Influence of dexmedetomidine upon sevoflurane end-expiratory concentration: evaluation by bispectral index, suppression rate and electroencephalographic power spectral analysis

Abstracts

BACKGROUND AND OBJECTIVES: Dexmedetomidine, an alpha2-adrenergic agonist, has been described as being able to decrease the demand for both venous and inhalational agents. This study aimed at evaluating the influence of Dexmedetomidine upon sevoflurane end-expiratory concentration (EC) with monitoring the depth of anesthesia. METHODS: Participated in this study 40 female adult patients, physical status ASA I, submitted to gynecological laparoscopy under general anesthesia maintained with sevoflurane, who were randomly divided in two groups: Group I (n=20), without dexmedetomidine; and Group II (n=20), with dexmedetomidine, in continuous infusion, as follows: Rapid phase (1 µg.kg-1 in 10 min-1) 10 minutes before anesthesia induction, followed by a maintenance phase (0,4 µg.kg-1.h-1) throughout the surgery. The following parameters were analyzed: BP, HR, BIS, SEF 95%, delta%, suppression rate (SR), rSO2, CE, SpO2 and P ET CO2, in the following moments: M1 - before dexmedetomidine or 0.9% saline infusion; M2 - prior to intubation; M3 - following intubation; M4 - before incision; M5 - following incision; M6 - before CO2 inflation; M7 - following CO2 inflation; M8 - 10 min after CO2 inflation; M9 - 10 min after M8; M10 - 20 min after M8; M11 - 30 min after M8; M12 - 40 min after M8; and M13 - at emergence. Time for emergence and hospital discharge were also recorded. RESULTS: Dexmedetomidine has decreased sevoflurane end-expiratory concentration from M4 to M13 (p<0.05) when comparing Group I and Group II. No clinically significant changes were observed in hemodynamic parameters. Time for emergence in Groups I and II was 11 ± 0.91 min. and 6.35 ± 0.93 min., respectively (p < 0.05). Time for hospital discharge was 7.45 ± 0.69 h in Group I and 8.37 ± 0.88 h in Group II (p < 0.05). CONCLUSIONS: Dexmedetomidine was effective in decreasing sevoflurane end-expiratory concentration while maintaining hemodynamic stability without impairing time for hospital discharge, in addition to promoting an earlier emergence.

ANALGESICS; ANESTHETICS, Volatile; MONITORING; MONITORING; MONITORING; MONITORING

JUSTIFICATIVA E OBJETIVOS: A dexmedetomidina, um alfa2-agonista adrenérgico, tem sido descrita como capaz de reduzir o consumo tanto de agentes venosos como inalatórios. O objetivo deste estudo foi avaliar a influência da dexmedetomidina na concentração expirada (CE) do sevoflurano, com monitorização da profundidade da anestesia. MÉTODO: Participaram do estudo 40 pacientes do sexo feminino, estado físico ASA I, submetidas à laparoscopia ginecológica sob anestesia geral mantida com sevoflurano, divididas aleatoriamente em dois grupos: Grupo I (20): sem dexmedetomidina, e Grupo II (20): com dexmedetomidina em infusão contínua no seguinte esquema: Fase rápida (1 µg.kg-1 em 10 minutos), 10 minutos antes da indução da anestesia, seguida por uma fase de manutenção (0,4 µg.kg-1.h-1) até o final da cirurgia. Foram analisados os seguintes parâmetros: PA, FC, BIS, SEF 95%, amplitude relativa na freqüência de banda delta (delta %), taxa de supressão (TS), rSO2, CE, SpO2 e P ET CO2, nos seguintes momentos: M1 - antes da infusão da dexmedetomidina ou solução fisiológica a 0,9%, M2: antes da intubação traqueal (IT), M3: após a IT, M4: antes da incisão, M5: após a incisão, M6: antes da insuflação do CO2, M7: após a insuflação de CO2, M8: 10 minutos após a insuflação de CO2, M9: 10 min após M8, M10: 20 min após M8, M11: 30 min após M8, M12: 40 min após M8 e M13: ao despertar. Anotamos também o tempo de despertar e de alta hospitalar. RESULTADOS: A dexmedetomidina reduziu a concentração expirada de sevoflurano de M4 até M13 (p<0,05), comparando-se GI e GII. Não foram observadas mudanças clinicamente significativas nos parâmetros hemodinâmicos. O tempo de despertar no GI foi 11 ± 0,91 minutos e no GII foi 6,35 ± 0,93 minutos (p < 0,05). O tempo de alta hospitalar no GI foi 7,45 ± 0,69 horas e no GII foi 8,37 ± 0,88 horas (p < 0,05). CONCLUSÕES: A dexmedetomidina é efetiva em reduzir a concentração expirada do sevoflurano, mantendo estabilidade hemodinâmica, sem comprometer o tempo de alta hospitalar, além de promover um despertar mais precoce.

