10.14639/0392-100X-N0920
Objective. To determine whether submucosal mesna (2-mercaptoethane sodium sulfonate) infiltration is superior to normal saline or adrenaline + lidocaine in mucoperichondrial hydrodissection. Methods. Twenty-one rabbits were administered adrenaline + lidocaine, saline or mesna. Bilateral septal mucoperichondrial flap elevations were performed following submucosal infiltration. The intraoperative bleeding amount, operation time, accessibility of the surgical plane, field quality and degree of mucoperichondrial injury were recorded. The three groups were compared histopathologically. Results. The amount of bleeding and duration of the operation were significantly higher and the accessibility of the surgical plane score was significantly lower in the saline group vs. the other groups (p &lt; 0.05). The mucosal damage rate was significantly higher in the saline group compared with adrenaline + lidocaine (p &lt; 0.05). The surgical field quality was significantly lower in the saline group compared with adrenaline + lidocaine (p &lt; 0.05). The accessibility of the correct surgical plane score was significantly lower in the saline group compared with the adrenaline + lidocaine and mesna groups (p &lt; 0.05). The amount of bleeding, duration of operation, surgical field quality and accessibility of the surgical plane did not differ significantly between the adrenaline + lidocaine and mesna groups (p &gt; 0.05). The pericondrium thickness was significantly lower in the saline group than the other groups. Cartilage thickness was significantly higher in the saline group compared with the mesna group (p &gt; 0.05). Conclusion. Use of mesna instead of normal saline or adrenaline + lidocaine in septoplasty was not more advantageous in terms of intraoperative parameters. The adrenaline + lidocaine group was superior to normal saline for all intraoperative parameters. In conclusion, the use of adrenaline may be more advantageous in facilitating septal mucoperichondrium elevation due to its widespread use, low cost and superiority to physiological saline.
&nbsp;
&nbsp;
application/xml
1827-675X
920
en
Sevim Baykal Koca
https://creativecommons.org/licenses/by-nc-nd/4.0
ACTA Otorhinolaryngologica Italica
mucoperichondrial flap elevation
A clinical and histopathological comparison of saline, adrenaline and 2-mercaptoethanesulfonate (MESNA) in mucoperichondrial elevation: which is superior?
Text.Serial.Journal
https://www.actaitalica.it/
41
Rhinology
2021-03-19
2020-06-15
2021-03-19
2021-03-24
51-58
1
Sevim Baykal Koca
2021/03/19
10.14639/0392-100X-N0920
51
Department of Pathology, Istanbul Training and Research Hospital, Istanbul, Turkey
1827-675X
mucoperichondrial flap elevation
en
58
A clinical and histopathological comparison of saline, adrenaline and 2-mercaptoethanesulfonate (MESNA) in mucoperichondrial elevation: which is superior?
https://www.actaitalica.it/article/download/920/524
41
ACTA OTORHINOLARYNGOLOGICA ITALICA 2021;41:51-58; doi: 10.14639/0392-100X-N0920




Rhinology


A clinical and histopathological comparison of saline,
adrenaline and 2-mercaptoethanesulfonate (MESNA)
in mucoperichondrial elevation: which is superior?
Studio comparativo istopatologico e clinico nello scollamento mucopericondrale
mediante infiltrazione di soluzione salina, mercaptoetanesuflonato (MESNA): quale
tecnica è migliore?
Zehra Çınar1, Özgür Yiğit1, Fulya Savran Turanoğlu1, Sevim Baykal Koca2
1
    Department of Otorhinolaryngology-Head and Neck Surgery, Istanbul Training and Research Hospital, Istanbul, Turkey;
2
    Department of Pathology, Istanbul Training and Research Hospital, Istanbul, Turkey


