The efficacy of convalescent plasma for coronavirus disease 2019 (COVID-19) is unclear. Although most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content could influence patient outcomes. We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 d of respiratory symptom onset (NCT04348656). Patients were allocated 2:1 to 500 ml of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 d. Exploratory analyses of the effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression. The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. In total, 940 patients were randomized, and 921 patients were included in the intention-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) patients in the convalescent plasma arm and 86/307 (28.0%) patients in the standard of care arm—relative risk (RR) = 1.16 (95% confidence interval (CI) 0.94–1.43, P = 0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% versus 26.4%; RR = 1.27, 95% CI 1.02–1.57, P = 0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standardized log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (odds ratio (OR) = 0.74, 95% CI 0.57–0.95 and OR = 0.66, 95% CI 0.50–0.87, respectively), whereas IgG against the full transmembrane spike protein increased it (OR = 1.53, 95% CI 1.14–2.05). Convalescent plasma did not reduce the risk of intubation or death at 30 d in hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavorable antibody profiles could be associated with worse clinical outcomes compared to standard care.
Acute hyperammonemia may induce a neurologic impairment leading to an acute life-threatening condition. Coma duration, ammonia peak level, and hyperammonemia duration are the main risk factors of hyperammonemia-related neurologic deficits and death. In children, hyperammonemia is mainly caused by severe liver failure and inborn errors of metabolism. In an acute setting, obtaining reliable plasma ammonia levels can be challenging because of the preanalytical difficulties that need to be addressed carefully. The management of hyperammonemia includes 1) identification of precipitating factors and cerebral edema presence, 2) a decrease in ammonia production by reducing protein intake and reversing catabolism, and 3) ammonia removal with pharmacologic treatment and, in the most severe cases, with extracorporeal therapies. In case of severe coma, transcranial Doppler ultrasound could be the method of choice to noninvasively monitor cerebral blood flow and titrate therapies.
Anemia and red blood cell (RBC) transfusion occur frequently in hospitalized patients with cardiac disease. In this narrative review, we report the epidemiology of anemia and RBC transfusion in hospitalized adults and children (excluding premature neonates) with cardiac disease, and on the outcome of anemic and transfused cardiac patients. Both anemia and RBC transfusion are common in cardiac patients, and both are associated with mortality. RBC transfusion is the only way to rapidly treat severe anemia, but is not completely safe. In addition to hemoglobin (Hb) concentration, the determinant(s) that should drive a practitioner to prescribe a RBC transfusion to cardiac patients are currently unclear. In stable acyanotic cardiac patients, Hb level above 70 g/L in children and above 70 to 80 g/L in adults appears safe. In cyanotic children, Hb level above 90 g/L appears safe. The appropriate threshold Hb level for unstable cardiac patients and for children younger than 28 days is unknown. The optimal transfusion strategy in cardiac patients is not well characterized. The threshold at which the risk of anemia outweighs the risk of transfusion is not known. More studies are needed to determine when RBC transfusion is indicated in hospitalized patients with cardiac disease.
Objective Determine the accuracy and confidence of CCM providers to identify seizures using amplitude-integrated EEG (aEEG) versus aEEG combined with Color Density Spectral Array electroencephalography (aEEG+CDSA) Design tutorial and questionnaire. Subjects Pediatric critical care providers (attendings, fellows, nurses). Interventions A standardized powerpoint tutorial on aEEG and CDSA followed by classification of 100 aEEG images and 100 aEEG combined with CDSA as displaying seizures or not displaying seizures. Measurements and Main Results EEG tracings were obtained from children monitored with continuous EEG after cardiac arrest. The gold standard for seizure identification was continuous EEG interpretation by a pediatric electroencephalographer. The same EEG tracings were used to generate images containing only aEEG or aEEG+CDSA. Twenty-three CCM providers underwent a 30-minute tutorial on aEEG and CDSA interpretation. They were then asked to determine if there were seizures on 100 aEEG images and 100 aEEG+CDSA. aEEG seizure detection sensitivity was 77% (95%CI: 73%–80%), specificity of 65% (95%CI: 62%–67%), negative predictive value (NPV) of 88% (95%CI: 86%–90%) and positive predictive value (PPV) of 46% (95%CI: 43%–49%). For aEEG+CDSA, sensitivity was 77% (95%CI: 74%–81%), specificity of 68% (95%CI: 66%–71%), NPV of 89% (95%CI: 87%–90%) and PPV of 49% (95%CI: 46%–52%). Sensitivity for status epilepticus detection was 77% (95%CI: 71%–82%) with aEEG and 75% (95%CI: 69%–81%) with aEEG+CDSA. The addition of CDSA to aEEG did not improve seizure detection. However, 87% of CCM providers qualitatively felt that combining both modalities increased their ability to detect seizures. Conclusions aEEG and aEEG+CDSA offer reasonable sensitivity and NPV for seizure detection by CCM providers. aEEG+CDSA did not improve seizure detection over aEEG alone, although CCM providers felt more confident using both tools combined. aEEG and CDSA require further evaluation as a tool for screening for seizures and should only be used in conjunction with professional cEEG review.
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