Latex allergy in the operating room:
diagnosis and perioperative management

PATRICK K. BIRMINGHAM, MD

aSpring 1999

AS LATE AS 1989,  latex allergy was described in the medical literature as "an unfamiliar condition."¹ Unfortunately it has become increasingly familiar, as allergic reactions to latex have increased dramatically within the last decade. Pediatric anesthesiologists were very involved in the early recognition of latex allergy, as many of the initial case reports occurred in operating rooms of children's hospitals. This article reviews the current diagnosis and management of latex allergy.

BACKGROUND

Latex, also referred to as natural rubber or natural rubber latex, is a processed plant product. While more than 200 plant species are capable of producing latex, over 99% of the world's supply is derived from the Hevea braziliensis tree of Southeast Asia and South America. The milky cytosol produced by lactifer cells in the tree contains lipids, phospholipids and over 240 proteins. It is some of the proteins that are responsible for allergic sensitization. About 25% of the naturally produced latex proteins can cause immunoglobin E(IgE)-mediated allergic reactions.²

After the latex is harvested, preservatives are added to prevent degradation, and accelerators are added to speed up vulcanization, the process by which the rubber precursors cross-link. Other chemicals are added to give latex its desired properties. Porcelain molds of different sizes and shapes are then dipped into the latex concentrate to produce the final commercial product. Synthetic rubber, such as is used in latex paint and in some rubber-stopped vials, should not be confused with natural rubber latex and are not a risk to latex-sensitive individuals.

LATEX REACTIONS

Contact Dermatitis

The most common clinical reaction associated with the use of latex is contact dermatitis. This reaction is largely attributed to chemical additives used in the latex manufacturing process. Irritant contact dermatitis is a non-allergic skin rash due to rubbing or sweating under the glove or from residual skin soaps and detergents in prolonged contact with the gloved skin surface. It is characterized by drying, scaling, cracking skin with erythema and sometimes vesicle formation.

Allergic or chemical-sensitivity contact dermatitis is a specific delayed hypersensitivity immune response of sensitized lymphocytes to chemical additives in latex products. There may be an acute eczematous dermatitis, with vesicle formation typically appearing 48 to 96 hours after exposure. The skin subsequently becomes dry, crusted and thickened.

Both irritant and allergic contact dermatitis may be involved in latex sensitization by reducing the barrier properties of skin and allowing absorption of larger amounts of latex proteins or chemicals. Development of latex allergy may be preceded by an increased frequency and severity of contact dermatitis. Non-latex gloves or cotton liners under latex gloves are recommended for individuals with irritant or contact dermatitis.

Immediate Allergic Reaction

Immediate IgE-mediated hypersensitivity allergic reactions almost always result from direct patient sensitization to latex proteins. Symptoms include rhinitis, conjunctivitis, urticaria, angioedema, asthma, anaphylaxis, and death. Sensitization can occur from direct contact with skin, mucosal or serosal surfaces, or by inhalation. Allergenic latex proteins can be adsorbed on the powder in latex gloves, which become airborne when the gloves are put on or removed.

Serious anaphylactic reactions have occurred not only in the operating room. They have also been reported with vaginal examinations, vaginal deliveries, dental work, barium enema procedures, or while simply donning latex gloves.

Chemical additives in latex are responsible for most local skin reactions but are virtually never the cause of immediate generalized allergic reactions or anaphylaxis. These latter reactions are almost always due to the latex proteins themselves.

RISK GROUPS

Spina bifida patients have a documented latex allergy prevalence as high as 73%³ and have been considered the surgical population most at risk for a latex reaction (see Table 1). They have been shown to be at higher risk for intraoperative anaphylaxis. It is not clear whether the high incidence is due to repeated latex exposure, especially early in life, during multiple operations, procedures and daily intermittent bladder catheterization, or if the spina bifida patient is at higher risk because of a higher incidence of atopy or some genetic predisposition. It was suggested that the number of surgical procedures rather than spina bifida per se correlates with development of allergy sensitization, as 55% of children without spina bifida who had undergone an average of 7.7 operations were latex sensitive, as compared to 59% of spina bifida patients who had had a similar number of operations.⁴

