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| Name | Class |
|---|---|
| European Society of Intensive Care Medicine | OTHER |
| Royal Centre for Defence Medicine | OTHER_GOV |
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Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Angiotensin II Infusion | Experimental | Angiotensin II infusion commenced alongside standard care vasopressor therapy (norepinephrine). Angiotensin II up titrated in a protocolised manner to a target/maximum dose of 40 ng/kg/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. |
|
| Vasopressin Infusion | Experimental | Vasopressin infusion commenced alongside standard care vasopressor therapy (norepinephrine). Vasopressin up titrated in a protocolised manner to a target/maximum dose of 0.04 IU/min whilst noradrenaline down titrated in order to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. |
|
| Norepinephrine Infusion | Active Comparator | Standard care vasopressor therapy which recruited participants already receiving, titrated to achieve/maintain target mean arterial pressure (MAP) as directed by attending clinician. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Angiotensin II | Drug | Angiotensin II infusion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Cortical mean transit time (mTT) measured in seconds | Contrast enhanced ultrasound measure of renal cortical tissue blood flow | Measured at +24 hours following study vasopressor infusion starting |
| Measure | Description | Time Frame |
|---|---|---|
| Cortical mean transit time (mTT) measured in seconds | Contrast enhanced ultrasound measures of renal cortical tissue blood flow | Measured at +1 hour and +24 hours following study vasopressor infusion starting |
| Cortical perfusion index (PI) measured in arbitrary units |
| Measure | Description | Time Frame |
|---|---|---|
| Perfused vessel density (PVD) measured in millimetres per square millimetre | Incident dark field video microscopy measures of the systemic microcirculation | Measured at +1 hour and +24 hours following study vasopressor infusion starting |
| Microvascular flow index (MFI) (unitless score from 0 to 3 where 3 is the value see in health). |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Sam Hutchings | Contact | 02032994957 | sam.hutchings@nhs.net |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| King's College Hospital | Recruiting | London | SE5 9RS | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38870103 | Derived | McDonald R, Watchorn J, Mehta R, Ostermann M, Hutchings S. The REPERFUSE study protocol: The effects of vasopressor therapy on renal perfusion in patients with septic shock-A mechanistically focused randomised control trial. PLoS One. 2024 Jun 13;19(6):e0304227. doi: 10.1371/journal.pone.0304227. eCollection 2024. |
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| ID | Term |
|---|---|
| D012772 | Shock, Septic |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
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| ID | Term |
|---|---|
| D000804 | Angiotensin II |
| D014667 | Vasopressins |
| D009638 | Norepinephrine |
| ID | Term |
|---|---|
| D000809 | Angiotensins |
| D036361 | Peptide Hormones |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
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| Vasopressin |
| Drug |
Vasopressin infusion |
|
| Norepinephrine | Drug | Standard care vasopressor therapy, norepinephrine infusion |
|
Contrast enhanced ultrasound measures of renal cortical tissue blood flow |
| Measured at +1 hour and +24 hours following study vasopressor infusion starting |
| Cortical wash in rate (WiR) measured in arbitrary units | Contrast enhanced ultrasound measures of renal cortical tissue blood flow | Measured at +1 hour and +24 hours following study vasopressor infusion starting |
| Urinary oxygen tension (pO2) across 24 hours study period measured in millimetres of mercury (mmHg) | Mean urinary pO2 | Across 24 hours study period |
| Tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7). Both measured in nanograms per millilitre (ng/ml) | Biomarker analysis - regulatory proteins involved in initiating cell cycle arrest and associated with AKI | Measured at baseline and +24 hours following study vasopressor infusion starting |
Incident dark field video microscopy measures of the systemic microcirculation |
| Measured at +1 hour and +24 hours following study vasopressor infusion starting |
| Syndecan 1, angiopoietin 1 & 2, Interleukin 6 & 8 (IL-6, IL-8) and tissue necrosis factor (TNF). All measured in nanograms per millilitre (ng/ml) | Biomarker analysis - markers of inflammation and endothelial activation/function | Measured at baseline and +24 hours following study vasopressor infusion starting |
| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D012898 | Autacoids |
| D018836 | Inflammation Mediators |
| D001685 | Biological Factors |
| D010909 | Pituitary Hormones, Posterior |
| D010907 | Pituitary Hormones |
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
| D015306 | Biogenic Monoamines |
| D001679 | Biogenic Amines |
| D002395 | Catecholamines |
| D002396 | Catechols |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |