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Case Reports  |   February 1995
Large Doses of Topical Lidocaine during Microvascular Surgery Are Not Associated with Toxic Blood Concentrations
Author Notes
  • (Johnstone) Professor and Vice Chairman, Department of Anesthesiology.
  • (Wax) Assistant Professor, Department of Otolaryngology-Head and Neck Surgery.
  • (Bishop) Resident, Department of Anesthesiology.
  • (Chafin) Resident, Department of Otolaryngology-Head and Neck Surgery.
  • Received from the Departments of Anesthesiology and Otolaryngology-Head and Neck Surgery, West Virginia University, Morgantown, West Virginia. Submitted for publication September 9, 1994. Accepted for publication October 26, 1994.
  • Address reprint requests to Dr Johnstone: Department of Anesthesiology, 3618 Robert C. Byrd Health Sciences Center, West Virginia University Morgantown, West Virginia 26506.
Article Information
Case Reports
Case Reports   |   February 1995
Large Doses of Topical Lidocaine during Microvascular Surgery Are Not Associated with Toxic Blood Concentrations
Anesthesiology 2 1995, Vol.82, 593-596. doi:
Anesthesiology 2 1995, Vol.82, 593-596. doi:
Key words: Anesthetic techniques; topical. Anesthetics, local; lidocaine. Pharmacokinetics. Surgery; microvascular. Toxicity.
SURGEONS performing microvascular anastomoses often apply lidocaine topically in doses exceeding published safe limits without apparent systemic toxicity. Standard pharmacology and anesthesiology references list maximal doses of lidocaine as 750 mg or less, [1–3 ] Reconstructive surgeons, however, may apply several thousand milligrams of lidocaine, at concentrations of 4–20%, directly on blood vessels being anastomosed, to prevent vasospasm during finger reattachment or tissue transfer surgery. [4,5 ] To acquaint anesthesiologists with our resolution of this dose dilemma, we report four consecutive patients requiring free-flap reconstruction, during which topical lidocaine doses of 1,340–1,900 mg were used. After institutional review board approval and with the consent of each patient, we measured systemic blood concentrations of lidocaine in these patients before and every 15 min during and for 1 h after topical application.
Case Reports
Case 1
A 54-yr-old, 72-kg man with squamous cell carcinoma of the hypopharynx underwent total laryngopharyngectomy with bilateral modified radical neck dissections. He had a history of alcoholic cirrhosis, took amitriptyline, and was rated an ASA physical status 3. His tumor was treated preoperatively with radiation therapy. Anesthesia was induced intravenously with thiopental and 70 mg lidocaine and maintained with nitrous oxide, isoflurane, and fentanyl. The mucosal defect was reconstructed with a free fasciocutaneous radial forearm flap. Arterial inflow to the graft was from the facial artery; outflow was into the superior thyroid vein. Vascular anastomoses were secured with 9–0 nylon sutures. The surgeons applied 1,900 mg 4% lidocaine, using a 10-ml syringe with an 18-G intravenous-catheter, onto the operative blood vessels during the 3 h required for anastomoses. Fifteen blood samples, collected from a radial artery catheter, throughout this period, all had less than 0.5 micro gram/ml lidocaine. Postoperatively the patient required surgical exploration for flap problems but was ultimately discharged in satisfactory condition. No evidence of systemic lidocaine toxicity was detected.
Case 2
A 67-yr-old, 81-kg man with squamous cell carcinoma of the oral cavity underwent composite resection of the floor of the mouth, mandible, and cervical skin with bilateral modified radical neck dissections. Before surgery, he took no medicines but had received radiation therapy. Anesthesia was induced intravenously with thiopental and 100 mg lidocaine and was maintained with nitrous oxide and isoflurane. The soft tissue defect was reconstructed with a latissimus dorsi myocutaneous free flap. While suturing the vascular anastomoses, the surgeons applied 1,400 mg 4% lidocaine onto the facial artery and superior thyroid vein. Anastomoses required 75 min. Before the anastomoses, the blood concentration of lidocaine was less than 0.5 micro gram/ml, during anastomoses it increased to 0.8 micro gram/ml, and was 0.9 micro gram/ml 1 h after the last topical application of lidocaine. The patient awoke in normal fashion and was discharged in a satisfactory condition.
