Early change of oxygen metabolism after isolated mitral valve replacement or mitral valve replacement and concomitant aortic valve replacement in patients with pulmonary hypertension – Kieu Van Khuong

Journal of military pharmaco-medicine n 0 3-2018 133 EARLY CHANGE OF OXYGEN METABOLISM AFTER ISOLATED MITRAL VALVE REPLACEMENT OR MITRAL VALVE REPLACEMENT AND CONCOMITANT AORTIC VALVE REPLACEMENT IN PATIENTS WITH PULMONARY HYPERTENSION Kieu Van Khuong*; Pham Thi Hong Thi**; Nguyen Quoc Kinh*** SUMMARY Objectives: To verify oxygen metabolic changes and to assess the corellation between oxygen consumption (VO2), oxygen delivery (DO2) and oxygen extraction (ERO2). Subjects and methods: 67 patients with pulmonary hypertension related left heart diseases who underwent elective (MVR) and/or aortic valve replacement (AVR) enrolled in the study. Calculated parameters by pulmonary artery catheter inserted at operation theater and monitor system. Results and conclusion: Cardiac output index (CI), ERO2 and VO2 increased significantly intra and after operation with respect to baseline levels. DO2 decreased after intubation and cardiopulmonary bypass stop but increased significantly at intensive care unit admission. The close corellation between VO2 and DO2, ERO2 was at all postoperative points of time. * Keywords: Mitral valve replacement; Pulmonary hypertension; Oxygen delivery; Oxygen metabolism; Aortic valve replacement. INTRODUCTION The important problems of postoperative cardiac care are those of cardiac output, tissue oxygenation, the ratio of myocardial oxygen supply and demand. Ideally, one should strive to obtain a cardiac index greater than 2.2 L/min/m2 with a normal mixed venous oxygen saturation while optimizing the oxygen supply/demand ratio. Oxygen delivery (DO2) is considered as principal target for adequate tissue perfusion [1]. When oxygen exceed a threshold value whereby sufficient DO2 can not be assured by increasing cardiac output (CO) or hematocrit levels, a shift from erobic to anerobic metabolism occurs. From this point, the resulting oxygen debt leads to increased arterial lactate production. This physiological dependence of oxygen consumption (VO2) on DO2 should be avoided, as hyperlactatemia is associated with increased postoperative mortality, morbidity and hospital length of stay. Previous studies have shown that a drop of DO2 levels under a critical level during cardiopulmonary bypass (CPB) is independently associated with acute kidney injury [2]. The postoperative course after heart valve surgery with CPB is characterized by a progressive increase in cellular oxygen demand. This increase, known as * 103 Military Hospital ** Vietnam Natinoal Heart Institute *** Vietduc Hospital Corresponding author: Kieu Van Khuong (icudoctor103@gmail.com) Date received: 10/01/2018 Date accepted: 06/03/2018 Journal of military pharmaco-medicine n o 3-2018 134 hypermetabolic status, persists for several hours [3, 4] or, in some experiences, for a few days [5] after surgery. Previous reports have suggested that CPB could be the main cause of the increased metabolism after cardiac surgery and of the perioperative changes between VO2 and DO2 [5, 6]. The aim of this study was to: Evaluate oxygen metabolism changes after isolated mitral valve replacement or mitral valve replacement and concomitant aortic valve replacement. SUBJECTS AND METHODS 1. Subjects. This study was carried out at Heart Center of Hue Center Hospital from May to November 2017. We enrolled 67 patients with pulmonary hypertension associated with left heart diseases who underwent isolated MVR or MVR and concomitant AVR. The study protocol was approved by Ethics Committee of Hospital and a written consent was obtained for each patient. Patients were excluded if they had any evidence of sepsis (temperature > 37.50C, WBC > 12 G/L), a history of hyper-or- hypothyroidism or claustrophobia or facial deformities (canopy kit intolerence or ill-fit). 2. Methods. * Preoperative assessment: A 4-lumen pulmonary artery catheter (PAC) (7.5F size) with a thermistor probe (B.Braund) was inserted via the right internal jugular vein. * Anesthesia: General anesthesia was induced with fentanyl, 3 - 5 µg/kg and mydazolam 0.2 mg/kg. The therapy for PAH was instituted with a nitroglycerin infusion (0.5 - 1 µg/kg/min), deliberate hypocarbia (arterial carbon dioxide tension < 35 mmHg), fractional inspired oxygen concentration (FiO2) of 1.0, and elective ventilation for at least 12h in the postoperative period. Rocuronium and vecuronium were used as muscle relaxants. * Technique of MVR: All patients were operated on CPB under moderate hypothermia (28 - 300C) using standard techniques. Mitral valve was approached either through the left atrium or via the interatrial septum (trans-septal approach). Whenever