Tài liệu Luan an tom tat (eng) nghiên cứu tác dụng giảm đau của các liều morphin tiêm trước mổ vào khoang dưới nhện và pca morphin tĩnh mạch sau mổ tầng bụng trên

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF DEFENSE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES ---------- DO KHAC HUNG STUDY ON ANALGESIC EFFECT OF MORPHINE DOSAGES INJECTED BEFORE SUBARACHNOID SPACE OPERATION COMBINED WITH IV-PCA MORPHINE INJECTED AFTER UPPER ABDOMINAL ONE Specialism: Code: Anesthesia Reanimation 62.72.01.22 THE SUMMARY OF MEDICAL DOCTORAL THESIS HANOI - 2018 THE THESIS HAS BEEN COMPLETED AT 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES Scientific supervisor: Prof. Nguyen Thu Associate Prof. PhD. Cong Quyet Thang Opponent 1: ....................................................................................... Opponent 2: ....................................................................................... Opponent 3:........................................................................................ Doctoral thesis will be evaluated at thesis evaluation council at 108 Institute of Clinical Medical and Pharmaceutical Sciences On: ………………, ……… /………./ 2018 You can find the thesis at: 1. The National Library 2. Library of 108 Institute Pharmaceutical Sciences. of Clinical Medical and 1 INTRODUCTION Pain affects the patients during and after surgery, causing many side-effects in respiratory, circulatory, endocrine, inflammatory process, prolonged hospital stay... The consequences of postoperative pain greatly affect the recovery of health and patients’ psychology. More pain caused after the upper abdominal operation, therefore, effective pain-killer measures must be required. Using Intrathecal morphine (ITM) injection is a direct injection of morphine into the subarachnoid space and has been proved to be good pain-relief in the first day postoperatively while Intravenous Patient-Controlled Analgesia (IV-PCA) reduces pain effectively, especially for surgeries cause little and moderate pain. The combination of spinal cord morphine injection with IVPCA has been studied by several authors to provide good analgesic effects after urological, obstetric, orthopedic surgery... To find the effective dose of this combination and to meet patient’s pain-killer need after upper abdominal operation, we studied the subject: “Study on analgesic effect of morphine before subarachnoid space operation combined with IV-PCA morphine injected after upper abdominal one” for below purposes: 1. To evaluate the analgesic effect of morphine at 0.2 mg and 0.4 mg when it’s injected before subarachnoid space operation combined intravenous PCA morphine injected after upper abdominal operation. 2. To evaluate the unexpected effects of morphine at 0.2 mg and 0.4 mg when it’s injected before subarachnoid space operation combined intravenous PCA morphine injected after upper abdominal operation. 2 SUMMARY OF THESIS’S NEW MAIN SCIENTIFIC CONTRIBUTION 1. Injection of morphine into the spinal cord before operation combined with PCA had a good analgesic effect after upper abdominal surgery, reducing a statistically significant amount of morphine (p <0.05) compared with using IV-PCA morphine. Patients injected with morphine 0.4 mg into the spinal cord before operation need titrated morphine and total IV- PCA morphine for postoperative pain after 24h, 48h, 72h were lower and statistically significant (p <0.05) compared with the group of patients with 0.2 mg into the spinal cord: 2.74 ± 1.88mg compared with 4.25 ± 2.12mg; 7.84 ± 6.14mg, 15.19 ± 9.51mg and 19.69 ± 11.71mg compared with 14.6 ± 11.65mg, 26 ± 18.54mg and 34.53 ± 22.39mg, respectively; the time to initiate using morphine IV- PCA after surgery in the 0.4mg morphine group injected into the spinal cord before surgery is longer and the A/D ratio in 72h is higher than that one in the group injected with 0.2mg morphine into the spinal cord: 17.42 ± 17.34 hours versus 5.0 ± 5.34 hours and 99.05 ± 3.69% versus 94.0 ± 9.56%. 