LIDOCAINE HYDROCHLORIDE
Clinical safety rating: safe
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
Lidocaine hydrochloride is a sodium channel blocker that inhibits voltage-gated sodium channels in neuronal and cardiac cell membranes, stabilizing the membrane and preventing depolarization, thereby blocking nerve impulses and exerting local anesthetic and antiarrhythmic effects.
| Metabolism | Lidocaine undergoes rapid hepatic metabolism primarily via cytochrome P450 enzymes, predominantly CYP3A4, and to a lesser extent CYP1A2. Major metabolites include monoethylglycinexylidide (MEGX) and glycinexylidide (GX), which are pharmacologically active. Less than 10% is excreted unchanged in the urine. |
| Excretion | Primarily hepatic metabolism (90% CYP3A4, also CYP1A2) to inactive metabolites (monoethylglycinexylidide, glycinexylidide); <10% excreted unchanged in urine. Renal elimination accounts for the majority of metabolite clearance. |
| Half-life | Terminal elimination half-life is 1.5–2 hours in adults. In patients with heart failure, hepatic cirrhosis, or those on CYP-inhibitors, half-life may be prolonged to ≥3 hours; in neonates, up to 3–6 hours. |
| Protein binding | 60–80% bound primarily to alpha-1-acid glycoprotein (AAG) and, to a lesser extent, albumin. Binding is saturable and increases in conditions with elevated AAG (e.g., inflammation, myocardial infarction). |
| Volume of Distribution | 1–1.5 L/kg in adults; higher in infants (2–3 L/kg). Distribution is rapid and extensive, reflecting high perfusion to well-perfused tissues (brain, heart, liver, kidneys). |
| Bioavailability | Oral: <35% (extensive first-pass metabolism) – not used orally for systemic effects. IM: 100% (complete absorption). Epidural: near 100%. Topical (intact skin): negligible (<1%); mucosal: 10–20% depending on site. |
| Onset of Action | IV: 45–90 seconds; IM: 5–15 minutes; Subcutaneous/local infiltration: <2 minutes; Epidural: 5–15 minutes; Topical (mucous membrane): 2–5 minutes. |
| Duration of Action | IV: 10–20 minutes (antiarrhythmic effect); IM: 30–90 minutes; Local infiltration: 0.5–1 hour (without epinephrine), 2–6 hours (with epinephrine); Epidural: 30–90 minutes; Topical: 15–45 minutes. |
| Molecular Weight | 234.34 |
IV: 1-1.5 mg/kg bolus, then 1-4 mg/min continuous infusion. Max: 3 mg/kg (300 mg) loading dose. For ventricular arrhythmias.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment recommended for GFR >10 mL/min. For GFR <10 mL/min, reduce maintenance infusion by 25-50% or use alternative agent due to risk of metabolite accumulation. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50%. Child-Pugh C: avoid use or reduce dose by 75% with close monitoring. |
| Pediatric use | IV: Loading dose 1 mg/kg, may repeat once. Maintenance infusion: 20-50 mcg/kg/min. Max total dose: 3-5 mg/kg for infiltration anesthesia. |
| Geriatric use | Consider reduced initial bolus (0.5-1 mg/kg) and lower maintenance infusion rates (1-2 mg/min) due to decreased hepatic clearance and increased risk of toxicity. |
| 1st trimester | Lidocaine is generally considered safe in the first trimester; no increased risk of major malformations has been observed at typical clinical doses. However, use only if clearly needed. |
| 2nd trimester | Safe for use in the second trimester; no known adverse effects on fetal development. Monitor for maternal toxicity. |
| 3rd trimester | Use with caution due to potential for fetal bradycardia and central nervous system depression. Avoid high doses and repeated administration near term. |
Clinical note
Beta-blockers may increase the risk of lidocaine toxicity Can cause CNS toxicity (seizures) and cardiovascular collapse.
