General skin and nasal decolonization with octenisan® set before and after elective orthopedic surgery in selected patients at elevated risk for revision surgery and surgical site infections-a single-center, unblinded, superiority, randomized controlled trial (BALGDEC trial).

BACKGROUND: The preoperative body surface and nasal decolonization may reduce the risk of surgical site infections (SSI) but yields conflicting results in the current orthopedic literature. METHODS: We perform a single-center, randomized-controlled, superiority trial in favor of the preoperative decolonization using a commercial product (octenidine® set). We will randomize a total number of 1000 adult elective orthopedic patients with a high risk for SSI and/or wound complications (age ≥ 80 years, chronic immune-suppression, American Society of Anesthesiologists score 3-4 points) between a decolonization (octenisan® wash lotion 1 × per day and octenisan® md nasal gel 2-3 × per day; during 5 days) and no decolonization. Decolonized patients will additionally fill a questionnaire regarding the practical difficulties, the completeness, and the adverse events of decolonization. The primary outcomes are SSI and revision surgeries for postoperative wound problems until 6 weeks postoperatively (or 1 year for surgeries with implants or bone). Secondary outcomes are unplanned revision surgeries for non-infectious problems and all adverse events. With 95% event-free surgeries in the decolonization arm versus 90% in the control arm, we formally need 2 × 474 elective orthopedic surgeries included during 2 years. DISCUSSION: In selected adult orthopedic patients with a high risk for SSI, the presurgical decolonization may reduce postoperative wound problems, including SSI. TRIAL REGISTRATION: ClinicalTrial.gov NCT05647252. Registered on 9 December 2022. PROTOCOL VERSION: 2 (5 December 2022).

Continuous Corneal Endothelial Damage by Chlorhexidine Alcohol Used for Disinfection in Nonophthalmic Surgery.

PURPOSE: To report a case of corneal endothelial damage caused by alcohol-containing chlorhexidine gluconate (CG-A) and its progression over time. METHODS: This was a case report. RESULTS: A 22-year-old man underwent neurosurgery under general anesthesia. CG-A (1%) was used for disinfection after the application of corneal protection tape. Postoperatively, the patient presented with hyperemia and swelling of the left conjunctiva and was referred to our department. Initial examination revealed left corneal epithelial erosion and corneal edema, which improved on postoperative day 14. The corneal endothelial cell density (ECD) was 3,345 cells/mm 2 on day 14, decreased rapidly to 2,090 cells/mm 2 on day 42, and slowly reduced to 1,122 cells/mm 2 on day 168. Thereafter, no decrease in ECD was observed. CONCLUSIONS: CG formulations can lead to a persistent decrease in ECD over several months, even after improvement of acute corneal edema.

Skin Antisepsis before Surgical Fixation of Extremity Fractures.

BACKGROUND: Studies evaluating surgical-site infection have had conflicting results with respect to the use of alcohol solutions containing iodine povacrylex or chlorhexidine gluconate as skin antisepsis before surgery to repair a fractured limb (i.e., an extremity fracture). METHODS: In a cluster-randomized, crossover trial at 25 hospitals in the United States and Canada, we randomly assigned hospitals to use a solution of 0.7% iodine povacrylex in 74% isopropyl alcohol (iodine group) or 2% chlorhexidine gluconate in 70% isopropyl alcohol (chlorhexidine group) as preoperative antisepsis for surgical procedures to repair extremity fractures. Every 2 months, the hospitals alternated interventions. Separate populations of patients with either open or closed fractures were enrolled and included in the analysis. The primary outcome was surgical-site infection, which included superficial incisional infection within 30 days or deep incisional or organ-space infection within 90 days. The secondary outcome was unplanned reoperation for fracture-healing complications. RESULTS: A total of 6785 patients with a closed fracture and 1700 patients with an open fracture were included in the trial. In the closed-fracture population, surgical-site infection occurred in 77 patients (2.4%) in the iodine group and in 108 patients (3.3%) in the chlorhexidine group (odds ratio, 0.74; 95% confidence interval [CI], 0.55 to 1.00; P = 0.049). In the open-fracture population, surgical-site infection occurred in 54 patients (6.5%) in the iodine group and in 60 patients (7.3%) in the chlorhexidine group (odd ratio, 0.86; 95% CI, 0.58 to 1.27; P = 0.45). The frequencies of unplanned reoperation, 1-year outcomes, and serious adverse events were similar in the two groups. CONCLUSIONS: Among patients with closed extremity fractures, skin antisepsis with iodine povacrylex in alcohol resulted in fewer surgical-site infections than antisepsis with chlorhexidine gluconate in alcohol. In patients with open fractures, the results were similar in the two groups. (Funded by the Patient-Centered Outcomes Research Institute and the Canadian Institutes of Health Research; PREPARE ClinicalTrials.gov number, NCT03523962.).

