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Alkalinization of Intracuff Lidocaine Improves Endotracheal Tube-Induced Emergence Phenomena

Estebe, Jean-Pierre MD*†,; Dollo, Gilles PharmD, PhD†,; Le Corre, Pascal PharmD, PhD†,; Le Naoures, Alain MD*,; Chevanne, François BS†,; Le Verge, Roger PharmD, PhD†, and; Ecoffey, Claude MD*

doi: 10.1213/00000539-200201000-00044

We sought to evaluate the effect of filling an endotracheal tube cuff with 40 mg lidocaine alone (Group L) or alkalinized lidocaine (Group LB) in comparison to an Air Control group (Group C) on adverse emergence phenomena in a randomized controlled study (n = 25 in each group). The incidence of sore throat was decreased for Group LB in comparison to Group L during the 24 postextubation hours. The difference between Group L and Group C remained significant in the two postextubation hours only. Plasma lidocaine levels increased when lidocaine was alkalinized (Cmax were 62.5 ± 34.0 ng/mL and 3.2 ± 1.0 ng/mL for Groups LB and L, respectively). Cough and restlessness before tracheal extubation were decreased in Group LB compared with Group L and in Group L compared with Group C. Nausea, postoperative vomiting, dysphonia, and hoarseness were increased after extubation in Group C compared with the liquid groups, and a better tolerance was recorded with Group LB compared with Group L. The increase of arterial blood pressure and cardiac frequencies during the extubation period was less in the liquid groups than in the control group and less in Group LB compared with Group L. We concluded that use of intracuff alkalinized lidocaine is an effective adjunct to endotracheal intubation.

*Service d’Anesthésie Réanimation Chirurgicale 2 and †Laboratoire de Pharmacie Galénique et Biopharmacie, Université de Rennes, Rennes, France

August 29, 2001.

Address correspondence and reprint requests to Jean-Pierre Estebe, MD, Service d’Anesthésie Réanimation Chirurgicale 2, Hôpital Hôtel Dieu, 2 Rue de l’Hôtel Dieu, 35000, Rennes, France. Address e-mail to

To improve the endotracheal tube (ETT)-induced emergence phenomena after general anesthesia, we proposed to fill the cuff with a gas mixture or saline to avoid overinflation of the cuff (1,2). Previous studies with in vitro and in vivo approaches (3–7) that used large doses (200 to 500 mg) of lidocaine hydrochloride (L-HCl) instead of saline have shown that L-HCl could slowly diffuse through the cuff, and this could be dangerous if the cuff ruptured.

Previously, we have shown that small amounts of L-HCl diffused slowly across the ETT cuff; the addition of NaHCO3 increases the diffusion (8). On the basis of this concept, a randomized, controlled study was performed to compare the clinical effect of filling the ETT cuff with L-HCl, L-HCl and NaHCO3, or air on adverse emergence phenomena.

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After obtaining institutional ethics committee approval and written informed consent, adult patients (ASA physical status I, II, or III) scheduled for spine lumbar surgery were consecutively enrolled. Patients were randomized into one of the three groups: the L-HCl group (Group L) or the L-HCl Alkalinized group (Group LB) were compared with the standard, which was air (Group C).

The anesthetic care team performed the standard anesthesia and the tracheal intubation (Rusch™ armored tracheal tube; Rusch AG, Kernen, Germany). Sterile water was used as a lubricant of the tracheal tube. The experimenter then inflated the cuff according to the randomized protocol. Because no data were available with increased cuff pressures with a manometer when the cuff is inflated with a liquid, the inflation of the ETT cuff was performed to obtain the minimal occlusive volume. The cuff was initially inflated slowly until no leak was heard under controlled ventilation, then 2 mL was added. For the liquid groups, after initial injection of 2 mL of L-HCl (Xylocaine® 2%; Astra, Rueil Malmaison, France) into the ETT cuff, a supplementary volume was added: sterile water for Group L and 8.4% NaHCO3 for Group LB. The cuff pressure was recorded, and the initial pressure was <30 cm H2O. The anesthesia care team, unaware of the filling protocol, delivered the anesthesia. Ventilation was controlled, and no gastric tube was inserted. Patients were then placed in the prone position. Maintenance of anesthesia included use of oxygen (30%) and N2O (70%), isoflurane, sufentanil, and rocuronium until prone patients were rolled to the supine position (time T0).

Tracheal extubation was performed just after suctioning at the discretion of the blinded anesthesia team when all of the extubation criteria were met. The time of extubation (time between T0 and extubation) and spontaneous ventilation time (time between emergence of spontaneous breathing and extubation) were recorded. The volumes withdrawn from ETT cuffs at extubation were recorded. Cough and restlessness before extubation were noticed and distinguished from cough attempt at suctioning and extubation times. The sore throat was measured in the recovery room by a blinded nurse with a visual analog scale (0–100 mm) at postextubation periods of 15 min and 1, 2, 3, and 24 h. On the second postoperative day, a nurse recorded the patient satisfaction scale graded from 0 (excruciating complaints) to 5 (no complaints). Other throat complaints—hoarseness, bucking, dysphonia, and dysphagia—evaluated with a binary scale (yes/no) were recorded. Trouble of the swallowing reflex was evaluated by absorption of water 15 min after extubation. Hemodynamic variables and postoperative nausea and vomiting were also recorded.

Venous blood samples were withdrawn according to a standard protocol. Plasma lidocaine concentration was measured by high-performance liquid chromatography (9). To check the influence of the volume of NaHCO3 on lidocaine release, an in vitro study was performed with 2 mL of 2% L-HCl alone or with 3 to 7 mL of NaHCO3 8.4%.

