Hypertension is common in continuous ambulatory peritoneal dialysis (CAPD) patients. It remains to be determined the extent to which fluid overload contributes to uncontrolled blood pressure (BP) in this population. The aim was to determine the association between fluid status as measured using bioimpedance spectroscopy (BIS) and BP in CAPD patients.A cross-sectional study was performed involving 50 stable CAPD patients at a single center in Cape Town, South Africa. All participants were known to have hypertension and were divided into two groups based on office BP measurements: an uncontrolled BP group (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) and a controlled BP group. Fluid status was determined using BIS .P = 0.01). The uncontrolled BP group was older  and had a shorter dialysis vintage . Significant correlations were found between OH and the extracellular water (ECW)  and ECW to total body water (TBW) ratio . Mixed ancestry, presence of residual kidney function, ECW, and ECW to TBW ratio were identified as predictors of OH on multivariable linear regression.There was a statistically significant difference in overhydration (OH) between the uncontrolled BP group and the controlled BP group (3.0 ± 2.3 L vs. 1.4 ± 1.6 L, respectively, We found that stable CAPD patients with uncontrolled BP had higher OH compared to patients whose BP was controlled. Patients on peritoneal dialysis (PD) frequently present with fluid overload. Depending on the type of hydration parameters used, the reported prevalence of fluid overload ranges from 53.4 to 72.1% [Optimizing the fluid status in the PD population is critical. Fluid overload in PD patients is associated with increased morbidity and mortality primarily related to cardiovascular disease , 6. AchiThe clinical examination has poor diagnostic accuracy with poor reproducibility and high interobserver variation . It was We aimed to determine the association between fluid status as measured using BIS and office BP in stable CAPD patients.This was a cross-sectional study of stable CAPD patients at Tygerberg Hospital (TBH) in Cape Town, South Africa. All adult patients (more than 18 years old), with a history of hypertension and a CAPD dialysis vintage of more than 1 month were included. Exclusion criteria included active peritonitis, hemodynamic instability, amputees, current deep vein thrombosis, any metallic intravascular device (such as a pacemaker) or articular prosthesis, pregnancy, automated PD, and patients with current malignancies. The calculated sample size was 58 using a margin of error of 5%, confidence level of 95%, prevalence of fluid overload in PD patients of 50% and a total population size of 67 patients .This study was approved by the Health Research Ethics Committee (HREC) of Stellenbosch University (HREC study number: S18/02/024) and was performed in accordance with the Declaration of Helsinki.After gaining informed consent, participants drained their existing PD fluid dwell and were kept dry during this short period of data collection. Those with RKF emptied their bladders.The following demographic data were recorded for each patient: age, sex, self-reported ethnicity, dialysis vintage (months), diabetic status, the number and types of antihypertensive drugs and data on the CAPD prescription were collected including the types of PD solutions used and the frequency of daily exchanges. We used self-reporting of RKF, which was defined as an estimated 24-h urine volume of more or equal to than 250 mL (1 cup) since self-reporting of RKF was reported to have a strong agreement with measured urine volumes . The cliPatients were asked to stop consumption of any foods and beverages containing caffeine at least 30 min before office BP were measured. BP was measured with the participants sitting upright in a chair with the back supported and the arm supported at the level of the heart. In participants with a mid-upper arm circumference of less than or equal to 33 cm, a standard cuff size of 12 cm was used, and a 15 cm cuff was used if the mid-upper arm circumference was more than 33 cm. BP was initially measured in both arms and the remaining BPs were measured in the arm with the highest BP. The initial BP recording was discarded. Patients were divided into two groups based on the average of three BP readings taken at least 1-min apart using a calibrated, automated BP machine . Participants with an average systolic BP of ≥140 mmHg and/or average diastolic BP of ≥90 mmHg were regarded as cases (uncontrolled BP group) while participants with an average systolic BP < 140 mmHg and diastolic BP < 90 mmHg were regarded as controls (controlled BP group).The bioimpedance spectroscopy device used to assess the fluid status was the Body Composition Monitor (BCM®), Fresenius Medical Care, Bad Homburg, Germany. Two electrodes were placed on the upper limb (wrist and dorsum of the hand) and two electrodes were placed on the ipsilateral lower limb (ankle and dorsum of the foot). The measurements were taken in a supine position and the average time of completion was 3 min. The following output data were recorded: total body water in liters (TBW), extracellular water in liters (ECW), ECW to TBW ratio, intracellular water in liters (ICW), lean tissue index (LTI) in kilograms per square meter, fat tissue index (FTI) in kilograms per square meter, dry weight in kilograms and OH in liters. Participants resumed PD after BIS was completed.P < 0.05 and 95% confidence intervals were used. Data were analyzed using Stata ver. 16.1 .All continuous variables with a normal distribution were reported as means and standard deviations and those that were not normally distributed were reported as median and interquartile range (IQR). Chi-squared and Fisher’s exact tests were used to compare categorical variables. Mann-Whitney U test was used to compare continuous variables that were not normally distributed while Student t-test was used for normally distributed data. Pairwise correlation was used to determine the correlation between OH and age, dialysis vintage, systolic BP, diastolic BP, mean arterial pressure, TBW, ECW, ICW, ECW to TBW ratio, LTI and FTI. Stepwise forward multiple regression was performed to identify predictors of OH. Statistical significance was regarded as a A total of 67 patients were screened. Seventeen patients were excluded for the following reasons: work-related restrictions (5), temporary modality change (3), inability to gain informed consent (3), peritonitis (2), PD for less than 1-month (2), PD stopped due to partial kidney recovery (1) and APD (1). Fifty patients were included in the final statistical analysis of which 17 (34%) of the patients were in the controlled BP group and 33 (66%) were in the uncontrolled BP group.P = 0.04). There were no differences in ethnicity or sex. The median PD vintage for the controlled BP group was 31  months vs. 15  months in the uncontrolled BP group; P = 0.02. There were no differences in self-reported RKF, diabetes mellitus status, the mean or absolute number and types of antihypertensive drugs or the timing of antihypertensive drugs relative to the BIS measurements. There were no differences in the type of PD solutions used or the frequency of exchanges between the two groups. None of the patients were using 4.25% PD solutions, shown in Table Table P < 0.01) and mean diastolic BP .The uncontrolled BP group had a higher mean systolic BP    , ECW  and ECW to TBW ratio ; however, there were no significant correlations between OH and TBW , ICW , dialysis vintage , age , LTI  or FTI .There were statistically significant correlations between OH and systolic BP  , a measuMixed ancestry and RKF were identified as predictors of OH using multivariable regression. In the Western Cape province of South Africa, nearly half the population is of mixed ancestral descent , therefoAlthough most of the patients that were prescribed icodextrin were in the uncontrolled BP group, the reason for its prescription was unrelated to poor BP or volume control. All these patients were either employed or were scholars. The use of icodextrin allowed them to avoid daytime exchanges during work/school hours. Sub-analysis of the uncontrolled BP group using icodextrin indicated that six of the nine patients had OH volumes ranging from 1.6 L to 5.1 L. We suspect that poor adherence to exchanges along with poor dietary restrictions may have contributed to this finding.Although not statistically significant, FTI was higher in the normotensive group which may explain the higher BIS dry weight in this group since there were no differences in LTI. The higher body fat mass is probably related to the longer dialysis vintage in this group, which has been reported by others . A subgrAlthough no statistical difference in BIS dry weight was identified, it was lower in the uncontrolled BP group. Since we did not identify any differences in LTI or the ICW compartment between groups, we expected the volume of the ECW compartment in the uncontrolled BP group to be lower; however, there was a trend toward a higher ECW compartment in the uncontrolled BP group. This is supported by the findings of significant correlations as well as predictors on multivariable regression between OH and ECW, and OH and ECW to TBW ratio. Although the ECW compartment was expanded, there were very few clinical signs to suggest fluid overload. The documented clinically estimated dry weight was higher in the uncontrolled BP group and lower in the controlled BP group. Many studies have reported on the poor diagnostic accuracy of the clinical examination in identifying subclinical fluid overload –11. TherThis study would implicate that by improving OH through reducing dietary salt intake and the modification of and adherence to the PD prescription, better BP control may be achieved; however, a recent Kidney Disease Improving Global Outcomes Controversies Conference on BP and volume management in dialysis recommended that future investigations should focus on whether “bioimpedance-guided volume management will improve patient-centered and hard clinical outcomes” .This was a small, single center study. Performing 24-h ambulatory BP monitoring may have resulted in more accurate BP measurements as well as eliminate the white coat effect; however, the use of office BP measurements was more pragmatic. Due to logistical constraints, we were unable to quantify ultrafiltration volumes and RKF.We found that stable CAPD patients with uncontrolled BP had higher OH compared to patients whose BP was controlled. Overhydration was confined to the extracellular water compartment. BIS may assist with a more objective assessment of dry weight, particularly in CAPD patients without obvious clinical signs of fluid overload.


