Povidone iodine in dental practice

Introduction

Specialized interest has developed regarding dental-generated aerosols and the possibility for infection transmission between clinicians and patients. Aerosol is created when high-powered devices need compressed air and water to work effectively. [1] Aerosols are defined as liquid or solid particles suspended in the air by humans, animals, instruments, or machines. Bio-aerosols are aerosols consisting of particles of any organism.

Due to the nature of the profession, healthcare workers (HCWs) are at higher risk of microbial infections. Their risk of exposure is in line with the infectious nature of their patients, interventions, or instruments that produce bio-aerosols. [2] HCWs working inwards with patients suffering from pneumonia, who produce high virulence bio-aerosols, or HCWs exposed to bio-aerosol sources in dental practices, are at higher risk for developing disease or allergies. Careful compliance with established hygiene practices by healthcare workers and effective antiseptic options is essential for protecting patients from infectious agents.[1]

The mouth and throat of healthy individuals are known to be inhabited by hundreds of diverse bacteria, fungi, protozoa, and viruses that colonize different surfaces of the oral and oropharyngeal cavities. 

A change in the microbial flora reflects the transition from an asymptomatic ‘healthy’ carrier to invasive disease. [3] The exact mechanism of this change is unclear, although poor oral hygiene, a compromised immune response, and genetics are thought to play a part. This indicates a need for antiseptic agents with broad-spectrum activity and oral formulations that ensure complete oral and oropharyngeal antiseptic coverage.[2]

Povidone-iodine (Iodine with the water-soluble polymer polyvinylpyrrolidone, PVP-I) is considered to have the broadest antimicrobial spectrum and is active against many viruses antibiotic-resistant bacterial strains. It is a complex of iodine and povidone and contains not less than 9 % and not more than 12% available iodine. [4]

PVP-I was discovered by American scientists H.A Shelanski and M.V. Shelanski. It was developed to find an antimicrobial iodine complex that was less toxic than the tincture of iodine.[5]

Mechanism of action

It consists of a complex of povidone, hydrogen iodide, and elemental iodine (I). [5] On application, elemental iodine takes on several forms in an aqueous solution. The molecular I2 and hypo-iodous acid (HOI) are most effective in terms of antimicrobial activity. The iodine molecules oxidize structures like nucleic acid, amino acid, and membrane components. [3,4] 

Biochemical studies and Electron microscopy have suggested PVP-I cause the disruption of microbial cell walls by stimulating pore formation, leading to cytosol leakage. [2] Disruption of surface proteins of enveloped viruses has also been noted. Apart from the direct killing of bacteria, PVP-I inhibits the release of exotoxins, endotoxins, and certain tissue destroying enzymes. Iodine contributes to anti-inflammatory properties by scavenging free radical oxygen species. [6, 5]

Properties of PVP-I [4]

1. Broad-spectrum antimicrobial agent 

2. Detoxified Iodine 

3. No evident vapor pressure 

4. Is water-soluble 

5. Film-forming capacity

6. Formation of Stable complexes

7. Less irritating to the oral mucosa and skin

8. Does not require dissolvent’s

9. Stains are water washable

10. Less systemic toxicity

11.  Safe and convenient to use 

Virucidal activity

PVP-I has superior virucidal action than other used antiseptic agents, a gold standard proposed by WHO. In vitro studies conducted have shown PVP-I gargle inactivates several viruses, including adenovirus, rotavirus, herpes simplex virus, poliovirus (types 1 and 3), rubella, coxsackievirus, rhinovirus, measles, mumps, influenza, and human immunodeficiency virus (HIV). [7]

In a recent study, PVP-I gargle and throat spray established a fast antiviral action against avian influenza A virus strains. The viral titers drop below the exposure limits of the assay in only 10 seconds of PVP-I incubation. [8]

Eggers et al. have revealed the use of PVP-I 7.5% surgical scrub, 4% skin cleanser, 10% solution effective against Ebola virus and MERS-CoV. Also, the use of 1% PVP-I mouthwash or gargle was found effective against MERS-CoV within 15 seconds of application.

The concentration of 0.23% PVP-I used as throat spray was effective against the SARS-CoV2 virus. [6]

A more recent study on coronavirus strain revealed rapid inactivation of the virus by just a 2-minute treatment of PVP-I. Povidone-iodine gargle has shown efficacy against the H1N1 virus also. [9]

Povidone iodine and Covid 19

In addition to seasonal viruses, the newer virus outbreaks such as the Middle East respiratory syndrome coronaviruses and severe acute respiratory syndrome and (MERS-CoV and SARS-CoV) have caused epidemics in 2003 and 2013, respectively. [10] These viruses need close person-to-person contact to spread and can have nosocomial transmission. However, an effective preventive protocol like early viral diagnosis and hygiene practices can control the outbreak and decrease the risk of transmission. [11]

SARS-CoV-2 is homologous with SARS-CoV and is considered to have a close relation to SARS-CoV [10].

