The Antiseptic Efficacy of Povidone-Iodine in Reducing Early Surgical Site Infections in Orthopaedic Implant Surgeries

Background: Surgical site infection (SSI) is a dreaded nightmare for the Orthopaedic surgeon. Preoperative skin cleaning with antiseptics has been shown to reduce the microbial burden of the skin and results in reduced incidence of SSI. However, the ideal skin cleaning agent remains to be established. Aim: To compare the efficacy of Povidone-Iodine/Povidone-Iodine (PI-PI) combination with that of Chlorhexidine-Gluconate/Alcohol (CG-A) combination in reducing SSI in Orthopaedic surgeries. Methods: This was a prospective, randomized, double-blinded, controlled study. Subjects that met the selection criteria and gave consent were randomized into PI-PI group (test group) and the CG-A group (control group). Both the patients and the assessors for SSI were blinded to the group a participant belongs. Blocking was done on the type of surgery to cancel the confounding effect of surgery type on SSI. Standard perioperative protocols were applied to both groups. Assessment for features of SSI was done on the 3 day, 7 day, 14 day, 6 week and 12-week postoperative period. The diagnosis of SSI was made based on the Centers for Disease and Control (CDC) guidelines. Results: We recruited 124 patients for this study, 62 males and 54 females. The mean age of the subjects was 37.5 years (SD = 14.7 years). Sixty-two subjects were randomized into each group. There was no significant difference in the distribution of the genders in the study arms. Other possible confounders such as duration of hospital stay, use of drains, the surgeon involved and age were evenly distributed in the two groups. Eight patients did not complete the study. The overall incidence of SSI in the study was 2.6%. Subjects in the control group had an SSI of 3.4% while those in the PI-PI group had a rate of 1.8%; however, this was not significant, p = 0.579. Conclusion: Both CG-A How to cite this paper: Okoro, K.A., Ede, O., Enweani, U.U., Iyidobi, E.C., Nwadinigwe, C.U., Eyichukwu, G.O., Anyaehie, U.E., Ahaotu, F.N. and Ezeh, R.C. (2019) The Antiseptic Efficacy of Povidone-Iodine in Reducing Early Surgical Site Infections in Orthopaedic Implant Surgeries. Journal of Biosciences and Medicines, 7, 9-18. https://doi.org/10.4236/jbm.2019.79002 Received: August 5, 2019 Accepted: August 27, 2019 Published: August 30, 2019 Copyright © 2019 by author(s) and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Surgical site infection (SSI) is infection occurring within the surgical wounds, or within organs entered or manipulated during the surgical procedure, within 30 days after surgery or within one year if an implant is used and left in-situ [1].
The Centers for Disease and Control (CDC) has classified SSI into incisional and organ/space infection, with the former further subdivided into superficial and deep [1]. Incisional SSI is the most common type with most infection occurring within 30 days, peaking within the 5 th to 10 th postoperative period. The worldwide incidence of SSI is between 2.6% and 41.9% [2]. In Nigeria, the rate of SSI in Orthopaedic surgeries ranges from 4.6% to 16.7% [3]- [9].
Surgical site infections increase patients' morbidity and mortality. It increases the overall cost of the patient's care. These costs are incurred through increased lengths of hospital stay, prices of materials for wound care, pharmacy costs for antibiotics, increased outpatient and emergency room visits, diagnostic laboratory studies, reoperation rate, and physician expenses. Mortality can result from septicaemia and multiple organ failure or indirect consequence of prolonged admission, such as pulmonary embolism. The annual cost of treating SSI in the United States is $10 billion [10]. In Australia, the conservative estimate of annual direct healthcare costs of treating superficial wound complications following prosthetic joint replacement is $34 million [11].
