Regression of general anesthesia in patients with cerebral palsy: a comparative study using the bispectral index

Abstracts

JUSTIFICATIVA E OBJETIVOS: É descrito que os pacientes com paralisia cerebral (PC) são mais sensíveis aos agentes anestésicos que poderia comprometer o despertar da anestesia. O objetivo deste estudo foi avaliar a recuperação de pacientes com PC comparada com pacientes sem doença do SNC. MÉTODO: Participaram do estudo crianças de 5 a 15 anos, divididas em dois grupos: com diagnóstico de paralisia cerebral e sem doença do SNC. Todas foram submetidas à anestesia geral com sevoflurano associado a óxido nitroso e oxigênio a 50%. Além da monitorização habitualmente empregada, foram monitorizadas com o EEG-BIS. Durante o despertar da anestesia, a extubação traqueal e o pós-anestésico imediato, foi avaliada a regressão da anestesia segundo os critérios adotados por Saraiva. Avaliou-se também a velocidade de eliminação dos agentes anestésicos correlacionando-a com os valores de EEG-BIS e comparando os dois grupos de pacientes. A análise estatística foi realizada por meio da análise exploratória de dados e teste estatístico para comparação de médias, considerando como diferença estatística significativa o valor de p menor ou igual a 5%. RESULTADOS: Foram avaliados 56 pacientes, sendo 31 com PC e 25 sem doença do SNC. Os grupos foram homogêneos com relação à idade e ao sexo. O valor do EEG-BIS basal dos pacientes com PC foi menor do que o grupo-controle, com diferença estatística significativa (p = 0,04). Nos cinco primeiros minutos após a interrupção do sevoflurano, o valor do EEG-BIS dos pacientes com PC apresentou elevação mais lenta com relação ao controle. A velocidade de eliminação do agente anestésico foi semelhante nos dois grupos. Aos 15 minutos, 48% dos pacientes do grupo-controle estavam no estágio III de regressão anestésica, versus 29% do grupo com paralisia cerebral. Aos 30 minutos, 72% dos pacientes do grupo-controle estavam aptos para receber alta, no estágio IV de regressão anestésica, versus 41,9% dos pacientes com PC. CONCLUSÕES: Os pacientes com paralisia cerebral apresentaram retorno mais lento da consciência em comparação com o grupo-controle.

ANESTESIA, Geral; DOENÇAS, Neurológica; RECUPERAÇÃO PÓS-ANESTÉSICA

SCIENTIFIC ARTICLE

Regression of general anesthesia in patients with cerebral palsy. A comparative study using the bispectral index^*

Regresión de la anestesia general en pacientes con parálisis cerebral. Estudio comparativo utilizando el índice bispectral

Verônica Vieira da Costa, TSA, M.D.^I; Renato Ângelo Saraiva, TSA, M.D.^I; Leonardo Teixeira Domingues Duarte, TSA, M.D.^II

^IAnestesiologista do Hospital SARAH

^IICoordenador de Anestesiologia da Rede SARAH de Hospitais

^{Correspondence to}

SUMMARY

BACKGROUND AND OBJECTIVES: It has been said that patients with cerebral palsy (CP) present a higher sensitivity to anesthetic agents, which may affect adversely the awakening from anesthesia. The objective of this study was to evaluate the recovery of patients with CP compared with patients without CNS disease.

METHODS: The study population was composed of children ages 5 to 15, divided in two groups: those with a diagnosis of cerebral palsy and those without CNS disease. All of them underwent general anesthesia with sevoflurane associated with nitrous oxide and 50% oxygen. Besides the parameters commonly monitored, they also underwent EEG-BIS monitoring. Regression of general anesthesia during awakening from anesthesia, tracheal extubation, and the immediate postanesthetic period were evaluated according to the criteria adopted by Saraiva. The speed of elimination of the anesthetic agents was also evaluated, correlating it with the EEG-BIS values, and comparing the two groups of patients. Statistical analysis was done through exploratory analysis of the data and statistical testing comparing the means. The statistical difference was considered significant for values of p smaller or equal to 5%.

