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ORIGINAL ARTICLE
Year : 2018  |  Volume : 12  |  Issue : 3  |  Page : 625-629  

Inhalation of ketamine in different doses to decrease the severity of postoperative sore throat in surgeries under general anesthesia patients


Department of Anaesthesiology, Sardar Patel Medical College, Bikaner, Rajasthan, India

Date of Web Publication11-Sep-2018

Correspondence Address:
Dr. Mohd. Yunus Khilji
6C21, JNV Colony, Bikaner - 334 003, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/aer.AER_65_18

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   Abstract 

Context: Postoperative sore throat (POST) occurs in 21%–65% of patients. Nebulization of ketamine reduces POST. Aims: The aim of this study is to see the effectiveness of nebulized ketamine in different doses to reduce POST and observe adverse effects, if any. Settings and Design: This was a prospective, randomized, and double-blind controlled trial. One hundred and fifty patients of the American Society of Anesthesiologists physical status Classes I and II, in the age group of 18–60 years, of either sex, undergoing surgery under general anesthesia were randomized into three groups. Subjects and Methods: Patients had nebulized with 5 ml solution (Group K1 – 1 ml of ketamine [50 mg/ml] +4 ml normal saline, Group K2 – 0.5 ml of ketamine [50 mg/ml] +4.5 normal saline, and Group S – 5 ml normal saline). Preoperative, intraoperative, and postoperative hemodynamic monitoring was done. The POST monitoring was done at 2, 4, 8, 12, and 24 h postoperatively. POST was graded on a four-point scale (0–3). Statistical Analysis Used: Chi-square test using MSTAT software for POST and ANOVA test using INDOSTAT software for hemodynamics were used in this study. Results: The overall incidence of POST in the present study was 29.33% (44/150). In Group S, the incidence of POST was observed to be 46% (23/50). In Group K1, the incidence was 20% (10/50), and in Group K2, it was 22% (11/50) (P ≤ 0.05), and intraoperative vital signs were more stable at all time intervals. Conclusions: We concluded that both doses (25 and 50 mg) of nebulized ketamine were almost equally effective in preventing POST, with no adverse effects.

Keywords: Ketamine nebulization, pharyngitis, postoperative sore throat


How to cite this article:
Charan SD, Khilji MY, Jain R, Devra V, Saxena M. Inhalation of ketamine in different doses to decrease the severity of postoperative sore throat in surgeries under general anesthesia patients. Anesth Essays Res 2018;12:625-9

How to cite this URL:
Charan SD, Khilji MY, Jain R, Devra V, Saxena M. Inhalation of ketamine in different doses to decrease the severity of postoperative sore throat in surgeries under general anesthesia patients. Anesth Essays Res [serial online] 2018 [cited 2018 Sep 21];12:625-9. Available from: http://www.aeronline.org/text.asp?2018/12/3/625/240872


   Introduction Top


Postoperative sore throat (POST) occurs in 21%–65% of patients receiving general anesthesia (GA) with tracheal intubation.[1] Many studies have been carried out to assess the beneficial effects of gargling with ketamine to prevention of POST,[2],[3] but ketamine nebulization has few advantages over gargling. In previous studies, ketamine was used as 50 mg single dose for nebulization and reveals that it decreases the severity and incidence of POST.[4] Lower doses will have lesser systemic absorption and effects and more economical, so we planned to study the effect of nebulized ketamine in two different doses (25 and 50 mg single dose) to prevent or reduce the severity and incidence of POST and observe adverse effects, if any.


   Subjects and Methods Top


The present study was conducted after receiving approval by the Institute Ethics Committee of our hospital and written informed consent from 150 patients belonging to the American Society of Anesthesiologists (ASA) physical status Classes I–II, in the age group of 18 and 60 years, of either sex, undergoing surgery in supine position under GA lasting for up to 1 h. The study was comparative prospective randomized, double-blinded, control trial.

Calculation of sample size

It was based on the assumption that the incidence [1] of POST is 65%, and to show a 50% reduction in the incidence at α =0.05, confidence interval of 95%, and a power 90%, we required a sample size of 46 patients per group. On adding 10% patients for possible loss to follow-up, the sample size required was 50 patients per group.

Exclusion criteria

The exclusion criteria of this study were as follows: refusal by patient or relative, patients with known allergy to the drugs used in the study, patients with significant cardiac, respiratory, hepatic, or renal dysfunction, patients with neuromuscular disorders, an anticipated difficult airway, any history of psychosis, patients undergoing head, neck, or oral surgery, Mallampati grade >2, pregnant and lactating woman, recent nonsteroidal anti-inflammatory drug medications.

