|Year : 2012 | Volume
| Issue : 3 | Page : 175-179
Prophylactic ketamine gargle to reduce post-operative sore throat following endotracheal intubation
Gojendra Rajkumar, L Eshwori, P Yanang Konyak, L Deban Singh, Thokchom Rupendra Singh, M Bina Rani
Department of Anesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Web Publication||10-Jun-2013|
Department of Anesthesiology, Regional Institute of Medical Sciences, Imphal, Manipur
Source of Support: None, Conflict of Interest: None
DOI: 10.4103/0972-4958 .113242
Objective: To study, the effect of prophylactic ketamine (K) gargle in reduction of post-operative sore throat (POST) following endotracheal intubation. Materials and Methods: 90 adult patients between 18 years and 60 years with American Society of Anesthesiologists I and II, scheduled for elective open cholecystectomy surgery under general anesthesia were randomly assigned into 2 groups of 45 patients each. Group S-received 30 ml of normal saline (NS) and Group K-received 40 mg of K in 30 ml of NS. Then the patients were asked to gargle with the preparation for 30 s after their arrival in the operation room. Anesthesia was induced 5 min later. On arrival in the post-anesthesia care unit (0 h), and at 2 h, 4 h, and 24 h thereafter, the patients were questioned by a blinded investigator whether he/she had experienced sore throat or any other side- effects. POST was graded on a four-point scale (0-3). Results: The incidence of POST was higher in NS group compared with K group at 0 h, 2 h, 4 h, and 24 h. In addition, there is reduced incidence of hoarseness of voice in K group compared to NS group at 0 h, 2 h, 4 h, and 24 h after extubation. Conclusion: In conclusion, gargling with K decreases the incidence and severity of POST and hoarseness of voice.
Keywords: Endotracheal intubation, Ketamine, Post-operative, Sore throat
|How to cite this article:|
Rajkumar G, Eshwori L, Konyak P Y, Singh L D, Singh TR, Rani M B. Prophylactic ketamine gargle to reduce post-operative sore throat following endotracheal intubation. J Med Soc 2012;26:175-9
|How to cite this URL:|
Rajkumar G, Eshwori L, Konyak P Y, Singh L D, Singh TR, Rani M B. Prophylactic ketamine gargle to reduce post-operative sore throat following endotracheal intubation. J Med Soc [serial online] 2012 [cited 2020 Oct 30];26:175-9. Available from: https://www.jmedsoc.org/text.asp?2012/26/3/175/113242
| Introduction|| |
Post-operative sore throat (POST) and hoarseness are minor but frequent complications of endotracheal intubation with reported incidence of 10-85%, that is responsible for post-operative morbidity and patient dissatisfaction. ,,,, POST was rated by patients as the eighth most adverse effect in the post-operative period  and occasionally required treatment with supplementary analgesics. Numerous non-pharmacological and pharmacological trials have been used for attenuating POST with variable success. Smaller sized endotracheal tubes, lubricating the endotracheal tube with water-soluble jelly, careful airway instrumentation, intubation after full relaxation, gentle Oropharyngeal suctioning, minimizing intra-cuff pressure, and extubation when the tracheal tube cuff is fully deflated are some non-pharmacological measures that have been reported to decreased the incidence of POST.  The pharmacological measures include, beclomethasone inhalation and gargling with azulene sulfonate. , A simple, safe, and inexpensive perioperative intervention to prevent POST would be useful.
The ionotropic glutamate receptors N-methyl-D-aspartate (NMDA), α-amino-3-hdroxyl-5-methyl-4 isoxazol-epropionic acid, and the kainate receptors are found in the central nervous system as well as the peripheral nerves. Behavioral studies indicated that activation of these receptors results in nociceptive behaviors and contribute to inflammatory pain.  Peripherally administered NMDA receptor antagonists are involved with anti-nociception. 
The intravenous anesthetic, ketamine (K) was first used in humans in 1965 and is still applied in various clinical settings. K has many pharmacological properties, including analgesic, anesthetic, and sympathomimetic effects. Studies have shown that K attenuate symptoms of endotoxemia in a lipopolysaccharide (LPS)-induced rat model of sepsis, by reducing Nuclear Factor (NF)-beta(B) activity and tumour necrosis factor (TNF)-alpha production.  It has also been shown to play a protective role against lung injury, via its anti-inflammatory properties  and decreasing the expression of inducible nitric oxide synthase (iNOS),  which has been implicated in endotoxin-induced tissue injury. Studies into the nasal, oral, and rectal administration of K have suggested that local use of this drug is both effective and plausible.  K, a NMDA receptor antagonist is involved in anti-nociception and anti-inflammatory cascade. 
