Předoperační antisepse operačního pole a riziko anafylaxe

Súhrn

V průběhu času prokázala předoperační antisepse chirurgického místa významný pokrok jak v porozumění, tak v praktické aplikaci antiseptických postupů. Infekce chirurgického místa jsou stále jednou z nejvýznamnějších komplikací v poskytování zdravotní péče. Zdroj infekce může být buď endogenní z vlastní bakteriální flóry pacienta, nebo exogenní. Intervence ke snížení rizika SSI jsou nezbytné. Předoperační antisepse v místě operace je kritickým krokem v prevenci infekce v místě operace. V současnosti jsou nejpoužívanějšími antiseptiky chlorhexidin a povidon-jod. Tento článek popisuje současné postupy, účinnost různých antiseptických látek a doporučení pro klinickou praxi. Výsledky naznačují, že použití chlorhexidinu s alkoholem snižuje výskyt SSI více než povidon-jod, což podporuje doporučení pro jeho širší použití v chirurgické praxi. Používání antiseptik na denní báze může způsobit alergickou senzibilizaci, která vede k následné expozici během operace a může tak u některých pacientů vyvolat anafylaktické reakce. Studie NAP6 (National Audit Project 6: Perioperative Anaphylaxis) uvádí výskyt anafylaxe chlorhexidinu 0,78 na 100 000 expozic. Při výběru antiseptického roztoku pro přípravu operačního pole je důležité vzít v úvahu i možné riziko anafylaktické reakce, která může pacienta velmi ohrozit.

Klíčová slova:

anafylaktická reakce – infekce v místě operačního výkonu – předoperační antisepse – chlorhexidin – povidon-jód

Introduction

Infections that develop in the area of an invasive surgical procedure and known as surgical site infections (SSI). SSI are one of the most significant complications in surgery, leading to increased morbidity and mortality, prolonged hospitalization, higher healthcare costs and greater discomfort for the patient. SSI causes approximately 18% of the infections associated with the health care [1]. The European Centre for Disease Prevention and Control (ECDC) published in 2017 that the percentage of SSI was 0.5% to 10.1%, depending on the surgical procedure. The incidence of SSI was reported to be 0.1 to 5.7 per 1,000 postoperative days of hospitalization, depending on the surgical procedure [2]. By early detection of patients with an increased risk of healing disorders, it is possible to individualize the surgical procedure itself and the postoperative management of the incision site [1].

According to the source of the infection, there are endogenous and exogenous SSI. Endogenous infections are caused by patient’s own flora from a colonized organ or mucosal surface into the surrounding tissues and organs. The source of exogenous infections is hospital staff, other patients and visitors. The most commonly cultivated pathogens are Staphylococcus aureus, Escherichia coli, Enterococcus species and other gram-negative bacteria [3].

Interventions that serve to reduce the incidence of SSI are gradually being put into medical practice. Some of them are being used routinely in practice –⁠ hand washing, minimizing of shaving, antibiotic prophylaxis. Factors that may contribute to the development of a surgical wound infection include patient-related factors and health care provider-related factors. Some factors like age, obesity, chronical diseases, previous hospitalisations and surgeries cannot be modified before surgery. However, factors like preoperative shower, hair removal, antibiotic prophylaxis and disinfection of operating field can and should be taken into consideration and improved to minimise the risk of development of SSI.

Preoperative surgical site antisepsis (PSSA) is a key step to reduce the risk of SSI. Effective antisepsis can significantly improve the patient’s health condition.

