Main Article

Preoperative Systemic Tranexamic

Acid in Tonsillectomy and Adeno-
tonsillectomy: A Relevant Underrated
Outcome
https://doi.org/10.47210/bjohns.2021.v29i3.560

Rajarajeswari Nalamate,1 Jishana J,1 Mary Kurien,1 Mamie Zachariah,2 Sajeiv Koshy1

ABSTRACT
Introduction
Tranexamic acid, a synthetic anti-fibrinolytic plasminogen inhibitor, a relatively safe drug, is reported to reduce bleeding in
various surgical procedures. Our study was to identify the efficacy of tranexamic acid in reducing intraoperative bleeding
during tonsillectomy and adeno-tonsillectomy, a common paediatric ENT surgery done as day care procedure.
Materials and Methods
A randomised, placebo controlled, double blinded trial was undertaken with consecutive patients undergoing above
procedures, sample size being 100, with 50 patients in each arm. Post induction, injection tranexamic acid 15mg /kg body
weight and saline was given to the test and control group respectively. Intraoperative bleeding was measured and operating
time was also noted.
Results
There were 80 participants, with 41 and 39 patients in treatment and placebo group respectively ranging from 4 to 32 years
age. There was no significant difference in the amount of blood loss between the two groups. However, the duration of surgery
was significantly lowered in tranexamic acid as compared to placebo group (p = 0.008).
Conclusions
Preoperative use of tranexamic acid in tonsillectomy or adeno-tonsillectomy, significantly reduced operating time though
no significant reduction of intra or postoperative bleeding was noted. This previously unreported outcome has surgical
implication, especially in children, for possible use of this widely accepted safe drug during these procedures..
Keywords
Adenoidectomy; Tonsillectomy; Haemorrhage; Operative Time; Tranexamic Acid

T
onsillectomy and adeno-tonsillectomy are minimise blood loss during surgery. Tranexamic acid
common major surgeries in ENT practice, (TXA) is a synthetic amino acid lysine, antifibrinolytic–
especially in paediatric ENT. Primary, reactionary plasminogen inhibitor, trans-4-aminomethyl-
and secondary bleeding related to surgery is a major cyclohexane carboxylic acid. It is a relatively safe drug
issue. About 50% of the patients are managed as day with weak non-competitive inhibition of conversion
care. Since blood volume in children is low, blood loss
measurement in paediatric surgery is also important. The
1 - Department of ENT, Pondicherry Institute of Medical
average amount of blood loss in cold knife dissection Sciences, Pondicherry
tonsillectomy is about 100 ml.1 Blood loss also depends 2 - Department of Anaesthesia, Pondicherry Institute of
on various factors like age, sex, type of tonsillectomy, Medical Sciences, Pondicherry
method of dissection, haemoglobin concentration, Corresponding author:
clotting time and the use of antibiotics. Dr Rajarajeswari Nalamate
Tranexamic acid has been used for many years to email: [email protected]

Bengal Journal of Otolaryngology and Head Neck Surgery Vol. 29 No. 3 December, 2021
 252 Main Article

