TITLE: 
Efficacy and Safety of Using Air Versus Alkalinized 2% Lignocaine for Inflating Endotracheal Tube Cuff and Its Pressure Effects on Incidence of Postoperative Coughing and Sore Throat



ABSTRACT.BACKGROUND AND OBJECTIVE:
We wished to compare the endotracheal tube (ETT) cuff pressure inflated with air or alkalinized lignocaine during anesthesia and evaluate clinical symptoms such as coughing and sore throat (postoperative sore throat [POST]) following tracheal extubation.

ABSTRACT.MATERIALS AND METHODS:
This was a prospective randomized controlled study conducted in a tertiary care set up over a period of 1 year. We included 100 patients in age group of 18–65 years posted for elective surgeries of duration more than 90 min under general anesthesia with N2O-O2 mixture. Patients were randomized using computer-generated randomization table into air and lignocaine group. The ETT cuff was inflated with air or alkalinized lignocaine (2% lignocaine with 7.5% sodium bicarbonate, in the proportions of 19.0:1.0 ml) to the volume that prevented air leak using cuff pressure manometer. After extubation, an independent observer blinded to study group recorded the presence or absence of coughing and POST at immediately, 1 h and 24 h postoperatively.

ABSTRACT.RESULTS:
Demographic data, baseline characteristics (American Society of Anesthesiologists grade, intracuff volume/cuff pressure at start of surgery), and duration of anesthesia were comparable among study groups (P > 0.05). Cuff pressure and volume achieved in the end of surgery were much higher in air group as compared to lignocaine group (P < 0.05). Incidence of coughing and POST at immediately, 1 h and 24 h postoperatively was significantly higher in air group compared to lignocaine group. Impact of duration of anesthesia on rise in cuff pressure was significantly higher in air group and its effect on cuff-induced laryngotracheal morbidity was significant in both air and lignocaine group.

ABSTRACT.CONCLUSION:
This study showed the significance of use of alkalinized 2% lignocaine in prevention of rise of cuff pressure and incidence of coughing and POST. Duration of anesthesia has also a significant effect on incidence of postoperative trachea-laryngeal morbidity.

BODY.I:NTRODUCTION
Coughing, sore throat, and hoarseness are most common postoperative complications after emergence from general anesthesia[1] which are very distressing and unpleasant and become more upsetting than surgery itself. Postoperative sore throat (POST) being the most undesirable symptom occurs in more than 50% of surgical patients.[2] Among the various methods of airway management such as the use of facial mask, laryngeal mask airways, and endotracheal tube (ETT), ETT is most frequently associated with such postoperative complications ranging from 30% to 70%.[34] The cause of these morbidities could be either patient's bucking or coughing or friction between the tracheal mucosa or increase in ETT cuff pressure during general anesthesia.[4] This has deleterious effects as it may increase intracranial, intrathoracic or intra-abdominal pressure, bronchospasm, wound dehiscence, bleeding, and laryngeal complication such as sore throat, hoarseness, or dysphonia.[2]
The ETT cuff pressure is most important factor which when elevated compromises of the blood supply of tracheal mucosa followed by serious morbidities such as ciliary loss, inflammation, ulceration, hemorrhage, tracheal stenosis, and trachea-esophageal fistula.[15] Maintenance of ideal cuff pressure during whole surgery is also challenging as many factors govern it like anesthetic gases such as N2O, agent used to fill the cuff, and material and type of cuff[1678] Most commonly used anesthetic gas N2O in conjunction with other gases frequently causes rise in intracuff pressure with the progression of surgery. N2O and oxygen readily diffuse in air-filled cavities such as ETT cuff leading to gradual rise in volume and cuff pressure of ETT. Consequently, this pressure change results in more severe form of POST.[1910] Various literature in the past has proven the relation of rise in cuff pressure and volume with the usage of N2O. Intracuff use of saline and lignocaine is recently being reviewed for the effectiveness in preventing coughing, POST, and postoperative hoarseness (PH).[1811]
Lignocaine being liquid in nature not only inhibits the entry of N2O in the cuff but also permeates through semipermeable cuff membrane to tracheal mucosa and provides direct anesthetic effect. Alkalinization of lignocaine with sodium bicarbonate (NaHCO3) increases the nonionized form of lignocaine which considerably increases the diffusion of lignocaine through polyvinyl cuff walls (63 folds).[1] Thus, lesser amount of lignocaine can provide rapid and prolong action over mucosa.[12]
Hence, in our study, we have studied the effect and safety of use of intracuff alkalinized lignocaine over conventional air and evaluated incidence of coughing and POST after tracheal extubation.

