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Anesth Analg 2004;98:81-88 © 2004 International Anesthesia Research Society
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Abstract |
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With the availability of preservative- and antioxidant-free 2-chloroprocaine (2-CP), there may be an acceptable short-acting alternative to lidocaine for spinal anesthesia. We examined the safety, dose-response characteristics, and effects of epinephrine with spinal 2-CP. Six volunteers per group were randomized to receive 30, 45, or 60 mg of spinal 2-CP with and without epinephrine. Intensity and duration of sensory and motor blockade were assessed. When 11 of the 18 volunteers complained of vague, nonspecific flu-like symptoms, breaking of the blind revealed that all spinal anesthetics associated with the flu-like symptoms contained epinephrine. There were no complaints of flu-like symptoms in the volunteers who received 2-CP without epinephrine. No further spinal anesthetics containing epinephrine were administered, resulting in 29 anesthetics (11 with epinephrine, 18 without epinephrine.) Plain 2-CP demonstrated a dose-dependent increase in peak block height and duration of effect at all variables except time to 2-segment regression and time to regression to T10. Time to complete sensory regression with plain 2-CP was 98 ± 20, 116 ± 15, and 132 ± 23 min, respectively. 2-CP with epinephrine produced times to complete sensory regression of 153 ± 25, 162 ± 33, and 148 ± 29 min, respectively. Preservative and antioxidant free 2-CP can be used effectively for spinal anesthesia in doses of 30–60 mg. Epinephrine is not recommended as an adjunct because of the frequent incidence of side effects.
IMPLICATIONS: Hyperbaric spinal 2-chloroprocaine is effective and has an anesthetic profile appropriate for use in the surgical outpatient over the dose range of 30–60 mg without signs of transient neurologic symptoms. The addition of epinephrine is not recommended because of the frequent incidence of side effects.
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Introduction |
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The choice of local anesthetic for spinal anesthesia in the ambulatory surgery patient remains a problem. Lidocaine is plagued by the frequent symptoms of transient neurologic syndrome (TNS) (1). Procaine is unreliable (14%–17% failure rate) and associated with nausea (15%–17%) (2–4). As bupivacaine can produce an excessively long block even in markedly reduced doses, there is considerable debate whether it is appropriate for ambulatory surgery.
In 1952, Foldes and McNall described the successful use of preservative-free chloroprocaine for spinal anesthesia in 214 patients (5). Subsequently, 2-chloroprocaine (Nesacaine-CE) became a widely used local anesthetic for epidural anesthesia, particularly in the obstetric population. However, accidental intrathecal injection resulted in several cases of neurotoxicity with significant morbidity in the 1980s, when eight patients who developed lower extremity paralysis and sacral nerve dysfunction after receiving large volumes of Nesacaine-CE intended for the epidural space were reported (6–9). It was determined that the combination of the antioxidant sodium bisulfite in the presence of low pH was responsible for the neurotoxicity (10,11). In response to these reports, the formulation of 2-chloroprocaine was subsequently changed. Currently, two of the three commercially available formulations of 2-chloroprocaine (Nesacaine-MPF; Astra Pharmaceuticals, Wilmington, DE, and generic chloroprocaine; Bedford Pharmaceuticals, Bedford, OH) are preservative free and antioxidant free.
As chloroprocaine is of shorter duration than lidocaine for epidural anesthesia, we investigated the dose-response effects (and the influence of adding epinephrine) of the new preservative-free and antioxidant-free formulations of 2-chloroprocaine in volunteers as a possible alternative to lidocaine for outpatient spinal anesthesia.
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Methods |
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After IRB approval and informed consent were obtained, 18 healthy volunteers were initially enrolled in this randomized, crossover study. Although 2-chloroprocaine is approved by the Food and Drug Administration, it is not specifically indicated for use in spinal anesthesia. Its use for spinal anesthesia is thus considered "off-label." All current manufacturers of 2-chloroprocaine distinctly label the product "Not for Spinal Anesthesia." All subjects in this study were made aware of this information, which was also included within their written informed consent.
