Spinal lidocaine was extensively used for outpatient orthopedic procedures until transient neurological symptoms (TNS) were consistently reported (1–2). Small doses of long-acting drugs (such as bupivacaine, levobupivacaine, or ropivacaine), with or without additives, have been suggested as a possible alternative (3–6), but many practitioners report frequent failure with this technique, and recovery may be delayed (4,6).
2-chlororprocaine is an amino-ester local anesthetic with a very short half-life and a potentially favorable evolution of spinal block for short outpatient procedures (7,8). Concerns for chloroprocaine-related neurotoxicity emerged two decades ago with eight cases of neurological injury associated with large doses of a chloroprocaine solution containing the antioxidant sodium bisulfite (9–11). Toxicological studies indicated sodium bisulfite as the likely cause (12,13), though an animal study in rats challenged this conclusion (14). Clinical reports on off-label intrathecal use of preservative-free chloroprocaine in more than 1000 patients (7,15,16), as well as rigorous investigations in more than 100 volunteers and outpatients (8,17–19) have not reported any cases of neurological toxicity.
Comparing 40 mg of either lidocaine or chloroprocaine in eight volunteers, Kouri and Kopacz (8) reported a similar duration of surgical block (ranging between 30 and 60 min), but faster recovery from spinal anesthesia and simulated home discharge with chloroprocaine than lidocaine. However, little information is available directly comparing the clinical profile of spinal block produced with 2-chlorprocaine and lidocaine in a true outpatient setting. We, therefore, conducted this prospective, randomized, double-blind study to test the hypothesis that 50 mg of 1% preservative-free 2-chloroprocaine would provide a faster time to complete resolution of sensory and motor blocks as compared to the same dose of 1% plain lidocaine in patients undergoing outpatient knee arthroscopy.
With Ethical Committee approval and patients' written consent, 30 ASA physical status I–II outpatients, undergoing elective knee arthroscopy were prospectively studied. All patients were informed about the current controversy on the toxicological profile of chloroprocaine in the informed consent. Patients with central or peripheral neuropathies, thyroid dysfunction, severe respiratory or cardiac diseases, as well as those with contraindications to the spinal anesthesia were excluded.
Standard monitoring was used, including electrocardiography (Lead II), heart rate, pulse oximetry, and noninvasive arterial blood pressure.
An 18-gauge IV cannula was inserted at the forearm opposite to the surgical side and standard premedication was given with midazolam 0.03 mg/kg IV. Spinal anesthesia was performed at the L3–4 or L4–5 interspace using the midline approach and a 25 gauge Whitacre needle (Becton Dickinson, Franklin Lakes, NJ) with the needle bevel cranially oriented. Using a computer-generated sequence of numbers, and sealed envelopes patients were randomly allocated to receive spinal injection of 50 mg of either 1% lidocaine (SALF, Bergamo, Italy) (group lidocaine, n = 15) or preservative-free 2-chloroprocaine 1% (Sintetica, Mendrisio, Switzerland) (group chloroprocaine, n = 15). The anesthesiologist performing the spinal injection, as well as the observers making assessments were blinded to patient grouping.
After spinal injection, a blinded observer recorded the evolution of spinal block until achievement of home discharge criteria. Sensory block was assessed using loss of pinprick sensation (22 gauge hypodermic needle), while motor block was assessed using a 4-point modified Bromage score (0 = no motor block, 1 = hip blocked; 2 = hip and knee blocked; 3 = hip, knee and ankle blocked). The onset of surgical anesthesia was defined as loss of pinprick sensation at ≥T12 with a Bromage score ≥2. The inability to reach a sensory block at T12 within 30 min after spinal injection was considered as block failure.
Clinically relevant hypotension (decrease in systolic arterial blood pressure >30% of baseline) was initially treated with rapid infusion of 200 mL of normal saline over 10 min. If this was ineffective, 5 mg ephedrine (SALF, Bergamo, Italy) was given IV. Bradycardia (defined as a decrease in heart rate below 45 bpm) was treated with 0.5 mg atropine IV.
The evolution of sensory and motor block was recorded every 3 min for the first 15 min, then every 5 min for the following 15 min, then every 15 min for the following 30 min. Further assessments were made every 30 min until fulfillment of home discharge criteria. At the same time, arterial blood pressure and heart rate values were also recorded. If patients complained of pain during surgery, supplemental analgesia with IV fentanyl 100 μg was given. If this proved to be inadequate to complete surgery, general anesthesia was given with placement of a laryngeal mask airway. The use of fentanyl supplementation or general anesthesia to complete surgery was recorded.