SUMMARY
Objective. To determine whether submucosal mesna (2-mercaptoethane sodium sulfonate)
infiltration is superior to normal saline or adrenaline + lidocaine in mucoperichondrial hy-
drodissection.
Methods. Twenty-one rabbits were administered adrenaline + lidocaine, saline or mesna.
Bilateral septal mucoperichondrial flap elevations were performed following submucosal
                                                                                                  Received: June 13, 2020
infiltration. The intraoperative bleeding amount, operation time, accessibility of the surgical
                                                                                                  Accepted: October 1, 2020
plane, field quality and degree of mucoperichondrial injury were recorded. The three groups
were compared histopathologically.
                                                                                                  Correspondence
Results. The amount of bleeding and duration of the operation were significantly higher
                                                                                                  Zehra Çınar
and the accessibility of the surgical plane score was significantly lower in the saline group     Istanbul Training and Research Hospital, De-
vs. the other groups (p < 0.05). The mucosal damage rate was significantly higher in the          partment of Otorhinolaryngology & Head and Neck
saline group compared with adrenaline + lidocaine (p < 0.05). The surgical field quality          Surgery, Kasap İlyas Mah., Org. Abdurrahman
was significantly lower in the saline group compared with adrenaline + lidocaine (p < 0.05).      Nafiz Gürman Cd., 34098 Fatih/İstanbul, Turkey
The accessibility of the correct surgical plane score was significantly lower in the saline       Tel. +90 212 459 60 00. Fax +90 212 459 61 45
group compared with the adrenaline + lidocaine and mesna groups (p < 0.05). The amount            E-mail: drzehradonmez@hotmail.com
of bleeding, duration of operation, surgical field quality and accessibility of the surgical
plane did not differ significantly between the adrenaline + lidocaine and mesna groups            Funding
(p > 0.05). The pericondrium thickness was significantly lower in the saline group than           None.
the other groups. Cartilage thickness was significantly higher in the saline group compared
with the mesna group (p > 0.05).                                                                  Conflict of interest
                                                                                                  The Authors declare no conflict of interest.
Conclusion. Use of mesna instead of normal saline or adrenaline + lidocaine in septoplasty
was not more advantageous in terms of intraoperative parameters. The adrenaline + lido-
caine group was superior to normal saline for all intraoperative parameters. In conclusion,         How to cite this article: Çınar Z, Yiğit O, Savran
the use of adrenaline may be more advantageous in facilitating septal mucoperichondrium             Turanoğlu F, et al. A clinical and histopatho-
elevation due to its widespread use, low cost and superiority to physiological saline.              logical comparison of saline, adrenaline and
                                                                                                    2-mercaptoethanesulfonate (MESNA) in muco-
KEY WORDS: adrenaline, mesna, saline, septoplasty, mucoperichondrial flap elevation                 perichondrial elevation: which iıs superior? Acta
                                                                                                    Otorhinolaryngol Ital 2021;41:51-58. https://
                                                                                                    doi.org/10.14639/0392-100X-N0920
RIASSUNTO
Obiettivo. Determinare se l’infiltrazione sottomucosa di mesna (2-mercaptoetano sodico            © Società Italiana di Otorinolaringoiatria
solfonato) è superiore nell’idrodissezione mucopericondriale.                                     e Chirurgia Cervico-Facciale
Metodi. Ventuno conigli sono stati divisi in due gruppi a seconda del trattamento: adrenali-
na + lidocaina, soluzione salina e mesna. Sono stati eseguiti scollamenti mucopericondria-                       OPEN ACCESS
li del setto per infiltrazione sottomucosa. Sono stati registrati la quantità di sanguinamento    This is an open access article distributed in accordance with
intraoperatorio, il tempo dell’intervento, l’accessibilità del piano chirurgico, la qualità       the CC-BY-NC-ND (Creative Commons Attribution-Non-
del campo operatorio e il grado di lesione mucopericondriale. Questi tre gruppi sono stati        Commercial-NoDerivatives 4.0 International) license. The
                                                                                                  article can be used by giving appropriate credit and mentio-
confrontati istopatologicamente.
                                                                                                  ning the license, but only for non-commercial purposes and
Risultati. La quantità di sanguinamento e la durata dell’operazione erano significativa-          only in the original version. For further information: https://
mente più alte, tuttavia l’accessibilità del piano chirurgico era significativamente inferiore    creativecommons.org/licenses/by-nc-nd/4.0/deed.en




                                                                                                                                                            51
Z. Çınar et al.




nel gruppo trattato con soluzione salina rispetto agli altri gruppi (p < 0,05). Il tasso di lesione della mucosa era significativamente più alto nel
gruppo trattato con soluzione salina rispetto al gruppo adrenalina + lidocaina (p < 0,05). La qualità del campo chirurgico era significativa-
mente inferiore nel gruppo trattato con soluzione salina rispetto al gruppo adrenalina + lidocaina (p < 0,05). L’accessibilità del piano chirur-
gico era significativamente inferiore nel gruppo con soluzione salina rispetto ai gruppi adrenalina + lidocaina e mesna (p < 0,05). La quantità
di sanguinamento, la durata dell’intervento, la qualità del campo chirurgico e l’accessibilità al piano chirurgico non differivano significativa-
mente tra i gruppi adrenalina + lidocaina e mesna (p < 0,05). Lo spessore del pericondrio era significativamente inferiore nel gruppo salino
rispetto agli altri gruppi. Lo spessore della cartilagine era significativamente più alto nel gruppo salina rispetto al gruppo mesna (p < 0,05).
Conclusione. L’uso di mesna al posto della normale combinazione di soluzione fisiologica o lidocaina e adrenalina nella settoplastica non è
risultato più vantaggioso in termini di parametri intraoperatori. Il gruppo trattato con lidocaina e adrenalina è risultato superiore rispetto al
trattamento con soluzione salina normale in termini di tutti i parametri intraoperatori. In conclusione, l’uso dell’adrenalina può essere più
vantaggioso nel facilitare l’elevazione del mucopericondrio settale a causa del suo uso diffuso, del basso costo e della superiorità alla solu-
zione salina fisiologica.
PAROLE CHIAVE: adrenalina, mesna, soluzione salina, settoplastica, elevazione del lembo mucopericondriale



