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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.54 no.2 Campinas Mar./Apr. 2004
Remifentanil versus dexmedetomidine as coadjutants of standardized anesthetic technique in morbidly obese patients*
Remifentanil versus dexmedetomidina como coadyuvantes de técnica anestésica de modelo en pacientes con obesidad mórbida
Eliana Cristina Murari Sudré, TSA, M.D.I; Maria do Carmo Salvador, M.D.II; Giuseppina Elena Bruno, M.D.II; Dalton Valentim Vassallo, M.D.III; Gabriela Rocha Lauretti, M.D.IV; Gilberto Neves Sudré Filho, M.D.V
IResponsável pelo CET/SBA AFECC
- Hospital Santa Rita de Cássia; Mestre em Ciências Fisiológicas
IIMédica Assistente, Anestesiologista no Hospital Metropolitano
IIIProfessor Doutor do Programa de Pós-Graduação do Departamento de Ciências Fisiológicas da FMUFES e EMESCAM
IVProfessora Livre Docente do Departamento de Biomecânica, Medicina e Reabilitação do Aparelho Locomotor - FMRP-USP
VProfessor Titular da Disciplina de Sistemas Operacionais do Curso de Sistema de Informação da FAESA - Faculdades Integradas Espiritossantenses
BACKGROUND AND OBJECTIVES: Two coadjuvant
anesthetic drugs - remifentanil and dexmedetomidine - were compared in terms
of anesthetic recovery, arterial pH and PaCO2 evolution, in morbidly
obese patients submitted to Capellas surgery.
METHODS: Participated in this prospective, randomized and double blind study 92 patients divided in two groups and submitted to standardized anesthetic technique (general/epidural). Remifentanil Group (Group R) and Dexmedetomidine Group (Group D) received continuous intravenous infusion of these drugs (0.1 µg.kg-1.min-1 and 0.5 µg.kg-1.h-1, ideal body weight plus 30% for both) immediately after tracheal intubation. Monitoring consisted of invasive mean blood pressure, pulse oximetry, BIS EEG, capnography, peripheral nerve stimulator and EKG. The following parameters were evaluated: 1) different anesthetic recovery times (eye opening, return to spontaneous ventilation, tracheal extubation time, time for post anesthetic recovery unit and hospital discharge); 2) arterial blood gas analysis evolution; and 3) postoperative analgesia.
RESULTS: Evaluation was possible in 88 patients. Patients group R had earlier eye opening (9.49 ± 5.61 min versus 18.25 ± 10.24 min, p < 0.0001), faster return to spontaneous ventilation (9.78 ± 5.80 min versus 16.58 ± 6.07 min, p < 0.0001), and earlier tracheal extubation (17.93 ± 10.39 min versus 27.53 ± 13.39 min, p < 0.0001). There were no differences in times for post-anesthetic recovery unit (105.18 ± 50.82 min versus 118.69 ± 56.18 min) and hospital (51.13 ± 6.37 hours versus 52.50 ± 7.09 hours) discharge. Both groups showed arterial pH and PaO2 decrease immediately after tracheal extubation as compared to preoperative values, still present at PACU discharge. Group D patients showed higher arterial PaCO2 after tracheal extubation, as compared to preoperative values in the same group (p < 0.05), and opposed to Group R. 41% of Group R and 60% Group D patients (p < 0.02) required rescue analgesia during the first postoperative day.
CONCLUSIONS: In the studied population, the association of remifentanil to standardized anesthetic technique has resulted in faster anesthetic recovery, stability of preoperative arterial PaCO2 values during the immediate postoperative period and lower postoperative rescue analgesics consumption, as compared to dexmedetomidine.
Key Words: ANALGESICS: Opioids: remifentanil; DISEASES: morbid obesity; DRUGS, a2-agonist: dexmedetomidine
JUSTIFICATIVA Y OBJETIVOS: Comparamos
la acción de dos drogas coadyuvantes de la anestesia, remifentanil y
dexmedetomidina, en la recuperación anestésica y en la evolución
del pH y de la PaCO2, en pacientes con obesidad mórbida que
fueron sometidos a cirugía de Capella.