ANALGÉSICOS; ANESTÉSICOS, Volátil; MONITORIZAÇÃO; MONITORIZAÇÃO; MONITORIZAÇÃO; MONITORIZAÇÃO

JUSTIFICATIVA Y OBJETIVOS: La dexmedetomidina, un alfa2-agonista adrenérgico, ha sido descrita como capaz de reducir el consumo tanto de agentes venosos como inhalatorios. El objetivo de este estudio fue evaluar la influencia de la dexmedetomidina en la concentración expirada (CE) de sevoflurano, con monitorización de la profundidad de la anestesia. MÉTODO: Participaron del estudio 40 pacientes del sexo femenino, estado físico ASA I, sometidas a laparoscopia ginecológica bajo anestesia general mantenida con sevoflurano, divididas aleatoriamente en dos grupos: Grupo I (20): sin dexmedetomidina, y Grupo II (20): con dexmedetomidina en infusión continua en el siguiente esquema: Fase rápida (1 µg.kg-1 en 10 minutos), 10 minutos antes de la inducción de la anestesia, seguida por un periodo de manutención (0,4 µg.kg-1.h-1) hasta el final de la cirugía. Fueron analizados los siguientes parámetros: PA, FC, BIS, SEF 95%, amplitud relativa en la frecuencia de banda delta (delta%), tasa de supresión (TS), rSO2, CE, SpO2 yP ET CO2, en los siguientes momentos: M1 - antes de la infusión de la dexmedetomidina o solución fisiológica a 0,9%, M2: antes de la intubación traqueal (IT), M3: después a IT, M4: antes de la incisión, M5: después de la incisión, M6: antes de la insuflación de CO2, M7: después de la insuflación de CO2, M8: 10 minutos después de la insuflación de CO2, M9: 10 min. después M8, M10: 20 min después M8, M11: 30 min después M8, M12: 40 min después M8 y M13: al despertar. Anotamos también el tiempo de despertar y de alta hospitalar. RESULTADOS: La dexmedetomidina redució la concentración expirada de sevoflurano de M4 hasta M13 (p < 0,05), comparándose GI y GII. No fueron observados cambios clínicamente significativos en los parámetros hemodinámicos. El tiempo de despertar en el GI fue 11 ± 0,91 minutos y en el GII fue 6,35 ± 0,93 minutos (p < 0,05). El tiempo de alta hospitalar en el GI fue 7,45 ± 0,69 horas y en el GII fue 8,37 ± 0,88 horas (p < 0,05). CONCLUSIONES: La dexmedetomidina es efectiva en reducir la concentración expirada del sevoflurano, manteniendo estabilidad hemodinámica, sin comprometer el tiempo de alta hospitalar, además de promover un despertar mas precoz.

SCIENTIFIC ARTICLE

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by bispectral index, suppression rate and electroencephalographic power spectral analysis^*

Influencia de la dexmedetomidina en la concentración expirada del sevoflurano. Evaluación por el índice bispectral, tasa de supresión y análisis espectral de la potencia del eletroencefalograma

Rogean Rodrigues Nunes, TSA, M.D.^I; Sara Lúcia Cavalcante, TSA, M.D.^II

^IDiretor Clínico e Chefe do Serviço de Anestesiologia do São Lucas - Hospital de Cirurgia e Anestesia; Mestre em Cirurgia pela Faculdade de Medicina da Universidade Federal do Ceará

^IICoordenadora do Centro de Estudos do São Lucas - Hospital de Cirurgia e Anestesia

^{Correspondence}

SUMMARY

BACKGROUND AND OBJECTIVES: Dexmedetomidine, an a₂-adrenergic agonist, has been described as being able to decrease the demand for both venous and inhalational agents. This study aimed at evaluating the influence of Dexmedetomidine upon sevoflurane end-expiratory concentration (EC) with monitoring the depth of anesthesia.