RESULTS: Fifty-six patients were evaluated: 31 with CP and 25 without CNS disease. Both groups were homogenous regarding age and gender. Baseline EEG-BIS values for CP patients were smaller than those for the control group, and this difference was statistically significant (p = 0.04). During the first five minutes after discontinuation of sevoflurane, the elevation of the EEG-BIS values for CP patients was slower than for the control group. The speed of elimination of the anesthetic agent was similar in both groups. At 15 minutes, 48% of the patients in the control group were in stage II of anesthetic regression versus 29% of the patients with cerebral palsy. At 30 minutes, 72% of the patients in the control group were in condition to be discharged, in stage IV of anesthetic regression, versus 41.9% of the patients with CP.

CONCLUSIONS: Patients with cerebral palsy presented a slower return to the conscious state when compared with patients in the control group.

Key Words: ANESTHESIA, General: inhalational; DISEASES, Neurological: cerebral palsy; POSTANESTHETIC RECOVERY: anesthesia regression.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: Se ha descrito que los pacientes con parálisis cerebral (PC) son más sensibles a los agentes anestésicos, lo que podría comprometer el despertar de la anestesia. El objetivo de este estudio fue el de evaluar la recuperación de pacientes con PC comparada a los pacientes sin enfermedad del SNC.

MÉTODO: Participaron del estudio niños de 5 a 15 años, divididos en dos grupos: con diagnóstico de parálisis cerebral y sin la enfermedad del SNC. Todos se sometieron a anestesia general con sevoflurano asociado a óxido nitroso y oxígeno a 50%. Además de la monitorización habitualmente empleada fueron monitorizados con el EEG-BIS. Durante el despertar de la anestesia, la extubación traqueal y el posanestésico inmediato, se avaluó la regresión de la anestesia según los criterios adoptados por Saraiva. También se evaluó la velocidad de eliminación de los agentes anestésicos correlacionándola con los valores de EEG-BIS y comparándola con los dos grupos de pacientes. El análisis estadístico se realizó a través del análisis de exploración de datos y prueba estadística para la comparación de promedios, considerando como diferencia estadística significativa el valor de p menor o igual a 5%.

RESULTADOS: Se evaluaron 56 pacientes siendo 31 con PC y 25 sin enfermedad del SNC. Los grupos fueron homogéneos con relación a la edad y el sexo. El valor del EEG-BIS basal de los pacientes con PC fue menor que el grupo control, con diferencia estadística significativa (p = 0,04). En los cinco primeros minutos después de la interrupción del sevoflurano, el valor del EEG-BIS de los pacientes con PC presentó una elevación más lenta con relación al control. La velocidad de eliminación del agente anestésico fue semejante en los dos grupos. A los quince minutos 48% de los pacientes del grupo control estaba en el estadio III de regresión anestésica, versus 29% del grupo con parálisis cerebral. A los treinta minutos, el 72% de los pacientes del grupo control estaba apto para recibir el alta, estadio IV de regresión anestésica, versus 41,9% de los pacientes con PC.

CONCLUSIONES: Los pacientes con parálisis cerebral presentaron un regreso más lento de la conciencia en comparación con el grupo control.

INTRODUCTION

Cerebral palsy (CP) is defined as a disorder that affects posture and movements, secondary to a static lesion of the developing brain ¹. In developed countries, it is the most common cause of motor dysfunction in children, and its prevalence in school age children is about 2 in 1,000 live births ². Several studies state that CP patients present a higher sensitivity to anesthetic agents, which affect the central nervous system (CNS) ^3-5. This can be observed in the electroencephalogram with bispectral index (EEG-BIS), which has demonstrated to be a reliable tool to monitor the hypnotic effect of anesthetic drugs in the CNS of young adults and children without CNS disease ^6,7.

It is possible that this increased sensitivity would compromise awakening from anesthesia. We did not find any specific study in the literature that compared the awakening from anesthesia of CP patients with that of patients without CNS disease.

The objective of this study was to compare the awakening of CP patients with that of patients without CNS disease.

METHODS

The parents signed an informed consent allowing their children to participate in the study, which was approved by the Ethics Committee of the hospital. Fifty-six children with ages between 5 and 15 years, of both genders, physical status ASA I and II, that would be submitted to surgical procedures under general anesthesia associated with regional anesthesia, were included in the study. Patients were divided in two groups: patients with a diagnosis of cerebral palsy (CP group) and patients without CNS disease (control group). All patients received oral midazolan, as premedication, 0.7 mg.kg^-1 about 40 minutes before anesthetic induction.

