Bioreactance assessment of cardiac output lacks reliability for the follow-up of patients with pulmonary hypertension.

Cardiac output (CO) is one of the primary prognostic factors evaluated during the follow-up of patients treated for pulmonary hypertension (PH). It is recommended that it be measured using the thermodilution technique during right heart catheterization. The difficulty to perform iterative invasive measurements on the same individual led us to consider a non-invasive option. The aims of the present study were to assess the agreement between CO values obtained using bioreactance (Starling™ SV) and thermodilution, and to evaluate the ability of the bioreactance monitor to detect patients whose CO decreased by more than 15% during follow-up and, accordingly, its usefulness for patient monitoring. A prospective cohort study evaluating the performance of the Starling™ SV monitor was conducted in patients with clinically stable PH. Sixty patients referred for hemodynamic assessment were included. CO was measured using both the thermodilution technique and bioreactance during two follow-up visits. A total of 60 PH patients were included. All datasets were available at the baseline visit (V0) and 50 of them were usable during the follow-up visit (V1). Median [IQR] CO was 4.20 l/min [3.60-4.70] when assessed by bioreactance, and 5.30 l/min [4.57-6.20] by thermodilution (p<0.001). The Spearman correlation coefficient was 0.51 [0.36-0.64], and the average deviation on Bland-Altman plot was -1.25 l/min (95% CI [-1.48-1.01], p<0.001). The ability of the monitor to detect a variation in CO of more than 15% between two follow-up measurements, when such variation existed using thermodilution, was insufficient for clinical practice (AUC = 0.54, 95% CI [0.33-0.75]).

Clinical study: the impact of goal-directed fluid therapy on volume management during enhanced recovery after surgery in gastrointestinal procedures.

Background: Goal-directed fluid therapy, as a crucial component of accelerated rehabilitation after surgery, plays a significant role in expediting postoperative recovery and enhancing the prognosis of major surgical procedures. Methods: In line with this, the present study aimed to investigate the impact of target-oriented fluid therapy on volume management during ERAS protocols specifically for gastrointestinal surgery. Patients undergoing gastrointestinal surgery at our hospital between October 2019 and May 2021 were selected as the sample population for this research. Results: 41 cases of gastrointestinal surgery patients were collected from our hospital over 3 recent years. Compared with T1, MAP levels were significantly increased from T2 to T5; cardiac output (CO) was significantly decreased from T2 to T3, and significantly increased from T4 to T5; and SV level was significantly increased from T3 to T5. Compared with T2, HR and cardiac index (CI) were significantly elevated at T1 and at T3-T5. Compared with T3, SVV was significantly decreased at T1, T2, T4, and T5; CO and stroke volume (SV) levels were increased significantly at T4 and T5. In this study, pressor drugs were taken for 23 days, PACU residence time was 40.22 ± 12.79 min, time to get out of bed was 12.41 ± 3.97 h, exhaust and defecation time was 18.11 ± 7.52 h, and length of postoperative hospital stay was 4.47 ± 1.98 days. The average HAMA score was 9.11 ± 2.37, CRP levels were 10.54 ± 3.38 mg/L, adrenaline levels were 132.87 ± 8.97 ng/L, and cortisol levels were 119.72 ± 4.08 ng/L. Prealbumin levels were 141.98 ± 10.99 mg/L at 3 d after surgery, and 164.17 ± 15.84 mg/L on the day of discharge. Lymphocyte count was 1.22 ± 0.18 (109/L) at 3 d after surgery, and 1.47 ± 0.17 (109/L) on the day of discharge. Serum albumin levels were 30.51 ± 2.28 (g/L) at 3 d after surgery, and 33.52 ± 2.07 (g/L) on the day of discharge. Conclusion: Goal-directed fluid therapy (GDFT) under the concept of Enhanced Recovery After Surgery (ERAS) is helpful in volume management during radical resection of colorectal tumors, with good postoperative recovery. Attention should be paid to the influence of pneumoperitoneum and intraoperative posture on GDFT parameters.

Monitoring CO2 kinetics as a marker of cardiopulmonary efficiency.