Case 3
A 45-yr-old, 83-kg man with squamous cell carcinoma of his left alveolar ridge underwent mandibulectomy and left modified radical neck dissection. He had a history of alcohol abuse. His tumor was treated preoperatively with radiation therapy. Anesthesia was induced intravenously with thiopental and 100 mg lidocaine and was maintained with 12 micro gram/kg fentanyl, nitrous oxide, and isoflurane. The surgeons injected 70 mg 1% lidocaine with epinephrine into the gingiva before teeth extraction. The soft tissue defect was closed with a left latissimus dorsi free flap. Vascular anastomoses started 8 h 40 min after anesthetic induction and 6 h after teeth extraction and required 90 min to complete. The surgeons applied 1.340 mg 4% lidocaine onto the exposed vessels during this period. Before lidocaine was applied topically, the lidocaine blood concentration was 0.6 micro gram/ml. During anastomoses of the graft vessels, the peripheral blood concentration of lidocaine rose to 1.5 micro gram/ml and 60 min after the last topical application of lidocaine, remained at 1.3 micro gram/ml. The patient awoke and recovered in routine fashion.
Case 4
A 64-yr-old, 63-kg woman with mucoepidermoid carcinoma of her tongue base underwent composite resection of the tonsil, tongue base, and mandible, along with a left modified radical neck dissection. Medical history included hypertension treated with atenolol and hydrochlorothiazide. Anesthesia was induced intravenously with thiopental and 60 mg lidocaine and maintained with nitrous oxide and isoflurane. Oral surgeons injected 150 mg 1% lidocaine with epinephrine before teeth extraction. The tissue defect after resection was closed with a radial forearm free flap. The surgeons applied 1,400 mg 4% lidocaine over 84 min. starting 9 h after induction of anesthesia and 8 h after teeth extraction, to the graft vessels during anastomosis. Before the anastomoses, the peripheral blood concentration of lidocaine was less than 0.5 micro gram/ml. The lidocaine concentration peaked at 0.6 micro gram/ml shortly after the last topical application, and declined to less than 0.5 micro gram/ml 1 h later. The patient awoke in the operating room after 13 h of anesthesia and was discharged in satisfactory condition.
Discussion
Surgical reconstruction of patients after tissue ablation for extensive cancer or trauma is often complex and difficult. Free-tissue transfers of muscle and skin have greatly facilitated both the cosmetic and the functional rehabilitation of these patients. Spasm of the blood vessels in the transferred tissue, during and after the surgery, can contribute to death of the transferred tissue. To prevent vasospasm, the liberal use of topical lidocaine has become a standard surgical procedure. [4,5 ] The quantity of lidocaine used depends on the duration of the procedure, the number of vessels, anastomosed, and the amount of traumatic vasospasm, but the quantity usually exceeds the maximum recommended doses published in the anesthesia literature. Laboratory studies demonstrate that the greater the concentration of lidocaine used, up to 12% and 20%, the better the protective effect on the vascular anastomoses. [6,7 ] The response to lidocaine may even be biphasic, with low concentrations constricting arterioles, whereas high concentrations dilate them. [8 ] Our clinical experience is that direct application of 4% lidocaine, which is commercially available, is adequate to achieve vascular relaxation.
Lidocaine causes systemic toxicity because of actions upon the cardiovascular and central nervous systems after sufficient drug has been absorbed. These toxic effects generally occur after blood concentrations of lidocaine exceed 5–10 micro gram/ml. [9 ] The dose of lidocaine that leads to a toxic blood concentration varies with the site of injection, the use of adjuvant drugs, the ability of the patient to metabolize lidocaine, and other pharmacokinetic factors. [10,11 ] Lidocaine doses of 400 mg administered for intercostal nerve block produce peak blood concentrations of 4–6 micro gram/ml and, for epidural block, produce peak blood concentration of 2–4 micro gram/ml. [12 ] Absorption of local anesthetics applied topically to tracheal membranes can be rapid and cause death from overdosage. [13 ] Any assumption, however, that occurrences of toxicity from all topical applications of lidocaine are similar is unfounded. Hou et al., investigating the absorption of 10% lidocaine applied topically to anastomosed iliac and femoral arteries in rabbits, determined that peak absorption occurs between 5 and 15 min. is significantly greater through intact vessels than anastomosed ones, and changes at different anatomic sites and that most absorption of lidocaine is through perivascular tissue. [14 ].
