Study on the hemodynamic efects of phenylephrine in the management of hypotension during spinal anesthesia for cesarean section

accurate measurement results. 1.7. Many studies have managed to hypotension and hemodynamic monitoring: *Viet Nam: - In 2016, Nguyen Quoc Kinh, prevented of hypotension in SA by ephedrine continuous perfusion or fluid infusion. - In 2012, Nguyen Van Minh assessed the effect of stabilizing BP of the hydroxyethyl starch 6% infused before SA for cesarean section. - In 2016, Pham Le Hoan, Đo Van Loi, Sam Thi Qui comparing efficacy of treatment of hypotension due to SA in caesarean section of phenylephrine with ephedrine, these studies have not yet evaluated in detail the hemodynamic changes in surgery and umbilical cord pH value systemically. **Research on hemodynamic monitoring application by Niccomo: - In 2013, Ji-Yeon Kim, to compare the two methods of measuring CO by FloTrac ™/Vigileo ™ monitor and ICG monitor niccomo™ for similar results, the CO value varies by +/- 0.45 liters /minute. - In 2014, Lorne compared measurement of CO by ICG and esophagial doppler in surgery showed the CO value correlated closely between the two methods (r = 0.88 6 (0.82-0.94), p <0.001); ICG is a non-invasive and reliable method. - In 2014, Staelens used to monitor SV with ICG related to the women position during surgery, there is a strong correlation when compared with hemodynamic monitoring by Fick principle. - In 2017, Elwan hemodynamic exploration by USCOM compared with Niccomo showed higher CO and SV values in the Niccomo measurement group. - In 2018, Mansouri observed that CO increased significantly after 2 to 3 minutes of phenylephrine compared with baseline (p <0.05) in patients undergoing SA for cesarean section. CHAPTER 2 – OBJECTS AND METHODS 2.1. Objects 2.1.1. Criteria for selecting a patient: Patients with ASA 1-2; Pregnant women; pregrammed cesarean; Full term (≥ 38 weeks), no fetal failure; Anesthetic cesarean section by SA. 2.1.2. Criteria for exclusion of patients: *Standards related to obstetrics: Abnormal pregnancy diagnosed. Emergency cesarean section for mother and / or fetal failure. Pre-eclampsia, eclampsia, hypertension. Rejected. SA unsucced must switch to anesthesia. *General standards: contradications of SA. Cardiovascular disease. Patient is currently taking cardiovascular medication and BP control medication. Patients with insulin dependent diabetes. History of nausea, vomiting after surgery. History of chronic opioids. Allergy to anesthetics, morphine drugs, drugs used in study. 2.1.3. Standards taken out of study: SA not enough blockade to switch anesthesia. The level of blockade is over T4. Bleeding during surgery > 500 ml. Complications during cesarean section. 2.2. Research methods 2.2.1. Research design: Comparative, single blind, randomized controlled clinical study: group P (phenylephrine) and group E (ephedrine). 2.2.2. Study sample size: 140 patients divided each group 70 patients. 2.2.3. Time, research place: from 10/2016 to 9/2018: Department of Obstetrics and Gynecology, Department of Anethesiology, NgheAn General Friendship Hospital. 