Log-transformed VRI (log-VRI) positively correlated with serum creatinine and negatively correlated with A-FABP by multivariate linear regression analysis. We concluded that A-FABP correlated with endothelial dysfunction in chronic HD patients.Adipocyte fatty acid binding protein (A-FABP) is associated with atherosclerosis, and endothelial dysfunction is one of the reasons for adverse cardiovascular outcomes in patients undergoing hemodialysis (HD). This study investigated the correlation between serum A-FABP levels and endothelial function in HD patients. Fasting blood samples were collected from 90 HD patients. A-FABP levels were measured using a commercial enzyme immunoassay kit. Endothelial function was evaluated by a digital thermal monitoring test to measure vascular reactivity index (VRI). VRI < 1.0, 1.0 ≤ VRI < 2.0, and VRI ≥ 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. In total, 14 (15.6%), 38 (42.2%), and 38 (42.2%) HD patients had poor, intermediate, and good VRI, respectively. Patients with poor VRI had lower pre-HD and post-HD body weight, body mass index, and serum creatinine level but higher serum A-FABP level ( Cardiovascular disease (CVD) is the main cause of mortality in patients with chronic kidney disease (CKD), including those receiving dialysis . Risk faAdipocyte fatty acid binding protein (A-FABP), a member of the FABP family, is primarily expressed in adipocytes and macrophages and has been linked to CVD as well as metabolic diseases such as obesity, DM, HTN, chronic inflammation, and atherosclerotic processes ,13,14,15From October 2017 to February 2018, with the approval of the Research Ethics Committee, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (IRB106-108-A), we enrolled 90 patients aged >20 years who were maintained on HD using standard bicarbonate dialysate  thrice a week for more than three months. Patients who refused to provide informed consent or had amputated limbs, active infection, malignancy, heart failure, and bedridden status were excluded. The basic characteristics, duration of receiving HD, and medical history that included DM, HTN, and medications used were reviewed from the medical charts.After measuring height and post-HD body weight, the body mass index (BMI) was calculated as post-HD body weight (kg) divided by height (m) squared . About 5The patients fasted overnight and abstained from using tobacco, alcohol, caffeine, and vasoactive medications, after which endothelial function was measured using a digital thermal monitoring device . After resting in a temperature-controlled room for 30 min, blood pressure cuffs were placed on the patient’s arm without arteriovenous vascular access, and skin temperature sensors were placed on bilateral index fingers. Digital thermal monitoring of both hands was performed with each step of 5-min stabilization, cuff inflation, and deflation as the blood pressure cuff was rapidly inflated to 50 mmHg greater than systolic blood pressure for 5 min and then rapidly deflated to invoke a reactive hyperemic response in the fingertip distally. The more the temperature rebounded, the better the vascular reactivity. Vascular reactivity index (VRI) was defined as the maximal temperature difference between the rebound curve and zero reactivity curves during the reactive hyperemia period, calculated using the VENDYS software. VRIs were found to be in the range of 0.0–3.5, where a VRI of <1.0 indicated poor vascular reactivity, a VRI of 1.0–1.9 indicated intermediate vascular reactivity, and a VRI of ≥2.0 indicated good vascular reactivity ,22,23.p-value of <0.05 was considered statistically significant.Continuous variables were tested for normal distribution by the Kolmogorov–Smirnov test and expressed as mean ± standard deviation or median with interquartile range accordingly. Comparisons of continuous variables among groups  were performed by Kruskal–Wallis analysis  or one-way analysis of variance according to results of the Kolmogorov–Smirnov test. Categorical variables were analyzed using the chi-square test and expressed as numbers and percentages. HD duration, VRI, triglyceride, glucose, alkaline phosphatase, and iPTH levels were log-transformed to fulfill normality for further analyses. Simple and multivariable linear stepwise regression analyses were conducted to examine the correlation between VRI and clinical and biochemical variables of HD patients. Univariate and multivariate logistic regression analysis was used to analyze the A-FABP level for vascular reactivity dysfunction (intermediate vascular reactivity and poor vascular reactivity) or poor vascular reactivity. Analyses were performed using SPSS for Windows . G*power was used to calculate the sample size and power . A p = 0.016), post-HD body weight (p = 0.013), BMI (p = 0.034), and serum creatinine level (p = 0.010), and higher serum A-FABP levels (p = 0.001) were found in groups with worse VRI. Regarding comorbid conditions, 52 patients (57.8%) were identified to have HTN, and 49 patients (54.4%) had DM. No significant differences were observed in the following factors among the different groups: gender, blood pressure, presence of HTN or DM, and use of antihypertensive drugs and anti-lipid drugs.r = −0.404, p < 0.001) correlated negatively with log-VRI values, whereas pre-HD body weight , post-HD body weight , BMI , and serum creatinine level  correlated positively with log-VRI values in HD patients. Multivariate forward stepwise linear regression analysis of the variables that were significantly associated with log-VRI revealed that serum A-FABP level  and serum creatinine level  were significantly and independently associated with log-VRI values in HD patients. Two-dimensional scatter plots of VRI values with serum creatinine level and serum A-FABP level among patients undergoing HD are presented as The correlations between the clinical characteristics and serum log-transformed VRI (log-VRI) values of the 90 HD patients are presented in p = 0.011) and poor vascular reactivity index  showed A-FABP was positively and independently associated with poor vascular reactivity, respectively, by univariate and multivariate logistic regression analysis adjusted data for factors including pre-HD body weight, post-HD body weight, BMI, creatinine, and A-FABP levels  (odds ratio (OR) = 1.010; 95% confidence interval (CI) = 1.002–1.018; P levels .This study demonstrated that after adjusting for confounders, serum A-FABP level correlated negatively with VRI, and creatinine level correlated positively with VRI measured by digital thermal monitoring in HD patients.Along with traditional risk factors for CVD in patients with advanced CKD, including those on dialysis, endothelial dysfunction is additionally considered as a progressive factor ,3,6,8. EAfter its discovery in 1972, A-FABP, a small cytosolic polypeptide abundantly expressed in tissues with active lipid metabolism, such as the heart and liver or cells specialized for lipid storage, trafficking, and signaling such as adipocytes and macrophages, was well known to be associated with several metabolic disorders and CVD ,13. In tThere were limitations of this study. Firstly, this was a cross-sectional design study. Secondly, there was a limited number of HD patients, which may have affected the statistical significance. Only 90 HD participants were enrolled in this study, and the power to predict endothelial function was only 0.73. Third, this study did not measure the B-type natriuretic peptide or hydration status of patients. However, the findings of our previous studies ,38 suggeThis study elucidated the risk factors for endothelial dysfunction measured by VRI and showed that along with serum lower creatinine levels, higher A-FABP levels could be a potential biomarker of endothelial dysfunction in HD patients.


Hepatectomy is a complex procedure with high morbidity and mortality. Early prediction/prevention of major complications is highly valuable for patient care. Surgical APGAR score (SAS) has been validated to predict post-surgical complications (PCs). We aimed to define a simple complications classification following hepatectomy based on a therapy-oriented severity Clavien-Dindo classification (CDC). 119 patients undergoing liver resection were included. PCs were determined at follow-up based on CDC. Clinicopathological factors were used to calculate SAS. A receiver-operator characteristic (ROC) curve analysis estimated the predictive value of SAS for PCs. Circulating markers levels of liver injury were analyzed as critical elements on PCs. SAS (P=0.008), estimated blood-loss (P=0.018) and operation time (P=0.0008) were associated with PCs. SAS was reduced in patients with (+) compared to those without (−) complications . The area-under-the-curve was 0.646 by ROC, indicating an acceptable discrimination with 65% possibility to distinguish (−) and (+) groups (P=0.004). Best cutoff value for SAS was ≤6/≥7, at which sensitivity and specificity were maximal. ALT/ASL levels were significantly different within the group with 9-10 SAS points (P=0.01 and 0.02). In conclusion, SAS provides accurate risk stratification for major PCs after hepatectomy, and might help improving the overall patient outcome. However, hepatectomy is associated with high postoperative morbidity, high 30-day complications and high mortality -3. The mMany groups have previously demonstrated that SAS is a useful model to predict early complications after a variety of procedures, such as radical cystectomy, colon and rectal resection, herniorraphy, thyroidectomy, parathyroidectomy, endovascular repair of abdominal aortic aneurysm, cytoreduction, esophageal resection, gastrectomy, etc. -22. It w2.2.1st 2002 until January 1st 2012, in the department for Hepatobiliary and Transplant Surgery of the Medical University of South Carolina, USA, were identified. Thirteen patients had MELD score ≥ 9 (9-15). Forty-one patients underwent ≤ 2 segment hepatic resections, and seventy-eight underwent > 2 segment hepatic resections. Liver resection was defined as partial resection of hepatic tissue for the treatment of hepatic diseases, excluding liver transplantation or segmental liver procurement for living donor transplantation. Postoperative complications were determined by the surgeon team in the course of the hospital stay or at a postoperative presentation, based on the Clavien-Dindo classification system (CDC). Clinicopathological parameters, including lowest mean arterial pressure, lowest heart rate, and estimated blood loss, were gathered and used to calculate SAS points  undergoing liver resection from January 1S points . We used2.2Patient data collected included demographics, operative procedure and indications for surgery, anesthetic approach, intraoperative physiologic data, and outcomes before discharge from the hospital. A total of 132 variables were extracted from the electronic information management system. The following preoperative variables were collected: demographics, diagnosis, cancer stage, liver function, coagulation function, hepatitis serology data, comorbidities, and a routine blood test results. We collected additional 28 variables from the intraoperative anesthesia records including highest systolic blood pressure, highest diastolic blood pressure, MAP , heart rate , central vein pressure , estimated blood loss (EBL), operation routine and protocol, operative duration (incision-to-skin closure time), temperature and oxygen saturation , volume of urine output, volume of IV fluids with colloid, crystalloid, and blood products administered, use of pressure support medication, and anesthesia type and time. Hemodynamic variables were recorded every 5 minutes, and other variables were updated hourly. The complications mentioned below were also collected.2.3Dependent variables related with outcomes were mortalities or morbidities within 30 days after operation. The following events were defined as major complications; acute renal failure, bleeding requiring ≥ 4 U red cell transfusion within 72 hours after operation, cardiac arrest requiring CPR, coma for 24 hours