All the patients were subjected to preoperative evaluation 1 day before surgery including detailed history taking, physical examination, and investigations including preoperative urine analysis, blood urea, serum creatinine, complete blood count and blood sugar, liver function tests, electrocardiography (ECG), and X-ray chest. All patients were advised for fasting at least 8 h before surgery. The procedure of GA and our study was explained to each patient, and a written informed consent was taken from the patient and his relatives in the presence of independent witness. Patients were enrolled a day before surgery by investigators in the surgical ward. Patients were randomized into three groups with the help of computer-generated random number tables in opaque sealed envelopes prepared by an anesthesiologist not part of the study. The envelopes were opened by the staff nurse, and nebulization solution was prepared according to group allocation. Group saline (S) patients received a saline nebulization 5.0 ml and Group ketamine (K1) patients received ketamine 50 mg (1.0 ml) (with 4.0 ml of the saline) nebulization, and Group K2 patients received ketamine 25 mg (0.5 ml) (with 4.5 ml of the saline) nebulization. The preparations of 5.0 ml each were administered by the staff nurse. The patients received the study drug through nebulization mask connected to wall-mounted oxygen-driven source (8 L, 50 psi) for 15 min preoperatively. The staff nurse later did not participate in the subsequent assessment of these patients. Patients were blinded as both the preparations were tasteless because we used preservative free ketamine. After nebulization patients were shifted to the operating room and intraoperative monitoring gadgets including continuous ECG, noninvasive blood pressure (BP), pulse oximetry (SpO2), and end-tidal carbon dioxide were applied. GA was induced 10 min after completion of nebulization of the patients. An intravenous (i.v.) cannula was inserted into the dorsum of patients' hand, and crystalloid infusion was started.

Preanesthetic medication included injection glycopyrrolate 0.2 mg + injection fentanyl 100 μg intravenously. GA was induced with i.v. propofol 2 mg/kg. Tracheal intubation was facilitated with injection succinylcholine 2 mg/kg intravenously, and trachea was intubated with a Soft Seal cuffed sterile polyvinyl chloride tracheal tube with an internal diameter of 7–7.5 mm for women and 8–8.5 mm for men. Tracheal intubation was performed by an experienced anesthesiologist after ensuring adequate neuromuscular blockade. The tracheal tube cuff was inflated until no air leakage could be heard with a stethoscope at peak airway pressure of 20 cm H2O. GA was maintained with 50% nitrous oxide and 50% oxygen supplemented with halothane. Muscle relaxation was maintained by injection vecuronium 4 mg i.v. stat and 1 mg SOS. Injection ondansetron 4 mg was administered 30 min before the end of surgery and then after 8 h in the postoperative period. At the completion of surgery, with the patient adequately anesthetized, the oropharynx was gently suctioned, and the halothane was turned off. Inspiratory oxygen concentration was increased to 100%. The neuromuscular block was reversed with neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg intravenously after exhibited the return of spontaneous respiration. If a patient excessively bucks, i.v. lignocaine 1.5 mg/kg was administered as a rescue medicine. Trachea was extubated when the patient was conscious with full motor power.

Hemodynamic (mean BP, mean pulse rate, and SpO2) recording was done at prenebulization (baseline parameters), preinduction, after induction, 15 min, 30 min, 45 min, and 60 min of GA. Sore throat assessment was done at immediate recovery (0 h), 2 h, 4 h, 8 h, 12 h, and 24 h postoperatively. POST was graded on a four-point scale (0–3), 0 = no sore throat; 1 = mild sore throat (complaints of sore throat only on asking); 2 = moderate sore throat (complaints of sore throat by his/her own); and 3 = severe sore throat (change of voice or hoarseness, associated with throat pain). Other side effects, if any, were noted. All the observations were noted by an anesthesia resident who was unaware of medication used. Intravenous paracetamol 1 g 6 hourly and tramadol 100 mg SOS were used for postoperative pain relief. The primary aim of the study was to measure the efficacy of different doses of nebulized ketamine in prevention of POST. The secondary aim was to find adverse effects, if any.


   Results Top


The data were analyzed using INDOSTAT software (Hyderabad India). ANOVA test was applied for all quantitative parameters and critical difference (CD) was calculated. The mean values were compared for their statistical difference using CD values. Chi-square test was applied for all qualitative parameters and “P” values calculated using MSTAT software (Michigan State University East Lansing, MI 48824, USA).

All the groups were comparable in distribution of patients regarding age, sex, weight, ASA class, time of intubation, duration of anesthesia, and vitals such as mean BP and pulse.