MÉTODO: El estudio fue aleatorio, prospectivo y duplamente encubierto. Noventa y dos pacientes fueron designados a uno de dos grupos y sometidos a la técnica anestésica (general/peridural) de modelo. El grupo Remifentanil (Grupo R) y el de la dexmedetomidina (Grupo D) recibieron infusión continua por vía venosa de estas drogas (0,1 µg.kg-1.min-1 y 0,5 µg.kg-1.h-1 peso ideal más 30% para ambas) luego después de la intubación traqueal. Los pacientes fueron monitorizados con presión arterial media invasiva, oximetría de pulso, BIS, capnografia, estimulador de nervio periférico y electrocardiograma. Fueron evaluados: 1) diferentes tiempos de recuperación anestésica (abertura de los ojos, reinicio de la respiración espontanea, tiempo de extubación traqueal, tiempo para el alta de la sala de recuperación pos-anestésica y hospitalar), 2) la evolución de la gasometria arterial, y 3) analgesia pos-operatoria.
RESULTADOS: Ochenta y ocho pacientes fueron evaluados. Los pacientes del grupo R presentaron abertura ocular mas precoz (9,49 ± 5,61 min versus 18,25 ± 10,24 min, p < 0,0001), menor tiempo para reiniciar la ventilación espontanea (9,78 ± 5,80 min versus 16,58 ± 6,07 min, p < 0,0001), y menor tiempo para la extubación traqueal (17,93 ± 10,39 min versus 27,53 ± 13,39 min, p < 0,0001). No hubo diferencia cuanto al tiempo para el alta anestésica (105,18 ± 50,82 min versus 118,69 ± 56,18 min) y para el alta hospitalar (51,13 ± 6,37 horas versus 52,50 ± 7,09 horas). Los dos grupos presentaron disminución de los valores de pH y de la PaO2 inmediatamente después la extubación traqueal cuando comparados con los valores pre-operatorios, hasta la alta de la sala de recuperación pos-anestésica. El grupo D presentó valores mayores de PaCO2 después de la extubación traqueal, comparado con valores pre-operatorios en el mismo grupo (p < 0,05), divergente del Grupo R; 41% de los pacientes del Grupo R y 60% del Grupo D (p < 0,02) solicitaron medicación analgésica de rescate en el primer día de pos-operatorio.
CONCLUSIONES: En la población evaluada, la asociación de remifentanil en técnica anestésica de modelo resultó en recuperación anestésica mas rápida, manutención de los valores de PaCO2 durante el período pos-operatorio inmediato y menor consumo de analgésicos de rescate en el período pos-operatorio, cuando comparada a la dexmedetomidina.
Morbidly obese patients are at high risk for perioperative cardiopulmonary dysfunction and mortality due to decreased pulmonary volume and compliance and to increased oxygen consumption, which are responsible for a high incidence of atelectasis and hypoxemia 1. Optimal anesthetic technique objectives include early anesthetic recovery, minimum effects on respiratory function allowing for early extubation 1 and possibility of postoperative physical therapy 2.
The addition of drugs such as remifentanil and dexmedetomidine to the anesthetic technique, which allow for early return to previous consciousness level and respiratory function recovery, would help early mobilization, thus increasing morbidly obese patients safety 1. Remifentanil results in early emergence due to its metabolism by plasma and tissue esterases, in addition to potentiating spinal morphine analgesic effects 3. It has already been shown that the a2-adrenergic agonist dexmedetomidine has not interfered with respiratory patterns providing residual analgesia, thus being considered safe for continuous intravenous infusion 4,5.
Our study aimed at comparing remifentanil and dexmedetomidine as coadjuvants of standardized anesthetic technique in morbidly obese patients submitted to Capella's surgery 6. The following parameters were evaluated: 1) different anesthetic recovery times (eyes opening, return to spontaneous ventilation, tracheal extubation time, time for post anesthetic recovery unit and hospital discharges); 2) arterial blood gas analysis evolution; and 3) postoperative analgesia.
After the Hospital Metropolitano, Vitória, Ethics Committee approval and their informed consent, participated in this prospective, randomized and double-blind study 92 patients of both genders, aged 18 to 65 years, physical status ASA III with history of morbid obesity and body mass index (BMI) 40 kg.m2 or above and submitted to Capella's surgery. The same anesthetic team participated in all surgeries.
