Reactions to Local Anaesthetics

Skin tests are often useful. They are commonly carried out by intradermal injection, but prick, scratch and patch tests may be used (Aldrete and Johnson 1969, 1970). Incaudo et al. (1978) obtained positive results only in 5 (8%) of the 59 patients they reported. Furthermore, the information gained from the skin test results was of little value since some of these were false positives. We had a similar experience in 18 patients with suspected acute reactions to local anaesthetics. Clearly positive results were obtained in only 2 patients, but further investigations carried out in those 18 patients cast further doubt on the validity of skin tests. These investigations are detailed in Chap. 6. 

The ability of local anaesthetics to produce contact dermatitis is well known (Rothman et al. 1945 de Swarte 1972). Hence patch tests may be of relatively greater value than in other allergies. In fact, cross-sensitisation with p-aminoben-zoate (used topically to prevent sunburn) was first reported in contact dermatitis studies (Gaul 1955). 

In summary, the value of skin tests in suspected reactions to local anaesthetics is limited, and the situation is no different from that with the majority of drugs. Both false negatives and false positives account for their low predictive value. 

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Breit S, Rueff F, PrzybiUa B Deep impact contact allergy after subcutaneous injection of local anesthetics. Contact Dermatitis 2001 45 296-297. Orasch CE, Helbling A, Zanni MP, Yawalkar N. Hari Y Pichler WJ T-cell reaction to local anaesthetics relationship to angioedema and urticaria after subcutaneous application-patch testing and LTT in patients with adverse reaction to local anaesthetics. Clin Exp Allergy 1999 29 1549-1554. 

Most anaphylactoid reactions are due to a direct or chemical release of histamine, and other mediators, from mast cells and basophils. Immune-mediated hypersensitivity reactions have been classified as types I-IV. Type I, involving IgE or IgG antibodies, is the main mechanism involved in most anaphylactic or immediate hypersensitivity reactions to anaesthetic drugs. Type II, also known as antibody-dependent hypersensitivity or cytotoxic reactions are, for example, responsible for ABO-incompatible blood transfusion reactions. Type III, immune complex reactions, include classic serum sickness. Type IV, cellular responses mediated by sensitised lymphocytes, may account for as much as 80% of allergic reactions to local anaesthetic. 

The leucocyte histamine release test (referred to in greater detail in Chaps. 1-7) is one of the in vitro correlates of immediate allergy which may find useful application in investigating reactions to local anaesthetics. It is of some value in detecting acute reactions, whether they are truly anaphylactic or due to direct (non-immune) histamine release (anaphylactoid). It is also more accurate (quantitative), more reliable and more predictive than skin tests, and above all it is free from risk. 

In three of the patients with reactions to local anaesthetics in whom both the skin and the leucocyte histamine release tests were negative, it was thought that their reaction might have been due to an immune mechanism other than anaphylaxis. The lymphocyte transformation test was carried out in these three patients, but the results were negative. 

Adrian J (1972) Etiology and management of adverse reactions to local anaesthetics. Int Anesthesiol Clin 10 127-151... 

Allergic reactions are characterised by cutaneous lesions, urticaria, edema or anaphylactoid reactions may occur as a result of sensitivity to local anaesthetic agent. 

Clarkson A, Choonara I, O Donnell K. Localized adverse skin reactions to topical anaesthetics. Paediatr Anaesth 1999 9(6) 553-5. 

Allergy to local anaesthetics is possible, although this is not common. It is most likely in people who have regular contact with local anaesthetics such as dentists and anaesthetists. See Chapter 3 for details of allergic reactions to drugs. 

C. It is secreted along with noradrenaline by the adrenal medulla, from which it may be obtained. It may be synthesized from catechol. It is used as the acid tartrate in the treatment of allergic reactions and circulatory collapse. It is included in some local anaesthetic injections in order to constrict blood vessels locally and slow the disappearance of anaesthetic from the site of injection. Ultimately it induces cellular activation of phosphorylase which promotes catabolism of glycogen to glucose. 

Allergic reactions to modern local anaesthetics are very rare. A possible allergy can be investigated in consultation with an allergist, should reactions like falling blood pressure, bronchospasm, edema or urticaria occur. 

Systemic reactions to added adrenaline (norepinephrine) are unusual, but can occur and are usually expressed as temporary blood pressure increase, palpitations and anxiety. These reactions rarely require any other treatment than calming explanations. Adrenaline containing local anaesthetics should only be given with particular caution to individuals with increased susceptibility to adrenaline effects - e.g. patients treated with noradrenaline reuptake inhibitors or patients with certain heart diseases. 

Infiltration anaesthesia is applied fan-shaped, with as few needle punctures as possible, in close proximity of the wound or the skin area to be treated. An aspiration should always take place to avoid intravascular injection. Suitable alternatives are lidocaine (lignocaine) or prilocaine for injection 5-10 mg/ml, with or without adrenaline. When making an incision of an abscess it is sometimes difficult to use a local anaesthetic if there is a pronounced inflammatory reaction, since the effect of the anaesthetic is reduced due to an increased acidity level. While adrenaline reduces bleeding and delays dispersion of the anaesthetic, local anaesthetic/adrenaline combinations are contraindicated for local anaesthesia of digits, on the face or where the skin survival is at risk. 

These are generally metabolised in the hepatic endoplasmic reticulum, the initial reaction being N-dealkylation, with subsequent hydrolysis. An exception to this is prilocaine, where the initial step is hydrolysis, forming o-toluidine. This is further metabolised to 4- and 6-hydro toluidine. The latter is believed to be responsible for the methaemoglobinaemia which may follow high doses. The amidelinked local anaesthetics are extensively protein-bound (between 55% and 95%) particularly to ol-acid glycoprotein. 

The test chemical should be placed in the conjunctival sac of one eye of each animal after gently pulling the lower lid away from the eyeball. The lids are then gently held together for about 1 second to prevent loss of the material. The other eye, which remains untreated, serves as a control. If it is considered that the chemical could cause extreme pain, a local anaesthetic may be used prior to installation of the test chemical. The type and concentration of the local anesthetic should be carefully selected to ensure that no significant differences in reaction to the test chemical would result from its use. The control eye should be similarly anesthetized. 

Anaphylactoid reactions are very rare with amide local anaesthetics and some of those reported have been due to preservatives. Most reported reactions to amide local anaesthetics are due to co-administration of adrenaline (epinephrine), intravascular injection or psychological effects (vasovagal episodes). Reactions with ester local anaesthetics are more common. 

His academic research was focused to provide training for the 50 Ph.D. students who benefited from his tutelage. Work on the synthesis and reactions of azodicarboxylic esters that had been started at Goodyear was continued, p-dialkylaminoethyi esters of stericaily hindered alkyl-substituted benzoic acids were made that had longer local anaesthetic action than Procaine, and azo-nitrogen analogs of unsaturated acids and their derivatives were studied for potential... 

In addition to their action as local anaesthetics, the following actions on other parts of the body are possible. These effects are not clinically significant except in intolerant individuals, those with idiosyncratic reactions, in cases where absorption into the blood stream is unexpectedly rapid or in those with impaired metabolism and/or excretion. 

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