Eur Arch Otorhinolaryngol

DOI 10.1007/s00405-014-3433-4

REVIEW ARTICLE

The efficacy of honey for ameliorating pain after tonsillectomy:

a meta-analysis
Se Hwan Hwang • Jee Nam Song • Yeon Min Jeong •

Yeon Ji Lee • Jun Myung Kang

Received: 13 October 2014 / Accepted: 5 December 2014

Ó Springer-Verlag Berlin Heidelberg 2014

Abstract Postoperative pain and wound healing follow- meta-analysis shows that postoperative administration of
ing tonsillectomy can result in dissatisfaction for the honey after tonsillectomy significantly reduces pain and
patient. However, there is no consensus on whether post- promotes wound healing. Further trials comparing honey
operatively administered honey effectively reduces mor- with good research methodology should be conducted to
bidity after tonsillectomy. Therefore, a systematic review confirm these results.
with a meta-analysis of the efficacy of honey as a treatment
for postoperative pain and wound healing was performed. Keywords Tonsillectomy
Pain
Wound
Healing

Two authors independently searched the database records Systematic review
Meta-analysis
(MEDLINE, SCOPUS, and Cochrane databases) dating
from inception to June 2014. Studies comparing postop-
erative oral administration of honey with administration of Introduction
placebo where the outcomes of interest were pain and
wound healing on postoperative days were included. In the field of otorhinolaryngology, tonsillectomy contin-
Baseline study characteristics, study quality, numbers of ues to be one of the most common surgical procedures
patients in steroid-treated and control groups, and treatment performed on children and adults. Despite advancements in
outcomes were extracted. Sufficient data for meta-analysis surgical and anesthetic techniques, severe pain and diffi-
were retrieved from 4 trials with a total of 264 patients. We culty swallowing are common complaints encountered in
analyzed patient-reported pain scores and quantities of children and adults after tonsillectomy [1]. Because pain
administered analgesics during the first 5 postoperative relief after tonsillectomy can help patients recommence
days. The pain score was significantly decreased in the food intake and prevent patient dehydration secondary to
honey-treated patients in comparison with the placebo- low food intake, various studies have been performed to
treated patients on postoperative day 1 only, but the anal- identify effective methods of pain management, with
gesic intake of the honey-treated patients on the first 5 varying results. Several pain management techniques have
postoperative days was significantly less than that of the been developed for use during and after surgery, including
placebo-treated patients. In addition, honey significantly treatment with steroids, analgesics, antibiotics, and anti-
increased tonsillectomy bed wound healing in comparison nausea medications, all of which have shown some positive
with placebo during the first 2 weeks after surgery. This outcomes in randomized trials without increasing serious
complications such as postoperative bleeding [2–6]. How-
ever, no ideal pain management strategy has been devel-
S. H. Hwang
J. N. Song
Y. M. Jeong
oped for tonsillectomy patients.
Y. J. Lee
J. M. Kang (&) Honey has been used for millennia in widespread
Department of Otolaryngology-Head and Neck Surgery, College cultures as a medicine and food [7]. Although the exact
of Medicine, The Catholic University of Korea, Bucheon St.
mechanisms through which the biological activity and
Mary’s Hospital, 2 Sosa-dong, Wonmi-gu, Bucheon,
Gyeonggi 420-717, Republic of Korea therapeutic properties of honey in wound healing are
e-mail: entkjm@catholic.ac.kr mediated are still unknown, honey has been used

