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Revista Brasileira de Anestesiologia

versão impressa ISSN 0034-7094

Rev. Bras. Anestesiol. vol.51 no.6 Campinas dez. 2001 



Transient neurological changes during emergence from enflurane, isoflurane or sevoflurane anesthesia*


Alteraciones transitorias del examen neurológico durante el despertar de la anestesia con enflurano, isoflurano o sevoflurano



Luiz Fernando Soares, M.D.I; Pablo Escovedo Helayel, M.D.I; Getúlio Rodrigues de Oliveira Filho, M.D.II; Rogério do Amaral, M.D.III

IAnestesiologista do Hospital Governador Celso Ramos
IIResponsável pelo CET/SBA do SES-SC





BACKGROUND AND OBJECTIVES: Transient neurological findings are seen during emergence from halothane, enflurane, and isoflurane anesthesia. Little is known about neurological changes during recovery from sevoflurane anesthesia. This study was aimed at comparing the incidence of such findings during recovery from enflurane (Group E), isoflurane (Group I) and sevoflurane (Group S) anesthesia.
METHODS: Forty four patients were assigned to receive enflurane, isoflurane or sevoflurane anesthesia in 50% N2O. Evaluated parameters were: tympanic temperature, consciousness level, muscle tone, pupillary, eyelash, bicipital, patellar and plantar reflexes and shivering, which were recorded before induction, immediately after anesthesia withdrawal and at 5, 10, 15, 20, 30 and 40 minutes thereafter.
RESULTS: Pupillary, eyelash, patellar and plantar reflexes were significantly related to the level of consciousness. Groups did not differ regarding the incidence of increased muscle tone, bicipital response, plantar clonus and extension plantar response. Increased patellar response was more frequent in group E than in group I. Shivering was more frequent in groups E and I as compared to group S. No difference in tympanic temperature could be detected among patients with or without shivering.
CONCLUSIONS: Transient neurological changes can be detected up to 40 minutes during emergence from enflurane, isoflurane or sevoflurane anesthesia.

Key Words: ANESTHETICS, Inhalational: enflurane, isoflurane, sevoflurane; POSTANESTHETIC RECOVERY


JUSTIFICATIVA Y OBJETIVOS: Anormalidades transitorias del examen neurológico ocurren durante el despertar de la anestesia con halotano, enflurano e isoflurano. Poco se conoce sobre la ocurrencia de anormalidades del examen neurológico durante la recuperación de la anestesia con sevoflurano. Este estudio tuvo como objetivo comparar la prevalencia de tal comportamiento durante la recuperación de la anestesia con enflurano (Grupo E), isoflurano (Grupo I) y sevoflurano (Grupo S).
MÉTODO: Fueron estudiados 44 pacientes que recibieron anestesia con enflurano, isoflurano o sevoflurano en N2O a 50%. Fueron anotados antes de la inducción, inmediatamente después de la cesación de la administración del anestésico y 5, 10, 15, 20, 30 e 40 minutos después: temperatura timpánica, nivel de consciencia, tono muscular, reflejos pupilar, ciliar, bicipital, patelar y cutaneo-plantar, bien como la ocurrencia de calofríos.
RESULTADOS: Las respuestas de los reflejos pupilar, ciliar, patelar y cutaneo-plantar se correlacionaron con el nivel de consciencia. Los grupos no difirieron cuanto a la prevalencia de hipertonia muscular, hiperreflexia bicipital, clonus plantar y respuesta extensora cutaneo-plantar. Hiperreflexia patelar fue mas frecuente en el grupo del enflurano de que en el grupo del isoflurano. Calofríos fueron mas frecuentes en los grupos E e I de que en el grupo del sevoflurano. La temperatura timpánica no difirió entre los pacientes que presentaron o no calofríos.
CONCLUSIONES: Alteraciones reversibles del examen neurológico pueden estar presentes por hasta 40 minutos durante la recuperación de la anestesia con enflurano, isoflurano o sevoflurano.




