Assessment of Cognitive Functions and Quality of Life in Patients Undergoing Surgery for Supratentorial Brain Tumor

Cognitive dysfunction is a common complication in primary or metastatic brain tumors and can be correlated to disease itself or various treatment modalities. The symptoms of cognitive deficits may include problems with memory, attention and information processing. There is a study which suggest that psychological distress is an important factor in reducing health related QOL in patients with brain tumors. However in some studies, depression was found to be another important independent predictor of QOL and has strong impact on survival. QOL is a extensive term that comprises physical or functional status, emotional well-being, and social well-being. It has been studied that QOL in patients with high-grade tumors do not differ those with grade III and grade IV tumors. Compared to patients with non-CNS cancers, brain tumor patients report more fatigue, cognitive dysfunction, and altered mood states. However, different levels of impairments have been observed in patients with brain tumors. To spread awareness of the illness, psychiatric interventions may be useful in these patients. Cognitive dysfunction may affect basic functions including attention or behavior or advanced functions like taking decisions or making plans. According to Yoshii Y et.al, Cognitive dysfunction before or after the surgery may not correlate with stage of tumor malignancy and degree of tumor resection. Cognitive function has been correlated to increased fatigue and depression in newly diagnosed malignant glioma patients.

After approval from Institute Ethics Committee and consent from the patient or guardian, we will include all adult patients between 18 - 65 years, of either gender scheduled for craniotomy for supratentorial brain tumors. We will exclude patients with a history of previous surgery for brain tumor, emergency surgery and non-consenting patients. To calculate the sample size we will first conduct a pilot study enrolling 30 patients, 15 in each group. Block randomization will be followed with blocks size of 10 patients. Patients will be randomized using the computer generated program. Demographic details will be noted. Patients will be adequately fasted prior to elective surgery. A standard anaesthesia protocol will be followed for all patients. Patients will be randomized in to two groups, Group S (Inhalational) and Group P (Intravenous). .Allocation of the group will be performed using an opaque sealed envelope method. General anaesthesia will be induced with Propofol 1.5 - 2 mg/kg.Anaesthesia will be maintained with either propofol (Group P) or Sevoflurane (Group S) along with mixture of oxygen and air [1:1] at flow rate of 2 liters per minute..The Minimum Alveolar Concentration (MAC) of Sevoflurane would be maintained between 0.8 - 1.2. In Group P, depth of anaesthesia will be guided by clinical signs such as tachycardia and hypertension. Intra-operative analgesia and muscle relaxation will be provided by boluses of fentanyl 1 mcg/kg and vecuronium 0.1 mg/kg, respectively. Intra-operative monitoring will include ECG, heart rate, invasive and non-invasive blood pressure, gases, end-tidal carbon dioxide, pulse oximetry, temperature and fluid input and output. Mannitol 1 gm/kg would be administered over a period of 20 minutes at the time of skin incision. Immediately after craniotomy, brain relaxation would be assessed using Brain Relaxation Score (BRS) in which the blinded surgeon will assess the condition of the brain as 1 = perfectly relaxed, 2 = satisfactorily relaxed, 3 = firm (leveled) brain, 4 = bulging brain.(27)At the end of surgery, propofol would be discontinued at the beginning of skin closure and Sevoflurane at the end of the skin closure. Neuromuscular block will be reversed with neostigmine 0.1 mg/kg and glycopyrrolate 0.01 mg/kg. If patients are planned for elective mechanical ventilation in the post-operative period, neuromuscular block will not be reversed.

Emergence and extubation times will be noted. Emergence time is defined as time from discontinuation of anaesthetic to time to follow verbal commands and eye opening. Extubation time is defined as time from anesthetic discontinuation to tracheal extubation. Recovery of the patient will be assessed using the modified Aldrete score. Intraoperative and postoperative complications, if any, will be noted. Various complications (tachycardia, bradycardia, hypotension, hypertension) will be treated with fentanyl, atropine, mephentramine and labetalol. All patients will be shifted to the ICU for supportive care and further management. Cognitive functions would be assessed preoperatively (baseline), between 2 to 3 hours postoperative, 24 hours post-operative, three months and six month. Quality of life (QOL) will be assessed at three month, six month and one year. Cognitive function will be assessed for memory, learning, executive functioning, sustained attention and verbal fluency and QOL by neuro-psychologist as shown in Appendix below. The difference of brain relaxation by two grades between the two study groups will be considered clinically significant and sample size calculated on this basis.

Appendix

NEUROPSYCHOLOGICAL ASSESSMENT

FUNCTION TEST [1]: Memory \& Learning, TEST: Auditory Verbal Learning Test (AVLT), DOMAINS: Verbal Memory, Learning \& Retention, TIME TAKEN: 20 minutes, AVAILABILITY: Property of Clinical Neuropsychology (CNP). FUNCTION TEST [2]: Executive Functioning, TEST: Stroop Test, DOMAINS: Response Inhibition, perceptual set, TIME TAKEN:10 minutes, AVAILABILITY: Property of Clinical Neuropsychology (CNP). FUNCTION TEST [3]: Speed, TEST: Digit Symbol Substitution Test (DSST), DOMAINS: Mental speed, visuomotor coordination, motor persistence, sustained attention, response speed, TIME TAKEN:10 minutes, AVAILABILITY: Property of Clinical Neuropsychology (CNP). FUNCTION TEST [4]: Verbal Fluency, TEST: Controlled Oral Word Association (COWA) Test, DOMAINS: Phonemic fluency, language, TIME TAKEN:5 minutes, AVAILABILITY: Property of Clinical Neuropsychology (CNP). FUNCTION TEST [5]: Quality of life, TEST: WHO QOL - BREF, DOMAINS: QOL, TIME TAKEN:5 minutes, AVAILABILITY: Property of Clinical Neuropsychology (CNP).