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Revista Brasileira de Anestesiologia

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

Rev. Bras. Anestesiol. vol.57 no.1 Campinas Jan./Feb. 2007 



Consequences of the addition of nitrous oxide to anesthesia during pneumoperitoneum in videolaparoscopic surgeries*


Efectos de la adición del óxido nitroso en la anestesia durante pneumoperitoneo en intervención quirúrgica videolaparoscópica



Cláudia Regina Fernandes, TSAI; Lenilson Marinho Souza FilhoII; Josenilia Maria Alves Gomes, TSAIII; Erik Leite MessiasIV; Rodrigo Dornfeld EscalanteV

IDoutora em Medicina pela Universidade de São Paulo; Responsável pelo CET/SBA – Hospital Universitário Walter Cantídio da UFC
IIIDoutora em Clínica Cirúrgica pela Faculdade de Medicina de Ribeirão Preto; Chefe do Serviço de Anestesiologia do Hospital Universitário Walter Cantídio, UFC; Co-Responsável pelo CET/SBA – Hospital Universitário Walter Cantídio da UFC
IVDoutor em Bioestatística e Epidemiologia Psiquiátrica pela Jonhs Hopkins University – EUA
VDoutor em Clínica Cirúrgica pela Faculdade de Medicina de Ribeirão Preto; Pesquisador Associado da Pós-Graduação do Departamento de Cirurgia da Faculdade de Medicina da UFC; Cirurgião Coloproctologista do Hospital Universitário Walter Cantídio da UFC

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BACKGROUND AND OBJECTIVES: The use of pneumoperitoneum during videolaparoscopic surgeries activates neuroendocrine mechanisms, and causes cardiovascular and hormonal changes. The aim of this study was to evaluate the effects of the addition of nitrous oxide, to maintain adequate anesthetic levels, on the cardiovascular sympathetic response and in the expired concentration of sevoflurane (ECsevo) during pneumoperitoneum, by evaluating hemodynamic parameters, BIS, and SEF95%, during videolaparoscopic cholecystectomies.
METHODS: Thirty-one patients, physical status ASA I and II, ages 19 to 76 years, were included in the study. Anesthetic induction was accomplished with sufentanyl 0.3 µ, propofol (2.5, and cisatracurium (0.15 During the maintenance phase of anesthesia, the dose of ECsevo was adjusted to maintain BIS between 40 and 60. The administration of increasing concentrations of nitrous oxide, 20%, 40%, and 60%, was initiated after inducing pneumoperitoneum. The bispectral index, SEF95%, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were evaluated at M1 – 5 minutes after the pneumoperitoneum; M2 – when the expired concentration of N2O = 20% (ECN2O = 20%); M3 – ECN2O = 40%; M4 – ECN2O = 60%.
RESULTS: There were no significant differences among SBP, DBP, MAP, and HR in the moments studied. There was a significant difference in ECsevo in those same moments, with a 35% reduction when M1 and M4 were compared.
CONCLUSIONS: When nitrous oxide is administered in association with sevoflurane during pneumoperitoneum in videolaparoscopic cholecystectomy, it provides for hemodynamic stability and reduces the amount of sevoflurane needed while, at the same time, maintaining electroencephalographic parameters compatible with adequate anesthesia.

Key Words: ANESTHETICS, Gases: nitrous oxide, MONITORING: bispectral index, SURGERY: videolaparoscopic cholecystectomy.


JUSTIFICATIVA Y OBJETIVOS: La instalación del pneumoperitoneo durante la intervención quirúrgica videolaparoscópica activa mecanismos neuroendócrinos, alteraciones cardiovasculares y hormonales. El objetivo de este estudio fue el de evaluar los efectos de la adición del óxido nitroso sobre la respuesta simpática cardiovascular y la concentración expirada de sevoflurano (CEsevo) durante el pneumoperitoneo, para mantener la adecuación anestésica evaluada a través de parámetros hemodinámicos, del BIS y SEF95% en colecistectomías videolaparoscópicas.
MÉTODO: Se incluyeron en el estudio 31 pacientes, estado físico ASA I y II, con edad entre 19 y 76 años. La inducción anestésica se realizó con sufentanil (0,3 µ, propofol (2,5 y cisatracurio (0,15 Durante la anestesia, la CEsevo se ajustó para mantener el BIS entre 40 y 60. Posteriormente a la instalación del pneumoperitoneo, se inició la administración de óxido nitroso en concentraciones aumentadas de 20%, 40% y 60%. Se comprobaron los parámetros BIS, SEF95%, presión arterial sistólica (PAS), presión arterial diastólica (PAD), presión arterial promedio (PAM) y frecuencia cardiaca (FC), en los momentos M1 – 5 minutos después pneumoperitoneo, M2 – cuando la concentración expirada del N2O = 20% (CEN2O = 20%); M3 – CEN2O = 40%; M4 – CEN2O = 60%.
RESULTADOS: No hubo diferencia significativa entre PAS, PAD, PAM y FC durante los momentos estudiados. Hubo diferencia significativa en la CEsevo en los momentos estudiados, con una reducción de un 35% cuando se la comparó a M1 y M4.
CONCLUSIONES: El óxido nitroso, cuando se administra en asociación con el sevoflurano durante el pneumoperitoneo en colecistectomía videolaparoscópica, propicia estabilidad hemodinámica y la reducción del consumo de sevoflurano, manteniendo los parámetros electroencefalográficos compatibles con la adecuación anestésica.