2.2.4. Research protocol: 2 groups are the same: - Mother: Patients are eligible to choose. Administer 3 litres/min oxygen through the nose. One peripheral G18 line is connected to a 3 ways- lock (01 infusion line, 01 vasoconstrictor drug line from Terumo-B.braun electric syringe). Transfusion of 10 7 ml /kg of ringer lactate via peripheral venous catheter in 15 minutes before SA and then maintenance of 100 ml /h during surgery. SA posture lateral left or seat, puncture level L2-3. Dosage of bupivacaine 0.5% heavy 8-10 mg plus fentanyl 0.05 mg. Put your right hip pillow so the uterus is left. *Group P (phenylephrine): as soon as SA, continuous infusion of phenylephrine by electric syringe through separate peripheral intravenous catheter, prophylactic dose of 15 mcg /min until skin closure. If SBP is low ≥20% of baseline, bolus phenylephrine 50 mcg - 100 mcg - 100 mcg / time every 2 minutes if BP is still low. *Group E (ephedrine): Immediately after SA, ephedrine continuous infusion by electric syringe through separate peripheral intravenous catheter, prophylactic dose of 1.5 mg /min until skin closure. If the systolic BP is low ≥ 20% of the baseline, bolus ephedrine 5 mg - 10 mg - 10 mg once every 2 minutes if BP is still low. *If BP is still low after 3 consecutive bolus injections (250 mcg of phenylephrine or 25 mg of ephedrine), then rapid infusion in 15 minutes with 7 ml /kg of Voluven colloid combined plus adrenalin infusion (if maternal heart rate <75 beats/minute) or noradrenalin (if maternal heart rate ≥75 beats/minute) intravenously via an electric syringe with a starting dose of 0.05 mcg/kg/min and then follow the BP dose. *If BP increases by ≥ 20% of the baseline, reduce the prophylactic dose by 1/3. *If bradycardia <60 beats/ minute, intravenous atropine 0.5 mg. *After anesthetic injection into the spinal fluids, the level of numbness was assessed by pain stimulation and temperature sensation (using an alcohol swab to assess) before incision. *Immediately after caesarean section, inject 10 oxytocin into the uterine muscle. *Monitor BP (systolic, mean, diastolic), heart rate, breathing rate, SpO2 by Phillips monitor 2 minutes/1 time in the first 20 minutes and then 5 minutes/1 time for the rest of surgery. *Continuous monitoring of hemodynamic by monitoring Niccomo: CO, SVR, SV, HR, SpO2, respitarory rate, BP, numbness level blockage, sensory recovery, leg movements; vomiting, nausea, headache, uterine contraction at 23 points (from t1 to t23) and 6 at the recovery room (HT1 to HT6). Take patients out of the recovery room with Aldrete > 9 points. - Child: Measuring fetal heart rate: clamp the SpO2 sensor by monitoring Phillips from the toes. Evaluate Apgar scores in 1 and 5 minutes. Umbilical cord blood gas tested. 2.2.5. Evaluation criteria: 8 Objective 1: Compare the effects of phenylephrine with ephedrine on hemodynamics by non-invasive method Niccomo in the management of hypotension during SA for cesarean section: *Blood pressure: Changes in blood pressure (systolic, mean, diastolic). The percentage of patients with hypotension, the ratio of patients with hypotension per patient, the average level of the lowest BP, comparing the 2 groups. The rate of hypertension after using vasoconstrictor (reactive hypertension). *Heart rate: HR changes of 2 groups at any times. Proportion of patients with bradycardia ( 100 beats/minute). Proportion of patients requiring atropine for management of bradycardia. *CO: Lowest average CO value; highest; change in CO at any times (comparing the two groups). *SVR: SVR change, average SVR lowest, highest for each group, SVR difference