The Effect of Honey on Post-Tonsillectomy Pain Relief: A Randomized Clinical Trial

www.bjorl.org

Brazilian Journal of

OTORHINOLARYNGOLOGY

ORIGINAL ARTICLE

The effect of honey on post-tonsillectomy pain relief:

a randomized clinical trial

Azmeilia Syafitri Lubis

^a,∗

, H.R. Yusa Herwanto

^a

, Andrina Y.M. Rambe

^a

, Delfitri Munir

^a

, Harry A. Asroel

^b

, Taufik Ashar

^b

, Aznan Lelo

^c

aUniversitasSumateraUtara,FacultyofMedicine,DepartmentofOtorhinolaryngology,Medan,Indonesia

bUniversitasSumateraUtara,FacultyofPublicHealth,DepartmentofEnvironmentalHealth,Medan,Indonesia

cUniversitasSumateraUtara,FacultyofMedicine,DepartmentofPharmacology,Medan,Indonesia

Received4June2021;accepted23August2021 Availableonline18October2021

HIGHLIGHTS

• Honeyhaseffectivenessacceleratesandfacilitateswoundhealing.

• Garglingwithhoneyledtoreducedpainfollowingtonsillectomy.

• Honeywasfoundtolowerprostaglandinlevelsandelevatenitricoxide.

• Honeycanbeusedasanadjunctiveregimenaftersurgeryforbetterpaincontrol.

• Honeyiseasytouse,safetoconsumeorallyandavailableatlowcostlocally.

KEYWORDS Tonsillectomy;

Pain;

Honey;

Painrelief;

Complementary therapy

Abstract

Objective: Thestudyaimedtoevaluatetheeffectsofhoneyontheincidenceofpost-operative paininpatientsundergoingtonsillectomy.

Methods:Thisstudyisadouble-blindandrandomizedcontrolledtrialdesign.Twenty-fouradult malepatientsunderwenttonsillectomysurgeryandwererandomizedassignedintothreegroups consist ofhoneygroup,placebogroup,andcontrolgroup.Allsubjectswere givenstandard analgesiaandantibiotics,alsohoneyforthehoneygroupandplacebofortheplacebogroup, andonlystandardpost-operativeregimens forthecontrolgroup.Thisstudyusedsilk-cotton treeorkapoktreehoney(Ceibapentandra).Honeywasusedbygarglingeverysixhoursforten days.Likewise,thesamemethodwasappliedintheplacebogroup.Painscalewasassessedfor tendaysusingtheVisualAnalogueScalequestionnaire,andthefrequencyofanalgesicdrugs wasrecordedondays1,2,4,7,and10.

Result: Honeygroupshowedsignificantlyhigherpainreductionwhencomparedtoplaceboand controlgroups,withasignificantreductioninthepainscaleonday1,2,4,7and10(p=0.034;

p=0.003;p<0.001;p=0.001;p=0.001)gradually;Significantdifferenceswerealsoobserved inanalgesicuse,especiallyonday2,4and7(p=0.028;p=0.001;p=0.003).

∗Correspondingauthor.

E-mail:azmeilialubis@gmail.com(A.S.Lubis).

PeerReviewundertheresponsibilityofAssociac¸ãoBrasileiradeOtorrinolaringologiaeCirurgiaCérvico-Facial.

https://doi.org/10.1016/j.bjorl.2021.08.007

1808-8694/©2021Associac¸˜aoBrasileiradeOtorrinolaringologiaeCirurgiaC´ervico-Facial.PublishedbyElsevierEditoraLtda.Thisisanopen accessarticleundertheCCBYlicense(http://creativecommons.org/licenses/by/4.0/).

Conclusions:Administration ofKapok tree honey (C. pentandra) after tonsillectomy might reducepost-operativepainandreducetheneedforanalgesia.Therefore,honeycanbeconsid- eredacomplementarymedicineandcanbeadministeredroutinelyasadjunctivetherapyfor post-operativepatients.

© 2021 Associac¸˜ao Brasileira de Otorrinolaringologia e Cirurgia C´ervico-Facial. Published by Elsevier Editora Ltda. This is an open access article under the CC BY license (http://

creativecommons.org/licenses/by/4.0/).

