Clinical trial NCT05694455: Micro and Macro Circulation in Sepsis
Official title: Clinical Utility of Longitudinal Measurement of Hemodynamic Incoherence and Endothelial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Sepsis
Septic Shock
Lead sponsor: Denver Health and Hospital Authority
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2023-01-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Patients diagnosed with septic shock in the emergency department admitted to the hospital will be enrolled within 4 hours of the emergency physician's decision to admit the patient to the hospital.

On enrollment, On enrollment and at hours 10-14, 22-26, and 44-48, the research team will assess micro hemodynamic incoherence and Macro hemodynamic incoherence as well as the total amount of IV fluids and vasoactive medications administered, demographics, Charlson morbidity scale and Sofa score.

Healthy controls will have sublingual microscopy and urine collection performed at time of intubation for elective procedure.
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Initiation and Duration Renal Replacement Therapy
timeFrame: 90 day
Secondary outcomes:
measure: Rate of Inpatient Mortality
timeFrame: 90 day
measure: Rate of 90 day survival
timeFrame: 90 day
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Health Medical Center
state: Colorado
Study officials:
References: