You are here: Urology Textbook > Drugs in Urology > Local anesthetics

Local Anesthetics: Mechanism, Adverse Effects, Contraindications, and Dosage

Chemical Classification

Local Anesthetics of the Ester Type:

Procaine, tetracaine, benzocaine, chloroprocaine.

Local Anesthetics of the Amide Type:

Lidocaine, prilocaine, mepivacaine, bupivacaine, ropivacaine.

Mechanism of Action of Local Anesthetics

Local anesthetics block voltage-gated sodium channels in the neuronal cell membrane, inhibit sodium influx into the cells, and thereby prevent depolarization and propagation of the action potential. In clinical practice, one distinguishes between infiltration anesthesia (injection into the operative field) and nerve block anesthesia (injection around the supplying nerves).

Pharmacokinetics

Amide-type local anesthetics undergo predominantly hepatic metabolism via cytochrome P450 enzymes, whereas ester-type local anesthetics are rapidly hydrolyzed by the pseudocholinesterase. The resulting metabolites undergo primarily renal elimination, so hepatic and renal function substantially influence the pharmacokinetics of local anesthetics.

Influence of Epinephrine Addition

Epinephrine produces local vasoconstriction, thereby prolonging the duration of action of local anesthetics while simultaneously reducing systemic absorption. It can increase the maximum safely injectable dose and reduce bleeding at the injection site. Product information usually lists use in end-artery territories (such as the penis or fingers) as contraindicated because of concerns about ischemia.

Although older teaching and many product labels advise against epinephrine-containing local anesthetics in end-artery areas, contemporary studies and systematic reviews show that low-dose epinephrine (1:100,000–1:200,000) can be used safely in digital blocks and in penile nerve blocks (e.g., hypospadias repair) in patients without vascular compromise (Schnabl et al., 2014; Alizadeh et al., 2016). Such use is off-label and should follow current specialty guidelines and institutional policies.

Adverse Effects of Local Anesthetics

Adverse effects arise primarily from systemic absorption or inadvertent intravascular injection of local anesthetics (LAST: local anesthetic systemic toxicity). In a dose-dependent manner, they cause vasodilation through direct effects on vascular smooth muscle, disturbances of central nervous system function, and depression of myocardial contractility and conduction. Risk factors for systemic adverse effects include overdose, accidental intravascular injection, high injection speed, highly vascularized injection sites, low body weight, and organ dysfunction (liver, heart, and kidney).

Central Nervous System Adverse Effects

Initial excitatory symptoms may include dizziness, nausea, restlessness, perioral paresthesias, tinnitus, a metallic taste, and seizures. Such excitatory symptoms are early signs of impending systemic toxicity, and further administration of the drug should be stopped immediately. With increasing plasma concentrations of the local anesthetic, central nervous system depression develops with the risk of loss of consciousness, respiratory depression, and coma.

Cardiovascular Adverse Effects

At high systemic concentrations, local anesthetics depress cardiac impulse formation and conduction, which may lead to prolongation of conduction time (widening of the QRS complex), bradycardia, atrioventricular block, hypotension, ventricular tachycardia, ventricular fibrillation, and asystole. Bupivacaine is notably more cardiotoxic than many other local anesthetics.

Allergy

Allergic reactions to amide-type local anesthetics are rare and may be triggered by the local anesthetic itself or by additives such as preservatives. The clinical spectrum ranges from mild reactions to anaphylaxis. Ester-type local anesthetics have a higher risk of allergic reactions because they are metabolized to para-aminobenzoic acid (PABA).

Treatment of Local Anesthetic Systemic Toxicity (LAST)

Toxic adverse effects can manifest clinically as immediate or delayed reactions. Inadvertent intravascular injections lead to immediate reactions within 1–3 minutes. Delayed reactions occur as a result of systemic absorption from the injection site, with toxic plasma concentrations developing 5–45 minutes after injection, depending on the tissue type. The overall clinical picture is referred to as local anesthetic systemic toxicity (LAST).

Basic Measures

Basic measures include immediate discontinuation of local anesthetic administration, securing the airway, administering oxygen, continuous monitoring of electrocardiogram, blood pressure, and oxygen saturation, and rapid volume replacement with isotonic crystalloid infusion solutions (e.g., 0.9% sodium chloride or balanced electrolyte solutions). In the presence of hemodynamic instability, the team should prepare for cardiopulmonary resuscitation at an early stage.

