Comparison of Preoperative Nebulization with 4% Lignocaine and Ketamine in Reduction of Incidence of Postoperative Sore Throat.

Background: Postoperative sore throat (POST) is a common occurrence following general anesthesia with endotracheal intubation although clinicians often regard it as a minor complication. The incidence of POST is estimated to be 21%-65% in different studies. The administration of the drug through aerosol route gained popularity among anesthesiologists with good acceptance from the patients. Hence, we conducted the study with the aim to compare the efficacy of preoperative nebulization with 4% lignocaine and ketamine, in the prevention of POST. Materials and
Methods: The study is a prospective, randomized double-blinded study comparing the effects of comparison between preoperative nebulization with ketamine and 4% lignocaine in preventing POST. Hemodynamic parameters, Ramsay sedation score, and visual analog scale (VAS) at 0, 6, and 24 h were observed in both groups.
Results: Ketamine nebulization provides better prophylaxis against the occurrence of moderate-to-severe POST as compared to lignocaine. At 0 h, none of the patients had ST in both the groups; at 6 and 24 h, the ST was significantly higher in lignocaine group (28.9% and 8.9%) as compared to ketamine group (8.9% and 0%), with P = 0.04. Mild, moderate, and severe VAS was observed in 51%, 33%, and 16% of Group 1, respectively, while in Group 2, it was observed in 16%, 36%, and 49% of study population, respectively, and this difference was statistically significant.
Conclusion: Patients undergoing surgery under general anesthesia with endotracheal intubation were benefitted from ketamine nebulization as prophylaxis against moderate-to-severe POST. Copyright:

INTRODUCTION

Postoperative sore throat (POST) is a common occurrence following general anesthesia with endotracheal intubation although clinicians often regard it as a minor complication.[1] The incidence of POST is estimated to be 21%–65% in different studies. Irritation and inflammation of the airway are considered to be the causes of POST. Various pharmacological and nonpharmacological methods have been tried to decrease the incidence of POST with varying success rates.[2] Some of them include beclomethasone gel, magnesium sulfate gargle, ketamine gargle, ketamine nebulization, magnesium sulfate nebulization, lidocaine spray, smaller size endotracheal tubes, minimizing cuff pressure to <20 mmHg, and minimizing laryngoscopy attempts. Among the interventions, the use of ketamine gargle or lozenges has the highest success rates. The problem with gargle or lozenges is the bitter taste of the drug and the risk of aspiration while gargling which may lead to serious complications. Hence, the administration of the drug through aerosol route gained popularity among anesthesiologists, with good acceptance from the patients.

Nebulization is primarily used for safety and ease of administration to the patient, with the benefit of the drug reaching the lower airways. In this study we wanted to compare the efficacy of preoperative nebulization with 4%lignocaicaine and ketamine to reduce Post operative Sore Throat(POST). The drugs are easily available and nebulization may be simple, cost-effective method to decrease POST symptoms.

Ketamine has pharmacological properties such as analgesia, anesthesia, and sympathetic action. Some studies have been done which show that ketamine decreases tumor necrosis factor-alpha production in a lipopolysaccharide-induced rat model of sepsis,[3] and it demonstrates a protective mechanism in lung injury by decreasing the expression of inducible nitric oxide synthase and by its anti-inflammatory properties.[4] Studies have suggested its role in endotoxin-induced tissue injury. It has been observed that local use of this drug through the nasal, oral, and rectal routes is both effective and plausible in antinociception and anti-inflammatory cascade.[5]

Local anesthetic drugs act by producing a reversible block to the transmission of peripheral nerve impulses.[6] Lignocaine is used commonly for infiltration in concentrations of 0.5%–1.0% and for peripheral nerve blocks if an intermediate duration is required. Lidocaine 2%–4% is used by many anesthetists as a topical solution for anesthesia of the upper airway before awake intubation.[7]

It is known that N-methyl-D-aspartate (NMDA) receptors have a role in nociception and inflammation. NMDA receptors are found not only in the central nervous system but also in the peripheral nervous system and spinal cord. The antinociceptive and the anti-inflammatory properties of ketamine and magnesium sulfate[58910] with the available data suggest that both have a potential role in reducing POST.

Nebulization is primarily used for safety and ease of administration to the patient with the benefit of the drug reaching the lower airways. In this study we wanted to compare the efficacy of preoperative nebulization with 4%lignocaicaine and ketamine to reduce Post operative Sore Throat(POST). The drugs are easily available and nebulization may be simple, cost-effective method to decrease postoperative symptoms.

