Anesth Analg 2000;91:1024-1026
© 2000 International Anesthesia Research Society
CASE REPORTS
The Efficacy and Safety of EMLA® Cream for Awake Fiberoptic Endotracheal Intubation
Ghassem E. Larijani, PharmD,
David Cypel, MD,
Irwin Gratz, DO,
Lynn Mroz, MD,
Robert Mandel, MD,
Mary Afshar, PharmD, and
Michael E. Goldberg, MD
Department of Anesthesiology, Cooper Health System, University of Medicine and Dentistry of New Jersey, Camden, New Jersey
Address correspondence and reprint requests to G. E. Larijani, PharmD, Department of Anesthesiology, One Cooper Plaza, Camden, NJ 08103. Address e-mail to larijage{at}umdnj.edu
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Abstract
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EMLA® Cream (EC; Astra, Westborough, MA) has been widely used as a local anesthetic. Limited safety information is available with respect to the application of EC to the oral mucous membranes. The purpose of this pilot study was to evaluate the efficacy and safety of EC when applied to oral mucosa for fiberoptic intubation. Twenty ASA physical status I–IV patients (11 women and 9 men), 28–57 yr old, who were scheduled for awake, fiberoptic, intubation participated in this open-label study. A total of 4 g of EC was used for 5 min until the patient showed no evidence of a gag reflex (this was evaluated clinically by the patient’s acceptance of the William’s airway and considered the endpoint for assessing adequate topicalization of the oropharynx). The measured peak plasma concentration of lidocaine or prilocaine did not reach toxic levels in any patient. Methemoglobin levels did not exceed normal values (1.5%) in any patient, and there was no relationship between methemoglobin levels and patient weight, amount of EC used, measured peak plasma concentration, or times to measured peak concentrations of prilocaine or lidocaine. We conclude that EC provided satisfactory topical anesthesia allowing for successful oral fiberoptic intubation in all patients and should be considered a safe alternative for anesthetizing the airway of patients requiring awake oral fiberoptic intubation.
Implications: EMLA® Cream (Astra, Westborough, MA) provides satisfactory topical anesthesia of the oropharynx and should be considered a safe and effective alternative for anesthetizing the airway for awake oral fiberoptic intubation.
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Introduction
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EMLA® Cream (EC; Astra, Westborough, MA) is a 1:1 eutectic mixture of lidocaine (2.5%) and prilocaine (2.5%) and has been widely used as a local anesthetic to reduce the pain and discomfort associated with venipuncture, arterial and venous cannulation, and lumbar puncture. EC has also been used to provide topical anesthesia for small skin grafts and genitourinary, laryngopharngeal, and dental surgeries (1,2). EC provides local anesthesia by blocking the initiation and transmission of impulses. After topical application, its absorption, onset, and duration of analgesic effect depends on blood flow, thickness, and pathology of the skin. Limited safety information is available with respect to the application of EC to the oral mucous membranes, particularly as it applies to the plasma concentration of lidocaine, prilocaine, or the development of methemoglobinemia. Hassio et al. (3) conducted a study whereby 4 g of EC was applied to the upper gingiva for 4 min. The largest individual venous lidocaine concentration was 470 ng/mL at 5 min, and no toxic reaction was reported. Another study conducted by Holst and Evers (2) found that EC significantly reduced the pain from needle insertions into the oral mucosa 2–5 min after its placement. Despite the proven efficacy of EC to relieve pain when applied to intact skin, information about its use on the mucous membranes is limited.
Fiberoptic intubation is used for airway control in situations that may present difficult intubation, often requiring the use of local anesthetics. We have previously used EC to anesthetize the mouth and oral pharynx for awake, fiberoptic, orotracheal intubation. The purpose of this study was to evaluate the efficacy and to determine the serum levels of prilocaine, and lidocaine, as well as methemoglobin levels after application of EC to oral mucosa for fiberoptic intubation.
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Methods
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After we obtained institutional review committee approval and informed consent, 20 ASA physical status I–IV patients (11 women and 9 men) who were scheduled for awake, fiberoptic, intubation participated in this open-label study. Patients with congestive heart failure, congenital or idiopathic methemoglobinemia, sensitivity to amide type local anesthetics, and those receiving antiarrhythmic drugs were excluded from the study.
Patients were premedicated with midazolam (2 mg IV) and glycopyrrolate (0.2–0.4 mg IV). In the holding area, EC was first applied in a small globule to a tongue depressor and placed (topical anesthetic side down) on the tongue. The patient was asked to hold the depressor there for 1–2 min. Next, small amounts of EC were placed on a cotton applicator tip and applied to the soft palate, uvula, tonsillar pillars, and posterior wall of the oropharynx. This was repeated for the next 5 min until the patient showed no evidence of a gag reflex (or until it was greatly diminished) or a total of 4 g EC was used. In the operating room (once the gag was diminished), a William’s airway, coated on the exterior with EC, was placed. Additional sedation was provided by small doses of a benzodiazepine and narcotic given in doses that allowed the patient to be calm but capable of obeying commands. If the patient tolerated this process, fiberoptic intubation was initiated through the William’s airway. Patient acceptance of the William’s airway was considered the endpoint for assessing adequate topicalization of the oropharynx. A small amount of EC was placed on the end of the fiberscope and, if necessary, on the vocal cord immediately before intubation. After fiberoptic intubation, the patient underwent anesthesia and surgery as planned. If local anesthesia of the oropharynx was unsuccessful after the application of approximately 4 g of EC, a rescue protocol was to be initiated as deemed necessary by the investigators.
