- Email: [email protected]
Carbon Dioxide as Contrast Medium to Guide Endovascular Aortic Aneurysm Repair
Accepted Manuscript Carbon dioxide as contrast medium to guide endovascular aortic aneurysm repair Cynthia de Almeida Mendes, MD, Alexandre de Arruda Martins, MD, Marcelo Passos Teivelis, MD, Sergio Kuzniec, MD, PhD, Andrea Yasbek Monteiro Varella, MD, Nelson Wolosker, MD, PhD PII:
S0890-5096(16)30843-3
DOI:
10.1016/j.avsg.2016.06.028
Reference:
AVSG 3013
To appear in:
Annals of Vascular Surgery
Received Date: 6 April 2016 Revised Date:
15 June 2016
Accepted Date: 17 June 2016
Please cite this article as: de Almeida Mendes C, de Arruda Martins A, Teivelis MP, Kuzniec S, Varella AYM, Wolosker N, Carbon dioxide as contrast medium to guide endovascular aortic aneurysm repair, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2016.06.028. 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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Carbon dioxide as contrast medium to guide endovascular aortic aneurysm repair.
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2 Cynthia de Almeida Mendes MD- Hospital Israelita Albert Einstein and Hospital Municipal Dr
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Moyses Deutsch- Mboi Mirim ( [email protected])
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Alexandre de Arruda Martins MD - Hospital Israelita Albert Einstein and Hospital Municipal Dr
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Moyses Deutsch- Mboi Mirim ( [email protected])
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Marcelo Passos Teivelis MD- Hospital Israelita Albert Einstein ([email protected])
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Sergio Kuzniec MD, PhD- Hospital Israelita Albert Einstein ([email protected])
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Andrea Yasbek Monteiro Varella MD- Hospital Israelita Albert Einstein ([email protected]) Nelson Wolosker MD, PhD- Hospital Israelita Albert Einstein ([email protected])
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Corresponding author- Cynthia de Almeida Mendes
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[email protected]
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Av Albert Einstein 627 - Bloco A1 - 4º andar - sala 423
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Morumbi - São Paulo - SP – Brasil-CEP 05652-000
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Supports: Ministério da Saúde do Brasil
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Original Article
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Keywords- aortic aneurysm, endovascular, carbon dioxide
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Abstract
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Background Iodine contrast medium (ICM) is considered gold standard in endovascular procedures, but nephrotoxicity and hypersensitivity limit its widespread use. Carbon dioxide (CO2) is considered an alternative for endovascular procedures in
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patients with contraindication to ICM. However no studies have compared the outcomes of
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EVAR (endovascular aneurysm repair) performed with ICM or CO2 in patients with no
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contraindication to ICM.
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Methods and Results
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From May 2012 to April 2014, 36 patients with abdominal aortic aneurysms underwent
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EVAR in a prospective, randomized and controlled study. Patients were randomized into 2
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groups, either the CO2 or ICM group. We were able to perform the proposed procedures in all
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patients in this study. There were no conversions to open surgery and no CO2-related
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complications. Endovascular material costs, duration of surgery and time of fluoroscopy were
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similar between groups, and the cost of the contrast-media was smaller in the CO2 group than
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in the ICM group. In the CO2 group, it was necessary complement with ICM in 62.5% of the
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patients.
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Conclusions
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The use of CO2 as a contrast for EVAR is an alternative in patients with no restriction for
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ICM, with similar outcomes when compared to ICM, regarding duration of surgery, duration of
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fluoroscopy and endovascular material costs. With CO2, there were no associated changes in
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creatinine clearance and no risk of hypersensitivity reactions; moreover, there was a reduction
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in contrast-related costs for EVAR procedures. However, in our study, most cases needed a
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supplement of ICM to visualize the internal iliac artery.
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INTRODUCTION
57 Abdominal aortic aneurysm (AAA) is a common condition, with a prevalence rate of
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5.7 % in the population. Even though there is a rationale for medical treatment (1), ,surgery is
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considered the best treatment. Endovascular aneurysm repair (EVAR) has emerged as a less
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invasive and less morbid option when compared to conventional open surgery. In the USA, the
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overall use of EVAR (2)has risen sharply in the past 10 years (5.2% to 74% of the total number
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of AAA repairs) even though the total number of AAAs remains stable at 45.000 cases per year
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(3).
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The use of iodine contrast medium (ICM) is currently considered the gold standard in
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endovascular procedures, but its nephrotoxicity and hypersensitivity reactions limit its
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widespread use (4), (5)(6).
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Carbon dioxide (CO2) was initially described as an endovascular contrast media in 1970
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by Hawkins et al. However, because it is a gaseous contrast agent and had some particularities,
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its use was not widespread until the 2000s, when the endovascular treatment became
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mainstream and the use of ICM presented as a limitation to treat patients with renal impairment.
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Currently, CO2 can be considered an alternative for aortic (,7), aorto-iliac(,8) and
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femoro-popliteal (9) procedures only in patients with formal contraindication to ICM ( renal
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impairment or iodine-related hypersensitivity). However, to our knowledge, no studies have
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compared the outcomes EVAR performed with either ICM or CO2 in patients eligible for use of
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both contrast media by a randomized and prospective approach. Attempting to evaluate if CO2
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is as effective as ICM for EVAR in patients with no contra indication to ICM we elaborated this
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prospective study to compare the feasibility, quality of the angiographic images, clinical
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outcomes and the relative costs of EVAR using CO2 or ICM as contrast mediums, and here we
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show our results.
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METHODS
87 From May 2012 to April 2014, 36 patients with infra-renal aortic aneurysms (identified
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on preoperative angioCT scan) and normal renal function underwent EVAR in a prospective,
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randomized and controlled study. This study was approved by the Ethics Committee for
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Analysis of Research Projects on Human Experimentation at our institution. Regarding the
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anatomy of the cases none of the included patients had proximal aortic neck with angle greater
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than 60 degrees, proximal aortic neck length less than 20mm or thrombus or calcification in
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more than 50% of the proximal aortic neck. The clinical exclusion criteria were chronic
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obstructive pulmonary disease, severe heart failure (on whom surgery was contra-indicated
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because they were deemed to be very high risk on clinical grounds) or kidney failure (creatinine
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clearance less than 30 ml/min using the CocKroft Gault formula), pregnancy or patients who
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had the aortic anatomy described above.
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All patients signed informed consent forms agreeing upon the use of either contrast medium.
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Patients were randomized into 2 groups, the CO2 and ICM groups, according to the
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contrast media used in the procedure. Randomization was performed by a computer-generated
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list immediately prior to the beginning of the surgeries, in a one to one ratio. An endovascular suite operating room (Philips Allura Xper FD – Netherlands) was used
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in all procedures. This equipment has a specific CO2 mode for performing procedures with CO2
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as contrast.
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The patients were operated under general anesthesia with cardiac monitoring, invasive
arterial pressure monitoring and bladder catheterization. The patients underwent the procedure by the same surgical team (four surgeons) using a constant surgical technique throughout the study. Surgical procedures were performed using conventional technique for EVAR with
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bilateral oblique inguinal incisions, followed by a bilateral dissection of the common femoral ACCEPTED MANUSCRIPT
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arteries. We finished the procedure with femoral artery suture, hemostasis, and closure of the
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incision in multiple layers. As routine in our hospital, all patients were referred to the intensive care unit
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immediately after the operation for at least 24 hours and received intravenous fluids following a
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fixed protocol for renal protection regardless of the contrast media used. The protocol for renal
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protection included intravenous fluids pre-procedure in addition to endovenous acetylcysteine,
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followed by intravenous fluid maintenance for 24 hours. Thereafter, patients remained
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hospitalized for the time needed to recover (at least 72 hours), with daily monitoring of renal
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function, blood count and electrolytes.
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The CO2 injection was performed manually, without any specific pump system. A
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cylinder with medicinal CO2 , a particle filter (Millex® Durapore® hydrophilic 0.22 μm pore)
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and a three-way stopcock were used to aspirate CO2 ; This was performed inside a bowl with
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saline solution. After acquiring the required volume of CO2,, an additional 5 ml of saline solution
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was aspired into the syringe to provide a water seal while the needle tip was kept down. This
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way, a physical barrier was created between the room air and carbon dioxide content, which is
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independent of manual compression and is protected from air contamination (10). Twenty or
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60 ml syringes were used for the intra-arterial CO2 injection, performed using a femoral
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introducer or through an end hole catheter.
