate was 7% (N=221) and 1-year amputation
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rate 12% (N=390). The 30-day risk for claudicants to have major amputation was
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0.5% (4 amputees out of 675 claudicants) whereas it was 21% (79 out of 374)
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when the patient had gangrene (table 5).
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The 30-day overall mortality rate was 5%, with a mortality rate of 1% for
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claudicants and 8% for acute peripheral ischemia (table 5). The significant risk
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factors for mortality were female gender; OR 2.13 (CI 1.34-3.39), Age>80 years; OR
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1.86 (CI 1.09-3.17), cardiac disease; OR 3.24 (CI 1.93-5.45), renal disease; OR 2.13
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(CI 1.33-3.41) and high ASA; OR 2.10 (CI 1.24-3.58).
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1-year mortality rate was 15% (N=475) and the combined amputation and
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mortality rate at one-year was 19% (N=612) (table 5).
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Discussion
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This study identified some of the risk factors influencing the perioperative
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complication rate in patients undergoing peripheral open vascular surgery. The
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findings indicated that the patients with the highest risk of postoperative
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complications were; Octogenarians, patients having surgery in general anaesthesia
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and patients rated high ASA. But also female gender, cardiac disease and renal
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disease increased the risk of complications. Some of these risk factors may be
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modified before elective surgery. Cardiac and renal disease and ASA-score may be
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influenced at least to some extent and if time allows. As opposed to the non-
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modifiable risk factors such as gender and age.
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However, there is often insufficient time to optimize the vascular patients’ medical
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conditions for more than a few days, if even this.
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The odds ratio for developing a general complication when having known cardiac
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disease was 1.76. Therefore almost a doubling of the risk must be taken into
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account when a decision for surgery is made, and this correlates well with other
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studies showing increased risks for patients with cardiac co-morbidities[16,17].
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Chronic kidney disease patients have an increased risk of cardiovascular disease
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and of developing postoperative complications[18,19]. Even a relative small
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increase in P-creatinine >105 µmol/l has a significant effect on postoperative
8
complications in our study. The accuracy in P-creatinine as a predictor for renal
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insufficiency has been criticised and using the patients’ glomerular filtration rate
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(GFR) could be more correct in staging renal disease[20], but other studies confirm
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a correlation between the risk of complications after cardiac and vascular surgery
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even with mild kidney dysfunction (eGFR 60-90 mL/min)[21,22].
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General anaesthesia was also an independent risk factor confirming previous
14
findings[23-25], and is to some extent modifiable. The preferred form of
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anaesthesia in our study population was general anaesthesia, used in 73% of the
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cases. Urgent surgery could be a reason for choosing general anaesthesia as well as
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being the preference of some anaesthesiologists, surgeons and patients. But given
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that it increases the risk of complications with an odds ratio of 1.50, actions should
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be taken in our department to increase the use of regional or local anaesthesia
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whenever feasible, and the surgeon and the anaesthesiologist should carefully
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consider type of anaesthesia together with the patient.
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Among the non-modifiable risk factors, female gender increased the risk of general
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complications with an OR 1.55 and the mortality rate OR 2.13. This has also been
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shown previously for lower extremity bypass procedures[26,27] as well as for
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other vascular procedures like endovascular aneurysm repair[28]. Octogenarians
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also had an enhanced risk for complications. This is of no surprise and has been
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shown numerous times before[29-31], and even though the older patient has an
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increased risk it is important to emphasize that age alone should never preclude
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peripheral vascular surgery.
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Others have found complication rates between 14%-31% after peripheral vascular
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occlusive disease depending whether the patients had disabling claudication or
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critical limb ischemia[32,33]. We found 19% to have wound complications.
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Reports from general surgery show wound complications between 6%-16%
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depending on whether the surgery was elective or acute[34] and overall
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complications of 28%[35], comparable with the 30% in our study.
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We pooled all procedures together in our analysis and did not distinguish between
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the different types of surgery performed when assessing the complications. This
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could have an effect on the complication rate since the surgical trauma of a
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peripheral by-pass is often greater than that of an embolectomy. On the other hand
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mortality and amputation rates after urgent embolectomy are much higher than
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after a peripheral bypass [36], which our data also show.
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We expected smokers to have a higher rate of complications than former smokers
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since smoking is a well-documented risk factor for developing postoperative
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complications[34,37-40], but no difference in complication rates were found
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between the groups. This seemingly inconsistent finding points to one of the
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weaknesses of this dataset. Data has been collected prospectively, but as part of
9
the routine surgical management of the patients and by different members of the
10
staff and not as part of a well-defined protocol with predefined analyses. Smoking
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status was self-reported and not biochemically verified, probably underestimating
12
the smoking prevalence[41-43].
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It is potentially life threatening to have surgically demanding peripheral occlusive
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disease, though peripheral surgery generally is considered less risky than surgery
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to the aorta. The 30-day mortality rate in this study population was 5%, with the
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greatest risk of death for acute critical limb ischemia of 8% compared to 1% for
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claudicants. A little more than 1/3 of our study population (34%) were operated
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upon urgently and other studies for infrainguinal vascular surgery have shown
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mortality rates of 2.7%-4% for elective surgery [1,44] and up to 20% for acute
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limb ischemia[45]. The independent risk factors for 30-day mortality were, not
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surprisingly, being rated high ASA; OR 2.10, having known cardiac disease; OR 3.24
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or renal disease; OR 2.13. Again risk factors that can be modified to some extent if
4
time is available. The 1-year mortality rate for our study population is as high as
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15% and confirms our clinical assumption that patients in need of peripheral
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vascular surgery are often less fit than other population groups.
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Major amputation rates in our population were 7% at 30-days postoperatively and
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12% at 1-year. As many as 15% of the acutely operated patients were amputated
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after 30 days in our study population and for 1-year it was 23%. This corresponds
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well with results found by others. Patients with critical limb ischemia have a 1 year
11
risk of major amputation or death of 20-40% without intervention[46]. Data from
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the US Medicare population show in-hospital amputations rates from 6.4-8.1% and
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1-year amputation rates from 11-14.8% in patients with acute critical limb
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ischemia after intervention (2008-1998 respectively)[45,47].
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As touched upon above, the main limitation in this study was in the collection of
16
data in the Karbase. Even though the Karbase has been validated, all data were
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manually recorded by the operating surgeon from patient records with the
18
possibility of entering false data. The patients' alcohol consumption and smoking
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status are self-reported and thereby giving risk of bias. Grouping the analysed data
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in dichotomous variables could also increase the risk of non-differential
2
misclassification, underestimating of the measured association. We have also used
3
ASA as a dichotomous variable in our analyses, which in itself increases bias since
4
the ASA classification consists of several of the other included variables. Knowing
5
this we still chose to include the ASA score since it is a good endpoint for the
6
patients' physical state pre-operatively.
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The Karbase has many clinical variables, but only few variables concerning the
8
patients’ socio-economic status, which would give more information on non-
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medical risk factors. Despite these limitations this study emphasises important
10
information. The study population is a large sample of a very specific type of
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surgery adding to the results of the statistical analysis.
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Conclusion
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Overall 30% had one or more complications after peripheral vascular surgery for
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occlusive disease. The major risk factors for developing a complication were age,
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cardiac and renal disease, ASA-score and being operated on in general
17
anaesthetics. Our findings correlated well with complication rates found in other
18
studies. The amputation and mortality rates are high in the vascular population.
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30-day mortality was 5% (1% for claudicants and 8% for acute peripheral
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ischemia) and 30-day amputation rate was 7% (0.5% for claudicants and 21% for
2
patients with gangrene). After 1-year a total of 19% were either amputated or
3
dead.
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Risk factors are modifiable or non-modifiable. When managing vascular patients it
5
is important that we are aware of the modifiable risk factors so patients, if
6
possible, can be treated and optimized prior to surgery and thereby reduce their
7
risk of postoperative complications. At our department actions must be taken to
8
ensure the indications for vascular surgery using general anaesthesia versus local
9
or regional anaesthesia, since general anaesthesia was a major risk factor for
10
complications and 73% of our patients were operated upon in general anaesthesia.
