Intraoperative hypotension is a risk factor for postoperative acute kidney injury (AKI). Elderly patients are susceptible due to reduced responses to acute hemodynamic changes.Determine the association between hypotension identified from anesthetic charts and postoperative AKI in elderly patients.Retrospective cohort study of elective noncardiac surgery patients ≥65 years, at an Australian tertiary hospital (December 2019–March 2021), with the primary outcome of AKI ≤48 h of surgery. Factors of interest were intraoperative hypotension determined from anesthetic charts  and intraoperative vasopressor use.In 830 patients (mean age 75 years), systolic hypotension was more frequent than mean arterial hypotension (25.7% vs. 11.9%). Most hypotensive episodes were brief  but vasopressors were used in 84.7% of cases. The incidence of postoperative AKI was 13.9%. Systolic hypotension >20 min was associated with AKI , which was not significant after adjusting for vasopressors, creatinine, American Society of Anesthesiologists class, and hemoglobin drop. The cumulative dose of any specific vasopressor >20 mg (or >10 mg epinephrine) was independently associated with AKI . Every 5 mg increase in the total dose of all intraoperative vasopressors used during surgery was associated with 11% increased odds of AKI (95% CI: 3–19%).High vasopressor use was associated with postoperative AKI in elderly patients undergoing noncardiac surgery, independent of hypotension identified from anesthetic charts. Intraoperative hypotension is a common complication of general anesthesia and surgery which is associated with postoperative acute kidney injury (AKI) ,2. The dElderly patients may be more at risk of intraoperative hypotension and AKI due to a number of age-related changes in cardiovascular physiology. These include endothelial dysfunction, increased arterial stiffness, reduced left ventricular compliance and cardiac reserve, and impaired β-adrenergic and parasympathetic function . The bluThe aims of this study were to determine the incidence of early postoperative AKI in elderly patients after elective noncardiac surgery and the association between AKI and intraoperative hypotension or vasopressor/inotrope support. We hypothesized that evidence of intraoperative hypotension and vasopressor or inotrope use obtained from standard anesthetic charts could be used to predict postoperative AKI in the initial 48 h after surgery.We conducted a retrospective cohort study of elective noncardiac surgery patients at three major metropolitan hospitals in the Monash Health Network in the state of Victoria, Australia , from December 2019 to March 2021. This study was approved by the Monash Health Human Research Ethics Committee as a Quality Initiative as all data were obtained from standard medical documentation and laboratory results generated during routine clinical practice, and the requirement for patient consent was waived .Participants were identified from the network database of elective admissions during the study period. Our study inclusion criteria were (1) age ≥65 years, (2) hospital length of stay ≥48 h, which is the time required to diagnose postoperative AKI, and (3) noncardiac surgery, but also excluding obstetric and ophthalmology. Our study exclusions were patients who (1) did not require a general anesthetic, (2) had missing or inadequate hemodynamic data, (3) had missing baseline or postoperative serum creatinine measurement, (4) are receiving chronic dialysis therapies.The primary outcome of this study was the development of AKI of any stage (severity) within 48 h postoperatively. We used the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria to define and describe the severity of AKI: Stage 1 is a serum creatinine increase of ≥0.3 mg/dL (27 µmol/L) within 48 h, or increase ≥1.5 times baseline; Stage 2 is a serum creatinine increase 2.0–2.9 times baseline; and Stage 3 is a serum creatinine increase 3.0 times baseline, increase to ≥4.0 mg/dL (≥354 µmol/L), or initiation of renal replacement therapy [Intraoperative hypotension was defined as a mean arterial pressure (MAP) <60 mmHg or a systolic blood pressure (SBP) <90 mmHg. Baseline blood pressures were obtained from the preoperative and pre-induction readings. Intraoperative blood pressures were obtained from the anesthetic chart, which were documented at 5-min intervals. Most patients received standard noninvasive assessment of blood pressure, and only 2% of patients received preemptive insertion of an intra-arterial catheter for continuous measurements prior to surgery commencement. Due to the limited number of patients receiving invasive monitoring, we did not analyze these patients separately. We determined the number and duration of hypotensive episodes and calculated the cumulative duration of intraoperative hypotension. Postoperatively, blood pressure readings were examined for evidence of hypotension for 24 h. In conjunction with blood pressure readings, we determined the cumulative dose of vasopressor agents used intraoperatively and noted if hemodynamic support were used postoperatively in the intensive care unit. A high dose of any specific vasopressor used was defined as a cumulative dose of metaraminol, ephedrine, phenylephrine, or norepinephrine >20 mg, or a cumulative dose of epinephrine >10 mg, over the duration of surgery (not time-averaged).We collected data on age, sex, comorbidities, body mass index, surgery type, surgery duration, and the American Society of Anesthesiologists physical status (ASA) classification. The ASA offers a simple classification for assessing perioperative clinical risk, which can be easily communicated for risk-benefit assessment. The assignment of ASA class is made by the anesthetist on the day of surgery based on symptoms, comorbidities, and functional limitations, and it is accepted standard practice in preoperative assessments. Although there are six status classes in this system, only ASA classes 1 to 4 were relevant to this study: ASA 1 , ASA 2 (mild systemic disease), ASA 3 (severe systemic disease), ASA 4 (severe systemic disease that is a constant threat to life), ASA 5 (moribund patient not expected to survive without the operation), ASA 6 (brain-dead organ donor). A full description with examples can be found on the ASA website .2 using the CKD Epidemiology Collaboration (CKD-EPI) equation [From the medical records and medication charts, we also determined the baseline use of β-blockers, renin-angiotensin system inhibitors and diuretics, exposure to potential nephrotoxic medications  within 24 h pre-operatively and postoperatively, and exposure to intravenous or intra-arterial iodinated contrast within 72 h preoperatively. We determined the postoperative hemoglobin as the nadir within 48 h of surgery and calculated the drop in hemoglobin compared to preoperative levels. The hemoglobin drop was corroborated with any intraoperative red blood cell transfusions, and transfusions within 24 h after surgery. Based on the established baseline serum creatinine, chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 mequation .SD), while the distribution of skewed data was described with the median and interquartile range (IQR). Categorical data analysis was performed using the chi-squared test (χ2) or Fisher’s exact test. Initial univariable comparisons of continuous data was conducted with a t-test or nonparametric Wilcoxon rank sum test. For the regression of vasopressor use on the first SBP reading, we used a zero-inflated negative binomial approach as not all patients developed hypotension and needed vasopressors. We used logistic regression (purposeful selection method) to determine the association between AKI and the variables of interests  while adjusting for covariates. All clinically relevant and statistically significant covariates (p < .20) were entered into a base model. This was followed by backwards elimination and a stepwise approach, to retain variables with a p < .05 or significantly confounded the association between hypotension and AKI (change in b-coefficient >10%). We used Akaike’s and Bayesian information criteria or likelihood ratio tests to compare model fit. We assessed for collinearity by examining the strength of the correlation between variables and estimated the variance inflation factor. Model diagnostics included analysis of model residuals, goodness-of-fit, outliers, and influential observations. Analyses were performed using STATA 16.1 . A p < .05 was considered statistically significant.Normally distributed continuous variables were described using mean and standard deviation (2).We included a total of 830 patients aged ≥65 years in the final analysis as shown in the study flowchart . The meaThe incidence of postoperative AKI was 13.9% (115 of 830 patients). Of patients experiencing AKI, 84.4% were stage 1 (97 of 115 patients), 4.4% were stage 2 (5 of 115 patients), and 11.3% were stage 3 (13 of 115 patients). There were significant differences in the incidence of AKI between surgical units, with the highest incidence noted in general surgery (30.2%), urology (26.7%), vascular (17.2%), and orthopedic (16.4%). The surgical units with a low incidence of AKI (<5%) were neurosurgery , plastics (including breast), faciomaxillary, otolaryngology, and thyroid, noncardiac thoracic surgery, and gynecology. There were some baseline differences between patients with and without postoperative AKI . CompareThere was no significant difference between patients with and without AKI in the use of renin-angiotensin system inhibitors, or exposure to intravenous contrast and nephrotoxic medications . Common p = .65). The mean SBPs and mean MAPs were comparable at the beginning and conclusion of surgery between the two groups. The average final SBP was 25 mmHg lower, and the final MAP was 15 mmHg lower, than the initial values of these parameters  receiving a vasopressor at least once intraoperatively, and there was an association between vasopressor use and postoperative AKI . The comb = −0.040, 95% CI: −0.068 to −0.011, p = .007). Thus, in patients who received vasopressors, a higher initial SBP was associated with lower intraoperative vasopressor requirement. We estimated that total vasopressor dose was 4% lower for every 10 mmHg increase in initial SBP.Based on the scatterplot of initial SBPs versus duration of SBP hypotension , we furtp = .27) that the risk of developing postoperative AKI were not significant until the cumulative duration of SBP hypotension exceeded 20 min. Thus, we used this SBP threshold to create a binary variable of SBP hypotension >20 min for testing multivariable models. There was strong evidence that the baseline serum creatinine and a significant drop in hemoglobin was associated with AKI. CKD is a well-known risk factor for AKI and is associated with increased cardiovascular disease risk. A significant hemoglobin drop is a marker severe blood loss, another known risk factor for AKI as well as hypotension. We also included the intraoperative vasopressor variables, and the postoperative vasopressor support in the 24 h postoperatively given