How I approach membrane lung dysfunction in patients receiving ECMO.
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ABSTRACT:
SUBMITTER: Zakhary B
PROVIDER: S-EPMC7704102 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDespite the surge in use of extracorporeal membrane oxygenation (ECMO) in the adult intensive care unit, little guidance is available on the appropriate dosing of antimicrobials in this setting. Ceftriaxone is an antimicrobial with a high affinity to plasma protein, a property identified in the literature as susceptible to sequestration into extracorporeal circuits and hypothesised to require dosage adjustments in this setting.ObjectiveThe aim of this study was to describe the pharmacokinetics of ceftriaxone and identify the best dosing regimen for critically ill adult patients receiving ECMO.MethodsSerial blood samples were taken from patients receiving both ECMO and ceftriaxone. Total and unbound drug concentrations were measured in plasma by chromatographic assay and analysed using a population pharmacokinetic approach with Pmetrics®. Dosing simulations were performed to identify the optimal dosing strategy: 60 and 100% of time with free (unbound) drug concentration exceeding the minimum inhibitory concentration (fT>MIC).ResultsIn total, 14 patients were enrolled, of which three were receiving renal replacement therapy (RRT). Total and unbound ceftriaxone was best described in a two-compartment model with total body weight, serum albumin concentrations, creatinine clearance (CrCL), and the presence of RRT included as significant predictors of pharmacokinetics. Patients not on RRT generated a mean renal clearance of 0.90 L/h, non-renal clearance of 0.33 L/h, and central volume of distribution of 7.94 L. Patients on RRT exhibited a mean total clearance of 1.18 L/h. ECMO variables were not significant predictors of ceftriaxone pharmacokinetics. Steady-state dosing simulations found that dosages of 1 g every 12 h and 2 g every 24 h achieved >90% probabilities of target attainment in patients with CrCL of 0 mL/min with RRT and 30 and 100 mL/min and various serum albumin concentrations (17 and 26 g/L).ConclusionsDosing recommendations for critically ill adult patients not on ECMO appear to be sufficient for patients on ECMO. Patients exhibiting augmented renal clearance (> 130 mL/min) or treatment of less susceptible pathogens may require higher doses, which requires further investigation.
| S-EPMC9249724 | biostudies-literature
Project description:Extracorporeal membrane oxygenation (ECMO) is used for patients with cardiopulmonary failure and is associated with severe bleeding and poor outcome. Platelet dysfunction may be a contributing factor. The aim of this prospective observational study was to characterize platelet dysfunction and its relation to outcome in ECMO patients. Blood was sampled from thirty ECMO patients at three timepoints. Expression of CD62P, CD63, activated GPIIb/IIIa, GPVI, GPIbα and formation platelet-leukocyte aggregates (PLA) were analyzed at rest and in response to stimulation. Delta granule storage-pool deficiency and secretion defects were also investigated. Fifteen healthy volunteers and ten patients with coronary artery disease served as controls. Results were also compared between survivors and non-survivors. Compared to controls, expression of platelet surface markers, delta granule secretion and formation of PLA was reduced, particularly in response to stimulation. Baseline CD63 expression was higher and activated GPIIb/IIIa expression in response to stimulation was lower in non-survivors on day 1 of ECMO. Logistic regression analysis revealed that these markers were associated with mortality. In conclusion, platelets from ECMO patients are severely dysfunctional predisposing patients to bleeding complications and poor outcome. Platelet dysfunction on day 1 of ECMO detected by the platelet surface markers CD63 and activated GPIIb/IIIa is associated with mortality. CD63 and activated GPIIb/IIIa may therefore serve as novel prognostic biomarkers, but future studies are required to determine their true potential.
