Background: The relationship between venous congestion in cardiopulmonary bypass (CPB) and acute kidney injury (AKI) in cardiac surgery has not utterly substantiated. This study aimed at investigate the relationship between CVP in CPB and the occurrence of AKI. Methods: We retrospectively reviewed 2048 consecutive patients with cardiovascular disease undergoing cardiac procedure with CPB from January 2018 to December 2022. We used the median CVP value obtained during CPB for our analysis and patients were grouped according to this parameter. The primary outcomes were AKI and renal replacement therapy(RRT). Multivariable logistic regression was used to explore the association between CVP and AKI. Results: A total of 2048 patients were enrolled in our study and divided into high CVP group (CVP ≥ 6.5 mmHg) and low CVP group (CVP < 6.5 mmHg) according to the median CVP value. Patients in high CVP group had the high AKI and RRT rate when compared to the low CVPgroup[(367/912,40.24%)vs.(408/1136,35.92%),P = 0.045;(16/912,1.75%vs.9/1136;0.79%), P = 0.049]. Multivariate logistic regression analysis displayed CVP played an indispensable part in development of renal failure in surgical. Conclusions: Elevated CVP(≥ 6.5mmH2OmmHg) in CPB during cardiac operation is associated with an increased risk of AKI in cardiovascular surgery patients. Clinical attention should be paid to the potential role of CVP in predicting the occurrence of AKI.
Keywords: Acute kidney injury; Central venous pressure; Cardiac surgery; Venous congestion; Cardiopulmonary bypass
Lei Wang, Lanxin Hu, Qiong yan Dai and HaoYu Qi authors contributed equally to this work.
As technologies in medicine have advanced, negative cardiac surgery complications, such as mortality within hospitals, have reduced significantly [[
According to the logic underlying the association between CVP and AKI among patients who are critically ill, a high CVP can impede renal venous return to the reservoir and disrupt microcirculatory flow of blood, thereby impairing organ function and increasing the risk of death. Moreover, elevated CVP indicates inadequate venous drainage in CPB will affect renal venous blood drainage and lead to renal congestion, resulting in deterioration of acute kidney injury (AKI) [[
Unfortunately, studies regarding the relationship between CVP and renal function protectable in CPB are originated from post-CPB so that miss the relevant research during CPB. Accordingly, we conducted this study to investigate the relationship between high CVP during AKI and CPB among cardiac patients upon adulthood, with the hypothesis that CSA-AKI in these patients is related to venous obstruction during CPB.
The present study was approved by the Regional Human Research Ethics Committee of Nanjing First Hospital. Reference number: KY20220805-03.
The CVP value was conducted using electronic health records (EHRs). After calculation, the median CVP value of 2048 patients was 6.5 mmH
The following were the criteria for inclusion: (
During the operation, intravenous inhalation and anesthesia were used routinely. Blood pressure in the left radial artery and oxygen saturation in the veins of peripheral tissues is measured. In the procedure, esophageal ultrasound and the bispectral index were utilized to assess postoperative cardiac function and intraoperative anesthesia depth. The bladder was implanted with a foley catheter equipped with a temperature probe to monitor the patient's central body temperature. In our center, the right internal jugular vein is routinely selected as the CVP measurement channel, and CVP measurement is performed after the venous catheter is placed. We continuously recorded the CVP value during CPB and obtained the average value.
In numerous cases, the aortic artery cannula is the primary choice for perfusion. The femoral artery was selected as the intraoperative perfusion vessel in some ascending aorta cases. A 2-stage venous cannula (28/32# for ≤ 80 kg, 32/40# for>80 kg; Wei Gao, Shan Dong, China) were implemented to manage venous drainage during CPB. The patient's BMI was considered when selecting a cannula size.
Venous drainage and CPB related parameters.
CPB was initiated by draining the venous blood of the patient into a venous reservoir (max volume: 4.5 L) and completing oxygenation with a hollow fiber membrane oxygenator (Terumo, Japan). The intraoperative level of the venous reservoir is maintained at least 1000 ml, and if the venous volume is less than 1 L, we will use VAVD(vacuum-assisted venous drainage) to assist drainage. During CPB, the VAVD (Medtronic, America) approach a negative pressure target between − 30 mmHg and − 60 mmHg were utilized. A Stockert S5 roller pump was used to transport arterial blood to the vascular system, and a heat exchanger was used to maintain a constant body temperature. Priming extracorporeal circuit was realized with Plasma-Lyte A (500 mL), Hydroxyethyl starch 130/0.4 (1 L), a hematocrit of at least 20% with red blood cells, plasma products, 20% albumin, mannitol, and heparin with low molecular weight. CPB was managed to use goal-directed perfusion (IDO
Acute kidney dysfunction, such as AKD and AKI, was the primary result. AKI was defined using the KDIGO (Kidney Disease, Improving Global Outcomes) standard. First, within 48 h of surgery, the creatinine level rose by at least 0.3 mg/dl or at least 26.5 µmol/L. Second, a known or suspected rise in creatinine to at least 1.5 times the baseline within the prior week. Third, a urine volume of less than 0.5 ml/kg/h for more than 6 h [[
For data analysis, SPSS Statistics version 24.0 (SPSS, Chicago, IL, USA) was utilized. The patient's attributes were expressed using the median and interquartile range (IQR). Non-parametric analyses analyzed the distinctions between the two groups and the associations between various indices. The incidence of variables in contingency tables was evaluated by means of Fisher's exact test or the χ2 test. Utilizing univariate analysis screening, variables with substantial differences and prior studies' suggestions were selected. After the indicators associated with AKI incidence became part of the Logistic multivariate regression analysis, the risk factors and respective coefficients were determined, and the prediction model for AKI was developed. The risk association between CVP during AKI and CPB was assessed using multiple logistic regression. In all analyses, P<0.05 was deemed to have statistical significance.
