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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.54 no.1 Campinas Jan./Feb. 2004 



Influence of intravenous clonidine in the cost of sevoflurane anesthesia for outpatient middle ear procedures*


Influencia de la clonidina por vía venosa en el costeo de anestesia con sevoflurano en cirugías de oído medio en régimen ambulatorial



Renato Mestriner Stocche, TSA, M.D.I; Luís Vicente Garcia, TSA, M.D.I; Jyrson Guilherme Klamt, TSA, M.D.I; Marlene Paulino dos Reis, M.D.II; Daniela Rocha Gil, M.D.III; Karin Luiza Magno Mesquita, M.D.III

IProfessor da Disciplina de Anestesiologia da FMRP-USP
IIProfessora da Disciplina de Anestesiologia da FMRP-USP
IIIEx-ME do CET do HC da FMRP-USP; Assistente do HCRP-USP





BACKGROUND AND OBJECTIVES: Clonidine is an a2-agonist which decreases intravenous and inhalational anesthetics consumption. This study aimed at evaluating the cost-benefit ratio of preanesthetic medication with intravenous clonidine for general anesthesia with sevoflurane in outpatient procedures.
METHODS: Forty five patients aged 15 to 52 years were included in this double-blind, randomized and placebo controlled study, and were distributed in 3 groups of 15: Group S (placebo), Group C3 (3 µ clonidine) and Group C5 (5 µ clonidine). Anesthesia was induced with sevoflurane, alfentanil (30 µ and pancuronium (0.08 The following parameters were recorded: incidence of complications, halogenate consumption and anesthesia duration, as well as phase I and II recovery time. Cost analysis has considered direct and indirect costs.
RESULTS: There were no differences among groups in demographics data, incidence of complications and phase I anesthetic recovery. Phase II anesthetic recovery was prolonged in Group C5 (p < 0.05). Sevoflurane consumption per minute of surgery was 0.54 ± 0.14, 0.33 ± 0.09 and 0.34 ± 0.13 in Groups S, C3 and C5 respectively (p < 0.05). Costs were approximately 35% lower in the clonidine groups.
CONCLUSIONS: Intravenous clonidine (3 µ decreases sevoflurane consumption without prolonging phase I recovery. Although decreasing sevoflurane consumption, 5 µ clonidine prolongs phase II recovery, thus being inadequate for outpatient procedures.

Key Words: ANESTHESIA: Ambulatory; ANESTHETICS, Volatile: sevoflurane; DRUGS, a2- agonist: clonidine


JUSTIFICATIVA Y OBJETIVOS: La clonidina es un agente a2-agonista que diminuye el consumo de anestésicos venosos e inhalatorios. Este estudio visó evaluar la relación costeo-beneficio de la medicación pre-anestésica con clonidina por vía venosa en anestesia general con sevoflurano en régimen ambulatorial.
MÉTODO: Se trata de estudio encubierto, aleatorio, controlado con placebo, realizado con pacientes con edad entre 15 y 52 años. Los pacientes fueron divididos en 3 grupos de 15: Grupo S (placebo), C3 (clonidina 3 µ y C5 (5 µ La inducción anestésica fue hecha con sevoflurano, alfentanil (30 µ y pancuronio (0,08 Fueron anotados la frecuencia de complicaciones, consumo de halogenados, tiempo de anestesia, tiempo de recuperación parte I y II. El análisis de gastos consideró gastos directos e indirectos.
RESULTADOS: No hubo diferencias entre los grupos en relación a los datos demográficos, frecuencia de complicaciones y tiempo para recuperación anestésica parte I. La recuperación anestésica parte II fue prolongada en el grupo C5 (p < 0,05). El consumo de sevoflurano por minuto de cirugía fue 0.54 ± 0,14 en el grupo S y 0,33 ± 0,09 y 0,34 ± 0,13 en los grupos C3 y C5, respectivamente (p < 0,05). En los grupos que recibieron clonidina, el costeo fue diminuido en aproximadamente 35%.
CONCLUSIONES: La clonidina (3 µ por vía venosa diminuye el consumo de sevoflurano sin aumentar el tiempo de recuperación parte II. La dosis de 5 µ, a pesar de disminuir el consumo de sevoflurano, prolonga la recuperación parte II, no adecuándose al régimen ambulatorial.




Since the mid 1980s, there is a world trend to replace hospital by outpatient procedures. Early hospital discharge provides more comfort, autonomy and satisfaction for patients, in addition to decreasing the risk for nosocomial infections and the total cost of hospitalization 1. Aiming at this early discharge, fast excretion anesthetic drugs are used in those patients. However, the high cost of such drugs may limit their use 2.

