Chloroprocaine is a local anesthetic drug used primarily in epidural and spinal anesthesia during surgical procedures, childbirth, or other medical procedures requiring regional anesthesia. It belongs to the amino ester group of local anesthetics.

One of its advantages is its relatively rapid onset of action and short duration of effect compared to other local anesthetics, making it suitable for procedures where a fast recovery is desired. It's metabolized quickly by plasma esterases, which contributes to its shorter duration of action.

Chloroprocaine is an anaesthetic drug that inhibits the initiation and transmission of neuronal impulses primarily in the sensory nerves. It has the following uses:

• By local infiltration and peripheral nerve block as a local anaesthetic (with preservatives).
• When injected into the subarachnoid space in adults, chloroprocaine (without preservatives) is used for nerve block, local infiltration, epidural & caudal administration, and spinal anaesthesia.

Note:

• It is only utilised in quick (before delivery) and ambulatory operations because of its rapid onset of effect and brief duration of activity.
• For spinal or epidural anaesthesia, preservative-containing chloroprocaine should not be utilised.

Chloroprocaine Dose in Adult

Chloroprocaine in the treatment of Local anaesthesia:  

Local Anesthesia:

• Use the smallest amount needed for the desired effect.
• Dosage depends on factors like the procedure type, tissue blood supply, depth of anesthesia, muscle relaxation needed, duration required, and patient's health.
• Lower doses for weaker patients or those with heart issues.
• For epidural use, a small test dose before full administration is recommended.

Clorotekal (Spinal Anesthesia):

• Intrathecal (into the spinal canal): 50 mg of 1% solution for a single dose, usually effective up to the T 10 level.
• Other formulations (like Nesacaine-MPF) can be used off-label for short procedures, with dosages ranging from 20 to 60 mg.

Nesacaine, Nesacaine-MPF:

• Max single dose (without epinephrine): 11 mg/kg, max total dose: 800 mg.
• Max single dose (with epinephrine 1:200,000): 14 mg/kg, max total dose: 1,000 mg.

Caudal Block:

• Preservative-free: 2% or 3% solution, 15 to 25 mL; can repeat every 40-60 minutes.

Infiltration and Peripheral Nerve Block:

• Digital (without epinephrine): 1%; 3 to 4 mL; total dose: 30 to 40 mg.
• Infraorbital: 2%; 0.5 to 1 mL; total dose: 10 to 20 mg.
• Mandibular: 2%; 2 to 3 mL; total dose: 40 to 60 mg.
• Paracervical: 1%; 3 mL each for four sites; total dose: up to 120 mg.
• Pudendal: 2%; 10 mL each side; total dose: 400 mg.

Lumbar Epidural Anesthesia:

• For Cesarean delivery: Preservative-free: 3%; 15 to 25 mL total dose (including a 2- or 3-mL test dose).
• For non-pregnant patients: Preservative-free: 2% or 3%; 2 to 2.5 mL per segment; usual total volume: 15 to 25 mL; can repeat with smaller doses every 40 to 50 minutes.

Chloroprocaine Dose in Children

• The amount of chloroprocaine used depends on factors like the type of procedure, how deeply and for how long anesthesia is needed, how relaxed the muscles should be, the blood flow in the tissues, the patient's health, and age.
• It's important to use the smallest effective dose and concentration.
• For patients who are frail or have heart problems, the dose should be reduced.

Chloroprocaine dose As an Anesthetic agent for local and peripheral nerve block:  

Children (Over 3 Years) and Adolescents:

• Max dose without epinephrine: 11 mg/kg.
• For infiltration: Recommended concentrations of 0.5% to 1%.
• For nerve block: Recommended concentrations of 1% to 1.5%.

Pregnancy Risk Factor C

• During pregnancy, chloroprocaine is classified as a Risk Factor C.
• Studies on animals regarding its effects during pregnancy haven't been done.
• Local anesthetics can quickly pass through the placenta, which may lead to various levels of harm to the mother, fetus, and newborn.
• Close monitoring of both the mother and fetus, including heart rate and electronic fetal monitoring, is necessary during its use in obstetrics.
• Maternal low blood pressure has occurred due to regional anesthesia, but adjusting the patient's position and elevating her legs may help.
• Some types of anesthesia during childbirth can affect the strength of uterine contractions or the mother's pushing efforts.
• Using certain local anesthetics during labor may reduce muscle strength and tone in newborns for the first couple of days.
• Paracervical block isn't recommended for pregnant women with toxemia, fetal distress, or premature labor.
• Administering this block early in pregnancy has led to seizures and cardiovascular collapse in mothers and fetal distress.
• Fetal bradycardia, acidosis, and depression have also been reported due to unintended fetal injection during a paracervical or pudendal block.

