FEATURES ABOUT LOCAL ANESTHETIC SYSTEMIC TOXICTY

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