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© Borgis - Anaesthesiology Intensive Therapy 1/2001
Krzysztof Duda, Marek Mizianty, Barbara Machowska, Agnieszka Kubisz
Effect of a heavy lidocaine admixture to 0.5% bupivacaine on the rate and spread of subarachnoid analgesia
Department of Intensive Care, Marie Curie-Sklodowska Memorial Institute - Oncology Centre;
Head: prof. K. Duda, Cracow, Poland
Summary
We have assessed the rate of development and spread of the subarachnoidal analgesia in eighty-one oncologic patients. Sheduled for lower body surgery. Patients were randomly allocated to three groups, according to the following preparations of hyperbaric analgesic solutions: A - 9 cc of 0.5% bupivacaine + 1 cc "heavy" lidocaine; B - 8.5 cc of 0.5% bupivacaine + 1.5 cc of "heavy" lidocaine; and C - 8 cc of 0.5% bupivacaine and 2 cc of "heavy" lidocaine. The rate of the block development depended of the amount of lidocaine added. Patients in the group A did not require any cardiotonic treatment. We conclude that 1% glucose concentration in the analgesic preparation is sufficiently hyperbaric to predit the rate of black development and spread of analgesia.
The major drawback of subarachnoid analgesia with a 0.5% solution of bupivacaine is its unpredictable spread and slow development of motor block [1, 2, 3, 4, 5]. At the beginning of the eighties this was attributed to hypotonicity of the solution in the physiological temperature range [4, 6, 7, 8]. So - called "heavy" solutions of bupivacaine warrant better control of the spread of block, although its onset is slow. The duration of analgesic and motor block is shortened, as compared to isobaric 0.5% bupivacaine solutions [9, 10, 11, 12]. Substitution of 1cc of isotonic 0.5% bupivacaine with 1cc of "heavy" lidocaine resulted in shortening of the onset time of analgesia. This also increased the extent of motor block [7, 13]. These observations raise the question whether the variable proportion of the "heavy" lidocaine to an isobaric 0.5% solution of bupivacaine change the onset of subarachnoid analgesia and the frequency of cardiodepressive episodes (hypotonia), as well as the predictability of the quality of analgesia.
MATERIAL AND METHODS
The study was performed in eighty one patients undergoing surgery for cancer involving lower extremities, inguinal region, perineum and hypogastrium. The informed consent for subarachnoid analgesia was obtained.
Preoperative medication consisted of diazepam 10 mg and promethazine 25 mg administered i.m. about 40 minutes before the subarachnoid puncture. The patient was positioned in lateral decubitus position and the local analgesic solution was injected intratecally in L3/L4 or L4/L5 intervertebral space using a spinal needle 22-25G.
Different proportions of 0.5% bupivacaine and "heavy" lidocaine were the basis to classifying the patients into 3 groups:
A) 26 patients - 9.0 cc 0.5% bupivacaine + 1.0 cc "heavy" lidocaine,
B) 26 patients - 8.5 cc 0.5% bupivacaine + 1.5 cc "heavy" lidocaine,
C) 29 patients - 8.0 cc 0.5% bupivacaine + 2.0 cc "heavy" lidocaine,
At a temperature of 37°C the specific gravity values of a 0.5% bupivacaine solution (in 0.8% solution of saline) and a 5% solution of "heavy" lidocaine are respectively of 0.99862 and 1.0265 g/cc. The calculated values of the specific gravity of analgesic solutions for groups A, B and C were: 1.0014, 1.0028 and 1.0042 g/cc. As the specific gravity of cerebrospinal fluid equals 1.003 ± 0.003 g/cc [6,8,14], all these analgesic solutions investigated in this study were hyperbaric.
Subarachnoid injection was started with the administration of 1/4 volume of analgesic solution calculated according to Bromage nomogramme (equivalent to analgesia spread in extradural space) [13, 15]. For example: a 77-year old woman, 160 cm. tall, in order to block lower 13 spinal segments (i.e. up to the umbilical line) requires: (13 x 0.82cc /4) = 2.7cc of analgesic solution. The rate of injection (in ambient temperature) was of 0.3cc/sec. Immediately after the injection the patient was placed in the supine position. The extent (level) of analgesia was assessed by the pinprick test (25G needle) during 30 minutes after injection.
Differences between the mean values of the results were statistically compared using Student's T-test. Time intervals to reach an analgesia level of Th12 and Th10 were analysed by a non-parametric Kruskall-Wallis test. The level of statistical significance equalled 0.05.
RESULTS
Anthropometric/demographic parameters did not differ significantly between the groups of patients studied (Table I).
Table I. Demographic parameters
GroupNo. of patientsMenWomenAge*Height*
(cm)
Weight* (kgs)
A26111551±14 (22-72)166±11 (151-190)69±15 (49-105)
B26111552±13 (30-78)165±9 (150-184)72±13 (39-94)
C29121752±15 (18-71)164±8(154-182)70±15 (49-110)
Statistical significancensnsnsnsns
* mean ± SD, range
ns = non significant