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successfully in the treatment of burns, graft donor sites, Data extraction and risk of bias assessment
necrotizing fasciitis, neonatal postoperative wound
infections, and skin ulcers. Honey has been reported to Data from the included studies were extracted using the
be particularly effective as a wound treatment for standardized forms and checked independently by two
patients receiving chemotherapy, in which the physio- reviewers. The primary outcomes were degree of postoper-
logical process of wound healing is impaired and pro- ative pain [1, 8, 9], quantity of administered analgesics [1, 8,
longed. Clinical and experimental studies have 9], and wound healing [1, 8, 10], with postoperative honey
documented that honey prevents infection around administration (including honey alone and honey with anti-
wounds, decreases inflammation, and expedites tissue biotics) compared with placebo administration on postoper-
healing and epithelization [8]. ative days (PDs). Postoperative pain and wound healing were
Despite these promising findings on the therapeutic evaluated separately using a grading scale or by evaluating
effects of honey, the evidence in the literature is insuffi- the healed area. Analgesic intake after surgery was evaluated
cient to support the use of honey as a standard treatment for as an objective assessment of postoperative pain.
post-tonsillectomy morbidity, such as pain and wound The influence of oral administration of honey on pain
healing. Because tonsillectomy continues to be a common was separately analyzed using the visual analog scale
operation, and post-tonsillectomy pain is the most common (VAS) during the procedure. The VAS score was usually
morbidity associated with tonsillectomy, it is important to reported by the patients, with the smallest number corre-
provide clinicians with information that allows them to sponding to no complaint and the greatest number corre-
follow effective postoperative practices that decrease such sponding to the most severe complaint imaginable. The
morbidity. Therefore, this literature review aims to assess influence of the administered honey on wound healing was
the evidence for the efficacy of honey as a treatment to analyzed using a grading scale or by evaluating the healed
improve the postoperative patient experience after area. The VAS evaluation was usually performed by the
tonsillectomy. physician, with the smallest number corresponding to a
tonsillectomy bed completely covered with slough, and the
greatest number corresponding to a fully healed tonsillec-
Materials and methods tomy bed. From studies concerning the influence of oral
honey on pain and wound healing, we abstracted data
Search strategy and selection of studies regarding patient number, grading scale, and p values of
comparisons of oral administration of honey versus pla-
Studies published in English were identified from MED- cebo. Data reported only in graphical plots were not
LINE, SCOPUS, and the Cochrane Register of Controlled extracted for pooled meta-analysis unless specific numeral
Trials up to June 2014. Search terms included ‘tonsillec- points were discernible or the authors of the relevant
tomy’, ‘honey’, ‘pain’, ‘wound’, ‘healing’, and ‘epitheli- studies were able to verify the data. In the event of missing
zation’. The reference lists of the identified studies were or incomplete data, attempts were made to request data
also checked to ensure that no relevant studies were directly from the authors.
neglected. Two reviewers independently screened all The risk of bias in each study was evaluated using the
abstracts and titles of candidate studies and discarded Cochrane ‘risk of bias’ tool, which tested for selection bias
studies that were not related to the postoperative adminis- (random sequence generation and allocation concealment),
tration of honey. Full texts of studies that were potentially performance bias (blinding of participants and personnel),
relevant were obtained if a decision for selection could not detection bias (blinding of outcome assessment), attrition
be made from the abstract. Randomized and controlled bias (incomplete outcome data), and reporting bias
trials that evaluated patients undergoing tonsillectomy (selective reporting).
(cold or thermal) that utilized treatment with honey derived
from any region were eligible for review. Studies were not Statistical analyses
eligible if the patients underwent additional procedures,
such as uvulopalatopharyngoplasty, or if reports were The meta-analysis of selected studies with continuous data
duplicated. In addition, studies were excluded from the was performed using the R package for statistical com-
analysis if outcomes of interest were not clearly reported puting (R Foundation for Statistical Computing, Vienna,
with quantifiable data or appropriate data could not be Austria). The standardized mean difference (SMD) was
extracted from the published results. Figure 1 summarizes chosen as the method to calculate effect sizes for the
the search strategy used to identify the studies selected for assessment of postoperative pain, analgesic intake, and
the meta-analysis. wound healing across studies. Heterogeneity was

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Fig. 1 Diagram of the study selection process

calculated with the I2 test. We used a funnel plot and within the studies. The results of bias assessment and study
Egger’s test simultaneously to detect publication bias. characteristics are described in Table 1.
Additionally, we used Duval and Tweedie’s trim and fill
method to adjust for missing studies and to correct overall The effect of honey on postoperative pain
effect size for publication bias. after tonsillectomy

The postoperative pain results from three studies that

Results compared patients treated with honey to patients treated
with placebo are summarized in Table 2. Postoperative
Four studies with 264 participants were reviewed in this pain levels on postoperative day 1 (PD 1) (SMD = -1.39;
report. Overall patient characteristics could not be calcu- p = 0.0319) and PD 5 (SMD = -0.31; p = 0.0284), but
lated due to incomplete reporting on patient variables not on PD 3 (SMD = -1.13; p = 0.1490), were

Table 1 Summary of the studies included in the meta-analysis

References Sample Comparison Outcome measure analyzed Judgment of
size risk of bias

Letchumanan 42 Postoperative honey alone vs. Placebo (glucose Pain (0–10 scale), painkiller intake (continuous Low
[1] with caramel) parameter), and wound healing grade (1–5
scale)
Boroumand 104 Postoperative honey plus antibiotics vs. placebo Pain (1–10 scale), painkiller intake (continuous Low
[9] (sugar syrup) parameter)
Mat Lazim 63 Postoperative honey plus antibiotics vs. placebo Wound healing (continuous parameter) Low
[10] (not indicated)
Ozlugedik [8] 55 Postoperative honey plus antibiotics vs. placebo Pain (1–5 scale), painkiller intake (continuous Low
(physiological serum prepared with food dyes) parameter), and wound healing grade (1–5
scale)