Patients with congenital urogenital anomalies such as bladder extrophy represent another high-risk group. Predisposition to allergic reactions in these patients may also be from frequent bladder catheterizations and multiple operative and diagnostic procedures. Patients with a history of atopy, defined as the presence of allergic rhinitis, asthma, or eczema, are also at risk, as are workers in the natural rubber industry and in health care. Physicians and nurses working in the operating room appear to have a higher incidence of latex sensitization than other hospital personnel; a 1998 study of a large university anesthesiology department found a 12.5% prevalence of latex allergy among its personnel.⁵

In addition to these risk groups, individuals with certain food allergies may also have a coexisting latex allergy. Food allergies associated with latex sensitization include banana, kiwi, avocado, and chestnut. These and other foods or food products may contain proteins similar to latex that can be allergenic. Latex sensitivity can appear before, at the same time as, or after development of food sensitivity. Not all patients with latex allergies are sensitized to these foods, and not all patients with these food allergies will be latex allergic.

Finally, patients with no recognized risk factor can still be latex allergic. A recent study of 1000 volunteer blood donors found a 6.4% prevalence of anti-latex IgE antibody.⁶ The clinical relevance of such findings is unclear, but symptomatic reactions have been reported in the absence of known risk factors.

There are probably several reasons for the recent increased prevalence of latex allergy. The introduction of universal precautions in 1987 to prevent the spread of diseases such as hepatitis and AIDS led to a much greater exposure of health care workers and patients to latex gloves. The increased demand for gloves also led to shorter washing and shelf times, which increased the amount of latex protein antigens in the gloves. There has also been a greater awareness and recognition of latex allergy.

DIAGNOSIS

While an accurate history and patient testing are useful, neither is completely reliable in the diagnosis of latex sensitivity.

A preoperative latex-directed history is the primary method of identifying latex-sensitive patients, as recommended by both the Food and Drug Administration and the American Academy of Allergy and Immunology. While a detailed patient history is important (Table 2) and some authors claim it is the most sensitive means of detecting individuals at risk, one recent study showed history to be somewhat unreliable in predicting the presence of anti-latex (IgE) antibodies.⁷

Both blood and skin testing may be done to detect the presence of latex-specific IgE antibodies. The latex extract for skin prick testing is being standardized to improve test sensitivity. Skin prick testing is preferred to intradermal skin testing, because the latter carries a greater risk of systemic reaction because the antigen can not be wiped from the skin. Skin testing should be done by a qualified specialist with full resuscitative equipment and medications available.

In vitro immunoassays are designed to measure IgE anti-latex antibody in serum. Currently available serum assay methods include the enzyme-linked immunosorbent assay (ELISA) and the radioallergosorbent test (RAST). In earlier studies the RAST had only a 53% sensitivity compared to skin tests.⁸ More recent studies show improved sensitivity.

Neither skin nor blood testing necessarily predict clinical reactions to latex exposure. In addition, a negative latex-specific IgE skin or blood test does not rule out a latex allergy. It is probably safest to recommend latex precautions for all individuals with a positive skin test, a positive blood test or a positive history.

PERIOPERATIVE MANAGEMENT

Premedication

Premedication with histamine antagonists and/or corticosteroids has been used for patients with known latex allergy. Although this has been successful in adults with allergies to radiocontrast media, the timing and efficacy of premedication in latex-sensitive children has not been established. Patients have had latex reactions despite such prophylaxis. The most recent studies indicate that premedication is neither necessary nor effective.⁹ However, if premedication is given, under no circumstance should it be considered a substitute for attempts to minimize direct patient exposure to latex.

LATEX PRECAUTIONS

The most important preventive measure to take in care of patients with or at risk for latex allergy is latex avoidance.

