Dilute Povidone-Iodine Irrigation: The Science of Molecular Iodine (I2) Kinetics and Its Antimicrobial Activity

Abstract

Dilute povidone-iodine (polyvinylpyrrolidone iodine [PVP-I]) irrigation in spine surgery and total joint arthroplasty has seen a rapid and substantial increase in its use during the past decade. Yet, most surgeons do not know the chemistry and biochemistry that explain its efficacy in preventing infections. PVP-I forms a complex with molecular iodine (I2), facilitating the delivery of I2 to the membrane of the infectious organism. Here, PVP-I establishes an equilibrium between complexed and noncomplexed (free) I2 in the aqueous solution. The I2 acts at numerous cellular targets of infecting organisms augmenting its role as a biocidal molecule. The paradoxical increase in the concentration of I2 that occurs with dilution of PVP-I is a result of equilibrium kinetics and is associated with an enhanced antimicrobial activity. Cytotoxicity studies have yielded conflicting results, but most endorse diluted concentrations as being less damaging to tissues. Clinical studies have verified notable reductions in surgical site infections with a 3-minute soak of 0.35% dilute povidone-iodine irrigation. Guidelines from the World Health Organization, Centers for Disease Control and Prevention, and International Consensus Meeting on Musculoskeletal Infection support the use of prophylactic incisional wound irrigation with aqueous PVP-I to reduce and prevent surgical site infections.

Figure 1

Graph demonstrating the percentage of revision total hip and revision total knee arthroplasties in which the dilute povidone-iodine irrigation protocol was used at Mayo Clinic from 2013 to 2017 (Reproduced/adapted with permission from Hart A, Hernandez NM, Abdel MP, Mabry TM, Hanssen AD, Perry KI: Povidone-iodine wound lavage to prevent infection after revision total hip and knee arthroplasty: an analysis of 2884 cases. J Bone Joint Surg Am 2019;101(13):1151-1159). Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

Figure 2

Illustration demonstrating the PVP-I (povidone-iodine) complex serving as a carrier and as a reservoir for molecular iodine (I2). When noncomplexed I2 is removed from the solution as it penetrates and disrupts the pathogen membrane, it is replaced by I2 released from the tri-iodide that diffuses off the PVP-I complex because of equilibrium kinetics (Reproduced with permission from I2Pure).

Figure 3

Graph demonstrating paradoxical increase in I2 (free iodine or molecular iodine) in dilute povidone-iodine aqueous solutions (Reproduced/adapted with permission from Zamora JL: Chemical and microbiologic characteristics and toxicity of povidone-iodine solutions. Am J Surg 1986;151:400-406). Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

Figure 4

Image demonstrating the active moiety I2, oxidizing pathogen nucleotides and fatty/amino acids and thus disrupting the pathogen membrane and deactivating proteins and DNA/RNA (Adapted by I2Pure, licensed under the Creative Commons Attribution-Share-Alike 4.0 international licenses/by/4.0/). Adaptations are themselves works protected by copyright. So in order to publish this adaptation, authorization must be obtained both from the owner of the copyright in the original work and from the owner of copyright in the translation or adaptation.

Figure 5

Plot demonstrating correlation of S aureus survival data with the concentration of I2 and length of exposure (Reproduced/adapted with permission from Berkelman RL, Holland BW, Anderson RL: Increased bactericidal activity of dilute preparations of povidone-iodone solutions. J Clin Microbiol 1982;15(4):635-639).