4. Local Anaesthetics: Toxicity Flashcards
Factors that predispose a patient to local anaesthetic toxicity
Site of injection
Drug dosage and concentration
Vasoconstrictors
Binding:
Mechanisms of toxicity
Site of injection
ascularity of the anatomical site of
injection and the presence locally of tissue such as fat, which may bind local
anaesthetics.
after intercostal
and paracervical block,
sacral extradural (caudal) block,
lumbar and thoracic extradural block,
brachial plexus block,
sciatic and
femoral
nerve block and subcutaneous infiltration
Drug dosage and concentration
not only the peak level but also the rate of rise
that may contribute to local anaesthetic toxicity.
total mass less important than its concentration
lidocaine 3.0 mg kg−1,
7.0 mg kg−1
with adrenaline;
bupivacaine 2.0 mg k
convulsive activity supervenes when
bupivacaine concentrations reach around 4 μg ml
lidocaine levels reach 10–12 μgm
Vasoconstrictors
use of vasoconstrictors lowers the maximum blood concentrations
but does not prolong the time to peak.
There is also a complex interrelation
with the inherent vasoactivity of local anaesthetics
At very low concentrations all enhance vascular smooth muscle activity and cause vasoconstriction
clinical doses they demonstrate vasodilator activity that is dose-dependent and which
varies for each drug.
Binding
local anaesthetics bind mainly to α1-acid glycoprotein,
which is a high affinity,
low-capacity site and,
to a lesser extent,
to low-affinity,
high-capacity sites on albumin.
The binding decreases as pH decreases,
and so toxicity is increased by hypoxia and acidosis.
A decrease in intracellular pH will lead to increased ionization
within the axoplasm and ion trapping.
The convulsive threshold is inversely related to arterial PCO2
Mechanisms of toxicity
cardiovascular and CNS toxicities that may be seen are
common to all local anaesthetic agents
are predictable in light of the known
mechanism of action of these drug
Local anaesthetics work by stabilizing the axonal
membrane, and will stabilize all excitable membranes, including those of skeletal,
smooth and cardiac muscle
Myocardial
the block of Ca2+ channels in the myocardium
Mg-adenosine triphosphate (Mg ATP) concentrations
Inhibition of the carrier, carnitine acylcarnitine transferase which transports
AcylCoA moieties
utilization by myocyte mitochondria
Symptoms, Signs and Immediate Management of Local Anaesthetic Toxicity
Clinical features
complain of circumoral tingling and paraesthesia,
light-headedness and dizziness. They may have visual and auditory disturbance
manifested by difficulty in focusing and tinnitus.
They may be disorientated.
The objective signs are usually excitatory,
with shivering, twitching, and tremors in the
face and extremities preceding full grand mal convulsions
Cardiac arrhythmias may be obvious on
ECG monitoring, but these do not usually supervene until blood concentrations
exceed by several times the convulsant levels.
Generic management:
the generic supportive ABC approach includes ventilation
and inotropes as indicated
Cardiac arrhythmias
: if bupivacaine has been used,
then resuscitation may be prolonged.
Amiodarone (5 mg kg−1 in glucose 5% as the drug is incompatible with
saline solutions) is the drug of choice for most induced arrhythmias, apart from
ventricular fibrillation
infusion of lipid emulsion. The effects of the intramyocardial inhibition
of carnitine acylcarnitine transferase may be attenuated
enhanced energy
substrate for myocardial mitochondria
lipid sink’ hypothesis
which suggests that the lipophilic drugs are bound preferentially by the locally
high concentration of intravascular lipid rather than to tissues
intravenous Intralipid
20%, 1.5 ml kg−1 stat over 1 minute,
followed by an infusion at a rate of 15 ml kg–
Grand mal convulsions
BZD
phenytoin (usually given in a starting dose of 15 mg kg−1)
has a membrane-stabilizing local anaesthetic action.
A better choice might be thiopental
It is a very effective anticonvulsant which, in small bolus doses of
50 mg, should suppress a fit that has been induced by local anaesthetic toxicity,
but if necessary can be given as an infusion of 1–3 mg
Pulmonary sequestration:
high blood levels may be attenuated by temporary
sequestration of local anaesthetic within the lung. A high lung:blood partition
coefficient encourages some uptake by the lung, and because the extravascular pH
of lung is lower than that of plasma, this encourages ion trapping. Prilocaine is
sequestered more effectively than bupivacaine, whose uptake in turn is greater than
that of lidocaine.
Allergic reactions:
genuine allergy to amides is extremely rare, but is commoner
with esters.
Allergic reactions are due mainly to para-aminobenzoic acid (PABA),
which is a product of the metabolism of ester local anaesthetics such as procaine,
benzocaine, chloroprocaine and amethocaine.
Cardiovascular effects
Lidocaine can be used as a primary treatment for ventricular arrhythmias.
It decreases the maximum
rate of depolarization but
does not alter the resting membrane potential
Cardiac depolarisation
Depolarization is related to sodium influx through fast channels
calcium influx through slow channels
slow channels are responsible for the spontaneous
depolarization of the sinoatrial node (SAN).