The overall incidence of POST in the present study was 29.33% (44/150). In Group S, the incidence of POST was observed to be 46% (23/50). In Group K1, the incidence was 20% (10/50), and in Group K2, it was 22% (11/50) [Figure 1].
Figure 1: Incidence of postoperative sore throat at various time intervals

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At postoperatively 2 h, incidence of POST occurred in 13 patients (7 patients had score 1 of POST and 6 patients had score 2 of POST) in Group S while 3 patients in Group K1 (POST score 1) and 3 patients in Group K2 (POST score 1), which was statistically significant (P = 0.002) [Table 1].
Table 1: Incidence of postoperative sore throat according to severity

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At postoperatively 4 h, incidence of POST occurred in 13 patients (8 patients had score 1 of POST and 5 patients had score 2 of POST) in Group S while 3 patients in Group K1 (POST score 1) and 4 patients in Group K2 (3 patients had score 1 of POST and 1 patient had score 2 of POST), which was statistically significant (P = 0.005) [Table 1].

The incidence also reduced at time intervals 8 h, 12 h, and 24 h in both Groups K1 and K2 as compared to Group S (P< 0.05). Not a single case was reported of POST score 3 [Table 1].

Overall, we observed that the incidence of POST was significantly reduced in both Groups K1 and K2 when compared to Group S.

Intergroup comparability of intraoperative vitals showed that vitals were stable in all three groups but were more stable in Group K1 compared to Groups K2 and S [Figure 2] and [Figure 3].
Figure 2: Intraoperative mean pulse at various time intervals

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Figure 3: Mean arterial pressure at different time intervals in all three groups

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   Discussion Top


POST is due to mucosal injury in the trachea and other factors such as oropharyngeal suctioning, intracuff pressure, use of throat pack, and size of the endotracheal tube. Duration of surgery, difficult in intubation, use of stylet, and prone position also contribute as risk factors for POST.[5] To overcome this problem, many studies had been conducted using various nonpharmacological and pharmacological methods to attenuating POST but with variable success.

Various nonpharmacological and pharmacological methods have been used for attenuating POST. Among the nonpharmacological methods, tube size also affects incidence of POST.[6] Other nonpharmacological methods that have been reported to decrease the incidence of POST include lubricating the endotracheal tube with water-soluble jelly, careful airway instrumentation, intubation after full relaxation, gentle oropharyngeal suctioning, minimizing intracuff pressure, and extubation when the tracheal tube cuff is fully deflated.[7]

The pharmacological methods to reduce POST include the use of various steroid preparations through different routes such as widespread application of betamethasone gel over the tracheal tube,[8] and the prophylactic use of dexamethasone 0.2 mg/kg intravenously significantly decreases the incidence and severity of sore throat.[9]

Among the pharmacological methods, nonsteroid drugs are also used in different preparations through different routes, such as gargling with azulene sulfonate,[10] ketamine,[11] licorice, and inhalation with magnesium sulfate.[12] All these methods reduce severity of POST.

Ketamine is shown to be a promising agent to reduce POST. It is a phencyclidine derivative. It is a noncompetitive antagonist of N-methyl-D-aspartic acid (NMDA) receptor. The primary site of action is in the central nervous system (CNS) and parts of the limbic system. It is known that NMDA receptors have a role in inflammation and nociception. NMDA receptors are found not only in CNS but also in the peripheral nerves. Experimental studies show that peripherally administered NMDA receptor antagonists are involved with antinociception and anti-inflammatory cascade, thus preventing POST.[13]

Ketamine has been used as a gargle for reducing the incidence and severity of POST due to its antinociceptive and anti-inflammatory effects. It also has been used in the form of nebulization to prevent POST. Nebulization is considered better than gargle as it is easy way to administer the drug, smaller volume of drug is required and better patient cooperation is likely. Also there is no risk of aspiration and the drug reaching lower airways.

The present study was done to evaluate the role of ketamine nebulization on incidence and severity of POST in different doses (50 and 25 mg) because there is no study indicating systemic absorption and hemodynamic changes caused by nebulized ketamine and efficacy of low-dose ketamine in prevention of POST.

We observed that the overall incidence of POST in the present study was 29.33% (44/150). In Group S, the incidence of POST was observed to be 46% (23/50). In Group K1, the incidence was 20% (10/50), and in Group K2, it was 22% (11/50).

POST is found to be at peak at 2–4 h postoperatively. By this time, the patients were completely conscious and more cooperative to participate in the study. The incidence of POST was significantly higher in Group S when compared to Groups K1 and K2 at all time intervals but more at 2 h and 4 h postoperatively. Hence, overall, we observed that both severity and incidence were reduced in both Groups K1 and K2.

Ahuja et al.,[4] Aditya et al.,[14] Mehrotra et al.,[15] Kumar and Kumar,[16] and Jain and Kumar [17] studies showed reduced incidence and severity of POST with ketamine use by any route and the findings were consistent with our results.

We observed that the mean BP and mean pulse were significantly stable on laryngoscopy in both Groups K1 and K2 when compared to Group S. We also observed that intraoperative mean vitals were stable in both Groups K1 and K2 when compared to Group S but more stable in Group K1.