A pragmatic randomized trial evaluating pre-operative aqueous antiseptic skin solutions in open fractures (Aqueous-PREP): statistical analysis plan.

BACKGROUND: Approximately 1 in 10 patients with a surgically treated open fracture will develop a surgical site infection. The Aqueous-PREP trial will investigate the effect of 10% povidone-iodine versus 4% chlorhexidine in aqueous antiseptic solutions in reducing infections after open fracture surgery. The study protocol was published in April 2020. METHODS AND DESIGN: The Aqueous-PREP trial is a pragmatic, multicenter, open-label, randomized multiple period cluster crossover trial. Each participating cluster is randomly assigned in a 1:1 ratio to provide 1 of the 2 study interventions on all eligible patients during a study period. The intervention periods are 2 months in length. After completing a 2-month period, the participating cluster crosses over to the alternative intervention. We plan to enroll a minimum of 1540 patients at 14 sites. RESULTS: The primary outcome is surgical site infection guided by the Centers for Disease Control and Prevention's National Healthcare Safety Network reporting criteria (2017). All participants' surgical site infection surveillance period will end 30 days after definitive fracture management surgery for superficial infections and 90 days after definitive fracture management surgery for deep incisional or organ/space infections [1]. The secondary outcome is an unplanned fracture-related reoperation within 12 months of the fracture. CONCLUSION: This manuscript serves as the formal statistical analysis plan (version 1.0) for the Aqueous-PREP trial. The statistical analysis plan was completed on February 28, 2022.

Evidence-based review of chlorhexidine gluconate and iodine in the preoperative skin preparation of young infants.

PURPOSE: The preoperative preparation of young infants' skin requires special considerations. Commonly used solutions for preparing the skin preoperatively include chlorhexidine (CHG) and iodine. The Centers for Disease Control and Prevention (CDC) has recommendations for preparing skin for surgery and other invasive procedures for adults, but they do not have recommendations for young infants' skin. The purpose of this evidence-based literature review is to synthesize the literature, compare, and inform healthcare providers about the safety and efficacy of CHG and iodine as preoperative preparation solutions for young infants' skin. For this project young infants is defined as infants less than 48 weeks' postmenstrual age and those born prematurely and less than 28 days old. CONCLUSIONS: We analyze 19 articles that met the inclusion criteria. Three discussion themes emerge: systemic absorption, dermatologic burns, and CHG and iodine efficacy. PRACTICE IMPLICATIONS: We need more research regarding the safety and efficacy of CHG and iodine solutions for preoperative preparation of young infants' skin. Findings suggest the cautious use of CHG and iodine solutions on patients born at or before 28 weeks' postmenstrual age, especially those less than 28 days postnatal age.

Chlorhexidine in Dentistry: Pharmacology, Uses, and Adverse Effects.

