JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Yoos, J. R. Articles by Kopacz, D. J. Search for Related Content PubMed PubMed Citation Articles by Yoos, J. R. Articles by Kopacz, D. J.

---

REGIONAL ANESTHESIA

Spinal 2-Chloroprocaine for Surgery: An Initial 10-Month Experience

Department of Anesthesiology, Virginia Mason Clinic, Seattle, Washington

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Spinal 2-chloroprocaine (2-CP) is currently being investigated as a short-acting alternative to lidocaine, which frequently causes transient neurologic symptoms (TNS) in surgical patients. TNS has not been reported with 2-CP in volunteers in doses ranging from 30 to 60 mg and appears to provide an excellent level of surgical anesthesia. In this retrospective study, we describe the experience with spinal 2-CP in surgical patients during its first 10 mo of clinical use at our institution. Most patients had ambulatory surgery, including 39 orthopedic, 30 general surgical, 18 gynecologic, and 34 genitourinary procedures. Chloroprocaine 30 or 40 mg, with or without fentanyl (10–20 µg), was the most common (92%) dose combination used. Mean peak block height averaged T6 to T8. The surgical procedure time was 32.3 ± 18.4 min. Time from placement of the block to the end of the surgical procedure was 53.1 ± 20.7 min. Times to ambulation and discharge were 155.1 ± 34.7 min and 207.9 ± 69.4 min, respectively. 2-CP spinal anesthesia has proven to be a safe and effective alternative to lidocaine and procaine for ambulatory surgical procedures of 1 h, with a predictable regression of block height. No patients reported TNS after surgery.

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
The search for an ideal local anesthetic for spinal anesthesia in the ambulatory surgical patient has spanned decades. Lidocaine has been a routine choice because of its predictable onset time and duration, as well as its dependable surgical anesthesia. However, it is often associated with transient neurologic symptoms (TNS), which is a non-life-threatening but short-term quality of life-diminishing side effect (1). Procaine is another short-acting alternative, but it is reportedly ineffective in 17% of cases and is associated with frequent nausea (2–4). Although bupivacaine spinal anesthesia is rarely associated with TNS, its use in the ambulatory surgical population is controversial. In larger doses (>9 mg), its duration is unpredictable, and the return of bladder function can be a limiting factor for a timely discharge (5). In smaller doses (7.5 mg), block failure is unacceptably common (6).

In 1952, Foldes and McNall (7) reported 214 patients who received preservative-free 2-chloroprocaine (2-CP) spinal anesthesia. Subsequently, the antioxidant sodium bisulfite was added to 2-CP, and this combination was used extensively for epidural anesthesia, particularly in obstetrics. Case reports in the 1980s described inadvertent large-volume subarachnoid injection of 2-CP, which led to lower-extremity paralysis and sacral nerve dysfunction in 8 patients (8–11). The combination of the antioxidant sodium bisulfite and low pH (<3.3) was thought to be the cause of the apparent neurotoxicity. Two new formulations of 2-CP, both preservative and antioxidant free, have been released (Nesacaine-MPF, Astra Pharmaceuticals, Wilmington, DE; and generic chloroprocaine, Bedford Pharmaceuticals, Bedford, OH). Until recently, the anesthesia community has been reluctant to use these new formulations for spinal anesthesia because of the previous cases of bisulfite-associated neurotoxicity.

In early 2002, volunteer studies commenced at our institution investigating the use of preservative-free 2-CP for spinal anesthesia. Four separate randomized, controlled trials were performed to establish an appropriate dose range and to compare 1) plain 2-CP versus 2-CP with added epinephrine, 2) plain 2-CP versus 2-CP with fentanyl, and 3) plain 2-CP versus 2-CP with dextrose (12–14). The fourth study compared 40 mg of spinal 2-CP and 40 mg of lidocaine (15). No volunteers reported TNS with spinal 2-CP, and all volunteers developed anesthesia of adequate duration and density for surgery in a simulated ambulatory setting.

Beginning in September of 2002, anesthesiologists at the Virginia Mason Medical Center began using 2-CP spinal anesthesia for clinical ambulatory procedures as a replacement to the aforementioned drugs. The purpose of this report was to review perioperative records from our initial 10-month clinical experience with the use of spinal 2-CP in surgical patients.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
After IRB approval, the hospital records of all patients who received 2-CP spinal anesthesia at the Virginia Mason Medical Center from September 2002 through June 2003 were retrospectively reviewed. Data from intraoperative anesthesia records and postanesthesia care unit (PACU) records were collected by a single reviewer and were recorded manually onto a data-collection template. Multiple data points were collected, including the anesthesiologist administering the anesthetic; the patient’s ASA class, age, height, weight, and sex; the surgical procedure; spinal 2-CP dose and adjuvant drugs added; route of administration (spinal or combined spinal/epidural); time of injection; patient position during injection; block height over time; surgical position, surgical start and end times; sedation and vasopressors given; IV fluid administration; time of first recorded ambulation; side effects in the PACU; and discharge time. All patients received a follow-up phone call the day after surgery by the PACU nursing team, and a report note was placed in the chart.

For comparison, the number of patients who underwent spinal anesthesia with lidocaine and procaine at our institution during this same time period was tallied. Data are expressed as mean ± sd, unless otherwise specified. The incidence of side effects was evaluated by using ² analysis, with P < 0.05 accepted as significant.

	Results

Top Abstract Introduction Methods Results Discussion References

 
During this 10-mo period, 122 patients received 2-CP spinal anesthesia, of which 27 were ASA class I, 73 ASA class II, 21 ASA class III, and 1 ASA class IV. There were 52 male and 70 female patients (age, 55 ± 16 yr; weight, 79 ± 20 kg; height, 173 ± 20 cm). Most patients had ambulatory procedures, including 40 orthopedic, 30 general surgical, 18 gynecologic, and 34 genitourinary procedures (Table 1). One patient received spinal 2-CP on 2 occasions for separate procedures. Surgery was performed in the lithotomy position in 56 patients (46%), the supine position in 53 patients (43%), the prone jackknife position in 12 patients (10%), and the lateral position in 1 patient (1%).

All blocks were conducted at L2-3, L3-4, or L4-5 with a 25-gauge Sprotte® needle (B. Braun Medical Inc., Bethlehem, PA), with the choice of level and dose of spinal 2-CP at the discretion of the administering anesthesiologist. Both formulations of preservative- and antioxidant-free 2-CP were used. Spinal anesthesia was most often (82%) performed in the lateral decubitus position, with 14% performed in the sitting position and 4% performed in the prone jackknife position. The dose of chloroprocaine ranged from 20 to 60 mg; 40 mg (2 mL of 2% plain 2-CP) was most common (80%). Fentanyl (10 or 20 µg) was the most common additive (33 patients), whereas dextrose was added to increase baricity in 3 patients and sterile water was added to make a hypobaric solution in 1 patient (Table 1).

Most patients (n = 98) received midazolam and fentanyl sedation before the administration of spinal anesthesia, and 57 patients received intraoperative propofol sedation (<100 µg · kg^–1 · min^–1). Fifty of these patients received a combination of propofol, midazolam, and/or fentanyl. Twenty-four percent of patients received vasoactive drugs. Twenty-two patients required intraoperative treatment with ephedrine for systolic blood pressure (SBP) <90 mm Hg in doses ranging from 5 to 30 mg. Five patients received 100–300 µg of phenylephrine, and 4 patients received 0.4–0.8 mg of atropine for heart rate (HR) <50 bpm. Two patients received both ephedrine and phenylephrine, and one patient received both ephedrine and atropine. Two patients received ephedrine 10 mg in the PACU for SBP <90 mm Hg, and 1 patient received 0.4 mg of atropine in the PACU for HR <50 bpm. The requirement for vasopressors was associated with doses larger than 40 mg (P < 0.04) but was not associated with the addition of fentanyl (P = 0.45). Intraoperative IV fluid administration was uniformly provided to all patients, with a mean quantity of 710 ± 293 mL of lactated Ringer’s solution.

Block height data were collected from operative records (n = 82) when recorded by the clinician or PACU nursing staff. Sufficient data were available only for the 30- and 40-mg doses to plot dose of 2-CP (plain or with adjuncts) versus block height (Fig. 1). Mean block height was more than T10 for all groups within 20 min and peaked between T6 and T8. Dermatomal regression tended to occur more rapidly with the smaller dose (30 mg).

View larger version (38K): [in this window] [in a new window]   Figure 1. Sensory block height over time as recorded for 82 of the 122 surgical patients who received spinal 2-chloroprocaine (30 or 40 mg) (mean ± sd).

Surgical time was longer than anticipated in 4 cases (99 ± 12 min), and conversion to general anesthesia was necessary to complete the procedure. Three patients had combined spinal/epidural anesthesia, all with 2-CP spinal anesthetic before catheter placement, and two of these patients required dosing through the epidural catheter because of prolonged surgical time. These two patients and the four who required general anesthesia were therefore excluded from further analysis. Surgical procedure time in the remaining 116 patients was 32 ± 18 min. The time from placement of the block to the end of the surgical procedure was 53 ± 21 min, and none of these patients required any additional anesthesia. Times from injection to first ambulation and discharge were 155 ± 35 min and 208 ± 69 min, respectively (Fig. 2).

View larger version (30K): [in this window] [in a new window]   Figure 2. Scattergram of individual patient times and elapsed time (mean ± sd) from the injection of spinal 2-chloroprocaine (CP) to the time of ambulation and hospital discharge on the basis of 2-CP doses of 30 and 40 mg with and without fentanyl as an additive. *The 4 outliers in the plain 40-mg group consisted of two inguinal hernia patients, one transurethral resection of a bladder tumor (TURBT) patient, and one cervical laser patient whose delay to ambulation was not explained in the postanesthesia care unit nursing notes. +Four patients with delayed hospital discharge were of the group unable to void on the first attempt (three TURBT patients and one perirectal surgery patient).

Eleven patients complained of nausea in the PACU, with symptom resolution before discharge (eight patients required treatment with ondansetron). The incidence of nausea was not associated with either the 2-CP dose or the addition of fentanyl (P = 0.14 and 0.82, respectively). Two patients complained of itching in the PACU, both of whom had fentanyl (10 µg) added to spinal 2-CP. One required treatment with a single dose of diphenhydramine 25 mg. Five patients were unable to void on the first attempt (four patients had transurethral resection of a bladder tumor (TURBT), and one patient had perirectal surgery), which was not associated with either the 2-CP dose or the addition of fentanyl (P = 0.0.89 and 0.71, respectively). No patients reported symptoms of TNS in the immediate postoperative period or with nursing follow-up.

Before the use of spinal 2-CP at our institution, 62% of short-acting spinal anesthetics were with lidocaine, and 38% were with procaine (Fig. 3). By the end of the review period (June 2003), 2-CP use comprised 73% of this total. In contrast, at the conclusion of this review, lidocaine use had decreased to 24%, and procaine was being used only 3% of the time.

View larger version (25K): [in this window] [in a new window]   Figure 3. Change in spinal use of 2-chloroprocaine, lidocaine, and procaine (percentages) over the 10-mo review period at Virginia Mason Medical Center (September 2002 to June 2003).

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This chart review of our initial 10-month experience illustrates that the preservative-free formulation of 2-CP appears to be a safe, reliable, and effective alternative for spinal anesthesia in the ambulatory surgical setting. No patients at our institution have reported TNS with spinal 2-CP, and all have tolerated short surgical procedures without complications.

Surgical procedures were all initially scheduled for 60 minutes, and only six of these exceeded the scheduled procedure time. Four patients required conversion to general anesthesia because of block resolution midway through the procedure. Two of the three patients with combined spinal/epidural anesthesia required dosing of their epidural catheters during the procedure because of excessive surgical length. The 116 remaining patients tolerated the duration of surgery with adequate block height for surgical anesthesia. These results are consistent with the duration of simulated surgical block in volunteer studies with spinal 2-CP (12–15).

Chloroprocaine 40 mg was the most common spinal dose used in this survey. Because most of the volunteers studied in our preclinical trials also received this dose, it was logical to transfer the 40-mg dose to the surgical patients. However, because the comfort level of using spinal 2-CP has progressed, we are noticing increased use of a 30-mg dose. Furthermore, there has also been a reduction in the use of the additive fentanyl, which increases the duration of anesthesia by 15 minutes (13). Although a very frequent incidence (100%) of pruritus was seen with the addition of fentanyl in volunteers, only 2 (6%) of 33 patients who received fentanyl with spinal 2-CP in this study reported pruritus, and only 1 patient eventually required treatment with diphenhydramine.

Even though dermatome levels were assessed only as dictated by the clinical situation, and not at regular intervals, as is done in a rigid prospective protocol, the variability in block height was more than one might expect. Despite this variability, the mean spinal block height profiles shown in Figure 1 are consistent with those produced for the same doses of 2-CP in previous volunteer studies. Likewise, the time until ambulation for 30 and 40 mg of spinal 2-CP in our surgical patients is also comparable to that observed in preclinical volunteers (12,14). Although the time until hospital discharge is somewhat longer in surgical patients, compared with preclinical volunteers, this is not unexpected, because surgical patients tend to have more side effects (pain, urinary retention, and so on) because of the surgical procedure, sedation, and analgesics administered. For example, nearly all preclinical volunteers are able to void spontaneously as soon as they are able to ambulate, whereas five patients in this review had urinary retention in the PACU. All five of these patients had procedures after which urinary retention is a common side effect (TURBT and perirectal surgery) (16).