Preoperative skin antisepsis has been shown to reduce the epidermal bacterial load [12]. Their routine use in surgery has been recommended by professional and public health organizations including the Royal College of Surgeons of England, National Institute for Health and Care Excellence (NICE) and the United States Centre for Disease Control and Prevention (CDC) [13] [14] [15]. The three main preoperative skin antiseptics are iodine or iodophor, alcohol, and aqueous or alcoholic chlorhexidine gluconate [15]; however, the question of which is superior is still unresolved, with studies giving conflicting results. At our institution, we routinely use a combination of 4% Chlorhexidine Gluconate and 70% Isopropyl alcohol to prepare our skin site. We intend to compare the antiseptic efficacy of a combination of 7.5% Povidone Iodine and 10% Povidone Iodine to our routine antiseptic combination. Journal of Biosciences and Medicines South-East Nigeria, from November 2017 to October 2018. It is a tertiary hospital and regional centre for Orthopaedics and Trauma. Ethical approval was obtained from the hospital's Research, Ethics and Training Committee under IRB/HEC number S.313/IV and protocol number 942. Written informed consent was obtained from the patients recruited for the study. The minimum sample size for the study was determined using the formula to compare two independent proportions as shown [16]: Blocking was first done on the type of surgery. The surgery was divided into arthroplasty, spine surgery, trauma and others. From within each block, randomization was done to either the control group (CG-A) or the test group (PI-PI).
We used the random number generator application downloaded from Google play store. If an even number is generated, the subject is allocated to the control group. If an odd number is generated, the participant is allocated to the test group. Whenever a subject from a block is allocated to a treatment group, the next subject from the same block is automatically allocated to the other group.
The operative area, in the control group, was scrubbed with 4% Chlorhexidine gluconate in water for 5 minutes, dried and then painted with 70% isopropyl alcohol, which is allowed to air dry. In the test group, scrubbing was with 7.5% Povidone-iodine for 5 minutes, and then 10% Povidone-iodine was then used to paint the skin. The hospital's pharmacy department provided both antiseptics.
Prophylactic antibiotic (Intravenous Ceftriaxone 1 g) was given at induction of anaesthesia in both groups and tourniquet, where applicable, was applied ten minutes after antibiotics were given.
Postoperatively, two further courses of Ceftriaxone were given, consistent with the hospital's protocol. Drains, if used, were removed when the wound drain is less than 50 mls the previous day. Two designate senior registrars who were blinded to the treatment group of the subject, inspected the wounds for signs of SSI on the 3rd, 7th and 14th postoperative days, and on the 6th and 12th postoperative week. However, if there is a suspicion of SSI, the wound was examined immediately, and swabs were taken for microscopy, culture and sensitivity analysis and appropriate protocol of wound care commenced. Other postoperative protocols, including analgesia, anticoagulation and physiotherapy were identical in both groups. Skin reactions were also monitored in both groups. Chi-square analysis was used to test for significant differences in the rate of SSI in the two groups. It was also used to test for any difference in the incidence of cofounding variables between the two groups. All the tests were 2-tailed, and a p-value less than 0.05 was considered significant.

