Local anesthetics work by blocking sodium channels and interrupting nerve conduction. They are classified based on their chemical structure as esters or amides. Amides like lidocaine and bupivacaine are metabolized in the liver and have a lower risk of allergic reactions compared to esters. The potency, onset, and duration of local anesthetics depends on factors like lipid solubility, dose, pH, and addition of vasoconstrictors. Toxicity from local anesthetics is related to the dose administered and rate of absorption. Early symptoms of toxicity involve the central nervous system like agitation and seizures. Later, cardiovascular symptoms like arrhythmias and hypotension can occur. Treatment involves stopping administration, managing

1. LOCAL ANESTHETIC
SYSTEMIC TOXICTY
( LAST )
Chairperson- Presented by -
PROF. DR. L.D. DASH DR. RAMKRISHNA
Head of Dept. 2ND YEAR PG
DEPT. OF ANESTHESIOLOGY DEPT. OF ANESTHESIOLOGY

2. LOCAL OR REGIONAL ANESTHESIA
• Local anesthetics produce a transient and reversible
loss of sensation (analgesia) in a circumscribed
region of the body without loss of consciousness.
• Normally, the process is completely reversible.

3. MECHANISM
• Interrupting nerve conduction – alpha subunit of Na+
channel & prevent Na+ influx
• Activated Na+ channel are more sensitive than the
resting one

4. STRUCTURE
• LA has 2 domain with either an ester or amide linkage
- hydrophilic
- lipophilic
• Greater the lipid solubility greater the potency and
duration of action
• More potency means increase toxicity and decreased
therapeutic index

5. STRUCTURAL CLASSIFIACTION
AMINOESTERASE
• Procaine, chloroprocaine,
tetracaine, benzocaine, cocaine
• Metabolised by
pseudocholinesterase , except
cocaine in liver
• High incidence of allergy PABA
• Soln are not stable
AMINOAMIDES
• Lignocaine, bupivacaine,
ropivacaine, mepivacaine,
etidocaine
• Metabolised in liver
• Less chance of allergic rxn
• Soln are stable

6. CLASSIFICATION DURATION OF ACTION
• SHORT ACTING- procaine, choloroprocaine (shortest)
• INTEREMEDIATE – Lignocaine, mepivacaine, prilocaine,
cocaine
• LONG ACTING- Bupivacaine, levo- bupivacaine,
tetracaine, ropivacaine, etidocaine,
dibucaine (longest )

8. PROPERTIES OF LA
• POTENCY- increase with lipid solubility
• ONSET - Dose – fastens the onset
Conc.- fastens the onset
PH – LA are weak bases, so pKa closer to
physiological pH gives more unionized drug
diffuses axonal membrane – quicker onset
so NaHco3 is added to increase pH

9. • Types of Nerve Fibres
- Diameter – thin diameter fibres more sensitve
diameter type A>B>C
sensitive C>B>A
- Myelination- Mylinated fibres more sensitive
fibre type A & B are mylinated

12. DURATION OF ACTION
• Mainly depends on extent of LA remains vicinity of
nerve, depends of factors
• LIPID SOLUBILITY - increases duration
• VASCULARITY OF TISSUE – more vascularity decrease
duration by increase in metabolic uptake
• VASOCONSRICTOR- decreases vascular uptake – increase
duration e.g adrenaline, more the intrinsic vasodilatory
effect more prolongation by addition of vasoconstrictor
• METABOLISM- esters have shorter duration as
metabolized by pseudocholineasteraes
•

13. • DOSE - increases duration but not significant
• PLASAMA PROTEIN BINDING –alpha 1 acid glycoprotein
binding agents have longer duration like
bupivacaine
NaHCO3 – increases duration by releasing CO2 into
axon making acidic medium, more ionic form to
Na+ channel binding

14. LAST (LOCAL ANESTHETIC SYSTEMIC TOXICITY)
• Adverse rxn proportional to plasma conct. LA
• Dose of drug administered
• Rate of absorption
• Site of injection
• Vasoactivity of drug
• use of vasoconstrictor
• Biotransformation & elimination

15. TOXIC DOSES OF LA
• EASTERS
• Prilocaine – 12mg/kg
• Chloroprocaine- 12mg/kg
• Cocaine- 3mg/kg
• Tetracaine - 3mg/kg

16. TOXIC DOSES OF LA
• AMIDES
• Lignocaine- 4.5mg/kg (max300mg, without Adr)
7mg/kg (max 500mg, with Adr.)
• Bupivacaine – 2.5mg/kg (175mg max)
• Levobupivacaine- 2.5mg/kg (max175mg)
• Ropivacaine - 3mg/kg ( max 225mg)
• Prilocaine – 8mg/kg
• Dibucaine – 1mg/kg
• Etidocaine- 4.5mg/kg

20. RATE OF ABSORPTION
• Drugs injected rapidly and in bolus have high LA
plasma concentration
• SITE OF INJECTION
• LA used in more vascular tissue poses risk of systemic
toxicities , intercostals block more than epidural than
brachial

21. VASOACTIVITY OF DRUG
• Esters LA being metabolized by Psuedocholineasterse
are short acting & safer
• Amides are long acting , more potent less therapeutic
index risk for toxicities
• Peak plasma level of ester – rate of biotransformation
& elimination
• In case of amides – on rate of absorption

22. USE OF VASOCONSTRICTOR
• Vasoconsrictors decreases the vascular uptake of LA
and increases the safety dose .
• Efficiency of vasoconstrictor depends on intrinsic
vasodilatory effect of LA
• E.g. Toxic dose of ligno. 4.5mg/kg without Adr
7mg/kg with Adr