OBJECTIVES: The aim of this work was to review the current uses of chlorhexidine (CHX) in dentistry based on its mechanism of action, whilst highlighting the most effective protocols that render the highest clinical efficacy whilst limiting adverse drug reactions. METHODS: A literature search was conducted using the key words chlorhexidine, mechanism of action, adverse effects, and dentistry using databases in the University of Toronto library system. The titles and abstracts were read, and relevant articles were selected. RESULTS: A total of 1100 publications were identified, 100 were investigated, and 67 of them were used. Out of the 67 selected articles, 12 were reviews on CHX; 5 articles focussed on CHX gels; 13 focussed on CHX mouthwashes; 8 focussed on CHX products; 13 discussed adverse effects associated with CHX; 13 focussed on periodontal pathology and treatment; 6 focussed on implant periodontal and dental surgeries; 7 evaluated effects on caries; 6 looked at the mechanisms of action; and 12 focussed on the antibacterial and antimicrobial impact on the oral biome. There were multiple areas of overlap amongst the articles, and results showed that CHX provides different uses, but mainly as an adjunct to various treatments. Mouthwash was the most superior medium when used in short time spans when mechanical prophylaxis was not possible for the prevention of gingivitis and maintenance of oral hygiene. CHX products are often used in periodontics, post-oral surgical procedures, and as a prophylaxis for multiple invasive procedures with minimal adverse effects. Tooth staining was the most negative adverse effect reported by patients. CONCLUSIONS: CHX's antimicrobial properties make it an ideal prophylactic when mechanical debridement is not possible. CHX mouthwash appears to be more effective compared to gels. Concentrations of 0.12% to 0.2% are recommended; any mouthwash with concentrations above 0.2% will unnecessarily increase the unwanted side effects. CHX is useful amongst various areas of dentistry including oral surgery, periodontics, and even general dentistry. For long-term treatments, especially in periodontitis patients (stage I-III) undergoing nonsurgical treatments, CHX chips are recommended. CHX chips are also recommended as an adjunct to implant debridement in patients with peri-implant mucositis and peri-implantitis over CHX mouthwash and gels.

Compounded Cerium Nitrate-Silver Sulfadiazine Cream is Safe and Effective for the Treatment of Burn Wounds: A Burn Center's 4-Year Experience.

Wound infections and sepsis are significant causes of morbidity after burn injury and can be alleviated by early excision and grafting. In situations that preclude early surgery, topical agents allow for a safer delay. Cerium nitrate compounded with silver sulfadiazine (Ce-SSD) is a burn cream that provides broad antibacterial activity, forms a temporary barrier, and promotes re-epithelialization. Methemoglobinemia is a rare, but oft-cited, systemic complication of Ce-SSD. In this retrospective review, 157 patients treated with Ce-SSD between July 2014 and July 2018 were identified, and the monitoring protocol for methemoglobinemia during Ce-SSD treatment was evaluated. The median age was 59 years (interquartile range [IQR], 47-70.5 years), with TBSA of 8.5% (IQR, 3-27), adjusted Baux score of 76 (IQR, 59-94), and inhalation injury present in 9.9% of patients. Primary endpoints included incidence of symptomatic and asymptomatic methemoglobinemia. Of the 9.6% (n = 15) of patients with methemoglobinemia, 73.3% (n = 11) had maximum methemoglobin levels ≥72 hours from the time of the first application. One patient developed clinically significant methemoglobinemia. Patients with TBSA ≥20% were more likely to develop methemoglobinemia (odds ratio 9.318, 95% confidence interval 2.078-65.73, P = .0078); however, neither Ce-SSD doses nor days of exposure were significant predictors. Ce-SSD application to temporize burn wounds until excision and grafting is safe, effective, and, in asymptomatic patients with TBSA <20%, can be used without serial blood gas monitoring. Vigilant monitoring for symptoms should be performed in patients with TBSA ≥20%, but routine blood gases are not necessary.

Implants and Breast Pocket Irrigation: Outcomes of Antibiotic, Antiseptic, and Saline Irrigation.

