Post Extubation Airway Conditions after Direct Laryngoscopic Biopsy: A Comparative Evaluation between Lignocaine Nebulization and Lignocaine Lozenges - A Randomized Trial.

CONTEXT: Postextubation airway complications are one of the most undesired side effects of airway manipulation. Pharmacological and nonpharmacological measures have been utilized for minimizing the morbidity. Lignocaine lozenges, a new modality, used to reduce post-extubation airway complications is an area yet to be explored. AIMS: The aim of this study is to evaluate and compare the effects of lignocaine nebulization versus lignocaine lozenges in decreasing immediate postextubation airway complications in patients presenting for direct laryngoscopic biopsy. SETTINGS AND
DESIGN: This randomized study was conducted at tertiary care teaching hospital in northern state of India. SUBJECTS AND METHODS: A total of 90 patients, 40-70 years, the American Society of Anesthesiologists (ASA) physical status Classes I, II, and III of either sex, posted for elective direct laryngoscopic biopsy, requiring general anesthesia with endotracheal intubation were included and randomly divided into groups (n = 30) to receive lignocaine nebulization (Group A), lignocaine lozenge (Group B), control (Group C). The patients were assessed for a cough after extubation after 5 min then every 10 min up to 30 min postextubation. STATISTICAL ANALYSIS USED: Categorical variables were compared using the Chi-square test or Fisher's exact test and continuous variables by using one-way Analysis of variance and Kruskal-Wallis test, respectively.
RESULTS: Comparison of a cough at various time intervals starting from extubation up to 30 min in post-extubation period was highly significant in between groups. Among Group A (lignocaine nebulization) 33% of patients had a decrease in the severity of a cough within the first 5 min; although among Group B (Lignocaine Lozenges), the decrease in the severity of a cough (40%) was more as compared to that of Group A. Similar decrease in the severity of a cough was observed through various time interval from 10 min to 30 min postextubation. After 30 min, 73% of patients in Group A and 76% of patients in Group B had an incidence of a decrease in the severity of cough.
CONCLUSIONS: Lignocaine Lozenges have been found to have a better result.

INTRODUCTION

Laryngeal malignancy is the second most prevalent head-and-neck malignancy in men.[1] Direct laryngoscopy is used to examine laryngeal and supraglottic anatomy and can be used to directly visualize and take biopsy from areas in and around the larynx, therefore, making it a valuable tool in establishing an early diagnosis of pathologies of this region.[2]

However, few minor complications are inevitable in spite all the advances in the latest technology.[3] Especially, cough and postoperative pharyngeal discomfort or “postoperative sore throat” is an untoward outcome tracheal intubation leading to psychological distress in the postoperative period.

Different factors have been implicated in causing airway complications which include the size of endotracheal tube, type of cuff, pressure of the tube cuff,[4] number of attempts taken and duration of tracheal intubation and nature of surgery (like procedures related to throat and upper airways).[5]

Smoking is a modifiable risk factor to be considered as smokers are more prone to cough due to upper airway reflex sensitivity.

To blunt the aforementioned airway responses to tracheal extubation, lignocaine, a commonly used local anesthetic having an amide side chain can be used preoperatively through a different route of administration, thus reducing the severity of postoperative airway complications.[6]

Lignocaine lozenge on a stick (like a lollipop) is a novel method of providing anesthesia in the oropharyngeal region by swallowing the saliva which is mixed with the local anesthetic resulting in a homogenous and slow spread of the drug, thereby providing adequate time for exerting its effects in the desired local site.[7]

Lignocaine pneumatic nebulizers work on the principle of conversion of droplets into aerosols of smaller size (1–5 mm) by using baffles such as they can be inhaled. Nebulization is favored for being a safe and easy route of administration to the patients in addition to its benefit of drug reaching lower airways.

To the best of our knowledge, no previous study has compared the efficacy of lignocaine nebulization and lignocaine lozenges for direct laryngoscopic biopsy. Therefore, the present study was designed to evaluate the effect of lignocaine nebulization and lignocaine lozenges in patients undergoing direct laryngoscopy and biopsy under general anesthesia with tracheal intubation.

The aim of the present study was to evaluate and compare the effects of lignocaine administered by two different formulations on immediate postextubation respiratory complications (cough being the primary outcome) after the direct laryngoscopic biopsy.