Assuming that the composition of the solutions were: A - 0.445% bupivacaine, 0.5% lidocaine and 0.75% glucose; B - 0.42% - 0.75% and 1.12%, as well as C - 0.395%, 1% and 1.5% respectively, the amount of administered bupivacaine diminished, and of lidocaine and glucose increased from group A to C patients (Table II).
Table II. Course of analgesia (values expressed as mean ± SD)
GroupPredicted spread 
of block (spinal 
segments)
Subarachnoid injectionSpread of block (spinal segments) in time
Volume 
(ml)
Bupivacaine
 (mg)
Lidocaine 
(mg)
Glucose 
(mg)
10 min.20 min.30 min.
A13.4±1.64.0±1.617.6±4.319.8±4.829.7±0.112.2±1.6b14.6±2.114.8±2.5a
B13.1±1.63.8±0.616±2.728.5±4.942.8±0.112.5±1.814.6±2.8a15.5±3.1c
C13.4±1.33.8±0.514.8±1.937.6±5.156.4±0.113.4±2.315.0±2.5b15.7±2.5c
A-Bnsns0,050,010,01nsnsns
A-Cnsns0,010,010,01nsnsns
B-Cnsnsns0,010,01nsnsns
ns - non significant
a b c - difference of the of block level as compared with that anticipated p<0.05; p<0.01 and p<0.001, respectively

There were no differences between groups in terms of the planned extent of block, volume of analgesic solution administered intrathecally, nor the extent of block after 10, 20 and 30 minutes from injection (Table III). Significant differences were noted, however, in the extent of blockade as compared with the anticipated (planned) level: 1) after 10 minutes from injection the extent of blockade in group A was of 1 segment lower than previewed; 2) after 20 minutes (group B and C) it was about 1.5 segment higher; and 3) after 30 minutes (all groups) it was higher from 1.5 to 2.5 spinal segments.
Time to reach maximal level of analgesia in all groups averaged 25 minutes, although Th10 and, specially, Th12 level were reached significantly faster in group C patients (Table III).
Table III. The development of block in time
GroupTime to reach maximum block (minutes)Time to reach the level of Th10/Th12 (minutes)Time to the beginning of surgery (minutes)
 Median valuex±SDRangex±SDx±SDx±SDRange
A30.025.0±5.815-304.8±2.210.5±3.715.0±6.06-30
B30.025.0±5.815-304.3±2.29.7±5.313.0±6.55-30
C25.024.0±5.710-30m2.9±1.7**n7.6±4.2*15.0±6.07-32
X ± SD: mean ± standard deviation
* p<0.01
** p<0.05

Mean time from injection of analgesic solution to the beginning of the surgical procedure equalled 15 minutes. In each group, however, there were cases in which the procedure started earlier (5-7 minutes). The maximal extent of block and its range were similar in all groups. The need for use of ephedrine and/or atropine occurred only in patients from groups B and C (Table IV).
Table IV. The extent of block and the need to use ephedrine and/or atropine
GroupMedian valueMaximal extent of blockNeed for:
x±SD(Range)ephedrineatropine
A98.8±2.512-300
B97.5±3.111-23/265/26
C87.7±2.510-32/296/29
X ± SD: mean ± standard deviation