BACKGROUND: Breast implant-associated infection and capsular contracture are challenging complications that can result in poor outcomes following implant-based breast surgery. Antimicrobial irrigation of the breast pocket or implant is a widely accepted strategy to prevent these complications, but the literature lacks an evidence-based consensus on the optimal irrigation solution. OBJECTIVES: The objective of this systematic review was to compare clinical outcomes, specifically capsular contracture, infection, and reoperation rates, associated with the use of antibiotic, antiseptic, and saline irrigation. METHODS: A systematic review was performed in March 2020 based on the following search terms: "breast implant," "irrigation," "antibiotic," "bacitracin," "antiseptic," "povidone iodine," "betadine," "low concentration chlorhexidine," and "hypochlorous acid." Capsular contracture, infection, and reoperation rates were compared by analysis of forest plots. RESULTS: Out of the 104 articles screened, 14 met the inclusion criteria. There was no significant difference in capsular contracture rates between antibiotic and povidone-iodine irrigation, although the data comparing these 2 groups were limited and confounded by the concurrent use of steroids. Antibiotic irrigation showed a significantly lower rate of capsular contracture compared with saline irrigation and a lower rate of capsular contracture and reoperation compared with no irrigation at all. Povidone-iodine was associated with lower rates of capsular contracture and reoperation compared with saline irrigation but there were no data on infection rates specific to povidone-iodine irrigation. CONCLUSIONS: Our study supports the use of antibiotics or povidone-iodine for breast implant irrigation. Further research is required to better determine which of these 2 irrigation types is superior.

Suppressive activity of RGX-365 on HMGB1-mediated septic responses

Abstract RGX-365 is the main fraction of black ginseng conmprising protopanaxatriol (PPT)-type rare ginsenosides (ginsenosides Rg4, Rg6, Rh4, Rh1, and Rg2). No studies on the antiseptic activity of RGX-365 have been reported. High mobility group box 1 (HMGB1) is recognized as a late mediator of sepsis, and the inhibition of HMGB1 release and recovery of vascular barrier integrity have emerged as attractive therapeutic strategies for the management of sepsis. In this study, we examined the effects of RGX-365 on HMGB1-mediated septic responses and survival rate in a mouse sepsis model. RGX-365 was administered to the mice after HMGB1 challenge. The antiseptic activity of RGX-365 was assessed based on the production of HMGB1, measurement of permeability, and septic mouse mortality using a cecal ligation and puncture (CLP)-induced sepsis mouse model and HMGB1-activated human umbilical vein endothelial cells (HUVECs). We found that RGX-365 significantly reduced HMGB1 release from LPS- activated HUVECs and CLP-induced release of HMGB1 in mice. RGX-365 also restored HMGB1-mediated vascular disruption and inhibited hyperpermeability in the mice. In addition, treatment with RGX-365 reduced sepsis-related mortality in vivo. Our results suggest that RGX- 365 reduces HMGB1 release and septic mortality in vivo, indicating that it is useful in the treatment of sepsis.

Examination of the efficacy of olanexidine gluconate for surgical site infections in colorectal cancer elective surgery.

INTRODUCTION: The preoperative skin antiseptic, olanexidine gluconate (OLG), which has been available in Japan since 2015, is also known to be effective against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and Pseudomonas aeruginosa. This study attempted to clarify OLG efficacy against surgical site infections and antiseptic-related adverse events as compared to conventionally used povidone iodine (PVP-I). METHODS: Propensity score matching was performed on 307 patients who underwent surgery for colorectal tumors at our hospital. All 116 cases (58 PVP-I cases, 58 OLG cases) who were diagnosed with colorectal cancer were included. We examined surgical site infection rate after disinfection using PVP-I and OLG, length of hospitalization stay (days) after surgery, adverse events associated with antiseptics, and additional medical costs associated with adverse events caused by antiseptics. RESULTS: The surgical site infection rate was 8.6% in both the PVP-I and OLG groups, with no significant difference observed. The number of postoperative hospitalization days in the PVP-I group was 12.9 (±6.9) days and 16.4 (±14.6) days in the OLG group, which exhibited no significant difference (p = 0.10). Although no complications due to antiseptics were observed in the PVP-I group, skin-related side effects were observed in 8 patients (13.8%) in the OLG group. The median additional medical cost was 730 [120-1823] yen. CONCLUSIONS: OLG was as effective as the conventional PVP-I for surgical site infections during colorectal cancer elective surgery. However, significantly higher skin disorders occurred in OLG, thereby making it necessary to evaluate antiseptic use in conjunction with patient burden.

