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Brief Reports, Book & Media Reviews, Correspondence, Errata: Letter to the Editor

In Response: "Perioperative COVID-19 Defense: An Evidence-Based Approach for Optimization of Infection Control and Operating Room Management"

Loftus, Randy W. MD; Dexter, Franklin MD, PhD, FASA; Parra, Michelle C. MM; Brown, Jeremiah R. PhD

Author Information
doi: 10.1213/ANE.0000000000004854

Dr Maguire1 considers the use of patient decolonization to aide in the prevention of perioperative viral transmission.2 The evidence, outlined below, favors our recommended approach, given the coronavirus disease 2019 (COVID-19) pandemic.2

First, the patient reservoir is a critical factor contributing to disease transmission that must be addressed.3–5 We evaluated the impact of an evidence-based, multifaceted approach on perioperative Staphylococcus aureus transmission and surgical-site infections (SSIs) in a randomized clinical trial.6 Attention to improved hand hygiene, patient decolonization, vascular care, and environmental cleaning generated substantial reductions in S. aureus transmission and SSIs, especially when optimized by surveillance of transmission.6

Second, povidone-iodine and chlorhexidine have broad-spectrum activity. Povidone-iodine is a complex of povidone, hydrogen iodide, and elemental iodine that targets structures needed for survival and replication (eg, neuraminidase for viral propagation via infection of noninfected cells and hemagglutinin for attachment). This results in multimodal activity.7 Povidone-iodine has rapid and effective virucidal activity against the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA) with at least a 4 log10 (99.99%) inactivation of both pathogens within 15 seconds.7,8 This represents more antiviral potency than alcoholic and nonalcoholic hand sanitizers and soaps.7 Our reason for using chlorhexidine gluconate was that it is available in the United States as Peridex oral rinse. While chlorhexidine gluconate is less effective than povidone-iodine,8 it has activity against enveloped viruses on skin and in the oral cavity (0.12%) with viral inactivation in as little as 30 seconds.9 The inactivity of chlorhexidine rinse against the poliovirus is presumed to be related to lack of an envelope.9 Because the COVID-19 virus is enveloped, chlorhexidine gluconate 0.12% is likely to have similar activity against the virus as it does against other enveloped viruses.10

Third, povidone-iodine and chlorhexidine gargle reduce the spread of viruses. The MERS outbreak showed that human-to-human transmission often involved close contact and the health care arena.7,8 Therefore, improvements in hygiene practices, such as patient decolonization, can help combat the spread of COVID-19. Povidone-iodine preparations reduce viral loads of the patient skin, oropharynx, and nasopharynx.7,8 The agent is included in the World Health Organization’s list of essential medicine for addressing the spread of other viral pathogens of global concern (ie, hepatitis A, influenza, and the MERS).7,8 Povidone-iodine is provided in both skin preparation and oral gargle formulations, has anti-inflammatory activity, has an excellent safety profile, and no resistance identified to date.7,8 Finally, povidone-iodine and alcohol-based hand rubs are more effective than soap-based hand washes for hand hygiene in the presence of transmissible viruses11,12 and povidone-iodine has been shown to prevent the spread of contagious conjunctivitis.13

Fourth, nasal povidone-iodine is formulated to prevent nasal irritation.14 Nasal povidone-iodine is thickened, and pH balanced, to be nonirritating, to have a sustained effect, and to address the physiology of the nose.14 We observed no issues with sneezing or coughing induced by nasal povidone-iodine14 in our randomized trial.6 The product14 was well tolerated and without adverse events. The authors are unaware of reports suggesting otherwise.

Fifth, the authors are unaware of evidence suggesting that chlorhexidine gluconate 0.12% oral rinse is associated with inducing cough. This hypothetical concern raised by Dr Maguire1 should be balanced against the substantial evidence that the oral reservoir contains a high viral load that should be attenuated to prevent the spread of COVID-19 and that 0.12% chlorhexidine gluconate may be useful in achieving this goal.7–9 Whether the alternative of povidone-iodine oral rinse is more effective is currently unknown.7,8,11,12

(Note: After this letter was accepted, Chin et al15 published that SARS-CoV-2 was undetectable after 5-minute exposure to chlorhexidine in lower concentration [0.05%].)