Introduction

Tonsillectomy and adenotonsillectomy are two common surgeriesintheENT(ear,nose,andthroat)·Generally,ton- sillectomy is a safe procedure.^1,2 However, complications suchaspost-tonsillectomypain,difficultyinswallowing,dry throat, infection, bleeding, airway obstruction, nasopha- ryngealobstruction, pulmonaryedema,fever,paintojaw, otalgia, foreign body aspiration, poor healing, and vello- pharyngeal insufficiency mayoccur.^3---5 Post-operative pain isthemajorcomplicationduringswallowingduetostimu- lationoftonsillarnerveendings,pharyngealmusclespasm, andpost-ingestioninflammation.⁶ Severepainmayreduce oral nutritional intake, leading to dehydration, impaired or delayed recovery after surgery.⁷ Based on some stud- ies,antibioticsonlyarenoteffectiveenoughtotreatpain, eventheadditionofanalgesicsandsteroidsmaynotreduce pain rapidly and significantly. Another common method of controlling pain is the administration of opioids and Non-SteroidalAnti-InflammatoryDrugs(NSAIDs),whichhave various adverse effects.⁸ Therefore, post-operative pain controlrequiresamethodwithminimumcomplicationsand maximumefficiency.⁹

One of the non-drugmethods toreduce pain is honey, with variousmethods that have been reported in several studies.Honey hasbeenusedsinceancienttimestotreat severalailments.Hippocratesusedhoneysince400BCfor healing wounds, even the ancient Egyptians used honey totreat cornealand conjunctival inflammation and burns since5000 years ago.¹⁰ Honey hasbeen shown topossess antibacterial and anti-inflammatory properties.¹¹ Antioxi- dant, anti-inflammatory, and antibacterial properties, as well as accelerated wound recovery and pain relief, are the benefits reported for honey as a natural therapeutic method.^11,12Inmodernmedicine,honeyhasbeenusedsuc- cessfully to treat burns, graft donor sites, post-operative wound infections, skin ulcers.¹³ Moreover, honey has also been reportedtobenefitwoundcare ofpatientsundergo- ingchemotherapy,thosewithphysiologicalwounddisorders, andprolongedinjury.¹³Inpreviousstudies,thereisnoreport forhoneysideeffectsinwoundhealing.¹⁴Allergytohoneyis rare,butanallergicreactiontohoney’sproteinsandaller- gensispossible.^13,14

Mechanicalorthermalinjuriesmayoccurinthetonsillar fossaduringtonsillectomy,andthislocationremainsanopen woundaftersurgery.¹⁵ Therefore,patientscomplainabout throatpain,particularlyduringswallowing.^16,17 Whenused regularlyafter tonsillectomy,honeymay have benefitson tissuerepair,therebyreducingpost-operativepains.¹⁷ The

applicationofhoneymayreduceinflammation ofinfected woundsandfacilitatethehealingtimeduration.¹⁸

These Randomized Controlled Trials (RCTs) aimed to investigate the efficacy of honey gargle on post- tonsillectomypain.

LevelofEvidence:SystematicReviewofRCT(LevelI).

Methods

Thisstudyisarandomizedcontrolledtrial.Thirtypatients clinicallyindicatedtoundergotonsillectomyandreferredto ENToutpatientclinicfromseveralhospitals,wererecruited inthisstudy.ThisstudywasapprovedbytheResearchEthics Committee(Approval number: 61/KEP/USU/2021).Partic- ipating patients were determined based on the following inclusionandexclusioncriteria(Table1).

The age of subjects was 18---30 years and all subjects were male. Subjects were randomized divided into three groupswithasimplerandomsamplingtechnique.Thisstudy usedrandomnumbertablesinside theenvelopesprovided uponadmissionofthepatients,storedintheirfolders,and couldonlybeopenedaftersurgerytodeterminetheirgroup.

Allstudysubjectsunderwentcolddissectiontonsillectomy method, and hemostasis was controlled using monopolar diathermy.Astandardpost-operativeregimenconsistingof analgesic (mefenamic acid at a dose of 15mg/kg, used, if necessary, a maximum dose of five times a day) and antibiotic (cefadroxil at a dose of 2×500mg/day) were administrated to all post-operative study subjects, plus honeyforthehoneygroup,placebofortheplacebogroup, and only standard post-operative regimen for the control group.

This study used silk-cotton tree or kapok tree honey (Ceiba pentandra), which is certified by Indonesian Food and Drug Administration (Certificate n^o DEPKES RI- 137611001072). For the honey group, 15mL honey mixed with5mLof waterwasgiven tothepatienttogargle for twominutes,thenswallowed,whichisdoneeverysixhours.

