Effects of intramuscular and perineural clonidine on sciatic nerve block with 0.5% ropivacaine

Abstracts

JUSTIFICATIVA E OBJETIVOS: Foram estudados os efeitos da clonidina sobre a latência, a qualidade da anestesia e a duração da analgesia do bloqueio do nervo isquiático com ropivacaína a 0,5%. MÉTODO: Quarenta pacientes adultos foram submetidos a cirurgias sobre o pé e/ou a face lateral do tornozelo sob bloqueios combinados de nervos femoral e isquiático, por via anterior, em que foram alocados, segundo números aleatórios em grupo 1: 25 mL de ropivacaína a 0,5% e placebo perineural; grupo 2: 2 µg.kg-1 de clonidina por via muscular e 25 mL de ropivacaína a 0,5% perineural; e grupo 3: 2 µg.kg-1 de clonidina e 25 mL de ropivacaína a 0,5% perineural, injetados após obtidas respostas motoras com correntes de 0,2 e 0,5 mA. A sensibilidade e a motricidade foram avaliadas por 30 minutos após o bloqueio. Um escore de efetividade total do bloqueio foi atribuído. A qualidade da anestesia cirúrgica foi classificada com sucesso ou falha, segundo a necessidade de suplementação sistêmica. A duração foi o tempo desde a realização do bloqueio até a primeira solicitação de analgésico. RESULTADOS: As latências medianas foram 5, 12,5 e 17,5 minutos nos grupos 1 a 3, respectivamente (p = 0,11). As taxas de sucesso foram de 100%, 93% e 75%, respectivamente (p = 0,12). A duração da analgesia pós-operatória foi de 14,5, 13,5, e 13,75 horas, respectivamente (p = 0,15). CONCLUSÕES: A clonidina por via muscular ou perineural não influenciou a latência, a qualidade de anestesia ou a duração da analgesia do bloqueio do nervo isquiático com ropivacaína a 0,5%.

ANALGÉSICOS; ANESTÉSICOS; ANESTÉSICOS; TÉCNICAS ANESTÉSICAS; TÉCNICAS ANESTÉSICAS

SCIENTIFIC ARTICLE

Effects of intramuscular and perineural clonidine on sciatic nerve block with 0.5% ropivacaine ^*

Efectos de la clonidina por vía muscular y perineural en el bloqueo del nervio isquiático con ropivacaína a 0,5%

Pablo Escovedo Helayel, TSA, M.D.^I, Luciano Kroth, M.D.^II, Gustavo Luchi Boos, M.D.^III, Márcio Tagliari Jahns, M.D.^IV, Getúlio Rodrigues de Oliveira Filho, TSA, M.D.^V

^IInstrutor Co-Responsável, Chefe do Núcleo de Pesquisa em Anestesia Regional (NEPAR) do CET/SBA Integrado de Anestesiologia da SES/SC

^IICirurgião Ortopédico, Instrutor do Programa de Residência Médica em Ortopedia e Traumatologia, Hospital Governador Celso Ramos

^IIIME₃ do CET/SBA Integrado de Anestesiologia da SES/SC

^IVME₂ do CET/SBA Integrado de Anestesiologia da SES/SC

^VResponsável do CET/SBA Integrado de Anestesiologia da SES/SC

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: This study evaluated the effects of clonidine on anesthesia onset, quality and duration of analgesia of sciatic nerve block using 0.5% ropivacaine.

METHODS: Forty adult patients scheduled for foot or lateral aspect of the ankle procedures under combined anterior femoral/sciatic nerves block were randomly assigned to group 1, receiving 25 mL of 0.5% ropivacaine plus placebo perineurally, group 2, receiving intramuscular 2 µg.kg^-1 clonidine and perineural 25 mL of 0.5% ropivacaine and group 3, receiving perineural 2 µg.kg^-1 clonidine and 25 mL of 0.5% ropivacaine injected after motor responses were obtained with stimulations between 0.2 and 0.5 mA. Sensory and motor blocks were assessed for 30 minutes after blockade. A total block effectiveness score was calculated. The quality of surgical anesthesia was classified as success or failure according to the need for systemic intraoperative supplementation. Duration of anesthesia was defined as time from blockade placement until the first analgesic request.

RESULTS: Median onset times were 5, 12.5, and 17.5 minutes for groups 1, 2 and 3, respectively (p = 0.11). Success rates were 100%, 93% and 75% (p = 0.12), and postoperative analgesia duration was 14.5, 13.5 and 13.75 hours (p = 0.15) for groups 1, 2 and 3, respectively.

