Influence of midazolam and clonidine premedication on hypnosis level after anesthetic induction with propofol and alfentanil in children: bispectral index monitoring

Abstracts

JUSTIFICATIVA E OBJETIVOS: A medicação pré-anestésica (MPA) é adjuvante da anestesia e diminui tanto a necessidade de concentrações elevadas de anestésicos como a ansiedade perioperatória, produzindo amnésia e contribuindo para estabilidade hemodinâmica. Dentre as drogas administradas na MPA de crianças, encontram-se o midazolam e a clonidina. O objetivo desta pesquisa foi avaliar se a MPA com midazolam e clonidina exerce influência no nível de hipnose, avaliado pelo BIS, em crianças após indução anestésica com propofol e alfentanil. MÉTODO: Participaram do estudo 30 pacientes, com idades entre 2 e 12 anos, estado físico ASA I, submetidos a cirurgias eletivas, que foram distribuídos em 3 grupos: G1 - sem MPA, G2 - midazolam (0,5 mg.kg-1) e G3 - clonidina (4 µg.kg-1), por via oral, 60 minutos antes da cirurgia. Todos os pacientes receberam alfentanil (30 µg.kg-1), propofol (3 mg.kg-1) e atracúrio (0,5 mg.kg-1). Avaliou-se o valor derivado do BIS antes da indução da anestesia (M1) e após a intubação (M2). O método estatístico utilizado foi a análise de variância para idade, peso e altura, e análise de perfil para o BIS, sendo o valor de p < 0,05 considerado significativo. RESULTADOS: Quando se comparou o mesmo momento (M1 ou M2) entre os três grupos, não foram observadas diferenças estatisticamente significativas. Quando se compararam os dois momentos de um mesmo grupo, M1 foi maior que M2 nos três grupos. CONCLUSÕES: A medicação pré-anestésica com midazolam e clonidina não influenciou o nível de hipnose em crianças induzidas com propofol e alfentanil.

HIPNÓTICOS; HIPNÓTICOS; MEDICAÇÃO PRÉ-ANESTÉSICA; MEDICAÇÃO PRÉ-ANESTÉSICA; MONITORIZAÇÃO

SCIENTIFIC ARTICLE

Influence of midazolam and clonidine premedication on hypnosis level after anesthetic induction with propofol and alfentanil in children. Bispectral index monitoring

Eliana Marisa Ganem, TSA, M.D.^I; Norma Sueli Pinheiro Módolo, TSA, M.D.^II; Pedro Thadeu Galvão Vianna, TSA, M.D.^III; Yara Marcondes Machado Castiglia, TSA, M.D.^III

^IProfessora Adjunta Livre Docente do CET/SBA da FMB UNESP

^IIProfessora Assistente Doutora do CET/SBA da FMB UNESP

^IIIProfessor (a) Titular do CET/SBA da FMB UNSP

SUMMARY

BACKGROUND AND OBJECTIVES: Premedication is an anesthetic adjuvant which decreases both perioperative anxiety and the need for high anesthetic concentrations, in addition to producing amnesia and contributing to hemodynamic stability. Midazolam and clonidine are among preanesthetic drugs indicated for children. This study aimed at evaluating whether preanesthetic midazolam or clonidine influences hypnosis in children induced with propofol and alfentanil.

METHODS: Participated in this study 30 patients aged 2 to 12 years, physical status ASA I, undergoing elective surgeries, who were divided into 3 groups: G1- without premedication, G2 - oral midazolam (0.5 mg.kg^-1), and G3 - oral clonidine (4 µg.kg^-1), both administered 60 minutes before anesthesia. All patients received alfentanil (30 µg.kg^-1), propofol (3 mg.kg^-1), and atracurium (0.5 mg.kg^-1). BIS values were evaluated before anesthesia induction (M1) and after tracheal intubation (M2). Analysis of variance was the statistical method used for age, weight, and height, and profile analysis was used for BIS values, considering significant p < 0.05.

RESULTS: In comparing the same moment (M1 or M2) among the three groups there were no significant differences. When comparing the two moments of a same group, M1 values were higher than M2 values in all groups.

CONCLUSIONS: Midazolam and clonidine premedication have not influenced hypnosis level of propofol and alfentanil in children.

