Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 7  |  Issue : 4  |  Page : 370-375

Evaluation of carbon dioxide angiography in lower limb angioplasties of peripheral arterial disease patients with borderline chronic kidney disease compared to the standard contrast agent


Department of Vascular Surgery, Institute of Vascular and Endovascular Sciences, Sir Ganga Ram Hospital, Delhi, India

Date of Submission13-May-2020
Date of Decision01-Jun-2020
Date of Acceptance06-Jun-2020
Date of Web Publication24-Dec-2020

Correspondence Address:
Nikhil Vilas Chaudhari
Department of Vascular Surgery, Institute of Vascular and Endovascular Sciences, Sir Ganga Ram Hospital, Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_61_20

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  Abstract 


Introduction: Assessment of carbon dioxide (CO2) angiography for its efficacy and limitations in lower limb angioplasties for chronic limb-threatening limb ischemia needs to be evaluated in detail, as the use of CO2 as a contrast agent has a distinct advantage over conventional iodinated contrast medium (ICM) in patients with borderline chronic kidney disease (CKD), with respect to nephrotoxicity caused by the later. Aims and Objectives: To study the quality of angiography images obtained with CO2 as a contrast agent and the efficacy of CO2 angiography in guiding lower limb angioplasties for critical limb ischemia. Design: This was a prospective, observational, comparative, cohort study. Study Period: September 2017–December 2018. Materials and Methods: Patients of critical limb ischemia with raised serum creatinine level (>1.49 mg/dL) who were not on the dialysis and undergoing endovascular revascularization were enrolled in the study. Hand injections were made using CO2 Angioset. Intraoperative evaluation of image quality obtained using CO2 was done by two vascular surgeons and compared with conventional contrast medium. Necessary therapeutic intervention was performed using CO2 angiography image if reliable image was acquired using the same. Results: A total of 100 patients were evaluated consisting of 176 arterial segments, out of which 145 segments required use of ICM and 31 segments were intervened using CO2 only as a contrast agent (19 superficial femoral artery, 6 common iliac artery, 2 pop artery, 3 external iliac artery, and 1 anterior tibial artery). Assessment of scores given by the observer 1 and observer 2 was performed by their comparison for the statistical significance using McNemar–Bowker test and was found to be statistically significant with P = 0.02. Kendall's Tau b coefficient is 0.74 (significant) and Cohen's kappa is 0.63 (significant). Good-quality images were seen in above the knee (ATK) segment in 39.3% and moderate in 57.8%. However, below the knee (BTK) segments received poor image quality score in majority, i.e., 82.6%. There was significant reduction observed in the total volume of ICM. No major adverse reaction/complication encountered during the procedures was observed, except pain being the most common and distressing complication. Conclusions: CO2 angiography is a very useful tool in the armamentarium of vascular surgeon, especially while performing angioplasties for peripheral arterial disease in borderline CKD patients, not on dialysis, because it not only reduces the amount of iodinated contrast used but also has good imaging ability in ATK vessels. It was fought with multiple issues while imaging BTK vessels, leading to reduction in its reliability and feasibility in that segment.

Keywords: Carbon dioxide angiography, contrast agent for angiography, critical limb ischemia, iodinated contrast medium, peripheral arterial disease


How to cite this article:
Chaudhari NV, Agarwal S, Bedi VS, Satwik A, Yadav A, Srivastava A. Evaluation of carbon dioxide angiography in lower limb angioplasties of peripheral arterial disease patients with borderline chronic kidney disease compared to the standard contrast agent. Indian J Vasc Endovasc Surg 2020;7:370-5

How to cite this URL:
Chaudhari NV, Agarwal S, Bedi VS, Satwik A, Yadav A, Srivastava A. Evaluation of carbon dioxide angiography in lower limb angioplasties of peripheral arterial disease patients with borderline chronic kidney disease compared to the standard contrast agent. Indian J Vasc Endovasc Surg [serial online] 2020 [cited 2021 Jan 28];7:370-5. Available from: https://www.indjvascsurg.org/text.asp?2020/7/4/370/304640




