Clinical trial NCT01726595: Ultrasound Measurement of Reactive Hyperemia in Critical Care
Official title: Ultrasound Measurement of Reactive Hyperemia in Critical Care: Prognostic and Pathophysiologic Significance
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Severe Sepsis
Critical Illness
Keywords: critical care
severe sepsis
microvascular function
ultrasound
Lead sponsor: University of Rochester
Sponsor class: OTHER
First posted: 2012-11-15
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Critically ill Patients:

Patients admitted to University of Rochester Medical Center ICU services with 2 of the 4 systemic inflammatory response syndrome (SIRS) criteria and acute organ dysfunction will be considered for enrollment.

Healthy Control subjects:

Healthy control subjects \>= 18 years of age will be recruited from the University and Rochester region at large.

Brief summary: The investigators hypothesize that doctors and nurses can undergo a brief period of training and then use ultrasound to accurately measure blood flow in a forearm artery after a brief period when this flow is interrupted with a blood pressure cuff, a measurement the investigators call reactive hyperemia. Reactive hyperemia indicates whether the small blood vessels in the body are healthy -- lower reactive hyperemia indicates worse small blood vessel function. When measured by experienced ultrasound experts, low reactive hyperemia strongly predicts death in critically ill patients with infection (severe sepsis).

The investigators are conducting this study to determine if doctors and nurses, without specific pre-existing expertise in ultrasound, can be trained to make these measurements accurately. If so, the investigators will prove that these measurements can be applied reliably in real-world practice.

The investigators also hypothesize that reactive hyperemia predict the outcomes of illness not just in patients with severe infection, but in other critically ill patients as well.

Finally, the investigators hypothesize that reduced blood flow after blood pressure cuff occlusion is linked with other abnormalities of blood, previously identified in critically ill patients. For example, red blood cells from patients with severe sepsis have been shown to be stiffer than normal, so they are less able to flow along the small blood vessel passages of the body. Red blood cells become stiffer when there is a certain type of stress in the body known as "oxidative stress."

If the investigators show that low reactive hyperemia, stiff red blood cells, and oxidative stress are linked, the investigators hope to develop new treatments that reduce oxidative stress, reduce the stiffness of red blood cells, and in turn improve reactive hyperemia. Improvements in reactive hyperemia indicate improvements in small blood vessel function. Better small blood vessel function means better delivery of oxygen throughout the body. The investigators believe that this will improve outcomes for critically ill patients.


Eligibility criteria: Inclusion Criteria:

* Patients admitted to University of Rochester Medical Center ICU services with 2 of the 4 systemic inflammatory response syndrome (SIRS) criteria and acute organ dysfunction will be considered for enrollment.
* Healthy control subjects \>= 18 years of age will be recruited from the University and Rochester region at large.

Exclusion Criteria

* Critically ill patients:

  1. Refusal of patient or designated surrogate decision-maker to provide written informed consent, or inability to obtain consent within 48 hours of diagnosis
  2. Attending physician refusal
  3. Hematocrit (Hct) \< 21%
  4. Acute bleeding requiring PRBC transfusion
  5. History of chronic, dialysis dependent renal failure
  6. End-stage liver disease and Child-Pugh Grade C
  7. History of organ, bone marrow, or stem cell transplant
  8. Pregnancy
  9. Cardiac surgery (including ventricular assist device prior to first sample collection)
  10. Do not resuscitate at screening or plans for withdrawal of life support imminent
  11. Suicide attempt or intentional drug overdose;
  12. Jehovah's witness
* Healthy Control subjects:

  1. Absent doppler signal in brachial or radial arteries.
  2. Asymmetric cyanosis, poor capillary refill or cold temperature
  3. Known venous thrombosis or there is asymmetric swelling (arm circumference \> 2 inches larger than opposite side).
  4. Evidence of inflammation or impaired skin integrity of the involved limb.
  5. History of surgery involving the blood or lymphatic vessels of this limb, including axillary lymph node dissection, will preclude this testing.
  6. History of Anemia or G6PD deficiency

Primary outcomes:
measure: hospital mortality
timeFrame: vital status at hospital discharge, an expected average of 3 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
Study officials:
affiliation: University of Rochester
name: Anthony P. Pietropaoli, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wexler O, Morgan MA, Gough MS, Steinmetz SD, Mack CM, Darling DC, Doolin KP, Apostolakos MJ, Graves BT, Frampton MW, Chen X, Pietropaoli AP. Brachial artery reactivity in patients with severe sepsis: an observational study. Crit Care. 2012 Dec 12;16(2):R38. doi: 10.1186/cc11223.