Preoperative care included blood count, glycemia, activated partial thromboplastin time (aPTT), prothrombin time (PT), ECG in 12 leads, chest antero-posterior and profile X-rays, high digestive endoscopy, abdominal ultrasound, echocardiogram and pulmonary function test. Mean blood pressure was monitored by noninvasive method for three consecutive times at 10-minute intervals. Care the night before surgery included oral preanesthetic medication (10 mg metoclopramide, 150 mg ranitidine or 20 mg omeprazol) and 40 mg subcutaneous sodium enoxiparin 1,7. Oral medication was repeated two hours before the procedure, associated to 8 mg ondansetron. Peripheral venous access was obtained in the preoperative room with 18G catheter and radial artery was catheterized with 18G catheter for mean blood pressure monitoring. Two blood samples were collected in this environment for arterial blood gases analysis: one with patient in the supine position and the other with patient in the sitting position in a 45º angle.
Initial intraoperative monitoring consisted of ECG in 5 leads, continuous blood oxygen saturation (SpO2) and invasive mean blood pressure. An epidural thoracic catheter was inserted (T11-T12) with patient in the sitting position respecting a mean time of 15 hours (12 to 18 hours) after subcutaneous enoxiparin. Epidural catheter positioning was checked with 2 ml of 1% lidocaine with epinephrine. Slow 38 ml of 0.375% ropivacaine associated to 2 mg morphine without preservatives were injected only after tracheal intubation and vital signs stabilization. After oxygenation under facial mask and spontaneous ventilation during 3 minutes, intravenous 3 mg rocuronium, 150 µg fentanyl, succinylcholine (1 mg.kg-1 actual weight) and propofol (2 mg.kg-1 ideal weight plus 30% or until BIS reached 30 to 40) were administered. Tracheal intubation was performed with pressure on cricoid cartilage and elevated dorsum. Hypnosis depth was monitored by bispectral EEG. Neuromuscular block intensity was monitored through peripheral nerve stimulator. Patients were artificially ventilated with positive pressure. Tidal volume was 7 ml.kg-1 actual weight until the limit of 1000 mL tidal volume, admitting intratracheal pressure below 30 mmHg. All patients received 3 cmH2O positive end expiratory pressure (PEEP) and plateau during 25% of inspiratory time. Inspiratory to expiratory phase was cycled by volume. PETCO2 (expired CO2) was measured by capnography and respiratory rate was adjusted to be maintained in 38 ± 3 mmHg. Patients received an indwelling vesical catheter for diuresis monitoring. Whenever BIS indicated hypnosis reversion, 25 to 50 mg bolus propofol were injected. Intraoperative adverse-events were evaluated and controlled. Ephedrine (5 mg) was available for blood pressure control. Postoperative pain, nausea and vomiting were recorded and controlled.
After anesthetic induction, 92 patients were prospectively, randomized and double-blindly allocated to two groups (n = 46). Remifentanil Group (Group R) received continuous intravenous remifentanil infusion (0.1 µg.kg-1.min-1 ideal weight plus 30%). Dexmedetomidine Group received continuous intravenous dexmedetomidine infusion (0.5 µg.kg-1.h-1 ideal weight plus 30%). The equivalence of remifentanil and dexmedetomidine doses was based on a preliminary study of ours, to maintain intraoperative inhalated sevoflurane consumption similar between groups. All patients received sevoflurane in 0.5% to 1% inspired concentration in 100% O2 to maintain mean blood pressure in approximately 20% of baseline values. Continuous remifentanil and dexmedetomidine infusion pumps were prepared and connected to patients by one of the authors, who remained in charge of continuous checking their adequate operation. Intra and postoperative periods were followed up by a different anesthesiologist, who was blind to the infused drug. Muscle relaxation was obtained with rocuronium (0.15 mg.kg-1.h-1 ideal weight) until aponeurosis closing completion.
Evaluation of Different Moments
Evaluated moments are shown in chart I and were: 1) different anesthetic recovery times (eyes opening, return to spontaneous ventilation, tracheal extubation time, time for post anesthetic recovery unit and hospital discharges); and 2) perioperative arterial blood gases analysis evolution. During the last aponeurosis suture (Chart I) and simultaneously to drug withdrawal (remifentanil or dexmedetomidine), other drugs were also withdrawn (rocuronium and sevoflurane). M0 was established as initial time for other moments, which are shown in chart I. As from M0 patients were ventilated with 100% O2 in open system. In case of neuromuscular reversion indication, this was obtained with intravenous atropine (25 µg.kg-1 ideal weight) and neostigmine (50 µg.kg-1 ideal weight). Tracheal extubation criteria were: 1) PETCO2 below 50 mmHg; 2) oximetry above 90% mmHg without additional oxygen; 3) ability to maintain head risen for 10 seconds; 4) tongue protrusion ability; 5) ability to open eyes without the aid of accessory muscles; and 6) T4/T1 ratio above 70%.