Introduction                                                                from the surrounding tissues. Therefore, numerous surgical
                                                                            branches, from otolaryngology to gynaecology and orthopae-
Nasal airway obstruction is a common complaint in oto-                      dics, use mesna for intraoperative chemical dissection 13,14.
rhinolaryngology and has been described as a source of                      The effectiveness of mesna in facilitating dissection of the
significant patient discomfort and financial burden 1. Di-                  cholesteatoma matrix from surrounding tissues has been
agnosis of nasal obstruction includes symptom assessment                    demonstrated 15. It has been reported that mesna facilitates
via the Nasal Obstruction Symptom Evaluation (NOSE)                         elevation of the tympanic membrane in atelectatic ears
instrument and physical exam of the septum and the other                    and adhesive otitis media 16. It is also known to be used
nasal anatomical subunits 2. Nasal obstruction is associ-                   in acoustic neuroma, glomus tumour, meningioma and all
ated with anatomical as well as mucosal conditions. The                     other skull base tumours because it facilitates finding the
most frequent anatomical cause is a deviated nasal septum,                  right surgical plan between solid tissue and tumour tissue 14.
which can be accompanied by hypertrophy of the turbinate                    In severe septum deviations, mucoperichondrium elevation
contralateral to the deviation 2,3. Although the actual preva-              cannot always be as successful as expected. This situation
lence of nasal septal deviation is not known, one study re-                 increases the possibility of complications, such as septal
ported a prevalence of 90% 4. Septoplasty, i.e., surgical cor-              mucoperichondrial perforation and need for revision sur-
rection of the deviated nasal septum, is the most common                    gery. The earlier we perform the elevation of the mucoperi-
ENT-operation in adults 5. Indications for septoplasty are                  chondrium, which is the first stage of septoplasty, the easier
practice-based rather than evidence-based, and internation-                 we can perform surgery in conditions where bleeding and
ally accepted guidelines are lacking 6. Septoplasty (with or                mucoperichondrial perforation are minimal: the rate of
without concurrent turbinate surgery) is performed to wid-                  complications decreases and surgical success increases.
en nasal passages and improve nasal airflow 7.                              In patients with traumatic septal deviation in whom mu-
Mucoperichondrial flap elevation is the first step of septo-                coperichondrium elevation is expected to be difficult, we
plasty and is used to lessen the amount of bleeding, obtain                 theorised that mesna could facilitate mucoperichondrium
better vision of the surgical area, shorten the operation time              elevation, which is the first step of septoplasty.
and minimise mucosal damage 8,9.                                            Because vasoconstrictor agents and saline do not provide
Prior to mucoperichondrial flap elevation, vasoconstric-                    satisfactory outcomes regarding intraoperative parameters,
tor agents combined with local anaesthetics are frequently                  we hypothesised that mesna would be superior to adrena-
used to reduce bleeding and increase the surgical field of                  line and saline regarding the facilitation of the septal muco-
view in nasal surgeries. Using increasing pressure, this hy-                perichondrial flap elevation. For this purpose, submucosal
drodissection technique aims to dissect the perichondrium                   mesna infiltration was compared with submucosal saline
from the nasal septum 10,11. There are also studies where                   and adrenaline in terms of intraoperative parameters and
only saline has been applied for hydrodissection 12. In these               histopathological findings.
studies, it was concluded that vasoconstrictor agents were
not superior to saline in terms of intraoperative parameters.
Mesna, which is the sulphur salt of 2-mercaptoethanolsul-
                                                                            Materials and methods
phamic acid, received a patent for ‘chemical assisted dis-                  Study design
section’ and enables de-adhesion between pathological and                   Twenty-one adult female albino New Zealand rabbits
healthy tissues, thus facilitating healthy tissues in dissociating          (3000-4500 g, mean 3500 g) were equally divided into