The first 12 volunteers enrolled were randomized to receive 2 spinal anesthetics, separated by more than 7 days, each with an equal milligram dose (45 or 60 mg) of hyperbaric 2-chloroprocaine with or without the addition of 0.2 mg of epinephrine. Initially, an additional 6 volunteers were planned to receive a spinal anesthetic of 75 mg if the smaller doses were of inadequate duration or density. When spinal anesthetics in the first 12 subjects (45 or 60 mg) produced peak block heights of T4 or higher (up to C5) and adequate duration (more than 60 min), the protocol was amended with IRB approval such that the third group would instead be given a dose of 30 mg of chloroprocaine.
When 11 of the 18 volunteers complained of vague, nonspecific flu-like symptoms (see Results) after one of their spinal anesthetics, it was decided to break the blind of the study. All of the spinal anesthetics associated with flu-like symptoms were found to contain epinephrine. There were no complaints of flu-like symptoms in the volunteers who received 2-chloroprocaine without epinephrine. No further spinal anesthetics containing epinephrine were administered, resulting in 29 anesthetics (11 with epinephrine, 18 without epinephrine.) Because of this, the methodology beyond this point in the study cannot be considered a true "crossover" design.
Hyperbaric study solutions were created by combining 3% 2-chloroprocaine (1.0 mL, 1.5 mL, or 2.0 mL) with an equal volume of 10% dextrose because volume is not a confounding factor in hyperbaric spinal anesthesia. All patients had fasted for 6 h and received no sedatives throughout the study. Before subarachnoid block, a 20-gauge peripheral IV line was placed and an IV infusion of lactated Ringer’s solution was administered. Vasoactive drugs were administered only if symptoms of hypotension or bradycardia developed.
Spinal anesthesia was administered with the volunteers in the left lateral decubitus position. Under sterile conditions and after local infiltration of the skin with 1% lidocaine, the subarachnoid space was entered at approximately the L2-3 interspace via the midline approach using a 20-gauge introducer and a 24-gauge Sprotte needle. With the spinal needle orifice facing cephalad, 0.2 mL of cerebrospinal fluid was aspirated, followed by injection of the study solution at a rate of 0.25 mL/s. After drug administration, a second 0.2-mL aspiration and reinjection of cerebrospinal fluid was used to confirm intrathecal injection. Subjects were immediately laid supine for the remainder of the study. The duration of the blockade was assessed using the following previously described (3) modalities: 1) sensory block to pinprick, 2) tolerance to transcutaneous electrical stimulation (TES), 3) tolerance to thigh tourniquet, and 4) motor blockade by electromyography (abdomen), isometric force dynamometry (quadriceps), and modified Bromage scale (lower extremity).
Bilateral sensory block to pinprick was tested by a blinded assessor in a cephlad-to-caudad direction with a disposable dermatome tester every 5 min after injection for the first 60 min, then at 10-min intervals until complete resolution of sensory anesthesia. The right C5-6 dermatome was used as an unblocked reference point.
Tolerance to TES was determined at six common surgical sites: at the lateral ankle (S1) bilaterally, at the medial knee (L3) bilaterally, at the pubis midline (T12), and at the umbilicus midline (T10). TES was performed with a peripheral nerve stimulator (Model NS252; Fisher & Paykel, Auckland, New Zealand) using 50 Hz tetanus for 5 s initially at 10 mA and then with increasing increments of 10 mA to a maximum of 60 mA (previously shown to be equivalent to surgical incision (12). Testing began in a systematic cephlad-to-caudad order at 4 min after injection and continued at 10-min intervals until the subject could no longer tolerate 60 mA on 2 successive tests. If the subject was never able to tolerate 60 mA, the testing was terminated at 34 min.
Thirty minutes after injection, duration of the tolerance to left thigh tourniquet was assessed using a 34-in. pneumatic cuff that was inflated to 300 mm Hg after exsanguination by gravity. This is similar to the tourniquet application used in lower extremity orthopedic procedures at our institution. The subjects were instructed to request deflation of the tourniquet when the discomfort level reached a pain score of 5 on a 10-point scale or at a maximum time limit of 120 min.
