Alkalinization of intra-cuff lidocaine and use of gel lubrication protect against tracheal tube-induced emergence phenomena

J.-P. Estebe*,1,2, S. Delahaye1, P. Le Corre2, G. Dollo2, A. Le Naoures1, F. Chevanne2 and C. Ecoffey1

1 Service d’Anesthésie Réanimation Chirurgicale 2, Université de Rennes 1, Rennes, France. 2 Laboratoire de Pharmacie Galénique et Biopharmacie, Université de Rennes 1, Rennes, France

*Corresponding author: Service d’Anesthésie Réanimation Chirurgicale 2, Hôpital Hôtel Dieu, 2 rue de l’Hôtel Dieu, 35000, Rennes, France. E-mail: jean-pierre.estebe{at}chu-rennes.fr

Accepted for publication: October 28, 2003


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. We sought to determine the benefits of using alkalinized lidocaine 40 mg to fill the cuff of a tracheal tube (ETT) in combination with water-soluble gel lubrication to prevent post-intubation sore throat.

Methods. The work included an in vitro study of the diffusion of alkalinized lidocaine solution through the low-pressure, high-volume cuff of an ETT. We also performed a randomized controlled study (n=20 patients in each group) that included a group who received an alkalinized lidocaine-filled ETT cuff with lubrication of the tube using water-soluble gel (Group G), and two control groups who received an alkalinized lidocaine-filled cuff with ETT lubrication with water (Group W) or an air-filled cuff with ETT lubrication with water (Group C).

Results. Water-soluble gel lubrication (Group G) produced a lower incidence of sore throat during the 24-h post-extubation period than lubrication with water alone in the cuffs filled with alkalinized lidocaine (Group W), and compared with the air control group. The ability of lidocaine to pass through the cuff of an ETT when water-soluble gel and/or water alone was used as a lubricant was similar, as determined by lidocaine plasma concentrations (Cmax 45 ng ml–1). Cough and restlessness before tracheal extubation were decreased in patients with the alkalinized lidocaine-filled cuffs compared with the air-filled cuffs. After extubation, nausea, vomiting, dysphonia and hoarseness were greater for patients with air-filled cuffs compared with the lidocaine-filled cuffs. No significant difference between the groups was recorded in arterial blood pressure and heart rate. In vitro data suggest that the lower the NaHCO3 injection volume, the greater the release of lidocaine across a low-pressure, high-volume cuff.

Conclusions. These data show benefits of using an alkalinized lidocaine-filled ETT cuff in combination with water-soluble gel lubrication in preventing post-intubation sore throat.

Br J Anaesth 2004; 92: 361–6

Keywords: anaesthetics local, lidocaine, alkalinization; complications, sore throat; intubation tracheal; lubrication, water-soluble gel


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Postoperative sore throat occurs in up to 90% of intubated patients and is the most common complaint after tracheal intubation.1 It is referred to as a tracheal tube (ETT)-induced emergence phenomenon, as are laryngeal oedema and ischaemia. To reduce such complications, it was suggested that the expansion of air in an ETT cuff should be prevented by replacing it with nitrous oxide2 and closely monitoring the nitrous oxide concentration.3 Deflation of the cuff 4 and filling it with saline have also been thought to be useful.5 Cuffs filled with lidocaine have been used for in vitro and in vivo studies.610 Typically, high doses of lidocaine (200–500 mg) that slowly diffuse through the cuff have been used.8 However, large doses of lidocaine could be dangerous if the cuff ruptures. We have reported that the addition of sodium bicarbonate (i.e. alkalinization) increased diffusion of low doses of lidocaine (40 mg) across an ETT cuff,11 thus preventing sore throat and the other side-effects of intubation, such as haemodynamic changes, restlessness, dysphonia and hoarseness.12

When used as an ETT cuff lubricant, lidocaine spray and jelly result in a significant increase in the incidence of cough and sore throat.13 Water-soluble gel lubrication, however, reduces pulmonary aspiration, particularly when used with the high-volume, low-pressure cuff.14