PURPOSE OF REVIEW: To describe current and near future developments and applications of CO2 kinetics in clinical respiratory and cardiovascular monitoring. RECENT FINDINGS: In the last years, we have witnessed a renewed interest in CO2 kinetics in relation with a better understanding of volumetric capnography and its derived parameters. This together with technological advances and improved measurement systems have expanded the monitoring potential of CO2 kinetics including breath by breath continuous end-expiratory lung volume and continuous noninvasive cardiac output. Dead space has slowly been gaining relevance in clinical monitoring and prognostic evaluation. Easy to measure dead space surrogates such as the ventilatory ratio have demonstrated a strong prognostic value in patients with acute respiratory failure. SUMMARY: The kinetics of carbon dioxide describe many relevant physiological processes. The clinical introduction of new ways of assessing respiratory and circulatory efficiency based on advanced analysis of CO2 kinetics are paving the road to a long-desired goal in clinical monitoring of critically ill patients: the integration of respiratory and circulatory monitoring during mechanical ventilation.

Heat-related changes in the velocity and kinetic energy of flowing blood influence the human heart's output during hyperthermia.

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( Q ̇ $\dot Q$ ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and Q ̇ $\dot Q$ . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3 h control (normothermic condition); (2) 3 h of single-leg heating; (3) 3 h of two-leg heating; and (4) 2.5 h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, Q ̇ $\dot Q$ increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2 ≥ 0.803; P < 0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and Q ̇ $\dot Q$ through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: Q ̇ $\dot Q$ ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and Q ̇ $\dot Q$ . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented Q ̇ $\dot Q$ with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.

Comparison of cardiac output estimates obtained from the Antares oscillometric pulse wave analysis algorithm and from Doppler transthoracic echocardiography.

BACKGROUND: In cardiology, cardiac output (CO) is an important parameter for assessing cardiac function. While invasive thermodilution procedures are the gold standard for CO assessment, transthoracic Doppler echocardiography (TTE) has become the established method for routine CO assessment in daily clinical practice. However, a demand persists for non-invasive approaches, including oscillometric pulse wave analysis (PWA), to enhance the accuracy of CO estimation, reduce complications associated with invasive procedures, and facilitate its application in non-intensive care settings. Here, we aimed to compare the TTE and oscillometric PWA algorithm Antares for a non-invasive estimation of CO. METHODS: Non-invasive CO data obtained by two-dimensional TTE were compared with those from an oscillometric blood pressure device (custo med GmbH, Ottobrunn, Germany) using the integrated algorithm Antares (Redwave Medical GmbH, Jena, Germany). In total, 59 patients undergoing elective cardiac catheterization for clinical reasons (71±10 years old, 76% males) were included. Agreement between both CO measures were assessed by Bland-Altman analysis, Student's t-test, and Pearson correlations. RESULTS: The mean difference in CO was 0.04 ± 1.03 l/min (95% confidence interval for the mean difference: -0.23 to 0.30 l/min) for the overall group, with lower and upper limits of agreement at -1.98 and 2.05 l/min, respectively. There was no statistically significant difference in means between both CO measures (P = 0.785). Statistically significant correlations between TTE and Antares CO were observed in the entire cohort (r = 0.705, P<0.001) as well as in female (r = 0.802, P<0.001) and male patients (r = 0.669, P<0.001). CONCLUSIONS: The oscillometric PWA algorithm Antares and established TTE for a non-invasive estimation of CO are highly correlated in male and female patients, with no statistically significant difference between both approaches. Future validation studies of the Antares CO are necessary before a clinical application can be considered.

Aortic pulse wave analysis and functional capacity of heart transplantation candidates: a pilot study.

We compared cardiovascular parameters obtained with the Mobil-O-Graph and functional capacity assessed by the Duke Activity Status Index (DASI) before and after Heart Transplantation (HT) and also compared the cardiovascular parameters and the functional capacity of candidates for HT with a control group. Peripheral and central vascular pressures increased after surgery. Similar results were observed in cardiac output and pulse wave velocity. The significant increase in left ventricular ejection fraction (LVEF) postoperatively was not followed by an increase in the functional capacity. 24 candidates for HT and 24 controls were also compared. Functional capacity was significantly lower in the HT candidates compared to controls. Stroke volume, systolic, diastolic, and pulse pressure measured peripherally and centrally were lower in the HT candidates when compared to controls. Despite the significant increase in peripheral and central blood pressures after surgery, the patients were normotensive. The 143.85% increase in LVEF in the postoperative period was not able to positively affect functional capacity. Furthermore, the lower values of LVEF, systolic volume, central and peripheral arterial pressures in the candidates for HT are consistent with the characteristics signs of advanced heart failure, negatively impacting functional capacity, as observed by the lower DASI score.

Intraoperative Goal-Directed Perfusion in Cardiac Surgery with Cardiopulmonary Bypass: The Roles of Delivery Oxygen Index and Cardiac Index.

PURPOSE: Goal-directed perfusion (GDP) refers to individualized goal-directed therapy using comprehensive monitoring and optimizing the delivery of oxygen during cardiopulmonary bypass (CPB). This study aims to determine whether the intraoperative GDP protocol method has better outcomes compared to conventional methods. METHODS: We searched the PubMed, Central, and Scopus databases up to October 12, 2023. We primarily examined the GDP protocol in adult cardiac surgery, using CPB with oxygen delivery index (DO2I) and cardiac index (CI) as the main parameters. RESULTS: In all, 1128 participants from seven studies were included in our analysis. The results showed significant differences in the duration of intensive care unit (ICU) stays (p = 0.01), with a mean difference of -0.33 (-0.59 to 0.07), and hospital length of stay (LOS) (p = 0.0002), with a mean difference of -0.84 (-1.29 to -0.39). There was also a notable reduction in postoperative complications (p <0.00001), odds ratio (OR) of 0.43 (0.32-0.60). However, there was no significant decrease in mortality rate (p = 0.54), OR of 0.77 (0.34-1.77). CONCLUSION: Postoperative acute kidney injury and ICU and hospital LOS are significantly reduced when GDP protocols with indicators of flow management, oxygen delivery index, and CI are used in intraoperative cardiac surgery using CPB.

Pulmonary blood volume measured by 82Rb-PET in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

In patients with chronic obstructive pulmonary disease (COPD), pulmonary vascular dysfunction and destruction are observable before the onset of detectable emphysema, but it is unknown whether this is associated with central hypovolemia. We investigated if patients with COPD have reduced pulmonary blood volume (PBV) evaluated by 82Rb-positron emission tomography (PET) at rest and during adenosine-induced hyperemia. This single-center retrospective cohort study assessed 6,301 82Rb-PET myocardial perfusion imaging (MPI) examinations performed over a 6-yr period. We compared 77 patients with COPD with 44 healthy kidney donors (controls). Cardiac output ([Formula: see text]) and mean 82Rb bolus transit time (MBTT) were used to calculate PBV. [Formula: see text] was similar at rest (COPD: 3,649 ± 120 mL vs. control: 3,891 ± 160 mL, P = 0.368) but lower in patients with COPD compared with controls during adenosine infusion (COPD: 5,432 ± 124 mL vs. control: 6,185 ± 161 mL, P < 0.050). MBTT was shorter in patients with COPD compared with controls at rest (COPD: 8.7 ± 0.28 s vs. control: 11.4 ± 0.37 s, P < 0.001) and during adenosine infusion (COPD: 9.2 ± 0.28 s vs. control: 10.2 ± 0.37 s, P < 0.014). PBV was lower in patients with COPD, even after adjustment for body surface area, sex, and age at rest [COPD: 530 (29) mL vs. 708 (38) mL, P < 0.001] and during adenosine infusion [COPD: 826 (29) mL vs. 1,044 (38) mL, P < 0.001]. In conclusion, patients with COPD show evidence of central hypovolemia, but it remains to be determined whether this has any diagnostic or prognostic impact.NEW & NOTEWORTHY The present study demonstrated that patients with chronic obstructive pulmonary disease (COPD) exhibit central hypovolemia compared with healthy controls. Pulmonary blood volume may thus be a relevant physiological and/or clinical outcome measure in future COPD studies.

Hemodynamics of ventricular-arterial coupling under enhanced external counterpulsation: An optimized dual-source lumped parameter model.