METHODS: Participated in this study 40 female adult patients, physical status ASA I, submitted to gynecological laparoscopy under general anesthesia maintained with sevoflurane, who were randomly divided in two groups: Group I (n=20), without dexmedetomidine; and Group II (n=20), with dexmedetomidine, in continuous infusion, as follows: Rapid phase (1 µg.kg^-1 in 10 min^-1) 10 minutes before anesthesia induction, followed by a maintenance phase (0,4 µg.kg^-1.h^-1) throughout the surgery. The following parameters were analyzed: BP, HR, BIS, SEF 95%, d %, suppression rate (SR), rSO₂, CE, SpO₂ and P_ETCO₂, in the following moments: M₁ - before dexmedetomidine or 0.9% saline infusion; M₂ - prior to intubation; M₃ - following intubation; M₄ - before incision; M₅ - following incision; M₆ - before CO₂ inflation; M₇ - following CO₂ inflation; M₈ - 10 min after CO₂ inflation; M₉ - 10 min after M₈; M₁₀ - 20 min after M₈; M₁₁ - 30 min after M₈; M₁₂ - 40 min after M₈; and M₁₃ - at emergence. Time for emergence and hospital discharge were also recorded.

RESULTS: Dexmedetomidine has decreased sevoflurane end-expiratory concentration from M₄ to M₁₃ (p<0.05) when comparing Group I and Group II. No clinically significant changes were observed in hemodynamic parameters. Time for emergence in Groups I and II was 11 ± 0.91 min. and 6.35 ± 0.93 min., respectively (p < 0.05). Time for hospital discharge was 7.45 ± 0.69 h in Group I and 8.37 ± 0.88 h in Group II (p < 0.05).

CONCLUSIONS: Dexmedetomidine was effective in decreasing sevoflurane end-expiratory concentration while maintaining hemodynamic stability without impairing time for hospital discharge, in addition to promoting an earlier emergence.

Key words: ANALGESICS: dexmedetomidine; ANESTHETICS, Volatile: sevoflurane; MONITORING: electroencefalography, bispectral index, SEF 95%, power spectral analysis

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La dexmedetomidina, un a₂-agonista adrenérgico, ha sido descrita como capaz de reducir el consumo tanto de agentes venosos como inhalatorios. El objetivo de este estudio fue evaluar la influencia de la dexmedetomidina en la concentración expirada (CE) de sevoflurano, con monitorización de la profundidad de la anestesia.

MÉTODO: Participaron del estudio 40 pacientes del sexo femenino, estado físico ASA I, sometidas a laparoscopia ginecológica bajo anestesia general mantenida con sevoflurano, divididas aleatoriamente en dos grupos: Grupo I (20): sin dexmedetomidina, y Grupo II (20): con dexmedetomidina en infusión continua en el siguiente esquema: Fase rápida (1 µg.kg^-1 en 10 minutos), 10 minutos antes de la inducción de la anestesia, seguida por un periodo de manutención (0,4 µg.kg^-1.h^-1) hasta el final de la cirugía. Fueron analizados los siguientes parámetros: PA, FC, BIS, SEF 95%, amplitud relativa en la frecuencia de banda delta (d%), tasa de supresión (TS), rSO₂, CE, SpO₂ yP_ETCO₂, en los siguientes momentos: M₁ - antes de la infusión de la dexmedetomidina o solución fisiológica a 0,9%, M₂: antes de la intubación traqueal (IT), M₃: después a IT, M₄: antes de la incisión, M₅: después de la incisión, M₆: antes de la insuflación de CO₂, M₇: después de la insuflación de CO₂, M₈: 10 minutos después de la insuflación de CO₂, M₉: 10 min. después M₈, M₁₀: 20 min después M₈, M₁₁: 30 min después M₈, M₁₂: 40 min después M₈ y M₁₃: al despertar. Anotamos también el tiempo de despertar y de alta hospitalar.