11
This will be to the benefit of patients as well as the society with fewer re-
12
operations and faster discharge of patients.
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Reference List
2 1. Nowygrod R, Egorova N, Greco G, Anderson P, Gelijns A, Moskowitz A et al.: Trends, complications, and mortality in peripheral vascular surgery. J Vasc Surg 2006, 43: 205-216.
6 7 8 9
2. Ozaki CK, Hamdan AD, Barshes NR, Wyers M, Hevelone ND, Belkin M et al.: Prospective, randomized, multi-institutional clinical trial of a silver alginate dressing to reduce lower extremity vascular surgery wound complications. J Vasc Surg 2015, 61: 419-427.
SC
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3 4 5
3. Bakker EJ, Valentijn TM, van de Luijtgaarden KM, Hoeks SE, Voute MT, Goncalves FB et al.: Type 2 diabetes mellitus, independent of insulin use, is associated with an increased risk of cardiac complications after vascular surgery. Anaesth Intensive Care 2013, 41: 584-590.
14 15 16
4. Bechter-Hugl B, Falkensammer J, Gorny O, Greiner A, Chemelli A, Fraedrich G: The influence of gender on patency rates after iliac artery stenting. J Vasc Surg 2014, 59: 1588-1596.
17 18 19
5. Matsi PJ, Manninen HI: Complications of lower-limb percutaneous transluminal angioplasty: a prospective analysis of 410 procedures on 295 consecutive patients. Cardiovasc Intervent Radiol 1998, 21: 361-366.
20 21 22
6. Oppedal K, Moller AM, Pedersen B, Tonnesen H: Preoperative alcohol cessation prior to elective surgery. Cochrane Database Syst Rev 2012, 7: CD008343.
23 24 25
7. Nasell H, Adami J, Samnegard E, Tonnesen H, Ponzer S: Effect of smoking cessation intervention on results of acute fracture surgery: a randomized controlled trial. J Bone Joint Surg Am 2010, 92: 1335-1342.
26 27 28
8. Thomsen T, Tonnesen H, Moller AM: Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation. Br J Surg 2009, 96: 451-461.
29 30
9. Thomsen T, Villebro N, Moller AM: Interventions for preoperative smoking cessation. Cochrane Database Syst Rev 2014, 3: CD002294.
AC C
EP
TE D
M AN U
10 11 12 13
19
ACCEPTED MANUSCRIPT
10. Laustsen J, Jensen LP, Hansen AK: Accuracy of clinical data in a population based vascular registry. Eur J Vasc Endovasc Surg 2004, 27: 216-219.
3 4 5 6
11. Andersen LV, Mortensen LS, Lindholt JS, Faergeman O, Henneberg EW, Frost L: Completeness and positive predictive value of registration of upper limb embolectomy in the Danish National Vascular Registry. Clin Epidemiol 2009, 1: 27-32.
7
12. https://cpr.dk/in-english/
8
13. http://www.ssi.dk/English.aspx
9
14.
M AN U
http://www.karbase.dk/English/english.htm
SC
RI PT
1 2
15. http://sundhedsstyrelsen.dk/da/sundhed/overvaegt/bmi.aspx (http://sundhedsstyrelsen.dk/en)
12 13 14
16. Fleischmann KE, Beckman JA, Buller CE, Calkins H, Fleisher LA, Freeman WK et al.: 2009 ACCF/AHA focused update on perioperative beta blockade. J Am Coll Cardiol 2009, 54: 2102-2128.
15 16
17. Manley AM, Reck SE: Patients with vascular disease. Med Clin North Am 2013, 97: 1077-1093.
17 18 19
18. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 351: 1296-1305.
20 21 22
19. Patel VI, Mukhopadhyay S, Guest JM, Conrad MF, Watkins MT, Kwolek CJ et al.: Impact of severe chronic kidney disease on outcomes of infrainguinal peripheral arterial intervention. J Vasc Surg 2014, 59: 368-375.
23 24 25 26
20. AbuRahma AF, Srivastava M, Chong B, Dean LS, Stone PA, Koszewski A: Impact of chronic renal insufficiency using serum creatinine vs glomerular filtration rate on perioperative clinical outcomes of carotid endarterectomy. J Am Coll Surg 2013, 216: 525-532.
27 28 29 30
21. Gaber AO, Moore LW, Aloia TA, Suki WN, Jones SL, Graviss EA et al.: Crosssectional and case-control analyses of the association of kidney function staging with adverse postoperative outcomes in general and vascular surgery. Ann Surg 2013, 258: 169-177.
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22. Howell NJ, Keogh BE, Bonser RS, Graham TR, Mascaro J, Rooney SJ et al.: Mild renal dysfunction predicts in-hospital mortality and post-discharge survival following cardiac surgery. Eur J Cardiothorac Surg 2008, 34: 390-395.
4 5 6 7
23. Hausman MS, Jr., Jewell ES, Engoren M: Regional Versus General Anesthesia in Surgical Patients with Chronic Obstructive Pulmonary Disease: Does Avoiding General Anesthesia Reduce the Risk of Postoperative Complications? Anesth Analg 2014.
8 9 10
24. Pugely AJ, Martin CT, Gao Y, Mendoza-Lattes S, Callaghan JJ: Differences in short-term complications between spinal and general anesthesia for primary total knee arthroplasty. J Bone Joint Surg Am 2013, 95: 193-199.
11 12 13 14 15
25. Edwards MS, Andrews JS, Edwards AF, Ghanami RJ, Corriere MA, Goodney PP et al.: Results of endovascular aortic aneurysm repair with general, regional, and local/monitored anesthesia care in the American College of Surgeons National Surgical Quality Improvement Program database. J Vasc Surg 2011, 54: 1273-1282.
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26. Flu HC, Ploeg AJ, Marang-van de Mheen PJ, Veen EJ, Lange CP, Breslau PJ et al.: Patient and procedure-related risk factors for adverse events after infrainguinal bypass. J Vasc Surg 2010, 51: 622-627.
19 20 21
27. Jain AK, Velazquez-Ramirez G, Goodney PP, Edwards MS, Corriere MA: Gender-based analysis of perioperative outcomes associated with lower extremity bypass. Am Surg 2011, 77: 844-849.
22 23 24 25
28. Abedi NN, Davenport DL, Xenos E, Sorial E, Minion DJ, Endean ED: Gender and 30-day outcome in patients undergoing endovascular aneurysm repair (EVAR): an analysis using the ACS NSQIP dataset. J Vasc Surg 2009, 50: 486-91, 491.
26 27 28
29. Scott SW, Bowrey S, Clarke D, Choke E, Bown MJ, Thompson JP: Factors influencing short- and long-term mortality after lower limb amputation. Anaesthesia 2014, 69: 249-258.
29 30 31
30. Sheetz KH, Waits SA, Krell RW, Campbell DA, Jr., Englesbe MJ, Ghaferi AA: Improving mortality following emergent surgery in older patients requires focus on complication rescue. Ann Surg 2013, 258: 614-617.
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31. Turrentine FE, Wang H, Simpson VB, Jones RS: Surgical risk factors, morbidity, and mortality in elderly patients. J Am Coll Surg 2006, 203: 865877.
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32. Lange CP, Ploeg AJ, Lardenoye JW, Breslau PJ: Patient- and procedure-specific risk factors for postoperative complications in peripheral vascular surgery. Qual Saf Health Care 2009, 18: 131-136.
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33. Lees T, Troeng T, Thomson IA, Menyhei G, Simo G, Beiles B et al.: International variations in infrainguinal bypass surgery - a VASCUNET report. Eur J Vasc Endovasc Surg 2012, 44: 185-192.
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34. Sorensen LT, Hemmingsen U, Kallehave F, Wille-Jorgensen P, Kjaergaard J, Moller LN et al.: Risk factors for tissue and wound complications in gastrointestinal surgery. Ann Surg 2005, 241: 654-658.
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35. Longo WE, Virgo KS, Johnson FE, Oprian CA, Vernava AM, Wade TP et al.: Risk factors for morbidity and mortality after colectomy for colon cancer. Dis Colon Rectum 2000, 43: 83-91.
