Upper Extremity Discoloration Caused by Subcutaneous Indigo Carmine Injection

Indigo carmine (indigotin disulfonate sodium) is usually used as a marker dye to locate the ureteral orifice, severed ureters, or fistulas ^[1]. Although it is considered pharmacologically inert, it can cause significant problems, some of which are very important for anesthesiologists (Table 1) ^[2-18]. The most commonly encountered cardiovascular effect of intravenous indigo carmine administration is transient alpha-receptor stimulation, which causes increases in peripheral vascular resistance, diastolic and systolic blood pressure, and central venous pressure, with compensatory decreases in cardiac output, stroke volume, and heart rate ^[14]. We report an unusual complication that resulted from accidental subcutaneous injection of indigo carmine into a patient's forearm during general anesthesia: transient blue discoloration of the entire infiltrated area. This rare complication and the duration of tissue discoloration have never been described.

Table 1: Most Frequently Described Complications from Indigo Carmine

Case Report

A 75-yr-old woman was scheduled to undergo elective vaginal hysterectomy. Before anesthetic induction, a 16-gauge peripheral intravenous catheter was inserted in the dorsum of the left hand. Routine monitors were applied, including a noninvasive blood pressure cuff to the right arm and a pulse oximeter probe on the second digit of the left hand. General anesthesia and muscle relaxation were induced uneventfully with thiopental, fentanyl, and succinylcholine followed by endotracheal intubation. Onset of anesthesia and succinylcholine-induced muscle fasciculations occurred as expected, suggesting that the venous catheter was appropriately placed. After anesthetic induction and during the surgery, both arms were placed on arm boards at 90 degrees angles to the patient's body, padded, and covered. Her wrists were oriented in the neutral and supinated position. No muscle relaxation was required throughout the surgery, and anesthesia was maintained with isoflurane and a mixture of oxygen and nitrous oxide.

Two and a half hours into the procedure, 5 mL of 0.8% indigo carmine was given as a bolus via the intravenous catheter at the surgeon's request. Several minutes after the injection of dye, the urine acquired the blue color characteristic of indigo carmine. During surgery, we did not notice any operational difficulty with the intravenous line, and the 16-gauge intravenous catheter appeared to be working as would be expected. The crystalloid solutions used during this patient's surgery were hung 3 ft above the level of the operating table. The infusion bags were never pressurized.

Nearly 2 h after the dye was injected, the surgery was completed and the patient was allowed to resume spontaneous breathing. After the patient awakened and was able to follow commands, her trachea was extubated. The surgical drapes were then removed, and we noticed that the entire left forearm was blue. The discoloration extended from the elbow to the fingers, mainly affecting the dorsal parts of the hand and forearm, but sparing the fingertips. In addition, swelling extended to the distal forearm, indicating infiltration of the intravenous line. Motor, sensory, and neurovascular examinations of the affected forearm were entirely normal.

Not knowing how long this discoloration would last or whether it would continue to spread, we drew demarcation lines at the borders. The affected arm was then elevated and warm compresses were applied. The patient was very concerned and repeatedly asked how long the discoloration would last. At the time, we knew little about whether the discoloration would be temporary or permanent, which unfortunately further alarmed the patient. However, both reabsorption and redistribution of the discoloration began within a few hours. The discoloration shifted from more elevated areas to dependent areas, suggesting that the extravasated indigo carmine moved freely within the extracellular fluid compartment. During the first 24 postoperative hours, the dye was almost completely reabsorbed, and at 48 h it was no longer noticeable.

Discussion

In addition to helping locate ureteral openings and urine spillage ^[1], indigo carmine is useful in detecting endotracheal tube cuff leakage ^[10], studying mucociliary transit time ^[11], marking nonpalpable breast lesions ^[12], and localizing poorly defined flat adenomas of the esophagus ^[13]. None of the published reports indicate how long dye-induced tissue discoloration lasts, because all the above applications were internal (esophagus, trachea). Skin discoloration caused by subcutaneous extravasation of indigo carmine has never been described. Although not life threatening, this complication imposed significant anxiety on the patient and on us. We immediately contacted the hospital pharmacy, our dermatology department, and the manufacturer (American Regent Laboratories, Inc., Shirley, NY) for information about the destiny of extravasated dye, but none of them offered definitive information regarding local tissue toxicity or the potential duration of discoloration. We also searched MEDLINE (1966-1995), but found no definitive information about what we could expect from this complication. Imokawa and Mishima ^[15] reported using indigo carmine as an acidic indicator dye to study cumulative injury of the stratum corneum of the skin. This report at least indicated to us that indigo carmine can be used as a skin marker in vivo. The American Hospital Formulary Service indicated that indigo carmine can be administered intramuscularly,¹ implying that the tissue discoloration it causes is not permanent, and is subject to reabsorption. The same source states that large doses of indigo carmine may cause blue skin discoloration in infants, children, and underweight patients, but does not say how long this discoloration lasts. By drawing demarcation lines on our patient's forearm, we were able to monitor the changes in discoloration. It became apparent that the discoloration was shifting in a gravity-dependent fashion. Indigo carmine is soluble in water ^[16] but not in lipids, and therefore does not readily cross cell membranes. This all suggests that indigo carmine injected subcutaneously primarily moves within the extracellular fluid space and that the destiny of the dye resembles the destiny of the extravasate.

1 McEvoy GK, ed. Drug information, American Hospital Formulary Service (AHFS) 95. Bethesda, MD: American Society of Health-System Pharmacists, Inc., 1995:1654-5.

(Figure 1) In conclusion, we have presented a case of unintended subcutaneous injection of indigo carmine during anesthesia, which caused temporary blue discoloration of the forearm. When this happens, one may expect it to resolve within 48 hours without tissue toxicity.

Figure 1: Left forearm showing discoloration with indigo carmine after intravenous catheter infiltration. Arrow identifies the site of where the infiltrated catheter was inserted.

The authors thank Ray Borazanian, Department of Scientific Publications, Cleveland Clinic Foundation, for help in preparing this manuscript.