Plasma lidocaine concentrations following insertion of 2% lidocaine gel into the uterine cavity after uterine balloon thermal ablation

G. F. Rousseau*,1, M. Oram2, J. Barrington3, M. Priston4 and M. Swart2

1 Department of Anaesthesia, North Devon District Hospital, Barnstaple EX31 4JB, UK. 2 Department of Anaesthesia and Intensive Care and 3 Department of Obstetrics and Gynaecology, Torbay Hospital, Torquay TQ2 7AA, UK. 4 Pharmacy Department, Derriford Hospital, Plymouth PL6 8DH, UK guy.rousseau@virgin.net

Accepted for publication: June 17, 2002


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. Uterine balloon thermal ablation is used to treat menorrhagia. We thought that intrauterine application of 2% lidocaine gel could reduce postoperative pain after this procedure. Before using this technique we wished to establish how much lidocaine is absorbed systemically from the uterine cavity after thermal ablation.

Methods. Ten ASA I–II patients (age 38–50 yr) underwent uterine balloon thermal ablation under general anaesthesia. They each had 11 ml of 2% lidocaine gel (InstillagelTM) inserted into the uterine cavity at the end of the procedure. Blood samples were taken at 5, 15, 30 and 60 min after insertion and lidocaine concentrations were measured using high-performance liquid chromatography.

Results. Mean (range) plasma lidocaine concentrations at 5, 15, 30 and 60 min were 40.3 (0–221.9), 66.3 (0–271.9), 64.9 (0–208) and 75 (0–212) ng ml–1, respectively.

Conclusion. There was minimal systemic absorption of lidocaine from the uterus following uterine balloon thermal ablation. Measured concentrations were well below the toxic plasma concentration for lidocaine (8–10 µg ml–1).

Br J Anaesth 2002; 89: 846–8

Keywords: anaesthetics local, lidocaine; uterus, thermal ablation


    Introduction
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Uterine balloon thermal ablation (Thermochoice Gynecare) is a new method for treating menorrhagia.1 2 The technique involves inserting a balloon-tipped catheter through the dilated cervix and inflating the balloon with 5% dextrose solution. The balloon, which is now in contact with the walls of the uterine cavity, is heated to 87°C for 8 min. This results in a thermal ablation of the endometrium and adjacent myometrium to a depth of up to 15 mm.3 A number of different anaesthetic techniques have been used for the procedure, ranging from local anaesthetic blocks under sedation, to regional and general anaesthesia. Intrauterine administration of 2% lidocaine gel (InstillagelTM) may be a simple method for reducing postoperative pain. We were concerned that there may be greater systemic absorption of lidocaine when it is applied to tissues that have just had a thermal injury compared with lidocaine gel applied to undamaged tissues. Before using intrauterine lidocaine gel for analgesia, we wanted to assess how much systemic absorption of lidocaine occurs when lidocaine gel is applied to the uterine cavity after balloon thermal ablation.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The local Research and Ethics Committee approved the study and informed written consent was obtained. Ten patients over 18 yr of age who were undergoing uterine balloon thermal ablation were entered into the study. Patients who were allergic to the study drugs, had a history of epilepsy or liver disease, or who were unable to give consent were excluded from the study. A Clinical Trials Exemption Certificate was obtained from the UK Medicines Control Agency. Before surgery, patients were given diclofenac 100 mg, metoclopramide 10 mg and acetaminophen 1 g orally. Oxygen was administered via a Hudson mask at 4 litre min–1. Fentanyl 100 µg i.v. was given for analgesia and ondansetron 4 mg i.v. as a prophylactic antiemetic. Anaesthesia was induced and maintained by an infusion of 1% propofol with alfentanyl 20 µg ml–1.

In the postoperative recovery area, patients received additional fentanyl 50 µg i.v. until comfortable. TylexTM (acetaminophen 500 mg and codeine phosphate 30 mg), two tablets every 6 h, and diclofenac 50 mg orally every 8 h were given as required for further analgesia.

