Local Anesthetic Toxicity
Clinical Manifestations & Management:
1-CNS manifestations:
➧ Early signs: circumoral numbness (Earliest sign), tongue paresthesia, dizziness
➧ CNS Excitation: (restlessness and agitation)
➧ CNS Depression: (slurred speech, drowsiness, unconsciousness)
➧ Muscle twitching, tonic-clonic seizures
➧ Respiratory arrest often follows
Management:
1-Stop LA injection or infusion
2-Call for help
3-Oxygenation
4-Hyperventilation (to decrease cerebral blood flow)
5-Anti-seizures: Benzodiazepines (diazepam 0.1-0.2 mg/kg), Thiopental (1-2 mg/kg)
2-Respiratory manifestations:
➧ Local anesthetics (LAs) depress hypoxic drive (ventilatory response to low PaO₂)
➧ Apnea can result from phrenic and intercostal nerve paralysis
Management:
➧ Respiratory support
3-CVS manifestations:
➧ In general, LAs depress myocardial automaticity (spontaneous phase IV depolarization) and reduce the refractory period causing: bradycardia, heart block (varying degrees), and hypotension which may lead to cardiac arrest.
➧ The R (+) isomer of bupivacaine rapidly blocks cardiac sodium channels and dissociates slowly.
➧ Major cardiovascular toxicity requires about 3× the concentration required to produce seizures.
➧ Ropivacaine is 70% less likely to cause severe cardiac arrhythmias than bupivacaine.
Management:
1-ACLS protocols
2-Vasopressors: Ephedrine, Norepinephrine, Epinephrine
3-Lipid emulsion infusion:
➧ Use of Lipid Emulsion:
-IV bolus of Intralipid 20% (1.5 ml/kg over 1 min) about 100 ml and start infusion of (0.25 ml/kg/min)
-If adequate circulation has not been restored: Repeat the bolus dose twice at 5 min intervals and increase the infusion rate to (0.5 ml/kg/min)
-Continue infusion until an adequate circulation has been restored
-Measure LA & triglyceride levels
Patient-related factors to consider during large volume peripheral nerve block (PNB):
1-Age:
➧ Newborns have about half the adult concentration of α-acid glycoprotein (AAG) which binds free LAs.
➧ Persons over 70 years show increased sensitivity to LAs and decreased clearance.
Recommendation: Reduce LAs dose by 10-20%.
2-Renal dysfunction:
➧ There may be a change in clearance of LAs in uremic patients.
➧ Uremic patients show a rapid rise in LAs plasma levels probably secondary to a hyperdynamic circulation, but uremic patients have increased AAG levels.
Recommendation: Reduce LAs bolus and continuous dose by 10-20% in uremic patients.
3-Hepatic dysfunction:
➧ Clearance of LAs can be dramatically decreased but plasma concentrations remain close to normal secondary to increased volume of distribution (Vd). These patients also can have renal and cardiac dysfunction.
Recommendation: Initial bolus dose can be in the normal dose range but the continuous infusion dose should be reduced by 10-50%.
4-Heart Failure:
➧ Decreased blood flow to the liver and kidneys can cause a decrease in clearance
Recommendation: Repeat or continuous dosing of LAs should be reduced by 10-20%
5-Pregnancy:
➧ Progesterone may increase the sensitivity of nerve axons
➧ There is an enhanced risk of cardiotoxicity by bupivacaine and ropivacaine induced by progesterone. Increased cardiac output causes increased uptake of LAs
Recommendation: Avoid large volume PNB in 1st trimester and reduce doses in epidural and spinal anesthesia in pregnancy
6-Drug interaction:
➧ Amide LAs are cleared by the liver cytochrome P450 enzymes
➧ Propanolol, Cimetidine and Itraconazole can decrease bupivacaine clearance by 30-35%
➧ Ciprofloxacin and Fluvoxamine decrease the clearance of ropivacaine
Recommendation: Single bolus dose is of little concern but continuous infusion should be altered (10-20% decrease)
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