MATERIALS AND METHODS

A randomized controlled double-blinded study was carried out in the department of anesthesia, of our institute after obtaining institutional ethical clearance with number IMS. SH/SOA/180270. Ninety patients, aged between 18 and 60 years of both genders planned for elective surgical procedures, belonging to American Society of Anesthesiologists (ASA) physical status Class I and Class II, were included in this study after obtained informed written consent from all the patients.

Patients were randomly allocated into two groups, Group 1 and Group 2, with 45 patients in each, using computer-allocated random numbers.

Group 1-45 patients received nebulization with ketamine 50 mg (1 mL) plus normal saline 2 mL

Group 2-45 patients received nebulization with 1 mL 4% lignocaine plus 2 mL normal saline.

Sample size was calculated based on previous studies with confidence level estimated at 95%, Z value of 1.96, and margin of error estimated at ±12. Patients not willing to participate, those allergic to local anesthetics or study drugs, those having cardiovascular, renal, liver, and coagulation disorders, and those having previous history of POST were excluded from this study.

Preanesthetic checkup and all routine investigations such as complete blood count, serum creatinine, and electrocardiogram were done. Patients were kept nil by mouth for 6 h. All patients were clinically examined in the preoperative period where the whole procedure was explained, and informed written consent was taken. Nebulization was given with one of the study drugs 5 min before shifting to the operation theater. Patients were randomized using computer-generated random numbers into Group 1 and Group 2. Group 1 patients received ketamine 50 mg (1 mL) + normal saline (2 mL), while Group 2 received lignocaine 4% (1 mL) + normal saline (2 mL). Patients enrolled for the study were randomized according to computer-generated numbers into two equal groups. 10-point visual analog scale (VAS) (0, no pain and 10, worst pain imaginable) was also explained during the preoperative visit. The patient was then shifted to the operating room, and general anesthesia was conducted using the standard operating protocols and all standard monitoring were done. Laryngoscopy was performed by a skilled anesthesiologist, and the time of laryngoscopy and the number of attempts were noted. Patients requiring more than two attempts were excluded from the study. Ramsay sedation score was noted at the time of extubation and 1 h postoperatively to assess the level of sedation. Pain assessment was done using the VAS. Pain was classified as no pain (VAS = 0), mild (1–3), moderate (4–6), and severe (7–10) at 0, 6, and 24 h postsurgery.

All procedures were followed according to the Institutional Ethical Standards and the Helsinki Declaration of 1975, as revised in 1983. Continuous variables were analyzed with the unpaired t-test, and categorical variables were analyzed with Chi-square test and Fisher's exact test. Statistical significance was taken as P < 0.05 and data were analyzed using SPSS Software (version 20.000) and Microsoft Excel 2016 (SPSS 16 devloper IBM,chicago).

RESULTS

Ninety patients were included in the study: Group 1 (n = 45) receiving ketamine and Group 2 (n = 45) receiving 4% lignocaine. The mean age of the patients in Group 1 and Group 2 was 41.77 ± 5 years and 40.27 ± 4.4 years, respectively. Statistically, there was no significant difference between the groups (P = 0.22). The mean height and weight of the patients in Group 1 and Group 2 was also statistically insignificant, with P value being 0.687 and 0.599, respectively. The mean body mass index of the patients in Group 1 and Group 2 was 27.3 ± 4.1 and 27.4 ± 3.9, respectively. Statistically, there was no significant difference between the groups (P = 0.632).

The mean systolic blood pressure (SBP) in patients of Group 1 was 134.4 ± 5.8 mmHg, diastolic blood pressure (DBP) was 77.87 ± 2 mmHg , while in patients of Group 2,meanSystolic blood pressure was 133.4 ± 4.8 mmHg,diastolic blood pressure was 77.2 ± 3.9 mmHg. Both the groups were comparable and there was no statistically significant difference in the preoperative baseline SBP, DBP, pulse rate, and SpO2 in patients of both the groups [Table 1].

Table 1

Demographic profile of patients

Parameters	Group 1	Group 2	P
Age (years)	41.77±5	40.27±4.4	0.227
Weight (kg)	75.17±9	72.43±9.4	0.599
Height (cm)	159±6.5	160±9.4	0.681
BMI	27.3±4.1	27.4±3.9	0.632
Gender (male/female)	25/20	23/22	0.417
ASA (I/II)	35/10	33/12	0.754

BMI=Body mass index, ASA=American Society of Anesthesiologists

After induction, there was fall in heart rate in patients of both groups which is statistically not significant. Significant fall in heart rate was observed at 15 min in Group 2 as compared to Group 1. Even there is significant fall in the heart rate in Group 2 as compared to Group 1 from 1 min postoperatively till 60 min (P = 0.0001) [Table 2].

