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.).

It is not always chlorhexidine: Identification of benzoxonium chloride and lauramine oxide as culprit allergens in a popular antiseptic in Switzerland.

BACKGROUND: A popular antiseptic spray in Switzerland (Merfen spray), containing chlorhexidine digluconate, benzoxonium chloride and lauramine oxide, is frequently used to treat skin wounds. However, it is also increasingly reported as a major cause of adverse skin reactions, including allergic contact dermatitis (ACD). OBJECTIVES: To investigate the contact allergens responsible for ACD from this antiseptic. PATIENTS/METHODS: Patch tests were performed on seven patients with a clinical history compatible with contact dermatitis from this antiseptic mixture. RESULTS: All patients presented with acute eczematous reactions following contact with either Merfen spray alone, or with multiple products including this spray. Patients showed positive reactions to this product in both patch tests and repeated open application tests (ROATs). Four patients showed dose-dependent reactions to both benzoxonium chloride and lauramine oxide. One patient showed a dose-dependent reaction to the former and a non-dose-dependent reaction to the latter. Finally, two subjects showed responses only to lauramine oxide. One patient reacted to chlorhexidine digluconate 0.5% aq. in addition to both other allergens. CONCLUSIONS: Two commercially unavailable allergens, that is, benzoxonium chloride and/or lauramine oxide were identified as major causes of ACD from Merfen antiseptic spray, whereas chlorhexidine digluconate was a contributing culprit in only one patient.

Combating chlorhexidine allergy in perioperative setting.

Chlorhexidine is labelled as hidden allergen as the health care professionals (HCPs) are unaware of the wide range of products containing chlorhexidine. Adverse events from chlorhexidine allergy can be reduced by appropriate perioperative management especially heeding on positive history during preoperative assessment, awareness regarding this hidden allergen, and educating HCPs on possible chlorhexidine-containing products. The regulatory agencies all over the world have issued recommendations regarding safety and risk of hypersensitivity reactions with chlorhexidine-containing products. The onus lies on HCPs to disseminate this knowledge to the stakeholders. We present a brief update to combat chlorhexidine allergy in perioperative setting.

Effects and Safety of Different Silver Preparation in Burns Treatment: A Bayesian Network Meta-analysis.

Silver formulation has been used for external use of burn wounds for several decades, mainly including silver sulfadiazine (SSD), nanosilver dressing (NSD), and silver ion dressing (SID). At present, there is no simultaneous comparison of the effects of silver formulation on burn wounds. The databases were retrieved in an orderly manner from the dates of their establishment to May 2020, including PubMed, the Cochrane Library, Web of Science, and Clinical Trials. Then a network meta-analysis was conducted using R and RevMan 5.1 software. A total of 13 randomized controlled trials (RCTs) involving 945 patients with burns were included. A pairwise meta-analysis of the results was presented: the wound healing time in the SID or NSD treatment group was less than that in the SSD group; and in relieving the pain there was a statistical difference between the SSD, SID, or NSD groups. Network meta-analysis of the results was presented: the wound healing time and relieving the pain in the SID or NSD treatment group were less than that in the SSD group, but there was no statistical difference between the SID and NSD groups. The possibility of NSD in the wound healing time being the best treatment was 75.2%, followed by SID (36.6%), and finally SSD (1.1%); and the possibility of NSD being the best relieving the pain was 83.5%; followed by SID (60.0%), and finally SSD (16.3%). According to the evidence, treatment for burns with NSD can improve the wound healing time and relieve the pain of wounds.

Allergic contact dermatitis to chlorhexidine-containing antiseptics and their excipients in children: A series of six cases.

Contact allergy to skin disinfectants is not often recognized in children. We report the cases of six children (1-16.5 years old) with allergic contact dermatitis to ingredients commonly contained in commercial antiseptic and cosmetic products. Patch test responses to chlorhexidine, benzyl alcohol, and benzalkonium chloride varied from one child to another one, but most children were sensitized to at least two components. In several of the cases, exposure had initially occurred in the neonatal period, but diagnosis occurred only after multiple reactions of increasing severity.

Triclosan and Its Consequences on the Reproductive, Cardiovascular and Thyroid Levels.