2. Injection of morphine into the spinal cord before surgery combined with IV-PCA for reducing postoperative pain in the upper abdomen did not affect the patients’ hemodynamics and respiration. The incidence of itching, nausea and sedation with the injection of 0.4 mg in comparison of the one with 0.2 mg morphine into the spinal cord before surgery was not statistically significant (p> 0.05): 38.3%, 43.3% and 46.6% compared to 36.7%, 40% and 48.3%, respectively. 3 THESIS STRUCTURE The thesis has 124 pages, not including annexes and references, 2 pages of introduction. The thesis has four chapters:  Chapter 1: Overview, 32 pages.  Chapter 2: Research subjects and methods, 18 pages.  Chapter 3: Research result, 24 pages.  Chapter 4: Discussion, 45 pages; Conclusion and recommendations, 3 pages. The thesis has 30 tables, 3 charts, 10 images and 121 references. Chapter 1 OVERVIEW 1.1 Pain definition. According to International Association for Study of Pain IASP, “Pain is unpleasant sensory and emotional experience associated with actual or potential tissue damage, or describe in terms of such damage”. 1.2. Characteristics of pain after upper abdominal surgery Pain after abdominal surgery has been proven by many authors to be subject to severe pain group (both in intensity and duration) as well as with thoracic and spine surgery and knee replacement and postoperative pain management. - Skin incision: the usual incision is above or below the navel, which is a long incision and directly affects the respiratory muscles (especially the diaphragm). - Abdominal surgery usually involves the removal or cutting of organs, mesentery or arteries, causing neurological damage, blood vessels in the surgical area, or setting up drainage causes severe pain. - Pain due to regional blood-shortage in the surgical site: When the blood supply to the tissue is reduced, pain occurs within a few minutes. Pain intensity is directly proportional to the level of tissue 4 metabolism. In particular, if the level of metabolism in the higher the tissue, the anemia, the pain in that tissue will be more intense. The cause of pain is the accumulation of large amounts of lactic acid in the diseased tissue during anaerobic metabolism (without the involvement of oxygen) which liberates the acid metabolite products, bradykinin, Atrophy in the damaged cell stimulates the nociceptor receptors at the nerve terminal. - Pain due to the spasm of the hollow organs: contraction of the stomach, colon, and gallbladder through mechanical stimulation of the neurotransmitter receptor, and contraction also reduces tissue perfusion in combination with increased transfusion of smooth muscle causes the pain level to increase. - Pain due to excessive stretching in the empty organs such as intestines, stomach, colon after surgery can cause pain by stretching the tissue. At the same time when the stretching of empty organs also cracked or broken up, blood vessels around the body causes anemia to nourish the pain increases. - In addition, the cause of pain is due to chemical stimulation: it can be leaked digestive fluid, pancreatic fluid in surgery into the peritoneal cavity. These infections cause inflammation and the destruction of the peritoneal mucus also creates intense racing stimuli. 1.3. Effect of pain after abdominal surgery - Pain aggravates the body's stress response to injury: adverse reactions to stress affect many different organs including cardiovascular, respiratory, immune, and blood clots. - Pain causes immunosuppression by increasing cortisol and epinephrine concentrations, increasing the risk of surgical site infections and infection. 