 

History of antisepsis

The history of PSSA is rich and has undergone significant development from ancient times to the present. Ancient civilisations used various substances to clean wounds and surgical instruments, for example the Egyptians used honey, wine and different herbs, Hippocrates suggested the use of wine for washing wounds and honey as an antiseptic dressing. In the 19^th century, Ignaz Semmelweis, a Hungarian doctor, noticed that washing hands with chlorine water significantly reduced the incidence of puerperal fever in hospitals. Semmelweis’ findings were one of the first steps toward the development of antisepsis. Louis Pasteur, a French chemist and microbiologist, provided evidence of microbes as the cause of infections, supporting the need for antiseptic procedures. William Halsted introduced the use of  rubber gloves in 1889 during surgical procedure as his nurse developed dermatitis to disinfectants [4]. Joseph Lister, a British surgeon, began using carbolic acid (phenol) to clean surgical wounds and instruments. This procedure significantly reduced the incidence of postoperative infections and is considered the beginning of modern antiseptic techniques. In the early 20^th century new antiseptic agents such as povidone-iodine (PVI), chlorhexidine and other iodine and alcohol solutions were discovered and commercially available. It was also the beginning of the use of sterilization of instruments by steam and high temperatures in hospitals. After the discovery of penicillin in 1928 by Alexander Fleming and its widespread use during and after World War II, the dependence on antiseptic agents decreased, but antisepsis remained crucial in prevention SSI. The history of PSSA shows continuous progress in the understanding and application of antiseptic techniques to reduce the risk of surgical infections, which has greatly contributed to improved surgical outcomes and increased patient safety [5].

 

Preoperative surgical site antisepsis

The skin is a physical barrier against external microorganisms, it is not sterile, and thousands of bacteria live on it, which maintain a stable microflora that prevents harmful yeast and fungal infections. We refer to these bacteria as “resident flora”. By transfer from other people or from the environment, bacteria are found on the skin for a short time, forming a transient flora [6].

Since the patient’s skin is the largest source of pathogens, it is believed that improving skin antisepsis can reduce the number of surgical wound infections. So far, there are no specific recommendations regarding the preparation of the surgical field, which would be the most effective in preventing infection at the surgical site. We know six basic types of antiseptics that are intended for topical application: iodine or iodophors, alcohol, chlorhexidine gluconate, hexachlorophene, parachlorometaxylenol and triclosan. The ideal agent kills all bacteria, viruses, fungi and spores, is non-toxic, hypoallergenic and safe for use on the human body, has residual activity and is safe for repeated use [7].

Currently, it is a common practice to bathe or shower the entire body with a skin antiseptic to prevent SSI before surgery. When choosing an antiseptic, it is important to balance the effort to reduce the risk of infection and minimize the cytotoxic effects of substances applied to the patient’s skin.

The patient’s pre-operative shower serves to eliminate transient and partially resident flora. Normal and antiseptic soaps containing chlorhexidine gluconate and PVI are used. Some surgical workplaces recommend a precise preoperative hygiene procedure to patients in the form of a shower or bath using a specific preparation, other workplaces only have general recommendations to shower the day before surgery. There are also surgical departments without a specific recommendation regarding preoperative body hygiene. Several studies focus on comparing the effects of individual types of soaps on the development of infections at the surgical site.

 

Chlorhexidine

Chlorhexidine was introduced as an effective antiseptic in the 1950s and became one of the most widely used agents in surgery.

Chlorhexidine is a synthetic biguanide, a topical antiseptic that binds to proteins present in human skin and mucous membranes. It is slowly released from the tissues, which conditions its prolonged activity. It is bacteriostatic at lower concentrations and rapidly bactericidal at higher concentrations [8]. Chlorhexidine is effective against gram-positive and gram-negative bacteria, viruses and fungi [9].

Cheong et al. investigated the cytotoxicity and antimicrobial efficiency of chlorhexidine both ex vivo and in vivo after inoculation of human skin on mice. Ex vivo on excised skin models he found that short exposure to chlorhexidine leads to significant cytotoxicity. Eight weeks after engraftment and normalization of the skin architecture on the xenografts, they created wounds that were treated with chlorhexidine. On histological sections, they observed a clear loss of cell viability of the epidermis. They also observed only short-term antiseptic activity, with the bacterial bioburden quickly recovering after 48 hours despite repeated application of chlorhexidine [10].

Johnson published a paper in 2018 where he described the results of monitoring the effectiveness of a bath with 4% chlor­hexidine gluconate in a neonatal intensive care unit, where they observed that after a chlorhexidine bath the bacterial load decreased, but after 72 hours it reappeared, so they recommend chlorhexidine baths more often than 2× a week to maintain the effect on the bacterial flora [11]. Epstein did not observe any infections at the site of laminectomies when they prescribed 2 weeks of 4% chlorhexidine preoperatively [12].

