MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEATH HANOI MEDICAL UNIVERSITY NGUYEN THI THANH HUYEN COMPARISON OF THE INDUCTION, RELEASE OF ANESTHESIA AND INFLUENCE IN CIRCULATORY BETWEEN PROPO[.]
MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEATH HANOI MEDICAL UNIVERSITY NGUYEN THI THANH HUYEN COMPARISON OF THE INDUCTION, RELEASE OF ANESTHESIA AND INFLUENCE IN CIRCULATORY BETWEEN PROPOFOL TCI COMBINED WITH KETAMIN AND ETOMIDAT WITH SEVOFLURAN IN ELDERLY PATIENTS Specialism : Anesthesia Code : 9720102 ABSTRACT OF THESIS HA NOI - 2022 The thesis has been completed at HANOI MEDICAL UNIVERSITY Supervisor: Professor Nguyen Huu Tu Reviewer 1: Reviewer 2: Reviewer 3: The thesis will be present in front of board of university examiner and reviewer lever at… on ….20 This thesis can be found at: National Medical Informatics Library Library of Hanoi Medical University QUESTION These days, how to choose drugs and methods in the induction stage of anesthesia for elderly patients has still been a topical issue There are many different opinions because all drugs have undesirable effects The induction stage of anesthesia using Etomidat and maintaining anesthesia by Servofluran is a classical method of anesthesia for old people because it has little effect on hermodynamic but it has several unwanted impacts, especially it causes inhibition of hormone secretion in the adrenal cortex Target Controlled Infusion anesthesia with propofol is a modern method of anesthesia, leading to the least hermodynamic with using propofol However, according a study of Do Ngoc Hieu (2012) and Nguyen Thi Thu Ha (2015), when conducting the induction stage of anesthesia in old patients, the maximum blood pressure is still reduced by 28% - 30%, compared to basic blood pressure Ketamin is the only intravenous anesthetic medicine that has function to increase pulse and blood pressure Therefore, for elderly people, in the induction stage of anesthetic, does the use of etomidat or propofol TCI combined with low dose of ketamine have lower effect to heart rate and blood pressure? When there is a combination with a low dose of keratin, in the induction stage of anesthetic, does the use of propofol TCI controlling the target concentrations at the brain or blood plasma have more benefits? Does ketamine affect to recovery quality? With the above issues, we study the topic “Compare the efficiency of the induction stage and release stage in anesthesia and the effect on the circulation system between the anesthesia combining propofol TCI with ketamine and etomidat with sevofluran in the elderly patients” with objectives Comparing the effectiveness between the use of propofol TCICp and propofol TCI-Ce based on the Schnider model combining ketamine with etomidat in the induction stage of anesthesia in the elderly patients Comparing the effect on heart frequency and blood pressure between the use of propofol TCI-Cp and propofol TCI-Ce based on the Schnider model combining ketamin with etomidat in the induction stage of anesthesia in the elderly patients Comparing recovery quality and some undesirable effects between the use of propofol TCI-Cp and propofol TCI-Ce based on the Schnider model combining ketamine with etomidat in the induction stage of anesthesia in the elderly patients Instancy The increasing life expectancy of Vietnamese people means that the number of elderly patients with indications for surgical anesthesia is increasing However, surgical anesthesia for elderly patients has many risks of complications and death, especially in the induction and release stage of anesthesia due to cardiovascular and respiratory disorders Therefore, choosing an effective method of anesthesia, good quality of anesthesia, minimizing the combinations of anesthesia and surgery for the elderly is always the desire of anesthesiologists Target controlled infusion with propofol is a modern, safe, and good quality anesthetic modality but it still causes a significant reduction of blood pressure at the induction stage in the elderly The combination of ketamine 0.3 mg/kg with propofol TCI during induction stage of anesthetic in the elderly has been studied in the world proving its effectiveness in stabilizing blood pressure but this method has not been studied in Viet nam yet We hope that this study can contribute to providing more choices for anesthesiologists when anesthetizing elderly patients New contributions of the thesis - The duration of the induction