5 - Pain causes hormonal and metabolic disorders (especially glucose metabolism) then this cause hyperglycemia and decrease the anabolic hormones such as insulin, testosterone. - Pain that slows recovery after surgery, increased complications from hospitalization and increased costs. - Pain at high risk of chronic pain despite the wound healed, greatly affecting the life and work of the patient. - Pain has a negative effect on patients’ psychology, sympathy and hospital, especially children. - Post-operative abdominal pain in patients with poor breathing causes collapse of the lungs and may cause respiratory failure. 1.4. The rules of pain prevention after abdominal surgery - Apply systematic preoperative and postoperative pain management measures. - The preparation of patients before surgery to help them have a good psychological comfort and good coordination with the physician to make the treatment of pain more effective. - VAS pain assessment and pain management at the time of patient discharge. - Tacit assay for patients with VAS score ≥ 4 in the recovery room before using other analgesia (e.g. IV-PCA). - It should be based on the degree of pain of the surgery, the existing equipment and the capacity of the treating staff to select appropriate pain management techniques. - For patients with severe pain, strategies for applying multi modal therapy are needed. - Pain prevention should be performed concurrently with vomiting and postoperative vomiting, especially when using morphine. Vaginal suppositories should be used systemically in surgery, such as steroids or 5-HT3 receptor antagonists (ondansetron). 6 - Anti-pain patients should be monitored postoperatively to ensure effective pain relief (VAS <4) by adjusting the dosage, even by more appropriate methods, to ensure that there are no serious complications (respiratory, circulatory, peripheral blood, infections) and minimize unwanted effects such as paralysis, numbness, vomiting, nausea, urinary retention, itching ... - Catheter used in pain relief as well as other instruments, should not save more than 3 days. Chapter 2 RESEARCH SUBJECTS AND METHODS 2.1 Research subjects The study was conducted in patients undergoing endotracheal anesthesia for open surgery under the plan of upper abdominal ailments at Department of Anesthesiology and Resuscitation - Bac Ninh General Hospital. Study period from August 2012, to June 2016. Criteria for choosing patients to study - Age is over 18 regardless of gender. - Health Status ASA I, II. - No contraindication with spinal anesthesia. - No contraindications to morphine. - Patients know how to use PCA after being instructed. - The patient agrees to cooperate with the physician to participate in the study. Criteria to exclude patients from the study. - Patients with heart failure, respiratory failure, kidney failure. - Patients with difficulty communicating, having a history of or present with epilepsy or mental illness. - Patients with a history of drug addiction. - Patients with prostatic hypertrophy and cholecystitis. 7 - Patients who have had painkillers morphine before surgery for 7 days or have chronic illness often have to use painkillers. - Patients require other painkillers and / or tranquilizers. 2.2. Research methods 2.2.1. Study categories Prospective study, randomized, controlled clinical trials and compare. 