Chloroprocaine use during breastfeeding:

• It's uncertain whether chloroprocaine is present in breast milk.
• The manufacturer advises considering the risks of exposing the infant to the medication, the benefits of breastfeeding for the baby, and the advantages of treatment for the mother when deciding whether to continue or stop breastfeeding during therapy.

Chloroprocaine Dose in Renal Disease:

• The manufacturer's labeling doesn't offer dosage adjustments for renal impairment with chloroprocaine.

Chloroprocaine Dose in Liver Disease:

• The manufacturer's labeling doesn't specify exact dosage adjustments for hepatic impairment with chloroprocaine.
• However, it's advised to reduce the dosage and proceed with caution due to the heightened risk of adverse effects in patients with liver issues.

Common Side Effects of Chloroprocaine include:

• Central nervous system:
  • Procedural pain

Less Common Side Effects of Chloroprocaine include:

• Central nervous system:
  • Headache
• Cardiovascular:
  • Hypotension
• Gastrointestinal:
  • Nausea
• Endocrine & metabolic:
  • Hyperglycemia
• Local:
  • Injection site pain

Frequency not defined.

• Hypersensitivity:
  • Anaphylactoid reaction
  • Angioedema
• Cardiovascular:
  • Syncope
  • Ventricular arrhythmia
• Dermatologic:
  • Diaphoresis
  • Erythema
• Central nervous system:
  • Central nervous system stimulation
  • Central nervous system depression
  • Increased body temperature
• Gastrointestinal:
  • Loss of anal sphincter control
• Respiratory:
  • Laryngeal edema
  • Respiratory arrest
  • Sneezing

Contraindications to Chloroprocaine include:

• Chloroprocaine should not be used in individuals with a known hypersensitivity to chloroprocaine, other para-aminobenzoic acid (PABA) ester type anesthetics, or any component of the formulation.
• Additionally, specific contraindications outlined in the Clorotekal labeling, which may apply to other products, include conditions such as decompensated cardiac insufficiency, hypovolemic shock, coagulopathy, serious cardiac conduction issues, local infection at the lumbar puncture site, and septicemia.
• Spinal anesthesia is contraindicated in these conditions.
• Similarly, intravenous regional anesthesia is also contraindicated.

Warnings and Precautions

Cardiovascular effects

• Cardiovascular effects are common with high systemic concentrations of local anesthetics, often leading to hypotension and bradycardia, particularly when accidentally administered intravascularly.
• Preventive measures such as limiting the cumulative dose and using techniques like ultrasound or direct visualization for catheter placement can help mitigate these risks.
• It's crucial to carefully monitor the patient's cardiovascular vital signs during and after each local anesthetic injection.
• If cardiovascular collapse or severe central nervous system toxicity occurs, treatment should follow the guidelines outlined in the American Society of Regional Anesthesia and Pain Medicine’s Checklist for Treatment of Local Anesthetic Toxicity.

CNS toxicity:

• Following each local anesthetic injection, it's important to carefully and continuously monitor the patient's level of consciousness.
• Early signs of central nervous system (CNS) toxicity may include restlessness, anxiety, ringing in the ears (tinnitus), dizziness, blurred vision, tremors, depression, or drowsiness.
• Patients with existing neurological conditions require extra caution.
• Seizures due to systemic toxicity leading to cardiac arrest have been reported, often following unintended injection into blood vessels.
• In cases of cardiovascular collapse or severe CNS toxicity, treatment should align with the guidelines provided by the American Society of Regional Anesthesia and Pain Medicine’s Checklist for Treatment of Local Anesthetic Toxicity.

Infusion-related intra-articular chondrolysis

• Continuous intra-articular infusion of local anesthetics after arthroscopic or other surgical procedures is not an approved use due to the risk of chondrolysis, which is the destruction of cartilage tissue.
• Chondrolysis, primarily observed in the shoulder joint, has occurred in some cases following infusion, with severe cases necessitating arthroplasty or shoulder replacement surgery.
• Therefore, this method of treatment should be avoided.

Methemoglobinemia:

• Methemoglobinemia, a condition where abnormal levels of methemoglobin are present in the blood, has been reported with the use of local anesthetics.
• Clinically significant methemoglobinemia requires immediate treatment and discontinuation of the anesthetic, as well as any other oxidizing agents.
• Symptoms can appear immediately or several hours after exposure to the anesthetic.
• Patients with conditions such as G6PD deficiency, congenital or idiopathic methemoglobinemia, cardiac or pulmonary issues, exposure to oxidizing agents, or infants under six months of age are more vulnerable and should be closely monitored for signs such as cyanosis (bluish skin), headache, rapid pulse, shortness of breath, dizziness, and fatigue.

