post - operative sore throat ( post ) occurs in 21 - 65% of patients receiving general anaesthesia ( ga ) with tracheal intubation . though considered as a minor complication , but it may cause significant post - operative morbidity and patient dissatisfaction . various non - pharmacological and pharmacological trials have been used for attenuating post with no proven single modality . the pharmacological methods used to reduce post include use of beclomethasone gel , gargling with azulene sulphonate , ketamine and licorice . ketamine is an n - methyl - d - aspartate ( nmda ) receptor antagonist and has been used as a gargle for reducing the incidence and severity of post due to its anti - nociceptive and anti - inflammatory effects . ketamine nebulization has a few advantages over gargle : it spares the patient from the bitter taste of ketamine , much smaller volume is required as opposed to larger volumes required for gargle with risk of aspiration if accidentally swallowed ; hence better patient cooperation is likely . so far no study has been conducted to evaluate efficacy of nebulized ketamine for prevention of post . the main objective of this study was to evaluate the role of nebulized ketamine for attenuation of post in patients undergoing surgeries under ga with tracheal intubation . the present study was conducted after receiving approval by the institute ethics committee of our hospital and written informed consent from 100 patients belonging to asa physical status i - ii , in the age group of 20 and 60 years , of either sex , undergoing surgery in supine position under ga lasting for up to 1 h. patients with a history of pre - operative sore throat , oral surgeries , asthma , chronic obstructive pulmonary disease , head and neck surgeries , mallampati grade > 2 , known allergies to study drug , recent non - steroidal anti - inflammatory drug medication , and those who required more than one attempt at intubation were excluded from the study . a pilot study carried out in ten patients revealed that nebulised ketamine ( aneket 50 mg / ml ampoule 2 ml , neon laboratories ltd . , mumbai , india , active ingredient ketamine , preservative free ) was tasteless . patients were randomised into two groups with the help of computer - generated random number tables in opaque sealed envelopes prepared by an anaesthesiologist not part of the study . the envelopes were opened by the staff nurse , and nebulisation solution was prepared according to group allocation . group saline ( s ) received a saline nebulisation 5.0 ml and group ketamine ( k ) received ketamine 50 mg ( 1.0 ml ) ( with 4.0 ml of the saline ) nebulisation . the preparations of 5.0 ml each were administered by the staff nurse . the patients received the study drug via nebulisation mask connected to wall - mounted oxygen driven source ( 8 l , 50 psi ) for 15 min . the intra - operative monitoring included continuous electrocardiography , non - invasive blood pressure , pulse oximetry ( spo2 ) , and end - tidal carbon dioxide . ga was induced with intravenous ( iv ) morphine100 g / kg and propofol 2 mg / kg . tracheal intubation was facilitated with iv vecuronium bromide 0.1 mg / kg , iv lignocaine 1 mg / kg and the trachea was intubated with a soft seal cuffed sterile polyvinyl chloride tracheal tube ( portex , smith medical , hansraj nayyar medical , mumbai , maharashtra , india ) 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 anaesthesiologist after ensuring maximum neuromuscular blocking effect as assessed by train of four ( tof ) count < 2 . iv ondansetron 4 mg was administered 30 min prior to end of surgery and then 8 h in the post - operative period . the tracheal tube cuff was inflated until no air leakage could be heard with a stethoscope at peak airway pressure of 20 cm h2o . at the completion of surgery , with the patient adequately anesthetised , the oropharynx was gently suctioned , and the isoflurane was then turned off . the neuromuscular block was reversed with iv neostigmine 50 g / kg and glycopyrrolate 10 g / kg while awaiting the return of spontaneous ventilation . during extubation , if a patient had excessive coughing , iv lignocaine 1.5 mg / kg was administered as a rescue measure . sore throat assessment , and haemodynamic recording were done at pre - nebulisation ( baseline parameters before nebulisation of patient ) , pre - induction ( parameters after nebulization and just before induction of ga ) , immediate recovery ( 0 h ) , 2 , 4 , 6 , 8 , 12 and 24 h post - operatively . 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 ) . iv paracetamol 1 gm 6th hrly and diclofenac 100 mg suppository twice daily were used for post - operative pain relief . the primary outcome of the study was to measure the incidence of post at 4 h post - operatively in adult patients undergoing surgery of duration of up to 1 h under ga . the secondary outcomes included the incidence and severity of post at immediate recovery , and post - operatively , evaluation of side - effects including nausea , vomiting , cough and dry mouth in both the groups . calculation of sample size was based on the assumption that the incidence of post is 65% and to show a 50% reduction in the incidence at  = 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 collected data were analysed using statistical package for social sciences ( spss inc . , chicago , il , usa , version 15.0 for windows ) . kolmogorov - smirnov test was used to see normality of age , weight and haemodynamics and differences in the age and weight were done using an independent t - test . haemodynamic variables between the groups were compared with t - test and within the group over time were compared using analysis of variance . differences in the incidence of post among the groups were compared with fisher 's exact test or chi - square test whichever was applicable . we screened 108 patients for this prospective , randomized and placebo - controlled trial . out of these eight patients were excluded as they did not fulfil the inclusion criteria ; three patients had pre - operative sore throat , two patients were scheduled for oral surgery , one patient had asthma and two patients had mallampati grade > 2 . hence , a total of 100 patients were enrolled and randomized into two groups of 50 patients each . all the patients completed the study , and the results were analysed [ figure 1 ] . there were no significant differences between the two groups regarding age , body weight , gender distribution , asa grade or duration of surgery [ table 1 ] . surgeries in both the groups included abdominal surgeries , fibroadenoma breast , incision hernia , and restoration of bowel continuity . group s - saline group ; group k - ketamine group the overall incidence of post in the present study was 33% : 23 ( 46% ) patients in group s and 10 ( 20% ) patients in group k had post at some point of the study ( fisher 's exact p = 0.01 ) . incidence of post was significantly higher in group s when compared to group k at 2 h and 4 h post - operatively [ figure 2 ] . incidence of post - operative sore throat at 0 , 2 , 4 , 6 , 8 , 12 and 24 h post - operatively in both the groups . * group s  saline group ; group k  ketamine group the primary outcome was to observe the incidence of post at 4 h , post - operatively . post occurred in 13 patients in group s versus 4 patients in group k ( p = 0.03 ) , which was significant . 13 patients in group s versus 3 patients in group k ( p = 0.01 ) experienced post at 2 h post - operatively [ figure 2 ] . post was significantly attenuated at 2 h in group k compared to group s ; 6 patients in group s and none in group k experienced post score 2 ( p = 0.02 ) [ table 2 ] . during extubation of the trachea , none of the patients required rescue iv lignocaine . severity of post in patients patients in both the groups remained haemodynamically stable with no nausea , vomiting , stridor , laryngospasm , cough , dry mouth , hoarseness , dissociative symptoms or any other adverse effect during the entire study period . the present study is the first to evaluate the role of ketamine nebulisation on incidence and severity of post . we observed reduction in the incidence at 2 h and 4 h , and attenuation of severity of post at 2 h , in patients receiving ketamine nebulisation as compared to control group , following ga with tracheal intubation lasting for up to 1 h. the incidence of post was 21 - 65% in earlier studies . out of this post occurred only in 20% of the patients in the ketamine group that was lower as compared to other studies . in the present study , the incidence of post at 2 and 4 h was significantly reduced , and the attenuation of severity of post occurred in the ketamine group at 2 h. the mechanism of effect was possibly the topical effect of ketamine nebulization that attenuated the local inflammation and also due to peripheral analgesic effect of ketamine . literature supports the topical effect of ketamine via its nmda - antagonistic action and anti - inflammatory effect based on animal model data . ketamine is an nmda receptor antagonist with the primary site of action in the central nervous system , and parts of the limbic system while its use via nasal route , gargle , and rectal route suggests its peripheral effect . experimental animal studies have shown a protective effect on airway inflammatory injury with ketamine nebulisation . in an earlier study , pre - operative nebulisation with 3.0 ml ( 225 mg ) of isotonic magnesium sulphate , also a nmda receptor antagonist showed a decrease in incidence and severity of post at 0 , 2 , 4 and 24 h post - operatively . the primary outcome of the study was the incidence of post at 4 h as by this time the patents are generally awake , alert , and more cooperative to participate in the study . attenuation of post at 2 h and not at 24 h post - operatively after pre - operative ketamine gargles was observed in women undergoing gynaecological surgeries . the authors measured serum ketamine levels intra - operatively and suggested that with such low levels of serum ketamine , the systemic absorption of ketamine was unlikely to have role in the attenuation of post and rather suggested a topical effect of ketamine . ketamine gargle has been found to be effective in reducing the incidence and severity of post due to its anti - inflammatory effects . however , there are a few demerits of gargle ketamine over nebulization due to its bitter taste , large volume required for gargle with risk of aspiration if accidentally swallowed and patient cooperation . our rationale of using the nebulized form of ketamine rather than its other forms ( oral , iv , gargle ) was primarily oriented for safety and ease of administration to the patient in the immediate pre - operative period . the topical effect of ketamine nebulisation probably attenuated post at 