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36. Kempe K, Starr B, Stafford JM, Islam A, Mooney A, Lagergren E et al.: Results of surgical management of acute thromboembolic lower extremity ischemia. J Vasc Surg 2014, 60: 702-707.
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37. Delgado-Rodriguez M, Medina-Cuadros M, Martinez-Gallego G, Gomez-Ortega A, Mariscal-Ortiz M, Palma-Perez S et al.: A prospective study of tobacco smoking as a predictor of complications in general surgery. Infect Control Hosp Epidemiol 2003, 24: 37-43.
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38. Myles PS, Iacono GA, Hunt JO, Fletcher H, Morris J, McIlroy D et al.: Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers. Anesthesiology 2002, 97: 842-847.
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39. Sorensen LT, Jorgensen T, Kirkeby LT, Skovdal J, Vennits B, Wille-Jorgensen P: Smoking and alcohol abuse are major risk factors for anastomotic leakage in colorectal surgery. Br J Surg 1999, 86: 927-931.
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40. Gronkjaer M, Eliasen M, Skov-Ettrup LS, Tolstrup JS, Christiansen AH, Mikkelsen SS et al.: Preoperative smoking status and postoperative
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complications: a systematic review and meta-analysis. Ann Surg 2014, 259: 5271. 41. Connor GS, Schofield-Hurwitz S, Hardt J, Levasseur G, Tremblay M: The accuracy of self-reported smoking: a systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res 2009, 11: 12-24.
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42. From AM, Herlitz J, Berndt AK, Karlsson T, Hjalmarson A: Are patients truthful about their smoking habits? A validation of self-report about smoking cessation with biochemical markers of smoking activity amongst patients with ischaemic heart disease. J Intern Med 2001, 249: 145-151.
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43. Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y: Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987, 77: 1435-1438.
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44. LaMuraglia GM, Conrad MF, Chung T, Hutter M, Watkins MT, Cambria RP: Significant perioperative morbidity accompanies contemporary infrainguinal bypass surgery: an NSQIP report. J Vasc Surg 2009, 50: 299-304, 304.
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45. Baril DT, Patel VI, Judelson DR, Goodney PP, McPhee JT, Hevelone ND et al.: Outcomes of lower extremity bypass performed for acute limb ischemia. J Vasc Surg 2013.
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46. Chung J, Modrall JG, Valentine RJ: The need for improved risk stratification in chronic critical limb ischemia. J Vasc Surg 2014.
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47. Baril DT, Ghosh K, Rosen AB: Trends in the incidence, treatment, and outcomes of acute lower extremity ischemia in the United States Medicare population. J Vasc Surg 2014, 60: 669-677.
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Table 1: Patient Characteristics, surgical indication and procedures performed: Age (mean) 70 years (SD ± 11 years). N=3202 (%) 1931 (60)
Female gender
1271 (40)
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Male gender
659 (21)
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Age >80 General anaesthetics
2328 (73)
Urgent surgery
1083 (34)
Diabetes
848 (26)
Former cerebral event Renal disease (P-crea>105) High ASA (III-IV) Previously vascular surgery BMI<18.5 Smoker
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Pulmonary disease
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Cardiac disease
2049 (64)
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Hypertension
1299 (41) 665 (21) 399 (12) 832 (26) 1575 (49) 1318 (41) 238 (8) 1380 (43)
Former smoker >3 months
1249 (39)
Alcohol >5 U daily
156 (5)
Claudicants
675 (21) 24
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645 (20)
Ischemic ulcer
827 (26)
Gangrene
374 (12)
Acute peripheral ischemia
681 (21)
Exploration of the femoral artery, popliteal artery and branches
77 (2.5)
Thrombectomy/embolectomy of the femoral artery, popliteal artery and branches
436(13.5)
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Thrombenarterectomy of the femoral artery and branches
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Rest pain
922 (29)
1767 (55)
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Bypass from the femoral artery and branches to the popliteal artery and branches
Table 2: Definition of complications according to the Danish Vascular Database.
Necrosis
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Wound complication*:
Infection
Lymphorrhea> 2 days or lymphocele. Bowel obstruction
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Bleeding (requiring surgery)
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Surgical complication:
Intestinal ischemia
Emboli or thrombosis of the reconstruction Peripheral nerve lesion
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General complication:
Cardiac complications (acute myocardial infarction, congestive heart failure, severe arrhythmia), Pulmonary complication requiring treatment,
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ATN (acute tubular necrosis)/dialysis, TCI (transitory cerebral ischemia)/stroke, DVT (deep venous thrombosis),
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* Only recorded if requiring surgical treatment or prolonged admission
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Compartment syndrome,MODS (multi organ dysfunction syndrome)
Table 3: Univariate model: Frequencies of complications (%) and given as odds ratio, OR, with confidence interval (CI).
%
OR (CI)
Female gender (MI 0)
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Age >80 (MI 0)
Surgical complication rate 6%
General complications 10%
%
OR (CI)
%
OR (CI)
%
OR (CI)
1.16 (0.99-1.35)
19
1.08 (0.90-1.29)
6
0.85 (0.63-1.16)
12
1.26 (0.99-1.59)
35
1.34 (1.11-1.61)*
20
1.15 (0.92-1.43)
7
1.15 (0.81-1.63)
15
1.70 (1.32-2.21)*
General anaesthetics (MI 0)
32
1.47 (1.23-1.76)*
20
1.43 (1.15-1.77)*
6
1.05 (0.76-1.46)
11
1.50 (1.13-1.99)*
Urgent surgery (MI 0)
29
0.91 (0.77-1.07)
16
0.78 (0.64-0.95)*
6
0.90 (0.66-1.23)
12
1.30 (1.03-1.65)*
Diabetes (MI 17)
31
1.12 (0.94-1.33)
19
1.05 (0.85-1.28)
6
1.02 (0.73-1.41)
12
1.27 (0.99-1.64)
Hypertension (MI 16)
31
1.24 (1.05-1.46)*
20
1.28 (1.05-1.55)*
6
0.83 (0.61-1.11)
12
1.54 (1.19-1.99)*
Cardiac disease (MI 40)
32
1.22 (1.05-1.43)*
19
1.07 (0.89-1.28)
6
1.08 (0.80-1.45)
14
2.09 (1.65-2.64)*
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Wound complication rate 19%
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Overall complication rate 30%
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1.26 (1.05-1.52)*
21
1.17 (0.94-1.45)
5
0.81 (0.56-1.19)
14
1.54 (1.18-2.00)*
Former cerebral event (MI 55)
35
1.32 (1.05-1.65)*
22
1.24 (0.95-1.60)
7
1.05 (0.68-1.62)
13
1.45 (1.06-2.00)*
Renal disease (MI 119)
32
1.17 (0.99-1.40)
17
0.83 (0.67-1.03)
9
1.68 (1.24-2.28)*
16
2.14 (1.68-2.74)*
High ASA (III-V) (MI 5)
34
1.52 (1.34-1.82)*
21
1.40 (1.16-1.67)*
7
1.33 (0.99-1.78)
14
2.24 (1.75-2.85)*
Previously vascular surgery (MI 0)
31
1.15 (0.99-1.35)
20
1.13 (0.95-1.36)
7
1.30 (0.97-1.73)
10
0.96 (0.76-1.21)
BMI<18.5(MI 190)
29
0.97 (0.72-1.31)
19
0.99 (0.70-1.40)
4
0.57 (0.29-1.13)
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1.15 (0.75-1.76)
Smoker (MI 34)
30
1.01 (0.85-1.20)
10
0.98 (0.80-1.19)
7
1.06 (0.76-1.46)
10
1.03 (0.80-1.33)
Alcohol >5 U daily (MI 62)
30
1.01 (0.70-1.44)
20
1.11 (0.74-1.67)
7
1.09 (0.57-2.12)
9
0.90 (0.52-1.59)
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Pulmonary disease (MI 23)
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* Statistically significant with P > 0.05 in the chi -test. MI: missing information.
