Chloroprocaine: Mechanism and Uses 

Chloroprocaine (CP) is a local anesthetic classified as an amino ester because of its ester bond between the lipophilic component and aliphatic chains of the molecule. It was first introduced as a spinal anesthetic in 1952 but is now also used for infiltration, nerve block, caudal anesthesia, and epidural anesthesia [1]. Chloroprocaine has a short half-life, and its mechanism has been leveraged to identify accidental intravascular catheter placement [2]. Because of its low potential for maternal or fetal toxicity (owing, in large part, to its short half-life), CP can be administered in large doses in the obstetric setting to provide fast onset epidural anesthesia [3]. 

Neurons fire when positively charged sodium ions enter across the cell membrane into the cell above a certain threshold. Chloroprocaine’s mechanism functions by decreasing the nerve permeability to sodium and thus causes reversible nerve conduction blockade. By inhibiting volage-gated sodium channels, CP increases the threshold for nerve excitation and slows impulse propagation [4].  

Fast-onset anesthetics are typically weak bases (pKa, or dissociation constant, < 7.0). Despite having a pKa of 8.7 (higher than other amino ester anesthetics), Chloroprocaine’s mechanism can provide fast-acting anesthesia because it is rapidly metabolized by the enzyme pseudocholinesterase, allowing for administration of high doses [4]. CP also has a low partition coefficient – a measure of lipophilicity – which prevents it from crossing the lipid-filled nerve membrane to the same degree as other local anesthetics, translating to its relatively low potency [4]. 

Chloroprocaine, which has a shorter half-life than lidocaine, is commonly used for outpatient spinal anesthesia. In 2005, Yoos and Kopacz [5] conducted a study in which 122 volunteers, who differed in their American Society of Anesthesiologists (ASA) classification (I-IV) and the surgeries they were receiving (orthopedic, general surgical, gynecologic, genitourinary), received CP administered in the L2-L5 range before surgery. None of the volunteers reported transient neurological symptoms (TMS; these typically include double vision, weakness in the extremities, slurred speech) after surgery, and the mean block height was more than T10, demonstrating that CP is a safe and effective option for spinal anesthesia. rocaineCP, which has a shorter half-life than lidocaine, is commonly used for outpatient spinal anesthesia. In 2005, Yoos and Kopacz [5] conducted a study in which 122 volunteers, who differed in their American Society of Anesthesiologists (ASA) classification (I-IV) and the surgeries they were receiving (orthopedic, general surgical, gynecologic, genitourinary), received CP administered in the L2-L5 range before surgery. None of the volunteers reported transient neurological symptoms (TMS; these typically include double vision, weakness in the extremities, slurred speech) after surgery, and the mean block height was more than T10, demonstrating that CP is a safe and effective option for spinal anesthesia. 

Chloroprocaine is also used to provide analgesia during labor. In a recent study, Zhu et al [6]. assigned parturients to three groups, one of which was administered lidocaine, one of which received the conventional 6 mL dose of 1.5 % CP, and one of which received a 7.5 mL dose of 1.2% CP. As expected, patients in the CP groups achieved a shorter onset of analgesia than those in the lidocaine group, with the 1.5% group reporting a slightly more rapid onset of action. Maternal satisfaction with the onset of analgesia was also higher in the CP groups. Labor and newborn outcomes, along with the incidence of adverse effects, were similar between all three groups. The authors suggest that 6 mL of 1.5% CP is an effective option for labor-related analgesia. 

There are reports of chloroprocaine being used to quickly begin anesthesia during emergency caesarean section, though anesthesiologists should exercise caution when doing so. In one report [7], a patient who required a caesarean section was administered a dose of CP, and shortly afterwards struggled to breath and lost control of her legs. The patient was ventilated immediately, the baby was delivered, and the patient quickly regained control of her breathing. Though rare, cases like these raise questions about protocols for using CP in emergent situations. 

References 

1. Chloroprocaine – FDA prescribing information, side effects and uses. Drugs.com.

2. Guay, J. The Epidural Test Dose: A Review. Anesth. Analg. 102, 921–929 (2006), DOI:10.1213/01.ane.0000196687.88590.6b 

3. Kuhnert, B. R. et al. The half-life of 2-chloroprocaine. Anesth. Analg. 65, 273–278 (1986). 

4. Tonder, S., Togioka, B. M. & Maani, C. V. Chloroprocaine. in StatPearls (StatPearls Publishing, 2022). 

5. Yoos, J. R. & Kopacz, D. J. Spinal 2-Chloroprocaine for Surgery: An Initial 10-Month Experience. Anesth. Analg. 100, 553–558 (2005), DOI: 10.1213/01.ANE.0000093361.48458.6E 

6. Zhu, H.-J., He, Y., Wang, S.-Y., Han, B. & Zhang, Y.  A Randomized Clinical Trial Comparing Different Concentrations of Chloroprocaine with Lidocaine for Activating Epidural Analgesia During Labor. Int. J. Gen. Med. 15, 1307–1317 (2022), DOI: 10.2147/IJGM.S351030 

7. Goudra, B. G., Singh, P. M., Jackson, M. & Sinha, A. C. Epidural chloroprocaine bolus in emergency cesarean section-lessons learned from a near mishap. J. Anaesthesiol. Clin. Pharmacol. 32, 263–265 (2016), DOI: 10.4103/0970-9185.173362