Electrocautery Smoke Effects on Larynx: A Rat Model Study

ARTICLE IN PRESS
Effects of Smoke Generated by Electrocautery
on the Larynx
*Yavuz Atar, *Ziya Salturk, *Tolgar Lutfi Kumral, *Yavuz Uyar, †Caglar Cakir, ‡Gurcan Sunnetci, and
*Guler Berkiten, *†Istanbul and ‡Kastamonu, Turkey
Summary: Objective. The aim of this study was to investigate effects of smoke produced by electrocautery on the
laryngeal mucosa.
Materials and Methods. We used 16 healthy, adult female Wistar albino rats. We divided the rats into two groups.
Eight rats were exposed to smoke for 60 min/d for 4 weeks, and eight rats were not exposed to smoke and served as
controls. The experimental group was maintained in a plexiglass cabin during exposure to smoke. At the end of 4 weeks,
rats were sacrificed under high-dose ketamine anesthesia. Each vocal fold was removed. An expert pathologist blinded
to the experimental group evaluated the tissues for the following: epithelial distribution, inflammation, hyperplasia, and
metaplasia. Mucosal cellular activities were assessed by immunohistochemical staining for Ki67. Results taken before
and after effect were compared statistically.
Results. There was a significant difference in the extent of inflammation between the experimental group and the
control group. Squamous metaplasia was detected in each group, but the difference was not significant. None of the
larynges in either group developed hyperplasia.
Conclusions. We showed increased tissue inflammation due to irritation by the smoke.
Key Words: Electrocautery–Smoke–Metaplasia–Inflammation–Larynx.
INTRODUCTION
In 1985, the National Institute for Occupational Safety and Health
recognized smoke generated by electrocautery as a potentially
hazardous chemical to health.1 This announcement by the National Institute for Occupational Safety and Health raised
awareness, and consequently, several studies focusing on the
chemical contents of this type of smoke were published.2–6 Exposure to smoke from electrocautery is unavoidable in procedures
that require both general and local anesthesia, and thus, not only
health-care professionals but also patients can easily become
exposed.
Smoke contents include dead and living cellular material,7,8
blood fragments,9 bacteria,10,11 viruses,12–15 toxic gases and
vapors,3,16 and lung-damaging particulates.17 Hensman et al16 reported the presence of 21 toxic chemicals in electrocautery smoke
produced in closed environments. Al Sahaf et al3 also detected
toxic material and found that the composition of the smoke that
is retained in various tissues differs among tissue type. As a result,
the United States recommended local exhaust ventilation to protect
health-care professionals.1
Although toxic materials have been detected in smoke generated by electrocautery and the risks are apparent, limited studies
have investigated the effects of this smoke on the respiratory
system.17–19 Therefore, the goal of this study was to investigate
the effects of exposure to external smoke generated by electrocautery on the laryngeal mucosa.
Accepted for publication May 16, 2016.
From the *ENT Clinic, Okmeydani Training and Research Hospital, Istanbul, Turkey;
†Pathology Clinic, Okmeydani Training and Research Hospital, Istanbul, Turkey; and the
‡ENT Clinic, Taskopru Government Hospital, Kastamonu, Turkey.
Address correspondence and reprint requests to Yavuz Atar, Department of
Otorhinolaryngology—Head and Neck Surgery, Okmeydani Training and Research Hospital,
Darulaceze Cad. No:25, Okmeydani—Sisli, Istanbul, Turkey. E-mail: [email protected]
Journal of Voice, Vol. ■■, No. ■■, pp. ■■-■■
0892-1997
© 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.jvoice.2016.05.012
MATERIALS AND METHODS
Approval from the Institutional Review Board was obtained from
the Istanbul University Experimental Animal Research Ethics
Committee. In total, we used 16 healthy, adult female Wistar
albino rats (weight range: 200–250 g, age range: 7–8 months).
The experimental group was maintained in a plexiglass cabin
during exposure to smoke. In the cabin, there were 10 holes (3 cm
in diameter) to provide fresh air and allow the smoke to exit.
For entry of electrocautery smoke into the cabin, we created a
cone shaped hole 12 cm in the base of the cabin. The source of
smoke was a PETKOK 500s electrocauterizer (PENTAS, Ankara,
Turkey) in monopolar mode. We used a power of 35 watts for
cut mode and 30 watts for coagulation mode for 30 minutes on
sheep liver.20 We chose a current of 3 amps and a frequency of
468 kHz.