As part of the diagnostic work up, CP patients underwent a specialized medical evaluation, and had an imaging exam done (brain MRI or CT scan).

In the anesthetic induction room, patients were monitored with continuous EEG, noninvasive blood pressure, pulse oximeter, capnograph with gas analyzer, nasopharyngeal temperature sensor, and EEG-BIS with electrodes placed according to the International System 10-20 of the International Clinical Neurophysiology Society (ICNS). Basal EEG-BIS values were then recorded.

Anesthetic induction was done with sevoflurane and nitrous oxide with 50% oxygen by face mask. Tracheal intubation was used to protect the airways. After intubation, patients were placed on lateral decubitus and epidural lumbar anesthesia was performed with ropivacaine, using concentrations and volumes according to the patient's age, up to a maximum of 3 mg.kg^-1 of the local anesthetic, so the surgical stimulus would not influence EEG-BIS values. General anesthesia was maintained with sevoflurane and nitrous oxide. EEG-BIS values were recorded in the following times: before induction of general anesthesia (baseline value), at the end of the surgical procedure (at the moment the vaporizer was turned off), every minute after the discontinuation of the anesthetics, and at the time of extubation.

At the end of the surgical procedure, after the EEG-BIS was recorded, the sevoflurane vaporizer was turned off, the nitrous oxide was discontinued, and we waited for the elimination of the drugs and the beginning of the awakening for 7 minutes. During this period, the EEG-BIS and the expired fraction of the anesthetic agents were recorded every minute, as well as the eventual awakening of the patient. The usual procedure of tracheal extubation was then initiated. The length of time from the discontinuation of the anesthetic agents until tracheal extubation and the EEG-BIS values at the moment of tracheal extubation were recorded. Tracheal extubation was performed when the patients were reacting to the presence of the tracheal tube and to painful stimuli.

In the postanesthetic recovery unit, patients were evaluated according to the stages of regression of anesthesia proposed by Saraiva ⁸ (Table I). The times when the patients reached each regression stage were recorded, as well as the length of time until the patient was discharged.

Statistical Analysis

Descriptive or exploratory analysis was used to verify the changes in the neurophysiological variable detected by the EEG-BIS monitor, the length of time necessary to eliminate the anesthetic agents, the length of time until the patient was discharged from the recovery unit, as well as the patient's age and weight. Paired t test was used to compare the means between both groups, and the Levene test was used for variance parity. A p value equal or smaller than 5% was considered statistically significant.

Mean and standard deviation values were used in every analysis and expressed in figures and tables to show the results.

The Chi-square test was used to compare gender, physical status (ASA), and stage of anesthetic regression between both groups.

RESULTS

Fifty-seven patients were evaluated. One patient in the CP group was excluded due to problems with the EEG-BIS monitor.

Both groups were homogenous regarding age and gender. The mean weight in the control group was higher that in the CP group (p = 0.04) (Table II).

The mean basal EEG-BIS value of CP patients (86.9) was smaller than in the control group (93.1). This difference was statistically significant (p = 0.04) (Figure 1).

Twenty-one of the 31 patients in the CP group had abnormal imaging exams (brain MRI or CT scan) (Chart I). The mean basal EEG-BIS of these patients (84.6) was lower than in the control group (93.1). The difference was statistically significant (p = 0.02).

During anesthetic maintenance, for the same final expiratory fraction (alveolar) of sevoflurane and nitrous oxide, the mean EEG-BIS value was smaller in CP patients than in the control group. The difference was not statistically significant (p = 0.02).

After the anesthetics were discontinued, the mean EEG-BIS values of CP patients returned more slowly to baseline values than in patients in the control group. This difference was significant (p = 0.02), and was maintained until the fifth minute after the sevoflurane vaporizer was turned off. After the 5^th minute the difference between both groups was not statistically significant (Figure 2). At this moment, the final expiratory fraction (alveolar) of the anesthetic agents was measured; it showed no statistically significant difference between both groups (Figure 3).

At the time of extubation, mean EEG-BIS values and the length of time between the time the anesthetics were discontinued and the removal of the tracheal tube were recorded. The mean EEG-BIS value recorded was 85 for CP patients and 83 for the control group. The mean length of time for tracheal extubation was 7.6 minutes for CP patients and 7.1 minutes for the patients in the control group. There were no differences between both groups.