Key Words: HYPNOTICS: alfentanil, propofol; MONITORING: bispectral index; PREANESTHETIC MEDICATION: clonidine, midazolam

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La medicación pré-anestésica (MPA) es adjuvante de la anestesia y diminuye tanto la necesidad de concentraciones elevadas de anestésicos, como la ansiedad perioperatoria, produciendo amnesia y contribuyendo para la estabilidad hemodinámica. De entre las drogas administradas en la MPA de niños, se encuentran el midazolam y la clonidina. El objetivo de esta pesquisa fue evaluar si la MPA con midazolam y clonidina ejerce influencia en el nivel de hipnosis, evaluado por el BIS, en niños después inducción anestésica con propofol e alfentanil.

MÉTODO: Participaron del estudio 30 pacientes, con edades entre 2 y 12 años, estado físico ASA I, sometidos a cirugías electivas, que fueron distribuidos en 3 grupos: G1 sin MPA, G2 - midazolam (0,5 mg.kg^-1) y G3 - clonidina (4 µg.kg^-1), por vía oral, 60 minutos antes de la cirugía. Todos los pacientes recibieron alfentanil (30 µg.kg^-1), propofol (3 mg.kg^-1) y atracúrio (0,5 mg.kg^-1). Se evaluó el valor derivado del BIS antes de la inducción de la anestesia (M1) y después de la intubación (M2). El método estadístico utilizado fue la análisis de variancia para edad, peso y altura, y análisis de perfil para el BIS, siendo el valor de p < 0,05 considerado significativo.

RESULTADOS: Cuando se comparó el mismo momento (M1 o M2) entre los tres grupos, no fueron observadas diferencias estadísticamente significativas. Cuando se compararon los dos momentos de un mismo grupo, M1 fue mayor que M2 en los tres grupos.

CONCLUSIONES: La MPA con midazolam y clonidina no influenció el nivel de hipnosis en niños inducidos con propofol y alfentanil.

INTRODUCTION

Premedication is an anesthetic adjuvant which decreases both perioperative anxiety and the need for high anesthetic concentrations, in addition to producing amnesia and contributing to hemodynamic stability ¹. Midazolam - a water-soluble benzodiazepine, effective in reducing anxiety and widely used ² - and clonidine - an a₂-adrenergic agonist providing preoperative sedation ³ - are among preanesthetic drugs administered in children for decreasing perioperative anesthetic concentrations ⁴.

EEG-derived bispectral index is a quantifiable measurement of the hypnotic effects of anesthetic drugs in the central nervous system ^5,6. Represented by a numeric scale from 100 (awaken) to 0 (isoelectric EEG) it shows, for anesthesia induction, maintenance and recovery in children, the same values found in adults, making it feasible for pediatric use.

This study aimed at evaluating by BIS whether premedication with midazolam and cloinidine would influence hypnosis levels in children induced with propofol and alfentanil.

METHODS

After the Clinical Research Ethics Committee approval and the consent of parents or guardians, participated in this study 30 patients of both genders, aged 2 to 12 years, physical status ASA I, submitted to elective surgeries. Patients were randomly distributed in 3 groups (G1, G2 and G3) according to the presence, absence or type of preanesthetic medication.

After an 8-hour fast, G1 patients received no premedication, G2 patients were premedicated with 0.5 mg.kg^-1 oral midazolam and G3 patients received 4 µg.kg^-1 oral clonidine (maximum dose of 150 µg.kg^-1), 60 minutes before being referred to the operating room. In the operating room, after installing a venous access, 4 ml.kg^-1.h^-1 lactated Ringer’s in continuous infusion was started and monitoring consisted of ECG in D_II, non-invasive blood pressure, pulse oximetry, digital thermometer and Bispectral Index. Anesthesia was induced with alfentanil (30 µg.kg^-1) and propofol (3 mg.kg^-1). Atracurium (0.5 mg.kg^-1) and manual ventilation with 100% oxygen (O₂) were used to help tracheal intubation. Next, tracheal intubation was performed and capnography was installed. Heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure, oxygen saturation (SpO₂) and BIS were evaluated before anesthetic induction (M1) and after intubation, which was performed 3 minutes after induction (M2). Aiming at comparing groups and statistically studying results, HR, SBP, DBP and BIS were evaluated at M1 and M2.

