Department of Anaesthesia, Norfolk and Norwich University Hospital, Colney Lane, Norwich NR4 7UY, UK
* Corresponding author. E-mail: nicholas.woodall{at}nnuh.nhs.uk
Accepted for publication June 21, 2005.
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Abstract |
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Methods. After i.v. glycopyrrolate 3 µg kg1 and intranasal xylometolazone 0.1%, lidocaine 4% 200 mg was administered by nebulizer. Supplementary lidocaine to a maximum total of 9 mg kg1 was applied directly and via a fibreoptic endoscope. Nasotracheal intubation was performed once the vocal cords became unreactive. Heart rate, non-invasive blood pressure and oxygen saturation were recorded at 5-min intervals. Blood sampling commenced with a baseline sample and continued at 10 min intervals until 60 min after final administration of local anaesthetic. Subjects graded levels of anxiety, pain and coughing using written and visual analogue scales.
Results. Conditions for fibreoptic endoscopy and intubation were good. Seventeen received the maximum lidocaine dose of 9 mg kg1. The average dose used was 8.8 mg kg1. All plasma lidocaine concentrations assayed were below 5 mg litre1. Four volunteers reported feeling lightheaded after the procedure, despite normal blood pressure. Of these, two had the highest plasma lidocaine concentrations recorded: 3.5 and 4.5 mg litre1. Twenty-two of the 25 subjects found endoscopy and intubation acceptable, three found it enjoyable and no subject rated it as distressing.
Conclusions. This method of airway anaesthesia was acceptable to this small group of unsedated subjects. It produced good conditions for fibreoptic intubation. A maximum calculated lidocaine dose of 9 mg kg1 did not produce toxic plasma concentrations of lidocaine.
Keywords: airway, tracheal intubation ; anaesthetics local, lidocaine ; anaesthetic techniques, fibreoptic ; anaesthetic techniques, laryngoscopy ; toxicity, local anaesthetics
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Introduction |
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A local anaesthetic technique acceptable to unsedated volunteers undergoing awake fibreoptic intubation may have applications where avoidance of sedation is desirable, when haemodynamic stability is important,6 7 or, as used here, when providing instruction in awake fibreoptic intubation. Though well tolerated, the acceptability of the procedure might be improved by the application of more lidocaine. However, when using this method of airway anaesthesia we have observed symptoms that could possibly be attributed to lidocaine toxicity.5 Therefore, we undertook this study to assess the acceptability of the technique and measure peak plasma lidocaine concentrations achieved.
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Methods |
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The subjects fasted for 4 h before endoscopy. The administration of local anaesthetic and performance of endoscopy took place in an anaesthetic room or operating theatre with a full range of resuscitation equipment immediately available. After initiation of non-invasive monitoring, a 20 gauge i.v. cannula was inserted and an infusion of Hartmann's solution was established. Intravenous glycopyrrolate 3 µg kg1 was administered and two puffs of xylometolazone 0.1% were delivered to each nostril. Over the following 20 min, with the subject sitting upright, lidocaine 4%, 200 mg, was nebulized with an Intersurgical Cirrus nebulizer using oxygen 8 litre min1 as a driving gas. After nebulization, 2 ml of 5% lidocaine (100 mg) containing 0.5% phenylephrine (Aurum) and 4 aliquots (40 mg) of 10% lidocaine were sprayed into the nose and oropharynx respectively. Endoscopy was then performed in the supine position; supplementary doses of lidocaine 4% up to a maximum total dose of 9 mg kg1 were administered to the airway via the fibrescope. Most of the drug delivered by nebulization is wasted.8 For purposes of lidocaine dose calculation, it was assumed that 75% of the nebulized drug was lost, therefore only 50 mg of the nebulized lidocaine was included in the dosage calculation.
A 1.1 mm end hole epidural catheter was threaded through the working channel of the endoscope. Proximally this was attached to a three-way tap and an oxygen supply of 1 litre min1 (Fig. 1A). Lidocaine injected via the three-way tap (Fig. 1B) emerged distally as a fine spray.9 When the vocal cords ceased to react to further lidocaine administration, the endoscope was advanced into the trachea and a nasotracheal tube was inserted.
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A baseline blood sample was taken using the i.v. cannula before any lidocaine was administered (T0). The second sample was taken 20 min later, after nebulization (T20). Subsequently, additional topical lidocaine was administered directly and via the endoscope to the lower airway. Further blood samples were taken at 10 min intervals until 60 min had elapsed after the last dose of lidocaine. Two 5 ml samples of blood were drawn via a three-way-tap from the cannula; the first 5 ml, containing dead space fluid, was discarded. Blood samples were then separated in a centrifuge and stored at 4°C. Assays were performed usinghigh-performance liquid chromatography with UV detection accurate to 0.01 mg litre1.10
After the procedure, all delegates completed an anonymous questionnaire. They graded levels of anxiety, pain and coughing using written and visual analogue scales. Subjects were asked to record any local anaesthetic side-effects they may have experienced.