In vitro and in vivo estrogenic activity of triclosan.

Triclosan (TCS) is an antibacterial and antifungal agent used in many consumer products and exhibits a chemical structure similar to non-steroidal estrogen, which is known to induce endocrine disruption. Triclosan has been found in human plasma, urine, and breast milk, and the safety of TCS-containing products has been disputed. Although studies attempted to determine the estrogenic activity of TCS, no clear results have emerged. The aim of the present study was to examine estrogenic activity of TCS using an in vitro E-screen assay and an in vivo uterotrophic assay. The in vitro E-screen assay demonstrated that TCS significantly enhanced proliferation of MCF-7 breast cancer cells, although not in a concentration-dependent manner. The in vivo uterotrophic results showed no significant change in the weight of uteri obtained from TCS-administered Sprague-Dawley rats. Further, to understand the estrogenic activity attributed to TCS at the molecular level, gene-expression profiling of uterus samples was performed from both TCS- or estrogen-treated rats and the genes and cellular processes affected by TCS or estrogen were compared. Data demonstrated that both the genes and cellular processes affected by TCS or estrogen were significantly similar, indicating the possibility that TCS-mediated estrogenic activity occurred at the global transcriptome level. In conclusion, in vitro and gene-profiling results suggested that TCS exhibited estrogenic activity.

Corneal Effects of Tea Tree Oil.

PURPOSE: The purpose of this study is to report a case of corneal epithelial defects resulting from topical treatment of blepharitis with tea tree oil (TTO). METHODS: A 44-year-old man with a 1 year history of blepharitis non-responsive to eyelid hygiene was found to have signs of Demodex infestation. He was treated with a topical, off-label 50% TTO solution. Shortly afterward, the patient complained of bilateral ocular discomfort. RESULTS: Slit-lamp examination revealed conjunctival injection and a corneal epithelial defect in both eyes. Treatment with lubricant, antibiotic, and steroid eye drops as well as bandage contact lenses was required to facilitate corneal healing. CONCLUSIONS: Topical use of off-label, 50% concentration TTO can result in corneal epithelial defects. Eye care professionals should remain aware of this risk and only use approved, low-concentration TTO products when treating Demodex-related blepharitis.

Randomized clinical trial of preoperative skin preparation with 2% chlorhexidine versus conventional hair shaving in percutaneous coronary intervention.

BACKGROUND: Preoperative skin preparation is associated with surgical site infection (SSI). Traditional preoperative shaving fails to reduce the risk of SSI. The efficacy of 2% chlorhexidine for preoperative skin preparation in percutaneous coronary intervention (PCI) is sketchy. The aim of this trial was to evaluate whether preoperative skin preparation performed with chlorhexidine was not inferior to a conventional hair removal method. METHODS: Seventy-eight patients undergoing PCI were randomized into 2 groups of 39 patients, receiving either single sterilization with 2% chlorhexidine or hair shaving respectively between July 2016 and October 2016. The primary endpoints were wound infection rate and bacterial counts. Secondary endpoints were rate of SSI and adverse effects of 2% chlorhexidine. RESULTS: The results showed that 2% chlorhexidine significantly reduced the colonization of Staphylococcus aureus (P = .032), S epidermidis (P = .000), and miscellaneous bacteria (P = .244) in comparison with hair shaving, respectively. Redness in 24 hours after surgery was observed in 6 patients in the control group (15.4%) and 5 patients (12.8%) in 2% chlorhexidine group. There was no statistically significant difference in SSI rate between 2 skin preparations. CONCLUSION: In PCI, preoperative skin preparation with 2% chlorhexidine was not inferior to conventional hair shaving in terms of the wound infection rate and SSI rate.