To evaluate the effect of using water-soluble gel lubrication in combination with a low dose of alkalinized lidocaine in the ETT cuff, we performed a randomized controlled study. We compared lubrication with water-soluble gel or water together with a solution of alkalinized lidocaine in the ETT cuff with a control group using an air-filled ETT cuff lubricated with water. We also performed an in vitro study to measure the release of lidocaine 2% in varying volumes of sodium bicarbonate through the cuff of the high-volume, low-pressure ETT.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Patient study
Institutional Ethics Committee approval and written informed consent were obtained. Adult patients scheduled for lumbar spinal surgery (ASA I, II or III) were consecutively enrolled. Patients with predicted difficult intubation were excluded. Patients were randomized into one of the three groups: ETT cuff lubricated with sterile water and filled with air (Group C); ETT cuff lubricated with sterile water and filled with alkalinized lidocaine (Group W); or ETT cuff lubricated with water-soluble gel and filled with alkalinized lidocaine (Group G).

Hydroxyzine 100 mg was administered orally 2 h before surgery. Thiopental 4–6 mg kg–1, sufentanil 0.5 µg kg–1 and rocuronium 0.5 mg kg–1 were used for anaesthesia. The cuffs were lubricated by an investigator with either 5 ml of sterile water or 5 ml of water-soluble gel (K-Y®; Johnson & Johnson, Paris, France) according to a randomized protocol. Tracheal intubation was performed using an armoured ETT (RuschTM, Paris, France), 6.5–7.0 mm internal diameter for women and 7.0–7.5 mm internal diameter for men, by another anaesthetist. ETT cuffs were inflated according to a predetermined protocol. The ETT cuffs were inflated to the minimal occlusive volume (i.e. no leakage detected under controlled ventilation) and 2 ml was added to avoid leakage when patients were rolled to the prone position. In the control group, the cuff was initially slowly inflated with air. For liquid-filled cuff groups, lidocaine 2%, 2 ml was initially injected into the cuff, and then a supplementary volume of sodium bicarbonate (NaHCO3) 8.4% was added to obtain the minimal occlusive volume. Cuff pressure was recorded throughout, ensuring a starting pressure below 30 cm H2O, using manometers set for pressure measurements in a cuff inflated with air, not with a liquid–air interface. The anaesthetic team were unaware of the experimental protocol. Ventilation was controlled and no nasogastric tube was inserted. Patients were then turned into the prone position. Maintenance of anaesthesia included oxygen–nitrous oxide (30/70%), isoflurane, sufentanil and rocuronium until the prone patients were rolled back to the supine position (time T0).

When all of the extubation criteria were met (full reversal of neuromuscular block, spontaneous ventilation and the ability to follow verbal commands, eye opening or handgrip), tracheal extubation was performed immediately after suctioning at the discretion of the anaesthetist in charge of the patient. Time of extubation (time from T0 to extubation) and spontaneous ventilation time (time between beginning spontaneous breathing and extubation) were recorded. The gas and liquid volumes withdrawn from the ETT cuffs at extubation were recorded. Cough reflex and restlessness were checked before extubation and for 24 h after extubation (15 min, 1, 2, 3, 12 and 24 h). A nurse blinded to the study groups measured the degree of sore throat in the recovery room using a visual analogue scale (VAS: 0–100 mm). Other evidence of throat discomfort, such as hoarseness, bucking, dysphonia, or dysphagia, was evaluated. Impairment of the swallowing reflex was evaluated by asking the patient to drink a glass of water 15 min after extubation. Haemodynamic variables and the incidence of postoperative nausea and vomiting (PONV) were also recorded.

Venous blood samples were taken before intubation and 15, 30, 60 120, 180 and 240 min after intubation, and 160 and 120 min after extubation, for measurement of plasma lidocaine concentration by HPLC.15 The limit of detection was 2 ng ml–1, and within-day and between-day reproducibility of the assay was 2.1 and 5.6% respectively.