52
                                                                                        Effects of saline, adrenaline and mesna in mucoperichondrial elevation




three groups as follows: adrenaline + lidocaine (Jetokain 2                       ble trauma from affecting the septal cartilage. Following
ml, Adeka İlaç, Istanbul, Turkey), physiological saline and                       flap elevation, the flap was laid on the septal cartilage us-
mesna (Uromitexan 400 mg, Eczacıbaşı, Baxter İlaç, Istan-                         ing the miniature Doyle splint (Fig. 1b). Doyle splints were
bul, Turkey).                                                                     placed bilaterally to reattach the mucoperichondrium onto
The study was approved by the Local Animal Ethics Com-                            the septal cartilage and were removed 48 hours later. The
mittee of the Bezmi Alem Foundation University (Animal                            learning curve needed to be overcome. In each group, the
Care and Use) (2016/291). All applicable international, na-                       operation duration was shortened after the first case.
tional and/or institutional guidelines for the care and use of                    The intraoperative evaluation criteria of this study were
animals were followed. All procedures performed in stud-                          determined by refering to the study of Gungor V. et al. 11.
ies involving animals were in accordance with the ethical                         During the operation, five parameters were recorded in all
standards of the institution at which the studies were con-                       three groups: intraoperative septal mucoperichondrial in-
ducted. The protocol was blinded to the investigators per-                        jury, amount of bleeding, operation duration, surgical site
forming the procedure. The same surgeon performed the                             quality and accessibility to the correct surgical plane. Sep-
operations, and each group underwent surgery on different                         tal mucoperichondrial injuries were defined as simple or
days. For general anaesthesia, 40 mg/kg phenobarbital and                         severe. Unilateral septal mucoperichondrial tear without
5 mg/kg xylazine were used. Afterwards, by using dental                           any mucosal loss was accepted as simple damage. Unilat-
injectors and being assisted by the original 10th magnifica-                      eral damage revealing the cartilage because of loss of mu-
tion of the dissection microscope (Imaging source, DFK                            coperichondrium and bilateral mucoperichondrial damage
31AU03, Germany), adrenaline + lidocaine (total amount                            were considered serious injuries. The same surgeon rated
0.5 ml; the dose of lidocaine and adrenaline that 20 mg/                          the surgical site quality and accessibility of the correct sur-
ml and 0.0125 mg/ml respectively), saline (total amount                           gical plane from 1 to 5. Regarding the surgical site quality,
0.5 ml) and mesna (total amount 0.5 ml), for the first, sec-                      1 was considered very poor (not suitable for a comfortable
ond and third group, respectively, were injected at multiple                      operation) and 5 was considered excellent (suitable for a
sides bilaterally through the anterior and posterior septal                       comfortable operation). A surgical site quality of 5 means
submucosal regions.                                                               that there is no mucoperichondrial damage and bilateral
The open rhinoplasty technique was used to access the sep-                        septal mucoperichondrial tunnels are opened without any
tum of rabbits (Fig. 1a). Microsurgical scissors were used                        difficulty. Technically, a much more comfortable surgery
to determine the caudal end of the nasal septum, which                            is performed. A surgical site quality of 1 means that there
was accessed with a sharp dissection starting from the                            is difficulty in opening bilateral submucoperichondrial tun-
columellar region. Mucoperichondrial flap elevation was                           nels due to multiple or severe mucoperichondrial damage
performed on both sides of the nasal septum using a blunt-                        and perforation, and therefore may cause interruption of
tipped elevator. The surgical plane was advanced up to the                        intervention to the septal cartilage safely. Regarding the ac-
nasal septal bone in the posterior region.                                        cessibility of the correct surgical plane, 1 was considered
Maximum precautions were applied to prevent any possi-                            to be very poor (very difficult to find a convenient surgical




Figure 1. (A, B) An open septoplasty technique was used to reach the nasal septum in the rabbits. (C) Totally removed septal cartilage.



                                                                                                                                                          53
Z. Çınar et al.




plane), and 5 was considered excellent (not hard to find a
convenient surgical plane).
4.0 vicryl (Ethicon Inc., Somerville, NJ) was used to close
the initial skin incision. Procaine penicillin (40,000 IU)
was administered intramuscularly (IM) for 3 days for infec-
tion prophylaxis. Six weeks after the operation, the animals
were sacrificed using 500 mg/g intracardiac phenobarbital
following sedation with 40 mg/kg 1M phenobarbital. The
nasal tip was incised through the frontonasal suture line
through the midline of the nasal dorsum. The nasal bone
was cut using bone scissors, the septal cartilage was incised
along the nasal base, the septum was separated from all the
insertion points, and the bloc was removed (Fig. 1c). Speci-
mens were fixed in 10% neutral buffered formol solution
and sent for histopathological examination.

