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Anesth Analg 2004;98:1789-1793 © 2004 International Anesthesia Research Society doi: 10.1213/01.ANE.0000116929.45557.CE
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Abstract |
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In this randomized prospective double-blind study we tested the hypothesis that compared with 40 mL chloroprocaine 0.5%, 40 mL chloroprocaine 1% results in an earlier onset to analgesia duration and improves distal tourniquet tolerance in 150 patients undergoing forearm surgery under IV regional anesthesia using a double-cuff technique, switching from the proximal to the distal cuff was performed if pain scores increased above 4 of 10. Switching to the distal cuff resulted in pain scores below 4 in 69% of patients in the 0.5% group and in 88% of patients in the 1% group (P = 0.047). In addition, both groups differed in the sustained effect on distal tourniquet pain (P = 0.020). Time between injection and onset to analgesia duration was 13 ± 1 min in the 0.5% group and 11 ± 1 min in the 1% group (P = 0.0006). On release of the tourniquet, signs of systemic local anesthetic toxicity occurred in 6 patients of the 0.5% group and 28 of the 1% group (P < 0.0001). We conclude that chloroprocaine 1% resulted in an earlier onset of analgesia and improved distal tourniquet tolerance. However, these beneficial effects must be weighed against a fourfold increase in side effects.
IMPLICATIONS: Compared to a standard dose of 40 mL 0.5% chloroprocaine, 40 mL 1% chloroprocaine resulted in an earlier onset of analgesia duration and improved distal tourniquet tolerance during IV regional anesthesia. These beneficial effects must be weighed against a fourfold increase in signs of systemic local anesthetic toxicity.
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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A double-cuff technique can improve the tourniquet tolerance during IV regional anesthesia (IVRA) (1). However, tourniquet pain may be relieved for only a short period or it may even persist after switching from the proximal to the distal cuff. The beneficial effect of both subcutaneous ring infiltration anesthesia and EMLA cream indicates a significant cutaneous component of tourniquet pain (1,2). This in turn suggests that the success of the double-cuff technique may depend on the quality of cutaneous analgesia in the region of the distal cuff. Whether increasing the dose of local anesthetics administered to establish IVRA can improve cutaneous analgesia, and hence the success rate of the double-cuff technique, is not known.
During IVRA, tourniquet pressure is applied before the injection of the local anesthetic and released after the end of surgery. The onset time of local anesthesia determines the start of surgery and hence influences the tourniquet time. Though increasing the dose of a local anesthetic generally results in a faster onset of anesthesia, it is not known whether this holds true in IVRA.
The present study was performed with 2-chloroprocaine, an ester-type local anesthetic that is rapidly hydrolyzed by plasma pseudocholinesterase. 2-chloroprocaine is commonly used for IVRA in Switzerland and other parts of Europe and is the drug of choice in our institution. Previous studies demonstrated that the quality of IVRA induced by 0.5% 2-chloroprocaine is equivalent to that induced by 0.5% prilocaine and 0.5% lidocaine (3,4). The aim of the present study was to test the hypothesis that compared with a standard dose of 40 mL 0.5% 2-chloroprocaine, 40 mL of 1% 2-chloroprocaine improves the tolerance of the distal tourniquet during IVRA. A second aim was to test the hypothesis that doubling the dose of the local anesthetic allows for an earlier onset of analgesia duration, thereby reducing total tourniquet time.
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Methods |
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The study took place in the Hospital of Thusis, a rural level III center. All adult (age
18 yr) patients with ASA physical status I–II scheduled for hand and forearm surgery under IVRA were eligible. Exclusion criteria were pregnancy and known allergy against local anesthetics or para-aminobenzoic acid. The study was approved by the regional Ethics Committee, and written informed consent was obtained from all patients. Approximately 60% of pilot patients undergoing IVRA with 0.5% 2-chloroprocaine did tolerate the distal cuff without major discomfort. The primary end-point with respect to efficacy of the 1% 2-chloroprocaine solution was a 50% improvement, i.e., a 90% tolerance of the distal tourniquet. Based on 0.9 power to detect a significant difference (P = 0.05, two-sided), 49 patients were required for each study group. To account for the observation that up to one-third of our pilot patients never requested to switch from the proximal to the distal cuff, we planned to enroll 75 patients per group. Patients were randomly allocated (via sealed envelopes) to receive either 0.5% or 1% 2-chloroprocaine. The study drug was prepared by diluting a commercially available plain 3% chloroprocaine solution (Nesacain®, AstraZeneca, Zug, Switzerland) with sodium chloride which resulted in a pH of 4.9 and 4.1 in the 0.5% and 1% solutions, respectively. To ensure a double-blind procedure, randomization and preparation of the syringes with study drug was done by a member of the anesthetic team not involved in patients’ care and assessment.