Table 4 Multivariate model:
Odds ratio, OR, and confidence intervals (CI) for the significant risk factors (p<0.05). Odds Ratio (OR) final adjusted (95% CI) Overall complication rate
Female gender
Wound complications
1.32 (1.03-1.69)
1.36 (1.03-1.81))
General anaesthetics
1.50 (1.20-1.86)
1.36 (1.04-1.76)
Hypertension Cardiac disease Pulmonary disease
Death
1.55 (1.15-2.06)
2.13 (1.34-3.39) 1.86 (1.09-3.17)
1.69 (1.16-2.47)
1.76 (1.31-2.40)
3.24 (1.93-5.45)
1.25 (1.00-1.56)
Former cerebral event Renal disease
General complications
0.78 (0.61-1.00))
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Diabetes
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Age >80 years
Urgent surgery
Surgical complications
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Variable
1.47 (1.00-2.15) 1.66 (1.16-2.37)
2.22 (1.65-3.00)
2.13 (1.33-3.41)
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High ASA
1.35 (1.11-1.62)
1.38 (1.11-1.71)
1.75 (1.29-2.39)
2.10 (1.24-3.58)
Previously vascular surgery
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BMI<18.5
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Alcohol >5 U daily
30-days. N (%) Overall major amputation rate
221 (7) 4 of 675 (0.5)
Risk of amputation within rest pain
28 of 645 (4)
Risk of amputation within ischaemic ulcers
78 of 827 (9)
Risk of amputation within acute peripheral ischemia
32 of 681 (5)
Overall mortality rate
Risk of mortality within rest pain Risk of mortality within ischaemic ulcers Risk of mortality within gangrene Risk of mortality within acute peripheral ischemia
Combined mortality and amputation rate
148 (5)
475 (15)
10 of 675 (1)
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Risk of mortality within claudicants
390 (12)
79 of 374 (21)
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Risk of amputation within gangrene
1-year. N (%)
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Risk of amputation within claudicants
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Table 5: Amputation and mortality levels
29 of 645 (4)
34 of 827 (4) 19 of 374 (5)
56 of 681 (8)
294 (9)
612 (19)
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S0890-5096(16)30423-X
DOI:
10.1016/j.avsg.2016.02.028
Reference:
AVSG 2845
To appear in:
Annals of Vascular Surgery
Received Date: 7 August 2015 Revised Date:
20 January 2016
Accepted Date: 17 February 2016
Please cite this article as: Kehlet M, Jensen LP, Schroeder TV, Risk factors for complications after peripheral vascular surgery in 3202 patient procedures, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2016.02.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Risk factors for complications after peripheral vascular surgery in 3202 patient procedures.
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1) Vascular Clinic, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark 2) Centre for Clinical Education, Capital Region, Blegdamsvej 9, 2100 Copenhagen, Denmark E-mail:[email protected] 3) Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark 4) Finsen Centre, Rigshospitalet, Blegdamsvej 9, Copenhagen, Denmark Email: [email protected]
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Mette Kehlet, MD, Ph.d (1, 3), Leif Panduro Jensen, MD (4) & Torben V Schroeder, MD, DMSc (1,2,3)
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Corresponding author:
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Mette Kehlet
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Department for Vascular Surgery, RK 3111
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Rigshospitalet
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Blegdamsvej 9
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2100 Copenhagen
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Denmark
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E-mail: [email protected]
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Acknowledgements
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We are grateful to Nikolaj Eldrup for his continuous work with the national Danish vascular registry -Karbase, and for providing data on numerous occasions.
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Conflict of interest
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The authors declare no conflict of interest.
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Abstract
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Background: Complications after open vascular surgery is a major health challenge
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for the health care system and the patients. Infrainguinal vascular surgery is often
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perceived as less risky than aortic surgery and the aim of this study was to identify
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which risk factors correlated with postoperative complications after open vascular
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surgery for infrainguinal occlusive disease in an 8-year cohort using the Danish
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National Vascular Registry –Karbase, which gathers information on all vascular
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procedures in Denmark.
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Methods: A retrospective cohort study. The Karbase was searched for the pre-
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defined procedures from January 1, 2005 through December 31, 2012 at our two
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vascular departments. Both elective and urgent surgery was included.
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Complications were defined as: wound-, surgical- or general complication
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according to Karbase.
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Results: 3202 procedures were identified. Median age was 70 years and 21% were
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octogenarians. 60% were male. There was an overall complication rate of 30%,
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with 19% being wound complications, 6% surgical and 10% general
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complications. The greatest risk factors for developing a complication were high
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age, cardiac and renal disease, high ASA-score and general anesthetics. The 30-day
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mortality was 5% (1% for claudicants and 8% for acute ischemia) and the 30-day
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amputation rate was 7% (0.5% for claudicants and 21% for gangrene)
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Conclusion: There is a high risk of complications in peripheral vascular surgery.
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Risk factors are modifiable or non-modifiable. It is important to identify the risk
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factors and treat and optimize the patient cardiac and renal status prior to surgery
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if time allows, and also to perform surgery in local or regional anesthesia
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whenever possible, to reduce the risk of postoperative complications.
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Keywords: Postoperative complications; Peripheral vascular surgery; Risk
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reduction; Danish National Vascular Registry; Karbase.
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Introduction
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Complications after surgery is a major health challenge, both financially for the
3
health care system and mentally, physically and emotionally for the patients. All
4
surgical procedures carry the risk of postoperative complications, increasing the
5
length of hospital stay, re-operations and risk of death.
6
Though huge improvements have been achieved in surgical practices, anaesthesia
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and postoperative management, vascular surgery is still burdened with a high rate
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of complications[1-3]. Vascular patients often have comorbidities, and are thereby
9
at a higher risk of developing postoperative complications. The increasing use of
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endovascular procedures has reduced this risk[4,5], but a substantial number of
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patients are not eligible for minimally invasive procedures. Among open vascular
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surgery, infrainguinal procedures are perceived as less demanding to the patient
13
and therefore often considered associated with fewer serious complications than
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aortic surgery. But there is also a tendency to offer peripheral surgery to less fit
15
patients.
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One could therefore ask the question whether surgery to the peripheral arteries
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gives fewer complications and which risk factors influence the occurrence of
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complications. Identifying risk factors for postoperative complications in specific
19
patient populations is important to balance the potential risks and benefits of
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surgical interventions offered to individual patients. For the physician advising the
2
vascular patient prior to surgery, it is also important knowledge. Several risk
3
factors may be modified pre-operatively in order to reduce the risks of
4
postoperative complications. Among others, cessation of drinking and smoking has
5
been shown to reduce the incidence of postoperative complications though there is
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no consensus on the optimal duration of abstinence[6-9].
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This study aimed at identifying risk factors correlated with postoperative
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complications occurring after open infrainguinal vascular surgery in an 8-year
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cohort.
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10 Materials
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This is a retrospective cohort study using patient data extracted from the Danish
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National Vascular Registry, Karbase, which is a validated database of prospectively
14
collected data of surgical procedures from all vascular departments in
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Denmark[10,11]. Inclusion criteria were patients, aged 35-99 years, operated on
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for vascular occlusive disease in the eight-year period between January 1, 2005
17
through December 31, 2012 at the Vascular Department, Gentofte Hospital and
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Rigshospitalet, Denmark. The hospitals serve as primary referral hospitals in
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vascular surgery for the Capital Region of Denmark (1.6 million inhabitants) as
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well as tertiary referral hospitals from Region Sjaelland (another 0.8 million
2
inhabitants). Elective as well as acutely admitted patients were included. Only
3
patients who underwent open surgery for infrainguinal occlusive arterial disease
4
were included. Thus patients who had thrombolysis or percutaneous transluminal
5
angioplasty (PTA) with or without stenting were not included.
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6 Methods
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Demographic data such as age, gender and known co-morbidities were registered
9
in the database at admission and urgency of surgical procedure, use of
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anaesthetics, surgical procedure etc. were registered postoperatively by the
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performing surgeon. Complications were registered in the database by a doctor
12
from the department at discharge or 30 days after surgery at the first visit to the
13
outpatient clinic. Mortality rates were obtained from the civil registration number
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registry[12], and amputation rates (below-knee, through-knee and femoral
15
amputations) from the National Patient Registry (LPR)[13]. Using the unique civil
16
registration numbers from our dataset when searching the LPR, the 30-day and
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12-months amputation rates could be determined. LPR data were merged with
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Karbase data to determine which limb was amputated and in doubt, the patients’
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medical records were manually searched for clarification.