Histopathologic study
Specimens were fixed in 10% buffered neutral formalde-
hyde solution for 24 hours. Following fixation, nasal sep-
tums were sliced in parallel fashion along the long axis.
Sliced tissues were placed in follow-up cassettes and em-
bedded in paraffin blocks following a routine 16-hour tissue
follow-up process. After follow-up, tissues were sectioned
with a microtome into 3 mm sections, which were then
stained with haematoxylin-eosin (H&E) for microscopic
examination. Microscopic evaluations were preformed us-
ing a binocular microscope (Olympus, BX53, Olympus
                                                                Figure 2. Inflammation limited to the mucosae (circle), Light microscopy, H-E
Corp., Tokyo, Japan). All specimens were evaluated by the       X400. (H-E: Haematoxylin-Eosin).
same pathologist (SBK).
The severity of inflammation in septum samples (0 = no
change, 1 = mild, 2 = moderate, 3 = severe), localisation
of the inflammation (E = epithelium, ES = epithelium and
submucosa, ESC = epithelium, submucosa and cartilage),
presence of mucosal erosion and ulceration (0 = none,
1 = visible), presence of foreign body reaction (0 = none,
1 = visible), chondrocyte necrosis and density (1-5% = 1,
6-25% = 2, 26-50% = 3, 51-100% = 4), mucosal, perichon-
drium and cartilage thicknesses were evaluated.
The severity of inflammation was scored as mild when a
small number of inflammatory cells infiltrated the nasal
septum epithelium only (Fig. 2), as moderate when more
severe inflammatory cells infiltrated the epithelium and
submucosa (Fig. 3) and severe when abundant inflamma-
tory cells infiltrated septal cartilage and mucosa in full
thickness (Fig. 4).
Mucosal, perichondrial and cartilage thicknesses were
measured at 400x magnification using a linear microm-
eter (Eyepiece Graticule, Olympus Corp.). The other pa-
rameters as severity of inflammation, mucosal erosion and
                                                                Figure 3. Severe inflammation in the mucosae (yellow circle) reached the
ulceration, chondrocyte necrosis (Fig. 5) and foreign body      submucosae (black circle), Light microscopy, H-E X400. (H-E: Haematoxylin-
reaction were evaluated semi-quantitatively.                    Eosin).



54
                                                                                                         Effects of saline, adrenaline and mesna in mucoperichondrial elevation




Figure 4. Cartilage affected by inflammation (circle) and chondrocyte necro-                      Figure 5. Chondrocyte necrosis area (yellow circle), light microscopy, H-E
sis, light microscopy, H-E X400. (H-E: Haematoxylin-Eosin).                                       X400. (H-E:Haematoxylin-Eosin).


Statistical analysis                                                                              significantly higher in the saline group compared with the
Regarding the descriptive statistics of the data, mean,                                           adrenaline + lidocaine and mesna groups (p < 0.05). The
standard deviation, median lowest, highest, frequency and                                         amount of bleeding and the duration of operation did not
ratio values were used. The distribution of the variables                                         differ significantly between the adrenaline + lidocaine and
was measured with the Kolmogorov-Simonov test. In the                                             mesna groups (p > 0.05) (Tab. I).
anakysis of quantitative independent data, Kruskal-Wallis                                         Mucosal damage was significantly greater in the saline
and Mann-Whitney U tests were used. The chi-square test                                           group compared with the adrenaline + lidocaine group
was used for analysis of qualitative independent data, and                                        (p < 0.05). The mucosal damage in the mesna group did
Fisher’s test was used when the chi-square test conditions                                        not differ significantly from the adrenaline + lidocaine and
were not met. SPSS 22.0 was used for statistical analyses.                                        saline groups (p > 0.05) (Tab. I).
                                                                                                  Surgical field quality was significantly poorer in the sa-
                                                                                                  line group compared with the adrenaline + lidocaine group
Results
                                                                                                  (p < 0.05). In the mesna group, surgical site quality did
Intraoperative findings                                                                           not differ significantly from the adrenaline + lidocaine and
No deaths or side effects were observed during the study.                                         saline groups (p > 0.05) (Tab. I).
The amount of bleeding and the duration of operation were                                         The accessibility of the correct surgical plane score was