In the posthanesthetic recovery unit, the Saraiva scale was used to evaluate the stages of anesthetic regression. The first evaluation was done 15 minutes after the discontinuation of the anesthetic: 29% of the CP patients were in stage I, 32.3% in stage II, 29% in stage III, and 9.7% in stage IV of anesthetic regression. The patients in the control group underwent the same evaluation: 8% were in stage I, 32% in stage II, 48% in stage III, and 12% in stage IV (Table III). The number of patients in stage I was compared with the number of patients in other stages, but there were no differences among the groups (p = 0.08). A new evaluation was done 30 minutes after the discontinuation of the anesthetic drugs. In the CP group, 12.9% remained in stage I, 19.4% in stage II, 25.8% in stage III, and 41.9% in stage IV. In the control group only 4% remained in stage I, 4% in stage II, 20% in stage III, and 72% were in stage IV (Table IV). Comparing the number of patients in stage IV with the number of patients in other stages, we found a statistically significant difference (p = 0.032), showing that a higher percentage of patients in the control group reached stage IV in less time (30 minutes) than patients in the CP group.

There was no difference between both groups regarding the length of time until they were discharged from the posthanesthetic recovery unit. Cerebral palsy patients stayed around 48.5 minutes in the postanesthetic recovery room, while the patients in the control group were in the recovery room for 40.6 minutes.

DISCUSSION

The data analyzed to establish the bispectral index of the electroencephalogram were based in studies done with adults. However, the first studies on EEG-BIS in children were published in 1998 ⁹. A study with children ages between 1 and 12 years concluded that the BIS is an adequate monitor to be used in pediatric patients of any age ¹⁰.

Cerebral palsy patients weighed less than patients in the control group. This difference was expected and confirms the results found by other authors ^5,13, since CP patients present swallowing deficits, gastroesophageal reflux, gastrostomy or tracheostomy, and malnutrition ¹², explaining their low weight when compared to same age patients without CP.

In this study, the mean EEG-BIS value was smaller in CP patients (86.9) than in the control group (93.1). All patients received oral midazolam (0.7 mg.kg^-1), as a premedication, 40 minutes before basal EEG-BIS values were measured. This can explain the reduction in basal EEG-BIS in both groups, and not only in patients with cerebral palsy.

It has been reported that the administration of oral midazolam, as a premedication, at a dose of 0.8 mg.kg^-1, does not interfere with basal EEG-BIS values in patients without CNS disease ¹¹. Our study also confirmed that since it did not find a reduction in EEG-BIS values in the control group.

During anesthetic maintenance, with the same final expiratory fraction (alveolar) of the anesthetic agents, the mean EEG-BIS of CP patients was smaller when compared with the patients in the control group. This confirms the results found by others authors ^3-5 and suggests that the neural deficit in CP patients is the reason for a smaller EEG-BIS in face of the same alveolar fraction of the anesthetic agent. The presence of brain lesion that hinders blood flow in a specific cerebral region could also be responsible for this result. If the neurons in an area are destroyed, it is expected that the same alveolar fraction of the anesthetic agent will lead to a similar blood concentration and more pronounced action in the presence of reduced tissue mass, with possible direct repercussions on the level of conscience. Twenty-one (70%) of the 31 CP patients presented abnormal imaging exams, the majority characterized by a reduction of the cerebral cortex.

In face of this change, one would wonder whether other drugs frequently used by CP patients, such as antiepileptic, could present the same results. In this study, 10% of the patients were on antiepileptic medications and, even though they represented a small fraction of the study population, one cannot ignore the influence of this variable in the results. Other authors have also questioned the influence of antiepileptic drugs in the EEG-BIS of CP patients ^5,13.

The slower return of EEG-BIS to baseline values in CP patients suggests increased action of the anesthetic agents in the CNS of these patients. Despite drug elimination being equal in both groups, there is a slower recovery of conscience in CP patients, which can be explained by their increased sensitivity to inhalational agents, as previously reported ^3-5.

There was no difference regarding the length of time between the discontinuation of the inhalational anesthetics and tracheal extubation. Similarly, there were no differences in mean EEG-BIS values at the moment the tracheal tube was removed.

In the first five minutes, shortly after the discontinuation of the anesthetic agents, it took longer for CP patients to regain conscience than the control group, which is demonstrated by the EEG-BIS. From the 5^th minute on, mean EEG-BIS values were similar, and the length of time to extubation was not prolonged.