our study includes a 48-h postoperative period. As these variables were clinically relevant, logical, and highly statistically significant, we selected them for inclusion as covariates in the initial multivariable model.From the initial univariable comparisons between patients with and without AKI, we examined the odds ratios from logistic regression of AKI on the relevant baseline, perioperative and intraoperative variables . With SBb-coefficient. In model 2, we substituted total vasopressor dose for the high dose use of any vasopressor, with consistent negative results even though the correlation (Φ coefficient) between SBP hypotension >20 min and the high dose use of any vasopressor was 0.150, and the estimated variance inflation factor did not indicate collinearity. However, if total intraoperative vasopressors were dropped (Model 3), the estimates for SBP hypotension >20 min changed by 19% but remained not significant (p = .12).It was clear from the univariable analysis that a measure of comorbidity burden is needed in our model. In stage 1 of our multivariable analysis , we inclb-coefficient for total intraoperative vasopressors . We also examined substituting total intraoperative vasopressor dose with the high dose use of any vasopressor (Model 5). Dropping SBP hypotension from Model 2 yielded a 5.3% change in the b-coefficient for high dose use of any vasopressor . Thus, we showed that SBP hypotension had no significant effect on the b-coefficients of these vasopressor variables and was not required in the final multivariable models.In stage 2 of the analysis , we dropAfter model diagnostics, we transformed baseline creatinine  and removed one influential atypical case  to improve model fit (Models 6 and 7). As an alternative to ASA class, the only comorbidities statistically significant in the multivariable model were COPD and hypertension (Models 8 and 9), but the model fit estimates were similar. Another option was to substitute creatinine for CKD status (Models 10 and 11), but this did not improve model fit statistics. There were no significant interactions between the covariates. Calibration plot and Hosmer–Lemeshow test showed a good fit for the data.p = .06) or sex . However, compared to included patients, there was a smaller proportion of patients with an ASA score >2 among those excluded . Patients who were excluded also experienced a shorter duration of surgery . This may partly be explained by the larger proportion of excluded patients who had plastics, otolaryngology, or maxillofacial surgery (10.8% vs. 20.7%) and orthopedic surgery (11.3% vs. 23.7%), but relatively fewer general  surgery (36.9% vs. 16.5%). The differences in surgery type between included and excluded patients were statistically significant (p < .001).To determine selection bias, we compared demographic and surgical data between patients who were included in the analysis and patients who were excluded. We found no significant difference in age , and no significant change for high dose vasopressor use (Model 7 covariates) with an OR = 2.54 .We conducted a sensitivity analysis by excluding 26 patients who had nephrectomy surgery for urological malignancy. There was no significant change in the estimates for total intraoperative vasopressor dose (Model 6 covariates) with an OR = 1.12 . One possible explanation for the high frequency of vasopressor and inotrope use is a preemptive approach taken by anesthetists based on declining blood pressure trends before it reached critical thresholds. We did not analyze for such trends, which may be an important consideration. A national or international study would be needed to determine if this observation was unique to our hospital network, or indeed very common practice in elective surgery. The mismatch between the frequency of documented hypotension and vasopressor use could also reflect under-documented hypotension, which is a possibility for episodes lasting <5 min which was rapidly corrected with a bolus of vasopressor agent.p = .006). Alternatively, intraoperative use of high dose vasopressors was associated with 2.5-fold increased odds of developing AKI .The prevalence of postoperative AKI was 13.9%, of which 84.4% were categorized as KDIGO Stage 1 AKI. The only intraoperative hemodynamic parameter associated with AKI was the total duration of SBP hypotension >20 min, with an odds ratio of 3.88 (95% CI: 1.38–10.8). However, this was not independent of intraoperative vasopressor use, and was not significant after allowing for baseline kidney function, ASA class, hemoglobin drop, and postoperative vasopressor use. After adjusting for covariates in the final model, every 5 mg increase in total intraoperative vasopressor use was associated with 11% increased odds of developing AKI  blood pressure monitoring. Thus, our findings may not be generalized to services who have a much higher proportion of patients who receive invasive monitoring. We did not specifically determine if patients transitioned from noninvasive intermittent monitoring to invasive continuous monitoring during surgery but relied on the standard anesthetic chart for blood pressure recordings.High doses of intraoperative vasopressor use were independently associated with postoperative AKI in elderly patients undergoing noncardiac surgery and showed a stronger association with AKI than intraoperative hypotension identified from standard anesthetic charts recording blood pressure at 5 min intervals, at a threshold of MAP <60 mmHg and SBP <90 mmHg. The use of vasopressor variables to predict postoperative AKI needs to be validated but could improve our ability to identify high risk individuals in the perioperative period. For clinical practice, we suggest examining the anesthetic charts for vasopressor use when considering the differential diagnosis of postoperative AKI, even if the documented duration of hypotension appeared brief in the charts. For future research, we recommend including vasopressor variables in risk modeling for AKI to see if they improve prediction.


Estimating energy requirements (ER) is crucial for nutritional attention to chronic kidney disease (CKD) patients. Current guidelines recommend measuring ER with indirect calorimetry (IC) when possible. Due to clinical settings, the use of simple formulas is preferred. Few studies have modeled equations for estimating ER for CKD. Nevertheless, variables of interest such as nutritional status and strength have not been explored in these models. This study aimed to develop and validate a model for estimating REE in patients with CKD stages 3–5, who were not receiving renal replacement therapy (RTT), using clinical variables and comparing it with indirect calorimetry as the gold standard.In this study 80 patients with CKD participated. Indirect calorimetry (IC) was performed in all patients. The calorimeter analyzed metabolic measurements every minute for 15 min after autocalibration with barometric pressure, temperature, and humidity. Bioelectrical Impedance Analysis (BIA) was performed. Fat-free mass (FFM) was registered among other bioelectrical components. Handgrip strength (HGS) was evaluated and an average of 3 repetitions was recorded. Nutritional status was assessed with the subjective global assessment (SGA). Patients categorized as B or C were then considered as having malnutrition.p < 0.01 significance level; Malnutrition was consistently associated with ER among other clinical variables in all models (p < 0.05). The model that included BIA-FFM had R2adjusted = 0.46, while the model that included weight (Kg) had an adjusted R2adjusted = 0.44. The models had moderate concordance, LC = 0.60–0.65 with the gold standard, whereas other energy expenditure estimation equations had LC = 0.36 and 0.55 with indirect calorimetry. Using these previously validated equations as a reference, our models had concordance values ranging from 0.66 to 0.80 with them.We analyzed 71 patients and 3 models were generated. Model 1a included FFM; Model 2a included weight; Model 3c included handgrip strength (HGS). All other variables were stepwise, computer-selected with a Models incorporating nutritional status and other clinical variables such as weight, FFM, comorbidities, gender, and age have a moderate agreement with REE. The agreement between our models and others previously validated for the CKD patient is good; however, the agreement between the latter and IC measurements is moderate. The KDOQI lowest recommendation  considering the 22% difference with respect to the IC for total energy expenditure rather than for REE. Estimating energy requirements (ER) is a crucial step in providing nutritional care to any population, especially to those at risk of malnutrition . PatientIn 2021, two distinct studies , 9 publiPrevious research has shown that SGA has an association with body composition when evaluated with BIA . Thus acAdditionally, renal patients experience hydration changes and are more prone to overhydration, which has been shown in previous work to alter ER as measured by IC in peritoneal dialysis patients . BioelecThis was a validity study involving 80 patients with CKD, who were seen in the outpatient clinic of our institution. It was conducted in accordance with the established standards of good clinical practice and with the approval of the ethics and the research institutional review boards. Patients with a diagnosis of CKD stages 3–5 without RRT, an eGFR estimated using the CKD-epi equation, and any comorbidity  were included if they consented to participate. Patients who were missing a limb or had a metal plate implanted in their bodies were excluded from the study. Those who agreed to participate in the study attended to the metabolic, body composition, and clinical tests after a minimum of 4 h of fasting.All the patients underwent IC using a CardioCoach VO2 max . The patients wore a face mask connected to the calorimeter, and a computer recorded variables such as VO2, CO2, FEO2, FECO2, and heart rate. After autocalibration with barometric pressure, temperature, and humidity, as well as the respiration stabilization phase, the calorimeter analyzed the aforementioned variables in a computer interphase every minute for 15 min. The patients were placed in a supine position for 5 min prior to the start of the test. The calorimeter software was programmed with the user’s weight, age, height, and gender. We considered data from the software from patients with stable calorimetry analysis defined as a respiratory coefficient between the physiological ranges [(QR) = 0.68–1.2] or having at least 1 period with less than 10% in coefficient variation , was used to conduct a bioelectrical impedance analysis (BIA). Following the IC, the patients were positioned supine. At 50 kHz, the reactance (Xc), resistance (R), and phase angle (PA) were measured and standardized by height. The FFM was determined in addition to other bioelectrical parameters such as phase angle.A hand dynamometer  was used to conduct strength tests. The patients were instructed and encouraged to squeeze as hard as possible and maintain their strength