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The dataset, patient characteristics and procedures performed are listed in table 1.
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The definitions from the Danish Vascular Registry - Karbase were used[14]. All
3
variables were reduced to binary form. According to the Karbase, known cardiac or
4
pulmonary disease is any form of medically or surgically treated heart or lung
5
disease. Former cerebral event consists of previous TCI (transitory cerebral event)
6
and stroke. We defined renal disease by plasma-creatinine levels in excess of 105
7
µmol/l for men as well as for women. Smoking is in the Karbase defined as: Never
8
smoker, former smoker (>3 months) and smoker. We compared former smoker
9
with smoker in the analysis. Urgency of surgery is grouped in three: Acute
10
(immediately), sub-acute (within a few days) or elective (>3 days after first clinical
11
assessment) surgery. We combined acute and sub-acute surgery to urgent surgery.
12
Similarly insulin and non-insulin dependent diabetes were pooled together. The
13
American Society of Anaesthesiologists (ASA) score was re-grouped into two
14
groups with the first two ASA groups (ASA I-II) as low ASA, and the three last
15
groups (ASA III-V) as high ASA. BMI (Body Mass Index) was recorded as
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underweight when BMI was less than 18.5 in accordance with the Danish Health
17
and Medicines Department[15]. Alcohol consumption was defined as >5 units a
18
day. Alcohol consumption and smoking status were self-reported.
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In the Karbase, the most common perioperative complications are grouped in
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three: Wound complications, surgical complications and general complications
3
(table 2).
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4 Statistics
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Statistical analysis was performed using SPSS version 19. Continuous variables
7
were described as mean (SD) and categorical variables as absolute number
8
(frequency). A univariate analysis was performed looking at frequencies of
9
complications and risk factors individually. The predefined binary variables were
10
assessed using the cross-table methods (chi2-test) with Fisher’s exact test (two
11
sided) and the univariate odds ratio (OR) and 95% confidence interval (CI) for
12
each variable is presented.
13
To identify the relative impact of the independent risk factors for having a
14
complication a logistic regression analysis was performed with the dependant
15
binary variable ‘complication yes/no’ and by entering all the predictors, followed
16
by the backward stepwise selection with an entry of 0,5 and removal 0.10. Missing
17
data were excluded from the analysis, and are reported in table 3.
18
Both the univariate and multivariate analysis were performed for each of the four
19
pre-defined groups: Overall Complication, Wound Complication, Surgical
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Complication and General Complication (table 3). The predictors for mortality are
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shown in table 4 and here only the independent significant predictors, as found in
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the multivariate analysis, are listed.
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Results
6
A total of 3202 patient procedures were identified in the Danish Vascular Database
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corresponding to the inclusion criteria of open infrainguinal vascular surgery.
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Indications for surgery were 675 (21%) with intermittent claudication, 645 (20%)
9
with rest pain, 827 (26%) with ischemic ulcers, 374 (12%) with gangrene and 681
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(21%) with acute peripheral ischemia. Patient characteristics are listed in table 1
11
and shows that the mean age was 70 years (SD ±11), 21% were octogenarians and
12
40% were women.
13
A total of 921 patients (30%) suffered one or more complications within 30 days of
14
the surgical procedure. Of these 583 (19%) suffered wound complications, 193
15
(6%) surgical complications and 320 (10%) experienced general complications. All
16
the potential risk factors and their odds ratios from the univariate analysis are
17
shown in table 3.
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Table 4 shows the multivariate analysis with the significant independent risk
19
factors for having one or more overall complications to be: Age>80 years; OR 1.32
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(CI 1.03-1.69), having surgery in general anaesthetics; OR 1.50 (CI 1.20-1.86),
2
pulmonary disease; OR 1.25 (CI 1.00-1.56) and being rated high ASA; OR 1.35 (CI
3
1.11-1.62).
4
The risk factors for being amongst one of the 583 patients with a wound
5
complication were also age>80 years; OR 1.36 (CI 1.03-1.81), having surgery in
6
general anaesthetics; OR 1.36 (CI 1.04-1.76) and being rated high ASA; OR 1.38; CI
7
1.11-1.71). Surprisingly urgent surgery seemed to be less risky than elective
8
surgery in terms of wound complications; OR 0.78 (CI 0.61-1.00).
9
When looking at risk factors for surgical complications the only significant variable
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was renal disease; OR 1.66 (CI 1.16-2.37).
11
The risk factors for developing a general medical complication were female
12
gender; OR 1.55 (CI 1.15-2.06), having surgery in general anaesthetics; OR 1.69 (CI
13
1.16-2.47), cardiac disease; OR 1.76 (CI 1.31-2.40), former cerebral event; OR 1.47
14
(CI 1.00-2.15), renal disease; OR 2.22 (CI 1.65-3.00) and high ASA; OR 1.75 (CI
15
1.29-2.39).
16
The 30-day overall major amputation rate was 7% (N=221) and 1-year amputation
17
rate 12% (N=390). The 30-day risk for claudicants to have major amputation was
18
0.5% (4 amputees out of 675 claudicants) whereas it was 21% (79 out of 374)
19
when the patient had gangrene (table 5).
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The 30-day overall mortality rate was 5%, with a mortality rate of 1% for
2
claudicants and 8% for acute peripheral ischemia (table 5). The significant risk
3
factors for mortality were female gender; OR 2.13 (CI 1.34-3.39), Age>80 years; OR
4
1.86 (CI 1.09-3.17), cardiac disease; OR 3.24 (CI 1.93-5.45), renal disease; OR 2.13
5
(CI 1.33-3.41) and high ASA; OR 2.10 (CI 1.24-3.58).
6
1-year mortality rate was 15% (N=475) and the combined amputation and
7
mortality rate at one-year was 19% (N=612) (table 5).
8
Discussion
9
This study identified some of the risk factors influencing the perioperative
10
complication rate in patients undergoing peripheral open vascular surgery. The
11
findings indicated that the patients with the highest risk of postoperative
12
complications were; Octogenarians, patients having surgery in general anaesthesia
13
and patients rated high ASA. But also female gender, cardiac disease and renal
14
disease increased the risk of complications. Some of these risk factors may be
15
modified before elective surgery. Cardiac and renal disease and ASA-score may be
16
influenced at least to some extent and if time allows. As opposed to the non-
17
modifiable risk factors such as gender and age.
18
However, there is often insufficient time to optimize the vascular patients’ medical
19
conditions for more than a few days, if even this.
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The odds ratio for developing a general complication when having known cardiac
2
disease was 1.76. Therefore almost a doubling of the risk must be taken into
3
account when a decision for surgery is made, and this correlates well with other
4
studies showing increased risks for patients with cardiac co-morbidities[16,17].
5
Chronic kidney disease patients have an increased risk of cardiovascular disease
6
and of developing postoperative complications[18,19]. Even a relative small
7
increase in P-creatinine >105 µmol/l has a significant effect on postoperative
8
complications in our study. The accuracy in P-creatinine as a predictor for renal
9
insufficiency has been criticised and using the patients’ glomerular filtration rate
10
(GFR) could be more correct in staging renal disease[20], but other studies confirm
11
a correlation between the risk of complications after cardiac and vascular surgery
12
even with mild kidney dysfunction (eGFR 60-90 mL/min)[21,22].
13
General anaesthesia was also an independent risk factor confirming previous
14
findings[23-25], and is to some extent modifiable. The preferred form of
15
anaesthesia in our study population was general anaesthesia, used in 73% of the
16
cases. Urgent surgery could be a reason for choosing general anaesthesia as well as
17
being the preference of some anaesthesiologists, surgeons and patients. But given
18
that it increases the risk of complications with an odds ratio of 1.50, actions should
19
be taken in our department to increase the use of regional or local anaesthesia
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whenever feasible, and the surgeon and the anaesthesiologist should carefully
2
consider type of anaesthesia together with the patient.