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significantly decreased in the patients who received oral PD 1 (SMD = -0.93; p = 0.0004), PD 3 (SMD = -0.93;
honey in comparison with those of the patients who p = 0.0008), and PD 5 (SMD = -1.12; p \ 0.0001) was
received placebo. Significant inter-study heterogeneity was significantly decreased in the patients who received oral
found on PD 1 and PD 3 (I2 [ 50 %). Egger’s test honey in comparison with that of the patients who received
(p \ 0.0001) for the data collected on PD 1 showed that a placebo. Significant inter-study heterogeneity was found on
bias source was evident in the selected sample of studies; PD 1 and PD 3 (I2 [ 50 %). Egger’s test (p [ 0.05) on all
however, application of Duval and Tweedie’s trim and fill postoperative days suggested that a bias source was not
method to PD 1 data showed that there was no difference evident in the selected sample of studies. Duval and
between the observed and adjusted values, while at PD 5 a Tweedie’s trim and fill method revealed no difference
significant difference was evident between the observed between the observed and adjusted values. Therefore, we
and adjusted values. Therefore, we concluded that the concluded that the results of these studies demonstrated a
results of these studies demonstrated a beneficial effect beneficial effect associated with oral administration of
associated with oral administration of honey with respect to honey with respect to pain after tonsillectomy.
pain on PD 1 after tonsillectomy (Table 2). We also performed a subgroup analysis on the effects of
We also performed a subgroup analysis on the effects of administration of honey with or without antibiotics. Sig-
administration of honey with or without antibiotics, and nificant results were evident for two studies that evaluated
found significant results. Notably, the effect sizes of all honey with antibiotics. Although the SMD values for the
measurements were not significant for the study that evalu- two subgroups were similar, the effect size (SMD) for the
ated treatment with honey alone, but the measurement effect study that evaluated honey alone was not statistically
sizes were significant for the two studies that evaluated significant.
treatment with honey with antibiotics. The SMD values for
the subgroups were similar; however, the SMD for the study The effect of honey on wound healing
that evaluated honey alone was not statistically significant. after tonsillectomy

The effect of honey on analgesic intake Results from three studies that compared wound healing in
after tonsillectomy patients treated with honey to that of patients treated with
placebo are summarized in Table 4. Wound healing on PD
The analgesic intake results from three studies that com- 1 (SMD = 0.86; p = 0.0407), PD 4 (SMD = 0.86;
pared patients treated with honey to patients treated with p = 0.0497), PD 7 (SMD = 1.13; p = 0.0446), and PD 14
placebo are summarized in Table 3. Analgesic intake on (SMD = 0.61; p = 0.0342) was significantly improved in

Table 2 Postoperative oral Study Honey total Control total Weight (%) Std. mean difference,
administration of honey versus random, 95 % CI
placebo in postoperative pain
(A) Standard mean difference of pain on postoperative days 1
Letchumanan [1] 21 21 33.0 -0.29 (-0.90, 0.31)
Boroumand [9] 52 52 33.7 -2.53 (-3.04, -2.01)
Ozlugedik [8] 28 27 33.3 -1.32 (-1.90, -0.73)
Total (95 % CI) 101 100 100 -1.39 (-2.66, -0.12)
Heterogeneity: I2 = 93.31 %; Test for overall effect: Z = -2.1454 (p = 0.0319)
(B) Standard mean difference of pain on postoperative days 3
Letchumanan [1] 21 21 33.1 -0.16 (-0.77, 0.44)
Boroumand [9] 52 52 33.5 -2.67 (-3.20, -2.14)
Ozlugedik [8] 28 27 33.4 -0.54 (-1.08, -0.00)
Total (95 % CI) 101 100 100 -1.13 (-2.66, -0.40)
Heterogeneity: I2 = 95.61 %; Test for overall effect: Z = -1.4432 (p = 0.1490)
(C) Standard mean difference of pain on postoperative days 5
Letchumanan [1] 21 21 21.2 0.00 (-0.60, 0.60)
Boroumand [9] 52 52 51.9 -0.34 (-0.73, 0.04)
Ozlugedik [8] 28 27 26.9 -0.54 (-1.04, 0.04)
Total: number of participants Total (95 % CI) 101 100 100 -0.31 (-0.59, -0.03)
per group; pain on postoperative Heterogeneity: I2 = 0.00 %; Test for overall effect: Z = -2.1923 (p = 0.0284)
days 1 (A), 3 (B), and 5 (C)

