Spinal anesthesia with 2% plain lidocaine for short orthopedic surgery: study in 250 patients

Abstracts

JUSTIFICATIVA E OBJETIVOS: Um dos mais importantes fatores que afeta o nível da analgesia após administração subaracnóidea de anestésicos locais é sua densidade em relação à densidade do líquido cefalorraquidiano. O objetivo deste estudo foi avaliar o inicio, a duração e a dispersão cefálica da lidocaína a 2% na raquianestesia após injeção em decúbito lateral em pacientes ortopédicos de cirurgia de curta duração. MÉTODO: Participaram do estudo 250 pacientes com idades entre 15 e 78 anos, estado físico ASA I e II escalados para diversos tipos de cirurgias ortopédicas, submetidos à raquianestesia com dose fixa de 3 ml de lidocaína a 2% (60 mg). Foram avaliados os seguintes parâmetros: latência, bloqueio motor, duração dos efeitos, dispersão cefálica da analgesia e alterações cardiocirculatórias. RESULTADOS: O tempo médio para a instalação da analgesia foi de 1,47 ± 0,75 min. Não houve correlação entre a idade e o tempo de latência. Ocorreu incidência de falhas em 1,75% dos pacientes. Houve diferença significativa entre os grupos para atingir o bloqueio motor completo, sendo mais rápido nos grupos mais idosos. O bloqueio motor completo ocorreu em 93% dos pacientes. A duração do bloqueio sensitivo foi de 102,32 ± 15,45 minutos e do bloqueio motor de 106,48 ± 16,48 minutos. Hipotensão arterial ocorreu em 5,6% e bradicardia em 1,2%. Observou-se três casos de sintomas neurológicos transitórios (1,2%) todos submetidos à videoartroscopia. CONCLUSÕES: Três ml de lidocaína a 2% isobárica proporcionam uma grande variação na dispersão da analgesia, com uma grande estabilidade cardiocirculatória e baixa incidência de SNT. A lidocaína a 2% pura é uma nova opção para cirurgias com tempo cirúrgico em torno de uma hora, podendo ser útil quando se pretende usar a raquianestesia em cirurgia ambulatorial.

ANESTÉSICOS, Local; TÉCNICAS ANESTÉSICAS, Regional

SCIENTIFIC ARTICLE

Spinal anesthesia with 2% plain lidocaine for short orthopedic surgery. Study in 250 patients

Luiz Eduardo Imbelloni, TSA, M.D.

Anestesiologista da Clínica São Bernardo e Casa de Saúde Santa Maria. Rio de Janeiro

SUMMARY

BACKGROUND AND OBJECTIVES: One of the most important factors affecting the level of analgesia after intrathecal administration of local anesthetics is their density relative to CSF density. This study evaluated the onset time, duration and cephalad spread of spinal anesthesia with 2% lidocaine in patients submitted to short orthopedic surgeries.

METHODS: 250 patients aged 15 to 78 years, physical status ASA I and II scheduled for different orthopedic surgeries were submitted to spinal anesthesia, in the lateral position, with 60 mg (3 ml) of plain 2% lidocaine. The following parameters were monitored: onset time for analgesia, degree of motor block, duration of effects, cephalad spread of analgesia and cardiovascular changes.

RESULTS: The mean analgesia onset time was 1.47 ± 0.75 min. No correlation between age and analgesia onset time was detected but the latency time until total motor block was shorter in the older patients. Total motor block was observed in 93% of patients. Blockade failed in 1.75% of patients. Sensory block duration was of 102.32 ± 15.45 min and motor block duration was of 106.48 ± 16.48 min. Hypotension and bradycardia were observed, respectively, in 5.6% and 1.2% of the patients. Transient neurological symptoms were observed in three patients (1.2%) submitted to video arthroscopy.

CONCLUSIONS: Isobaric lidocaine, in a fixed dose of 60 mg produced effective spinal anesthesia, with good cardio circulatory stability, low TNS incidence but a wide variation in the upper level of sensory block. Plain 2% isobaric lidocaine seems to be an option for spinal anesthesia for surgeries lasting up to one hour especially for ambulatory patients.