In vitro study
The same ETT (i.e. low-volume, high-pressure) was used for intubation as in our earlier studies (Rusch armoured tube).11 12 Although we have shown that for a low-volume, high-pressure cuff any variation in cuff volume did not modify the release of lidocaine across the cuff,12 no data are available concerning the diffusion of alkalinized lidocaine across a high-volume, low-pressure cuff.

We thus performed an in vitro study using the same dose of lidocaine (2 ml of 2%) with 8, 12.5 or 15 ml 8.4% NaHCO3 placed inside a high-volume, low-pressure cuff (Hi-Lo LanzTM ETT; 7.5 mm internal diameter; Mallinckrodt, France). Release of lidocaine from the ETT cuffs was measured using a Distek dissolution test system model 5100A (Distek INC, North Brunswick, NJ, USA). This consists of six independent cylindrical flasks with spherical bottoms, each containing 900 ml release medium containing phosphate buffer (pH 7.4) thermostated at 37°C, in which the ETT is inserted, and a rotating paddle apparatus operating at 100 r.p.m. The lidocaine concentration was measured at 205 nm every 15 min for a 6-h period using a Uvikon spectrophotometer Model 922 (Kontron Instrument, St Quentin en Yvelines, France).11 All the ETTs were tested only once.

Statistics
The sample size was calculated from our previous studies;11 12 our primary efficacy variable was the incidence of sore throat as measured by VAS. In contrast to alkalinized lidocaine, lidocaine alone does not diffuse across the cuff.11 For this reason, we consider the saline group to be a satisfactory control mimicking the effects of unmodified lidocaine.12 We postulated that if the water-soluble gel acted as a barrier for diffusion of alkalinized lidocaine, the results would be the same as in the saline group.5 We estimated, using the data that were available from our previous studies,11 12 that using water-soluble gel as a lubricant would increase the rate of sore throat from 25 to 30% compared with the water-lubricating group.12 Based on these estimates, we calculated a sample size that would permit a type I error of {alpha}=5% with a type II error of ß=5%, and power of 95%. Enrolment of 20 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 analysed using analysis of variance (ANOVA) followed by the unpaired Student’s t-test with Bonferroni correction for parametric data. The Kruskal–Wallis and Mann–Whitney U-tests were used for non-parametric data. Statistical significance was defined as P<0.05. Patient randomization was performed using a computed list; the same investigator (first author) undertook the filling of the ETT cuffs, but was excluded from all other parts of the study (i.e. anaesthesia, intubation and extubation).


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Sixty patients participated in the study and none was excluded. There were no statistically significant differences among the three groups regarding surgical or anaesthetic characteristics (Table 1). No problems with tracheal intubation or cuff inflation occurred. During controlled ventilation, no air leak was recorded in the prone position. There was no difference in the initial volume of alkalinized lidocaine injected into the cuff (4.6 (0.5) vs 4.8 (0.7) ml) for Groups W and G, respectively. The volume of liquid injected into the cuff was not significantly different from the volume removed from the cuff (4.2 (1.1) vs 4.2 (1.2) ml) for Groups W and G respectively. The initial air volume was significantly greater than the liquid volume (5.8 (0.9) ml; P<0.05). The gas volume withdrawn at extubation increased significantly in the air Group C (8.0 (2.4) ml; P<0.0001), correlating with the significantly increased pressure in the cuff in this group (15.8 (12.6) vs 57.5 (21.3) cm H2O initial vs final pressure; P<0.0001). In the liquid groups, the initial intra-cuff pressure (5.0 (0.9) and 5.3 (0.7) cm H2O for Groups W and G respectively) was significantly lower than the final intra-cuff pressure (7.0 (1.2) and 6.9 (0.9) cm H2O for Groups W and G, respectively; P<0.01).