for 3–4 s. The average of three repetitions with the dominant arm was recorded.Nutritional status was evaluated in 5 domains using SGA: (1) weight changes; (2) dietary changes; (3) functional capacity changes ; (4) muscle and fat storage changes; and (5) presence of edema or ascites. This tool categorizes a person’s nutritional status into three groups: (A) appropriate nutrition; (B) mild to moderate malnutrition; and (C) severe malnutrition. Malnutrition was then considered to be present in patients categorized into the B or C group.Recent laboratory data (within 1 month) were obtained from the medical record, including electrolytes, uremic waste products, and serum creatinine. The CKD-epi equation was used to calculate the estimated glomerular filtration rate (eGFR).In order to determine construct validity as secondary objective, we compared previously validated formulas to our data and vice versa. The following formulas were analyzed:•CKD–epi) – (152.3 if having diabetes mellitus); sex: 0 = woman, 1 = male (REE: 668 + (17.1*FFM-BIA kg)—(2.7*age years) – (92.7*sex) + (1.3*eGFR•CKD–epi) + (25.6 if having diabetes mellitus); sex: 0 = woman, 1 = male (REE: 854.5 + (7.4*weight kg) + (179.3*Sex) – (3.3*age years) + (2.1*eGFR•REE: 645.5 + (–4.7*age years) + (106*sex) + (13.1*weight kg) + (–51.6 if having DM) •REE: 25 kcal*actual weight (kg) •REE: Woman: 665 + (9.56 × weight Kg) + (1.85 × height cm) – (4.68 × edad)•REE: Male: 66.5 + (13.75 × weight Kg) + (5 × height cm) – (6.78 × edad)n = 10 (K + 1), where K is the model’s number of variables]. We considered five variables to include in the model, which resulted in a sample size requirement of 60 people plus 20% of possible missing data, or 72 patients.The sample size was determined using the Freeman equation , which sa priori model proposed by an expert panel. We used a modified Delphi methodology to determine the content validity of a hypothesized renal-specific REE equation (data not published). Discussion took place during three rounds where a moderator gave feedback using all the comments and suggestions provided by the panel. Accordance was set as the case when 80% of the board agreed with the statement. It was agreed to include age, sex, and fat-free mass and evaluate SGA and HGS. The Delphi panel assessed the plausibility of the variables to be included in the model.The descriptive statistics were consistent with the variable distribution using the Kolmogorov-Smirnoff test. This study aimed to evaluate an p-value of 0.1 for variable inclusion. Beta coefficients were calculated and used to predict fitted values, while standardized coefficients provided additional information. As suggested, the regression assumptions were analyzed. The model-fitted values were analyzed using the intraclass correlation coefficient (ICC), with IC measurements serving as the gold standard . The concordance analysis was evaluated with Bland-Altman (BA) graphs accompanied by the Lins concordance coefficient (LCC). The BA method determined the differences between the IC-REE and fitted values. The data was single paired measurements . Acceptable limits of agreement were considered for 300 Kcal. The BA assumptions were analyzed with the normality of the differences from methods with q-q graphs and the Kolmogorov-Smirnoff test. At the same time, homoscedasticity was evaluated qualitatively with residuals graphs post-regressing the methods’ means and their differences. If the assumptions were not satisfied, logarithmic transformation was considered. Proportional bias was analyzed using a regression line in the Bland-Altman figure. Any deviation from the zero line, indicating a linear trend, was considered proportional bias . In such case, BA figures were presented as percentage differences with bias, and LoA’s based on the regression analysis  as the dependent variable. The model was fitted stepwise, with a analysis –19. As f2. Additionally, 16.9% of the study population identified by SGA had mild to severe malnutrition. The patients had a higher prevalence of hypertension than diabetes. The population had a mean BMI of 26.48 ± 4.92 kg per square meter, an impedance phase angle (PA) of 5.66 ± 1.14, and an HGS of 25 ± 9.6 kg per strength. By IC, the mean ER was 1386.23 ± 393.5 kcal/day, with a median respiratory quotient of 0.67 (0.64–0.69).Eighty patients participated in the study, with 71 having an accurate IC measurement. via IC, with the strongest correlation being FFM . Impedance components such as R and Xc, on the other hand, were negatively correlated with IC measurements. The correlation coefficient between the eGFR CKD-EPI and the IC measurement was 0.19, p = 0.106. The correlation coefficients for categorical and quantitative data were 0.39 for hypertension and 0.11 for diabetes mellitus and IC measurements, respectively, whereas malnutrition was negatively correlated with the ER at r = −0.4.p = 0.01 significance level. The model that included BIA-FFM had an adjusted R2 of 0.46, while the model that included weight (kg) had an adjusted R2 of 0.44.The regression models are presented in Additional concordance analysis is presented in The ICC is presented in Estimating energy requirements is critical during the nutritional care process since it establishes a portion of the goals for treating the patient based on clinical evidence and critical thinking . SpecifiAccording to de Oliveira Fernandes et al.’s model , weight r = 0.46), The HGS is irrelevant for developing a predictive model. This could be because when other variables are considered, it loses significance in terms of REE. However, given the biological plausibility and proposal in the Delphi consensus described previously and the emphasis placed on evaluating muscle mass and its quality and strength, it is necessary to assess this possibility. Muscle strength loss has been linked to an increased risk of falls, loss of autonomy, and ultimately hospitalization and death, beginning as early as 30 years  (0.70–0.87). The concordance improved, having narrower LoA, however, when their models are applied to our population’s reference standard (CI), the concordance is moderate. These findings are consistent with our observations about the agreement of other equations, such as Harris-Benedict. This may indicate that, while the equations are similar, the estimates vary among populations.On the other hand, it is essential to note that the most significant difference we found is with the 25 Kcal/Kg/day of the KDOQI guidelines . HoweverAlthough there is no acceptable range between calories estimated by prediction equations and calorimetry measurement, 10% variations are considered clinically significant. It is essential to mention that most of the formulas proposed by our team or other authors meet this characteristic in our population assessed with the mean percentage difference, nevertheless LoA are greater than 20% in all cases. The BA figures showed a bias toward overestimating the REE, for that measured by the IC, in people with averages < 1,200 Kcal, nevertheless great percentage of the population is within the LoA when the REE is > 1,200 Kcal.per se, uremia, anorexia, inflammation, and insufficient physical activity) complicate studies on this subject. These variables are also proposed for consideration in the guidelines for estimating REE, nevertheless some of them are not feasible to in clinical settings .Certain characteristics of kidney patients . Additionally, the work incorporates the models proposed to examine the concordance of their results in our population, indicating that, while the equations are similar, the estimates are not entirely concordant, possibly due to differences in populations. Nevertheless, those weight-based-equations seems to be the more consistent, and concordant and possibly the more valid to estimate REE in CKD patients in stages 3–5.via IC and have moderate validity. The concordance between our models and others previously validated for the CKD patient is high; however, the agreement between the latter and IC measurements is moderate, noticing that the concordance and dispersion of the data are significantly biased in those with energy expenditure below 1,200 Kcal, nevertheless for values > 1,200 kcal, the patients were in between the LoA. to the results of this study, we suggest the use of formulas based on body weight, as well as the use of the KDOQI lowest recommendation  considering the 22% difference with respect to the IC for total energy expenditure rather than for REE.We can conclude that models incorporating nutritional status and other clinical variables such as weight, FFM, comorbidities, gender, and age have a moderate degree of agreement with REE measurements obtained The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Comité de Etica e Investigación del Instituto Nacional de Ciencias Médicas y Nutrición Salvaldor Zubirán No. 3045. The patients/participants provided their written informed consent to participate in this study.SR-A and LR-G participated in the research generation, carrying, collection, analysis of the data, and in writing the article. SL-C and AG-O participated in the interpretation of the data and revision of the manuscript. ÁE-C participated in study conception and design, revision, analysis of the data, writing the manuscript, revision, and approval of the final version of the manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. 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TAVI has shown to result in immediate and sustained hemodynamic alterations and improvement in health-related quality of life (HRQoL), but previous studies have been suboptimal to predict who might benefit from TAVI. The relationship between immediate hemodynamic changes and outcome has not been studied before. This study sought to assess whether an immediate hemodynamic change, reflecting myocardial contractile reserve, following TAVI is associated with improved HRQoL. Furthermore, it assessed whether pre-procedural cardiac power index (CPI) and left ventricular ejection fraction (LVEF) could predict these changes.