Latex gloves are the most common medical product implicated in latex allergies. Ideally, non-latex gloves should be the standard glove used. Substitute gloves, however, need further assessment of barrier effectiveness. Vinyl gloves, for example, have been shown to have a higher viral leakage rate than latex gloves.¹⁰ If non-latex gloves are not available, powder-free latex gloves are preferred to powdered gloves. This reduces the airborne latex allergens that can adsorb onto the glove powder. If the anesthesiologist or other health-care provider has contact dermatitis or immediate allergic reactions from latex exposure, cotton liners can be worn under latex gloves. The use of barrier creams for protection under latex gloves is discouraged because the creams can extract latex protein from latex gloves and enhance skin penetration of allergens. The misleading term "hypoallergenic" has also been applied to certain gloves. This generally refers to a reduction of latex chemical additives generally responsible for contact dermatitis. Nonetheless, so-called hypoallergenic gloves often contain latex proteins responsible for severe life-threatening allergic reactions. "Hypoallergenic" latex gloves should not be used on at-risk patients or by latex-sensitized health care providers.

It is virtually impossible to eliminate all latex from the operating room or hospital environment and all patient exposures to latex. Furthermore, what constitutes "significant" exposure to latex is unclear as are the exact measures that need to be taken. Two recent clinical studies provide some insight.

Birmingham, Dsida and colleagues at Children’s Memorial Hospital in Chicago studied 386 myelodysplasia patients undergoing 1025 anesthetics over a 36-month period.9 Institution of a latex precaution protocol resulted in a statistically and clinically significant reduction in both the overall number and severity of allergic reactions (Table 3). In addition to the latex avoidance measures taken, they also stated what measures weren’t taken (Table 4). No attempt was made to schedule elective procedures as the first case of the day. Others have proposed this measure to minimize exposure to aerosolized allergen from latex gloves or products used in preceding cases. Standard polypropylene syringes with a rubber-tipped piston were also used. Medications from rubber-capped vials were used, and there was no requirement that the rubber cap be removed before drawing up the medication. Whether these or additional precautions would have further reduced allergic reactions is unknown.

In this study, three of the five severe reactions occurring after instituting latex precautions were from recognized violations of the protocol. A fourth patient, scheduled for emergency surgery, was thought to have been exposed to latex on the ward just before transport to the operating room. He arrived at the operating room with a truncal rash and then had a severe reaction requiring epinephrine for resuscitation. This is consistent with others’ findings that onset of an allergic reaction after latex exposure can be delayed 20 minutes or longer, at which time the source of exposure may not be present or obvious.

Although the focus of this study was the intraoperative period, it was also emphasized that latex avoidance in at-risk patients must be a hospital-wide policy. Even food handled by cafeteria staff wearing latex gloves has been reported to cause a reaction in a latex-allergic patient.

A second study using almost identical latex avoidance measures audited 162 patients with latex allergy established by history and/or allergy testing who underwent 267 anesthetics.¹¹ Eighty-six percent of the patients had myelodysplasia, and 13% had bladder or cloacal extrophy. None of the patients received premedication for allergy prophylaxis. The only allergic reaction reported was wheezing, hypotension and urticaria attributed to an epidural injection of bupivacaine and fentanyl drawn up and stored for 1.5 weeks in a syringe with a latex-tipped plunger. The study’s author recommends checking syringe plungers and reconstituting medications every six hours, but stops short of recommending syringes with a non-latex plunger. It was recommended in this study that rubber stoppers be removed from multidose vials.

These two studies demonstrate that simple latex precautions can dramatically reduce intraoperative allergic reactions.

There have been case reports of allergic reactions after intravenous injection of medications through rubber injection ports; after injecting a fresh solution drawn up in a syringe with a latex-tipped piston; or after drawing up medication through a rubber-stopped vial. Some of these case reports, however, have been subsequently questioned. A study of highly latex-allergic patients examined the reaction to skin injections of extracts of a solution stored in syringes with latex plungers.¹² Only 1 of the 39 latex allergic patients showed any reaction to the injection, and the authors concluded the risk of an immediate hypersensitivity reaction would be very unlikely even in this high risk population.

Another study found latex allergenic proteins in the solution of a multi-dose vial with a latex stopper after 40 punctures of the stopper.¹³ In any case, some stoppers in multi-dose vials are made of synthetic butyl rubber, which is not a hazard to patients with latex sensitivity.

Intravenous tubing is now more commonly being made with non-latex injection ports and diaphragms. In addition to glass syringes, plastic syringes with a non-latex plunger are now being manufactured at prices approaching standard latex-tipped syringes. Manufacturers of the commonly used anesthesia machines in the United States now have ventilator hoses and bellows made of neoprene or other non-latex material. These can be requested and in some cases are already a standard component of the machine. Latex components of the anesthesia machine that are not in close contact with the patient appear to pose minimal risk of an allergic reaction.

