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References

Dewachter P, Mouton-Faivre C, Emala CW Anaphylaxis and anesthesia: controversies and new insights. Anesthesiology. 2009; 111:1141-1150
Smith CC Risk of latex allergy from medication vial closures. Ann Pharmacother. 1999; 33:373-374
Department of Health and Human Services. Food and Drug Administration: Natural rubber-containing medical devices user labeling. Fed Regist. 1997; 62:(189)51021-51030
US Department of Health and Human Services FDA, 2014. Recommendations for Labeling Medical Products to Inform Users that the Product or Product Container is not Made with Natural Rubber Latex. (Accessed 23 July 15)
Brown RS, Paluvoi S, Choksi S, Burgess CM, Reece ER Evaluating a dental patient for local anaesthesia allergy. Compend Contin Educ Dent. 2002; 23:125-134
Shojaei AR, Haas DA Local anesthetic cartridges and latex allergy: a literature review. J Can Dent Assoc. 2002; 68:10622-10626
Heitz JW, Bader SO An evidence-based approach to medication preparation for the surgical patient at risk for latex allergy: is it time to stop being stopper poppers?. J Clin Anesth. 2010; 22:477-483
Proposal to prohibit the use of natural rubber latex for use in elastomeric closures for injection. Pharmacopeial Forum. 1996; 22:2886-2887
Terrados S, Blanca M, Justicia JE, Moreno F, Mayorga C The presence of latex can induce false-positive skin tests in subjects tested with penicillin determinants. Allergy. 1997; 52:(2)200-204
Jones JM, Sussman GL, Beezhold DH Latex allergen levels of injectable collagen stored in syringes with rubber plungers. Urology. 1996; 47:898-902
Primeau MN, Adkinson NF, Hamilton RG Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions. J Allergy Clin Immunol. 2001; 107:958-962
Thomsen DJ, Burke TG Lack of latex allergen contamination of solutions withdrawn from vials with natural rubber stoppers. Am J Health-Syst Pharm. 2000; 57:44-47
Sengewald J Latex vial stoppers – a growing concern. J Emerg Nurs. 1997; 23
Hoffman RP Latex hypersensitivity in a child with diabetes. Arch Pediatr Adolesc Med. 2000; 54:281-282
Roest MA, Shaw S, Orton DI Insulin-injection-site reactions associated with type I latex allergy. N Engl J Med. 2003; 348:265-266
Asakura T, Seino H, Nozaki S, Abe R Occurrence of coring in insulin vials and possibility of rubber piece contamination by self-injection. Yakugaku Zasshi. 2001; 121:459-463
Kean T, McNally M Latex hypersensitivity: a closer look at considerations for dentistry. J Can Dent Assoc. 2009; 75:279-282
Roy A, Epstein J, Onno E Latex allergies in dentistry: recognition and recommendations. J Can Dent Assoc. 1997; 63:297-300

Natural rubber latex allergies from dental local anaesthetic: a review and guidance for the dental practitioner

From Volume 43, Issue 8, October 2016 | Pages 753-758

Authors

Joel Thomas

BDS, MFDS, RCSEd

Oral and Maxillofacial Surgery Dental Core Trainee, (jt6215@my.bristol.ac.uk)

Articles by Joel Thomas

Christopher Bell

BDS, MSc, FDSRCS (Eng)

Senior Clinical Lecturer, Bristol Dental Hospital, Lower Maudlin Street, Bristol BS1 2LY, UK

Articles by Christopher Bell

Abstract

Natural rubber latex (NRL) is present within many dental products including local anaesthetic (LA) cartridges. Patients with NRL sensitivity are at risk of developing type I and type IV allergic reactions from exposure to these products. Evidence from current literature is inconclusive yet highly suggestive that NRL contamination may occur in medicines stored within vials containing natural rubber components. It would therefore be prudent to avoid using such products in patients with a known NRL allergy. For dental practitioners this applies to LA cartridges and is easily achievable, as manufacturers now produce products not made with NRL. This article aims to provide guidance for dental health professionals regarding the use of LA in patients with a known NRL hypersensitivity.