2.2.2. Sample size and selection. We apply the following formula to calculate the sample size: Notes: n: number of patients in each study group. p1: According to research by Justin Sangwook Ko, the postoperative satisfaction rate was 83%. Assumptions in the study were: p2 = 55% α Type I error β: type II error P = 1/2 (P1 + P2) Z: coefficient of confidence Assumption of selection in the study was: α = 0.05; β = 0.10 Apply to formulas: P1 = 83% P2 = 55% P = 1/2 (P1 + P2) = 69.0% Z1-a / 2 = 1.96; Z1-β = 1.28 Replace these numbers into the formula for calculating the sample size, calculated as n = 54. Thus, each group was 54 patients. We selected 60 patients each. 8 2.2.3. Proceeding way 180 patients were divided into 3 groups: - Group 1 (N1): postoperative pain management with pure morphine IV-PCA. - Group 2 (N2): injection of 200 mcg morphine into the lower spinal cavity before surgery with IV-PCA morphine postoperatively. - Group 3 (N3): 400 mcg morphine injection into the lower spine before surgery with IV-PCA morphine postoperatively. 2.2.7. Perform anesthesia, maintain anesthesia and withdraw the NKQ following a unified procedure. 2.2.8. Facilities and research equipment. - PCA: Bbraun - Germany. - Blood gas meter: GEM Premier 3000 - Japan - Top flow measuring instrument. - Drugs and other necessary GMHS facilities. 2.3.9. Criteria for evaluation in the study: Data collection 2.3.9.1. Criteria related to pain effectiveness (1st Goal) - VAS points (T: 0, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72 hours) + VAS rating at break time + Evaluate VAS scores at mobilization - First time need pain relief - Amount of morphine used (in milligrams): + The amount of morphine used when titling. + Amount of morphine consumed through IV-PCA after surgery. - Results of peak supply: Before surgery, after surgery 24, 48 and 72 hours. - A / D ratio (%) - Patient satisfaction with analgesia; It is divided into three levels: Very satisfied, satisfied and dissatisfied. 9 2.3.8.2. Criteria for undesirable effects and complications (2nd Goal) - Changes in circulation, respiration, sedation. - Evaluate of vomiting and nausea, itching, urinary retention 2.6. Analysis and processing of data The data was analyzed and processed by computer statistics on computer using Stata software. Chapter 3 RESEARCH RESULT 3.1 Studied patient’s characteristics Table 3.1: Age, height, weight, sex and ASA of the three groups were not significantly different from p> 0.05. 3.2. Analgesic effect 3.2.1. Wake up time, time to extubation and first postoperative pain relief demand. Table 3.8. Wake up time, time to extubation and first pain relief demand. Group 1 Group 2 Group 3 p n = 60 n = 60 n = 60 Wake up time after surgery (minutes) ±SD 23,25 ± 13,3 26,5 ± 13,54 27,3 ± 15,52 >0,05 Min÷Max 5÷70 10÷80 5÷70 Time to extubation (minutes) ±SD 35,62 ± 18,04 34,73 ± 19,44 40,75 ± 19,0 Min÷Max 10÷110 First pain relief demand (hours) ±SD Min÷Max 0,52 ± 0,34 0,08÷2 10÷120 5,0± 5,34 0,5÷20 >0,05 15÷90 17,42 ± 17,34 <0,05 1÷72 10 Evaluate: The wake up time and time to extubation are not different. The start average time must use PCA to relief pain in group 1is lowest, next group 2 and the highest in group 3. The difference among the three groups was statistically significant at p <0.05. 3.2.2. A/D ratio Table 3.9. A/D ratio Group 1 Group 2 Group 3 n = 60 n = 60 n = 60 Time p X + SD X + SD X + SD 4h 77,52 ± 12,63 91,55 ± 12,34 99,53 ± 1,92 <0,05 8h 75,45 ± 14,09 91,68 ± 12,43 98,5 ± 5,23 <0,05 12h 72,05 ± 14,54 91,27 ± 12,55 98,98 ± 2,93 <0,05 16h 72,52 ± 14,53 89,37 ± 13,21 99,15 ± 2,12 <0,05 24h 72,53 ± 13,81 89,67 ± 12,78 98,88 ± 2,43 <0,05 32h 72,52 ± 15 87,48 ± 13,84 98,57 ± 2,7 <0,05 40h 73,37 ± 14,66 87,1 ± 13,72 98,35 ± 3,38 <0,05 48h 73,55 ± 14,17 86,63 ± 13,8 98,57 ± 2,28 <0,05 56h 72,92 ± 13,88 90,33 ± 11,57 98,85 ± 2,15 <0,05 64h 74,23 ± 13,89 91,67 ± 10,88 99,18 ± 2,38 <0,05 72h 75,53 ± 13,51 94 ± 9,56 99,05 ± 3,69 <0,05 (p:compare among three groups in each evaluated time) Evaluate: The differance of the median A/D ratio among 3 groups in each evaluated time was statistically significant at p <0.05. 