Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Abstracts

JUSTIFICATIVA E OBJETIVOS: A clonidina é um composto imidazolínico agonista parcial dos receptores a2-adrenérgicos com propriedades ansiolíticas e hipnóticas. Administrada no espaço subaracnóideo produz efeitos seletivos na modulação da dor, podendo aumentar a duração da anestesia cirúrgica e do bloqueio motor. O objetivo do estudo foi avaliar o efeito da clonidina associada à bupivacaína a 0,5% hiperbárica na anestesia subaracnóidea. MÉTODO: Foram estudados 30 pacientes de ambos os sexos, escalados para herniorrafia inguinal, estado físico ASA I ou II, com idades entre 16 e 57 anos, distribuídos aleatoriamente em três grupos. Após monitorização, os pacientes foram sedados com midazolam (2 mg), por via venosa, 10 minutos antes do procedimento anestésico, seguindo-se de punção subaracnóidea, L3-L4, paramediana, com agulha Quincke 25G, em decúbito lateral esquerdo. Após saída do LCR injetou-se 1 ml de uma das soluções propostas, de acordo com o grupo estudado juntamente com 15 mg de bupivacaína hiperbárica: Grupo I - 150 µg de clonidina, Grupo II - 75 µg de clonidina + 0,5 ml de água bidestilada e Grupo III - 1 ml de água bidestilada. Foram avaliados o nível do bloqueio com 5, 20 e 30 minutos, tempo para regressão de dois metâmeros, sedação pela escala de 0 a 3, bloqueio motor pela escala modificada de Bromage, dor pós-operatória e necessidade de analgésico. RESULTADOS: Houve uniformidade dos dados antropométricos nos grupos. O nível do bloqueio anestésico (moda) nos pacientes estudados foi uniforme nos grupos. A regressão da anestesia foi retardada no grupo I, assim como o relaxamento muscular, em relação aos outros grupos. Não houve diferença em relação à sedação e aos parâmetros hemodinâmicos entre os grupos. O grupo I apresentou analgesia prolongada em relação aos demais grupos, confirmado pela menor necessidade de analgésicos em função do tempo. CONCLUSÕES: A clonidina não alterou a dispersão cefálica e os efeitos hemodinâmicos do bloqueio subaracnóideo com bupivacaína a 0,5% hiperbárica. Porém, foi efetiva em melhor analgesia observada com quatro horas após o bloqueio, bem como prolongou o tempo de anestesia.

ANALGÉSICOS; ANESTÉSICOS, Local; TÉCNICAS ANESTÉSICAS, Regional

SCIENTIFIC ARTICLE

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia^*

Efecto de la clonidina asociada a la bupivacaína a 0,5% hiperbárica en la anestesia subaracnóidea

Neuber Martins Fonseca, M.D. ^I ; Clarissa Aires de Oliveira, M.D. ^II

^IProfessor Adjunto de Anestesiologia do Departamento de Clínica Cirúrgica e Responsável pelo CET-SBA da Disciplina de Anestesiologia da Faculdade de Medicina da Universidade Federal de Uberlândia, Membro da Comissão de Normas Técnicas da Sociedade Brasileira de Anestesiologia

^IIAnestesiologista do HC/FAEPU da FMUFU

Correspondence

SUMMARY

BACKGROUND AND OBJECTIVES: Clonidine is an imidazolynic compound which exhibits partial alpha₂-receptor agonist action, with anxiolytic and hypnotic properties. When spinally administered, it produces selective effects in pain modulation and may prolong surgical anesthesia and motor block. This study aimed at evaluating the effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia.

METHODS: Thirth ASA I or II patients off both genders, aged between 16 and 57 years and scheduled to undergo surgical inguinal hernia repair were randomly divided into three groups in this prospective double blind study. After monitoring, patients were sedated with 2 mg venous midazolam 10 minutes before surgery, followed by paramedian spinal puncture (L₃-L₄) in the left lateral position with a 25G Quincke needle. After CSF confirmation, 1 ml of one of the proposed solutions were injected with 15 mg hyperbaric bupivacaine: Group I - 150 µg clonidine; Group II - 75 µg clonidine + 0.5 ml bi-distilled water; and Group III - 1 ml bi-distilled water. The following parameters were evaluated: sensory block level at 5, 20 and 30 minutes, time for two metamers regression, sedation scores through a 0 to 3 scale, motor block by a modified Bromage's scale, postoperative pain and analgesics requirement.

