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1.
Brain ; 147(4): 1321-1330, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38412555

ABSTRACT

The pathophysiological underpinnings of critically disrupted brain connectomes resulting in coma are poorly understood. Inflammation is potentially an important but still undervalued factor. Here, we present a first-in-human prospective study using the 18-kDa translocator protein (TSPO) radioligand 18F-DPA714 for PET imaging to allow in vivo neuroimmune activation quantification in patients with coma (n = 17) following either anoxia or traumatic brain injuries in comparison with age- and sex-matched controls. Our findings yielded novel evidence of an early inflammatory component predominantly located within key cortical and subcortical brain structures that are putatively implicated in consciousness emergence and maintenance after severe brain injury (i.e. mesocircuit and frontoparietal networks). We observed that traumatic and anoxic patients with coma have distinct neuroimmune activation profiles, both in terms of intensity and spatial distribution. Finally, we demonstrated that both the total amount and specific distribution of PET-measurable neuroinflammation within the brain mesocircuit were associated with the patient's recovery potential. We suggest that our results can be developed for use both as a new neuroprognostication tool and as a promising biometric to guide future clinical trials targeting glial activity very early after severe brain injury.


Subject(s)
Brain Injuries , Coma, Post-Head Injury , Humans , Coma/complications , Coma, Post-Head Injury/complications , Prospective Studies , Magnetic Resonance Imaging/methods , Brain/metabolism , Brain Injuries/complications , Hypoxia/complications , Receptors, GABA/metabolism
2.
Am J Respir Crit Care Med ; 209(7): 798-804, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38285595

ABSTRACT

Composite outcomes are commonly used in critical care trials to estimate the treatment effect of an intervention. A significant limitation of classical analytic approaches is that they assign equal statistical importance to each component in a composite, even if these do not have the same clinical importance (i.e., in a composite of death and organ failure, death is clearly more important). The win ratio (WR) method has been proposed as an alternative for trial outcomes evaluation, as it effectively assesses events based on their clinical relevance (i.e., hierarchical order) by comparing each patient in the intervention group with their counterparts in the control group. This statistical approach is increasingly used in cardiovascular outcome trials. However, WR may be useful to unveil treatment effects also in the critical care setting, because these trials are typically moderately sized, thus limiting the statistical power to detect small differences between groups, and often rely on composite outcomes that include several components of different clinical importance. Notably, the advantages of this approach may be offset by several drawbacks (such as ignoring ties and difficulties in selecting and ranking endpoints) and challenges in appropriate clinical interpretation (i.e., establishing clinical meaningfulness of the observed effect size). In this perspective article, we present some key elements to implementing WR statistics in critical care trials, providing an overview of strengths, drawbacks, and potential applications of this method. To illustrate, we conduct a reevaluation of the HYPO-ECMO (Hypothermia during Venoarterial Extracorporeal Membrane Oxygenation) trial using the WR framework as a case example.


Subject(s)
Critical Care , Outcome Assessment, Health Care , Humans
3.
J Card Fail ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38851449

ABSTRACT

BACKGROUND: Prediction of outcomes remains an unmet need in candidates for LVADs. The development of right-heart failure portends an excess in mortality rates, but imaging parameters of right ventricular systolic function have failed to demonstrate a prognostic role. By integrating pulmonary pressure, right ventriculoarterial coupling could fill this gap. METHODS: The ASSIST-ICD registry was used to test right ventriculoarterial coupling as a surrogate parameter at implantation for the prediction of all-cause mortality. RESULTS: The ratio of the tricuspid annular-plane systolic excursion over the estimated systolic pulmonary pressure (TAPSE/sPAP) was not associated with long-term survival in univariate analysis (P = 0.89), nor was the pulmonary artery pulsatility index (PAPi) (P = 0.13). Conversely, the ratio of the right atrial pressure over the pulmonary capillary wedge pressure (RAP/PCWP) was associated with all-cause mortality (P < 0.01). After taking tricuspid regurgitation severity, LVAD indication, LVAD model, age, blood urea nitrogen levels, and pulmonary vascular resistance into account, RAP/PCWP remained associated with survival (HR 1.35 [1.10 - 1.65]; P < 0.01). CONCLUSION: Among pre-implant RVAC surrogates, only RAP/PCWP was associated with long-term all-cause mortality in LVAD recipients. This association was independent of established risk factors.

4.
Eur Heart J ; 44(48): 5110-5124, 2023 Dec 21.
Article in English | MEDLINE | ID: mdl-37941449

ABSTRACT

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.


Subject(s)
Heart Transplantation , Myocarditis , Adult , Humans , Myocarditis/complications , Biopsy/methods , Cardiac Catheterization , Magnetic Resonance Imaging , Retrospective Studies , Myocardium/pathology
5.
Am Heart J ; 265: 203-212, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37657594

ABSTRACT

CONTEXT: Despite 20 years of improvement in acute coronary syndromes care, patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) remains a major clinical challenge with a stable incidence and mortality. While intra-aortic balloon pump (IABP) did not meet its expectations, percutaneous mechanical circulatory supports (pMCS) with higher hemodynamic support, large availability and quick implementation may improve AMICS prognosis by enabling early hemodynamic stabilization and unloading. Both interventional and observational studies suggested a clinical benefit in selected patients of the IMPELLAⓇ CP device within in a well-defined therapeutic strategy. While promising, these preliminary results are challenged by others suggesting a higher rate of complications and possible poorer outcome. Given these conflicting data and its high cost, a randomized clinical trial is warranted to delineate the benefits and risks of this new therapeutic strategy. DESIGN: The ULYSS trial is a prospective randomized open label, 2 parallel multicenter clinical trial that plans to enroll patients with AMICS for whom an emergent percutaneous coronary intervention (PCI) is intended. Patients will be randomized to an experimental therapeutic strategy with pre-PCI implantation of an IMPELLAⓇ CP device on top of standard medical therapy or to a control group undergoing PCI and standard medical therapy. The primary objective of this study is to compare the efficacy of this experimental strategy by a composite end point of death, need to escalate to ECMO, long-term left ventricular assist device or heart transplantation at 1 month. Among secondary objectives 1-year efficacy, safety and cost effectiveness will be assessed. CLINICAL TRIAL REGISTRATION: NCT05366452.

6.
Crit Care Med ; 50(5): e426-e433, 2022 05 01.
Article in English | MEDLINE | ID: mdl-34974497

ABSTRACT

OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population. DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016. SETTING: Nineteen French centers. PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed. Patients were divided in three groups: those under TCS at the time of LVAD implantation (n = 173), those with TCS removal before LVAD surgery (n = 24), and those who did not undergo a bridging strategy (n = 152). Primary endpoint was 30-day mortality. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications. Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD. CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart Failure , Heart-Assist Devices , Extracorporeal Membrane Oxygenation/adverse effects , Heart Failure/complications , Heart Failure/surgery , Heart-Assist Devices/adverse effects , Humans , Retrospective Studies , Shock, Cardiogenic/etiology , Shock, Cardiogenic/surgery , Treatment Outcome
7.
Rev Cardiovasc Med ; 23(1): 38, 2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35092230

ABSTRACT

Takotsubo cardiomyopathy (TTC) is a clinical condition of transient acute heart failure correlated to regional wall motion abnormalities extending beyond the distribution of a single epicardial coronary artery. It is classified into four major types: apical, basal, mid-ventricular and focal. Sympathetic nerve stimulation and catecholamine storm are the main players in the pathogenesis of TTC. The clinical course of disease is generally benign but it may end with life-threatening complications. Coronary angiography, left ventriculogram, transthoracic echocardiography and cardiac magnetic resonance imaging (CMR) are the main tools for making diagnosis. Except for critical cases with hemodynamic instability and/or complications, the overall management is limited to conventional heart failure therapy.


Subject(s)
Coronary Artery Disease , Takotsubo Cardiomyopathy , Coronary Angiography/adverse effects , Echocardiography/adverse effects , Echocardiography/methods , Heart Ventricles/diagnostic imaging , Humans , Takotsubo Cardiomyopathy/diagnostic imaging , Takotsubo Cardiomyopathy/therapy
8.
JAMA ; 327(5): 442-453, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35103766

