Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.54 no.5 Campinas Sept./Oct. 2004
Effects of general anesthesia in elderly patients memory and cognition*
Efecto de la anestesia general en la cognición y memoria del paciente de edad avanzada
Régis Borges Aquino, TSA, M.D.I; Antonio Carlos Araújo de Souza, M.D.II; Irani de Lima Argimon, M.D.III; Patrícia F. Ritter dos Santos, M.D.IV
IProfessor Adjunto da Disciplina de
Anestesiologia da FM - PUCRS
IIMembro do Instituto de Geriatria do Hospital Universitário São Lucas da PUCRS, Professor da Disciplina de Geriatria da FM - PUCRS, Doutoramento em Geriatria
IIIPsicóloga; Membro do Serviço do Instituto de Geriatria e Gerontologia do Hospital Universitário São Lucas da PUCRS
IVAcadêmica de Psicologia da PUCRS
BACKGROUND AND OBJECTIVES: General anesthesia
and mental function have been subject to studies and considerations, especially
for the feeling that, especially in the elderly, it could induce changes in
cognition and memory. This study aimed at evaluating the effects of general
anesthesia in cognition and memory of elderly patients, correlating them to
gender, age and anesthesia duration.
METHODS: This is a cohort, controlled study with patients divided in two observation groups: a - anesthetic; b - clinical (control). Outcome variables studied were Mini-mental test, Verbal Fluency test and Numeric Remembrance test scores; general anesthesia with halothane, isoflurane, sevoflurane, thiopental, propofol, etomidate, fentanyl, alfentanil, succinylcholine, atracurium and pancuronium; intraoperative period with PaCO2 30 to 45 mmHg, hemoglobin saturation above 90% and blood pressure tolerance with up to 20% decrease as compared to baseline. Patients presenting any intra and postoperative adverse event were excluded from the study. Chi-square test was used for categorical data. Students t test for independent samples was used for initial comparison between groups at baseline moment (preanesthetic). Analysis of variance (ANOVA) for repeated measures was used to evaluate anesthetic process effects along time.
RESULTS: Groups were similar in the Mini-Mental test with increased scores along time. Both groups had virtually unchanged Verbal Fluency test scores. Both groups were very similar in Numeric Remembrance test with increased scores in both groups.
CONCLUSIONS: No postoperative cognition or memory decline has been observed in patients of both genders, aged 60 to 80 years, submitted to general anesthesia lasting 3 to 7 hours.
Key Words: ANESTHESIA, General: geriatric; CENTRAL NERVOUS SYSTEM: cognition, memory
JUSTIFICATIVA Y OBJETIVOS: La anestesia
general y la función mental han sido objetivos de estudios y consideraciones,
especialmente por el sentimiento de que ella, particularmente en paciente de
edad avanzada, podría inducir alteraciones en la cognición y en la
memoria. El objetivo de esa pesquisa fue evaluar el efecto de la anestesia general
en la cognición y en la memoria del paciente de edad avanzada correlacionándola
al sexo, a la edad y al tiempo de anestesia.
MÉTODO: Estudio de coorte controlado realizado en pacientes categorizados en dos grupos de observación: a- anestésico; b- clínicos (controle). Las variables del resultado consideradas fueron los escores del teste MiniMental, del teste de Fluencia Verbal y del test de Recuerdo Numérico. Anestesia general con halotano, isoflurano, sevoflurano, tiopental, propofol, etomidato, fentanil alfentanil, succinilcolina atracúrio, pancuronio. Intra-operatorio con PaCO2 entre 30 y 45 mmHg y saturación de hemoglobina superior a 90% y tolerancia de PA con disminución hasta 20% del valor basal. Fueron excluidos pacientes que presentaron algún evento adverso en el intra y pos-operatorio. Datos categóricos analizados por el test del Qui-cuadrado. La comparación inicial entre los grupos en el momento basal (pre-anestésico) fue realizada por la t de Student para muestras independientes. Para evaluación del efecto del proceso anestésico a lo largo del tiempo, fue utilizado el análisis de variancia (ANOVA) para medidas repetidas.
RESULTADOS: En el teste del MiniMental los grupos presentaron comportamiento semejante siendo notado aumento de escores a lo largo del tiempo. En el test de Fluencia Verbal, en ambos los grupos los escores se mantuvieron prácticamente inalterados. En el test de Recuerdo Numérico el comportamiento de los grupos fue muy semejante a lo largo del seguimiento siendo que los escores aumentaran en ambos los grupos.
