Show Notes

I. Pathophysiology & Mechanisms

Definition: Systemic toxicity secondary to local anesthetic (LA) via accidental intravascular injection or excessive systemic absorption.
Threshold: Occurs when plasma concentration exceeds the safety threshold for cardiac and neural tissue.
Agent Profile: Bupivacaine (High Risk)
- Highly lipophilic with high protein binding.
- “Fast-on, Slow-off” Kinetics: Strong $Na^{+}$ channel binding with extremely slow dissociation during diastole.
- Myocardial Depression: Direct inhibition of $Ca^{2+}$ release from the sarcoplasmic reticulum, impairing contractility.
- Low CC:CNS Ratio: The dose required for cardiac collapse is very close to the dose that triggers seizures (narrow safety margin).
Contributing Factors:
- Acidosis/Hypercapnia: Increases the fraction of free drug and promotes ion trapping in the brain/heart; shifts the LA-binding curve toward higher toxicity.
- Hypoxemia: Exacerbates myocardial depression and lowers seizure threshold.

Extremes of Age: Neonates (low $\alpha$ -1-acid glycoprotein) and elderly (reduced clearance).
Body Composition: Low muscle mass/frailty (decreased volume of distribution).
Organ Dysfunction:
- Hepatic: Reduced metabolism of amide LAs.
- Renal: Accumulation of metabolites; risk of metabolic acidosis lowering seizure threshold.
- Cardiac: Reduced cardiac output slows hepatic delivery/clearance; heart failure patients are more sensitive to $Na^{+}$ channel blockade.
Pregnancy: Increased sensitivity to cardiotoxicity.

Vascularity of Site (Highest to Lowest Risk):
1. Intercostal blocks (highest absorption rate).
2. Caudal/Epidural.
3. Interfascial plane blocks (e.g., TAP block).
4. Psoas compartment/Sciatic.
5. Brachial plexus.
Technique: Large volume infiltration, lack of ultrasound, lack of incremental injection.

Weight-Based Dosing:
- Lidocaine (Plain): Max $4.5\text{ mg/kg}$ .
- Lidocaine (with Epi): Max $7\text{ mg/kg}$ .
- Bupivacaine: Max $2.5\text{--}3\text{ mg/kg}$