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Results |
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Continuous oximetry and ECG monitoring revealed no abnormalities. The average increase in MAP was 16.2%, with a range of 1.033.3% (Fig. 2). HR values were more variable, with an average increase of 30.2% and a range of 0158.3% (Fig. 3).
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Seventeen volunteers received the maximum calculated lidocaine dose of 9 mg kg1. The median dose of lidocaine used was 8.9 mg kg1, with a range of 7.39.2 mg kg1. All levels assayed were below 5 mg litre1, a level commonly regarded as toxic.1114 These are represented graphically in Figure 4.
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All 25 subjects reported endoscopy and intubation to be acceptable; three found it enjoyable. The visual analogue scores for pain, anxiety and coughing/gagging averaged 6.3, 6.3 and 6.5 respectively (where 0 was described as absolutely awful and 10 as enjoyable).
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Discussion |
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Rapid absorption, or the administration of excessive doses of local anaesthetic (lidocaine), is well known to cause toxicity. The toxic plasma concentration of lidocaine is commonly accepted as 5 mg litre1,1114 though concentrations of up to 18 mg litre1 have been recorded without apparent toxicity.15 Side-effects of lidocaine administration1619 are reported to develop when plasma concentrations reach 4 mg litre1. Early features include tinnitus, lightheadedness and circum-oral numbness. Visual disturbances may occur with a plasma concentration of 6 mg litre1, involuntary muscle spasms at 8 mg litre1, convulsions at 10 mg litre1 and cardiac depression at 20 mg litre1. The adoption of 5 mg litre1 as a toxic plasma lidocaine concentration appears to be somewhat arbitrary; however, the acceptance of 5 mg litre1 as an upper limit affords a margin of safety with regard to serious side-effects, such as convulsions and cardiac arrest.
The highest plasma lidocaine concentration we observed was 4.5 mg litre1. Only two subjects experienced peak plasma lidocaine levels greater than 3 mg litre1. Both subjects complained of lightheadedness and of feeling unwell immediately after the procedure. Symptoms coincided with the peak plasma lidocaine concentration observed 2060 min after the last administration of lidocaine. These symptoms might alert the clinician to limit further administration or indicate the need for continued close monitoring after the procedure.
In eight of the 25 subjects studied, the highest lidocaine concentration was observed in the final sample, 60 min after the cessation of lidocaine administration (subjects 1, 6, 8, 10, 13, 16, 19 and 22). It is possible that plasma lidocaine levels continued to rise in these subjects. However in all eight cases the highest measured concentration level was less than 3 mg litre1 and the rate of increase was decreasing. The highest plasma lidocaine concentrations were noted in those subjects in whom concentrations increased most rapidly.
Lidocaine pharmacokinetics are complex;18 absorption varies with site and mode of delivery20 and the use of anticholinergic drugs.21 Direct application of an average lidocaine dose of 9.3 mg kg1 has been used for diagnostic bronchoscopy without clinical manifestations of toxicity,13 although a peak plasma lidocaine concentration of 9.5 mg litre1 was observed in one subject.
Parkes and colleagues12 reported peak plasma lidocaine concentrations of less than 0.5 mg litre1 after nebulization of 6 mg kg1. Mostafa and colleagues11 recorded a peak plasma lidocaine concentration of 1.51 mg litre1 with the same dose and delivery method. Where many factors influence the absorption of lidocaine, subtle changes in the overall technique, such as the use of anticholinergic drugs or possibly even the position of the subject, may alter the site or speed of absorption. Each method of airway anaesthesia must be assessed independently with regard to local anaesthetic toxicity, particularly where high doses of local anaesthetic are used.
The median dose of lidocaine we used was 8.9 mg kg1, with a range 7.39.2 mg kg1. It has been estimated that only 812% of lidocaine given by a nebulizer will reach the airway as a result of wastage.8 If the nebulized lidocaine is ignored, a median dose of 8.27 mg kg1 (range of 6.7 to 8.5 mg kg1) of lidocaine was administered to the airway. This correlates closely with recent guidelines issued by the British Thoracic Society;14 they recommend the total dose of lidocaine applied during bronchoscopy should be limited to 8.2 mg kg1.
The death of a healthy volunteer from presumed lidocaine toxicity has occurred after fibreoptic bronchoscopy for research purposes.22 23 This may indicate ignorance of the significance of lidocaine toxicity within the medical community. More recently, a report of anaesthetists attending a training course in airway local anaesthesia raises concerns.24 Doses of up to 14.77 mg kg1 of lidocaine were administered by a spray-as-you-go method; some delegates were reported to have experienced involuntary movementssymptoms which indicate cortical irritability and may precede convulsions.18 19 No involuntary movements were observed with the lower doses of lidocaine used during our study.
In conclusion, a combined method of nebulization and direct application of lidocaine to the airway was acceptable to this small group of unsedated subjects. It produced good conditions for fibreoptic intubation. In this series of 25 subjects a maximum calculated dose of 9 mg kg1 produced one peak plasma lidocaine concentration of 4.5 mg litre1 but none greater than 5 mg litre1. When using combined nebulization and topical anaesthesia for training purposes, calculated lidocaine administration should not exceed 9 mg kg1.
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References |
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