Blood samples (5 mL each) were taken before and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after the initial application of EC to measure plasma concentrations of lidocaine and prilocaine by gas chromatography/mass spectroscopy/single ion monitoring. Blood samples were centrifuged within 30 min of collection, and plasma samples were frozen at -20°C until analysis. This assay was validated for analyses of lidocaine and prilocaine over a nominal plasma concentration range of 2.5 to 125 ng/mL. The lower limit of quantitation for lidocaine and prilocaine in this assay is 2.5 ng/mL with an inter- and intraday coefficient of variation of <11% across the calibration curve of each analyte. Additional blood samples were obtained before and at 30, 60, 90, 120, 180, 240, 360 min after the initial EC application to determine the blood levels of methemoglobinemia.
Measured peak plasma concentration (Cmax) of prilocaine and lidocaine, as well as the times to measured peak concentrations (Tmax) were obtained by inspecting individual plasma concentration-time profiles. Individual estimates of the apparent elimination rate constant (k) for drugs were obtained by log-linear regression of the terminal portions of the plasma concentration-time curves. At least three data points were used to calculate k. Half-lives were calculated as ln(2)/k. Paired Student’s t-test was used for statistical analysis. A P < 0.05 was considered significant. Data were presented as mean ± SD.
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Results
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Patients ranged in age from 28 to 57 yr with a mean age of 44 ± 8 yr and a mean body weight of 91 ± 30 kg. The indications for fiberoptic intubations were either a history of difficult intubation or cervical spinal instability. The mean time from the application of EC to patient acceptance of the oral airway was 11 ± 6 min. An average of 3.96 ± 0.43 g EC was used for awake, fiberoptic intubation. All patients were successfully intubated fiberoptically, and no rescue protocol for supplemental local anesthesia was required. Coughing was observed in all patients once the fiberscope was passed into the trachea.
The Cmax of lidocaine or prilocaine did not reach toxic levels in any patient, and the elimination half-life of either drug was consistent with those previously reported after other routes of administration (4,5) (Table 1).
Methemoglobin levels did not exceed normal values (1.5%) (6,7) in any patient, and there was no relationship between methemoglobin levels and patient weight, amount of EC used, Cmax, or Tmax of prilocaine or lidocaine (Table 2).
However, compared with baseline values, statistically significant increases in methemoglobin levels occurred within 6 h after the application of EC (baseline mean = 0.47% ± 0.19% versus peak mean = 0.81% ± 0.25% P < 0.001).
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Discussion
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The use of fiberoptic tracheal intubation is well established and has been extensively supported in the literature for managing the difficult airway. An awake fiberoptic intubation allows the patient to maintain the tonicity of the airway muscles providing a degree of safety that may be lost in the anesthetized, paralyzed patient. In addition to difficult tracheal intubation, there are other conditions in which fiberoptic laryngoscopy may be superior to conventional techniques in securing the airway. These include, but are not limited, to the following: compromised airway, restricted or limited neck movement, anatomic deformities, and high risk for pulmonary aspiration.
Successful awake fiberoptic intubation requires cooperation from the patient. This can be enhanced by adequate explanation and preparation of the patient. Keys to successful intubation include control of secretions by the use of an antisialagogue, adequate sedation to alleviate anxiety, and adequate anesthesia to ensure patient comfort. Anesthesia for awake fiberoptic intubation can be accomplished by a variety of techniques, which include topical anesthesia, nerve blocks, and transtracheal injection of a local anesthetic. One or a combination of these anesthetic techniques can be used successfully with little evidence of the superiority of any one individual technique. Adequate anesthesia will improve intubating conditions and minimize repeat airway instrumentation that can cause mucosal bleeding complicating fiberoptic intubation.
In this study, we found that the application of EC (4 gm) provides good topical anesthesia to the mouth and oropharyngeal area for awake fiberoptic intubation. EC provided satisfactory topical anesthesia allowing for successful oral fiberoptic intubation in all of the study patients. In addition, plasma concentrations of prilocaine and lidocaine were below toxic levels with no evidence of significant methemoglobinemia. All patients described their anesthetic experience as satisfactory. No serious side effects were observed or reported. The described method allows for easy topical placement of local anesthetics to the oral mucosa without the use of special equipment and results in good patient cooperation. Adequate anesthesia was achieved in all patients in a relatively short period of time (<5 min). Although questions about the taste of EC were not specifically asked, it is our clinical impression that they did not consider it unpleasant, which agrees with previous clinical investigations (8). The study design limits conclusions that can be drawn about the efficacy of EC in that no comparisons groups were evaluated. Despite this, EC was well tolerated by all of the patients and can be considered to be a safe alternative for anesthetizing the airway of patients requiring awake oral fiberoptic intubation.
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Acknowledgments
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Supported, in part, by an educational grant from Astra-Zeneca Pharmaceutical Co.
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References
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Accepted for publication June 5, 2000.
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Intraoral Use of EMLA Cream for Fiberoptic Intubation
Journal Watch Emergency Medicine,
November 15, 2000;
2000(1115):
9 - 9.
[Full Text]
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Abstract
Introduction