RESULTADOS: La dexmedetomidina redució la concentración expirada de sevoflurano de M₄ hasta M₁₃ (p < 0,05), comparándose GI y GII. No fueron observados cambios clínicamente significativos en los parámetros hemodinámicos. El tiempo de despertar en el GI fue 11 ± 0,91 minutos y en el GII fue 6,35 ± 0,93 minutos (p < 0,05). El tiempo de alta hospitalar en el GI fue 7,45 ± 0,69 horas y en el GII fue 8,37 ± 0,88 horas (p < 0,05).

CONCLUSIONES: La dexmedetomidina es efectiva en reducir la concentración expirada del sevoflurano, manteniendo estabilidad hemodinámica, sin comprometer el tiempo de alta hospitalar, además de promover un despertar mas precoz.

INTRODUCTION

The association of different adjuvant drugs and anesthesia is becoming very popular due to their anxiolytic, analgesic or hypnotic properties. Alpha₂-agonists, for presenting all those properties, are useful in anesthesiology. Dexmedetomidine is a specific a₂-adrenergic very useful in intensive care and anesthesia for decreasing the need for several anesthetic agents ¹. Several clinical studies with dexmedetomidine have evaluated anesthesia depth almost exclusively through hemodynamic parameters ². So, since a₂-agonists directly interfere with the autonomous nervous system, responses such as heart rate and blood pressure increase may not be dependable criteria to evaluate anesthesia depth³. Reviewing the literature, no studies were found relating the synergistic effect (continuous infusion) of dexmedetomidine plus sevoflurane to anesthetic depth evaluation through bispectral index (BIS), EEG, power spectral analysis in SEF 95% and suppression rate analysis (SR) ^4-6.

This study aimed at evaluating the influence of intravenous dexmedetomidine in inhalational anesthesia with sevoflurane in adults, using BIS, SEF 95% and SR as anesthetic depth parameters.

METHODS

After the Hospital’s Medical Ethics Committee approval, participated in this double-blind study 40 female patients, aged 20 to 40 years, physical status ASA I, body mass index between 22 and 28, submitted to gynecologic laparoscopy (oophorectomy or myomectomy). Exclusion criteria were pregnancy, anemia, drug abuse, more than 30 g alcohol consumption per day and electrolytic changes at preoperative evaluation.

Patients were randomly distributed in two groups. Group I (n = 20) - submitted to general anesthesia without dexmedetomidine; and Group II (n = 20) - submitted to general anesthesia with intravenous dexmedetomidine.

Patients were not premedicated. All patients were monitored in the operating room with sphygmomanometer to automatically check systolic (SBP) and diastolic (DBP) blood pressure, heart rate (HR), pulse oximetry for hemoglobin peripheral saturation, brain regional hemoglobin saturation (rSO₂), capnography for P_ETCO₂ readings, anesthetic agents analyzer, cardioscopy in D_II and V5, BIS, SEF 95% in two channels, relative amplitude in delta band frequency (d%) in two channels, and SR.

After venous puncture, 8 µg.kg^-1 intravenous atropine was injected to prevent bradycardia during dexmedetomidine rapid infusion ^7,8. A total volume of 50 ml of 0.9% saline was prepared for Group I. Group II received dexmedetomidine in 50 ml saline in a final concentration of 4 µg.ml^-1. A dose of 1 µg.kg^-1 in continuous infusion was administered in 10 minutes (rapid phase) and was followed by an infusion dose corresponding to 0.4 µg.kg^-1 (maintenance) until the end of surgery (end of dressing). In Group I, saline was also administered in continuous infusion, following the same steps as Group II. Anesthesia was induced immediately after the 10 minutes of drug infusion (dexmedetomidine or 0.9% saline) with oxygen under mask during 5 minutes for both groups. Intravenous 0.8 µg.kg^-1 sufentanil , propofol until BIS = 30 and intravenous 0.15 mg.kg^-1 cisatracurium for 5 minutes to help tracheal intubation (TI) were also administered. Anesthetic depth was obtained through EEG with silver chloride electrodes distributed in two channels (F7 and F8), associated to reference (Fz) and ground (Fp1) (Figure 1). Impedance test was performed and readings were started when impedance reached 2KW while maintaining patients with their eyes closed. The following EEG parameters were evaluated: BIS, power spectral analysis through spectral edge frequency 95% (SEF - 95%), d % and SR defined as time percentage in the last 63 seconds when EEG has recorded amplitudes below 5 microvolts (low amplitude: deep anesthesia) ⁴.