Fortheplacebogroup,aplacebowasgiventothepatients (sugarsyrupin honey-likeconcentration,consistency,and colouring), and drugs regimen with the same method as the honey group. Meanwhile, the control group was only givenanalgesicsandantibioticsin thesameway.Adminis- trationofmedicine,honeyandplacebowasstartedsixhours aftersurgery,whenthepatientbeganoralintake.Thestudy wasdesigned doubleblindedtopreventbias.None ofthe patientsknewwhattheirgroupis,alsothesurgeonandthe researcher.

61

Table1 Inclusionandexclusioncriteriaofstudysubjects.

Inclusioncriteria Exclusioncriteria

Maleaged18yearsoldorolder Patientsunwillingtoparticipateinthisstudy Cooperative,well-oriented,andconscious Cognitivedeficitsandlimitedcommunicationskills

Signtheinformedconsent Patientswithdiabetesmellitus,allergytohoney,ordisliketo honey

Thepatientswerediagnosedwith

bilateral/unilateralchronicorrecurrenttonsillitis withorwithoutobstructivesymptoms

Coagulationdisorders

Withorwithoutadenoidectomy Post-operativebleedingandinfection Postoperative-ICUadmission

Adhesionsofthetonsilduringsurgery Addictiontoalcoholorsubstances

Inalong-termtreatment(e.g.,chemotherapy,HIV, Tuberculosis,autoimmunediseases,etc.)

From the 1^st, 2^nd, 3^rd, 7^th, and 10^th day after surgery, a Visual Analogue Scale (VAS) was applied for subjective assessmentofpost-operativepains,whilethefrequencyof analgesiawasusedfortheobjectiveevaluation.Afterbeing dischargedfromthehospital,allsubjectswereinstructedto recordpainandtheamountofanalgesiawasusedathome.

Whenever post-operative complications such as bleeding andinfectionwererecorded,thepatientwasexcludedfrom thestudy.

The Statistical Package of Social Science version 24.0 (SPSS)wasusedtoanalyzedata.Statisticalsignificancewas notedforap-valueof≤0.05.Differencesbetweengroupsin termsofVASandthenumberofanalgesicstakenwereeval- uatedbytheKruskalWallisandAnovatests.Poshocanalysis wasperformedusingtheMannWhitneyandBonferronitests withasignificancelevelof5%.

Results

Thisstudycovers36consecutivepatientswiththediagnosis ofrecurrent/chronic tonsillitisandindicatedfor tonsillec- tomy,however sixpatients wereexcluded becauseof not meeting in inclusion criteria, declined to participate and other reasons. A total of 30 patients underwent tonsil- lectomy were randomizedincluded in the studyprotocol.

Threepatients hadpost-operativebleedingandinfections requiringintravenousantibiotics.Furthermore,onepatient requestedtoquitthestudy,andtwopatientswerelossto follow-up.Theywereexcludedfromthisstudy.Therewasa totalofeightpatientsineachgroup(Honeygroup,Placebo group,andControlgroup)werefinallyanalyzed(Fig.1).

Thereweresignificantdifferencesofpainscale(p<0.05) amongthethreegroupsonthe1^st,2^nd,4^th,7^th,and10^thdays aftersurgery.Themeanpainofthehoneygroupwassigni- ficantly lowerthan the placebo and control group. There were nosignificant differencesof painscale between the honeygroupandtheplacebogrouponthe1^stday, alsono significant differences of pain scale between the placebo andcontrolgroupsonthe1^st,2^nd,4^th,and10^th daysafter surgery(Table2andFig.2).

Thenumberofanalgesicsintakeperdaywascalculated and analyzed fromday 1 today 10. The mean analgesics

intake in the honey group was significantly lower than placebo and control group, particularly at 2^nd day to 7^th day. From the 2^nd to7^th days after surgery, the need for analgesicswassignificantlydifferent(p<0.05)inthehoney groupcomparedtotheplacebo andcontrolgroups.There werenosignificant differencesanalgesics intakebetween thethreegroupsonthe1^stand10^thday(Table3andFig.3).

Thereisnoadverseeffectsorallergiescausedbyhoney wereobservedinthehoneygroup.