between the two groups. *SV: Changes SV of two groups at times. Compare the average SV value at the time of research. The proportion of patients with SV decreased (< 60 ml). *Response to infusion: Average amount of infusion (ringer lactate) (before, during, after procedure and total fluid volume). *Response to vasoconstrictor drugs: The average dose in each patient of the two groups (prophylactic infusion, bolus, total dose). The number of vasoconstrictor bolus used to treat hypotension in the two groups. *Relations between vasoconstrictor dose and hemodynamic parameters: The correlation of vasoconstrictor dose with BP, HR, CO, SVR, SV. *Risk: hypotension, frequency of hypotension, bradycardia, tachycardia for prevention of phenylephrine, ephedrine: odd ratio: OR. Objective 2: Assess some undesirable effects of phenylephrine and ephedrine on maternal and newborn infants in SA for cesarean section: Vomiting and nausea, chills, itching; Apgar: 1 minute, 5 minutes; Umbilical pH (arterial and venous umbilical cord) of the two groups. pO2, pCO2 and BE, HCO3- (artery, vein umbilical cord); Differences in the index of blood gases and acidosis /alkaline, umbilical cord; Other indicators (breathing frequency, SpO2; maternal age, weight, height, BMI, indication of cesarean section, special history, time to start numbness, extent of anesthesia; total time of surgery (characteristics; age, sex of infant, infant weight). 9 2.5. Study chart: Picture 2.1. Study chart Qualified patients, randomized in to 2 groups Analyze, process datas, comparision at 23 points times Group P, n = 70 patients *phenylephrine: continous perfusion 15mcg/min. Bolus 50- 100-100mcg every 2 min if hypotension >20% baseline Excluded patients: unqualified, not agree to join the research Patients admitted in Department of Obstertric -Gynaecology, indicated for cesarean Group E, n = 70 patients *ephedrine: continous perfusion 1,5mg/min. Bolus 5-10-10 mg every 2 min if hypotension >20% baselin Results Conclusions Group P: n = 70; Analyze: - BP, HR, SpO2, CO, SV, SVR - Umbilical blood gas - Undesirable effects Group E: n = 70; Analyze: - BP, HR, SpO2, CO, SV, SVR Umbilical blood gas - Undesirable effects 10 CHAPTER 3 – RESULTS 3.1. Gestational age and infant gender Bảng 3.1. Gestational age and infant sex Characteristics Goup P n = 70 Goup E n = 70 p Gestational age (weeks) 𝑋 ± SD; (Min-Max) 39,10 ± 0,91 (38-41) 39,26 ± 0,77 (38-42) > 0,05 Infant male/female 34/36 42/28 > 0,05 3.2. Anesthetic characteristics - surgery Table 3.2. The onset time, the Duration of surgery in two groups Characteristics Goup P n = 70 Goup E n = 70 p Onset time (min) 𝑋 ± SD; (Min-Max) 2,53 ± 0,56 (2-4) 2,54 ± 0,52 (2-3) > 0,05 Duration of operation (min) 𝑋 ± SD; (Min-Max) 62,51 ± 6,74 (50-100) 58,11 ± 6,39 (40-73) > 0,05 3.3. Management of hypotension during spinal anesthesia 3.3.1. Infusion during spinal anesthesia Table 3.3. The amount of fluids used in surgery Infusion volume (ringer lactat, ml) Group P n = 70 Group E n = 70 p Preload 𝑋 ± SD; (Min-Max) 447,8 ± 58,0 (300-500) 422,1 ± 75,0 (200-600) > 0,05 Coloading 𝑋 ± SD; (Min-Max) 206,4 ± 31,7 (100-300) 212,8 ± 76,4 (100-500) > 0,05 Infusion after vasocontriction stop 𝑋 ± SD; (Min-Max) 184,2 ± 40,4 (100-300) 144,2 ± 53,5 (100-300) > 0,05 Fluid Total 𝑋 ± SD, (Min-Max) 838,5 ± 66,5 (700-1000) 777,8 ± 150,5 (200-1300) > 0,05 3.3.2. Vasoconstrictor used