SUBJECTS AND METHODS

Patients

The study was conducted at Himalayan Hospital in the Department of Anaesthesiology after obtaining the Institutional Ethics Committee approval (RBR number– SRHU/HIMS/ETHICS/2018/78 Dated 13.07.2018) and written informed consent of patients. A total of 90 inpatients, aged 40–70 years of either sex, ASA physical status Classes I, II, and III, posted for elective direct laryngoscopic biopsy requiring general anesthesia with endotracheal intubation, were included in the study.

Exclusion criteria

Patients refusal for the procedure, weight <40 kg, patients requiring re-intubation or tracheostomy, history of active upper respiratory tract infection, Mallampatti grade III and above were excluded from the study. Patients were also excluded if there was a history of allergy to lignocaine, hepatic, renal or cardiopulmonary insufficiency, alcoholic, diabetes, long-term analgesic therapy.

Study protocol

Type of the study

This was randomized, experimental study. Sample size and sampling methods-Sample size calculation was based on data analyzed in similar studies performed in the past using G * Power (Version 3.2.1, Germany). Sample size estimation was based on cough (primary outcome) presuming the proportion of reduction in the incidence of cough postextubation was 78% in the study group. The total sample size was calculated to be 90 (30 patients in each group) from an effect size of 0.67, power of 80%, and α of 0.05 to detect the significant difference (P < 0.05) between any two groups.[8] Method of randomization: Randomization block design was used to randomize 90 patients who fulfil the inclusion and exclusion criteria among three groups such that each group had 30 patients. The randomized block size was 9.

Method of anesthesia

All the eligible patients were asked to refrain from smoking for at least 48 h before surgery and were kept nil per oral for solids for 6 h. tablet (tab) ranitidine 150 mg and tab alprazolam 0.25 mg were administered night before and 2 h before surgery.

Patients were divided into three groups:

Group A: Patients receiving lignocaine nebulization were explained the procedure and were nebulized with 4% lignocaine 200 mg (5 mL) through ultrasonic nebulizer 20 min before surgery.

Group B: Patients were explained about the procedure and were given lignocaine lozenge 200 mg to suck and not to swallow or chew the lozenge at least 20 min before being taken for surgery.

Group C: Patients were taken up for surgery without any intervention.

In the operation room after establishing intravenous access and applying mandatory monitoring, anesthesia in all the cases was induced with injection fentanyl 2 μg/kg and injection propofol 2 mg/kg till the loss of verbal contact. Ease of bag-mask ventilation was assessed and neuromuscular blockade established with injection succinylcholine 2 mg/kg. The patients were ventilated with 66% nitrous oxide (N2O) in oxygen (O2) and sevoflurane. Endotracheal intubation was completed utilizing Laryngoscopy was done using Macintosh laryngoscope and EndoTracheal Tube (ETT) of appropriate size was used.

Intubation and endotracheal tube placement were confirmed by auscultation of the chest, SpO2 >95% and capnogram recording. The duration of laryngoscopy and number of attempts were noted.

All the intubations were carried out by a single intubator with experience >2 years in anesthesia. Anesthesia was maintained with 66% N2O in O2, sevoflurane. With the resumption of spontaneous respiration, N2O was switched off, gentle suction was done, cuff of ETT deflated and the patient extubated once the patient gained consciousness and good spontaneous respiration. Harsh suctioning or bucking on ETT was avoided.

After extubation, cough was observed and graded by Harding and McVey[9] score [Table 1] at different time intervals that is at extubation, after 5 min, then every 10 min till maximum of 30 min postextubation.

Table 1

Harding and McVey score

Cough	Score
No cough at any time since the operation	0
Minimal cough or scratchy throat (light/single episode of cough)	1
Moderate cough (more than one episode of nonsustained cough)	2
Severe cough (sustained and repetitive cough with head lift)	3

Data management and statistical analysis

Data were analyzed using Statistical Package for the Social science System version SPSS 20 (IBM Corp. Released 2011. IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp). Qualitative data were expressed as frequency and percentage. Qualitative data followed normal distribution and were presented as mean ± standard deviation also skewed distribution, for example, duration was expressed as median (range). Categorical variables between the groups were compared using the Chi-squared test or Fisher's exact test as appropriate. Change in score in categorical variables was assessed using Stuart Maxwell test. The comparison of the normal and skewed distribution of continuous variables between the groups was performed using one-way analysis of variance and Kruskal–Wallis H test, respectively. Bonferroni and Dunn multiple comparison tests were also used for intergroup comparison.