Key Words: ANESTHETICS, Local: lidocaine; ANESTHETIC TECHNIQUES, Regional: spinal block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Un de los más importantes factores que afecta el nivel de la analgesia después de administración subaracnóidea de anestésicos locales es su densidad en relación a la densidad del líquido cefalorraquidiano. El objetivo de este estudio fue evaluar el inicio, la duración y la dispersión cefálica de la lidocaína a 2% en la raquianestesia después de inyección en decúbito lateral en pacientes ortopédicos de cirugía de corta duración.

MÉTODO: Participaron del estudio 250 pacientes con edad entre 15 y 78 anos, estado físico ASA I y II escalados para diversos tipos de cirugías ortopédicas, sometidos a raquianestesia con dosis fijas de 3 ml de lidocaína a 2% (60 mg). Fueron evaluados los siguientes parámetros: latencia, bloqueo motor, duración de los efectos, dispersión cefálica de la analgesia y alteraciones cardiocirculatorias.

RESULTADOS: El tiempo medio para la instalación de la analgesia fue de 1,47 ± 0,75 min. No hubo correlación entre la edad y el tiempo de latencia. Ocurrió incidencia de fallas en 1,75% de los pacientes. Hubo diferencia significativa entre los grupos para llegar al bloqueo motor completo, siendo máis rápido en los grupos de más edad. El bloqueo motor completo ocurrió en 93% de los pacientes. La duración del bloqueo sensitivo fue de 102,32 ± 15,45 minutos y del bloqueo motor de 106,48 ± 16,48 minutos. Hipotensión arterial ocurrió en 5,6% y bradicardia en 1,2%. Fueron observados tres casos de síntomas neurológicos transitorios (1,2%) todos sometidos a videoartroscopia.

CONCLUSIONES: Tres ml de lidocaína a 2% isobárica proporcionan una gran variación en la dispersión de la analgesia, con una grande estabilidad cardiocirculatoria y baja incidencia de SNT. La lidocaína a 2% pura es una nueva opción para cirugías con tiempo cirúgico de más o menos una hora, pudiendo ser útil cuando se pretende usar la raquianestesia en cirugía ambulatorial.

INTRODUCTION

In Brazil, the anesthetic of choice for short duration spinal anesthesia is 5% hyperbaric lidocaine, which is being used for more than 50 years for short procedures due to its fast sensory and motor block onset and recovery. Since the pioneer work of August Bier in 1898 that spinal blockade safety is being discussed. A case of cauda equina syndrome was reported after inadvertent spinal injection of high 2% lidocaine dose following attempt to induce epidural anesthesia ¹. The interest in studying the effect of low lidocaine concentrations has increased after reports of transient neurological symptoms (TNS) ^2-4 following spinal anesthesia with hyperbaric lidocaine. Transient neurological symptoms observed after spinal blockade are not followed by severe motor or sphincter changes and have a fast recovery to normality. Plain 2% lidocaine has a density similar to CSF ^5-8 and could be an alternative for short duration spinal anesthesia ^8-11.

Age, height and weight, interfere with local anesthetic spread in the intrathecal space. Isobaric bupivacaine has shown variable spread in different age groups ^12,13. A correlation between sensory block level and age was observed in patients aging from 15 to 92 years treated with 3 ml ¹⁴, and in patients aging from 33 to 97 years ¹⁵ treated with 4 ml of 0.5% isobaric bupivacaine. There are no reports in the literature about the cephalad spread of analgesia with 2% isobaric lidocaine as a function of patients’ age.

This study aimed at evaluating the characteristics of spinal block with 60 mg (3 ml) of 2% lidocaine in patients submitted to short orthopedic surgeries.

METHODS

After the Hospital’s Publication Board approval, 250 patients scheduled for lower limb orthopedic surgeries under spinal anesthesia with plain 2% lidocaine, from January 1998 to December 2000, participated in this study. Exclusion criteria were coagulation abnormalities, age below than 15 and above 80 years, weight below 40 and above 110 kg, height below 140 and above 190 cm and previous neurological diseases. The surgeries were knee video arthroscopy, correction of tibia fracture associated or not to fibula fracture and/or ankle ligament injury and removal of synthesis material in surgeries below the knee. Tourniquet was applied in all patients. All patients were previously informed about the procedure and gave their informed consent. Patients were distributed in subgroups according to age. Group 1: 15 to 20 years; Group 2: 21 to 30 years; Group 3: 31 to 40 years; Group 4: 41 to 50 years; Group 5: 51 to 60 years; Group 6: 61 to 70 years; Group 7: 71 to 80 years.

