10.1245/ASO.2004.05.015
Annals of Surgical Oncology 11:434-437 (2004)
© 2004 Society of Surgical Oncology
Pulse Oximetry Declines Due To Intradermal Isosulfan Blue Dye: A Controlled Prospective Study
Reza Momeni, MD and
Stephan Ariyan, MD, MBA
From the Melanoma Unit, Yale Cancer Center, Yale University School of Medicine, New Haven, Connecticut.
Correspondence: Address correspondence and reprint requests to: Reza Momeni, MD, Yale University School of Medicine, 60 Temple Street, New Haven, CT 06510; Fax: 203-785-5714; E-mail: reza.momeni{at}yale.edu
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ABSTRACT
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Background: Isosulfan blue dye is widely used in sentinel node surgery for malignant melanoma. Intravascular dye injection is known to interfere with pulse oximetry (SpO2), but the effects of intradermal dye injection are not well known. Our aim was to determine the effects of intradermal dye injection on SpO2.
Methods: This was a controlled, prospective study of 84 consecutive patients undergoing wide local excision of malignant melanoma and sentinel lymph node biopsy. The control group (n = 24) received no dye. The dye group (n = 60) received isosulfan blue dye intradermally at the biopsy site. SpO2 declines of 
2% were considered significant.
Results: Two patients in the control group (8%) and 20 patients in the dye group (33%) had a clinically significant SpO2 decline (P < .02). In those with significant declines in the dye group, the amount ranged from 2% to 4%. The latency of decline from the time of injection was 22.8 ± 12.7 minutes.
Conclusions: Patients who receive intradermal dye injection for sentinel lymph node surgery have a 4-fold increased rate of developing declines in SpO2. With the increasing trend toward using intradermal dye administration to map lymphatic drainage in melanoma and breast surgery, declines in SpO2 readings can be expected to occur frequently. To our knowledge, this is the first report of the effects of intradermal dye injection on SpO2 readings in a large series of patients.
Key Words: Melanoma • Blue dye • Sentinel lymph node • Pulse oximetry
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INTRODUCTION
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Pulse oximetry (SpO2) has become the standard of care for monitoring patients undergoing surgical procedures under general anesthesia. The use of light absorption to measure oxygen saturation was first proposed more than 60 years ago, but it was not until the 1960s that the noninvasive oximeter first became available.1 Intravenous injection of dyes has long been known to interfere with SpO2 measurements.2 Intravascular blue dyes, in particular, have been reported to lead to declines in SpO2 readings both in vitro and in vivo.3,4 This is believed to be caused by a surge in the serum concentration of the dye to a point at which light absorption by the dye in the red frequency becomes clinically significant.
The effects of intradermal injection of dyes have not been studied as extensively because absorption was believed to be slow, so that a lesser amount of dye would be absorbed. According to our review of the literature, only a single case report exists of oxygen desaturation due to intradermal injection of patent blue dye.5 To our knowledge, no prospective studies have been reported of the effects of intradermal injections of blue dyes on SpO2. Because we routinely use intradermal injection of isosulfan blue dye (Lymphazurin; US Surgical Corp., Norwalk, CT) in performing sentinel lymph node biopsies on patients with malignant melanoma, we observed a case of a decrease in SpO2. This led us to study the effects of intradermal dye injection on SpO2 readings in a prospective series.
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METHODS
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Study authorization was obtained from the Human Investigational Committee (Institutional Review Board) at Yale–New Haven Hospital. A series of 84 consecutive patients undergoing wide local excision of malignant melanoma and sentinel lymph node biopsy were enrolled prospectively over an 8-month period (August 2000 to April 2001). All procedures were performed with patients under general anesthesia. The fractional inspired oxygen (FIO2) was determined and set by the attending anesthesiologist such that oxygen saturation of 99% could be obtained transcutaneously before the surgical procedure was begun. Once set, this FIO2 was not changed throughout the procedure. In the experimental group (n = 60; the initial patients in the series of 84 patients), isosulfan blue dye (1%) was injected intradermally at the site of melanoma, with a volume of 1 to 2 mL. In the control group (n = 24; the last patients in the series), the procedure was performed without the aid of dye injection. All patients received nuclear tracer injection, and gamma probe guidance was used for sentinel lymph node excision in all patients. SpO2 data were collected by the anesthesiologist in each case, starting with the time of injection of isosulfan blue dye at the biopsy site (time 0) and continuing at 5-minute intervals up to 60 minutes or termination of the surgical procedure. All procedures were completed successfully.
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RESULTS
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A clinically significant decline in oxygen saturation was defined at the outset as a decrease of 2% in the SpO2 reading. Table 1 shows the details of the distribution of changes in recorded SpO2 for both groups. Two patients in the control group (8%) and 20 patients in the dye group (33%) had a clinically significant SpO2 decline (P < .02; 
2 test). However, although two thirds of the patients (40 patients; 67%) in the dye group showed no significant declines in SpO2 readings, this was exceeded by the vast majority of the patients in the control group (20 patients; 92%), who showed minimal or no changes. The distribution of changes is shown in Fig. 1. Figure 2 depicts the distribution of changes. No patient demonstrated a decline of 5% in SpO2 with intradermal dye injection.
