Services on Demand
Print version ISSN 0034-7094
On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.52 no.2 Campinas Mar./Apr. 2002
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
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 PETCO2, 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
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 yPETCO2, 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.
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.
After the Hospitals 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 PETCO2 readings, anesthetic agents analyzer, cardioscopy in DII 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.
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 PETCO2 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 PETCO2. 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; Tukeys test was used to compare a moment within the group and group within the moment, considering statistically significant p < 0.05.
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).
All SEF 95% values were considered statistically similar when comparing both groups (p > 0.05 - Figure 3).
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.
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).
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).
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).
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 Tukeys 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.
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 a2A, and a hypertensive response in high doses mediated by adrenoreceptors subtype a2B 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.
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).
01. Aantaa R, Jaakola ML, Kallio A et al - Reduction of the minimum alveolar concentration of isoflurane by dexmedetomidine. Anesthesiology, 1997;86:1055-1060. [ Links ]
02. Aantaa R, Scheinin M - Ahpha2-Adrenergic agents in anaesthesia. Acta Anaesthesiol Scand, 1993;37:433-448. [ Links ]
03. Prys-Roberts C - Anaesthesia: a practical or impractical construct? Br J Anaesth, 1987;59:1341-1345. [ Links ]
04. Rampil IJ - A primer for EEG signal processing in anesthesia. Anesthesiology, 1998;89:980-1002. [ Links ]
05. Schwender D, Daunderer M, Klasing S at al - Power spectral analysis of the electroencephalogram during increasing end-expiratory concentrations of isoflurane, desflurane and sevoflurane. Anaesthesia, 1998;53:335-342. [ Links ]
06. Schwender D, Daunderer M, Mulzer S et al - Spectral edge frequency of the electroencephalogram to monitor depth of anaesthesia with isoflurane or propofol. Br J Anaesth, 1996;77: 179-184. [ Links ]
07. Bloor BC, Ward DS, Belleville JP et al - Effects of intravenous dexmedetomidine in humans, II: hemodynamic changes. Anesthesiology, 1992;77:1134-1142. [ Links ]
08. Kallio A, Scheinin M, Koulu M et al - Effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on hemodynamic control mechanisms. Clin Pharmacol Ther, 1989;46:33-42. [ Links ]
09. Viby-Mogensen J, Engbaek J, Eriksson Ll et al - Good clinical research practice (GCRP) in pharmacodinamyc studies of neuromuscular blocking agents. Acta Anaesthesiol Scand, 1996;40:59-74. [ Links ]
10. Alkis N, Keçik Y, Oral Metal - Monitoring of cerebral oxygenation by spectroscopy and jugular bulb venous O2 saturation during carotid endarterectomy. Br J Anaesth, 1997;78:(A.52):15. [ Links ]
11. Hungria H - Otorrinolaringologia, 7ª Ed, Rio de Janeiro, Editora Guanabara Koogan SA, 1995;297-306. [ Links ]
12. Billard V, Gambus PL, Chamoun N et al - A comparison of spectral edge, delta power, and bispectral index as EEG measures of alfentanil, propofol, and midazolam drug effect. Clin Pharmacol Ther, 1997;61:45-58. [ Links ]
13. Bhana N, Goa KL, McClenllan KJ - Dexmedetomidine. Drugs, 2000;59:263-268. [ Links ]
14. Hall JE, Uhrich TD, Barney JA et al - Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg, 2000;93:699-705. [ Links ]
15. Guo TZ, Jiang JY, Buttermann AE et al - Dexmedetomidine injection into the locus ceruleus produces antinociception. Anesthesiology, 1997;84:873-881. [ Links ]
16. De Kock M, Crochet B, Morimont C et al - Intravenous or epidural clonidine for intra-and postoperative analgesia. Anesthesiology, 1993;79:525-531. [ Links ]
17. Schmeling WT, Ganjoo P, Staunton M - Pretreatment with dexmedetomidine: altered indices of anesthetic depth for halothane in the neuraxis of cats. Anesth Analg, 1999;88: 625-632. [ Links ]
18. Correa SC, Nacif CC, Reid K et al - Inhibition of adenylate cyclase in the locus ceruleus mediates the hypnotic response to alpha-2-agonist in the rat. J Pharmacol Exp Ther, 1992;236: 1046-1049. [ Links ]