Hygiene is essential to avoid diseases, and this is thanks to daily cleaning and disinfection habits. Currently, there are numerous commercial products containing antimicrobial agents, and although they are efficient in disinfecting, it is still not known the effect of the constant use of these products on human health. In fact, a massive use of disinfectants has been observed due to COVID-19, but the possible adverse effects are not yet known. Triclosan is one of the antimicrobial agents used in cosmetic products, toothpaste, and disinfectants. This compound is an endocrine disruptor, which means it can interfere with hormonal function, with its estrogenic and androgenic activity having already been stated. Even if the use of triclosan is well-regulated, with the maximum allowed concentration in the European Union of 0.3% (m/m), its effects on human health are still uncertain. Studies in animals and humans suggest the possibility of harmful health outcomes, particularly for the reproductive system, and in a less extent for the cardiovascular and thyroid functions. Thus, the purpose of this review was to analyse the possible implications of the massive use of triclosan, mainly on the reproductive and cardiovascular systems and on the thyroid function, both in animals and humans.

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.

Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available.

Should oral chlorhexidine remain in ventilator-associated pneumonia prevention bundles? / ¿Debe permanecer la clorhexidina oral en los paquetes de prevención de la neumonía asociada al respirador?

Ventilator-associated pneumonia (VAP) is related with high mortality, duration of mechanical ventilation and costs. Recent studies have questioned the safety and effectiveness of oral chlorhexidine to prevent VAP. We sought to verify whether the adverse effects of this substance outweigh its benefits. We searched several databases and selected studies that investigated the use of oral chlorhexidine and its impact on mortality. No association between oral chlorhexidine and lower VAP rates was found on meta-analyses of double-blind randomized trials, however significant increase in mortality was reported. It is speculated that chlorhexidine can cause damage to several organic sectors and cytotoxicity. Although it still can be beneficial in specific settings, robust evidence to recommend its routine application for all mechanically ventilated patients is lacking; therefore, given the possibility of harm, it would be better to follow the principle of non-maleficence until more studies becomes available (AU)

La neumonía asociada al respirador (VAP) está relacionada con una elevada mortalidad, mayor duración de la ventilación mecánica y costes elevados. Estudios recientes han cuestionado la seguridad y la eficacia de la clorhexidina oral para prevenir la VAP. Hemos intentado verificar si los efectos adversos de esta sustancia superan sus beneficios. Se realizaron búsquedas en diversas bases de datos y se seleccionaron estudios que habían investigado el uso de la clorhexidina oral y su impacto sobre la mortalidad. En los metaanálisis de los ensayos aleatorizados a doble ciego no se encontró ninguna asociación entre clorhexidina oral y tasas de VAP más bajas; sin embargo, sí se informó de un aumento significativo de la mortalidad. Se especula que la clorhexidina puede causar daño a varias partes del organismo y citotoxicidad. Pese a que todavía podría ser beneficiosa en entornos específicos, no se dispone de evidencias sólidas para recomendar su aplicación rutinaria para todos los pacientes sometidos a ventilación mecánica; por lo tanto, dada la posibilidad de ocasionar daños, sería mejor seguir el principio de no maleficencia hasta que se disponga de más estudios (AU)

Effect of vaginal antiseptic prior to caesarean section on the rate of post-caesarean complications: a blinded randomised controlled trial.

BACKGROUND: Rates of caesarean section (CS) delivery are increasing worldwide. CS delivery is often complicated by post-surgical infection, estimated to have ten times higher risk of infections than that of vaginal delivery. While widespread use of prophylactic antibiotics with CS has reduced post-CS infection, incidence may be reduced further by cleansing the vagina with betadine antiseptic wash prior to CS. However, reports are not consistent, and different antiseptics have been practised variably. Therefore, in order to ensure that the risks to the mother are as minimal as possible, it is important to determine whether vaginal irrigation with antiseptic wash reduces post-CS infection rate, and if so, which antiseptic is paramount. METHODS: Women giving birth by elective or emergency CS will be assigned into either the intervention (1% povidone iodine (n = 125) or chlorhexidine (n = 125)) or the control (no-irrigation (n = 125)) group by using a block randomisation technique. Participants will receive vaginal cleansing with an intervention or no vaginal cleansing prior to CS. Follow-up will occur at day 14 and day 28 post-CS. A predeveloped questionnaire will be completed with patients' socio-demographic characteristics and required clinical and pregnancy-related information. All the fever, infection and readmission-related information will be completed from either the patient's or their record or at follow-up visits. Occurrence of post-CS infection, as measured by primary and secondary outcomes, will be compared between the groups. DISCUSSION: The results of this study may provide important data to define the future uniform use of vaginal antiseptic wash immediately prior to CS and to determine the best antiseptic wash details in reducing post-operative infections or complications. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620000971932p . Registered on 28 September 2020.