® non-invasive monitor. HRQoL was evaluated pre-procedurally and 12 weeks after the procedure, using the EQ-5D-5L classification tool.During the TAVI procedure, blood pressure and systemic hemodynamics were prospectively collected with a Nexfinp < 0.005), and left ventricular ejection time (LVET) immediately decreased with 10 ms . Overall HRQoLindex increased from 0.810 [0.662–0.914] before to 0.887 [0.718–0.953] after TAVI (p = 0.016). An immediate decrease in LVET was associated with an increase in HRQoLindex . Pre-procedural CPI and LVEF did not predict hemodynamic changes or change in HRQoL.Overall, 97/114 (85%) of the included patients were eligible for analyses. Systolic, diastolic and mean arterial pressure, heart rate, and stroke volume increased immediately after TAVI (all TAVI resulted in an immediate hemodynamic response and increase in HRQoL. Immediate reduction in LVET, suggesting unloading of the ventricle, was associated with an increase in HRQoL, but neither pre-procedural CPI nor LVEF predicted these changes.https://clinicaltrials.gov/ct2/show/NCT03088787 The prevalence of severe aortic stenosis (AoS) in elderly >75 years) is 3.4%, with a yearly mortality rate of 25% , 2. Tran years isRepairing an aortic valve outflow obstruction results in significant hemodynamic alterations. Both immediate and sustained changes following TAVI have been studied, showing an overall increase in systolic blood pressure –11 and sIt has been hypothesized that a baseline difference in myocardial contractile reserve could affect hypertension onset and, consequently, the prognosis following TAVI . In addiSince myocardial contractility and the severity of the AoS can independently vary within and between patients, the averaged fraction of volume ejected by the heart might not be an ideal variable to classify left ventricular dysfunction in this particular population. The cardiac power index (CPI) is the product of simultaneously measured cardiac output and mean arterial pressure, indexed to the body surface area, representing the hydraulic function of the heart . CPI hasIn this study we hypothesize that an immediate hemodynamic response, reflecting a change in myocardial contractility  following TAVI is associated with a post-procedural change in health-related quality of life (HRQoL). Furthermore, we aim to assess whether baseline LVEF and CPI, can be used to predict both the immediate hemodynamic response and a change in HRQoL.This was a single center, prospective cohort study conducted at the Amsterdam University Medical Centre, location AMC, in Amsterdam, the Netherlands. Prior to the study, the local medical ethical committee approved the study protocol and the trial was registered with the NIH, U.S. National Library of Medicine at ClinicalTrials.gov (NCT03088787). The trial was conducted in accordance with the ICH Harmonised Tripartite Guideline for Good Clinical Practice, and written informed consent was obtained from each patient prior to inclusion. Patients were recruited on the day prior to their intervention, from the 30th of March 2017 until the 28th of February 2019.Patients ≥18 years old with severe degenerative aortic valve stenosis, scheduled for TAVI via femoral approach were eligible for inclusion. Patients with a congenital unicuspid or bicuspid valve; being treated with an intra-aortic balloon pump; with an inability to perform a Nexfin measurement at the left-hand side, or a bodyweight below 40 kg were excluded.The primary outcome of this study was the association of immediate hemodynamic alterations with a change in HRQoL following TAVI. Secondary outcomes were the association of baseline LVEF and CPI with hemodynamic alterations and change in HRQoL.® non-invasive blood pressure monitor at all time-points. Studied variables, at baseline, pre-procedure and post-procedure were: systolic, diastolic, and mean arterial pressure ; heart rate (beats·min−1); stroke volume ; cardiac output ; systemic vascular resistance ; left ventricular ejection time , and the maximal rate of rise of systolic pressure . SV was calculated with the ccNexfin CO-Trek algorithm, dividing the time-integral area under the systolic part of the arterial pressure curve by the aortic input impedance (−1).The studied hemodynamic variables were computed from the continuous blood pressure waveform that was collected using a Nexfinmpedance –25. CO w2) and was calculated as [(MAP * CO/451)] / body surface area  (−2) or normal (≧0.44 W·m−2) according to results by Grodin et al.  . CPI wasn et al. . The EQ-n et al.  was usedPatients were treated according to the TAVI-procedure standard of practice, were kept awake and received local anesthesia. All patients received an Edwards SAPIEN 3 Transcatheter Valve, with some patients requiring aortic valvuloplasty prior to valve implementation.index scores were calculated using the Dutch tariff value set  findings were collected from electronic patient records. Pre-procedural left ventricular function (LVF) grade was collected from TTE findings. Pre-procedural LVEF was determined using automatic whole-heart segmentation in 4D Coronary Computed Tomography Angiography (CCTA). This deep learning-based method segments the cardiac chambers and myocardium, allowing automatic identification of end-systolic and end-diastolic phases and subsequent calculation of the ejection fraction . HRQoL salue set , rangingBefore starting the procedure, a finger cuff with a light-emitting and light sensitive diode for plethysmography  was strapped around the middle phalanx of the middle or index finger at the left hand to obtain a non-invasive continuous blood pressure registration (sampled at 200 Hz). Measurements were stopped at the end of the procedure, at discharge to a nursing ward.Offline analysis of the blood pressure waveform data was performed with MATLAB . Two researchers (JS and EK) manually selected three pre-defined artifact-free time frames. The baseline time frame consisted of 10 min of blood pressure data, collected in the treatment room in a supine position before the start of the procedure. The direct pre-TAVI time frame consisted of 20 s of artifact-free waveform data and was selected in the 3 min of data measured directly before valve implantation, or before initial aortic valvuloplasty, when performed. The direct post-TAVI time frame was selected in the 3 min of data measured directly after valve implantation .Patients in whom no artifact-free waveform data could be selected, and patients who either needed pacemaker support or showed newly onset arrhythmia in the previously defined time windows, were excluded from further analysis.2) of TAVI on the average HRQoLindex score was estimated at 0.2. Given the a-priori interest in the association of ten predictors, 91 patients would provide 80% power to detect a statistically significant association for each predictor, with a 0.05 two sided significance level.The sample size calculation technique for multiple regression, as defined by Green , was uset-test when normally distributed, or using the Wilcoxon rank-sum test when non-normally distributed. Categorical data are presented as frequencies with percentages. Differences between categorical data were analyzed using the Fisher's exact test. Differences in the repeated measurements of hemodynamic variables (pre-TAVI vs. post-TAVI) were analyzed using the paired Student's t-test. During the planning stage of this study, valvuloplasty was identified as a possible confounding variable. It likely results in an increase in elapsed time between the pre- and post-TAVI measurement and has shown to induce ventricular stunning, potentially affecting pressure measurements (Continuous data are presented as median with interquartile range (IQR), or as a mean with standard deviation (SD) when normally distributed. Normality of distribution was assessed visually using histograms and Q-Q plots. Differences between continuous data were analyzed using the Student's urements . Potentip < 0.05 was considered statistically significant. Statistics were done using R v4.0.3 , employing the nlme (v3.1-152) and the mice (v3.13.0) packages. JS had full access to all the data in the study and takes responsibility for its integrity and the data analysis.Furthermore, generalized linear mixed-effect models were used to analyze: the association of immediate hemodynamic changes with change in HRQoL; the association of pre-procedural LVEF and CPI with immediate hemodynamic changes; and the association of pre-procedural CPI with change in HRQoL. Multiple imputation was used to impute missing data, assuming the data to be missing at random, validated by Little's MCAR test . When da−1 , and most patients suffered from pre-existing hypertension (60%). 2. The average aortic valve mean,- and maximum gradient were 38.8 ± 15.4 mmHg and 65.5 ± 24.3 mmHg, respectively. The average pre-procedural LVEF was calculated at 54 ± 17%, and showed agreement with the TTE graded left ventricular function  and the maximal rate of rise of systolic pressure (dP/dt) was increased by 67% . There was no statistically significant immediate change in systemic vascular resistance.The immediate change in hemodynamic variables was calculated for each patient and then averaged . On averp < 0.001) in elapsed time between pre-, and post-TAVI measurements when comparing patients with and without aortic valvuloplasty. When comparing these groups, no significant differences in immediate hemodynamic response were found.There was a 336 s difference . Baseline characteristics of patients with stable or improved HRQoL (n = 64) were comparable with those of patients with decreased HRQoL  and a larger immediate change in SVR . Baseline CPI classifications did not predict a change in HRQoL. There was no association of pre-procedural LVEF with any of the hemodynamic changes or change in HRQoL.Median baseline CPI was 0.50 [0.38–0.64], with CPI classified as low in 36 patients and normal in 60 patients. Normal baseline CPI predicted a higher immediate change in SV , following TAVI would be associated with a post-procedural change in HRQoL. We confirm that TAVI resulted in an overall significant increase in HRQoL and found that an immediate decrease in LVET was associated with an increase in HRQoL. We confirmed the immediate hemodynamic response found in previous research –9, showiTAVI resulted in a significant and clinically relevant improvement in HRQoL, which is in line with various other studies –38. PatiVarious studies have shown that an increase in heart rate can affect the LVET in a sample of patients without alterations to their cardiac structure. However, studies showing the linear relationship of heart rate with ejection time were conducted in a steady-state of circulating volume. We believe that, in this very specific sample, adjusting for the increase in heart rate would result in overcorrection and might induce a type II error. This is underlined by the fact that, besides an average 7% increase in HR, there also was an average 7% increase in stroke volume while LVET still decreased. The removal of the aortic stenosis thus allows the left ventricle to eject more volume, in a smaller amount of time. Moreover, when we analyzed the relationship between LVET and quality of life index in a multivariable regression and the change in heartrate (corrected for the change in stroke volume) is added as an effect modifying factor, the regression coefficient is altered by <10%, indicating that there is no significant effect modification .The immediate reduction in LVET might already be present after initial valvuloplasty, which we did not assess in this study. It would be interesting for future studies to measure whether the subsequent valve implementation would have any additional hemodynamic effect in patients that did not immediately show LVET reduction after valvuloplasty. When this is not the case, the immediate hemodynamic response after initial valvuloplasty might be indicative of the additional therapeutic effect of a subsequent valve implementation. This question was beyond the scope of this study. Furthermore, future studies might be able to provide