of plasminogen to plasmin. It has been widely and So, total of 100 patients with 95% confidence interval
successfully used to reduce bleeding in cardiac, and 80% power was finalised. Informed consent /
orthopaedic, prostate and caesarean surgeries.2 assent was obtained from the study participants / parent
Data available in the literature shows conflicting / legally authorized representative. The experimental
evidence regarding effect of tranexamic acid in reducing group was given injection Tranexamic acid 15mg/kg
the amount of bleeding in tonsillectomy and adeno- body weight made up to 10ml and the control group was
tonsillectomy. Regarding intraoperative bleeding, two given 10ml saline. Both groups were given the injection,
RCTs have reported preoperative use of Tranexamic preoperatively over a period of 5 minutes, just after
acid to have insignificant reduction3 or no reduction.4 intubation prior to the start of the surgery. Surgery was
A meta-analysis,5 another RCT6 and most recent done by cold steel method of tonsillectomy endoscopic
retrospective case control study7 reported significant assisted adenoidectomy, the operating surgeons were
reduction. Regarding reactionary or secondary bleeding, residents under faculty supervision, and all participants
two retrospective studies reported its use to reduce were given the same induction protocol. Both the
significantly.7,8 Considering these conflicting reports operating surgeon and faculty supervisor were blinded.
and the most accepted study design for therapeutic The preoperative and postoperative measurement of
outcome being randomized control trial (RCT) this blood loss was done by the operation theatre circulating
study was initiated. The aim was to identify the nurse, who was also blinded. Amount of blood loss
efficacy of tranexamic acid in reducing bleeding during during surgery was measured by comparing the weight
tonsillectomy and adeno-tonsillectomy. of the dry 4x4 gauze pads and cotton balls before
surgery and at the end of the case, added to the amount
of collected blood in the suction bottle9. Blood loss
Materials and Methods was assessed by finding out the difference in the weight
of the gauze, cotton balls and the amount of saline
Inclusion criteria: All patients posted for tonsillectomy
used before and after surgery, adjusting to the specific
or adeno-tonsillectomy between age of 3 and 40 years
gravity of blood (1.055). Any episodes of haemorrhage
with recurrent or chronic tonsillitis, adeno-tonsillitis
in immediate postoperative period and up to 10 days
and obstructive symptoms secondary to hypertrophied
postop were noted. Any occurrence of adverse drug
tonsils.
reactions was also noted.
Exclusion criteria: Patients with allergy to tranexamic
Unfortunately, sample collection had to be terminated
acid, bleeding disorders, age <3 and >40 years
when it reached 80 due to abrupt, unprecedented
and suspected cases of nasopharyngeal or tonsillar
suspension of elective surgeries due to the COVID
malignancy.
pandemic. Following clearance from the Institutional
Method of randomization: Computer generated block Research and Ethics Committee, Interim analysis
randomization. by Statistical Consultant was done. This showed no
A randomised, placebo controlled, double blinded clinically significant difference in the blood loss between
trial was undertaken in patients posted for tonsillectomy the two arms of the study. With 80% recruitment, there
and adenotonsillectomy. Following clearances was only a 13ml blood loss difference with p value of
from Institutional Research and Ethics committee 0.33. The result does not suggest that this would likely
(IEC Ref No: IEC: RC/18/57) and Drug Controller to show any statistical significance even if the study was
of India, this study was registration in the Clinical prolonged and total 100 cases recruited.
Trials Registry of India (CTRI registration number: Statistical Analysis:
CTRI/2019/04/018352). Sample size was calculated
The data was entered in MS excel and analysed using
based on the assumption that, to detect 50ml difference
SPSS version 20.0. Qualitative data was represented
in volume of blood loss, when the average blood loss is
frequency and percentage. Normality of the data
100ml/ patient, we need to study 50 patients per group.

Bengal Journal of Otolaryngology and Head Neck Surgery Vol. 29 No. 3 December, 2021
 Preoperative Systemic Tranexamic Acid in Tonsillectomy and Adeno-tonsillectomy: A Relevant Underrated Outcome 253

Fig.1. FlowChart

was assessed using Shapiro Wilk test. Since all the (Table I).
quantitative variables followed non normal distribution, The average amount of blood loss was 119 (61) ml
median and inter-quartile range was used to represent and 123 (114) ml in the Tranexamic acid group and
the data. Mann Whitney U test was used to find the placebo respectively. Though the amount of blood loss
difference between quantitative variables. Qualitative was higher in the placebo group compared to test group,
variables were assessed using Chi- Square test and there was no statistically significant difference in the
Fischer exact test wherever necessary. P value <0.05 amount of blood loss between them (p value was 0.573).
was considered significant. Reactionary haemorrhage was seen only in one patient
in placebo group, statistically not significant. Secondary
Results haemorrhage was seen in one patient in the test group.
The average duration of surgery in minutes was 75 (43)
There were eighty participants in this study with 39 in and 100 (35) in the test and placebo group respectively (p
the experimental and 41 in the control group (Fig. 1) value of 0.008), indicating that duration of surgery was
significantly lowered in group that received tranexamic
The age ranged between 3 to 40 years. The median
acid (TXA) as compared to placebo group (Table II).
age was 11 years and 12 years in the Tranexamic acid
(TXA) group and placebo group respectively. All the Comparative analysis of blood loss across the two
baseline characters were comparable in both the groups age groups of above and below twelve years of age,