Motor blockade of the abdominal and lower extremity muscles was assessed using electromyography (EMG), isometric force dynamometry, and modified Bromage scale. To test abdominal muscle strength, an EMG lead was placed at the midclavicular line to the left of the umbilicus. A restraining strap was placed across the body at the level of the xiphoid, and an isometric maximal contraction of abdominal muscle flexion against the strap was conducted. Using a commercially available surface EMG (MyoTrac2; Thought Technology Ltd., Montreal, PQ) an averaged, rectified measurement was taken during the middle 2 s of a 6-s maximal effort. Muscle strength of the right lower extremity was measured using a commercially available isometric force dynamometer (Micro FET, Hoggan Health Industries, Draper, UT) during a 5-s maximal force contraction of the right quadriceps muscle (straight leg lift against resistance.) Measurements for both tests were performed in triplicate and averaged at baseline and at 10-min intervals after injection until 
90% of baseline strength returned. Modified Bromage scores (0 = no block, 1 = able to dorsiflex the foot, 2 = able to bend the knee, and 3 = complete motor block) were recorded every 10 min after injection until the resolution of the motor block.
Each subject also underwent a simulated clinical discharge pathway. On recovery of S2 dermatome to pinprick, the subjects attempted ambulation without assistance. If ambulation was successful, they then attempted to void. If either ambulation or voiding were unsuccessful, then attempts were repeated at 15-min intervals until these end-points were achieved. Volunteers were questioned daily for 72 h for the presence of headache, backache, or other residual symptoms.
Dose-response relationships for pinprick anesthesia, TES tolerance, EMG, Bromage scores, and achievement of discharge criteria were determined by linear regression analysis for chloroprocaine without epinephrine. Because of the limited sample size (see Results), this analysis was not conducted for the epinephrine-containing groups. For statistical analysis, each dermatome above S3 was assigned an integer (i.e., S2 = "1," T10 = "10," and T1 = "19"), and all dermatome levels blocked to pinprick were averaged for each dose to determine the estimated time course of sensory anesthesia to pinprick. Peak block height comparisons were made using the Mann-Whitney U-test. Comparisons of dermatome regression over time, isometric force dynamometry, and hemodynamic data were made using repeated-measures analysis of variance with Bonferroni-Dunn correction for multiple comparisons. Differences between epinephrine and nonepinephrine groups were analyzed using paired Student’s t-test. Significance was defined as P < 0.05.
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Results |
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Successful spinal anesthesia was attained in all subjects (11 male, 7 female; age, 35 ± 9 yrs; height, 170 ± 8 cm; weight, 78 ± 23 kg) with complete return of neurologic function within 200 min of injection.
2-Chloroprocaine Without Epinephrine
Mean peak block height reached T5 (range, C5-L3) and correlated positively with increasing dose. With 30, 45, and 60 mg without epinephrine, mean peak block heights and ranges were as follows: T7 (L3-T4), T5 (T10-1), and T2 (T6-C5)(Fig. 1). 2-chloroprocaine without epinephrine also provided dose-dependent prolongation of sensory and motor block and time until achievement of discharge criteria (P values from <0.001 to 0.04) for all measures except time to 2-segment regression and tolerance to TES at T10 (Fig. 2, Table 1).
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For 30, 45, and 60 mg of 2-chloroprocaine without epinephrine, time to complete sensory regression was 98 ± 20, 116 ± 15, and 132 ± 23 min, respectively. Return of full lower extremity muscle strength was at 72 ± 12, 88 ± 15, and 100 ± 13 min (Table 1, Fig. 3). Time to ambulation was 100 ± 21, 119 ± 15, 133 ± 20 min, and time to micturition was 100 ± 22, 132 ± 19, and 141 ± 21 min (Table 1).
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2-Chloroprocaine With Epinephrine
As the sample size at each of the doses within this group (n = 3, 5, and 3) was limited because of side effects, linear regression was not performed.
2-Chloroprocaine with Epinephrine Versus Without Epinephrine
At equimilligram doses, the addition of epinephrine increased time to complete resolution of sensory block and time to ambulate at 30 mg (P = 0.009 and P = 0.013, respectively) and 45 mg (P = 0.015 and P = 0.018, respectively) but not at 60 mg (P = 0.273 and P = 0.338, respectively). At 30 mg, there was also an increased time to void as well as an increased tolerance to TES at the right S1 dermatome with the addition of epinephrine (P = 0.185 and P = 0.046, respectively.) At 45 mg, there was an increase in tolerance to tourniquet with the addition of epinephrine (P = 0.024). With 60 mg, the only variable to increase with the addition of epinephrine was time to 2-segment regression (P = 0.004.)