CONCLUSIONS: Intramuscular or perineural clonidine has not affected anesthetic onset, quality or the duration of postoperative analgesia of 0.5% ropivacaine-induced sciatic nerve block.

Key Words: ANALGESICS, clonidine; ANESTHETICS, Local, ropivacaine. ANESTHETIC TECHNIQUES, Regional, sciatic block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Se estudiaron los efectos de la clonidina sobre la latencia, la calidad de la anestesia y la duración de la analgesia de lo bloqueo del nervio isquiático con ropivacaína a 0,5%.

MÉTODO: Cuarenta pacientes adultos fueron sometidos a cirugías sobre el pie y/o la faz lateral del tobillo bajo bloqueos combinados de nervios femoral e isquiático, por vía anterior, en que fueron distribuidos, según números aleatorios en el grupo 1: 25 mL de ropivacaína a 0,5% y placebo perineural; grupo 2: 2 µg.kg^-1 de clonidina por vía muscular y 25 mL de ropivacaína a 0,5% perineural; y grupo 3: 2 µg.kg^-1 de clonidina y 25 mL de ropivacaína a 0,5% perineural, inyectados después de lograr respuestas motoras con corrientes de 0,2 y 0,5 mA. La sensibilidad y la motricidad fueron evaluadas por 30 minutos después del bloqueo. El resultado de la efectividad total del bloqueo fue atribuido. La calidad de la anestesia quirúrgica fue clasificada con éxito o falla, según la necesidad de suplementación sistémica. La duración fue el tiempo desde la realización del bloqueo hasta la primera solicitación de analgésico.

RESULTADOS: Las latencias medianas fueron 5, 12,5 y 17,5 minutos en los grupos 1 a 3, respectivamente (p = 0,11). Las tasas de éxito fueron del 100%, 93% y 75%, respectivamente (p = 0,12). La duración de la analgesia posoperatoria fue de 14,5, 13,5, y 13,75 horas, respectivamente (p = 0,15).

CONCLUSIONES: La clonidina por vía muscular o perineural no influenció la latencia, la calidad de la anestesia o la duración de la analgesia del bloqueo del nervio isquiático con ropivacaína a 0,5%.

INTRODUCTION

Clonidine is an imidazoline compound with partial agonist activity on a₂-adrenergic receptors, presenting sedative and analgesic action ^1,2. Clonidine antinociceptive mechanisms are still controversial. In C fibers of vagus nerves of rabbits, clonidine micromole concentrations increase hyperpolarizations dependent on activities generated by sodium-potassium pump during and after repetitive stimulations ³. Although peripheral nerve axons lack a₂-adrenergic receptors, clonidine prolongs tetrodotoxin-induced nervous block in animal models ⁴. These actions may result in nervous conduction delay or blockade, possibly explaining the origin of clonidine-induced antinociception. Other possible mechanisms may include local vasoconstrictor effect or analgesic effects on the central nervous system ¹.

Clonidine added to 1% mepivacaine for brachial plexus block has been associated to dose-dependent prolongation of anesthesia, motor block and postoperative analgesia ^5,6. Intramuscularly, clonidine has not such effect, suggesting a neural action site ⁶. In the brachial plexus, clonidine plus 1% lidocaine improves ⁷ or does not change ⁸ blockade quality or duration.

A study comparing onset and duration of 1% mepivacaine, 0.75% ropivacaine and 0.5% bupivacaine with and without 150 µg clonidine ⁹, has shown no effect on the onset of mepivacaine and ropivacaine, but a significant increase in bupivacaine onset. In the same study, clonidine has increased mepivacaine and bupivacaine-induced motor block duration, suggesting that clonidine has variable impact on each tested anesthetic drug in terms of blockade onset and duration. In addition, ropivacaine-induced blockade does not seem to be affected by clonidine. For sciatic nerve block, clonidine added to ropivacaine has improved ¹⁰ or has not changed ¹¹ blockade profile.

This study aimed at evaluating the effects of clonidine on anesthetic onset and quality, as well as on the duration of postoperative analgesia of sciatic nerve block with 0.5% ropivacaine.

METHODS

After the Ethics Committee approval and with informed consent, 40 patients of both genders, aged 18 to 65 years, physical status ASA I to III, scheduled for orthopedic surgeries on foot or lateral aspect of the ankle were included in this prospective study. Exclusion criteria were patients under chronic analgesic therapy, with counterindication to regional anesthesia, peripheral neuropathies, severe cardiovascular disease, known allergy to local anesthetics and with neurological or psychiatric disorders.

