Abstract
Epistaxis is one of the most common emergencies. Topical agents such as silver nitrate, is known to be a strong oxidizing agent and have been widely used, especially in recurrent and refractory cases. The extent of depth of coagulative necrosis is dependent on time of exposure and concentration. 2 mm wide bar of nasal septum from 30 patients was taken and AgNO3 was applied for 10, 20, 40 s. H&E staining was then performed to see depth of penetration and intensity of stain deposits. It was observed that with increase time of application, depth of penetration and density of deposits were increased for both 75% and 100% concentration of solution. Distribution in depth of penetration was significant when 75% concentration was applied for more than 20 s. But when 100% concentration was used, similar findings were found even after 10 s in young age group. Our study shows that when silver nitrate is used for chemical cauterization in different concentrations and for different times, their penetration is different. Moreover, the depth of penetration depends more on the time of contact than concentration of silver nitrate. We would recommend using 75% solution for use with a contact time not more than 20 s in adults and 10 s in children.
Keywords: Silver nitrate, Septal perforation, Nasal septum, Bleeding, Cautery, Little’s area
Introduction
Epistaxis is one of the most common emergencies presenting in otorhinolaryngological practice. Some authors have estimated that nearly half of population have had an episode of epistaxis in their life out of which almost 6% seek medical attention at some time as majority of bleeding episodes are self-limiting [1]. Incidence of epistaxis is bimodal in general population; its first peak is in teenage and second is in 5th and 6th decade of life with both age groups having a different etiology [2]. Majority of cases of epistaxis are due to bleeding from blood vessels of nasal septum as the blood vessels are superficial lying in the mucosa but sometimes bleeding can also be from lateral wall of nose [3]. The carotid artery system supplies the little’s area of nasal septum via kiesselbach’s plexus formed by anterior and posterior ethmoidal arteries, superior labial artery, sphenopalatine artery and greater palatine artery. This little’s area, which is situated in anterior septum is the most accessible and exposed mucosal surface of septum and is therefore subjected to multiple irritants like trauma in form of nose pricking or blunt impact and drying due to warm and dry air. Nose pricking does not give time for healing to mucosa and therefore the symptoms recur at intervals. Although the etiology of epistaxis is idiopathic in 80% cases, most common cause in children and teenagers is bleeding from little’s area or kiesselbach’s area and is known as anterior epistaxis [1]. Hypertension is considered to be the most common cause of posterior epistaxis from the woodruff’s plexus in elderly patients [2].
Stepwise approach to control epistaxis includes trotter’s maneuver or keeping ice pack over nose while bending forwards. This is effective in mild epistaxis but in cases with moderate bleeding this is not sufficient. Topical agents have been widely used by practitioners in such cases of epistaxis, especially recurrent and refractory cases. Use of topical agents find the first mention in “The paradise of wisdom 850 AD” by Ali-ibn Rabban-al Tabari [4]. Over the years, substances like tonsillar tissue and even salt pork have been used in treatment of epistaxis [5, 6]. When bleeding does not stop by primary aid, intervention in form of use of topical vasoconstrictors [7], nasal packing and electric or chemical cauterization becomes necessary. Nasal packing is an effective technique to control epistaxis but traditional packing of nose with paraffin and antibiotic soaked ribbon gauge is traumatic for patient and is not to be preferred in cases of recurrent epistaxis. Other methods are electro-cautery using a bipolar cautery to coagulate the bleeding blood vessels present in submucosal plane. If all these methods fail, surgical methods like endoscopic sphenopalatine artery ligation (ESPAL) or even external carotid artery ligation needs to be performed.