BODY.M:ATERIALS AND METHODS
This was a prospective randomized control study conducted in tertiary care teaching public hospital after obtaining ethical permission and well informed written consent from the patients. The study was conducted over a period of 1 year from June 2014 to August 2015. We enrolled patients with age group 18–65 years with American Society of Anesthesiologists (ASA) Class I and II, Mallampatti classification 1 being posted for surgeries under general anesthesia with minimum surgical duration of 90 min. We excluded patients with laryngeal disease/surgery/tracheostomized, ASA Class III and IV, difficult intubation, or failed extubation. Standard routine balanced general anesthesia was given as per the attending senior anesthesiologist's protocol and dosage according to the body weight of the patient. ETTs with high residual volume, low-pressure cuff, with an inner diameter of 7.0 mm for female and 8.5 mm for male were used in all patients.
Subjects were allocated in two groups as Air group (A) and Lignocaine group (L) according to computer-generated randomization sheet with fifty patients in each group.
In A group, ETT cuff was filled with air to prevent air leak during positive pressure ventilation guided with cuff manometer. While in L group, ETT cuff was filled with 2% lignocaine with 7.5% NaHCO3, in the proportions of 19.0:1.0 ml. Care was taken to ensure that starting cuff pressure as approximately 20 cm H2O adequate enough to just prevent leak around cuff during positive pressure ventilation. Volume and cuff pressure of air and lignocaine injected in the cuff was noted at start and end of surgery. Total duration of anesthesia was also noted. Immediately after extubation, an independent observer blinded from the study group recorded the presence or absence of coughing. Similarly, in postoperative care unit, occurrence of coughing and POST at 1 h and 24 h were recorded. Similarly, in postoperative care unit, occurrence of coughing and POST at 1 h and 24 h was recorded. Coughing/POST was recorded as present or absent.
Sample size is calculated with the help of the study of Navarro et al.[1] for a Type I error of 0.05 and a Type II error of 0.20 with a power equal to 80% and confidence interval of 95%. Thus, a total sample size was 100 patients with fifty patients in each group.
Data analysis is done with the help of SPSS Software ver 15 (SPSS Inc. Released 2006. SPSS for Windows, Chicago, USA) and Sigma plot Ver. 11 (Systat Software, Inc., San Jose, California, USA).

BODY.R:ESULTS AND ANALYSIS
The anthropometric parameters in term of age, sex, weight, and ASA were comparable in both groups with P > 0.05 [Tables 1–3]. The volume and cuff pressure of A group and L group introduced into the cuffs at the start of surgery for adequate seal were recorded and on analysis both were comparable (P > 0.05), [Table 4]. The mean cuff pressures obtained at the end of surgery were 49.86 cm H2O and 19.66 cm H2O in A and L group, respectively, proving statistically significant difference between the two groups [Table 4]. The duration of anesthesia in both groups was comparable with average duration in A group was 2.67 ± 0.72 h and in L group was 2.66 ± 0.70 h [Table 4]. This was well above the mean duration of anesthesia as set in inclusion criteria required for the effect of lignocaine over tracheal mucosa. Analysis of change in volume and pressure of cuff during surgery revealed significant difference in A group than L [Table 5].
Table 1Association between the two study groups on the basis of age and weight
Table 2Association between the study groups on the basis of sex
Table 3Association between the study groups on the basis of American Society of Anesthesiologists classes
Table 4Association between the two study groups on the basis of multiple variables
Table 5Association between change in cuff volume and pressure between two groups
The incidence of coughing immediately after extubation, postoperatively 1 h and 24 h after surgery is depicted in Figures 1 and 2. Significant difference determined by Pearson Chi-square test and Fisher's exact test showed P < 0.05 thereby substantiating the reduced incidence of coughing and POST in L group. Through the analysis, it was found that in A group, there was a high correlation between duration of anesthesia and cuff pressure achieved in the end of surgery with P < 0.001 [Figure 3] while no such correlation was obtained in lignocaine group [Figure 4].
Figure 1Incidence of coughing in air and lignocaine group
Figure 2Incidence of postoperative sore throat among air and lignocaine group
Figure 3Correlation between duration of anesthesia and cuff pressure at end in air group
Figure 4Correlation between duration of anesthesia and cuff pressure at end in lignocaine group
Further, association between duration of anesthesia with coughing and POST in A group revealed significant association at immediately after extubation, 1 h and 24 h postoperatively [Table 6]. In L group, such association was found only during coughing immediately after extubation and POST at 1 h and 24 h. This association was statistically significant with P < 0.05 (unpaired t-test) [Table 7].
Table 6Association between duration of anesthesia and incidence of coughing and postoperative sore throat in air group
Table 7Association between duration of anesthesia and coughing and postoperative sore throat in lignocaine group