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ICM injection was performed manually with 10 ml syringes using 3 ml iodinated
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contrast media and 7 ml saline solution per injection. During the final control aortography in the
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ICM group, an injection pump was used, with a half to half dilution of ICM and saline solution.
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The ICM used in all cases was Omnipaque (Iohexol) 300, a nonionic low osmolar contrast
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routinely used in our studies.
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The endovascular material (sheaths, guidewires, stents and endoprosthesis) used in all
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procedures was provided by Cook Medical Inc . The endoprosthesis used in all cases was
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Zenith Flex . The volumes of ICM and CO2, duration of the procedure, duration of X-ray
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exposure and the endovascularACCEPTED material used MANUSCRIPT in each intervention were precisely recorded for
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further analysis.
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In cases where it was necessary to perform internal iliac artery embolization, renal
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angioplasty, iliac angioplasty or when it was necessary to use a proximal cuff, we considered
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these as associated procedures, and all the material that was utilized was also accounted. All procedures were recorded on DVD for further analysis of the angiographic images.
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Two observers, also vascular surgeons, who did not take part in the intervention and had no
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experience with the use of CO2 analyzed the data. Each film was analyzed separately by the two
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observers.
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The images obtained with CO2 were analyzed separately for: renal arteries, internal iliac arteries, and final control angiography.
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Observers attributed a score for each image ranging from 1 to 3. A score of 1, considered
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poor, was assigned when there was significant loss of definition in the vessels, which precluded
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the procedure; a score of 2, considered fair, was assigned when there was some loss of
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definition in the vessels but did not hinder intervention; and a score of 3, considered good, was
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assigned when there was good contrast in the vessels.
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Each intervention was analyzed evaluating contrast media costs and endovascular
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material used (puncture needles, sheaths, guidewires, catheters, balloon, and endoprosthesis).
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It is important to emphasize that since ICM is required for balloon filling (Coda) during
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accommodation of the aortic prosthesis, we added the price of one 20 ml ICM flask to the total
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procedural cost for patients in the CO2 group who demanded less than 20 ml or no ICM .
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We evaluated the following outcomes in both groups: feasibility of the procedures;
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surgical outcomes; complications; total duration of the procedures and fluoroscopy time;
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glomerular filtration rate using the Cockcroft-Gault formula (11) before and three days after the
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procedure; quality of the angiographic images obtained with CO2; endovascular materials costs;
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and the costs of the contrasts.
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Statistical Analysis
169 Categorical variables were described using absolute frequencies and percentages and
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compared between groups by Fisher's exact test or Pearson's chi-square test. Numerical
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variables were analyzed for their distribution within Shapiro-Wilk and Boxplot graphs
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separately. Variables with normal distribution (Volume CO2, BMI, age and creatinine before and
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after surgery) were described by means and standard deviations and compared with Student's t
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tests. The homogeneity of variance was checked by Levene's test. The other numerical variables
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were described by medians and interquartile ranges and compared by nonparametric Mann-
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Whitney test. The minimum and maximum values were calculated for all variables.
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The level of significance was 5%.
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RESULTS
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We were able to perform the proposed procedure in all the patients treated in this
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series (ICM group and CO2 group). Conversion to open surgery was not necessary in any of the
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cases. However ,in the CO2 group, 10 of the 16 cases required ICM supplementation to finish the
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procedure.
The clinical results were good and all aneurysms were excluded from circulation. There
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was no mortality in this study and the patient who stayed in hospital the longest was discharged
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on post operative day four.
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The demographic and clinical profiles of the patients are presented in Table 1.
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Table 1 – Demographic and clinical profile of patients.
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No significant differences were observed for the demographic and clinical profiles of ACCEPTED MANUSCRIPT
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patients between the groups.
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Contrast volumes used in both groups are shown in Table 2. Among the 16 patients in the CO2 group, 10 (62.5%) received iodine supplement.
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Table 2- Operative details
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The use of CO2 as a contrast did not increase the duration of surgery or fluoroscopy time.
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The total duration of surgery and fluoroscopy time are also shown in Table 2.
In the CO2 group the treated aneurysms had a medium landing zone (distance from the
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lowest renal artery to the aneurysmatic aorta) of 28,1 mm (range 20 to 42mm) and medium
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angulation neck of 42,3 degrees (range 21 to 60 degrees).The medium diameter of the treated
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aneurysms was 65mm (range 52 to 85mm). In this group, associated procedures were
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necessary to adequately complete EVAR for eight patients. All these procedures, except the one
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who needed a loop snare, were previously predicted and not due to complications during the
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procedures. In 5 of these eight patients, embolization of the right internal iliac artery was
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necessary; in 1 patient, embolization of the left internal iliac artery and external iliac artery
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angioplasty (same case) were necessary; in another patient, renal artery angioplasty was
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performed; and in the last of the eight patients, after unsuccessful attempts to catheterize the
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contralateral limb, it was necessary to use a loop snare to capture the contralateral femoral
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guide.
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One case in the CO2 group had the left internal iliac artery covered unintentionally by
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the iliac endograft limb because we could not adequate visualize the origin of the artery. Since
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the right internal iliac artery remained patent, there were no repercussion in the postoperative
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period.
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In the ICM group the medium landingMANUSCRIPT zone of the treated aneurysms was 28,6 mm ACCEPTED
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(range 20 to 40mm) and angulation neck of 40,7 degrees (range 23 to 60 degrees) The medium
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diameter of the treated aneurysms was 63mm (range 50 to 88mm). In this group, 6 cases
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required associated procedures to complete EVAR: 1 needed proximal cuff insertion, 3 needed
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embolizations of the left internal iliac artery and 2 needed embolizations of the right internal
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iliac artery. These addictional procedures were also planned prior the surgery, with exception
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off the proximal cuff.
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The follow up time of the study vary from 9 to 55 months, and there were no
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reinterventions in either groups. As routine in our service we made a angioCTscan one month
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after the procedure in all patients. We found two type II endoleaks in the CO2 group and one
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type II endoleak in ICM group that were conservatively managed.
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Patients creatinine clearance levels (using Cockcroft-Gault formula) both pre- and postsurgery are illustrated in Table 3.
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Table 3 - Variations in creatinine clearance levels in the pre and post-operative period.
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post-operative period.
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There was no significant change in renal function in the ICM and CO2 groups in the
The evaluation of CO2 angiographies with the number of images from each location evaluated by each of the two observers are illustrated in Table V.
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Table 4- Evaluation of the images produced with CO2 by the observers, divided by
location.
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In evaluating images produced with CO2, we noticed the greatest amount of “poor” notes by both observers for internal iliac arteries.
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In the CO2 group, ACCEPTED 10 of the 16MANUSCRIPT cases required ICM supplementation. The
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supplementation with ICM was performed when the image produced with CO2 had significant
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loss of definition in the vessels, which precluded the safe completion of the procedure. In 5 of
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these cases, the only difficulty was to assess one internal iliac artery. In three cases, we needed
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ICM to assess one internal iliac artery and to assess the final angiography. In 2 cases, the
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iodinated contrast was used to assess only the final arteriography.
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Figures 1 and 2 illustrate images obtained using CO2 as contrast during EVAR.
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The endovascular materials costs and contrast media costs used are outlined in Table 5.
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Table 5 - Costs of endovascular materials and contrast media
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The endovascular material costs were similar in both groups; however, the contrast
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media cost in the ICM group was significantly more expensive than that observed in the CO2
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group.
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DISCUSSION
ICM is currently considered the gold standard for performing endovascular procedures,
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even though it is a nephrotoxic contrast and possesses high antigenicity. Knowing that CO2 is a
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therapeutic alternative for patients with contraindications to ICM, we aimed to investigate the
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possibility of a more widespread use for CO2. In this study, we attempted to establish the
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effectiveness of CO2 compared with iodinated contrast in patients with AAA who presented no
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contraindication to ICM. For this, we assigned the contrast media randomly.