In conclusion, the evidence shows a favorable risk/benefit profile for our recommendation of patient decolonization with nasal povidone and oral chlorhexidine rinse to help mitigate the perioperative spread of COVID-19.7–12 If substantial concerns remain (eg, sneezing and/or coughing), we would recommend using the agents after patient induction and stabilization. Given the severity of the COVID-19 pandemic, we believe that it would be ill-advised to avoid use of these evidence-based preventive measures. These steps are part of a comprehensive program that stands on a solid body of published evidence established during the past 14 years.2–6

Randy W. Loftus, MD
Franklin Dexter, MD, PhD, FASA
Michelle C. Parra, MM
Department of Anesthesia
University of Iowa
Iowa City, Iowa
[email protected]

Jeremiah R. Brown, PhD
Department of Epidemiology
Darmouth Geisel School of Medicine
Hanover, New Hampshire

REFERENCES

1. Maguire D. Oral and nasal decontamination for COVID-19 patients: more harm than good? Anesth Analg. 2020;131:e26–e27.
2. Dexter F, Parra MC, Brown JR, Loftus RW. Perioperative COVID-19 defense: an evidence-based approach for optimization of infection control and operating room management. Anesth Analg. 2020;131:37–42.
3. Loftus RW, Koff MD, Brown JR, et al. The epidemiology of Staphylococcus aureus transmission in the anesthesia work area. Anesth Analg. 2015;120:807–818.
4. Loftus RW, Dexter F, Robinson ADM. High-risk Staphylococcus aureus transmission in the operating room: a call for widespread improvements in perioperative hand hygiene and patient decolonization practices. Am J Infect Control. 2018;46:1134–1141.
5. Loftus RW, Campos JH. The anesthetists’ role in perioperative infection control: what is the action plan? Br J Anaesth. 2019;124:e475–479.
6. Loftus RW, Dexter F, Goodheart MJ, et al. Improving basic preventive measures in the perioperative arena to reduce S. aureus transmission and surgical site infections, a randomized trial. JAMA Netw Open. 2020;3:e201934.
7. Eggers M, Eickmann M, Zorn J. Rapid and effective virucidal activity of povidone-iodine products against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and Modified Vaccinia Virus Ankara (MVA). Infect Dis Ther. 2015;4:491–501.
8. Eggers M. Infectious disease management and control with povidone iodine. Infect Dis Ther. 2019;8:581–593.
9. Bernstein D, Schiff G, Echler G, Prince A, Feller M, Briner W. In vitro virucidal effectiveness of a 0.12%-chlorhexidine gluconate mouthrinse. J Dent Res. 1990;69:874–876.
10. Fehr AR, Perlman S. Coronaviruses: an overview of their replication and pathogenesis. Methods Mol Biol. 2015;1282:1–23.
11. Eggers M, Koburger-Janssen T, Ward LS, Newby C, Müller S. Bactericidal and virucidal activity of povidone-iodine and chlorhexidine gluconate cleansers in an in vivo hand hygiene clinical simulation Study. Infect Dis Ther. 2018;7:235–247.
12. Herruzo R, Vizcaino MJ, Yela R. Surgical hand preparation with chlorhexidine soap or povidone iodine: new methods to increase immediate and residual effectiveness, and provide a safe alternative to alcohol solutions. J Hosp Infect. 2018;98:365–368.
13. Hein AM, Gupta PK. Epidemic keratoconjunctivitis: prevention strategies in the clinic. 2017; Eyenet Magazine. February:33–34. Available at: https://www.aao.org/eyenet/article/epidemic-keratoconjunctivitis-prevention-strategie. Accessed March 31, 2020.
14. Safety & Efficacy Information 3M Skin and Nasal Antiseptic (Povidone-Iodine Solution 5% w/w [0.5% available iodine] USP) Patient Preoperative Skin Preparation. Available at: https://multimedia.3m.com/mws/media/716788O/3m-skin-and-nasal-antiseptic-safety-and-efficacy-brochure.pdf. Accessed March 31, 2020.
15. Chin AWH, Chu JTS, Perera MRA, et al. Stability of SARS-CoV-2 in different environmental conditions. Lancet. 2020 [Epub ahead of print].
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