ABSTRACT

IMPORTANCE: The optimal approach to the use of venoarterial extracorporeal membrane oxygenation (ECMO) during cardiogenic shock is uncertain. OBJECTIVE: To determine whether early use of moderate hypothermia (33-34 °C) compared with strict normothermia (36-37 °C) improves mortality in patients with cardiogenic shock receiving venoarterial ECMO. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial of patients (who were eligible if they had been endotracheally intubated and were receiving venoarterial ECMO for cardiogenic shock for <6 hours) conducted in the intensive care units at 20 French cardiac shock care centers between October 2016 and July 2019. Of 786 eligible patients, 374 were randomized. Final follow-up occurred in November 2019. INTERVENTIONS: Early moderate hypothermia (33-34 °C; n = 168) for 24 hours or strict normothermia (36-37 °C; n = 166). MAIN OUTCOMES AND MEASURES: The primary outcome was mortality at 30 days. There were 31 secondary outcomes including mortality at days 7, 60, and 180; a composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at days 30, 60, and 180; and days without requiring a ventilator or kidney replacement therapy at days 30, 60, and 180. Adverse events included rates of severe bleeding, sepsis, and number of units of packed red blood cells transfused during venoarterial ECMO. RESULTS: Among the 374 patients who were randomized, 334 completed the trial (mean age, 58 [SD, 12] years; 24% women) and were included in the primary analysis. At 30 days, 71 patients (42%) in the moderate hypothermia group had died vs 84 patients (51%) in the normothermia group (adjusted odds ratio, 0.71 [95% CI, 0.45 to 1.13], P = .15; risk difference, -8.3% [95% CI, -16.3% to -0.3%]). For the composite outcome of death, heart transplant, escalation to left ventricular assist device implantation, or stroke at day 30, the adjusted odds ratio was 0.61 (95% CI, 0.39 to 0.96; P = .03) for the moderate hypothermia group compared with the normothermia group and the risk difference was -11.5% (95% CI, -23.2% to 0.2%). Of the 31 secondary outcomes, 30 were inconclusive. The incidence of moderate or severe bleeding was 41% in the moderate hypothermia group vs 42% in the normothermia group. The incidence of infections was 52% in both groups. The incidence of bacteremia was 20% in the moderate hypothermia group vs 30% in the normothermia group. CONCLUSIONS AND RELEVANCE: In this randomized clinical trial involving patients with refractory cardiogenic shock treated with venoarterial ECMO, early application of moderate hypothermia for 24 hours did not significantly increase survival compared with normothermia. However, because the 95% CI was wide and included a potentially important effect size, these findings should be considered inconclusive. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02754193.


Subject(s)
Body Temperature , Extracorporeal Membrane Oxygenation/mortality , Hypothermia, Induced/mortality , Shock, Cardiogenic/mortality , Confidence Intervals , Erythrocyte Transfusion/statistics & numerical data , Extracorporeal Membrane Oxygenation/adverse effects , Female , France , Heart Transplantation/mortality , Heart-Assist Devices/statistics & numerical data , Hemorrhage/epidemiology , Hemorrhage/mortality , Hemorrhage/therapy , Humans , Intubation, Intratracheal , Male , Middle Aged , Renal Replacement Therapy , Respiration, Artificial , Sepsis/epidemiology , Stroke/epidemiology , Stroke/mortality , Time Factors
9.
Arterioscler Thromb Vasc Biol ; 40(1): 279-287, 2020 01.
Article in English | MEDLINE | ID: mdl-31766870

ABSTRACT

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.


Subject(s)
Embolism/etiology , Registries , Risk Assessment/methods , Takotsubo Cardiomyopathy/complications , Thrombosis/etiology , Aged , Australia/epidemiology , Coronary Angiography , Electrocardiography , Embolism/diagnosis , Embolism/epidemiology , Europe/epidemiology , Female , Follow-Up Studies , Heart Diseases/diagnosis , Heart Diseases/epidemiology , Heart Diseases/etiology , Heart Ventricles , Humans , Incidence , Magnetic Resonance Imaging, Cine , Male , Radionuclide Ventriculography , Risk Factors , Survival Rate/trends , Takotsubo Cardiomyopathy/diagnosis , Thrombosis/diagnosis , Thrombosis/epidemiology , Time Factors , United States/epidemiology
10.
Eur Heart J Suppl ; 23(Suppl A): A3-A9, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815008

ABSTRACT

Cardiogenic shock is a highly lethal syndrome, leading to rapid death or secondary multiorgan damage, but current shock therapies, including mechanical support devices, also have a significant side effect profile. The overarching goal of shock therapy is ensuring long-term survival with good quality of life. This implies averting death, modifying the disease course by promoting heart recovery and avoiding additional cardiac damage, protecting other organs, and circumventing complications. Monitoring and supportive therapies are subordinate to these goals. Rather than merely following preconceived notions, the rapid evolution in mechanical support technology requires iterative and critical review of the benefits of current procedures, protocols and drugs in view of their overall contribution to the therapeutic goals. This article discusses various monitoring and supportive pharmaceutical modalities typically used in patients with cardiogenic shock requiring mechanical support.