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Complications with the use of intra-arterial CO2 (12) are possible, but in our study no
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adverse events were observed, corroborating with other larger studies previously published.
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(13). Regarding severe COPD patients, CO2 might in fact not be a good alternative, because of ACCEPTED MANUSCRIPT
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the CO2 retention risk, so injecting large amounts of CO2 might be problematic. Previous studies have used CO2 for performing EVAR but in patients with renal
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dysfunction. A retrospective cohort (14)compared the use of CO2 and ICM to perform EVAR in
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patients with chronic renal failure and considered the CO2 safe but with an increase in
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operative time and fluoroscopy time. In a retrospective analysis Criado et al(7) using CO2 for
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EVAR in 114 patients found a lower operative and fluoroscopy time compared to the ICM.
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We observed that is possible to perform EVAR exclusively with CO2 or with the
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supplemental use of small amounts of ICM in patients with no contra indication to ICM either.
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The use of CO2 as a contrast did not increase the duration of surgery or fluoroscopy, and when
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overall procedure time was increased, it was due to associated procedures performed along
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EVAR, and not the type of contrast used.
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There were no cases of post-operative acute renal failure in either group. Pre- and post-
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operative creatinine clearance levels were similar in both groups, as well as the clearance
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change pre-and post-operatively. The use of CO2 is expected not to alter the renal function,
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since it is used in patients with renal impairment exactly because of its absence of
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nephrotoxicity. There are many studies describing the nephrotoxicity of ICM (15), and in this
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study we propose that this deleterious effect was not significant because of the low volume of
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ICM utilized (medium 35.5 ml) and due to the renal protection therapy performed in all patients
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in the perioperative period.
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comparable to that produced with iodinated contrast medias, enabling successful completion of
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the endovascular procedures, with the use of no or very little ICM.
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The manual injection of CO2 without the need for pumps or injection systems is
considered safe (16) and makes its use more affordable and easily reproducible.
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In 8 procedures of CO2 group, ICM complementation was necessary in order to identify
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the internal iliac artery. In all of these cases, despite performing maneuvers to change position
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and the use a higher volume of CO2, we needed to utilize ICM to identify these arteries.
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Because of the gaseousACCEPTED characteristicsMANUSCRIPT of CO2, it tends to "float" on the anterior wall of
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the large arteries and visualization of branches with posterior origins in the vessel are more
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difficult with this type of contrast. This difficulty can be predicted in the pre-operative CT. In
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cases with favorable anatomy (non-posterior origin of the hypogastric artery) CO2 is sufficient;
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conversely, in cases where the location of the internal iliac artery is more posterior, ICM
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supplementation may be necessary.
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In all of the cases in the CO2 group, we could identify the lowest renal artery using CO2,
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and we were able to perform safe release of the main body of the stent-graft. In order to
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accomplish this, we must position the tip of a diagnostic VS1 catheter near the ostium of the
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lowest renal artery, in the position estimated by the pre-operative CT scan, and then inject CO2
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at the presumed location. With this technique, we obtained good quality images of all renal
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arteries, and did not need supplemental ICM in any case. Control aortography at the end of the
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procedure was performed with only CO2 in 11 patients in this group. This is a technique that
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has proved to be quite sensitive in another study seeking to identify endoleaks (17). However,
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in five procedures, in which we did not considered safe to finish the procedure with only the
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image produced with CO2, we needed ICM supplementation in order to safely assess the
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absence of endoleaks after final ballooning and to assess patency of the arterial tree. Iodine
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contrast confirmed that no endoleaks were present, and that arteries were patent.
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The endovascular material costs used in the procedures performed with the CO2 were
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similar to those performed with ICM. The presence of associated procedures (and not the type
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of contrast used) was a predictor of the variation in costs. The costs specifically related with
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intravascular contrast agents were significantly lower in the CO2 group, despite the inclusion of
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a 20 ml flask of ICM in all cases for the balloon filling. The contrast agent utilized had no
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significant burden on costs and the use of CO2 did not increase intervention costs.
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For daily practice, it has already been demonstrated the safety of CO2 use in patients
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with chronic kidney failure and AAA, and our study added this information in patients without
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kidney failure.
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We conclude that it is possible to perform EVAR with only CO2 in patients with no contra ACCEPTED MANUSCRIPT
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indication to ICM with non-posterior origin of the hypogastric artery. The supplementation of
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small amounts of ICM, especially for evaluating the origin of the internal iliac artery when its
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origin is posteriorly located may be necessary which can be foreseen with criterious analyses of
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the pre-operative CT angiography. This information is very important in patients that have
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some contraindication to ICM and are candidates to EVAR with CO2. If the origin of the internal
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iliac artery is posteriorly located some preparation and care must be taken before the
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procedure, since we can predict the need of iodine supplementation.
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CO2 utilization leads to similar outcomes when compared to the gold standard contrast
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(iodine) regarding duration of surgery, time of fluoroscopy and endovascular material costs,
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with no associated changes in creatinine clearance. Moreover, we did not observe any risk of
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hypersensitivity reactions, and we found a reduction in contrast-related costs in EVAR
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procedures.
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CO2 use in patients with no contra indication to ICM may decrease overall costs, and,
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when supplementation with iodine is necessary, the burden of nephrotoxicity may be
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diminished, as its volume is significantly lowered.Owing to relatively small patient number, no
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patients with difficult aortic anatomy and the absence of a longer follow up in the renal function,
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further studies are welcome to support our findings.
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Funding- Ministério da Saúde do Brasil
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402 403 404 405
17.
Cronin P, Patel JV, KesselACCEPTED DO, RobertsonMANUSCRIPT I, McPherson SJ. Carbon dioxide angiography: a simple and safe system of delivery. Clin Radiol. 2005 Jan. p. 123–5. Huang SG, Woo K, Moos JM, Han S, Lew WK, Chao A, et al. A Prospective Study of Carbon Dioxide Digital Subtraction versus Standard Contrast Arteriography in the Detection of Endoleaks in Endovascular Abdominal Aortic Aneurysm Repairs. Annals of Vascular Surgery. 2013Jan.;27(1):38–44.
406
408
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407 Tables
409 Table 1 – Demographic and clinical profile of patients.
SC
410 411
412
ICM group
n-16
n-20
71.5 (6.4)
70.6 (9.3)
61-81
54-88
13 (81.3)
17 (85)
>.990*
25.7
27
.364§
1 (6.3)
5 (25)
.196*
10 (62.5)
18 (90)
.103*
8 (50)
11 (55)
.765 #
6 (37.5)
12 (60)
.180#
Cardiac Failure (%)
2 (12.5)
2 (10)
>.990*
Coronary disease (%)
3 (18.8)
6 (30)
.700*
Additional Procedures (%)
9 (56.3)
7 (35)
.313#
Age Average (SD) Age Range
BMI Average (Kg/m2) Diabetes (%)
EP
Hypertension (%)
TE D
Gender Male (%)
History of tobacco use (%)
AC C
Dyslipidemia (%)
P
M AN U
CO2 group
413 414
.900§
415 416 417 418 419 420 421 422 423 424 425
426
§: - Student’s t test
427
*: Fisher’s exact test
428
#: Pearson’s Chi square test
15
429
ICM - Iodine Contrast Media, BMI - Body Mass Index, CO2 -Carbon Dioxide ACCEPTED MANUSCRIPT
430 431 432 433
Table 2- Operative details
436 437 CO2 group
CO2 volume Iodine volume Duration of surgery
0
5.5 ml (0-15)
35.5 ml (28.5-56.5)
180 min (162,5-195)
180 min (145-195)
0.552*
29.7 ml (23.6-37.7)
0.735*
TE D
438
Median (interquartile interval)
31.1 ml (25.3-36.4)
EP
(minutes)
p
155.5 ml (64-207.5)
(minutes) Fluoroscopy time
Iodine group
M AN U
Median (interquartile interval)
SC
435
RI PT
434
440 441 442 443
AC C
439 *: Mann-Whitney non-parametric test
444 445 446 447
16
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448 449 450 451 452
454
RI PT
453 Table 3 - Variations in creatinine clearance levels in the pre and post-operative period.
455 ICM
Interquartile
P#
SC
CO2
Interquartile
Interval
Median
Interval
Clear creat pre
53.9
(41.9-86.5)
82.6
(56.8-100.6)
.080
Clear creat post
79.4
(49.2-96.4)
91.7
(58.2-110.2)
.226
Delta Clear *
11.1
(-3.1-22.6)
11.7
(-5.1-19.5)
.799
M AN U
Median
#: non parametric Mann-Whitney test
457
Clear creat pre - creatinine clearance pre-operative
458
Clear creat post - creatinine clearance post-operative
459
* Delta clearance= creatinine clearance post-operative minus creatinine clearance pre-operative
462 463 464
EP
461
AC C
460
TE D
456
465 466 467 468
17
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469 470 471 472 473
475
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474 Table 4- Evaluation of the images produced with CO2 by the observers, divided by location.