We divided the 16 rats into two groups. Eight rats were exposed
to smoke for 60 min/d for 4 weeks, and eight rats were not
exposed to smoke and served as controls. The animals had free
access to food and water and were kept under a 12 h:12 h lightdark cycle at 25°C.
At the end of 4 weeks, rats were sacrificed under high-dose
ketamine anesthesia. Each vocal fold was removed intact and
stored in 10% (v/v) buffered formalin solution. Specimens were
cut into 5-mm-thick sections. Standard tissue-processing methods
were applied, and sections were stained with hematoxylin and
eosin before analysis by light microscopy. An expert pathologist blinded to the experimental group evaluated the tissues for
the following: epithelial distribution, inflammation, hyperplasia, and metaplasia.
Inflammation was graded based on cell density, where grade
1 represented scattered inflammatory cells, grade 3 represented inflammatory cell density that forms lymphoid follicles,
and grade 2 represented a cell density between grades 1 and 3.
Mucosal cellular activities were assessed by immunohistochemical staining for Ki67, which is expressed during all phases
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2
Journal of Voice, Vol. ■■, No. ■■, 2016
of the cell cycle except for G0. Expression of Ki67 closely parallels [3H]-thymidine incorporation, which is a standard method
of measuring cell proliferation. Immunostaining of normal tissue
for the Ki67 antigen reveals nuclear activity in cells within the
germinal centers of cortical follicles, cortical thymocytes, and
neck cells of the gastrointestinal mucosa. Resting cells, such as
hepatocytes, renal cells, and Paneth cells of the gastrointestinal mucosa, are not stained.
For immunohistochemical evaluation, formalin-fixed paraffinembedded tissue blocks were cut into 5-μm-thick sections and
mounted on poly L-lysine coated slides, followed by staining
with an anti-Ki67 antibody (1:100 dilution, clone: BGX-Ki67;
BioGenex, San Ramon, CA, USA). All procedures were performed
using the standard Leica BOND-MAX autostainer protocol (Leica
Biosystems, Bannockburn, IL), with positive and negative controls included. Any identifiable nuclear staining, regardless of
intensity, was recorded as positive. Distribution of Ki67 in the
basal and parabasal areas of the laryngeal mucosa was evaluated.
Statistical analysis was performed using SPSS Statistics 17
(SPSS Inc., Chicago, Illinois, USA). Pearson chi-squared test
was used for data analysis. Because of the epithelial distributions and cellular activities of the mucosa being identical in both
groups, we did not analyze these data. A P value <0.05 was considered statistically significant.
RESULTS
No macroscopic differences were evident between the laryngeal
tissue from the study group and the laryngeal tissue from the control
group. Microscopically, three types of epithelial cells were detected in the control group. The ventral part of the glottis was
composed of striated ciliary epithelia adjacent to loose connective tissue. The free margins of the vocal folds and adjacent areas
were covered by striated non-ciliated columnar epithelium. The
arytenoid region and adjacent areas were covered with striated squamous epithelium, which was thinner on the arytenoid cartilage.
The laryngeal mucosa of the study group exhibited histopathologic features similar to the control group, showing typical
epithelial linings and basal membranes. There was a significant difference in the extent of inflammation between the
experimental group and the control group (P = 0.026) (Table 1).
Squamous metaplasia was detected in one of the eight rats from
the study group, as well as in one rat from the control group
(Table 2); the difference was not significant (P = 0.707). None
of the larynges in either group developed hyperplasia.
Ki67 expression levels were measured to evaluate cellular activity of the mucosal specimens. In the experimental group, five
rats had laryngeal tissue that showed basal proliferation and three
TABLE 1.
Results of Inflammation Grades
Inflammation
1+
2+
3+
Total
Control
1 (12.5%) 5 (62.5%) 2 (25%) 8 (100%)
Smoke-exposed 2 (25%) 0 (0%)
6 (75%) 8 (100%)
Total
3 (18.7%) 5 (31.3%) 8 (50%) 16 (100%)
Pearson chi-square: P = 0.026.
TABLE 2.