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Table 1 Physical characteristics of patients in each group. Alkalinized lidocaine cuff lubricated with water (Group W), alkalinized lidocaine cuff lubricated with water-soluble gel (Group G), or cuff containing air and the tracheal tube lubricated with water (Group C). Data are mean (range) for age or mean (SD). ns=not significant
 
Surgical pain was similar in the three groups, with comparable postoperative patient controlled analgesia morphine consumption. Compared with the air Group C, the alkalinized lidocaine group with water-soluble gel lubrication (Group G) had a significant reduction in sore throat (mean end-point for efficacy) throughout the 24 h postoperative period (P<0.001) (Table 2). The difference was also significant in the alkalinized lidocaine group with water lubrication (Group W) compared with the air group (P<0.01, except at 2 h after extubation). Throat pain was significantly less in the liquid group with water-soluble gel (Group G) than in the liquid group with water lubricate (Group W) 2 and 3 h after extubation. This increase in ETT tolerance was confirmed by the analysis of secondary and safety end-points (Table 3). There was a significant prolongation of spontaneous ventilation time and time to extubation in the liquid groups. Tolerance of the ETT was associated with less cough and restlessness before suctioning and extubation in the liquid groups. No difference was recorded in the cough reflex between groups at extubation. Neither laryngospasm nor depression of the swallowing reflex occurred in any patient. PONV, dysphonia and hoarseness were more common in Group C. There was no difference in side-effects between the liquid groups. No significant difference was recorded in arterial blood pressure and heart rate between groups (Table 3).


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Table 2 Visual analogue scale scores for sore throat (0–100 mm), mean (SD), after extubation in the three groups of patients at regular intervals for 24 h. Air cuff lubricated with water (Group C), and alkalinized lidocaine cuff lubricated with water (Group W) or with water-soluble gel (Group G). #P<0.01, G vs W; *P<0.001, **P<0.0001, G vs C; +P<0.01; ++P<0.001, +++P<0.0001, W vs C
 

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Table 3 Secondary end-points of tracheal-tube-induced emergence phenomena (mean (SD) or percentage). Alkalinized lidocaine cuff lubricated with water (Group W), alkalinized lidocaine cuff lubricated with water-soluble gel (Group G), or cuff containing air and the tracheal tube lubricated with water (Group C). P values are for Groups W and G vs Group C. ns=not significant
 
Plasma concentrations of lidocaine during the study in the liquid groups are given in Fig. 1. The Cmax was 43.2 (20.9) and 44.5 (23.4) ng ml–1 for Groups W and G respectively. The tmax corresponded to the last sampling before extubation. One minute after extubation, plasma concentrations were not significantly different (39.9 (18.9) and 42.1 (22.3) ng ml–1 for Groups W and G respectively).



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Fig 1 Mean (SD) plasma lidocaine concentrations (n=20 in each group) during and after tracheal intubation. ETT cuffs were filled with lidocaine 2% (2 ml, 40 mg) and NaHCO3 8.4%. The ETT cuff was lubricated with water or water-soluble gel.

 
After filling the high-volume, low-pressure cuff with lidocaine 2%, 2 ml and NaHCO3, the in vitro release of lidocaine varied as a function of total volume injected into the cuff (the lower the injected volume, the more lidocaine was released over time). Fifty per cent lidocaine release was observed at 5 h for 10 ml, 8 h for 12.5 ml, and 10 h for 15 ml (Fig. 2).



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Fig 2 Percent lidocaine release in vitro as a function of time from the cuff of a Mallinckrodt Hi-Lo LanzTM tracheal tube (internal diameter 7.5 mm) filled with lidocaine hydrochloride 40 mg and additional sodium bicarbonate 8.4% 10, 12.5 or 15 ml (n=2 for each group).

 

    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This is the first study showing that lubrication of an ETT cuff with water-soluble gel and alkalinized lidocaine injected into the cuff produces a significant improvement in ETT-induced emergence phenomena from general anaesthesia.

