PHOTODYNAMIC therapy (PDT) is becoming a popular treatment for early-stage esophageal, bronchial, stomach, and head and neck cancers. 1–3However, PDT has a major side effect: skin photosensitivity. The mechanism of the effectiveness of PDT is explained as the combined effects of a photosensitizing agent (photosensitizer) and visible light. Dougherty et al. 4reported that skin photosensitivity could last up to 2 months after the administration of a photosensitizer, but it is usually uncommon if there is no exposure to direct light and concentrated light. Only two cases of finger skin burn associated with a pulse oximeter during PDT have been reported. 5,6
We present the case of a patient who showed a severe facial burn caused by an operating light during a long operation undergone 52 days after PDT.
The patient is a 79-yr-old man (154 cm, 45 kg) with squamous cell carcinoma in the right maxillary sinus. He had a history of hypertension and had been treated with spironolactone medication since he was 60 yr old. He underwent partial maxillectomy after chemotherapy and radiation therapy. Six months after the first operation, PDT was scheduled for confirmed recurrence.
Forty-eight hours before PDT, the patient was given 96.7 mg porfimer sodium (Photofrin®; Wyeth Lederle Japan Co., Tokyo, Japan) intravenously. The patient then spent time in a dimly lit room (100–200 lux) to avoid induced skin photosensitivity. Three weeks after PDT, a dermatologist evaluated the patient's skin photosensitivity by exposing the back of the hand to sunlight for 5 min. The patient's skin reaction to this test was evaluated as negative. He was released from the dimly lit room and put in a normal hospital ward while using a sunscreen cream and avoiding the direct rays of the sun. Thereafter, the patient did not show any signs of skin photosensitivity during his hospital stay until an operation 52 days after PDT. He had a radical operation for maxillary cancer, with restoration of the forearm's free flap. The patient was premedicated with 0.5 mg atropine and 20 mg famotidine intramuscularly. During anesthesia, standard patient-monitoring devices, including a pulse oximeter, were applied. General anesthesia was induced with 5 mg/kg thiopental and 2 μg/kg fentanyl. Vecuronium, 0.15 mg/kg, was used to facilitate tracheal intubation. Anesthesia was maintained by inhalation of 67% nitrous oxide, 33% oxygen, and 1 to 2% sevoflurane. Intraoperatively, alprostadil alfadex and dopamine were continuously infused, and cefazolin sodium was administered as an antibiotic. Operating time was 14 h and 51 min. Two sets of operation room lights, Outer Space 9® (9-lamp type) and Outer Space 4® (4-lamp type; Yamada Shadowless Lamp Co., Tokyo, Japan), were used. These are standard lights used at our institution, and their average illuminations are 135,000 lux and 96,000 lux, respectively. Both operating lights were placed at a distance of about 120 cm from the patient. No lighting (e.g. , headlights) that illuminated the patient was used besides the operating lights.
After the operation, the patient showed severe swelling and erythema of the face, which was the site of surgery, and a dermatologist diagnosed a second-degree burn injury (fig. 1). There was also a slight reddening around the right forearm, which was the operating site for the donor of the graft. All other parts of the body were covered with clothing, and no burns were observed there. In addition, there was no burn injury on the left index finger, which is where the pulse oximeter probe was placed. Because the planted free flap became necrotic after surgery, the flap was removed on the fifth postoperative day in the same operating room. The time needed for flap removal was 1 h and 38 min. Although the same operating lights as for the first operation were used, the patient did not show any aggravation or new burn during this operation. After the second operation, the burn began to heal gradually, and the patient left the intensive care unit on the 13th postoperative day.
In this case report, we describe a serious burn caused by an operating light during a long operation, which was performed 52 days after PDT, despite an evaluation of skin photosensitivity producing a negative result. As far as we know, there have been no reports of burn injury due to an operating light after the administration of a photosensitizer, and only two cases of burn injury associated with a pulse oximeter during PDT have been reported. 5,6
In the two case reports of burns caused by a pulse oximeter, each patient had received PDT during general anesthesia for medical treatment of esophageal cancer or parietal malignant ependymoma. 5,6The two burn injuries were induced by exposure to light from pulse oximeters at between 24 and 96 h after injecting the photosensitizer. However, our patient showed a serious burn injury 4 weeks after the definitively negative result of the photosensitivity evaluation. Before anesthesia, we considered that the porfimer sodium concentration in normal tissue had already decreased to a concentration that was much less than that at the photosensitivity evaluation and there would be no possibility of an abnormal pharmacologic response. However, in this case, burn injury was caused by the activation of extant porfimer sodium injected.