All patients were extubated in the operating room and referred to the Post-Anesthetic Recovery Unit (PACU). PACU discharge criteria were defined as 4 consecutive evaluations at 30-minute intervals, where there were: a) pulse oximetry-evaluated O2 saturation above 90% without additional oxygen; b) pain Analog Visual Scale score below 4 cm; c) no vomiting; d) diuresis equal to or above 0.5 mL.kg-1.h1 ideal weight; e) absence of pruritus or pruritus tolerable by patients; f) Aldrette and Kroulik score 10; and g) Ramsay's scale score 2. Time to hospital discharge was freely determined by the surgeons' team who evaluated locomotion and communication ability, respiratory comfort and feeding comfort with the diet proposed by the surgical team, which has been similar to all patients.
Arterial Blood Gases Analysis (pH, PaO2, PaCO2)
Two preoperative blood samples were collected to evaluate pH, PaO2 and PaCO2: one with patient in the supine position and the other with patient in the sitting position (45 º angles). Arterial blood sample was collected immediately after tracheal extubation (coinciding with M3). Another arterial blood sample was collected at PACU discharge (M4) with patient in the supine semi-sitting position and under spontaneous ventilation with room air (FiO2: 0.21).
Postoperative Analgesia Evaluation
Pain was evaluated through 10-cm Visual Analog Numeric Scale (VAS). Zero was equivalent to "no pain" and 10 was equivalent to "the worst possible or imaginable pain". Pain equal to or above 4 at VAS was treated with 100 mg intravenous ketoprofen, which has been subsequently administered at 8-hour intervals. The number of patients requiring ketoprofen during the first 24 postoperative hours was recorded.
The number of patients per group was defined by statistical power test established in 80%, determining alpha equals to 0.05. Groups distribution normality was evaluated by Shapiro-Wilkings test. Physical characteristics were evaluated by Chi-square test for gender and Student's t test for independent samples of remaining attributes. Chi-square test was used to evaluate the incidence of adverse events and simultaneous diseases. Inhaled anesthetic consumption was evaluated by Student's t test for independent samples. Blood pressure, pulse and numeric VAS values between groups were compared using two-tailed Analysis of Variance for repeated measures followed by Tukey's Honesty and Significance test. Different recovery times and blood gases analysis values between groups were evaluated by Student's t test for independent samples. Blood gases analysis in a same group was evaluated by Friedman's test followed by Wilcoxon's test for paired samples. Data were expressed in mean ± standard deviation considering significant p < 0.05.
Final evaluation was possible in 88 patients. Four patients were excluded due to possible blockade failure and lack of data. Preoperative values of mean blood pressure, blood count, glycemia, PT and aPTT, ECG in 12 leads, chest antero-posterior and profile X-rays, high digestive endoscopy and abdominal ultrasound were similar between groups. Physical characteristics of groups are shown in table I (p > 0.05).
All patients were classified as physical status ASA III due to morbid obesity.
Major co-morbidities found were similar for both groups and consisted of diabetes, blood hypertension, hypothyroidism, osteoporosis, joint wear, cigarette smoking, allergy, sleep apnea, lower limb varicose veins, arrhythmias, dyslipidemia, hiatus hernia, regular use of psychotropics, regular use of prescribed amphetamine-containing drugs to loose weight. Mallampatti (Group R: 1.6 ± 0.88; Group D: 2 ± 1.07) and Cormack (Group R: 1.45 ± 0.88; Group D: 1.61 ± 0.97) classifications for tracheal intubation were similar for both groups (p > 0.05). Times for eye opening, return to spontaneous ventilation and tracheal extubation were shorter for Group R as compared to Group D (p < 0.0001; Table II). There were, however, no differences in PACU and hospital discharge (Table II).
Surgery duration was similar for both groups (213 ± 63 min and 210 ± 55 min for Groups R and D, respectively; p > 0.05). Inhaled anesthetic consumption (ml/hour) was also similar between groups (Group R: 5.04 ± 1.33; Group D: 4.6 ± 1.12; p > 0.05). Perioperative pH variations were similar for both groups (Table III).