The monitoring of blood pressure, heart rate, oxygen saturation, ECG in CM5 and a peripheral venous access were started before anesthesia. Patients were premedicated with intravenous midazolam (1.5 to 4.5 mg) and meperidine (20 to 40 mg). With the patient in the lateral position, and using a paramedian approach, lumbar puncture was performed in L₂-L₃ or L₃-L₄ interspace using disposable 27G or 29G Quincke needles without introducer. Once CSF was obtained, 60 mg of plain 2% lidocaine were injected without barbotage at 0.2 ml.s^-1 and patients were immediately placed in the supine position. In case of blockade failure, a new puncture was performed with the same needle size and 0.5% isobaric bupivacaine was injected.

The level of analgesia, defined as loss of pinprick sensation, was bilaterally tested initially at 1-minute intervals and, after detecting its onset time, at 5-minute intervals up to 20 minutes and at 15 minute intervals until complete blockade recovery. The degree of motor block of the lower extremities was evaluated through Bromage’s modified scale within the same intervals. Blockade onset time was defined as the time spent until loss of sensitivity in the region corresponding to the puncture’s metamer. Analgesia duration was determined by the spent until return of sensitivity in the dermatome corresponding to the puncture. Motor block duration was defined as the time spent until total recovery of muscular activity in lower limbs.

All patients were evaluated in the first postoperative day and were followed up by telephone after hospital discharge. Data were collected according to the protocol reported by Hampl et al. ¹⁶. Transient neurological symptoms (TNS) were defined as back, buttocks or legs pain or dysesthesia irradiating to lower extremities after spinal anesthesia recovery and resolving within 72 hours. Post-dural puncture headache was characterized by occipital or frontal pain that worsened in the standing or sitting position and that improved with decubitus.

Hypotension, defined as a systolic blood pressure decrease below 30% of baseline values, was primarily treated with volume replacement and, in case of no response, with successive doses of intravenous 2 mg ethylephrine. Bradycardia was defined as a decrease in heart rate below 50 bpm and was treated with 0.5 mg atropine. All patients received oxygen (1 to 2 L.min^-1) through a nasal catheter. Sedation during surgery was obtained with midazolam and meperidine in fractionated doses.

Chi-square, Kruskal-Wallis, ANOVA and Bonferroni non-parametric tests were used, when indicated, for statistical analysis of the studied variables. Linear correlation coefficient (r) was used to evaluate the correlation among age, onset time and total motor block, and Brieger’s F test was used for significance. Results are shown as the mean ± standard deviation. Significance level was determined as 5% (p < 0.05).

RESULTS

The study involved 250 patients submitted to spinal anesthesia with 27G (176 patients) or 29G (74 patients) Quincke needles. Surgeries were: knee video arthroscopy (n = 118), correction of tibia fracture associated or not to fibula fracture (n = 39), ankle fracture and/or ligament injury (n = 72) and synthesis material removal in surgeries below the knee (n = 21). The author performed all spinal blocks. Demographic distribution is shown in table I.

All patients had complete anesthesia recovery. Total blockade failure was observed in 4 patients (1.75%) without correlation with age, and a new block was performed with 0.5% isobaric bupivacaine (Table II). Tourniquet was applied in the remaining 246 patients which 242 did not refer any pain and only 4 patients (1.6%) needed general anesthesia complementation (Table II). The mean sensory block duration was of 1.42 h and the mean motor block duration was of 1.46 h (Table II).

Mean onset time for analgesia in the metamer corresponding to the puncture site was 1.47 ± 0.75 minutes. Onset was faster in the oldest group, although no correlation between onset time and patients’ age was detected (Table III).

The time needed for reaching different degrees of motor block is shown in table III. There were no significant differences among groups in the time to reach levels 1 and 2, although a significant difference was observed among groups for reaching total motor block that was faster in the older groups. Total lower limb motor block was obtained in 93% of patients without difference among groups. A correlation between total motor block level and increasing age was observed.

Cephalad spread reached its highest level at 20 minutes in all patients. The level of cephalad spread and analgesia recovery are shown in figure 1.

Upper sensory block level varied among groups (Table IV). The mode varied from T₈ to T₁₁ with a predominance of T₈ in Groups 1, 3 and 7.