In this review, the side effect profile of 2-CP spinal anesthesia was clinically excellent for a timely ambulatory discharge. Urinary retention is a common side effect of regional anesthesia, especially with the use of bupivacaine and/or the addition of epinephrine to the local anesthetic. Smith and Kopacz (12) reported no increase in urinary retention with the addition of epinephrine in their volunteer studies, but 100% of volunteers reported vague, flulike symptoms with its use—a side effect not previously reported with the addition of epinephrine to other local anesthetics. It is hypothesized that the low pH (3.5) of 2-CP in combination with the trace amounts of bisulfite in the epinephrine vials and/or the low pH of epinephrine in combination with 2-CP may have caused these symptoms. Because of these unusual findings, the use of epinephrine in combination with 2-CP for spinal anesthesia has been avoided at our institution.

It is encouraging that no patients who received spinal 2-CP complained of TNS symptoms in the PACU or on follow-up, though there are several limitations to this study. The first limitation is the retrospective nature of this investigation. Retrospective reviews are subject to the possibility of bias and Type II errors. In this review, it is possible that some cases of TNS that occurred with spinal 2-CP were not detected by our routine clinical follow-up arrangements. The association of TNS with lidocaine went undetected until nearly 40 years after its introduction as a spinal anesthetic, and its incidence is most frequent when patients are specifically questioned after surgery about the presence of any back pain with radiation to the lower extremities. To address this limitation, we are currently conducting a randomized, prospective clinical trial comparing spinal lidocaine and spinal 2-CP.

A second limitation is the absence of spinal bupivacaine use in our comparison of local anesthetic usage over time. Although spinal bupivacaine is still used in outpatient surgery by a few of our anesthesiologists, their number has rapidly diminished. Our database is unable to easily differentiate when bupivacaine is being used for outpatient surgery versus inpatient procedures. Despite this, we were surprised to see that spinal 2-CP has so rapidly overtaken lidocaine and procaine. At the conclusion of this review, 2-CP was used in most instances (73%) when 1 of these 3 short-acting drugs was selected for spinal anesthesia.

One of the possible reasons for this rapid increase in the use of spinal 2-CP at our institution is the ability to use spinal 2-CP in patients undergoing procedures in the lithotomy position. Surgical procedures in the lithotomy or flexed-knee position (knee arthroscopy) are an added risk factor for the development of postoperative TNS (17–19). Nearly 50% of the patients in our current survey were operated on in the lithotomy position, and there were no cases of TNS reported with spinal 2-CP. TNS has also been reported with spinal lidocaine after surgery in the prone jackknife position (20). An additional 10% of patients in this study were operated on in the prone jackknife position without the development of TNS.

In our clinical experience, the preservative-free formulation of 2-CP for spinal anesthesia appears to be a safe and effective alternative to lidocaine and procaine for short ambulatory procedures. The 8 cases of neurotoxicity reported in the 1980s occurred with inadvertent subarachnoid injection of 2-CP formulations that contained sodium bisulfite as a preservative. These cases have been extensively reviewed, and most clinicians have concluded that the neurotoxicity was the result of the aforementioned preservative in combination with the low pH of 2-CP. A formulation of 2-CP with large amounts of bisulfite is still commercially available (Abbott Laboratories, Chicago, IL; bisulfite 1.8 mg/mL) and should be avoided for spinal anesthesia. The clinician can easily distinguish this formulation from the preservative-free formulations because it is packaged in a clear vial, whereas the preservative-free formulations are packaged in a brown vial designed to prevent photodegradation. At our institution, both of the bisulfite-free formulations of 2-CP have been safely used for spinal anesthesia clinically and in volunteer studies.

In conclusion, the preservative-free formulation of 2-CP appears to be an excellent alternative for short-acting spinal anesthesia in the ambulatory surgical population. It has been well tolerated and effective in volunteer studies and clinically, as evidenced by this review of its first 10 months in use at our institution. We have had no cases of TNS-like symptoms or neurotoxicity, and 2-CP has become the short-acting local anesthetic of choice at our institution.