BACKGROUND AND OBJECTIVE: Enhanced external counterpulsation (EECP) is a mechanically assisted circulation technique widely used in the rehabilitation and management of ischemic cardiovascular diseases. It contributes to cardiovascular functions by regulating the afterload of ventricle to improve hemodynamic effects, including increased diastolic blood pressure at aortic root, increased cardiac output and enhanced blood perfusion to multiple organs including coronary circulation. However, the effects of EECP on the coupling of the ventricle and the arterial system, termed ventricular-arterial coupling (VAC), remain elusive. We aimed to investigate the acute effect of EECP on the dynamic interaction between the left ventricle and its afterload of the arterial system from the perspective of ventricular output work. METHODS: A neural network assisted optimization algorithm was proposed to identify the ordinary differential equation (ODE) relation between aortic root blood pressure and flow rate. Based on the optimized order of ODE, a lumped parameter model (LPM) under EECP was developed taking into consideration of the simultaneous action of cardiac and EECP pressure sources. The ventricular output work, in terms of aortic pressure and flow rate cooperated with the LPM, was used to characterize the VAC of ventricle and its afterload. The VAC subjected to the principle of minimal ventricular output work was validated by solving the Euler-Poisson equation of cost function, ultimately determining the waveforms of aortic pressure and flow rate. RESULTS: A third-order ODE can precisely describe the hemodynamic relationship between aortic pressure and flow rate. An optimized dual-source LPM with three energy-storage elements has been constructed, showing the potential in probing VAC under EECP. The LPM simulation results demonstrated that the VAC in terms of aortic pressure and flow rate yielded to the minimal ventricular output work under different EECP pressures. CONCLUSIONS: The ventricular-arterial coupling under EECP is subjected to the minimal ventricular output work, which can serve as a criterion for determining aortic pressure and flow rate. This study provides insight for the understanding of VAC and has the potential in characterizing the performance of the ventricular and arterial system under EECP.

Short-Chain Fatty Acid Butyrate Is an Inotropic Agent With Vasorelaxant and Cardioprotective Properties.

BACKGROUND: The heart can metabolize the microbiota-derived short-chain fatty acid butyrate. Butyrate may have beneficial effects in heart failure, but the underlying mechanisms are unknown. We tested the hypothesis that butyrate elevates cardiac output by mechanisms involving direct stimulation of cardiac contractility and vasorelaxation in rats. METHODS AND RESULTS: We examined the effects of butyrate on (1) in vivo hemodynamics using parallel echocardiographic and invasive blood pressure measurements, (2) isolated perfused hearts in Langendorff systems under physiological conditions and after ischemia and reperfusion, and (3) isolated coronary arteries mounted in isometric wire myographs. We tested Na-butyrate added to injection solutions or physiological buffers and compared its effects with equimolar doses of NaCl. Butyrate at plasma concentrations of 0.56 mM increased cardiac output by 48.8±14.9%, stroke volume by 38.5±12.1%, and left ventricular ejection fraction by 39.6±6.2%, and lowered systemic vascular resistance by 33.5±6.4% without affecting blood pressure or heart rate in vivo. In the range between 0.1 and 5 mM, butyrate increased left ventricular systolic pressure by up to 23.7±3.4% in isolated perfused hearts and by 9.4±2.9% following ischemia and reperfusion, while reducing myocardial infarct size by 81.7±16.9%. Butyrate relaxed isolated coronary septal arteries concentration dependently with an EC50=0.57 mM (95% CI, 0.23-1.44). CONCLUSIONS: We conclude that butyrate elevates cardiac output through mechanisms involving increased cardiac contractility and vasorelaxation. This effect of butyrate was not associated with adverse myocardial injury in damaged hearts exposed to ischemia and reperfusion.

The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.

Dynamic cerebral autoregulation is preserved during orthostasis and intrathoracic pressure regulation in healthy subjects: A pilot study.

Resistance breathing may restore cardiac output (CO) and cerebral blood flow (CBF) during hypovolemia. We assessed CBF and cerebral autoregulation (CA) during tilt, resistance breathing, and paced breathing in 10 healthy subjects. Blood velocities in the internal carotid artery (ICA), middle cerebral arteries (MCA, four subjects), and aorta were measured by Doppler ultrasound in 30° and 60° semi-recumbent positions. ICA blood flow and CO were calculated. Arterial blood pressure (ABP, Finometer), and end-tidal CO2 (ETCO2) were recorded. ICA blood flow response was assessed by mixed-models regression analysis. The synchronization index (SI) for the variable pairs ABP-ICA blood velocity, ABP-MCA velocities in 0.005-0.08 Hz frequency interval was calculated as a measure of CA. Passive tilting from 30° to 60° resulted in 12% decrease in CO (p = 0.001); ICA blood flow tended to fall (p = 0.04); Resistance breathing restored CO and ICA blood flow despite a 10% ETCO2 drop. ETCO2 and CO contributed to ICA blood flow variance (adjusted R2: 0.9, p < 0.0001). The median SI was low (<0.2) indicating intact CA, confirmed by surrogate date testing. The peak SI was transiently elevated during resistance breathing in the 60° position. Resistance breathing may transiently reduce CA efficiency. Paced breathing did not restore CO or ICA blood flow.