2 and 4 h post - operatively in the present study . the late onset of moderate pain in the control group reflects a more gradually developing local inflammation . other pharmacological agents used earlier , include aspirin gargles , benzydamine hydrochloride ( bh ) gargles , transdermal ketoprofen , lignocaine 10% spray , iv dexamethasone , beclomethasone gel on tracheal tube and magnesium lozenges . all have been shown to reduce the incidence and severity of post up to 24 h post - operatively . betamethasone gel applied over the endotracheal tube ( ett ) and ketamine gargle were found to be comparable in attenuating post during the first 24 post - operative hours after elective surgical procedures . however , the incidence of post - operative cough and hoarseness of voice was attenuated better with betamethasone application . lignocaine spray decreased incidence of cough at tracheal extubation in surgeries of < 2 h. medicated lozenges of licorice had efficacy of decreasing post in smokers for surgery under ga of more than 1 h. recently , siccoral and strefen have been found to be effective in relieving post in the early hours following extubation . a meta - analysis found that the topical application of bh reduced the incidence of post in patients following ga . however , dipping of whole ett cuff with benzydamine hydrochloride ( bh ) prior to anaesthesia induction had no influence on the incidence and severity of post during 24 h post - operatively . iv dexamethasone significantly reduced the risk and severity of post at 24 h in a meta - analysis . use of budesonide inhalation suspension 200 mcg 10 min prior to intubation and 6 and 24 h after extubation in thyroid surgery under ga exhibited significantly less severe sore throat and hoarseness at 1 h and 24 h following extubation . gabapentin ( 100 mg ) when administered orally , 1 h before anaesthesia had a lower incidence of post than the placebo group ( 47% vs. 78% , p = 0.038 ) . endotracheal intubation done with glide scope video laryngoscope was found to attenuate post in patients as compared to macintosh blade with normal airway patients , at 6 and 24 h after surgery . during the use of wall - mounted oxygen driven nebulization the aerosol produced is heterodisperse in size and is filtered within the nebulizer by baffles to remove the largest droplets . the pneumatic nebulisation method produces larger particles ( 10 - 25 m ) which mostly deposit in the mouth and throat and for those of 5 - 10 m diameter deposit in a transition from mouth to airway . deposition of aerosol in the mouth and upper airway probably reduced incidence and severity of post due to topical analgesia , anti - inflammatory effect and nmda receptor antagonist effect of nebulized ketamine . we used well - defined inclusion and exclusion criteria and experienced anaesthesiologists performed tracheal intubation . the tracheal intubation was performed at tof < 2 and tracheal tube cuff inflation was maintained guided by peri - cuff leak at peak airway pressure of 20 cm h2o . no formal sedation scale was used and we were also not able to measure plasma ketamine levels during the study period . we did not keep a record of the number of episodes of bucking at the time of extubation . further , it would be interesting to compare the efficacy between ketamine nebulization and ketamine gargle the use of pre - operative ketamine nebulisation reduced the incidence and severity of post during early post - operative period in patients receiving ga with tracheal intubation . this technique adds to the armamentarium of the anaesthetist in management of the  little big problem of post .
background and aims : post - operative sore throat ( post ) occurs in 21 - 65% of patients . 
 ketamine used earlier as gargle for reducing post has limitations . 
 the aim of this study was to see if nebulised ketamine reduces post.methods:we conducted a prospective , randomised , placebo - control , and double - blind controlled trial . 
 after written informed consent , 100 patients belonging to american society of anaesthesiologists physical status i - ii in the age group 20 - 60 years , of either sex undergoing surgery under general anaesthesia ( ga ) were enrolled . 
 patients were randomised into two groups ; group saline ( s ) received saline nebulisation 5.0 ml and group ketamine ( k ) received ketamine 50 mg ( 1.0 ml ) with 4.0 ml of saline nebulisation for 15 min . 
 ga was induced 10 min after completion of nebulisation in the patients . 
 the post and haemodynamic monitoring were done pre - nebulization , pre - induction , on reaching post - anaesthesia care unit , and at 2 , 4 , 6 , 8 , 12 and 24 h post - operatively . 
 post was graded on a four - point scale ( 0 - 3).results : the overall incidence of post was 33% ; 23 patients ( 46% ) in saline and 10 patients ( 20% ) in ketamine group experienced post ( fisher 's exact p = 0.01 ) . 
 the use of ketamine nebulization attenuated post at 2 h and 4 h post - operatively ( p < 0.05 ) . 
 the primary outcome was incidence of post at 4 h ; 13 patients in group s versus 4 patients in group k ( p = 0.03 ) experienced post at 4 h. the moderate sore throat occurred in 6 patients in group s and none in group k at 2 h , post - operatively ( p = 0.02).conclusion : ketamine nebulization significantly attenuated the incidence and severity of post , especially in the early post - operative period , with no adverse effects .