1. Local anesthetic systemic toxicity ( LAST)
Dr. S. Parthasarathy
MD, DA, DNB, Dip Diab.MD ,DCA, Dip software based statistics,
PhD (physiology) FICA

2. What is it ?? Allergic reactions
Tissue toxicity – TNS, lignocaine spinal
Probably blockade of calcium channels ----
LAST – systemic

3. Allergy True immunologic reactions to LAs are generally rare.
True allergic reactions to preservative-free amide-type local anesthetics are so rare.
True anaphylaxis appears more common with ester LAs that are metabolized directly to PABA
Accidental intravenous injections are often misdiagnosed as allergic reactions.
Some patients may react to preservatives, such as methylparaben, included with LAs.

4. History 1880 = cocaine invented and toxicity described
1960 = bupivacaine discovered =
Later levo bupi and ropi invented
Lipid emulsion for LAST ( 0.1 in 1000)

5. Mechanisms
Cardiovascular effects are caused by blockade of cardiac VASCs and K+ channels. Levobupivacaine and ropivacaine are thought less likely to interact with cardiac VASCs.
Possible calcium channel block
Mitochondrial dysfunction
Convulsions may be caused by the blockade of GABA A receptors in the CNS

6. Fast in fast out -- lignocaine
Fast in slow out --- bupivacaine
( dissociation constant – more with bupi )

7. Order of toxicity IVRA Intercostal Caudal Epidural Brachial plexus
Sciatic
IVRA

8. Why difference Age – extremes Additive Speed Which drug
Concurrent illness
Concurrent drugs
Site
Bupi – 2-3 mg / kg
Ligno – 4-5 mg/kg
Ligno with adrenaline
7 mg / kg
But beware of combinations – additive toxicity

9. Toxicity Cocaine worst Tetracaine Bupivacaine L. bupi Ropi Mepi Ligno
Prilo
2– chlorprocaine least

10. Moving towards safer molecules ?

11. Pick up here

12. Starts from to (auditory changes, circum oral numbness,
metallic taste, and agitation),
central nervous system (CNS) findings (seizure, coma, respiratory arrest)
Inhibitory neurons first !!- so seizures
cardiovascular events (hypertension, hypotension, tachycardia, bradycardia, ventricular arrhythmias, cardiac arrest)

13. Injection of lignocaine in the brain induced arrhythmias
Cause – for cardiac effects – CNS depression hypotension and rhythm disturbances .
Hypercarbia , acidosis enhance CNS toxicity

14. Differential diagnosis
Vasovagal
High spinal
Total spinal
Concomitant disease -
High epinephrine dosage

15. Prevention is the essence
Management
Prevention is the essence

16. Check dose of local and epinephrine
USG
Check dose of local and epinephrine
Effective dose in increments – catheters ??
Aspirate frequently
Discard bloody locals
Monitor CVS and IV access
Talk with the patient
Stop injecting
Negative aspiration not foolproof because probe will compress the vein
Hepatic or renal disease

17. (CC:CNS ratio 2 : 7.1 for the two LA)
Convulsion
Lethality
lignocaine
22 mg/kg
76mg/kg
Bupivacaine
5mg/kg
20mg/kg

18. Are they clinically relevant ??
the reduced toxic potential of the two pure left-isomers supports their use in those clinical situations in which the risk of systemic toxicity related to either overdosing or unwanted intravascular injection is high, such as during epidural or peripheral nerve blocks.

19. Treatment Convulsions Thiopentone 1-3 mg/kg Diazepam - 0.15 mg/kg
Midazolam – 0.1 mg / kg
Less doses – because thio itself is myocardial depressant .propofol may cause more hypotension
Benzodiazepines also decrease arrhythmias

20. Arrhythmias Better to use calcium channel blockers
Valproate ( fits and rhythm disturbances )
Phenytoin
Bretylium
NO XYLOCAINE

21. Resuscitation CPB ? Airway- breathing- circulation Oxygen - 100 %
Ventilation
Special
Vasopressin ?
GIK
Amiodarone
if preliminary resuscitation fails ----
CPB ?

22. Lipid emulsion Bolus of intralipid – 20 % - 1.5 ml/kg – 1 minute
Infusion – 0.25 ml /kg/minute
Chest compressions – lipid should circulate
Can increase to 0.5 ml/kg/min
Maximum of 8 ml/kg ml /kg – guidelines vary

23. Mechanism
Direct
Sink theory – sticks to lipid soluble LA and get rid of the drug out of the tissue
Indirect
Overrides mitochondrial translocase from the LA

24. Predominant CNS changes – anticonvulsants
Predominant CVS changes – Go for intra lipid early

25. Prilocaine More than 600 mg
Associated with – o toluidine and methemoglobinemia
IV methylene blue is the treatment

27. Summary Intercostal , IVRA Toxic doses Which local anesthetic
Symptoms and DD
Prevention
Treatment
Lipid emulsion or anticonvulsants -

28. Thank you all