DISCUSSION
Subarachnoid analgesia with "pure" bupivacaine solutions, introduced to clinical practice in the seventies, is characterised by slow onset of action and a low predicability of the extent of blockade [1, 2, 3, 4, 5]. The cause of this phenomenon may be the fact that 0.5% and 0.75% bupivacaine (both in water or physiological saline as a solvent) behave, at body temperature, as hypobaric solutions, and not (as anticipated from physical calculations) as isobaric ones [6, 8]. On the other hand, subarchnoid analgesia with "heavy" solution of lidocaine may lead to several untoward reactions, including: 1) rapid (several minutes) onset of block disabling, in some patients, the appropriate mechanisms of haemodynamic adaptation. This leads to nausea, hypotonia and bradycardia (including cardiac arrest) [16]; 2) short (about 90 minutes) time of duration of surgical analgesia; 3) local toxicity, attributed to the irritating effect of a high lidocaine concentration on the cauda equina [14, 17].
The observations mentioned above led to the studies, in which "isobaric" bupivacaine solutions were mixed with hyperbaric glucose or with other shorter-acting hyperbaric drugs (manufactured with glucose admixture), such as lidocaine or "heavy" mepivacaine [18, 19].
Commercially available, "heavy" analgesic solutions, contain glucose in concentrations ranging from 5 to 10%, i.e. about hundredfold higher than in the cerebrospinal fluid (CSF - 2.5-5 mmol/L). There is increasing interest in analgesic solutions containing less glucose and having viscosity closer to CSF. From the studies already published one can conclude that 1.25% and even 0.88% concentrations of glucose in an analgesic solution make it hyperbaric. On the contrary, the admixture of 0.33% glucose makes the extent of block unpredictable [18, 20].
Having all this in mind, the authors aimed at answering 2 questions:1) is the admixture of "heavy" lidocaine to 0.5% bupivacaine (increasing the glucose concentration from 0.75 to 1.5%) sufficient to make the extent of block relatively predictable; and 2) does the acceleration of the onset of block by an admixture of 2-4 ml "heavy" lidocaine do not provoke untoward cardiovascular effects (hypotonia, bradycardia).
It was found that all solutions behaved as "heavy" ones, causing blocks of comparable extent after 25-30 minutes from injection [1, 2, 3, 7, 18, 20]. The differences were noted in the rate of block development. The more "heavy" lidocaine was added to analgesic solution, the more rapidly the block developed. For solution C, it had already reached the desired level in about 10 minutes from injection (table III). The onset of block in group A patients was slower - after 10 minutes from injection only about 90% of the desired level had been obtained.
In all studied groups, the extent of block was higher than anticipated: from 10% in group A to 18% in groups B and C. The slower onset of a block in group A made adequate haemodynamic adaptation of the cardiovascular system to the developing sympathetic blockade possible. Hypotension and/or bradycardia observed in 16 patients from groups B and C required pharmacological cardiotonic treatment.
There exists an optimal proportion of "heavy" lidocaine to 0.5% bupivacaine, anabling moderate acceleration of the onset of analgesia without causing undesirable cardiovascular depression. It seems also that there is no need to use a high glucose load (5-10%) [11, 14, 17], and that the future may bring analgesic solutions of specific gravity and viscosity as close as possible to the CSF characteristics [4, 7, 12, 20].
The analyse of the composition of analgesic solutions used in this study, justify the conclusion that admixture of "heavy" lidocaine to 0.5% bupivacaine, resulting in a glucose concentration of about 1% may meet the following requirements:
a) moderate speed of blocking the dermatomes of the lower body enables adequate adaptation to the developing sympathetic block;
b) the beginning of the surgical procedure within 5-15 minutes from analgesic mixture injection;
c) in body temperature behaves as hyperbaric solution, which makes the extent of blockade more predictable, than with so called isobaric solutions.
Taking into account the multitude of factors influencing the extent of subarachnoid analgesia [5, 6, 8, 14] the observations presented in this paper need further evaluation. Only randomised clinical studies of low-glucose load analgesic solutions in different groups of patients and different extent of block required may prove their clinical usefulness.
CONCLUSIONS
1. Glucose concentration of about 1% gives an analgesic solution hyperbaric characteristics.
2. There is an optimal concentration of lidocaine and glucose in 0.5% bupivacaine solution, which moderately accelerates and influences the extent of subarachnoid block.

Originally published in Anestezjologia Intensywna Terapia 31; (1), 7-10, 1999.
Piśmiennictwo
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Adres do korespondencji:
Garncarska Str. 11; 31-115 KRAKÓW, Poland

Anaesthesiology Intensive Therapy 1/2001