| S-EPMC8444511 | biostudies-literature
Project description:This multicenter study describes the population pharmacokinetics (PK) of fluconazole in critically ill patients receiving concomitant extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) and includes an evaluation of different fluconazole dosing regimens for achievement of target exposure associated with maximal efficacy. Serial blood samples were obtained from critically ill patients on ECMO and CRRT receiving fluconazole. Total fluconazole concentrations were measured in plasma using a validated chromatographic assay. A population PK model was developed and Monte Carlo dosing simulations were performed using Pmetrics in R. The probability of target attainment (PTA) of various dosing regimens to achieve fluconazole area under the curve to minimal inhibitory concentration ratio (AUC0-24/MIC) >100 was estimated. Eight critically ill patients receiving concomitant ECMO and CRRT were included. A two-compartment model including total body weight as a covariate on clearance adequately described the data. The mean (±standard deviation, SD) clearance and volume of distribution were 2.87 ± 0.63 L/h and 15.90 ± 13.29 L, respectively. Dosing simulations showed that current guidelines (initial loading dose of 12 mg/kg then 6 mg/kg q24h) achieved >90% of PTA for a MIC up to 1 mg/L. None of the tested dosing regimens achieved 90% of PTA for MIC above 2 mg/L. Current fluconazole dosing regimen guidelines achieved >90% PTA only for Candida species with MIC <1 mg/L and thus should be only used for Candida-documented infections in critically ill patients receiving concomitant ECMO and CRRT. Total body weight should be considered for fluconazole dose.
| S-EPMC10777822 | biostudies-literature
Project description:Extracorporeal membrane oxygenation (ECMO) is a lifesaving technology in critically ill patients who present with cardiac/pulmonary/combined cardiopulmonary failure. These patients are the sickest of all patients in any critical care unit and will invariably have a prolonged course and rehabilitation. Spontaneous breathing and early mobilization can reduce the intensive care unit (ICU)-acquired weakness, improve functional recovery, and reduce superadded infections and length of stay in the hospital, thus decreasing the cost of treatment. In low socioeconomic countries, there is an associated challenge of the availability of specially trained personnel necessary to manage patients on ECMO. Managing and ambulating an awake patient on ECMO is very labour-intensive and poses various challenges. Every ECMO program should aim to develop goals, methods, and protocols to this end. These can be derived from best practices worldwide by suitably adapting to available personnel and equipment. In this review, we aim to highlight the advantages and associated challenges of awake ECMO and describe protocols to aid safe ambulation and physiotherapy for ECMO patients.Supplementary informationThe online version contains supplementary material available at 10.1007/s12055-020-01075-z.
| S-EPMC7811888 | biostudies-literature
Project description:The Bruton tyrosine kinase (Btk) inhibitor ibrutinib induces platelet dysfunction and causes increased risk of bleeding. Off-target inhibition of Tec is believed to contribute to platelet dysfunction and other side effects of ibrutinib. The second-generation Btk inhibitor acalabrutinib was developed with improved specificity for Btk over Tec. We investigated platelet function in patients with non-Hodgkin lymphoma (NHL) receiving ibrutinib or acalabrutinib by aggregometry and by measuring thrombus formation on collagen under arterial shear. Both patient groups had similarly dysfunctional aggregation responses to collagen and collagen-related peptide, and comparison with mechanistic experiments in which platelets from healthy donors were treated with the Btk inhibitors suggested that both drugs inhibit platelet Btk and Tec at physiological concentrations. Only ibrutinib caused dysfunctional thrombus formation, whereas size and morphology of thrombi following acalabrutinib treatment were of normal size and morphology. We found that ibrutinib but not acalabrutinib inhibited Src family kinases, which have a critical role in platelet adhesion to collagen that is likely to underpin unstable thrombus formation observed in ibrutinib patients. We found that platelet function was enhanced by increasing levels of von Willebrand factor (VWF) and factor VIII (FVIII) ex vivo by addition of intermediate purity FVIII (Haemate P) to blood from patients, resulting in consistently larger thrombi. We conclude that acalabrutinib avoids major platelet dysfunction associated with ibrutinib therapy, and platelet function may be enhanced in patients with B-cell NHL by increasing plasma VWF and FVIII.
