The original sins of clinical trials with intravenous immunoglobulins in sepsis

• Published in: Critical care (London, England) Vol. 19; no. 1; p. 90
• Main Authors: Almansa, Raquel, Tamayo, Eduardo, Andaluz-Ojeda, David, Nogales, Leonor, Blanco, Jesús, Eiros, Jose Maria, Gomez-Herreras, Jose Ignacio, Bermejo-Martin, Jesus F
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 26.02.2015; BioMed Central
• Subjects: Anti-Bacterial Agents - therapeutic use; Antibiotics; Blood & organ donations; Care and treatment; Clinical trials; Clinical Trials as Topic; Complications and side effects; Critical care; Dosage and administration; Health aspects; Humans; Immunoglobulins; Immunoglobulins, Intravenous - pharmacokinetics; Immunoglobulins, Intravenous - therapeutic use; Immunotherapy; Infection; Medical prognosis; Mortality; Nosocomial infections; Patients; Sepsis; Shock, Septic - drug therapy; Shock, Septic - mortality
• ISSN: 1364-8535; 1466-609X; 1364-8535; 1366-609X
• DOI: 10.1186/s13054-015-0793-0

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.