4. Local Anaesthetics: Toxicity Flashcards

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1
Q

Factors that predispose a patient to local anaesthetic toxicity

A

Site of injection

Drug dosage and concentration

Vasoconstrictors

Binding:

Mechanisms of toxicity

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2
Q

Site of injection

A

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

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3
Q

Drug dosage and concentration

A

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

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4
Q

Vasoconstrictors

A

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.

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5
Q

Binding

A

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

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6
Q

Mechanisms of toxicity

A

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

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7
Q

Symptoms, Signs and Immediate Management of Local Anaesthetic Toxicity

Clinical features

A

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.

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8
Q

Generic management:

A

the generic supportive ABC approach includes ventilation
and inotropes as indicated

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9
Q

Cardiac arrhythmias

A

: 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

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10
Q

intravenous Intralipid

A

20%, 1.5 ml kg−1 stat over 1 minute,

followed by an infusion at a rate of 15 ml kg–

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11
Q

Grand mal convulsions

A

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

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12
Q

Pulmonary sequestration:

A

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.

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13
Q

Allergic reactions:

A

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.

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14
Q

Cardiovascular effects

A

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

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15
Q

Cardiac depolarisation

A

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).

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16
Q

Conduction effects with levels

A

Cardiac conduction slows with increasing
blood levels, and this is manifest by an increased
PR interval and duration of the QRS
complex (ventricular depolarization).

High doses depress SAN pacemaker activity,
perhaps by inhibiting the slow calcium channels,
and they also depress atrioventricular nodal conduction.

17
Q

potency of the agents

A

local anaesthetics exert a dose-dependent negatively
inotropic action on the myocardium

Bupivacaine is more dangerous than lidocaine in overdose by predisposing
patients to arrhythmias and VF

underlying mechanism for this effect is
not known, but it appears to cause a unidirectional block with re-entrant tachyarrhythmias.

The drug binds avidly
to myocardial cells, and there is a decrease in the rate of depolarization and action
potential duration, with subsequent conduction block and electrical inexcitability

18
Q

Myotoxicity

A

: local anaesthetics will damage muscle into which they are injected
directly. Skeletal muscle is a regenerating tissue, and so this is not usually a clinical
problem, although persistent diplopia has been reported following the use of bupivacaine
0.75% concentrations for retrobulbar ophthalmic block.

19
Q

Prilocaine

A

toxicity: prilocaine is considered to be one of the safest local anaesthetics.
Its use in high doses may lead to methaemoglobinaemia.