or longer (intubation greater than 24 hours), deep venous thrombosis, septic shock, myocardial infarction, unplanned intubation, ventilator use for 48 hours or longer, pneumonia, pulmonary embolism, stroke, wound disruption, deep or organ-space surgical site infection, sepsis, systemic inflammatory response syndrome, and vascular graft failure, according to NSQIP established definitions. A group of physician reviewers determined by consensus the following special major complications after liver resection: biliary fistula or bleeding requiring further operation and acute hepatic failure requiring hepatic support or liver transplantation. Patients having complications categorized in the database as “other occurrence” were reviewed individually, and the severity of the occurrence was evaluated according to the CDC system. The complications of CDC Class III and greater  were also considered as major complications.2.4Univariate analysis was performed between each preoperative and intraoperative variable with major complications using Pearson’s Chi-square for nominal variables or Student t test for continuous variables. Complication rates by individual and categorized SAS or CDC were compared using Chi-square test. Patients with SAS 9-10 served as reference. The discrimination was computed with the c-statistic from a univariable logistic regression using SAS as a categorical predictor, and the incidence of major complications as the outcome. SAS statistical software version 9.1  was used to analyze all data. To access the potential of the SAS points system to predict major complications, receiver operator characteristic (ROC) analysis was performed and the area under the curve (AUC) was analyzed according to DeLong et al . The val3.3.1The clinicopathological preoperative and intraoperative characteristics of all 119 patients  are summarized in 3.2The surgical APGAR score (SAS) was calculated using three intraoperative variables : estimat3.3To determine the contribution of diverse clinicopathological factors, we compared the patients without (−) and with (+) postoperative complications according to the preoperative and intraoperative characteristics included in 4.Our work demonstrates a good performance of the surgical APGAR Score (SAS) for predicting postoperative complications after liver resection in patients either with hepatocellular carcinoma (HCC) or other benign/malign etiologies. To date, few groups have demonstrated the usefulness of the SAP score calculation in HCC patients with preoperative, but not intraoperative parameters. We detected novel parameters significantly altered in patients with postoperative complications compared to patients without complications. Thus, we propose for the first time the inclusion of two circulating markers in patients with high SAS points, which might suggest, upon further robust validation, an independent early-parameter positively correlating the SAS score prediction.Preoperative and intraoperative factors have significant contributions to the postoperative outcome of patients who undergo major surgeries including hepatectomy ,37. Hepa


Statistically significant negative correlations were also observed between red cell count and white blood cell count and HOMA-IR with a p < 0.01. Since discrete hematological but significant changes correlated with HRR and HRR-derived parameters, we consider that these measures are helpful in clinical settings to identify subclinical autonomic dysfunction that permits us to prevent or anticipate chronic and fatal clinical outcomes.There are several methods to assess the function of the autonomic nervous system. Among them, heart rate recovery (HRR) is an accepted, easy, low-cost technique. Different pathological conditions have been related to the development of autonomic dysfunction. Our study aimed to evaluate the relationship between HRR and HRR-derived parameters in ambulatory patients with asthma or type 2 diabetes followed at the National Institutes of Health in Mexico City. A total of 78 participants, 50 women and, 28 men were enrolled; anthropometric, respiratory evaluations, and fasting blood samples were taken before participants performed a 6-min walking test (6MWT). Abnormal HRR was defined as a drop of ≤8 and ≤11 beats/min at 1 or 2 min and correlated negatively with basal oxygen saturation at 1 min. Heart rate at 1 min, correlated negatively with final oxygen saturation ( The autonomic nervous system (ANS) is in charge of a series of reflex reactions. The maintenance of a stable internal environment depends on the balance between the sympathetic and parasympathetic systems. Changes in the activity of ANS can occur temporarily, but the majority of chronic diseases are associated with an important dysregulation of ANS. Asthma, diabetes, and obesity, common chronic diseases, are associated with each other as comorbidity, but also linked to meta-inflammation where a myriad of manifestations of autonomic alterations has been identified ,2. ThoseDifferent abnormal HRR (aHRR) cutoffs have been utilized in the past. For example, a cutoff of ≤42 beats/min after 2 min of recovery predicted cardiovascular death. A cutoff of ≤22 beats/min during the first 2 min after exercise anticipated the presence of coronary artery disease and death in males. Moreover, a decline of ≤42 beats/min after 2 min is associated with impaired fasting plasma glucose and an abnormal triglycerides/HDL cholesterol ratio (highest quartile) in healthy adults. Clinical deterioration in idiopathic pulmonary arterial hypertension is associated with less than 16 beats/min at the first minute. Abnormal HRR of 13 and 22 beats/min at the first and second minute, respectively, are good predictors of mortality in idiopathic pulmonary fibrosis. In chronic obstructive pulmonary disease (COPD), a cutoff of ≤12 beats/min in the first minute is related to pulmonary function, oxygen saturation, and disease severity .HRR is a predictive biomarker of clinical worsening, hospitalization, and survival of different diseases such as connective tissue disease-associated pulmonary hypertension, idiopathic pulmonary fibrosis, poorly controlled severe asthma, cystic fibrosis, chronic obstructive pulmonary disease (COPD), bronchiectasis, heart failure, and diabetes ,11,12. HAcute coronary syndrome has been associated with changes in blood cell count  and propWe undertook this study at the Instituto Nacional de Enfermedades Respiratorias Ismael Cosío Villegas (INER) in Mexico City at 2240 m above sea level and treating mainly uninsured patients. The institutional Ethics Committee granted ethical approval, code C22-14, and all the participants signed an informed consent form. Sensitive information was removed from the collected data to preserve the anonymity of the participants. We conducted the study under the ethical principles of the Declaration of Helsinki.2, individuals who had smoked at least 100 cigarettes and who smoked at the time of the study, treatment with beta-blockers and patients with an acute respiratory infection or asthma exacerbation within the previous 6 weeks at the time of the study were excluded. We did not analyze data from patients unable to perform the 6MWT.We conducted a cross-sectional study of ambulatory patients with controlled asthma from the Asthma Clinic of the INER and patients with type 2 diabetes (T2D) recruited from the nearby Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ). Males and females aged 18 to 65 years, free of major diabetes-related chronic complications, and displaying HbA1c levels < 12%, and healthy volunteers, were invited to participate. Patients with a previous diagnosis of a cardiac congenital condition, autoimmune disease (including type 1 diabetes), oncologic disease, total cholesterol > 200 mg/dL, triglycerides > 300 mg/dL, thyroid disease, a body mass index less than 20 or more than 40 Kg/m® mBCA-514 analyzer, Hamburg, Germany). Anthropometric measurements including neck and waist circumference, complete blood count (CBC), and blood chemistry (BC) were obtained. Respiratory function was evaluated with forced spirometry  following the ATS/ERS 2005 guidelines; fractional exhaled nitric oxide (FeNO) and exhaled carbon monoxide measurements were also performed. Exhaled carbon monoxide was measured with a Smokerlyzer® ; FeNO measurements were conducted at a constant flow of 50 mL·s−1 in line with the ATS/European Respiratory Society (ERS) recommendations using a portable handheld analyzer . The 6MWT was performed indoors, along a flat, straight, 30 m walking course, according to the guidelines of ATS/ERS 2014 [fHR is final heart rate and xHR is heart rate at rest.All participants were asked to stop short- and long-acting inhaled beta2 agonists as well as anticholinergic drugs such as ipratropium bromide 12 h before the 6-min walking test (6MWT). If they could not stop their medication, the 6MWT test was not performed. Body composition (BIA) was estimated with a bioimpedance analyzer  and an aneroid sphygmomanometer  to detect the appearance and disappearance of the Korotkoff sounds and performed by the same device and same pneumologist specialized in respiratory tests to minimize inter-device and interobserver variability. Blood pressure was categorized according to the American Heart Association criteria [https://amhigo.com/mi-diagnostico/calculadoras/indice-de-resistencia-a-la-insulina-homa-ir, accessed on 19 October 2019) with cutoffs for the Mexican population. We also obtained values for waist-to-height-ratio (WHtR) and neck circumference. Finally, based on the atherogenic indices, the groups were classified as low or high risk.Arterial blood pressure and blood samples were obtained before the 6MWT and the lung function tests; all tests were carried out during fasting at the same hour of the day to avoid circadian variations in the autonomic nervous system activity. Arterial blood pressure was measured after a 5-min rest in a seated position by auscultation of the brachial artery with a stethoscope  and 2 (aHRR2) with cutoff values set at ≤8 and ≤11 bpm, respectively, based on the first quartile of all the data; presence or absence of asthma; type 2 diabetes and metabolic syndrome (MetS); BMI classification; WHtR; and high or low atherogenic risk. All data are expressed as the median followed by the interquartile range 25–75 (IQR). Correlations between variables were performed with a Spearman’s test. Comparisons between more than two groups were made using a non-parametric Kruskal–Wallis test followed by a post-hoc Dunn’s test. A Wilcoxon rank-sum test was used to compare two groups. A chi-square test was used to compare frequencies between two categorical variables. All statistical analyses were conducted in STATA 13 . Graphs were created using GraphPad Prism version 6.00 for Windows .A total of 78 participants were enrolled. The general characteristics of the population are summarized in The atherogenic indices calculated related the studied population with a high risk for cardiovascular disease (CVD) Respiratory-related measurements and bioelectrical impedance, blood cell counts, and blood chemistry parameters are shown in Relationship between HR, HRR, and rHRR from the 6MWT (indicators of a dysautonomic state) and general health parameters, can be seen in a representative graph in We included basal, final oxygen pulse saturation  and FeNO from the respiratory-related measurements. A statistically significant positive correlation between SpO2b and HRR1 (rho 0.309) and rHRR1 (rho 0.289) was observed .Our data showed a statistically significant difference in SpO2b between the HRR1 group (95%) and the normal aHRR1 group (93%). Moreover, SpO2f correlated negatively with HR1. However, SpO2f was lower in the aHRR1 group compared to the group with normal HRR1. There was also a difference in FeNO concentration between the compared HRR2 and aHRR2 groups .p = 0.047), similarly, PA correlated negatively with rHRR1  and rHRR2   negatively correlated with rHRR1, but it displayed a trend to increase with aHRR1 and aHRR2 . Phase a= 0.015) . p = 0.045), which was