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

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

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.

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

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

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

Order of toxicity IVRA Intercostal Caudal Epidural Brachial plexus Sciatic IVRA

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

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

Moving towards safer molecules ?

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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)

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

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

Prevention is the essence Management Prevention is the essence

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

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

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.

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

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

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

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 - 12 ml /kg – guidelines vary

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

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

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

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

Thank you all