3
Among the non-modifiable risk factors, female gender increased the risk of general
4
complications with an OR 1.55 and the mortality rate OR 2.13. This has also been
5
shown previously for lower extremity bypass procedures[26,27] as well as for
6
other vascular procedures like endovascular aneurysm repair[28]. Octogenarians
7
also had an enhanced risk for complications. This is of no surprise and has been
8
shown numerous times before[29-31], and even though the older patient has an
9
increased risk it is important to emphasize that age alone should never preclude
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peripheral vascular surgery.
11
Others have found complication rates between 14%-31% after peripheral vascular
12
occlusive disease depending whether the patients had disabling claudication or
13
critical limb ischemia[32,33]. We found 19% to have wound complications.
14
Reports from general surgery show wound complications between 6%-16%
15
depending on whether the surgery was elective or acute[34] and overall
16
complications of 28%[35], comparable with the 30% in our study.
17
We pooled all procedures together in our analysis and did not distinguish between
18
the different types of surgery performed when assessing the complications. This
19
could have an effect on the complication rate since the surgical trauma of a
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peripheral by-pass is often greater than that of an embolectomy. On the other hand
2
mortality and amputation rates after urgent embolectomy are much higher than
3
after a peripheral bypass [36], which our data also show.
4
We expected smokers to have a higher rate of complications than former smokers
5
since smoking is a well-documented risk factor for developing postoperative
6
complications[34,37-40], but no difference in complication rates were found
7
between the groups. This seemingly inconsistent finding points to one of the
8
weaknesses of this dataset. Data has been collected prospectively, but as part of
9
the routine surgical management of the patients and by different members of the
10
staff and not as part of a well-defined protocol with predefined analyses. Smoking
11
status was self-reported and not biochemically verified, probably underestimating
12
the smoking prevalence[41-43].
13
It is potentially life threatening to have surgically demanding peripheral occlusive
14
disease, though peripheral surgery generally is considered less risky than surgery
15
to the aorta. The 30-day mortality rate in this study population was 5%, with the
16
greatest risk of death for acute critical limb ischemia of 8% compared to 1% for
17
claudicants. A little more than 1/3 of our study population (34%) were operated
18
upon urgently and other studies for infrainguinal vascular surgery have shown
19
mortality rates of 2.7%-4% for elective surgery [1,44] and up to 20% for acute
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limb ischemia[45]. The independent risk factors for 30-day mortality were, not
2
surprisingly, being rated high ASA; OR 2.10, having known cardiac disease; OR 3.24
3
or renal disease; OR 2.13. Again risk factors that can be modified to some extent if
4
time is available. The 1-year mortality rate for our study population is as high as
5
15% and confirms our clinical assumption that patients in need of peripheral
6
vascular surgery are often less fit than other population groups.
7
Major amputation rates in our population were 7% at 30-days postoperatively and
8
12% at 1-year. As many as 15% of the acutely operated patients were amputated
9
after 30 days in our study population and for 1-year it was 23%. This corresponds
10
well with results found by others. Patients with critical limb ischemia have a 1 year
11
risk of major amputation or death of 20-40% without intervention[46]. Data from
12
the US Medicare population show in-hospital amputations rates from 6.4-8.1% and
13
1-year amputation rates from 11-14.8% in patients with acute critical limb
14
ischemia after intervention (2008-1998 respectively)[45,47].
15
As touched upon above, the main limitation in this study was in the collection of
16
data in the Karbase. Even though the Karbase has been validated, all data were
17
manually recorded by the operating surgeon from patient records with the
18
possibility of entering false data. The patients' alcohol consumption and smoking
19
status are self-reported and thereby giving risk of bias. Grouping the analysed data
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in dichotomous variables could also increase the risk of non-differential
2
misclassification, underestimating of the measured association. We have also used
3
ASA as a dichotomous variable in our analyses, which in itself increases bias since
4
the ASA classification consists of several of the other included variables. Knowing
5
this we still chose to include the ASA score since it is a good endpoint for the
6
patients' physical state pre-operatively.
7
The Karbase has many clinical variables, but only few variables concerning the
8
patients’ socio-economic status, which would give more information on non-
9
medical risk factors. Despite these limitations this study emphasises important
10
information. The study population is a large sample of a very specific type of
11
surgery adding to the results of the statistical analysis.
12
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Conclusion
14
Overall 30% had one or more complications after peripheral vascular surgery for
15
occlusive disease. The major risk factors for developing a complication were age,
16
cardiac and renal disease, ASA-score and being operated on in general
17
anaesthetics. Our findings correlated well with complication rates found in other
18
studies. The amputation and mortality rates are high in the vascular population.
19
30-day mortality was 5% (1% for claudicants and 8% for acute peripheral
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ischemia) and 30-day amputation rate was 7% (0.5% for claudicants and 21% for
2
patients with gangrene). After 1-year a total of 19% were either amputated or
3
dead.
4
Risk factors are modifiable or non-modifiable. When managing vascular patients it
5
is important that we are aware of the modifiable risk factors so patients, if
6
possible, can be treated and optimized prior to surgery and thereby reduce their
7
risk of postoperative complications. At our department actions must be taken to
8
ensure the indications for vascular surgery using general anaesthesia versus local
9
or regional anaesthesia, since general anaesthesia was a major risk factor for
10
complications and 73% of our patients were operated upon in general anaesthesia.
11
This will be to the benefit of patients as well as the society with fewer re-
12
operations and faster discharge of patients.
15 16
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Reference List
2 1. Nowygrod R, Egorova N, Greco G, Anderson P, Gelijns A, Moskowitz A et al.: Trends, complications, and mortality in peripheral vascular surgery. J Vasc Surg 2006, 43: 205-216.
6 7 8 9
2. Ozaki CK, Hamdan AD, Barshes NR, Wyers M, Hevelone ND, Belkin M et al.: Prospective, randomized, multi-institutional clinical trial of a silver alginate dressing to reduce lower extremity vascular surgery wound complications. J Vasc Surg 2015, 61: 419-427.
SC
RI PT
3 4 5
3. Bakker EJ, Valentijn TM, van de Luijtgaarden KM, Hoeks SE, Voute MT, Goncalves FB et al.: Type 2 diabetes mellitus, independent of insulin use, is associated with an increased risk of cardiac complications after vascular surgery. Anaesth Intensive Care 2013, 41: 584-590.
14 15 16
4. Bechter-Hugl B, Falkensammer J, Gorny O, Greiner A, Chemelli A, Fraedrich G: The influence of gender on patency rates after iliac artery stenting. J Vasc Surg 2014, 59: 1588-1596.
17 18 19
5. Matsi PJ, Manninen HI: Complications of lower-limb percutaneous transluminal angioplasty: a prospective analysis of 410 procedures on 295 consecutive patients. Cardiovasc Intervent Radiol 1998, 21: 361-366.
20 21 22
6. Oppedal K, Moller AM, Pedersen B, Tonnesen H: Preoperative alcohol cessation prior to elective surgery. Cochrane Database Syst Rev 2012, 7: CD008343.
23 24 25
7. Nasell H, Adami J, Samnegard E, Tonnesen H, Ponzer S: Effect of smoking cessation intervention on results of acute fracture surgery: a randomized controlled trial. J Bone Joint Surg Am 2010, 92: 1335-1342.
26 27 28
8. Thomsen T, Tonnesen H, Moller AM: Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation. Br J Surg 2009, 96: 451-461.
29 30
9. Thomsen T, Villebro N, Moller AM: Interventions for preoperative smoking cessation. Cochrane Database Syst Rev 2014, 3: CD002294.
AC C
EP
TE D
M AN U
10 11 12 13
19
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10. Laustsen J, Jensen LP, Hansen AK: Accuracy of clinical data in a population based vascular registry. Eur J Vasc Endovasc Surg 2004, 27: 216-219.
3 4 5 6
11. Andersen LV, Mortensen LS, Lindholt JS, Faergeman O, Henneberg EW, Frost L: Completeness and positive predictive value of registration of upper limb embolectomy in the Danish National Vascular Registry. Clin Epidemiol 2009, 1: 27-32.
