Local Anesthetic Systemic Toxicity Study Guide.docx

**Local Anesthetic Systemic Toxicity (LAST)** What is it? - LAST= **L**ocal **A**nesthetic **S**ystemic **T**oxicity - Potential side effect of local anesthetics -\> neurologic and cardiovascular consequences - Can occur with ANY local anesthetic and ANY route of administration - Mi...

**Local Anesthetic Systemic Toxicity (LAST)** What is it? - LAST= **L**ocal **A**nesthetic **S**ystemic **T**oxicity - Potential side effect of local anesthetics -\> neurologic and cardiovascular consequences - Can occur with ANY local anesthetic and ANY route of administration - Minor LAST events: Tinnitus, Perioral numbness, Metallic taste - Major LAST events: Seizures, Cardiac Arrest - CAN BE FATAL Pharmacology - All local anesthetics have a *hydrophobic aromatic ring* and a *hydrophilic amine group* - Intermediary chain is either an ester link or an amide link - This chain determines whether the local anesthetic is classified as an AMINOESTER or AMINOAMIDE - This chain determines the metabolism of the local anesthetic - **[ESTERS]: Plasma Cholinesterase; synonymous with amino-esters** - **[AMIDES]: Hepatic oxidation** Most Toxic - Lower pKa - Higher lipophilicity - Lower protein binding - Epi or other vasoconstrictors reduce risk of toxicity How do LAs work? - **ALL local anesthetics BLOCK VOLTAGE-GATED SODIUM CHANNELS** - This prevents the influx of sodium and depolarization / action potential does NOT occur - This prevents the transmission of neuronal sensory impulses -\> brain Factors Affecting Systemic Absorption of Local Anesthetics - **Total local anesthetic dose** administered - Blocks requiring larger dose / larger volumes increase the risk of systemic absorption - "Repeated" dosing - **Site of administration**/vascularity of injection site - Rate of systemic absorption from highest to lower is: [Intrapleural \> Intercostal \> Caudal \> Epidural \> Brachial plexus \> Sciatic/femoral \> SQ] - **Properties of individual local anesthetics** - **Addition of vasoconstrictors** (epinephrine) **lowers risk** - **Anything that increases free plasma amount of LA --or- increases sensitivity to LA** - LAST has been reported with the use of EMLA cream and topical tetracaine in kids, with the use of oral viscous lidocaine, after topical administration for bronchoscopy - Always aspirate before injection rule out intravascular puncture - [Injection Site Systemic Absorption (In descending order]: - Intravenous - Tracheal - Intercostal - Caudal - Paravertebral - Epidural - Brachial - Spinal - Sciatic/Femoral - SQ Other Factors that Affect Risk - **Topical application** (mucous membrane absorption) - **Inadvertent Arterial Injection** - Interscalene blocks - Cervical blocks - Stellate ganglion blocks - **Continuous Infusions** - Catheters can migrate, and may see delayed, gradual onset (hours-\>days) - **Use caution with LA applied to the face!** - **Patient Factors** - Low alpha-1 acid glycoprotein (decreased protein binding = increased plasma levels) - Hyperdynamic circulation - Ex: pregnancy, Hyperthyroid, MH, Liver failure - Impaired hepatic clearance - Lower levels of amide clearance - Extremes of age - Metabolic Disturbances: acidosis, hypoxia, hypercarbia A screenshot of a medical report Description automatically generated Recommended Maximum Dosage  \*Base dosage off of IBW\* Safety Standards - **Emergency resuscitation equipment** should be available - Airway Management (Ambu, Suction, Stethoscope) - Vasoactive Drugs - Lipid Emulsion - Patients must have a **functioning IV** - **Monitoring**: continuous pulse oximetry, EKG, BP - **Supplemental oxygen** is recommended for peripheral nerve blocks Prevention of LAST - **Use the lowest doses possible!** - **Ultrasound guided blocks may be safer!