11.
Eur Heart J Suppl ; 23(Suppl A): A23-A26, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815011

ABSTRACT

The rationale for mechanical circulatory support (MCS) in cardiogenic shock is to restore cardiac output in selected patients when critically low or in case of refractory cardiac arrest. Furthermore, an MCS device that moves blood from either the left atrium or the left ventricle to the systemic circulation will potentially unload the ventricle. These devices are used alone or in combination with venoarterial extracorporeal membrane oxygenation (VA-ECMO). If a left-sided Impella device is used, it should be run at the highest possible performance level during treatment while avoiding suction events. When combined with VA-ECMO, the Impella device should be run at a lower performance level, ensuring sufficient left ventricular emptying but avoiding suction. Continuous monitoring is pivotal and patients managed outside the catheterization laboratory should be monitored with an arterial line, a central venous catheter, frequent use of pulmonary artery catheters and regular imaging by transthoracic echocardiogram.

12.
Eur Heart J Suppl ; 23(Suppl A): A35-A40, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815013

ABSTRACT

Cardiogenic shock (CS) is a clinical entity that includes a wide spectrum of different scenarios. Mechanical circulatory support (MCS) plays a fundamental role in the contemporary treatment of CS, and device selection is a key element in determining optimal treatment in this complex population. Cardiac support with mechanical devices should allow reduction and complete weaning from inotropes. Persistence of elevated left ventricular (LV) filling pressures, pulmonary congestion, metabolic decompensation, and end-organ damage during current MCS are criteria for MCS escalation. Precise diagnosis of the underlying cause of right ventricular (RV) failure is fundamental for undertaking the correct escalation strategy. In the setting of both MCS escalation and de-escalation, it is important to select a strategy in relation to long-term perspectives (bridge-to-recovery, bridge-to-LV assist device, or bridge-to-heart transplantation). Small retrospective studies have demonstrated that the BiPella approach is feasible, reduces cardiac filling pressures and improves cardiac output across a range of causes of CS. Simultaneous LV and RV device implantation and lower RV afterload may be associated with better outcomes in biventricular CS, but prospective studies are still required.

13.
Eur Heart J Suppl ; 23(Suppl A): A41-A45, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815014

ABSTRACT

Weaning of patients from Impella is complex and includes evaluation of the underlying disease, which is essential for estimating the potential for heart recovery. Monitoring during the weaning phase with echocardiography and pulmonary artery catheters will be discussed, as well as the use of intravenous and oral heart failure drugs. Patients who are candidates for weaning must be stable, without inotropes, and must have recovered from acute end-organ damage. Coronary artery disease and valvular heart diseases should be appropriately addressed before weaning to take the maximum advantage of haemodynamic stability provided by the support and to maximize the possibility of weaning. Tips and tricks for the mobilization of Impella patients will also be discussed.