775 out of 2,048 (37.84%) patients were verified to have AKI, and 25 patients acquired renal replacement therapy (3.23%). Incidence of AKI and RRT(renal replacement therapy, RRT) acquired in High-CVP group were higher than that in Low-CVP group [(367/912,40.24%) vs. (408/1136,35.92%), P = 0.045; (16/912,1.75% vs. 9/1136;0.79%), P = 0.049, respectively]. Moreover, patients in the high CVP group experienced more severe of AKI compared to those in low CVP group (p = 0.035; Figs. 1, 2 and 3).
Graph: Fig. 1 Incidence rates of AKI in two groups
Graph: Fig. 2 Incidence rates of RRT in two groups
Graph: Fig. 3 Stage of AKI in two group
As provided in Table 1, there were substantial variations between the two groups' baseline attributes. Patients with elevated CVP tended to be geriatric male. On admission, their BUN, BMI, cardiopulmonary bypass duration, the hypertension history, intraoperative blood product infusion, postoperative mechanical ventilation duration, and vacuum-assisted venous drainage (VAVD) was significantly higher.
Table 1 Characteristics of the cohort
Characteristics High-CVP group ( Low-CVP group ( Age(>65years) 375 404 0.010 Male, (n) % 479(61.81) 267(20.97) <0.001 BMI(kg/m2), median(IQR) 28.4(2.7) 25.0(2.9) 0.037 Hypertension(n) % 389(50.19) 239(18.77) 0.000 Diabetes, (n) % 20(2.58) 43(3.37) 0.491 Creatinine(mg/dl), median(IQR) 0.84(0.6) 0.85(0.5) 0.842 BUN(mg/dl), median(IQR) 85(24) 84(25) 0.757 eGFR(ml/min/1.73m2), median(IQR) 114(4) 115(5) 0.738 CPB time(min), median(IQR) 117(5) 88(6) 0.001 MAP during CPB(mmHg), median(IQR) 53(2) 52(3) 0.484 VAVD used(n) % 39(4.27) 100(8.80) 0.000 Aortic cross-clamp time(min), median(IQR) 65(13) 66(14) 0.356 HCT(%),median(IQR) 23(2) 24(3) 0.568 RBCs transfused(n) % 88(11.75) 92(7.22) 0.000 COPD(n) 23 49 0.377 High cholesterol 24 32 0.798 EF(%),median(IQR) 53(5) 54(6) 0.457 Intraoperative fluid input volume(ml), median(IQR) 2160(187) 2165(188) 0.663
EF: ejection fraction; BMI: Body mass index; BUN: Blood urea nitrogen; eGFR: estimated Glomerular filtration rate; CPB: Cardiopulmonary bypass; MAP: Mean average pressure; CVP: Central venous pressure; VAVD: Vacuum-assisted venous drainage; HCT: Hematocrit; RBCs: Red blood cells; COPD: chronic obstructive pulmonary disease; IQR: Interquartile range
The aggregate operative mortality rate was 3.81% (78/2048). No substantial difference existed among the groups regarding operative mortality. Mortality in AKI (40/775) group is higher than that in NO-AKI group [(40/775,5.16%) vs. (38/1237,3.07%), P = 0.012]. 44 patients dead in High-CVP group and 34 patients in Low-CVP group (infections, cardiogenic shock, low cardiac output syndrome, multi-organ failure, etc.).Operation classification and perfusion data are displayed in Table 2. There is no significant difference when it comes to MAP, urinary output, CPB time, aortic cross-clamp time, rate of defibrillations, and surgical classification between two groups(all P>0.05).
