Lu-177 Lutetium Dotatate Infusion Safety: Infiltration or Extravasation?

Introduction: Infiltration, extravasation, and safety of Lu-177 Lutetium Dotatate (Lutathera), was investigated. Understanding and managing such events, is imperative for safety in Nuclear Medicine. Phlebitis, infiltration, and/or extravasation are potential unfavorable events. Phlebitis is when a vein(s) becomes red and inflamed at the skin surface.1 An infiltration event occurs when a non-vesicant escapes from the vein, seeping into surrounding tissue, causing no harm.1 Extravasation is when a vesicant escapes the vein, causing mild to severe damage to surrounding soft tissue.1 Properties providing stability and physiologic compatibility such as osmolarity, pH, and mode of decay may pose concern in such events. A pH of 5-8, and osmolarity of 300-600 mOsm (similar to blood) are seen as low risk for infiltration/extravasation complications.2 Beta particles, such as Lu-177, deposit smaller amounts of energy over a longer distance and may cause damage if extravasated.3,4 Lutathera infusion pretreatment consists of anti-nausea medication Emend(150mg) infused over 30 minutes or Zofran(16mg) over 15 minutes. Amino Acids are infused at 250 ml/hour for 4 hours. 30 minutes into the Amino Acids, Lutathera is co-infused for 30 minutes, rinsing with saline after.

Methods: A Mayo Clinic Rochester nursing database was reviewed from November 2021 to January 2022 for infiltration/extravasation cases in Lutathera therapies. Literature case reports and publications were reviewed. Search terms included: Lutathera infiltration/extravasation, reactions, and prevention. Patients were observed for 3 months for cases of infusion reactions and infiltration/extravasation events. Lutathera properties were evaluated to gauge the risk associated with an infiltration or extravasation event.

Results: The Amino Acid pretreatment (pH 5-7, osmolarity of 450 mOsm) along with Lutathera, are not cytoxic. Lutathera has a pH of 5-6 formulated with 9 mg/mL NaCl with osmolarity around 300 mOsm. Properties of the Amino Acid pretreatment and Lutathera display low risk of damage due to extravasation if infiltrated. Data over the span of 3 months showed 5 of 64 therapy patients had documented cases of phlebitis. Phlebitis typically occurred before Lutathera infusion. No treatment or intervention was given, the phlebitis self-resolved. No significant safety events were discovered. Since 2017, Mayo Clinic Rochester has seen 1 documented infiltration case out of 926 Lutathera infusions. Infiltration protocol, such as hot and cold packs, were applied. Infiltration and extravasation symptoms presented as pain, swelling, color changes, skin temperature changes, site drainage, and flow resistance. Extravasation may present with blister formation or radiation burns. Strategies to prevent infiltration and extravasation included avoiding use in patients with impaired blood supply, ensure a free flowing IV (20 gauge or larger) with blood return is used, and monitor the pressure of the IV; it should be easily flushed. Heat and cold packs will circulate fluid out of soft tissue if infiltration/extravasation occurs. If extravasation occurs, more aggressive measures are taken such as massaging the site, and/or sloughing the skin.

Conclusions: Drug properties of Lutathera and Amino Acids suggests they are to be considered infiltration events, not extravasation events. Proper infusion technique, examining the IV site, and fast action, will reduce the odds of infiltration or extravasation and possible damage. Over 900 infusions showed no significant safety concerns. Phlebitis is possible, occurring in about 8% of treatments, usually posing no concern due to its ability to self-resolve with no other symptoms. It is not believed to be associated with infiltration; however, it may be a result of the Amino Acid contents or anti-nausea medications. It is crucial to continue to study infiltration and extravasation cases in hopes to create a specific plan of action for the different therapy radiopharmaceuticals in use.