Perioperative latex hypersensitivity reactions : an integrative literature review

Este estudo teve por objetivo caracterizar as reações de hipersensibilidade ao látex em procedimentos anestésico-cirúrgicos. Foi realizada revisão integrativa da literatura nas bases LILACS, CINAHL, COCHRANE e MEDLINE, com seleção de artigos publicados em periódicos indexados de 1966 a setembro de 2011. Foram identificados 17 relatos de caso, dois estudos de prevalência e um de coorte. As reações ao látex foram majoritariamente do tipo III, e a principal fonte desencadeadora de reações no intraoperatório foram as luvas de látex; o tempo médio para manifestação da reação foi de 59,8 minutos após a indução anestésica; 44,4% dos pacientes relataram episódio de reação ao látex na avaliação pré-anestésica. Identificouse que a história de episódios de reações a materiais de borracha, ou alimentos, na avaliação pré-anestésica não garante a segurança dos pacientes, se o profissional não estiver alerta à gravidade do problema; no caso de ocorrência de um evento anafilactoide, os profissionais tendem a suspeitar inicialmente dos medicamentos anestésicos.


Introduction
Latex gloves have been used since the 19th century to protect patients from the transmission of infectiouscontagious diseases.By the end of the 1980s, however, their use grew in frequency and importance mainly due to the emergence of the HIV virus, and an increase in the production of inadequate gloves was observed.These were produced with an excess of powder and residual proteins -agents that typically cause allergenic reactions in latex-sensitive individuals -unleashing a sensitization process (1)(2) .Thereafter, the first intraoperative cases of anaphylaxis were reported, which demanded that attention be paid by health workers to the seriousness of the problem (3) .
Natural Rubber Latex (NRL) is extracted from the sap of the Hevea brasiliensis, also known as the rubber tree.Its original form is a milky liquid composed of 60% water, 35% rubber and 5% of other substances, such as carbohydrates and minerals.Approximately 250 different proteins are found in NRL, but only 5% of them were identified as inducing hypersensitivity (4) .
Approximately 50% of medical devices contain latex.
Both residual proteins and chemical compounds used in its production are associated with the development of reactions (5) .The terminology used to discriminate the three potential reactions is confusing, namely: irritant contact dermatitis, allergic contact dermatitis, and type I hypersensitivity or immediate hypersensitivity.
Irritant contact dermatitis is a non-allergic skin and inflammatory reaction arising from chemical compounds or the products' mechanical action.Its response occurs in minutes or hours and is characterized by dry skin, cracking, redness, burning and itching (6) .
Allergic contact dermatitis or type IV delayed hypersensitivity is an allergic response mediated by lymphocytes T and generally located on the site of contact with the latex containing material (5) .It is also caused by the chemical substances added during the manufacture of latex; its clinical signs usually emerge 24 hours after exposure, including itching, erythema, blisters, and cracks similar to the irritant dermatitis (6) .
Type I hypersensitivity, or mediated by IgE cells, is a systemic response to residual proteins and, therefore, the only reaction classified as one allergic to latex.Studies indicate that type I reactions affect approximately 0.8% to 6.5% of the general population.
A total of 1,200 cases were recorded in 1997 alone, 13 of which were fatal (7) .Susceptibility in the risk groups is associated with the intensity and frequency with which an individual stays in contact with the latex: it affects 28% to 73% of individuals with myelodysplasia (8) and its risk increases 50% among patients with urogenital malformations (9) .One of the most frequent forms of becoming sensitive to latex occurs by the ingestion of certain foods, especially fruits (i.e.banana, kiwi and avocado) due to the cross reaction among the allergic compounds of these fruits common to latex (10)(11) .
There are many challenges to be overcome in the surgical environment where there is a high risk of exposure.The primary avenue of systemic exposure to latex is cutaneous, through tourniquets, electrodes, gloves, anesthetic masks, and bandages, generally leading to the development of rashes and angioneurotic edema (12) .However, the most severe reactions result from invasive procedures in which NRL comes into contact with the endothelium, mucosae (especially oral and vaginal mucosa, and mucosa of the urethra and rectum), internal organs and tissue (8) .
Inhaling residual proteins may also cause reactions, generally bronchospasms, rhino conjunctivitis, asthma, or airway edema.These airborne allergens are released during the anesthetic process through mechanical ventilation equipment and even by simply handling NRLcontaining products (13) .
Even though the possibility of patients presenting hypersensitivity to latex in the intraoperative period is acknowledged, patients are not frequently asked during the preoperative assessment, a time when prior allergy history is verified, whether they have had reactions to rubber and patients do not always have the initiative to mention dermatitis associated with the use of domestic gloves (5) .Such a fact motivated us to search the literature addressing manifestations of allergic reactions to latex in the intraoperative period.
The Evidence-Based Practice (EBP) approach, which connects research and care practice, was used in this study.When facing a problem, EBP enables one to seek and critically evaluate the best and most recent evidence available, implementing it into practice and analyzing the results.Therefore, this approach grounds care delivery in scientific knowledge, enabling better quality care coupled with more effective costs (14) .
For that, the use of scientific and systematic literature review methods to search, evaluate, and synthesize data, are required.This is an integrative review, which enables the synthesis and analysis of scientific knowledge already produced regarding the studied subject (15) .This type of study compiles data from different research designs (16) , including clinical papers and reviews (17) .
Given the previous discussion, this study sought scientific evidence related to the hypersensitivity reactions observed in anesthetic surgical procedures, according to factors related to the patients and types of surgery.