In this study, we have evaluated whether prophylactic K gargle reduces POST after orotracheal intubation and compare with normal saline (NS).
| Materials and Methods|| |
After obtaining permission from the institutional ethical committee and written informed consent, 90 adult patients between 18 years and 60 years with American Society of Anesthesiologists I and II, scheduled for elective open cholecystectomy surgery under general anesthesia were randomly assigned into two groups of 45 patients each. Patients with a history of pre-operative sore throat and asthma, Mallampati grade > 2, known allergies to study drugs, recent non steroidal anti inflammatory drugs (NSAID) medication were not included in the study.
In the operation room, 30 ml of NS and 40 mg preservative free K in 30 ml of NS was kept ready for Group S and Group K respectively. Then the patients were asked to gargle with the preparation for 30 s after their arrival in the operation room.
Anesthesia was induced 5 min later. Standard monitoring was established including, electro cardio gram (ECG), non-invasive arterial pressure, and pulse oximetry. Anesthesia was induced with propofol 2 mg/kg. IV. Then tracheal intubation was facilitated by vecuronium 0.1 mg/kg. And the trachea was intubated with a soft-seal cuffed sterile polyvinyle chloride endotracheal tube with a standard cuff and an internal diameter of 7-8 mm for females and 7.5-8.5 mm for males. Anesthesia was maintained by using halothane, oxygen 33% in nitrous oxide, tramadol, and vecuronium 0.05 mg/kg (repeated as required). The tracheal tube was inflated until no air leakage can be heard. Those patients who require more than one attempt for passage of tube were excluded from the study. At the cessation of surgery, glycopyrolate 0.5 mg and neostigmine 2.5 mg shall be administered IV to reverse the neuromuscular block. And then oropharyngeal suction was carried out under direct vision to avoid trauma to the tissue before extubation. On arrival in the post-anesthesia care unit (0 h), and at 2 h, 4 h, and 24 h thereafter, the patients were questioned by a blinded investigator whether he/she had experienced sore throat or any other side-effects. POST was graded on a four-point scale (0-3): 0: No sore throat; 1: Mild sore throat (complains of sore throat only on asking); 2: Moderate sore throat (complains of sore throat on his/her own); and 3: Severe sore throat (change of voice or hoarseness, associated with throat pain).
The statistical analyses were performed using ANOVA test. The demographic profile of the patients in both the groups, type of surgery, patient parameters (age in years, weight in kg, height in cm, sex, duration of surgery in hours, duration of tracheal intubation) were evaluated using ANOVA test, Chi-square test, and paired t-test. The results were considered significant (S) statistically, if P value was less than 0.05.
| Results|| |
Age, height, weight, smoking habit, duration of surgery, and intubation were similar in both the groups [Table 1]. It was observed that the incidence and severity of POST was definitely reduced in the number of patients in K group when compared with the NS (S) group during the 1 st 2 hours of post-operative period though statistically not significant, as shown in [Table 2]. Hoarseness of voice was reported less frequently in the K group when compared with NS (S) group [Table 3], which on further analysis shows that, though, at 0 h, 2 h, and 4 h, the difference between the two groups were not S statistically, there is S difference in the incidence of hoarseness of voice between the two groups at 24 h (P < 0.05). There was no correlation between the incidence and severity of POST at different time intervals with gender, age, smoking habit, duration of surgery, and intubation for both the groups [Table 4]. No local or systemic side-effects were observed.
|Table 2: Severity of post-operative sore throat in normal saline and ketamine groups|
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|ntblTable 4: Spearman's co-efficient for correlation (r) for gender, age, duration of surgery and smoking habit with post-operative sore throat|
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| Discussion|| |
We found that the incidence and severity of POST were reduced after pre-operative gargling with K compared with saline gargling in patients planned for open cholecystectomy under general anesthesia with endotracheal intubation for up to 24 h.