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TABLE 1. Distribution of decline in pulse oximetry readings in dye and control groups, categorized by significant (2%) versus insignificant (<2%) decline
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FIG. 1. Distribution, in percentages in each group, of patients with and without a change 2% in pulse oximetry reading.
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FIG. 2. Proportion of patients in each group who experienced a particular percentage decline in pulse oximetry reading.
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Figure 3 is a comparison of the trends in mean SpO2 in the control group and the subset of dye group patients who experienced significant declines: 24 and 20 patients, respectively. This comparison is made to allow an understanding of the latency of the decline in the dye group. A slow declining trend, starting approximately 10 minutes after intradermal injection and reaching a nadir at 35 minutes, can be observed in patients who received dye intradermally. In this select group of patients, the time required to reach the lowest oxygen saturation reading in each patient (latency) ranged from 10 to 55 minutes. Because two of these patients were undergoing sentinel lymph node biopsies only, without wide local lesional excision, data collection was stopped after only 15 minutes (termination of the procedure). In the remaining 18 patients, the latency of maximum SpO2 decline was 22.8 ± 12.7 minutes (Fig. 3).
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FIG. 3. Average progressive trend in oximetry for the control group versus the subgroup of patients with a 2% oximetry decline, showing a latency to nadir at 23 minutes. O2 Sat, oxygen saturation.
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DISCUSSION
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Schnapp and Cohen1 offer an elegant yet simple explanation of the history, development, and principles behind SpO2. SpO2 is based on Beer’s law, which relates the concentration of an unknown solute in a solvent to the absorption of light passing through that solution. The modern pulse oximeter consists of two light-emitting diodes of different wavelengths, one in the red range (typically 660 nm) and the other in the infrared range (typically 940 nm). The proportional absorption of both wavelengths by the soft tissues and venous blood is comparable. The variability in absorption, therefore, is attributable only to the pulsatile volume of arterial blood. An R value is calculated by the oximeter as the ratio of pulsatile to baseline absorption at each of the two wavelengths. The oximeter device then compares R with an experimentally derived calibration table, preset by the manufacturer, to arrive at a final oxygen saturation.
A multitude of factors, including lighting conditions, patient movement, electrocautery, vasopressors, cardiopulmonary bypass, hypothermia, and poor perfusion, may interfere with SpO2. Systemic administration of dyes may also cause alterations in SpO2 readings. Several dyes used widely in the clinical setting, such as methylene blue, indigo carmine, indocyanine green, patent blue, and fluorescein, have been shown to interfere with SpO2 when administered intravascularly.6 The spurious desaturation seen with dyes is attributed to the absorption of light emitted by the pulse oximeter by the dye, such that the absorption ratio R is shifted. This in turn causes a miscalculation of the oxygen saturation by the machine. For this reason, increasing the FIO2 will not reverse this apparent desaturation.
Several studies have evaluated the effects of intra-arterial dye administration. Saito et al.,3 in a case report of a patient undergoing superficial temporal artery catheter placement, described a clinically worrisome decline in SpO2 readings after intra-arterial injection of patent blue dye. This desaturation occurred approximately 30 seconds after administration and lasted approximately 20 minutes. In a study of 10 patients with breast carcinoma undergoing intra-arterial catheter insertion, Chia et al.4 measured arterial blood oxygen saturation (SaO2) and oxygen partial tension by blood gas analysis (PaO2) at baseline and at various intervals after intra-arterial patent blue dye injection. They concluded not only that postinjection SpO2 readings were significantly lower than baseline, but also that the SpO2 readings were related to total dosage of dye. The SpO2 reading did not seem to bear any relation to the patients’ hemoglobin concentration. The onset of desaturation occurred within 30 seconds after intra-arterial administration of dye, the mean SpO2 nadir was 53.5%, and the mean SaO2 was 98.7%. In our study, arterial blood samples were obtained in the first three enrolled patients and did not reveal a true decrease in PaO2.
Intravenous dye injection has also been reported to cause SpO2 changes. Scheller et al.2 injected 15 subjects—5 each with intravenous indigo carmine, indocyanine green, or methylene blue dye. Under this experimental design, they observed significant desaturations, with the latency of desaturation ranging from 35 to 80 seconds and the duration of desaturation ranging from 10 to 115 seconds. Recognizing the importance of elucidating the effects of dyes used in lymphatic mapping for surgery, Larsen et al.7 performed an in vitro study using patent blue V dye. Contrary to findings of prior studies, they confirmed that the dye effectively caused a shifting of the oxygen-binding curve to the right, leading to a lower reading of SaO2.