Results
There were 62 males (53.4%) and 54 females (46.6%). Table 1 shows the sex distribution across the study groups with a male: female ratio of 1.14:1. Eight patients did not complete the study, three from CG-A arm (two patients were lost to follow up, one had a breach of asepsis intraoperatively) and five from PI-PI division (three patients were lost to follow up, one had a violation of asepsis intraoperatively, and one died before completion of the 90-day follow up). Thus, 116 patients completed the study, 59 in the CG-A arm and 57 in in the PI-PI group.
The age of the patients ranged from 18 -68 years. There was no significant difference in the mean age of the study groups, p = 0.16. The preoperative and postoperative duration of admission in the two groups does not differ significantly. Table 2  The overall incidence of SSI in this study was 2.6% (three cases only), see Ta     Adverse skin reactions occurred in six patients (10.5%) of the PI-PI group and were not seen in the CG-A group. There were four cases of rashes around the wound, one blister and one erythema associated with pruritus. All resolved by the third week following surgery.

Discussion
This work has shown that there is no difference in the efficacy of both Chlorhexidine Gluconate-Alcohol combination and Iodophor combination in reducing early SSI. We limited our selection to clean Orthopaedic surgeries were an implant is used. We also blocked on type of surgery, which we believe can influence the incidence of SSI. From the results, it can also be seen that other possible confounding variables were evenly distributed in the two groups. The reason is to minimize the influence of these external factors on the observed response.
Aurobinda et al. [18] compared the efficacy of 4% CG-4% CG and 7.5% PI-10% PI in preventing SSI in 420 elective orthopaedic procedures. It was a multicentre prospective study with similar inclusion and exclusion criteria that divided the cases into two equal study groups; the patients were followed up for three weeks. The SSI rate in the PI-PI group was 12.3%, which is higher than the 1.8% reported in this study. The higher rate may be attributed to the multicentred nature of the study with variations in perioperative protocols. Also, the level of expertise of the surgeons was not stated in the research.
Another close study conducted by Paocharoen et al. [17] on a subset of 183 participants who underwent clean elective foot and ankle surgeries, and followed up for one month, reported SSI rates of 2.1% and 5.7% in the 4% CG/70% Isopropyl alcohol and 7.5% PI/10% PI groups respectively. These SSI rates are closer to those obtained in this study. Similarly, there was no significant difference between these rates, 95% CI [0.55 to 13.86].
In another related study, Saltzman et al. [19]  Darouiche et al. [21] reported an SSI rate of 9.5% even though 2% CG was used K. A. Okoro et al.
for skin preparation and the subjects recruited underwent clean contaminated abdominal and thoracic surgeries.
Conversely, Swenson et al. [20] documented an SSI rate of 0.84% when 10% PI was used as skin preparation in clean general surgery cases. This is similar to the SSI rate of 1.8% noted in the PI-PI arm of this study. Darouiche et al. [21] reported a 16.1% rate of SSI following 10% PI skin preparation for clean-contaminated surgeries while Srinivas et al. [22] recorded an SSI rate of 17.9%. In the latter study, however, 0.5% PI was used for skin preparation, and the patients had elective clean-contaminated upper abdominal surgeries. The inclusion of only clean surgeries as opposed to clean contaminated may have been responsible for the lower SSI rates found in this study.
The overall incidence of SSI in this study was 2.6%, which is higher than the accepted standard of less than 1% [23]. This is similar to the SSI rate of 3.0% reported by Ogugua et al. [24] in the same institution. This is lower than that obtained from other local studies by Onche et al. [4], Madu [7], and Ngim et al. [25] who documented SSI rates of 7.5%, 9.3%, and 9.38% respectively following orthopaedic implant surgeries. In another third world country, Amaradeep et al. [20] and Sunnet et al. [26] recorded higher rates of 4.44% and 6.89% respectively for elective orthopaedic implant surgeries. The difference in study methodologies, surgical setups, facilities and endpoints may have accounted for the variance in the SSI rates documented in these studies.
Adverse skin reactions occurred in 6 patients (10.5%) in the PI-PI study arm while none were observed in the CG-Alcohol study arm. These were judged to be related to study solution, and they manifested as erythema and bullae around the surgical wound. There were no cases of fire, chemical or diathermy skin burns in the theatre. Daroiuche et al. [21] reported similar events (pruritus, erythema, or both around the surgical wound) in the 0.7% of patients who had skin preparation with 10% Povidone Iodine. However, there were no such adverse events reported by Srinivas et al. [22], who used 5% Povidone-iodine as the study skin preparation solution. This may have been because a lower concentration of PI was used, although this requires further validation. In the same study, there were no such events following CG-Alcohol application even though the concentration of CG was 0.5%.

Conclusion
There is no significant difference in the risk of SSI with either Chlorhexidine Gluconate-Alcohol combination or Iodophor combination antiseptic in clean orthopaedic implant surgery. Skin preparation for clean orthopaedic implant surgeries should be done with either of the two while factoring the risk of adverse skin reaction reported with Povidone-Iodine solution.

Funding
The hospital management provided a financial grant for this work.