Times from the end of spinal injection to readiness for surgery (onset time), as well as the maximum level of sensory block, time for complete regression of sensory and motor blocks, recovery of unassisted ambulation, and first voiding were recorded. Criteria for home discharge included the presence of stable vital signs, able to tolerate liquids by mouth, walk unassisted with crutches, with nausea and pain controlled with oral medications. Since waiting for first voiding has been reported to be not mandatory in patients undergoing surgery at low risk of urinary retention and receiving short-acting spinal drugs (20), we calculated home discharge, both including and without including first voiding, among discharge criteria.
Postoperative analgesia consisted of 50 mg oral ketoprofen every 8 h for the first 24 h. Rescue analgesia with 50 mg oral tramadol was also available if required.
A telephone call follow-up was performed 24 h and 7 days after surgery so as to evaluate the incidence of side effects including dizziness, nausea, vomiting, disturbances in voiding and/or defecating, and TNS. TNS were defined as pain or abnormal sensations including hypoesthesias or dysesthesias in the gluteal region and radiating to the lower extremities, and their presence was assessed using a standardized questionnaire (1,2).
The null hypothesis we wanted to test with the present investigation was that 50 mg of 1% 2-chloroprocaine would have a faster recovery of sensory and motor function as compared to the same dose of 1% plain lidocaine. Thus, we considered the time from spinal injection to complete regression of both sensory and motor blocks as the main outcome variable. To calculate the required sample size we considered results of previous studies (6,8,15–19). We wished to detect a 20 min difference in the time for complete regression of spinal anesthesia with a treatment effect to standard deviation ratio ranging between 0.95 and 1.3, accepting a two-tailed α-error of 5% and a β-error of 20%. On the basis of these assumptions, 15 patients per group were required (21).
Statistical analysis was performed using the program Systat 7.0 (SPSS, Chicago, IL). Categorical variables were analyzed using the χ2 test. Normal distribution of continuous variables was analyzed using the Kolmogorov–Smirnov test. Continuous variables were compared using the Mann–Whitney U-test; while contingency table analysis with Pearson's χ2 and Fisher's exact tests was used to compare the distribution of categorical variables between the two groups. The Kaplan–Meyer log-rank test was also used to compare fulfillment of home discharge criteria both with and without including first voiding among home discharge criteria. Changes over time of continuous variables in the two groups were analyzed using a two-way analysis of variance for repeated measures. Continuous variables are presented as median (range); categorical variables are presented as number of cases recorded (%). A P value ≤0.05 was considered significant.
No significant differences in age, gender distribution, ASA physical status, duration of surgery or anthropometric variables were reported between the two groups (Table 1).
The median (range) onset time of spinal block was shorter in patients of group chloroprocaine [8 (5–20) min] than in patients of group lidocaine [12 (8–30) min] (P = 0.002). Spinal anesthesia was successful in all patients. Three patients [two in group chloroprocaine (13%) and one in group lidocaine (7%) (P = 0.99)] required analgesic supplementation with 100 μg fentanyl IV during surgery; however, in no case was general anesthesia required to complete surgery. No differences in the maximum level of sensory block [T10 (T12 - T8) in group lidocaine and T9 (T12 - T7) in group chloroprocaine (P = 0.14)] and degree of motor blockade [median (range) Bromage score: 3 (2–3) in group lidocaine and 3 (2–3) in group chloroprocaine (P = 0.53)] were reported between the two groups.
Clinically relevant hypotension requiring vasopressor administration was reported in two patients, one in group lidocaine (7%) and one in group chloroprocaine (7%) (P = 0.99); while one patient of group lidocaine only (7%) reported clinically relevant bradycardia requiring atropine administration (P = 0.99).
The resolution of sensory and motor blocks occurred later in patients of group lidocaine than in those of group chloroprocaine (Figs. 1 and 2).
Recovery of sensory and motor function, and unassisted ambulation was faster in patients receiving chloroprocaine than those receiving lidocaine (Table 2). When voiding was not included among discharge criteria the faster resolution of spinal block produced by chloroprocaine resulted in quicker fulfillment of home discharge criteria. On the contrary, if first voiding was included among these criteria, no differences in home discharge were reported (Fig. 3).
