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Prior Antiplatelet Therapy and Stroke Risk in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation.

ABSTRACT: We aimed to investigate whether prior exposure to antiplatelet therapy (anti-PLT) was associated with stroke incidence after the initiation of extracorporeal membrane oxygenation (ECMO) therapy. We conducted a population-based cohort study based on health records obtained from the National Health Insurance Service database in South Korea. Adult patients (aged ≥ 18 years) who underwent ECMO therapy in the intensive care unit during 2009-2018 were enrolled. In total, 17,237 patients who underwent ECMO therapy were included; stroke occurred in 779 (4.5%) of 17,237 patients within 7 days of initiating the ECMO therapy. The number of patients in the anti-PLT and control groups was 3909 (22.7%) and 13,328 (77.3%), respectively. In the multivariable logistic regression analysis, the anti-PLT group showed 33% lower incidence of stroke than the control group (odds ratio (OR): 0.67, 95% confidence interval (CI): 0.55-0.82; p < 0.001). The cardiovascular group showed 35% lower incidence of stroke than the control group (OR: 0.65, 95% CI: 0.52-0.78; p < 0.001), whereas the respiratory group (p = 0.821) and the other group (p = 0.705) did not show any significant association. Prior anti-PLT therapy was associated with a lower incidence of stroke within 7 days of initiating ECMO therapy, which was more evident in the cardiovascular group.

SUBMITTER: Oh TK

PROVIDER: S-EPMC8394632 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Sufentanil is commonly used for analgesia and sedation during extracorporeal membrane oxygenation (ECMO). Both ECMO and the pathophysiological changes derived from critical illness have significant effects on the pharmacokinetics (PK) of drugs, yet reports of ECMO and sufentanil PK are scarce. Here, we aimed to develop a population PK model of sufentanil in ECMO patients and to suggest dosing recommendations. METHODS:This prospective cohort PK study included 20 patients who received sufentanil during venoarterial ECMO (VA-ECMO). Blood samples were collected for 96?h during infusion and 72?h after cessation of sufentanil. A population PK model was developed using nonlinear mixed effects modelling. Monte Carlo simulations were performed using the final PK parameters with two typical doses. RESULTS:A two-compartment model best described the PK of sufentanil. In our final model, increased volume of distribution and decreased values for clearance were reported compared with previous PK data from non-ECMO patients. Covariate analysis showed that body temperature and total plasma protein level correlated positively with systemic clearance (CL) and peripheral volume of distribution (V2), respectively, and improved the model. The parameter estimates of the final model were as follows: CL?=?37.8?×?EXP (0.207?×?(temperature?-?36.9))?L h-1, central volume of distribution (V1)?=?229?L, V2?=?1640?×?(total plasma protein/4.5)2.46?L, and intercompartmental clearance (Q)?=?41?L?h-1. Based on Monte Carlo simulation results, an infusion of 17.5??g?h-1 seems to reach target sufentanil concentration (0.3-0.6??g?L-1) in most ECMO patients except hypothermic patients (33?°C). In hypothermic patients, over-sedation, which could induce respiratory depression, needs to be monitored especially when their total plasma protein level is low. CONCLUSIONS:This is the first report on a population PK model of sufentanil in ECMO patients. Our results suggest that close monitoring of the body temperature and total plasma protein level is crucial in ECMO patients who receive sufentanil to provide effective analgesia and sedation and promote recovery. TRIAL REGISTRATION:Clinicaltrials.gov NCT02581280 , December 1st, 2014.

