Lidocaine

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Lignocaine, Xylocaine

ICU INDICATIONS:

1. Ventricular arrhythmias

Note: This monograph is for intravenous lidocaine administration for ventricular arrhythmias only. It does not cover subcutaneous, topical or neuraxial use for local anaesthesia.

PRESENTATION AND ADMINISTRATION:

IV:

Lidocaine 2% (20 mg/mL) ampoules

Available as 100 mg in 5 mL or 400 mg in 20 mL

Check carefully before administration. Other strengths and formulations are available for other indications. Do NOT give any lidocaine preparation IV that also contains adrenaline.

IV bolus dose: Administer undiluted or dilute to a convenient volume (10 mL) to be given as a slow push over 1 - 2 min.

IV maintenance infusion:

Withdraw and discard 100 mL from a 500 mL glucose 5% bag. Add 2 g (100 mL) of lidocaine 2% (400 mg/20 mL) to make a final volume of 2 g in 500 mL. This is a 4 mg/mL solution for infusion.

Administer as per the rates shown in the table below:

If infusion continues beyond 24 hours, the infusion bag must be changed every 24 hours

Compatible with the following IV fluids: Sodium chloride 0.9%, glucose 5%

Store at room temperature. Use immediately once opened. Discard any residue.

DOSAGE:

During CPR for refractory ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT):

1 – 1.5 mg/kg IV bolus (max 100 mg)

For refractory VT/VF:

Repeat IV bolus 0.5 – 0.75 mg/kg (max 100 mg) at 5 - 10 min intervals

Maximum total dose 3 mg/kg or 300 mg within 1 hour

For perfusing ventricular arrhythmias (stable VT, ventricular ectopy causing haemodynamic compromise, wide-complex tachycardia):

0.5 - 1.5 mg/kg IV bolus (max 100 mg)

Repeat IV bolus 0.5 – 0.75 mg/kg (max 100mg) at 5 - 10 min intervals if refractory

Maximum total dose 3 mg/kg or 300 mg within 1 hour.

If infusion is required, commence within 10 min of the last bolus dose:

4 mg/min for first 30 min

2 mg/min for next 2 hours

1 mg/min for next 21.5 hours

If ventricular arrhythmias recur during infusion, administer additional bolus 0.5 mg/kg (max 100 mg) and increase infusion rate by 1 mg/min, not exceeding maximum rate of 4 mg/min.

Total duration of infusion should not normally exceed 24 hours due to the increasing risk of lidocaine toxicity. If infusion is still required beyond this period, reduce the rate to 0.5 mg/min.

DOSAGE IN RENAL, HEPATIC OR CARDIAC FAILURE:

Lidocaine metabolites are renally excreted. Lidocaine is not cleared by haemodialysis. Single dosing does not require dose reduction in renal impairment. If repeated doses are used or a maintenance infusion is commenced, protein binding and clearance are altered with an increased risk of lidocaine toxicity (see WARNINGS).

Lidocaine metabolism is dependent on hepatic blood flow, so continuous infusion should be started at half the usual rate (i.e. 2 mg/min) in hepatic impairment.

For patients with known left ventricular ejection fraction <30%, start infusion at half the usual rate (i.e. 2 mg/min).

Increase vigilance for lidocaine toxicity and reduce or stop any infusion if suspected.

DOSAGE IN PAEDIATRICS:

IV for ventricular arrhythmias:

0.5 - 1 mg/kg IV bolus

Maintenance infusion rate 10 - 50 mcg/kg/min

Do not exceed 20 mcg/kg/min in children with shock, hepatic disease or congestive heart failure. Not recommended for use in neonates or infants < 6 months old.

CLINICAL PHARMACOLOGY:

Lidocaine is a tertiary amine that suppresses action potentials in excitable tissues by blocking voltage-gated sodium channels. It is a class 1B antiarrhythmic agent. In cardiac myocytes, it slows the rise of the cardiac action potential during phase 0, thereby increasing the effective threshold potential and so reducing the automaticity of conduction tissue. It has a mild negative inotropic effect and weak neuromuscular blocking activity. Lidocaine has a rapid onset of action with a half-life of 90 - 120 min. However, for the first 30 minutes of an infusion, the plasma half-life is less than 10 minutes due to rapid distribution into tissues. The half-life may be prolonged in liver or cardiac failure as previously described. Lidocaine is mostly hepatically cleared, with two active metabolites cleared renally that can cause central nervous system toxicity.

