Local anesthetics


These drugs anesthetize the area to which they are applied by blocking nerve conduction and preventing depolarization of cell membranes.
 
There are two main families of local anesthetics:

Benzoic acid ester group (group I):

  • benzocaine, chlorprocaine, cocaine, piperocaine, procaine, propoxycaine, tetracaine.

Amides (group II):

  • aromatic: articaine, bupivacaine, dibucaine, etidocaine, lidocaine, mepivacaine, prilocaine.

    thiophenic: alphacaine

Amides are by far the most used today.
 

Incidence
2 to 3% of local anesthesias (faints). True allergic reactions are exceedingly rare (less than than 1% of all reactions).
 
Risk factors
Long term topical application of anesthetic drugs (contact dermatitis).
 
Clinical manifestations

Reactions unrelated to drugs:
  • psychomotor: hyperventilation, vaso-vagal, adrenergic
  • sympathetic stimulation
  • operative trauma

Toxic responses in normal subjects:

  • central nervous system effects
  • cardiovascular effects
Reactions due to either adjuvants or injection, but not to the local anesthetic itself:
  • associated drugs: epinephrine, sulfites, parabens, antibiotics, analgesics;
  • traumatic subcutaneous emphysema.

Type I allergic reactions: anaphylactic shock, urticaria, angioedema are exceptional.

Fixed drug eruptions: extremely rare (lidocaine, mepivacaine).

Delayed-type hypersensitivity (contact allergy) is more frequent due to the increasing use of topical preparations containing local anaesthetics of the amide group. Several of these cases have been reported in chronically treated patients with topical applications of Emla cream (lidocaine + prilocaine). Cases of contact allergy to lidocaïne have been also reported (antihemorroidal cream, phlebectasias treatment).

Historically, delayed-type hypersensitivity was reported mainly with esters which are much less commonly used nowadays.

Cross-reactivity among amides is not always encountered.
 

Diagnostic methods
Cutaneous testing
 
Prick-tests are mostly negative.
 
Intradermal skin-tests: false positive at 1/10 and pure concentration. Few case reports with type I clinical manifestations and positive intradermal skin-tests with 1/10 000 to 1/100 concentrations.
 
Patch-tests are useful in the diagnosis of type IV manifestations (contact dermatitis) to esters and amides.
 
No specific IgE found
 
Mechanisms
No absolute demonstration of IgE-mediated reactions.
 
The role of preservatives (parabens, sulfites) remains controversial.
 
Type IV reactions: contact dermatitis (esters and amides).
 
Management
Challenge test remains the "gold standard" in local anesthetic reactions. Many suggested dosing protocols exist: for example (at 15 minute intervals).
 

1° prick undiluted

2° S.C 0.1 ml undiluted

3° S.C 0.5 ml undiluted

4° S.C 1 ml undiluted

5° S.C 2 ml undiluted

 

Alternative therapies
preservative-free preparations

be aware of cross-reactivity between esters (frequent) and amides (less frequent)

antihistamines (diphenhydramine) may be used as anesthetics

general analgesia (N2O)

hypnosis

References

  1. Fisher M.M, Bowey C.J, "Alleged allergy to local anaesthetics", Anaesth. Intensive. Care., 1997 ; 25 (6): 611-4
  2. Cuesta-Herranz J, de las Heras M, Fernandez M, Lluch M, Figueredo E, Umpierrez A, Lahoz C, "Allergic reaction caused by local anesthetic agents belonging to the amide group", J.Allergy. Clin. Immunol., 1997 ; 99 (3): 427-8
  3. Eggleston S.T, Lush L.W, "Understanding allergic reactions to local anesthetics", Ann. Pharmacother, 1996 ; 30 (7.8): 851-7
  4. Gall H, Kaufmann R, Kalveram C.M, "Adverse reactions to local anesthetics: analysis of 197 cases", J.Allergy. Clin. Immunol, 1996 ; 97 (4): 933-7
  5. Wasserfallen J.B, Frey P.C, "Long-term evaluation of usefulness of skin and incremental challenge tests in patients with history of adverse reaction to local anesthetics", Allergy, 1995 ; 50: 162-5
  6. Sindel L.J, de Shazo R.D, "Accidents resulting from local anesthetics. True or false allergy ?", Clin. Rev. Allergy, 1991 ; 9 (3.4): 379-95.

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.