CPD/Clinical Relevance: NRL allergies are a rising concern amongst medical professions and these reactions should be avoided wherever possible.

Article

Natural rubber latex (NRL) is present in many medical products used within dentistry. Examples that are often forgotten include adhesive tape, fluid or gas tubing and bungs in medicine vials. Patients with NRL sensitivity are at risk of developing type I or type IV allergic reactions from exposure to either NRL proteins or chemical residues from the processing of NRL.

Type I reactions have immediate onset mediated by immunoglobulin E (IgE) antibiodies. This reaction is characterized by conjunctivitis (sore eyes), rhinitis (nasal congestion) and urticaria (itching of the skin). Type I reactions can also precipitate rapid bronchospasm or anaphylaxis requiring urgent medical treatment.

Type IV reactions often have delayed onset mediated by T-lymphocytes and are characterized by dermatitis (skin rash). This usually presents 6–48 hours following exposure and is managed with corticosteroids.

Those with NRL hypersensitivity should avoid contact with all products that contain it. Patients must be educated that NRL can be present not only in the product itself but also in the packaging or may be introduced to the product during the manufacturing process. The incidence of NRL-induced anaphylaxis has increased dramatically over the past two decades, especially in high-risk groups such as children, adults requiring multiple surgical procedures and healthcare workers.1 It is estimated that approximately 1% of the general population suffer from latex hypersensitivities.2

Dental LA cartridges have two possible sources of NRL contamination, the diaphragm through which the needle passes and the bung against which the piston of a self-aspirating syringe pushes to expel the LA. Direct contact of these components with LA stored within the cartridge may contaminate the LA with NRL proteins. The shaving or ‘coring’ of fragments from the diaphragm on inserting the needle when assembling the syringe may also introduce fragments within the needle lumen. Consequently, this may result in the injection of these NRL-containing fragments sub-mucosally when administering LA.

Similarly, larger glass vials used to store multi-dose medicines (more commonly used in medicine) often have a natural rubber ‘stopper’ through which a syringe needle is pushed to withdraw the required volume of substance stored within. Therefore, if the vial is agitated or stored horizontally, the substance within the vial will have direct contact with the rubber stopper. The substance contained will also be highly susceptible to ‘coring’ due to repeated puncturing of the stopper.

The United States Department of Health and Human Services Food and Drug Administration (FDA) began to enforce the labelling of medical devices containing NRL in 1997.3 However, rubber plungers in syringes and stoppers/bungs in medicine vials were exempt and therefore formed some of the only remaining medical equipment containing NRL without a warning. This was rectified in 2014 when the United States FDA released further guidance on labelling of medical products detailing that a statement should be made relating to specific components within the product if not made with NRL. ‘Vial stoppers’ are quoted as an example within this document.4

A PubMed literature search was carried out using the following terms and their combinations – ‘latex hypersensitivity from medicine vials’, ‘latex’, ‘latex hypersensitivity’, ‘local anaesthetic’ and ‘drug contamination’.

Cases

To date there have been no reported anaphylactic reactions to NRL occurring directly from the use of dental LA cartridges. A type IV latex allergy was suggested, but not proven however, by Brown et al.5 This case report describes a 76-year-old male patient with a complex medical history who experienced a skin rash and pruritus approximately 36 hours following multiple episodes of restorative work under LA. A negative response to a challenge procedure with ‘cardiac lidocaine’ suggested an allergy to a component of the commercial anaesthetic and a NRL allergy was presumed due to the natural rubber bung in the cartridge. This was not proven, as the patient requested no further testing.

Shojaei and Haas6 and Heitz and Bader7 published review articles of evidence for NRL allergies from fluids stored in containers containing NRL components. Whilst none of the evidence is specifically related to dental anaesthetic, both concluded that there is evidence suggesting NRL contamination may be possible from such containers and should therefore be avoided if possible in patients with a known NRL allergy.