7
12. https://cpr.dk/in-english/
8
13. http://www.ssi.dk/English.aspx
9
14.
M AN U
http://www.karbase.dk/English/english.htm
SC
RI PT
1 2
15. http://sundhedsstyrelsen.dk/da/sundhed/overvaegt/bmi.aspx (http://sundhedsstyrelsen.dk/en)
12 13 14
16. Fleischmann KE, Beckman JA, Buller CE, Calkins H, Fleisher LA, Freeman WK et al.: 2009 ACCF/AHA focused update on perioperative beta blockade. J Am Coll Cardiol 2009, 54: 2102-2128.
15 16
17. Manley AM, Reck SE: Patients with vascular disease. Med Clin North Am 2013, 97: 1077-1093.
17 18 19
18. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004, 351: 1296-1305.
20 21 22
19. Patel VI, Mukhopadhyay S, Guest JM, Conrad MF, Watkins MT, Kwolek CJ et al.: Impact of severe chronic kidney disease on outcomes of infrainguinal peripheral arterial intervention. J Vasc Surg 2014, 59: 368-375.
23 24 25 26
20. AbuRahma AF, Srivastava M, Chong B, Dean LS, Stone PA, Koszewski A: Impact of chronic renal insufficiency using serum creatinine vs glomerular filtration rate on perioperative clinical outcomes of carotid endarterectomy. J Am Coll Surg 2013, 216: 525-532.
27 28 29 30
21. Gaber AO, Moore LW, Aloia TA, Suki WN, Jones SL, Graviss EA et al.: Crosssectional and case-control analyses of the association of kidney function staging with adverse postoperative outcomes in general and vascular surgery. Ann Surg 2013, 258: 169-177.
AC C
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10 11
20
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22. Howell NJ, Keogh BE, Bonser RS, Graham TR, Mascaro J, Rooney SJ et al.: Mild renal dysfunction predicts in-hospital mortality and post-discharge survival following cardiac surgery. Eur J Cardiothorac Surg 2008, 34: 390-395.
4 5 6 7
23. Hausman MS, Jr., Jewell ES, Engoren M: Regional Versus General Anesthesia in Surgical Patients with Chronic Obstructive Pulmonary Disease: Does Avoiding General Anesthesia Reduce the Risk of Postoperative Complications? Anesth Analg 2014.
8 9 10
24. Pugely AJ, Martin CT, Gao Y, Mendoza-Lattes S, Callaghan JJ: Differences in short-term complications between spinal and general anesthesia for primary total knee arthroplasty. J Bone Joint Surg Am 2013, 95: 193-199.
11 12 13 14 15
25. Edwards MS, Andrews JS, Edwards AF, Ghanami RJ, Corriere MA, Goodney PP et al.: Results of endovascular aortic aneurysm repair with general, regional, and local/monitored anesthesia care in the American College of Surgeons National Surgical Quality Improvement Program database. J Vasc Surg 2011, 54: 1273-1282.
16 17 18
26. Flu HC, Ploeg AJ, Marang-van de Mheen PJ, Veen EJ, Lange CP, Breslau PJ et al.: Patient and procedure-related risk factors for adverse events after infrainguinal bypass. J Vasc Surg 2010, 51: 622-627.
19 20 21
27. Jain AK, Velazquez-Ramirez G, Goodney PP, Edwards MS, Corriere MA: Gender-based analysis of perioperative outcomes associated with lower extremity bypass. Am Surg 2011, 77: 844-849.
22 23 24 25
28. Abedi NN, Davenport DL, Xenos E, Sorial E, Minion DJ, Endean ED: Gender and 30-day outcome in patients undergoing endovascular aneurysm repair (EVAR): an analysis using the ACS NSQIP dataset. J Vasc Surg 2009, 50: 486-91, 491.
26 27 28
29. Scott SW, Bowrey S, Clarke D, Choke E, Bown MJ, Thompson JP: Factors influencing short- and long-term mortality after lower limb amputation. Anaesthesia 2014, 69: 249-258.
29 30 31
30. Sheetz KH, Waits SA, Krell RW, Campbell DA, Jr., Englesbe MJ, Ghaferi AA: Improving mortality following emergent surgery in older patients requires focus on complication rescue. Ann Surg 2013, 258: 614-617.
AC C
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31. Turrentine FE, Wang H, Simpson VB, Jones RS: Surgical risk factors, morbidity, and mortality in elderly patients. J Am Coll Surg 2006, 203: 865877.
4 5 6
32. Lange CP, Ploeg AJ, Lardenoye JW, Breslau PJ: Patient- and procedure-specific risk factors for postoperative complications in peripheral vascular surgery. Qual Saf Health Care 2009, 18: 131-136.
7 8 9
33. Lees T, Troeng T, Thomson IA, Menyhei G, Simo G, Beiles B et al.: International variations in infrainguinal bypass surgery - a VASCUNET report. Eur J Vasc Endovasc Surg 2012, 44: 185-192.
10 11 12
34. Sorensen LT, Hemmingsen U, Kallehave F, Wille-Jorgensen P, Kjaergaard J, Moller LN et al.: Risk factors for tissue and wound complications in gastrointestinal surgery. Ann Surg 2005, 241: 654-658.
13 14 15
35. Longo WE, Virgo KS, Johnson FE, Oprian CA, Vernava AM, Wade TP et al.: Risk factors for morbidity and mortality after colectomy for colon cancer. Dis Colon Rectum 2000, 43: 83-91.
16 17 18
36. Kempe K, Starr B, Stafford JM, Islam A, Mooney A, Lagergren E et al.: Results of surgical management of acute thromboembolic lower extremity ischemia. J Vasc Surg 2014, 60: 702-707.
19 20 21 22
37. Delgado-Rodriguez M, Medina-Cuadros M, Martinez-Gallego G, Gomez-Ortega A, Mariscal-Ortiz M, Palma-Perez S et al.: A prospective study of tobacco smoking as a predictor of complications in general surgery. Infect Control Hosp Epidemiol 2003, 24: 37-43.
23 24 25 26
38. Myles PS, Iacono GA, Hunt JO, Fletcher H, Morris J, McIlroy D et al.: Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers. Anesthesiology 2002, 97: 842-847.
27 28 29
39. Sorensen LT, Jorgensen T, Kirkeby LT, Skovdal J, Vennits B, Wille-Jorgensen P: Smoking and alcohol abuse are major risk factors for anastomotic leakage in colorectal surgery. Br J Surg 1999, 86: 927-931.
30 31
40. Gronkjaer M, Eliasen M, Skov-Ettrup LS, Tolstrup JS, Christiansen AH, Mikkelsen SS et al.: Preoperative smoking status and postoperative
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3 4 5 6
complications: a systematic review and meta-analysis. Ann Surg 2014, 259: 5271. 41. Connor GS, Schofield-Hurwitz S, Hardt J, Levasseur G, Tremblay M: The accuracy of self-reported smoking: a systematic review of the relationship between self-reported and cotinine-assessed smoking status. Nicotine Tob Res 2009, 11: 12-24.
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42. From AM, Herlitz J, Berndt AK, Karlsson T, Hjalmarson A: Are patients truthful about their smoking habits? A validation of self-report about smoking cessation with biochemical markers of smoking activity amongst patients with ischaemic heart disease. J Intern Med 2001, 249: 145-151.
11 12 13
43. Jarvis MJ, Tunstall-Pedoe H, Feyerabend C, Vesey C, Saloojee Y: Comparison of tests used to distinguish smokers from nonsmokers. Am J Public Health 1987, 77: 1435-1438.
14 15 16
44. LaMuraglia GM, Conrad MF, Chung T, Hutter M, Watkins MT, Cambria RP: Significant perioperative morbidity accompanies contemporary infrainguinal bypass surgery: an NSQIP report. J Vasc Surg 2009, 50: 299-304, 304.
17 18 19
45. Baril DT, Patel VI, Judelson DR, Goodney PP, McPhee JT, Hevelone ND et al.: Outcomes of lower extremity bypass performed for acute limb ischemia. J Vasc Surg 2013.