14.
Crit Care Med ; 48(1): 83-90, 2020 01.
Article in English | MEDLINE | ID: mdl-31714398

ABSTRACT

OBJECTIVES: Thyroid storm represents a rare but life-threatening endocrine emergency. Only rare data are available on its management and the outcome of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management and in-ICU and 6-month survival rates of patients with those most severe thyroid storm forms requiring ICU admission. DESIGN: Retrospective, multicenter, national study over an 18-year period (2000-2017). SETTING: Thirty-one French ICUs. PATIENTS: The local medical records of patients from each participating ICU were screened using the International Classification of Diseases, 10th Revision. Inclusion criteria were "definite thyroid storm," as defined by the Japanese Thyroid Association criteria, and at least one thyroid storm-related organ failure. MEASUREMENTS AND MAIN RESULTS: Ninety-two patients were included in the study. Amiodarone-associated thyrotoxicosis and Graves' disease represented the main thyroid storm etiologies (30 [33%] and 24 [26%] patients, respectively), while hyperthyroidism was unknown in 29 patients (32%) before ICU admission. Amiodarone use (24 patients [26%]) and antithyroid-drug discontinuation (13 patients [14%]) were the main thyroid storm-triggering factors. No triggering factor was identified for 30 patients (33%). Thirty-five patients (38%) developed cardiogenic shock within the first 48 hours after ICU admission. In-ICU and 6-month postadmission mortality rates were 17% and 22%, respectively. ICU nonsurvivors more frequently required vasopressors, extracorporeal membrane of oxygenation, renal replacement therapy, mechanical ventilation, and/or therapeutic plasmapheresis. Multivariable analyses retained Sequential Organ Failure Assessment score without cardiovascular component (odds ratio, 1.22; 95% CI, 1.03-1.46; p = 0.025) and cardiogenic shock within 48 hours post-ICU admission (odds ratio, 9.43; 1.77-50.12; p = 0.008) as being independently associated with in-ICU mortality. CONCLUSIONS: Thyroid storm requiring ICU admission causes high in-ICU mortality. Multiple organ failure and early cardiogenic shock seem to markedly impact the prognosis, suggesting a prompt identification and an aggressive management.


Subject(s)
Thyroid Crisis , Adult , Aged , Female , Humans , Intensive Care Units , Male , Middle Aged , Retrospective Studies , Survival Rate , Thyroid Crisis/diagnosis , Thyroid Crisis/mortality , Thyroid Crisis/therapy
15.
J Transl Med ; 18(1): 213, 2020 05 27.
Article in English | MEDLINE | ID: mdl-32460856

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in intensive care units and can modify drug pharmacokinetics and lead to under-exposure associated with treatment failure. Ceftolozane/tazobactam is an antibiotic combination used for complicated infections in critically ill patients. Launched in 2015, sparse data are available on the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam. The aim of the present study was to determine the influence of ECMO on the pharmacokinetics of ceftolozane-tazobactam. METHODS: An ex vivo model (closed-loop ECMO circuits primed with human whole blood) was used to study adsorption during 8-h inter-dose intervals over a 24-h period (for all three ceftolozane/tazobactam injections) with eight samples per inter-dose interval. Two different dosages of ceftolozane/tazobactam injection were studied and a control (whole blood spiked with ceftolozane/tazobactam in a glass tube) was performed. An in vivo porcine model was developed with a 1-h infusion of ceftolozane-tazobactam and concentration monitoring for 11 h. Pigs undergoing ECMO were compared with a control group. Pharmacokinetic analysis of in vivo data (non-compartmental analysis and non-linear mixed effects modelling) was performed to determine the influence of ECMO. RESULTS: With the ex vivo model, variations in concentration ranged from - 5.73 to 1.26% and from - 12.95 to - 2.89% respectively for ceftolozane (concentrations ranging from 20 to 180 mg/l) and tazobactam (concentrations ranging from 10 to 75 mg/l) after 8 h. In vivo pharmacokinetic exploration showed that ECMO induces a significant decrease of 37% for tazobactam clearance without significant modification in the pharmacokinetics of ceftolozane, probably due to a small cohort size. CONCLUSIONS: Considering that the influence of ECMO on the pharmacokinetics of ceftolozane/tazobactam is not clinically significant, normal ceftolozane and tazobactam dosing in critically ill patients should be effective for patients undergoing ECMO.


Subject(s)
Extracorporeal Membrane Oxygenation , Animals , Anti-Bacterial Agents/therapeutic use , Cephalosporins , Critical Illness , Humans , Swine , Tazobactam/pharmacology
16.
J Intensive Care Med ; 35(7): 679-686, 2020 Jul.
Article in English | MEDLINE | ID: mdl-29768983

ABSTRACT

PURPOSE: Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)-a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population. METHODS: All patients treated by venoarterial or venovenous ECMO in our intensive care unit between January 2014 and December 2015 were prospectively included. A concomitant measurement of the anti-Xa activity and ACT was performed on the same sample collected twice a day (morning-evening) for unfractionated heparin adaptation with an ACT target range of 180 to 220 seconds. RESULTS: One hundred and nine patients (men 69.7%, median age 54 years) treated with ECMO (70.6% venoarterial) were included. Spearman analysis found no correlation between anti-Xa and ACT (ρ < 0.4) from day 1 and worsened over time. Kappa analysis showed no agreement between the respective target ranges of ACT and anti-Xa. CONCLUSIONS: We demonstrate that concomitant measurement of ACT and anti-Xa activity is irrelevant in ECMO patients. Since ACT is poorly correlated with heparin dosage, anti-Xa activity appears to be a more suitable assay for anticoagulation monitoring.