In the anesthetic induction room, monitoring was installed, consisting of noninvasive blood pressure, ECG and pulse oximetry. A hand or forearm vein was catheterized for 2 mL.min^-1 saline infusion and 0.1 mg.kg^-1 midazolam administration.

Femoral nerve of the limb to be operated was blocked with the aid of a peripheral nerve stimulator and contraction response of the anterior rectus muscle of thigh, with intensity between 0.2 and 0.5 mA, with 15 mL of 0.5% ropivacaine, what allowed the use of a pneumatic tourniquet on the thigh.

Patients were then allocated in three groups according to randomized electronically generated numbers and using sealed envelopes.

The sciatic nerve was blocked thru the anterior route with stimulation of both components (tibial and common fibular). Group 1 patients (n = 10) were injected 25 mL of 0.5% ropivacaine added to saline in the same volume of clonidine solutions of other groups. Group 2 patients (n = 14) received 2 µg.kg^-1 intramuscular clonidine in the anterior rectus muscle of thigh and 25 mL of 0.5% ropivacaine perineurally. Group 3 patients (n = 16) were given 2 µg.kg^-1 clonidine plus 25 mL of 0.5% ropivacaine perineurally. The anesthetic solution was equally divided between both sciatic nerve components after respective motor responses with stimulations between 0.2 and 0.5 mA.

Nervous blocks were performed with insulated 25G 4¨ needles (B Braun Medical, Germany), connected to a peripheral nerve stimulator (Stimuplex, DG, Braun Medical, Germany). Stimulations frequency was 2 Hz. Initial current intensity was 1 mA, which was progressively decreased after elicited, foot plantar/inversion bend (tibial nerve) and foot dorsiflexion/eversion (common fibular nerve). Anesthetics were administered when motor response of respective muscle groups was obtained with current intensity between 0.2 and 0.5 mA. Paresthesias were not searched.

Immediately after sciatic nerve block, an investigator blind to patient's group would test skin sensitivity and motility in the territories innervated by its tibial and common fibular components. Sensory block was evaluated by the sensation produced by a 22G needle touch on foot dorsal (common fibular nerve) and plantar (tibial nerve) regions, according to the following scale: 0 = absent (acute sensation at needle touch), 1 = decreased (only tactile sensation at needle touch) and 2 = complete (no sensation at needle touch). Motility was classified as 0 = normal, 1 = decreased and 2 = absent, according to patients' ability to actively bend (tibial nerve) and extend (common fibular nerve) ankle and toes.

The global blockade effectiveness score was obtained by adding both sensitivity and motility scores of tibial and common fibular components, which varied from 0 (total failure) to 8 (complete sensory and motor block in the territories of both sciatic nerve components).

Quality of anesthesia was classified as success or failure, according to the need for anesthetic supplementation with systemic opioids or inhalational anesthesia. Hypotension, defined as mean blood pressure below 55 mmHg, was treated with 10 mg fractional ephedrine doses. Bradycardia, defined as heart rate below 50 bpm, was treated with 0.5 fractional atropine doses. Sedation was evaluated throughout the observation period (between studied solutions administration and first systemic analgesic request or 24 hours post-blockade) by the Observer's Assessment of Alertness/Sedation Scale (0 = deep sedation; 20 = alertness) ¹². Anesthetic duration was defined as time in hours between blockade and first systemic analgesic request.

Patients were interviewed 24 hours after blockade to evaluate their satisfaction with the technique, using two-way answers such as yes/no.

Assuming an interquartile range of 2.7 hours of difference in sensory block duration between studied and control groups found in a different study ¹⁰, sample size was calculated as 10 patients in each group to detect a 4-hour difference in comparisons among groups, with a = 0.05 and 1 - b = 0.2. Age, weight and height were compared between groups by single-factor analysis of variance. Gender, success rates, number of patients with highest global blockade effectiveness score and number of patients needing treatment for hypotension or bradycardia were compared between groups by Chi-square test with Yates correction.

Minimum sedation/alertness scores obtained during the observation period were compared between groups by Kruskal-Wallis test. Survival analysis using Kaplan-Meier test for multiple groups comparison was used to compare blockade onset and duration between groups. In this analysis, critical event for onset was blockade effectiveness score equal 8, while for duration, it was postoperative systemic analgesia request. Observation censoring was applied for onset when patients did not reach effectiveness score 8 at 30 minutes after blockade, and for duration when patients did not request postoperative systemic analgesia until the interview 24 hours after blockade. Significance level for all tests was p < 0.05.