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Tracheal intubation was performed in both groups when BIS = 30. Neuromuscular block monitoring was achieved with a specific monitor with acceleromyography and TOF stimulation was obtained at every 14 seconds. Extubation was scheduled for T4/T1 equal to 0.9 or above ⁹. Respiratory rate was adjusted after TI to maintain P_ETCO₂ between 35 and 40 mmHg, with a tidal volume of 8 ml.kg^-1. Ventilation was performed in a circle system with CO₂ reabsorber and 1 L.min^-1 O₂ flow. Sevoflurane was sprayed through a specific vaporizer. Perioperatively, sevoflurane end-expiratory concentrations were adjusted to maintain BIS between 40 and 60 and SEF below 14 Hz ⁶. At the end of the procedure the same respiratory rate was maintained, sevoflurane and dexmedetomidine were withdrawn and O₂ flow was increased to 7 L.min^-1 using a ventilator with patency loss compensator.

The following moments were clinically and statistically evaluated: M₁ - before dexmedetomidine or 0.9% saline infusion; M₂ - prior to intubation; M₃ - following intubation; M₄ - before incision; M₅ - following incision; M₆ - before CO₂ inflation; M₇ - following CO₂ inflation; M₈ - 10 min after CO₂ inflation; M₉ - 10 min after M₈; M₁₀ - 20 min after M₈; M₁₁ - 30 min after M₈; M₁₂ - 40 min after M₈; and M₁₃ - at emergence. The following parameters were evaluated for all moments: SBP, DBP, HR, rSO₂ (brain regional hemoglobin saturation - measured with a specific device and considering normal variations between 60 and 80 with a sensor adapted on the frontal region) ¹⁰, BIS, SEF 95%, d%, suppression rate (SR), CE, SpO₂ and P_ETCO₂. Nasopharyngeal temperature was maintained between 36 and 37 ºC in all patients, with the help of a forced convective hot air thermal blanket.

Emergence was considered as time elapsed between inhaled anesthetics and dexmedetomidine or 0.9% saline withdrawal until BIS equal to 90 or above. Surgery duration was considered as time elapsed from incision until dressing completion. Anesthesia duration was considered as time elapsed from dexmedetomidine infusion until tracheal extubation. Lower hemodynamic parameters limits were: SBP = 80 mmHg, DBP = 50 mmHg. Upper SBP and DBP limits were considered statistically significant when 20% above baseline. HR 25% above baseline was considered clinically significant. Respiratory rates below 8 cycles per minute (considered as respiratory depression) were also recorded both during dexmedetomidine rapid infusion and during the first 4 postoperative hours.

Time for discharge and interval between tracheal extubation and satisfactory Romberg were also evaluated, being the latter applied by asking the patient to remain standing up, still, with feet close together and eyes closed. Test was considered satisfactory when patients were able to maintain this posture for one minute ¹¹. The test was performed at 15-minute intervals and was started 10 minutes after patients being able to sit without help. Analysis of variance for repeated measures with two classification factors (group and moment) was the statistical method applied; Tukey’s test was used to compare a moment within the group and group within the moment, considering statistically significant p < 0.05.

RESULTS

Both groups were homogeneous in age, weight, physical status, height and gender (Table I). HR, SBP and DBP are shown in table II. BIS, SEF 95%, d% and CE are shown in table III.

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

There is a significant BIS difference in the interactive effect moment-group for significance levels below 5% in the following moments: M₃, M₄, M₅, M₆, M₇, M₈ and M₉, however without variations beyond pre-established limits for anesthesia maintenance (Figure 2).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

All SEF 95% values were considered statistically similar when comparing both groups (p > 0.05 - Figure 3).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Except for moments M₁ and M₁₃ (emergence), there has been a significant d% increase in all remainder moments for both groups (Figure 4), reflecting a relative power increase in this band frequency, which is compatible with deep hypnosis levels ^5,12.

