The clinical and cost-effectiveness of early, goal-directed, protocolised resuscitation for emerging septic shock

Not Applicable

Completed

• Conditions: Severe sepsis/septic shock; Infections and Infestations; Other septicaemia

• Registration Number: ISRCTN36307479
• Lead Sponsor: Intensive Care National Audit and Research Centre (ICNARC) (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-11-19
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 1260

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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. Mortality at 90 days<br>2. Incremental cost-effectiveness at one year