Agents with chlorhexidine not only have a positive effect on bacterial colonization, but also a potential risk of allergic reactions. Various reactions have been reported after using chlorhexidine preparations, such as contact dermatitis and urticaria, photosensitivity reactions, but also asthma attacks or anaphylactic shock. Krautheim, Buonomo and other authors have described cases of anaphylactic reaction due to local skin application of chlorhexidine [13,14]. In 2017, Kow et al. published a case of an anaphylactic reaction in a 20-year-old patient who underwent two surgeries for a fracture of the pelvis, tibia, and fibula, using chlor­hexidine to disinfect the surgical field in both surgeries. The day after the first operation, the patient developed eczema rashes on his back and lower limbs, which were not reported by the medical staff. During the second operation, the patient developed anaphylactic shock. The reaction to the used chlorhexidine was confirmed by increased specific IgE to chlorhexidine [15].

The main advantage of chlorine derivatives is their broad spectrum of action, including effect against sporulating bacteria. Chlorhexidine is significantly less active against gram-negative bacteria, subject to the phenomenon of reduced sensitivity, but has the advantage of an extended duration of action [16].

 

Povidone-iodine (PVI)

PVI has a wide spectrum of action including all bacteria and fungi, acquired resistance is not known, but it can be partially inactivated by protein material [16].

Veiga et al. prospectively followed patients before elective and clean plastic procedures on the chest and abdomen. Patients in the PVI group showered 2 hours before surgery with a PVI-based liquid preparation. No specific showering instructions were given in the control group. Just before preoperative of the surgical field, skin swabs were taken for microbial examination. Staphylococcus colonization was significantly lower in the PVI group. Colonies of moulds and enterobacteria were detected in both groups [17].

Gyorimolnar’s study involved 20 male patients before heart surgery who took two showers using a PVI preparation before surgery. The bacterial load did not change significantly after the first shower, but increased after the second shower. The results demonstrated that the PVI shower did not reduce the bacterial flora on the skin and recommend further investigation to obtain statistically significant results [18].

 

Octenisan

In 2021, Hachenberg et al. published their retrospective observations of postoperative complications and infection rates in reconstructive breast surgery from 2016 to 2019 in relation to the preoperative use of Octenisan 5 days before surgery. The patients were asked to wash themselves with the product 5 days before the operation, while in 96 cases out of 197 the recommended protocol was followed. In their observation, they did not note a significant reduction in perioperative and postoperative complications and in the rate of infections, which they attributed to the relatively small sample of patients. However, they consider Octenisan to be a safe agent in preoperative preparation, which is not associated with a higher risk for patients. They also recommend thorough patient education to increase compliance [19].

Darouiche observed the effect of using a solution of chlorhexidine based on alcohol and PVI in the disinfection of the surgical field on the incidence of infections at the surgical site. He found that patients treated with chlorhexidine had significantly lower rates of superficial and deep incisional infection. In the study, they found that there was no significant difference in the incidence of organ space infection or sepsis from SSI between the two groups [20].

The tolerance of chlorhexidine and PVI is generally good, but there are nevertheless hypersensitivity and allergic reactions to the preparations. In the literature, contact dermatitis, hypersensitivity, even anaphylactic shock are described after the use of chlorhexidine, extensive studies found a sensitization rate of around 2% after repeated application of chlorhexidine. Rare cases of allergic contact dermatitis have been observed following PVI use, with urticaria and anaphylactic shock being rare [16].

In recent years, Wade and Smith have questioned the superiority of chlorhexidine gluconate in the prevention of surgical wound infection in their studies [21,22].

The World Health Organization (WHO) conducted four meta-analyses of antiseptics for the latest SSI prevention guidelines, finding that alcohol-based antiseptic solutions for surgical skin preparation were more effective in reducing mild SSI compared to aqueous solutions. Also, the use of alcohol-based chlorhexidine had a greater effect on reducing SSI rates than alcohol-based PVI. Based on the findings, WHO issued a recommendation to use alcohol-based antiseptic solutions, preferably chlorhexidine-based, to prepare the surgical site on intact skin [23,24]. Czech National portal of clinics of recommended procedures recommends use of antiseptic solutions based on alcohol and chlorhexidine [25].