statistically significant. A statistically significant increase in intracellular water was observed in the aHRR1 group, 20.3 L (16.2–26), compared to those with normal HRR1, 17.05 L (15.1–20.3); p = 0.038, Intracellular water showed a negative correlation with rHRR1 , rHRR1 , and rHRR2 . Hydration was significantly lower in aHRR1 versus the normal HRR1 group  and HR2 (p < 0.05). By contrast, HOMA correlated negatively with HRR1 (p < 0.05), rHRR1 correlated negatively with insulin (p < 0.05) and HOMA-IR (p < 0.05). We can observe an increase in HOMA-IR in aHRR1 subjects, with a marginal p-value (p = 0.052) (The blood chemistry parameters used in the present study are shown in = 0.052) . p < 0.05) but, this correlation was marginal with AC (p = 0.05), HR1 and HR2 displayed a positive correlation with some dyslipidemia parameters as can be seen in As we mentioned earlier, there was a high prevalence of cardiovascular risk among the participants. rHRR2 showed a statistically significant correlation with Castelli-I . Our study proposes a relationship between BIA measurements and the HR recovery after exercise, implying a dysautonomic state of the patients. Phase angle, intracellular water, and hydration percentage showed statistical differences related to dysautonomia as determined by a slow HRR. At present, there are different indices to establish nutritional condition ; however, BIA provides additional information regarding the nutritional state than other parameters. Phase angle showed a significant correlation with HR, HRR, and rHRR whereas other indicators of a nutritional condition such as BMI, WHtr, NC and WC, did not show any statistical association. The SMM parameter showed marginal and discrete statistical differences. This result suggests an increase in muscle mass, possibly cardiac muscle mass. Bioimpedance cannot distinguish between skeletal and visceral muscle mass. Disturbances of the autonomic nervous system are present in heart hypertrophy of different etiologies, such as hypertension or atherogenic risk, and heart failure to compensate for the cardiac output .Studies report that the immune response can contribute to autonomic nervous system dysfunction through immune signaling molecules like cytokines, affecting heart rate variability , which cHematological parameters are related to oxygen transport and iron deficiency. Total erythrocytes, hemoglobin, and hematocrit showed a correlation and discrete changes related to HR recovery.Insulin resistance syndrome contributes to HRR in adolescents, adults, and elderly men ,26. It cIn summary, this study describes respiratory-related parameters, body composition, and cellular and biochemical blood changes in a population with asthma, type 2 diabetes and obesity, under medical control. These medical conditions lower life expectancy due to a higher risk of developing fatal cardiovascular events. Furthermore, overweight and obesity per se are also significant risks for CVD and have a negative impact on fitness performance independent of age . The 6MWThe time difference in heart rate recovery after cessation of exercise is a biomarker of the outcome. Van de Vegte, et al.  reportedOur study suggests that HR, HRR, and rHRR are related to biochemical, cellular, and physiological responses. Patients with dysautonomia showed lower oxygen saturation that harms the microvasculature because of oxygen restriction. These physiological changes contribute to the disruption of the autonomous nervous system. They also promote subclinical immunological and hematological modifications to compensate for a hypoxic environment. Immune cells promote inflammation that contributes to insulin resistance syndrome concomitant with dysregulation of the hydric state, expressed by water body composition. Inflammation and insulin resistance favor autonomic nervous dysregulation and the integrity of the vagal nerve.Heart rate variability (HRV) is another clinical tool used to evaluate autonomic nervous dysregulation. One methodological advantage of HRR using the 6MWT over HRV is the procedure and the cost of the equipment, which is more expensive for HRV compared to the 6MWT; however, HRV statistical or domain parameters are more refined than those of resting HR or the estimation of HRR. Nevertheless, the use of HRR methodology results in a low-cost test that is easy to perform and quickly interpreted by health or sports staff. Even though both HRV and HRR are accepted as non-invasive measurements of autonomic dysfunction, and useful biomarkers for worsening and death prognosis, there is still a debate about the lack of correlation between HRR and HRV, influenced by independent aspects of cardiac function  . These tLimitations of the present study are the low number of patients recruited and the poor relation of the biochemical and hematological parameters to the extended reported outcomes related to HRR, such as survival and clinical worsening. However, a relevant contribution of the present study is the relation of HRR and biochemical, cellular, and physiological parameters that can explain autonomic dysfunction and the increase of atherogenic risk to this condition. Evaluation of HR, HRR, and rHRR after a 6MWT, biomarkers of autonomic dysfunction, are simple clinical tools, responding to discrete changes in respiratory-related measures, body composition, blood cell count, and blood chemistry. Those biomarkers may identify abnormalities in apparently healthy patients that could prove clinically relevant for prognosis and treatment selection and proper follow-up.


Whereas more AFB sessions were performed in patients at risk of hemodynamic intolerance, episodes of intradialytic hypotension were significantly less frequent during AFB compared to B-IHD, whatever the classification used  and after adjustment on the use of vasoactive agent. Diastolic blood pressure readily increased throughout the dialysis session. The use of a bicarbonate zero dialysate allowed the removal of 113 ± 25 mL/min of CO2 by the hemofilter. After bicarbonate reinjection, the global CO2 load induced by AFB was +25 ± 6 compared to +80 ± 12 mL/min with B-IHD (p = 0.0002). Thus, notwithstanding the non-controlled design of this study, hemodynamic tolerance of AFB appears superior to B-IHD in mechanically ventilated patients. Its use as a platform for CO2 removal also warrants further research.Intradialytic hypotension can lead to superimposed organ hypoperfusion and ultimately worsens long-term kidney outcomes in critically ill patients requiring kidney replacement therapy. Acetate-free biofiltration (AFB), an alternative technique to bicarbonate-based hemodialysis (B-IHD) that does not require dialysate acidification, may improve hemodynamic and metabolic tolerance of dialysis. In this study, we included 49 mechanically ventilated patients requiring 4 h dialysis (AFB sessions  Because intradialytic hypotension can lead to superimposed organ hypoperfusion and ultimately mitigate long-term kidney outcomes after acute kidney injury, it remains a concern in critically ill patients requiring kidney replacement therapy. Intradialytic hypotension results from an inadequate compensatory response  to ultrafiltration rate, cardiac output decrease and/or arterial tonus changes during the session .Dialysate composition may influence hemodynamic tolerance of intermittent hemodialysis (IHD) performed in the ICU ,3. UsualAcetate-free biofiltration (AFB) is an alternative technique of IHD based on a bicarbonate-free dialysate  with post-filter reinjection of sodium bicarbonate. Few studies suggested that AFB may be better tolerated than B-IHD in patients receiving chronic dialysis , but resThis report describes our findings of hemodynamic and metabolic outcomes in mechanically ventilated patients receiving dialysis with AFB or B-IHD.Between February 2020 and March 2021, we prospectively included patients admitted to the ICU and receiving mechanical ventilation, who had intermittent sessions of hemodialysis.®, Toulouse, France) and Safebag  dialysates, respectively. Sodium conductivity was 13.5 to 13.7 mSv. Membranes were the Elisio 21H  or Evodial  polyethersulfone filters. AFB dialysate composition was the following: sodium 140 mmol/L, chloride 146 mmol/L, calcium 1.5 mmol/L, magnesium 0.5 mmol/L, glucose 5.5 mmol/L, potassium 3.5 mmol/L (sodium conductivity was settled at 13.5 to 13.7 mS/cm). Solution of sodium bicarbonate that was reinjected had a concentration of 167 mmol/L. B-IHD dialysate composition was the following: sodium 140, chloride 108 mmol/L, potassium 3 mmol/L, calcium 1.65 mmol/L, magnesium 0.5 mmol/L, citrate 0.8 mmol/L, and glucose 1 g/L (sodium conductivity was settled at 14–14.5 mS/cm). Dialysate temperature was 1 °C below the patient temperature. Blood flow was settled 250 to 300 mL/min.B-IHD and AFB were performed with the Citrasate  . In addi2 load induced by dialysis sessions was approximated with the following formula: CO2 load = [total inflow CO2 content minus total outflow CO2 content] × blood flow × time.In a subset of AFB and B-IHD sessions, blood gases were measured before and after the filter for B-IHD, or before and after the filter and after the bicarbonate reinjection for AFB. The global COContinuous variables were given as mean ± SEM and compared with the Mann–Whitney test. Discontinuous variables were given as number (percentages) and compared with Fisher’s exact test, after adjustment on the use of vasoactive agent at baseline. Hemodynamic parameters of AFB and B-IHD sessions were compared with a two-way ANOVA test with mixed-effects.All patients included in this study gave informed consent. This study was conducted according to the Best Clinical Practices guidelines and the Declaration of Helsinki, as revised in 2004, and approved by the French national ethics committee (COOBRA study no. ID-RCB 2019-A03261-56).n = 66) or B-IHD (n = 62) , who received 4 h sessions of AFB ((n = 62) . The meap = 0.002), with underlying chronic obstructive broncho-pneumopathy , admitted for sepsis  or with ongoing vasoactive support , episodes of intradialytic hypotension were significantly less frequent during AFB compared to B-IHD, whatever the classification used (decrease in mean blood pressure ≥ 10 mmHg: 36/66 (54%) vs. 46/62 (74%) sessions, p-value = 0.02; systolic blood pressure decrease >20 mmHg: 27/66 (41%) vs. 40/62 (64%) sessions, p-value = 0.007). After the adjustment on the use of vasoactive agent at the start of the session, an episode of systolic blood pressure decrease below 95 mmHg was more frequent during dialysis sessions with B-IHD (25/62 (40%)) compared to AFB (16/66 (24%); adjusted p-value 0.03). Hemodynamic monitoring showed significantly better global tolerance of AFB sessions owing to increased diastolic blood pressure and stable systolic blood pressure, without concomitant increase in norepinephrine , compared to 2.3 L/h and 300 mL/min, respectively .2, bicarbonate concentration and pH in blood returning to the patients were 60 ± 4.4 mmHg, 32 ± 2.3 mmol/L and 7.34 ± 0.04 compared to 45 ± 9.6 mmHg [p < 0.001], 24 ± 4.9 mmHg [pH < 0.001] and 7.35 ± 0.07 [p = 0.79], respectively  was characterized by very low concentration of bicarbonate and partial pressure of CO2, leading to a decrease in the total CO2 content from 23 ± 3.3 to 5.2 ± 2.6 mmol/L . The global CO2 load  induced by AFB sessions was +25 ± 6 compared to +80 ± 12 mL/min with B-IHD .Last, we estimated the net balance of CO2 in blood outflow during B-IHD may activate circulating inflammatory cells [2, high bicarbonate levels, normal pH) that returns to the patient during B-IHD may modulate the vascular tone of the pulmonary artery [In this study, we showed that hemodynamic tolerance was better in mechanically ventilated critically ill patients receiving AFB compared to conventional B-IHD, despite higher vasoactive support at the start of AFB sessions. This held true that the tolerance was assessed using the K/DOQI classification or the quantitative assessment of hemodynamic parameters. Because other dialysis and patient characteristics were balanced between the two groups