Little in 1932 published use of topical silver nitrate (AgNO3) in treating epistaxis [8]. Silver nitrate is known to be a strong oxidizing agent producing free radicals in aqueous environment resulting in coagulation of bleeding vessels causing epistaxis. AgNO3 comes in form of crystals which is prepared into a solution by dissolving those crystals in distill water and applied with help of a cotton swab-soaked solution on bleeding vessels directly. Also, silver nitrate tipped caustic pencils are commercially available in 75% and 95% concentrations [1]. Use of silver nitrate is more common in treating anterior epistaxis. After chemical cauterization with silver nitrate, patients sometimes complain of white stain in nasal mucosa, recurrent pain and burning sensation, hypertrophic scar tissue or excoriation of the local area for long time after application [9, 10]. This may be due to effect of coagulation on perichondrium disturbing its blood supply and in turn nutrition of septal cartilage. The coagulation caused by silver nitrate may cause a superficial partial thickness burn (SPT) without causing mucosal necrosis, a deep partial thickness burn (DPT) causing partial mucosal necrosis, or a full thickness burn (FT) causing necrosis reaching upto the perichondrium. The extent of depth of coagulative necrosis is dependent on time of exposure and concentration of silver nitrate. As commonly bleeding vessels are present in the mucosal layer therefore surgeons aim would be to achieve only deep superficial thickness coagulation thereby avoiding injury to perichondrium and septal cartilage which may later give rise to complications such as perichondritis, septal abscess or even perforation [11]. Researchers have pointed out that silver nitrate use causes formation of a necrotic wave front, cell death and area of vascular thrombosis [9].
Although studies have shown that unilateral or bilateral chemical cauterization is safe [12], those studies have short follow up period and small sample size. There has not been much research on qualitative and quantitative effect of application of various concentrations of silver nitrate on nasal septum, clinically or histologically. We aim to find out the histological effect of various concentrations and contact time of silver nitrate on nasal septum (septal cartilage) which may have clinical implications in management of epistaxis.
Material and Methods
This prospective, descriptive study was conducted in the Department of Otorhinolaryngology and Head Neck Surgery of a tertiary care center of Uttar Pradesh, India. Thirty patients of all age group attending ENT OPD with deviated nasal septum, angiofibroma, external deformity of nose and CSF rhinorrhea willing to be part of the study and posted for nasal surgeries which involved removal of a part of septum were included in the study. A written consent was obtained from patients. The study was conducted after taking permission from the Institutional ethics committee. The time period of this study was January 2017 to December 2019.
Details of patients were noted in a pre-formed proforma including name, age, sex and operative summary. During surgery, we obtained 2 mm wide bar of nasal septal cartilage with overlying perichondrium and mucosa using a sharp incision making sure there is no defect in septum or mucosa which cannot be repaired. Each specimen was handled by an assistant who would put the specimen in ringer lactate/normal saline and transport it to histology lab at the same time. In histology lab, each specimen was divided into full thickness sections and silver nitrate was applied in 75% and 100% concentrations for 10, 20 and 40 s. Soon after they were washed with normal saline and fixed in 10% formalin. Paraffin sections were then taken, and hematoxylin–eosin staining was performed. The slides were then assessed microscopically to see for depth of penetration through mucosa, perichondrium and septal cartilage and intensity of deposition in form of number of deposits in chondrocyte lacunae and extracellular matrix. Grading was done as mild: 0–3 deposits, moderate: 4–6 deposits and severe: ≥ 7 deposits per lacunae [2].
The data collected was grouped, tabulated and statistically analyzed using SPSS statistical software (version 23) package for correlations between age of patients, depth of penetration, intensity and contact time.
Observations and Results
Our study consisted of 18(60%) males and 12(40%) females. Majority of patients 14(46.67%) were from age group 31–50 years followed by 07(23.33%) patients from 11–30 years (Table 1).
Table 1.