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Table 3 Postoperative oral Study Honey total Control total Weight (%) Std. mean difference,
administration of honey versus random, 95 % CI
placebo in postoperative
analgesic intake (A) Standard mean difference of analgesic intake on postoperative days 1
Letchumanan [1] 21 21 28.9 -0.36 (-0.97, 0.25)
Boroumand [9] 52 52 38.5 -1.21 (-1.63, -0.80)
Ozlugedik [8] 28 27 31.6 -1.13 (-1.70, -0.57)
Total (95 % CI) 101 100 100 -0.93 (-1.45, -0.42)
Heterogeneity: I2 = 64.51 %; Test for overall effect: Z = -3.5741 (p = 0.0004)
(B) Standard mean difference of analgesic intake on postoperative days 3
Letchumanan [1] 21 21 30.6 -0.39 (-1.00, 0.22)
Boroumand [9] 52 52 37.2 -1.39 (-1.82, -0.96)
Ozlugedik [8] 28 27 32.2 -1.08 (-1.64, -0.51)
Total (95 % CI) 101 100 100 -0.93 (-1.45, -0.42)
Heterogeneity: I2 = 71.39 %; Test for overall effect: Z = -3.3561 (p = 0.0008)
(C) Standard mean difference of analgesic intake on postoperative days 5
Boroumand [9] 52 52 64.1 -1.21 (-1.63, -0.80)
Total: number of participants Ozlugedik [8] 28 27 35.9 -0.95 (-1.51, -0.39)
per group; analgesic intake on Total (95 % CI) 80 79 100 -1.12 (-1.45, -0.78)
postoperative days 1 (A), 3 (B), Heterogeneity: I2 = 0.00 %; Test for overall effect: Z = -6.5527 (p \ 0.0001)
and 5 (C)

Table 4 Postoperative oral Study Honey total Control total Weight (%) Std. mean difference,
administration of honey versus random, 95 % CI
placebo in postoperative wound
healing (A) Standard mean difference of wound healing on postoperative day 1
Letchumanan [1] 21 21 32.5 0.00 (-0.60, 0.62)
Mat Lazim [10] 35 28 34.6 1.23 (0.73, 1.73)
Ozlugedik [8] 28 27 32.9 1.32 (0.73, 1.90)
Total (95 % CI) 84 76 100 0.86 (0.04, 1.68)
Heterogeneity: I2 = 84.55 %; Test for overall effect: Z = 2.0463 (p = 0.0407)
(B) Standard mean difference of wound healing on postoperative day 4
Letchumanan [1] 21 21 32.9 0.00 (-0.60, 0.60)
Mat Lazim [10] 35 28 34.0 1.83 (1.33, 2.32)
Ozlugedik [8] 28 27 33.1 1.37 (0.78, 1.96)
Total (95 % CI) 84 76 100 0.86 (0.04, 1.68)
Heterogeneity: I2 = 90.88 %; Test for overall effect: Z = 1.9628 (p = 0.0497)
(C) Standard mean difference of wound healing on postoperative day 7
Letchumanan [1] 21 21 32.9 0.08 (-0.52, 0.69)
Mat Lazim [10] 35 28 34.0 2.03 (1.53, 2.52)
Ozlugedik [8] 28 27 33.1 1.26 (0.68, 1.84)
Total (95 % CI) 84 76 100 1.13 (0.03, 2.24)
Heterogeneity: I2 = 91.51 %; Test for overall effect: Z = 2.0080 (p = 0.0446)
(D) Standard mean difference of wound healing on postoperative day 14
Letchumanan [1] 21 21 31.3 0.00 (-0.60, 0.60)
Mat Lazim [10] 35 28 35.5 0.83 (0.34, 1.33)
Total: number of participants Ozlugedik [8] 28 27 33.2 0.94 (0.38, 1.50)
per group; wound healing on Total (95 % CI) 84 76 100 0.61 (0.05, 1.17)
postoperative days 1 (A), 4 (B), 2
Heterogeneity: I = 67.97 %; Test for overall effect: Z = 2.1177 (p = 0.0342)
7(C) and 14 (D)

the patients treated with honey in comparison with that of (I2 [ 50 %). Egger’s test (p = 0.0204) on PD 7 showed
patients that received the placebo. Significant inter-study that a bias source was evident in the selected sample of
heterogeneity was found on all postoperative days studies. Duval and Tweedie’s trim and fill method revealed