or in favor of B-IHD, the discrepancies between the contents of the blood that returns to the patients during AFB and B-IHD probably account for the divergent hemodynamic tolerance. We first hypothesized that large amounts of COry cells ,11 and iy artery ,13,14 an2 [2 load was significantly reduced during AFB sessions compared to B-IHD sessions. This may be of utmost interest in patients at risk to develop hypercapnic acidosis  but also at risk of hypercapnia-induced high intracranial pressure. Second, we report a case of COVID-19-related acute respiratory distress syndrome complicated by refractory hypercapnia and core pulmonal successfully reversed by AFB. Even if the development of customized “balanced” dialysates with low chloride concentrations and no bicarbonate will be helpful in developing true “respiratory dialysis” [Last, we confirmed in humans the potential of dialysis with low-bicarbonate dialysate to remove CO2 . We firsialysis” , AFB mayThis study has some limitations, mainly related to its uncontrolled design. First, the risk factors of hemodialysis intolerance were not balanced between the two groups, but these risk factors were more frequent in the AFB sessions group. The positive results in favor of AFB we observed thus reinforce its probable superiority. Secondly, at baseline, hemodynamic status of patients was heterogeneous. Further comparative randomized studies are thus required to confirm our results, especially in patients with vasoactive support . Last, the mechanisms by which tolerance of AFB is superior to B-IHD still remain elusive and will require additional studies in humans or in animals.2 removal also warrants further research.We showed that AFB is safe in critically ill patients. Notwithstanding the non-controlled design of this study and its potential biases, our findings suggest that hemodynamic tolerance of AFB is superior to B-IHD in mechanically ventilated patients. If confirmed, it may reduce superimposed artificial kidney-induced kidney injuries and improve long-term kidney outcomes. Its use as a platform for CO


Obstructive sleep apnea (OSA) is often accompanied by other complications, especially hypertension.The purpose of this study is to compare the application value of six tools in the screening of OSA in patients with hypertension. Compared with other questionnaires, we hypothesized that Berlin performed better in screening hypertensive patients suspected of OSA.In this study, we collected the basic data and polysomnography (PSG) data of patients diagnosed with hypertension who underwent PSG at the Sleep Medicine Center of the First Affiliated Hospital of Guangzhou Medical University from April 2012 to March 2021. The sensitivity, specificity, positive predictive value, negative predictive value, area under the curv (AUC) and diagnostic odds ratio (DOR) of the six screening tools were then calculated, and their correlation with the sleep apnea hypopnea index (AHI) analyzed.There were 303 males  out of 398 hypertension patients suspected of OSA. The area under the curve of the Berlin questionnaire's receiver operating characteristic (ROC) curve reached 0.753 (95%CI: 0.707–0.794). When the AHI was 5, 15 and 30 times/h as the cut‐off points, the sensitivity and negative predictive value of Berlin were the highest at 0.947 and 0.630, 0.970 and 0.851, and 0.988 and 0.957 respectively, while the specificity and positive predictive value of the Epworth Sleepiness Scale (ESS) were the highest at 0.696 and 0.729, 0.750 and 0.887, and 0.674 and 0.575 respectively. The DOR value of the Berlin questionnaire could reach 18.333 when the AHI cut‐off point was 30 times/h. Berlin had the largest rank correlation coefficient with AHI at 0.466.The Berlin questionnaire can be considered a priority for the screening and stratifying of hypertensive patients suspected of OSA. AHIapnea hypopnea indexAUCarea under the curveBMIbody mass indexCIconfident intervalDORdiagnostic odds ratioDPdiastolic pressureESSEpworth Sleepiness ScaleHRheart rateMean‐NOXmean nocturnal oxygen saturationMin‐NOXminimum nocturnal oxygen saturationNCneck circumferenceNPVnegative predictive valueOSAobstructive sleep apneaPPVpositive predictive valuePSGpolysomnographyROCreceiver operating curveSDBsleep disordered breathingSPsystolic pressureWCwrist circumference1Obstructive sleep apnea (OSA) is a kind of disease in which partial or complete upper airway obstruction occurs repeatedly during sleep, causing a series of clinical manifestations.At present, the gold standard for diagnosing OSA is polysomnography (PSG) at night, but this is expensive, time‐consuming and limited to areas with good medical care, which will cause delays in the diagnosis and treatment of a large number of patients with suspected OSA.22.1This study collected data on patients diagnosed with hypertension who underwent PSG examination at the Sleep Medicine Center of the First Affiliated Hospital of Guangzhou Medical University from April 2012 to March 2021. If a patient had a clear history of hypertension or was taking antihypertensive drugs, or they had systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg before and after monitoring, they were considered hypertensive. This study was approved by the medical ethics committee of the hospital (Ethics Number: 201705), and eligible patients were selected according to the inclusion and exclusion criteria. Inclusion criteria: (a) Patients who first came to the sleep respiratory center for PSG monitoring due to complaints of snoring, lethargy, high blood pressure or apnea; (b) Patients diagnosed with hypertension; (c) Patients aged between 18 and 80 years old (including 18 and 80 years old); (d) Patients who had autonomous behavioral ability and cognitive ability, had completed six scales in the sleep laboratory and agreed to sign the informed consent; (e) Patients with total sleep time > 4 h. Exclusion criteria: (a) Patients with coronary heart disease, diabetes, kidney disease, chronic lung disease, or cerebrovascular disease; (b) Patients with a history of brain tumors or epilepsy; (c) Patients with various mental and psychological diseases who were taking sedative and sleeping pills; (d) Patients with severe organ failure; (e) OSA patients who had received treatment; (f) Patients with incomplete answers on the scale; (g) Patients with sleep apnea hypopnea syndrome with predominantly central or mixed events.2.2In our study, we collected general information such as the patients' name, age, gender, occupation, education, smoking, drinking, height, weight, neck circumference, waist circumference, blood pressure, and so on. The patient and family members filled in the ESS, STOP, STOP‐Bang and Berlin scales together, and the sleep technician verified the items on the scales to ensure their reliability, then took back the completed questionnaires. The researchers then refined the NoSAS and No‐Apnea scores based on the general data.2.32 is 3 points, BMI ≥30 kg/m2 is 5 points; ③ Snoring is 2 points; ④ Age ≥ 55 years old is 4 points; ⑤ Male is 2 points. If the NoSAS score ≥ 8 points, it indicates that the patient is at high risk of OSA.NOSASNo‐ApneaESSSTOP2], A (age > 50 years old), N (neck circumference > 40 cm), G . Answer with “yes” or “no”; “yes” is 1 point, “no” is 0 points. If the STOP‐Bang score is ≥3 points, it indicates that the patient is at high risk of OSA.STOP‐BangBerlin2.4PSG monitoring was mainly used to diagnose sleep disordered breathing. Recording indicators include electroencephalogram, electrooculogram, mandibular electromyography, oral and nasal airflow and respiratory movement, electrocardiogram, blood oxygen saturation, snoring, limb movement, body position and other parameters. We used an Alice 5 polysomnograph made by the Philips Wellcome Company to record continuously and synchronously for at least 7 h. After automatic analysis, the original parameters were manually reviewed and corrected, and finally interpreted and analyzed by trained sleep physicians. Sleep apnea hypopnea index (AHI) refers to the number of apnea and hypopnea events per hour of sleep. Patients with AHI ≥5 times/h and obstructive apneas as the main respiratory event were judged to have OSA in the following disease grades: normal group (AHI < 5 times/h), mild OSA group (5 ≤ AHI < 15 times/h), moderate OSA group (15 ≤ AHI < 30 times/h), severe OSA group (AHI ≥30 times/h).2.5p value for comparing the area under the ROC curve of single and multiple indicators. The correlation between the six scales and AHI was analyzed using the bivariate correlation method. Pearson correlation analysis was used for the normal distribution data, and Spearman correlation analysis was used for the non‐normal distribution data. p < .05 was defined as statistically significant.SPSS 26.0 statistical software was used for analysis. The measurement data of normal distribution were expressed as mean ± SD, the measurement data of skewed distribution was expressed as median   and the count data was expressed as frequency. For the measurement data, a one‐way analysis of variance test was used for normal distribution, a multi‐group independent sample rank test  (w) multiple comparison) was used for skewed distribution data, and a chi‐square test or Fisher's exact probability method was used to count the data. The diagnostic results of the scales and PSG were calculated in the form of a four‐grid table for the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), and negative likelihood ratio (LR‐) of each scale, and reported with respective 95% confidence intervals (CI). The ROC curve was analyzed using MedCalc software to evaluate the diagnostic value of the five scales for OSA, and calculate the 33.1p < .001) with the disease predominantly affecting males, but there was no statistically significant difference for smoking and drinking. The average age of these patients was (51.8 ± 12.5) years old, average systolic blood pressure was (149.2 ± 17.6) mmHg, average diastolic blood pressure was (95.9 ± 11.6) mmHg, average heart rate was (79.4 ± 12.2) beats/min, average body mass index was (27.6 ± 3.8) kg/m2, average neck circumference was (39.4 ± 3.8) cm and average waist circumference was (98.6 ± 10.7) cm. There were no statistically significant differences in age, systolic blood pressure or diastolic blood pressure, but differences in heart rate, body mass index, neck circumference and waist circumference were statistically significant (p < .001). The medians of NoSAS, No‐Apnea, ESS, STOP, STOP‐Bang, Berlin, AHI, lowest nocturnal oxygen saturation, and mean nocturnal oxygen saturation were respectively 11  points, 4  points, 8  points, 3  points, 5  points, 2  points, 19.7 times/h, , 80%  and 94% , with statistically significant differences (p < .001). In the post test, except for drinking, age, systolic blood pressure and diastolic blood pressure, there were significant differences among the severe OSA group and normal group, and the mild OSA group and moderate OSA group respectively (p < .005) , 152 were smokers  and 105 cases were drinkers . Among them, the gender difference was statistically significant (3.2p < .001). When AHI was 20, 25, and 30 times/h as the cut‐off point, the predictive value of STOP‐Bang was significantly better than those of the other five scales with statistically significant difference (p < .005) , so it needs to be further verified in other environments.5In conclusion, for screening hypertensive patients suspected of OSA, although there are many test contents in Berlin, relatively speaking, it is still better than the other five screening tools, and can be considered a priority for the screening and stratification of hypertensive patients suspected of OSA. The screening of STOP‐Bang is better than that of STOP, NoSAS and ESS, and it can also be used to screen for hypertensive patients suspected of OSA. NoSAS is simple to use but requires further certification as a new screening tool. Finally, ESS is not effective and no‐apnea may not be suitable in screening for hypertensive patients suspected of OSA.The authors declare no conflicts of interest.