3.2.3. Amount of morphine titration Table 3.10. The average amount of morphine needed to titrate The average amount of Group 1 Group 2 Group 3 p morphine titration (mg) 60 58 52 n ± SD Min ÷ Max 6,28±2,16 4,25±2,12 2,74±1,88 <0,05 2÷10 2÷8 2÷6 11 Evaluate: The average amount of morphine needed to titrate is highest in group 1, next in group 2 and lowest in group 3. 3.2.4. Total consumption of postoperative pain-killer Morphine at times. Table 3.11. The consumption of pain-killer Morphine after 72 postoperative hours(mg) Time Value Group 1 Group 2 Group 3 p n 60 55 43 24h X + SD 27,67 ± 12,89 14,6 ± 11,65 7,84 ± 6,14 <0,05 Min÷Max 1÷62 1÷40 1÷26 n 60 58 52 42,3 ± 16,96 26 ± 18,54 15,19 ± 9,51 <0,05 48h X + SD Min÷Max 6÷77 2÷68 2÷42 n 60 58 52 72h X + SD 53,07 ± 21,9 34,53 ± 22,39 19,69 ± 11,71 <0,05 Min÷Max 9÷95 2÷76 3÷46 Evaluate: Morphine was used within 24 hours, 48 hours and 72 hours: group 1 was highest, then group 2 and lowest group 3, The difference among 3 groups in each evaluated time was statistically significant at p <0.05. Table 3.12. Number of patients used morphine 72 postoperative hours. Morphine (mg) Group 1 Group 2 Group 3 p 0 0 2 8 <0,05 ≤ 10 2 7 14 11 - 30 10 24 29 31 – 60 18 16 9 >60 30 11 0 Total 60 60 60 (p: compare among three groups) 12 Evaluate: - Patients with a total dose of ≤10 mg were significantly different in the three groups - Patients with a total dose of >60 mg were significantly different in the three groups 3.2.5. Visual Analog Scale (VAS) pain at postoperative times. Table 3.13. VAS pain scores in postoperative static sense Time Group 1 Group 2 Group 3 n = 60 n = 60 n = 60 X + SD X + SD X + SD p 0h 3,6 ± 2,39 2,17 ± 1,88 1,82 ± 1,23 <0,05 4h 3,42 ± 1,52 2,4 ± 1,12 1,83 ± 0,94 <0,05 8h 3,28 ± 1,39 2,15 ± 0,86 1,85 ± 0,95 <0,05 12h 3,25 ± 1,36 2,13 ± 0,87 1,85 ± 0,95 <0,05 16h 2,92 ± 1,15 2,13 ± 0,87 1,87 ± 0,98 <0,05 24h 3,07 ± 1,18 2,13 ± 0,77 2 ± 0,94 <0,05 32h 2,82 ± 0,91 2,13 ± 0,75 1,95 ± 0,93 <0,05 40h 2,57 ± 0,93 2,2 ± 0,75 2,08 ± 0,89 <0,05 48h 2,47 ± 0,93 2,15 ± 0,78 2,13 ± 0,96 <0,05 56h 2,35 ± 0,94 2,05 ± 0,7 1,88 ± 0,8 <0,05 64h 2,18 ± 0,77 2,12 ± 0,85 1,77 ± 0,74 <0,05 72h 2,13 ± 0,72 1,95 ± 0,72 1,7 ± 0,74 <0,05 (p:compare among three groups in each evaluated time) Evaluate: VAS scores were highest in group 1, followed by group 2 and lowest in group 3. The difference among the three groups was statistically significant at p<0.05. 13 Table 3.14. VAS pain scores in postoperative dynamic sense Group 1 Group 2 Group 3 n = 60 n = 60 n = 60 Time p X + SD X + SD X + SD 0h 4,79 ± 2,26 3,29 ± 2,15 2,58 ± 1,54 <0,05 4h 4,57 ± 1,53 3,57 ± 1,33 2,77 ± 1,16 <0,05 8h 4,38 ± 1,39 3,27 ± 1,16 2,83 ± 1,17 <0,05 12h 4,42 ± 1,37 3,25 ± 1 2,9 ± 1,13 <0,05 16h 3,98 ± 1,24 3,25 ± 1,02 3,05 ± 1,14 <0,05 24h 4,23 ± 1,21 3,35 ± 0,9 3,17 ± 1,04 <0,05 32h 4,08 ± 1,18 3,32 ± 0,85 3,08 ± 1,03 <0,05 40h 3,73 ± 1,04 3,33 ± 0,82 3,08 ± 1,01 <0,05 48h 3,65 ± 0,99 3,33 ± 0,99 3,12 ± 1,08 <0,05 56h 3,47 ± 1,07 3,07 ± 0,84 2,85 ± 0,88 <0,05 64h 3,25 ± 0,88 3,15 ± 0,99 2,7 ± 0,85 <0,05 72h <0,05 3,15 ± 0,88 2,93 ± 0,88 2,6 ± 0,91 (p:compare among three groups in each evaluated time) Evaluate: VAS scores were highest in group 1, followed by group 2 and lowest in group 3. The difference among the three groups was statistically significant at p <0.05. 3.2.6. Patient Satisfaction level Table 3.15. Patient Satisfaction Level Level Group 1 Group 2 Group 3 Total p n = 60 n = 60 n = 60 n=180 Extra P<0,05 19(31,7%) 27(45%) 37(61,7%) 83(46,1%) satisfied p1,2<0,05 Satisfied 21(35%) 20(33,3%) 11(18,3%) 52(28,9%) p1,3<0,05 Unsatisfied 20(33,3%) 13(21,7%) 12(20%) 45(25%) p2,3>0,05 (p:compare among three groups) 14 Evaluate: - The level of extra-satisfaction and satisfaction of group 2 is higher than that of group 1. This difference was statistically significant at p <0.05. - The level of extra-satisfaction and satisfaction of group 3 is higher than that of group 1. This difference was statistically significant at p <0.05. 