in spinal anessthesia Table 3.4. Vasoconstrictor infusion for solve hypotension Vasoconstrictor used Group P n = 70 Group E n = 70 p Patients need bolus n (%) 50 (71,4%) 56 (80,0%) > 0,05 Vasoconstrictor infusion (𝑋 ± SD) (Min-Max) 183,43 ± 56,77 mcg (100-300) 14,85 ± 6,58 mg (5-45) 11 Infusion time of vasocontrictor (min), (𝑋 ± SD) (Min-Max) 11,09 ± 3,63 (5-20) 10,50 ± 5,18 (5-35) > 0,05 *The bolus times of vasocontrictors: Chart 3.1. The bolus times of vasocontrictors 3.4. Change hemodynamic indicators at the research time 3.4.1. Cardiac output changes at point times Chart 3.2. CO changes in the point times (*p <0,05) Comment: Group P: from t4 to t9, CO decreased, CO(at t5) < CO(at t3) with p < 0,05. Minimun CO value at t6: 5,85 ± 0,89 litre/minutes. 14 5 26 10 9 4 27 26 27 8 1 1 0 0 5 10 15 20 25 30 35 0 lần 1 lần 2 lần 3 lần 4 lần 5 lần 6 lần bolus times Bệnh nhân nhóm P nhóm E p< 0,05 12 Group E: From t5 to t11, CO value decrease; CO (at t5) < CO (at t4) with p < 0,05; CO min at t8: 5,75 ± 1,33 litre/minutes. Comparision in two group: from t14 to t22: CO value in group P are lower than CO in group E (p < 0,05). 3.4.2. SVR changes in any research point times Table 3.5. The mean of SVR changes in any research point times Point times Group P 𝑋 ± SD, dyne-s/cm5 Group E 𝑋 ± SD, dyne-s/cm5 p t1 917,86 ± 130,30 991,12 ± 238,15 > 0,05 t2 905,76 ± 134,66 993,22 ± 234,19 t3 899,03 ± 118,30 975,45 ± 224,45 t4 865,06 ± 148,84 944,48 ± 242,18 t5 849,66 ± 174,93 900,71 ± 219,40 t6 822,97 ± 171,77 875,75 ± 224,55 t7 822,36 ± 165,09 866,52 ± 226,00 t8 908,21 ± 150,29 920,60 ± 264,99 t9 882,20 ± 165,34 920,25 ± 234,97 t10 889,90 ± 167,25 937,54 ± 258,54 t11 889,91 ± 170,58 926,38 ± 236,34 t12 890,06 ± 168,36 924,02 ± 226,39 t13 867,07 ± 148,17 913,08 ± 208,69 t14 849,77 ± 162,05 854,30 ± 186,83 t15 829,49 ± 169,15 857,17 ± 188,83 t16 828,14 ± 168,71 832,64 ± 181,32 t17 831,10 ± 158,80 807,08 ± 153,98 t18 828,20 ± 136,48 814,34 ± 167,42 t19 795,24 ± 157,43 810,81 ± 164,42 t20 789,61 ± 115,80 810,15 ± 193,71 t21 779,70 ± 123,43 807,80 ± 183,93 t22 784,54 ± 115,44 841,30 ± 197,86 t23 795,90 ± 109,15 858,00 ± 176,61 Comment: From t4, SVR values are lower than the original value. Comparing the degree of SVR change from t4 onwards was similar between the two groups 13 3.4.3. The SV changes at any research point time Chart 3.3. The SV changes at any research point time Comment: Group P: SV lowest at t6: 68.57 ± 17.08 ml. Group E: the lowest SV value at t7: 57.60 ± 13.18 ml. From t4 to t23, the SV in group P was always higher than SV in group E, the difference was significant with p <0.05. 3.4.4. SAP changes in any research point times Chart 3.4. SAP changes in any research point times Comment: Group P: The lowest SAP at t7: 104,29 ± 12,02 mmHg. Group E: The lowest SAP at t7: 100,09 ± 19,61 mmHg. Comparisons at times between the two groups are equivalent. 