Key words: Complication: burns. Monitoring: pulse oximetry. Photodynamic therapy.
IT was reported in 1967 that tumor destruction could be accomplished with the use of a porphyrin substance when exposed to light. Individually, the light and the chemical may be relatively innocuous, whereas the combination can have significant effects. This principle has been applied to cancer treatment with a technique called photodynamic therapy (PDT). [2,3]PDT is a relatively new cancer treatment modality undergoing clinical trials in the United States. The treatment involves a drug (photosensitizer) that accumulates preferentially in tumor cells and subsequently kills cells on activation by light. We present a case in which the use of conventional perioperative monitoring with a pulse oximeter during PDT resulted in the loss of skin integrity at the site of the pulse oximeter probe.
The patient is a 15-yr-old girl with recurrent parietal malignant ependymoma who presented for excision of her tumor and PDT. The patient had undergone multiple attempts at surgical excision, in addition to chemotherapy and radiation therapy. After patient and parental consent, she became the first subject in a study designed to determine the side effects of PDT and the maximum tolerable dose of photofrin in children with brain tumors.
Twenty-four hours before surgery, the patient received 0.75 mg *symbol* kg sup -1 photofrin intravenously, and photosensitivity precautions, including the use of sunglasses and avoidance of direct sunlight, were followed. In the operating room, standard patient monitoring equipment, including pulse oximetry, was instituted before induction and used throughout the perioperative period. Anesthesia was induced with thiopental and sufentanil and muscle relaxation facilitated with vecuronium. Anesthetic maintenance was accomplished with a continuous infusion of sufentanil and inhalation of 0.6% isoflurane. The lungs were mildly hyperventilated with 30% Oxygen2/70% air (44% Oxygen2) until tumor resection was complete. Intraoperatively, blood pressure and temperature were maintained within normal limits. The tumor bed was exposed to a total of 11,343 J of energy via an intralipid-filled balloon conduit for the 630 nm KTP (potassium-titanylphosphate) laser light. An exposure period of 3,780 s resulted in a total light dose of 100 J *symbol* cm sup -2. The trachea was extubated at completion of the procedure, and the patient was transferred to the intensive care unit, where she was alert and following commands.
The remainder of the postoperative course was uneventful with the exception of a new second-degree thermal injury to the finger observed 48 h postoperatively when the oximeter probe was removed. The pulse oximeter was Nellcor N-180, and the probe was oxisensor II N-25 (Nellcor, Pleasanton, CA). The probe had been applied in a "band-type" position, and the blister was located on the side of the finger adjacent to the light-emitting diodes. A dermatologist was consulted, and the blister was treated conservatively and healed without incident. The pulse oximeter and its sensor probe were subsequently tested and found to be without malfunction.
PDT requires a photosensitizing compound, oxygen, and a light source. The only approved photosensitizer available in the United States is photofrin (porfimer sodium). Photofrin is a concentrated distillate of hematoporphyrins, which are naturally occurring substances found in hemoglobin. This agent is relatively selective in that it is retained in greater concentrations in malignant tissue than in normal tissue, thus maximizing destruction of malignant tissue. Nevertheless the skin, liver, kidneys, and spleen also retain somewhat greater concentrations of the drug. Photofrin has no apparent pharmacologic effect in the absence of light activation, although in mice, the spleen and bone marrow demonstrate increased cellularity. The retention of photofrin in skin requires protection of patients from bright lights, especially sunlight, for a period of 4-6 weeks, because severe injury to the skin and retina have been described. [5,6]Photofrin can be best activated by light with wavelengths ranging from 380 to 640 nm, although absorbance of wavelengths both greater and less than this range occur. Although photofrin is best activated by blue light at 410 nm, red light at 630 nm is used because it penetrates better (5 mm) through most tissues. Red light with a wavelength of 630+/-2 nm is produced by a KTP-pumped dye laser and directed through flexible optical fibers to the tumor site.
Current pulse oximeters determine the functional oxygen saturation of hemoglobin by spectrophotometry. Pulse oximeters estimate hemoglobin saturation by analyzing the pulsatile absorbance ratio of red to infrared light transmitted through a tissue bed. The ratio of pulsatile absorbance is empirically calibrated to saturation data. Pulse oximeters measure the absorbance of two wavelengths of light to optimize the differences in absorption between oxyhemoglobin and deoxyhemoglobin: the 940 nm wavelength in the infrared region and the 660 nm wavelength in the red spectral range. The Nellcor N- 180 pulse oximeter device emits red light at the 660-nm wavelength and infrared light at 920-nm wavelength.* Although the etiology of the burn in this patient remains unclear, we postulate the skin injury was that of a chemically mediated thermal burn due to prolonged exposure of the photosensitizer in the skin. Photofrin was most likely activated by the red light emitted by the pulse oximeter.
Transcutaneous oxygen monitoring is limited by numerous difficulties, such as cutaneous burns, need for frequent calibration, and multiple variables affecting its accuracy. In contrast, reported perioperative complications, including burns, pressure necrosis, and UV skin-tanning related to pulse oximetry have been few. [9-11]The previously described pulse oximeter complications were related to either defective or misuse of equipment. This is the first report of a photofrin-activated burn due to conventional use of a normally functioning pulse oximeter. The manufacturer was contacted, and pulse oximeter sensors were prepared with light emitting diodes having the longest possible clinically useful wavelength (greater than 660 nm). Additionally, the study protocol was altered to include frequent changing of the pulse oximetry probe site, which was not performed in this patient. No study patient has since experienced any loss skin integrity.
The utilization of PDT has been applied to the treatment of several types of cancers, including bladder, lung, gynecologic, abdominal, head and neck, gastrointestinal, skin, and brain. The increasing popularity of this adjunctive treatment is due to the minimally invasive nature, high efficacy, and low morbidity. The anesthetic concerns have not been fully elucidated and, like the use of routine pulse oximetry, should be further examined.
*Nellcor pulse oximeter model N- 180 service manual. Pleasanton, Nellcor, 1991, p 3.