Major complications (Table V) were hypotension (5.6% of patients) and bradycardia (1.2% of patients). Post dural puncture headache was seen in two patients punctured with 27G needles, but was mild and lasted only for two days. Postoperative evaluation of TNS during three days has shown an incidence of 1.2%. Since these patients were all submitted to knee video arthroscopy, the incidence related to the type of surgery was 2.5%.

DISCUSSION

Our results have shown that, in patients aged 15 to 78 years, 60 mg (3 ml) of 2% plain lidocaine provided an effective fast onset and short duration spinal anesthesia, with a low incidence of failures, tourniquet perception and transient neurological symptoms thus being indicated for orthopedic surgeries lasting less than 90 minutes.

All patients received the same lidocaine dose (60 mg in 3 ml) regardless of height, since there is no consensus about the influence of height in isobaric solution spread in the CSF and because it was previously shown that this volume of anesthetic has a better performance in efficacy and hemodynamic changes than volumes of 2 or 4 ml ¹⁰.

The level of analgesia after intrathecal injection of local anesthetics depends on several factors and one of the most important is the baricity of the solution. Density is defined as the weight in grams divided by the solution volume in ml (g/ml) at a known temperature, while specific weight is the relation between the density of a certain solution and the density of water. Baricity is the relation between the densities of a solution at a known temperature divided by the CSF density at the same temperature. Because local anesthetics solution reaches CSF temperature very rapidly, densities should be measured at 37 ºC ⁵. Specific weight and density of 2% lidocaine used in this study, measured in a previous trial ⁸ , were virtually the same obtained by other authors ^5,7. The baricity of 0.9985 means that 2% lidocaine used in this study is, in fact, slightly hypobaric ⁸.

All patients were blocked lying in the left lateral decubitus and no interference in analgesia spread, cervical blockade or lower limb dumbness was observed, as it is the case when anesthesia is induced in the sitting position ⁸.

It is known that elderly patients need lower doses of most substances. This study did not show a trend for higher spread of spinal analgesia with 2% isobaric lidocaine in the oldest group. The number of metamers blocked was not correlated to age. Similarly to isobaric bupivacaine, where there is no consensus as to the correlation between age and cephalad spread of analgesia, 2% isobaric lidocaine has shown a wide spread variability.

Failure of spinal anesthesia has been observed with bupivacaine ^15,17, lidocaine ^9,17 and tetracaine ¹⁸. Failures in this study were characterized by lack of blockade and were observed in just 4 patients, or 1.6%. Because the appearance of transient neurological symptoms is more correlated to lidocaine, we decided for using 0.5% isobaric bupiva- caine for the new blockade without any additional problem. When tourniquet was used (246 patients), only 4 patients (1.6%) referred pain that was resolved by general anesthesia.

With 75 mg of 5% hyperbaric lidocaine, the upper analgesia level remained between T₁ and T₅ in 90% of patients ¹⁹. Equipotent doses of 5% hyperbaric lidocaine and 2% isobaric lidocaine induced the same sensory block level ²⁰. With 2% plain lidocaine, the level of analgesia remained below T₇ from 70% ²¹ to 88% of patients ⁸. In this study using a fixed dose of 60 mg (3 ml) of 2% lidocaine, analgesia level remained below T₇ in 80% of patients.

Hypotension during spinal anesthesia has been correlated to sympathetic block level, hydration and age. Few hypotension episodes during the beginning of spinal anesthesia and good cardiovascular stability during return to the supine position in the operating table were reported previously with lidocaine ^11,22. In this study 60 mg of 2% isobaric lidocaine, showed a hypotension incidence of 5.6%, similar to other studies ⁸, and slightly below the values of 8% ¹⁰ and 11% ²³ of other studies.

Studying different volumes of 2% lidocaine ¹⁰ the authors have found previously with 3 ml an analgesia duration of approximately 99 minutes and of approximately 113 minutes with 4 ml of solution. In this study the duration was virtually the same (102 minutes), but shorter than 176 minutes reported by a different study ²¹.

Lower extremities motor block is dose-dependent ^10,24 and total motor block is more often obtained with plain local anesthetics than when associated to glucose. Mean onset time for complete motor block seen in this study (6.6 minutes) was similar to trials with 2% plain lidocaine ^7,9 or 5% lidocaine plus glucose ¹⁹. In our study not all patients had total motor block and age did not influence its incidence.