Discussion

Chronictonsillitiswasmorecommonlyfoundinchildrenand adolescents or young adult, and based on Sumilo’s study therewasnosignificantdifferenceinsexdistribution.¹⁹

This study showedthat theaverage pain levelsof the honey group were the lowest than the placebo and the control groups. The results of this study showed a statis- ticallysignificant difference(p<0.05) betweenthehoney, placebo andcontrol groups onVAS fromday 1 (p=0.034) untilday10(p=0.001)postoperatively.Similartotheresults ofBoroundmanandLal’sstudy,itwasfoundthatthehoney groupsignificantlyloweredthepainscalefromdayone.^15,20 Ozlugedik’sstudyshowedthatthepainscaleexperienceda significantdecreaseinthehoneygroup(p<0.001)starting atthetwofirstpost-operativedays.¹⁰

Thedifferenceinamountofanalgesicsintakewasstatis- ticallysignificant fromthe 2^nd,4^th,and7^th day(p=0.028;

p=0.001;p=0.003).Inthisstudy,thehoneygroupshowed thelowest analgesic intake comparedtothe placeboand control groups. According to Ozlugedik and Boroundman, honeysignificantlyhelpsreducethefrequencyofanalgesic intake.^10,15

Inaddition,inthisstudy,theuseofplaceboalsohadan effectonpain; however,there werenosignificant differ- encesinboththepainscoreandthefrequencyofanalgesic intakecomparedtothecontrolgroup.Theeffectofreducing thepainscaleontheplacebowasbetteronthepainscale whencomparedtothecontrolgroup.Andthoughtherewere nosignificantdifferencesinboththepainscaleandthefre- quencyofanalgesicusebetweentheplacebogroupandthe controlgroup,theplacebogroup’seffectonthepainscale

Figure1 Flowchartofthetrialprocess(CONSORTFlowDiagram).

Table2 Painscoresofgroupsinthe1^st,2^nd,4^th,7^thand10^thdayaftertonsillectomy(variablesareexpressedasmean±SD).

Group Theintensityofpain(VAS)

Day1 Day2 Day4 Day7 Day10

Honey 4.75±1.28 4.13±1.36 3.13±0.99 2.00±1.07 0.88±0.64

Placebo 6.00±1.07 5.75±1.03 4.75±0.71 3.38±0.52 2.25±0.25

Control 6.50±1.30 6.88±0.83 5.75±0.89 4.50±0.76 2.88±0.64

p-Value 0.034^a 0.003^a <0.001^b 0.001^a 0.001^a

Hvs.P 0.052^d 0.021^d 0.004^c 0.012^d 0.004^d

Hvs.C 0.020^d 0.002^d <0.001^c 0.001^d <0.001^d

Pvs.C 0.396^d 0.050^d 0.095^c 0.010^d 0.130^d

H,honey;P,placebo;C,control.

a Kruskalwallis.

b Anova.

c Bonferroni.

d MannWhitney.

Table3 Numberofanalgesiatakenaftertonsillectomy(variablesareexpressedasmean±SD).

Group Numberofanalgesics

Day1 Day2 Day4 Day7 Day10

Honey 2.88±0.83 2.38±0.92 1.63±0.74 0.88±0.64 0.50±0.53

Placebo 3.38±0.52 3.13±0.64 2.50±0.53 2.13±0.64 1.13±0.83

Control 3.63±0.52 3.50±0.53 3.25±0.46 2.38±0.74 1.38±0.74

p-Value 0.122^a 0.028^a 0.001^a 0.003^a 0.069^a

Hvs.P 0.074^d 0.025^d 0.004^d

HvsC 0.015^d 0.001^d 0.003^d

Pvs.C 0.232^d 0.015^d 0.418^d

aKruskalWallis;^bAnova;^cBonferroni;^dMannWhitney;H,honey;P,placebo;C,control.

Figure2 Intensityofpainscale(day1,2,4,7,and10after tonsillectomy).

Figure3 Ratesofanalgesiaintake(day1,2,4,7,and10after tonsillectomy).

andthe frequency ofusing analgesicswaslowerthan the controlgroup.ThisresultmaybeconsistentwithYaghoobi’s statement that high sugar levels have an osmotic effect andantibacterialactivityonwounds,whichmaymoisturize wounds andreduce pain.²¹ However,perhaps the placebo effectisnotasgoodastheeffectofhoneyonwounds.