Results of Squamous Metaplasia
Metaplasia
Control
Smoke-exposed
Total
Negative
Positive
Total
7 (87.5%)
7 (87.5%)
14 (87.5%)
1 (12.5%)
1 (12.5%)
2 (12.5%)
8 (100%)
8 (100%)
16 (100%)
Fisher exact test: P = 0.767.
TABLE 3.
Results of Ki67 Expression Levels
Ki67
Control
Smoke-exposed
Total
Basal
Parabasal
Total
8 (100%)
5 (62.5%)
13 (81.3)
0 (0%)
3 (37.5%)
3 (18.7%)
8 (100%)
8 (100%)
16 (100%)
Fisher exact test: P = 0.100.
rats showed parabasal proliferation. In the control group, all laryngeal tissue had basal proliferation patterns (Table 3); no
intragroup differences were observed (P = 0.100).
DISCUSSION
This is the first study investigating the effects of electrocautery
smoke in the rat larynx. Our study revealed that externally generated electrocautery smoke caused inflammation in the larynx.
However, no difference in metaplasia and Ki67 staining was observed between the two groups.
Previous studies have focused mainly on the hazardous content
and the concentration of these chemicals within this type of
smoke. The most prominent hazardous chemicals within this
smoke are as follows: aliphatic hydrocarbons, amines, polycyclic hydrocarbons, aromatic hydrocarbons (eg, benzene), toluene,
and phenol.3,4,21–27 Gianella et al21 reported no differences between
monopolar and bipolar diathermy with regard to the concentration and content within smoke.
Al Sahaf et al3 found that the concentration of toluene,
ethylbenzene, and xylene in smoke generated from electrocautery was similar to the concentrations reported for cigarette
smoke.28 In contrast, Fitzgerald et al2 stated that both electrocautery smoke and ultrasonic scalpel smoke did have carcinogenic
compounds, but that the concentration was less than that observed in cigarette smoke. However, they suggested that
cumulative exposure may be a health concern. Wu et al4 found
that the patient’s age, surgery type, coagulation energy, and duration of the surgery were indicators of the concentration of
toluene. They suggested that these factors should be considered when studying the health risks.
There are a limited number of studies that have investigated
the effect of electrocautery smoke on humans. Navarro-Meza
et al19 performed a study with physicians and concluded that
neurosurgeons had the highest rate of exposure to smoke, but
that all physicians had respiratory symptoms such as sensation
of a lump in the throat, sore throat, and nasal congestion caused
by electrocautery smoke.
ARTICLE IN PRESS
Yavuz Atar et al
Effects of Smoke Generated by Electrocautery
The main limitations associated with this study were that we
evaluated only one type of tissue and that the smoke was delivered only for a short duration. Changing these parameters may
alter the effect on various tissue types and thus should be investigated in future studies.
Finally, Choi et al22 concluded that the risk of cancer caused
by smoke generated by electrocautery was higher for those individuals exposed to this smoke because of the toxic substances.
They believed that the risk was higher for patients and healthcare professionals who were exposed to laparoscopic surgery
and the released gases. It has been suggested that the nature
of the surgical procedure determines the composition of the
smoke.18
CONCLUSIONS
In this study, we showed increased tissue inflammation due to
irritation by the smoke. It will be necessary for future studies
to evaluate the effects of longer durations of smoke exposure
to various tissue types to evaluate the possible risks in greater
detail. In addition, longitudinal studies will also be of importance to understand the effects of smoke on health over time.
REFERENCES
1. NIOSH, Health Hazard Evaluation Report. HETA 85-126-1932, 1988.
p. 2.
2. Fitzgerald JE, Malik M, Ahmed I. A single-blind controlled study of
electrocautery and ultrasonic scalpel smoke plumes in laparoscopic surgery.
Surg Endosc. 2012;26:337–342.
3. Al Sahaf OS, Vega-Carrascal I, Cunningham FO, et al. Chemical composition
of smoke produced by high-frequency electrosurgery. Ir J Med Sci.
2007;176:229–232.
4. Wu YC, Tang CS, Huang HY, et al. Chemical production in electrocautery
smoke by a novel predictive model. Eur Surg Res. 2011;46:102–107.
5. Edwards BE, Reiman RE. Results of a survey on current surgical smoke
control practices. AORN J. 2008;87:739–749.