Results of a broad multicentric study suggest that the lithotomy position and early ambulation in outpatient surgery are predisposing factors for transient neurological symptoms ²⁵. The lithotomy position may increase vulnerability of nervous fibers exposed to 5% lidocaine due to the distension of lumbar-sacral roots. Patients’ position may be an important factor contributing to TNS as suggested by its higher incidence in patients submitted to knee arthroscopy and inguinal herniorhaphy ²⁶. Data of the multicentric study ²⁵ indicated that the incidence of post-lidocaine TNS was 3.1% in patients submitted to any surgery different from lithotomy and 24.3% in outpatient surgeries in the lithotomy position. The risk for TNS was not eliminated by decreasing lidocaine concentration from 5% to 2% and was observed even with a concentration of 0.5% ^27,28. In our study, 2% plain lidocaine was followed by a TNS incidence of just 1.2% (3 patients), showing that the type of surgery influences its incidence since all patients developing the symptoms were submitted to knee video- arthroscopy. The prevalence of TNS in videoarthroscopy was 2.5%. In a recent study using the same concentration of isobaric lidocaine the incidence of TNS was 2.5% ²⁹. In a study comparing 22G and 25G Quincke, 24G Sprotte and 25G Whitacre needles, the correlation between needle design and TNS was not evaluated ¹⁶, but in our study using 27G and 29G Quincke needles the incidence was significantly lower.

Several clinical and anatomic studies have shown the importance of inserting the bevel of Quincke needles in parallel to the dural fibers to prevent post-dural puncture headache. In our study, all insertions were parallel to the fibers and the prevalence of headache was 0.8%, observed only in two cases with 27G needles. In our study, the 1.7% incidence of headache with 27G Quincke needles was twice the incidence of that observed in a study with 5050 patients ³⁰ but, on the other hand, with the 29G Quincke needle we did not observe any case of headache, as opposed to the above mentioned study ³⁰.

In conclusion, spinal anesthesia with 60 mg of 2% isobaric lidocaine, showed a significant variation in analgesia spread but good cardiocirculatory stability. TNS incidence is very low, not exceeding 2%. Total motor block was faster in the oldest group. Plain 2% lidocaine seems to be a new option for spinal anesthesia for surgeries lasting approximately one hour, especially in outpatient surgeries.

ACKNOWLEDGEMENT

2% lidocaine was kindly prepared by Cristália Produtos Químicos Ltda.