Hemodynamic and Metabolic Responses to Moderate and Vigorous Cycle Ergometry in Men Who Have Had Transtibial Amputation.

Adults who have had an amputation face barriers to having an active lifestyle which attenuates cardiorespiratory fitness. Prior studies in amputees typically involve treadmill walking or arm ergometry, yet physiological responses to bilateral leg cycling are less understood. This study assessed the hemodynamic and metabolic responses to moderate and vigorous cycle ergometry in men who have had a transtibial amputation (TTA). Five men who had had a unilateral TTA (age = 39 ± 15 yr) and six controls (CONs) without an amputation (age = 31 ± 11 yr) performed two 20 min bouts of cycling differing in intensity. Cardiac output (CO), stroke volume (SV), and oxygen consumption (VO2) were measured during moderate intensity continuous exercise (MICE) and high intensity interval exercise (HIIE) using thoracic impedance and indirect calorimetry. In response to MICE and HIIE, the HR and VO2 levels were similar (p > 0.05) between groups. Stroke volume and CO were higher (p < 0.05) in the CONs, which was attributed to their higher body mass. In men with TTAs, HIIE elicited a peak HR = 88%HRmax and substantial blood lactate accumulation, representing vigorous exercise intensity. No adverse events were exhibited in the men with TTAs. The men with TTAs show similar responses to MICE and HIIE versus the CONs.

Is crystalloid co-loading necessary to prevent spinal hypotension during elective cesarean delivery? A randomized double-blind trial.

BACKGROUND: Hypotension is common during spinal anesthesia for cesarean delivery. Preventive strategies include fluid loading and phenylephrine. We hypothesized that if prophylactic phenylephrine infusion is used, omission of fluid loading would be non-inferior to fluid co-loading in maintaining cardiac output. We assumed that if there was a difference, the increase in cardiac output would be greater in the no-loading than in the co-loading group. METHODS: Term pregnant women scheduled for elective cesarean delivery were randomized to receive 1 L crystalloid co-loading or maintenance fluids only. Phenylephrine was titrated to maintain blood pressure. Changes in cardiac output following spinal anesthesia were the primary outcome. The study was powered as a non-inferiority trial, allowing the no-loading arm to have a 50% greater change in cardiac output. Heart rate, dose of phenylephrine, occurrence of nausea and vomiting, Apgar scores and neonatal acid base status were secondary outcomes. RESULTS: Data from 63 women were analyzed. In contrast to our hypothesis, there was 33% less increase in cardiac output with no loading (ratio 0.67, 95% CI 0.15 to 1.36), and 60% greater reduction of cardiac output with no loading (ratio 1.6, 95% CI 1.0 to 2.7). Total dose of phenylephrine was higher in the no-loading group. There may be a less favorable neonatal acid base status without volume loading. CONCLUSION: Omission of crystalloid co-loading leads to a decrease in cardiac output which has a potentially unfavorable impact on neonatal acid base status. We conclude that crystalloid co-loading may be useful in the presence of phenylephrine infusion.

NButGT Reinforces the Beneficial Effects of Epinephrine on Cardiac Mitochondrial Respiration, Lactatemia and Cardiac Output in Experimental Anaphylactic Shock.