  Introduction Top


Digital subtraction angiography (DSA) using iodinated contrast medium (ICM) is the standard method, by which vascular imaging is performed and roadmap is generated for endovascular intervention during peripheral angioplasties. However, despite development of low-osmolar contrast agents, premedication regimens, and careful patient selection, adverse reactions to contrast medium, including idiosyncratic reactions and contrast-induced nephropathy, continue to occur in a small number of patients.[1],[2],[3] Use of carbon dioxide (CO2) as a contrast agent helps to reduce this risk as it is free from any such complications.[4] CO2 angiography, as a tool for intervention during endovascular intervention, needs to be evaluated in detail, as it is fought with poor quality of images in infrapopliteal arterial segments compared to conventional iodinated contrast material.[5],[6] Use of CO2 as a contrast agent also demands availability of the necessary software and gas delivery system.

In this study, we have assessed the CO2 as a contrast agent for the peripheral arterial angioplasties, with respect to its ability to deliver quality of images necessary for the safe and precise endovascular intervention.


  Materials and Methods Top


Study description

The study was conducted in the tertiary healthcare setup with necessary endovascular skills and setup, on patients of chronic limb-threatening ischemia with raised serum creatinine level (>1.49 mg/dL) who were not on the dialysis, undergoing endovascular revascularization.

Study type

This is a prospective, comparative, observational, cohort study.

Study period

The study was conducted during the period of September 2017–December 2018.

Study design

The study design is depicted in [Flowchart 1].



Inclusion criteria

  1. Patients with infrarenal peripheral arterial disease (PAD) presenting with critical limb ischemia, irrespective of type of arterial lesions, posted for the endovascular revascularization procedure
  2. Serum creatinine >1.49 mg/dL (not on dialysis)
  3. Informed written consent.


Exclusion criteria

  1. Refusal to written informed consent
  2. Severe chronic obstructive airway disease or pulmonary insufficiency
  3. Pulmonary hypertension
  4. Contraindications to anticoagulation or radiation exposure
  5. Past history of allergy to iodinated contrast material.


Methodology

Detail history of the patients and prior investigations were noted. Preprocedural workup included a thorough clinical examination, complete blood count, baseline biochemical examination (blood urea, serum creatinine, blood glucose levels, and prothrombin time). Preprocedural assessment of the patients with color Doppler and ankle brachial pressure index calculation were done. Two observers (one being the operating endovascular surgeon) scored the image obtained during procedure as the score 1 for poor image, score 2 for acceptable image, and score 3 for good image – according to the quality of the image obtained by CO2 and ICM. Given scores were compared using appropriate statistical tests.

Technical details of using carbon dioxide angiography in angioplasty

All the procedures were conducted in the Cath Lab. Patient was placed in the supine position. The procedure was performed under local anesthesia with SOS IV analgesia supplement. The access used was retrograde transfemoral using the standard Seldinger technique. A 5F arterial sheath was inserted in all patients. In patients with bilateral disease, DSA images were obtained with the tip of the pigtail catheter slightly above the aortic bifurcation. In unilateral limb disease, subsequent evaluation of infrainguinal arteries was performed selectively using a 5F multipurpose or Vert catheter, introduced from the contralateral femoral arterial sheath. Artificial CO2 injections were made using CO2 Angioset (Optimed, Aquilant Interventions, Dublin, Ireland).

Patient position

The limb of interest was elevated by 15°–20° above the horizontal to allow adequate filling and hence better visualization of the target vessels.

Carbon dioxide injection

Syringe and the tubing were flushed five times before use as a part of standard practice, to avoid contamination with the room air and explosive delivery of the gas. All CO2 DSA injections were made by hand. A controlled hand injection of the gas in the syringe was made over 1–2 s by rotating the stop valve. Syringe was set at the 40 ml volume mark for the CO2 injection in above the knee (ATK) vessels and at the 20 ml mark for below the knee (BTK) vessels. CO2 gas was injected with total volume of 15–75 cc of CO2 gas.

Time gap between injections

Injections were spaced approximately 1 min apart to allow CO2 to wash out and the extremities were returned to the horizontal position to improve clearing of the gas and to avoid vapor lock.