Side Effects
Eleven patients complained of vague, nonspecific flu-like symptoms (malaise, myalgias, arthralgias, back stiffness, loss of appetite) that did not require treatment or bedrest for up to 48 h after their spinal anesthetics. All of the spinal anesthetics associated with flu-like symptoms were found to contain the addition of epinephrine. There were no complaints of flu-like symptoms in the volunteers who received 2-chloroprocaine without epinephrine (Table 2).
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Two volunteers who received 2-chloroprocaine with epinephrine complained of radiating back pain in addition to the flu-like symptoms. An additional four volunteers complained of non-radiating low backache (in addition to the flu-like symptoms) after 2-chloroprocaine with epinephrine. Only one patient who received 2-chloroprocaine without epinephrine complained of non-radiating low back pain. It was noted at the time of the spinal blockade that the investigator had difficulty with spinal placement, resulting in several needle redirections and contact with periosteum (Table 2). The remaining spinal anesthetics were performed without difficulty.
Four volunteers complained of headache after the spinal anesthetic; all resolved within 48 h with conservative management. Two of these were consistent with postdural puncture headache lasting 24–48 h; both occurred in volunteers whose blocks did not contain epinephrine. The remaining two headaches were nonpostdural puncture in nature. One of these occurred in a volunteer whose spinal anesthetic contained the addition of epinephrine. The other occurred as an isolated complaint in a volunteer whose anesthetic did not contain epinephrine. One volunteer complained of mild nasal congestion during both anesthetics, when the block height was above T6, but developed flu-like symptoms only after the spinal anesthetic with epinephrine (Table 2).
Four volunteers (3 with epinephrine, 1 without) required atropine or ephedrine for heart rate <50 bpm or systolic blood pressure <80 mm Hg during the 29 spinal anesthetics. There was a significant decrease in heart rate compared with baseline for all groups (P < 0.01). There was also a significant decrease in systolic blood pressure compared with baseline for all groups (P < 0.01). The 60-mg dose caused a significantly larger decrease in systolic blood pressure compared with the 30 mg and 45 mg groups (P = 0.02) (Fig. 4).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Spinal 2-chloroprocaine without epinephrine produced dose-dependent prolongation of sensory block, tolerance to tourniquet pain, motor block, and time until full recovery from anesthesia for all variables assessed with the exception of time to 2-segment regression and tolerance to TES at T10. These data can guide clinical selection for dosage of 2-chloroprocaine (without epinephrine) based on the desired duration of clinical anesthesia for various surgical sites.
When 2-chloroprocaine was compared at equal doses, with and without epinephrine, there was a statistically significant increase in time to complete sensory regression and time to ambulate at smaller doses with the addition of epinephrine (30 and 45 mg). Previous studies have noted prolongation of sensory anesthesia and time to micturition for spinal lidocaine with the addition of epinephrine (13). We observed variable effects of epinephrine at varying doses, likely attributable in part to the small sample size and therefore limited power (10%–20%) of the analysis to compare the two groups. However, because of the unreliable effect of epinephrine and the numerous reported side effects in the group of volunteers in this study who received epinephrine as an adjunct to 2-chloroprocaine, the authors recommend avoiding epinephrine in combination with intrathecal 2-chloroprocaine.
Block height also increased with increasing dose of spinal 2-chloroprocaine without epinephrine (Fig. 1a). This effect is seen with other local anesthetics used in the intrathecal space and can also help guide clinical selection of drug dosage (14). Similar to Foldes and McNall (5), (who used a hyperbaric solution containing approximately 82.5–100 mg) the authors of this study noted sensory anesthesia to high cervical segments at the largest dose, although there were no signs of respiratory problems and assisted ventilation was not required for these volunteers. When compared at equal doses, the addition of epinephrine does not significantly increase peak block height (Mann-Whitney U-test, P > 0.46). Again, this observation may be limited by the power of the study to detect a difference between the epinephrine versus no-epinephrine groups with a small sample size, particularly in the epinephrine-containing group. Altering the baricity of the solution may also affect the spread of the local anesthetic in the intrathecal space and is the subject of further investigation.