Anemia and electrolyte disturbances are adverse outcomes of chronic kidney disease (CKD). This study explored the association between metabolic parameters with anemia and electrolyte and mineral disorders among CKD patients in Taiwan.This cross-sectional study with a total of 2176 CKD stages 3–5 patients were collected from the Department of Nephrology at Shuang Ho Hospital, Taipei Medical University through the “Chronic Kidney Disease Common Care Network” database from December 2008 to April 2019. A multivariable-adjusted logistic regression expressed as odd ratios (OR) was performed to assess the association of metabolic parameters with anemia and electrolyte and mineral disorders.P for both < 0.01) and hypercalcemia . There was no significant association in serum lipid levels with presence of anemia. However, total triglycerides, total cholesterol and low-density lipoprotein-cholesterol were only associated with presence of hypercalcemia .Elevated diastolic blood pressure, fasting blood glucose, and glycated hemoglobin A1c (HbA1c) were associated with presence of anemia. Similarly, elevated fasting blood glucose and HbA1c were associated with hyponatremia (OR = 1.59 and 1.58, Elevated diastolic blood pressure, fasting blood glucose, HbA1c and blood lipids are associated with anemia or electrolyte and mineral disorders in CKD patients.The online version contains supplementary material available at 10.1186/s12882-021-02590-w. The United States Renal Data System reported in 2016 that Taiwan has the largest incidence and prevalence of end-stage renal disease (ESRD), the advanced stage of chronic kidney disease (CKD), and has continued to rank first in the world since 2002 . MoreoveAdditionally, the kidneys play a critical role in regulating body fluid, electrolytes, and acid-base balance, and CKD can lead to metabolic acidosis, hyperkalemia, hyponatremia, hypercalcemia, and hyperphosphatemia, resulting in serious adverse outcomes such as bone mineral disorders, vascular calcification, and even mortality , 7. HypeHypertension, diabetes, and lipid abnormalities are the major causes of CKD , 16. PreIn this cross-sectional study, pre-ESRD patients (CKD stages 3 to 5 with proteinuria) were enrolled in the Department of Nephrology at Shuang Ho Hospital, Taipei Medical University, Taiwan from December 2008 to April 2019. The data were retrieved from the “Chronic Kidney Disease Common Care Network” that has been developed by the physician of the hospital for more than 10 years. We retrieved the patients’ data including sociodemographic information, lifestyle, medical records, anthropometry, and blood biochemical data. Before visiting the hospital for CKD treatment and participating in the pre-ESRD nutrition education program, all patients signed an informed consent allowing their data to be used without personal identification for research only. The Taipei Medical University Joint Institutional Review Board approved this study (N202001055).n = 1072), a history of chronic liver disease and cancer (n = 232), tuberculosis and autoimmune disease (n = 48), current erythropoietin treatment (n = 353) and a lack of estimated glomerular filtration rate (eGFR) measurement (n = 4). The reason for excluding patients with presence of CVD and other comorbidities was because the predictor variables were highly associated with CVD, thus presence of CVD may become a confounding factor in our study. Finally, 2176 CKD patients were analyzed in this study.The data of 4094 patients who had participated in the pre-ESRD program were retrieved from the platform. Among the 4094 CKD patients, 3885 were stages 3–5 CKD patients, and a total of 1709 patients were excluded due to a history of cardiovascular disease (CVD) (2). Systolic and diastolic blood pressure (BP) was determined by oscillometry . For blood biochemical measurements, all patients were required to fast at least 8 h prior to blood tests. Blood biochemical data including hemoglobin (Hb), fasting blood glucose, albumin, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, potassium (K), sodium (Na), calcium (Ca), and phosphorus (P) were determined using an auto chemical analyzer . Glycated hemoglobin A1c (HbA1c) was determined by capillary electrophoresis .Anthropometric data, including body weight and height, were measured using high-accuracy ultrasonic sensors . BMI was determined using body weight (kg) divided by height squared (mC if ≥6.5% with treatment [2), 3b (30–44 mL/min/1.73 m2), 4 (15–29 mL/min/1.73 m2) and 5 (< 15 mL/min/1.73 m2).Anemia was defined as Hb < 130 g/Lfor men and < 120 g/L for women, or current iron supplementation according to the Kidney Disease Improving Global Outcomes (KDIGO) Anemia Work Group . Serum creatment . Moreovereatment . The valreatment . MoreoveWe also retrieved sociodemographic and lifestyle data such as age, sex, marital status, educational level, occupation , cigarette smoking, alcohol consumption, and physical activity from the database. Marital status was dichotomized as no  and yes (currently married). Educational level was categorized as low (high school or below) and high (above high school). Cigarette smoking and alcohol use were categorized as no, former (quit smoking or drinking), and current. Data on type of physical activity , frequency (5 response options: from never to ≥7 times/week), and duration (5 response options: from never to > 90 min) were collected and retrieved from the database. Physical activity was defined as no (< 30 min/week) and yes (≥30 min/week). Current medication use, including angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, calcium channel blockers, calcium phosphate binders, iron supplements, antihypertensives, hypolipidemic agents, hypoglycemic agents, or insulin injections were also queried. Patients were categorized as no (never) and yes (≥once) for participation in the nutrition education program.P-value of < 0.05 was considered statistically significant, and STATA software version 13  was used to perform the statistical analysis.Data are presented as numbers and percentages for categorical variables or mean ± standard deviation (SD) for continuous variables. For categorical variables, a chi-square test was performed to examine differences in characteristics of CKD patients with or without anemia, whereas the general linear model was used to examine differences in means for continuous variables. The association between metabolic parameters and anemia or electrolyte and mineral disorders was analyzed using a multivariable-adjusted logistic regression model, and the data are reported as odds ratio (OR) and 95% confidence interval (CI). Considering different Hb cut-off values for anemia in men and women, the association between metabolic parameters and anemia was stratified by sex. The regression models were adjusted for age, marital status, educational level, occupation, smoking status, drinking status, physical activity, drug use, nutritional education, and BMI in the association between metabolic parameters and anemia. Besides the confounders adjusted in the regression model, sex was also adjusted in the association between metabolic parameters and electrolyte and mineral disorders. Patients with ‘normal’ status in all dependent variables were selected as the reference group. A 2), diastolic BP (72 ± 14 vs. 75 ± 13 mmHg), albumin (39.5 ± 5.9 vs. 43.1 ± 4.5 g/L) and triglycerides (1.8 ± 1.9 vs. 1.9 ± 1.3 mmol/L) compared to those without anemia. The characteristics of CKD patients stratified by electrolyte and mineral disorders are shown in Additional file Table P = 0.015), fasting blood glucose  or HbA1c  were associated with presence of anemia compared to those with normal values (Table P = 0.017) compared to those with normal diastolic BP. Patients with elevated fasting blood glucose were associated with presence of hyponatremia , hypercalcemia  or hyperphosphatemia . Additionally, CKD patients with elevated HbA1c were significantly associated with presence of hyperkalemia , hyponatremia  or hypercalcemia . Meanwhile, CKD patients with high levels of triglycerides , total cholesterol  and LDL-cholesterol  were significantly associated with hypercalcemia only. Moreover, anemic CKD patients had a significant association with presence of hyperkalemia , hyponatremia  and hyperphosphatemia   was increased in diabetic patients with uncontrolled HbA1c levels (> 7.5%) compared to those with controlled HbA1c levels (≤7.5%) . ChronicP = 0.049). Similarly, a study in Benin found that mean serum potassium levels were significantly higher in diabetic patients compared to non-diabetic controls of the same age and sex [Electrolyte and mineral imbalances are common in patients with impaired renal function because the kidney plays an important role in regulating body fluid, electrolytes, acid-base balance, and iron metabolism . Additio and sex .Our results showed that high fasting blood glucose and high HbA1c were associated with presence of hyponatremia in CKD patients. Similarly, a previous study found that hyperglycemia in healthy adults with acute insulin deficiency rapidly decreased serum sodium levels, and hyponatremia was reversed by normoglycemia . The plaThe present study showed an association between blood lipids and hypercalcemia in CKD patients. Similarly, previous studies also found a positive association between serum calcium and triglycerides, total cholesterol or HDL-cholesterol , 51. EleThis study had several limitations. First, this study was a cross-sectional design, making it difficult to draw a causal conclusion using our model. A longitudinal study is needed to clarify the relationship. Second, we did not collect data on patients’ dietary habits in relation to mineral or iron sources. Third, the definition of anemia in the present study lacks other parameters such as serum iron, ferritin, transferrin saturation, and total iron-binding capacity. For clinical diagnosis of anemia in CKD patients, measurement of hemoglobin along with body iron status is recommended. The strength of our study is that it includes a large sample population of CKD patients, which provides better evidence for general public interpretation.In summary, fasting blood glucose and HbA1c are associated with presence of anemia, hyperkalemia, hyponatremia, hypercalcemia, and hyperphosphatemia in patients with stage 3–5 CKD. Moreover, the results of the present study suggest that there is a discordant association of blood pressure or serum lipid concentrations with anemia or electrolyte and mineral imbalances. A longitudinal study with prospective measurements is needed to further investigate this association.Additional file 1: Table S1. Characteristics of CKD patients stratified by electrolyte and mineral disorders.