stage using propofol TCI installed target concentration at brain (effect site concentration) in combination with ketamin 3mg/kg is longer than the induction stage using etomidat but shorter and lower dose than the induction stage using propofol TCI installed target concentration at blood plasma - The induction stage and intubating NKQ using propofol TCI effect site concentration combination with ketamin 0.3mg/kg have little effect to heart rate and blood pressure than the install of targeting concentration at blood plasma and the induction stage using etomidat - Eligible time for extubation of the anesthesia using propofol in combination with ketamine is shorter than the anesthesia using etomidat in combination with sevofluran Stimulating rate, vomiting, nausea, post anesthesia hallucinations of these methods have low rate and there are no differences The thesis layout - The thesis is presented in 119 pages, including pages of problem statement, 35 pages of overview, 16 pages of object and method, 23 pages of results, 41 pages of discussion, page of conclusion and page of recommendation - The thesis contains 33 tables, 13 charts, figures, 165 references, which are arranged in order of appearance in the thesis CHAPTER OVERVIEW DOCUMENT 1.1 Characteristics of elderly people in relation to anesthesia 1.1.1 Physiological characteristics of the elderly in relation to anesthesia Cardiovascular system: Aging is accompanied by changes in the structure and function of the cardiovascular system, including the arteries veins, and heart, and their response to the body's neuroendocrine system tend to lower blood pressure more than young people under both anesthesia and a anesthetize especially after induction, even a moderate drop in blood pressure can cause serious complications due to fibrosis mortar of the feeding arteries Respiratory system: For the elderly, there is a decrease in lung vital capacity, decreased ventilation response to hypercapnia and hypoxia, and decreased airway protective reflex, which easily leads to the risk of respiratory failure after surgery 1.1.2 Pharmacokinetic changes in elderly patients 1.1.2.1 Changes in pharmacokinetics Drug absorption: For drinking medicine, absorption is reduced due to decreased intestinal motility as well as decreased blood circulation to the intestine For intravenous anesthetics, the prolonged hand-brain circulation time increases the amount of time from taking medicine of the induction stage of anesthesia to when the drug takes effect Drug distribution: For the elderly, tissue and water volume decrease, but overall fat volume increases, therefore, the concentration of water-soluble drugs will be increased, and fatsoluble drugs such as propofol, benzodiazepines and opioids are increased in distribution into the fat tissue, so they are delayed in onset but have an increase in action, which easily leads to accumulation of toxicity Drug metabolism and elimination: The liver's detoxification ability as well as the kidney's ability to excrete is poor, so it is easy to cause toxicity due to overdose and prolonged effects 1.1.2.2 Changes in the pharmacokinetics of drugs The need for all intravenous and volatile anesthetics decreases with age The number of active receptors, nerve and neuromuscular receptors and organ receptors all decrease with age, which can easily lead to drug overdose 1.2 Target Controlled Infusion (TCI) 1.2.1 Conception: Target Controlled Infusion can be defined as follows: TCI is a infusion system which is controlled by a computer software It allows anesthesiologists to choose the attainable anesthetic concentration required by surgery and can easily test anesthesia concentration by adjusting changes in drug levels in the blood or target organs 1.2.2 Pharmacokinetic model Cavity models: This model uses the concept of compartments when describing variation in drug concentrations in the body The 3chamber model is a typical model that when the drug is injected first into the central compartment (V1), then the drug is distributed into the other compartments Distribution into the second compartment is the rapid phase of distribution because it is distributed into highly perfused tissues The process of distribution into the third compartment is the slow distribution phase because it is the distribution into the less perfused tissue Cavity models TCI with propofol include: Marsh and Schnider models in adults, Kataria and Paedfudor models in children Working