Methods
This integrative review consisted of the following steps: developing the guiding question, searching the literature, categorizing the studies found, evaluating those included in the review, discussion and interpretation of results, and synthesis of knowledge found in the analyzed papers (16) .
The guiding question was: "What are the reactions due to hypersensitivity to latex frequently observed in anesthetic-surgical procedures?" The study period involved all the studies identified in the electronic search in the databases LILACS, CINAHL, COCHRANE and MEDLINE.Since the oldest Rev. Latino-Am.Enfermagem 2012 Mar.-Apr.;20(2):411-20.
database hosts papers beginning in 1966, we searched the period from 1996 to 2011.We used the search PICO methodology (18) , in which P stands for Patient, I for Intervention, C for Comparison group and O for Outcomes.The search structure with the health descriptors was organized as: P (surgery OR anesthetics), I (latex OR rubber OR surgical gloves), O (latex hypersensitivity OR dermatitis OR dermatitis contact OR hypersensitivity).We used the same structure with the Boolean term AND to make a connection between the search boxes in the databases that did not interface with this strategy.
Allergy latex and type I hypersensitivity, or mediated by IgE cells, were considered to be a systemic response to residual proteins developed within a few minutes after contact or handling NRL -containing material (5) .
The following inclusion criteria were adopted for the papers: articles that focused on the surgical and anesthetic complications related to latex hypersensitivity in individuals older than 18 years.The exclusion criteria were: studies addressing the latex allergic process mechanism of action, clinical and obstetric cases of latex allergies, studies with children, experimental studies with animals, laboratory tests, protocols, preventive measures, allergies to condoms and medications, studies addressing anaphylaxis in the dental field and theoretical trials.
A guiding instrument developed by the authors was used to guide summarization of information with the following variables: year of publication, type of study, objective, study period, place of publication, population, age, gender, type of surgery, characteristic of reaction, prior history of allergies, results and conclusions.
Hypersensitivity reactions were characterized according to the Laxenaire Classification (19) , which identifies four categories of reaction according to severity and symptomatology, namely: type I, which subdivides into: Ia (localized erythema) and Ib (erythema, hives, face or mucosa edema); type II that includes the same symptoms in skin and mucosae from IB reactions but also includes nausea, cough, dyspnea, tachycardia above 30% or hypotension above 30%; type III, which in addition to the same symptoms of skin and mucosae, includes nausea, vomiting, diarrhea, bronchospasm, cyanosis, or shock; type IV, considered the most severe, including the same symptoms of skin and mucosae in addition to gastrointestinal reaction type III plus respiratory or cardiac arrest.
The studies found were classified according to the level of evidence using the Oxford Centre for Evidence-Based Medicine (CEBM) (20) , which are: 1A level -systematic review (with homogeneity) of controlled and randomized clinical trials; 1B levelcontrolled and randomized clinical trial with a narrow confidence interval; 1C level -therapeutic outcomes all-or-nothing"; 2A level -systematic reviews of cohort studies; 2B level -cohort studies (including lower quality randomized clinical trials); 2C levelobservation of therapeutic results, ecological studies; 3A level -systematic review (with homogeneity) of case control studies; 3B level -case control study; 4 levelcase reports (including cohort and case control of lower quality) and 5 level -opinion deprived from critical evaluation or based on basic material (physiological or animal studies).

