Micro and Macro Circulation in Sepsis

Not Applicable

Recruiting

• Conditions: Septic Shock; Sepsis
• Interventions: Diagnostic Test: Starling Stroke Volume (Starling SV)- Passive Leg Raise; Other: Urine Collection; Diagnostic Test: Microscan Sublingual Microscopy; Diagnostic Test: Venous Excess Ultrasound Scoring (VExUS)

• Registration Number: NCT05694455
• Lead Sponsor: Denver Health and Hospital Authority

Brief Summary

Purpose: To assess the prognostic role of Handheld Vital Microscopy (HVM) and evaluate levels of endothelial glycocalyx (eGC) breakdown in patients demonstrating Hemodynamic Incoherence (HI), to elucidate a mechanistic link between the eGC and HI in order to inform prognostic enrichment of future resuscitation trials. We will serially evaluate microhemodynamics (MiH) and macro hemodynamics (maH) and the perfused boundary region (PBR, an visual proxy for eGC thickness) using HVM, and a validated circulating biomarker of eGC integrity.

Detailed Description

There are few reliable prognostic indicators in early sepsis to predict disease progression, in part because the pathophysiologic mechanism of vascular dysregulation remains incompletely understood. The global Coronavirus Disease 2019 (COVID-19) pandemic has increased the number of patients with sepsis, straining hospital systems and illustrating the need for research into prognostic and therapeutic strategies. An important area of research is the role of the eGC, a thin vascular lining composed of proteoglycans, glycosaminoglycan side-chains, and plasma proteins that play a central role in microvascular homeostasis, the function of which is compromised in sepsis. Another growing field of inquiry is the phenomenon of HI, a condition in which MiH remain dysfunctional despite normalization of conventionally targeted MaH measures such as mean arterial pressure (MAP), leading to poor end-organ perfusion. It has been hypothesized that HI due to persistently deranged MiH and reduced end-organ perfusion result in an ongoing state of "microvascular shock", leading to worsening end-organ damage despite apparent normalization of conventionally targeted parameters. Importantly, HI has been shown to predict poor patient outcomes, with abnormal MiH predicting patient mortality despite normalization of MAP after administration of vasoactive medications. MiH measures have also been shown to differ significantly between septic patients and healthy controls. In one study of a large sepsis cohort, MiH parameters were predictive of adverse outcomes, while MaH parameters were not, suggesting that MiH measurements, and HI in particular may be more sensitive than conventional measures for predicting outcomes in sepsis. One hypothesis is that HI in sepsis is mediated by degradation of the eGC, with subsequent loss of microvascular homeostasis, though the role of the eGC as a vascular barrier remains controversial.

One question that remains is whether or not microvascular changes can predict patient outcomes in patients judged to be adequately fluid resuscitated, as measured by MAP or Starling Stroke Volume/Non-invasive cardiac monitor (NICOM) testing.

Study Timeline

• Study Start: 2022-07-01
• Study First Submitted: 2023-01-05
• Study First Submitted QC: 2023-01-13
• Study First Posted: 2023-01-23
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-16
• Last Update Posted: 2024-02-20
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Septic Patient Cohort:

1. Greater than or equal to 18 years of age
2. Diagnosed with sepsis or septic shock
3. Require admission to the Hospital

Control Cohort:

1. Greater than or equal to 18 years of age
2. Undergoing elective surgery requiring intubation and general anesthesia

Exclusion Criteria

Patients with any of the following characteristics will be excluded

1. Less than 18 years old
2. Chronic Kidney disease on dialysis
3. Currently pregnant
4. Incarcerated persons

Control Cohort:

1. Less than 18 years old
2. History of Chronic Kidney disease on dialysis, uncontrolled diabetes, cirrhosis, heart failure, or nephritic or nephrotic syndromes.
3. Currently pregnant
4. Incarcerated persons

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Control Patient Interventions	Urine Collection	Control patients will have urine collection and sublingual microscopy performed when intubated
Septic Patient Interventions	Microscan Sublingual Microscopy	Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy
Septic Patient Interventions	Venous Excess Ultrasound Scoring (VExUS)	Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy
Septic Patient Interventions	Urine Collection	Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy
Septic Patient Interventions	Starling Stroke Volume (Starling SV)- Passive Leg Raise	Septic Patients will have all interventions performed: Urine collection, Passive Leg Raise, Ultrasound and sublingual microscopy
Control Patient Interventions	Starling Stroke Volume (Starling SV)- Passive Leg Raise	Control patients will have urine collection and sublingual microscopy performed when intubated

Primary Outcome Measures

Name	Time	Method
Initiation and Duration Renal Replacement Therapy	90 day	Renal Replacement Therapy will be monitored while hospitalized for Sepsis/Septic Shock for initiation and days receiving Renal replacement will be counted.

Secondary Outcome Measures

Name	Time	Method
Rate of Inpatient Mortality	90 day	Patient Death while hospitalized for the admission of Sepsis/Septic Shock
Rate of 90 day survival	90 day	Patient death within 90 days of admission to the hospital for Sepsis/Septic Shock

Trial Locations

Locations (1)

Denver Health Medical Center; 🇺🇸 Denver, Colorado, United States