General Considerations

Local anesthetics are low-cost, non-controlled drugs that are readily available worldwide. They are administered routinely for the prevention and treatment of intraoperative and early postoperative pain. These drugs are key players in multimodal analgesia especially when they are administered in combination with NSAIDs and opioid analgesics.^1,2

Other advantages may include:

 Blunting of stress response to surgery

 Reduction of intravenous and inhalant anesthetics requirements

 Reduction of analgesic requirements. For example, opioids are not required intraoperatively if an anesthetic block is successful

Mechanism of Action

Local anesthetics block the generation and propagation of nociceptive input by blocking Na⁺ channels in a reversible manner. Transient loss of sensory, motor and autonomic function will result. LAs block small unmyelinated C-fibres and myelinated Aδ fibres before other sensory and motor fibres (unmyelinated Ay, Aß and Aα). In a neuraxial blockade (epidural, intrathecal) from least to most sensitive to local anesthetics are: autonomic, pain, proprioception, and motor fibers.³

Knowledge of canine/feline anatomy and clinical pharmacology of local anesthetics are paramount for the application of loco-regional anesthetic techniques. On the other hand, it is important to appreciate possible complications associated with these techniques and the use of local anesthetics in practice.

Physicochemical Properties and Pharmacodynamics

Most of these drugs are formulated as a racemic mixture (1:1). Ropivacaine and levobupivacaine are the exceptions. Local anesthetics have a non-ionized lipid-soluble form (base) and an ionized water-soluble form (conjugated acid). The dissociation constant (pKa) corresponds to the value of pH at which the acid and base forms exist in equal amount (Henderson-Hasselbalch equation).

Local anesthetics have a pKa between 7.5 and 9 and are formulated as acid solutions of hydrochloride salts (pH 3.5–5.0). This formulation gives a net prevalence of the ionized form and thus a water-soluble solution. Once the local anesthetic solution is injected into the body, the non-ionized lipid-soluble form will prevail. This is important for the drug effect since the non-ionized form crosses the biological membranes. In inflamed tissues, the ionized form prevails and this explains why local anesthetics do not usually "work" in inflammation (acidic pH).

Protein binding influences the activity of the drug since only the unbounded free fraction is pharmacologically active. Higher protein binding of a local anesthetic is associated with a longer duration but slow onset of action. Lipid solubility promotes sequestration of the local anesthetic into lipophilic compartments (e.g., myelin) from where the drug is slowly released. Lipid solubility is directly correlated with potency. It also contributes to the slower onset and longer duration of action of these drugs. Therefore, increased protein binding, potency and the activity of the local anesthetic on vascular tone correlate with increased duration of action. The following factors influence the onset and duration of action of a local block: site of injection, dose, volume and concentration of local anesthetic, physical and chemical characteristics (potency, lipid solubility, protein binding), and metabolism.

Adverse Effects

Neurotrauma can occur with intraneural injection. For this reason, there are three main rules to be respected:

 Lack of resistance to injection is important before the administration of local anesthetics. Resistance to injection is associated with intraneural injection and tissue damage.

 In addition, maximum doses should always be calculated based on lean body weight before administration.

 There should be always negative aspiration of blood before injection. This is particularly important with bupivacaine because of its cardiotoxic profile.

Local anesthetic toxicity occurs when doses and concentrations are not respected, or with accidental intravascular administration. Adverse effects with neurological (nystagmus, muscle tremors, seizures, stupor and coma) and cardiovascular (bradycardia, hypotension and ventricular tachycardia) signs may occur. This lecture will discuss how to treat these adverse effects.

Suggested maximum doses* are presented below:

*These doses of bupivacaine are also suggested for intraperitoneal analgesia.
Doses for intratesticular anesthesia or dental blocks: 0.25–1 ml.

Suggested Reading

www.wsava.org/guidelines/global-pain-council-guidelines

References

1.  Lemke KA, Dawson SD. Local and regional anesthesia. Vet Clin North Am Small Anim Pract. 2000;30:839–857.

2.  de Vries M, Putter G. Perioperative anaesthetic care of the cat undergoing dental and oral procedures: key considerations. J Fel Med Surg. 2015;17:23–36.

3.  Duke T. Local and regional anesthetic and analgesic techniques in the dog and cat: part I, pharmacology of local anesthetics and topical anesthesia. Can Vet J. 2000;41:883–884.