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

With regard to hemodynamic parameters, there is a significant SBP difference (p < 0.05) in the interactive effect moment-groups (I and II) in the following moments: M₂, M₄, M₆, M₇ and M₈. No group, however, went below 80 mmHg (Figure 5). Analysis by moment between groups has shown a significant DBP difference in M₃, however no values below 50 mmHg were observed (Figure 6).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Except for M₁, HR showed significant levels below 5% in all moments, with lower values for Group II. However, there were no values beyond the clinical limits defined in this study (Figure 7).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

There were no significant differences in rSO₂ when comparing both groups in each moment (p > 0.05), or when comparing each group separately (p < 0.05) (Figure 8).

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Hemoglobin peripheral saturation for both groups remained above 96%.

Groups analysis of variance has shown a significant CE difference by group, by moment and by moment versus group (p < 0.05). At Tukey’s test, it was observed that within each moment both groups showed significant differences in all moments as from M₄, with lower values for Group II (p < 0.05) - (Table III and Figure 9). Anesthesia duration was 117 ± 7.1 minutes for Group I, and 113.55 ± 5.56 minutes for Group II (p > 0.05). Surgery duration was 81.8 ± 4.81 for Group I, and 74.5 ± 7.2 minutes for Group II (p < 0.05). Emergence time was 11 ± 0.91 minutes for Group I and 6.35 ± 0.93 minutes for Group II (p < 0.05) (Table IV). All patients were in conditions for tracheal extubation soon after emergence. Hospital discharge time was 7.45 ± 0.69 hours for Group I, and 8.37 ± 0.88 hours for Group II (p < 0.05), without clinical relevance.

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

Brazilian Journal of Anesthesiology, 2002; 52: 2: 133-145

Influence of dexmedetomidine upon sevoflurane end-expiratory concentration. Evaluation by

bispectral index, suppression rate and electroencephalographic power spectral analysis

Rogean Rodrigues Nunes; Sara Lúcia Cavalcante

DISCUSSION

Dexmedetomidine is a selective a₂-agonist (T ½ b of 2 hours) with potent analgesic and sedative action and 8 times higher affinity for a₂-adrenoreceptors as compared to clonidine ¹³. Central a₂-adrenoreceptors in the locus ceruleus and spinal cord dorsal horn are probably involved in such effects ^14-16. Some studies report that dexmedetomidine has a differential anesthetic action when subcortical (CAM and CAM bar) and telencephalic regions are compared, the latter evaluated by anesthetic depth rates (CAM bs and CAM isoe), observing that such differential actions may be a consequence of a₂-adrenergic receptors distribution or of differences in receptors binding ability ¹⁷. More specifically, hypnotic action mechanisms have been attributed to adenylcyclase inhibition with changes in transmembrane ion conduction and neural cell hyperpolarization ^1,18,19. A two-phase cardiovascular response has been described when an intravenous dexmedetomidine bolus is administered. So, low-dose a₂-agonists have a predominantly sympathicolytic action mediated by adrenergic receptors subtype a_2A, and a hypertensive response in high doses mediated by adrenoreceptors subtype a_2B^20-24. Previous studies have shown than when 1 µg.kg^-1 bolus demedetomidine was administered, a transient blood pressure increase was observed, and some authors ^7,25 recommend to avoid bolus doses. Other authors ²⁶ indicate the routine use of anticholinergics associated to a₂-agonist adrenoreceptors. Respiratory effects of dexmedetomidine have been widely discussed and the consensus seems to be that it promotes only mild respiratory depression ^14,27-30. However, obstructive apnea may be seen when high doses are infused in a short period (2 min) ³¹ as a consequence of deep sedation, because a₂-adrenoreceptors do not play an active role in the respiratory center. Irregular breathing, mild hypoxemia and hypercarbia have also been reported. Some authors have shown that dexmedetomidine decreases the need for thiopental ³², fentanyl ³³ and isoflurane ^34,35, with a major additive subcortical effect between opioids and demedetomidine³⁶ which would be responsible for the CAM decreasing effect of inhaled anesthetics. Aho et al. ³⁷ have reported that intravenous dexmedetomidine during hysterectomies has decreased sevoflurane consumption in 90%. Other authors have shown that after total noradrenergic transmission suppression, there has been a 40% halothane CAM decrease ³⁸, which reached 90% when dexmedetomidine was infused, thus suggesting an additional anesthetic action mechanism by this additional decrease ³⁹. There are also evidences that dexmedetomidine changes intravenous agents distribution, possibly due to a decrease in cardiac output ⁴⁰. Studies have also shown that dexmedetomidine significantly decreases midazolam or propofol consumption ^41,42 as compared to placebo in patients under mechanical ventilation and sedation. Recent studies with dexmedetomidine have shown a sevoflurane CAM decrease of 17% in adults aged 55 to 70 years ^23,43, as compared to halothane CAM decrease of 90%. Dexmedetomidine-induced halothane CAM decrease is much higher than clonidine ²³, probably due to the higher specificity of dexmedetomidine for a₂-adrenoreceptors. Several studies have used hemodynamic parameters to evaluate anesthesia depth, which may change with risk for emergence when coadjuvant drugs, such as dexmedetomidine, which acts directly on the cardiovascular system promoting hypotension and bradycardia ¹ are used. In our study, BIS monitoring allowed for maintaining anesthetic depth within a standard variation, since BIS was considered adequate to measure dexmedetomidine sedative action ⁴⁴. In addition, other EEG parameters, such as power spectral analysis (SEF 95%), d % evaluation and SR estimate ^4,5,12 were used in an attempt to obtain more dependable data on BP, HR, CE and emergence time. In both groups, BP and HR variations have not gone beyond upper or lower limits, although statistically significant differences in moments M₂, M₄, M₆, M₇ and M₈ when comparing SBP between groups (Figure 5). There were also statistically significant DBP differences in moment M₃ (Figure 6). HR presented most important variations with lower values for group II as compared to group I in all moments (p < 0.05), except for M₁ (Table II and Figure 7). Such hemodynamic variations have not reflected brain hemoglobin regional saturation changes (Figure 8). Suppression rate was zero in all moments, showing that voltages below 5 uV were not recorded in any EEG channel (1 and 2), which would represent a too deep anesthesia. CE analysis, measured as from M₄ (immediately before incision), showed statistically significant differences when comparing means for both groups in all corresponding moments, with a 58.22% decrease in sevoflurane CAM for group II as compared to group I (Table III and Figure 9). Our data are in disagreement with other authors who have shown just a 17% decrease in sevoflurane CAM ⁴³.