A study was done evaluating PVP-I mouthwash and surgical scrub against MERS-CoV. The viral titer was reduced by 99.99% inactivation level within 15 seconds of its application as 7.5% PVP-I surgical scrub and 1% mouthwash.[8]

Eggers et al. demonstrated the virucidal activity of PVP-I 4% skin cleanser and 1% gargle/ mouthwash against MERS-CoV within 15 s of application. [9] These preparations are believed to show similar results against SARS-CoV-2 as well.

Additionally, one author in a recent study has suggested using 0.5% PVP-I in a concentration of 0.3ml in each nostril as a nasal spray. Also, using 9ml of 0.5% PVP-I as a mouth wash for 30 seconds and then gargling to the throat for another 30 seconds before spitting. [7, 9]

An oral swab soaked in 2ml of 0.5% PVP-I to be applied to the oral mucosa in unconscious patients. [6,7,9]

It is also recommended to use 10% PVP-I diluted 1:9 with water as an irrigant in high-speed handpieces and use it in a bottle attached to the dental chair in the same ratio. [10]

Method and protocol for use in Covid 19 [12]

1. It is proposed that 0·5% (5 mg/ml) PVP-I solution can be applied to the oral and oro/ nasopharyngeal of patients with suspected or confirmed COVID-19 cases and the healthcare workers in contact with these known cases.

2. It is also proposed to use the same preparation (0.5%) PVP-I in all the patients requiring procedure or even examination of the oral cavity or oro/nasopharynx. All healthcare professionals carrying out these procedures are not just limited to dental procedures only. However, it includes ENT, endoscopy, endotracheal intubation, and bronchoscopy cases also.

Exclusion criteria: Cases with known allergy to PVP-I or its ingredients, thyroid disease, lithium therapy, pregnancy, ongoing radioactive iodine treatment should be excluded. [12, 13]

The commercially available 10% PVP-I solution recommended for use in oral mucosa is diluted to 1:20 using water to give 0.5% solution. [12, 13]

Patients are informed about the risk and benefits of the treatment proposed, and consent is taken. Healthcare workers will be offered to work with a PPE kit.

Steps performed: [12,13]

1.     All patients and healthcare workers: 0.5% PVP-I is administered in a dose of 0.3ml in each nostril using a syringe with contralateral nostril occluded, and the patient inhales slowly. This will give a total of 0.33 mg of Iodine dose.

9 ml of 0.5% PVP-I solution is used as mouthwash/ gargle in the oral cavity. The solution is swished in the oral cavity for 30 seconds and then gargled and held in the throat for another 30 seconds and then spit out. With this, 2ml of a solution is absorbed, giving a maximum dose of 1.1 mg of iodine.

2.     Unconscious patients: oral swab soaked in 2ml of 0.5% solution of PVP-I is used to wipe oral mucosa. This gives a maximum dose of 1.1 mg Iodine.

Confirmed/ suspected Covid 19 cases with hospitalization and healthcare workers in contact with these cases: The steps mentioned above should be performed every six hourly for patients and four hourly for healthcare workers. The healthcare workers should perform the step before patient contact, and if frequent contact occurs, it should be done 2-3 hourly up to 4 times a day. 

Patients undergoing dental, oral surgical procedures, ENT cases, endoscopy, bronchoscopy, and endotracheal intubation: Similar steps for the patients undergoing treatment and healthcare workers involved in performing these procedures.  

Role of PVP-I in oral surgery and dental procedure

PVP-I is not only a broad-spectrum antimicrobial agent but also has anti-inflammatory and hemostyptic effects in dental and oral surgical procedures. Irrigation of extraction socket and during periapical surgeries using 0.5mg/ml PVP-I leads to the cessation of bleeding. Reduction in swelling and trismus has been noted when PVP-I was used as irrigant and coolant in third molar disimpaction cases. [14] This was ascribed to the inhibitory effect on leukotriene B4 and leucocyte extravasation.

Pre-procedural 0.5% PVP-I mouthwash has been shown to reduce bioaerosol generated with rotator instruments during dental procedures.