 

Anaphylaxis in the perioperative period

The perioperative anaphylaxis is classified as a life-threatening reaction to an allergen occurring in patients immediately during surgery or in the perioperative period. The incidence of perioperative anaphylaxis due to its multifactorial aetiology correlates with antiseptic agents used in ensuring surgical antisepsis. It depends, among other things, on the anaesthetics, drugs, agents used during the surgery and to a high degree on the individual sensitivity of the patient.

Current studies and scientific knowledge indicate that the incidence of perioperative anaphylaxis ranges from 1 : 10,000 to 1 : 20,000 of performed anaesthesia. This is a relatively less frequent complication, but it is essential for medical personnel to be prepared for a quick, professional response in the event of anaphylactic symptoms in patients and to know how to proceed professionally in order to preserve the patient’s life.

The goal of surgical antisepsis is to minimise the risk of infections during surgical procedures in patients as much as possible. Ensuring of surgical antisepsis consists of a set of steps such as the sterility of the hands and work clothes of the operating team, the preparation of the operating field and surgical tools, aids and equipment up to the post-operative care of the surgical wound.

Currently, to ensure surgical antisepsis in the preoperative phase, various types of antiseptic agents are used to minimise the risk of surgical wound infection. The most frequently used antiseptics for the preparation of the operating field are chlorhexidine, PVI, peroxides and alcohol solutions, which, due to their commercial availability on the public market, are classified as significant allergens.

The most widely used antiseptic is chlorhexidine gluconate, characterised as a broad-spectrum antiseptic, whose activity includes effect on gram-positive and gram-negative bacteria, yeast and HIV. Chlorhexidine is also contained in products of daily consumption, such as toothpastes, plasters, ointments, suppositories and cleaning agents. Frequent use of the products can cause allergic sensitisation, which leads to subsequent exposure during surgery and thus can cause an anaphylactic reaction in some patients. The results of NAP6 study indicate a chlorhexidine anaphylaxis incidence of 0.78 per 100,000 exposures. The incidence of anaphylactic reactions to chlorhexidine is statistically low, but not negligible. The use of chlorhexidine as an antiseptic in surgical procedures is increasing, as studies have shown that it is more effective in preventing SSI than PVI.

Nowadays, the incidence of perioperative anaphylaxis is low, but the cause of this life -⁠ threatening condition is often caused by drugs and agents used during surgery. The most common drugs and agents causing anaphylaxis that are not only mentioned in scientific studies but also from practical medical knowledge, are anaesthetics, muscle relaxants, antibiotics, non-steroidal anti-inflammatory drugs, opiates, latex, contrast agents, antiseptics, blood products and substitutes.

A thorough preoperative history of the patient, including any allergies, is the basis for successful prevention of anaphylaxis. It is necessary to carefully consider the choice of antiseptic agents during surgical interventions and to take into account the individual risks for the patient [26–29].

 

Conclusions

The results of the studies indicate that chlorhexidine in combination with alcohol is more effective in reducing SSI compared to PVI. These recommendations are in line with the recommendations of ECDC and WHO. However, it is also necessary to consider possible allergic reactions and contraindications associated with the use of chlorhexidine. Taking a thorough preoperative history of the patient, including allergy history, is the core of a successful prevention of anaphylaxis. It is necessary to carefully consider the choice of antiseptic agents during surgical procedures and to take into account the individual risks for

the patient. In the future, research should focus on long-term results and effectiveness of antiseptic agents in various surgical disciplines. Continuous research focuses on the optimization of antiseptic procedures, development of new substances and methods of application. The aim is the development of techniques and protocols tailored to individual patients based on their health status, type of operation and individual risk factors.

 

Conflict of interests

The authors declare that they have no conflict of interest related to the creation of this article, and that this article has not been published in any other journal with access to congress abstracts.