23. BIOTRANSFORMATION & ELIMINTION
• Ester are safer than amides
• Liver dysfunction increases toxicity
• Elderly and neonates prone to toxicities
• Shock increase the toxicity risk as circulation is
diverted to CNS & CVS ,more LA binds

24. CLINICAL PRESENTATION
• All system are affected but specially CNS & CVS
• CNS fibres are more sensitive than CVS
• Usually CNS symptoms appear earlier, as plasma
level increases CVS symptoms appears

25. CNS TOXICITY
• LA produces stimulation followed by CNS depression
as inhibitory neurons are blocked first
• CLINICAL FEATURES ( Excitatory)
• SUBJECTIVE- lightheadedness, Dizziness – difficulty
in focusing - parasthesia in mouth & tongue –
Tinnitus & auditory hallucinations , confusion
• OBJECTIVE – shivering ,tremors, muscle contraction
Seizure , convulsion

26. • SEIZURES – appears due to initial blockade of
inhibitory neurons
• 10-12 mc/ml plasma level for lignocaine & 4 mc/ml
for bupivacaine
• Seizures – causes hypoxia – metabolic acidosis further
increases toxicity by increase in cerebral blood flow-
increasing LA conct. For binding

27. CNS DEPRESSION
• cessation of seizures ,coma
• respiratory depression & respiratory arrest
• Plasma level 20mic/ml lignocaine &
4mic/ml bupivacaine
• Respiratory depression cause hypercarbia – increase
cerebral circulation, intracellular acidosis- increase in
ionic form LA – increase duration of Na+
channel binding – increase LA toxicity

29. CVS TOXICITY
• All LA can induces dysrythmia except Cocaine –
myocardial depression
• All LA are vasodilator except cocaine, levobupivacaine
& ropivacaine are vasoconstrictor
• Negative ionotropic action on myocardium –
conduction delays – increase PR interval, increase QRS
duration, even sinus arrest, complete heart block
• Toxic dose ratio CNS:CVS = 1:7 (lignocaine) & 1:3 for
(bupivacine)

30. • Low dose LA – increase BP, HR & cardiac output by
sympathetic activity & direct vasoconstriction
• Increase in Plasma LA- vasodilatation due to vascular
smooth muscles relaxation – hypotension – decrease
peripheral vascular resistance
• Reduced cardiac out put – extreme hemodynamic
instability – arrythmia and cardiac arrest
• CVS toxic plasma level – 30 mic/ml lignocaine
6mic/ml bupivacaine

31. ALLERGIC RXN
• Easter LA contains allergens PABA derivative
( para aminobenzoic acid)
• Preservatives used in LA
• Symptoms – rashes , urticaria
• Anaphylaxis – wheeze, anxiety, hyperventilation,
shock, bronchospasm, respiratory distress
• Methemoglobinemia – conversion of prilocaine to
ortholuidine which changes HBS to MethHBS –
treated with inj methylene blue 1mg/kg i.v.

32. DIAGNOSIS OF LAST
• LAST can occur any time from during administration
of LA to 45 minutes after admist.
• High degree of suspicion (most imp for diagnosis)
• CNS excitation – agitation, confusion, twitching,
seizures, convulsions
• CNS depression – drowsiness, coma, apnea,
• NON specific CNS- metallic taste, circumoral
parathesia, tinnitus, dizziness

33. • CVS SIGN – initially – hypertension, tachycardia or
hypotension or bradycardia
• CVS hallmark- ventricular ectopic, multi form
ventricular tachycardia, ventricular fibrillation,
• Progressive hypotension and bradycardia leading to
Asystole and latter to cardiac arrest

34. TREATMENT
• Early recognition
• Immediately stop LA administration
• Call for help
• Secure airway & 100% O2 supplement – intubate if
required
• Control seizures – benzodizepines (preferred) inj.
Midazolam 0.2mg/kg bolus repeat after 5 min
infusion 2mg/kg/hr or inj propofol @ 1mg/kg or
inj. Thiopentone 2-5mg/kg, muscle relaxant use
intractable seizures.

35. • Shocks – use IV fluid and vasopressin
• Ventricular arrhythmia – inj amiadarone 150mgover
10 minutes followed by 360mg in 6 hours and 540mg
in next 18 hours
• CVS Dysrythmia – cardiopulmonary resususitation
• avoid calcium channel blocker, beta blocker

36. INTRA-LIPID TREATMENT
• Mechanism- lipid sink – increase clearance by
extraction of LA from cardiac tissue
• Lipid counteract LA inhibition of myocardial fatty acid
oxidation , release energy – reverse cardiac depression
• Inj. 20% intralipid – 1.5ml/kg over 1 minutes (100ml)
infusion @ 0.25ml/kg/min ( 500ml over 30 mins)
• Repeat bolus every 5 mins for persistent cvs collapse
• Double the infusion rate if BP returns but remain low
• Infuse for minimum 30 mins

38. PREVENTION
• Maintain vigilance, suspicion
• Monitor ECG, NIBP, Aterial 02 sat.
• Communicate with patient if feasible
• Be conservative in dosing of LA – low concentration
but optimum dose
• Aspirate in every 3-5ml of LA
• Inject slowly (<20ml/min) avoid high pressure
injection
• Use additives to decrease dose of LA

39. • Use of Benzopdiazipines premedication can prevent
mild CNS toxicity
• Monitor the patient atleast 30 mins
• BE prepared with – emergency airway , drugs
• 20% intralipid is highly recommend and kept ready

40. THANK YOU