Severe sepsis/septic shock Infections and Infestations Other septicaemia
Conditions
Interventions
Intervention arm: Early goal-directed protocolised resuscitation
targeting of specific haemodynamic goals including central venous pressure, mean arterial pressure and central venous oxygen saturation.
Control arm: Usual care
Patients admitted to Emergency Depart
Sponsors
Intensive Care National Audit and Research Centre (ICNARC) (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Greater than or equal to 18 years of age, either sex 2. Known or presumed infection 3. Two or more systemic inflammatory response syndrome (SIRS) criteria: 3.1. Core temperature less than or equal to 36°C or greater than or equal to 38°C 3.2. Heart rate greater than or equal to 90 beats/min 3.3. Respiratory rate greater than or equal to 20 breaths/min (or hyperventilation indicated by partial pressure of carbon dioxide in arterial blood [PaCO2] 4.3 kPa or mechanical ventilation for an acute process) 3.4. White blood cell count less than or equal to 4 x 10^9 l or greater than or equal to 12 x 10^9 l (or the presence of greater than 10% immature neutrophils "bands") 4. Refractory hypotension or hypoperfusion: 4.1. Hypotension is confirmed by the presence of systolic blood pressure less than 90 mmHg despite an intravenous (IV) fluid challenge of at least 20 ml/kg within 30 minutes of Emergency Department (ED) arrival (including IV fluids administered by pre-hospital/Emergency Medical Services [EMS] personnel) 4.2. Hypoperfusion is confirmed by a blood lactate concentration greater than or equal to 4 mmol/L) 5. First dose of IV antimicrobial therapy commenced prior to randomisation
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 04/01/2013: 1. Age less than 18 years 2. Known pregnancy 3. Primary diagnosis of: 3.1. an acute cerebral vascular event 3.2. acute coronary syndrome 3.3. acute pulmonary oedema 3.4. status asthmaticus 3.5. major cardiac arrhythmia (as part of primary diagnosis) 3.6. seizure 3.7. drug overdose 3.8. injury from burn or trauma 4. Haemodynamic instability due to active gastrointestinal haemorrhage 5. Requirement for immediate surgery 6. Known history of AIDS 7. Do-Not-Attempt-Resuscitation (DNAR) status 8. Advanced directives restricting implementation of the resuscitation protocol 9. Contraindication to central venous catheterization 10. Contraindication to blood transfusion 11. Attending clinician deems aggressive resuscitation unsuitable 12. Transferred from another in-hospital setting 13. Not able to commence resuscitation protocol within one hour of randomisation or complete six hours of protocol treatment from commencement Previous exclusion criteria until 04/01/2013: 1. Aged less than 18 years 2. Known pregnancy 3. Primary diagnosis of acute cerebral vascular event, acute coronary syndrome, acute pulmonary oedema, status asthmaticus, major cardiac arrhythmia (as part of primary diagnosis), seizure, drug overdose, injury from burn or trauma 4. Haemodynamic instability due to active gastrointestinal (GI) haemorrhage 5. Immunosuppressive agents including chemotherapy for uncured cancer, immunosuppression for organ transplantation or from systematic disease 6. Requirement for immediate surgery 7. Do not resuscitate status 8. Advanced directives restricting implementation of the protocol 9. Contraindications to central venous catheterisation 10. Contradiction to blood transfusion (i.e. Jehovah's Witness) 11. Attending physician deems aggressive care unsuitable 12. Participation in another interventional study 13. Transferred from another in-hospital setting 14. Not able to start within 1 hour of randomisation or finish within 6 hours
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Mortality at 90 days 2. Incremental cost-effectiveness at one year | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 04/01/2013: 1. To compare: 1.1. Mortality at one year 1.2. Health-related quality of life at 90 days and one year 1.3. Resource use and costs at 90 days and one year 1.4. Requirement for, and duration of, critical care unit organ support 1.5. Length of stay in the ED, critical care unit and acute hospital 2. To estimate: 2.1. Lifetime incremental cost-effectiveness Previous secondary outcome measures until 04/01/2013: 1. Duration of survival 2. Mortality at 28 days 3. Mortality at discharge from critical care and discharge from hospital 4. Mortality at one year 5. Sequential Organ Failure Assessment (SOFA) score at 6 hours and 72 hours (adjusted for baseline) 6. Requirement for, and duration of, monitoring and support of specific organ systems (CCMDS) 7. Duration of ED, critical care unit and hospital stay 8. Health-related quality of life (EQ-5D) at 90 days and one year 9. Resource use and costs at 90 days and one year 10. Lifetime incremental cost-effectiveness | — |
Countries
United Kingdom
Outcome results
None listed