principle: When the target concentration is increased, the central system will push a bolus dose at a rapid rate to fill the central cavity, the amount of drug injected is calculated based on the volume of the central cavity and the difference between the present concentration and the concentration of the central cavity request destination When the new target concentration is reached, the system will stop pumping the bolus but maintain it at a low rate to replace the amount of drug lost by distribution and elimination TCI systems repeat the calculation and vary the infusion rate every 10 seconds to maintain a constant target concentration When the target concentration is decreased, the system will stop the infusion and wait until the calculation software shows that the blood concentration has reached the target concentration, it will restart the infusion at a lower rate, the software system always calculate to change the infusion rate so that the required target concentration is maintained There are two ways to set the target concentration of the TCI system: The first method is to set the target concentration at blood plasma (Cp) The computer's software system will calculate the required drug concentration in the blood from which it will calculate the amount of bolus injection and the infusion rate to maintain anesthesia The second way is to set the target concentration in the brain (effect-site concentration -Ce) The software system will calculate the estimated drug concentration in the brain from which it will calculate the amount of bolus injection and the infusion rate to maintain anesthesia 1.2.3 The pharmacokinetic model of propofol in target controlled infusion Currently, propofol commonly uses two pharmacokinetic models, the Marsh model and the Schnider model The earlier Marsh model, based on a single-chamber model, assumes that the central compartment volume is proportional to the patient's body weight The age variable is entered into the machine but is not used for the calculation The Schnider model is built on the 3-chamber model Age, height, weight variables are entered into the software Lean body weight - “Slim weight” is calculated and used as the basis for calculating the dose and rate of propofol infusion The main difference between the Marsh and Schnider models is the volume of the central cavity The Schnider model has a smaller central compartment size (4,7 liters in an 85 kg patient) than the Marsh model (19,4 liters) 1.2.4 Some of domestic and foreign studies Thomas W Schnider et al (2016) published research on the safety of TCI use The authors concluded: Although in many cases, reports emphasize that intravenous anesthesia is more technically demanding than inhalation anesthesia, there is no data to showing that the drug distribution way of TCI cause unsafe cases for the patients Nguyen Thi Thu Ha (2015) studied 60 patients ≥ 60 years old, compared the induction of anesthesia between two groups: group (n = 30) initiated anesthesia with propofol to control the target concentration in the brain (Ce) with additional combination ketamine 0.5 mg/kg injected minutes before induction of anesthesia; group (n = 30) was the same as group but did not add ketamine The study results showed that when induction of anesthesia with propofol TCI in combination with ketamine at a dose of 0.5 mg/kg made the patient's heart rate more stable, blood pressure decreased less than in the group that did not add ketamine In 2019, Angela Ongewe et al combined a low dose of ketamine with propofol in the induction stage of anesthesia The authors concluded: the combination of ketamine 0,5 mg/kg with propofol helps to limit the vascular response, blood pressure after glotoscopy and intubation and also prevents hypotension after the procedure of anesthesia Chapter SUBJECTS AND METHODS 2.1 Research subjects 2.1.1 Criteria for selecting patients into the study: - Age 60 - 80 years old; ASA I - II - Programmatic surgery - Indications for endotracheal anesthesia (intracheal intubation) - Possibility to remove the endotracheal tube soon after surgery - No liver or kidney failure; - Results of blood tests, blood chemistry, echocardiography are within normal limits 2.1.2 Criteria to exclude patients from the study: - The patient did not agree to participate in the study - Patients with cardiovascular disease including arrhythmia, heart valve disease, coronary artery disease, heart failure - The patient has a history and currently