476
SC
477
Grade poor
fair
8
5
poor
fair
good
11
8
9
7
(20.8)
(45.8)
(33.3)
(37.5)
(29.1)
6
10
1
7
9
(35.2)
(58.8)
(5.8)
(41.1)
(52.9)
2
8
2
3
8
1
(16.6)
(66.6)
(16.6)
(25.0)
(66.6)
(8.3)
artery
(33.3)
Renal Artery 1
(5.8)
AC C
Final
EP
angiography
TE D
angiography
n-17 (%)
Grade
good
Internal Iliac
n-24 (%)
Observer 2
M AN U
Observer 1
angiography n-12 (%)
478 479
N- number of images
480 481 482
18
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483 484 485 486 487
RI PT
488 489 490
Table 5 - Costs of endovascular materials and contrast media
SC
491 Group
endovascular material Median (interquartile Interval) contrast media
#: nonparametric Mann-Whitney test
493
Values in American dollars
495
(10884.8-12557.7)
(10898.4-11888.8)
10.12
25.00
(10.12-10.12)
(25.0-50.0)
.567 #
<.001 #
AC C
494
10984.8
EP
492
ICM
11483.8
TE D
Median (interquartile Interval)
M AN U
CO2
P
19
ACCEPTED MANUSCRIPT
Table 1 – Demographic and clinical profile of patients.
BMI Average (Kg/m2) Diabetes (%) Hypertension (%)
n-16
n-20
71.5 (6.4)
70.6 (9.3)
61-81
54-88
13 (81.3)
17 (85)
25.7
27
.364§
1 (6.3)
5 (25)
.196*
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Gender Male (%)
P
.900§
>.990*
SC
Age Range
ICM group
M AN U
Age Average (SD)
CO2 group
10 (62.5)
18 (90)
.103*
8 (50)
11 (55)
.765 #
Dyslipidemia (%)
6 (37.5)
12 (60)
.180#
Cardiac Failure (%)
2 (12.5)
2 (10)
>.990*
Coronary disease (%)
3 (18.8)
6 (30)
.700*
9 (56.3)
7 (35)
.313#
TE D
History of tobacco use (%)
Additional Procedures (%)
EP
§: - Student’s t test *: Fisher’s exact test
AC C
#: Pearson’s Chi square test
ICM - Iodine Contrast Media, BMI - Body Mass Index, CO2 -Carbon Dioxide
ACCEPTED MANUSCRIPT Table 2- Operative details
Iodine group
Median (interquartile interval)
Median (interquartile interval)
155.5 ml (64-207.5)
Iodine volume
5.5 ml (0-15)
Duration of surgery
180 min (162,5-195)
(minutes) 31.1 ml (25.3-36.4)
35.5 ml (28.5-56.5) 180 min (145-195)
M AN U
Fluoroscopy time (minutes)
AC C
EP
TE D
*: Mann-Whitney non-parametric test
p
0
SC
CO2 volume
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CO2 group
29.7 ml (23.6-37.7)
0.552*
0.735*
ACCEPTED MANUSCRIPT
Table 3 - Variations in creatinine clearance levels in the pre and post-operative period.
P# CO2
ICM Interquartile
Interval
Median
Clear creat pre
53.9
(41.9-86.5)
82.6
Clear creat post
79.4
(49.2-96.4)
91.7
Delta Clear *
11.1
(-3.1-22.6)
Interval
(56.8-100.6)
.080
(58.2-110.2)
.226
(-5.1-19.5)
.799
SC
Median
RI PT
Interquartile
M AN U
11.7
#: non parametric Mann-Whitney test
Clear creat pre - creatinine clearance pre-operative
Clear creat post - creatinine clearance post-operative
* Delta clearance= creatinine clearance post-operative minus creatinine clearance pre-
AC C
EP
TE D
operative
ACCEPTED MANUSCRIPT Table 4- Evaluation of the images produced with CO2 by the observers, divided by location.
Observer 2
Grade
Grade
fair
good
8
5
11
(33.3)
(20.8)
1
6
(5.8)
(35.2)
n-24 (%) Renal Artery
n-17 (%) Final
2 angiography
(16.6)
AC C
N- number of images
good
9
7
(33.3)
(37.5)
(29.1)
10
1
7
9
(58.8)
(5.8)
(41.1)
(52.9)
8
2
3
8
1
(66.6)
(16.6)
(25.0)
(66.6)
(8.3)
EP
n-12 (%)
fair
(45.8)
TE D
angiography
8
M AN U
angiography
poor
SC
poor Internal Iliac artery
RI PT
Observer 1
ACCEPTED MANUSCRIPT
Table 5 - Costs of endovascular materials and contrast media
CO2
P
RI PT
Group
ICM
endovascular material
11483.8
10984.8
Median (interquartile Interval)
(10884.8-12557.7)
(10898.4-11888.8)
contrast media
10.12
25.00
M AN U
Median (interquartile Interval)
(10.12-10.12)
#: nonparametric Mann-Whitney test
AC C
EP
TE D
Values in American dollars
SC
.567 #
(25.0-50.0)
<.001 #
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Figure 1. Legend: Aortic CO2 injection
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Figure 2. Legend: Iliac CO2 injection
S0890-5096(16)30843-3
DOI:
10.1016/j.avsg.2016.06.028
Reference:
AVSG 3013
To appear in:
Annals of Vascular Surgery
Received Date: 6 April 2016 Revised Date:
15 June 2016
Accepted Date: 17 June 2016
Please cite this article as: de Almeida Mendes C, de Arruda Martins A, Teivelis MP, Kuzniec S, Varella AYM, Wolosker N, Carbon dioxide as contrast medium to guide endovascular aortic aneurysm repair, Annals of Vascular Surgery (2016), doi: 10.1016/j.avsg.2016.06.028. 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.
1
Carbon dioxide as contrast medium to guide endovascular aortic aneurysm repair.
ACCEPTED MANUSCRIPT
2 Cynthia de Almeida Mendes MD- Hospital Israelita Albert Einstein and Hospital Municipal Dr
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Moyses Deutsch- Mboi Mirim ( [email protected])
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Alexandre de Arruda Martins MD - Hospital Israelita Albert Einstein and Hospital Municipal Dr
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Moyses Deutsch- Mboi Mirim ( [email protected])
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Marcelo Passos Teivelis MD- Hospital Israelita Albert Einstein ([email protected])
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Sergio Kuzniec MD, PhD- Hospital Israelita Albert Einstein ([email protected])
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Andrea Yasbek Monteiro Varella MD- Hospital Israelita Albert Einstein ([email protected]) Nelson Wolosker MD, PhD- Hospital Israelita Albert Einstein ([email protected])
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Corresponding author- Cynthia de Almeida Mendes
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[email protected]
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Av Albert Einstein 627 - Bloco A1 - 4º andar - sala 423
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Morumbi - São Paulo - SP – Brasil-CEP 05652-000
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Supports: Ministério da Saúde do Brasil
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Original Article
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Keywords- aortic aneurysm, endovascular, carbon dioxide
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Abstract
30 31 32 33
Background Iodine contrast medium (ICM) is considered gold standard in endovascular procedures, but nephrotoxicity and hypersensitivity limit its widespread use. Carbon dioxide (CO2) is considered an alternative for endovascular procedures in
35
patients with contraindication to ICM. However no studies have compared the outcomes of
36
EVAR (endovascular aneurysm repair) performed with ICM or CO2 in patients with no
37
contraindication to ICM.