insight in the correlation of immediate LVET reduction following TAVI with sustained increased blood pressure and mortality.We found no relevant differences in baseline characteristics between patients with reduced HRQoL and patients with stable or improved HRQoL. Even though severely reduced pre-procedural LVEF has shown to predict mortality after TAVI , LVEF waIt has previously been shown that rapid ventricular pacing used for aortic valvuloplasty and valve deployment can result in ventricular stunning, which could have affected pressure measurements . HoweverccNexfin CO-Trek algorithm. Employing this algorithm to calculate stroke volume has shown to be less precise in specific subgroups of critically ill patients : Amsterdam University Medical Centre, location AMC, Amsterdam, the Netherlands. The patients/participants provided their written informed consent to participate in this study.JS: conception, design, analysis and interpretation of data, and drafting of the manuscript. EK: analysis and interpretation of data and final approval of the manuscript submitted. SR and MV: conception and design and final approval of the manuscript submitted. JK, AV, JB, BW, and SB: final approval of the manuscript submitted. MM and HJ: conception and final approval of the manuscript submitted. BS: interpretation of data and final approval of the manuscript submitted. RI: design and final approval of the manuscript submitted. DV: conception, design, interpretation of data, and final approval of the manuscript submitted. All authors contributed to the article and approved the submitted version.Author AV has received personal fees and other from Edwards Lifesciences and Philips outside the submitted work. Author RI has received a grant from Edwards Lifesciences outside the submitted work. Author JB has received a grant from Edwards Lifesciences outside the submitted work. Author DV has received personal fees and other from Edwards Lifesciences, Philips and Hemologic outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The authors performed a meta‐analysis to assess the efficacy of non‐atenolol β‐blockers as add‐on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β‐blockers with diuretics, calcium channel blockers (CCBs), angiotensin‐converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β‐blockers add‐on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non‐β‐blocker monotherapy . These results were consistent across the comparisons with diuretics , CCBs , and ACEIs/ARBs . There was no significant difference in blood pressure lowering effects between combinations with and without a β‐blocker . Metoprolol add‐on or combination therapy had a significantly greater blood pressure reduction than non‐β‐blocker therapy . In conclusion, non‐atenolol β‐blockers are effective in lowering blood pressure as add‐on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β‐blockers can and should be used in combination with other antihypertensive drugs. The Chinese Hypertension League (CHL) guidelines recommend β‐blockers as one of the first‐line antihypertensive drugs,There is emerging clinical trial evidence that antihypertensive therapy with a β‐blocker other than atenolol may be particularly efficacious in blood pressure control.22.1We performed systematic review of randomized controlled trials with a parallel‐group design that compared blood pressure lowering effects of non‐atenolol β‐blockers as add‐on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. We searched MEDLINE (PubMed) databases from inception to 28 November 2021. The complete search strategy is provided in Other components of combination therapy included diuretics, CCBs, angiotensin‐converting enzyme inhibitors (ACEIs), and ARBs. Among β‐blockers, atenolol was excluded, and metoprolol, bisoprolol, acebutolol, esmolol, carvedilol, labetalol, arotinolol, bevantolol, celiprolol, nebivolol, and bucindolol were included in the search. There was no restriction in terms of study duration or type of blood pressure measurement device; however, studies with a sample size smaller than 50 participants were excluded.2.2Studies retrieved from the MEDLINE database search were first assessed for relevance through screening of titles and abstracts. The full texts of relevant studies were then assessed for eligibility according to the inclusion and exclusion criteria set for this meta‐analysis. Prespecified data were extracted from each of the included studies by one researcher using a standardized Excel data extraction sheet, and independently reviewed by two researchers. The prespecified data extracted for each eligible study included study design, intervention characteristics, baseline characteristics of interest, and study outcomes. Any disagreements during data extraction were resolved by consensus Figure .2.3The outcomes of interest for the present meta‐analysis included change from baseline in clinic systolic and diastolic blood pressure and heart rate and the proportion of patients with blood pressure response.2.4Selection bias in eligible trials was assessed by the Cochrane collaboration's tool (version 2.0); further details are provided in Supplementary 2.5P ≤ .05 was considered statistically significant. For all the outcomes of interest, subgroup analyses were performed according to therapeutic regimen.All statistical analyses  were performed using the Stata software (version 15.0). Data were extracted using a standardized data form. The relative risks or weighted mean difference (WMD) and 95% confidence intervals (95% CIs) were calculated for each outcome using a fixed‐effects  and random‐effects model, respectively, in the absence and presence of heterogeneity. All tests were two‐sided and 2 statistic and chi‐squared test. I2 statistic with values < 25, 25–50, and > 50% indicated low, moderate, and high heterogeneity, respectively. The chi‐squared test was used as inferential statistics of heterogeneity with a significance level at P < .1. Potential publication bias was evaluated using the funnel plot and the Harbord or Egger's test. To evaluate the influence of each study on the overall estimate, sensitivity analysis was performed in which the meta‐analysis was re‐estimated by omitting each study in turn. An individual study was suspected of excessive influence if the point estimate of its omitted analysis laid outside the CI of the combined analysis, or its omitted analysis estimate differed in significance relative to the combined analysis.Statistical heterogeneity was assessed using the I33.1Of the 1117 titles and abstracts identified in the initial search of the database, a total of 66 studies were shortlisted for full‐text review; of these, 26 papers met the inclusion criteria and reported at least one outcome of interest.The study selection process is described in Figure 3.2Of the 15 add‐on therapy trials, nine and 11 reported changes in sitting/supine systolic and diastolic blood pressure, respectively. Overall, the β‐blocker add‐on therapy significantly reduced systolic and diastolic blood pressure more than the non‐β‐blocker monotherapy . In the analysis according to the antihypertensive medication, systolic blood pressure reduction was significantly and consistently greater for the β‐blocker add‐on to a diuretic , a CCB , or an ACEI/ARB . Overall, the probability of patients achieving a diastolic blood pressure response was 34% higher with the β‐blocker add‐on therapy than non‐β‐blocker monotherapy . In the analysis according to antihypertensive medication, the likelihood of achieving a diastolic blood pressure response was higher for the β‐blocker add‐on to a diuretic  and to an ACEI/ARB , but not to a CCB , compared to the respective non‐β‐blocker monotherapies Figure .Three trials  reported treatment effects on heart rate. β‐blocker add‐on led to a greater reduction in heart rate by 6.9 bpm  than non‐β‐blocker monotherapy in a fixed‐effect model ,N = 4240) had a lower risk of mortality than those receiving other antihypertensive therapy. The risk reduction in mortality was sustained for 15 years , with a 2–3 year delayed effect after the combination of β‐blocker therapy.If used properly, such as in combination with other classes of antihypertensive drugs, β‐blockers could be particularly effective in blood pressure lowering and in cardiovascular disease prevention. The observed 3–4 mm Hg superior blood pressure lowering effect may explain the results from several recent observational studies demonstrating outcome benefits of β‐blockers in cardiovascular disease prevention.The observed greater blood pressure lowering effect of β‐blockers add‐on to combination ACEIs/ARBs is noteworthy. Such a combination is not recommended by any current hypertension guidelines, because β‐blockers suppress renin secretion and reduce the plasma levels of angiotensin II and, therefore, perceived to be less additive in antihypertensive efficacy to ACEIs/ARBs.The present meta‐analysis should be interpreted within the context of its limitations. First, the analysis was based on summary statistics instead of individual patient data, hence reaching less standardization. Second, the number of trials and study patients were relatively small for some of the subgroup analyses, for example, the combination of β‐blockers and ACEIs/ARBs and the metoprolol versus non‐metoprolol subgroup analyses. The pooled estimates on the subgroup analyses require confirmation in further randomized controlled trials. In addition, the dose of the study drugs varied across studies. However, sensitivity analyses did not show any excessive influence of any individual study on the pooled estimates. Finally, the duration of the included studies was relatively short (ranged from 4 to 36 weeks). The study results cannot be extrapolated to longer‐term duration. Nonetheless, metoprolol demonstrated sustained blood pressure lowering effects in the long‐term MAPHY trial with a median follow‐up of 4.2 years.In conclusion, this meta‐analysis showed that β‐blockers (excluding atenolol) as add‐on to several other classes of antihypertensive drugs, such as diuretics, CCBs and even ACEIs/ARBs, were efficacious in further lowering blood pressure and that combination therapy with β‐blockers is as effective as non‐β‐blocker combination therapy. Thus, in line with the current guideline recommendations, β‐blockers can and should be used in combination with other classes of antihypertensive drugs at any stage of treatment.All authors contributed to the meta‐analysis design and data analysis, and to the drafting, review and final approval of the manuscript.Qian‐Hui Guo and Ji‐Guang Wang were financially supported by grants from the National Natural Science Foundation of China  and the Ministry of Science and Technology (2018YFC1704902), Beijing; the Shanghai Commissions of Science and Technology (19DZ2340200) and Health ; and the Clinical Research Program, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (grant number: 2018CR010), Shanghai, China.Zhi‐Ming Zhu, Ying‐Qing Feng, Jin‐Xiu Lin declare no conflict of interest.Supporting InformationClick here for additional data file.