Clonidine is a central action a2-agonist which decreases sympathetic tone and exhibits sedative, antisialogogue, antiemetic and analgesic properties. It has also proven to be safe in the anesthetic practice, according to several studies. When used as preanesthetic medication, it decreases the need for intravenous and inhalational anesthetics 3,4. Intravenous 1.5 µ clonidine in outpatient procedures has not shown anxiolytic effects 5. However, the effects of preanesthetic medication with clonidine on outpatient procedure anesthetic costs have not been evaluated, thus making necessary a cost-benefit ratio analysis 6.

This study aimed at evaluating the cost-benefit ratio of preanesthetic medication with intravenous clonidine for general anesthesia with sevoflurane in outpatient procedures.



After the Hospital das Clinicas, Ribeirão Preto Ethics Committee approval and patients their informed consent, 45 individuals aged 15 to 52 years, physical status ASA I and II, weighing 40 to 85 kg, undergoing middle ear procedures were included in this double-blind, randomized and placebo controlled study. Exclusion criteria were patients with history of studied drugs allergy, with baseline heart rate lower than 50 bpm and those under chronic use of CNS depressing drugs, antidepressants, anticonvulsivants or drugs/alcohol abusers.

All patients were monitored with cardioscopy, pulse oximetry, capnometry and noninvasive blood pressure. After venous puncture with 20G catheter, hydration was standardized with 250 ml rapid infusion followed by 6 lactated Ringer's infusion.

Patients were randomly distributed in 3 groups: Group C3 was given 3 µ clonidine, Group C5 was given 5 µ clonidine and Group S was given 0.9% sodium chloride as preanesthetic medication. Solutions containing 30 µ clonidine for Group C3, 50 µ clonidine for Group C5 and 0.9% sodium chloride for Group S were prepared by an anesthesiologist not involved with the research. They were intravenously administered to all groups in a volume of 1 ml solution for each 10 kg of body weight.

Inhalational anesthesia was induced 15 minutes after preanesthetic medication with sevoflurane at initial concentration of 3%, followed by 0.5% increase at 15-second intervals until loss of eyelid reflex. Alfentanil (30 µ and pancuronium (0.08 were then administered. Anesthesia was maintained with sevoflurane, N2O and O2 (1:1) aiming at maintaining MBP and HR within a 20% range above or below baseline values. All patients received 100 mg ketoprofen in the beginning of the procedure.

At surgery completion, 100% oxygen was administered and the respiratory system was commuted to non-rebreathing. Tracheal extubation was performed when patients presented spontaneous and rhythmic ventilation for at least 30 seconds, maintaining PETCO2 below 50 mmHg, in addition to answering to verbal commands. Time elapsed between sevoflurane withdrawal (surgery completion) and eye opening at command (asked at 20-second intervals) was recorded, as was the time between sevoflurane withdrawal and tracheal extubation. Total sevoflurane consumption was also recorded.

The incidence of adverse events was recorded. Tachycardia was defined as heart rate (HR) above 100 bpm, bradycardia as HR below 50 bpm and arterial hypotension as blood pressure below 30% of baseline value in two consecutive measurements. Adverse events were also recorded in the PACU (nausea, vomiting, mild or severe pain, urinary retention, postural arterial hypotension, sleepiness and dizziness). Oxygen nebulization (8 L.min-1) with Venturi mask was used until patients presented spontaneous emergence periods. Nausea and vomiting were treated with metochlopramide and the cost of this drug was added to total cost of anesthesia. Time for outpatient anesthetic discharge according to Chung's criteria 8 was evaluated, namely, score 9 according to parameters scale described in table I.

Total anesthetic cost was calculated adding all expenditures with anesthetic drugs, oxygen, N2O, disposable materials and cost of PACU stay (minutes). Monitors and ventilators depreciation and expenditures with reusable materials (drapes, pads, intermediaries and others) were not taken into consideration. The set of disposable materials contained one tracheal tube, one intravenous 20G catheter, one serum therapy equipment, ¼ tape roll, one plastic probe for aspiration and two pairs of latex gloves. Costs of drugs and disposable materials were obtained from Brasíndice published in July 20, 2002, discounting taxes built in the price. When drug or material had more than one manufacturer in Brasíndice, value considered for calculations was the arithmetic mean of values. Cost of PACU stay hour was obtained from the hospital's cost control center and corrected for July 2002. Oxygen and N2O cubic meter values were obtained directly from the supplier (price list) (Table II).

Data are shown in frequency, relative frequency (%) or mean ± SD. Variables expressed in frequency were statistically analyzed by Chi-square or Fisher's Exact tests. Data expressed in means were analyzed by Kruskal-Wallis test. In case of statistical significance (p < 0.05), Dunn's multiple comparisons test was used to between groups analysis.