No premedication was given. If required, patients received up to 2 mg of IV midazolam for sedation. Routine monitoring was commenced and a 20-gauge cannula was inserted in a vein of the nonoperative arm. A 22-gauge cannula was inserted into a vein of the dorsum of the hand of the operative arm and a double-cuff pneumatic tourniquet was placed on the upper arm. The operative arm was exsanguinated using an Esmarch bandage. After inflating the distal cuff to 300 mm Hg the proximal cuff was inflated to 300 mm Hg; the distal cuff was then released and the Esmarch bandage removed; to establish IVRA 40 mL of 2-chloroprocaine, either 0.5% or 1%, was administered over 3 min by an anesthesiologist blinded as to the concentration. Pain or discomfort during injection was recorded. After removal of the 22-gauge cannula the extremity was disinfected and draped for surgery. All operations were performed by one of two surgeons. The surgeon, blinded as to the concentration of the local anesthetic, assessed the development of sensory block in 1-min intervals using pinprick, and surgery was started immediately after the complete loss of sensation to pinprick in the field of operation. Twenty minutes after inflation of the tourniquet, the anesthesiologist asked the patients to rate their pain at the site of the tourniquet using a 10-cm visual analog scale. Thereafter, pain scores were assessed every 5 min. A pain score of <4 was defined as acceptable. As soon as a pain score of 4 or higher was noted the double-cuff technique was used: the distal cuff was inflated to 300 mm Hg and the proximal cuff was released. After switching to the distal cuff, pain scores were again assessed every 5 min. In patients with intolerable pain or discomfort despite the double-cuff technique, incremental doses of alfentanil (0.25 mg) and/or midazolam (1 mg) were administered as clinically required. Otherwise, no opiates or analgesics were given pre- or intraoperatively to any patient. After the completion of surgery, the tourniquet was released. For safety reasons we did not release the tourniquet before a time period of 30 min had elapsed after its inflation.
A checklist was used to record signs of systemic local anesthetic toxicity. Thirty seconds after the release of the tourniquet, patients were asked whether they experienced nausea, dizziness, tinnitus, metallic taste, or any other unusual symptoms. Moreover, patients were observed for convulsions, ventricular dysrhythmias, bradycardia, muscle twitching, and vomiting. Patients exhibiting signs of systemic toxicity were kept under observation until all symptoms had disappeared and the time of the observation period was noted.
Data, presented as means ± SD, were analyzed using the unpaired Student’s t-test, Fisher’s exact test and the log-rank test as appropriate. A P < 0.05 was considered to represent statistical significance.
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Results |
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During the study period ending with the completion of the protocol in the 150th patient, 181 consecutive eligible patients were identified. Two had to be excluded because of pregnancy, 9 refused to participate, and the enrollment of 17 was missed mainly because of high workload. One-hundred-fifty-three patients were randomized and received the allocated treatment. Three patients had to be excluded from analysis: in one patient of each group general anesthesia had to be induced as a result of an incomplete IVRA and in one patient of the 1% group switching of the cuff was impossible because of a technical problem. In the remaining 150 patients the study protocol was successfully completed and all were included in the analysis. Patients of the 0.5% group and the 1% group did not differ in sex (39 male versus 40 male), age (46 ± 22 yr versus 44 ± 18 yr), weight (69 ± 13 kg versus 70 ± 12 kg), or height (169 ± 9 cm versus 169 ± 8 cm). IV midazolam was given in 52 of 75 patients of the 0.5% group and in 55 of 75 patients of the 1% group (P = not significant) The tourniquet remained inflated during 45 ± 12 min in the 0.5% group and during 45 ± 14 min in the 1% group (P = not significant). Because of persistent pain scores of 4 or less, the tourniquet was never switched from the proximal to the distal cuff in 26 of the 75 patients in the 0.5% group (total tourniquet time 39 ± 5 min) and in 27 of the 75 patients in the 1% group (total tourniquet time 37 ± 9 min; P = not significant). Thus, the effect of switching from the proximal to the distal cuff on tourniquet pain could be assessed in 49 patients receiving 0.5% 2-chloroprocaine and in 48 patients receiving 1% 2-chloroprocaine. The proximal cuff was switched to the distal cuff after 33 ± 10 min in the 0.5% group and after 34 ± 11 min in the 1% group (P = not significant); thereafter the distal cuff remained inflated during 13 ± 12 min in the 0.5% group and 11 ± 11 min in the 1% group (P = not significant). By switching from the proximal to the distal cuff a pain score of 4 or less could initially be achieved in 34 of 49 patients (69%) in the 0.5% group and in 42 of 48 patients (88%) of the 1% group. This difference was of marginal statistical difference (P = 0.047). As displayed in Figure 1, the initial difference between groups was maintained during the follow-up period. This resulted in a significant difference (P = 0.020) in the sustained effect on tourniquet pain after switching from the proximal to the distal cuff as assessed by the log-rank test. After switching to the distal cuff 19 patients of the 0.5% group and 11 patients of the 1% group received IV alfentanil to relieve tourniquet pain (P = 0.12).