Table 2

Heart rate at different time interval

Heart rate	Mean±SD		P
	Group 1	Group 2
Intraoperative (min)
0	96.93±5.3	97.8±5.8	0.58
1	98.67±6.2	97.13±4.9	0.88
2	96.93±5.3	92.93±4.6	0.121
3	94.73±4.3	91.6±4.4	0.069
5	93.73±4.5	90.13±4.1	0.712
10	90.53±4.3	87.67±3.6	0.775
15	87.93±3.6	77.27±1.8	0.0001**
Postoperative (min)
0	85.47±2.7	73.53±2.1	0.0001**
5	85.8±2.5	72.13±2.2	0.0001**
10	83.33±1.7	73.07±1.9	0.0001**
15	84.4±1.9	72.07±1.9	0.0001**
30	93.4±2.5	83.47±1.4	0.0001**
45	94.93±2.4	82.53±1.627	0.0001**
60	95.67±2.42	80.27±1.721	0.0001**

SD=Standard deviation, **p value < 0.05 was taken as significant

Significant fall in SBP was observed from 2 to 15 min in Group 2 as compared to Group 1. There was significant fall in the SBP in Group 2 as compared to Group 1 from 0 min postoperatively till 5 min (P = 0.0001). There was fall in DBP in patients of both groups after induction which is statistically not significant. Significant fall in DBP was observed from 2 to 15 min in Group 2 as compared to Group 1. Postoperatively, there was no significant difference in the DBP in both groups. After induction, there was fall in mean arterial pressure (MAP) in patients of both groups with statistically not significant difference. Significant fall in MAP was observed from 2 to 10 min in Group 2 as compared to Group 1. Postoperatively, there was no significant difference in the MAP in both groups [Table 3].

Table 3

Mean Arterial Blood Pressure (MAP) at different time interval

Mean arterial pressure	Mean±SD		P
	Group 1	Group 2
Intraoperative (min)
0	89.47±6	92.13±5.5	0.079
1	87.6±5.7	90.33±6	0.076
2	89.53±6	79.33±3.6	0.0001**
3	89.33±5.8	81.4±2.7	0.0001**
5	85.8±5	77.93±2.9	0.0001**
10	83±2.6	78.2±3	0.0001**
15	80.93±4.4	79.33±3.6	0.125
Postoperative (min)
0	80.87±2.6	78.67±2.7	0.079
5	81.27±2.4	78.67±3.3	0.596
10	83.07±2.3	77.73±3.4	0.658
15	84.87±2.6	78.87±3.7	0.23
30	85.2±3	77.53±3.5	0.05
45	86.07±3.542	76.2±3.547	0.351
60	89.33±5.833	77.8±2.845	0.374

SD=Standard deviation, **p value < 0.05 was taken as significant

There were no significant differences in two groups in Ramsay sedation score.

At 0 h, none of the patients had ST in both the groups; at 6 and 24 h, the ST was significantly higher in lignocaine group (28.9% and 8.9%) as compared to ketamine group (8.9% and 0%) with P = 0.04 [Table 4].

Table 4

Sore throat at 0, 6, and 24 h

	Groups		Total	P
	Group 1	Group 2
Sore throat at 0 h
No				1.00
Count	45	45	90
Percentage	100.00	100.00	100.00
Yes
Count	0	0	0
Percentage	0.00	0.00	0.00
Sore throat at 6 the hours
No				0.02
Count	41	32	73
Percentage	91.10	71.10	81.10
Yes
Count	4	13	17
Percentage	8.90	28.90	18.90
Sore throat at 24 h
No				0.04
Count	45	41	86
Percentage	100.00	91.10	95.60
Yes
Count	0	4	4
Percentage	0.00	8.90	4.40

Mild, moderate, and severe VAS was observed in 51%, 33%, and 16% of Group 1, respectively, while in Group 2, it was observed in 16%, 36%, and 49% of the study population, and this difference was statistically significant [Table 5].

Table 5

Visual analog scale of the study population at 24 h

VAS	Groups		Total
	Group 1	Group 2
Mild
Count	23	7	30
Percentage	51.00	16.00	33.00
Moderate
Count	15	16	31
Percentage	33.00	36.00	34.00
Severe
Count	7	22	29
Percentage	16.00	49.00	32.00
Total
Count	45	45	90
Percentage	100.00	100.00	100.00

VAS=Visual analog scale

DISCUSSION

ST is a common postoperative complication following endotracheal intubation during general anesthesia. Although POST is a self-limiting condition, it contributes to patient discomfort. The incidence of POST varies from 21% to 66%.[1] Localized traumas to the mucosa during laryngoscopy and intubation lead to aseptic inflammation of the pharyngeal mucosa, leading to POST.[2]

Patients’ age, weight, height, gender ratio, and ASA physical status were considered as demographic parameters. Age, weight, and height were analyzed by using t-test, while gender ratio and ASA physical status were analyzed using Chi-square test. Both the groups were comparable in terms of age, weight, height, gender ratio, and ASA physical status. These findings were in agreement with the study conducted by Aigbeda.[11] Patient sociodemographic characteristics and duration of surgery were comparable between the groups.