20 21
46. Chung J, Modrall JG, Valentine RJ: The need for improved risk stratification in chronic critical limb ischemia. J Vasc Surg 2014.
22 23 24 25 26
47. Baril DT, Ghosh K, Rosen AB: Trends in the incidence, treatment, and outcomes of acute lower extremity ischemia in the United States Medicare population. J Vasc Surg 2014, 60: 669-677.
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Table 1: Patient Characteristics, surgical indication and procedures performed: Age (mean) 70 years (SD ± 11 years). N=3202 (%) 1931 (60)
Female gender
1271 (40)
SC
Male gender
659 (21)
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Age >80 General anaesthetics
2328 (73)
Urgent surgery
1083 (34)
Diabetes
848 (26)
Former cerebral event Renal disease (P-crea>105) High ASA (III-IV) Previously vascular surgery BMI<18.5 Smoker
EP
Pulmonary disease
AC C
Cardiac disease
2049 (64)
TE D
Hypertension
1299 (41) 665 (21) 399 (12) 832 (26) 1575 (49) 1318 (41) 238 (8) 1380 (43)
Former smoker >3 months
1249 (39)
Alcohol >5 U daily
156 (5)
Claudicants
675 (21) 24
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645 (20)
Ischemic ulcer
827 (26)
Gangrene
374 (12)
Acute peripheral ischemia
681 (21)
Exploration of the femoral artery, popliteal artery and branches
77 (2.5)
Thrombectomy/embolectomy of the femoral artery, popliteal artery and branches
436(13.5)
SC
Thrombenarterectomy of the femoral artery and branches
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Rest pain
922 (29)
1767 (55)
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Bypass from the femoral artery and branches to the popliteal artery and branches
Table 2: Definition of complications according to the Danish Vascular Database.
Necrosis
TE D
Wound complication*:
Infection
Lymphorrhea> 2 days or lymphocele. Bowel obstruction
EP
Bleeding (requiring surgery)
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Surgical complication:
Intestinal ischemia
Emboli or thrombosis of the reconstruction Peripheral nerve lesion
25
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General complication:
Cardiac complications (acute myocardial infarction, congestive heart failure, severe arrhythmia), Pulmonary complication requiring treatment,
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ATN (acute tubular necrosis)/dialysis, TCI (transitory cerebral ischemia)/stroke, DVT (deep venous thrombosis),
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* Only recorded if requiring surgical treatment or prolonged admission
SC
Compartment syndrome,MODS (multi organ dysfunction syndrome)
Table 3: Univariate model: Frequencies of complications (%) and given as odds ratio, OR, with confidence interval (CI).
%
OR (CI)
Female gender (MI 0)
31
Age >80 (MI 0)
Surgical complication rate 6%
General complications 10%
%
OR (CI)
%
OR (CI)
%
OR (CI)
1.16 (0.99-1.35)
19
1.08 (0.90-1.29)
6
0.85 (0.63-1.16)
12
1.26 (0.99-1.59)
35
1.34 (1.11-1.61)*
20
1.15 (0.92-1.43)
7
1.15 (0.81-1.63)
15
1.70 (1.32-2.21)*
General anaesthetics (MI 0)
32
1.47 (1.23-1.76)*
20
1.43 (1.15-1.77)*
6
1.05 (0.76-1.46)
11
1.50 (1.13-1.99)*
Urgent surgery (MI 0)
29
0.91 (0.77-1.07)
16
0.78 (0.64-0.95)*
6
0.90 (0.66-1.23)
12
1.30 (1.03-1.65)*
Diabetes (MI 17)
31
1.12 (0.94-1.33)
19
1.05 (0.85-1.28)
6
1.02 (0.73-1.41)
12
1.27 (0.99-1.64)
Hypertension (MI 16)
31
1.24 (1.05-1.46)*
20
1.28 (1.05-1.55)*
6
0.83 (0.61-1.11)
12
1.54 (1.19-1.99)*
Cardiac disease (MI 40)
32
1.22 (1.05-1.43)*
19
1.07 (0.89-1.28)
6
1.08 (0.80-1.45)
14
2.09 (1.65-2.64)*
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Variable
Wound complication rate 19%
EP
Overall complication rate 30%
26
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34
1.26 (1.05-1.52)*
21
1.17 (0.94-1.45)
5
0.81 (0.56-1.19)
14
1.54 (1.18-2.00)*
Former cerebral event (MI 55)
35
1.32 (1.05-1.65)*
22
1.24 (0.95-1.60)
7
1.05 (0.68-1.62)
13
1.45 (1.06-2.00)*
Renal disease (MI 119)
32
1.17 (0.99-1.40)
17
0.83 (0.67-1.03)
9
1.68 (1.24-2.28)*
16
2.14 (1.68-2.74)*
High ASA (III-V) (MI 5)
34
1.52 (1.34-1.82)*
21
1.40 (1.16-1.67)*
7
1.33 (0.99-1.78)
14
2.24 (1.75-2.85)*
Previously vascular surgery (MI 0)
31
1.15 (0.99-1.35)
20
1.13 (0.95-1.36)
7
1.30 (0.97-1.73)
10
0.96 (0.76-1.21)
BMI<18.5(MI 190)
29
0.97 (0.72-1.31)
19
0.99 (0.70-1.40)
4
0.57 (0.29-1.13)
11
1.15 (0.75-1.76)
Smoker (MI 34)
30
1.01 (0.85-1.20)
10
0.98 (0.80-1.19)
7
1.06 (0.76-1.46)
10
1.03 (0.80-1.33)
Alcohol >5 U daily (MI 62)
30
1.01 (0.70-1.44)
20
1.11 (0.74-1.67)
7
1.09 (0.57-2.12)
9
0.90 (0.52-1.59)
SC
RI PT
Pulmonary disease (MI 23)
2
M AN U
* Statistically significant with P > 0.05 in the chi -test. MI: missing information.
Table 4 Multivariate model:
Odds ratio, OR, and confidence intervals (CI) for the significant risk factors (p<0.05). Odds Ratio (OR) final adjusted (95% CI) Overall complication rate
Female gender
Wound complications
1.32 (1.03-1.69)
1.36 (1.03-1.81))
General anaesthetics
1.50 (1.20-1.86)
1.36 (1.04-1.76)
Hypertension Cardiac disease Pulmonary disease
Death
1.55 (1.15-2.06)
2.13 (1.34-3.39) 1.86 (1.09-3.17)
1.69 (1.16-2.47)
1.76 (1.31-2.40)
3.24 (1.93-5.45)
1.25 (1.00-1.56)
Former cerebral event Renal disease
General complications
0.78 (0.61-1.00))
AC C
Diabetes
EP
Age >80 years
Urgent surgery
Surgical complications
TE D
Variable
1.47 (1.00-2.15) 1.66 (1.16-2.37)
2.22 (1.65-3.00)
2.13 (1.33-3.41)
27
ACCEPTED MANUSCRIPT
High ASA
1.35 (1.11-1.62)
1.38 (1.11-1.71)
1.75 (1.29-2.39)
2.10 (1.24-3.58)
Previously vascular surgery
RI PT
BMI<18.5
SC
Alcohol >5 U daily
30-days. N (%) Overall major amputation rate
221 (7) 4 of 675 (0.5)
Risk of amputation within rest pain
28 of 645 (4)
Risk of amputation within ischaemic ulcers
78 of 827 (9)
Risk of amputation within acute peripheral ischemia
32 of 681 (5)
Overall mortality rate
Risk of mortality within rest pain Risk of mortality within ischaemic ulcers Risk of mortality within gangrene Risk of mortality within acute peripheral ischemia
Combined mortality and amputation rate
148 (5)
475 (15)
10 of 675 (1)
AC C
Risk of mortality within claudicants
390 (12)
79 of 374 (21)
EP
Risk of amputation within gangrene
1-year. N (%)
TE D
Risk of amputation within claudicants
M AN U
Table 5: Amputation and mortality levels
29 of 645 (4)
34 of 827 (4) 19 of 374 (5)
56 of 681 (8)
294 (9)
612 (19)
28