Page 481 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 26 Local Anesthetics 467

in modalities, it is not possible with conventional techniques to and (2) neurotoxicity resulting from local effects produced by
produce surgical anesthesia without some loss of motor function. direct contact with neural elements.
A. Effect of Added Vasoconstrictors A. Systemic Toxicity
Several benefits may be derived from addition of a vasoconstrictor The dose of local anesthetic used for epidural anesthesia or
to a local anesthetic. First, localized neuronal uptake is enhanced high-volume peripheral blocks is sufficient to produce major
because of higher sustained local tissue concentrations that can clinical toxicity, even death. To minimize risk, maximum recom-
translate clinically into a longer duration block. This may enable mended doses for each drug for each general application have
adequate anesthesia for more prolonged procedures, extended been promulgated. The concept underlying this approach is that
duration of postoperative pain control, and lower total anesthetic absorption from the site of injection should appropriately match
requirement. Second, peak blood levels will be lowered as absorp- metabolism, thereby preventing toxic serum levels. However, these
tion is more closely matched to metabolism and elimination, recommendations do not consider patient characteristics or con-
and the risk of systemic toxic effects is reduced. Moreover, when comitant risk factors, nor do they take into account the specific
incorporated into a spinal anesthetic, epinephrine may not only peripheral nerve block performed, which has a significant impact
contribute to prolongation of the local anesthetic effect via its on the rate of systemic uptake (Figure 26–2). Most importantly,
vasoconstrictor properties, but also exert a direct analgesic effect they fail to afford protection from toxicity induced by inadvertent
mediated by postsynaptic α adrenoceptors within the spinal cord. intravascular injection (occasionally into an artery, but more com-
2
Recognition of this potential has led to the clinical use of the α monly a vein).
2
agonist clonidine as a local anesthetic adjuvant for spinal anesthesia.
Conversely, inclusion of epinephrine may also have untoward 1. CNS toxicity—All local anesthetics have the ability to produce
effects. The addition of epinephrine to anesthetic solutions can sedation, light-headedness, visual and auditory disturbances, and
potentiate the neurotoxicity of local anesthetics used for periph- restlessness when high plasma concentrations result from rapid
eral nerve blocks or spinal anesthesia. Further, the use of a vaso- absorption or inadvertent intravascular administration. An early
constrictor agent in an area that lacks adequate collateral flow (eg, symptom of local anesthetic toxicity is circumoral and tongue
digital block) is generally avoided, although some have questioned numbness and a metallic taste. At higher concentrations, nystag-
the validity of this proscription. mus and muscular twitching occur, followed by tonic-clonic con-
vulsions. Local anesthetics apparently cause depression of cortical
B. Intentional Use of Systemic Local Anesthetics inhibitory pathways, thereby allowing unopposed activity of excit-
Although the principal use of local anesthetics is to achieve anes- atory neuronal pathways. This transitional stage of unbalanced
thesia in a restricted area, these agents are sometimes deliberately excitation (ie, seizure activity) is then followed by generalized
administered systemically to take advantage of suppressive effects CNS depression. However, this classic pattern of evolving toxicity
on pain processing. In addition to documented reductions in has been largely characterized in human volunteer studies (which
anesthetic requirement and postoperative pain, systemic adminis- are ethically constrained to low doses) and by graded administra-
tration of local anesthetics has been used with some success in the tion in animal models. Deviations from such classic progression
treatment of chronic pain, and this effect may outlast the dura- are common in clinical toxicity and will be influenced by a host
tion of anesthetic exposure. The achievement of pain control by of factors, including patient vulnerability, the particular anesthetic
systemic administration of local anesthetics is thought to derive, at administered, concurrent drugs, and rate of rise of serum drug
least in part, from the suppression of abnormal ectopic discharge, levels. A recent literature review of reported clinical cases of local
an effect observed at concentrations of local anesthetic an order of anesthetic cardiac toxicity found prodromal signs of CNS toxicity
magnitude lower than those required for blockade of propagation in only 18% of cases.
of action potentials in normal nerves. Consequently, these effects When large doses of a local anesthetic are required (eg, for
can be achieved without the adverse effects that would derive from major peripheral nerve block or local infiltration for major plastic
failure of normal nerve conduction. Escalating doses of anesthetic surgery), premedication with a parenteral benzodiazepine (eg,
appear to exert the following systemic actions: (1) low concentra- diazepam or midazolam) will provide some prophylaxis against
tions may preferentially suppress ectopic impulse generation in local anesthetic-induced CNS toxicity. However, such premedi-
chronically injured peripheral nerves; (2) moderate concentrations cation will have little, if any, effect on cardiovascular toxicity,
may suppress central sensitization, which would explain therapeu- potentially delaying recognition of a life-threatening overdose. Of
tic benefit that may extend beyond the anesthetic exposure; and note, administration of a propofol infusion or general anesthesia
(3) higher concentrations will produce general analgesic effects accounted for 5 of the 10 cases presenting with isolated cardiovas-
and may culminate in serious toxicity. cular toxicity in the aforementioned literature review of reported
clinical cases.
Toxicity If seizures do occur, it is critical to prevent hypoxemia and
acidosis, which potentiate anesthetic toxicity. Rapid tracheal intu-
Local anesthetic toxicity derives from two distinct processes: (1) bation can facilitate adequate ventilation and oxygenation, and
systemic effects following inadvertent intravascular injection or is essential to prevent pulmonary aspiration of gastric contents
absorption of the local anesthetic from the site of administration; in patients at risk. The effect of hyperventilation is complex, and