Videolaparoscopic cholecystectomy is considered the golden standard in the treatment of symptomatic cholelithiasis. This technique requires a pneumoperitoneum that is achieved by insufflating carbon dioxide (CO2) under pressure, which activates neuroendocrine mechanisms and causes cardiovascular changes, leading to an increase in blood pressure and heart rate 1-3.

Nitrous oxide (N2O) is used as an adjuvant during anesthesia, and has important interactions with inhalational anesthetics, reducing MAC and the need for intravenous anesthetics 4,5, and also possesses and important analgesic component when administered in concentrations above 30% in human beings 6.

The bispectral index (BIS) quantifies the relationship among the several frequency bands of the electroencephalogram (EEG). When used in general anesthesia in the context of other variables it reduces the incidence of intra-operative awakening and the dose of the hypnotic agent used to maintain the patient unconscious, having been validated as a quantifiable measure of the hypnotic effect of anesthetics 7-9. The spectral edge frequency, SEF95%, reflects the frequency of the predominant spectral power, i.e., at that moment 95% of the existing frequencies are below that value 10.

In this study we evaluated the effects of adding increasing concentrations of nitrous oxide on the sympathetic cardiovascular response and on the expired concentration of sevoflurane during the penoumorepitoneum in order to maintain adequate anesthetic level, by measuring hemodynamic parameters, BIS, and SEF95% during videolaparoscopic cholecystectomies.



The study protocol was submitted to and approved by the Research Ethics Committee of the Hospital Universitário Walter Cantídio da Universidade Federal do Ceará. Every patient that fulfilled the inclusion criteria and agreed to and signed an informed consent participated in this study.

Thirty-one patients, ASA I and II, ages between 19 and 76 years, of both genders, without a history of cardiopathy, lung disease, or liver disease were chosen prospectively and consecutively.

The same protocol for induction and maintenance of general anesthesia was used for every patient: pre-anesthetic evaluation (without pre-anesthetic medication), venous cannulation performed in the operating room, administration of Ringer's lactate, non-invasive blood pressure monitoring, cardioscope in the DII and V5 derivations, and pulse oxymeter.

To evaluate the bispectral index, SEF95%, and suppression rate, the BIS electrodes were placed on the frontal region (BIS Sensor XP, Aspect Medical System, USA). The recording was initiated after performing the impedance test, when it was below 2 kW.

Anesthetic induction with 0.3 µ of sufentanyl, 2.5 of propofol, and 0.15 of cisatracurium was initiated after the patient had been breathing 100% oxygen via face mask for 5 minutes. After tracheal intubation, the respiratory rate was adjusted to maintain a PETCO2 between 30 and 35 mmHg with a tidal volume of 8 and a PEEP of 5 cmH2O. Inhalational anesthesia was administered in a circular system that absorbs CO2 and with an initial O2 flow of 1 L.min-1. During the maintenance phase of the anesthesia, the expired concentrations of sevoluorane (ECsevo) were adjusted to maintain BIS between 40 and 60. The inspired and expired concentrations of O2, CO2, and inhalational anesthetics were monitored continuously through a gas analyzer. Pneumoperitoneum was induced and maintained under an intraabdominal pressure of 12 mmHg. Increasing concentrations of nitrous oxide, 20%, 40%, and 60%, were added 5 minutes after the beginning of the penumoperitoneum, respecting a 10-minute interval to allow for the stabilization between the inspired and expired concentrations of N2O. At the end of this interval, with stable concentrations of nitrous oxide, the following parameters were measured: BIS, SEF95%, suppression index, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR). Those parameters were measured three times with a 3-minute interval between each measurement, and the mean of the three evaluations represented the variables in the following moments: M1 – 5 minutes after pneumoperitoneum was induced; M2 – when the expired concentration of N2O -20% (ECN2O -20%); M3 – when ECN2O -40%; M4 – when ECN2O -60%. This last concentration was maintained until desinsufflation of the pneumoperitoneum.

The parameters evaluated during the penumoperitoneum (BIS, SEF95%, suppression index, SBP, DBP, MAP, HR, and ECsevo) were expressed as mean and standard deviation in moments M1-M4. Statistical analysis was done with the Analysis of Variance for repeated measurements (ANOVA) followed by application of Tukey post-test to determine which measurements showed statistically significant differences. Values of p < 0.05 were considered statistically significant.



The data of the 31 patients, of which 22 were women (71%), with a mean age of 42.9 years (42.9 ± 15), and mean weight of 61 kg (61 ± 12.2) were analyzed.