Bengal Journal of Otolaryngology and Head Neck Surgery Vol. 29 No. 3 December, 2021
254 Main Article

Table I: Baseline characters of the study participants

BASELINE CHARACTERS TRANEXAMIC ACID PLACEBO P VALUE
Age (years) [median & IQR] 11.00 (7) 12.00 (6) 0.969*
F 21 17
Sex 0.495#
M 20 22
Chronic
27 30
adenotonsillitis
Chronic tonsillitis 12 7
Hypertrophic
Indication 0 1 0.489#
tonsils
Obstructive
1 1
hypertrophic tonsils
Tonsillar cyst 1 0
Adenotonsillectomy 28 31
Surgery done 0.255#
Tonsillectomy 13 8
H/O allergy to
41 39 NA
Tranexamic acid
Bleed/coagulation
41 39 NA
diseases
H/O altered colour vision 41 39 NA
H/O renal diseases 41 39 NA
1+ 0 1
2+ 12 6
Grade of Tonsils 0.335#
3+ 25 29
4+ 4 3
0+ 7 2
1+ 8 7
Nasopharynx-Adenoids 2+ 7 6 0.206#
3+ 16 15
4+ 3 9
Weight (kg) [median &
28.00 (17) 30.00 (14) 0.609*
IQR]
IQR: Inter quartile range; *Mann Whitney U test; #Chi-square test;

Bengal Journal of Otolaryngology and Head Neck Surgery Vol. 29 No. 3 December, 2021
 Preoperative Systemic Tranexamic Acid in Tonsillectomy and Adeno-tonsillectomy: A Relevant Underrated Outcome 255

Table II: Effect on duration of surgery, post operative bleeding episodes and side effects
CHARACTERS TXA PLACEBO P VALUE
Duration of surgery (minutes) [median & IQR] 75.00 (43) 100.00 (35) 0.008*
Total blood loss (ml) [median & IQR] 119.00 (61) 123.00 (114) 0.573*
Nil 41 (100.0%) 37 (94.9%)
Reactionary haemorrhage Primary h’age 0 (0.0%) 1 (2.6%)
0.340#
(h’age)
Reactionary
0 (0.0%) 1 (2.6%)
h'age
Nil 40 (97.6%) 39 (100.0%)
Secondary haemorrhage Secondary 1.000$
(h’age) h’age 5th Post- 1 (2.4%) 0 (0.0%)
operativeDay
Final follow up Fossa healthy 41 (100.0%) 39 (100.0%) NA
Any A/E Nil 41 (100.0%) 39 (100.0%) NA
IQR: Inter quartile range; *Mann Whitney U test; #Chi-square test; $Fisher’s exact test; h’age – haemorrhage,

percentage of body weight, and duration of time between therapeutic intervention, an experimental study, being
tonsillectomy and adenotonsillectomy did not show any the best design previously published RCTs reported that
statistical significance. (Tables III and IV). preoperative use of TXA showed no statistical significant
reduction in intraoperative bleeding volume.5,7 One
RCT has reported significant reduction in intraoperative
Discussion bleeding though statistical analysis were not clarified6.
The present double blinded RCT, like majority of the
Tranexamic acid (TXA) has been widely and successfully
previous RCTs did not reveal significant reduction in
used to reduce bleeding in cardiac, orthopaedic,
intraoperative bleeding.
prostate and caesarean surgeries. It’s preoperative use
in reducing the amount of bleeding in tonsillectomy Considering post tonsillectomy reactionary and
and adeno-tonsillectomy has had conflicting reports to secondary bleeding, systemic and meta-analysis study5
date.3,5-8 reported five studies (n=1,670) when compared the
number of patients with post tonsillectomy haemorrhage
TXA has been reported to be a statistically significant
between TXA and control groups, did not show significant
reduction in intraoperative blood loss was noted in two
reduction. Similarly, there was no significant decrease
trials (n=180), when tranexamic acid was given as a
in secondary haemorrhage with the use of tranexamic
single dose at induction (32.73ml, 95%CI -42.66, -22.78,
acid in few reported RCTs. The present RCT too did not
P<0.001). This was reported in a systemic review and
show significantly reduced postoperative haemorrhage.
meta-analysis5 where most studies were done before
However, recent retrospective case-control study,
1980. Similarly, a retrospective review of clinical
reported a benefit in the acute management of paediatric
records between 2007 and 2013 showed perioperative
secondary haemorrhage, reducing readmission to
tranexamic acid in a single, parenteral dose reduces the
theatres for surgical re-intervention.7
incidence of primary haemorrhage following paediatric
tonsillectomy, facilitating discharge on the day of The present study revealed significantly reduced
surgery.8 operating time in the group that received TXA as
compared to the placebo group. This is being reported
However, considering the study of effect of