Both groups had similar pH decrease in moments 3 (after tracheal extubation) and 4 (PACU discharge) as compared to preoperative values (Table III). PaO2 values were similar for both groups in different moments. Both groups had PaO2 decrease immediately after tracheal extubation (M3) and at PACU discharge (M4) as compared to preoperative values in the sitting and supine position (p < 0.05). Other comparisons in different moments for the same group have not shown differences (Table IV). PaO2 in moments 3 and 4 was lower for both groups as compared to preoperative semi-sitting position (p < 0.02) and preoperative supine position (p < 0.01). Other comparisons in the same group have not shown differences (p > 0.05). PaCO2 values were similar between groups in different moments (Table V). There were no differences in PaCO2 among different Group R moments (Table V). However, there has been PaCO2 increase (45.8 ± 4.7 mmHg) immediately after tracheal extubation in Group D as compared to preoperative values of the same group (42 ± 4.9 mmHg and 42.6 ± 3.8 mmHg; p < 0.05; Table V).
Postoperative vomiting was present in 8 Group R and 5 Group D patients (p > 0.05) and 11 Group R and 8 Group D patients have referred pruritus (p > 0.05). Rescue analgesia was needed for 18 Group R (40%) and 24 Group D (54%) patients during the first 24 postoperative hours (p < 0.02).
Our results obtained have shown that patients receiving intravenous remifentanil had earlier eye opening, faster return to spontaneous ventilation and earlier tracheal extubation as compared to patients receiving dexmedetomidine according to study standardization. However, there have been no differences in time for PACU and hospital discharge.
In our study, patients were induced with general anesthesia associated to epidural block with ropivacaine and morphine. To decrease the risk of postoperative respiratory complications, an anesthetic technique allowing early consciousness and spontaneous ventilation recovery should be considered, including short-lasting anesthetic drugs and neuromuscular blockers allowing the early start of respiratory physical therapy, especially encouraged breathing in cooperative patients. With this same purpose, one should consider early and effective analgesia, and epidural morphine is a satisfactory alternative. Sevoflurane was the inhaled agent of choice for promoting earlier anesthetic recovery and hospital discharge as compared to isoflurane in morbidly obese patients 8,9. The association of intravenous general anesthesia and epidural block may result in better postoperative analgesia and significant decrease in the incidence of respiratory failure, as compared to patients receiving intravenous anesthesia alone 10.
Dexmedetomidine and remifentanil doses used were based on literature data 11. Although remifentanil pharmacological studies have shown that intravenous doses should be based on ideal weight of obese patients 12, we decided to add 30% of calculated ideal weight. This decision was based on a preliminary study of ours and aimed at maintaining intraoperative sevoflurane consumption similar between groups, as shown by our results. This 30% increase in remifentanil dose has not delayed time for eye opening, for return to spontaneous ventilation or for tracheal extubation as compared to the group receiving dexmedetomidine. It has been previously shown that hypnosis monitoring with bispectral index, routinely performed in morbidly obese patients in our service, has resulted in decreased anesthetic consumption to maintain adequate anesthetic depth 13. Alghouth fast onset and metabolism of adjuvant drugs (remifentanil and dexmedetomidine) favor anesthetic depth control, acute postoperative pain had to be simultaneously controlled. So, all patients received 2 mg epidural morphine as part of the protocol.
Data have shown that 40% of Group R and 54% of Group D patients needed rescue analgesia during the immediate postoperative period, reflecting a better analgesic effect of the association of two different opioids (intravenous remifentanil and epidural morphine) as compared to the analgesic effect of dexmedetomidine associated to epidural morphine in the studied population. Questions whether increased epidural morphine doses would have changed these results deserve further evaluations. The association of epidural morphine to intravenous remifentanil still seems to be a promising alternative for pain control 14. It has been previously shown that remifentanil plasma concentration when there were 50% of chance of adequate analgesia for patients submitted to abdominal procedures was 30% higher in females and depended upon surgical procedure 15. In our study, however, populations were similar in gender distribution and all patients were submitted to the same surgical procedure by the same surgical team, which would minimize these factors in the postoperative evolution of those patients.