In the posthanesthetic recovery unit, at 15 minutes, 29% of CP patients remained in stage I of anesthetic regression (reacting only to painful stimuli), while only 8% of the patients in the control group were in this stage. Despite the considerable difference between both groups, it was statistically non-significant. At the 30-minute evaluation, 72% of the patients in the control group were already in stage IV, clinically able of being discharge to the regular ward, but only 41.9% of CP patients were at the same stage. This result indicates that total clinical regression of anesthesia was faster in the control group when compared to CP patients. The cognitive deficit presented by a few patients in the CP group may have interfered with the clinical evaluation of anesthetic regression, since it is possible they did not understand properly the questions asked. The scale used in this evaluation ⁸ was developed for patients without cognitive deficits. However, this is the scale used to evaluate every patient submitted to general anesthesia by the department responsible for this study.

One should take into consideration that the objective of this study was to include all clinical forms of CP. However, due to the selection of patients for the anesthetic technique (general associated with epidural) and for orthopedic surgery (patients with walk deficits), and the need for patient cooperation in the posthanesthetic recovery unit to evaluate regression of anesthesia, very few cases of the most serious forms of CP were included. This might have been one of the reasons the differences between the groups were not higher. The results of this study suggest that anesthetic regression of patients with cerebral palsy, regardless of their clinical classification, is slower than that of patients without any CNS disease.

REFERENCES

Submitted for publication 09 de fevereiro de 2006

Accepted for publication 30 de junho de 2006

• 01. Bax MC Terminology and classification of cerebral palsy. Dev Med Child Neurol, 1964;6:295-297.
• 02. Paneth N, Kiely J The Frequency of Cerebral Palsy: A Review of Population Studies in Industrialized Nations since 1950, em: Stanley F, Alberman E The Epidemiology of Cerebral Palsies: Clinics in Developmental Medicine. London: Blackwell, 1984;46-56.
• 03. Frei FJ, Haemmerle MH, Brunner R et al Minimum alveolar concentration for halothane in children with cerebral palsy and severe mental retardation. Anaesthesia, 1997;52:1056-1060.
• 04. Mello SS, Saraiva RA Alterações eletroneurofisiológicas em anestesia com sevoflurano: estudo comparativo entre pacientes saudáveis e pacientes com paralisia cerebral. Rev Bras Anestesiol 2003;53:150-159.
• 05. Choudhry DK, Brenn BR Bispectral index monitoring: a comparison between normal children and children with quadriplegic cerebral palsy. Anesth Analg, 2002;95:1582-1585.
• 06. McDermott NB, VanSickle T, Motas D et al Validation of the bispectral index monitor during conscious and deep sedation children. Anesth Analg, 2003;97:39-43.
• 07. Degoute CS, Macabeo C, Dubreuil C et al EEG bispectral index and hypnotic component of anaesthesia induced by sevoflurane: comparison between children and adults. Br J Anaesth, 2001;86:209-212.
• 08. Saraiva RA Estágios clínicos da regressão da anestesia. Rev Bras Anestesiol, 1976;26:37-43.
• 09. Rampil IJ, Kim JS, Lenhardt R et al Bispectral EEG index during nitrous oxide administration. Anesthesiology, 1998;89:671-677.
• 10. Denman W, Swanson E, Rosow D et al Pediatric evaluation of the bispectral index (BIS) monitor and correlation of BIS with end-tidal sevoflurane concentration in infants and children. Anesth Analg, 2000;90:872-877.
• 11. Costa VV, Saraiva RA Ação do óxido nitroso no sistema nervoso central: estudo eletrofisiológico como agente único e como agente coadjuvante. Rev Bras Anestesiol 2002;52:255-271.
• 12. Wongprasartsuk P, Stevens J Cerebral palsy and anaesthesia. Paediatr Anaesth, 2002;12:296-303.
• 13. Saricaoglu F, Celebi N, Celik M et al The evaluation of propofol dosage for anesthesia induction in children with cerebral palsy with bispectral index (BIS) monitoring. Pediatr Anesth, 2005; 15:1048-1052.

*

Received from do Hospital SARAH – Brasília, DF

Publication Dates

• Publication in this collection
  22 Sept 2006
• Date of issue
  Oct 2006

History

• Accepted
  30 June 2006
• Received
  09 Feb 2006