RESULTS

Groups were homogeneous in demographics data and surgery duration (Table I).

Thirty minutes after blockade, 8/10 group 1, 9/14 group 2 and 10/16 group 3 patients had effectiveness scores equal 8, differences statistically not significant (c² (8 gL) = 7.18, p = 0.51). Figure 1 shows cumulative percentages of patients remaining with lower limbs effectiveness scores below 8 (total sensory and motor block in the territories of tibial and common fibular components). Onset time medians (lower; upper quartiles) were 5 (5; 13.75), 12.5 (6.25; 26.25) and 17.5 (10; 30) minutes in groups 1, 2 and 3, respectively. There were also no differences between groups (c² (2 gL) = 4.27, p = 0.11).

Blockade success rates (surgeries performed without supplementation with systemic opioids or inhalational anesthesia) were 100%, 93% and 75%, for groups 1, 2 and 3, respectively (c² (2 gL) = 4.08, p = 0.12).

Figure 2 shows Kaplan-Meier curves related to postoperative analgesia duration for all groups. Analgesia duration medians (lower; upper quartiles) were 14.5 (12.25; 17.5), 13.5 (12.25; 21.25) and 13.75 (12; 15.5) hours for groups 1, 2 and 3, respectively (c² (2 gL) = 0.15, p = 0.92).

There was no bradycardia or hypotension. Median scores (25^th and 75^th quartiles) for minimum sedation score (deeper sedation) were 16 (0; 18.5), 16 (12; 18), 15 (0; 18.5) for groups 1, 2 and 3, respectively (H (2.52) = 0.69; p = 0.70). Satisfaction with the technique was reported by 100% of group 1 patients, 93% of group 2 patients and 100% of group 3 patients (c² (2 gL) = 1.83; p = 0.39).

DISCUSSION

Major results of this study relate to the inability of showing effects of intramuscular or perineural clonidine (2 µg.kg^-1) on anesthetic onset, quality and on duration of postoperative analgesia after sciatic nerve block with 0.5% ropivacaine.

These results are in line with other authors ¹¹ who have compared intramuscular and perineural 50 mg clonidine for sciatic and femoral nerve block with 0.75% ropivacaine and could not show clonidine effects on blockade onset, quality or duration. Similarly, it has been shown that ropivacaine does not seem to be influenced by clonidine for brachial plexus block ⁹.

Sciatic nerve block median duration with 0.5% ropivacaine is 16 hours, with extremes of 8 and 24 hours ¹².

Other authors ¹¹ have shown that 1 µg.kg^-1 clonidine added to 0.75% ropivacaine for sciatic nerve block was related to significant increase in postoperative analgesia (median duration of 16.8 hours for the clonidine group versus 13.7 hours for the plain 0.75% ropivacaine group), although no effects were observed on anesthetic onset and quality. This study is different from ours for having included only patients submitted to surgical hallux vagus correction, predominantly females and aged approximately 60 years.

Although our study has included not only patients submitted to foot surgeries but also to lateral ankle, both innervated by sciatic nerve divisions, analgesia duration medians were similar for the control groups of both studies (14.5 hours and 13 hours, respectively), thus being unlikely that the type of surgery could be responsible for the difference in results between studies.

Demographic profile may be responsible for contrasting factors related to prolonged blockade by clonidine. Gender-related differences in analgesics effectiveness have been reported. For example, in a study evaluating the effectiveness of ibuprofen to decrease experimental pain, only males had statistically significant analgesic response and results could not be attributed to pharmacokinetic differences ¹³.

In a different study ¹⁴, the effects of cold stimulation-induced pain on thermal nociceptive heterotopic stimulation indices have been investigated in different age brackets. Older adults showed more thermal pain facilitation than inhibition during cold stimulation, while only young adults have shown the expected diffuse inhibitory control of nociceptive stimulation, a measure of endogenous pain inhibition, suggesting decreased modulation ability in the elderly. However, in the absence of data on the effects of age or gender on intramuscular and perineural clonidine pharmacodynamics, above-mentioned considerations should be interpreted only as speculation.

In addition, assuming the dose-dependence shown for peripheral analgesic effects of clonidine added to local anesthetics ^15,16, it should be expected that 2 µg.kg^-1 used in this study would be associated to a higher effect as compared to the described dose of 1 µg.kg^-1.