Introduction: The role of near-infrared spectroscopy (NIRS) for the evaluation of cerebral haemodynamics is gaining increasing popularity because of its noninvasive nature. The aim of this study was to evaluate the role of the integral components of regional cerebral oxygenation (rSO2) measured by NIRS , as indirect surrogates of cerebral blood flow (CBF) in a cohort of critically ill patients with coronavirus disease 2019 (COVID-19). We compared these findings to the gold standard technique for noninvasive CBF assessment, Transcranial Doppler (TCD).Methods: Mechanically ventilated patients with COVID-19 admitted to the Intensive Care Unit (ICU) of Policlinico San Martino Hospital, Genova, Italy, who underwent multimodal neuromonitoring (including NIRS and TCD), were included. rSO2 and its components  were compared with TCD . Changes (Δ) in CBFV and rSO2, ΔO2Hbi, ΔHHbi, and ΔcHbi after systemic arterial blood pressure (MAP) modifications induced by different manoeuvres  were assessed using mixed-effect linear regression analysis and repeated measures correlation coefficients. All values were normalised as percentage changes from the baseline (Δ%).Results: One hundred and four measurements from 25 patients were included. Significant effects of Δ%MAP on Δ%CBF were observed after rescue manoeuvres for CBFV, ΔcHbi, and ΔO2Hbi. The highest correlation was found between ΔCBFV and ΔΔO2Hbi , and the poorest between ΔCBFV and ΔΔHHbi .Conclusions: ΔO2Hbi had the highest accuracy to assess CBF changes, reflecting its role as the main component for vasomotor response after changes in MAP. The use of indexes derived from the different components of rSO2 can be useful for the bedside evaluation of cerebral haemodynamics in mechanically ventilated patients with COVID-19. Several neuromonitoring tools have been adopted as surrogate or indirect measures of cerebral blood flow (CBF) –3. Among2Hbi)- and -deoxy(HHbi) haemoglobin based on the transmission and absorption of near-infrared light as it passes through biological tissues  changes, specifically considering the arterial component of rSO2, thus minimising any confounding factors from the venous compartment. Such assessments can be relevant in acute critical care patients, especially those in risk of developing neurological complications due to non-traumatic brain injuries. In the temporal context of the present work, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has led to insurmountable clinical challenges regarding the assessment of such potential, unknown neurological complications that could become another major burden to coronavirus disease 2019 (COVID-19) survivors.Near-infrared spectroscopy (NIRS) represents a promising but not highly utilised technique in critical care. NIRS measures the relative proportion of oxy ” statement guidelines for observational cohort studies  9)..9).This single centre prospective, observational study was performed at Policlinico San Martino Hospital, IRCCS for Oncology and Neuroscience, Genoa, Italy, from October 1, to December 15, 2020, and the protocol was approved by the local ethical review board . Written consent was obtained from the next of kin, as the patients were unconscious at the time of inclusion.Adult mechanically ventilated patients admitted to ICU . Comparisons between different variables at T0 and T1 were performed by the Wilcoxon-signed rank test.Dependent variables were expressed as a change from the baseline (T0) in both absolute (Δ change) and relative terms (Δ% change). Changes in CBFV, NIRS parameters, CVCi, and CVRi (both derived from the ratio of mean CBFV/NIRS parameters and MAP) from the baseline were used to show changes for these dependent variables across the range of MAP in response to the rescue manoeuvres.The correlations coefficients [95% confidence interval (CI)] between CBFV and the different NIRS variables were verified using the Bland and Altman method for repeated measurements , 13.2, ΔO2Hbi, ΔHHbi, and ΔcHbi) with Δ% MAP were expressed as linear mixed effects models  cm/s (p = 0.03); ΔO2Hbi decreased by −1.3 (−1.9-0.3) (μM.cm) (p < 0.001); ΔHHbi significantly increased by 0.9 (0.1–1.3) (μM.cm) (p < 0.0001). PaCO2 decreased by −1.0 [−5.25–3.0] mmHg, although not statistically significant (p = 0.06). SpO2 significantly increased by 6.0 (−0.0–29.2) % (p < 0.0001).Main variables at T0 and T1 are described in 2Hbi; R = 0.88 (0.81–0.92), p < 0.0001), followed by ΔcHbi and ΔrSO2 values (R = 0.79 (0.68–0.86), p < 0.0001 and R = 0.62 (0.46–0.74), p < 0.0001)  . The lowp = 0.001) and for ΔcHbi and ΔO2Hbi  (2. Inclusion of PaCO2 as a covariate did not improve any of the models fits. Boxplot panels showing the delta difference (T1-T0) for each patient concerning the different parameters analysed are shown in ESM Individual data of CBF responses to changes in MAP from T0 to T1 and linear mixed-effects models marginal mean values of CBF are presented in ctively) , Table 32Hbi was better correlated with ΔCBFV than ΔHHbi and other components of cerebral oxygenation. ΔHHbi showed the poorest correlation with ΔCBFV; (2) CVCi indices derived from NIRS parameters, especially rSO2, correlated consistently better with CBFV than CVRi; (3) changes in MAP led to cerebral vasoreactive responses, which could be detected using the arterial component of rSO2, but not total rSO2 or its venous component. Our data suggest that, as the arterial compartment is responsible for the major changes in cerebrovascular tone following arterial blood pressure changes, the ΔO2Hbi component of NIRS can more specifically describe these variations.In a cohort of mechanically ventilated patients with COVID-19 undergoing different rescue therapies and haemodynamic manipulations, we found that: (1) ΔO2 to assess CBF, which is allowed by the Masimo® device. We believe that this is important, as there is a knowledge gap concerning the comparison of specific components of the NIRS signal with CBFV.To our knowledge, this is the first study evaluating the role of NIRS in response to secondary changes in systemic haemodynamics in mechanically ventilated patients with COVID-19. Compared to our previous work , where CAlthough NIRS has been previously used as surrogate of cerebral blood flow in the dynamic measurement of autoregulation , 16, its2 could improve the accuracy in estimating CBF changes, eliminating the venous contamination  of 60–70 mmHg in patients who are traumatically brain injured . HoweverAmongst the methods proposed as possible surrogates of CBF , neuroimA number of indirect techniques have been proposed based on invasive surrogates of CBF  and non-invasive methods  . OpticalCBF and CA can be evaluated by measuring relative blood flow changes in response to a steady-state change in the blood pressure (static methods) or during the response to spontaneous changes in blood pressure (dynamic methods) . Althougvia neuromonitoring software platforms , the simple assessment of CVRi/CVCi in response to systemic stimuli can be performed. Although routine assessment of these metrics is not always feasible, they present wide clinical applications, from the determination of stroke risk in individuals with severe asymptomatic carotid or intracranial steno-occlusive disease to concussions and patients with neurodegenerative conditions, such as Alzheimer's disease. In fact, previous works have described that changes in conductance (CVCi) better reflect the response in pressure regulation than do changes in resistance (CVRi) (2 correlated consistently better with CBFV when compared to CVRi in response to rescue therapies and haemodynamic changes.Outside the assessment of CA using TCD-based indices obtained e (CVRi) . This hy2 could potentially be applied as surrogate of CBF, as NIRS- similarly to TCD- is a low cost, easy available, and safe neuromonitoring tool . This could lead to a decoupling between large and micro vessels. However, both methods are currently considered as surrogate of CBF , 33. Fin2 had the highest accuracy in assessing CBF changes, reflecting its role as the main component for vasomotor response after changes in MAP. These findings indicate that CBF assessed with NIRS, specifically through ΔO2Hbi, is comparable to TCD in this patient population. The use of indices derived from the different components of rSO2 can be useful for the bedside evaluation of cerebral haemodynamics in patients who are critically ill in order to optimise haemodynamics of patients and potentially improve their outcome. Further studies are warranted to better define the role of this technique in the clinical practise, especially the continuous assessment of cerebral autoregulation in mechanically ventilated patients with COVID-19, with acute respiratory syndrome.The arterial component of rSOOspedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genoa, Italy: Iole Brunetti, Maurizio Loconte, Fabio Tarantino, Marco Sottano, Francesco Marramao, Angelo Gratarola, Paolo Frisoni. Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Italy: Elena Ciaravolo. Infectious Diseases Unit, Ospedale Policlinico San Martino, Genoa, Italy: Chiara Dentone, Lucia Taramasso, Laura Magnasco, Antonio Vena. Department of Neurosurgery, Ospedale Policlinico San Martino, Genoa, Italy: Gianluigi Zona. Department of Neurosurgery, Ospedale Policlinico San Martino, Genoa, Italy: Pietro Fiaschi.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 Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020. The patients/participants provided their written informed consent to participate in this study.CR writing of the manuscript, paper revision, fundamental conceptual contribution, and data analysis. LB, DB, DG, WD, MB, MC, RB, PP, and BM paper revision and fundamental conceptual contribution. DC, paper revision, fundamental conceptual contribution, and data analysis. All authors contributed to the article and approved the submitted version.BM is the senior medical director of Masimo. CR, PP, and RB report personal fees from Masimo. MB reports personal fees and others from Angelini, personal fees and others from AstraZeneca, others from Bayer, personal fees and others from Cubist, personal fees and others from Pfizer, personal fees and others from Menarini, personal fees and others from MSD, others from Nabriva, others from Paratek, others from Roche, others from Shionogi, others from Tetraphase, others from the Medicine Company, personal fees and others from AstellasPharma Inc., personal fees from Gilead Sciences, personal fees from Teva, personal fees from Novartis, grants from Ranbaxy, personal fees from Correvio, personal fees from Molteni, personal fees from Thermo Fisher, outside the submitted work. Dr Herrmann is a cofounder and shareholder in OscillaVent, Inc, and a consultant for ZOLL Medical Corporation, both outside the submitted work. MC is recipient of part of the licensing fee for ICM+ software  outside the submitted work. DG reports personal fees from Stepstone Pharma GmbH, personal fees from MSD Italia and personal fees from Correvio Italia, 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.