| S-EPMC5728643 | biostudies-literature
Project description:ObjectiveDetermine the feasibility, strengths, and barriers of offering extracorporeal membrane oxygenation (ECMO) telerounding to neonatal intensive care unit (NICU) care providers.Study designNICU providers were invited to join ECMO rounds by teleconference. Data were collected on telerounding participation and ECMO concepts discussed. A survey was sent to all providers.ResultsFrom March 2018 to February 2020, telerounding on 24 neonatal ECMO patients (168 ECMO days) was performed in a Level IV NICU. A mean of four providers joined telerounds per ECMO day with an increase from 3 to 6 providers over the study period. Nearly all respondents felt telerounding lowered barriers to attending ECMO rounds (94%), promoted engagement (89%), and improved continuity of care (78%). Barriers to ECMO telerounding were suboptimal audio connections and limited ability to participate in the clinical discussion.ConclusionECMO telerounding is well-received by NICU providers. It can improve provider participation, complement existing in-person ECMO rounds, and ECMO education.
| S-EPMC7505939 | biostudies-literature
Project description:Venovenous (VV) and venoarterial (VA) extracorporeal membrane oxygenation (ECMO) are effective support modalities to treat critically ill patients. ECMO-associated hemolysis remains a serious complication. The aim was to disclose similarities and differences in VA- and VV ECMO-associated hemolysis. This is a retrospective single-center analysis (January 2012 to September 2018) including 1,063 adult consecutive patients (VA, n = 606; VV, n = 457). Severe hemolysis (free plasma hemoglobin, fHb > 500 mg/l) during therapy occurred in 4% (VA) and 2% (VV) (p≤0.001). VV ECMO showed significantly more hemolysis by pump head thrombosis (PHT) compared to VA ECMO (9% vs. 2%; p≤0.001). Pretreatments (ECPR, cardiac surgery) of patients who required VA ECMO caused high fHb pre levels which aggravates the proof of ECMO-induced hemolysis (median (interquartile range), VA: fHb pre: 225.0 (89.3-458.0); VV: fHb pre: 72.0 (42.0-138.0); p≤0.001). The survival rate to discharge from hospital differed depending on ECMO type (40% (VA) vs. 63% (VV); p≤0.001). Hemolysis was dominant in VA ECMO patients, mainly caused by different indications and not by the ECMO support itself. PHT was the most severe form of ECMO-induced hemolysis that occurs in both therapies with low frequency, but more commonly in VV ECMO due to prolonged support time.
| S-EPMC6984694 | biostudies-literature
Project description:Background:Based on promising results over the past 10 years, the method of extracorporeal membrane oxygenation (ECMO) has developed from being used as a 'rescue therapy' to become an accepted treatment option for patients with acute lung failure (ARDS). Subsequently, the indication was extended also to patients suffering from cardiogenic and septic shock. Our aim was to evaluate hospital mortality and associated prognostic variables in patients with lung failure, cardiogenic, and septic shock undergoing ECMO. Furthermore, a cumulative sum (CUSUM) analysis was used to assess the learning curve of ECMO-treatment in our department. Methods:We retrospectively analysed the data of 131 patients undergoing ECMO treatment in the intensive care unit of the Asklepios Hospital of Langen over the time period from April 2011 to July 2016. We categorised the patients into three groups: lung failure (n?=?54); cardiogenic shock (n?=?58); and septic shock (n?=?19). The primary outcome variable was hospital mortality along with identification of prognostic variables on mortality before initiating ECMO using logistic regression. Second outcome variable was the learning curve of our department in patients with ECMO. Results:6-year hospital mortality was 54% in patients with lung failure, 59% in patients with cardiogenic shock, and 58% in patients with septic shock.The CUSUM analysis revealed a typical learning curve with a point of inflection in the year 2014. Patients treated before 2014 had a worse outcome (p?=?0.04 whole cohort; p?=?0.03 for lung failure). Furthermore, less than 20 treatments per year respectively treatment before 2014 were associated negatively with hospital mortality of lung failure patients showing an odds ratio of 4.04, as well as in the entire cohort with an odds ratio of 3.19. Conclusion:For the first time, a steep ECMO-learning curve using the CUSUM tool has been described. Obviously, the experience with ECMO has to be taken into account when defining the role of ECMO in ARDS, cardiogenic, and septic shock.