Foldes and McNall, using combined data for 82.5 and 100 mg, reported on the total duration of sensory anesthesia (defined as "perception of pinprick at the inguinal fold"–essentially L1) and motor blockade (defined as "ability to flex either knee voluntarily"). Substantially more epinephrine (600 µg) was also used. Despite these differences in dosage and methodology, our 60 mg groups produced comparable durations of sensory anesthesia at L1 (plain 2-CP, 92 ± 13 min; with epinephrine, 103 ± 15 min versus Foldes and McNall plain, 82 ± 2.8 min and with epinephrine, 121 ± 3.0 min). Although we did not specifically measure the ability to flex either knee voluntarily, it can be extrapolated from the points in Figure 3 where quadriceps strength begins to reappear after blockade (50 min for plain 2-CP, 100 min for 2-CP with epinephrine). These values for 60 mg are also consistent to Foldes and McNall’s data for 82.5–100 mg (plain, 70 min ± 2.2 min; with epinephrine, 110 ± 2.8 min).
Spinal lidocaine is frequently associated with TNS, and many practitioners have abandoned its use (1). Therefore, an alternative short-acting local anesthetic for outpatient spinal anesthesia is desirable. In this study, 2 of 29 spinal anesthetics were associated with radiating back pain; both occurred in the group that received the addition of epinephrine. In this group, there were also 4 volunteers who complained of nonradiating low back pain in addition to their flu-like symptoms. Only one volunteer who received plain 2-chloroprocaine complained of low back pain that was nonradiating in nature. As previously noted, technical performance during the spinal anesthetic in this subject was the only occasion when multiple needle redirections and contact with periosteum occurred. Studies directly comparing the incidence of TNS between 2-chloroprocaine and lidocaine are continuing at this time.
The addition of epinephrine was strongly associated with significant systemic side effects that cannot be fully explained. There was a 100% incidence of generalized malaise and flu-like symptoms in the group of volunteers who received 2-chloroprocaine with epinephrine. The spinal anesthetics were separated in time over the course of several summer months and are unlikely to be attributed to a local viral outbreak or other chance cause. In addition, several spinal anesthetics without the addition of epinephrine were administered over the same period and were not associated with the systemic symptoms noted with epinephrine.
Epinephrine, at the dose used in this study (0.2 mg), has been added to numerous other local anesthetics without producing the symptoms we observed (13–16). However, all of the other commercially available local anesthetics have a much higher pH (>5.0) than 2-chloroprocaine (pH 
3.5). Possible explanations for the observed side effects include the effect of the small amount of bisulfite in the epinephrine vials (0.9 mg/mL) and/or the low pH of epinephrine. Although the small volume of epinephrine added to the intrathecal solution (0.2 mL = 0.18 mg bisulfite) seems insignificant, it may contribute to these observations. These symptoms may actually be representative of a short-term, aseptic (chemical) meningitis induced by the epinephrine/bisulfite, although no further testing was done to confirm or refute this diagnosis. The symptoms of aseptic meningitis can be equally subtle and nondescript. Phenylephrine has also been used successfully as an adjunct to prolong block time with other local anesthetics (17). However, phenylephrine also contains bisulfite (up to 2 mg/mL) and is prepared at a low pH (3–6.5). Therefore, the addition of phenylephrine may cause similar side effects as those seen with epinephrine and is not recommended at this time. Also, one commercially available preparation of 2-chloroprocaine still contains a large concentration of bisulfite (1.8 mg/mL)(Abbott Laboratories, North Chicago, IL), and should not be used for spinal anesthesia. This preparation is packaged in a clear vial, as distinguished from the bisulfite-free preparations, which both come in a brown vial to prevent photodegradation. Further investigations could include the addition of sodium bicarbonate to the chloroprocaine-epinephrine solution to increase the pH or the use of bisulfite-free epinephrine. A unique interaction between chloroprocaine and epinephrine in the intrathecal space that is not seen with other local anesthetics is possible. Nonetheless, the authors recommend avoiding the use of epinephrine as an adjunct to spinal 2-chloroprocaine because of the frequent (100%) incidence of side effects noted in this study. Investigation of the effects of alternative adjunctive drugs (e.g., fentanyl or clonidine) on spinal 2-chloroprocaine anesthetic quality and duration are warranted.
In conclusion, we determined the dose-response relationship between spinal 2-chloroprocaine and sensory block, motor block, and time until full recovery from spinal anesthesia. These data show spinal 2-chloroprocaine to be reliable and may serve as a guideline for the selection of dose in outpatient procedures. As the number of subjects in this initial study is quite small, large-scale clinical trials will be necessary to further delineate the safety of spinal 2-chloroprocaine. The authors recommend avoiding the use of epinephrine in combination with intrathecal 2-chloroprocaine because of the frequent incidence of side effects associated with the use of epinephrine in this study.
