None listed
Conditions
Brief summary
This prospective nested cohort study of Acute Kidney Injury (AKI) in a cohort of patients recruited to the ARISE FLUIDS randomised controlled trrial aims to describe the incidence of AKI with differing strategies of vasopressor use/ fluid resuscitation in patients presenting to the Emergency Department (ED) with septic shock, and to describe the relationship between these resuscitation strategies and sensitive biomarkers of AKI. As part of the ARISE FLUIDS trial, patients will be randomised to either 1. A ‘restricted fluids and early vasopressor strategy’ whereby ongoing hypotension is managed by a vasopressor infusion titrated to the desired blood pressure, or 2. A ‘larger initial intravenous fluid volume and later introduction of vasopressor strategy’ whereby an additional litre of intravenous fluid will be given for persisting hypotension, and then further, more liberal boluses of fluid as required. Patients recruited to this nested cohort will have additional granular renal data (creatinine, urine output, etc) collected through the subsequent admission, to determine the incidence and severity of AKI, and important renal outcomes. In addition, a novel sensitive biomarker (urinary insulin-like growth-factor binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases (TIMP-2) will be measured at enrolment and 24 hours. The relationship between this biomarker, resuscitation strategy, and renal outcomes will be explored.
Interventions
As part of the ARISE FLUIDS trial (ClinicalTrials.gov Identifier: NCT04569942), patients presenting to the emergency department with presumed septic shock will be randomised to either
1. A ‘restricted fluids and early vasopressor strategy’ whereby ongoing hypotension is managed by a vasopressor infusion titrated to the desired blood pressure, or
2. A ‘larger initial intravenous fluid volume and later introduction of vasopressor strategy’ whereby an additional litre of intravenous fluid will be
As part of the ARISE FLUIDS trial (ClinicalTrials.gov Identifier: NCT04569942), patients presenting to the emergency department with presumed septic shock will be randomised to either 1. A ‘restricted fluids and early vasopressor strategy’ whereby ongoing hypotension is managed by a vasopressor infusion titrated to the desired blood pressure, or 2. A ‘larger initial intravenous fluid volume and later introduction of vasopressor strategy’ whereby an additional litre of intravenous fluid will be given for persisting hypotension, and then further, more liberal boluses of fluid as required. No additional treatment intervention will be imposed by participation in this nested cohort study. Participation in this nested cohort study will involve collection of two urine samples at ARISE FLUIDS enrolment and at 24 hours after enrolment (measured for urinary TIMP-2/IGFBP7 biomarker and markers of urine concentration), and additional data related to renal function from the healthcare record until hospital discharge, censored at 90 days.
Sponsors
The George Institute for Global Health
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Eligible for the ARISE FLUIDS RCT. This study's inclusion criteria are as follows: 1. Clinically suspected infection 2. Systolic blood pressure (SBP) <90 mm Hg or mean arterial pressure (MAP) <65 mm Hg, despite a 1000 mLs cumulative total bolus of IV fluid administered over a maximum of 60 minutes; including pre-hospital boluses 3. Arterial or venous blood lactate >2.0 mmol/L 4. At least one dose of an intravenous antimicrobial has been commenced
Exclusion criteria
Ineligible for the ARISE FLUIDS RCT. This study's exclusion criteria are as follows: 1. Age < 18 years 2. Confirmed or suspected pregnancy 3. Transferred from another acute care facility 4. >2L total IV fluid administered (including prehospital fluids but excluding drugs and flushes) 5. Hypotension suspected to be due to a non-sepsis cause 6. More than 6 hours has elapsed since presentation to the ED or more than 2 hours has elapsed since last Inclusion criterion has been met 7. Treating clinician considers that one or both of the treatment regimens are not suitable for the patient or the study protocol cannot be delivered e.g. limitation of care, requirement for immediate surgery 8. Death is considered imminent or inevitable 9. Underlying disease that makes survival to 90 days is unlikely 10. Inability to follow patient up to day-90 e.g. unstable accommodation, overseas visitor 11. Previously enrolled in ARISE FLUIDS
Outcome results
None listed