Chloroprocaine is an ester class local anesthetic and is indicated for neuraxial anesthesia (caudal, epidural and spinal), as well as peripheral nerve blocks and obstetric anesthesia (pudendal and paracervical blocks). Due to its short duration, it has been used in test doses to evaluate the function of peripheral nerve and epidural catheters.
Spinal anesthesia is not FDA approved. Spinal injection was initially linked to neurologic injuries in the 1980s. However, subsequently, it was determined that these injuries were due to either the preservative or accidental injection of epidural doses. Spinal anesthesia for outpatient knee arthroscopy leads to faster discharge times, lower pain scores and lower costs than general anesthesia and shorter motor blockade than spinal bupivacaine.
Chloroprocaine causes a reversible nerve conduction blockade by decreasing nerve membrane permeability to sodium. Like other local anesthetics, it binds to a specific region of the alpha subunit on the cytoplasmic region to inhibit voltage-gated sodium channels. This binding activity increases the threshold for excitation in the nerve and slows nerve impulse propagation down the nerve fiber. The order of nerve blockade follows autonomic nerves > sensory > motor.
Local anesthetic activity is determined by pKa, lipid solubility, and protein binding. It is pKa that determines the onset of action, as it is the unprotonated form that crosses the nerve plasma membrane. Chloroprocaine is an exception to this rule. With a relatively high pKa, it's fast onset is due to high concentrations used. Lipid solubility determines the potency of local anesthetics with more soluble molecules allowing more local anesthetic to cross the plasma membrane. Protein binding determines the duration of the block with highly protein-bound molecules such as bupivacaine exhibiting a longer duration of action than lesser protein-bound molecules such as lidocaine. Chloroprocaine has the lowest protein binding of all clinically used local anesthetics.
Local anesthetics are not specific for peripheral nerves, central nervous system or cardiac conducting systems. Because of this many of the more severe symptoms of overdose involve CNS or cardiac pathology.
Chloroprocaine is rapidly metabolized by pseudocholinesterase and consequently has a lower risk of systemic toxicity than other local anesthetics. Because of this, high doses (3%) may be used which leads to a quicker onset of nerve block (6-12 minutes) and time to peak levels (10-20 minutes). The rapid metabolism leads to quick recovery following nerve block (30-60 minutes).
Chloroprocaine is supplied as both 2% and 3% solutions and may be administered as a single injection or continuous infusion via catheter for epidural, caudal, spinal or peripheral nerve block. The maximum dose for Chloroprocaine is 11mg/kg not to exceed a maximum total dose of 800 mg; with epinephrine (1:200,000), 14 mg/kg, not to exceed a maximum total dose of 1000 mg.
The most common adverse effect is pain related to the procedural injection of chloroprocaine. Other effects are related to systemic absorption via unintentional intravascular injection or rapid systemic absorption from a nerve block. Due to its rapid metabolism, these effects are low but include hypotension, seizures, respiratory and cardiac arrest, hyperglycemia, nausea, and headache.
Initial CNS symptoms include altered mental status which may rapidly progress to convulsions and loss of consciousness
Cardiac toxicity may manifest as myocardial depression, hypotension, bradycardia, ventricular arrhythmias, and cardiac arrest.
Anaphylaxis to local anesthetics may be to the ester or amide component of these medications or preservatives used in packaging. Esters such as chloroprocaine have a higher incidence of allergic reactions due to one of their metabolites, para-aminobenzoic acid (PABA) which is structurally similar to methylparaben.
Chloroprocaine is pregnancy category C (animal reproduction studies show adverse effects on the fetus; no adequate and well-controlled studies have been conducted in humans, but potential benefits may justify the use of the drug in pregnant women) and may be given to pregnant patients if needed. No unchanged chloroprocaine and only trace amounts of its byproducts (2-chloro-aminobenzoic acid and 2-dimethylaminoethanol) have been found in umbilical arterial or venous plasma after properly administered paracervical blocks (the rate of systemic absorption of local anesthetics increases paracervical > epidural > IM > spinal). Unlike other local anesthetics which cross the placenta, chloroprocaine’s rapid metabolism by pseudocholinesterase minimizes the amount that reaches the placenta. Additionally, chloroprocaine is supplied with a pKa of 8.7 and does not participate in ion trapping, a phenomenon in which molecules become protonated in the acidic fetal environment and are unable to cross the placenta back to the maternal circulation.
It is unknown how much chloroprocaine is excreted into breast milk but based on the low amounts of other local anesthetics as well as low oral absorption it is assumed safe to use in lactating mothers.
Chloroprocaine should be used with caution in patients with hepatic disease as it is metabolized by pseudocholinesterase. Similarly, there are case reports of prolonged epidural blockades in parturients with known pseudocholinesterase deficiency.
Chloroprocaine metabolites are renally excreted and as such may accumulate in patients with renal dysfunction.
Dosing for pediatric patients younger than four years old has not been established.
Standard monitoring required during the administration of bupivacaine includes continuous EKG, SpO2, and blood pressure.
Doses higher than 11 mg/kg may cause systemic side effects (Local anesthetic systemic toxicity: LAST) generally related to high plasma levels and effects on the CNS and cardiovascular systems. Careful attention to prevention of overdose is necessary with monitoring of the cardiovascular system and level of consciousness following each injection. If overdose is suspected, full hemodynamic support may be required. Benzodiazepines are the preferred treatment for seizures. Airway management for local anesthetic toxicity may range from supplemental oxygen to assisted ventilation to initiation of invasive airway devices and positive pressure ventilation.
Critical differences in the treatment of local anesthetic-induced cardiac arrest include reduced doses of epinephrine (<1mcg/kg), and avoidance of vasopressin, calcium channel blocks, beta blockers or other local anesthetics. 100ml (or 1.5ml/kg for patients less than 70kg) 20% Lipid emulsion given as a bolus followed by infusion is the treatment of choice for LAST.
Other significant concerns related to toxicity involve the potential for accidental intrathecal injection during epidural placement. Larger epidural doses injected into the intrathecal space can lead to a high spinal with symptoms of nausea, hypotension, and agitation and can lead to loss of consciousness (“total spinal”). Other symptoms may include urinary retention, backache, and hypoventilation secondary to thoracic or cervical spread.
Management of chloroprocaine related toxicity (LAST) includes prompt recognition of the signs and symptoms and an interprofessional team to manage the potential consequences. It is an emergency condition which requires the full attention of nurses, technicians, etc. to maintain the airway, seizures arrhythmias and possible cardiac arrest.
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