To alleviate the rising mortality burden due to hypertension and other non-communicable diseases, a new public health policy initiative in 2009 called the Basic Public Health Services (BPHS). Program was introduced by the Chinese government. The goal of the study is to assess the feasibility and impact of a nationwide health care service—the “BPHS”.From January to December 2021, a stratified multistage random sampling method in the survey was conducted to select 6,456 people from 8 cities/districts in Yunnan Province, China, who were above the age of 35 years. 1,521 hypertensive patients were previously aware of their high blood pressure status were matched to the BPHS program database based on ID number and then further divided into BPHS group and non-BPHS (control) group. The results of the current study are based on their responses to a short structured questionnaire, a physical examination, and laboratory tests. The association between BPHS management and its effect on the control of hypertension was estimated using multivariable logistic regression models. We evaluated the accessibility and efficacy of BPHS health care services by analyzing various variables such as blood pressure, BMI, lifestyle modification, anti-hypertensive drugs taken, and cardiovascular risk factors.Among the 1,521 hypertensive patients included in this study, 1,011 (66.5%) were managed by BPHS programme. The multivariable logistic regression model demonstrated that the BPHS facilitated hypertension control . A higher proportion of participants receiving lifestyle guidance from the BPHS management showed lowering of total cholesterol. In comparison to the non-BPHS group, those under BPHS management adhered better to antihypertensive medications either single drug (54.3%) or in combination (17.3%) of drugs. Additionally, we also noticed that urban areas with centralized and well-established digital information management system had better hypertension treatment and control.Nearly two-thirds of the hypertensive patients in Yunnan Province were included in BPHS management. The impact of the national BPHS program was evident in lowering risk factors for cardiovascular diseases, promoting healthy lifestyles, lowering blood pressure, increasing medication adherence, and the better control rate of hypertension. The number of people with hypertension increases from 650 to 1.28 billion worldwide from 1990 to 2019 in the age group of 30–79 years , and hypControlling blood pressure to a normal state reduces the risk of cardiovascular events and all-cause mortality –8. The tIn 2009, China's new healthcare reform introduced the “National Basic Public Health Service Program” (BPHS), which provides free of cost health services throughout the country by partnering with community health organizations. The management of hypertensive patients aged 35 and over was one of the 12 kinds of voluntary free services contents in BPHS , 16, incThis study comprehensively evaluated the BPHS hypertension management in Yunnan Province, a relatively economically backward in southwest China. Hypertensive patients who were aware of their high blood pressure from a representative sampling survey and BPHS system matched, to compare matched BPHS group and unmatched non-BPHS groups' coverage and current hypertension status, CVD risk factors, management and effectiveness, blood pressure control rate and antihypertensive drug use, etc. This study supports the World Health Organization's (WHO) suggestion that developing nations should increase their access to management-controlled hypertension-related healthcare services . Rarely The survey was conducted in Yunnan province from January to December 2021, and samples were chosen using a stratified multistage random sampling method. As shown in The target population for BPHS hypertension management is patients who are residents of the jurisdiction aged 35 years and older , so we evia face-to-face short structured questionnaires that included details of their socio-demographics like age, gender, ethnicity, place of residence, educational attainment, occupation, annual household income, and wellness behaviors like smoking, drinking, dieting, exercising, and finally about hypertension perse like the history of hypertension, treatment followed from the time of diagnosis. Additionally, we measured height with RGZ-160 measuring instrument , and body weight was measured with an InBody H20B  removing shoes, hats, coats, or weight in pockets. Body mass index (BMI) is a person's weight (kg) divided by the square of height (m)  .Diastolic blood pressure (DBP) and systolic blood pressure (SBP) were measured in the right upper arm using an OMRON HBP-1,300  at 5 min intervals; three readings were recorded and the average of the three measurements was used for this study. In the meantime, participants were asked to fast for more than 8 h before collecting 8 ml of blood samples for cryopreservation and then sent to Beijing ZhongtongLanbo Medical Test Laboratory for measurement of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC). The findings and readings were recorded on the iPad in specially designed survey tables see , and theAccording to the 2018 Chinese Guidelines  and 20202, obesity was a BMI of 25 kg/m2 and above. Risk factors for cardiovascular disease (CVD) as per 2020 ISH Guidelines  were skewed distribution data by Kolmogorov-Smirnov test, described by median and inter quartile range, and the differences between groups were tested by Wilcoxon rank sum test.All statistical analyses use IBM SPSS 22.0 . Categorical variables from the BPHS and non-BPHS groups were presented as numbers (proportions), and differences between groups were compared using the chi-square test or Fisher's exact test. Mean ± standard deviation (SD) and Eleven characteristic variables as age , residence , gender , ethnicity (Han or other minorities), annual household income , education attainment , current smoker (yes or no), current drinker (yes or no), insufficient vegetable and fruit intake (yes or no), insufficient physical activity (yes or no), overweight and obesity (yes or no) were compared between the two groups.p < 0.05 was considered statistically significant.The ggplot2 package of R 4.0.5  was used to construct the visible distribution of blood pressure and a stacked column chart of “controlled with treatment”, “treated but not controlled”, and “diagnosed but untreated”. Unadjusted and full adjusted binary logistic regression models were conducted to assess the association between hypertension control with BPHS, the first model did not adjust for potential influencing factors. Next, second model was performed to adjust for potential influencing factors, including age, gender, ethnicity, residence, household income and educational level. Then, the odds ratio (OR) and 95% confidence interval (CI) were estimated. All tests were two-sided and The mean age of the 1,521 hypertensive patients was 62.6 ± 12.6 years old, with 737 men (48.5%) and 858 people living in urban areas (56.4%), 1,118 Han people (73.5%), 1,104 people (72.6%) with an annual family income of <4,487 USD/year, and 898 people (59.0%) with primary school education or below .p < 0.05). Furthermore, the BPHS group had a lower proportion of current smokers and their consumption of fruits and vegetables was inadequate .1011 (66.5%) and 510 (33.5%) hypertensive patients came from the BPHS and non-BPHS groups. Hypertensive patients included in BPHS management were more likely to be older, female, non-Han Chinese, and had lower family economics and literacy , the average SBP was (146.8±18.8 vs. 149.7 ± 19.1) mm Hg, and DBP (85.7 ± 12.5 vs. 91.2 ± 12.7) mm Hg, respectively . The non-BPHS group showed greater variation in SBP and DBP distribution than the BPHS group (As shown in HS group . FurtherThe BPHS group indicated higher hypertension control rate (33.2%) than the non-BPHS group (22.2%) shown in p < 0.05)  .Further analysis proved that patients with BPHS had lower TC after receiving weight reduction guidance, smoking cessation guidance, and alcohol consumption restriction guidance than those who did not receive such services. In addition, patients who received weight loss, smoking cessation, alcohol consumption restriction, and stress guidance also had lower HDL-C, however within the normal range. No significant differences were observed in TG and LDL-C levels between those who received lifestyle modification services and those who did not .p < 0.001).In A lower blood pressure control rate was observed from male patients aged 65 years and above, especially at Dayao, Xinping, Anning, and Chengjiang counties in rural areas. In general, it was observed that, there was a higher prevalence of hypertension treatment and better control among women than men. Patients with hypertension of any gender who are older than 65 can access antihypertensive medications and have better control over their condition. There is no significant difference noticed between subjects with different income levels among the groups of “diagnosed but untreated,” “treated but not controlled,” and “controlled with treatment.” .This study showed the status of BPHS coverage and the effectiveness in the management of hypertensive patients in Southwest China (Yunnan Province) was corroborated by provincial-specific investigation results. Patients' ID in the survey matched with the BPHS system and found that 66.5% of hypertensive patients were included in BPHS and received related management services. The accessibility of BPHS for hypertensive patients in Yunnan Province was higher than the national accessibility rate . BPHS inUncontrolled hypertension may result in ~24,914,000 years of life lost and 28,657,000 quality-adjusted life years lost in 1.7 million Chinese adults . TherefoThe study also found, in the BPHS group, 71.6% of hypertensive patients used antihypertensive medication (vs. non-BPHS 45.9%), which was higher than the national treatment rate of 61.3% . It may Generally, the control rate of hypertension is the standard for evaluating the effectiveness of interventions, resulting in effectively preventing or delaying the occurrence of stroke, myocardial infarction, heart failure, renal insufficiency, and other complications . Our stuLimitations include the design method in this survey, this might not substantiate causation, particularly the link between the services offered by the BPHS program and the management of hypertension without these services. Recall bias can also be a challenge with self-reported data. Some subjects lacked information, such as height or weight, which can skew the data. Therefore, information collection and interpretation of risk factor changes should be conducted with utmost care.Since its launch in 2009, the BPHS program run by provincial authority healthcare providers has made a substantial contribution to bettering hypertension management and balancing access to healthcare across inhabitants of urban and rural areas as well as among various socioeconomic strata.Results showed that program participants kept healthy lifestyles, had lower blood pressure, higher control rate of hypertension, and took their medications more consistently, which could account for some of the benefits of this program. In districts or counties with fully operational digitalized and centralized data management systems, it was easier to include the participants compared to “non-matched ID” in rural areas, therefore health information management may further be improved to address this limitation in rural areas. In order to better diagnose and treat hypertension at its early stages, a customized program has to be designed to cater to the requirements of hypertension control in the younger population through the BPHS program.