Age of source patients of septal cartilage
| Age in years | Male | Female | Total |
|---|---|---|---|
| 0–10 | 02 | 01 | 03 (10.00%) |
| 11–30 | 04 | 03 | 07 (23.33%) |
| 31–50 | 08 | 06 | 14 (46.67%) |
| 51–70 | 04 | 02 | 06 (20.00%) |
| TOTAL | 18 (60.00%) | 12 (40.00%) | 30 (100.00%) |
When 75% conc. is used for 10 s, we get 26(86.67%) SPT and when done for 20 s we have 20(66.67%) SPT but when contact time is for 40 s, 18(60%) samples show a DPT and 04(13.34%) even had FT penetration. On using 100% conc for 10 s, 25(83.33%) samples show a SPT whereas when having contact time of 20 and 40 s, more than 2/3rd of samples show DPT and FT penetration. Density of deposits was mild when samples were exposed for 10 or 20 s but when contact time was more than 20 s, majority of samples showed moderate to severe grade of silver deposits. Density of deposits increased on increasing concentration of silver nitrate (Fig. 1).
Fig. 1.
H&E Staining showing a Superficial Partial thickness (SPT) Staining with 75% AgNO3 for 20 s. b Deep Partial thickness (DPT) Staining with 75% AgNO3 for 20 s. c Full thickness (FT) Staining with 100% AgNO3 for 20 s
It was observed that with increase in time of application, depth of penetration and density of deposits were increased for both 75% and 100% concentration of solution and this association of increased time of application with depth of penetration/ density of deposits was statistically significant. Majority of samples showed SPT when AgNO3 was applied for around 20 s (Table 2).
Table 2.
Deposition of silver nitrate deposits according to contact time and concentrations
| Duration of exposure | Conc. of AgNO3 (%) | Depth of penetration | Density of deposits | ||||
|---|---|---|---|---|---|---|---|
| SPT | DPT | FT | Mild | Moderate | Severe | ||
| 10 s | 75 | 26 (86.67%) | 04 (13.33%) | – | 21 (70.00%) | 09 (30.00%) | – |
| 100 | 25 (83.33%) | 05 (16.67%) | – | 16 (53.33%) | 10 (33.33%) | 04 (13.34%) | |
| 20 s | 75 | 20 (66.67%) | 10 (33.33%) | – | 19 (63.33%) | 09 (30.00%) | 02 (06.67%) |
| 100 | 16 (53.33%) | 12 (40.00%) | 02 (06.67%) | 12 (40.00%) | 13 (43.33%) | 05 (16.67%) | |
| 40 s | 75 | 08 (26.67%) | 18 (60.00%) | 04 (13.34%) | 08 (26.67%) | 10 (33.33%) | 12 (40.00%) |
| 100 | 06 (20.00%) | 16 (53.33%) | 08 (26.67%) | 04 (13.33%) | 10 (33.33%) | 16 (53.34%) | |
| P value | At 75% Conc. Depth with time | < 0.0001 | < 0.0001 | ||||
| At 100% conc. Dept. with time | < 0.0001 | 0.0011 | |||||
| Time with concentration | 0.8207 | 0.8300 | |||||
But on comparing the effect of concentration on depth and deposits, similar results were observed with both kind of concentration and no statistically significant difference was observed (Table 3).
Table 3.
Correlation between contact time, depth of penetration and age of patient
| Contact time | Age group | 75% AgNO3 | P value | 100% AgNO3 | P value | ||||
|---|---|---|---|---|---|---|---|---|---|
| SPT | DPT | FT | SPT | DPT | FT | ||||
| 10 s | 0–10 years | 01 (33.33%) | 02 (67.67%) | – | 0.072 | – | 03 (100.00%) | – | 0.0149 |
| 11–30 years | 06 (85.71%) | 01 (14.29%) | – | 06 (85.71%) | 01 (14.29%) | – | |||
| 31–50 years | 13 (92.85%) | 01 (7.14%) | – | 12 (85.71%) | 02 (14.28%) | – | |||
| 51–70 years | 06 (100.00%) | – | – | 06 (100.00%) | – | – | |||
| 20 s | 0–10 years | – | 03 (100.00%) | – | 0.0079 | – | 02 (66.67%) | 01 (33.33%) | 0.1479 |
| 11–30 years | 03 (42.85%) | 04 (57.14%) | – | 03 (42.85%) | 03 (42.85%) | 01 (14.30%) | |||
| 31–50 years | 11 (78.57%) | 03 (21.42%) | – | 08 (57.15%) | 06 (42.85%) | – | |||
| 51–70 years | 06 (100.00%) | – | – | 05 (83.33%) | 01 (16.67%) | – | |||
| 40 s | 0–10 years | – | 01 (33.33%) | 02 (66.67%) | 0.0529 | – | – | 03 (100.00%) | 0.006757 |
| 11–30 years | 01 (14.29%) | 04 (57.14%) | 02 (28.57%) | – | 03 (42.85%) | 04 (57.14%) | |||
| 31–50 years | 06 (42.85%) | 08 (57.15%) | – | 04 (28.57%) | 09 (64.28%) | 01 (07.14%) | |||
| 51–70 years | 01 (16.67%) | 05 (83.33%) | – | 02 (33.33%) | 04 (66.67%) | ||||