In our study, sample sizes were calculated to detect a minimum 4-hour difference between groups, considered clinically significant, and assuming a 2.7-hour interquartile range of the control group of a previous study ¹⁰. However, mean difference in analgesia duration between groups was 0.75 hour. To detect such difference, probably without clinical significance, and considering mean and standard deviation of residues (groups mean - original values) equal to 5.41 hours, 985 patients would have been necessary in each group assuming error probabilities type I and II equal to 0.05 and 0.2, respectively ¹⁷, which would make the study unfeasible in our institution. It is possible that the study has not been robust enough to reject the null hypothesis with regard to onset time.

This study adds to current controversy about the effects of clonidine on peripheral nerve blocks, because it was unable to show the effects of intramuscular or perineural clonidine on anesthetic onset and quality and on postoperative analgesia duration, when associated to 0.5% ropivacaine for sciatic nerve block.

REFERENCES

Submitted for publication January 11, 2005

Accepted for publication May 23, 2005

• 01. Eisenach JC, De Kock M, Klimscha W - Alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology, 1996;85:655-674.
• 02. Alves TCA, Braz JRC, Vianna PTG - a₂-Agonistas em Anestesiologia: aspectos clínicos e farmacológicos. Rev Bras Anestesiol, 2000;55:396-404.
• 03. Dalle C, Schneider M, Clergue F et al - Inhibition of the I(h) current in isolated peripheral nerve: a novel mode of peripheral antinociception? Muscle Nerve, 2001;24:254-261.
• 04. Kohane DS, Lu NT, Cairns BE et al - Effects of adrenergic agonists and antagonists on tetrodotoxin-induced nerve block. Reg Anesth Pain Med, 2001;26:239-245.
• 05. Singelyn FJ, Gouverneur JM, Robert A - A minimum dose of clonidine added to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. Anesth Analg, 1996;83:1046-1050.
• 06. Singelyn FJ, Dangoisse M, Bartholomee S et al - Adding clonidine to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. Reg Anesth, 1992;17:148-150.
• 07. Bernard JM, Macaire P - Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology, 1997;87: 277-284.
• 08. Gaumann D, Forster A, Griessen M et al - Comparison between clonidine and epinephrine admixture to lidocaine in brachial plexus block. Anesth Analg, 1992;75:69-74.
• 09. Erlacher W, Schuschnig C, Koinig H et al - Clonidine as adjuvant for mepivacaine, ropivacaine and bupivacaine in axillary, perivascular brachial plexus block. Can J Anaesth, 2001;48: 522-525.
• 10. Casati A, Magistris L, Fanelli G et al - Small-dose clonidine prolongs postoperative analgesia after sciatic-femoral nerve block with 0.75% ropivacaine for foot surgery. Anesth Analg, 2000;91:388-392.
• 11. McNamee D, Convery PN, Parks L et al - An assessment of the addition of clonidine to ropivacaine in combined femoral and sciatic block. Eur J Anaesthesiol, 2000;17:(Suppl19):113.
• 12. Casati A, Borghi B, Fanelli G, et al - A double-blinded, randomized comparison of either 0.5% levobupivacaine or 0.5% ropivacaine for sciatic nerve block. Anesth Analg, 2002;94: 987-990.
• 13. Chernik DA, Gillings D, Laine H et al - Validity and reliability of the Observer's Assessment of Alertness/Sedation Scale: study with intravenous midazolam. J Clin Psychopharmacol, 1990;10: 244-251.
• 14. Walker JS, Carmody JJ - Experimental pain in healthy human subjects: gender differences in nociception and in response to ibuprofen. Anesth Analg, 1998;86:1257-1262.
• 15. Edwards RR, Fillingim RB, Ness TJ - Age-related differences in endogenous pain modulation: a comparison of diffuse noxious inhibitory controls in healthy older and younger adults. Pain, 2003;101:155-165.
• 16. Bernard JM, Macaire P - Dose-range effects of clonidine added to lidocaine for brachial plexus block. Anesthesiology, 1997;87:277-284.
• 17. Glantz AS - Primer of Biostatistics, 4^th Ed, New York, McGraw- Hill, 1997;266-271.

^*

Received from Hospital Governador Celso Ramos, CET/SBA Integrado de Anestesiologia da Secretaria de Estado da Saúde de Santa Catarina (SES/SC), Florianópolis, SC

Publication Dates

• Publication in this collection
  13 Feb 2006
• Date of issue
  Oct 2005

History

• Received
  11 Jan 2005
• Accepted
  23 May 2005