Table 2 Operative data
Characteristics High-CVP group Low-CVP group Surgical classification Isolated CABG surgery, n (%) 406(44.52) 562(49.48) 0.849 Isolated aortic valve surgery, n (%) 305(33.44) 401(35.30) 0.903 CABG and aortic valve surgery, n (%) Vascular-related surgery, n(%) 100(10.97) 101(11.07) 72(6.35) 78(6.87) 0.952 0.887 MAP during CPB, median(IQR) 54(6) 55(6) 0.366 Mean pump flow(L/min.m2), median(IQR) 2.5(0.2) 2.5(0.3) 0.676 HCT(%),median(IQR) 23(4) 24(3) 0.443 RBCs transfused(n,%) 18(1.97) 29(2.55) 0.370 Defibrillation (n) 92(10.09) 123(10.83) 0.258 Urinary volume(ml), median(IQR) 818(77) 820(75) 0.348 Furosemide prescribed(n,%) 48(5.26) 66(5.81) 0.089 Low output syndrome(n,%) 3(0.33) 8(0.70) 0.445 Cerebrovascular accidents(n) Temporary(POCD/TIA) 56/3 72/7 0.773 Permanent(cerebral hemorrhage/stroke) 4/2 6/3 0.851 Ultrafiltrate output(ml), median(IQR) 687(36) 704(42) 0.538
POCD: Postoperative cognitive dysfunction; TIA: Transient ischemic attack; HCT: Hematocrit; RBCs: Red blood cells; MAP: Mean average pressure; CABG: Coronary artery bypass grafting
Table 3 Multivariable analysis determining covariate factors associated with AKI development in eligible subjects
All eligible subjects( Variable standardizedβ OR 95%CI Male 0.532 1.77 1.27–2.79 0.046 BMI 0.344 1.53 1.05–3.68 0.039 Age>65 years 0.731 1.91 1.28–2.90 0.015 Hypertension 0.578 1.54 1.06–2.81 0.001 Red blood cell transfused 0.536 1.71 1.14–2.44 0.001 CPB duration 0.758 1.98 1.53–3.73 <0.001 Mechanical ventilation time 0.119 1.03 1.16–2.44 0.045 VAVD used -4.19 0.74 0.28–0.96 0.003 High-CVP 0.771 2.01 1.56–3.54 0.017
BMI: Body mass index; CPB: Cardiopulmonary bypass; CVP: Central venous pressure; VAVD: Vacuum-assisted venous drainage
Using multivariate logistic regression, prospective protective and risk factors in AKI progression were identified. As demonstrated in the data below, a low CVP may be protectively against CSA-AKI. The association between CVP and AKI incidence is depicted in Fig. 4. Such incidence rose as CVP rose, particularly when CVP exceeded 5 mmHg. Meanwhile, age>65years, high BMI, hypertension, prolonged CPB, prolonged postoperative mechanical ventilation time, RBCs transfused and VAVD were independently correlated with CSA-AKI. (Table 3)
Graph: Fig. 4 The linear relationship between CVP and AKI incidence
Approximately 30-40% of patients who underwent cardiac surgery experience AKI, and almost 2-6% of AKI will require hemodialysis [[
CSA-AKI pathophysiology is not completely understood, but includes nephrotoxin, hemodynamic disturbance, inflammatory response, hypoxia, CPB, and neuroendocrine activation [[
CVP (normal 5–12 mmHg) is a pressure measured from the superior vena cava or right atrium that denotes the pressure index of cardiac preload and equivalent to the right ventricle end-diastolic pressure [[
These factors may have enabled this event. First, reduced blood flow in the kidney can lead to neutrophil accumulation in the peritubular capillaries [[
We continue to analyze other effects of CSA-AKI and explore potential mechanisms. Due to hemolysis, iron burden, and pro-inflammatory aspects, RBCs transfused intraoperatively can cause renal injury [[
It is considered that CVP is an alternative indicator for early prediction of acute kidney injury due to the linear relationship between CVP and the incidence of AKI. Some suggestions should be given to reduce the risk of AKI after cardiac surgery, such as by using a large bore venous cannula, increasing the height of the operating table and actively using ultrafiltration during or after CPB. However, objective limitations can not be neglected. Our investigation is retrospective at one point, which indubitably introduces bias. In addition, individual differences in baseline CVP values are typical yet frequently unavailable among clinical aspects, which is another design limitation. In a future prospective study, the relationship of CVP in CPB and CSA-AKI in other cardiac surgeries will be an important supplement to improve the conclusion of this study. At last, the central venous catheter was placed in the superior vena cava at a depth of about 13–15 cm, which may lead to inaccurate measurement of CVP.
Wang Lei, Daiqiongyan, Qi Haoyu and Hulanxin wrote the main manuscript text and Wangzhenhong and Chenxin prepared Figs. 1, 2, 3 and 4. All authors reviewed the manuscript.
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By Lei Wang; Lanxin Hu; Qiong yan Dai; HaoYu Qi; ZhenHong Wang and Xin Chen
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