	Footnotes

 
Although 2-chloroprocaine is approved by the Food and Drug Administration, it is not specifically indicated for spinal anesthesia. Its use for spinal anesthesia is thus considered off-label. Manufacturers of 2-chloroprocaine distinctly label the product "not for spinal anesthesia."

Accepted for publication February 20, 2004.

Address correspondence to Dan J. Kopacz, MD, Department of Anesthesiology, Virginia Mason Clinic, 1100 Ninth Ave., B2-AN, PO Box 900, Seattle, WA 98111. Address e-mail to anedjk{at}vmmc.org.

Reprints will not be available.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Pollock JE. Transient neurologic symptoms: etiology, risk factors, and management. Reg Anesth Pain Med 2002;27:581–6.[Web of Science][Medline]
2. Le Truong JJ, 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]
3. 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]
4. 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]
5. Kamphuis ET, Ionescu TI, Kuipers PWG, et al. Recovery of storage and emptying functions of the urinary bladder after spinal anesthesia with lidocaine and with bupivacaine in men. Anesthesiology 1998;88:310–6.[Web of Science][Medline]
6. Ben-David B, Solomon E, Levin H, et al. Intrathecal fentanyl with small-dose dilute bupivacaine: better anesthesia without prolonging recovery. Anesth Analg 1997;85:560–5.[Abstract]
7. Foldes FF, McNall PG. 2-Chloroprocaine: a new local anesthetic agent. Anesthesiology 1952;13:287–96.[Web of Science][Medline]
8. Winnie AP, Nadar AM. Santayana’s prophecy fulfilled. Reg Anesth Pain Med 2001;26:558–64.[Web of Science][Medline]
9. 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]
10. 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]
11. Moore DC, Spierdijk J, van Kleef JD, et al. Chloroprocaine toxicity: four additional cases. Anesth Analg 1982;61:158–9.
12. Smith KN, Kopacz DJ. Spinal 2-chloroprocaine: a dose-ranging study and the effect of added epinephrine. Anesth Analg 2004;98:81–8.[Abstract/Free Full Text]
13. Vath JS, Kopacz DJ. Spinal 2-chloroprocaine: the effect of added fentanyl. Anesth Analg 2004;98:89–94.[Abstract/Free Full Text]
14. Warren DT, Kopacz DJ. Spinal 2-chloroprocaine: the effect of added dextrose. Anesth Analg 2004;98:95–101.[Abstract/Free Full Text]
15. Kouri M, Kopacz DJ. Spinal 2-chloroprocaine: a comparison with lidocaine in volunteers. Anesth Analg 2004;98:75–80.[Abstract/Free Full Text]
16. Pavlin JD, Pavlin EG, Fitzgibbons DR, et al. Management of bladder function after outpatient surgery. Anesthesiology 1999;91:42–50.[Web of Science][Medline]
17. Schneider M, Ettlin T, Kaufmann M, et al. Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth Analg 1993;76:1154–7.[Free Full Text]
18. Pollack JE, Neal JM, Stephenson CA, Wiley CA. Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology 1996;84:1361–7.[Web of Science][Medline]
19. Freedman J, Li D, Drasner K, et al. Risk factors for transient neurologic symptoms after spinal anesthesia. Anesthesiology 1998;89:633–41.[Web of Science][Medline]
20. Alley EA, Pollock JE. Transient neurologic symptoms in a patient receiving hypobaric lidocaine in the prone jack-knife position. Anesth Analg 2002;95:757–9.[Abstract/Free Full Text]

This article has been cited by other articles:

				R. K. Baumgarten Spinal Anesthesia Research: Let's Not Be Hasty Anesth. Analg., December 1, 2007; 105(6): 1862 - 1862. [Full Text] [PDF]

				K. Drasner Chloroprocaine Spinal Anesthesia: Back to the Future? Anesth. Analg., February 1, 2005; 100(2): 549 - 552. [Full Text] [PDF]

				B. R. Davis and D. J. Kopacz Spinal 2-Chloroprocaine: The Effect of Added Clonidine Anesth. Analg., February 1, 2005; 100(2): 559 - 565. [Abstract] [Full Text] [PDF]

				J. R. Yoos and D. J. Kopacz Spinal 2-Chloroprocaine: A Comparison with Small-Dose Bupivacaine in Volunteers Anesth. Analg., February 1, 2005; 100(2): 566 - 572. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Yoos, J. R. Articles by Kopacz, D. J. Search for Related Content PubMed PubMed Citation Articles by Yoos, J. R. Articles by Kopacz, D. J.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999