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no difference between the observed and adjusted values. Therefore, this study assessed postoperative pain and
Therefore, we concluded that the results of these studies wound healing associated with oral administration of
demonstrated a beneficial effect associated with oral honey and placebo via the SMD.
administration of honey on wound healing after In comparison with patients treated with placebo, post-
tonsillectomy. operative pain on PD 1 and PD 5 and analgesic use on PD
We also performed a subgroup analysis on the effects of 1, PD 3, and PD 5 were significantly decreased in the
administration of honey with or without antibiotics. Sig- patients treated with honey. Wound healing in the honey
nificant results were found for two studies that evaluated group was significantly improved in comparison with that
honey with antibiotics. Although the SMD values for the of the placebo group on all postoperative days. Although
two subgroups were similar, the effect size (SMD) for the the group differences in wound healing and postoperative
study that evaluated honey alone was not statistically pain were statistically significant, statistical improvement
significant. and clinical improvement might not occur simultaneously.
The common representation of the SMD is Cohen’s d,
which suggests that a larger effect size indicates that a
Discussion treatment is more clinically effective. An effect size (SMD)
between two means of around 0.206 is considered a small
Post-tonsillectomy pain is a universal complaint of patients effect (possibly clinically non-significant), an effect size of
and remains a considerable clinical problem. In particular, around 0.506 is considered a medium effect, and an effect
intense postoperative pain can have adverse effects, such as size of 0.806 or greater is considered a large and clinically
increased heart rate and blood pressure, when sensed by the significant effect [18]. The SMD values for the measure-
body via the sympathetic autonomous nervous system [11], ments of pain and analgesic intake mostly exceeded 0.8,
which lead to elevated cardiac output and postoperative although the SMD for pain on PD 5 was around 0.2.
exhaustion. In addition to exhaustion, intense postoperative Considering that analgesic intake is more objective than the
pain may necessitate the use of non-steroidal anti-inflam- pain scale as a criterion for the assessment of pain reported
matory drugs (NSAIDs) and their negative effects on by patients and that the effect sizes of the treatment on
hemostasis may be associated with increased postoperative analgesic intake during the postoperative period indicated
hemorrhage [12]. clinically significant effects during the first 5 postoperative
Pain assessment and control after tonsillectomy must be days, our results show that oral administration of honey
included in routine post-tonsillectomy patient management. after tonsillectomy had an appreciable suppressive effect
The VAS pain assessment scale, which allows patients to on postoperative pain. This finding suggests that honey
mark a point along a scale that best represents their level of could reduce analgesic requirements in tonsillectomy
pain, is easy to use, but is subjective. Therefore, analgesic patients.
intake following tonsillectomy was adopted as an objective The SMD values for the wound healing measurements
criterion for pain assessment [8, 13]. This study used both typically exceeded 0.8, although the SMD for pain on PD
approaches to assess the extent of postoperative pain. 14 was around 0.5 and was thus considered to be a medium
Pain following tonsillectomy is mainly the result of the effect. These results showed a pattern similar to that of the
disruption of the mucosa and irritation of open nerve postoperative pain results, which could be explained by the
endings of the glossopharyngeal and vagus nerves, as well fact that the postoperative pain was probably the result of
as of spasms of the exposed pharyngeal and palatal muscles the disruption of mucosa and expression of inflammatory
due to mechanical or thermal damage to the surrounding mediators that irritated pharyngeal nociceptors, and wound
tissue. Oral flora may also increase throat pain by inducing healing has been shown to correlate with decreased pain
inflammation and infection [14]. In recent years, honey has levels [19]. In addition, the decreased beneficial effect of
been increasingly used in modern medicine as a potent honey on wound healing on PD 14 could be explained by
wound healing agent due to its anti-bacterial and anti- the results of Sertal et al., who showed that complete
inflammatory effects. Honey has a wide range of clinical healing of tonsillar fossa took place spontaneously at
applications; in particular, it is widely used in the treatment 14–21 days after the tonsillectomy operation [20].
of wounds, ulcers, and burns [15, 16]. Honey promotes Of the four evaluated studies, three routinely used
wound epithelization; reduces inflammation, edema, and postoperative antibiotics and one did not. Interestingly, in
exudation; accelerates collagen synthesis; and increases the study that did not use antibiotics, all measured
DNA content in granulation tissue [17]. Because an open parameters for the honey group did not show significant
wound is present in the tonsillar fossa after tonsillectomy, improvement relative to those for the placebo group, which
honey is expected to accelerate wound recovery and caused significant inter-study heterogeneity in the analyses
decrease postoperative pain in tonsillectomy patients [8]. of pain, analgesic intake, and wound healing among the

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studies. Although honey showed synergistic effects with 2. Bameshki AR, Razban M, Khadivi E, Razavi M, Bakhshaee M
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