0 10 20 30 40 50 60 70 80 90 100 t1 t2 t3 t4 t5 t6 t7 t8 t9 t10t11t12t13t14t15t16t17t18t19t20t21t22t23 Point time SV (ml) nhóm P nhóm E *p 0 20 40 60 80 100 120 140 160 t1 t2 t3 t4 t5 t6 t7 t8 t9 t10t11t12t13t14t15t16t17t18t19t20t21t22t23 Point time HATT (mmHg) nhóm P nhóm E 14 3.4.5. MAP changes in any research point times Chart 3.5. MAP changes in any research point times Comment: Group P: The MAP is stable throughout the operation. Group E: the lowest MAP at t7: 66.89 ± 15.80 mmHg. 3.5. Mean HR changes in any research point times Table 3.6. Mean HR changes in any research point times Point time Group P (𝑋 ± SD); (time/min) (Min-Max) Group E (𝑋 ± SD); (time/min) (Min-Max) p t1 82,46 ± 6,39 (60-97) 84,76 ± 12,62 (73-100) >0,05 t2 81,97 ± 6,41 (61-96) 85,34 ± 13,04 (71-89) t3 80,67 ± 6,67 (67-98) 86,40 ± 14,49 (74-90) t4 81,00 ± 8,56 (60-109) 100,00 ± 16,46 (73-95) <0,05 t5 79,77 ± 10,94 (55-107) 101,57 ± 20,40 (63-147) t6 79,34 ± 10,90 (53-110) 101,31 ± 20,55 (61-159) t7 77,26 ± 10,57 (52-109) 102,79 ± 20,92 (53-149) t8 78,36 ± 10,19 (56-96) 104,39 ± 20,42 (62-155) t9 76,99 ± 10,09 (53-98) 102,13 ± 19,70 (65-148) t10 76,63 ± 9,37 (56-99) 100,69 ± 19,55 (66-154) t11 76,67 ± 10,04 (57-94) 99,74 ± 18,74 (64-138) t12 76,69 ± 10,75 (56-106) 101,73 ± 19,74 (67-152) t13 76,67 ± 10,85 (55-110) 100,00 ± 19,37 (65-156) t14 77,39 ± 9,64 (53-105) 102,99 ± 16,65 (68-144) 0 20 40 60 80 100 120 t1 t2 t3 t4 t5 t6 t7 t8 t9 t10t11t12t13t14t15t16t17t18t19t20t21t22t23 Thời điểm nghiên cứu HATB (mmHg) nhóm P nhóm E 15 t15 77,30 ± 9,24 (56-104) 103,16 ± 16,18 (70-142) t16 78,43 ± 9,68 (56-109) 100,67 ± 15,89 (68-138) t17 77,77 ± 8,08 (59-92) 102,17 ± 16,68 (60-142) t18 77,60 ± 8,26 (61-96) 100,36 ± 15,69 (61-138) t19 77,90 ± 7,58 (63-94) 100,14 ± 15,01 (67-148) t20 77,77 ± 7,37 (64-95) 98,93 ± 15,56 (65-146) t21 77,61 ± 7,10 (64-90) 97,91 ± 15,13 (68-143) t22 77,70 ± 7,03 (65-96) 96,70 ± 15,09 (63-135) t23 77,13 ± 7,20 (62-92) 96,81 ± 15,82 (61-134) 3.6. Undesirable effects 3.6.1. The rate of hypotension, hypertension Table 3.7. The rate of hypotension, hypertension Characteristics Group P n = 70 Group E n = 70 p Hypotension patients numbers n (%) 56 (80,0) 63 (90,0) > 0,05 Reactive hypertension n (%) 3 (4,28) 39 (55,7) < 0,05 Table 3.8. The number of the hypotension in two groups Hypotension times Group P n (%) Group E n (%) p 0 14 (20) 7 (10,0) > 0,05 1 5 (7,14) 26 (37,24) < 0,05 2 26 (37,14) 27 (38,56) > 0,05 3 10 (14,28) 8 (11,40) 4 9 (12,9) 1 (1,4) 5 4 (5,7) 1 (1,4) 6 2 (2,9) 0 Table 3.9. The number of the hypertension in two groups Number of hypertension Group P; n (%) Group E; n (%) 0 67 (95,71%) 31 (44,29%) 1 3 (4,29%) 21 (30%) 2 0 14 (20%) 3 0 3 (4,29%) 4 0 1 (1,42%) 16 Table 3.10. The risk of hypotension when taking vasocontrictors Risk Hypotension patients n (%) BP normal n (%) OR Ephedrin n = 70 56 (80%) 14 (20%) 0,44 Phenylephrin n = 70 63 (90%) 7 (10%) 1 *OR = 0,44 Comments: The risk of hypotension: ephedrine is 0,44 times less than phenylephrine. Table 3.11. The risk of hypertension when taking vasocontrictors Risk Hypertesion patients n (%) BP normal n (%) OR Ephedrin n = 70 28 (40%) 42 (60%) 14,88 Phenylephrin n = 70 3 (4,3%) 67 (95,7%) 1 Comment: The risk of hypertension: ephedrin is 14,88 times more than phenylephrine 3.6.2. Other undesirable effects Table 3.12. Other undesirable effects Characteristics Group P n = 70 Group E n = 70 p Nôn, buồn nôn, n (%) 4 (5,71) 15 (21,43) < 0,05 Tachycardia, n (%) 5 (7,14) 59 (84,28) < 0,05 Bradycardia, n (%) 10 (14,28) 3 (4,23) < 0,05 Patients need to inject atropine, n (%) 10 (14,28) 3 (4,28) < 0,05 Chills, n (%) 4 (5,8) 4 (5,8) > 0,05 Itching, n (%) 1 (1,4) 6 (8,6) Headache, n (%) 0 1 (1,4) Table 3.13. The risk of bradycardia after taking vasocontrictors Risk Bradycardia n (%) Normal HR n (%) OR Phenylephrin n = 70 10 (14,28%) 60 (85,72) 3,72 Ephedrin n = 70 3 (4,23%) 67 (95,77%) 1 *OR = 3,72; (95%CI: 0,97-14,16). Comment: The risk of phenylephrin causing bradycardia was 3.72 times higher than ephedrine (95%CI: 0,97-14,16). 