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34
Methods and Results
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From May 2012 to April 2014, 36 patients with abdominal aortic aneurysms underwent
41
EVAR in a prospective, randomized and controlled study. Patients were randomized into 2
42
groups, either the CO2 or ICM group. We were able to perform the proposed procedures in all
43
patients in this study. There were no conversions to open surgery and no CO2-related
44
complications. Endovascular material costs, duration of surgery and time of fluoroscopy were
45
similar between groups, and the cost of the contrast-media was smaller in the CO2 group than
46
in the ICM group. In the CO2 group, it was necessary complement with ICM in 62.5% of the
47
patients.
48
Conclusions
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The use of CO2 as a contrast for EVAR is an alternative in patients with no restriction for
50
ICM, with similar outcomes when compared to ICM, regarding duration of surgery, duration of
51
fluoroscopy and endovascular material costs. With CO2, there were no associated changes in
52
creatinine clearance and no risk of hypersensitivity reactions; moreover, there was a reduction
53
in contrast-related costs for EVAR procedures. However, in our study, most cases needed a
54
supplement of ICM to visualize the internal iliac artery.
55 2
56
ACCEPTED MANUSCRIPT
INTRODUCTION
57 Abdominal aortic aneurysm (AAA) is a common condition, with a prevalence rate of
59
5.7 % in the population. Even though there is a rationale for medical treatment (1), ,surgery is
60
considered the best treatment. Endovascular aneurysm repair (EVAR) has emerged as a less
61
invasive and less morbid option when compared to conventional open surgery. In the USA, the
62
overall use of EVAR (2)has risen sharply in the past 10 years (5.2% to 74% of the total number
63
of AAA repairs) even though the total number of AAAs remains stable at 45.000 cases per year
64
(3).
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The use of iodine contrast medium (ICM) is currently considered the gold standard in
66
endovascular procedures, but its nephrotoxicity and hypersensitivity reactions limit its
67
widespread use (4), (5)(6).
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Carbon dioxide (CO2) was initially described as an endovascular contrast media in 1970
69
by Hawkins et al. However, because it is a gaseous contrast agent and had some particularities,
70
its use was not widespread until the 2000s, when the endovascular treatment became
71
mainstream and the use of ICM presented as a limitation to treat patients with renal impairment.
72
Currently, CO2 can be considered an alternative for aortic (,7), aorto-iliac(,8) and
73
femoro-popliteal (9) procedures only in patients with formal contraindication to ICM ( renal
74
impairment or iodine-related hypersensitivity). However, to our knowledge, no studies have
75
compared the outcomes EVAR performed with either ICM or CO2 in patients eligible for use of
76
both contrast media by a randomized and prospective approach. Attempting to evaluate if CO2
77
is as effective as ICM for EVAR in patients with no contra indication to ICM we elaborated this
78
prospective study to compare the feasibility, quality of the angiographic images, clinical
79
outcomes and the relative costs of EVAR using CO2 or ICM as contrast mediums, and here we
80
show our results.
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81 82 83
3
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84 85 86
METHODS
87 From May 2012 to April 2014, 36 patients with infra-renal aortic aneurysms (identified
89
on preoperative angioCT scan) and normal renal function underwent EVAR in a prospective,
90
randomized and controlled study. This study was approved by the Ethics Committee for
91
Analysis of Research Projects on Human Experimentation at our institution. Regarding the
92
anatomy of the cases none of the included patients had proximal aortic neck with angle greater
93
than 60 degrees, proximal aortic neck length less than 20mm or thrombus or calcification in
94
more than 50% of the proximal aortic neck. The clinical exclusion criteria were chronic
95
obstructive pulmonary disease, severe heart failure (on whom surgery was contra-indicated
96
because they were deemed to be very high risk on clinical grounds) or kidney failure (creatinine
97
clearance less than 30 ml/min using the CocKroft Gault formula), pregnancy or patients who
98
had the aortic anatomy described above.
100
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All patients signed informed consent forms agreeing upon the use of either contrast medium.
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Patients were randomized into 2 groups, the CO2 and ICM groups, according to the
102
contrast media used in the procedure. Randomization was performed by a computer-generated
103
list immediately prior to the beginning of the surgeries, in a one to one ratio. An endovascular suite operating room (Philips Allura Xper FD – Netherlands) was used
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104
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101
105
in all procedures. This equipment has a specific CO2 mode for performing procedures with CO2
106
as contrast.
107 108 109 110 111
The patients were operated under general anesthesia with cardiac monitoring, invasive
arterial pressure monitoring and bladder catheterization. The patients underwent the procedure by the same surgical team (four surgeons) using a constant surgical technique throughout the study. Surgical procedures were performed using conventional technique for EVAR with
4
112
bilateral oblique inguinal incisions, followed by a bilateral dissection of the common femoral ACCEPTED MANUSCRIPT
113
arteries. We finished the procedure with femoral artery suture, hemostasis, and closure of the
114
incision in multiple layers. As routine in our hospital, all patients were referred to the intensive care unit
116
immediately after the operation for at least 24 hours and received intravenous fluids following a
117
fixed protocol for renal protection regardless of the contrast media used. The protocol for renal
118
protection included intravenous fluids pre-procedure in addition to endovenous acetylcysteine,
119
followed by intravenous fluid maintenance for 24 hours. Thereafter, patients remained
120
hospitalized for the time needed to recover (at least 72 hours), with daily monitoring of renal
121
function, blood count and electrolytes.
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The CO2 injection was performed manually, without any specific pump system. A
123
cylinder with medicinal CO2 , a particle filter (Millex® Durapore® hydrophilic 0.22 μm pore)
124
and a three-way stopcock were used to aspirate CO2 ; This was performed inside a bowl with
125
saline solution. After acquiring the required volume of CO2,, an additional 5 ml of saline solution
126
was aspired into the syringe to provide a water seal while the needle tip was kept down. This
127
way, a physical barrier was created between the room air and carbon dioxide content, which is
128
independent of manual compression and is protected from air contamination (10). Twenty or
129
60 ml syringes were used for the intra-arterial CO2 injection, performed using a femoral
130
introducer or through an end hole catheter.
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ICM injection was performed manually with 10 ml syringes using 3 ml iodinated
132
contrast media and 7 ml saline solution per injection. During the final control aortography in the
133
ICM group, an injection pump was used, with a half to half dilution of ICM and saline solution.
134
The ICM used in all cases was Omnipaque (Iohexol) 300, a nonionic low osmolar contrast
135
routinely used in our studies.
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136
The endovascular material (sheaths, guidewires, stents and endoprosthesis) used in all
137
procedures was provided by Cook Medical Inc . The endoprosthesis used in all cases was
138
Zenith Flex . The volumes of ICM and CO2, duration of the procedure, duration of X-ray
5
139
exposure and the endovascularACCEPTED material used MANUSCRIPT in each intervention were precisely recorded for
140
further analysis.
141
In cases where it was necessary to perform internal iliac artery embolization, renal
142
angioplasty, iliac angioplasty or when it was necessary to use a proximal cuff, we considered
143
these as associated procedures, and all the material that was utilized was also accounted. All procedures were recorded on DVD for further analysis of the angiographic images.
145
Two observers, also vascular surgeons, who did not take part in the intervention and had no
146
experience with the use of CO2 analyzed the data. Each film was analyzed separately by the two
147
observers.
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The images obtained with CO2 were analyzed separately for: renal arteries, internal iliac arteries, and final control angiography.
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Observers attributed a score for each image ranging from 1 to 3. A score of 1, considered
151
poor, was assigned when there was significant loss of definition in the vessels, which precluded
152
the procedure; a score of 2, considered fair, was assigned when there was some loss of
153
definition in the vessels but did not hinder intervention; and a score of 3, considered good, was
154
assigned when there was good contrast in the vessels.
