ESTABLISHMENT OF MAXIMUM RECOMMENDED DOSES ON THE BASIS OF TOXICOLOGICAL AND PHARMACOKINETIC DATA

Since Heinrich Braun added adrenaline to cocaine (and later also to procaine) in 1903 to allow clinical use of this local anesthetic, "limiting dosages" for local anesthetics have been "recommended" with no reference to the technique of administration, on the assumption that adrenaline will lower the toxicity of the local anesthetic used. However, the limiting dosages determined up to now do not take account of important pharmacokinetic and toxicological data: (1) The dependence of blood levels measured on the technique of regional anesthesia and (2) the raised toxicity of a local anesthetic solution containing adrenaline following inadvertent intravascular (intravenous) injection. A maximum dose recommendation that differs according to the technique of local anesthesia is suggested for (A) subcutaneous injection, (B) injection in regions of high absorption, (C) single injection (perineural, e.g. plexus), (D) protracted injection (catheter, combined techniques), (E) injection into vasoactive regions (near to the spinal cord, spinal, epidural, sympathetic). This sequential categorization also underscores the need for selection of appropriate techniques as well as for concomitant monitoring referred to the technique of administration and to the expected and the possible plasma level curve. The "maximum recommended doses" of mepivacaine for use with five different techniques of regional anesthesia (those in parentheses are for when it is combined with the vasoconstrictor adrenaline) are A: 400 (500); B: 200; C: 400 (500); D: 500; E: 1-25 ml; those for lidocaine, A: 400 (500); B: 200; C: 400 (500); D: 500; E: 1-25 ml; those for prilocaine, A: 600; B: 300; C: 600; D: 700; E: 1-25 ml; those for bupivacaine, A: 150; B: 75; C: 150; D: 200; E: 1-25 ml and those for etidocaine, A: 300; B: 150; C: 300; D: 300; E: up to 25 ml (no spinal anesthesia). These recommended maximum doses are low for zones of raised absorption and higher for protracted injection techniques. For prilocaine, bupivacaine and etidocaine, the recommended maximum doses are not different whether or not the solutions contain adrenaline. The preparation containing adrenaline is limited by the total adrenaline content (0.25 mg). The dose spectrum must be specified for all injections carried out close to the spinal cord because of the specific risk: even very tiny volumes can have an intensive effect and they involve high risks. The values specified for techniques C and D also restrict the overall doses for the techniques specified under E when high doses are necessary. The recommended maximum doses given here relate to normal conditions (70 kg). They must be varied individually depending on the body weight and condition of the patient. Recommended maximum doses are important as guidelines, but they are not absolute maximum doses.