Neurological changes can be seen during emergence from halothane, enflurane and isoflurane and are characterized by signs of central desinhibition of motor pathways. So, it is possible to find exacerbated responses to monosympathetic reflexes and tonico-clonic activity1,2. These transient manifestations are clinically irrelevant, but are part of a set of signs characterizing inhalational anesthesia emergence which are easily detected by a brief neurological exam, thus being didactically important. Neurological manifestations during emergence from sevoflurane anesthesia are not known.

The aim of this study was to describe and to compare neurological changes during emergence from inhalational enflurane, isoflurane and sevoflurane anesthesia.



After Hospital Governador Celso Ramos Medical Ethics Committee approval, participated in this study 44 adult patients of both genders, physical status ASA I or II scheduled for elective surgeries under general anesthesia. Patients submitted to intracranial surgeries or with neurological disorders were excluded from this study. Patients were given no premedication and were allocated into the following groups: enflurane group (n=14) - inhalational anesthesia with 50% N2O/O2 and enflurane; isoflurane group (n=15) - inhalational anesthesia with 50% N2O/O2 and isoflurane; and sevoflurane group (n=15) - inhalational anesthesia with 50% N2O/O2 and sevoflurane. Patients were monitored with ECG (MC5), non-invasive blood pressure, pulse oximetry, capnography, anesthetic gas analyzer and neuromuscular function monitor. Anesthesia was induced with propofol (2, succinylcholine (1.5 followed by tracheal intubation. Atracurium and vecuronium were administered during the procedure, as needed. Neuromuscular function was reverted with neostigmine (35 to 50 µ, preceded by atropine (20 µ until T4/T1 ratio of TOF stimulation was equal to or higher than 0.9. Inhalational anesthetic inspired concentration was adjusted to maintain systolic blood pressure and heart rate within approximately 20% of preanesthetic values.

The following parameters were evaluated immediately before induction (MP), at the end of anesthesia before withdrawing inhalational agents (M0), and at 5, 10, 15, 20, 30 and 40 minutes thereafter (M5 to M40): consciousness level (4 = conscious, 3 = somnolent, awakens with verbal command, 2 = somnolent, wakens when touched, 1 = agitated, disoriented, 0 = comma), photomotor reflex (1 = present, 0 = absent), eyelash reflex (1 = present, 0 = absent), muscle tone (3 = increased, 2 = normal, 1 = decreased, 0 = absent), bicipital reflex (3 = increased, 2 = normal, 1 = decreased, 0 = absent), patellar reflex (3 = increased, 2 = normal, 1 = decreased, 0 = absent), plantar clonus (2 = sustained for more than 5 seconds, 1 = sustained for 5 seconds or less, 0 = absent), plantar reflex (2 = extension response, 1 = flexion response, 0 = absent), reaction to tracheal tube (1 = present, 2 = absent), shivering (1 = present, 0 = absent).

Evaluations were performed by an observer blind to the inhalational anesthetic drug. For such, vaporizers were covered and the observer left the operating room after initial evaluation returning only after anesthesia withdrawal.

Demographics data were compared between groups by unifactorial analysis of variance and Chi-square test. The incidence of neurological abnormalities was compared between groups by Chi-square and Fisher exact tests. Spearman R coefficients were calculated between scores of each neurological parameters and consciousness scores. Tympanic temperature of patients with or without shivering was compared by Student's t test. Significance level was stablished to 5%.



There were no difference in demographics data or anesthesia duration between groups (Table I).

Sevoflurane group patients (Figure 1) had an earlier recovery. There was no difference between groups in times to return to normal photomotor and eyelash reflexes (Figures 2 and 3). There was no significant difference between groups in muscle hypertonia in M20, except for its lower incidence in sevoflurane group compared to enflurane group (Figure 4). Enflurane group patients presented a higher incidence of increased patellar reflex as compared to isoflurane group patients from M10 to M40 (Figure 5). Plantar clonus was more frequent in the enflurane group as compared to groups I and S in M15, M20 and M40. There was a significant difference in M30 only between groups E and I (Figure 6). Sevoflurane group patients showed extension plantar response only in M5. In spite of this, there was no significant difference in extension plantar response between other groups or when compared to the sevoflurane group (Figure 7). There was no difference between groups in increased  bicipital reflex incidence (Figure 8).