When 2 mg/kg porfimer sodium, a photosensitizer having an affinity to tumor cells, is injected intravenously, the concentration in normal tissue is about one fourteenth of that in tumor tissue at 48–72 h after injection. This difference between normal tissue and tumor tissue is maximized at this time. PDT is a selective treatment by which a laser beam is irradiated at the focus according to this period to destroy tumor cells using a photochemical reaction. 7Porfimer sodium is in an excitation state and produces energy if it receives light of the proper wavelength. It activates oxygen in tissue, produces super oxide, and, finally, demonstrates an antitumor function. 8The most frequent side effect of porfimer sodium is photosensitivity. Its incidence was 20.6% at the time the drug was recognized in Japan in October 1994. Therefore, patients must avoid direct light and concentrated light for at least 1 month after porfimer sodium injection and be kept under observation in a dimly lit room. An evaluation of skin photosensitivity is performed at 1 month after medication. The test involves exposing the back of the hand to the direct rays of the sun for 5 min. If the test result is negative, patients may be moved to a general ward; if it is positive, patients continue to be protected for an additional 2 weeks, after which the same test is repeated.
Porfimer sodium has its highest absorption peak in the area of 405 nm (blue–violet). However, this wavelength overlaps with the absorption band of hemoglobin in vivo . Because of its low tissue permeability, it is not used as an excitation light. We generally use the Excimer Dye Laser® (PDT EDL-1; Hamamatsu Photonics K.K., Hamamatsu,Japan) for PDT, which is a pulse laser that radiates 630-nm red light and has good tissue permeability despite its much lower absorption than 405-nm blue light. 2,8One of the wavelengths of the pulse oximeter that Radu et al. 5used was also 630 nm. We measured the wavelength of our operating light, and it had a spectrum ranging from 250 to 800 nm, with a peak of 600 nm. Both the pulse oximeter and the operating light emit light that can excite porfimer sodium.
Some agents have been reported to be photosensitizing drugs: antibiotics (tetracyclines, fluoroquinolones, and sulfonamides), nonsteroidal antiinflammatory drugs, thiazide diuretics, antimitotic drugs, psychiatric drugs, calcium channel blockers, fibric acid derivatives, and so forth. 9,10Our patient had not received such photosensitizing agents besides porfimer sodium prior to anesthesia. There is no report in the literature of skin photosensitivity induced by anesthetic agents. Therefore, there is a very small possibility that agents besides porfimer sodium participated in causing the burns.
The evaluation of photosensitivity is a qualitative evaluation to determine whether a patient can be moved to a normal ward. It is not intended to determine whether patients can bear a special state, such as long exposure to light during an operation. We think that a quantitative measurement of photosensitizer in tissue is more effective for estimating the risk of burn injury and also for determining the possible exposure time to operating light. Based on our experience with the present case, we recommend the following: (1) the method of evaluation of photosensitivity should be reevaluated; (2) the operating time should be shortened as much as possible; and (3) second-generation photosensitizers that have a shorter duration of photosensitivity than porfimer sodium, such as those that are now used throughout Europe and the United States, should be used. 2,3,11The duration of skin photosensitivity caused by such drugs is shown in table 1. The high clearance rate of these drugs results in a very short light-shielding time. Using a filter that can cut wavelengths that show a high absorbance to a photosensitizer should be adopted as a fourth measure. There is a case report of a patient who had photosensitivity because of erythropoietic protoporphyria, and in perioperative management, an operation was performed using light sources in the operating room covered with yellow acrylate filters to avoid exposure of sensitive skin near the 400 nm spectrum. 12Consideration of these factors will serve to prevent burn injury during post-PDT operation and PDT during general anesthesia.
In the future, together with the popularization of PDT, there may be an increase in surgical cases of patients with potential photosensitivity, including cases of PDT during general anesthesia. To prevent the occurrence of burn injury during these procedures, in addition to evaluating the patient's skin photosensitivity and recording the time elapsed after injection of photosensitizer, it is also important to check the wavelengths of any lighting facilities in the operating room.