Objective: Adverse factors of postoperative hemodynamic and myocardial performance remain largely unexplored in children with congenital heart disease following cardiopulmonary bypass due to technical limitations. Pressure recording analytical method (PRAM) is a continuous hemodynamic and myocardial performance monitoring technique based on beat-to-beat arterial pressure waveform. Using PRAM, we examined the temporal trends and adverse factors, in clinical management, of these performances.Methods: We monitored blood pressure, cardiac index, cardiac cycle efficiency (CCE), dP/dTmax, and systematic vascular resistance index in 91 children (aged 186 ± 256 days) during their first 48 h after cardiopulmonary bypass. Above parameters, inotropic and vasoactive drug dosages, and serum lactate were recorded 3-hourly. NT-proBNP was measured daily.Results: CCE and dP/dTmax gradually increased (Ps < 0.0001), while systematic vascular resistance index, diastolic blood pressure and inotrope dosages decreased (Ps < 0.0001) over time. Cardiac index, systolic blood pressure, and heart rate did not change significantly (Ps ≥ 0.231). Patients undergoing deep hypothermic circulatory arrest had significantly higher heart rate and lower CCE (Ps ≤ 0.006) over time. Multivariate analyses indicated that epinephrine dose significantly correlated with systolic blood pressure, cardiac index, CCE, and dP/dTmax after polynomial transformation, with the peak ranging from 0.075 to 0.097.Conclusions: Systemic hemodynamic and myocardial performance gradually improved in the first 48 h after cardiopulmonary bypass without the “classic” nadir at 9–12 h. Deep hypothermic circulatory arrest and higher epinephrine doses were adversely associated with these performances. CCE, rather than cardiac index or other common-used parameters, was the most sensitive and consistent indicator. Hemodynamic monitoring is the definite cornerstone of the postoperative management in children with congenital heart disease (CHD) undergoing cardiopulmonary bypass surgery (CPB) . The earSince the invention of the Fick principle in 1870 , there hMore recently, there have been several systems developed to directly monitor cardiac output and other hemodynamic parameters based on the arterial pulse contour analysis methods such as PiCCO2 and MostCare, etc . They arBy using PRAM, we aimed to examine the temporal trends of systemic hemodynamic and myocardial performance parameters of children with CHD during the first 48 post-CPB hours, and more importantly to identify adverse factors of these parameters in routine clinical management.After ethics approval (No. 46201), 91 children with CHD undergoing CPB were enrolled from July 2019 to June 2020. The informed consent was waived since PRAM monitoring by MostCare is our clinical routine. More complex CHD patients were selected daily when MostCare devices were available. Patients with other congenital anomalies or previous CPB were excluded.Standard procedures were performed . DHCA  and dexmedetomidine (2 μg/kg/min) and intermittent injections of midazolam (0.1 mg/kg). Hematocrit is maintained at 34–45%. Inotropic and vasoactive drugs include dopamine, milrinone, and epinephrine to maintain arterial blood pressure . Despite the protocol, management varied among clinicians.Patients receive time-cycled pressure control/pressure support ventilation on arrival in the CICU, followed by non-invasive ventilation when appropriate. Ventilation settings are adjusted to maintain a PaCOmax), and cardiac cycle efficiency (CCE)  arterial pressure waveform. In any artery, volume changes with the radial expansion in response to pressure variations, which is mutually determined by left ventricle contraction, arterial elasticity, and backward pressure reflections . To esticy (CCE) . dP/dTmaactility . CCE is actility :t)sys is the power of the systolic stage of the heartbeat, W(t)beat is the power of the whole cycle of the heartbeat, and K(t) is the ratio of mean pressure expected and mean pressure measured.W indicate the difference in the level of each measure between groups. Those of the time and group interaction (Pgroup × time) indicate the difference in the trend of each measure between groups; (3) analyze correlations between measures. The fixed predictors were clinical variables, and outcomes were hemodynamic and myocardial variables. Polynomial transformation of the drug dose was tested regarding the best fit for the drug dose, in which the parameter estimate and P-value of dose (parameter estimatedose and Pdose) indicated lower doses, those for time2 or dose2 indicated higher doses. The peak value in the polynomial trend was determined by the following equation: Xpeak = parameter estimatedose/, or frequency (%) when appropriate. Mixed linear regression for repeated measures was used to (1) analyze the temporal trend of variables; (2) compare the difference between DHCA group and non-DHCA group in levels and trends with the analysis of the group effect and interaction between time and group. The parameter estimate and max gradually and significantly increased (Ps < 0.0001), while SVRI and DBP decreased (Ps ≤ 0.0003). The doses of epinephrine, dopamine, and milrinone decreased significantly (Ps < 0.0001). CI, SBP, and heart rate did not change significantly (Ps ≥ 0.231)  .n = 17), compared with those without (n = 74), had or trended to have significantly higher heart rate (Pgroup = 0.006) and SVRI (Pgroup = 0.064), and lower CCE (Pgroup = 0.001) and dP/dTmax (Pgroup = 0.099) over time. They received significantly higher epinephrine (Pgroup = 0.020) and lower dopamine (Pgroup = 0.002), but were not different in milrinone (Pgroup = 0.479) (Pgroup = 0.031) and CCE (Pgroup = 0.006), but not in dP/dTmax (Pgroup = 0.395) and SVRI (Pgroup = 0.208) (P > 0.280).Patients undergoing DHCA (= 0.479) . After a= 0.208) . CI did max, lactate, and NT-proBNP (Ps ≤ 0.002). It significantly correlated with CCE after polynomial transformation, being positive at lower doses <0.083 mcg/kg/min (parameter estimate dose = 2.63 Pdose <0.0001), and negative at higher doses (P < 0.0001), negatively correlated with SVRI and NT-proBNP (Ps ≤ 0.020). Milrinone dose significantly and positively correlated with CI (P = 0.033), negatively correlated with SVRI and lactate (Ps ≤ 0.031). When tested as the dependent variable, epinephrine dose significantly and positively correlated STAT category and CPB time .As presented in P < 0.0001) but not with lactate (P = 0.627). No significant correlations were found between CI and NT-proBNP (P = 0.764) or lactate (P = 0.721).Additionally, CCE significantly correlated with NT-proBNP (parameter estimate = −9072.59 and Ps ≤ 0.015 for both). Its correlations with other variables were different from the linear ones shown in the univariate analyses. After polynomial transformation, epinephrine dose significantly correlated with SBP (Ps ≤ 0.001 for both), CI (Ps ≤ 0.041 for both), and dP/dTmax (Ps ≤ 0.001 for both). SBP, CI, CCE, and dP/dTmax peaked at an epinephrine dose of 0.078, 0.075, 0.097, and 0.093 mcg/kg/min, respectively. Epinephrine dose linearly and positively correlated with heart rate, DBP, SVRI, lactate, and NT-proBNP (Ps ≤ 0.003). Dopamine dose positively correlated with CCE (P = 0.010). Age significantly and negatively correlated with heart rate, and positively with SBP and CCE (Ps ≤ 0.014). CPB time significantly and negatively correlated with CCE (P = 0.036). No significant correlation was found between other clinical and hemodynamic variables (Ps ≥ 0.074).As presented in max and CCE, and higher heart rate, DBP, SVRI, lactate, and NT-proBNP; (4) CCE was the most sensitive and consistent indicator among all PRAM parameters.By monitoring children with CHD during the first 48 post-CPB hours using PRAM, we found the followings: (1) systemic hemodynamics and myocardial status gradually improved without the “classic” nadir at 9–12 h; (2) patients undergoing DHCA had significantly higher heart rate and lower CCE; (3) higher epinephrine doses were adversely associated with overall systemic hemodynamics and myocardial performance, indicated by lower SBP, CI, dP/dTmax and the decrease in SVRI and inotropic and vasoactive drug doses; CI did not change significantly and no other parameters showed the nadir. This profile is consistent with our other studies that used more advanced monitoring techniques, such as respiratory mass spectrometry to oxygen consumption combined with the Fick principle in the past two decades, in which CI gradually increased over 72 h in post-CPB children including neonates following the Norwood procedure and infants with less complex CHDs following complete repair  increased systemic and myocardial oxygen consumption but failed to increase CI and oxygen delivery, therefore exerting an adverse effect on systemic and myocardial oxygen transport . The patFinally, CCE significantly and positively correlated with NT-proBNP, while CI did not, consistent with previous findings in adults , 37. TakThe observational nature of this study has several limitations. First, the causal relationship between epinephrine dose and hemodynamic outcomes showed by regression analysis remains speculative. Second, the epinephrine doses were relatively high and often combined with dopamine in our center. The situation is suboptimal but allowed us to reveal the curvilinear effect of epinephrine. The cut-off value might be different if not combined with dopamine or other inotropic and vasoactive drugs. This might also be applicable to the effect of dopamine if used along. Third, our cohort included a heterogeneous group of less complex CHDs with a lower proportion of neonatal surgery compared to contemporary patient populations from the advanced centers. A larger multi-center cohort study, including neonatal surgeries and complex cases and using more advanced techniques, is warranted to confirm our findings, in particular to the temporal trends of hemodynamics.In CHD children early after CPB, systemic hemodynamic and myocardial performance improved gradually during the first 48 h without the “classic” nadir at 9–12 h. These performances were worse in patients undergoing DHCA and adversely associated with higher doses of epinephrine >0.08–0.10 mcg/kg/min. CCE, rather than CI or other parameters, was most consistent and sensitive to reflect patient's hemodynamic status.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 Guangzhou Women and Children's Hospital. Written informed consent from the participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.XL and YL has contributed to the conducting and reporting of the work described in the article. YC, JianL, LL, LM, and MZ has contributed to the conducting of the work. XC has contributed to the planning and conducting of the research. JiaL has contributed to the planning, conducting, and reporting of the research. 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.