Medical doctoral thesis summary: Study on the hemodynamic efects of phenylephrine in the management of hypotension during spinal anesthesia for cesarean section

This topic is conducted with the two following objectives: Compare the effects of phenylephrine with ephedrine on hemodynamic measured by the non-invasive method Niccomo in the management of the hypotension during SA for cesarean section; to evaluate some undesirable effects of phenylephrine and ephedrine on mother and newborn during SA for cesarean section.

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY STUDY ON THE HEMODYNAMIC EFECTS OF PHENYLEPHRINE IN THE MANAGEMENT OF HYPOTENSION DURING SPINAL ANESTHESIA FOR CESAREAN SECTION Specialized in : Anesthesiology Code : 62 72 01 21 MEDICAL DOCTORAL THESIS SUMMARY HA NOI - 2019 WORKS ARE COMPLETED AT HANOI MEDICAL UNIVERSITY Science instructor: Professor NGUYEN Quoc Kinh The thesis will be presented in School thesis council At … h00, day …… month … year 2019 The thesis can be found at: - National library - Library of Hanoi Medical University ABBREVIATIONS BMI : Body Mask Index CO : Cardiac Output CI : Cardiac Index ECG : Electrocardiogram GTTS : Spinal anesthesia – SA HA : Blood pressure – BP HATT : Systolic arterial blood pressure – SBP – SAP HATTr : Diastolic arterial blood pressure – DBP, DAP HATB : Mean blood pressure – MAP HR : Heart Rate ICG : Impedance Cardiogram NMC : Epidural anesthesia Niccomo : Non Invasive Continuous Cardiac Output Monitoring SpO2 : Saturation of oxygenation SV : Stroke Volume SVV : Stroke Volume Veriation SVR : Systemic Vascular Resistance INTRODUCTIONS Anesthesia in obstetrics for cesarean section increased due to the increasing the rate of cesarean section, which is a great concern of the anesthesiology because of the achievement of analgesic effect, good muscle relaxation to maximum facilitate the operation, ensuring safety for both mother and infant Spinal anesthesia is preferred to anesthesia, is the first choice for cesarean section, hypotension when the Spinal anesthesia accounts for as high as 70% -80% It is the most dangerous complication, causing bad consequences for mothers and children Therefore, the problem of managing hypotension is always concerned and studied The mechanism of hypotension in the spinal anesthesia (SA) is due to blockade of the sympathetic ganglion, leading to dilatation of the arterial system (resistance system), which reduces SVR and veinous dilatation (storage system) reduces venous return in a reduction of the preload and a decrease CO The blood pressurs (BP) is directly proportional to CO and SVR Thus hypotension can be due to decreased SVR and / or decreased CO But reducing SVR also reduces afterload so it can improve CO There have been studies on infusions around the world (comparing preload with coload, crystalloid and colloid fluids) Compare phenylephrine effect with ephedrine on the mother and children At present, there are no or less invasive hemodynamic monitoring methods such as CNAP, Clearsight, Niccomo, USCOM… So in the world there are only a few studies on hemodynamic changes in SA There have been no studies to assess the hemodynamic changes of pregnant women, umbilical cord blood gas in during the cesarean, of phenylephrine and ephedrine in particular when used to treat hypotension Therefore, this topic is conducted with the two following objectives: Compare the effects of phenylephrine with ephedrine on hemodynamic measured by the non-invasive method Niccomo in the management of the hypotension during SA for cesarean section To evaluate some undesirable effects of phenylephrine and ephedrine on mother and newborn during SA for cesarean section *New contributions of the thesis: Scientific and practical meanings: - The research is very necessary, to be new, especially when applying noninvasive hemodynamic monitoring method (Niccomo monitoring), the thesis has scientific and practical significance Proper, scientific and logical research design; The datas and the datas processing are reliable, the number of patients are large enough - Ever, the main drug used is ephedrine to treat hypotension in the spinal anesthesia However, the ephedrin is suspected of causing fetal acidosis in recent years Therefore, foreign and domestic authors have come to phenylephrine to replace ephedrin - The authors only researched and used the phenylephrine to increase blood pressure No authors studied hemodynamic changes (BP, CO, SV, SVR, HR) by phenylephrine This is the new point, the contribution of the topic to clinical practice and science The thesis has scientific significance, is up to date and very valuable in clinical gynaeco-obstertrical anesthesia: - The thesis compares the efficacy of the new vasoconstrictor that is phenylephrine versus the previously used vasoconstrictor, ephedrine, both of which are infused continuously to prevent the hypotension in the spinal anesthesia for cesarean section - This study used a new hemodynamic monitoring method that is Niccomo system to continuously monitor hemodynamic indicators: heart rate, arterial blood pressure, cardiac output, stroke volume and the systemic vascular resistance This hemodynamic monitoring method helps to accurately assess the effectiveness of the two vasoconstrictor drugs above and helps to guide the fluid infusion to manage hypotension during spinal anesthesia for cesarean section *Layout of the thesis: The thesis consists of 113 pages (excluding references and appendices) of which: Introduction: 02 pages; Chapter - Overview: 32 pages; Chapter - Objects and Methods: 16 pages; Chapter - Results: 27 pages; Chapter - Discussion: 34 pages; Conclusion: pages The thesis has 38 tables; 12 photos; 10 charts; 124 references (25 documents in Vietnamese and 99 documents in foreign languages) CHAPTER - OVERVIEW 1.1 Physiological and anatomial changes in pregnant women are related to anesthesia: During pregnancy, there are many changes in the circulation and cardiovascular Total blood volume increased to 35%, plasma volume increased to 45%, hemoglobin decreased by 15% compared to normal, HR increased by 15% compared to the original, the SV increased by 30%, but SVR 15% off CO increased by 30% to 40% in the first trimester, the months after, it increased less During labor, CO increases due to increased HR and SV Each contraction of the uterus increases CO and maternal circulation by 10-25% The highest increase in CO immediately after having the birth, it can exceed 80% of the pre-labor value 1.2 Uterine circulation: At term, uterine blood flow accounts for 10% of CO, which is 600-700 ml/min compared to 50 ml/min in a non-pregnant uterus Up to 80% of uterine blood flow is for placenta, the rest for uterine muscle During pregnancy, the uterine vascular system maximum dilated, so it loses its self-regulation mechanism, although it is still sensitive to α receptor stimulants The uterine vascular system has many α receptors and few β receptors 𝐔𝐭𝐫𝐢𝐧𝐞 𝐛𝐥𝐨𝐨𝐝 𝐟𝐥𝐨𝐰 = 𝐌𝐀𝐏 − 𝐔𝐭𝐞𝐫𝐢𝐧𝐞 𝐯𝐞𝐧𝐨𝐮𝐬 𝐩𝐫𝐞𝐬𝐬𝐮𝐫𝐞 𝐔𝐭𝐞𝐫𝐢𝐧𝐞 𝐯𝐚𝐬𝐜𝐮𝐥𝐚𝐫 𝐫𝐞𝐬𝐢𝐬𝐭𝐚𝐧𝐜𝐞 Uterine blood flow is directly proportional to the difference in pressure between the arteries and uterine veins, inversely proportional to uterine vascular resistance Normally, MAP is 80 mmHg in torsion arteries, the uterine venous pressure at rest is 10 mmHg, so the Uterine blood flow - the fetus at rest is 70 mmHg 1.3 Comparision general anesthesia and spinal anesthesia for cesarean Table 1.1 Comparision general anesthesia and spinal anesthesia for cesarean Spinal anesthesia General anesthesia The patient is awake, witnessing the moment Patient