Results
A total of 836 studies were initially found, and after selection and analysis through the application of inclusion and exclusion criteria, 20 papers were chosen.
Most of these (n=12) were conducted in Europe, followed by the United States (n=7), and Oceania (n=1).
Studies were mainly published in the 1990s (n=19), and case reports predominated (n=17) when compared to epidemiological studies (n=3), while the latter included two prevalence studies and one cohort study.According to the classification of CEBM levels of evidence, the studies presented a level of evidence 4. Following, we present a synthesis of case reports and epidemiological studies.
The procedure was interrupted in six (33.3%) cases because of the reaction (E1, E4, E6, E7, E12, E15,).In the remaining, the anaphylactoid reaction was controlled during the surgery up to the end of the reaction.
Postoperative tests were performed to investigate the anaphylactoid reaction in 15 (83.3%) patients.There was a predominance of specific IgE dosage (RAST) for latex (55.5%), followed by cutaneous testing for the anesthetics used and NRL (Figure 2).The provocation test was conducted in study E1, which consists of a controlled administration of a substance for the diagnosis of hypersensitivity reactions, considering the use of an intubation tube and cardiac monitoring electrodes.Four reports (E3, E4, E5, E8) defended the prophylactic use of antihistaminic drugs and/or corticoids for those with a history of pre-anesthetics allergies.The patients from two of the studies (E4, E5) were medicated prior to their procedures and the environment was free of latex.In another two studies (E16, E12) however, such practices were not adopted.The prevalence of positive skin tests to latex was 4.9% and specific IgE was 7.1% in the study E18.

Synthesis of epidemiological studies
Atopy, which is a predisposition of individuals to present a response from the immunological system to common substances and particles, was found in 33.2% of the patients and 19.4% of these were allergic.Cases of latex allergies were observed in patients with more than ten prior surgeries (5.6%).
In study E19, 20.9% of those allergic to latex were among patients from the Head and Neck (H&N) department; only 1.0% had reported a latex allergy, and 77.0% were atopic.Among those from the abdominal surgery department, 11.3% were allergic to latex; only 0.5% reported latex allergy symptoms and 68% were atopic.