After induction of anaesthesia, a 14-gauge i.v. cannula was placed in the antecubital fossa for postoperative blood sampling. The cervix was dilated with a size-5 Hagar dilator and the depth of the uterine cavity measured with a uterine sound. The balloon-tipped catheter was inserted into the uterine cavity up to this depth. The balloon was inflated with 5% dextrose 5–15 ml until a pressure of 160–180 mm Hg was reached. The dextrose solution was then heated to 87°C for 8 min. To maintain contact with the endometrium, the pressure in the balloon was kept at 160–180 mm Hg. At the end of the procedure, 2% lidocaine 11 ml was inserted into the uterus using an introducer (Instillaquil). Blood samples were taken at 5, 15, 30 and 60 min after insertion of the lidocaine gel. The plasma was separated using 4-ml Vacuette tubes (Greiner Turbotechnik) within 3 h and stored at –20°C. Plasma lidocaine concentration was measured using high-performance liquid chromatography and the values expressed in ng ml–1 plasma.4 The extraction method was shown to be accurate and precise over the concentration range investigated: the intraday precision coefficients of variation and relative error were, respectively, 6.70% and 2.90% at 50 ng ml–1, 5.14% and 3.50% at 100 ng ml–1 and 3.88% and 9.03% at 200 ng ml–1. Interday precision coefficients of variation and relative error were, respectively, 6.47% and 0.12% at 50 ng ml–1, 3.84% and 2.14% at 100 ng ml–1 and 2.80% and 2.19% at 200 ng ml–1.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Patient characteristics and peak plasma concentrations of lidocaine are shown in Table 1. The maximum plasma concentration measured was 272 ng ml–1, which is below the toxic concentration. Plasma lidocaine concentrations measured at 5, 15, 30 and 60 min after application of intrauterine lidocaine for each subject are shown in Figure 1.This indicates that the plasma lidocaine concentration had peaked or reached a plateau. There were no clinical symptoms or signs of local anaesthetic toxicity.


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Table 1 Patient characteristics and peak plasma lidocaine concentrations
 


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Fig 1 Plasma lidocaine concentrations in individual patients at 5, 15, 30 and 60 min after intrauterine insertion of 2% lidocaine gel 11 ml.

 

    Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
We found that plasma lidocaine concentrations after the insertion of lidocaine gel 220 mg into the uterine cavity after uterine balloon thermal ablation were well below those reported to cause symptoms and signs of toxicity. The highest concentration recorded was 272 ng ml–1 at 15 min after insertion. In a study by Folds and colleagues,5 volunteers began to experience symptoms and display signs of lidocaine toxicity at a mean plasma concentration of 8–10 µg ml–1, which is tenfold higher than our highest recorded level. Our results demonstrate no early peak at 5 min, which could have occurred from direct intravascular administration. Peak concentrations were recorded at 15 and 60 min, indicating that concentrations are either still rising at 15 min or reaching a plateau, making the likelihood of an early missed peak unlikely. If there were to be an early peak plasma concentration before 5 min, the neurological symptoms and signs may go unrecognized as patients would still be under the effect of general anaesthesia, which would both mask the symptoms and protect the patient by raising the seizure threshold.

We chose to use lidocaine in a gel because it is available in this form. In addition, it is supplied in a syringe that is incompatible with i.v. needles and cannulae, which reduces the risk of inadvertent i.v. injection. The dose of lidocaine was not adjusted for weight or body mass index (BMI) because we wanted to evaluate a simple one-dose regimen for adults. Other factors may affect how much lidocaine is absorbed, such as uterine cavity size and uterine muscle spasm, both of which will alter the volume of lidocaine that remains in the uterine cavity. Peak plasma concentrations in those with a lower body weight or BMI were below toxic concentrations.

In conclusion, the amount of lidocaine absorbed systemically after 11 ml of 2% lidocaine gel is placed in the uterine cavity following intrauterine balloon thermal ablation is low. Further studies are needed to evaluate the analgesic effects of intrauterine lidocaine gel after balloon thermal ablation.


    Acknowledgements
 
This study was supported by a grant from the Torbay Special Medical Projects and Research Fund.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Meyer WR, Walsh BW, Grainger DA, et al. Thermal balloon and rollerball ablation to treat menorrhagia: a multicenter comparison. Obstet Gynecol 1998; 92: 98–103[Abstract/Free Full Text]

2 Amso NN, Stabinsky SA, McFaul P, et al. Uterine thermal balloon therapy for the treatment of menorrhagia: the first 300 patients from a multi-centre trial. Br J Obstet Gynaecol 1998; 105: 517–23[ISI][Medline]

3 Anderson LF, Meinert L, Rygaard C, et al. Thermal balloon endometrial ablation: safety aspects evaluated by serosal temperature, light microscopy and electron microscopy. Eur J Obstet Gynecol Reprod Biol 1998; 79: 63–8[ISI][Medline]

4 Zivanovic L, Agatonovic-Kustrin S, Vasiljevic M, Nemcova I. Comparison of high-performance and thin-layer chomatographic methods for the assay of lidocaine. J Pharm Biomed Anal 1996; 14: 1229–32[ISI][Medline]

5 Foldes FF, Malloy R, McNall PG, Koukal LR. Comparison of toxicity of intravenously given local anaesthetic agents in man. JAMA 1960; 172: 1493–8[ISI]





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