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Each intervention was analyzed evaluating contrast media costs and endovascular
156
material used (puncture needles, sheaths, guidewires, catheters, balloon, and endoprosthesis).
157
It is important to emphasize that since ICM is required for balloon filling (Coda) during
158
accommodation of the aortic prosthesis, we added the price of one 20 ml ICM flask to the total
159
procedural cost for patients in the CO2 group who demanded less than 20 ml or no ICM .
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We evaluated the following outcomes in both groups: feasibility of the procedures;
161
surgical outcomes; complications; total duration of the procedures and fluoroscopy time;
162
glomerular filtration rate using the Cockcroft-Gault formula (11) before and three days after the
163
procedure; quality of the angiographic images obtained with CO2; endovascular materials costs;
164
and the costs of the contrasts.
165 166
6
ACCEPTED MANUSCRIPT
167 168
Statistical Analysis
169 Categorical variables were described using absolute frequencies and percentages and
171
compared between groups by Fisher's exact test or Pearson's chi-square test. Numerical
172
variables were analyzed for their distribution within Shapiro-Wilk and Boxplot graphs
173
separately. Variables with normal distribution (Volume CO2, BMI, age and creatinine before and
174
after surgery) were described by means and standard deviations and compared with Student's t
175
tests. The homogeneity of variance was checked by Levene's test. The other numerical variables
176
were described by medians and interquartile ranges and compared by nonparametric Mann-
177
Whitney test. The minimum and maximum values were calculated for all variables.
178
The level of significance was 5%.
179 180 181
RESULTS
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We were able to perform the proposed procedure in all the patients treated in this
184
series (ICM group and CO2 group). Conversion to open surgery was not necessary in any of the
185
cases. However ,in the CO2 group, 10 of the 16 cases required ICM supplementation to finish the
186
procedure.
The clinical results were good and all aneurysms were excluded from circulation. There
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188
was no mortality in this study and the patient who stayed in hospital the longest was discharged
189
on post operative day four.
190
The demographic and clinical profiles of the patients are presented in Table 1.
191 192
Table 1 – Demographic and clinical profile of patients.
193 194
7
No significant differences were observed for the demographic and clinical profiles of ACCEPTED MANUSCRIPT
195 196
patients between the groups.
197 198
Contrast volumes used in both groups are shown in Table 2. Among the 16 patients in the CO2 group, 10 (62.5%) received iodine supplement.
199 200
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Table 2- Operative details
201 202
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The use of CO2 as a contrast did not increase the duration of surgery or fluoroscopy time.
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The total duration of surgery and fluoroscopy time are also shown in Table 2.
In the CO2 group the treated aneurysms had a medium landing zone (distance from the
207
lowest renal artery to the aneurysmatic aorta) of 28,1 mm (range 20 to 42mm) and medium
208
angulation neck of 42,3 degrees (range 21 to 60 degrees).The medium diameter of the treated
209
aneurysms was 65mm (range 52 to 85mm). In this group, associated procedures were
210
necessary to adequately complete EVAR for eight patients. All these procedures, except the one
211
who needed a loop snare, were previously predicted and not due to complications during the
212
procedures. In 5 of these eight patients, embolization of the right internal iliac artery was
213
necessary; in 1 patient, embolization of the left internal iliac artery and external iliac artery
214
angioplasty (same case) were necessary; in another patient, renal artery angioplasty was
215
performed; and in the last of the eight patients, after unsuccessful attempts to catheterize the
216
contralateral limb, it was necessary to use a loop snare to capture the contralateral femoral
217
guide.
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One case in the CO2 group had the left internal iliac artery covered unintentionally by
219
the iliac endograft limb because we could not adequate visualize the origin of the artery. Since
220
the right internal iliac artery remained patent, there were no repercussion in the postoperative
221
period.
8
In the ICM group the medium landingMANUSCRIPT zone of the treated aneurysms was 28,6 mm ACCEPTED
223
(range 20 to 40mm) and angulation neck of 40,7 degrees (range 23 to 60 degrees) The medium
224
diameter of the treated aneurysms was 63mm (range 50 to 88mm). In this group, 6 cases
225
required associated procedures to complete EVAR: 1 needed proximal cuff insertion, 3 needed
226
embolizations of the left internal iliac artery and 2 needed embolizations of the right internal
227
iliac artery. These addictional procedures were also planned prior the surgery, with exception
228
off the proximal cuff.
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The follow up time of the study vary from 9 to 55 months, and there were no
230
reinterventions in either groups. As routine in our service we made a angioCTscan one month
231
after the procedure in all patients. We found two type II endoleaks in the CO2 group and one
232
type II endoleak in ICM group that were conservatively managed.
234
Patients creatinine clearance levels (using Cockcroft-Gault formula) both pre- and postsurgery are illustrated in Table 3.
235
Table 3 - Variations in creatinine clearance levels in the pre and post-operative period.
237 238
241 242 243 244 245
post-operative period.
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There was no significant change in renal function in the ICM and CO2 groups in the
The evaluation of CO2 angiographies with the number of images from each location evaluated by each of the two observers are illustrated in Table V.
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Table 4- Evaluation of the images produced with CO2 by the observers, divided by
location.
246 247 248 249
In evaluating images produced with CO2, we noticed the greatest amount of “poor” notes by both observers for internal iliac arteries.
9
In the CO2 group, ACCEPTED 10 of the 16MANUSCRIPT cases required ICM supplementation. The
251
supplementation with ICM was performed when the image produced with CO2 had significant
252
loss of definition in the vessels, which precluded the safe completion of the procedure. In 5 of
253
these cases, the only difficulty was to assess one internal iliac artery. In three cases, we needed
254
ICM to assess one internal iliac artery and to assess the final angiography. In 2 cases, the
255
iodinated contrast was used to assess only the final arteriography.
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256
Figures 1 and 2 illustrate images obtained using CO2 as contrast during EVAR.
257
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258 259
The endovascular materials costs and contrast media costs used are outlined in Table 5.
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Table 5 - Costs of endovascular materials and contrast media
262
The endovascular material costs were similar in both groups; however, the contrast
264
media cost in the ICM group was significantly more expensive than that observed in the CO2
265
group.
267
269 270
DISCUSSION
ICM is currently considered the gold standard for performing endovascular procedures,
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271
even though it is a nephrotoxic contrast and possesses high antigenicity. Knowing that CO2 is a
272
therapeutic alternative for patients with contraindications to ICM, we aimed to investigate the
273
possibility of a more widespread use for CO2. In this study, we attempted to establish the
274
effectiveness of CO2 compared with iodinated contrast in patients with AAA who presented no
275
contraindication to ICM. For this, we assigned the contrast media randomly.
276
Complications with the use of intra-arterial CO2 (12) are possible, but in our study no
277
adverse events were observed, corroborating with other larger studies previously published.
10
278
(13). Regarding severe COPD patients, CO2 might in fact not be a good alternative, because of ACCEPTED MANUSCRIPT
279
the CO2 retention risk, so injecting large amounts of CO2 might be problematic. Previous studies have used CO2 for performing EVAR but in patients with renal
281
dysfunction. A retrospective cohort (14)compared the use of CO2 and ICM to perform EVAR in
282
patients with chronic renal failure and considered the CO2 safe but with an increase in
283
operative time and fluoroscopy time. In a retrospective analysis Criado et al(7) using CO2 for
284
EVAR in 114 patients found a lower operative and fluoroscopy time compared to the ICM.
RI PT
280
We observed that is possible to perform EVAR exclusively with CO2 or with the
286
supplemental use of small amounts of ICM in patients with no contra indication to ICM either.
287
The use of CO2 as a contrast did not increase the duration of surgery or fluoroscopy, and when
288
overall procedure time was increased, it was due to associated procedures performed along
289
EVAR, and not the type of contrast used.
M AN U
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There were no cases of post-operative acute renal failure in either group. Pre- and post-
291
operative creatinine clearance levels were similar in both groups, as well as the clearance
292
change pre-and post-operatively. The use of CO2 is expected not to alter the renal function,
293
since it is used in patients with renal impairment exactly because of its absence of
294
nephrotoxicity. There are many studies describing the nephrotoxicity of ICM (15), and in this
295
study we propose that this deleterious effect was not significant because of the low volume of
296
ICM utilized (medium 35.5 ml) and due to the renal protection therapy performed in all patients
297
in the perioperative period.