Our previous work has shown increased cuff pressure and volume over time after air inflation. During anaesthesia using nitrous oxide, the cuff pressure increases as the temperature of the cuff rises and nitrous oxide diffuses into it more rapidly that it leaves.2 This overinflation of the ETT cuff has been associated with damage to pharyngeal mucosa and recurrent laryngeal nerve palsy.6 These complications are decreased by filling the ETT cuffs with liquid.17 18

It has been reported that lidocaine alone has a low diffusion rate across an ETT cuff (1% released during a 6-h period).12 Only high doses of lidocaine (200–500 mg) produce a clinical effect when used to inflate the cuff,610 but they have no advantage over saline5 and could be dangerous if the ETT cuff ruptures. The use of alkalinized local anaesthetic in the ETT cuff offers the advantages of minimal stress response to extubation and cough-free emergence. We reported that alkalinization of lidocaine allowed the diffusion of 65% of the neutral base form of lidocaine through the hydrophobic structure of the cuff within a 6-h period, and showed that use of a low dose (40 mg) reduced postoperative side-effects.12 We have also shown that the amount of lidocaine diffusing across the ETT cuff in the presence of NaHCO3 is proportional to the dose of lidocaine used between 20 and 40 mg.11 Our in vitro and in vivo studies showed no evidence of cuff rupture or obstruction.11 12 These results are in agreement with previous studies using lidocaine alone.610

Lidocaine has been used to lubricate ETTs. However, used as a spray or a jelly, it increased ETT-induced emergence phenomena from anaesthesia.13 It can also cause cuff rupture.19 The use of water-soluble gel reduces pulmonary aspiration, particularly when using the high-volume, low-pressure cuffs.14 Conversely, compared with water lubrication, tolerance of the ETT using gel was increased. The mechanism remains unclear. However, water used for lubrication would be rapidly absorbed by pharyngeal mucosa, but gel would disappear more slowly. The plasma lidocaine concentrations in the two groups were similar (Fig. 1), showing that the gel used did not modify the diffusion of lidocaine. It is not possible to determine whether the plasma concentrations of lidocaine produced in this study had a systemic effect. It has been demonstrated that i.v. lidocaine is effective in blocking the adverse effects of intubation, although it was necessary to use lidocaine 1.5 mg kg–1, resulting in much higher plasma concentrations (1.5–5 µg ml–1)20 21 than those observed in our study (50 ng ml–1).

Our in vitro study using a high-volume, low-pressure cuff is the first confirming the diffusion of alkalinized lidocaine across such a device. It is interesting to note some differences from our previous results obtained with low-volume, high-pressure cuffs.11 12 With high-volume, low-pressure cuffs, the lidocaine release profile seems to be slightly less than that obtained with low-volume, high-pressure cuffs (50% in 3 h). Moreover, variable volumes of NaHCO3 (1–7 ml) injected into the low-volume, high-pressure cuffs had no effect on the diffusion of lidocaine 40 mg; however, large volumes of NaHCO3 (10–15 ml) injected into the high-volume, low-pressure cuffs did have an effect.

In conclusion, our study demonstrated a decrease in sore throat during the postoperative period when the cuff of an ETT was inflated with a low dose of alkalinized lidocaine rather than air. This effect was potentiated when the ETT cuff was lubricated with water-soluble gel compared with lubrication with water alone. Plasma lidocaine concentrations showed the lack of any barrier effect from the water-soluble gel on lidocaine diffusion through the cuff. Using a low dose of alkalinized lidocaine (40 mg) instead of air is a relatively easy and safe practice.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Lev R, Rosen P. Prophylactic lidocaine use preintubation: a review. J Emerg Med 1994; 4: 499–506

2 Tu HN, Saidi N, Lieutaud T, Bensaid S, Menival V, Duvaldestin P. Nitrous oxide increases endotracheal cuff pressure and the incidence of tracheal lesions in anesthetized patients. Anesth Analg 1999; 89: 187–90[Abstract/Free Full Text]

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