Intravenous dexmedetomidine for sedation does not interfere with sensory and motor block duration during spinal anesthesia

Abstracts

JUSTIFICATIVA E OBJETIVOS: A anestesia locorregional é uma prática freqüente e de grande aplicabilidade em Anestesiologia. Contudo, o paciente pode tornar-se ansioso, fazendo-se necessária a sedação. Os agentes benzodiazepínicos, opióides e o propofol são amplamente utilizados com este objetivo. Os agonistas alfa2-adrenérgicos possuem propriedades hipnóticas e sedativas e são uma alternativa no arsenal terapêutico, conferindo estabilidade hemodinâmica e mínima depressão respiratória. O objetivo deste estudo foi avaliar a segurança e a interferência do uso da dexmedetomidina ou do midazolam, por via venosa, na duração dos bloqueios motor e sensitivo em raquianestesia. MÉTODO: Foram estudadas 35 pacientes adultas, do sexo feminino, estado físico ASA I e II, submetidas à raquianestesia com bupivacaína a 0,5% hiperbárica (15 mg), para cirurgia ginecológica eletiva, distribuídas de modo aleatório em dois grupos: grupo M (n = 17) - sedação com midazolam em infusão contínua a 0,25 µg.kg-1.min-1 e grupo D (n = 18) - sedação com dexmedetomidina em infusão contínua a 0,5 µg.kg-1.min-1. A velocidade de infusão foi ajustada para manter o valor de BIS entre 60 e 80. Foram analisados os valores de PAS, PAD, FC, SpO2, BIS, extensão e duração dos bloqueios sensitivo motor (escala de Bromage). RESULTADOS: Não houve diferença estatística significativa entre os grupos quanto à idade, peso, nível de bloqueio sensitivo, variação na pressão arterial e freqüência cardíaca e na duração dos bloqueios sensitivo e motor. CONCLUSÕES: A dexmedetomidina utilizada em sedação, por via venosa, não interferiu nos parâmetros hemodinâmicos, duração ou extensão dos bloqueios sensitivo e motor na raquianestesia, representando boa opção para sedação durante anestesia locorregional.

ANALGÉSICOS; ANESTÉSICOS, Local; TÉCNICAS ANESTÉSICAS, Regional

SCIENTIFIC ARTICLE

Intravenous dexmedetomidine for sedation does not interfere with sensory and motor block duration during spinal anesthesia^*

La dexmedetomidina para sedación, por vía venosa, no interfiere con la duración del bloqueo sensitivo y motor de la raquianestesia

Edno Magalhães, TSA^I; Luís Cláudio de Araújo Ladeira, TSA^II; Cátia Sousa Govêia, TSA^II; Beatriz Vieira Espíndola^III

^IProfessor Adjunto da Área de Clínica Cirúrgica da Faculdade de Medicina da Universidade de Brasília (UnB); Responsável pelo CET da Clínica de Anestesiologia da Universidade de Brasília

^IIMédico Assistente da Clínica de Anestesiologia do Hospital Universitário de Brasília, Universidade de Brasília (UnB); Co-responsável pelo CET da Clínica de Anestesiologia da Universidade de Brasília

^IIIMédica Assistente da Clínica de Anestesiologia do Hospital Universitário de Brasília, Universidade de Brasília (UnB)

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: The association among local and regional anesthesia is a very useful and common practice. However, some patients may become anxious and require sedation. Benzodiazepines, opioids and propofol are widely used for this aim. Alpha₂-adrenergic agonists have hypnotic and sedative properties and represent an alternative to promote hemodynamic stability and minor respiratory depression. This study aimed at evaluating the safety and the interference of intravenous dexmedetomidine or midazolam on sensory and motor block duration spinal anesthesia.

METHODS: Thirty five adult female patients, physical status ASA I and II, were submitted to spinal anesthesia with hyperbaric 0.5% bupivacaine (15 mg) for elective gynecologic surgery. The patients were randomized and distributed in two groups: Group M (n = 17) - sedation with 0.25 µg.kg^-1.min^-1 midazolam continuous infusion and Group D (n = 18) sedation with 0.5 µg.kg^-1.min^-1 dexmedetomidine continuous infusion. Infusion rate was adjusted to maintain BIS between 60 and 80. The following parameters were evaluated: SBP, DBP, HR, SpO₂, BIS sensory and motor block extension and duration (Bromage scale).

RESULTS: There were no statistically significant differences between groups in age, weight, sensory block level, blood pressure and heart rate variation and sensory and motor block duration.

CONCLUSIONS: Intravenous dexmedetomidine for sedation has not interfered with hemodynamic parameters, spinal anesthesia sensory and motor block duration or extension and it is a good option for sedation during local/regional anesthesia.