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There was a significant difference in the time period between completion of the injection of the local anesthetic and the onset to analgesia (Fig. 2). Time between completion of injection until onset to analgesia was 13 ± 0.4 min in the 0.5% group and 11 ± 0.4 min in the 1% group (P = 0.0006). However, this difference of 1.9 min (95% confidence interval 0.8–2.9 min) was comparatively small and did not result in a significant difference in total tourniquet time.
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Pain on injection occurred in 1 patient of the 0.5% group and in 2 patients of the 1% group (P = not significant). Compared to the 0.5% group, there were significantly more signs of systemic local anesthetic toxicity in the 1% group on release of the tourniquet (Table 1). However, no serious or life-threatening side effects were observed. The median time to complete resolution of symptoms of systemic toxicity in the 1% group was 5 min (range, 3–11 min). In three patients of the 1% group and in 1 patient of the 0.5% group an urticaria was seen at the dorsum of the hand and/or the forearm after the release of the tourniquet. In all four patients urticaria was visible for a short period only (3–8 min) and not associated with pain or discomfort.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Doubling the dose of 2-chloroprocaine for IVRA resulted in an earlier onset of analgesia duration, an improved tolerance of the distal tourniquet, and a fourfold increase in symptoms of systemic local anesthetic toxicity.
Differences between local anesthetics suitable for IVRA have been reported to be of marginal, if any, clinical relevance (3–12). Thus the choice of a local anesthetic for IVRA appears to depend at least partly on availability, local preferences, and historic reasons. 2-chloroprocaine is an ester-type local anesthetic that is rapidly hydrolyzed by plasma pseudocholinesterase. 2-chloroprocaine is commonly used for IVRA in Switzerland and other parts of Europe and is the drug of choice in our institution. Therefore, the present study was performed using 2-chloroprocaine as the anesthetic. In the 1960s, there were reports of thrombophlebitis associated with IVRA using a solution of 2-chloroprocaine containing a preservative and antioxidant (13). Solutions with additive free 2-chloroprocaine became available in the 1990s. Using plain 2-chloroprocaine for IVRA, Pitkanen et al. (11) observed signs of venous irritation and/or urticaria after release of the tourniquet in 60% of healthy volunteers (14) and in 33% of patients undergoing minor hand surgery. However, there were no cases of thrombophlebitis attributable to plain 2-chloroprocaine. This frequent incidence of venous irritation and/or urticaria reported by Pitkänen et al. does not correspond to the experience of practitioners in Switzerland using 2-chloroprocaine routinely for IVRA. Moreover, in the present study we found both a small incidence of pain during injection (3 of 150) and urticaria (4 of 150). There is no obvious explanation for the difference in the signs of venous irritation between our study and the aforementioned work of Pitkänen et al. (11,14).
Extrapolations from findings obtained with a specific drug should be made cautiously. However, previous studies demonstrated that the quality of IVRA induced by 0.5% 2-chloroprocaine is equivalent to that induced by 0.5% prilocaine and 0.5% lidocaine (3,4). Therefore, we hypothesize that our results reflect the effect of doubling the dose of a local anesthetic for IVRA rather than being specific for 2-chloroprocaine.
Hitherto proven measures to reduce tourniquet pain during IVRA include a double-cuff technique (1), subcutaneous ring infiltration anesthesia (1), EMLA cream (1,2), as well as clonidine (15–17), ketorolac (18), and ketamine (16) administered as adjuncts to the local anesthetic. The present study is the first to demonstrate that doubling the dose of local anesthetic does significantly improve the tolerance of the distal tourniquet. In keeping with previous observations that both EMLA cream and subcutaneous ring infiltration anesthesia can significantly reduce tourniquet pain, our findings indicate that tourniquet pain has a relevant cutaneous component. However, doubling the dose of the local anesthetic did neither affect the tolerance of the proximal cuff nor completely abolish distal tourniquet pain. Thus, important factors in the genesis of tourniquet pain (e.g., ischemia) are not influenced by the quality of cutaneous analgesia.