6. Ulmer BC. The hazards of surgical smoke. AORN J. 2008;87:721–734.
7. Fletcher JN, Mew D, DesCoteaux JG. Dissemination of melanoma cells
within electrocautery plume. Am J Surg. 1999;178:57–59.
8. Nduka CC, Poland N, Kennedy M, et al. Does the ultrasonically activated
scalpel release viable airborne cancer cells? Surg Endosc. 1998;12:1031–
1034.
9. Ott DE, Moss E, Martinez K. Aerosol exposure from an ultrasonically
activated (Harmonic) device. J Am Assoc Gynecol Laparosc. 1998;5:29–32.
3
10. McKinley IB Jr, Ludlow MO. Hazards of laser smoke during endodontic
therapy. J Endod. 1994;20:558–559.
11. Capizzi PJ, Clay RP, Battey MJ. Microbiologic activity in laser resurfacing
plume and debris. Lasers Surg Med. 1998;23:172–174.
12. Ferenczy A, Bergeron C, Richart RM. Human papillomavirus DNA in CO2
laser-generated plume of smoke and its consequences to the surgeon. Obstet
Gynecol. 1990;75:114–118.
13. Taravella MJ, Weinberg A, May M, et al. Live virus survives excimer laser
ablation. Ophthalmology. 1999;106:1498–1499.
14. Garden JM, O’Banion MK, Shelnitz LS, et al. Papillomavirus in the vapor
of carbon dioxide laser-treated verrucae. JAMA. 1988;259:1199–1202.
15. Baggish MS, Poiesz BJ, Joret D, et al. Presence of human immunodeficiency
virus DNA in laser smoke. Lasers Surg Med. 1991;11:197–203.
16. Hensman C, Baty D, Willis RG, et al. Chemical composition of smoke
produced by high-frequency electrosurgery in a closed gaseous environment.
An in vitro study. Surg Endosc. 1998;12:1017–1019.
17. Baggish MS, Elbakry M. The effects of laser smoke on the lungs of rats.
Am J Obstet Gynecol. 1987;156:1260–1265.
18. Barrett WL, Garber SM. Surgical smoke: a review of the literature. Is this
just a lot of hot air? Surg Endosc. 2003;17:979–987.
19. Navarro-Meza MC, González-Baltazar R, Aldrete-Rodríguez MG, et al.
Respiratory symptoms caused by the use of electrocautery in physicians being
trained in surgery in a Mexican hospital. Rev Peru Med Exp Salud Publica
2013;30:41–44.
20. Kwok A, Nevell D, Ferrier A, et al. Comparison of tissue injury between
laparosonic coagulating shears and electrosurgical scissors in the sheep
model. J Am Assoc Gynecol Laparosc. 2001;8:378–384.
21. Gianella M, Hahnloser D, Rey JM, et al. Quantitative chemical analysis of
surgical smoke generated during laparoscopic surgery with a vessel-sealing
device. Surg Innov. 2014;21:170–179.
22. Choi SH, Kwon TG, Chung SK, et al. Surgical smoke may be a biohazard
to surgeons performing laparoscopic surgery. Surg Endosc. 2014;28:2374–
2380.
23. Näslund Andréasson S, Mahteme H, Sahlberg B, et al. Polycyclic aromatic
hydrocarbons in electrocautery smoke during peritonectomy procedures.
J Environ Public Health. 2012;2012:929053.
24. WHO International Agency for Research on Cancer. Benzene. IARC
Monograph Suppl. 1987;7:120–122.
25. Dobrogowski M, Wesołowski W, Kucharska M, et al. Chemical composition
of surgical smoke formed in the abdominal cavity during laparoscopic
cholecystectomy—assessment of the risk to the patient. Int J Occup Med
Environ Health. 2014;27:314–325.
26. O’Grady KF, Easty AC. Electrosurgery smoke: hazards and protection.
J Clin Eng. 1996;21:149–155.
27. Karsai S, Däschlein G. “Smoking guns”: hazards generated by laser and
electrocautery smoke. J Dtsch Dermatol Ges. 2012;10:633–636.
28. Darrall KG, Figgins JA, Brown RD, et al. Determination of benzene and
associated volatile compounds in mainstream cigarette smoke. Analyst.
1998;123:1095–1101.