CONTRAINDICATIONS:

1. Known hypersensitivity to lidocaine or other amide local anaesthetics
2. Heart block or conduction abnormality without a functioning pacemaker. This includes second or third degree heart block, severe sinoatrial of intraventricular block, and Wolff-Parkinson-White or Adam-Stokes syndrome
3. Co-administration with other sodium channel blocking antiarrhythmic drugs (e.g. flecainide)

WARNINGS:

Monitoring:

Continuous ECG monitoring is mandatory during lidocaine administration, with a baseline 12-lead ECG obtained prior to commencing any infusion. Resuscitation equipment must be available and easily accessible. Monitoring for any signs or symptoms of toxicity should be frequent - see toxicity below.

Lidocaine toxicity:

Effects are predominantly seen within the central nervous system (CNS), then the cardiovascular system as toxicity progresses.

CNS signs of lidocaine toxicity may be biphasic with an initial excitation phase followed by a depression phase. - Excitation: blurred vision, tinnitus, restlessness, tongue or lip numbness, vertigo, slurred speech, visual or auditory hallucinations shivering, muscle twitching, or seizures.

• Depression: decreased level of consciousness or apnoeas. In awake patients, specific symptoms should be enquired about frequently with patients encouraged to report any abnormality early. In sedated or anaesthetised patients, toxicity may only become apparent when cardiovascular signs appear.

Cardiovascular signs may initially be tachycardia and hypertension, followed by sinus bradycardia, hypotension (which may be profound), conduction defects on ECG (prolonged PR & QRS duration), ventricular arrhythmias, or cardiac arrest.

If any signs or symptoms appear, the lidocaine infusion should be stopped and medical staff notified.

Mild agitation, restlessness or seizures may be managed with midazolam boluses. If the patient deteriorates to the point they require resuscitation, CPR (if appropriate) should be prolonged.

Additional actions should include:

• Hyperventilation and/or bicarbonate administration to reduce acidosis AND
• Administration of lipid emulsion (intralipid 20%) as an antidote. This will extract lidocaine from the tissues. Intralipid should be administered as soon as possible as a loading dose of 1.5 mL/kg IV bolus over 1 minute. A repeat bolus can be considered if there is a failed or transient response to the first bolus. If there is clinical response to either bolus, start an IV infusion at 0.25 mL/kg/min. This should be increased to 0.5 mL/kg/min if the patient remains hypotensive. Continue the infusion for at least 10 min after haemodynamic stability or until a total dose of no more than 12 mL/kg is reached.

PRECAUTIONS:

General: See WARNINGS

Laboratory Tests: No additional laboratory tests are required

Laboratory Test Interactions: None known

Pregnancy: Lidocaine has been frequently administered to pregnant women without evidence of increased incidence of malformations. Lidocaine readily crosses the placental barrier and metabolism has been demonstrated by a term fetus. Fetal or neonatal bradycardia or tachycardia have been shown, as have neonatal hypotonia or respiratory depression.

Nursing Mothers: Lidocaine may enter breast milk and considered to have minimal effects on a neonate.

IMPORTANT DRUG INTERACTIONS FOR THE ICU:

Drugs that lower the seizure threshold such as tramadol or selective serotonin reuptake inhibitors (SSRIs) can increase the risk of CNS toxicity.

Amiodarone may increase the serum concentrations of lidocaine.

Cimetidine and propranolol alter lidocaine metabolism by affecting hepatic blood flow, requiring a dose reduction of lidocaine.

Co-administration with clarithromycin or voriconazole may increase lidocaine concentration, contributing to toxicity.

Lidocaine should be used with caution if co-administering other local anaesthetics. The safe total dose of local anaesthetics are additive, inclusive of all routes of administration. Appendix 9 describes local anaesthetic safety calculations.

Mexiletine is an oral analogue of lidocaine and should not be administered in conjunction with IV lidocaine.

Suxamethonium action may be prolonged in the presence of high-dose lidocaine.

Lacosamide my increase lidocaine toxicity with a prolonged PR interval, bradycardia, or ventricular tachyarrhythmias.

ADVERSE REACTIONS:

Nervous System: See 'local anaesthetic toxicity' under WARNINGS above

Cardiovascular System: See 'local anaesthetic toxicity' under WARNINGS above

Digestive: Nausea, vomiting

Haematological: Methaemoglobinaemia

Ophthalmic: Blurred vision, diplopia

Otic: Tinnitus

Respiratory: Respiratory depression