possible, total chordal preservation was carried out. The valve used was ATS or St.Jude Mediacal bileaflet mechanical prosthesis. * Measurements and formulas: Measurements were obtained at the following time points: - T0: baseline, pre-induction; T1: post- intubation; T2: immediate post-CPB; T3: at ICU admission; T4: first 6 hours at ICU and Toff (T14): before PAC removing and the hemodynamics had been stabilized. - Mixed venous samples were taken via the distal port of the PAC. Calculate DO2 = CO x CaO2 (1) while CaO2 = Hb x 1.34 x SaO2 + (0,003 x PaO2). VO2= CO x (CaO2 - CvO2). ERO2 = (CaO2 - CvO2)/CaO2 [7]. - Cardiac output (CO) was measured by the thermodilution technique using 10 mL of 0.9% ice-cold saline and a hemodynamic monitor (Phillip MP70) having inbuilt capacity to measure CO Journal of military pharmaco-medicine n 0 3-2018 135 and calculate hemodynamic parameters. Three consecutive successful determinations were averaged and the difference between any two readings did not exceed 15%. Mean value of systolic pulmonary artery pressure, pulmonary capillary wedge pressure (PAOP), pulmonary vascular resistance (PVR) and cardiac index (CI) were calculated. Baseline (control) hemodynamics, total complete blood count and arterial blood gas (ABG) measurements were obtained before the induction of anesthesia. * Statistical analysis: All values are mentioned as mean ± standard deviation (SD) and range. Unpaired student’s t-test and Chi-square test were used for comparison of data of the two groups, where applicable. For statistical analysis, the statistical software SPSS version 19.0 for windows (SPSS Inc., Chicago, IL) was used. p value < 0.05 was considered statistically significant. RESULTS 1. Patients, demographic and intra-operative characteristics. Table 1: Patient characteristics. Variables Mean ± SD or number Range Age (year) 45.5 ± 10.7 20 - 68 Gender [m/f, (%)] 15/52 (22.4/77.6) Body surface area (m2) 1.44 ± 0.11 1.2 - 1.7 Body mass index (kg/m2) 19.8 ± 2.4 15.4 - 25.2 Weight (kg) 48.0 ± 6.5 33 - 67 Height (cm) 155.9 ± 7.0 142 - 170 PAPs (mmHg) 52.7 ± 15.0 35 - 95 Echocardiographic EF (%) 53.5 ± 8.0 Mitral valve replacement [n (%)] 45 (67.2) Aortic valve replacement [n (%)] 22 (32.8) CPB (min), mean (range) 114.2 ± 57.7 54 - 466 ACC (min), mean (range) 79.8 ± 36.8 31 - 185 Ventilation time (hour) 20.9 ± 31.7 (Abbreviation: ACC: Aortic cross-clamp time; CPB: Cardiopulmonary bypass time) Among 67 patients, 45 patients underwent isolated mitral valve replacement and 22 patients underwent MVR and concomitant AVR. The study group was mainly female (77.6%), mean age 45.51 ± 10.74 years. All patients were pulmonary hypertension related left heart diseases (PAPs ≥ 35 mmHg measured by echo). Journal of military pharmaco-medicine n o 3-2018 136 2. Oxygen metabolism and hemodynamic changes. Table 2: Changes in oxygen consumption and delivery. (ap < 0.0001 vs. baseline; bp < 0.05 vs. baseline) There was a progressive increase in CI, ERO2 and VO2 after operation with respect to baseline levels, but significantly decrease in SvO2. No significant differences in DO2 level at T4 and Toff time point. CI, SvO2, DO2, ERO2, VO2 was in mean value. 2. Correlation between oxygen consumption and oxygen delivery, oxygen extraction in MVR at diffirent time points. Table 3: Relation between oxygen consumption and oxygen delivery, oxygen extraction in MVR at diffirent time points. VO2 and DO2 (Spearman’s correlation) VO2 and ERO2 (Spearman’s correlation) Time points r p r p T0 0.189 > 0.05 0.686 < 0.001 T1 0.477 < 0.001 0.492 < 0.001 T2 0.553 < 0.001 0.631 < 0.001 T3 0.726 < 0.001 0.658 < 0.001 T4 0.538 < 0.001 0.558 < 0.001 Toff 0.479 < 0.001 0.719 < 0.001 No significant relation between VO2 and DO2 could be demonstrated before anesthesia induction (T0 time point). Since that time point a constantly significant linear relation between VO2 and DO2 was demonstrated up to remove PAC postoperatively. There was a negative correlation between VO2 and ERO2 at base time point. Time points CI (L/min/m 2) SvO2 (%) DO2 (mL.min-1 .m-2) ERO2 (%) VO2 (mL.min-1.m-2) T0 2.43 ± 0.77 71.2 ± 12.2 616.4 ± 194.6 27.9 ± 11.9 159.5 ± 51.8 T1 1.66 ± 0.42a 72.4 ± 8.2 372.9 ± 111.9a 27.2 ± 8.6 96.8 ± 26.6a T2 2.58 ± 0.61a 74.4 ± 9.0 521.1 ± 167.9 25.9 ± 8.8 131.7 ± 58.8a T3 3.02 ± 0.80a 69.1 ± 10.5 689.7 ± 215.9a 29.7 ± 9.9 203.8 ± 102.3a T4 2.65 ± 0.55a 63.2 ± 12.5a 541.4 ± 159.5a 36.1 ± 12.4 187.9 ± 72.9a Toff 3.00 ± 0.69a 58.6 ± 11.3a 591.6 ± 141.3 39.3 ± 11.3 228.9 ± 75.2a Journal of military pharmaco-medicine n 0 3-2018 137 DISCUSSION Some intraoperative and postoperative results showed in table 1. The mean CPB (114.18 ± 57.71 mins) and the mean aortic cross-clamp time (79.76 ± 36.78 mins) was similar to Xiaochun Song’s study outcome (CPB 119.9 ± 37.4 mins and