Groups were significantly different in emergence time with means of 11 ± 0.91 minutes for group I, and 6 ± 0.93 minutes for group II (p < 0.05). In addition, no respiratory depression was seen during rapid dexmedetomidine infusion or in the postoperative period evaluated up to 4 hours after tracheal extubation. Some authors ²⁶ consider inconvenient the sedative effect of a₂-agonists for outpatient procedures, but in 8.37 ± 0.88 hours all group II patients were able to maintain Romberg test-based balance, considered, in this study as final criteria for hospital discharge. Time for discharge in group I, using the same criteria, was 7.45 ± 0.69 hours, without clinical relevance although statistically significant (p < 0.05).

In conclusion, dexmedetomidine, in the doses used in this study, has caused a significant sevoflurane consumption decrease in young patients, without clinically significant differences in hemodynamic parameters and promoting an earlier emergence in addition to time to hospital discharge compatible to outpatient procedures, and is a good choice both for intravenous agents association ^41,42 and sevoflurane.

ACKNOWLEDGEMENTS

This paper counted on the invaluable support of Tulius Augustus Ferreira de Freitas, M.D. (TEGO) and Fábio Eugênio Magalhães Rodrigues, M.D. (TEGO), both sterility specialists, and of the Board of Directors of São Lucas Hospital, Salustiano Gomes de Pinho Pessoa, M.D. and Lucas de Castro Pamplona (plastic surgeon).

REFERENCES

Submitted for publication July 10, 2001

Accepted for publication October 16, 2001

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Correspondence to

Dr. Rogean Rodrigues Nunes

Rua Gothardo Moraes 7797/1201 - Bl Dunas - Papicu

60190-800 Fortaleza, CE

^*

Received from Serviço de Anestesiologia do São Lucas - Hospital de Cirurgia e Anestesia, Fortaleza, CE

Publication Dates

• Publication in this collection
  08 Nov 2006
• Date of issue
  Apr 2002

History

• Received
  10 July 2001
• Accepted
  16 Oct 2001