The purpose of this study was to evaluate the clinical relevance of high values of central venous-to-arterial carbon dioxide difference (PCO2 gap) in high-risk surgical patients admitted to a ...postoperative ICU. We hypothesized that PCO2 gap could serve as a useful tool to identify patients still requiring hemodynamic optimization at ICU admission.
One hundred and fifteen patients were included in this prospective single-center observational study during a 1-year period. High-risk surgical inclusion criteria were adapted from Schoemaker and colleagues. Demographic and biological data, PCO2 gap, central venous oxygen saturation, lactate level and postoperative complications were recorded for all patients at ICU admission, and 6 hours and 12 hours after admission.
A total of 78 (68%) patients developed postoperative complications, of whom 54 (47%) developed organ failure. From admission to 12 hours after admission, there was a significant difference in mean PCO2 gap (8.7 ± 2.8 mmHg versus 5.1 ± 2.6 mmHg; P = 0.001) and median lactate values (1.54 (1.1-3.2) mmol/l versus 1.06 (0.8-1.8) mmol/l; P = 0.003) between patients who developed postoperative complications and those who did not. These differences were maximal at admission to the ICU. At ICU admission, the area under the receiver operating characteristic curve for occurrence of postoperative complications was 0.86 for the PCO2 gap compared to Sequential Organ Failure Assessment score (0.82), Simplified Acute Physiology Score II score (0.67), and lactate level (0.67). The threshold value for PCO2 gap was 5.8 mmHg. Multivariate analysis showed that only a high PCO2 gap and a high Sequential Organ Failure Assessment score were independently associated with the occurrence of postoperative complications. A high PCO2 gap (≥6 mmHg) was associated with more organ failure, an increase in duration of mechanical ventilation and length of hospital stay.
A high PCO2 gap at admission in the postoperative ICU was significantly associated with increased postoperative complications in high-risk surgical patients. If the increase in PCO2 gap is secondary to tissue hypoperfusion then the PCO2 gap might be a useful tool complementary to central venous oxygen saturation as a therapeutic target.
The main risk factor for bleeding in patients with continuous-flow mechanical circulatory support (CF-MCS) is the acquired von Willebrand factor (VWF) defect related to the high shear-stress forces ...developed by these devices. Although a higher bleeding rate has been reported in CF-MCS recipients who had reduced pulsatility, the relation between pulsatility and the VWF defect has never been studied.
The purpose of this study was to investigate the relation between pulsatility and VWF under CF-MCS.
We assessed the effect of 2 CF-MCS on VWF multimer degradation in a mock circulatory loop (model 1). Using these devices, we investigated in a dose-effect model (model 2) 3 levels of pulsatility in 3 groups of swine. In a cross-over model (model 3), we studied the effects of sequential changes of pulsatility on VWF. We reported the evolution of VWF multimerization in a patient undergoing serial CF-MCS and/or pulsatile-MCS.
We demonstrated the proteolytic degradation of VWF multimers by high shear CF-MCS in a circulatory loop without pulsatility. We observed both in swine models and in a patient that the magnitude of the VWF degradation is modulated by the pulsatility level in the high shear-stress level condition, and that the restoration of pulsatility is a trigger for the endothelial release of VWF.
We demonstrated that the VWF defect reflects the balance between degradation induced by the shear stress and the endothelial release of new VWF triggered by the pulsatility. This modulation of VWF levels could explain the relationship between pulsatility and bleeding observed in CF-MCS recipients. Preservation of pulsatility may be a new target to improve clinical outcomes of patients.
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...the difference in mean PTT is uninterpretable without providing for each PTT assay, the heparin therapeutic range is corresponding to the anti-FXa range of 0.3–0.7 UI/ml 3. ...these confounders ...were not included in the multivariate analysis. Since the baseline coagulation covariates (fibrinogen, d-dimers, antithrombin) included in the model are likely to fluctuate daily during ECMO, they should be analyzed as time-varying covariates in the multivariate model. ...this study has compared the ECMO management procedures of two centers beyond heparinization alone, in two different populations with a methodology that may lead to misinterpretation. ...our retrospective comparison of real-world data from two centers found lower rates of oxygenator change and thromboembolic complications in the center employing higher doses of heparin.
