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REGIONAL ANESTHESIA

The Influence of Hyperbaric Bupivacaine Temperature on the Spread of Spinal Anesthesia

Young-Chang P. Arai, MD^*, Wasa Ueda, MD, Eri Takimoto, MD^*, and Masanobu Manabe, MD

*Department of Anesthesiology, Kochi Municipal Hospital, Marunouchi; and Departments of Anesthesiology, Clinical Physiology, and Pharmacology, School of Nursing, Kochi Medical School, Japan

Address correspondence and reprint requests to Young-Chang P. Arai, MD, Multidisciplinary Pain Center, Aichi Medical University, 21 Karimata, Nagakutecho, Aichigun, Aichi, 480-1195, Japan. Address e-mail to arainon{at}aichi-med-u.ac.jp.

	Abstract

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The distribution of spinal anesthesia is affected by the density and viscosity of the local anesthetic solution that, in turn, may be influenced by the temperature of the injectate. Our hypothesis in the present study was that the temperature of the injectate influences its distribution into the subarachnoid space. We measured the density and viscosity of hyperbaric 0.5% bupivacaine at 25°C and 37°C and tested the onset and extent of spinal anesthesia achieved by these solutions in 36 patients. The densities of the two solutions were similar (mean [sd]): 25°C, 1.028 [0.000], versus 37°C, 1.028 [0.000] (g/mL), but the viscosity was more at 25°C than at 37°C (0.01116 [0.00003] versus 0.00843 [0.00002] g · cm^–1 · s^–1; P < 0.001). The maximum cephalad extent of loss of pinprick sensation was significantly higher with 37°C (T2 with 37°C versus T5 with 25°C; P < 0.001), but the time to achieve peak block height was similar. In conclusion, we showed a consistent, but modest, increase in the cephalad level of spinal anesthesia by warming hyperbaric bupivacaine 0.5% from 25°C to 37°C. Viscosity was reduced in the warmed solution, but it is unclear if this or other factors led to the difference in spinal anesthetic level.

	Introduction

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The distribution of spinal anesthesia is affected by many factors such as the density and viscosity of injectate (1–6) that, in turn, may be influenced by the temperature of the injectate. Warming plain bupivacaine solution to 37°C increases the distribution of spinal anesthesia performed in the sitting position, compared with bupivacaine at 4°C, 20°C, or 22°C (7–10). Because we routinely use hyperbaric and plain spinal bupivacaine, we questioned whether temperature affects the spread of spinal anesthesia with hyperbaric solution. We therefore measured the density and viscosity of 0.5% bupivacaine containing 7% dextrose at a temperature of 25°C and 37°C and then tested the onset and extent of spinal anesthesia achieved by these 2 solutions.

	Methods

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Before starting the present study, we obtained stability information for 0.5% bupivacaine with 7% dextrose from AstraZeneca, Tokyo, Japan. Proprietary data show that the content of bupivacaine remains between 99.8% and 101.3% of the original concentration and that potentially toxic dextrose degradation products, such as 5 hydroxymethylfufural (11,12), increase only minimally after storage at 40°C for 6 mo. Thus, these data confirm the safety of the solutions.

After approval by the hospital's Ethics Committee and written informed patient consent, 36 patients (ASA I-II) scheduled for minor urologic surgery under spinal anesthesia were recruited. Exclusion criteria included contraindication to spinal anesthesia, allergy to study drugs, or previous lumbosacral spinal surgery.

The patients were randomly allocated to one of two groups using sealed envelopes. All patients received 2.4 mL of hyperbaric bupivacaine 0.5% containing 7% dextrose (Marcain spinal 0.5% hyperbaric, AstraZeneca, Japan). Patients in Group 1 underwent subarachnoid block with a solution and a syringe that had been stored in a stove (Miwa, Electric Medical Co., Tokyo, Japan) warmed to 37°C ± 0.2°C for more than 24 h. Patients in Group 2 underwent subarachnoid block using a solution and a syringe that had been stored at 25°C ± 0.5°C (room temperature) for more than 24 h.

All patients received diazepam 0.2 mg/kg orally 1 h before anesthesia. Standard monitoring was placed (noninvasive arterial blood pressure, electrocardiogram, and pulse oximetry) on arrival in the operating room. Before the induction of spinal anesthesia, 10 mL/kg of lactated Ringer's solution were administered by rapid IV infusion followed by 4 mL · kg^–1 · h^–1 of the solution. Dural puncture was performed in the right lateral decubitus position at the L3-4 interspace using a paramedian approach and a 25-gauge Quincke needle. After free flow of cerebrospinal fluid was obtained for Group 1, the bupivacaine and syringe were retrieved from the stove. The study drug was drawn into the syringe within 20 s of retrieval, and in both groups, bupivacaine was injected with the patient in the right lateral decubitus position over approximately 15 s by an anesthesiologist who did not know the aim of the present study. The patient was placed supine immediately after spinal injection. Sensory blockade was assessed by loss of pinprick sensation (a 26-gauge needle) in the midclavicular line on both sides 5, 10, 20, 30, 40, and 60 min after the injection by a blinded investigator who was unaware of the injectate temperature. A 30% decrease in systolic blood pressure less than the baseline was treated with 4–12 mg IV of ephedrine, and a decrease in heart rate <45 bpm was treated with 0.5 mg IV of atropine.

Although we did not measure the actual temperature of the injectates, we assessed the change in temperature of 5 Amp of bupivacaine after removal from the stove in 10-s intervals for 50 s. The densities and viscosities of hyperbaric bupivacaine 0.5% (n = 3) at 25°C and 37°C were measured by using a pyknometer and a capillary tube viscometer, respectively (Smika Chemical Analysis Service, Oita, Japan). A capillary tube viscometer measured viscosity by timing down flow of a finite volume of liquid through a capillary tube.