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Acknowledgments |
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Supported, in part, by the Department of Anesthesiology, Virginia Mason Medical Center, Seattle, Washington.
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Footnotes |
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Presented, in part, at the 77th International Anesthesia Research Society Congress, March, 2003, and at the 41st Annual Western Anesthesia Residents’ Conference, Palo Alto, California, April, 2003.
Disclaimer: Although 2-chloroprocaine has been approved by the FDA, it is not specifically indicated for use in spinal anesthesia. Its use for spinal anesthesia is thus considered "off-label." All current manufacturers of 2-chloroprocaine distinctly label the product "Not for Spinal Anesthesia." All subjects in this study were made aware of this information, which was also included within their written informed consent.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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- Pollock JE. Transient neurologic symptoms: etiology, risk factors, and management. Reg Anesth Pain Med 2002; 27: 581–6.[Web of Science][Medline]
- Le Truong HH, Girard M, Drolet P, et al. Spinal anesthesia: a comparison of procaine and lidocaine. Can J Anaesth 2001; 48: 470–3.[Web of Science][Medline]
- Hodgson PS, Liu SS, Batra MS, et al. Procaine compared with lidocaine for incidence of transient neurologic symptoms. Reg Anesth Pain Med 2000; 25: 218–22.[Web of Science][Medline]
- Bergeron L, Girard M, Drolet P, et al. Spinal procaine with and without epinephrine and its relation to transient radicular irritation. Can J Anaesth 1999; 46: 846–9.[Web of Science][Medline]
- Foldes FF, McNall PG. 2-chloroprocaine: a new local anesthetic agent. Anesthesiology 1952; 13: 287–96.[Web of Science][Medline]
- Winnie AP, Nadar AM. Santayana’s prophecy fulfilled. Reg Anesth Pain Med 2001; 26: 558–64.[Web of Science][Medline]
- Ravindran RS, Bond VK, Tasch MD, et al. Prolonged neural blockade following regional anesthesia with 2-chloroprocaine. Anesth Analg 1980; 59: 447–51.
[Free Full Text] - Reisner LS, Hochman BN, Plumer MH. Persistent neurologic deficit and adhesive arachnoiditis following intrathecal 2-chloroprocaine. Anesth Analg 1980; 59: 452–4.
[Free Full Text] - Moore DC, Spierdijk J, van Kleef JD, et al. Chloroprocaine toxicity: four additional cases. Anesth Analg 1982; 61: 158–9.
- Gissen AJ, Datta S, Lambert D. The chloroprocaine controversy II: is chloroprocaine neurotoxic? Reg Anesth 1984; 9: 135–45.
- Wang BC, Hillman DE, Spielholz NI. Chronic neurological deficits and Nesacaine-CE: an effect of the anesthetic, 2-chloroprocaine, or the antioxidant, sodium bisulfite? Anesth Analg 1984; 63: 445–7.
[Abstract/Free Full Text] - Petersen-Felix S, Zbinden AM, Fischer M, et al. Isoflurane minimum alveolar concentration decreases during anesthesia and surgery. Anesthesiology 1993; 79: 959–65.[Web of Science][Medline]
- Chiu AA, Liu SS, Carpenter RL, et al. The effects of epinephrine on lidocaine spinal anesthesia: a cross-over study. Anesth Analg 1995; 80: 735–9.[Abstract]
- Liu SS, Ware PD, Allen HW, et al. Dose-response characteristics of spinal bupivacaine in volunteers: clinical implications for ambulatory anesthesia. Anesthesiology 1996; 85: 729–36.[Web of Science][Medline]
- Kito K, Kato H, Sibata M, et al. The effect of varied doses of epinephrine on duration of lidocaine spinal anesthesia in the thoracic and lumbosacral dermatomes. Anesth Analg 1998; 86: 1018–22.[Abstract]
- Moore JM, Liu SS, Pollock JE, et al. The effect of epinephrine on small-dose hyperbaric bupivacaine spinal anesthesia: clinical implications for ambulatory surgery. Anesth Analg 1998; 86: 973–7.[Abstract]
- Vaida GT, Moss P, Capan LM, et al. Prolongation of lidocaine spinal anesthesia with phenylephrine. Anesth Analg 1986; 65: 781–5.
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