McKay et al. (6), Morris and Whish (1), and Morris et al. (2) suggested that chloroprocaine may be the local anesthetic of choice for local skin infiltration, based on their analysis of pain scores. Their findings are in contrast with the results of Nuttall et al. (4) and Prien (3). The contradictory results seem to be related to study design, e.g., use of nonequivalent drug concentrations, different manufacturers, different additives, undifferentiated pain score of needle stick versus injection of local anesthetics (7), statistical type II error, or injection technique.
In our study, chloroprocaine 2% was significantly better tolerated than lidocaine 1% (Fig. 1). Plain chloroprocaine had smaller pain scores than buffered lidocaine, approaching the statistical significance (P = 0.054).
We studied, for the first time, the effect of the alkalinizing of chloroprocaine on pain at skin infiltration using an equipotent concentration with lidocaine.
2-Chloroprocaine with bicarbonate had the lowest mean pain score among the tested solutions. There were no differences in pain scores between alkalinized (pH, 7.7) and acidic (pH, 3.4) solutions of chloroprocaine, regardless of the very different pH (Fig. 2).
In our study, pH of the solutions did not correlate with pain scores. Solutions at extreme pH values had similar pain scores, and solutions with similar pH values had extreme pain scores (Fig. 1, Fig. 2). Our results support the hypothesis of other studies that the pain mechanism is not simply related to the pH of the solution (3,10,11).
Alkalinized solutions of local anesthetics would require additional time to prepare, because no commercial preparation is available. Additionally, the short shelf life, chemical instability, photodegradation, and aldehyde formation make the use of buffered lidocaine impractical in a busy emergency room, in an outpatient surgery clinic, or in a pediatric department. Therefore, the choice of local anesthetic, not the pH, may determine pain at injection.
We observed that sodium bicarbonate, the most alkaline solution that we tested, at the same concentration as the one used as additive to local anesthetics, caused the highest pain score among the solutions injected (Fig. 1). Perhaps the experienced pain is not simply an additive function of each substance in the mixture. This finding might support the McKay et al. (6) hypothesis that the pain-reducing effect of sodium bicarbonate results from a shift of the equilibrium between the ionized and unionized form of local anesthetics and factors other than pH, such as intrinsic properties, play a role in pain mechanism.
The similar mean pain scores of labeled and blinded normal saline solutions support the reliability of pain assessment by visual analog scoring. We tried to eliminate the biases of previous studies by using preservative-free local anesthetics manufactured by one drug company, equipotent concentrations, and a standardized technique of injection by a single investigator.
2-Chloroprocaine 2% is an aminoester drug that contains in its molecule a p-aminobenzoic acid ring known to be allergenic. In a MEDLINE search of the years 1966–2001, there are no reports of local or systemic allergic reactions from 2-chloroprocaine. Most of the studies have used procaine as an ester-type local anesthetic. The intradermal injection of procaine resulted in positive skin reactions in up to 30% of patients (13); however, true allergic reactions from local anesthetics are very rare (1%) (10). Because of a lack of data regarding 2-chloroprocaine, it might be safe to assume that 2-chloroprocaine would have local allergic reactions in a certain percentage of patients, in the same manner as procaine does. Because prevention is the best medicine, a careful history of true allergic reactions from factors such as local anesthetic, ester versus amide, and preservatives in drugs and foods would distinguish those patients with a risk of allergic reactions and indicate the safest approach of using local anesthetics. Although aminoamide local anesthetics, such as lidocaine, seemed to be free of allergic reactions, methylparaben contained in the preservative can cause such reactions. In our study, we did not observe any allergic reactions locally or systemically. This can be the result of the small number of patients, “no allergic reactions history” used as exclusion criteria, infrequent incidence of true allergy, or lack of preservatives.
The potential of local nerve damage from chloroprocaine has been questioned in medical literature after reports of prolonged sensory and motor block in patients with chloroprocaine epidural or spinal anesthesia. Chloroprocaine itself does not appear to be neurotoxic (14). The neurotoxic effects reported in the literature might be caused by the sodium bisulfite preservative, large volume, and probably low pH. The reports and studies were performed with 2-chloroprocaine 3% for epidural, spinal, or peripheral nerve block.
In the MEDLINE search of years 1966–2001, we did not find any reports of neurotoxic effects of preservative-free 2-chloroprocaine 2% used for infiltration anesthesia.
In conclusion, we consider that 2-chloroprocaine 2%, independent of pH, causes less pain than the more commonly used lidocaine at skin infiltration.
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© 2002 International Anesthesia Research Society
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