The mean length of time between anesthetic induction and the pneumoperitoneum was of 36.6 minutes (36.6 ± 11.2).

Analysis of the data regarding the evolution of the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR), using the ANOVA, showed there were no statistically significant differences during the study (Table I).



Regarding the ECsevo (Table II and Figure 1), the Analysis of Variance for repeated measurements (ANOVA) showed a significant difference. Tukey test showed statistically significant differences between M1 and the other moments in the study, indicating a significant reduction in the amount of sevoflurane used when 60% nitrous oxide is added during the penumoperitoneum in videolaparoscopic surgeries.






This study demonstrated that the administration of increasing concentrations of nitrous oxide reduces significantly the need for sevoflurane during the penumoperitoneum in videolaparoscopic cholecystectomy, while promoting hemodynamic stabilization and an adequate level of anesthesia.

The use of the bispectral index as a measurement of the adequacy of the anesthesia is the first aspect that should be analyzed. The bispectral index is a quantifiable measurement of the hypnotic effect of anesthetic agents 9,10. Despite the wide use of BIS, which makes it the standard regarding monitoring EEG during anesthesia, some studies demonstrated limitations, mostly as a consequence of several factors that led to false BIS values, including the depth of anesthesia, hypoperfusion of the brain 11, and artifact in the EEG 12,13. The most common causes of altered BIS values are electric artifacts 12, electromyographic activity 13, or deep neuromuscular blockade with inadequate hypnosis. Although almost every equivocal BIS value is elevated, one condition that could cause a sudden decrease of this index is known as "paradoxal awakening" 14. This response may be elicited by a strong nociceptive stimulus in the presence of inadequate anesthesia/analgesia, such as during irrigation of the abdominal cavity under an inadequate anesthetic level 15. In this study, BIS parameters indicated proper anesthetic levels by remaining between 40 and 60.

Mean arterial pressure and HR remained within the normal range, suggesting an adequate anesthetic plane, which was expressed indirectly through hemodynamic parameters. Although pneumoperitoneum is an important nociceptive stimulus, there were no changes in the values related to the electroencephalographic monitorization, especially SEF95%, indicating that nitrous oxide is a potent analgesic, capable of maintaining hemodynamic stability and an adequate anesthetic plane when associated with sevoflurane. This potent analgesic component of nitrous oxide had already been observed through electroencephalographic parameters when administered to human beings 16,17.

Since nitrous oxide is an antagonist of NMDA receptors 18, it is possible that it may have anti-hyperalgesic properties, simulating ketamine, that might contribute to its antinociceptive effects. Clinical studies 19,20 have demonstrated that large doses of opioids during surgeries may, paradoxically, facilitate the activation of pronociceptive systems NMDA-dependent, increasing postoperative pain. Although postoperative pain was not evaluated in this study, a small dose of an opioid (0.3 µ sufentanil) was used only during the anesthetic induction. Thus, the antinociceptive effects of nitrous oxide associated with sevoflurane during a strong stimulus (pneumoperitoneum) were observed. Considering the antagonistic properties of the NMDA receptor, nitrous oxide represents an important role in the prevention of acute tolerance to the analgesic effects of opioid agonists 21.

The interaction between nitrous oxide and potent inhalational anesthetics is well known. Katoh and Ikeda observed that the addition of 63.5% of N2O allows for a 61% reduction in the MAC of sevoflurane 22; Jakobson et al. demonstrated a 60% reduction in the amount of sevoflurane used when 63% N2O was added to the oxygen 4, leading to a marked reduction in the costs with anesthetics besides increasing the speedy of awakening from anesthesia. In this study we observed a significant reduction in the expired concentration of sevoflurane needed in every moment N2O was administered, indicating that even in small concentrations (20%) it has a positive and statistically significant influence in the reduction of the amount of sevoflurane used. When 60% of nitrous oxide was added, there was a 35% reduction in the concentration of sevoflurane necessary. Compared to other studies, there was a smaller reduction in the amount of the halogenated agent needed, which can be attributed to the greater need of sevoflurane to maintain adequate anesthetic plane at the moment of a potent surgical stimulus, pneumoperitoneum, since no additional doses of opioid were used.

We concluded that the association of nitrous oxide in the conditions of the present study was beneficial, since it reduced the amount of sevoflurane used and the need of opioids in the intraoperative period, and avoided the hypertensive episodes commonly seen during the pneumoperitoneum, which can be deleterious, especially in the most susceptible patients.



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Correspondence to:
Dra. Cláudia Regina Fernandes
Rua Marcelino Lopes, 4.520 –
Casa 09 – Edson Queiroz
60834-370 Fortaleza, CE

Submitted em 03 de fevereiro de 2006
Accepted para publicação em 16 de outubro de 2006



* Received from Hospital Universitário Walter Cantídio da Universidade Federal do Ceará (UFC), Fortaleza, CE

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