10% PVP-I topical application was found to help control severe childhood caries by reducing the bacterial count of streptococcus mutans to only one or two smooth surface caries. Bimonthly topical application of this solution to kids with high risk for childhood caries leads to increased caries-free survival. [15]

The efficacy of 10% PVP-I has been analyzed in periodontitis and gingivitis. PVP-I, used as an adjunct to scaling and root planing, was seen to have a beneficial effect on reducing pocket depth. [14,15] 

Ultrasonic scaling using 0.5% PVP-I showed marked improvement in pocket depth compared to Widman flap surgery in pockets up to 7mm depth. [16]

1% PVP-I in combination with 0.3% hydrogen peroxide led to marked reductions in porphyromonas gingival levels. Also, there was an improvement in periodontal parameters in 3 months. Gingival inflammation was reduced with a lower plaque and papillary bleeding scores by 24 weeks. [17, 18]

2% PVP-I used as an endodontic irrigant has virucidal, fungicidal, and bactericidal effects. This is because iodine attacks key group proteins, fatty acids, and nucleotides, which cause cell death. [18] 10% PVP-I for 5 minutes has shown sanitization of gutta-percha cones contaminated with bacteria.[19] 1% PVP-I was effective against dentoalveolar abscess. [20]

Short-term use of PVP-I has not shown any irritation to oral mucosa nor any other effects like discoloration of teeth, tongue, or taste changes.

Clinical usage 

PVP-I is used universally as an agent for handwashing (7.5% solution) and skin asepsis before any surgical procedure (10% solution). It is used in ophthalmic surgeries as a 5% solution and oral surgery as a 10% solution. [16]

In Vancouver, St. Paul’s Sinus Centre team has recommended topical use of 0.8% PVP-I intranasally for chronic rhinosinusitis. This concentration was found to be effective without causing any thyroid dysfunction or olfaction. [14,21]

Trials were conducted by Gluck et al. at a concentration of 2.2% and 4.4% PVP-I in liposomal dispersions, and it was found not to affect olfaction, mucosal appearance, or nasal airflow. The treatment was well tolerated without any genotoxicity. [22] The mucin clearance rate in the oral cavity is between 1 and 8mm per minute, depending upon location and rate of flow. [21,22]

Efficacy of PVP-I in comparison to other antiseptic agents

Numerous studies have shown that PVP-I has a broad antimicrobial spectrum compared to other antiseptics like chloroxylenol, chlorhexidine, and quaternary ammonium compounds. [10] Chlorhexidine is the mainly used antimicrobial mouthwash. It is a bisbiguanide molecule binding to hydroxyapatite, which forms the organic pellicle of the oral mucosa, tooth, salivary proteins, and bacterias. [15] 

Due to this binding, 30% of the drug is released post rinsing and then slowly over a period of time. Due to its cationic nature, chlorhexidine is also found to be very effective in killing enveloped viruses. As SARS-CoV-2 is an enveloped virus, so chlorhexidine has its effectiveness against coronavirus infection. [23]

Essential oils like thymol, eucalyptol, menthol, and methyl salicylate in an alcohol base lessen bacterial activity and diminish the pathogenicity of plaque. [16,17]

Even though alcohol-based antiseptic agents have an overall potency, they are ineffective against fungal or bacterial spores. Honey and maggots have shown antibacterial action to heal wounds, but their efficacy against viruses and endospores is yet to be determined. [15,16,22]

Limitations

An increase in serum thyroid-stimulating hormone (TSH) concentrations occurs at prolonged usage of PVP-I (24 weeks). Hence, PVP-I usage should be avoided in patients with hyperthyroidism and other diseases of the thyroid. Also, PVP-I gargles should not be used in pregnancy and should be kept to an absolute minimum during lactation. [20]

Conclusion

Antiseptic agents like PVP-I pose a challenge in a clinical situation, where infections need to be prevented. However, by having a localized effect and preventing the use of antibiotics, PVP-I provides a feasible alternative to many viral and common oropharyngeal infections.

References: 