Image processing

The images were viewed with the DICOM viewer software (Philips Medical Systems, Eindhoven, The Netherlands) installed with a special software for CO2 angiography provided with image invert option and stacking. This helped to project the images similar to the conventional iodinated liquid contrast. The arteries of the lower limbs were grouped into six segments: iliac (common iliac artery/external iliac artery [CIA/EIA]); femoral (superficial femoral artery [SFA]); popliteal; anterior tibial, peroneal, and posterior tibial artery.


  Results Top


[Table 1] shows the clinical details and demographic parameters of the patients in the study.
Table 1: Clinical data and demographic characteristics of patients in the study

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Segments involved in the disease

A study of 100 symptomatic PAD patients included 176 diseased arterial segments, consisting of 109 BTK segments, 11 popliteal segments, and 56 ATK vessels [Graph 1]. Twenty-eight arterial segments/arteries in the BTK segment were completely occluded with no distal reformation and endovascular intervention was not possible, hence not considered in the study.



Intervention performed using carbon dioxide angiography and use of iodinated contrast medium

Of 176 arterial segments intervened, 31 segments were intervened using only CO2 as a contrast agent [Graph 2]. All the other interventions required use of ICM in the some form or the other; for example, to confirm the percentage of stenosis/to visualize distal reformation.



Assessment of image quality by two observers

Overall scoring of quality of the images obtained using CO2 angiography by operating surgeon that is observer 1 suggestive of poor score (Score 1) in 54% of segments, moderate (Score 2) in 33% of segments, and good score (Score 3) in 13.1% of segments in lower limb PAD.

Considering the individual segments, peroneal artery segment has received maximum poor image quality score (96.8%) followed by PTA (81.6%) and ATA (72.5%). Comparative images obtained using ICM and CO2 angiogram at various levels are depicted in [Figure 1], [Figure 2], [Figure 3], [Figure 4].
Figure 1: Carbon dioxide angiography of aorto-iliac segment showing a large atherosclerotic plaque in left external iliac artery

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Figure 2: Comparison of digital subtraction angiography image of superficial femoral artery segment using (a) iodinated contrast medium, (b) carbon dioxide

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Figure 3: Digital subtraction angiography image of below the knee vessels using iodinated contrast medium

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Figure 4: Digital subtraction angiography image same patient's below the knee vessels using carbon dioxide for comparison

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In this study, it was noticed that CO2 angiography was able to achieve good-quality images (Score 3) in the segments: CIA (61.5%), EIA (33.3%), and SFA (32.4%). Popliteal segments received Score 2 in all the patients, suggesting adequate quality of imaging by CO2 angiography at this level [Graph 3]. Scoring of the image quality by observer 2 is correlating with the observer 1 [Table 2].
Table 2: Distribution of image quality scores as per various segments by observer 1

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There was no incidence of any major complication or cardiac event during the procedure.

Repeat CO2 angiograms were taken to overcome the artifacts caused due to the movement of patient position in response to pain on injection of CO2 gas, especially in case of imaging of the BTK segment.

Incidence of pain noticed to be higher in the BTK vessels on injection of the CO2 gas compared to ATK vessels. Eighty percent of the patients with BTK disease complained of pain during the procedure on injection of CO2 gas.

Assessment of scores given by the observer 1 and observer 2 was performed by their comparison for the statistical significance using McNemar–Bowker test being found to be statistically significant with P = 0.02. Kendall's Tau b coefficient is 0.74 which is significantly correlating the values/scores given by the two observers. Cohen's kappa is 0.63 which denoted strong inter-rater agreement in this study, regarding the scores assigned by two observers [Table 3].
Table 3: Comparison of the image quality scores given by two observers

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To summarize, good or acceptable quality of images is obtained in 91.1% of cases in ATK segment, acceptable images (100%) in popliteal segment, and 17.4% of good/acceptable images in the BTK segments using CO2 angiography. Total quantity of ICM used was 1563 mL with an average of 12.02 mL per patient, which suggests significant reduction in quantity of ICM used during revascularization compared to conventional method which was roughly approximated to 4225 mL.