Subject(s)
Anticoagulants/administration & dosage , Blood Coagulation Tests/statistics & numerical data , Drug Monitoring/statistics & numerical data , Extracorporeal Membrane Oxygenation , Factor Xa Inhibitors/blood , Blood Coagulation/drug effects , Blood Coagulation Tests/methods , Drug Monitoring/methods , Female , Heparin/administration & dosage , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Statistics, Nonparametric
17.
Echocardiography ; 37(5): 706-714, 2020 05.
Article in English | MEDLINE | ID: mdl-32364272

ABSTRACT

BACKGROUND: Right ventricular (RV) systolic parameters are difficult to assess in heart transplant recipients (HTRs) compared to healthy people because of discordant data, and their impact on exercise capacity remains undefined. We sought to retrospectively assess the impact of RV systolic function on exercise capacity after heart transplantation. METHODS: We analyzed data from 61 HTRs who underwent transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR), and exercise capacity assessment by 6-minute walking test (6MWT) and cardiopulmonary exercise testing (CPET) at 1- and 2-year follow-ups. RESULTS: Transthoracic echocardiography RV longitudinal systolic function including tricuspid annular plan systolic excursion (TAPSE), peak systolic S' wave tricuspid annular velocity (PSVtdi) and RV free wall longitudinal strain was decreased at 1 year (respectively, 15 ± 3 mm, 10 ± 3 cm/s, and -19 ± 5%) and at 2 years (respectively, 15 ± 3 mm, 10 ± 2 cm/s, and -20 ± 5%) with no significant difference between both evaluations; meanwhile, RV ejection fraction (RVEF) measured by CMR was preserved. Mean percentage of predicted peak oxygen consumption was altered, but improved between the first and second year (55 ± 18 vs 60 ± 18%, P = .038). PSVtdi was weakly correlated with 6MWT distance (r = .426, P = .017) and RVEF with the predicted distance at 6MWT (r = .410, P = .027) at the 1-year follow-up. CONCLUSIONS: Despite decreasing values, RV longitudinal systolic function has a weak impact on exercise capacity of HTRs. PSVtdi and RVEF are the most pertinent parameters to assess the impact of RV systolic function on exercise capacity after heart transplantation. These results should lead to redefine normal RV systolic function thresholds for HTRs.


Subject(s)
Heart Transplantation , Ventricular Dysfunction, Right , Exercise Tolerance , Humans , Retrospective Studies , Sensitivity and Specificity , Stroke Volume , Ventricular Dysfunction, Right/diagnostic imaging , Ventricular Function, Right
18.
Indian Pacing Electrophysiol J ; 20(1): 33-34, 2020.
Article in English | MEDLINE | ID: mdl-31751602

ABSTRACT

Use of 3D navigation systems may be sometimes impossible in patients with left ventricular assist devices because of major electromagnetical interferences with some 3D systems based on magnetic localization. Mapping with the Rhythmia ™ system in patients implanted with an Impella ™ is described to be non feasible. We relate how to overcome this technical issues in this case.