Sample-size calculation was performed on the basis of a previous pilot study (8). We postulated that using lidocaine would reduce the rate of sore throat 25% to 30% compared with the Air group (control). On the basis of these estimates, we calculated a sample size that would permit a type I error of α = 0.05 with a type II error of β = 0.05 and power of 80%. Enrollment of 25 patients in each group was required. Patients were withdrawn from the study when the trachea was not intubated at the first attempt. Results are presented as mean ± sd. Data were analyzed with analysis of variance followed by the unpaired Student’s t-test with Bonferroni correction for parametric data. The Kruskal-Wallis and Mann-Whitney U-test were used for nonparametric data. Statistical significance was defined as P < 0.05.

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Seventy-nine patients participated in the study. Four of them were excluded because the trachea was not intubated on the first attempt (Table 1). There were no problems with endotracheal intubation or cuff inflation. During controlled ventilation, no air leak was recorded in the prone position. There was no difference in the initial volume injected into the cuff (6.7 ± 2.2 mL, 5.8 ± 1.8 mL, and 6.3 ± 1.5 mL for Groups C, L, and LB, respectively). Compared with the liquid volume inflated, the liquid volume removed from the cuff decreased significantly (5.3 ± 1.4 mL and 5.9 ± 1.6 mL for Groups L and LB, respectively;P < 0.001). The air volume withdrawn at extubation time increased significantly in Group C (11 ± 2.7 mL;P < 0.0001).

Sore throat was decreased significantly only during the two postoperative hours for Group L compared with Group C (Table 2). This decrease was always more pronounced in Group LB during the 24-h evaluation period for the visual analog scale. The global satisfaction scale confirmed the better tolerance retrospectively. This increase in ETT tolerance was confirmed (Table 3) by the prolongation of spontaneous ventilation time and the time to extubation. The good tolerance of the ETT was associated with less cough and restlessness before extubation. No difference was recorded in cough reflex at the extubation time. Neither laryngospasm nor depression of the swallowing reflex was recorded. On the basis of postoperative nausea and vomiting, dysphonia, and hoarseness, Group C displayed less tolerance, and a better tolerance was recorded in Group LB compared with Group L. Arterial blood pressures and heart rates were increased in Group C compared with the liquid groups.

There was a very large difference between groups in plasma lidocaine concentrations (Fig. 1). The Cmax was 52.4 ± 22.4 ng/mL and 3.2 ± 1.0 ng/mL for Group LB and Group L, respectively, and the Tmax was similar (139 ± 63 min and 160 ± 49 min for Group L and Group LB, respectively). Only 1.1% L-HCl was released during the 6-h period, whereas 65% was released with NaHCO3. After filling the cuff with 2 mL of L-HCl 2% and 3 mL of NaHCO3, the in vitro release of lidocaine was not modified, no matter what supplementary NaHCO3 volume was added (Fig. 2).

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This is the first study in which a small amount of L-HCl (40 mg) was used to improve the ETT-induced emergence phenomena from anesthesia. The use of a small dose of L-HCl without alkalinization improved postoperative sore throat and hoarseness during the first two postoperative hours only; this is in agreement with the results of Bennett et al. (2), who inflated the cuff with saline. However, use of a small dose of alkalized L-HCl markedly improved ETT tolerance during a more prolonged period of time. The use of alkalinized local anesthetics in the ETT cuff offers the advantages of minimal stress response to smooth extubation and cough-free emergence.

No cuff rupture was recorded in our study as in previous studies (3,4,6,7). This result confirmed that introduction of lidocaine is not deleterious for the cuff. Previous works (3,4,6,7) have shown that L-HCl placed inside the cuff of an ETT can slowly diffuse through its hydrophobic structure. The use of 200 to 500 mg of lidocaine, leading to a Cmax of approximately 167 ± 30 ng/mL, has been required to obtain clinical improvements (3,7), but this could be dangerous in the case of cuff rupture. The addition of NaHCO3 to L-HCl dramatically increased the amount of lidocaine released. The in vivo plasma profiles obtained, reflecting lidocaine release, were in good accordance with in vitro release profiles for both L-HCl and L-HCl/NaHCO3. Alkalinization of L-HCl with NaHCO3 allowed the diffusion of 65% (vs 1% without NaHCO3) of the neutral base form of lidocaine during six hours. These results were in agreement with previous in vitro studies (8,11,12). The amount of lidocaine diffusing across the ETT cuff with NaHCO3 was proportional to the dose of L-HCl used (8).

If alkalinization of L-HCl improved the cuff tolerance, the local anesthetic effect did not depress the swallowing reflex, which would have revealed palsy of the vocal cords. The decrease of cough before extubation should not be attributed to a depression of cough reflex, which always occurs during the suction-extubation act, but the decrease does result from an increase in ETT tolerance.

Such a drug delivery system could be evaluated with other types of cuffs to improve patients’ tolerance of anesthesia and intensive care unit and emergency care.

In conclusion, our study demonstrated a decrease in sore throat in the postoperative period when the cuff was inflated with a small dose of alkalinized lidocaine rather than with L-HCl or air. This effect is clinically relevant to all other indirect effects of extubation, i.e., hemodynamic effects, restlessness, dysphonia, and hoarseness. Plasma lidocaine levels confirmed the increased diffusion of lidocaine through the cuff when lidocaine was alkalinized. This increased diffusion was not accompanied by a palsy of vocal cords. Use of a small dose of alkalinized lidocaine (40 mg) instead of air is a relatively easy and safe practice that avoids the use of large doses of lidocaine.

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