BODY.D:ISCUSSION
The most bothersome postoperative complaint in the setting of general anesthesia after extubation of ETT is coughing and sore throat affecting more than half of the patients.[124] Various factors contribute to the emergence of these symptoms that may adversely affect the outcome if not monitored adequately. ETT cuff pressure is the indirect measure of pressure exerted by cuff over tracheal mucosa that is not monitored routinely.[1]
The critical function of ETT cuff is to provide adequate seal to airway during positive pressure ventilation to prevent aspiration due to under inflation. Long duration of cuff inflation can result in mucosal ischemia and further complications such as coughing, POST, PH, tracheal ulceration, stenosis, and tracheoesophageal fistula.[110] In humans, endotracheal (ET) cuff pressures at approximately 30 cm H2O can impair tracheal mucosal perfusion, and a critical perfusion pressure is reached at 50 cm H2O which has been demonstrated by endoscopic studies.[13]
N2O anesthesia which is a common conjunct with other volatile anesthetics is the main factor, which increases the intracuff pressure by easily diffusing into the cuff with the advent of surgery.[18910] Various factors have been evaluated to reduce this rise in cuff pressure such as repeated inflation-deflation technique, use of O2-N2O mixture, polyurethane cuff, and liquid cuff media.[910]
Lignocaine, an amide local anesthetic in its several preparations such as topical jelly, intracuff, aerosolized, or intravenous form has evolved as an effective measure in reducing POST. We compared the traditional practice of use of air as inflation media with lignocaine for determining the rise in cuff pressure and thereby incidence of signs of tracheal morbidity such as coughing and sore throat 24 h postoperatively. The basis of our study was that lignocaine inserted intracuff act as a reservoir of local anesthetic which being a liquid not only prevents the diffusion of N2O intracuff but also permeates through semipermeable membrane of polyvinyl chloride cuff to provide soothing effect on tracheal mucosa and helps in reducing pressure induced necrosis, cough reflex.[1414] The study of Estebe et al.[15161718] reported that alkalinization of intracuff lignocaine increases the diffusion of its nonionized neutral base across hydrophobic structure of cuff membrane from 1% to 65% within 6 h. They studied both in vitro and in vivo effect of alkalinized lignocaine across tracheal mucosa and showed significant decrease in dose requirement of lignocaine in alkalinized form to as low as 20–40 mg as compared to nonalkalinized lignocaine dose of 200–500 mg.[11418] This report encouraged us to design our study using alkalinized lignocaine for more safety and efficacy in the study subjects. No form of external lubrication in the form lignocaine jelly was used over the cuff during intubation for facilitation of cuff beyond the vocal cords. Multiple studies have shown that cuff lubrication in form of jelly or topical spray is associated with unfavorable phenomena at the time of emerging from anesthesia.[1419] The lignocaine spray contains additives such as l-methanol and ethanol which are more associated in causing POST and hoarseness.[19] The intravenous form of lignocaine is more associated with sedation or deepening plane of anesthesia which is not suitable at the time of extubation.[14]
Demographic data (age, sex, weight) of study subjects, baseline characteristics (ASA class, intracuff volume/cuff pressure inflated at start of surgery), and duration of anesthesia were comparable among study groups (P > 0.05) [Tables 1–4].
Our study has demonstrated that using N2O anesthesia, filling of ET cuff with air despite initial cuff pressure set well below critical pressure of 30 cm H2O rises toward the end of surgery. Average volume of air injected to achieve adequate seal was 4.54 ± 0.63 ml with average cuff pressure at the start of surgery as 20.42 ± 0.73 cm H2O [Table 4]. Toward the end of surgery, mean volume of cuff reached to 6.00 ± 0.78 ml and mean cuff pressure rose to 49.86 ± 0.72 cm H2O [Table 4]. Our data confirmed the increased cuff pressure and cuff volume after air inflation with N2O-oxygen anesthesia.[1814202122] Significance of continuous cuff pressure monitoring to prevent POST and hoarseness was emphasized by Suzuki et al.,[23] Sengupta et al.,[24] Hoffman et al.,[13] Liu et al.,[6] and Manissery et al.[10]