When septum sample was exposed to silver nitrate for 10 s, we noted SPT in majority of them with both 75% and 100% concentrations for adult age group but in age group of 0–10 years even DPT were seen. When exposed for 20 s with 75% conc., DPT was seen in majority of samples from age 11–50 years but in samples over 50 years of age, the samples show SPT. Some samples from age group 31–50 showed DPT when conc. was raised to 100%. On exposure for 40 s with 75% conc., FT was seen in age groups 0–30 years and DPT in majority samples of age group 31–70 years. Similar findings were noted when 100% conc. was used.
While comparing the effect of age on different concentration for different time, it was observed that distribution in depth of penetration was only significant when 75% concentration was applied for 20 s. After 20 s, samples of peoples less 10 years showed higher proportion of partial deep thickness penetration as comparison to peoples older than 10 years who showed only superficial partial thickness penetration. While keeping contact time more than 20 s, samples of all ages showed deeper penetration (Fig. 2).
Fig. 2.
Silver nitrate deposits inside chondrocytes
But when 100% concentration was used, similar findings were found even after 10 s. Also, even after using 100% concentration for 40 s, people aged more than 30 years showed higher proportion of superficial penetration whereas people less than 30 years had more full thickness and deeper penetration and this difference in distribution was found statistically significant.
Discussion
In majority of patient’s the epistaxis is self-limiting. Patients generally come to hospital when it becomes recurrent. The patients and accompanying family are very apprehensive at the time of presentation due to the bleeding. It is very important to comfort the mind of patient else hypertensive bleeds tend to aggravate. In cases of epistaxis where first aid methods do not work and a bleeding point is visible on anterior septal area, chemical cauterization is a suitable choice. If there is bleeding from large caliber blood vessels, then it is difficult to control bleeding with chemical cautery alone as it is washed away by bleeding giving inadequate coagulation. Limitations of this method lies in cases where there is severe deviated nasal septum or bleeding point is situated beneath or behind a spur. Chemical cauterization followed by packing is the method of choice to control such bleeding.
Cautery is preceded by anaesthetizing the area with 4% lignocaine and providing vasoconstriction by 1:1000 adrenaline applied on cotton wool pledges [13]. Researchers are of opinion that there are chances of septal damage and perforation if overlying perichondrium is damaged, or its blood supply is compromised leading to avascular necrosis and perforation. As the blood vessels responsible for epistaxis are present in the mucosa, it is desirable to cautery only the mucosa but there is less control over depth of penetration once sufficient amount of silver nitrate is used. As reported by young et al. [14] 7% cases of septal perforation were caused by chemical cauterization. Other complications reported were asymptomatic argyremia and hypersensitivity reaction. To avoid this, we must aim for achieving only a superficial partial burn with right combination of contact time and concentration and totally avoid a full thickness burn. In our study when we exposed the cartilage for around 20 s with 7% AgNo3, majority of adult samples showed SPT penetration. Samples from children showed DPT penetration even with less contact time which implies that chemical cauterization should be used with a lot of caution in children. Although we found no significant difference in depth of penetration on using higher conc. of AgNO3 in most of cases, some samples of higher age group showed DPT to FT on using 100% conc., we therefore advice use of 75% AgnO3 which is much safer to use.
