title: The original sins of clinical trials with intravenous immunoglobulins in sepsis.
abstract: Intravenous immunoglobulins (IVIGs) have not yet demonstrated robust evidence in the benefit for treatment of sepsis. In spite of multiple clinical trials performed with IVIG in sepsis, it remains an experimental therapy for this severe condition. Nonetheless, these trials do not address a number of potential confounding factors, concerning both the patient and the IVIG preparations, which could greatly affect the final result. To name a few, endogenous levels of immunoglobulin isotypes and subclasses are not assessed prior to treatment. The presence/absence of patient antibodies against the microorganism(s) causing sepsis is not evaluated. The accuracy of antibiotic prescription is not included as an adjusting variable. The degree of patient immunosuppression (previous or induced by sepsis) is not documented. In turn, the concentration and antimicrobial specificities of the antibodies contained in the batches of IVIG are not assessed. Neither the pharmacokinetics of IVIG nor its potential immunomodulatory effects are evaluated. In addition, the concept of 'window of opportunity' for IVIG administration following diagnosis of sepsis is not considered. In conclusion, addressing these factors could help to individualise treatment with IVIG for sepsis, which could enhance the opportunities of this drug to show benefits in terms of survival in this severe condition.
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. ralmansa@saludcastillayleon.es.
authors.forename: Raquel
authors.initials: R
authors.lastname: Almansa
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. tamayo@med.uva.es.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Tamayo
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. davidandaluz78@yahoo.es.
authors.forename: David
authors.initials: D
authors.lastname: Andaluz-Ojeda
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. leonor_nm@yahoo.es.
authors.forename: Leonor
authors.initials: L
authors.lastname: Nogales
authors.affiliation: Servicio de Medicina Intensiva, Hospital Universitario Rio Hortega, Calle Dulzaina, 2, 47012, Valladolid, Spain. jblancov@saludcastillayleon.es.|Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Calle Sinesio Delgado, 4, 28029, Madrid, Spain. jblancov@saludcastillayleon.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Blanco
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. eiros@med.uva.es.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Eiros
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. jgomez012001@yahoo.es.
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Gomez-Herreras
authors.affiliation: Group of Biomedical Research in Critical Care Medicine (BioCritic), Hospital Clínico Universitario de Valladolid, Avda. Ramón y Cajal, 3. 47005, Valladolid, Spain. jfbermejo@saludcastillayleon.es.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Bermejo-Martin
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012772:Shock, Septic / Q000188:drug therapy* / Q000401:mortality
chemical_list: D000900:Anti-Bacterial Agents; D016756:Immunoglobulins, Intravenous