EP
The use of CO2 by experienced physicians provides angiographic imaging quality
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298
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290
299
comparable to that produced with iodinated contrast medias, enabling successful completion of
300
the endovascular procedures, with the use of no or very little ICM.
301 302
The manual injection of CO2 without the need for pumps or injection systems is
considered safe (16) and makes its use more affordable and easily reproducible.
303
In 8 procedures of CO2 group, ICM complementation was necessary in order to identify
304
the internal iliac artery. In all of these cases, despite performing maneuvers to change position
305
and the use a higher volume of CO2, we needed to utilize ICM to identify these arteries.
11
Because of the gaseousACCEPTED characteristicsMANUSCRIPT of CO2, it tends to "float" on the anterior wall of
307
the large arteries and visualization of branches with posterior origins in the vessel are more
308
difficult with this type of contrast. This difficulty can be predicted in the pre-operative CT. In
309
cases with favorable anatomy (non-posterior origin of the hypogastric artery) CO2 is sufficient;
310
conversely, in cases where the location of the internal iliac artery is more posterior, ICM
311
supplementation may be necessary.
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306
In all of the cases in the CO2 group, we could identify the lowest renal artery using CO2,
313
and we were able to perform safe release of the main body of the stent-graft. In order to
314
accomplish this, we must position the tip of a diagnostic VS1 catheter near the ostium of the
315
lowest renal artery, in the position estimated by the pre-operative CT scan, and then inject CO2
316
at the presumed location. With this technique, we obtained good quality images of all renal
317
arteries, and did not need supplemental ICM in any case. Control aortography at the end of the
318
procedure was performed with only CO2 in 11 patients in this group. This is a technique that
319
has proved to be quite sensitive in another study seeking to identify endoleaks (17). However,
320
in five procedures, in which we did not considered safe to finish the procedure with only the
321
image produced with CO2, we needed ICM supplementation in order to safely assess the
322
absence of endoleaks after final ballooning and to assess patency of the arterial tree. Iodine
323
contrast confirmed that no endoleaks were present, and that arteries were patent.
TE D
M AN U
SC
312
The endovascular material costs used in the procedures performed with the CO2 were
325
similar to those performed with ICM. The presence of associated procedures (and not the type
326
of contrast used) was a predictor of the variation in costs. The costs specifically related with
327
intravascular contrast agents were significantly lower in the CO2 group, despite the inclusion of
328
a 20 ml flask of ICM in all cases for the balloon filling. The contrast agent utilized had no
329
significant burden on costs and the use of CO2 did not increase intervention costs.
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330
For daily practice, it has already been demonstrated the safety of CO2 use in patients
331
with chronic kidney failure and AAA, and our study added this information in patients without
332
kidney failure.
12
We conclude that it is possible to perform EVAR with only CO2 in patients with no contra ACCEPTED MANUSCRIPT
334
indication to ICM with non-posterior origin of the hypogastric artery. The supplementation of
335
small amounts of ICM, especially for evaluating the origin of the internal iliac artery when its
336
origin is posteriorly located may be necessary which can be foreseen with criterious analyses of
337
the pre-operative CT angiography. This information is very important in patients that have
338
some contraindication to ICM and are candidates to EVAR with CO2. If the origin of the internal
339
iliac artery is posteriorly located some preparation and care must be taken before the
340
procedure, since we can predict the need of iodine supplementation.
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333
CO2 utilization leads to similar outcomes when compared to the gold standard contrast
342
(iodine) regarding duration of surgery, time of fluoroscopy and endovascular material costs,
343
with no associated changes in creatinine clearance. Moreover, we did not observe any risk of
344
hypersensitivity reactions, and we found a reduction in contrast-related costs in EVAR
345
procedures.
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CO2 use in patients with no contra indication to ICM may decrease overall costs, and,
347
when supplementation with iodine is necessary, the burden of nephrotoxicity may be
348
diminished, as its volume is significantly lowered.Owing to relatively small patient number, no
349
patients with difficult aortic anatomy and the absence of a longer follow up in the renal function,
350
further studies are welcome to support our findings.
353 354 355 356
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Funding- Ministério da Saúde do Brasil
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357 358 359 360
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References
362 1.
Kurosawa K, Matsumura JS, Yamanouchi D. Current status of medical treatment for abdominal aortic aneurysm. Circ. J. 2013Jan.1;77(12):2860–6.
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Puech-Leão P, Wolosker N, Zerati AE, Nascimento LD. Impact of endovascular technique in vascular surgery training at a large university hospital in Brazil. J Surg Educ. 2011Jan.;68(1):19–23.
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3.
Dua A, Kuy S, Lee CJ, Upchurch GR, Desai SS. Epidemiology of aortic aneurysm repair in the United States from 2000 to 2010. J. Vasc. Surg. 2014Feb.20.
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4.
Tepel M, Aspelin P, Lameire N. Contrast-Induced Nephropathy. Circulation. 2006.
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5.
Morcos S, Thomsen H. Adverse reactions to iodinated contrast media. European radiology. Springer; 2001;11(7):1267–75.
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6.
Wolosker N, Nakano L, Anacleto MMM, Puech-Leão P. Primary utilization of stents in angioplasty of superficial femoral artery. Vasc Endovascular Surg. 2003Jul.;37(4):271–7.
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Criado E, Upchurch GR, Young K, Rectenwald JE, Coleman DM, Eliason JL, et al. Endovascular aortic aneurysm repair with carbon dioxide-guided angiography in patients with renal insufficiency. J. Vasc. Surg. 2012Jun.;55(6):1570–5.
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8.
Kawasaki D, Fujii K, Fukunaga M, Masutani M, Nakata A, Masuyama T. Safety and efficacy of endovascular therapy with a simple homemade carbon dioxide delivery system in patients with ileofemoral artery diseases. Circ. J. 2012;76(7):1722–8.
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9.
de Almeida Mendes C, de Arruda Martins A, Teivelis MP, Kuzniec S, Nishinari K, Krutman M, et al. Carbon dioxide is a cost-effective contrast medium to guide revascularization of TASC A and TASC B femoropopliteal occlusive disease. Annals of Vascular Surgery. 2014Apr.2.
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10.
Mendes C de A, Wolosker N, Krutman M. A simple homemade carbon dioxide delivery system for endovascular procedures in the iliofemoral arteries. Circ. J. 2013Feb.25;77(3):831.
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Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41.
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12.
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13.
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14.
Chao A, Major K, Kumar SR, Patel K, Trujillo I, Hood DB, et al. Carbon dioxide digital subtraction angiography–assisted endovascular aortic aneurysm repair in the azotemic patient. J. Vasc. Surg. 2007Mar.;45(3):451–60.
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15.
Guidelines on the use of iodinated contrast media in patients with kidney disease 2012: digest version: JSN, JRS, and JCS Joint Working Group. Circ. J. 2013. p. 1883–914.
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Johnson PL, Neperud J, Arnold J, Thomas J. Livedo reticularis and bowel ischemia after carbon dioxide arteriography in a patient with CREST syndrome. J Vasc Interv Radiol. 2011Mar.;22(3):395–9. Moos JM, Ham SW, Han SM, Lew WK, Hua HT, Hood DB, et al. Safety of carbon dioxide digital subtraction angiography. Arch Surg. 2011Dec.;146(12):1428–32.
14
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16.
402 403 404 405
17.
Cronin P, Patel JV, KesselACCEPTED DO, RobertsonMANUSCRIPT I, McPherson SJ. Carbon dioxide angiography: a simple and safe system of delivery. Clin Radiol. 2005 Jan. p. 123–5. Huang SG, Woo K, Moos JM, Han S, Lew WK, Chao A, et al. A Prospective Study of Carbon Dioxide Digital Subtraction versus Standard Contrast Arteriography in the Detection of Endoleaks in Endovascular Abdominal Aortic Aneurysm Repairs. Annals of Vascular Surgery. 2013Jan.;27(1):38–44.