For all statistical tests, a value of P < 0.05 was taken to indicate a significant difference and value ≤0.01 was considered as highly significant.

RESULTS

All the patients included completed the study [Figure 1]. The demographic profile and intubation characteristics are depicted in Tables 2 and 3 and the three groups were comparable for age, sex, weight, duration of laryngoscopy, number of attempts, and duration of surgery and anesthesia (P > 0.05).

Figure 1

Flow diagram showing sequential assessment of patients enrolled in the study

Table 2

Demographic profile of patients in different group sample size (n=90)

Criteria	“Group A (n=30), n (%)	Group B (n=30), n (%)	Group C (n=30), n (%)	P
Age (years), mean±SD	56.4±8.5	56.6±8.14	53.8±9.9	0.383*
Weight (kg), mean±SD	57.1±9.5	55.8±8.5	57.8±11.6	0.741*
Sex, mean±SD
Male	25 (83.3)	27 (90)	29 (96.6)	0.284#
Female	5 (16.6)	3 (10)	1 (3.33)
ASA physical status classes
I	11 (36.6)	13 (43.3)	9 (30)	0.787#
II	15 (50)	15 (50)	18 (60)
III	4 (13.4)	2 (6.6)	3 (10)
MPG
I	8 (26.6)	5 (16.6)	4 (13.3)	0.441#
II	22 (73.3)	24 (80)	26 (86.6)
III	0	1 (3.3)	0 (0)
History of smoking (%)
Nonsmoker	7 (23.3)	4 (13.3)	3 (10)	0.439#
Smoker	23 (76.6)	26 (86.6)	27 (90)

*One-way ANOVA, #Chi-square test. SD=Standard deviation, ASA=American Society of Anesthesiologists, MPG=Mallampatti grade, ANOVA=Analysis of variance

Table 3

Intubation characteristics of patients in different groups sample size (n=90)

Variable	Group A	Group B	Group C	P
Cormack-Lehane grade
I	6 (20)	7 (23.3)	5 (16.6)	0.925#
II	19 (63.3)	20 (66.6)	20 (66.6)
III	5 (16.6)	3 (10)	5 (16.6)
Number of attempts (%)
1	18 (60)	23 (76.6)	20 (66.6)	0.491#
2	11 (36.6)	7 (23.3)	8 (26.6)
3	1 (3.3)	0 (0)	2 (6.6)
Duration of laryngoscopy (mean±SD), median (minimum-maximum)	22.6±12.8, 20 (8-52)	25.9±12.8, 22.5 (10-60)	21.4±11.0, 17.5 (9-56)	0.272$
Duration of anesthesia (mean±SD), median (minimum-maximum)	39.6±13.9, 42 (14-67)	36.4±9.8, 38 (18-56)	39.5±10.7, 40.5 (19-60)	0.496$
Duration of surgery (mean±SD), median (minimum-maximum)	30.3±12.7, 31 (6-50)	27±9.3, 26 (12-45)	29.7±8.8, 30 (8-42)	0.297$

#Chi-square test, $Kruskal-Wallis test. SD=Standard deviation

Post-extubation cough was scored on 4 point scale, After extubation, no cough was seen in 1 (3.3%) patients (Group A) compared to 2 (6.6%) in Group B and 1 (3.3%) in Group C. Severe cough (score 3) was present in 05 (16%) (Group A) compared to 8 (26.6%) (Group B) and 12 (40%) patient in Group C. Incidence of no cough increased to 4 (13.3%), 9 (30%), 10 (33%) patients after 5, 10, and 20 min, respectively, in Group A, similar trend was seen for patients in Group B, whereas in Group C, all patients had some intensity of cough.

After 30 min, no cough was found to be highly significant in the association of a cough with the passage of time (P < 0.05) [Table 4].