REFERENCES

• 01. Drasner K, Rigler ML, Sessler DI et al - Cauda equina syndrome following intend epidural anesthesia. Anesthesiology, 1992;77:582-585.
• 02. Schneider M, Ettlin T, Kaufmann M et al - Transient neurologic toxicity after hyperbaric subarachnoid anesthesia with 5% lidocaine. Anesth Analg, 1993;76:1154-1157.
• 03. Salmela L, Aromaa U, Cozanitis DA  - Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine. Anaesthesia, 1996;51:391-393.
• 04. Snyder R, Hui G, Flugstad P et al - More cases of possible neurologic toxicity associated with single subarachnoid injections of 5% hyperbaric lidocaine. Anesth Analg, 1994;78:411.
• 05. Davis H - Specific gravity and density. Anesthesiology, 1976;44:270-271.
• 06. Rosemberg H, Goldberger N - Density of local anesthetics: clinical implications. Reg Anesth, 1978;3:4-5.
• 07. Horlocker TT, Wedel DJ - Density, specific gravity, and baricity of spinal anesthetic solutions at body temperature. Anesth Analg, 1993;76:1015-1018.
• 08. Imbelloni LE, Carneiro ANG - Efeito da postura nas características do bloqueio subaracnóideo com lidocaína 2% pura. Rev Bras Anestesiol, 1998;48:1-6.
• 09. Lawrence VS, Rich CR, Magistsky L et al - Spinal anesthesia with isobaric lidocaine 2% and the effect of phenylephrine. Reg Anesth, 1984;9:17-21.
• 10. Imbelloni LE, Carneiro ANG, Sobral MGC - Anestesia subaracnóidea isobárica com lidocaína 2%. Efeitos de diferentes volumes. Rev Bras Anestesiol, 1992;42:131-135.
• 11. Johnson A, Taylor S - Spinal anaesthesia with 2% plain xylocaine in the elderly. Anaesth Intensive Care, 1990;18:153-155.
• 12.Sheskey MC, Rocco AG, Bizzarri-Schmid M et al - A dose-response study of bupivacaine for spinal anesthesia. Anesth Analg, 1983;62:931-935.
• 13. Imbelloni LE, Sobral MGC - Influencia da idade na anestesia subaracnóidea com bupivacaína 0,5% isobárica. Rev Bras Anestesiol, 1991;41:167-171.
• 14. Pitkanen M, Haapaniemi L, Tuominen M et al - Influence of age on spinal anesthesia with isobaric 0.5% bupivacaine. Br J Anaesth, 1984;56:279-284.
• 15. Cameron AE, Arnold RW, Ghoris MW et al - Spinal analgesia using bupivacaine 0.5% plain. Variation in the extent of the block with patient age. Anaesthesia, 1981;36:318-322.
• 16. Hampl KF, Schneider M, Ummenhofer W et al - Transient neurologic symptoms after spinal anesthesia. Anesth Analg, 1995;81:1148-1153.
• 17. Imbelloni LE, Sobral MGC, Carneiro ANG - Incidencia e causas de falhas em anestesia subaracnóidea em Hospital Particular: estudo prospectivo. Rev Bras Anestesiol, 1995;45:159-164.
• 18. Moore DC - Spinal anesthesia: bupivacaine compared with tetracaine. Anesth Analg, 1980;59:743-750.
• 19. Ewart MC, Rubin AP - Subarachnoid block with hyperbaric lignocaine. Anaesthesia, 1987;42:1183-1187.
• 20. Toft P, Bruun-Morgensen C, Kristensen J et al - A comparison of glucose-free 2% lidocaine and hyperbaric 5% lidocaine for spinal anaesthesia. Acta Anaesthesiol Scand, 1990;34:109-113.
• 21. McKeown DW, Stewart K, Littlewood DG et al - Spinal anesthesia with plain solutions of lidocaine (2%) and bupivacaine (0.5%). Reg Anesth, 1986;11:68-71.
• 22. Berry FR - 2% lignocaine for anaesthesia. Anaesth Intensive Care, 1990;18:581.
• 23.  Kristensen J, Helbo-Hansen HS, Toft P et al - Spinal anaesthesia with glucose-free 2% lignocaine. Effect of different volumes. Acta Anaesthesiol Scand, 1989;33:53-57.
• 24. Kalso E, Tuominen M, Rosenberg PH - Effect of posture and some CSF characteristics on spinal anaesthesia with isobaric 0.5% bupivacaine. Br J Anaesth, 1982;54:1179-1184.
• 25. Freedman JM, De-Kun Li, Drasner K et al - Transient neurologic symptoms after spinal anesthesia: an epidemiologic study of 1,863 patients. Anesthesiology, 1998;89:633-641.
• 26. Pollock JE, Neal JM, Stephenson CA et al - Prospective study of the incidence of transient radicular irritation in patients undergoing spinal anesthesia. Anesthesiology, 1996;84:1361-1367.
• 27. Hampl KF, Schneider MC, Pargger JM et al - A similar incidence of transient neurologic symptoms after spinal anesthesia with 2% and 5% lidocaine. Anesth Analg, 1996;83:1051-1054.
• 28. Pollock JE, Liu SS, Neal JM et al - Dilution of spinal lidocaine does not after the incidence of transient neurologic symptoms. Anesthesiology, 1999;90:445-450.
• 29. Salazar F, Bogdanovich A, Adalia R et al - Transient neurologic symptoms after spinal anaesthesia using isobaric 2% mepivacaine and isobaric 2% lidocaine. Acta Anaesthesiol Scand, 2001;45:240-245.
• 30. Imbelloni LE, Sobral MGC, Carneiro ANG - Cefaléia pós-raquianestesia e o desenho das agulhas. Experiência com 5050 casos. Rev Bras Anestesiol, 2001;1:43-52.

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Raquianestesia con lidocaína a 2% pura en cirugías ortopédicas de corta duración. Estudio en 250 pacientes

Correspondence

Publication Dates

• Publication in this collection
  14 Jan 2011
• Date of issue
  Feb 2002

History

• Accepted
  18 July 2001
• Received
  27 Apr 2001