Precautions

Adverse Effects

Adverse reactions to lidocaine are rare and usually the result of intravascular injection, excessive dosage or rapid absorption from highly vascular areas. The following adverse effects were identified in our literature search.

• Cardiovascular: Decreased cardiac output, cardiovascular depression, and decreased oxygen delivery to tissues have been reported. PR and QRS interval prolongation and QT interval shortening have also been reported. Lidocaine can produce cardiac arrhythmias but has a more significant effect on abnormal than normal cardiac tissue (Papich, 2011; SPC Data).

• Epidural Administration:  Use may result in hypotension, urinary retention, and/or ataxia (SPC Data).

• Epinephrine Formulations: Systemic absorption or IV injection may cause tachycardia and hypertension (Papich, 2011; SPC Data).

• Central Nervous System: Drowsiness, ataxia, muscle tremors, depression, and seizures have been reported progressing to grand-mal convulsions. An initial phase of excitation is followed by CNS depression, progressing to coma and, ultimately, respiratory arrest (Beecroft and Davies, 2013; Verlinde et al., 2016).

• Haemolysis and Methemoglobinemia:  Methemoglobinemia and hemolysis have been reported in humans and cats (Katsuki et al., 2004; Khajavirad et al., 2023; Papich, 2011)

• Local Administration: Nerve damage due to needle injury, hematoma, or local anaesthetic toxicity has been reported (Beecroft and Davies, 2013; Verlinde et al., 2016).

Contraindications

The following contraindications relate to using preparations containing adrenaline (epinephrine).

• Cardiovascular Disease: Avoid lidocaine/epinephrine formulations in patients with cardiovascular disease or hyperthyroidism (SPC Data).

• Extremities: Lidocaine/epinephrine formulations should not be used in extremities (e.g. digits, ears, nose, or penis) as ischemic injury may result (SPC Data).

• Intravenous Use: Lidocaine/epinephrine formulations should not be used intravenously (SPC Data).

Reproductive Safety

• Pregnancy: Avoid Use; lidocaine should not be administered during early pregnancy unless the benefits are considered to outweigh the risks. Lidocaine crosses the placental barrier after epidural or intravenous administration but recommended dose levels are unlikely to have adverse effects (Demeulemeester et al., 2018; Hagai et al., 2015; Morishima et al., 1990; Ramanathan et al., 1986; Reynolds, 2011; Smith et al., 1986).

• Lactation: Small amounts of Lidocaine are secreted into breast milk, but recommended dose levels are not expected to cause any adverse effects in breastfed infants. No special precautions are required (LactMed, 2006; Reynolds, 2011; Zeisler et al., 1986).

• Male Fertility: No data available (SPC data).

• Female Fertility: No data available (SPC data).

• Neonates: No data available (SPC data).

Potentially Significant Interactions

Significant Interactions are unlikely when lidocaine is administered as recommended.

• Acidic Solutions: Because lidocaine preparations are acidic, mixing with alkaline solutions may interfere with stability and should be avoided (Papich, 2011).

• Anaesthetic Agents: Lidocaine infusions perioperatively reduce MAC requirements of volatile agents, e.g., isoflurane and sevoflurane; Local application may also help stabilise anaesthesia and reduce additional agent requirements during minor procedures (El-Hawari et al., 2022; Hamp et al., 2013; Marzok et al., 2022; Matsubara et al., 2009; Moran-Muñoz et al., 2014; Rezende et al., 2011; Thengchaisri and Mahidol, 2019; Wilson et al., 2008).

• Antiarrhythmics If systemically absorbed, lidocaine may cause additive or antagonistic cardiac effects to some antiarrhythmic agents (e.g., procainamide, propranolol, quinidine), and toxicity may be enhanced (Wyse et al., 1988).

• β-Adrenergic Antagonists: Lidocaine levels or effects may be increased if administered simultaneously with β-Adrenergic Antagonists, e.g., atenolol, esmolol, propranolol, and sotalol (Wyse et al., 1988).

• Morphine: Coadministration of morphine and lidocaine has demonstrated a beneficial synergistic interaction regarding visceral pain (Penning and Yaksh, 1992).

Safe and Toxic Dose

Rabbits

• Maximum Safe Dose:  We recommend a maximum therapeutic dose of 2 mg/kg per administration regardless of route, with a maximum administration of 0.5 mg/kg at any site.

• Toxic Dose: Doses above 4mg/kg are potentially toxic. However, several studies have safely administered 2mg/kg multiple times intravenously or through deep body injection without adverse effects, and therefore, dosing as high as 4mg/kg appears well tolerated, and rabbits are presumed to metabolise this agent faster than most major pet species (Di Bella et al., 2021; Schnellbacher et al., 2017, 2013)

• Lethal Dose: Regard doses above 20 mg/kg as potentially lethal (Schnellbacher et al., 2013).

• Convulsive Dose: The cumulative convulsive and lethal (cardiotoxic) doses are above 25 mg/kg (Schnellbacher et al., 2013).

• Cardiotoxic Dose: The cumulative convulsive and lethal (cardiotoxic) doses are above 25 mg/kg (Schnellbacher et al., 2013).

Dogs

• Maximum Safe Dose:

• Toxic Dose:

• Lethal Dose: the minmum cumulative lethal dose located in the literature was 80 mg/kg IV.

• Convulsive Dose: The cumulative IV dose for CNS toxicity resulting in convulsive activity in conscious dogs is around 20-22 mg/kg (Feldman, Arthur, & Covino, 1989; Liu, Feldman, Giasi, Patterson, & Covino, 1983)

• Cardiotoxic Dose:  the IV dose resulting in death from cardiovascular toxicity in pentobarbital anaesthetized dogs was 80 mg/kg (Liu, Feldman, Covino, Giasi, & Covino, 1982) and 127 mg/kg in fentanyl/midazolam anaesthetized dogs (Groban, Deal, Vernon, James, & Butterworth, 2001)

Cats

• Maximum Safe Dose:

• Toxic Dose:

• Lethal Dose:

• Convulsive Dose: The mean convulsive dose is 11.7 mg/kg IV (Chadwick, 1985).

• Cardiotoxic Dose: the mean cardiotoxic dose was 47.3 mg/kg IV (Chadwick, 1985).

Acute Toxicity

In veterinary species, significant local anaesthetic toxicity is associated with cardiotoxicity and neurotoxicity. A specific presentation will depend upon the species, the agent used, the dose administered, the administration route (s), and the time and number of administrations. Some agents, such as bupivacaine, are more cardiotoxic than others, such as Lidocaine. For this reason, we recommend that clinicians become familiar with the concept of a maximum safe dose, a toxic dose, and a lethal dose. Ideally, clinicians should calculate a maximum safe dose for their patient before administration and ensure that the dose administered is significantly lower than this.  This information is not yet available for all species.

Management of Acute Toxicity

• Oxygen: If signs of overdose are present, management must begin with the delivery of oxygen via a patent airway, as successful oxygen delivery may prevent convulsions caused by toxicity (Barletta and Reed, 2019).

• Vascular Decontamination: Intravenous lipids may be helpful where available. Lipid emulsion 20% 1.5 mL/kg IV over 30 minutes can benefit veterinary lidocaine toxicity (Markert et al., 2023).