In comparative group, mean initial volume of alkalinized lignocaine required to inflate the ETT cuff was 4.40 ± 0.60 ml and initial cuff pressure as 20.60 ± 0.78 cm H2O [Table 4]. Both of the volume and cuff pressure at start of surgery in air and lignocaine group were similar and statistically not significant (Mann–Whitney test, P > 0.05), [Table 4]. Toward the end of surgery, mean volume obtained and average cuff pressure was 4.14 ml and 19.66 ± 0.74 cm H2O, respectively. This showed a highly significant difference in the two groups (Mann-Whitney test, P < 0.001), [Table 4].
In A group, the volume and cuff pressure during surgery increased by 1.46 ± 0.48 ml and 29.44 ± 7.16 cm H2O, respectively. On the other hand, in L group, volume and cuff pressure decreased by 0.26 ml and 0.94 cm H2O, respectively. This change in volume and pressure was statistically significant between both groups (Unpaired t-test, P < 0.05), [Table 5]. This clearly showed the cuff volume and pressure did not change with time in lignocaine group as compared with air group. Lignocaine, being liquid in media, prevents hyperinflation of cuff with N2O with the course of surgery.[1] Lignocaine diffuses through cuff membrane in time and concentration-dependent fashion and influence local tracheal receptors by inducing local anesthesia and increase ETT tolerance.[11]
Moreover, incidence of coughing and POST at immediately, 1 h and 24 h postoperatively was significantly higher in air group in comparison to lignocaine group [Figures 1 and 2]. These results are coherent with the studies of Navarro et al. 2007,[1] Navarro et al. 2012,[21] Jaichandran et al. 2009,[25] Shroff and Patil, 2009.[26] Wetzel et al. could not find attenuation in coughing and POST when intracuff lignocaine group used where procedures lasted for <1.5 h in patients who smoke.[27] Thus, using these lignocaine instilled cuffs for longer duration, surgeries would result in better outcome as diffusion across the cuff membrane is a function of time.[20]
Although lignocaine was instilled in the cuff, it does not cause any depression of swallowing reflex and other protective reflexes. This has been confirmed by other study done by Estebe et al. which stated that alkalinized intracuff lignocaine improves cuff tolerance; however, the local anesthetic effect does not depress the swallowing reflex so that the patient can protect the airway.[15]
In an extensive review by Tanaka et al. (Cochrane 2009) concluded that topical and systemic lignocaine therapy reduces the prevalence and severity of sore throat after general anesthesia with ET intubation.[4] Recent meta-analysis by Lam et al. showed the beneficial effect of alkalinized and nonalkalinized lignocaine intracuff over conventional inflation medias. The incidence of early and late POST, agitation, coughing, hoarseness, dysphonia like post intubation emergence phenomena was significantly lower in lignocaine group.[2]
It was clearly evident that with the prolongation of duration of anesthesia cuff pressure also increased significantly in air group in comparison to lignocaine group [Figures 3 and 4]. Similarly, the outcome of rise in cuff pressure in such patients whose duration of surgery was prolonged showed significant increase in coughing and POST in air group [Table 6]. Furthermore, the analysis showed the increase in duration of anesthesia influenced the incidence of coughing and POST in lignocaine group [Table 7].
Mitchell et al. demonstrated linear rise in cuff pressure with time in air group. They suggested that the rise in cuff pressure causes tracheal mucosa ischemia due to lateral contact pressure exerted by cuff.[28] In our study, all the cases were extubated without any complication. The present study was not without limitations as we did not included children and elderly in our study subjects. Severity of coughing and sore throat were not graded rather only incidence of its presence was evaluated. Measurement of concentration of plasma lignocaine was not done.

BODY.C:ONCLUSION
In the setting of general anesthesia with the use of N2O and O2 mixture, rise in cuff pressure with the progression of surgery is better overcome when ETT cuff is inflated with lignocaine as compared to air. Alkalinized 2% lignocaine provides an improved protective effect in preventing postoperative laryngotracheal morbidity in form of coughing and POST. Duration of anesthesia is another risk factor, which has significant impact on increase in cuff pressure and consequently increased the incidence of coughing and POST in ETT cuff filled with air.
BODY.FINANCIAL SUPPORT AND SPONSORSHIP:
Nil.

BODY.CONFLICTS OF INTEREST:
There are no conflicts of interest.

Question: Compared to air group what was the result of lignocaine group on Cuff pressure and volume achieved in the end of surgery?
Evidence: Cuff pressure and volume achieved in the end of surgery were much higher in air group as compared to lignocaine group (P < 0.05).
Answer: significantly decreased