Measures for Central Nervous System Adverse Effects

In patients with agitation or anxiety, clinicians may administer midazolam or diazepam in fractionated doses according to clinical effect, while simultaneously implementing the basic measures described above. In the event of cerebral seizures, clinicians should increase the benzodiazepine dose as needed and arrange for intensive care management.

Measures in Shock

In the setting of impending or manifest respiratory failure, clinicians should perform endotracheal intubation and controlled ventilation. Circulatory support includes appropriate vasopressor therapy (for example, noradrenaline as fractional i.v. doses, start with 10–20 μg/minute for adults according to effect), administration of atropine (0.5 mg for adults) intravenously in the presence of bradycardia, correction of acidosis, and intensive care management according to current resuscitation guidelines. In addition, lipid rescue (20% lipid emulsion i.v.) should be initiated early, for example, with a bolus of 1.5 mL/kg, followed by a continuous infusion of 0.25 mL/kg per minute for about 10 minutes, with further dosing guided by current LAST treatment protocols.

Contraindications of Local Anesthetics

Do not administer local anesthetics to patients with known allergy or hypersensitivity to the respective agent, with severe cardiac conduction disturbances, or with cardiogenic shock.

Exercise caution when using local anesthetics in inflamed tissue, as they act less effectively in an acidic environment and are absorbed more rapidly. Dose reduction is advisable in patients with heart failure, renal insufficiency, hepatic insufficiency, cachectic diseases, pregnancy, advanced age, and in highly vascularized injection sites.

Dosing of Local Anesthetics

For the dosing of commonly used local anesthetics, see the table Properties of Commonly Used Local Anesthetics. The maximum doses listed in the table are general reference values; adjust the actual dose always based on body weight (mg/kg), injection site, comorbidities, and concurrent epinephrine administration.

Infiltration Anesthesia

For minor surgical procedures, lidocaine or mepivacaine is a suitable standard local anesthetic. Both agents have a rapid onset of action, and a 1% solution is usually used. In an adult patient without risk factors and weighing 70 kg, clinicians can safely administer approximately 3–5 mg/kg (corresponding to about 20–30 mL of 1% lidocaine without epinephrine).

For more extensive and painful procedures, ropivacaine 0.2–0.5% is advantageous because it is generally better tolerated, allows higher injection volumes, and has a longer duration of action. Do not exceed the maximum dose of 3 mg/kg.

Nerve Block Anesthesia

For nerve block anesthesia in pain management (for example, intercostal block, spermatic cord block), preferably use a long-acting local anesthetic such as ropivacaine. Depending on the required injection volume, choose a 0.2% or 0.5% solution, Do not exceed the maximum dose of 3 mg/kg.

References

Alizadeh F, Fakoor A, Haghdani S. A comparison between tourniquet application and epinephrine injection for hemostasis during hypospadias surgery: The effect on bleeding and postoperative outcome. J Pediatr Urol. 2016 Jun;12(3):160.e1-5. doi: 10.1016/j.jpurol.2016.02.005.

Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog. 2012 Summer;59(2):90-101; quiz 102-3. doi: 10.2344/0003-3006-59.2.90.

Prabhakar H, Rath S, Kalaivani M, Bhanderi N. Adrenaline with lidocaine for digital nerve blocks. Cochrane Database Syst Rev. 2015 Mar 19;2015(3):CD010645. doi: 10.1002/14651858.CD010645.pub2.

Schnabl SM, Ghoreschi FC, Scheu A, Kofler L, Häfner HM, Breuninger H. Use of local anesthetics with an epinephrine additive on fingers and penis - dogma and reality. J Dtsch Dermatol Ges. 2021 Feb;19(2):185-196. doi: 10.1111/ddg.14434. PMID: 33586877.

Sommerkamp, H. und O. Hakenberg (1993).
Lokalanästhesie in der Urologie.
Stuttgart, New York: Georg Thieme Verlag.

  Deutsche Version: Nebenwirkungen, Kontraindikationen und Dosierung von Lokalanästhetika

Urology-Textbook.com – Choose the Ad-Free, Professional Resource

This website is designed for physicians and medical professionals. It presents diseases of the genital organs through detailed text and images. Some content may not be suitable for children or sensitive readers. Many illustrations are available exclusively to Steady members. Are you a physician and interested in supporting this project? Join Steady to unlock full access to all images and enjoy an ad-free experience. Try it free for 7 days—no obligation.

New release: The first edition of the Urology Textbook as an e-book—ideal for offline reading and quick reference. With over 1300 pages and hundreds of illustrations, it’s the perfect companion for residents and medical students. After your 7-day trial has ended, you will receive a download link for your exclusive e-book.