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408
RI PT
407 Tables
409 Table 1 – Demographic and clinical profile of patients.
SC
410 411
412
ICM group
n-16
n-20
71.5 (6.4)
70.6 (9.3)
61-81
54-88
13 (81.3)
17 (85)
>.990*
25.7
27
.364§
1 (6.3)
5 (25)
.196*
10 (62.5)
18 (90)
.103*
8 (50)
11 (55)
.765 #
6 (37.5)
12 (60)
.180#
Cardiac Failure (%)
2 (12.5)
2 (10)
>.990*
Coronary disease (%)
3 (18.8)
6 (30)
.700*
Additional Procedures (%)
9 (56.3)
7 (35)
.313#
Age Average (SD) Age Range
BMI Average (Kg/m2) Diabetes (%)
EP
Hypertension (%)
TE D
Gender Male (%)
History of tobacco use (%)
AC C
Dyslipidemia (%)
P
M AN U
CO2 group
413 414
.900§
415 416 417 418 419 420 421 422 423 424 425
426
§: - Student’s t test
427
*: Fisher’s exact test
428
#: Pearson’s Chi square test
15
429
ICM - Iodine Contrast Media, BMI - Body Mass Index, CO2 -Carbon Dioxide ACCEPTED MANUSCRIPT
430 431 432 433
Table 2- Operative details
436 437 CO2 group
CO2 volume Iodine volume Duration of surgery
0
5.5 ml (0-15)
35.5 ml (28.5-56.5)
180 min (162,5-195)
180 min (145-195)
0.552*
29.7 ml (23.6-37.7)
0.735*
TE D
438
Median (interquartile interval)
31.1 ml (25.3-36.4)
EP
(minutes)
p
155.5 ml (64-207.5)
(minutes) Fluoroscopy time
Iodine group
M AN U
Median (interquartile interval)
SC
435
RI PT
434
440 441 442 443
AC C
439 *: Mann-Whitney non-parametric test
444 445 446 447
16
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448 449 450 451 452
454
RI PT
453 Table 3 - Variations in creatinine clearance levels in the pre and post-operative period.
455 ICM
Interquartile
P#
SC
CO2
Interquartile
Interval
Median
Interval
Clear creat pre
53.9
(41.9-86.5)
82.6
(56.8-100.6)
.080
Clear creat post
79.4
(49.2-96.4)
91.7
(58.2-110.2)
.226
Delta Clear *
11.1
(-3.1-22.6)
11.7
(-5.1-19.5)
.799
M AN U
Median
#: non parametric Mann-Whitney test
457
Clear creat pre - creatinine clearance pre-operative
458
Clear creat post - creatinine clearance post-operative
459
* Delta clearance= creatinine clearance post-operative minus creatinine clearance pre-operative
462 463 464
EP
461
AC C
460
TE D
456
465 466 467 468
17
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469 470 471 472 473
475
RI PT
474 Table 4- Evaluation of the images produced with CO2 by the observers, divided by location.
476
SC
477
Grade poor
fair
8
5
poor
fair
good
11
8
9
7
(20.8)
(45.8)
(33.3)
(37.5)
(29.1)
6
10
1
7
9
(35.2)
(58.8)
(5.8)
(41.1)
(52.9)
2
8
2
3
8
1
(16.6)
(66.6)
(16.6)
(25.0)
(66.6)
(8.3)
artery
(33.3)
Renal Artery 1
(5.8)
AC C
Final
EP
angiography
TE D
angiography
n-17 (%)
Grade
good
Internal Iliac
n-24 (%)
Observer 2
M AN U
Observer 1
angiography n-12 (%)
478 479
N- number of images
480 481 482
18
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483 484 485 486 487
RI PT
488 489 490
Table 5 - Costs of endovascular materials and contrast media
SC
491 Group
endovascular material Median (interquartile Interval) contrast media
#: nonparametric Mann-Whitney test
493
Values in American dollars
495
(10884.8-12557.7)
(10898.4-11888.8)
10.12
25.00
(10.12-10.12)
(25.0-50.0)
.567 #
<.001 #
AC C
494
10984.8
EP
492
ICM
11483.8
TE D
Median (interquartile Interval)
M AN U
CO2
P
19
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Table 1 – Demographic and clinical profile of patients.
BMI Average (Kg/m2) Diabetes (%) Hypertension (%)
n-16
n-20
71.5 (6.4)
70.6 (9.3)
61-81
54-88
13 (81.3)
17 (85)
25.7
27
.364§
1 (6.3)
5 (25)
.196*
RI PT
Gender Male (%)
P
.900§
>.990*
SC
Age Range
ICM group
M AN U
Age Average (SD)
CO2 group
10 (62.5)
18 (90)
.103*
8 (50)
11 (55)
.765 #
Dyslipidemia (%)
6 (37.5)
12 (60)
.180#
Cardiac Failure (%)
2 (12.5)
2 (10)
>.990*
Coronary disease (%)
3 (18.8)
6 (30)
.700*
9 (56.3)
7 (35)
.313#
TE D
History of tobacco use (%)
Additional Procedures (%)
EP
§: - Student’s t test *: Fisher’s exact test
AC C
#: Pearson’s Chi square test
ICM - Iodine Contrast Media, BMI - Body Mass Index, CO2 -Carbon Dioxide
ACCEPTED MANUSCRIPT Table 2- Operative details
Iodine group
Median (interquartile interval)
Median (interquartile interval)
155.5 ml (64-207.5)
Iodine volume
5.5 ml (0-15)
Duration of surgery
180 min (162,5-195)
(minutes) 31.1 ml (25.3-36.4)
35.5 ml (28.5-56.5) 180 min (145-195)
M AN U
Fluoroscopy time (minutes)
AC C
EP
TE D
*: Mann-Whitney non-parametric test
p
0
SC
CO2 volume
RI PT
CO2 group
29.7 ml (23.6-37.7)
0.552*
0.735*
ACCEPTED MANUSCRIPT
Table 3 - Variations in creatinine clearance levels in the pre and post-operative period.
P# CO2
ICM Interquartile
Interval
Median
Clear creat pre
53.9
(41.9-86.5)
82.6
Clear creat post
79.4
(49.2-96.4)
91.7
Delta Clear *
11.1
(-3.1-22.6)
Interval
(56.8-100.6)
.080
(58.2-110.2)
.226
(-5.1-19.5)
.799
SC
Median
RI PT
Interquartile
M AN U
11.7
#: non parametric Mann-Whitney test
Clear creat pre - creatinine clearance pre-operative
Clear creat post - creatinine clearance post-operative
* Delta clearance= creatinine clearance post-operative minus creatinine clearance pre-
AC C
EP
TE D
operative
ACCEPTED MANUSCRIPT Table 4- Evaluation of the images produced with CO2 by the observers, divided by location.
Observer 2
Grade
Grade
fair
good
8
5
11
(33.3)
(20.8)
1
6
(5.8)
(35.2)
n-24 (%) Renal Artery
n-17 (%) Final
2 angiography
(16.6)
AC C
N- number of images
good
9
7
(33.3)
(37.5)
(29.1)
10
1
7
9
(58.8)
(5.8)
(41.1)
(52.9)
8
2
3
8
1
(66.6)
(16.6)
(25.0)
(66.6)
(8.3)
EP
n-12 (%)
fair
(45.8)
TE D
angiography
8
M AN U
angiography
poor
SC
poor Internal Iliac artery
RI PT
Observer 1
ACCEPTED MANUSCRIPT
Table 5 - Costs of endovascular materials and contrast media
CO2
P
RI PT
Group
ICM
endovascular material
11483.8
10984.8
Median (interquartile Interval)
(10884.8-12557.7)
(10898.4-11888.8)
contrast media
10.12
25.00
M AN U
Median (interquartile Interval)
(10.12-10.12)
#: nonparametric Mann-Whitney test
AC C
EP
TE D
Values in American dollars
SC
.567 #
(25.0-50.0)
<.001 #
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT Figure 1. Legend: Aortic CO2 injection
AC C
EP
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M AN U
SC
RI PT
Figure 2. Legend: Iliac CO2 injection