In our study, the incidence of POST at 0 h, 2 h, 4 h, and 24 h was 24%, 27%, 22%, and 18% in NS group compared to 13%, 13%, 18%, and 18% in K group.
Our finding was consistent with Canbay et al.  who found the incidence of POST to be 74%, 74%, 56.5%, and 60.8% compared to 35%, 40%, 40%, and 30% at 0 h, 2 h, 4 h, and 24 h for NS and K group respectively. Their study was carried out on patients undergoing septorhinoplasty operation, during general anesthesia with endotracheal intubation. They had used pharyngeal packing which they thought might be the cause of sore throat. In our study, pharyngeal packing was not required in any of the cases.
Rudra et al.  also found that the incidence of POST at 4 h, 8 h, and 24 h to be 85%, 75%, and 60% compared to 40%, 35%, and 25% for NS and K group respectively.
Some contributing factors for sore throat after surgery have been reported, including, patient sex, age, use of succinylcholine, large tracheal tube, cuff design, and intra-cuff pressure. , In the present study, no correlation was observed between pain, age, gender, smoking habits, duration of surgery, and intubation. The cause of sore throat may be due to localized trauma, leading to throat aseptic inflammation of pharyngeal mucosa. It may also be associated with edema, congestion and pain.  Reduction of inflammation by K gargling may be the reason for decrease in POST in our study.
Biro et al.,  Christensen et al.  and Higgin et al.  found that the incidence of POST was Sly higher in females than males (17.7% vs. 9%). However, in our study, out of the total 90 cases, there were only 10 (11%) male and 80 (88.9%) female, the fact being that we chose only open cholecystectomy. Out of these 10 male patients, only one patient had mild sore throat NS and one patient had hoarseness of voice K.
In a recent animal study for asthma, Zhu et al. have indicated that nebulized K attenuated many of the central components of inflammatory changes. K has been shown to attenuate symptoms of endotoxemia in a LPS-induced rat model of sepsis, by reducing NF-kappa-B activity and TNF-alpha production  and diminishing the expression of iNOS.  Additionally, studies have shown that K plays a protective role against lung injury by means of its anti-inflammatory properties. 
In our study, we did not use humidity moisture exchangers in the gas delivery circuit, and the dry (unhumidified) gases have been implicated in the development of POST. 
Zhu et al. have also proposed a protective effect of K on allergen-induced airway inflammatory injury and high airway reactivity in asthma in an experimental model with rats. With respect to this potential protective effect, we propose that K gargle might be effective in reducing the incidence and severity of POST due to its anti-inflammatory effects. Studies into the nasal, oral, and rectal administration of K also suggest that local use of this drug is both effective and conceivable.  A study by Carlton and Coggeshall  has indicated that NMDA receptors are present in the central nervous system (CNS) and in the peripheral nerves. Besides, experimental studies with rats, it was pointed out that peripherally administered K (NMDA receptor antagonist) was capable of activating the l-arginine/Nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway and eliciting peripheral anti-nociception. 
In our study, we did tracheal suctioning under direct vision with the help of laryngoscope and utmost care was taken to minimize any trauma to the pharyngeal mucosa with the suction catheter. We also did not use any jelly or spray for lubrication of tracheal tube or local anesthesia for intubation. In previous study by Hung et al.  POST was reduced by spraying the endotracheal tube cuff with benzydamine hydrochloride, 10% lidocaine, and 2% lidocaine or NS.
In the present study, the pressure in tracheal cuff was not monitored during surgery. Increased pressure in the cuffs could be a contributing factor for the POST. Loeser et al.  suggested that the major cause of POST was due to tracheal mucosal damage secondary to cuff-trachea contact. They found that POST was highly correlated with cuff length and that the POST could be significantly decreased by using endotracheal tubes with narrow cuffs by reducing the area of cuff-trachea contact.
A drawback of our study was the absence of the measurements of plasma K levels and hence we cannot rule out the contribution of the systemic effect of K in our results. As a result, either systemic or topical anti-inflammatory or anti-hyperalgesic effect of K might contribute to this outcome. Comparing with the previous reports with topical K with higher doses, our doses were relatively low and we did not observe any CNS side-effects.
In conclusion, gargling with K decreases the incidence and severity of POST in-patients undergoing open cholecystectomy under general anesthesia.
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[Table 1], [Table 2], [Table 3], [Table 4]