  Discussion Top


This study has many advantages as it was a combined approach of use of CO2 and ICM whenever it was not possible to perform endovascular intervention due to poor image quality with CO2. Primary aim kept in this study was to assess up to what extent endovascular revascularization procedure could be preceded using CO2 as a contrast agent to guide the therapy without affecting the confidence of operating surgeon or compromising the postoperative outcome. Many studies in the literature lack above advantage which helped to include more patients in the study.[7],[8],[9],[10] Very few studies have evaluated role of CO2 angiography beyond the diagnostic purpose in lower limb peripheral arterial occlusive disease (PAOD).[9],[11] The number of patients involved in the previous studies is less as compared to this study which gave us significant results.[9],[10],[11] This study included 100 patients who undergone endovascular intervention for the symptomatic PAD consisting of 176 segments.

Diaz-Sandoval et al. carried out similar study from November 2014 to January 2015, consisting of 36 consecutive diabetic patients with CLI in which they performed endovascular intervention using CO2 effectively guided angioplasty in all patients without complications. The diagnostic accuracy of CO2 was 89.8% (sensitivity 92.3%; specificity 75%; positive predictive value 95.5%; negative predictive value 63.1%). There was no statistically significant difference in the qualitative diagnostic accuracy between the media (P = 0.197).

Madhusudhan et al.[10] studied 21 patients (27 limbs; all men; mean age, 47.6 years) who presented with PAOD of the lower limbs. DSA was done using both intra-arterial CO2 and ICM. They performed conventional ICM DSA performed first and used as gold standard. CO2 was then injected by hand using a locally improvised homemade plastic bag delivery system. They reported good or acceptable image quality of CO2 DSA in over 95% of patients with inadequate visualization of infrapopliteal arteries. Mild pain was seen in six (28.6%) patients with both contrast agents; one patient developed severe pain during CO2 DSA. Inter-observer agreement was good (k > 0.75) at 70% of the segments. Use of ICM DSA first do not give advantage for the patients with high risk of contrast induced nephropathy and requires more quantity of ICM. Prior knowledge of lesion/disease segment creates clinical bias. In our study, we performed CO2 angiography on 176 segments, scoring for quality of image was done by two observers independently, and decision was taken for the supplement of ICM or proceeding with CO2 only.

Total quantity of ICM used was 1563 mL with average 12.02 mL per patient, which suggests significant reduction in quantity of ICM used per patient during revascularization. A routine endovascular procedures use 30–40 mL of ICM per patient. Increased quantity of ICM used is risk factor for the CIN.[3]

The automated CO2 angiography is a newer technique and considered safer due to the internal circuit of the injector, which maintains positive pressure to prevent the introduction of air from outside the system. The CO2 procedure can be done fully automatic; it is repeatable, and independent of the operator.[8] Once the volume and pressure parameters are set up, the injector automatically handles the injection of the gas toward the infusion line. Consideration must be given to the ability of the automated CO2 procedure to be painless for the patient. The definition and control of injection pressure allow the operator to maintain an acceptable pressure of the gas injection into the artery. Excessive pressure normally causes pain for the patient in the manual procedures, because it is basically impossible to control low pressure values. In our study, 80% of the patients with BTK disease experienced transient leg pain after CO2 injection despite following all technical measures before CO2 injection. Scalise et al. reported pain in only three patients out of 40 patients in their study.

In each X-ray acquisition, the CO2 will sometimes fail to opacify the entire field during the same run. For postprocessing visualization of the entire vasculature, “stacking” techniques are used to stack the individual images on top of each other to form a single composite image.[12]

CO2 as a contrast agent is very inexpensive; the cost of CO2 Angioset used in this study is also minimal. Automated CO2 injectors are costly, and the connectors that transmit CO2 from the injector to the catheter must also be considered.