Previous studies have compared different local anesthetics with regard to the onset of anesthesia in IVRA (3,5,6,10–12,19). Current knowledge indicates that a variety of different local anesthetics suitable for IVRA do not differ in their speed of onset. Articaine might be the sole exception, although data available are conflicting (11,12,19). According to a survey of IVRA in North America, 14% of the respondent anesthesiologists use lidocaine in concentrations larger than the recommended 0.5% (20). However, the present study is the first to investigate the effects of different concentrations of the same drug on the onset of analgesia duration. Doubling the standard dose of 2-chloroprocaine resulted in earlier onset of analgesia, thus enabling an earlier start of surgery. However, though this finding was highly significant in statistical terms, the mean gain in time was only 2 min, i.e., <5% of the mean total tourniquet time of approximately 45 min. Not surprisingly, the earlier start of analgesia and surgery did not translate into a reduction in total tourniquet time, rendering the clinical significance negligible.
IVRA is a remarkably safe technique. In a large prospective survey in France, only 3 serious complications (all seizures) and no deaths were noted in more than 11,000 IVRAs (21). In the present study, doubling the dose of the local anesthetic resulted in a more than fourfold increase in symptoms of systemic local anesthetic toxicity. Although these signs were short-lived and no life-threatening complications occurred, one must recognize that our sample size is far too small to draw any conclusions regarding serious complications. Moreover, we think it is prudent to assume that a technique resulting in an increased incidence of minor symptoms of local anesthetic toxicity has an inherently higher risk of serious complications.
In conclusion, compared with 40 mL of 0.5% 2-chloroprocaine, 40 mL of 1% 2-chloroprocaine resulted in an earlier onset of analgesia and significantly improved the tolerance of the distal tourniquet during IVRA. Balancing these beneficial effects against a more than fourfold increase in signs of systemic local anesthetic toxicity, we recommend using 0.5% rather than 1% 2-chloroprocaine for IVRA.
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References |
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- Tsai YC, Lai YY, Chang CL. Comparison of the effect of EMLA cream, subcutaneous ring anaesthesia and a double cuff technique in the prevention of tourniquet pain. Br J Anaesth 1993; 70: 394–6.
[Abstract/Free Full Text] - Lowrie A, Jones MJ, Eastley RJ. Effect of a eutectic mixture of local anaesthetic agents (EMLA) on tourniquet pain in volunteers. Br J Anaesth 1989; 63: 751–3.
[Abstract/Free Full Text] - Lavin PA, Henderson CL, Vaghadia H. Non-alkalinized and alkalinized 2-chloroprocaine vs lidocaine for intravenous regional anesthesia during outpatient hand surgery. Can J Anaesth 1999; 46: 939–45.[Web of Science][Medline]
- Pitkanen M, Kytta J, Rosenberg PH. Comparison of 2-chloroprocaine and prilocaine for intravenous regional anaesthesia of the arm: a clinical study. Anaesthesia 1993; 48: 1091–3.[Web of Science][Medline]
- Atanassoff PG, Ocampo CA, Bande MC, et al. Ropivacaine 0.2% and lidocaine 0.5% for intravenous regional anesthesia in outpatient surgery. Anesthesiology 2001; 95: 627–31.[Web of Science][Medline]
- Atanassoff PG, Aouad R, Hartmannsgruber MW, Halaszynski T. Levobupivacaine 0.125% and lidocaine 0.5% for intravenous regional anesthesia in volunteers. Anesthesiology 2002; 97: 325–8.[Web of Science][Medline]
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- Simon MA, Gielen MJ, Alberink N, et al. Intravenous regional anesthesia with 0.5% articaine, 0.5% lidocaine, or 0.5% prilocaine: a double-blind randomized clinical study. Reg Anesth 1997; 22: 29–34.[Web of Science][Medline]
- Dickler DJ, Friedman PL, and Susman IC. Intravenous regional anesthesia with chloroprocaine. Anesthesiology 1965; 26: 244–5.
- Pitkanen MT, Suzuki N, Rosenberg PH. Intravenous regional anaesthesia with 0.5% prilocaine or 0.5% chloroprocaine: a double-blind comparison in volunteers. Anaesthesia 1992; 47: 618–9.[Web of Science][Medline]
- Gentili M, Bernard JM, Bonnet F. Adding clonidine to lidocaine for intravenous regional anesthesia prevents tourniquet pain. Anesth Analg 1999; 88: 1327–30.
[Abstract/Free Full Text] - Gorgias NK, Maidatsi PG, Kyriakidis AM, et al. Clonidine versus ketamine to prevent tourniquet pain during intravenous regional anesthesia with lidocaine. Reg Anesth Pain Med 2001; 26: 512–7.[Web of Science][Medline]
- Lurie SD, Reuben SS, Gibson CS, et al. Effect of clonidine on upper extremity tourniquet pain in healthy volunteers. Reg Anesth Pain Med 2000; 25: 502–5.[Web of Science][Medline]
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