Testicular varicocele embolization using CO2, gadolinium and lipiodol as contrast agents in a patient with an iodinated contrast allergy

Abstract

A 44-year-old gentleman was referred to IR for varicocele embolization (VE) by the fertility clinic following investigation for oligospermia. A testicular ultrasound identified a left grade II varicocele. The patient had known anaphylaxis to water-soluble iodinated contrast. We planned to perform VE with a combination of alternative contrast agents. The procedure was performed under general anesthetic to mitigate the pain related to carbon dioxide angiography. Following standard venous access techniques of the right internal jugular vein, carbon dioxide was used as the main contrast agent with digital subtraction venogram, to confirm catheter selection of left testicular vein. This demonstrated a large varicocele. After coil deployment the gadolinium-based contrast agent Dotarem, was injected and venography used to confirm occlusion of the left testicular vein. Then a combination of 4 mL of 3% Fibro vein and 2 mL of Lipiodol was injected to achieve embolization of the testicular vein collaterals. The patient made an uneventful recovery. This is the first reported case of both carbon dioxide angiography and gadolinium being used in VE. It appears safe and effective. The use of alternative contrast media appears safe and effective in VE in those patients with contraindications to ionic agents. Due to their different properties, a combination of alternative contrast agents can be more effective than a single agent. We provide a pictorial review of the case and an educational summary on the indications and practical uses of various alternative contrast agents in IR procedures in a patient with a water-soluble iodinated contrast allergy.

Introduction

A varicocele consists of abnormally dilated and tortuous veins within the pampiniform plexus of the spermatic cord [1]. They are common with an incidence rate of approximately 15%-20% in men. They are associated with subfertility and impaired testicular function and are present in 45% and 80% in those presenting with primary and secondary infertility [2]. Diagnosis is made via a combination of clinical history, examination and ultrasound assessment [3]. Both surgical and nonsurgical approaches to the treatment of varicocele have been described [4]. Percutaneous varicocele embolization (VE) has been increasingly utilized in the treatment of varicoceles for both infertility measures and symptomatic relief as it is performed as an outpatient procedure on a supine patient under moderate sedation, and is considered a safe and effective technique [5]. Venography is conventionally performed using iodinated contrast media (ICM) [6].

Allergy, anaphylaxis and renal failure are potential barriers to the use of ICM for endovascular interventions [[7], [8], [9]]. Anaphylactic reactions have been reported to occur in 0.7 to 3% of patients receiving low osmolar ICM [10]. Steroids can be administered pre-procedurally to reduce the reaction in mild to moderate allergy but are less effective in anaphylaxis [11].

This prompts the use of alternative contrast media. Carbon dioxide (CO2) with its non-allergenic and non-nephrotoxic qualities, is ideal for patient use. It is readily available, relatively cheap and unlimited in quantity [12]. Uniquely, its low viscosity permits visualization of small collateral vessels, a paramount feature for the success of VE [13]. However, it can have potential complications such as neurotoxicity and air trapping [14,15]. Similarly, gadolinium is a readily available, inexpensive option for use in patients with an eGFR >60 [16]. However, commercially available chelates of gadolinium are in such low concentration that it cannot be visualized with fluoroscopy. Therefore, digital subtraction angiography is often required [17]. Also due to the risk of nephrogenic systemic sclerosis (NSS) its use is not recommended for those in renal failure [18]. Therefore, its main indication is in those with normal renal function who have had an anaphylactic reaction to ICM. Dotarem is a gadolinium-based contrast agent which consists of an aqueous solution of 0.5 mmol/mL of gadoterate meglumine. Each milliliter of Dotarem contains 376.9 mg of gadoterate meglumine, 0.25 mg of the chelating agent DOTA, and water for injection. Lipiodol, one of the earliest successfully used non-particulate oil-based iodinated contrast agents, can additionally be used in angiography [19]. It is mainly utilized in chemoembolization of hepatocellular carcinoma and has features of selective target and site-specific delivery to lesions [20]. In addition, its fatty acid structure makes it a good solute for hydrophobic agents [21].

Here we present a successful case of a varicocele embolization with the use of a combination of alternative contrast agents when there was a direct contraindication to the use of water-soluble ICM.

Materials, methods and results

A 44-year-old gentleman was referred to our Interventional Radiology department for VE by the fertility clinic following investigation for oligospermia. A testicular ultrasound identified a left, grade II varicocele. The patient had known anaphylaxis to water-soluble iodinated contrast previously.

Following careful counselling and consent of the patient, it was planned to perform embolization of his varicocele with a combination of alternative contrast agents. The procedure was performed in the interventional radiology suite under general anesthesia to mitigate the pain related to carbon dioxide angiography. Additionally, the patient was extremely needle phobic.