Central venous oxygen saturation (ScvO2) is a useful therapeutic target in septic shock and high-risk surgery. We tested the hypothesis that central venous-to-arterial carbon dioxide difference ...(P(cv-a)CO2), a global index of tissue perfusion, could be used as a complementary tool to ScvO2 for goal-directed fluid therapy (GDT) to identify persistent low flow after optimization of preload has been achieved by fluid loading during high-risk surgery.
This is a secondary analysis of results obtained in a study involving 70 adult patients (ASA I to III), undergoing major abdominal surgery, and treated with an individualized goal-directed fluid replacement therapy. All patients were managed to maintain a respiratory variation in peak aortic flow velocity below 13%. Cardiac index (CI), oxygen delivery index (DO2i), ScvO2, P(cv-a)CO2 and postoperative complications were recorded blindly for all patients.
A total of 34% of patients developed postoperative complications. At baseline, there was no difference in demographic or haemodynamic variables between patients who developed complications and those who did not. In patients with complications, during surgery, both mean ScvO2 (78 ± 4 versus 81 ± 4%, P = 0.017) and minimal ScvO2 (minScvO2) (67 ± 6 versus 72 ± 6%, P = 0.0017) were lower than in patients without complications, despite perfusion of similar volumes of fluids and comparable CI and DO2i values. The optimal ScvO2 cut-off value was 70.6% and minScvO2 < 70% was independently associated with the development of postoperative complications (OR = 4.2 (95% CI: 1.1 to 14.4), P = 0.025). P(cv-a)CO2 was larger in patients with complications (7.8 ± 2 versus 5.6 ± 2 mmHg, P < 10-6). In patients with complications and ScvO2 ≥ 71%, P(cv-a)CO2 was also significantly larger (7.7 ± 2 versus 5.5 ± 2 mmHg, P < 10-6) than in patients without complications. The area under the receiver operating characteristic (ROC) curve was 0.785 (95% CI: 0.74 to 0.83) for discrimination of patients with ScvO2 ≥ 71% who did and did not develop complications, with 5 mmHg as the most predictive threshold value.
ScvO2 reflects important changes in O2 delivery in relation to O2 needs during the perioperative period. A P(cv-a)CO2 < 5 mmHg might serve as a complementary target to ScvO2 during GDT to identify persistent inadequacy of the circulatory response in face of metabolic requirements when an ScvO2 ≥ 71% is achieved.
Clinicaltrials.gov Identifier: NCT00852449.
: This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the ...series can be found online at http://ccforum.com/series/yearbook. Further information about the Yearbook of Intensive Care and Emergency Medicine is available from http://www.springer.com/series/2855.
Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in ...high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR.
We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation.
After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year.
The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).
We report an original alkane elimination approach, entailing the protonolysis of triisobutylaluminum by the acidic hydrides from Cp*IrH4. This strategy allows access to a series of well-defined tri- ...and tetranuclear iridium aluminum polyhydride clusters, depending on the stoichiometry: Cp*IrH3Al(iBu)22 (1), Cp*IrH2Al(iBu)2 (2), (Cp*IrH3)2Al(iBu) (3), and (Cp*IrH3)3Al (4). Contrary to most transition-metal aluminohydride complexes, which can be considered as AlH x+3x– aluminates and LnM+ moieties, the situation here is reversed: These complexes have original structures that are best described as Cp*IrH x n− iridate units surrounding cationic Al(III) fragments. This is corroborated by reactivity studies, which show that the hydrides are always retained at the iridium sites and that the Cp*IrH3− moieties are labile and can be transmetalated to yield potassium (KIrCp*H3, 8) or silver ((AgIrCp*H3 n , 10) derivatives of potential synthetic interest. DFT calculations show that the bonding situation can vary in these systems, from 3-center 2-electron hydride-bridged Lewis adducts of the form Ir–H⇀Al to direct polarized metal–metal interaction from donation of d-electrons of Ir to the Al metal, and both types of interactions take place to some extent in each of these clusters.