has anesthesia when the child is born in the happiness Simple technique, easy to Need more equipments, ventilator machine, more complex drugs Avoid the risk of reflux inhalation of gastro The risk of reflux, may be difficult content, to avoid the difficult intubation intubation Patients are at risk of hypotension if not Less risk of hypotension managed effectively The time to inject the drugs to surgery is 0,05 (5,7) (1,4) (2,9) Table 3.9 The number of the hypertension in two groups Number of hypertension Group P; n (%) Group E; n (%) 67 (95,71%) (4,29%) 0 31 (44,29%) 21 (30%) 14 (20%) (4,29%) (1,42%) 16 Table 3.10 The risk of hypotension when taking vasocontrictors Hypotension patients BP normal Risk OR n (%) n (%) Ephedrin 56 (80%) 14 (20%) 0,44 n = 70 Phenylephrin 63 (90%) (10%) n = 70 *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 Hypertesion patients BP normal Risk OR n (%) n (%) Ephedrin 28 (40%) 42 (60%) 14,88 n = 70 Phenylephrin (4,3%) 67 (95,7%) n = 70 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 Group P Group E Characteristics p n = 70 n = 70 Nôn, buồn nôn, n (%) (5,71) 15 (21,43) < 0,05 Tachycardia, n (%) (7,14) 59 (84,28) < 0,05 Bradycardia, n (%) 10 (14,28) (4,23) < 0,05 Patients need to inject atropine, n (%) 10 (14,28) (4,28) < 0,05 Chills, n (%) (5,8) (5,8) Itching, n (%) (1,4) (8,6) > 0,05 Headache, n (%) (1,4) Table 3.13 The risk of bradycardia after taking vasocontrictors Bradycardia Normal HR Risk OR n (%) n (%) Phenylephrin 10 (14,28%) 60 (85,72) 3,72 n = 70 Ephedrin (4,23%) 67 (95,77%) n = 70 *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 Tachycardia Normal HR Risk OR n (%) n (%) Ephedrine 59 (84,28%) 11 (15,72%) 69,72 n = 70 Phenylephrine (7,14%) 65 (92,86) n = 70 *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 Nausea, vomiting Normal Risk OR n (%) n (%) Phenylephrine (7.14%) 65 (92.86%) 0.22 n = 70 Ephedrine 15 (21.42%) 55 (78.58%) n = 70 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 Group P Group E Characteristics p n = 70 n = 70 Apgar minutes points (n, %) 18 (25,70%) 29 (41,43%) > 0,05 points (n, %) 52 (74,29%) 41 (58,57%) Apgar minutes 10 points (n, %) 70 (100%) 70 (100%) 3,39 ± 0,29 3,47 ± 0,29 Infant weight, kg (𝑋 ± SD) (3,0-4,0) (2,8-4,5) (Min-Max) 3.7.2 The results of umbilical cord blood gas Table 3.17 Umbilical cord blood gas results Group P Group E Chracteristics n = 70 n = 70 Umbilical arterial blood gas 7,32 ± 0,04 7,25 ± 0,06 pH (𝑋 ± SD) (7,23-7,45) (7,01-7,40) (Min-Max) > 0,05 p < 0,05 18 PaCO2 (mm Hg) (𝑋 ± SD) (Min-Max) PaO2 (mm Hg) (𝑋 ± SD) (Min-Max) HCO3 (mEq/l) (𝑋 ± SD) (Min-Max) BE (mmol/l) (𝑋 ± SD) (Min-Max) Umbilical venous blood gas pH (𝑋 ± SD) (Min-Max) pCO2 (mm Hg) (𝑋 ± SD) (Min-Max) pO2 (mm Hg) (𝑋 ± SD) (Min-Max) HCO3- mEq/l) (𝑋 ± SD) (Min-Max) BE (mmol/l) (𝑋 ± SD) (Min-Max) 51,47 ± 8,60 (38,0-81,3) 16,81 ± 5,65 (3,5-35,4) 23,37 ± 1,92 (18,9-28,8) -1,98 ± 1,74 (-5,9—2,0) 56,55 ± 7,96 (37,8-90,0) 18,78 ± 5,93 (3,2-31,0) 22,17 ± 1,81 (13,3-25,8) -2,03 ± 1,79 (-10,7—2,20) 7,34 ± 0,03 (7,26-7,39) 46,03 ± 6,59 (32,7-75,1) 25,60 ± 6,58 (9,5-37,0) 23,36 ± 1,57 (19,2-28,6) -1,70 ± 1,19 (-4,8—0,6) 7,29 ± 0,07 (7,1-7,42) 48,23 ± 9,18 (33,2-85,2) 27,39 ± 7,07 (8,7-42,6) 22,51 ± 2,05 (16,6-34,5) -1,62 ± 2,27 (-9,4—12,7) < 0,05 < 0,05 < 0,05 > 0,05 < 0,05 > 0,05 > 0,05 < 0,05 > 0,05 CHAPTER - 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 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 times, at most times (chart 3.1) In group P had 14 (20.0%) patients, group E has (10%) patients not be needed vasopressor bolus Most patients in the groups need and bolus vasoconstrictor bolus to raise BP Bolus vasopressor time in group P had patients (7.14%) less significant than group E with 26 patients (37.24%) with p 0.05; CO value at t5 is lower than CO at t3 with p