Standard procedures were used to obtain vascular access via the right internal jugular vein to cannulate the left renal vein and subsequently the ipsilateral testicular vein with a 4 French multipurpose catheter (Cordis, Cardinal Health, United states). A digital subtraction angiography (DSA) CO2 venogram was then performed to confirm position within the left renal vein and subsequently following successful cannulation of the left testicular vein (Fig. 1). 3 mL of Dotarem was then injected with DSA which demonstrated a large, refluxing varicocele (Fig. 2). Pushable Nester embolization coils were then deployed (COOK medical, USA) as per standard protocol distally. 3 mL of Dotarem was subsequently injected with DSA to confirm occlusion of the left testicular vein. Then a combination of 4 mL of 3% sodium tetradecyl sulfate (Fibrovein, STD Pharmaceutical Products Ltd) and 2 mL of Lipiodol (Guerbet, France) was injected to achieve embolization of the testicular vein collaterals (Fig. 3). The patient was discharged later the same day and made an uneventful recovery from the procedure with no complications.

Fig. 1.

DSA CO2 venogram to confirm catheter position in left renal vein.

Fig. 2.

DSA following injection of Dotarem to demonstrate varicocele.

Fig. 3.

Fluoroscopic image where Fibro vein/Lipiodol was injected to achieve embolization of the testicular vein collaterals.

Discussion

As previously discussed, CO2 angiography has a well-documented safety profile for endovascular procedures with safe use in renal failure [12,13]. The use of CO2 DSA in testicular vein embolization has previously been described by Iaccarino et al. [22]. They cite its advantages for use in those considered to be at high risk of iodinated contrast rection but also, due to its low viscosity, to identify small collateral branches. Known complications of CO2 angiography include neurotoxicity and air trapping [14,15].

Whilst Lipiodol is indeed an iodinated contrast agent, its use in this case was considered due to its unique physicochemical properties and the nature of the patient's prior contrast reaction. The patient had a documented allergy to non-ionic, water-soluble ICM, which are commonly associated with immediate hypersensitivity reactions. Lipiodol, by contrast, is an oil-based iodinated agent which has a different molecular structure and pharmacokinetic profile. There is limited cross-reactivity between water-soluble iodinated contrast agents and oil-based agents such as Lipiodol. Allergic reactions to Lipiodol are extremely rare [23]. Also, as the Lipiodol was only used in an embolized vein a minimal amount would have entered into the systemic circulation, further reducing the risk of hypersensitivity. Prior to its use, a careful risk-benefit analysis was conducted, and the procedure was performed under close monitoring. No adverse reaction occurred, supporting the safety of this approach in select patients.

Combining Lipiodol with a hydrophobic embolic agent such as glue, during testicular vein embolization, is also well documented [[24], [25], [26], [27]]. Authors highlight reduced fluoroscopic screening time and radiation as an advantage of this method over coil embolization. However, certain precautions need to be taken such as filling the microcatheter dead space with an anionic solution, such as 5% dextrose, to prevent intra-catheter glue polymerization [24]. There is limited literature on the combined use of Lipiodol and sodium tetradecyl sulfate in VE, but it has a well-documented safety profile and use in other venous sclerotherapy procedures such as balloon retrograde transvenous obliteration (BRTO) [28,29].

There is limited available literature on the use of gadolinium-based contrast agents during endovascular interventions. Safriel et al. [30] demonstrated gadolinium to be a safe alternative to standard non-ionic contrast in percutaneous spinal procedures in those considered to be at high risk of contrast rection. 92 patients underwent 127 procedures using gadolinium as the contrast agent to confirm needle position during intralaminar and foraminal epidural steroid injections, nerve blocks, facet injections and discograms in the spine. All patients were discharged without complication. As previously discussed, limitations of gadolinium include poor visualization with fluoroscopy and the risk of NSS if used in renal failure [18].

In conclusion, impaired renal function and allergic reactions can limit the use of ICM in interventional procedures. Multiple alternative contrast agents exist each with their own benefits and limitations. The use of CO2, gadolinium and Lipiodol in interventional procedures as alternative contrast agents has been widely reported [31]. However, this is the first reported case of both CO2 angiography and gadolinium being used in a varicocele embolization procedure. The combined use of alternative contrast agents appears safe and effective in VE. Due to their different properties, a combination of alternative contrast agents can be more effective than a single agent. Careful counselling and consent of the patient, for the off-label use of these agents, is required prior to the IR procedure. However, it can allow patients to undergo procedures that would otherwise not be available to them.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for Publication

Written consent for publication was obtained for every individual person’s data included in the study.

Contribution statement

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Virjen Patel, Benedict Thomson, Bisher Ghazal-Aswad, Gregory Makris and Athanasios Diamantopoulos. The first draft of the manuscript was written by Virjen Patel, Bisher Ghazal-Aswad and Benedict Thomson and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Patient consent

Written informed consent was obtained from all individual participants included in the study.