Mayall et al. [15] reported tattoo of nasal mucosa by silver nitrate cautery. They concluded that although it is not pathological but may mimic melanoma and may warrant unnecessary biopsy. Toner et al. [13] observed that rate and nature of complications were similar in using chemical cauterization with silver nitrate and with electro-cautery. Lou et al. [16] in his study observed that chemical cauterization is better in flat bleeding lesions of epistaxis whereas microwave cautery is better in convex lesions.
We found that density of silver deposits was similar in contact time of 10 and 20 s with severe deposition seen in almost half samples when 100% conc. was used for 40 s. Lloyd et al. [2] in their histological study over nasal septum demonstrated that silver nitrate deposits found their way on septal cartilage after application of silver nitrate cautery and duration of exposure had no significance in depth of penetration. They also commented that there was no histological damage to integrity of cartilage because of chemical application instantly but smudging of chondrocytic nuclei was present which may point towards early damage to chondrocyte which later may lead to destruction of cartilage. Bastianpillai et al. [1] in their study on septal cartilage covered with mucosa observed that only partial thickness burns were seen when chemical was used for less than 30 s whereas Lloyd et al. [2] reported that there was no significant difference in depth of penetration after 30 s on nasal septal cartilage without mucosa. They also observed that while 75% concentration was safe to use, 95% concentration was more penetrating and may be reason for possible complications.
Hanif et al. [9] while evaluating effect of silver nitrate on tonsillar tissue reported that on using 75% silver nitrate, depth of penetration was same in between 5 and 20 s. In contrast, in a study by Amin et al. [17] 95% concentration reached twice the depth than compared to 75% when applied for 5 s, and therefore they concluded that there are more chances of complications with this concentration. Felek et al. [18] in their study used bilateral chemical cauterization using 75% concentration for 5 s and found it to be safe for use in children. Glynn et al. [19] in their comparison of various concentration of silver nitrate use in children with idiopathic epistaxis observed better efficacy of 75% solution in complete resolution than 95% silver nitrate. In their study 88% of children who were treated with 75% solution showed complete resolution at 2 weeks and 98% at 8 weeks, whereas in patients in which 95% concentration was used, 35% patients still complained of bleeding episodes at 2 weeks and 10% at 8 weeks. They suggested that this finding may be due to formation of a large necrotic area around application site when higher concentration was used leading to more crusting and ulceration, which later may slough off and give rise to repeat episodes of bleeding. They also reported less pain in patients who were treated with 75% concentration [20].
We have based our study on ex vivo findings of effects of silver nitrate application on nasal septal cartilage obtained from nasal surgeries where part of septum is removed. Still our study points towards a favorable concentration and appropriate contact time. Further studies should study the long-term effects of various concentrations and different contact time of chemical cauterization on septum of patients in clinical practice in relation to symptoms or even perforations.
Conclusion
Our study shows that when silver nitrate is used for chemical cauterization in different concentrations and for different times, their penetration is different. Moreover, the depth of penetration depends more on the time of contact than concentration of silver nitrate. This knowledge may be useful in clinical practice to safely apply chemical cauterization and not overdo it in attempt to stop bleeding in cases where safe contact time and concentration is unable to stop the bleed completely but rather use nasal packing in such cases. We would recommend using 75% solution for use with a contact time not more than 20 s in adults, as it appears to give adequate cauterization and may help in reducing the complications of repeated bleeding, is less painful and may prevent possible septal perforations. In children less than 10 s of age, we recommend contact time of 10 s with 75% concentration. In elderly age group above 50 years of age we may use even 100% conc. safely.
Funding
No funding was received by the authors for this study.
Compliance with Ethical Standards
Conflict of interest
The authors declare that they do not have any potential conflict of interest.
Ethical approval
Ethical clearance was given by the institutional ethics committee for this study in accordance with the 1964 Helsinki Declaration.
Informed consent
A written informed consent was taken by all study participants taking permission for participation and publication of their data.
Footnotes
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