Analysis of variance was adopted for age, weight and height, and profile analysis was used for HR, SBP, DBP and BIS, considering significant p < 0.05.

RESULTS

The three groups were homogeneous in weight, age and height (Table I). There were no statistically significant differences in SBP, DBP, HR and BIS when comparing the same moment (M1 or M2) among groups (G1, G2 and G3) (Table II).

When comparing moments within a same group, SBP and DBP for G1 and G3 were statistically higher in M1. HR was identical in both moments for all groups. BIS values were lower in M2 for all groups (Table II).

DISCUSSION

In our study, premedication with midazolam or clonidine has not influenced BIS-evaluated hypnosis level in children after anesthetic induction with propofol (3 mg.kg^-1) and alfentanil (30 µg.kg^-1).

Midazolam was chosen because it is the routine drug in our hospital, and clonidine for its desirable sedative effects ^3,8. Clonidine acts by activating locus coeruleus a₂-adrenergic receptors, suppressing their activity and resulting in increased inhibitory interneurons, such as those found in the gamma aminubutiric acid (GABA) way, determining central nervous system (CNS) depression ⁹. In a previous study in children premedicated with 0.5 mg.kg^-1 midazolam and 4 µg.kg^-1 clonidine identical levels of sedation and decreased anxiety were seen when clinical parameters were used to evaluate both medications ⁸.

Our study has evaluated patients by BIS values and it was observed that the presence and type of medication have not influenced hypnosis levels since BIS values were similar to those observed in non-premedicated children.

Although the lack of data on oral clonidine bioavailability in children ⁹, studies have shown that sedation is already present 30 minutes after 4 µg.kg^-1 oral clonidine and is intensified at 60 minutes ³. And 60 minutes was the interval between premedication and referral to the operating room, that is, enough time for the drug to be fully active.

The moment immediately after laryngoscopy and tracheal intubation was chosen to evaluate hypnosis level determined by propofol and alfentanil induction dose because such maneuvers trigger major stimuli and may lead to an increase in blood pressure, heart rate and circulating catecholamines in pediatric patients ¹⁰ when induction is inadequate to block such stimuli. Clonidine (4 µg.kg^-1) have prevented adverse hemodynamic effects caused by tracheal intubation, probably by decreasing circulating catecholamine levels ¹⁰. Alfentanil, for its fast onset, high safety margin and excellent hemodynamic stability is widely used for anesthetic induction in short pediatric procedures. In therapeutic doses, it determines analgesia, sedation and ansiolysis ¹¹.

In our study, SBP, DBP and HR associated to BIS were used aiming at obtaining additional clinical parameters to assure anesthetic induction quality. It was observed that SBP and DBP decreased after induction in non-premedicated patients and in those receiving clonidine. Clonidine action on the cardiovascular system may be peripheral and central. Pre-synaptic a₂-adrenergic receptors activation on peripheral nervous terminations inhibiting norepinephrine exocytosis partially explains drug’s hypotensive effects ¹²; however, the activation of pre-synaptic receptors in blood vessel muscles causes vasoconstriction ¹³. In the CNS, the activation of a₂-receptors decreases sympathetic eflux, increasing parasympathetic nervous activity and inducing hypotension ¹².

Midazolam has minor cardiocirculatory effects since benzodiazepines act in specific GABA_A sites which are exclusively located in CNS post-synaptic nervous terminations ¹⁴.

However, non-premedicated children have also shown decreased SBP and DBP, showing that propofol had a fundamental action in decreasing blood pressure. Propofol causes hypotension because it relaxes vessels’ smooth muscles by decreasing vasoconstrictor sympathetic response ¹⁵.

In conclusion, our results suggest that premedication with 0.5 mg.kg^-1 midazolam and 4 µg.kg^-1 clonidine have not increased the hypnotic effects of 3 mg.kg^-1 propofol associated to 30 µg.kg^-1 alfentanil for anesthetic induction in pediatric patients.

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Influencia de la medicación pré-anestésica con midazolam y clonidina en el nivel de hipnosis después de inducción anestésica con propofol y alfentanil en niños. Monitorización por el índice bispectral

Correspondence

Publication Dates

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

History

• Received
  16 Mar 2001
• Accepted
  08 Aug 2001