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SGO Clinical Practice Advisory: Indocyanine Green (ICG) Dye National Shortage

Member UpdateSGO Statement

Sep 20, 2024

Currently, a United States (U.S.) shortage of indocyanine green (ICG) dye exists that may persist for several weeks to months. ICG dye, widely used for sentinel lymph node (SLN) biopsy in gynecologic oncology, was first reported in shortage by the American Society of Hospital Pharmacists on August 20, 2024¹.

Subsequently, the U.S. Food and Drug Administration reported this shortage on August 23, 2024².

The recommendations below address how gynecologic oncologists can conserve ICG dye, allocate the limited supply to those patients who will experience the most significant benefit, and use dye alternatives for SLN biopsy in patients with endometrial, cervical, and vulvar cancers. When considering alternative dyes, appropriate dosing and administration are critical to ensure continued high standards of patient care.

Strategies to Preserve Dye

Discuss with your institution any sources of ICG and whether they can be re-purposed. There may be premade kits that include ICG.
Optimize Dosage and Efficient Usage:
- Conventional Dosing: Under sterile conditions, reconstitute one 25 milligram (mg) vial of ICG lyophilized powder for injection, United States Pharmacopeia (USP) using one 10 milliliter (mL) sterile water for injection, USP vial^3,4. Shake or invert the vial to gently dissolve the ICG powder. After reconstitution, a 25 mg vial of ICG contains 2.5 mg of dye per mL of solution, so a 1.0 mL injection contains a 2.5 mg dose of ICG. The ICG dye is further diluted with 10 mL of sterile water to create a dose of 1.25-mg/mL solution for cervical injection. Only 2-4 mLs are needed in a surgical case.
- Use Minimal Effective Dose: Determine the lowest effective dose of ICG required for successful SLN mapping. Studies suggest that lower doses may still be effective, so consider adjusting the standard dosage protocols and use ~2 mLs instead of ~4 mLs/surgical case. Note: the superficial injection is mandatory and may be sufficient in most cases.
- Avoid Waste: Carefully calculate the amount of ICG needed for each case to avoid wastage. Use sterile techniques to prevent contamination and waste of the dye.
Multi-Use Vials: Consider multi-use vials, ensuring that each vial is used to its full potential.
- Schedule multiple SLN mapping procedures in the operating room (OR) simultaneously or consecutively to make the most of each vial of ICG, as the dye has a limited shelf life once opened. ICG dye must be used within six hours after reconstitution.
- Coordinate with OR pharmacy if plastic, urology, colorectal surgery, or other services are also using ICG to share vials.
- If considering using one vial for up to two surgical cases, it is strongly encouraged to consider pharmacy distribution of dye (and not OR distribution) under sterile conditions once reconstitution occurs^4,5. Discussion of the shortage with the pharmacy team is crucial.Table: Stability and Sterility of ICG^4,5

- Ensure that all surgical and nursing staff are well-trained in the efficient use of ICG to minimize wastage.
Considerations for Disease Sites
- Until the shortage is lifted, ICG use should be reserved for presumed early stage endometrial cancer, unifocal vulvar cancers with a tumor size <4 centimeters (cm) and a negative clinical groin exam, and cervical cancers with a tumor size ≤2 cm.
- At institutions where the shortage is critical, consider utilizing the Mayo criteria in presumed early-stage endometrial cancers^6,7.
- ICG use should not be used in cases of complex atypical hyperplasia or endometrial intraepethlial neoplasia (EIN) if frozen section is available. The decision for lymphadenectomy can be based on Mayo criteria in patients found to have endometrial cancer at the time of surgery^6,7,8.
- At institutions where expert gynecologic pathology expertise is not available, lymphadenectomy is advised.
- Consider conserving ICG use to cases where it is proven to be superior to other lymph node mapping techniques (e.g., endometrial cancer)⁹.
- It is critical to note that as with ICG, alternative dyes and radiotracers that fail to map should trigger ipsilateral systematic lymphadenectomy in the hemipelvis¹⁰.

Recommended Alternatives to ICG

Isosulfan Blue (can be used alone or in conjunction with ICG)¹¹:
- Indication: Lymphatic mapping.
- Dosage: 4 mLs of a 1% solution is injected intracervically (2 mLs each injected in the cervix at 3- and 9-o’clock, superficial and deep, or intradermally around a vulvar or perineal tumor).
- Considerations: This dye has been well studied in Phase II and retrospective trials in the literature in patients with cervical and endometrial cancer. Be aware of potential for anaphylactic reactions; anaphylaxis occurs in approximately 2% of patients¹². Reactions are more likely to occur in patients with a history of bronchial asthma, allergies, drug reactions, or prior reactions to triphenylmethane dyes or related compounds.
Methylene Blue 1%¹³:
- Indication: Lymphatic mapping¹⁴.
- Dosage: Inject 4 mLs of 1% methylene blue without dilution (2 mLs each injected in the cervix at 3- and 9- o’clock or intradermally around a vulvar or perineal tumor)¹⁴.
- Considerations: Serotonin syndrome has been reported when combining with serotonergic agents, but typically not seen at doses used for SLN mapping. Detection rates may be lower than observed with isosulfan blue.
Lymphoscintigraphy with technetium-99 sulfur filtered colloid (used in conjunction with blue dye)^15,16:
- Indication: Can be used for lymphatic mapping with a gamma probe.
- Dosage: Inject 0.5 millicurie (mCi) (0.1 mCi/ml) of 0.45 millimeter filtered technetium-99 sulfur colloid (CIS-Sulfur Colloid™; Mallinkrodt) intradermally around the perineal tumor or intra-cervically in four quadrants, 2-4 hours prior to surgery. Lymphoscintigraphy should be performed 1-2 hours post-injection.
- Considerations: Injections must be performed preoperatively while the patient is awake, with potential pain at the injection sites. This requires a gamma probe to detect a signal.

Use for perfusion assessment:

ICG may be used for perfusion assessment of flap viability and in assessment of bowel anastomosis perfusion at the time of cytoreductive surgery procedures¹⁷.
A multidisciplinary approach should be used if the primary surgeon is not comfortable performing these procedures without the use of near infrared imaging.

We understand the challenges posed by the ICG dye shortage and are committed to supporting you in providing the best possible care for your patients. Please email us at sgo@sgo.org.

References

SGO Clinical Practice Advisory: Indocyanine Green (ICG) Dye National Shortage

Strategies to Preserve Dye

Recommended Alternatives to ICG

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