Influence of Granulocyte-Macrophage Colony-Stimulating Factor or Influenza Vaccination on HLA-DR, Infection and Delirium Days in Immunosuppressed Surgical Patients: Double Blind, Randomised Controlled Trial

• Published in: PloS one Vol. 10; no. 12; p. e0144003
• Main Authors: Spies, Claudia, Luetz, Alawi, Lachmann, Gunnar, Renius, Markus, von Haefen, Clarissa, Wernecke, Klaus-Dieter, Bahra, Marcus, Schiemann, Alexander, Paupers, Marco, Meisel, Christian
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.12.2015; Public Library of Science (PLoS)
• Subjects: Aged; Anesthesiology; Angina pectoris; Antigens; Care and treatment; Clinical trials; Colonies; Colony-stimulating factor; Complications; Critical care; Deactivation; Delirium; Delirium - metabolism; Delirium - physiopathology; Diagnosis; Dosage and administration; Double-Blind Method; Double-blind studies; Esophagus; Esophagus - surgery; Female; Granulocyte-macrophage colony stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - administration & dosage; Granulocytes; Health risks; Hepatitis; Histocompatibility antigen HLA; HLA-DR Antigens - metabolism; Humans; Immunocompromised Host; Immunosuppression; Infections; Inflammation; Influenza; Influenza vaccines; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza, Human - metabolism; Influenza, Human - physiopathology; Influenza, Human - prevention & control; Intensive care; Intensive care units; Macrophages; Male; Management; Medicine; Mental disorders; Middle Aged; Monoclonal antibodies; Monocytes; Monocytes - metabolism; Mortality; Neurosciences; Pancreas; Pancreas - surgery; Patients; Randomization; Risk factors; Sepsis; Surgery; Vaccination; Vaccines; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0144003

Surgical patients are at high risk for developing infectious complications and postoperative delirium. Prolonged infections and delirium result in worse outcome. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and influenza vaccination are known to increase HLA-DR on monocytes and improve immune reactivity. This study aimed to investigate whether GM-CSF or vaccination reverses monocyte deactivation. Secondary aims were whether it decreases infection and delirium days after esophageal or pancreatic resection over time. In this prospective, randomized, placebo-controlled, double-blind, double dummy trial setting on an interdisciplinary ICU of a university hospital 61 patients with immunosuppression (monocytic HLA-DR [mHLA-DR] <10,000 monoclonal antibodies [mAb] per cell) on the first day after esophageal or pancreatic resection were treated with either GM-CSF (250 μg/m2/d), influenza vaccination (Mutagrip 0.5 ml/d) or placebo for a maximum of 3 consecutive days if mHLA-DR remained below 10,000 mAb per cell. HLA-DR on monocytes was measured daily until day 5 after surgery. Infections and delirium were followed up for 9 days after surgery. Primary outcome was HLA-DR on monocytes, and secondary outcomes were duration of infection and delirium. mHLA-DR was significantly increased compared to placebo (p < 0.001) and influenza vaccination (p < 0.001) on the second postoperative day. Compared with placebo, GM-CSF-treated patients revealed shorter duration of infection (p < 0.001); the duration of delirium was increased after vaccination (p = 0.003). Treatment with GM-CSF in patients with postoperative immune suppression was safe and effective in restoring monocytic immune competence. Furthermore, therapy with GM-CSF reduced duration of infection in immune compromised patients. However, influenza vaccination increased duration of delirium after major surgery. www.controlled-trials.com ISRCTN27114642.