ACC: 82.5 ± 31.8 mins) [8]. This result was higher than that Abu El-Hussein’s (CPB 55 mins; ACC 28 mins) [9]. The reason for this difference is the patient group of that study was replaced one valve surgery only. Our results showed a significant decrease in DO2 and VO2 during operation in comparison of baseline data (table 2). We consider that it may be due to the effect of sedation following premedication and anesthesia drugs. Besides, we can see the early increase in VO2 and DO2 at ICU admission (T3 time point), which was mostly attributed to rewarming (early phase) and the neurohumeral catabolic response to major surgery. These findings are similar to those in the reports of oxygen metabolism changes in patients with rheumatic mitral valve disease at different intervals after MVR. In the study by P.S. Myles [5], the mean DO2 as well as VO2 decreased significantly at post-induction (DO2: from 954 to 681 mL/mins, VO2: from 202 to 139 mL/mins) and after CPB (DO2: 709 mL/mins, VO2: 199 mL/mins) in patients undergoing coronary artery bypass and valvular surgery. Another study conducted by Parolary et al [10] showed effects of time on the changes in DO2 were significant. There was a significant postoperative DO2 decrease in both groups, starting after anesthesia induction and lasting up to 9 and up to 18 postoperative hours. Only time affected the changes of VO2 significantly: after surgery, starting from “skin” time point, VO2 significantly increased in both groups with respect to baseline levels. ERO2 behavior was similar to VO2, both of which increased dramatically. Only time indicated a remarkable effect and there was a significant ERO2 increase over time in both groups. ERO2 value in the study did not change at T1, T2 and T3 time point but increased significantly at T4 and T14 time point (table 2). In our opinion, it may be due to inadequate cardiac output and increased oxygen extraction in an attempt to meet oxygen needs. Such an increase in oxygen extraction frequently is associated with a prolonged postoperative recovery period. The relation between VO2 and DO2, this study revealed that in the intraoperative and early postoperative period of cardiac surgery, oxygen metabolism was substantially different from normal conditions, where a biphasic relation can be demonstrated [11]. There was a significant relationship between DO2 and VO2 during postoperative period. During physical activities or experiments, the increase in oxygen demand is met by an increase in both cardiac output and oxygen extraction ratio. This case was not our patient after cardiopulmonary bypass. As usual, SvO2 and thus oxygen extraction remained relatively stable during operation and up to ICU admission, whereas the increase in VO2 was primarily matched by an increase in cardiac output and DO2. Hence, there was a remarkably close Journal of military pharmaco-medicine n o 3-2018 138 relationship between VO2 and DO2. Similarly, the recent study by Christina Routsi [11] identified relationship between VO2 and DO2 in 36 patients (159 measurements): VO2 = 28 + 0.27 x DO2, r = 0.79, p < 0.0001, which was similar to our results at postoperative various time points (table 3). There was a highly significant correlation between VO2 and DO2 intra-and post- operation. The congruent or significant relationship between VO2 and DO2 expressed the stable balance oxygen between demand and consumption after valve replacement. Furthermore, dramatic relationship between ERO2 and VO2 strongly suggests that the increase in VO2 was primarily accomplished by an increase in ERO2, and usually not by an increase CI. Because patients had pre- existing heart failure and cardiac damage due to surgery, their ability to increase cardiac output was limited. There was a significant effect of time and surgery on this relation: the close relation between VO2 and DO2 increased over time, peaking after surgery at 6 hour postoperative time point (T4). These findings suggest that careful management of the patients remains an important issue, especially in the early postoperative period, when patients are at higher risk for the occurrence of oxygen debt and, consequently, of anaerobic metabolism. CONCLUSION Our data indicates that the progressive increase in VO2 after isolated MVR or MVR and concomitant aortic valve replacement is accomplished primarily by an increase in cardiac index and DO2. There was a significant change in the relation between VO2 and DO2. Both changes do not depend on CPB use. REFERENCES 1. Bojar R.M. Perioperative care in adult cardiac surgery. 2011. 2. Burtman D.T.M, A. Stolze, S.E. Kaffka Genaamd Dengler et al. Minimal invasive determinations of oxygen delivery and consumption in cardiac surgery, an observational study. 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