has neurological and psychiatric diseases - Patients who are allergic to propofol, etomidate, ketamine, rocuronium fentanyl - Patients with difficult prognosis for intubation; The patient needs rapid intubation - Patients taking β-blocker, α-blocker or sympathomimetic within 24 hours before anesthesia 2.1.3 Criteria for taking out of the study - Patients have severe complications after surgery and need to be transferred to the intensive care room with mechanical ventilation for more than hours - Patients have surgical complications 2.2 Methods: 2.2.1 Research design Single-blind randomized controlled intervention 2.2.2 Sample size Including 210 patients divided into three groups (n1 = n2 = n3 = 70) by random drawing when entering the operating room Group 1: induction with propofol TCI - Cp in combination with ketamine Group 2: induction with propofol TCI - Ce in combination with ketamine Group 3: induction with etomidat 2.2.3 Conducting research 2.2.3.1 Preparation before anesthesia * Prepare the patients At the hospital room: Patients were given basic preoperative tests, echocardiography, anesthesia examination before surgery and prepared as other routine surgery In the operating room: Install a monitor to monitor heart rate, blood pressure, electrocardiogram (ECG), SpO2, BIS; Invasive arterial blood pressure; install a muscle relaxation monitor (TOF-Scan); Ringer lactate ml/kg infusion over 20 minutes before induction * Prepare facilities and anesthetics Anesthetics: - Propofol 1% (Diprivan) tube 500mg/50ml of Atra-Zeneca - Etomidate tube 20mg/10ml of B/Braun - Ketamine 500mg/10ml bottle of Pan Pharma - Germany - Fentanyl tube 0.1mg/2ml Warsam Pharma - Poland - Rocuronium (Esmeron) 50mg/10ml vial of Glaxo Smith Kline - Respiratory and circulatory resuscitation drugs: Ephedrine, atropine, adrenaline, noradrenalin, ventolin; Infusion: ringerlactate 500ml bottle, voluven 6% Anesthesia facilities - Spacelabs Ultraview SL monitor: Monitor heart rate, invasive arterial blood pressure, ECG, SpO2 - B Braun's Schnider TCI and propofol (Diprivan PFS) by Astra Zeneca - TOF-Scan machine; BIS monitor, BIS measuring electrode - Intubation equipments: Ambu bulb, Mask, intubation lamp, endotracheal tube with numbers, suction tube, suction machine 2.2.3.2 Induction * Group 1: Induction with propofol TCI - Cp in combination with ketamine: - Enter the numeric height (cm); weight (kg); age (year) of the patient Set Cp = 1.2 µg/ml - Fentanyl at a dose of µg/kg intravenously - After minutes ketamine 0.3 mg/kg (intravenously) just before propofol infusion - Infuse propofol according to the TCI program When Cp reaches 1.2 µg/ml but BIS has not fallen below 60, increase by 0.3 µg/ml every minutes until BIS falls below 60 then maintain anesthesia at that concentration 11 - Some undesirable effects during the recovery period and within 24 hours after surgery: Hallucinations: yes/no; Stimulus: yes / no; Nausea, vomiting: yes/no 2.2.4.4 Other evaluation criteria - Patient characteristics: age (years), gender (male/female), height (meters), weight (kg), type of surgical pathology, comorbidities; Body mass index (BMI); ASA - Time to administer the last dose of rocuronium until the patient comes in recovery room - Anesthesia time (minutes); Total amount of fentanyl (mg), total amount of rocuronium (mg) 2.2.5 Definitions and standards applied in the study 2.2.5.1 Definitions - Waiting time for intubation (minutes): The time from the start of anesthesia until having enough condition for intubation with BIS ≤ 60 and TOF = - Induction time (minutes): The time from the start of anesthesia to the completion of the intubation - Eligible time for extubation: Eligible time for extubation: is the time from the patient arrival to recovery room until the patient is eligible for extubation 2.2.5.2 Standards applied in the study Health classification according to the American Society of Anesthesiology ASA 1: Patient is in good health ASA 2: The patient has a mild illness that does not affect his health and daily activities 2.2.6 Data analysis The collected data were cleaned and processed according to medical statistical algorithms using SPSS 19.0 software The difference was statistically significant when p < 0,05 2.3 Research time and place - Time: From January 2017 to August 2020 12 - Place: Department of anesthesia and pain management, Hanoi Medical University Hospital 2.4 About the ethics of the research The study was approved by the Ethics