Evidence of NRL contamination in medicines stored in vials with rubber stoppers

The possibility of NRL contamination of fluids contained within vials with natural rubber stoppers or injected with syringes using rubber plungers is well documented. Evidence of this is described by Heitz and Bader.7 In brief, they highlight how the US Pharmacopeia rejected a proposal to ban the use of NRL-containing rubber stoppers in pharmaceutical vials, yet new evidence emerged in recent years to challenge the rationale behind this decision.8

Terrados et al9 investigated 20 patients who were positive to skin testing with penicillin yet showed good tolerance to penicillin when prescribed. When repeating the skin test with vials of penicillin without a rubber stopper the results were negative in almost all cases, suggesting that it was the NRL contamination of the substance that caused the reactions.

A clinical study by Jones et al10 directly investigated the possibility of NRL within rubber plungers causing allergic reactions in patients with a known NRL allergy. Skin prick testing was used containing collagen solutions before and after storage in syringes with rubber plungers. Results showed than one of 39 patients gave a positive reaction to collagen samples that had been stored in contact with NRL and no reactions were seen in the control samples in which the collagen had not come in contact with NRL. This again supports the idea that direct contact with NRL for prolonged periods is sufficient to contaminate fluid samples with NRL proteins and therefore elicit an allergic reaction in NRL-sensitive subjects.

One key study by Primeau et al11 showed positive skin test reactions in 2 out of 12 volunteers with known NRL allergies when tested with phenol-saline-human albumin stored in contact with rubber stoppers within vials for a 9-month period. In this same study, 5 of 12 subjects showed a positive skin test result when the rubber stopper was punctured 40 times. This not only suggests that NRL contamination is possible when the integrity of the stopper is breached, but also from direct contact with NRL over a prolonged period, as is the case for dental LA cartridges. The authors concluded that clinical risk would not be reduced by removing the rubber stopper immediately prior to administering the drug. It was consequently suggested that a ‘single-stick’ technique may be most appropriate when using multi-dose vials, in which the rubber stopper would only be punctured once before disposal. This was supported by Thomsen and Burke,12 who showed that there was no significant difference between NRL contamination levels seen in storage vials when removing the stopper and penetrating just once. This is a technique that is currently widely accepted in the field of anaesthetics and also one which applies to 'Dental LAs', as cartridges are single use and therefore the needle is only punctured once through the diaphragm prior to use on each patient. This does not however account for the possibility of NRL contamination occurring through direct contact with the rubber bung at the opposite end of the cartridge, implicated by the work of Primeau.

Coring

The issue of puncturing the source of NRL and its possible effect on increasing NRL contamination was noted amongst diabetic patients using self-injection insulin pens. Numerous case reports have shown skin reactions following subcutaneous injection of insulin from vials containing rubber stoppers in diabetic patients. This reaction appears to be resolved when the subjects use insulin from vials without a rubber stopper.13,14,15 This may be explained by the theory of ‘coring’ discussed by Asakura et al.16 This study suggested that the repeated puncturing of rubber diaphragms within insulin vials caused the shaving of rubber fragments which then contaminate the insulin within the vial, or even stay within the needle lumen and are therefore injected directly into the patient. Results showed that the incidence of ‘coring’ fragments within the lumen was 73% with the first injection and 43% with the second. Since dental needles puncture the diaphragm of the LA cartridge and are then screwed into position when assembling the syringe, there is a possibility that ‘coring’ could occur in a very similar way to insulin pens.

In recent years there has been a move towards the manufacture of medical products without NRL owing to increased concern regarding allergic reactions described above. This includes manufacturers of dental products such as Septodont (Maidstone, Kent).

In 2012 UK Medicines Information (UKMi) began publishing a table indicating which dental LAs available in the UK do not contain NRL components. (Table 1). This table will be updated annually and can be viewed at the following website (www.evidence.nhs.uk).