1. Amend D.F., and I.P. Pietsch, “Virucidal Acitivity of two Iodophors to Salmonid Viruses” J.Fish. Res. Board Can. 1972;29:61-65.
2. Avila M, Ojcius M, Yilmaz O. The oral microbiota: living with a permanent guest. DNA Cell Biol 2009; 28: 405–11.
3. Gorman SP, Scott EM, Hutchinson EP. Effects of aqueous and alcoholic povidone-iodine on spores of Bacillus subtilis. J Appl Bacteriol.1985;59:99–105.
4. Kawana R, Kitamura T, Nakagomi O, et al. Inactivation of human viruses by povidone-iodine in comparison with other antiseptics. Dermatology.1997;195(2):29–35.
5. Nagatake T, Ahmed K, Oishi K. Prevention of respiratory infections by povidone-iodine gargle. Dermatology. 2002;204(1):32–6.
6. Kariwa H, Fujii N, Takashima I. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents. Dermatology. 2006;212(1):119–23.
7. Sauerbrei A, Wutzler P. Virucidal efficacy of povidone- iodine-containing disinfectants. Lett Appl Microbiol. 2010;51:158–63.
8. Gottardi W. Iodine and iodine compounds. In: Block SS, editor. Disinfection, sterilization and preservation. Philadelphia: Lea & Febiger; 1991.p. 152–66
9. Eggers M, Koburger-Janssen T, Eickmann M, Zorn J. In Vitro Bactericidal and Virucidal Efficacy of Povidone-Iodine Gargle/Mouthwash Against Respiratory and Oral Tract Pathogens. Infectious diseases and therapy 2018; 7: 249–59.
10. Chitguppi R. generating virus free aerosols to minimize the virus spread (SARS-CoV-2) in dental practice. Dental tribune 2020.
11. Kariwa H, Fujii N, Takashima I. Inactivation of SARS coronavirus by means of povidone-iodine, physical conditions and chemical reagents. Dermatology (Basel, Switzerland) 2006; 212 Suppl: 119–23.
12. Gottardi W. Iodine and iodine compounds. In: Block SS, editor. Disinfection, sterilization and preservation. Philadelphia: Lea & Febiger; 1991.p. 152–66.
13. Wu C, Liu Y, Yang Y, et al. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharmaceutica Sinica B
14. To KK-W, Tsang OT-Y, Chik-Yan Yip C, et al. Consistent detection of 2019 novel coronavirus in saliva. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2020; 361: 1319.
15. Shiraishi T, Nakagawa Y. Evaluation of the bactericidal activity of povidone-iodine and commercially available gargle preparations. Dermatology (Basel, Switzerland) 2002; 204 Suppl: 37–41.
16. Kawana A, Kudo K. [A trial of povidone-iodine (PVP-I) nasal inhalation and gargling to remove potentially pathogenic bacteria colonized in the pharynx]. Kansenshogaku zasshi The Journal of the Japanese Association for Infectious Diseases 1999; 73: 429–36.
17. Ader AW, Paul TL, Reinhardt W, et al. Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function. Journal of Clinical Endocrinology and Metabolism
18. Nelson N, Palmes ED. The absorption, excretion, and physiological effect of iodine in normal human subjects. The Journal of clinical investigation 1947; 26: 301–10.
19. Gluck U, Martin U, Bosse B, Reimer K, Mueller S. A clinical study on the tolerability of a liposomal povidone-iodine nasal spray: Implications for further development. ORL
20. Kanagalingam J, Feliciano R, Hah JH, Labib H, Le TA, Lin JC. Practical use of povidone-iodine antiseptic in the maintenance of oral health and in the prevention and treatment of common oropharyngeal infections. International Journal of Clinical Practice
21. Berkelman RL, Holland BW, Anderson RL. Increased bactericidal activity of dilute preparations of povidone-iodine solutions. Journal of clinical microbiology 1982; 15: 635–9.
22. Himratul Aznita WH, Zainal-Abidin Z, Aznan E, Razi MN. The effectiveness of Chlorhexidine, Hexetidine and Eugenia caryophyllus extracts in commercialized oral rinses to reduce dental plaque microbes. Res J Biol Sci 2009; 4: 716–9.
23. Hanna Huang BA, Jong T, Huang MD. Use of chlorhexidine to eradicate oropharyngeal SARS-CoV-2 in COVID-19 patients. Journal of Medical Virology 2021;93(7): 4370-73.

Authors:

1. Dr. Pradakhshana Vijay, Senior Resident, Department of Oral Pathology and Microbiology, KGMU, Lucknow
2. Dr. Shaleen Chandra, Prof, and Head, Department of Oral Pathology and Microbiology, KGMU, Lucknow
3. Dr. Mohd Parvez Khan, Professor, Department of Anesthesia and Critical care, KGMU, Lucknow
4. Dr. Ved Prakash, Head, Department of pulmonary and critical care medicine, KGMU, Lucknow
5. Dr. Nilesh Pardhe, Head, Clove Dental hospital, Jaipur
6. Dr. Priyanka Singh, Associate Professor, Department of Oral Pathology and Microbiology, KGMU, Lucknow

Corresponding author: Dr. Nilesh Pardhe, drpardhenilesh@hotmail.com

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