Table I. Amount of bleeding, operation time, surgical site quality, mucosal injury, finding the correct surgical plane for the study groups
                                                                     Adrenaline +                    Mesna                        Saline                             p
                                                                       Lidocaine
    Amount of bleeding                           Med( I.Q-3.Q)/                  1.0 (0.50-1.0)/                1.0 (1.0-1.0)/           1.5 (1.0-2.0)/
                                                                                                                                                                  0.010 K
    (number of pads)                                Min-Max                        0.50-1.50*                     0.50-1.00*               1.00-3.50
    Operation Time (Minutes)                 Med (I.Q-3.Q)/ Min-Max               4.5 (3.5-7.0)/                7.0 (5.0-8.0)/          10.5 (6.0-16.5)/
                                                                                                                                                                  0.012 K
                                                                                   3.50-8.00*                     3.50-9.00*               6.00-18.50
    Surgical site quality (1-5)              Med (I.Q-3.Q)/ Min-Max               5.0 (5.0-5.0)/                4.0 (3.0-5.0)/           3.0 (2.0-4.0)/
                                                                                                                                                                  0.027 K
                                                                                    2.00-5.00                     2.00-5.00                 1.00-4.00
    Finding the correct surgical plane Med (I.Q-3.Q)/ Min-Max                     5.0 (3.0-5.0)/                4.0 (3.0-5.0)/           3.0 (2.0-3.0)/
                                                                                                                                                                  0.021 K
    (1-5)                                                                          2.00-5.00*                     3.00-5.00*                2.00-3.00
    Mucosal Injury                       None          n-%                       6          85.7%*              2         28.6%          0           0.0%
                                        Simple         n-%                       0           0.0%               3         42.9%          5          71.4%       p < 0.05 x²
                                        Serious        n-%                       1          14.3%               2         28.6%          2          28.6%
K
    Kruskal-wallis (Mann-Whitney U test); X² Chi-square test (Fisher’s exact test); * Difference with saline group p < 0.05




                                                                                                                                                                            55
Z. Çınar et al.




significantly lower in the saline group compared with the                                groups regarding these two parameters. Based on these
adrenaline + lidocaine and mesna groups (p < 0.05). The                                  findings, mesna does not appear to be superior to adrena-
accessibility of the correct surgical plane score did not dif-                           line. However, saline should not be the first choice in the
fer significantly between the adrenaline + lidocaine and                                 surgical field.
mesna groups (p > 0.05) (Tab. I).                                                        There are few studies evaluating the efficacy of adrenaline
                                                                                         in septum surgery 12,17,18. In a clinical study, submucoperi-
Histopathological findings                                                               chondrial vasoconstrictor injection was compared with
The severity of inflammation, mucosal erosion and ulcera-                                saline injection and was not superior to saline for intraop-
tion, mucosal thickness, chondrocyte necrosis and foreign                                erative findings 11. In another study, adrenaline and saline
body reactions did not differ significantly between the                                  infiltrations were compared, and no significant difference
adrenaline + lidocaine, mesna and saline groups (p > 0.05)                               was detected at the surgical site 12. In contrast, adrenaline
(Tabs. II, III).                                                                         was shown to be superior to saline intraoperative findings,
The thickness of the perichondrium was significantly lower                               such as the amount of bleeding, operation duration, surgi-
in the saline group compared with the adrenaline + lidocaine                             cal site quality, mucosal damage and accessibility of the
and mesna groups (p < 0.05). The thickness of the pericon-                               correct surgical plane in the current study.
drium did not differ significantly between the adrenaline +                              Eren et al. 19 demonstrated the superiority of mesna com-
lidocaine and mesna groups (p > 0.05) (Tab. III).                                        pared with saline in terms of intraoperative findings in septal
Cartilage thickness was significantly higher in the saline                               surgery. In our study, operation time and amount of bleeding
group compared with the mesna group (p < 0.05). There                                    were significantly higher in the saline group compared with
was no significant difference regarding cartilage thickness                              the other groups, and these findings were similar to the study
in the adrenaline + lidocaine group compared with the mes-                               by Eren et al. However, in their study mesna was compared
na and saline groups (p > 0.05) (Tab. III).                                              with saline, although a comparison with other vasoconstric-
                                                                                         tor agents was not included. In our study, saline, vasocon-
                                                                                         strictor agents (adrenaline and lidocaine) and mesna were
Discussion
                                                                                         compared histopathologically. In this respect, the current
In the current study, only the amount of bleeding, opera-                                study is different from that by Eren et al. 19.
tion duration and cartilage thickness were significantly                                 The preservation of perichondrium integrity during septal
higher in the saline group compared with the mesna and                                   surgery is important for prevention of scar tissue formation
lidocaine+adrenaline groups, but the accessibility of the                                and cartilage viability 20-22. The thickness of the perichon-
correct surgical plane score and the thickness of the peri-                              drium increases as a result of the trauma, which is caused by
chondrium were found to be significantly lower. In terms                                 the elevation of the nasal mucosal flap. This increase is due
of mucosal damage and surgical field quality, the saline                                 to scar tissue formation because of increased fibroelastic
group had significantly worse results compared with the                                  activity and trauma-induced oedema 20. Genç et al. 20 found
adrenaline+lidocaine group. No significant difference                                    an increase in perichondrium thickness in both the suture
was found between the mesna and adrenaline + lidocaine                                   and nasal tamponade groups. In the current study, a min-