There have been no differences between groups in demographics data (Table III). Blood pressure and heart rate before and after preanesthetic medication were also not different between them. Surgical and anesthetic times were similar between groups, as well as time elapsed from sevoflurane withdrawal to eye opening at command (phase I anesthetic recovery). However, time for outpatient discharge (phase II anesthetic recovery), calculated from anesthetic withdrawal to score 9 by adopted recovery criteria, was higher in group C5 as compared to Group S (p < 0.01) (Table IV). At the end of 2 PACU hours, 7 Group S and no Group C5 patients were discharged. At the end of 3 PACU hours, all Group S patients had been discharged, while 4 Group C5 patients still remained in observation (Figure 1).

Sevoflurane consumption in milliliters per minute of surgery was 0.54 ± 0.14, 0.33 ± 0.09 and 0.34 ± 0.13 in Groups S, C3 and C5 respectively. Consumption was higher in Group S as compared to Groups C3 and C5 (p < 0.001 and p < 0.01 respectively). There was no difference between Groups C3 and C5 (Figure 1).

General perioperative adverse events incidence was similar for all groups, as shown in table V. However, the incidence of prolonged drowsiness was higher in Group C5 where 4 patients had delayed discharge, as compared to zero in Group S and one in Group C3. Mean anesthetic costs in Reals were 260.6 ± 107.6, 171.4 ± 55.23 and 170.8 ± 39.76 for Groups S, C3 and C5 respectively, with statistical difference between groups S/C3 and S/C5 (p < 0.05).



Anesthesiology is a medical specialty which has shown a major technical-scientific evolution in the last decades. The development of new anesthetic drugs and alike, specific materials and techniques has increased direct anesthetic costs, which may be attenuated by cost contention programs 9. Increased costs have resulted in better understanding and higher concern of specialists in decreasing them, while maintaining anesthetic quality 10. A study performed with Canadian anesthesiologists has shown that 94% of them take into consideration costs when inducing anesthesia 11. In a country such as Brazil, with few health care resources and depending on the import for the pharmaceutical industry, cost reduction programs are crucial.

Health care cost analysis poses major difficulties, many of them related to the diversity of terminologies involving this type of analysis, as well as to the method used 6. This study adopted the cost-benefit ratio analysis, taking into consideration direct costs (e.g.: cost of drugs), indirect or associated direct costs (e.g.: cost of anesthetic recovery) 6 and benefits quantified through sevoflurane consumption and total anesthetic costs. However, part of fixed costs could not be assessed due to the lack of validated Brazilian indices to calculate ventilators, monitors and materials depreciation costs (laryngoscope and others). These costs were excluded from our analysis and may be influenced by utilization time. However, surgical and anesthetic times were similar between groups and resources were used in a standardized way to minimize the impact on our results 11.

Our results have shown that intravenous clonidine decreased sevoflurane consumption in 40% to 50%. These results are in line with the literature which shows 40% to 60% decrease in anesthetic consumption 5. With our method, sevoflurane consumption decrease has represented final savings of approximately 35%. This high impact of sevoflurane savings on total anesthetic costs does not agree with data obtained in a study which has shown that costs of all anesthetic agents contribute with no more than 30% of total anesthetic costs 11. However, this study was carried out in a country where human resources expenditures have high impact on final costs, thus reducing drugs influence. So, this disagreement could be explained by the fact that drugs have international prices while expenditures with salaries and professional fees are substantially lower in countries such as Brazil. Another important factor differentiating the above-mentioned study from ours was the exclusion of anesthesiologists' fees, thus decreasing the impact of drug costs savings.

Clonidine at 5 µ did not decrease consumption beyond what was observed with 3 µ On the other hand, in addition to having no advantage as compared to the lower dose, it substantially prolonged phase II anesthetic recovery, being inadequate for outpatient procedures.

Total incidence of adverse events was similar for all groups. As expected, patients not receiving clonidine presented more restlessness and less dry mouth or postural arterial hypotension 12.

In conclusion, clonidine is an anesthetic adjuvant drug which decreases anesthetics consumption. Its use in outpatient general anesthesia with sevoflurane may represent savings of up to 35% in total anesthetic costs, excluding anesthesiologists' fees. In the conditions of our study, 3 µ clonidine was the best option for outpatient procedures because it has not delayed emergence as compared to control group. Clonidine at 5 µ was related to longer phase II anesthetic recovery and higher incidence of postural arterial hypotension. Due to substantial differences in anesthetic costs composition between countries, it is clear the need for further Brazilian studies involving anesthetic costs decrease.



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Correspondence to
Dr. Renato Mestriner Stocche
Address: Rua Adolfo Serra, 237 Alto da Boa Vista
ZIP: 14025-520 City: Ribeirão Preto, Brazil

Submitted for publication February 7,  2003
Accepted for publication May 5, 2003



* Received from Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (HC FMRP-USP), Ribeirão Preto, SP

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