Committee of Hanoi Medical University (Decision No 187/HĐĐĐĐHYHN, June 20, 2016) and obtained the consent of the Hanoi Medical University Hospital Chapter RESEARCH RESULTS 3.1 Research object characteristics Table 3.1 Characteristics of age, gender, height, weight, body mass index, ASA distribution Group Group Group P Characteristics (n = 70) (n = 70) (n = 70) Age ±SD 67,9 ± 6,42 67,6 ± 6,49 69,8±7,83 > 0,05 (year) Min-Max 60 - 85 60 - 85 60 - 90 Height ± SD 1,56 ± 0,07 1,56 ± 0,07 1,58 ± 0,07 > 0,05 (meters) Min-Max 1,40 - 1,71 1,44 - 1,70 1,40 - 1,70 Weight ± SD 53,3 ± 9,11 54,0 ± 8,91 54,0 ± 9,14 > 0,05 (kg) Min-Max 36 - 83 39 - 80 37 - 78 BMI ±SD 21,9±3,43 22,0± 3,08 21,6±2,69 > 0,05 (kg/m2) Min-Max 15,6 - 31,1 16,3 - 35,5 15,6 - 28,6 Male 26 (37,1%) 35 (50%) 33 (47,1%) Sex > 0,05 n (%) Female 44 (62,9%) 35 (50%) 37 (52,9%) ASA I 19 (27,1%) 22 (31,4%) 18 (25,7%) ASA > 0,05 n (%) ASA II 51 (72,9%) 48 (68,6%) 52 (74,3%) Comment: The characteristics of age, gender, height, weight, BMI, ASA distribution among the three study groups were not different with p > 0,05 (p compared between 03 groups) 13 Table 3.3: Distribution characteristics of surgical pathology of the three studied groups did not differ with p > 0,05 (p compared between three groups) 3.2 Anesthetic effect Table 3.4 Waiting time for loss of consciousness, waiting time for intubation; anesthesia onset time ( X SD; - max) Time Group Lose consciousness (minutes) BIS ≤ 60 (minutes) Group Group Group (n = 70) (n = 70) (n = 70) P 3,2 ± 1,60* 2,8 ± 1,05* 2,2 ± 0,95 < 0,01 (1,48 - 9,33) (1,00 - 5,22) (0,92 - 4,90) 8,4 ± 3,17* 7,3 ± 1,88*ǂ (4,0 - 14,1) 3,7 ± 1,37 (1,5 - 8,3) < 0,01 waitting for intubation (minutes) 8,7 ± 3,00* 7,5 ± 2,04*ǂ (3,8 - 16,0) (4,0 - 14,1) 5,4 ± 1,2 (4,0 - 9,0) < 0,01 Induction time (minutes) 9,6 ± 3,09* (4,8 - 16,6) 6,4 ± 1,28 (4,8 - 9,8) < 0,01 (3,0 -16,0) 8,5 ±2,09*ǂ (5,5 - 15,3) *: p < 0,001 when comparing group 1, group with group 3; ǂ: p < 0,05 when comparing group with group 1; p: compare the difference between the three groups Comment: Waiting time for loss of consciousness, for BIS reduced to 60, for intubation, average time for induction of anesthesia in group was the shortest then group finally group with p < 0,01 (p compared between three groups) 14 Table 3.5: Intubation conditions between the three groups did not differ with p > 0,05 BIS *p < 0,05 compared between group with group and group Chart 3.3 Average BIS value at time points Comment: At the time before intubation (T2); immediately after intubation (T3); minutes after intubation (T4), the mean BIS values of group were lower than those of group and group 2, the difference was statistically significant with p < 0,001 Table 3.6: The mean BIS difference between before and after intubation between the three groups did not differ with p > 0,05 Table 3.7: The target propofol concentration and the induction propofol concentration between group and group had no difference with p > 0,05 However, the dose of propofol inducting of group was lower than that of group 1(1,39 0,35 mg/kg vs 1,53 0,48 mg/kg; p < 0,05) 15 3.3 Cardiovascular effects of the three groups at the time of induction 3.3.1 Affects heart rate heart rate (time/minute) group T0: before induction; T1: loss of consciousness; T2: before intubation; T3: minute after intubation T4: minutes after intubation *: p < 0,001 when comparing group 1, group and group Chart 3.4 Change in heart rate of three groups at time points Comment: At the time of T3, T4: The mean heart rate of group was higher than that of group and group and higher than that at time of T0, the difference was statistically significant with p < 0,001 ( p compare group 1, group with group 3) Table 3.9: At the time of T2, the heart rate of all three groups mainly decreased by < 20% compared to the pre-anesthesia heart rate The difference in heart rate reduction rate between the three groups was not statistically significant with p > 0,05 (p compared between three groups) 16 Chart 3.5 Rate of increase in heart rate between groups at T3 Comment: Group had a higher rate of patients with heart rate increase > 20% than group and group with p < 0,05 (p compared between three groups) 3.3.2 Changes in blood pressure during induction Table 3.13 Systolic blood pressure of the three groups at the time of induction Groups Group (n = 70) Group (n = 70) Group (n = 70) 136,4 18,41 137,5 18,72 135,4 21,56 102 - 184 100 - 179 100 -180 X SD 124,9 21,84* (mmHg) - max 