Inrecentyears,honeyhasbeenincreasinglyusedinmod- ernmedicineasa‘‘potentagent’’inwoundhealingdueto itsantibacterialandanti-inflammatoryeffects.Themecha- nismforpainreliefinwoundsisassociatedwiththepresence of antioxidantsinhoneysuchasflavonoids, monophenols, polyphenols, vitamin C, and methylsyringate that inter- fere with the inflammatory amplification process by ROS (Reactive Oxygen Species).^13,21,22 The clinical applications ofhoney,particularlyintreatingwounds,ulcers,andburns, areprettystriking.Honeyhasbeenreportedthatpromotes wound epithelization, reduces inflammation, edema, and exudation,acceleratescollagensynthesis,andincreasesthe DNAcontentofthegranulationtissue.^13,23,24

After tonsillectomy, the most common morbidities are bleeding, edema, insufficient oral intake, and pain after tonsillectomy.Despiteadvances inanestheticandsurgical techniques, post-tonsillectomy morbidityremains a major clinical problem.²¹ Post-tonsillectomy pain is caused by mechanicalandthermalinjuriestothetonsillarfossalead- ing to post-operative inflammation, nerve irritation, and pharyngeal spasm.^10,25 Withthese considerations,it could be expected that honey accelerates wound recovery and reducepost-operativepain.²⁵ However,itisnotpossibleto

keephoney in continuous contactwiththe tonsillar fossa asitis inwound dressings. Therefore,the honeyapplica- tionintervalisdoneasoftenaspossible.^15,23Inthisstudy, honeywasdissolvedwithwaterandusedwithdirectadmin- istrationbygarglingthenswallowed,sothatthehoneycould reachallareasthatexperiencedpost-operativetrauma,and itwasperformedevery6-h.SimilartoRaoufian’sstudy,sub- jectswho receivedhoney mixedwith normal salinewere gargledevery6-hforfurthercontactofhoney.²⁵

This studyaimedtoevaluate theroleofhoney incon- trollingpainaftertonsillectomy.Thisstudyusedkapoktree honey(C. pentandra). This honeyis certified and easy to obtain.Kapoktree,alsoknownbythenameof‘‘Javacot- ton’’,isatropicaltreethatiswidelygrowninAsia,America, andAfrica.²⁶Kapoktreehoneyalsoknownhaseffectiveness againstwoundscomparabletomanukahoney’sproperties.

Kapoktreehoneyhasbeenusedinseveralclinicaltrialsand manystudieshavebeenconductedonthishoneytodemon- strate its superior quality, which has potent antioxidant, anti-inflammatory,andantibacterialactivity.^24,27 However, therehavebeen manyother studies examiningthe useof varioustypes of honey.Therefore, any typeof honeycan certainlybebeneficial.

No adverse effects or allergies caused by honey were observedinthisstudy.AccordingtoNanda,therearenoside effectsor resistancetohoney; hencehoneyis considered a safemedicine.²⁴ However,allergic reactions may rarely developagainstsomeofthepollensincludedinhoneyand sometimescontainclostridiasporesthatleadtobotulism.¹⁶ Therefore, the patients receiving honey should be asked whethertheyareallergictohoney.¹⁷

This study is not without limitation. First, the current studyhasrelativelysmallsamplesizeduetolimitedelective procedureduringpandemic (COVID-19)condition. Alarger samplesizecouldpossiblyshowsignificantdifferenceout- comes.Second,VAScannotadequatelyrepresentallaspects ofpainperceptionbecausepainexperiencedbythepatients woulddifferbased onmanyfactors suchaspersonal pain threshold,psychosocialfactors,lengthofrecoveryorunder- lyingdisease.Despitetheselimitationsitremainsasawidely used,validatemeasureofpain.Final,theminimaldoseand durationthatshowedsomebeneficialeffectsofhoneyisnot clearlyknownduetolackofdata.

Conclusion

According to our study, kapok tree honey (C. pentandra) usedin thepatientgroupaftertonsillectomy appeared to beeffectiveinthemanagementofpost-operativepainand mayreducetheneedforanalgesic,withoutsideeffectsor allergies.Themethods usedaremorecost-effective,sim- pler,safer,andmoreaccessible.Apartfromthat,honeyis easytoobtainandaffordable.

Therefore, this study suggests that honey as an adju- vanttherapymightreducepost-operativepainandbenefit inreducingpost-operativeanalgesicrequirement.

Conflicts of interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgments

This articleresults fromamedicalstudentthesis,andwe would like to thank all the subjects who participated in thestudy.Thekindassistanceoftherespectivedeputy,col- leagues,andpatientswhohelpeduswiththisstudyishighly appreciated.

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