As to arterial gases analysis, both groups had decreased pH and PaO2 immediately after tracheal extubation, which was maintained until PACU discharge, showing that the anesthetic agent had no influence on postoperative hypoxemia. In morbidly obese patients, postoperative hypoxemia is an expected event, since there are: 1) increased O2 consumption and CO2 production; 2) pulmonary volumes decrease, especially functional residual capacity (FRC) at the expenses of decreased expiratory reserve volume; 3) decrease in total pulmonary compliance and respiratory muscles efficacy; 4) increased respiratory work; and 5) increased airway closing ability favoring changes in ventilation-perfusion ratio with increased intrapulmonary shunt. According to Eichenberger 15, morbidly obese patients already present with atelectasis the day of the surgery, before the administration of any anesthetic drug. High abdominal surgery predisposes to more repercussion on ventilatory mechanics, resulting in decreased pulmonary volumes and capacities, especially vital capacity and FRC which are maintained for 10 to 14 days. Although there are studies showing that 75% of morbidly obese patients have PaO2 below 60 mmHg in the first 24 postoperative hours of gastric shunting surgeries 16, lower mean PO2 value in our study was 69 ± 10 mmHg obtained in Group R immediately after tracheal extubation. Two hours after, PO2 values in the same group were 78 ± 17 mmHg. Although this mean PaO2 value was still statistically different from mean preoperative value (90 ± 20 mmHg), there have been no clinical repercussions in time for Group R patients reach pre-established requirements for PACU discharge. These results are not in line with Melero et al. 17, who have compared isoflurane, fentanyl and halothane effects on postanestetic recovery quality (time elapsed for emergence and extubation, in addition to arterial blood gases analysis evolution) of morbidly obese patients. Regardless of the agent, those authors have observed severe and long-lasting PaO2 decrease, which had not returned to baseline values 7 days after. In our study, weight, BMI and preoperative spirometry were not predicting factors for postoperative hypoxemia. Decreased FRC, and closing and FRC ratio are the indices best related to postoperative hypoxemia.
Morbidly obese patients have anatomo-physiologic changes which increase anesthetic and surgical risks. The incidence of post-anesthetic mortality is 20% higher in the obese population. Postoperative morbidity is also higher with reports of 50% incidence of sleep apnea syndrome, 5% of pulmonary atelectasis and 5% to 12% of acute pulmonary embolism 1. Decreased pulmonary volumes and compliance and increased oxygen consumption are responsible for the high incidence of postoperative atelectasis and hypoxemia 1,2,16. During morbidly obese anesthetic induction there might be hypoxia due to rapid desaturation 1 and tracheal intubation technique with succinylcholine and propofol was based on previous studies 18. Several studies have also shown the influence of position, type of surgical incision, diaphragm displacement in the cephalad direction and placement of compressive bandages on the intensity of postoperative hypoxemia. In our study, there has been no mean PaCO2 change in Group R patients in any postoperative measurements and there has been transient PaCO2 increase in patients receiving dexmedetomidine. This increase was probably due to drug sedative effect and not to respiratory depressing effect, since a2-adrenergic agonists alone do not promote respiratory depression and do not potentiate morphine's respiratory depressing effect 19. Other authors have found significant PaCO2 increase in the immediate postoperative period, which started to normalize 3 hours later and have reached values close to baseline only 24 hours later 17.
As to hospital discharge, the Royal College of Surgeons (1992) has published guidelines for obese patients. It was considered that, in the presence of BMI above 30, the case should not be handled in outpatient regimen 20. In our study, hospital discharge time was similar between groups, varying 2 to 3 days. Other studies report mean hospital discharge as 5 days for videolaparoscopic surgeries for morbid obesity correction 21 and 15 days for open surgeries 22.
In conclusion, continuous intravenous remifentanil had 8 to 10 minutes advantage over dexmedetomidine in time for eye opening, return to spontaneous ventilation and tracheal extubation in morbidly obese patients under standardized anesthetic technique. Although statistically significant, 8 to 10 minutes had no major clinical repercussion, since PACU and hospital discharge times were similar between groups. However, the level of analgesia offered by the association of remifentanil has shown additional advantage which could positive influence postoperative evolution.
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Dra. Eliana Cristina Murari Sudré
Rua Prof. Elpídio Pimentel 51/302
29066-060 Vitória, ES
Apresentado (Submitted) em 12 de
março de 2003
Aceito (Accepted) para publicação em 10 de julho de 2003
* Recebido do (Received from) Hospital Metropolitano, Laranjeiras. Serra, ES