Study of Albumin to Reduce Inflammation Following Surgery

Imperial College London

Status and phase

Terminated

Phase 2

Conditions

Cardiopulmonary Bypass

Systemic Inflammatory Response Syndrome

Treatments

Drug: Gelofusin

Drug: 20% Human albumin solution

Study type

Interventional

Funder types

Other

Identifiers

NCT00773110

CRO888

DHTCA_P09889

Details and patient eligibility

About

The purpose of this study is to determine whether albumin administration during cardiac surgery is effective in attenuating the development of inflammation following surgery.

Full description

The host response to infection and other forms of tissue injury has been termed the systemic inflammatory response syndrome (SIRS). SIRS is seen in association with a wide variety of non-infective insults, including major trauma and surgical procedures, including those necessitating cardiopulmonary bypass (CPB). In this population the incidence of SIRS is high, afflicting up to 70% of patients. This may be manifest from an increased vasopressor requirement, to refractory hypotension, and multiple organ dysfunction syndrome (MODS) with liver, renal, myocardial, and neurological problems. MODS is associated with significant mortality rates of around 30-45%. Survivors require prolonged and costly intensive care, thereby representing a considerable burden for the healthcare services. Survivors often suffer considerable morbidity and have significantly impaired health related quality of life.

Despite intense investigations of anti-inflammatory therapies in SIRS and its sequelae, the case of patients is largely supportive whilst underlying triggers (such as infection) for the process are treated. Indeed, the only therapy drotrecogin alfa (activated) demonstrated to reduced mortality in a randomised study has only been investigated in patients with the most severe SIRS consequent of infection (i.e. severe sepsis) and is contra-indicated in those who have just undergone surgery.

Haemolysis is a common feature of surgery requiring CPB and may potentiate the development of SIRS and organ injury through the release of heme/iron. Furthermore, haemolysis during CPB may lead to the depletion of important mechanisms which scavenge free heme/hemoglobin from the circulation. Albumin, the most abundant plasma protein, has specific and non-specific heme and iron binding sites which are used under circumstances in which standard scavengers are overwhelmed. However, albumin is also depleted following CPB. It is therefore hypothesised that by priming the CPB circuit with albumin the heme/iron scavenging capability of the plasma will be maintained following surgery and that the systemic inflammatory response will be attenuated.

Enrollment

232 patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

All patients over sixteen years of age undergoing surgery that requires cardiopulmonary bypass who provide informed written consent

Exclusion criteria

Lack of informed consent
Pregnancy
Cyanotic congenital heart disease (due to high haemoglobin levels and increased haemolysis)
Patients undergoing other extracorporeal interventions (ventricular assist devices, extracorporeal membrane oxygenators, pre-admission dialysis)
Patients with congenital haemoglobinopathies (e.g. thalassaemia, cryoglobinuria, etc)
Patients with disorders of iron metabolism (e.g. haemochromatosis)
Religious objections to transfusion of a plasma-derived product
Patients with known blood borne infection
Patients with known hypersensitivity to gelofusine or human albumin solution
Patients with an additive EUROSCORE of 10 or more