  Conclusions Top


Definitely getting conversant with the use of CO2 gas as the contrast agent requires knowledge of basic properties of the gas, safe, and controlled delivery system; postimaging processing software and efforts to eliminate technical errors will help standardize the practice of using CO2 as a primary contrast agent in the peripheral arterial revascularization in patients with high risk for ICM-related complications in all the centers in India. CO2 angiography is very useful tool in the armamentarium of vascular surgeon, especially while performing angioplasties for PAD in borderline chronic kidney disease patients, not on dialysis, because it not only reduces the amount of iodinated contrast used but also has good imaging ability in ATK vessels. We observed that it fought with multiple issues while imaging BTK vessels, leading to reduction in its reliability and feasibility in that segment. Although confidence of vascular surgeon while performing endovascular revascularization in BTK disease using CO2 angiography is highly dependent on the quality of images obtained, ICM may be used to supplement the procedure. This helped reduce the risk of nephrotoxicity significantly as the quantity of ICM used was reduced because procedure began with CO2 angiography. CO2 angiography has the definite role in primary diagnostic angiography. This approach represents a potential imaging alternative or adjunctive f or standard contrast agents for patients who are candidates for an endovascular procedure but are at high risk for contrast-related complications.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. Report from the Japanese Committee on the Safety of Contrast Media. Radiology 1990;175:621-8.  Back to cited text no. 1
    
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Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol 1991;87:867-72.  Back to cited text no. 2
    
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Barrett BJ, Carlisle EJ. Metaanalysis of the relative nephrotoxicity of high- and low-osmolality iodinated contrast media. Radiology 1993;188:171-8.  Back to cited text no. 3
    
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Kerns SR, Hawkins IF, Sabatelli FW. Current status of carbon dioxide angiography. Radiol Clin North Am 1995;33:15-29.  Back to cited text no. 4
    
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Oliva VL, Denbow N, Thérasse E, Common AA, Harel C, Giroux MF, et al. Digital subtraction angiography of the abdominal aorta and lower extremities: Carbon dioxide versus iodinated contrast material. J Vasc Interv Radiol 1999;10:723-31.  Back to cited text no. 5
    
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Ehrman KO, Taber TE, Gaylord GM, Brown PB, Hage JP. Comparison of diagnostic accuracy with carbon dioxide versus iodinated contrast material in the imaging of hemodialysis access fistulas. J Vasc Interv Radiol 1994;5:771-5.  Back to cited text no. 6
    
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Seeger JM, Self S, Harward TR, Flynn TC, Hawkins IF Jr. Carbon dioxide gas as an arterial contrast agent. Ann Surg 1993;217:688-97.  Back to cited text no. 7
    
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Scalise F, Novelli E, Auguadro C, Casali V, Manfredi M, Zannoli R. Automated carbon dioxide digital angiography for lower-limb arterial disease evaluation: Safety assessment and comparison with standard iodinated contrast media angiography. J Invasive Cardiol 2015;27:20-6.  Back to cited text no. 8
    
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Eschelman DJ, Sullivan KL, Bonn J, Gardiner GA Jr. Carbon dioxide as a contrast agent to guide vascular interventional procedures. AJR Am J Roentgenol 1998;171:1265-70.  Back to cited text no. 9
    
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Madhusudhan KS, Sharma S, Srivastava DN, Thulkar S, Mehta SN, Prasad G, et al. Comparison of intra-arterial digital subtraction angiography using carbon dioxide by ' home made ' delivery system and conventional iodinated contrast media in the evaluation of peripheral arterial occlusive disease of the lower limbs. J Med Imaging Radiat Oncol 2009;53:40-9.  Back to cited text no. 10
    
11.
De Angelis C, Mauri G, Casilli F, Secchi F, Inglese L, Sardanelli F. Carbon Dioxide as a Contrast Agent to Guide Vascular Interventional Procedures Learning Objectives. Available from: http://www.myESR.org. [Last accessed on 2019 Jun 19].  Back to cited text no. 11
    
12.
Rolland Y, Duvauferrier R, Lucas A, Gourlay C, Morcet N, Rambeau M, et al. Lower limb angiography: A prospective study comparing carbon dioxide with iodinated contrast material in 30 patients. AJR Am J Roentgenol 1998;171:333-7.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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