Table II. Inflammation and inflammation severity, localisation of inflammation for the study groups.
                                                                      Adrenaline + Lidocaine                     Mesna           Saline             p
 Inflammation                                (-)             n-%               1             14.3%            1       14.3%   0         0.0%    p > 0.05 x²
                                            (+)              n-%               6             85.7%            6       85.7%   7        100.0%
 Inflammation severity                         I             n-%               3             42.9%            2       28.6%   4         57.1%
                                              II             n-%               3             42.9%            4       57.1%   2         28.6%
                                              III            n-%               0              0.0%            0        0.0%   1         14.3%
 Localization of inflammation                M               n-%               1             14.3%            1       14.3%   1         14.3%
                                            MS               n-%               5             71.4%            5       71.4%   5         71.4%
                                            MSC              n-%               0              0.0%            0        0.0%   1         14.3%
 Inflammation severity                                     Med (I.Q-             1.0 (1.0-2.0)/              2.0 (1.0-2.0)/   1.0 (1.0-2.0)/     0.868 K
                                                            3.Q)/                  1.00-2.00                   1.00-2.00        1.00-3.00
                                                           Min-Max
X²
     Chi-square test (Fisher’s exact test). M: Mucosa; MS: Mucosa +Submucosa; MSC: Mucosa + Submucosa + Cartilage.




56
                                                                                                     Effects of saline, adrenaline and mesna in mucoperichondrial elevation




Table III. Mucosal erosion and ulceration, mucosal thickness, pericondrium thickness, cartilage thickness, chondrocyte necrosis, foreign body reaction for the
study groups.
                                                  Adrenaline + Lidocaine                      Mesna                       Saline                     p
    Mucosal               (-)           n-%                      6                 85.7%                 4             57.1%              6              85.7%    p > 0.5 x²
    erosion and          (+)            n-%                      1                 14.3%                 3             42.9%              1              14.3%
    ulceration
    Mucosal                       Med (I.Q-3.Q)/       0.32 (0.25-0.40)/                            0.28 (0.23-                     0.31 (0.21-                    0.646 K
    thickness (mm)                  Min-Max               0.23-0.48                                    0.38)/                          0.43)/
                                                                                                    0.18-0.43                       0.20-0.50

    Pericondrium                  Med (I.Q-3.Q)/       0.04 (0.035-0.05)/                           0.04 (0.03-                    0.03 (0.025-                    0.025 K
    thickness (mm)                  Min-Max               0.03-0.08*                                  0.045)/                         0.03)/
                                                                                                    0.03-0.06*                      0.02-0.03

    Cartilage                     Med (I.Q-3.Q)/       0.98 (0.88-1.48)/                            1.30 (1.20-                     0.98 (0.75-                    0.038 K
    thickness (mm)                  Min-Max               0.86-1.48                                    1.70)/                          1.15)/
                                                                                                    1.10-1.90*                      0.68-1.30

    Chondrocyte          (-)            n-%                      1                 14.3%                 4             57.1%              3              42.9%    p > 0.5 x²
    necrosis
                           I            n-%                      4                 57.1%                 2             28.6%              3              42.9%
                          II            n-%                      2                 28.6%                 1             14.3%              1              14.3%
    Foreign body         (-)            n-%                      6                 85.7%                 7             100.%              7              100.0%   p > 0.5 x²
    reaction
                         (+)            n-%                      1                 14.3%                 0             0.0%               0              0.0%
K
    Kruskal-wallis (Mann-Whitney U test); X² Chi-square test (Fisher’s exact test); * Difference with saline group p < 0.05; Min: Minimum/Max: Maximum