Our experience, as illustrated by these case reports, is that doses up to 2,000 mg 4% lidocaine applied topically to arteries and veins being anastomosed during free-tissue transfer surgery do not cause toxic blood concentrations (Table 1). The relatively low serum concentrations measured in our patients suggest that most of the administered lidocaine was never absorbed. We measured lidocaine concentrations in serum using commercially available fluorescence polarization immunoassay technology with a sensitivity of 0.1 micro gram/ml between 0.5 and 10 micro gram/ml. Decreased absorption of lidocaine drug from the surgical wound may be due to sludging of blood and drying of the transferred tissues during prolonged environmental exposure or due to changes induced by preceding radiation therapy of the underlying tissues. Also, after squirting lidocaine through an intravenous catheter onto the vessels being anastomosed, our surgeons absorb any excess with gauze sponges.
Table 1. Summary of Lidocaine Doses and Results
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Table 1. Summary of Lidocaine Doses and Results
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Fifty years after its induction, lidocaine remains the most widely used local anesthetic because of its extraordinary efficacy and safety. [1 ] The worldwide medical literature contains more than 20,000 articles referencing lidocaine.* Despite this massive database, the maximum safe dose of lidocaine for topical application during microvascular surgery is unclear. Our surgeons have successfully limited their topical applications of lidocaine to 2,000 mg of 4% solution. Laboratory studies would support greater concentrations to prevent vasospasm, but these may be toxic to exposed nerves. [15 ] Until addition clinical experience with large concentrations and doses of topically applied lidocaine during microvascular surgery is reported, we advocate continued caution, because toxicity could vary with surgical technique and anatomic site. Determinations of blood lidocaine concentrations are generally available in most hospitals that perform microvascular surgery and could be done whenever the lidocaine dose exceeds 750 mg. Our experience is that these measurements are not necessary, in the absence of clinical signs of toxicity, with topical doses less than 2,000 mg. We have not used regional anesthesia during these surgical operations except for the extraction of teeth, but we do inject 1–1.5 mg/kg lidocaine intravenously during anesthetic induction in patients with perioral tumors to decrease airway irritability. We keep midazolam or propofol available to treat central nervous system toxicity. [16 ].
In summary, microvascular surgeons often apply large doses of lidocaine topically to vessels undergoing anastomosis to prevent vasospasm. Clinically, doses of 4% lidocaine up to 2,000 mg are not associated with toxic blood concentrations. Pharmacokinetic studies are warranted to define the safe maximum topical doses.
*Astra: Personal communication. 1994.
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Shaw WW, Tark KC: Principles of microvascular surgery. Plastic Surgery. Edited by Smith JW. Aston SJ. Boston, Little, Brown, 1991. pp 1015-1028.
Swartz WM: Microvascular surgery. Vascular Surgery. Edited by Rutherford RB. Philadelphia, WB Saunders. 1989, pp. 351-355.
Geter RK, Winters RW. Puckett CL: Resolution of experimental microvascular spasm and improvement in anastomotic patency by direct topical agent application. Plast Reconstr Surg 77:105-115, 1986.
Beekiman WH, Dammeijer PF, Sluimers JE: Kort WJ, van des Meulen JHC: Improvement in blood flow and diameter of the postanastomotic rat tail artery by topical application of lidocaine in varying concentrations. Ann Plast Surg 24: 248-251, 1990.
Johns RA, DiFazio CA, Longnecker DE: Lidocaine constricts or dilates rat arterioles in a dose-dependent manner. ANESTHESIOLOGY 62:141-144, 1985.
Foldes FF, Molloy R, McNall PG, Koukal LR: Comparison of toxicity of intravenously given local anesthetic agents in man. JAMA 172: 1493-1498, 1960.
Tucker GT: Pharmacokinetics of local anesthetics. Br J Anaesth 58:717-731, 1986.
Thomson PD, Melmon KL, Richardson JA, Cohn K, Steinbrunn W, Cudihee R, Rowland M: Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Ann Int Med 78:499-508, 1973.
Braid DP, Scott DB: The systemic absorption of local analgesic drugs. Br J Anaesth 37:394-404, 1965.
Adriani J, Campbell D: Fatalities following topical application of local anesthetics to mucous membranes. JAMA 162:1527-1530, 1956.
Hou S-M, Liu T-K, Yu H-Y: Absorption of lidocaine following topical application in microvascular procedures on rabbits. J Orthop Res 9:545-549, 1991.
Lambert LA, Lambert DH, Strichartz GR: Irreversible conduction block in isolated nerve by high concentrations of local anesthetics. ANESTHESIOLOGY 80:1082-1093, 1994.
Bishop D, Johnstone RE: Lidocaine toxicity treated with low-dose propofol. ANESTHESIOLOGY 78:788-789, 1993.
Table 1. Summary of Lidocaine Doses and Results
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Table 1. Summary of Lidocaine Doses and Results
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