No patient reported nausea and vomiting at the 24 h follow-up, and rescue tramadol analgesia was not required in any patient.
TNS were reported in five patients in group lidocaine (33%) only (P = 0.042). These patients were routinely receiving nonsteroidal antiinflammatory drugs for pain treatment, and TNS resolved spontaneously within the first week after surgery without requiring any specific treatment or diagnostic investigation.
Lidocaine had been the traditional local anesthetic for outpatient spinal anesthesia until TNS were consistently reported (1,2). Intrathecal 2-chloroprocaine has been reported as a potentially interesting option in small numbers of young, healthy volunteers (8,17,18), but few data were available on its use in a clinical setting. This study was designed to verify previous findings reported in volunteers, testing the hypothesis that 2-chloroprocaine would provide similarly effective spinal block with a faster recovery of sensory-motor functions as compared to an equivalent dose of 1% plain lidocaine. Results of this prospective, randomized, double-blind investigation confirmed initial observations in volunteers, showing that 50 mg of preservative-free 2-chloroprocaine 1% is as effective as the same dose of 1% lidocaine, with a faster recovery of sensory/motor functions and unassisted ambulation, and a lower incidence of TNS. The faster resolution of spinal block could accelerate home discharge in those patients undergoing procedures at low risk of urinary retention in whom recovery of first voiding can be excluded from standard home discharge criteria (20).
In the present investigation we compared equal doses and concentrations of the two studied drugs; however, it has been reported that chloroprocaine may be less potent than lidocaine (8). This different potency between the two local anesthetics may influence the clinical profile of spinal block, and must be considered when evaluating implications for the findings of the study.
Though statistically significant, the 4 min difference in the onset time of spinal block between the two drugs may be clinically irrelevant; while recovery profiles reported in the present study are consistent with those previously described in volunteers. Smith et al. (17) reported complete sensory regression within 98, 116, and 132 min after 30, 45, and 60 mg of 2-chloroprocaine, respectively; with times for recovery of ambulation ranging between 100 and 133 min, while voiding occurred nearly 10 min later. Kouri and Kopacz (8) directly compared 40 mg lidocaine and 40 mg 2-chloroprocaine in a cross-over, volunteer study using objective assessment of tolerance to transcutaneous electrical stimulation and thigh tourniquet: in agreement with present findings they reported a faster resolution spinal block and ambulation. Contrasting with our findings, in their volunteers first voiding occurred at the same time of recovery of ambulation, resulting in earlier micturition with chloroprocaine than lidocaine. This difference is reasonably related to the different population of the two studies, since the present study population was mostly 50-yr-old males, significantly older than the 35-yr-old volunteers studied by Kouri and Kopacz. This difference in the population characteristics, as well as the different doses used in the two studies, may explain the observed difference in first voiding (22).
When first voiding was included among home discharge criteria, chloroprocaine failed to accelerate patient discharge. Conversely, when first voiding was not included among standard discharge criteria, chloroprocaine patients achieved home discharge earlier than those receiving lidocaine. Mulroy et al. (20) suggested a relaxation of the requirements for voiding before home discharge in outpatients receiving spinal block with short-duration drugs, and undergoing surgery at low risk of urinary retention, such as knee arthroscopy. However, such an aggressive approach to home discharge after spinal anesthesia is not extensively accepted throughout the world, and is still debated in the academic community (23).
Although the study was not powered to assess the safety of the two drugs, we reported TNS in 33% of lidocaine patients, but not in chloroprocaine patients. TNS can influence patient satisfaction and rehabilitation, resulting in higher pain scores and postoperative analgesic consumption, slower functional recovery and poorer patient satisfaction (24). In agreement with present findings, Kouri and Kopacz (8), reported TNS in 7 of the 8 subjects after spinal lidocaine and none after chloroprocaine. Larger studies are required to evaluate the incidence of TNS after spinal chloroprocaine.
In conclusion, intrathecal injection of 50 mg of preservative-free 2-chloroprocaine 1% produced a faster onset spinal block for outpatient knee arthroscopy, with quicker recovery of sensory/motor function and unassisted ambulation, and a lower incidence of TNS than the same dose of 1% lidocaine.
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© 2007 International Anesthesia Research Society
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