Discussion
Data from the literature indicate that latex is responsible for approximately 22.3% of the episodes of perioperative anaphylaxis (21) .The epidemiological studies (22)(23) presented a prevalence of 10 to 20% depending on the type of the procedure.
The literature reports that patients undergoing urological procedures and/or frequently exposed to latex material are more vulnerable to latex-sensitivity, as are those with spina bifida (8,(21)(22) .This investigation frequently reported cases in gastrointestinal and H&N surgeries in the epidemiological studies because studies addressing pediatric patients, just those involved with surgeries due to spina bifida, were excluded.
The reactions more frequently occurred among women, which has been attributed to their frequent exposure to latex by the routine use of rubber gloves while performing home chores and the high number of gynecological and obstetrical interventions, which may be even higher in cases of artificial insemination.
Studies show that these interventions may account for up to 50% of intraoperative anaphylaxis (23) .According to the literature, abdominal surgeries are the second most frequent surgical procedure involving latex-sensitivity, after gynecological and obstetrical surgeries, and represent approximately 20% of the cases (24) .
Even though nurses and anesthetists checked for allergic antecedents in the preoperative, it was not sufficient to avoid intraoperative hypersensitivity reactions because some patients had reported an anaphylactoid reaction after ingesting certain foods or having contact with rubber material before the surgical procedure.
Latex allergies are linked to allergies to fruits and vegetables due to a likely cross-reactivity between latex antigens and those contained in certain foods or by the presence of polypeptides that have enzymatic functions.
The frequency of sensitization ranges from 18.4% to 32.1% in patients allergic to latex and there are many foods that trigger it: avocado, banana, kiwi, grapefruit, papaya, chestnuts, nuts, pineapple, melon, fig, passion fruit, tomato, dates, potatoes, and peach (10) .
Later hypersensitivity depends on a detailed investigation to identify patients belonging to risk groups.
The employment of forms with specific questions may aid the identification of signs and symptoms not deemed significant by patients and which can suggest the need for a more detailed evaluation through laboratory exams whose results can affect decision-making related to surgical conditions.
The literature reports the use of an algorithm (25) to help decision-making concerning the diagnosis of latex allergy when the patient presents some risk factor or symptomology that suggests a potential contact dermatitis or hives.Initially, the scheme recommends a patch test (it tests chemical substances that may cause a reaction) is initially performed to evaluate the possibility of delayed hypersensitivity and then the RAST test is performed if there is a suspicion of immediate hypersensitivity.In the case of negative or inconclusive results, the scratch test or skin prick test and/or provocation test is performed.
None of the analyzed studies performed the patch test because the objective was to evaluate a reaction that had already occurred and not the possibility of delayed hypersensitivity.But if the algorithm had been used to detect information regarding a prior history of allergic reactions in the pre-anesthetic evaluation, the intraoperative reactions could have been avoided.
Whenever there is a history suggesting an allergy and confirmatory laboratory results, nurses should make sure the surgical procedure is latex free during the entire perioperative period, preferably rescheduling the surgery to the first hour, so that the level of aeroallergens is at the lowest possible.It is also important to warn the entire multidisciplinary staff by hanging alerts on the doors of the patients' rooms and noting on the patients' medical files, and, whenever possible, to perform trolley maintenance using only latex free material for potential emergencies (26) .It is also necessary that whenever nurses instruct patients and families, they emphasize that information concerning potential allergies is crucial for the safety of the surgical procedure.(2) patient under sedation -facial swelling, hives, rash, flushing, bronchospasm, laryngeal edema, hypotension, tachycardia, cardiac arrest (1) .
The use of pharmacological prophylaxis through antihistamine drugs and/or corticoids was a controversial issue in the analyzed studies.There is a premedication protocol that includes the use of Diphenhydramine, Cimetidine and Prednisone (27) .Other authors (28) argue that in addition to a lack of scientific evidence, the use of these medications prior to a surgical procedure can harm the identification of the first signs of a hypersensitivity reaction.
An important aspect observed in one of the reported cases was the fact that the source of the allergy in the patient previously known for being latex-sensitive was the donated organ.Even though there are no studies addressing the need to use latex free gloves when removing an organ intended for donation, it seems that this case should be considered a sentinel event indicating the need to use latex free gloves.
The identification of allergies to fruits or reactions to latex material and the number of prior surgeries above ten, as observed in some studies, should warn nurses of the need to implement a latex free surgical environment to avoid adverse events in the intraoperative.

Conclusions
Latex hypersensitivity is an adverse event that can be avoided when the surgical staff is sensitive to the patient's history concerning skin reactions to food and NRL material, number of prior surgeries or complications in prior surgical events.Type II reactions were frequent, which shows the severity of clinical conditions, and the need for interventions to complete the surgery and in some cases, interrupt the surgery.
Even though the selected studies presented a level of evidence considered to be weak, some findings allow us to conclude that the history of allergic reactions to latex in the pre-anesthetic evaluation does not ensure the safety of patients if the staff is not attentive to the problem's severity; there is a tendency to initially attribute the anaphylactoid event to the anesthetics; and, finally, there is a possibility of a latex hypersensitivity reaction in response to the latex gloves used when harvesting transplantation organs.
The surgical staff in the transplantation organ surgery knew the receptor patient was latex-sensitive but the latex free environment was not sufficient to avoid an allergic reaction because they had not considered the donated organ could be "contaminated" by latex proteins.Considering the complexity of transplantation procedures and the risk posed to patients, further studies

Figure 1 -
Figure 1 -Synthesis of care reports identified in the integrative literature review from 1996 to September 2011

Figure 2 -
Figure 2 -Distribution of the number of patients according to the type of test used to identify anaphylactoid reactions in the postoperative.

Figure 3
Figure 3 presents a synthesis of epidemiological studies.The average time of observation for data collection in these studies was 15 months, ranging from 6 to 24 months (E18, E20).Two studies addressed patients according to surgical specialty: 325 patients were awaiting urological procedures and 204 patients were from the Ear, Throat and Nose (ETN) Department in study E18; while 206 from the abdominal surgery department were included in study E19.The studies' main objective was to evaluate the prevalence of latex hypersensitivity.A total of 39 patients with hypersensitivity reactions or adverse reactions from unknown causes manifested during the anesthetic process were included in study E20.The study evaluated the incidence of these reactions through skin and blood tests for histamine and tryptase.

Figure 3 -
Figure 3 -Presentation of epidemiological studies identified in the integrative literature review from 1966 to September 2011