3.3. Indicators for monitoring complications, undesirable effects 3.3.1. Indicators of complications. Heart rate: table 3.16; Mean arterial pressure: table 3.17; Systolic arterial pressure: table 3.18; diastolic arterial pressures: table 3.19; Respiratory rate: table 3.20; SpO2: table 3.21. Evaluate: The difference among Heart rate mean arterial pressure, systolic arterial pressure, diastolic arterial pressures, respiratory rate and SpO2 was statistically significant at p <0.05. 3.3.2. Measurement result of ventilation function Table 3.22. Measurement result of peak flow (liter/min) Group 1 Group 2 Group 3 n = 60 n = 60 n = 60 Time p X X X ( + SD) ( + SD) ( + SD) Prenursery 402,5 ± 62,86 413,67 ± 55,36 415,75 ± 55,21 >0,05 24h 178,0 ± 77,24 227,83 ± 49,58 247,67 ± 53,31 <0,05 48h 216,33 ± 66,31 267,08 ± 42,79 309,33 ± 43,49 <0,05 72h 248,25 ± 64,26 303,17 ± 33,42 353,17 ± 41,76 <0,05 (p:compare among three groups) Evaluate: - The preoperative peak flow of three groups was not significantly different with p> 0,05. - The postoperative peak flow of three groups was lower than preoperative peak flow. These difference is statistically signification at p<0,05. 15 3.3.3. Arterial blood gas test results Table 3.23. PaO2 result (mmHg) Group 1 n = 60 Group 2 n = 60 X + SD Min ÷Max 95,4 ± 11,86 67÷118 93,28 ± 14,23 63÷119 94,82 ± 12,15 >0,05 65÷133 X + SD Min ÷Max X + SD Min ÷Max X + SD Min ÷Max 82,42 ± 11,65 64÷112 80,03 ± 13,13 64÷115 83,43 ± 10,56 >0,05 63÷103 81,25 ± 11,51 63÷113 78,98 ± 11,78 65÷107 82,75 ± 8,83 >0,05 65÷99 81,13 ± 13,67 63÷120 80,88 ± 11,36 65÷110 84,58 ± 8,33 >0,05 68÷100 Time Value Prenursery 24h 48h 72h Group 3 n = 60 p (p:compare among three groups in each evaluated time) Evaluate: - At preoperative point, the difference among 3 groups was not statistically signification with p> 0,05. - After each postoperative point, the difference among 3 groups is not statistically signification at p>0,05. - After each postoperative point, 3 groups compared with preoperative point was statistically significant at p <0.05. Table 3.24. PaCO2 result (mmHg) Time Prenursery 24h 48h 72h Value X + SD Min ÷Max X + SD Min ÷Max X + SD Min ÷Max X + SD Min ÷Max Group 1 n = 60 Group 2 n = 60 Group 3 n = 60 p 36,32 ± 4,05 35,6 ± 3,88 36,83 ± 3,69 >0,05 27÷44 28÷44 29÷45 36,42 ± 3,86 35,78 ± 3,76 36,3 ± 3,67 >0,05 29÷45 28÷45 28÷44 36,63 ± 3,6 36,85 ± 3,68 36,65 ± 3,66 >0,05 27÷43 27÷43 28÷43 38,13 ± 4,25 38,32 ± 3,71 38,17 ± 3,54 >0,05 27÷44 29÷43 30÷45 Evaluate: PaCO2 among three groups was not different at the time of study with p> 0.05. 16 3.3.4. Unexpected side-effects Table 3.27. Unexpected side-effects Group 1 n = 60 Vomiting n (%) and nausea Level 0 34(56,7%) Level 1 15(25%) Level 2 10(16,7%) Level 3 1(1,7%) Rash and Itching Level 0 43(71,7%) Level 1 16(26,7%) Level 2 1(1,7%) Level 3 0(0%) Sedation SS0 21(35%) SS1 34(56,7%) SS2 5(8,3%) SS3 0(0%) Respiratory effects R0 48(80%) R1 11(18,3%) R2 1(1,7%) R3 0(0%) Retention Group 2 n = 60 Group 3 n = 60 Total n = 180 n (%) n (%) n (%) 36(60%) 19(31,7%) 3(5%) 2(3,3%) 34(56,7%) 20(33,3%) 3(5%) 3(5%) 104(57,8%) 54(30%) 16(8,9%) 6(3,3%) >0,05 38(63,3%) 21(35%) 0(0%) 1(1,7%) 37(61,7%) 23(38,3%) 0(0%) 0(0%) 118(65,6%) 60(33,3%) 1(0,6%) 1(0,6%) >0,05 31(51,7%) 27(45%) 2(3,3%) 0(0%) 32(53,3%) 26(43,3%) 2(3,3%) 0(0%) 84(46,7%) p<0,05 87(48,3%) p1,3<0,05 p1,2<0,05 9(5%) p2,3>0,05 0(0%) 53(88,3%) 53(88,3%) 7(11,7%) 7(11,7%) 0(0%) 0(0%) 0(0%) 0(0%) Undetermined 154(85,6%) 25(13,9%) 1(0,6%) 0(0%) p >0,05 (p:compare among three group; p1,3:compare group 1 with group 3; P2,3: compare group 2 with group 3; p1,2: compare group 1 with group 2). Evaluate: - The unexpected side-effects such as vomiting and nausea, rash and itching and respiratory effects was not different among 3 groups with p> 0.05. - Sedation SS1 and SS2 on group 1 differ from group 2 and group 3. These difference is statistically signification at p<0,05. 