| FDA category | Animal |
| Placental transfer | Lidocaine crosses the placenta readily via passive diffusion; peak fetal concentrations reach 50-70% of maternal levels. Fetal acidosis can lead to ion trapping and accumulation. |
■ FDA Black Box Warning
WARNING: LIFE-THREATENING AND FATAL ADVERSE EVENTS HAVE BEEN REPORTED WITH THE USE OF LIDOCAINE HYDROCHLORIDE, INCLUDING CARDIAC ARREST, SEIZURES, AND RESPIRATORY DEPRESSION. INTRAVASCULAR INJECTION OF LOCAL ANESTHETICS CAN CAUSE CARDIAC TOXICITY. RESUSCITATIVE EQUIPMENT AND MEDICATIONS FOR THE MANAGEMENT OF TOXIC REACTIONS MUST BE IMMEDIATELY AVAILABLE.
| Common Effects | ventricular arrhythmias |
| Serious Effects |
Hypersensitivity to lidocaine or amide-type anestheticsSevere heart block (without pacemaker)Severe hypotension or cardiogenic shock
| Precautions | May cause cardiac toxicity, including bradycardia, hypotension, and cardiac arrest, especially with high doses or rapid IV administration., Central nervous system toxicity can lead to seizures, confusion, and respiratory depression., Use with caution in patients with hepatic impairment (reduced clearance), severe renal disease, or heart failure., Risk of methemoglobinemia with high doses or concurrent use of oxidizing agents., Not recommended for routine use in pregnancy; only if benefit outweighs risk to fetus., May cause local irritation or allergic reactions; discontinue if signs of hypersensitivity occur. |
Loading safety data…
| Breastfeeding | Lidocaine is excreted into breast milk in small amounts (less than 1% of maternal dose). It is unlikely to harm a nursing infant when used locally or intravenously at typical doses. Monitor for signs of toxicity (e.g., drowsiness, irritability) in the infant, especially with high-dose or prolonged use. |
| Lactation Rating | L2 (Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies. Lidocaine crosses the placenta; fetal plasma concentrations are approximately 50-60% of maternal levels. No increased risk of major congenital anomalies reported with standard doses. Second and third trimester: use with caution due to potential fetal bradycardia and acidosis, especially with high doses or repeated administration. First trimester: low risk, but avoid unnecessary use. |
| Fetal Monitoring | Monitor maternal heart rate, blood pressure, and ECG for arrhythmias or toxicity (CNS depression, seizures). Monitor fetal heart rate for bradycardia, especially with higher doses or repeated administration. Assess for signs of fetal acidosis if prolonged use. Observe neonate for respiratory depression if used near delivery. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment of fertility at subtoxic doses. Lidocaine is not associated with altered sperm parameters or ovulation. |
| Food/Dietary | No significant food interactions. However, grapefruit juice may theoretically increase lidocaine levels (CYP3A4 inhibition), though clinical significance is not established. Avoid alcohol due to additive CNS depression. |
| Clinical Pearls | Lidocaine hydrochloride is an amide-type local anesthetic. For local infiltration, maximum dose without epinephrine is 4.5 mg/kg (not to exceed 300 mg); with epinephrine, 7 mg/kg (not to exceed 500 mg). Onset: 2-5 minutes, duration: 0.5-2 hours. Toxic effects include CNS excitement (tinnitus, metallic taste, perioral numbness) then depression (seizures, respiratory arrest). Cardiac toxicity: QRS widening, bradycardia, hypotension. Use with caution in hepatic impairment (ametabolized by liver) and in patients with low cardiac output. For IV administration for arrhythmias, bolus 1-1.5 mg/kg, then infusion. |
| Patient Advice | Do not drive or operate machinery after receiving lidocaine until numbness has worn off and you are fully alert. · If you are using a lidocaine patch or cream, do not apply to broken or irritated skin or near eyes/mouth. · Seek immediate medical attention if you experience difficulty breathing, swelling of the face/lips/tongue, or severe dizziness. · Avoid alcohol consumption while using lidocaine, as it may increase side effects like drowsiness. · Inform your healthcare provider if you have heart disease, liver disease, or a history of allergic reactions to anesthetics. |