LAST AND TOXIC DOSES OF LA

Well-placed local anaesthetics (LAs) can yield great clinical benefits. But systemic toxicity
related to their use can be devastating.
`A life-threatening adverse reaction resulting from local anesthetic reaching significant systemic
circulating levels. Local Anesthetic Systemic Toxicity (LAST) is rare and almost always occurs
within minutes of injection of the local anesthetic.

LAST is due to an excess plasma concentration of the drug. Plasma concentrations of local
anesthetics are determined by the rate of drug entrance into the systemic circulation relative to
their redistribution to inactive tissue sites and clearanceby metabolism. Accidental direct
intravascular injection of local anesthetic solutions during performance of peripheral nerve
block anesthesia or epidural anesthesia is the most common mechanism for production of excess
plasma concentrations of local anesthetics.
The magnitude Of this systemic absorption depends on the
(a) dose administered into the tissues,
(b) vascularity of the injection site,
(c) presence of epinephrine in the solution,
(d) physicochemical properties of the drug

Causes:
Injection of local anesthetic into the systemic circulation (either errantly as part of a regional
block i.e. Bier block)
Rapid absorption of local anesthetic injected into a highly vascular area

Mechanism of action:
LA reaches the circulation via systemic absorption or accidental intravascular injection.
Systemic absorption normally has a delayed onset.Lipophilic LAs rapidly cross cell membranes
and toxicity reflects action at a large number of sites including ionotropic, metabotropic, and
other targets. In the brain, LA affects the balance between inhibitory and excitatory pathways. In
the heart, LAs can cause conduction blocks through effects on sodium, potassium, and calcium
channels. These alone might cause dysrhythmia and reduce contractility. But excess LA may
have more widespread effects still: it can disrupt intracellular signals originating at metabotropic
receptors, leading to reduced cyclic adenosine monophosphate concentrations and thence
reduced contractility.
Signs and symptoms:
 CNS Symptoms
 Minor Signs/Symptoms
 Tongue and perioral numbness
 Parasthesias
 Restlessness
 Tinnitus
 Muscle fasciculations + tremors
 Major Signs/Symptoms
 Tonic-clonic seizures
 Global CNS depression
 Decreased level of consciousness
 Apnea
 Neurologic symptoms typically precede cardiovascular symptoms in lidocaine
toxicity
 Cardiovascular Symptoms
 Early Signs: Hypertension and tachycardia
 Late Signs
 Peripheral vasodilation + profound hypotension
 Sinus bradycardia, AV blocs
 Conduction defects (Prolonged PR, Prolonged QRS)
 Ventricular dysrhythmias
 Cardiac arrest
 Cardiovascular symptoms typically present first in bupivacaine toxicity

Maximum doses of LA:

Management:

• Stop injecting the LA

• Call for help
• Maintain the airway and, if necessary, secure it with a tracheal tube
• Give 100% oxygen and ensure adequate lung ventilation (hyperventilation may help by
increasing plasma pH in the presence of metabolic acidosis)
• Confirm or establish intravenous access
• Control seizures: give a benzodiazepine, thiopental or propofol in small
incremental doses
• Assess cardiovascular status throughout
Consider drawing blood for analysis, but do not delay definitive treatment to do this.

In circulatory arrest Without circulatory arrest

• Start cardiopulmonary resuscitation (CPR) Use conventional therapies to treat:
using standard protocols • hypotension,
• Manage arrhythmias using the same • bradycardia,
protocols, recognising that arrhythmias may • tachyarrhythmia
be very refractory to treatment
• Consider the use of cardiopulmonary
bypass if available
Give intravenous
lipid emulsion
(following the regimen overleaf)
• Continue CPR throughout treatment with lipid emulsion
• Recovery from LA-induced cardiac arrest may take >1 h
Give an initial intravenous bolus injection of 20% lipid emulsion 1.5 ml.kg1 over
1 min and
Start an intravenous infusion of 20% lipid emulsion at 15 ml.kg.h
Give a maximum of two repeat boluses (same dose) if:
• cardiovascular stability has not been restored or
• an adequate circulation deteriorates
Leave 5 min between boluses
A maximum of three boluses can be given (including the initial bolus)

Continue infusion at same rate, but:

Double the rate to 30 ml.kg–1.h–1 at any time after 5 min, if:
• cardiovascular stability has not been restored or
• an adequate circulation deteriorates
Continue infusion until stable and adequate circulation restored or maximum dose
of lipid emulsion given
Give an initial intravenous bolus injection of 20% lipid emulsion 100 ml over 1
min
Start an intravenous infusion of 20% lipid emulsion at 1000 ml.h
Give a maximum of two repeat boluses of 100 ml
Continue infusion at same rate but double rate to 2000 ml.hif indicated at any time
Maximum cumulative dose is 840ml