17 Table 3.14. The risk of tachycardia after taking vasocontrictors Risk Tachycardia n (%) Normal HR n (%) OR Ephedrine n = 70 59 (84,28%) 11 (15,72%) 69,72 Phenylephrine n = 70 5 (7,14%) 65 (92,86) 1 *OR = 69,72; (95% CI: 22,8-212,5); p < 0,05. Comment: The risk of ephedrin causing tachycardia was 69.72 times higher than phenylephrin (95%CI = 22,8-212,5); p < 0,05. Table 3.15. The ratio of nausea, vomiting when taking the vasocontrictors Risk Nausea, vomiting n (%) Normal n (%) OR Phenylephrine n = 70 5 (7.14%) 65 (92.86%) 0.22 Ephedrine n = 70 15 (21.42%) 55 (78.58%) 1 OR = 0,22 (95%CI = 0,07-0,71). Comment: The risk of nausea, vomiting when taking phenylephrine less than ephedrine is 0.22 (95%CI: 0.07-0.71). 3.7. Indicators related to newborns 3.7.1. Infant characteristics Table 3.16. Infant characteristics in the two groups Characteristics Group P n = 70 Group E n = 70 p Apgar 1 minutes 5 points (n, %) 18 (25,70%) 29 (41,43%) > 0,05 7 points (n, %) 52 (74,29%) 41 (58,57%) Apgar 5 minutes 10 points (n, %) 70 (100%) 70 (100%) Infant weight, kg (𝑋 ± SD) (Min-Max) 3,39 ± 0,29 (3,0-4,0) 3,47 ± 0,29 (2,8-4,5) > 0,05 3.7.2. The results of umbilical cord blood gas Table 3.17. Umbilical cord blood gas results Chracteristics Group P n = 70 Group E n = 70 p Umbilical arterial blood gas pH (𝑋 ± SD) (Min-Max) 7,32 ± 0,04 (7,23-7,45) 7,25 ± 0,06 (7,01-7,40) < 0,05 18 PaCO2 (mm Hg) (𝑋 ± SD) (Min-Max) 51,47 ± 8,60 (38,0-81,3) 56,55 ± 7,96 (37,8-90,0) < 0,05 PaO2 (mm Hg) (𝑋 ± SD) (Min-Max) 16,81 ± 5,65 (3,5-35,4) 18,78 ± 5,93 (3,2-31,0) < 0,05 HCO3- (mEq/l) (𝑋 ± SD) (Min-Max) 23,37 ± 1,92 (18,9-28,8) 22,17 ± 1,81 (13,3-25,8) < 0,05 BE (mmol/l) (𝑋 ± SD) (Min-Max) -1,98 ± 1,74 (-5,9—2,0) -2,03 ± 1,79 (-10,7—2,20) > 0,05 Umbilical venous blood gas pH (𝑋 ± SD) (Min-Max) 7,34 ± 0,03 (7,26-7,39) 7,29 ± 0,07 (7,1-7,42) < 0,05 pCO2 (mm Hg) (𝑋 ± SD) (Min-Max) 46,03 ± 6,59 (32,7-75,1) 48,23 ± 9,18 (33,2-85,2) > 0,05 pO2 (mm Hg) (𝑋 ± SD) (Min-Max) 25,60 ± 6,58 (9,5-37,0) 27,39 ± 7,07 (8,7-42,6) > 0,05 HCO3- mEq/l) (𝑋 ± SD) (Min-Max) 23,36 ± 1,57 (19,2-28,6) 22,51 ± 2,05 (16,6-34,5) < 0,05 BE (mmol/l) (𝑋 ± SD) (Min-Max) -1,70 ± 1,19 (-4,8—0,6) -1,62 ± 2,27 (-9,4—12,7) > 0,05 CHAPTER 4 - DISCUSSIONS 4.1. Features of gestational age and infant gender The full gestational age in both groups, the group P: the average gestational age was 39.10 ± 0.91 weeks, equivalent to group E; The average gestational age was 39.26 ± 0.77 weeks. The proportion of male/female newborn in two groups is similar. This ensures the similarity of the 2 groups when conducting research (Table 3.1). 4.2. Anesthesia characteristics, surgery time *Operation time: group P is 62.51 minutes, group E is 58.11 minutes, similar, these are short, medium surgery, suitable for SA method (table 3.2). *Onset time: Average in group P is 2.53 ± 0.56 minutes; Group E is 2.54 ± 0.52 minutes are equivalent (Table 3.4). 