CONCLUSIONES: No fue detectado declinio de cognición o de memoria en el post operatorio de paciente com edad 60 a 80 años de ambos los sexos, sometidos a la anestesia general con duración de 3 a 7 horas.
General anesthesia predominantly affects central nervous system with repercussions in all body tracts and systems. Its intrinsic action mechanism is still not totally understood and for such, the possibility of some temporary or permanent cognitive and memory impairment has always been subject to considerations. Elderly patients are of special concern for being more susceptible to homeostatic and environmental changes 1,2. Cognition is defined as the ability to understand the world, reasoning and decisions 3,4. Memory is defined as the ability to remember facts and situations, in addition to the story of ones life. It is not a single factor, but rather a set of interlinked situations and active interactions 5. For study and teaching purposes, it has been classified in several types: a) anterograde memory, which allows to retain new information 6,7; b) retrograde memory, which allows the access to past information and where remote memory is located 6,7; c) explicit memory, related to conscious and intentional memories of facts or situations which may be accessed by recognition tests: and d) implicit memory, able to influence both behavior and performance of an action and which does not require any intentional or conscious recognition of such experiences, implying unconscious memories 8-13. This study focuses anterograde and explicit memories of the elderly, exactly because it is the most fragile, and aims at correlating the effects of general anesthesia to cognitive and memory postoperative changes in elderly of both genders, aged 60 to 80 years.
After the Research Ethics and Scientific Committee, Faculdade de Medicina, PUCRS and Hospital São Lucas, Porto Alegre, RS approval, a short duration (72 hours) cohort and controlled study was performed, in which patients were classified in two observation groups: group A (anesthetic) - research group (n = 50) with surgical patients; and group C (clinical) - control group (n = 30) with patients admitted for clinical diseases. Group A patients were submitted to cognitive and memory state evaluation in the following moments: baseline (preanesthetic), first postoperative day (24 hours) and 3rd postoperative day (72 hours). Group B patients were evaluated at baseline moment and 72 hours later. Basic outcome variables of this study were the scores of the following tests: a) Mini-Mental State, to evaluate mental state with cutoff at score 20 14; b) Numeric Remembrance Test with cutoff at 5 15; c) Verbal Fluency Test in the animal category in one minute, with cutoff at 4 16.
Population and sample: patients aged 60 to 80 years, admitted to the Hospital Universitário São Lucas, PUCRS.
Inclusion criteria were: a) physical conditions considered regular or good, according to the American Society of Anesthesiology classification (ASA) I to IV 17; b) age: 60 to 80 years submitted to surgery under general anesthesia for a minimum period of 3 hours; c) sensory: lucid, able to answer to applied tests, agreement in participating of the research and signed authorized consent. Exclusion criteria were: a) patients with cognitive changes unable to answer the questionnaires or with psychiatric disease; b) perioperative or immediate postoperative adverse event; c) myocardial surgery with cardiopulmonary bypass, neurosurgeries, or open chest surgeries; d) urgency surgeries.
Monitoring in group A consisted of noninvasive blood pressure, pulse oximetry, cardiac monitor, stethoscope, capnography and venoclysis. Anesthesia was induced with intravenous thiopental, propofol or etomidate, fentanyl, alfentanil or sufentanil, and tracheal intubation was helped with succinylcholine or atracurium. Anesthesia was maintained with halothane, enflurane, isoflurane or sevoflurane, 33% minimum oxygen inspired fraction (O2) with or without nitrous oxide (N2O), manual or mechanical ventilation. Hemoglobin saturation was maintained above 90%, expired CO2 between 30 and 45 mmHg, and blood pressure not below or above 20% of baseline. Postoperative analgesia was induced with dipirone or opioids. General anesthesia was induced by the Anesthesiology team of Hospital Universitário São Lucas, PUCRS, who did not know about the study.
Quantitative data were described in mean and standard deviation in respective evaluation moments (baseline, 24 and 72 hours). Students t test for independent samples was used for initial comparisons between groups at baseline moment. Analysis of Variance (ANOVA) for repeated measures was used to evaluate anesthetic effects along time. Categorical data were described by absolute and percentage frequencies, with significance determined by chi-square test. Significance level was a = 0.05. Calculations and charts were performed with the aid of Statistical Package for the Social Sciences (SPSS) v. 9.0 and SigmaPlot v. 7.0 software packages.
Groups A and C had no significant differences in basic demographics (gender and age) and preanesthetic conditions estimated by the American Society of Anesthesiologists (ASA) score, as shown in table I.