Demographic data, the densities and viscosities, and the changes of bupivacaine temperature are presented as mean ± sd. Data on level of sensory block and time are presented as median (range). When there was a difference in the level of block between left and right, we used their mean as the achieved level. Data were analyzed by the unpaired t-test and the Mann-Whitney test where appropriate. Data on sex and adverse events were analyzed using Fisher's exact test. A P value of < 0.05 was considered to be statistically significant. Level of the cephalad extent of loss of pinprick sensation is presented as median (range) and was analyzed using analysis of variance for a two-factor experiment with repeated measures on time. The two factors were subject group (normal and warm) and time (6 time points). Main effects and interaction were assessed at the 0.05 levels of significance. Fisher's least significant difference procedure was used for multiple comparisons of means with Bonferroni adjustment for the number of comparisons. Data analysis was conducted using PROC MIXED in SAS®, Release 8.2 (SAS Institute Inc., Cary, NC; SAS/STAT® User's Guide, ver. 8; SAS Institute).

The size of the sample was based on the results of a pilot study of 5 patients in each group (mean [sd]: T2.8 (2.5) in Group 1 versus T6.0 (1.5) in Group 2) to show a significant difference in spread of anesthesia of 2 or 3 dermatomes with a sd of 2 dermatomes an alpha risk at 0.01 and a ß risk at 0.10. Sample size was 15 in each group.

	Results

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The densities of hyperbaric bupivacaine 0.5% at 25°C and 37°C were similar (1.028 ± 0 g/cm³ for both temperatures), whereas the viscosity at 25°C was more than that at 37°C (0.01116 ± 0.00003 g · cm^–1 · s^–1 versus 0.00843 ± 0.00002 g · cm^–1 · s^–1; P < 0.001).

The temperature of bupivacaine was 36.9°C ± 0.0°C at 20 s after retrieval from a stove. Thereafter, temperature gradually decreased to 36.6°C ± 0.2°C at 50 s after the retrieval.

Eighteen patients were included in each group. The two groups were comparable with regard to age, sex, height, and weight (Table 1). The cephalad extent of loss of pinprick sensation was always more in Group 1 (Fig. 1), and the maximal cephalad spread in Group 1 was significantly larger than that in Group 2 (T2 versus T5; P < 0.001) (Table 2). Both groups required 20 min to achieve maximal cephalad block of pinprick sensation. There was no significant difference in the frequency of hypotension or bradycardia between the groups (Table 2).

View larger version (9K): [in this window] [in a new window]   Figure 1. Development of the cephalad extent of loss of pinprick sensation during the study period in both groups. Values are presented as median. The bars represent upper and lower quartiles. •, Group 1 (37°C). , Group 2 (25°C). *, significantly different from Group 2 (P < 0.05).

	Discussion

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The hyperbaric bupivacaine containing 7% dextrose warmed to 37°C led to greater cephalad spread of block assessed by loss of pinprick sensation when injected into the subarachnoid space with the patients in the right lateral position. Warming reduced the viscosity but did not change the density of the solution.

The density of hyperbaric bupivacaine at 37°C is similar to that at 25°C (1.028 ± 0 g/cm³ for both temperatures), which is in agreement with manufacturer's information. Carbohydrates have a very high affinity to water (13) and inhibit motion of water molecules (14,15). This effect may explain the absence of density change in the temperature range tested. Because the densities of hyperbaric bupivacaine at 25°C and 37°C were similar, density was not a factor that led to the present results.

Viscosity of injectates affects the distribution of spinal anesthesia. The present study showed that warming, in contrast to the density, induced a decrease in the viscosity of bupivacaine 0.5% in dextrose. Okutomi et al. (16) showed that the more viscous the injectates, the higher the maximum level of spinal anesthesia, which is not in agreement with our results. This discrepancy might be explained by a possibility that in the present study, the change of thermal energy rather than viscosity might have greatly influenced the behavior of the injectate into the subarachnoid space.

Based on thermodynamics, temperature serves to gauge the intensity of the thermal energy that is an actual energy of motion (kinetic energy) of the individually mobile particulate constituents of matter (17). That is, increased temperature indicates increased molecular kinetic energy. In addition, the number of individually mobile particles increases with increased temperature (17). Thus, we postulate that an increase in motion of the anesthetic solution by warming might have extended the spread of spinal anesthesia in the present study.

Local anesthetic uptake by mammalian nerve increases with increased temperature, and this may be explained by a decrease in pKa of local anesthetic solution produced by increased temperature, which would increase the fraction of unionized drug (18).

One of the limitations of our study is that the injectate temperature was not directly measured, but we showed only a small decrease in temperature over 50 seconds in test ampoules after removal from the heater. Another limitation is that we did not completely characterize the spinal block by measuring regression of sensory anesthesia.

In conclusion, we showed a consistent but modest increase in the cephalad level of spinal anesthesia by warming hyperbaric bupivacaine 0.5% from 25°C to 37°C. Viscosity was reduced in the warmed solution, but it is unclear if this or other factors led to the difference in spinal anesthetic level.

We thank Dr. Masashi Hojo of Department of Chemistry, Faculty of Science, Kochi University, for editorial support and Tatsuo Uchida of Office of Biostatistics, University of Texas Medical Branch for statistical suggestions.

	Footnotes

 
Accepted for publication July 11, 2005.

	References

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