Key Words: ANALGESICS: dexmedetomidine; ANESTHETICS, Local: hyperbaric bupivacaine; ANESTHETIC TECHNIQUES, Regional: spinal block

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La anestesia regional se practica con frecuencia en anestesiología. No obstante, algunos pacientes pueden mostrar ansiedad, necesitando en ese caso sedación. Los benzodiazepínicos, opioides y propofol son ampliamente utilizados para este propósito. Los agonistas alfa 2-adrenérgicos tienen propiedades hipnóticas y sedativas y son una alternativa terapéutica por la estabilidad hemodinámica y mínima depresión respiratoria. El objetivo de este estudio es evaluar la seguridad e interacciones de dexmedetomidina y midazolam por vía intravenosa en la duración del bloqueo sensitivo y motor de la raquianestesia.

MÉTODO: Fueron estudiadas 35 pacientes adultas, estado físico ASA I y II, que recibieron raquianestesia con bupivacaína a 0,5% hiperbárica (15 mg), para cirugía ginecológica electiva, distribuidas de modo aleatorio en 2 grupos: grupo M (n = 17) - sedación con midazolam en infusión continua a 0,25 µg.kg^-1.min^-1 y grupo D (n = 18) - sedación con dexmedetomidina en infusión continua a 0,5 µg.kg^-1.min^-1. La velocidad de infusión fue ajustada para mantener el valor del BIS entre 60 y 80. Fueron analizados los valores de PAS, PAD, FC, SpO₂, BIS, extensión y duración del bloqueo sensitivo motor (escala de Bromage).

RESULTADOS: No hubo diferencia estadística entre los grupos en edad, peso, nivel de bloqueo sensitivo y duración bloqueo sensitivo motor, como de la frecuencia cardíaca y presión arterial.

CONCLUSIONES: La dexmedetomidina utilizada en sedación, por vía venosa, no alteró los parámetros hemodinámicos, duración o extensión de los bloqueos sensitivo y motor de la raquianestesia, representando una buena opción para sedación durante anestesia regional.

INTRODUCTION

The combined local/regional anesthesia is widely accepted as an effective method for modern anesthetic practice. This technique allows the control of endocrine and metabolic response to trauma, decreases intraoperative blood loss and the incidence of postoperative thromboembolism, and promotes postoperative analgesia¹.

Regional anesthesia, however, may promote some type of discomfort caused by the procedure itself or by a prolonged perioperative period, requiring the simultaneous administration of hypnotic, sedative and amnesic drugs. Benzodiazepines, propofol and opioids have these properties and provide some comfort to patients. However, they affect the ventilatory regulatory mechanisms and may lead to respiratory depression, with consequent hypercarbia and hypoxemia.

A promising alternative to these drugs in Anesthesiology is the group of alpha₂-adrenergic agonists, which have excellent sedative and analgesic properties without respiratory depression. Dexmedetomidine is an alpha₂-agonist with strong selectivity to the specific receptor and has been used as preanesthetic medication, as adjuvant to general anesthesia, as sedative during trans and postoperative period^2-4.

Dexmedetomidine associated to local/regional anesthesia would provide a synergistic pharmacological interaction prolonging the action of local anesthetics, improving hemodynamic stability, sedation and analgesia and not causing respiratory depression^2,4.

This study aimed at comparing physiological parameters of intravenous sedation with midazolam and dexmedetomidine and at evaluating the influence of dexmedetomidine in doses clinically indicated for sedation, on the duration of sensory and motor block promoted by spinal hyperbaric bupivacaine.

METHODS

After the Research Ethics Committee, Universidade de Brasília approval and their informed consent, participated in this study 35 adult female patients, physical status ASA I and II, submitted to spinal anesthesia and intravenous sedation with dexmedetomidine or midazolam continuous infusion for elective gynecologic procedures. Exclusion criteria were patients with known renal, liver or heart function disorders, morbidly obese, under anti-hypertensive medication or counterindicated to regional anesthesia.

Patients were premedicated with diazepam (10 mg) the day before and in the morning of the surgery day. Monitoring consisted of continuous ECG, noninvasive blood pressure (NIBP), oxygen peripheral saturation (SpO₂) and EEG analysis by bispectral index (BIS).

Patients were randomly distributed in two groups. Group M (n = 17) - sedation with midazolam - intravenous midazolam continuous infusion at initial rate of 0.25 µg.kg^-1.min^-1 adjusted according to BIS (values maintained between 60 and 80). Group D (n = 18) - sedation with dexmedetomidine - intravenous dexmedetomidine continuous infusion at initial infusion rate of 0.5 µg.kg^-1.min^-1, adjusted according to BIS (values maintained between 60 and 80). Infusion regimen was adjusted in both groups to limit hypnosis to mild or superficial characterizing sedation (BIS between 60 and 80).

Considering the easily identified difference between infusion rates for dexmedetomidine and midazolam aiming at the same BIS level, this study was not blind.