Respiratory effects

• Local anesthetics have been linked to rare instances of sudden respiratory arrest.
• It's crucial to monitor the patient's respiratory status closely and consistently, assessing the adequacy of ventilation, following each injection of local anesthetic.

Cardiovascular disease

• Extreme caution should be exercised when using chloroprocaine in patients with cardiovascular disease, including those with severe hypertension, hypotension, heart block, and severe cardiac decompensation.
• These conditions can increase the risk of complications or adverse effects associated with chloroprocaine administration.

Hepatic impairment

• Chloroprocaine should be used with caution in patients with severe hepatic impairment.

Myasthenia gravis:

• Chloroprocaine should be used with extreme caution in patients with myasthenia gravis, as it may exacerbate the condition.

Plasma cholinesterase disorders:

• Chloroprocaine should be used with caution in patients with genetic deficiency of plasma cholinesterase.

Renal impairment

• Chloroprocaine should be used with caution in patients with severe renal impairment.

Chloroprocaine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use    

Monitor:

Cardiovascular and Respiratory Status:

• Monitor heart rate and blood pressure regularly.
• Check for any signs of breathing difficulties or changes in respiratory rate.

Mental Status:

• Keep track of the patient's consciousness level and mental alertness.
• Watch out for signs of confusion or drowsiness.

Vital Signs:

• Monitor vital signs such as temperature, pulse, and oxygen levels.
• Look for any abnormalities in these parameters.

Signs of CNS Toxicity:

• Watch for symptoms like restlessness, anxiety, dizziness, or blurred vision.
• Be alert to any signs of confusion or seizures.

How to Administer Chloroprocaine?

Infiltration or Peripheral Nerve Block:

• Administer locally either as a single injection or continuously via a catheter.
• Avoid rapid injection to prevent complications.
• Perform aspiration before administration to avoid intravascular injections.
• Reposition the needle if blood is drawn during aspiration; however, absence of blood doesn't ensure no intravascular injection.

Epidural and Subarachnoid Block:

• Solutions without preservatives should be used.
• Use a filter needle when drawing solution from ampules, especially with Clorotekal.
• Avoid injecting into areas of infected or inflamed skin.
• Aspiration before administration is crucial to prevent intravascular injections.
• Clorotekal is meant for intrathecal use only; epidural use is not recommended by the manufacturer.
• Continuous spinal catheter use with Clorotekal is not advised due to safety concerns.

These guidelines help ensure safe and effective administration of chloroprocaine in various procedures.

Mechanism of action of chloroprocaine:

• Chloroprocaine is a type of local anesthetic known as an ester.
• It works by stabilizing the membranes of nerve cells, preventing the initiation and transmission of nerve signals.
• This action blocks the sensation of pain in the area where it's applied.
• Chloroprocaine achieves this by temporarily reducing the ability of nerve cells to allow sodium ions to pass through their membranes, which is essential for transmitting electrical impulses.
• Different nerve fibers vary in their sensitivity to chloroprocaine; smaller fibers are more sensitive and take longer to recover from its effects.
• Typically, pain fibers are blocked first, followed by those responsible for transmitting sensations of temperature, touch, and pressure.
• Higher concentrations of chloroprocaine can also block sympathetic nerves responsible for regulating bodily functions and motor nerves controlling movement.
• The extent of anesthesia depends on how far the drug spreads, which is mainly determined by the volume injected.

Onset of Action:

• Typically occurs within 6 to 12 minutes after administration.

Duration:

• Duration varies depending on factors such as patient characteristics, type of block, concentration used, and method of anesthesia, lasting up to 60 minutes.

Distribution:

• Distribution varies based on the route of administration. High concentrations are found in well-perfused organs like the liver, lungs, heart, and brain.

Metabolism:

• Chloroprocaine is rapidly broken down by enzymes in the blood plasma into 2-chloro-4-aminobenzoic acid and betadiethylaminoethanol. About 80% of the drug is conjugated before elimination.

Half-life Elimination:

• In vitro, the half-life of chloroprocaine in plasma is approximately 21 to 25 seconds in adults, slightly longer in females compared to males, and around 43 seconds in neonates.

Excretion:

• Chloroprocaine and its metabolites, primarily chloro-aminobenzoic acid and beta-diethylaminoethanol, are excreted mainly through urine. However, only a small amount of the drug is excreted unchanged in urine.

International brands of Chloroprocaine:

• Ampres
• Clorotekal
• Ivracain
• Nesacaine

Chloroprocaine Brands in Pakistan:

 No brands available in Pakistan