| S-EPMC6299557 | biostudies-literature
Project description:Background: The use of extracorporeal membrane oxygenation (ECMO) for critically ill patients is growing rapidly given recent developments in technology. However, adverse events are frequently reported that have potentially devastating impacts on patient outcomes. The information on predictors and risk factors for thrombotic events, especially that focusing on the comparison of veno-arterial and veno-venous ECMO configurations, are still inconsistent and sparse; therefore, we aimed to close this gap. Methods: We performed a retrospective analysis of all patients on extracorporeal life support admitted to the intensive care units of a tertiary university center in Europe. Results: From 645 patients, 417 who received extracorporeal life support due to cardiogenic shock (290, 70%), respiratory failure (116, 28%) or hypothermia (11, 3%) were included. In total, 22% (92) of the patients experienced thrombotic events with a similar incidence in both ECMO configurations. Anticoagulation consisted of unfractionated heparin (296, 71%) and argatroban (70, 17%). Univariate Cox analyses identified hemoconcentration and increased maximal clot firmness (thromboelastometry) as risk factors for thrombosis. Moreover, the patients experiencing thrombosis had longer ECMO duration and intensive care stays. Conclusions: ECMO is a specialized life-support modality with a high risk of complications. A longer ECMO duration is associated with thrombosis occurrence in patients receiving ECMO support. Following hemorrhage, thromboembolic complications are common adverse events. However, in contrast to major bleeding, no impact on mortality was observed. The question arises if a protocol with less anticoagulation may have a role to play in the future.
| S-EPMC9917555 | biostudies-literature
Project description:BackgroundSince March 2020, health care systems were importantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak, with some patients presenting severe acute respiratory distress syndrome (ARDS), requiring extra-corporeal membrane oxygenation (ECMO). We designed an ambispective observational cohort study including all consecutive adult patients admitted to 5 different ICUs from a university hospital. The main objective was to identify the risk factors of severe COVID-19 ARDS patients supported by ECMO associated with 90-day survival.ResultsBetween March 1st and November 30th 2020, 76 patients with severe COVID-19 ARDS were supported by ECMO. Median (interquartile range IQR) duration of mechanical ventilation (MV) prior to ECMO was of 6 (3-10) days. At ECMO initiation, patients had a median PaO2:FiO2 of 71 mmHg (IQR 62-81), median PaCO2 of 58 mmHg (IQR 51-66) and a median arterial pH of 7.33 (IQR 7.25-7.38). Forty-five patients (59%) were weaned from ECMO. Twenty-eight day, 60-day and 90-day survival rates were, respectively, 92, 62 and 51%. In multivariate logistic regression analysis, with 2 models, one with the RESP score and one with the PRESERVE score, we found that higher BMI was associated with higher 90-day survival [odds ratio (OR): 0.775 (0.644-0.934), p = 0.007) and 0.631 (0.462-0.862), respectively]. Younger age was also associated with 90-day survival in both models [OR: 1.1354 (1.004-1.285), p = 0.044 and 1.187 (1.035-1.362), p = 0.014 respectively]. Obese patients were ventilated with higher PEEP than non-obese patients and presented slightly higher respiratory system compliance.ConclusionIn this ambispective observational cohort of COVID-19 severe ARDS supported by ECMO, obesity was an independent factor associated with improved survival at 90-day.
| S-EPMC8591429 | biostudies-literature