Gas embolism after periproctal abscess incision and lavage with hydrogen peroxide a case report Should the use of hydrogen peroxide in surgery be continued?

INTRODUCTION: Hydrogen peroxide is an antiseptic solution still often used in surgical departments for lavage of wounds. Its use is nevertheless linked to an important risk of gas embolism. Such a case report has not yet been published in the Czech literature and awareness of this danger is low among surgeons. CASE REPORT: The author describes the case of gas embolism in a 40 years old patient after lavage of a periproctal abscess incision with 3% hydrogen peroxide. The lavage resulted in a cardiopulmonary arrest with the need of cardiopulmonary resuscitation. Fortunately, the patient recovered without any health consequences. CONCLUSION: In the view of important risks and questionable and insufficiently proven benefits it may be the time to possibly reconsider the use of hydrogen peroxide in surgery and replace it with a different antiseptic agent.

[Establishing Evidence for Use of Appropriate Medicines in the Operating Room].

Various issues related to clinical use of medicines remain unclear, and pharmacists are expected to establish evidence for appropriate use of medicines. The present review summarizes our findings from three areas of research regarding the use of medicines in the operating room: 1) We evaluated the extent of extravasation injury due to thiopental (2.5 mg/100 µL) and propofol (1.0 mg/100 µL) at the macroscopic and histopathologic levels in a rat model. Thiopental, which causes tissue necrosis, can be classified as a "vesicant", and propofol can be classified as an "irritant". Moreover, warming strongly exacerbated the degeneration or necrosis induced by extravasation of thiopental. 2) The cytotoxicity of povidone-iodine solution (PVP-I) for ophthalmic use and that of polyvinyl alcohol-iodine solution (PAI) was compared using a human corneal epithelial cell line. Despite exhibiting equivalent antiseptic effects, the cytotoxicity of PVP-I diluted 16-fold was greater than that of PAI diluted 6-fold. After inactivation of iodine, the cytotoxicity of PVP-I persisted; therefore, to avoid corneal damage, antisepsis should be achieved with PAI. 3) The stability of 1 µg/mL adrenaline when used as an intraocular irrigating solution to maintain pupil dilation was evaluated. After mixing for 6 h, the adrenaline concentration was 65.2% (pH 8.0) of the initial concentration. Moreover, the low concentration of sodium bisulfite in the irrigating solution could have caused adrenaline reduction. Our results strongly suggest that intraocular irrigation solution containing adrenaline should be prepared just prior to use in surgery.

How irritant are n-propanol and isopropanol? - A systematic review.

BACKGROUND: The use of alcoholic-based hand rubs (ABHRs) is an important tool for hand hygiene, especially in times of the COVID-19 pandemic. Possible irritant effects of ABHR may prevent their use by persons at risk of infection. METHODS: This systematic review is based on a PubMed search of articles published between January 2000 and September 2019 in English and German, and a manual search, related to the irritation potential of alcohol-based disinfectants restricted to n-propanol (1-propanol) and its structural isomer isopropanol (isopropyl alcohol, 2-propanol). RESULTS: The majority of the included studies show a low irritation potential of n-propanol alone. However, recent studies provide evidence for significant barrier damage effects of repeated exposure to 60% n-propanol in healthy, as well as atopic skin in vivo. The synergistic response of combined irritants, (ie, a combination of n-propanol or isopropanol with detergents such as sodium lauryl sulfate) is greater, compared with a quantitatively identical application of the same irritant alone. CONCLUSION: While recent studies indicate a higher risk of skin irritation for n-propanol and isopropanol than reported in the past, this risk still seems to be lower than that for frequent handwashing with detergents, as recommended by some to prevent COVID-19 infections.