In the Mini-Mental score baseline comparison (Table II), group A mean has been higher as compared to group C, with statistical significance when Students t test for independent samples was used (24.3 vs. 22.5; t(0.05;78) = 2.12; p = 0.038). When this score was evaluated by ANOVA for repeated measures, a global increase has been observed for both groups from baseline moment to 72 postoperative hours moment (F(0.05;1;78) = 7.95; p = 0.006). However, statistically significant difference between groups has not been confirmed by ANOVA (F(0.05;1;78) = 2.11; p = 0.150). A significant interaction effect of the ANOVA model (F(0.05;1;78) = 4.23; p = 0.043) has confirmed the finding that although starting from slightly different points at baseline moment (Table II), both groups had very similar Mini-Mental scores at 72 postoperative hours (24.6 vs. 24).
There have been no significant Verbal Fluency score differences between groups at baseline moment (t(0.05;78) = 0.834; p = 0.407) and during follow up (time factor) (F(0.05;1;78) = 0.08; p = 0.781). In addition, groups had no relevant differences among them (F(0.05;1;78) = 0.11; p = 0.747) (Table II).
As shown in table II, Numerical Remembrance scores have not differed between groups in baseline (t(0.05;78) = 0.46; p = 0.645) and any other follow up moment (F(0.05;1;78) = 1.69; p = 0.197). The score, however, has suffered an increase in both groups during the study period (F(0.05;1;78) = 8.19; p = 0.005), although of minor magnitude. Interaction between groups has not been relevant, confirming similar (and minor) score increase between groups (F(0.05;1;78) = 1,55; p = 0.218).
Surgical trauma triggers hormone discharges, such as catecholamines, growth hormone and others, but to date there is no research pointing them as promoting mental decline 27. So, it is natural that general anesthesia is the major suspicious for causing postoperative cognition and memory decline, because it is the less known fact of the surgical process. However, other postoperative situations, such as lack of sleep, dehydration, restriction to bed and opioids may contribute for mental decline. There are studies in the literature pointing general anesthesia as promoting cognitive decline based only on family information 18-20. In this case, there is poor scientific value due to the lack of quantification of the phenomenon and the inconsideration of other factors following intra and postoperative period. There are studies referring cognition and memory decline in the 1st, 3rd and 5th postoperative days. Others refer it in the first week and still others some months later 7,21-26. In some of these studies, opioids were used to control postoperative pain, which by itself could promote mental decline 7,11,18,19,27. On the other hand, there are studies exempting general anesthesia as promoting postoperative mental dysfunction evaluated at 1, 2, 3 and 4 weeks, and at 3, 6 and 12 months. Most studies do not mention inclusion criteria and some do not refer evaluation tests 25 or anesthetic conditions, such as pressure and arterial gases level tolerance 7,18,21-23,26,27.
For memory studies, tests allow for changes to be expressed in numbers and evaluate them with statistical significance. We have chosen three tests as tools to evaluate cognition and memory. Mini-Mental questionnaire is internationally known and used in several researches for this aim. Numeric Remembrance and Verbal Fluency tests are also adopted in our country. Selection criteria were patients with similar situations before, during and after anesthesia so that the only new factor with chances to change mental function would be general anesthesia. Considering observation conditions, cognition and memory evaluation tools, anesthetic technique and selected samples, our results allow us to conclude that no postoperative cognition or memory decline has been observed in elderly patients aged 60 to 80 years, submitted to surgeries lasting 3 to 7 hours under general anesthesia.