Whereas the effects of intravascular administration of dyes are widely acknowledged, there is little in the literature regarding the effects of small amounts of local intradermal administration of dyes. We found only a single report of false desaturation due to intradermal blue dye injection, by Morell et al.,5 who reported that SaO2 readings started to decline approximately 23 minutes after the first injection and remained decreased for several hours.5 Arterial blood gas analysis demonstrated this desaturation to be false. In our study, this was confirmed when we obtained arterial blood gas results on the first three patients who developed a >2% SaO2 decline. We stopped the routine collection of arterial blood samples because the next few patients refused to have arterial blood samples drawn.
With the increasing trend toward the use of intradermal dye to map the lymphatic drainage in surgery for malignant melanoma, it is important to elucidate the effects on SpO2. The sigmoidal shape of the hemoglobin oxygen-binding curve dictates that a very small change in oxygen saturation may imply a far greater and clinically significant disturbance in PaO2. For this reason, we defined a change of 2% in the SpO2 reading as significant. We found that one third of our sample experienced clinically meaningful declines in oxygen saturation with intradermal administration of isosulfan blue dye (Fig. 1). Approximately half of the patients experienced a 1% decline.
In the group that experienced 2% declines, the latency of desaturation was 22.8 ± 12.7 minutes. This finding was in agreement with the 23-minute latency reported by Morell et al.5 in their single-patient case report. This delayed onset, compared with latencies in the 30- to 80-second range reported in studies of intravascular administration of dyes, must be kept in mind by the operating surgeon and the treating anesthesiologist. As noted in this discussion, multiple prior studies have shown this effect to be erroneous and not supported by arterial blood gas analysis.
We found that the SpO2 reading for these patients may decline progressively until 35 to 40 minutes (Fig. 3). Although our study was limited in that SpO2 data collection stopped at 60 minutes after dye injection, the 35- to 40-minute time point may represent the nadir in the SpO2 readings with intradermal dye injection. There is no effect on the true arterial oxygen levels; therefore, no treatment may be needed.
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CONCLUSIONS
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With the increasing trend toward using intradermal administration of dyes to map lymphatic drainage in melanoma and breast surgery, we should be aware of the possibility of decreased SpO2 readings in the intraoperative and postoperative periods. In this study, we found that up to one third of patients may demonstrate significant but erroneous oxygen desaturation as recorded with SpO2 with intradermal isosulfan blue dye. The onset of this decline is not immediate, as was previously reported with intravascular administration of dyes, but usually occurs approximately 23 minutes after injection. Additionally, the desaturation may last much longer than that seen with intravascular dye injection. Further studies will be needed to define the relationship between SpO2 reading declines and factors such as body mass index, primary melanoma site, smoking, and cardiopulmonary disease history. We expect our findings to be of interest to clinicians in diverse disciplines who care for patients receiving intradermal dye. These clinicians will need to rely on clinical judgment and ancillary laboratory testing to differentiate these observed decreases in SpO2 readings from true oxygen desaturation.
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ACKNOWLEDGMENTS
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Supported by National Institutes of Health Research Grant CA-16359 from the National Cancer Institute.
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FOOTNOTES
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A large number of patients undergoing sentinel lymph node mapping with intradermal Lymphazurine blue dye may display a decline in pulse oximetry readings in the perioperative period.
Received for publication May 13, 2003.
Accepted for publication December 3, 2003.
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REFERENCES
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- Schnapp LM, Cohen NH. Pulse oximetry. Uses and abuses. Chest 1990; 98: 1244–50.[Abstract/Free Full Text]
- Scheller MS, Unger RJ, Kelner MJ. Effects of intravenously administered dyes on pulse oximetry readings. Anesthesiology 1986; 65: 550–2.[CrossRef][Medline]
- Saito S, Fukura J, Shimada H, Fujita T. Prolonged interference of blue dye "patent blue" with pulse oximetry readings. Acta Anaesthesiol Scand 1995; 39: 268–9.[Medline]
- Chia Y-Y, Liu K, Kao P-F, Sun G-C, Wang K-Y. Prolonged interference of patent blue on pulse oximetry readings. Acta Anaesthesiol Sin 2001; 39: 27–32.[Medline]
- Morell RC, Heyneker T, Kashtan HI, Ruppe C. False desaturation due to intradermal patent blue dye. Anesthesiology 1993; 78: 363–4.[Medline]
- Ralston AC, Webb RK, Runciman WB. Potential errors in pulse oximetry. III. Effects of interferences, dyes, dyshaemoglobins, and other pigments. Anaesthesia 1991; 46: 291–5.[Medline]
- Larsen VH, Freudendal-Pedersen A, Fogh-Andersen N. The influence of patent blue V on pulse oximetry and haemoximetry. Acta Anaesthesiol Scand Suppl 1995; 107: 53–5.[Medline]
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ABSTRACT
INTRODUCTION