19.
Am Heart J ; 214: 69-76, 2019 08.
Article in English | MEDLINE | ID: mdl-31174053

ABSTRACT

BACKGROUND: Left ventricular assist device (LVAD)-associated infections may be life-threatening and impact patients' outcome. We aimed to identify the characteristics, risk factors, and prognosis of LVAD-associated infections. METHODS: Patients included in the ASSIST-ICD study (19 centers) were enrolled. The main outcome was the occurrence of LVAD-associated infection (driveline infection, pocket infection, or pump/cannula infection) during follow-up. RESULTS: Of the 652 patients enrolled, 201 (30.1%) presented a total of 248 LVAD infections diagnosed 6.5 months after implantation, including 171 (26.2%), 51 (7.8%), and 26 (4.0%) percutaneous driveline infection, pocket infection, or pump/cannula infection, respectively. Patients with infections were aged 58.7 years, and most received HeartMate II (82.1%) or HeartWare (13.4%). Most patients (62%) had implantable cardioverter-defibrillators (ICDs) before LVAD, and 104 (16.0%) had ICD implantation, extraction, or replacement after the LVAD surgery. Main pathogens found among the 248 infections were Staphylococcus aureus (n = 113' 45.4%), Enterobacteriaceae (n = 61; 24.6%), Pseudomonas aeruginosa (n = 34; 13.7%), coagulase-negative staphylococci (n = 13; 5.2%), and Candida species (n = 13; 5.2%). In multivariable analysis, HeartMate II (subhazard ratio, 1.56; 95% CI, 1.03 to 2.36; P = .031) and ICD-related procedures post-LVAD (subhazard ratio, 1.43; 95% CI, 1.03-1.98; P = .031) were significantly associated with LVAD infections. Infections had no detrimental impact on survival. CONCLUSIONS: Left ventricular assist device-associated infections affect one-third of LVAD recipients, mostly related to skin pathogens and gram-negative bacilli, with increased risk with HeartMate II as compared with HeartWare, and in patients who required ICD-related procedures post-LVAD. This is a plea to better select patients needing ICD implantation/replacement after LVAD implantation.


Subject(s)
Catheter-Related Infections/etiology , Heart-Assist Devices/adverse effects , Prosthesis-Related Infections/etiology , Catheter-Related Infections/epidemiology , Catheter-Related Infections/microbiology , Catheter-Related Infections/mortality , Defibrillators, Implantable/statistics & numerical data , Device Removal/statistics & numerical data , Female , France/epidemiology , Heart Ventricles , Heart-Assist Devices/statistics & numerical data , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Prosthesis-Related Infections/epidemiology , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/mortality , Retrospective Studies , Risk Factors
20.
Crit Care ; 23(1): 2, 2019 01 07.
Article in English | MEDLINE | ID: mdl-30616669

ABSTRACT

BACKGROUND: Prolonged weaning is a major issue in intensive care patients and tracheostomy is one of the last resort options. Optimized patient-ventilator interaction is essential to weaning. The purpose of this study was to compare patient-ventilator synchrony between pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA) in a selected population of tracheostomised patients. METHODS: We performed a prospective, sequential, non-randomized and single-centre study. Two recording periods of 60 min of airway pressure, flow, and electrical activity of the diaphragm during PSV and NAVA were recorded in a random assignment and eight periods of 1 min were analysed for each mode. We searched for macro-asynchronies (ineffective, double, and auto-triggering) and micro-asynchronies (inspiratory trigger delay, premature, and late cycling). The number and type of asynchrony events per minute and asynchrony index (AI) were determined. The two respiratory phases were compared using the non-parametric Wilcoxon test after testing the equality of the two variances (F-Test). RESULTS: Among the 61 patients analysed, the total AI was lower in NAVA than in PSV mode: 2.1% vs 14% (p < 0.0001). This was mainly due to a decrease in the micro-asynchronies index: 0.35% vs 9.8% (p < 0.0001). The occurrence of macro-asynchronies was similar in both ventilator modes except for double triggering, which increased in NAVA. The tidal volume (ml/kg) was lower in NAVA than in PSV (5.8 vs 6.2, p < 0.001), and the respiratory rate was higher in NAVA than in PSV (28 vs 26, p < 0.05). CONCLUSION: NAVA appears to be a promising ventilator mode in tracheotomised patients, especially for those requiring prolonged weaning due to the decrease in asynchronies.


Subject(s)
Interactive Ventilatory Support/methods , Neural Pathways/physiology , Respiration, Artificial/standards , Tracheostomy/methods , Aged , Female , France , Humans , Interactive Ventilatory Support/instrumentation , Interactive Ventilatory Support/standards , Male , Middle Aged , Noninvasive Ventilation/instrumentation , Noninvasive Ventilation/methods , Positive-Pressure Respiration/methods , Prospective Studies , Respiration, Artificial/instrumentation , Respiration, Artificial/methods , Severity of Illness Index , Simplified Acute Physiology Score , Tracheostomy/standards , Ventilator Weaning/instrumentation , Ventilator Weaning/methods
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