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.

Treatment of Impetigo with Antiseptics-Replacing Antibiotics (TIARA) trial: a single blind randomised controlled trial in school health clinics within socioeconomically disadvantaged communities in New Zealand.

BACKGROUND: Impetigo is a common and contagious bacterial skin infection, affecting children worldwide, but it is particularly prevalent in socioeconomically disadvantaged communities. In New Zealand, widespread prescribing of the topical antibiotic fusidic acid had led to an increase in antimicrobial resistance of Staphylococcus aureus. Alternative treatments are urgently being sought, and as impetigo is a superficial infection, it has been suggested that topical antiseptics such as hydrogen peroxide or simple wound care alone may treat impetigo while avoiding the risk of increased antimicrobial resistance. METHODS: This protocol for a non-inferiority, single-blind randomised controlled trial compares topical fusidic acid with topical hydrogen peroxide and with simple wound care in the treatment of childhood impetigo. Participants are randomised to one of the three treatments for 5 days. The primary outcome is clinical improvement assessed through paired photographs analysed by graders blinded to treatment arm. The trial is based in school health clinics in an urban centre in New Zealand. Comparison of antimicrobial resistance patterns pre- and post-treatment is also performed. DISCUSSION: Special note is made of the need to involve the communities most affected by impetigo in the design and implementation of the clinical trial to recruit the children most in need of safe and effective treatments. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) 12616000356460 . Registered on March 10, 2016  Protocol amendment number: 05 EB and AL contributed equally as senior authors.

Multiple cases of sensitization to an antiseptic containing chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol with different profiles of sensitization in adults and children.

BACKGROUND: An aqueous antiseptic containing "chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol" (CBB) is widely used in France. The only previous documented study dealing with allergic contact dermatitis (ACD) to this antiseptic is one small case series in children. The French Vigilance Network for Dermatology and Allergy (REVIDAL-GERDA) has collected many cases in the last few years. OBJECTIVES: To evaluate the clinical and sensitization profiles of patients diagnosed with ACD to CBB. METHODS: We performed a retrospective study of patients with contact dermatitis to CBB and positive tests to CBB and/or at least one of its components. All patients had to be tested with all components of CBB. RESULTS: A total of 102 patients (71 adults and 31 children) were included. The lesions were extensive in 63% of patients and 55% had delayed time to diagnosis. CBB patch tests were positive in 93.8% of cases. The allergen was identified in 97% of patients, mainly benzyl alcohol in adults (81.7%) and chlorhexidine digluconate in children (54.8%). About 32.4% of the patients were sensitized to several components. CONCLUSION: CBB is a cause of ACD at all ages. The components of the antiseptic should be tested. The sensitization profile seems to be different between adults and children.

Review of allergic reactions from use of chlorhexidine on medical products in clinical settings over 40 years: Risks and mitigations.

Chlorhexidine is an antimicrobial agent widely used for infection prevention in medical settings. Nevertheless, allergic reactions ranging from mild to severe have been reported following its use. In this review, we analyzed all case reports published between the introduction of chlorhexidine and the end of 2019 for allergic responses associated with the use of medical devices and or other medical products containing chlorhexidine (CHX) to ascertain the prevalence of severe CHX allergic reactions and what practices might best mitigate those risks.In total, 77 publications containing 124 reported cases of allergic reactions were grouped into 3 product categories, catheters, semisolids, and fluid products. The country, type of reaction, route of sensitization, allergy confirmation, and intervention or mitigation was extracted for each case. Overall, 30 cases were associated with catheters, 46 cases were associated with semisolid products, and 48 cases were associated with the use of other medical products. Severe cases were managed with intravenous fluids, steroids, and epinephrine (adrenaline). None of the reported cases were fatal. The allergy risks can be mitigated by better warning and training clinicians and by recording and screening patient histories for CHX presensitization from prior exposure. For patients undergoing pre-use blood tests, IgE antibody screens can also be performed. Finally, as a precaution in the event a rare severe allergic reaction occurs, procedure carts and rooms can be prestocked with injectable epinephrine and other rapidly acting anti-inflammatory medications.