Anaphylactic shock (AS) is the most severe form of acute systemic hypersensitivity reaction. Although epinephrine can restore patients' hemodynamics, it might also be harmful, supporting the need for adjuvant treatment. We therefore investigated whether NButGT, enhancing O-GlcNAcylation and showing beneficial effects in acute heart failure might improve AS therapy. Ovalbumin-sensitized rats were randomly allocated to six groups: control (CON), shock (AS), shock treated with NButGT alone before (AS+pre-Nbut) or after (AS+post-Nbut) AS onset, shock treated with epinephrine alone (AS+EPI) and shock group treated with combination of epinephrine and NButGT (AS+EPI+preNBut). Induction of shock was performed with an intravenous (IV) ovalbumin. Cardiac protein and cycling enzymes O-GlcNAcylation levels, mean arterial pressure (MAP), heart rate, cardiac output (CO), left ventricle shortening fraction (LVSF), mitochondrial respiration, and lactatemia were evaluated using Western blotting experiments, invasive arterial monitoring, echocardiography, mitochondrial oximetry and arterial blood samples. AS decreased MAP (-77%, p < 0.001), CO (-90%, p < 0.001) and LVSF (-30%, p < 0.05). Epinephrine improved these parameters and, in particular, rats did not die in 15 min. But, cardiac mitochondrial respiration remained impaired (complexes I + II -29%, p < 0.05 and II -40%, p < 0.001) with hyperlactatemia. NButGT pretreatment (AS+pre-Nbut) efficiently increased cardiac O-GlcNAcylation level as compared to the AS+post-Nbut group. Compared to epinephrine alone, the adjunction of NButGT significantly improved CO, LVSF and mitochondrial respiration. MAP was not significantly increased but lactatemia decreased more markedly. Pretreatment with NButGT increases O-GlcNAcylation of cardiac proteins and has an additive effect on epinephrine, improving cardiac output and mitochondrial respiration and decreasing blood lactate levels. This new therapy might be useful when the risk of AS cannot be avoided.

In silico parametric analysis of femoro-jugular venovenous ECMO and return cannula dynamics: In silico analysis of femoro-jugular VV ECMO.

BACKGROUND: Increasingly, computational fluid dynamics (CFD) is helping explore the impact of variables like: cannula design/size/position/flow rate and patient physiology on venovenous (VV) extracorporeal membrane oxygenation (ECMO). Here we use a CFD model to determine what role cardiac output (CO) plays and to analyse return cannula dynamics. METHODS: Using a patient-averaged model of the right atrium and venae cava, we virtually inserted a 19Fr return cannula and a 25Fr drainage cannula. Running large eddy simulations, we assessed cardiac output at: 3.5-6.5 L/min and ECMO flow rate at: 2-6 L/min. We analysed recirculation fraction (Rf), time-averaged wall shear stress (TAWSS), pressure, velocity, and turbulent kinetic energy (TKE) and extracorporeal flow fraction (EFF = ECMO flow rate/CO). RESULTS: Increased ECMO flow rate and decreased CO (high EFF) led to increased Rf (R = 0.98, log fit). Negative pressures developed in the venae cavae at low CO and high ECMO flow (high CR). Mean return cannula TAWSS was >10 Pa for all ECMO flow rates, with majority of the flow exiting the tip (94.0-95.8 %). CONCLUSIONS: Our results underpin the strong impact of CO on VV ECMO. A simple metric like EFF, once supported by clinical data, might help predict Rf for a patient at a given ECMO flow rate. The return cannula imparts high shear stresses on the blood, largely a result of the internal diameter.

A multimodal stacked ensemble model for cardiac output prediction utilizing cardiorespiratory interactions during general anesthesia.

This study examined the possibility of estimating cardiac output (CO) using a multimodal stacking model that utilizes cardiopulmonary interactions during general anesthesia and outlined a retrospective application of machine learning regression model to a pre-collected dataset. The data of 469 adult patients (obtained from VitalDB) with normal pulmonary function tests who underwent general anesthesia were analyzed. The hemodynamic data in this study included non-invasive blood pressure, plethysmographic heart rate, and SpO2. CO was recorded using Vigileo and EV1000 (pulse contour technique devices). Respiratory data included mechanical ventilation parameters and end-tidal CO2 levels. A generalized linear regression model was used as the metalearner for the multimodal stacking ensemble method. Random forest, generalized linear regression, gradient boosting machine, and XGBoost were used as base learners. A Bland-Altman plot revealed that the multimodal stacked ensemble model for CO prediction from 327 patients had a bias of - 0.001 L/min and - 0.271% when calculating the percentage of difference using the EV1000 device. Agreement of model CO prediction and measured Vigileo CO in 142 patients reported a bias of - 0.01 and - 0.333%. Overall, this model predicts CO compared to data obtained by the pulse contour technique CO monitors with good agreement.