Sir: We appreciate the interest and comments of Dr. Knobloch et al. regarding our article “Serum Cotinine Concentration and Wound Complications in Head and Neck Reconstruction” published recently in the Journal. Our study concluded that elevated serum cotinine concentrations above 10 ng/ml were predictive of increased postoperative wound complications in head and neck reconstruction after ablative oncologic surgery.1 Dr. Knobloch and colleagues raise several interesting points that reinforce our experimental findings. First, they point out—and our findings support—that there is a tendency for actively smoking patients to underreport their smoking habits and an increasing incidence of postoperative wound problems with increasing preoperative serum cotinine levels.1,2 Thus, we fully agree with the suggestion that both patients and surgeons would benefit from a preoperative stratification according to patient cotinine levels. Second, we agree completely that the timing of measurement is important. As we pointed out, our data were limited in that our cotinine measurement was not on the day of surgery and was only a single data point on presentation (not a fixed time ahead of the surgery date). A more powerful means of stratification would be a series of measurements over time to provide a linear trend and a source of feedback for both patient and treating physician. As we now have a prospective tobacco treatment program, our cessation clinicians can provide such feedback ahead of surgery during the period of workup. Currently in the United States, the cost of the serum cotinine assay ranges from $15 to $40. However, not all laboratories are able to process the measurement, thus limiting access to such testing. Cotinine is concentrated in the urine at 10-fold the serum concentration, and urine cotinine appears to be as reliable as serum measurements.3 There exist many in-office urine assays that are as simple to conduct as a preoperative urine pregnancy test. Disposable assays range from $1.20 to $9.95, depending on the manufacturer and number of tests purchased. Thus, we would agree that using urine testing could alleviate the issue of cost, make the test more convenient, and provide a rapid result. The $6 spent for a series of three preoperative measurements, we argue, would be well worth the cost, as it provides an assessment of a patient’s preoperative smoking risk profile. This would allow the surgeon to delay a procedure where appropriate until more aggressive smoking cessation measures could be instituted, or provide objective documentation of a patient’s failure to comply with recommended smoking abstinence. Finally, there is clear evidence that transdermal nicotine is metabolized to serum cotinine, which is directly related to the dosage applied to the skin.4 As for the role of transdermal nicotine in patients undergoing microsurgical reconstruction, Dr. Rohrich et al. aptly summarized the vascular effects of serum nicotine as the following: “Nicotine is the principal vasoactive component, inducing endothelial wall injury, inhibiting capillary blood flow, and releasing catecholamines. It also decreases epithelialization and stimulates thromboxane A2, a potent vasoconstrictor increase[ing] platelet adhesiveness.”5 Thus, for these reasons, we feel that nicotine, regardless of the mode of delivery (including transdermal patches), should for now be routinely avoided in any patient with planned microvascular reconstruction, especially in cases such as deep inferior epigastric perforator flaps, where the microcirculation of the watershed regions may be sensitive to minor reductions in flow. We would encourage controlled, blinded, prospective studies to further elucidate the predictive value of cotinine measurement, to establish successful preoperative tobacco cessation interventions, and to test the role of pharmaceutical agents in blocking the effects of nicotine. Vincent P. Marin, M.D. Kristen B. Pytynia, M.D., M.P.H. Howard N. Langstein, M.D. Kristina R. Dahlstrom, M.S. Qingyi Wei, M.D., Ph.D. Erich M. Sturgis, M.D., M.P.H. Department of Plastic Surgery University of Texas Southwestern Medical Center Dallas, Texas DISCLOSURE None of the authors has a financial interest in any of the drugs, devices, or products mentioned in this communication.