Table 4

Comparison of cough at different time intervals in between groups (sample size n=90)

Variable cough	Group A (n=30), n (%)	Group B (n=30), n (%)	Group C (n=30), n (%)	P
At extubation
0	1 (3.3)	2 (6.6)	1 (3.3)	0.018#
1	11 (36.6)	9 (30)	1 (3.33)
2	13 (43.3)	11 (36.6)	16 (53.3)
3	5 (16.6)	8 (26.6)	12 (40)
After 5 min
0	4 (13.3)	5 (16.6)	0 (0)	0.001#
1	9 (30)	8 (26.6)	1 (3.3)
2	8 (26.6)	12 (40)	12 (40)
3	9 (30)	5 (16.6)	17 (56.6)
After 10 min
0	9 (30)	9 (30)	0 (0)	0.002#
1	6 (20)	11 (36.6)	6 (20)
2	9 (30)	7 (23.3)	14 (46.6)
3	6 (20)	3 (10)	10 (33.3)
After 20 min
0	10 (33.3)	11 (36.6)	0 (0)	0.000#
1	9 (30)	15 (50)	12 (40)
2	10 (33.3)	4 (13.3)	16 (53.3)
3	1 (3.3)	0	2 (6.6)
After 30 min
0	14 (46.6)	13 (43.3)	1 (3.3)	0.000#
1	12 (40)	14 (46.6)	15 (50)
2	4 (13.3)	2 (6.6)	12 (40)
3	0	1 (3.3)	2 (6.6)

#Chi-square test

Comparison of a cough at various time intervals starting from extubation up to 30 min in postextubation period was highly significant in between groups. However, severe postextubation cough was most common in control group (67%) followed by lignocaine nebulization group (47%) with least common occurrence in lignocaine lozenges group (40%) [Figure 2].

Figure 2

Comparison of the severity of cough in between groups

DISCUSSION

Just like any foreign-body and medical procedure, tracheal intubation can cause iatrogenic trauma to oro-laryngo-tracheal structures. Moreover, when surgical procedures (diagnostic or interventional) are concomitantly performed on these structures, the incidence of symptoms related to iatrogenic trauma may increase.

It has already been documented by Tanaka et al. that laryngeal reflexes’ attenuation happens even with laryngeal mask airway insertion despite no “foreign body” (tube) traversing through the larynx and into the trachea; however, changes in laryngeal reflexes induced by tracheal tubes were significantly measurable.[10]

Therefore, the present research was designed to explore (a) if postoperative symptoms as related to iatrogenic trauma of oro-laryngo-tracheal structures increase with concomitant tracheal intubation by anesthesiologists and laryngoscopic biopsy by oto-rhino-laryngologists and (b) whether two different formulations of lignocaine differentially effect the incidence of these symptoms.

Study conducted by Gupta et al. concluded that the incidence of cough had decreased from 54% with placebo to 22% with Strepsils® given preoperatively.[8]

Banihashem et al. conducted a study and found that incidence of cough within one hour of extubation was effectively reduced when their tracheal tubes had been sprayed with 10% lidocaine (17% cough incidence) or 50% beclomethasone (0% cough incidence) prior to intubation as compared to if their tracheal tubes had been sprayed with placebo (normal saline; 33% cough incidence).[11]

In this study, comparison of cough at various time intervals starting from extubation up to 30 min in postextubation period was highly significant in between groups. Among Group A (lignocaine nebulization), 33% of patients had a decrease in severity of cough within the first 5 min; although among Group B (lignocaine lozenges), the decrease in the severity of cough was 40%. A similar decrease in the severity of cough was observed through various time interval from 10 min to 30 min postextubation. After 30 min, 73% of patients in Group A and 76% of patients in Group B had incidence of decrease in the severity of cough. Therefore, lignocaine lozenges were more effective in decreasing the severity of cough in comparison to Lignocaine nebulization. A remarkable finding was that occurrence of severe postextubation cough was most common in control group (67%) followed by lignocaine nebulization group (47%) with the least common incidence in lignocaine lozenges group (40%).

CONCLUSIONS

Airway instrumentation during tracheal intubation and laryngoscopic biopsy cause post-operative airway complication such as a cough, sore throat, and hoarseness of voice. Two different formulations of lignocaine, which is nebulization and lozenges, are found to be effective in reducing airway complications.

Lignocaine lozenges have been found to have a better result in reducing cough than lignocaine nebulization. However, both lignocaine nebulization and lozenges demonstrated to be beneficial in improving airway outcome and in improving patient's satisfaction.

Limitations of study

The drawbacks in this study were, we did not record coughing and other airway complications beyond 30 min after extubation in the postoperative period.

We did not take into account the sedation score at the time of extubation. Therefore, patients’ response could not be relied on precisely in terms of hoarseness and sore throat (interview method was used for assessment).

The further study can be planned to take into account the aforementioned limitations.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.