Does GM-CSF Restore Neutrophil Phagocytosis in Critical Illness?

Inclusion criteria

• Fulfil criteria for systemic inflammatory response syndrome on admission to ICU (see appendix 1)
• Has required support of one or more organ systems (invasive ventilation, inotropes or haemofiltration) during current ICU stay
• Survival over next 48 hours deemed most likely outcome by responsible ICU clinician
• Admitted to ICU within last 72 hours
• Neutrophil phagocytic capacity <50%

Exclusion criteria

• Absence/refusal of informed consent
• Current prescription of a colony stimulating factor
• Any history of allergy/adverse reaction to GM-CSF
• Total white cell count >30x109/litre at time of screening
• Haemoglobin < 7.5g/dl at the time of screening
• Age < 18 years
• Pregnancy or lactation
• Known in-born errors of neutrophil metabolism
• Known haematological malignancy and/or known to have >10% peripheral blood blast cells
• Known aplastic anaemia or pancytopaenia
• Platelet count <50x109/litre
• Chemotherapy or radiotherapy within the last 24 hours
• Solid organ or bone marrow transplantation
• Use of maintenance immunosuppressive drugs other than maintenance corticosteroids (allowed up to 10mg prednisolone/day or equivalent)
• Known HIV infection
• Active connective tissue disease (e.g. rheumatoid disease, systemic lupus erythematosus) requiring active pharmacological treatment.
• ST-segment elevation myocardial infarction, acute pericarditis (by ECG criteria) or pulmonary embolism (radiographically confirmed) in previous week
• Involvement in any study involving an investigational medicinal product in the previous 30 days