Several organizations have compiled lists of available non-latex products for use in the operating room and hospital environment. Manufacturers’ non-latex product lists exist and can be accessed through the American College of Allergy, Asthma and Immunology (allergy.mcg.edu). If a certain non-latex piece of equipment is not available, the latex counterpart should at least be thoroughly rinsed (e.g. reservoir bag or mask) or covered with tape or cotton gauze (e.g. blood pressure cuff or tubing).

Patients at risk for latex allergy should have a prominently displayed easy-to-read sign on both their bed and chart indicating that latex precautions be taken. It is also recommended that allergic patients wear a medical alert bracelet to indicate their allergy.

Pediatricians and anesthesiologists are also in a position to prevent later development of latex allergy in previously unsensitized patients in high-risk groups such as those with spina bifida or bladder extrophy. This may be accomplished by instituting latex precautions from birth onward in these patients, thus avoiding intense exposure to latex allergen during operative procedures where mucous membrane integrity is violated, tissue barriers are destroyed, and blood and secretions provide an environment for absorption of latex allergen in large amounts.

TREATMENT

If a latex allergic reaction occurs, any identified source of latex in direct contact with the patient should be removed immediately. If the reaction is life-threatening, treatment is the same as anaphylaxis caused by other antigens (see Table 5). Epinephrine is the pharmacologic cornerstone of treatment and was needed in 7 of 14 severe reactions reported by Birmingham, Dsida et al.⁹ The dose of epinephrine depends on the severity of symptoms, but generally the initial intravenous dose is much less than the recommended resuscitation dose of 10 mg/kg. This is done to avoid unwanted hypertension or arrhythmias.

An initial epinephrine dose of 0.1 mg/kg has been recommended. Additional administration of the same or escalating doses, and/or use of a continuous infusion may also be needed. If the intravenous route is available, it is preferable to subcutaneous or endotracheal administration. Other pharmacologic measures include aerosolized beta-2 agonists, intravenous corticosteroids and histamine antagonists, and occasionally other inotropes in addition to epinephrine.

Anesthetic agents may need to be decreased or discontinued because of hypotension. Other measures include intravascular fluid administration, ventilation with 100% oxygen, and maintenance of the airway. Massive angioedema involving the face and airway can necessitate delayed extubation and postoperative ventilation.

Symptoms consistent with a latex allergic reaction, such as wheezing, elevated peak airway pressures, arterial desaturation or systemic hypotension, may result from other allergic or non-allergic etiologies. While latex allergy has been shown to be the main cause of perioperative anaphylactic reactions in children, other causes must also be considered in the differential diagnosis.¹⁴

SUMMARY

Since the early case reports of latex allergy, much has been learned in a short time. High-risk groups have been identified, most notably children with spina bifida but also operating room personnel. A directed patient history, supplemented by skin prick or serum tests for latex antibody will identify most individuals at risk. Relatively simple latex avoidance measures, most notably the use of non-latex gloves, will reduce the likelihood and severity of a reaction. Vigilance on the part of all operating room personnel and hospital workers is important in making the hospital environment safe for care of patients predisposed to latex allergy.

REFERENCES

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8. Turjanmaa K, Reunala T, Rasanen L: Comparison of diagnostic methods in latex surgical contact urticaria. Contact Dermatitis 1988;19:241–247.

9. Birmingham PK, Dsida RM, Grayhack JJ, Han J, Wheeler M, Pongracic JA, Coté CJ, Hall SC: Do latex precautions in children with myelodysplasia reduce intraoperative allergic reactions? J Pediatr Orthop 1996;16:799–802.

10. Korniewicz D, Kirwin M, Cresci K, et al: In-use comparison of latex gloves in two high risk units: Surgical intensive care and acquired immunodeficiency syndrome. Heart Lung 1992;21:81–84.

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14. Murat I: Anaphylactic reactions during pediatric anesthesia: Results of the survey of the French Society of Pediatric Anesthetists (ADARPEF) Pediatr Anesth 1993;3:339–343.

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