Controversy exists with the context to the effect of gender on the occurrence of postoperative throat pain. While Higgins et al.[2] and Ahmed et al. reported a female predominance in relation to the development of postoperative throat pain, Stout et al.[12] found no gender difference in their study. Our study showed that female patients had higher incidence of postoperative throat pain in the lidocaine group, while their male counterparts had a higher incidence in the ketamine group. A possible explanation is the fact that females have narrower airways than males. This could predispose them to postoperative throat pain when intubated. It is however not clear why males had higher incidence of postoperative throat pain in the ketamine group in our study.

Ketamine increases sympathetic tone, leading to increase in heart rate, cardiac output, and blood pressure. This effect usually lasts for about 20 min and probably the reason for higher heart rate values in Group 1 compared to Group 2. In the present study, there was significant fall in the SBP in Group 2 compared to Group 1 from 0 min postoperatively till 5 min postoperatively (P = 0.0001), after which SBP changes in both groups were not statistically significant (P = 0.647).

In the present study, after induction, there was a fall in DBP and MAP in patients of both groups which was not statistically significant. Significant fall in DBP and MAP was observed from 2 to 10 min in Group 2 as compared to Group 1 (P = 0.001). There was no significant difference in the DBP and MAP in both groups postoperatively.

In the present study, ST was not observed in any of the study groups at 0 h and 6 h postoperatively. However, 24 h postoperatively, ST was significantly higher in lignocaine group (28.9%) as compared to ketamine group (8.9%). These findings were in agreement with the study conducted by lidocaine jelly group which recorded higher incidence of moderate and severe postoperative throat pain, 44.1% and 23.5%, respectively, compared to the ketamine gargle group which recorded 4.2% and 1% moderate and severe throat pain, respectively. This is in agreement with the study of Rudra et al.[13] and Canbay et al.[14] In both studies, ketamine gargle was compared against placebo and postoperative throat pain assessment done as in our study. Ketamine gargle had no incidence of severe postoperative throat pain with less than 5% incidence of moderate throat pain. Postoperative analgesia was uniform, and the method of pain assessment was also uniform in both of these studies. The lower incidence of moderate and severe postoperative throat pain in the ketamine group may be due to its anti-inflammatory effect. These findings were in agreement with the studies conducted by Chan, Rudra et al., and Canbay et al., which observed that ketamine gargle is effective in attenuation of POST; however, it is known to have a bitter taste and patients are at a risk for aspiration due to large volume of the drug. In contrast to this, Ahuja in her study stated that nebulized preservative-free ketamine was tasteless which is in concurrence with our study. Nebulized ketamine is safer and easier to administer with better patient compliance. Pneumatic nebulization produces large-sized particles which get deposited in the mouth and throat during the process of nebulization, hence reducing the incidence and severity of POST. According to literature, all other studies have used a fixed dose of 50 mg ketamine nebulization, irrespective of patient body weight. Hence, we conducted a study to evaluate dose-dependent effectiveness of ketamine nebulization in attenuation of POST and to assess patient satisfaction and acceptability with ketamine nebulization. Similarly, a study conducted by Reddy et al.[15] reported that at 0 h, 51.9% of patients had mild ST and 11.1% of patients had moderate ST in Group A, while only 22.2% patients in Group B and 14.8% patients in Group C had mild ST. This difference was found to be statistically significant among the three study groups.

Limitations of the study

Plasma ketamine and 4% lignocaine levels were not measured intraoperatively

Number of episodes of bucking at the time of extubation was not recorded

Patients were followed up only up to 24 h, so long-term effects are not known. A similar study with a larger study sample size could add strength to the findings. As the response of POST incidence and severity as well as hoarseness was enquired from study patients, there was a chance of subjective bias. Further, we followed patients up to 24 h only, so we could not asses the long-term effects of the study drugs.

CONCLUSION

It can be concluded from our study that patients undergoing surgery under general anesthesia with endotracheal intubation were benefitted from ketamine nebulization as prophylaxis against moderate-to-severe POST.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.