There were few limitations with our study. We did not record incidence of coughing or bucking on extubation. Another drawback in our study was lack of measurement of plasma drug levels. We cannot rule out the contribution of the systemic effect of the drugs in our results. The safety and dosage of the drugs used for inhalation need further investigation even though we did not find any adverse effects after their use as doses which were used in the study were quite less compare to those causing adverse effects.

Bigger sample size in the similar study could add strength to the findings.


   Conclusions Top


On the basis of our study, we concluded that both doses (25 and 50 mg) of nebulized ketamine were almost equally effective in preventing incidence and reducing severity of POST with no any adverse effects.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
McHardy FE, Chung F. Postoperative sore throat: Cause, prevention and treatment. Anaesthesia 1999;54:444-53.  Back to cited text no. 1
    
2.
Safavi M, Honarmand A, Fariborzifar A, Attari M. Intravenous dexamethasone versus ketamine gargle versus intravenous dexamethasone combined with ketamine gargle for evaluation of post-operative sore throat and hoarseness: A randomized, placebo-controlled, double blind clinical trial. Adv Biomed Res 2014;3:212.  Back to cited text no. 2
    
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Mayhood J, Cress K. Effectiveness of ketamine gargle in reducing postoperative sore throat in patients undergoing airway instrumentation: A systematic review. JBI Database System Rev Implement Rep 2015;13:244-78.  Back to cited text no. 3
    
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Ahuja V, Mitra S, Sarna R. Nebulized ketamine decreases incidence and severity of post-operative sore throat. Indian J Anaesth 2015;59:37-42.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Hari Kumar S, Saravanan D, Ranganathan. Post-operative sore throat-incidence and contributory factors. J Pharm Biomed Sci 2013;26:286-92.  Back to cited text no. 5
    
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Jaensson M, Olowsson LL, Nilsson U. Endotracheal tube size and sore throat following surgery: A randomized-controlled study. Acta Anaesthesiol Scand 2010;54:147-53.  Back to cited text no. 6
    
7.
Al-Qahtani AS, Messahel FM. Quality improvement in anesthetic practice-incidence of sore throat after using small tracheal tube and various others methods. Middle East J Anesthesiol 2005;18:179-83.  Back to cited text no. 7
    
8.
Tabari M, Soltani G, Zirak N, Alipour M, Khazaeni K. Comparison of effectiveness of betamethasone gel applied to the tracheal tube and IV dexamethasone on postoperative sore throat: A randomized controlled trial. Iran J Otorhinolaryngol 2013;25:215-20.  Back to cited text no. 8
    
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Park SH, Han SH, Do SH, Kim JW, Rhee KY, Kim JH, et al. Prophylactic dexamethasone decreases the incidence of sore throat and hoarseness after tracheal extubation with a double-lumen endobronchial tube. Anesth Analg 2008;107:1814-8.  Back to cited text no. 9
    
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Ogata J, Minami K, Horishita T, Shiraishi M, Okamoto T, Terada T, et al. Gargling with sodium azulene sulfonate reduces the postoperative sore throat after intubation of the trachea. Anesth Analg 2005;101:290-3.  Back to cited text no. 10
    
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Canbay O, Celebi N, Sahin A, Celiker V, Ozgen S, Aypar U, et al. Ketamine gargle for attenuating postoperative sore throat. Br J Anaesth 2008;100:490-3.  Back to cited text no. 11
    
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Yadav M, Chalumuru N, Gopinath R. Effect of magnesium sulfate nebulization on the incidence of postoperative sore throat. J Anaesthesiol Clin Pharmacol 2016;32:168-71.  Back to cited text no. 12
[PUBMED]  [Full text]  
13.
Miller RD, Eriksson LI, Fluisher LA, Wiener-Kronish JP, Young L, editors. In Millers Anesthesia. The International 8th edition. Philadelphia PA: Elsevier Publication; 2015. p. 845-50.  Back to cited text no. 13
    
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Aditya AK, Das B, Mishra DK. Assessment of nebulized ketamine for reductions of incidence and severity of post-operative sore throat. Int J Med Health Res 2017;3:130-2.  Back to cited text no. 14
    
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Mehrotra S, Kumar N, Khurana G, Bist SS. Post operative sore throat incidence after nebulization with ketamine, lidocaine and budesonide. Int J Med Sci Clin Inventions 2017;4:2994-8.  Back to cited text no. 15
    
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Kumar R. Relative assessment of ketamine nebulisation and ketamine gargle in attenuating post-operative sore throat. JMSCR 2017;5:25277-9. Available from: https://dx.doi.org/10.18535/jmscr/v5i7.160. [Last accessed on 2018 Jun 12].  Back to cited text no. 16
    
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Jain S, Kumar SB. A comparative study of preoperative ketamine and MgSO4 nebulisation for incidence of post operative sore throat after endotracheal intubation. IJCMR 2017;4:1356-9.  Back to cited text no. 17
    


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