Effect of Depth of Total Intravenous Anesthesia Using Propofol on Postoperative Cognitive Dysfunction

The purpose of this study is to investigate whether the depth of anesthesia with propofol affects the incidence of early postoperative cognitive dysfunction

INTRODUCTION

1.1 Rationale for the study

There is a significant relation between postoperative cognitive dysfunction and increasing age, increasing duration of surgery. But, up to now, the effect of the depth of anesthesia on POCD remains controversial. This study is designed to investigate whether the depth of anesthesia affects the incidence of POCD, we will use propofol for total intravenous anesthesia in elderly patients whose depth of anesthesia was monitored and adjusted by bispectral index (BIS). The early and long-term incidence of POCD will be compared between deep and light-anesthesia groups.

1.2 Background

We hypothesize that depth of anesthesia may exert an influence on the early postoperative cognitive dysfunction. One reason that deep anesthesia might protect cognitive function is the prevention of the stress response to noxious stimulation. The noxious stimulation of surgery can induce stress responses whose severity correlates with the intensity of surgery (major versus minor).Light anesthesia with a serious stress response to noxious stimulation may increase the incidence of POCD. Furthermore, major surgery causing a serious stress response can give rise to a higher incidence of early postoperative cognitive dysfunction than minor. This may also prove our hypothesis on the other hand. The elderly patients who received major surgery had a higher incidence of early POCD than those who received minor surgery. A deleterious stress response can be associated with major surgery or light anesthesia, and it can cause excessive production of corticosteroids that target receptors in the cerebral cortex and subcortical nucleus, eventually resulting in neuron injury. This may explain why the elderly has a higher incidence of early POCD after surgery. However, the effect of the depth of anesthesia on POCD remains controversial. Farag E et al. randomized 74 patients to either a low Bispectral Index (BIS) regimen or a high BIS regimen during the surgical procedure. Preoperatively and 4-6 week after surgery, the patients' cognitive status was assessed with a cognitive test battery consisting of processing speed index, working memory index, and verbal memory index. Processing speed index was higher in the low BIS group versus the high BIS group. But no difference was observed in the other two test battery components. Certainly one of the limitations of their data is that the observed difference in cognitive ability occurred in only one of three assessments. Recently, we have made a randomised, double-blind, controlled study to demonstrate that deeper general anesthesia, as defined by a median BIS of 38, when compared with a median BIS of 58, was associated with a reduced incidence of early POCD(at 1 week postoperationly). This study has been published in J Neurosurg Anesthesiol , Volume 23, Number 1, January 2011. as it was just a small sample(n=40) study without considering incidence of long-term POCD, we hope to obtain more reliable data from a multi-center study to investigate whether the depth of total intravenous anesthesia using propofol affects the early and long-term incidence of POCD.

The bispectral index（BIS）can reflect the depth of anesthesia of propofol combined with opioids. In our study, BIS will still be used to provide a reference for the selection of a suitable depth of anesthesia.

Eligibility Criteria:
Inclusion Criteria:

* Written informed consent provided by legal guardians or patients
* Male or female patients between 50 and 70 years of age.
* ASA physical status I or II patients.
* Education Years of patients are more than 6 years.
* The operation going to be received is the first operation in patient's life (a second operation was a risk factor for early post- operative cognitive dysfunction);
* The operation going to be received is presenting for a moderate surgery, such as pulmonary lobectomy, subtotal gastrectomy, prostatectomy and so on.

Exclusion Criteria:

* The patient has the history of neurologic or mental disease.
* The patient has renal dysfunction, serum creatinine \>177 mmol/L.
* The patient has an active liver disease.
* The patient has cardiac dysfunction.
* The patient has pulmonary dysfunction.
* The patient has an endocrine disease.
* The patient has a metabolic disease.
* The patient has a history of surgery.
* The patient is going to receive surgery of thyroid, intracranial procedure, joint replacement, major fracture.
* The patient's education history is shown less than 6 years of school.
* The patient is unable to complete neuropsychologic testing.
* The patient has vision dysfunction.
* The patient has auditory dysfunction.
* The operation going to be received is a laparoscopic surgery.
* The patient is hypersensitive to propofol or any other anesthetic agents.
* Involvement in the planning and conduct of the study
* Participation in another drug trial within 28 days prior enrolment into this study