Bengal Journal of Otolaryngology and Head Neck Surgery Vol. 29 No. 3 December, 2021
 256 Main Article

Table III: Blood loss and duration of surgery of participants above and below 12yrs of age.
STANDARD P
AGE CATEGORY DRUG USED N MEAN
DEVIATION VALUE
TXA 24 8.71 2.074
Age 0.169
Placebo 26 9.58 2.318

Estimated blood volume TXA 24 1796.67 502.088

0.26
(ml) Placebo 26 1960 510.623

total blood loss during TXA 24 134.33 61.451

</=12 yrs 0.595
surgery (ml) Placebo 26 144.58 73.87
TXA 24 8.046 4.1445
% blood loss 0.878
Placebo 26 7.854 4.685

duration of surgery TXA 24 87.08 28.281

0.061
(minutes) Placebo 26 102.65 29.174
TXA 17 19.29 5.924
Age 0.149
Placebo 13 16.85 2.853

Estimated blood volume TXA 17 3115.29 834.971

0.87
(ml) Placebo 13 3156.92 542.208

total blood loss during TXA 17 126.35 61.882

>12 yrs 0.493
surgery (ml) Placebo 13 142 60.477
TXA 17 4.353 2.3423
% blood loss 0.792
Placebo 13 4.569 2.0918

duration of surgery TXA 17 73.24 27.038

0.091
(minutes) Placebo 13 91.54 29.182
Student’s t test - *Mann Whitney U test
Among </=12 years, there was a statistically significant difference between the TXA & placebo groups with respect to
duration of surgery.
Among >12 years, there was a statistically significant difference between the TXA & placebo groups with respect to
duration of surgery.

for the first time. Even though, all surgeries were done vision noted in study participants.
by the residents under faculty supervision, the noticeable
point was that, amount of blood loss among the groups Conclusion
was not significantly different, but the reduced operating
time with tranexamic acid group was very much Preoperative use of tranexamic acid in tonsillectomy and
observable. There were no significant adverse side adenotonsillectomy, besides being safe, significantly
effects like vomiting, hypotension or change in colour reduced operative time though does not significantly

Bengal Journal of Otolaryngology and Head Neck Surgery Vol. 29 No. 3 December, 2021
 Preoperative Systemic Tranexamic Acid in Tonsillectomy and Adeno-tonsillectomy: A Relevant Underrated Outcome 257

Table IV: Blood loss and duration of surgery based on percentage of body weight of participants.
STANDARD P
WEIGHT CATEGORY DRUG USED N MEAN
DEVIATION VALUE
TXA 9 6.89 2.028
Age
Placebo 7 7 2.38 0.923

Estimated blood volume TXA 9 1324.44 174.865

(ml) Placebo 7 1325.71 200.571 0.99

total blood loss during TXA 9 139.78 48.987

</=20kg
surgery (ml) Placebo 7 154 92.416 0.721
TXA 9 10.611 3.6498
% blood loss
Placebo 7 11.2 5.9961 0.824

duration of surgery TXA 9 78.33 16.394

(minutes) Placebo 7 103.57 26.412 0.052
TXA 32 14.84 6.471
Age
Placebo 32 13.09 3.779 0.193

Estimated blood volume TXA 32 2630 843.158

(ml) Placebo 32 2585 650.38 0.812

total blood loss during TXA 32 128.56 64.427

>20kg
surgery (ml) Placebo 32 141.47 64.313 0.426
TXA 32 5.363 3.2052
% blood loss
Placebo 32 5.787 3.1661 0.596

duration of surgery TXA 32 82.19 30.977

(minutes) Placebo 32 97.94 30.161 0.044

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