Brand Name Ingredients Presentation Company
Artikent Articaine 4% with adrenaline 1:100,000 2.2 mL cartridge Kent Express, Gillingham, Kent
Bartinest Articaine 4% with adrenaline 1:100,000 2.2 mL cartridge Dental Directory, Witham, Essex
Espestesin Articaine 4% with adrenaline 1:100,000 1.8 mL cartridge 3M ESPE AG, Seefeld, Germany
Articaine 4% with adrenaline 1:200,000 1.8 mL cartridge
Isonest Articaine 4% with adrenaline 1:100,000 2.2 mL cartridge Henry Schein, Gillingham, Kent
Septanest Articaine 4% with adrenaline 1:100,000 2.2 mL cartridge Septodont, Maidstone, Kent
Articaine 4% with adrenaline 1:200,000 2.2 mL cartridge
Eurocaine Lidocaine 2% with adrenaline 1:80,000 2.2 mL cartridge Septodont, Maidstone, Kent
Lignokent Lidocaine 2% with adrenaline 1:80,000 2.2 mL cartridge Kent Express, Gillingham, Kent
Lignospan Special Lidocaine 2% with adrenaline 1:80,000 1.8 and 2.2 mL cartridge Septodont, Maidstone, Kent
Rexocaine Lidocaine 2% with adrenaline 1:80,000 2.2 mL cartridge Henry Schein, Gillingham, Kent
Utilycaine Lidocaine 2% with adrenaline 1:80,000 2.2 mL cartridge Dental Directory, Witham, Essex
Oraqix periodontal gel Lidocaine 2.5% and prilocaine 2.5% 25 g tube Dentsply, Weybridge, Surrey
Xylonor gel Lidocaine 5% 15 g tube Septodont, Maidstone, Kent
Xylonor spray Lidocaine 10% spray 36 g bottle
Scandonest Special Mepivacaine 2% and adrenaline 1:100,000 2.2 mL cartridge Septodont, Maidstone, Kent
Scandonest Plain Mepivacaine 3% 2.2 mL cartridge
Citanest with Octapressin Prilocaine 3% and felypressin 0.03units/mL 2.2 mL standard and 2.2 mL self-aspirating cartridge Dentsply, Weybridge, Surrey

Brand Name Ingredients Presentation Company
Xylocaine * Lidocaine 2% with adrenaline 1:80,000 2.2 mL standard and 2.2 mL self-aspirating cartridge Dentsply, Weybridge, Surrey
Emlaä cream $ Lidocaine 2.5% and prilocaine 2.5% 5 g tube (with or without dressings) AstraZeneca, London
Xylocaine spray Lidocaine 10% spray 50mL bottle
Ametopä gel $ Tetracaine 4% 1.5g tube Smith & Nephew Healthcare, London
* The product has not been tested for the presence of NRL - it is assumed, therefore, to contain NRL.

Conclusions

With the capability of routine products to cause potential life-threatening allergic reactions, the management of patients with a known NRL hypersensitivity is a growing concern among medical and dental professionals.17

To date there have been no reported anaphylactic reactions to NRL occurring directly from the use of dental LA cartridges. However, numerous case reports and clinical studies have shown allergic reactions to other drugs stored in a very similar manner to dental LA with natural rubber components. Whilst evidence is often contradictory, it has been shown that direct contact of fluids with natural rubber containing latex (particularly when punctured) may be sufficient to cause NRL contamination and an allergic reaction in patients with a NRL hypersensitivity. Further studies are indicated to investigate NRL contamination within dental LA cartridges specifically and its effect on those with a known NRL hypersensitivity.

Guidance for dental practitioners

When managing a patient with a known NRL hypersensitivity, dentists should take a full history of the previous event from which the diagnosis was made during the treatment planning appointment. If a true allergy is suspected or diagnosed, dentists should follow routine latex allergy protocols.18 In particular, possible NRL-containing products should be avoided and therefore LA manufactured without NRL should be used (Table 1). High-risk patients should be given early morning appointments to avoid contact with aerosolized allergens17 and allow for monitoring post-operatively.

If an allergy to LA is suspected following treatment of a patient without a current diagnosis, the patient should be monitored for symptoms of anaphylaxis over the proceeding 30 minutes. Type IV reactions can be managed with topical corticosteroids. Type I reactions involving respiratory distress require high flow oxygen and immediate administration of 0.3–0.5 mL intramuscular doses of 1:1000 epinephrine (0.1 mL/kg every 5 minutes for children) and activation of the emergency medical services.17 The patient should be referred to an allergist in order to establish the exact causative allergen. Until the causative agent has been identified, NRL-containing products should be avoided.