4.3. Management of hypotension during spinal anesthesia 4.3.1. Infusion during spinal anesthesia *The average ringer lactate volume infused for patients before surgery of group P was 447.8 ± 58.0 ml, equivalent to group E was 422.1 ± 75.0 ml (Table 3.3). *During the surgery, the patients continued to be given infusion of ringer lactate (coload) in the group P is 206.4 ± 31.7 ml, equivalent to group E of 208.5 ± 79.8 ml. *The Ringer 19 lactate total infused after surgery (from stopping vasoconstrictor to patients transfered in the recovery room) of group P is 184.2 ± 40.4 ml, equivalent to group E is 144.2 ± 53.5 ml. *The Ringer lactate total in group P was 838.5 ± 66.5 ml more than that in group E, which was 777.8 ± 150.5 ml but there was no significant difference. *The total duration of vasoconstrictor use, in group P is 11.09 ± 3.63 minutes, equivalent to group E is 10.50 ± 5.18 minutes. This is a relatively short time indicating that the short time of hypotension during surgery. Therefore, with vasopressor protocol of this study ensure safety to maintain of BP during surgery. 4.3.2. The Use of vasoconstrictors to manage hypotension in spinal anesthesia a) Vasoconstrictors ferfusion for management of hypotension The total average dose of continuous infused phenylephrine is 183.43 ± 56.77 mcg, the total continuous infusion dose of ephedrine is 14.85 ± 6.58 mg; these consistent results and effective effect to manage hypotension in this study (Table 3.4). Group P had 56 patients (80.0%) who had blood pressure drop above 20% of baseline, who needed phenylephrine bolus to raise BP. Group E had 63 patients (90.0%) equivalent to group P who needed a bolus ephedrine dose to raise BP. b) Number of bolus vasoconstrictor bolus (phenylephrine, ephedrine): The lowest number of vasoconstrictive bolus is 0 times, at most 6 times (chart 3.1). In group P had 14 (20.0%) patients, group E has 7 (10%) patients not be needed vasopressor bolus. Most patients in the 2 groups need 1 and 2 bolus vasoconstrictor bolus to raise BP. Bolus vasopressor 1 time in group P had 5 patients (7.14%) less significant than group E with 26 patients (37.24%) with p <0.05. The number of patients who need bolus 2 times in group P had 26 (37.14%); group E had 27 patients (38.56%). 4.4. Change hemodynamic indicators at the point times 4.4.1. The CO changes in any point times Group P: from t4 to t9, the CO value begins to decrease, comparing the CO at t4 to decrease lower than the CO at t3 with p> 0.05; CO value at t5 is lower than CO at t3 with p <0.05. The lowest CO value at time t6 (5.85 ± 0.89 liters/minute. Then the CO increases gradually to the initial value. Comparing CO at t11 is higher than CO at t10, and increasing compared with CO at t9 with p <0.05 (chart 3.2). Group E: From t5 to t11, the average value of CO decreases; comparing CO at t5 is lower than CO at t4 with p <0.05; The lowest CO at the time of t8 is 5.75 ± 1.33 liters/minute. From t12, the average CO value increased gradually to the initial value; when considering CO at t12 is higher than CO at t11 with p <0.05. 20 Comparing 2 groups: from t5 to t11: average CO of group P is higher than average of group E with p> 0.05. From t12 to t23: average CO in group P is lower than average of group E; Especially from the time of t14 to t22, the CO value in group E is higher than that of group P value of p <0.05. Monitoring during surgery, group P tends to have more stable CO than group E. 4.4.2. The SVR changes at any points times Since the t4, in both research groups, the SVR has decreased, especially at t6 and t7; Clinically relevant, when BP is low, additional bolus doses of vasoconstrictor drugs need to be injected, based on SVR and BP to use subsequent dos