01. Evers AS - Cellular and Molecular Mechanisms of Anesthesia, em: Barash PG, Cullen BF, Stoelting RK - Clinical Anesthesia. 3rd Ed, Philadelphia: Lippincott-Raven, 1989;119-136. [ Links ]
02. Oskvig RM - Special problems in elderly. Chest, 1999;115: (Suppl5)158S-164S. [ Links ]
03. Blazer D - Epidemiologia dos Transtornos Psiquiátricos no Idoso, em: Busse EW, Blazer DG - Psiquiatria Geriátrica. 2ª Ed, Porto Alegre: Artes Médicas; 1999;167-183. [ Links ]
04. Folstein M, Anthony JC, Parhad I et al - The meaning of cognitive impairment in the elderly. J Am Geriatr Soc, 1985;33: 228-235. [ Links ]
05. Callicott JH, Mattay VS, Bertolino A et al - Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex, 1999;9:20-26. [ Links ]
06. Larry RS - Mechanisms of memory. Science, 1986;232: 1612-1619. [ Links ]
07. Guyton AC, Hall JE - O Córtex Cerebral; Funções Intelectuais do Cérebro; Aprendizagem e Memória, em: Tratado de Fisiologia Médica. 9ª Ed, Rio de Janeiro, Guanabara Koogan; 1997;661-673. [ Links ]
08. Lubke GH, Kerssens C, Gershon RY et al - Memory formation during general anesthesia for emergency cesarean sections. Anesthesiology, 2000;92:1029-1034. [ Links ]
09. Cork RC, Kihlstrom JF, Schacter DL - Absence of explicit or implicit memory in patients anesthetized with sufentanil/nitrous oxide. Anesthesiology, 1992;76:892-898. [ Links ]
10. Echevaria M, Caba F, Rodriguez J et al - Memória explícita e implícita durante anestesia inhalatória e intravenosa. Rev Esp Anestesiol Reanim, 1998;45:220-225. [ Links ]
11. Renna M, Lang EM, Lockwood GG - The effect of sevoflurane on implicit memory: a double- blind, randomised study. Anaesthesia, 2000;55:634-640. [ Links ]
12. Ghoneim MM, Block RI - Learning and memory during general anesthesia an update. Anesthesiology, 1997;87:387-410. [ Links ]
13. Veselis RA - Memory function during anesthesia. Anesthesiology, 1999;90:648-650. [ Links ]
14. Folstein MF, Folstein SE, McHugh PR - "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res, 1975;12:189-198. [ Links ]
15. Seidenberg M, O´Leary DS, Berent S et al - Changes in seizure frequency and test-retest scores on the Wechler Adult Intelligence Scale. Epilepsia, 1981;22:75-83. [ Links ]
16. Brucki SM Malheiros SMF, Okamotto IH et al - Normative data on the verbal fluency test in the animal category in our milieu. Arq Neuropsiquiatr, 1997;55:56-61. [ Links ]
17. Firestone LL - General Preanesthetic Evaluation, em: Firestone LL, Lebowitz PW, Cook CE - Clinical Anesthesia Procedures of the Massachusetts General Hospital. 3rd Ed, Boston, Little Brown; 1988;3-14. [ Links ]
18. Ritchie K, Polge C, de Roquefeuil G et al - Impact of anesthesia on the cognitive functioning of the elderly, Int Psychogeriatr, 1997;9:309-326. [ Links ]
19. Brewer KK, Haq A, Cullum CM et al - Anesthesia exposure as a possible risk factor for cognitive decline in the elderly. Facts Res Gerontol, 1996;7:161-170. [ Links ]
20. Bedford PD - Adverse cerebral effects of anesthesia on old people. Lancet, 1955:6:259-263. [ Links ]
21. Storms LH, Stark AH, Calverley RK et al - Psychological functions after halothane or enflurane anesthesia. Anesth Analg, 1980;59:245-249. [ Links ]
22. Crul BJ, Hulstijn W, Burger IC - Influence of the type of anaesthesia on post-operative subjective physical well-being and mental function in elderly patients. Acta Anaesthesiol Scand, 1992:36:615-620. [ Links ]
23. Rollason WN, Robertson GS, Cordiner CM et al - A comparison of mental function in relation to hypotensive and normotensive anaesthesia in the elderly. Br J Anaesth, 1971;43 561-566. [ Links ]
24. Rosenberg J, Kehlet H - Postoperative mental confusion-association with postoperative hypoxemia. Surgery, 1993;114:76-81. [ Links ]
25. Hole A, Terjesen T, Breivik H - Epidural versus general anaesthesia for total hip arthroplasty in elderly patients. Acta Anaesthesiol Scand, 1980;24:279-287. [ Links ]
26. Davison LA, Steinhelber JC, Eger EI et al - Psychological effects of halothane and isoflurane anesthesia. Anesthesiology, 1975;43:313-324. [ Links ]
27. Faintuch J, Machado CCM - Alterações Clínicas e Metabólicas no Período Pós-Operatório, em: Raia AA, Zerbini EF - Clínica Cirúrgica Alípio Correa Neto. 4ª Ed, São Paulo, Savier, 1988;24-31. [ Links ]
Submitted for publication June 6, 2003
Accepted for publication February 11, 2004
* Received from Hospital Universitário São Lucas da Faculdade de Medicina da Pontifícia Universidade Católica de Porto Alegre (FM PUCRS), Porto Alegre, RS