82 - 172 124,7 20,89* 127,3 23,06* 79 - 176 90 - 184 X SD 96,7 15,43*† (mmHg) - max 66 -140 99,7 16,58* 104,9 25,53* 71 - 160 75 -172 X SD 130,7 21,52*ǂ (mmHg) - max 100 - 180 130,9 23,26*ǂ 151,5 24,12* 83 - 189 108 - 193 X SD 109,5 16,87*ǂ (mmHg) - max 80 - 150 111,4 14,51*ǂ 128,6 20,2* 83 - 150 99 - 170 Time T0 T1 T2 T3 T4 X SD (mmHg) - max P > 0,05 > 0,05 < 0,05 < 0,001 < 0,001 *: p < 0,05 when compared with blood pressure index at time T0; †: p < 0,05 when comparing group with group 3; ǂ: p < 0,001 when comparing between group 1, group and group 17 Comment: At T2: SBP of group was lower than that of group and group (p < 0,05); At T3 and T4: SBP of group was higher than that of T0 and higher than that of group and group (p < 0,001) Table 3.14: At the time immediately before intubation (T2), the percentage of patients with a decrease in SBP compared to T between the three groups did not differ (p > 0,05) Table 3.15: At the time of minute after intubation (T 3), the proportion of patients with SBP increased from 20% to 30% and > 30% compared to the time before induction of anesthesia was higher in group than in group and group with p < 0,001 Table 3.16: At T2 DBP of group was lower than group (p < 0,05); At T3, T4 DBP of group was higher than that of group 1, group and higher than before anesthesia with p < 0,001 Table 3.17: Mean blood pressure of three groups at time points (mmHg) Groups Group Group Group P Time (n=70) (n=70) (n=70) T0 T1 X SD - max 97,6 12,57 98,3 11,13 72,6 - 131,6 72,6 - 132,3 96,4 13,90 66,6 - 130 > 0,05 91,2 15,09* 90,26 13,36* 91,4 14,56* > 0,05 - max 64,3 - 132,6 63,6 - 126,0 59,3 - 134,67 X SD 79,6 17,72* < 0,05 - max 50, 0- 99,6 46,3 - 110 53,3 - 119,3 < 98,2 14,61ǂ 97,0 14,70ǂ 112,2 17,05* T3 X SD 0,001 - max 69,6 - 136,6 63,6 - 136,3 79 - 147,6 < 80,6 11,03*ǂ 82,6 9,66*ǂ 94,7 14,79 T4 X SD 0,001 - max 55,3 - 103,3 63,6 - 110,0 72,3 - 130,0 *: p < 0,05 when compared with blood pressure index at time T0 ; †: p < 0,05 when comparing group with group 3; ǂ: p < 0,001 when comparing group 1, group with group 3; p: comparison between three groups T2 X SD 72,7 10,78*† 75,3 12,60* 18 Comment: At T2 MBP of group was lower than group (p < 0,05); At T3 MBP of group was higher than that of group and group and higher than that at T0 (p < 0,001) Table 3.20: At the time of minute after intubation (T3), the proportion of patients with SBP increased from 20 to 30% and > 30% compared to the time T0 of group was higher than that of group and group The difference was statistically significant with p < 0,001 3.3.3 Awakening quality and some unwanted effects Table 3.22: The average time of anesthesia, the time of last injection of rocuronium until leaving the operating room of the three groups did not differ with p > 0,05 Table 3.23: The total amount of fentanyl used in anesthesia of group and group was lower than that of group 3, the difference was statistically significant with p < 0,01; There was no difference in the total amount of rocuronium used in anesthesia between the three groups (p > 0,05) Table 3.24: The time from leaving the operating room until TOF = of group and group was shorter than that of group (p < 0,05); Waiting time to qualify for extubation of group and group was shorter than that of group with p < 0,05) Table 3.25: After extubation minutes, 30 minutes and 60 minutes, the percentage of patients with Aldrete score = 10 between the three groups did not differ with p > 0,05 Table 3.26 Some undesirable effects of three groups Groups Group Group Group P (n = 70) (n = 70) (n = 70) undesirable effects Irritation (5,7% (7,1%) 11 (15,7%) > 0,05 n(%) Hallucination (0%) 01 (1,4%) (0%) > 0,05 n(%) Vomiting/nausea (5,7%) (4,3%) (4,3%) > 0,05 n (%) Comment: The rate of undesirable effects including irritability, hallucinations, vomiting, nausea among the three groups did not differ with p > 0,05 ... induction stage using propofol TCI installed target concentration at blood plasma - The induction stage and intubating NKQ using propofol TCI effect site concentration combination with ketamin 0.3mg/kg... between the use of propofol TCI- Cp and propofol TCI- Ce based on the Schnider model combining ketamine with etomidat in the induction stage of anesthesia in the elderly patients Instancy The increasing... induction stage using propofol TCI installed target concentration at brain (effect site concentration) in combination with ketamin 3mg/kg is longer than the induction stage using etomidat but