iature Doyle nasal splint was placed in both nasal cavities.                                  line + lidocaine, which is much more widely used in septum
The perichondrium thickness was significantly lower in the                                    surgery than mesna. We demonstrated that mesna, which
saline group compared with the other groups. This leads to                                    is more commonly used in otologic surgery, especially for
the question of whether the substances that are injected into                                 chemically assisted dissection in ENT practice, does not
the submucoperichondrial region cause chemical irritation                                     create enough hydrodissection to make itself preferable
in addition to the trauma caused by the mucoperichondrial                                     in septum surgery. The perichondrium was significantly
flap elevation. Saline, which is very similar to human and                                    thicker and the cartilage was significantly thinner in adren-
animal plasma, has no irritant properties.                                                    aline + lidocaine and mesna groups. However, we think that
In the literature, numerous studies have been conducted to                                    this disadvantage will not cause problems in the stability
emphasise the need to preserve perichondrium integrity for                                    and durability of septum in the long term. In the light of all
cartilage viability 21,22. Verwoerd et al. 21 showed that new                                 these findings, we think that adrenaline, which is widely
cartilage formation started within 2 weeks after submu-                                       used for submucopericondrial hydrodissection in septum
cosal cartilage resection in young rabbits; they attributed                                   surgery for many years, is preferable over mesna or saline.
                                                                                              Because the study was performed using a small number of
this to the high reactivity of the perichondrium. Lee et al. 23
                                                                                              rabbits and because it is unethical to harvest a full-thickness
revealed that bilateral elevation of septal mucoperichon-
                                                                                              septum in human studies to compare histopathological param-
drium had no visible effect on chondrocyte viability, and
                                                                                              eters with that of rabbits, these are limitations of our study.
also concluded that bilateral flap elevation caused a marked
                                                                                              This is the first study to compare saline, adrenaline and
weakness in cartilage when performed with interventions
                                                                                              mesna at the same time in septal mucoperichondrial flap
to the septal cartilage.                                                                      elevation in terms of intraoperative parameters and histo-
In the current study, cartilage thickness was significantly                                   pathological effects of these agents on the septum.
higher and perichondrial thickness was significantly lower
in the saline group compared with the mesna group, which
was attributed to chemical irritation by mesna.                                               Conclusions
When comparing intraoperative parameters, we found that                                       The results of this experimental study showed that using
mesna had no significant differences compared to adrena-                                      mesna instead of normal saline or lidocaine + adrenaline



                                                                                                                                                                             57
Z. Çınar et al.




in septoplasty was not more advantageous in terms of ob-                       8
                                                                                    Aksoy F, Yıldırım YS, Demirhan H, et al. Structural characteris-
                                                                                    tics of septal cartilage and mucoperichondrium. J Laryngol Otol
jective parameters tested, amount of bleeding, duration of                          2012;126:38-42. https://doi.org/10.1017/S0022215111002404
operation, mucosal injuries as well as surgical field quality                  9
                                                                                    Vuyk HD, Olde Kalter P. Open septorhinoplasty. Experiences in 200
and accessibility of the correct surgical plane during sur-                         patients. Rhinology 1993;31:175-82.
gery. The combination of adrenaline and lidocaine was su-                      10
                                                                                    Tahery J, Belloso A, Zarod AP. New method for raising the muco-
perior to normal saline for intraoperative parameters. Mes-                         perichondrial flap in septal surgery: microscope assisted hydrodis-
na was not superior to normal saline in terms of mucosal                            section technique. J Laryngol Otol 2004;118:715-6. https://doi.
                                                                                    org/10.1258/0022215042244723
damage and surgical site quality. With all these findings, we                  11
                                                                                    Gungor V, Baklaci D, Kum RO, et al. Infiltration with lidocaine and
conclude that the combination of lidocaine and adrenaline                           adrenaline instead of normal saline does not improve the septoplas-
might be more advantageous in septoplasty since it is inex-                         ty procedure. Eur Arch Otorhinolaryngol 2016;273:2073-7. https://
pensive, almost always available in every operating room,                           doi.org/10.1007/s00405-015-3870-8
much easier access worldwide and reduces bleeding due to
                                                                               12
                                                                                    Vanniasegaram I. Prospective study of the use of vasoconstric-
                                                                                    tor and saline in septal surgery for infiltration. J Laryngol Otol
the vasoconstriction effect of adrenaline. Further studies on                       1991;105:638-9. https://doi.org/10.1017/s0022215100116895
a larger sample size may be beneficial to provide additional                   13
                                                                                    Bogiatzi S, Pagonopoulou O, Simopoulou M, et al. The cytogenetic
information.                                                                        action of ifosfamide, mesna, and their combination on peripheral rab-
                                                                                    bit lymphocytes: an in vivo/in vitro cytogenetic study. Cytotechnol-
                                                                                    ogy 2014;66:753-60. https://doi.org/10.1007/s10616-013-9624-9
Acknowledgements                                                               14
                                                                                    Casale M, Di Martino A, Salvinelli F, et al. MESNA for chemically
                                                                                    assisted tissue dissection. Expert Opin Investig Drugs 2010;19:699-
Presented at the 40 Turkish National Otorhinolaryngology
                         th
                                                                                    707. https://doi.org/10.1517/13543784.2010.485192
and Head and Neck Surgery Congress, Antalya, Turkey,                           15
                                                                                    Vincenti V, Magnan J, Saccardi MS, et al. Chemically assisted dis-
07-11 November 2018.                                                                section by means of mesna in cholesteatoma surgery. Otol Neurotol
                                                                                    2014;35:1819-24 https://doi.org/10.1097/MAO.0000000000000514
                                                                               16
                                                                                    Yilmaz M, Goksu N, Bayramoglu I, et al. Practical use of MESNA
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