** - *Base max doses on [lean] body weight (not ABL)* - *Reduce doses in patients:* - *At risk of increased uptake (pregnancy, uremia)* - *Decreased levels of alpha-1 acid glycoprotein (pregnancy, neonates)* - *Increased sensitivity to effects of local anesthetics (elderly, pregnancy)* - *Reduce doses in patients with impaired clearance of LAs (renal, hepatic, cardiac disease)* - *Adding epinephrine can slow rate of absorption 20-50%* - *Use safe injection practices* - *Awake patients/ light sedation* - *Aspirate before injecting* - *Slow incremental dosing (no more than 5-ml at a time, allow 30-45 seconds between injections)* - *Use test doses to assess for intravascular injection (Epi)* - ***\*\*Positive test dose if HR increases \> 10bpm and SBP \>15 mm Hg within 20-40 sec\*\**** Use Caution - PNBs + IV lido w/ induction - PNBs + surgeon injection at incision - IV induction + surgeon injection at incision - **Use of Exparel** - **Encapsulated liposomal lidocaine, slowly releases** Epinephrine - Most common additive to local anesthetic solutions - Avoid injecting in areas that may lack collateral flow (**fingers, toes, penis, nose)** - Avoid in patients at risk of dysrhythmias or systemic HTN - Used as a marker for inadvertent intravascular injection - 5 μg/mL or 1:200,000 of epinephrine - False negatives and false positives can occur (parturients, patients on beta-blockers) - Test dose is considered positive if HR increases by 10 bpm or more and SBP increases 15 mmHg or more within 20-40 seconds - Added to LA solutions to decrease the rate of vascular absorption - Improves depth and duration of anesthesia Bupivacaine - The ratio of the dosage required for irreversible circulatory collapse and the dosage that will produce CNS toxicity (CC/CNS ratio) is *lower* for bupivacaine and etidocaine than for lidocaine - Resuscitation is [more difficult] after bupivacaine-induced cardiac collapse - Acidosis and hypoxia further potentiate bupivacaine cardiotoxicity - Pregnant patients are more susceptible to cardiac toxicity (Epidural max. concentration 0.5%) Clinical Presentation - CLASSIC ONSET: - Follows soon after LA injection - CNS excitation (early) -\> CNS inhibition (late) -\> CV Excitation -\> CV Collapse - Only 60% of patients present this way! - 40% of cases present with seizure -\> cardiac arrest - CV Symptoms can also occur alone - [CNS Symptoms]: perioral numbness, metallic taste, tinnitus, mental status changes, anxiety, agitation, visual changes, muscle twitching loss of consciousness -\> seizures - [CV Symptoms]: tachycardia and HTN (initial sympathetic stimulation) OR bradycardia and hypotension -\> heart conduction abnormalities, decreased contractility, ventricular dysrhythmias, asystole - **Presentation onset timing and symptoms vary** Initial Treatment - **STOP INJECTION of local anesthetic** - **Call for HELP!** - **Manage the airway/ 100% FiO2** - **Treat seizures to reduce oxygen consumption, avoid acidosis** - Benzodiazepine (Midazolam 1-2 mg) - Propofol (small 10-20 mg doses) - Muscle relaxants stop skeletal muscle activity but DO NOT suppress neurological involvement - **Manage arrhythmias** - Amiodarone should be administered as first-line anti-arrhythmic - AVOID lidocaine - AVOID Na+ channel blockers (Quinidine, Procainamide, Mexiletene, Disopyramide, Tocanide) - Reduce doses of epinephrine (\< 1 mcg/kg IV) - AVOID VASOPRESSIN - AVOID CALCIUM CHANNEL LOCKERS and BETA BLOCKERS - **Administer LIPIDS** - Lipid Rescue with 20% lipid emulsion (NOT Propofol!) - **1.5 ml/kg IV for patients \< 70 kg and then 0.25 ml/kg/min** - **100 ml IV for patients \> 70 kg and then 250 ml over 15-20 min** - **Maximum lipid dose is 12 ml/kg** - Exact MOA is unclear - *"**Lipid sink**" theory (Lipid binds local anesthetic to remove from target tissue vs."**Lipid shuttle**" theory (Lipid carries LA from heart & CNS* - Propofol is NEVER an acceptable substitute - Dose Recommendations: - *[ASRA]: 100 ml for patients \>70 kg then infusion of 0.25 ml/kg/min. Continue at least 15 min after hemodynamic stability restored* A diagram of a medical procedure Description automatically generated