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the central Ethics Committee at the Fuwai Hospital, CAMS/National Center for Cardiovascular Diseases approved this project . The survey was conducted in accordance with the ethical principles of the Declaration of Helsinki, and the informed consent and electronic signature of the participants were obtained before the investigation. The patients/participants provided their written informed consent to participate in this study.LP and LK were co-first authors and drafted the manuscript. ZG and YZ initiated, conceived, and supervised the study. LD, WL, and MF guided the analysis and modified the article. LP, JF, and HF were involved in data curation and analysis. YS and MT completed field execution and coordinated all divisions. XW, MM, and HW checked the integrity of the data. LK and DM reviewed and edited the manuscript. LD conceptualized and supervised this project. All authors have read and approved the final version of the manuscript.This work was supported by Key Research and Development Program from Yunnan Province Science and Technology Department (Grant No. 202103AF140002); Yunnan Provincial Clinical Research Center for Cardiovascular Diseases-New Technology Research and Development Project for Diagnosis and Treatment of Major Cardiovascular Diseases (Grant No. 202102AA310002); and Provincial Innovation Team Project of Heart Failure Diagnosis and Treatment in Fuwai Yunnan Cardiovascular Hospital (Grant No. 202005AE160020).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Hydralazine is a traditional antihypertensive drug that was developed several decades ago. Its most well-known effect is blood pressure lowering by arterial vasodilation. While mainly used an adjunct treatment for clinical hypertension or chronic heart failure, this old drug has also shown potential as a repurposing drug for the atherosclerosis vascular disease and various kidney diseases. Recent experimental studies suggest that hydralazine exerts antioxidative, anti-apoptotic, and HIF-1α stabilization effects for angiogenesis and vascular protection. Hydralazine also exerts reno-protective effects via its antioxidation, DNA demethylation, and anti-inflammation abilities. The above evidence provides advanced rationales for new applications of this drug beyond blood pressure lowering and arterial vasodilation. Here, we summarized the recent experimental advances in the use of hydralazine for either a vascular disease or kidney diseases, or both. Given the wide populations of people with cardiovascular and/or kidney diseases, future studies are worth validating the potential impacts of hydralazine on the clinical outcomes in selected patients. It is suggested as an effective arterial vasodilator that directly reduces peripheral resistance by relaxing the smooth muscle cell layer in the arterial blood vessels and has been used as an adjunct treatment for hypertension and chronic heart failure for a long time . The mosh muscle . In addih muscle . It was h muscle . Taken tHydralazine is usually used as an adjunct treatment in patients with hypertension and/or chronic heart failure. While the clinical benefits of hydralazine may be related to its vasodilation and hemodynamic effects, several current studies have documented connections between hydralazine and cardiac mitochondria . In a reCirculating endothelial progenitor cells (EPCs) are a specific cohort of monocytes originally derived from bone marrow that may promote vascular endothelial repair and even differentiate into endothelial cells for neovascularization in various physiological and pathological processes. EPCs express CXCR4, which allows homing to neovascularization sites. Hydralazine was purposed to upregulate CXCR4 in EPCs and thereby enhance their function and capacity to home to target tissues via hypoxia-inducible factor (HIF) 1α stabilization in the presence of cardiovascular risk factors . HydralaRegarding atherosclerosis, the antiatherogenic effect of hydralazine has been suggested in several hypercholesterolemic mice models. Hydralazine was shown to reduce the extent of atherosclerosis, which is thought to result from the in vivo mechanical effects of blood pressure reductions in apolipoprotein E-deficient mice . On the While the majority of the effects of hydralazine are confined to cardiovascular protection, the accumulating experimental data have also revealed its substantial effects on kidney protection. It was further suggested as a potential repurposing drug, especially for chronic kidney disease (CKD) . HydralaHydralazine was shown to demethylate RASAL1 via reno-protective effects in a mouse model of acute kidney injury (AKI) with IRI. Meanwhile, hydralazine-induced CpG promoter demethylation followed attenuated renal fibrosis and preserved the renal function independently of its blood-pressure-lowering effects in a mouse model of AKI-to-CKD progression ,24. AddiDiabetic kidney disease (DKD) is one of the major causes of end-stage renal disease. Different from other chronic renal diseases, DKD is characterized by the early presence of glomerular hyper-infiltration and hyper-albuminuria, which may be associated with significant systemic inflammation and are largely influenced by fluctuations in blood sugar and blood pressure. Hydralazine decreased protein glycation and down-regulated RAGE, NADPH oxidase, and super oxide dismutase expression in the kidneys of STZ-induced diabetic mice . A hydraRecent experimental data suggest some novel cardiovascular and renal protective effects of hydralazine, which may be related to multiple and differential mechanisms in each individual disease . The accThe intracellular mechanisms for the antioxidative capacity of hydralazine may be complex, which could be related to its functions of mitochondrial inhibition, NADPH oxidase inhibition, XO inhibition, and nuclear factor erythroid 2-related factor 2/heme oxygenase 1 activation. Hydralazine was also shown to have anti-apoptosis and HIF-1α stabilization capabilities. Furthermore, hydralazine was shown to down-regulate RAGE, iNOS, COX-2, TNF-α, IL-1β, and IL-6 signaling via both redox-dependent and -independent mechanisms . Future While hydralazine has been used for a long time in the treatment of hypertension and chronic heart failure, its clinical mechanisms remain to be further explored. Given the limited evidence directly supporting its mechanisms in each specific disease, here we attempted to summarize the general beneficial effects, especially in cardiovascular and renal diseases. Altogether, the experimental evidence suggests novel and complex antioxidative and anti-inflammatory mechanisms of hydralazine, including mitochondrial inhibition, NADPH oxidase inhibition, XO inhibition, heme oxygenase induction, cytokine modulation, and others for both cardiovascular and renal protection. The potential impacts of hydralazine other than vasodilation may provide this old drug with a new scenario.These experimental studies open up the possibility of repurposing hydralazine as a potential cardio- and reno-protective agent through its antioxidative and anti-inflammatory mechanisms. Further investigations may be indicated to verify whether the potential clinical benefits of hydralazine could be related to its antioxidative and anti-inflammatory capacity, particularly in patients with high levels of ROS and/or inflammation. In this regard, the proper doses and regimens should be also established. Given the worldwide prevalence and clinical significance of cardiovascular as well as kidney diseases, future studies are worthwhile to validate the potential impacts and long-term safety of hydralazine as a complex antioxidant in selected clinical diseases.


Extracorporeal membrane oxygenation (ECMO) to support cardiopulmonary resuscitation (CPR), also known as extracorporeal cardiopulmonary resuscitation (ECPR), has shown encouraging results in refractory cardiac arrest (RCA) resuscitation. However, its therapeutic benefits are linked to instant and uninterrupted chest compression (CC), besides early implementation. Mechanical CC can overcome the shortcomings of conventional manual CC, including fatigue and labor consumption, and ensure adequate blood perfusion. A strategy sequentially linking mechanical CPR with ECPR may earn extra favorable outcomes.We present a four-case series with ages ranging from 8 to 94 years who presented with prolonged absences of return of spontaneous circulation (ROSC) after CA associated with acute fulminant myocarditis (AFM) and myocardial infarction (MI). All the cases received VA-ECMO  assisted ECPR, with intra-aortic balloon pump (IABP) or continuous renal replacement treatment (CRRT) appended if persistently low mean blood pressure (MAP) or ischemic kidney injury occurred. All patients have successfully weaned off ECMO and the assistant life support devices with complete neurological recovery. Three patients were discharged, except the 94-year-old patient who died of irreversible sepsis 20 days after ECMO weaning-off. These encouraging results will hopefully lead to more consideration of this lifesaving therapy model that sequentially integrates mechanical CPR with ECPR to rescue RCA related to reversible cardiac causes.This successful case series should lead to more consideration of an integrated lifesaving strategy sequentially linking mechanical cardiopulmonary resuscitation with ECPR, as an extra favorable prognosis of refractory cardiac arrest related to this approach can be achieved.The online version contains supplementary material available at 10.1186/s40001-022-00711-1. Despite advancements in prevention, intervention, and advanced cardiac life support (ACLS) –3, refraWhen RCA is prolonged, reperfusion of the vital organs by uninterrupted and effective chest compression (CC) before ECMO establishment is the most critical intervention for successful ECPR , 22. HowOn July 27, 2021, a 51-year-old male complaining of unrelieved chest distress and pain called emergency medical services. Five minutes after the ambulance's arrival, he suddenly developed CA. His heartbeat was restored but unstable after 10 min of resuscitation on the scene. He was instantly transported to the emergency department (ED), where he continued manifesting ventricular fibrillation (VF) and absence of ROSC for more than 15 min despite the support of mechanical CC by AHS 200B (Physio control), invasive mechanical ventilation (MV), and electric defibrillation. He was then transferred to ICU, where venoarterial ECMO (VA-ECMO) was implemented in about 20 min. After 50 min of ECPR, he reverted to consciousness. Considering his medical history of ischemic heart disease, he was transferred to the interventional radiotherapy room for PCI. Coronary angiography revealed a 90% narrowness of the coronary artery at the proximal anterior descending branch, where a stent was implanted to open clogged vessels. VF was analyzed on ECG monitoring at the end of PCI and transformed to sinus rhythm after the external