RESULTS: Demographics and maximum sensory level (mode) were similar for all groups. Anesthesia regression and muscle relaxation were longer for Group I. There were no difference in sedation and hemodynamic parameters between groups. Group I had a prolonged analgesia as compared to other groups, what was confirmed by the less need for analgesics as a function of time.

CONCLUSIONS: Clonidine has not changed cephalad spread and hemodynamic effects of spinal anesthesia with 0.5% hyperbaric bupivacaine. However, it has promoted better analgesia during the four hours observed after blockade and a prolonged anesthesia.

Key Words: Analgesics: Clonidine; ANESTHETICS, Local: bupivacaine; ANESTHETIC TECHNIQUES, Regional: spinal block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La clonidina es un compuesto imidazolínico agonista parcial de los receptores a₂-adrenérgicos con propiedades ansiolíticas e hipnóticas. Administrada en el espacio subaracnóideo produce efectos selectivos en la modulación del dolor, pudiendo aumentar la duración de la anestesia quirúrgica y del bloqueo motor. El objetivo del estudio fue evaluar el efecto de la clonidina asociada a la bupivacaína 0,5% hiperbárica en la anestesia subaracnóidea.

MÉTODO: Fueron estudiados 30 pacientes de ambos sexos, escalados para herniorrafia inguinal, estado físico ASA I ó II, con edades entre 16 e 57 años, distribuidos aleatoriamente en tres grupos. Después de monitorización, los pacientes fueron sedados con midazolam (2 mg), por vía venosa, 10 minutos antes del procedimiento anestésico, seguido de punción subaracnóidea, L₃-L₄, paramediana, con aguja Quincke 25G, en decúbito lateral izquierdo. Después de la salida del LCR se inyectó 1 ml de una de las soluciones propuestas de acuerdo con el grupo estudiado juntamente con 15 mg de bupivacaína hiperbárica: Grupo I - 150 µg de clonidina, Grupo II - 75 µg de clonidina + 0,5 ml de agua bidestilada y Grupo III - 1 ml de agua bidestilada. Fueron evaluados el nivel del bloqueo con 5, 20 e 30 minutos, tiempo para regresión de dos metámeros, sedación por la escala de 0 a 3, bloqueo motor por la escala modificada de Bromage, dolor pós-operatorio y necesidad de analgésico.

RESULTADOS: Hubo uniformidad de los datos antropométricos en los grupos. El nivel del bloqueo anestésico (moda) en los pacientes estudiados fue uniforme en los grupos. La regresión de la anestesia fue retardada en el grupo I, así como el relajamiento muscular, en relación a los otros grupos. No hubo diferencia en relación a la sedación y a los parámetros hemodinámicos entre los grupos. El grupo I presentó analgesia prolongada en relación a los demás grupos, confirmado por la menor necesidad de analgésicos en función del tiempo.

CONCLUSIONES: La clonidina no alteró la dispersión cefálica y los efectos hemodinámicos del bloqueo subaracnóideo con bupivacaína a 0,5% hiperbárica; sin embargo, fue efectiva en una mejor analgesia observada con cuatro horas después del bloqueo, bien como prolongó el tiempo de anestesia.

INTRODUCTION

Clonidine is an imidazolynic compound with partial alpha₂-receptor agonist action, exhibiting anxiolytic and hypnotic properties¹. It was first introduced in the clinical practice as a nose decongestive and then as an anti-hypertensive drug. Its further use in anesthesia was dictated by its sedative, hypnotic and analgesic effects, both in preanesthetic medication and in general or spinal anesthesias^2-5.

Spinal clonidine produces intense and selective effects, with the activation of a₂ post-synaptic receptors of noradrenergic descending pathways and of cholinergic neurons. It plays an important role in pain modulation by inhibiting nervous conduction through Ad and C fibers and by activating gray matter a₂-adrenoreceptors in the dorsal spinal cord^1,3-7, thus prolonging intrathecal local anesthetic effect^8-11.