After venous puncture and monitoring, spinal anesthesia was induced with disposable 25G Quincke needle and hyperbaric 0.5% bupivacaine (15 mg). With patients in the supine position sensory block level started to be investigated (tactile sensitivity) one minute after spinal puncture and then at 5-minute intervals. Motor block intensity (Bromage) was initially evaluated until total motor block installation and then at surgery completion at 10-minute intervals for blockade regression. Midazolam or dexmedetomidine infusion was started 10 minutes after anesthetic induction.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), BIS, sensory level and motor block intensity were evaluated every 5 minutes in the perioperative period. At surgery completion patients were referred to the post-anesthetic recovery unit (PACU) and were observed to check motor and sensory block duration. Motor block duration was considered time elapsed before patients were able to bend the knee and raise the stretched leg (no motor block according to Bromage scale).

Student’s t test was used for statistical analysis considering significant p < 0.05.

RESULTS

Demographics data (Table I) were not statistically different between groups. All patients had total motor block (impossibility of bending feet - Bromage) and sensory block level mode was T₄ (Table II) for both groups. Hemodynamic variables - systolic blood pressure, diastolic blood pressure and heart rate (Figure 1, Figure 2 and Figure 3) - were not statistically different between groups in studied moments. Time for total motor block regression according to Bromage scale (Figure 4) was 249.7 ± 31.8 min for group D and 240.6 ± 39.2 min for group M, without statistically significant difference (p = 0.455) (Table III). Time for total sensory block regression was 219.7 ± 25.4 min for group D and 197.5 ± 40.9 min fir group M, without statistically significant difference (p = 0.062).

DISCUSSION

Alpha₂-adrenergic receptor agonists are beneficial for anesthesia. They provide hemodynamic stability and sedation, decrease the need for anesthetics and analgesics⁵, and have no marked depressing effects on ventilation. Their action mechanism is not related to neurotransmitters synthesis, storage or metabolism and is reversible with vasoactive agents, agonists of these receptors, or by withdrawing the drug^6,7. Dexmedetomidine is more selective to alpha₂-adrenergic receptors as compared to clonidine. Dexmedetomidine has fast onset and short half-life promoting decreased norepinephrine plasma levels, hemodynamic stability, sedation and analgesia without respiratory depression⁸.

Some proposed mechanisms for the action of alpha₂-adrenergic agonists combined to local anesthetics include vasoconstriction, facilitation of C fibers blockade by local anesthetics, interference on retrograde axonal transportation at medullary level and action on peripheral nerve receptors⁹. Some reports discuss longer sensory and motor block duration induced by alpha₂-adrenergic agonists during neuraxial blocks⁹.

Rhee et al. have observed increased sensory and motor block duration induced by intravenous clonidine associated to spinal anesthesia¹⁰. Memis et al. have observed faster motor block installation and slower recovery of total motor activity when dexmedetomidine was associated to intravenous regional anesthesia with lidocaine¹¹. The interference of alpha₂-adrenergic agents on motor activity was not the objective of the above-mentioned studies. Studies aiming at determining the actual interference of such drug on motor and sensory block duration are needed and should be reproduced.

Single or repeated dose in anesthesia could be an inadequate alternative to measure the effects of a drug. Hu et al., using mathematical simulations, have forecasted twice the variation coefficient in plasma concentration of a drug in bolus as compared to continuous infusion¹². This may promote high plasma concentrations of drugs and the presence of adverse effects. Continuous infusion allows the maintenance of constant plasma concentration of drugs, preventing decreased effects and the possibility of adverse reactions.

Systemic single dose as opposed to continuous infusion may be responsible for unexpected motor block duration increase. Sudo et al. have found this characteristic in an animal study where high systemic dexmedetomidine doses have increased motor block duration in animals submitted to spinal anesthesia with levobupivacaine, which was partially decreased by ioimbine¹³. Our study has not shown differences between dexmedetomidine or midazolam continuous infusion, in doses limited to promote sedation, with regard to sensory and motor block duration promoted by spinal anesthesia with hyperbaric 0.5% bupivacaine.

Dexmedetomidine for sedation has not changed blood pressure and heart rate values as compared to midazolam. It is possible that preanesthetic diazepam, a long half-life benzodiazepine may have influenced the level of perioperative sedation. However, both groups received the same preanesthetic medication and midazolam and dexmedetomidine infusion rates were adjusted for a target BIS value. So, we believe that decreased anesthetic need promoted by diazepam was similar for both groups. Our conclusion was that intravenous dexmedetomidine for sedation of patients submitted to spinal anesthesia is a good option for sedation, with hemodynamic stability, adequate hypnosis and without changing motor and sensory block duration.

REFERENCES

Submitted for publication July 4, 2005

Accepted for publication October 10, 2005

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*

Received from Hospital Universitário de Brasília, Universidade de Brasília, Brasília, DF

Publication Dates

• Publication in this collection
  22 Mar 2006
• Date of issue
  Feb 2006

History

• Accepted
  10 Oct 2005
• Received
  04 July 2005