17 Chapter 4 DISCUSSION 4.1. Studied patients’ general characteristics. As shown in Table 3.1, our patients in terms of age, sex, height, weight and ASA were not significantly different from p <0.05, similar to An Thanh Cong, Bui Ngoc Chinh and Nguyen Toan Thang. Thus, our research patients are homogeneous. 4.2. Evaluate the results of pain relief. 4.2.1. Time of first pain relief request. As shown in Table 3.8, the PCA start-up time in group 1 was 0.52 ± 0.34 hours, group 2 was 5.0 ± 5.34 hours and group 3 was 17.42 ± 17.34 hours. Group 1 was the lowest, followed by group 2 and the highest group 3, the difference between the three groups was statistically significant at p <0.05. This demonstrates that the administration of morphine into the spinal cord prior to surgery is effective in preventing postoperative pain. In the study of Khaled Mohamed, the PCA initiation time of group 1 (morphine 0.2 mg) was 0.5 ± 0.66 hours; group 2 (morphine 0.5 mg) was 22.13 ± 5.21 hours; Group 3 (morphine 1mg) was 30.83 ± 4.89 hours. According to Hala (2016), postoperative analgesia in large tumors of the abdomen, resulting in a 0.5 mg spinal morphine injection, the initial initiation of analgesia was 22, 13 ± 5.2 hours. Our time lower than Khaled Mohamed and Hala is due to the lower morphology of our spinal cord. In the study of An Thanh Cong using 0.3 mg spinal morphology before surgery in the cases of abdominal surgery, found the time to start the need for pain first is 4.59 ± 3.97 hours and The authors also found that preoperative morphine injection was effective in preventing postoperative pain. Thus, the time needed to relieve pain after surgery is not only dependent on the type of surgery, anesthesia and analgesia during 18 and after surgery, but also depends on the time and dose of morphine injection in the spinal cord. 4.2.2. A /D ratio and need for painkillers. As shown in Table 3.9, the mean A/D ratio of group 1 in each postoperative period was lower than in group 2 and group 3, and the difference was significant at p <0.05, suggesting that with upper abdominal surgery Simply applied IV-PCA-morphine, pain relief may not meet the need, so it should be combined with other methods (such as spinal morphine injection) to support postoperative pain. The results showed a good analgesic effect when combining ITM with IV-PCA-morphine, especially in group 3 using ITM 0.4mg injection before surgery. Our results in groups 2 and 3 had a higher A / D ratio than Nguyen Toan Thang with 24 hours 71.6 ± 7.7%, after 48 hours 76.3 ± 6.2%. The reason for this is that in group 2 and group 3 we have used spinal morphology before surgery so that postoperative pain relief is better and the need for postoperative analgesia decreases significantly at p<0,05. 4.2.3. The amount of triturative pain-killer morphine after operation PCA pain-killer method is essentially maintenance therapy, so the patient should achieve adequate analgesia (equivalent to VAS <4) before putting the PCA. The results in Table 3.10, group 1 were the highest, followed by group 2 and lowest group 3, significant differences were found between groups at p<0,05. In the An Thanh Cong’s study, the preoperative ITM group was 3.27 ± 3.30 mg (maximum of 10 mg and at least 2 mg) and in the S group was 7.29 ± 3.38 mg (4-18 mg) and the difference between the two groups was statistically significant at p <0.05. Thus, our titrated dose in group 1 was equivalent to postoperative ITM (S), group 2 was equivalent to preoperative (T) and lower group (ITM).