19. Nacif CC, Correa SC, Chang LL et al - Perturbation of ion conductance in the locus ceruleus alters the hypnotic response to the alpha-2-adrenergic agonist dexmedetomidine in the locus ceruleus in rats. Anesthesiology, 1994;81:1527-1534. [ Links ]
20. Kamibayashi T, Maze M - Clinical uses of alpha-2-adrenergic agonists. Anesthesiology, 2000;93:1345-1349. [ Links ]
21. Lakhlani PP, MacMillan LB, Guo TZ et al - Substitution of a mutant alpha2A-adrenergic receptor via hit and run gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci USA, 1997;94:9950-9955. [ Links ]
22. McCallum JB, Boban N, Hogan Q et al - The mechanism of alpha-2-adrenergic inhibition of sympathetic ganglionic transmission. Anesth Analg, 1998;87:503-510. [ Links ]
23. Scholz J, Tonner PH - [alpha]-2-adrenoceptor agonists in anaesthesia: a new paradigm. Curr Opin Anaesthesiol, 2000;13: 437-442. [ Links ]
24. Link RE, Dessai K, Hein L et al - Cardiovascular regulation in mice lacking alpha-2-adrenergic receptor subtypes b and c. Science, 1996;273:803-305. [ Links ]
25. Ebert TJ, Hall JE, Barney JA et al - The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology, 2000;93:382-394. [ Links ]
26. Khan ZP, Ferguson CN, Jones RM - Alpha-2 - and imidazoline receptor agonists: their pharmacology and therapeutic role. Anaesthesia, 1999;54:146-165. [ Links ]
27. Benhamou D, Veillette Y, Narchi P et al - Ventilatory affects of premedication with clonidine. Anesth Analg, 1991;73: 799-803. [ Links ]
28. Ooi R, Pattison J, Feldman AS - The effects of intravenous clonidine on ventilation. Anaesthesia, 1991;46:632-633. [ Links ]
29. Penon C, Ecoffey C, Cohen SE - Ventilatory response to carbon dioxide after epidural clonidine injection. Anesth Analg, 1991;72:761-764. [ Links ]
30. Zornow MH - Ventilatory, hemodynamic and sedative effects of the alpha 2 adrenergic agonist, dexmedetomidine. Neuropharmacology, 1991;30:1065-1071. [ Links ]
31. Belleville JP, Ward DS, Bloor BC - Effects of intravenous dexmedetomidine in humans. Anesthesiology, 1992;77: 1125-1133. [ Links ]
32. Aantaa R, Kanto J, Scheinin M et al - Dexmedetomidine, an alpha-2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing gynecologic surgery. Anesthesiology, 1990;73:230-235. [ Links ]
33. Scheinin H, Jaakola ML, Sjovall S et al - Intramuscular dexmedetomidine as premedication for general anesthesia. Anesthesiology, 1993;78:1065-1075. [ Links ]
34. Erkola O, Korttila K, Aho M et al - A comparison of IM dexmedetomidine and midazolam premedication for elective abdominal hysterectomy. Anesth Analg, 1994;79:646-653. [ Links ]
35. Aho MS, Erkola O, Scheinin H et al - Effects of intravenously administered dexmedetomidine on pain after laparoscopic tubal ligation. Anesth Analg, 1991,73:112-118. [ Links ]
36. Ossipov MH, Harris S, Lloyd P et al - Antinociceptive interaction between opioids and dexmedetomidine: systemic addtivity and spinal synergy. Anesthesiology, 1990;73:1227-1235. [ Links ]
37. Aho M, Erkola O, Kallio A et al - Dexmedetomidine infusion for maintenance of anesthesia in patients undergoing abdominal hysterectomy. Anesth Analg, 1992;75:940-946. [ Links ]
38. Roizen MF, White PF, Eger EI et al - Effects of ablation of serotonin or norepinephine brain stem areas on halothane and cyclopropane MACs in rats. Anesthesiology, 1978;78:252-255. [ Links ]
39. Segal IS, Vickery RG, Walton JK et al - Dexmedetomidine diminishes halothane anesthetic requirements in rats through a postsynaptic alpha-2-adrenergic receptor. Anesthesiology, 1988;69:818-823. [ Links ]
40. Buhrer M, Mappes A, Lauber R et al - Dexmedetomidine decreases thiopental dose requirement and alters distribution pharmacokinetics. Anesthesiology, 1994;80:1216-1227. [ Links ]
41. Bachand R, Scholz J, Pinaud M et al - The effects of dexmedetomidine in patients in the intensive care setting. Intensive Care Med, 1999;25:(Suppl1):S160. [ Links ]
42. Mantz J, Goldfarb G, Lehot J-J et al - Dexmedetomidine efficacy for ICU postoperative sedation. Anesthesiology, 1999;V91: A197. [ Links ]
43. Fragen RJ, Fitzgerald PC - Effect of dexmedetomidine on the minimum alveolar concentration (MAC) of sevoflurane in adults age 55 to 70 years. J Clin Anesth, 1999;11:466-470. [ Links ]
44. Brown DV, Avramov MN, Tuman KJ et al - The effect of dexmedetomidine on EEG-bispectral index. Anesth Analg, 1999;88:52S. [ Links ]
Submitted for publication July 10, 2001
Accepted for publication October 16, 2001
* Received from Serviço de Anestesiologia do São Lucas - Hospital de Cirurgia e Anestesia, Fortaleza, CE