Project description:Amikacin infusion requires targeting a peak serum concentration (Cmax) 8-10 times the minimal inhibitory concentration, corresponding to a Cmax of 60-80 mg/L for the least susceptible bacteria to theoretically prevent therapeutic failure. Because drug pharmacokinetics on extracorporeal membrane oxygenation (ECMO) are challenging, we undertook this study to assess the frequency of insufficient amikacin Cmax in critically ill patients on ECMO and to identify relative risk factors.This was a prospective, observational, monocentric study in a university hospital. Patients on ECMO who received an amikacin loading dose for suspected Gram-negative infections were included. The amikacin loading dose of 25 mg/kg total body weight was administered intravenously and Cmax was measured 30 min after the end of the infusion. Independent predicators of Cmax?<?60 mg/L after the first amikacin infusion were identified with mixed-model multivariable analyses. Various dosing simulations were performed to assess the probability of reaching 60 mg/L?<?Cmax <?80 mg/L.A total of 106 patients on venoarterial ECMO (VA-ECMO) (68%) or venovenous-ECMO (32%) were included. At inclusion, their median (1st; 3rd quartile) Sequential Organ-Failure Assessment score was 15 (12; 18) and 54 patients (51%) were on renal replacement therapy. Overall ICU mortality was 54%. Cmax was <?60 mg/L in 41 patients (39%). Independent risk factors for amikacin under-dosing were body mass index (BMI)?<?22 kg/m2 and a positive 24-h fluid balance. Using dosing simulation, increasing the amikacin dosing regimen to 30 mg/kg and 35 mg/kg of body weight when the 24-h fluid balance is positive and the BMI is ??22 kg/m2 or?<?22 kg/m2 (Table 3), respectively, would have potentially led to the therapeutic target being reached in 42% of patients while reducing under-dosing to 23% of patients.ECMO-treated patients were under-dosed for amikacin in one third of cases. Increasing the dose to 35 mg/kg of body weight in low-BMI patients and those with positive 24-h fluid balance on ECMO to reach adequate targeted concentrations should be investigated.

Project description:BackgroundNeurologic injury is one of the most frequent causes of death in patients undergoing extracorporeal membrane oxygenation (ECMO). As neurological examination is often unreliable in sedated patients, additional neuromonitoring is needed. However, the value of electroencephalogram (EEG) in adult ECMO patients has not been well assessed. Therefore, the aim of this study was to assess the occurrence of electroencephalographic abnormalities in patients treated with extracorporeal membrane oxygenation (ECMO) and their association with 3-month neurologic outcome.MethodsRetrospective analysis of all patients undergoing venous-venous (V-V) or venous-arterial (V-A) ECMO with a concomitant EEG recording (April 2009-December 2018), either recorded intermittently or continuously. EEG background was classified into four categories: mild/moderate encephalopathy (i.e., mostly defined by the presence of reactivity), severe encephalopathy (mostly defined by the absence of reactivity), burst-suppression (BS) and suppressed background. Epileptiform activity (i.e., ictal EEG pattern, sporadic epileptiform discharges or periodic discharges) and asymmetry were also reported. EEG findings were analyzed according to unfavorable neurological outcome (UO, defined as Glasgow Outcome Scale < 4) at 3 months after discharge.ResultsA total of 139 patients (54 [41-62] years; 60 (43%) male gender) out of 596 met the inclusion criteria and were analyzed. Veno-arterial (V-A) ECMO was used in 98 (71%); UO occurred in 99 (71%) patients. Continuous EEG was performed in 113 (81%) patients. The analysis of EEG background showed that 29 (21%) patients had severe encephalopathy, 4 (3%) had BS and 19 (14%) a suppressed background. In addition, 11 (8%) of patients had seizures or status epilepticus, 10 (7%) had generalized periodic discharges or lateralized periodic discharges, and 27 (19%) had asymmetry on EEG. In the multivariate analysis, the occurrence of ischemic stroke or intracranial hemorrhage (OR 4.57 [1.25-16.74]; p = 0.02) and a suppressed background (OR 10.08 [1.24-82.20]; p = 0.03) were independently associated with UO. After an adjustment for covariates, an increasing probability for UO was observed with more severe EEG background categories.ConclusionsIn adult patients treated with ECMO, EEG can identify patients with a high likelihood of poor outcome. In particular, suppressed background was independently associated with unfavorable neurological outcome.

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Prior Antiplatelet Therapy and Stroke Risk in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation.

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