Local Anesthetics - Toxicity
Allergic ReactionsTrue allergic reactions to local anesthetics are uncommon. It is important to differentiate them from common nonallergic responses such as vasovagal episodes and responses to intravascular injection of local anesthetic and/or epinephrine.
- Ester-type local anesthetics may cause allergic reactions from the metabolite p-aminobenzoic acid. These anesthetics also may produce allergic reactions in persons sensitive to sulfa drugs (e.g., sulfonamides or thiazide diuretics).
- Amide-type local anesthetics are nearly devoid of allergic potential. Multidose vials of anesthetic solutions containing methylparaben as the preservative may produce an allergic reaction in patients sensitive to p-aminobenzoic acid.
- Local hypersensitivity reactions may produce local erythema, urticaria, edema, or dermatitis.
- Systemic hypersensitivity reactions are rare and can present with generalized erythema, urticaria, edema, bronchoconstriction, hypotension, and cardiovascular collapse.
- Treatment is supportive (see Chapter 18).
- Tissue toxicity is rare with short-term use.
- Post spinal pain syndrome (PSPS), previously known as “transient radicular irritation” (TRI) or “transient neurologic symptoms” (TNS), may occur after subarachnoid injection of local anesthetics. This usually manifests as pain or dysesthesia in the buttocks or legs. (Please see Chapter 16 for more details.)
- Reports of sensory and motor deficits after intrathecal chloroprocaine solutions containing the antioxidant sodium bisulfite resulted in a change in its formulation. EDTA has replaced bisulfite. Nevertheless, intense back pain has been reported after epidural administration of large volumes (≥40 mL) of solution. The back pain is thought to be caused by spasms of the paraspinal muscles due to the calcium-binding properties of EDTA.
Local Anesthetic Systemic Toxicity (LAST)
Local Anesthetic Systemic Toxicity (LAST) usually results from intravascular injection or overdose. However, toxicity can also occur from rapid absorption from tissue depot, especially in highly vascular areas.
- Incidence of systemic toxic reaction is reported to be 7.5 to 20/10,000 peripheral nerve blocks.
- Intravascular injection most commonly occurs during nerve blockade in areas with large blood vessels (e.g., axillary or vertebral artery and epidural veins). This can be minimized by the following:
- Aspiration before injection
- Use of epinephrine-containing solutions for test doses
- Use of small incremental volumes in establishing the block (e.g., 5 mL for each injection)
- Use of proper technique during intravenous regional anesthesia (see Chapter 17)
- CNS toxicity
- Clinical features
- An initial excitatory phase may be due to blockade of inhibitory pathways, as well as release of glutamate (an excitatory neurotransmitter).
- Early signs include dizziness, lightheadedness, tinnitus, perioral numbness, metallic taste.
- Late signs include muscle twitching, tremors, seizures, and coma.
- Respiratory and metabolic acidosis will decrease seizure threshold; therefore, airway management should take precedence in suspected LAST.
- Transversus abdominis plane block techniques after cesarean delivery recently have been linked to CNS toxicity in patients.
- Clinical features
- CVS toxicity
- Toxicity of the cardiovascular system is due to a decrease in rate of depolarization of Purkinje fibers and ventricular muscle, due to sodium channel blockade.
- EKG changes are common.
- Early changes include a prolonged PR interval and an increase in QRS duration.
- Late changes include sinus bradycardia and asystole.
- Cardiodepressant potency correlates with nerve block potency.
- Bupivacaine > lidocaine > chloroprocaine
- Pregnancy increases sensitivity to cardiotoxicity.
- Acidosis and hypoxia markedly worsen cardiotoxicity, making airway management a priority for treatment.
- Treatment of LAST (see Table 16.4)
- Initial Focus
- Airway management: ventilate with 100% O2 and consider advanced airway techniques as acidemia may worsen the clinical picture.
- Seizure suppression: benzodiazepines are preferred. Avoid propofol in patients having signs of cardiovascular instability.
- Alert the nearest facility having cardiopulmonary bypass capability
- Management of cardiac arrhythmia
- BLS/ACLS will require adjustment of common medications (below) and perhaps prolonged effort
- Avoid vasopressin, calcium channel blockers, β-blockers, or local anesthetic
- Reduce individual epinephrine doses to <1 mcg/kg
- Lipid emulsion (intralipid 20%), particularly after intravascular injection of bupivacaine
- Bolus 1.5 mL/kg (lean body mass) intravenously over 1 minute (~100 mL for a 70-kg patient).
- Continuous infusion at 0.25 mL/kg/min
- Repeat bolus once or twice for persistent cardiovascular collapse
- Double the infusion rate to 0.5 mL/kg/min if blood pressure remains low
- Continue infusion for at least 10 minutes after attaining circulatory stability
- Recommended upper limit: approximately 10 mL/kg lipid emulsion over the first 30 minutes
- Initial Focus
- Pathophysiology: The oxidation of heme groups within deoxyhemoglobin (Fe2+) results in methemoglobinemia (Fe3+), which cannot transport oxygen and thus produces a functional anemia.
- Common local anesthetics that cause methemoglobinemia include prilocaine (an ingredient of EMLA cream), which is metabolized to o-toluidine in the liver and oxidizes hemoglobin to methemoglobin, and benzocaine, which is found in topical sprays.
- Treatment is with methylene blue (1 to 2 mg/kg intravenously over 5 minutes), which converts methemoglobin back to reduced hemoglobin.
ASRA Check List for Managing LAST. 2012 Version (Table 16.4)
Used with permission from Neal JM, Mulroy MF, Weinberg GL; ASRA. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med 2012;37:16–18.
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