Previous studies have shown that clonidine seems to prolong surgical anesthesia and motor block, as well as to improve anesthetic blockade quality, showing also a sedative activity and promoting postoperative analgesia, specially when associated to opioids^3,11. Other studies, however, have not shown longer spinal anesthesia with clonidine association, what makes this subject still controversial^12,13.

This study aimed at evaluating the effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia.

METHODS

After Hospital de Clínicas da Faculdade de Medicina, Uberlandia';s, committee approval, 30 ASA I or II patients of both genders, aged between 16 and 57 years and scheduled to undergo surgical inguinal hernia repair were randomly allocated into three groups following their written informed consent. Exclusion criteria were refusal to the blockade or to take part of the study, neurological, cardiopulmonary, liver-kidney and psychiatric diseases, or drug abusers.

No patient was premedicated. In the operating room, perioperative monitoring consisted of cardioscope at D_II lead, sphygmomanometer for blood pressure control by Riva-Rocci's method with measurements at 5-minute intervals and pulse oximetry with continuous oxygen saturation readings. Hydration was performed with lactated Ringer's through a venous 18G catheter in an upper limb vein.

After 10 minutes of 2 mg venous midazolam sedation, spinal anesthesia was performed with the patient in the left lateral position, in L₃-L₄ interspace, with a 25G Quincke needle with no local anesthetic infiltration. After subarachnoid space identification, one of the proposed solutions was injected by the anesthesiologist,unaware of its nature, according to the studied group:

Group I - 150 µg clonidine

Group II - 75 µg clonidine + 0.5 ml bi-distilled water

Group III - 1 ml bi-distilled water

After the proposed solution administration in each group, prepared in 1 ml syringes, all patients received 15 mg hyperbaric bupivacaine and were immediately positioned in the supine position. All patients received the same volume in the subarachnoid space, that is, 1 ml of the proposed solution plus 3 ml of the anesthetic solution in separate syringes.

Block level was evaluated by skin pinprick at 5, 20 and 30 minutes after anesthetic injection, being registered the reached metamer at each point.

Time for 2 metamer regression was evaluated 60 minutes after puncture and at every 10 minutes after, until the exact regression time was defined.

Sedation was evaluated by Filos et al. modified numeric scale⁴ at 30, 60, 120 and 240 minutes. According to this scale, zero = patient awaken and oriented, 1 = drowsiness, 2 = patient sleeping but easily awakened, 3 = patient deeply asleep and hard to awake.

Motor block was evaluated by Bromage's¹⁴ modified scale (0 = complete block, 1 = feet movement, 2 = knees bending, 3 = absence of blockade) at 90, 105, 120, 135, 150 and 240 minutes after anesthesia performing.

Pain was evaluated by the following questions:

1. Is there pain or not?

2. If there is pain, how is it:

a) mild;

b) moderate;

c) severe.

After surgery patients were referred to PACU and were evaluated by the same anesthesiologist who performed the blockade and was blind to the studied group. Patients remained in PACU until total motor and sensory block recovery.

Analgesics were administered only after spontaneous request by the patient and postoperative pain intensity was also evaluated.

Friedman's^15,16 analysis of variance by posts was used to evaluate systolic and diastolic blood pressure results within groups.

Analysis of variance for non independent groups¹⁷ was used to evaluate heart rate and was complemented by Tukey's contrasts test when significant differences were detected. Kruskal-Wallis test^15,16 was applied to confirm the existence of significant differences between groups by comparing data at each moment measurements were made. Student's t test was applied to compare two samples with interval or reason scale data. Motor block, blockade level, pain and sedation scores do not need statistical analysis because data are presented in nominal scale. For all tests, 5% was established as the level for null hypothesis rejection and significant values are highlighted by a star (*).