Background. Unfractionated heparin is administered in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Anticoagulation monitoring is recommended, with an ...anti-activated factor X (anti-Xa) targeting 0.3 to 0.7 IU/mL. Owing to heparin’s heterogeneous pharmacokinetic properties, anti-Xa is unpredictable, generating a challenge in anticoagulation practices. The aim of this study was to build a pharmacokinetic model of heparin accounting for potential confounders, and derive an optimized dosing regimen for a given anti-Xa target. Methods. Adult patients undergoing VA-ECMO were included between January 2020 and June 2021. Anticoagulation was managed with an initial 100 IU/kg heparin loading dose followed by a continuous infusion targeting 0.2 to 0.7 IU/mL anti-Xa. The data were split into model development and model validation cohorts. Statistical analysis was performed using a nonlinear mixed effects modeling population approach. Model-based simulations were performed to develop an optimized dosing regimen targeting the desired anti-Xa. Results. A total of 74 patients were included, with 1703 anti-Xa observations. A single-compartment model best fitted the data. Interpatient variability for distribution volume was best explained by body weight, C-reactive protein and ECMO indication (post-cardiotomy shock or medical cardiogenic shock), and interpatient variability for elimination clearance was best explained by serum creatinine and C-reactive protein. Simulations using the optimized regimen according to these covariates showed accurate anti-Xa target attainment. Conclusion. In adult patients on VA-ECMO, heparin’s effect increased with serum creatinine and medical indication, whereas it decreased with body weight and systemic inflammation. We propose an optimized dosing regimen accounting for key covariates, capable of accurately predicting a given anti-Xa target.
Abstract
Background
The mortality rate for a patient with a refractory cardiogenic shock on venoarterial (VA) extracorporeal membrane oxygenation (ECMO) remains high, and hyperoxia might worsen this ...prognosis. The objective of the present study was to evaluate the association between hyperoxia and 28-day mortality in this setting.
Methods
We conducted a retrospective bicenter study in two French academic centers. The study population comprised adult patients admitted for refractory cardiogenic shock. The following arterial partial pressure of oxygen (PaO
2
) variables were recorded for 48 h following admission: the absolute peak PaO
2
(the single highest value measured during the 48 h), the mean daily peak PaO
2
(the mean of each day’s peak values), the overall mean PaO
2
(the mean of all values over 48 h), and the severity of hyperoxia (mild: PaO
2
< 200 mmHg, moderate: PaO
2
= 200–299 mmHg, severe: PaO
2
≥ 300 mmHg). The main outcome was the 28-day all-cause mortality. Inverse probability weighting (IPW) derived from propensity scores was used to reduce imbalances in baseline characteristics.
Results
From January 2013 to January 2020, 430 patients were included and assessed. The 28-day mortality rate was 43%. The mean daily peak, absolute peak, and overall mean PaO
2
values were significantly higher in non-survivors than in survivors. In a multivariate logistic regression analysis, the mean daily peak PaO
2
, absolute peak PaO
2
, and overall mean PaO
2
were independent predictors of 28-day mortality (adjusted odds ratio 95% confidence interval per 10 mmHg increment: 2.65 1.79–6.07, 2.36 1.67–4.82, and 2.85 1.12–7.37, respectively). After IPW, high level of oxygen remained significantly associated with 28-day mortality (OR = 1.41 1.01–2.08;
P
= 0.041).
Conclusions
High oxygen levels were associated with 28-day mortality in patients on VA-ECMO support for refractory cardiogenic shock. Our results confirm the need for large randomized controlled trials on this topic.
Multicellular organisms initiate adaptive responses when oxygen (O
2) availability decreases, but the underlying mechanism of O
2 sensing remains elusive. We find that functionality of complex III of ...the mitochondrial electron transport chain (ETC) is required for the hypoxic stabilization of HIF-1α and HIF-2α and that an increase in reactive oxygen species (ROS) links this complex to HIF-α stabilization. Using RNAi to suppress expression of the Rieske iron-sulfur protein of complex III, hypoxia-induced HIF-1α stabilization is attenuated, and ROS production, measured using a novel ROS-sensitive FRET probe, is decreased. These results demonstrate that mitochondria function as O
2 sensors and signal hypoxic HIF-1α and HIF-2α stabilization by releasing ROS to the cytosol.
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