defibrillator delivered two electric shocks. After sustaining a regular CPR lasting 62 min, followed by an ECPR lasting 190 min, the patient ultimately gained ROSC. Due to prolonged ischemic injury, multi-organ insults involving the heart, lung, liver, kidney, and coagulopathy ensued. Under all means of supportive care by IABP, MV, CRRT, and anti-infective agents, he was weaned off ECMO on Day 6 from admission to ICU and off IABP on Day 11. He was transferred out of ICU on Day 30 and discharged on Day 86 with a cerebral performance category (CPC) of 1.On July 28, 2021, a 17-year-old girl suddenly collapsed on the street without recording primary diseases. A passer-by, a doctor, immediately identified the CA and started CPR. Further helped by the paramedics dispatched to the site, her heartbeat revived. However, she fell into a coma, manifesting cyanosis, hypopnea of 5 breaths per minute, cardiac acceleration of 130 beats/min, and extreme hypotension hardly to be measured. She was delivered to the ICU in the local hospital for further rescue after an epinephrine injection, where she received intubation and MV to increase oxygen saturation and vasoactive drugs to maintain blood pressure, and finally turned conscious about 2 h later. Unfortunately, about 15 h later, her condition took a sharp turn for the worse, with blood pressure continuing to collapse, leading to a final cardiac arrest. Mechanical CPR started when the absence of ROSC protracted. Our ECPR team was consulted to join the rescue. Instantly, the ECPR team was dispatched about 76 km far away using a transportable ECMO device . About 40 min later, the team arrived and established the VA-ECMO support in 33 min. The girl was then transferred to our hospital for further ECPR and extensive monitoring.Severe metabolic acidosis was detected, with the blood lactic acid higher than 15 mmol/L lingering for 10 h. Meanwhile, methylprednisolone , intravenous immunoglobulin , a high dose of vitamin C (10 g iv drip QD over 1 week), antivirus agents (oseltamivir phosphate capsules 75 mg p.o bid) were medicated for a suspected AFM. Vasoactive drugs , antibiotics , and nutritional formula  were also put on. Due to prolonged low perfusion, she suffered as many as six major organ insults, including brain, heart, lung, liver, kidney, and blood, which necessitated additional support from IABP, CRRT, and MV. After careful brain safeguarding by mild hypothermia therapy and adequate sedation and analgesia, the patient became conscious on Day 2 from ICU admission. After 115 min of mechanical CPR and nearly 44 h of ensued ECPR, she eventually gained spontaneous circulation. Through multidisciplinary discussions, we pursued strict but dynamic protocol on fluid management, blood pressure modulation, and prevention of complications related to ECMO, as detailed in Additional file On November 20, 2021, an 8-year-old girl was transferred from a local hospital to our hospital for carcinogenic shock resulting from suspected AFM. She had a history of runny nose with cough for 2 weeks and syncope for 1 day. Serum troponin I and creatine kinase elevated to 29.79 ng/mL and 2066.61 U/L, respectively. ECG monitor captured ventricular tachycardia rapidly exacerbating to VF. After electric defibrillation, sinus rhythm was restored but unstable. On ICU admission, the girl was lethargic with cold, clammy skin, measuring artery pulse at 54 beats per minute, rapid breathing at 25 beats per minute, and hypotension at 80/51 mmHg with continuous dopamine input through a syringe pump. AFM was clinically diagnosed considering prodromal symptoms of cold accompanied by severe myocardial damage. Methylprednisolone sodium succinate , IVIG (0.4 g per kilo of body weight iv drip over 3 days), anti-oxidative (vitamin C 5 g iv drip QD over 1 week) were simultaneously medicated.Moreover, ECG showed complete atrioventricular block and ventricular escape rhythm, and an ultrasonic cardiogram saw weak cardiac contractions. Cardiogenic shock aggravated despite all intensive care, leading to final asystole. The little girl was intubated and ventilated to start CPR immediately. Unfortunately, stable ROSC was difficult to appear, while continuous CPR largely under mechanical CC lasted more than seventy minutes. The child fell into a deep coma with slowed pupillary light reflex. With her father’s consent, VA-ECMO was established in 30 min to start ECPR. The heart revived to ventricular tachycardia and then sinus rhythm by defibrillation seven hours later. Forty minutes after this ROSC, the girl became conscious again. However, sustaining on-and-off cardiac arrest for 7 h with organs perfused by an advection pressure of about 60 mmHg, she developed a typical ischemic kidney injury. CRRT was introduced to treat oliguria, electrolytic disorder, and acid–base imbalance. ECMO was weaned off on Day 6. On Day 8, for more special children's intensive care, she was transferred to the local Children’s Health Care Hospital, where she got rid of the ventilator and eventually restored her organ’s functionality. She was discharged on Day 32 with a CPC of 1.On December 30, 2021, a 94-year-old female was admitted to ICU due to breathlessness and unconsciousness. She was clinically diagnosed with pulmonary encephalopathy secondary to acute exacerbation of the chronic obstructive pulmonary disease, which required emergent intubated ventilation. After critical care, she restored consciousness and was later extubated and improved to a generally stable condition which allowed her to be transferred out. On January 14, 2022, the patient suddenly lost consciousness with an ECG monitored VF. She was again intubated, and ventilated by mechanical CC. After 55 min of CPR, the desired ROSC was still absent, whereas the pupils remained responsive to light. Considering her previously relatively fine organ functions, the chance to survive by ECPR still existed. With the consent of the guardians, VA-ECMO support was established. After ECPR started for about 40 min, the ROSC was restored with her upper limbs involuntarily moving. She became utterly conscious two hours later. VF occurred persistently until recurrent electric defibrillation. The patient's condition gradually improved after maintaining electrolyte balance, addressing coagulopathy and anemia, and suppressing infection. No IABP or CRRT was required for the heart rate, and blood pressure tended to be stable. On Day 6, from the initiation of ECPR, ECMO was removed. On Day 14, vasoactive drugs were terminated as blood pressure was normal. On Day 20, she received a tracheotomy to expectorate copious sputum with the expected need for prolonged MV. On Day 26, after the successful removal of ECMO, she died of severe sepsis.As detailed in Additional file The four patients included in this ECPR series were diagnosed with refractory cardiac arrest (RCA), with prolonged absences of ROSC crossing from 100 to 2752 min. They had received protracted mechanical CPR before ECMO establishment. All overcame low perfusion, survived the multi-organ failure of the post-cardiac arrest syndrome (PCAS), and eventually recovered to a favorable neurological prognosis. They were discharged from the hospital, except for the very old patient regrettably dying of irreversible sepsis 20 days after successful ECMO removal, as illustrated in Fig. No one should doubt that ECPR has played a vital role in the remarkable success of these 4-case series. ECPR can significantly promote the ROSC in RCA patients, with the rapid initiation of VA-ECMO providing prompt and stable MAP and sufficient oxygenated blood for various organs, especially the brain, heart, liver, and kidney. ECPR reduced cardiac oxygen consumption and preload to rest the damaged myocardium, which broadly enlarged the window of opportunity for ROSC. Meanwhile, controllable target temperature management in resuscitation via ECMO water tank was associated with a more significant reduction in brain injury. It improved the long-term survival and prognosis of the nervous system.However, the results of ECPR for RCA, traditionally following manual rather than mechanical CPR, are far from satisfactory. It is conventionally believed that short CPR duration was associated with favorable neurological outcomes , 30, andMechanical CC provides constant, rhythmic, and high-quality CCs that feed blood and oxygen to vital organs. Continuous mechanical CC can reduce medical personnel variance of the compression rhythm and amplitude and fit the heterogeneity of the patient's shape with a fixed device position. Even though many existing studies –28 do noFirst, treatment of reversible underlying causes of RCA is of vital importance, sticking to the American Heart Association CPR guidelines and European Resuscitation Council guidelines , 33. OneSecond, strict management of fluid balance, ECMO flow, and blood pressure plays an essential role in cardio-pulmonary–cerebral resuscitation. On the heart side, the recovery of myocardial function becomes the fundamental problem. At the same time, the reverse flow from VA-ECMO inflated the heart and increased the intraventricular pressure, leading to long-term myocardial injury. Bedside echocardiography helped us perceive the cardiac movement state. When myocardial contraction collapsed during ECPR, the administration of IABP was required to relieve the cardiac afterload and lower the left ventricle pressure of the expanding heart, as the patients of Cases 1 and 2 demonstrated. On the brain side, the association of blood flow and blood pressure with brain perfusion should be individually or personally assessed in light of patients’ primary diseases and age. Prolonged CPR essentially led to brain swelling. We maintained neither excessively low nor overly high cerebral perfusion pressure to avoid aggravating cerebral ischemia or brain edema. Keeping blood oxygen pressure at an adequate but not unduly high level at the early ECPR stage was essential to prevent excessive oxygen from damaging ischemic neurons through oxidative stress.Third, it is worthy of optimizing the treatment of PCAS, which is mechanistically ascribed to acute systemic ischemia/reperfusion injury after prolonged asystole. All 4 cases suffered multi-organ insults during ECPR, summarized in Table As summarized in Table About the transferability of this sequential strategy, some premises are required. The first thing is to establish a quick-response ECMO team capable of being dispatched to the CA scene and establish the ECMO as soon as possible. Our ECPR team consists of trained ICU physicians and nurses with substantial practical experience of over 150 cases of ECMO and several cardiovascular surgeons to backup when surgical cannulation is occasionally required. The time for our team to initiate ECPR averages 25 min. As our team and existing study  demonstrBesides, as shown in Fig. However, despite the practicality and safety of mechanical CC in RCA, related injuries should be carefully monitored . The lonExtracorporeal cardiopulmonary resuscitation (ECPR) can be used to support patients with refractory cardiac arrest. This successful case series should lead to more consideration of an integrated lifesaving strategy sequentially linking mechanical cardiopulmonary resuscitation with ECPR as favorable neurological survival can be achieved.Additional file 1: Table S1. General principle and individual treatments during our ECPR.