RESULTS

Demographic data were homogeneous between groups, as shown in table I.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Anesthetic blockade levels (mode) were uniform between groups, as shown in table II.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Table III shows a significant difference in group I, with longer anesthesia regression time, as compared to other groups.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Table IV shows motor block uniformity between groups and anesthetic motor block regression, according to Bromage's modified scale¹⁴. Motor regression was shorter in group III. There was no significant difference in sedation between groups, as shown in table V.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Table VI shows that group I patients had prolonged analgesia as compared to other groups. This was also confirmed by the lesser need for analgesics as a function of time: 321 ± 76, 284 ± 102 and 206 ± 45 minutes, respectively for Groups I, II and III.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

The differences in mean systolic and diastolic blood pressure values between groups were not statistically significant, as shown in figures 1 and 2.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

Figure 3 compares heart rates between groups, with no significant difference.

Brazilian Journal of Anesthesiology, 2001; 51: 6: 483-492

Effects of combined clonidine and 0.5% hyperbaric bupivacaine on spinal anesthesia

Neuber Martins Fonseca; Clarissa Aires de Oliveira

DISCUSSION

Clonidine, an a₂-adrenergic agonist, has been extensively studied as an anesthetic adjuvant, which promotes sedation^2,18, reduces hemodynamic responses to laryngoscopy and tracheal intubation^2,19, improves perioperative hemodynamic stability^2,20 and decreases analgesics^2,21 and volatile anesthetics requirements^2,22. When spinally injected, it has no motor block properties and seems to decrease local anesthetics vascular absorption by reducing spinal blood flow, thus prolonging local anesthetics blockade, as confirmed by this study. This effect is probably due to a direct action of clonidine blocking Ad and C fibers stimuli conduction, increasing potassium conductance in isolated neurons and intensifying local anesthetics conduction block, as well as indirectly decreasing their absorption by a vasoconstrictor effect mediated by a₂ post-synaptic receptors^1,2.

Clonidine action in prolonging spinal anesthesia is not uniform and still controversial^{3-6,8,9,23,24}. Brunschwiler et al.²⁵ have shown an increase in surgical anesthesia time with the spinal administration of 0.15 mg clonidine associated to bupivacaine, fact confirmed by our study and by some authors^3,26-30, but not by others^31,32, especially when administered as oral premedication^6,12,13,31. It is possible that spinal clonidine promotes higher local anesthetics concentrations in the central nervous system, thus prolonging the sensory and motor blocks. This effect would possibly be related to a higher side-effect rate shown by some authors¹³, but not confirmed by this study or by other authors^3,6. As to analgesic and motor block onset, our results are in line with other studies^12,13,29,30, which obtained similar results with spinal clonidine.

Clonidine's hemodynamic effects, usually hypotension and bradycardia, result from the activation of a₂ pre-synaptic receptors of peripheral nervous terminations, as well as from its action on brain stem and spinal cord, decreasing sympathetic outflow^1,14,33,34. Peripheral activation of a₂ receptors, which inhibit norepinephrine's exocytosis, partially explains clonidine-induced hypotension and bradycardia^30-32. Central activation of a₂ receptors in the vasomotor center decreases sympathetic outflow and circulating catecholamines, which together with the exacerbation of parasympathetic activity, induces blood pressure decrease^35,36. Our study has not shown significant hemodynamic differences between groups, probably due to the doses used, what was different from other findings^30,32.

Clonidine's analgesic action is due to its ability to promote central sensitization produced by repeated stimulation of afferent C fibers, resulting in central release of P substance, A neurokinine, glutamate and aspartate which, once released, may act on AMPA, NMDA and metabotrophic receptors, preventing spinal cord central facilitation and synaptic plasticity phenomena^37,38. These effects were confirmed in this study by the lower pain level in patients receiving spinal clonidine, and also in agreement with another study²³.

In the conditions of our study, one may conclude that clonidine has not changed cephalad spread and hemodynamic effects of spinal anesthesia with hyperbaric bupivacaine; it was however effective in improving analgesia observed until the fourth hour after the blockade, as well as in prolonging anesthesia duration, being therefore useful as a coadjuvant of spinal blocks with hyperbaric bupivacaine.

REFERENCES

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*

Recebido do CET/SBA da Faculdade de Medicina da Universidade Federal de Uberlândia (FMUFU), Uberlândia, MG

Publication Dates

• Publication in this collection
  10 Nov 2010
• Date of issue
  Dec 2001

History

• Accepted
  15 May 2001
• Received
  12 Mar 2001