Sevoflurane group patients had shivering only in M20. In M30, the incidence of shivering was significantly higher in groups E and I as compared to the sevoflurane group. In M40, only the enflurane group was significantly different from the sevoflurane group (Figure 9). Mean tympanic temperatures were 35.19 ± 0.61 ºC and 35.46 ± 0.9 ºC for patients with  and  without  shivering respectively (p = 0.33).

The incidence of neurological changes throughout the observation period is shown in table II. There was a significant difference in increased patellar reflex incidence in the enflurane group as compared to the sevoflurane group. The incidence of shivering was also higher in groups E and I as compared to the sevoflurane group.

Photomotor, eyelash, patellar and plantar reflexes recovery was significantly related to the consciousness recovery (Spearman R coefficients - 0.61, 0.79, 0.23 and 0.11, respectively).



Extension plantar response, muscle hypertonia, increased bicipital and patellar reflexes as well as plantar clonus are signs of piramidal pathway injury3. However, they may also occur in the immediate postanesthetic period and not represent permanent neurological damage1,2. In general, these abnormal neurological signs do not last more than 60 minutes2, in contrast to psychomotricity4 and to the apnea test after hyperventilation5, which may persist altered for up to 120 minutes after anesthesia.

In our study, the enflurane group presented a significantly higher incidence of increased patellar reflex as compared to the isoflurane group. Other authors have also reported that enflurane results in a higher incidence of transient neurological changes as compared to halothane1 or isoflurane2, although a different study comparing enflurane with isoflurane has not found significant differences between both agents4. The sevoflurane group, however, was not different from the others regarding the increased patellar reflex incidence.

The exact mechanism of such findings is still unknown, but could be the result of different recovery rates of various CNS centers6. These motor neuronal desinhibition signs could be caused by the reticular activator system recovery preceding the recovery of cortical centers, since inhibitory pathways of such system depend on cortical center impulses while excitatory cells have their own spontaneous activity. Hence, during anesthesia recovery, there might to be a hyper-excitability period of spinal cord anterior horn cells, which could explain such findings.

On the other hand, a direct excitatory effect on the CNS could explain such abnormalities. A study with rats anesthetized with isoflurane has shown that dopamine processing is significantly increased in basal glanglia and that this finding could be the cause for animals hypermotility observed in the postanesthetic recovery period7.

In our study, the incidence of shivering was significantly higher in the enflurane and isoflurane groups as compared to the sevoflurane group. However, there was no difference in tympanic temperature when comparing patients with and without postanesthetic shivering. In a different study8, shivering was observed in patients anesthetized with isoflurane who were normothermic at the end of anesthesia, although 80% presented with thermoregulating peripheral vasoconstriction. The authors suggest that shivering could have a multifactorial origin depending on temperature and type of anesthesia. Electromyographic studies suggest the existence of at least two different types of shivering: the first  with tonic pattern resembling normal thermoregulating shivering, and the other with clonic pattern, specific of volatile anesthetics recovery9. It is possible that this specific shivering pattern could result from an anesthetic-induced desinhibition of the normal control over spinal reflexes8,9.

Previous studies have shown that consciousness recovery is related to pupillary and eyelash reflexes recovery 1,2. In our study, in addition to being related to pupillary and eyelash reflexes recovery, consciousness was also related to the disappearance of increased patellar reflex and extension plantar response.

The conclusion was that enflurane, isoflurane and sevoflurane induce qualitatively similar transient neurological changes during anesthesia emergence, but enflurane induces a higher incidence of increased patellar reflex as compared to isoflurane. Shivering was more frequent with enflurane and isoflurane. As in previous studies1,2, neurological abnormalities were more evident in lower limbs. It is worth stressing that, within our study, neurological changes disappeared in 40 minutes.



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Correspondence to
Dr. Getúlio Rodrigues de Oliveira Filho
Address: Rua Luiz Delfino 111/902
ZIP: 88015-360 City: Florianópolis, Brazil

Submitted for publication February 22, 2001
Accepted for publication May 2, 2001



* Received from Hospital Governador Celso Ramos, CET/SBA Integrado de Anestesiologia da SES-SC, Florianópolis, SC

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