Hemodynamic Measurements of Macrocirculatory and Perfusion Parameters in ICU

Effects of Norepinephrine on Hemodynamic Measurements of Macrocirculatory and Perfusion Parameters in ICU Patients with Septic Shock

In septic shock there is growing evidence of a state of hemodynamic "disconnection" with seemingly adequate macrocirculatory values despite actual microcirculation failing to meet cellular demand. Norepinephrine (NE) is recommended as first choice vasoactive agent for the treatment of septic shock. However, the dynamic effects of NE on macro- and microcirculation and perfusion parameters has not been described in detail in the context of septic shock, precluding rational individualized titration of NE and fluids, as recommended recently. In the present prospective observational multicenter study in adult septic shock patients, we intend to explore the effects of NE on preload dependency and tissue perfusion by evaluating the correlation and potential discrepancies between macro- and microcirculation both during titration of NE and after fluid resuscitation. The conclusions drawn from our study will contribute to the physiological knowledge necessary for establishing individualized evidence-based bedside management of hemodynamics in the setting of septic shock.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock; Vasoconstriction; Hemodynamic Instability
• Intervention / Treatment: Drug: Hemodynamic measurements during reduction in Norepinephrine and fluid boli.

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

• Study Contact: Name: Henrik Wolsted, MD; Phone Number: +45 21 49 44 85; Email: Henrik.wolsted.01@regionh.dk
• Study Contact Backup: Name: Nicolai Bang Foss, MD, DMsC; Email: nicolai.bang.foss@regionh.dk

Study Locations

• Denmark
  • Copenhagen
    • Hvidovre, Copenhagen, Denmark, 2665
      • Recruiting
      • Hvidovre Hospital
      • Contact: Henrik Wolsted; Phone Number: 21494485; Email: Hwolsted@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

45 adult patients with septic shock according to inclusion criteria admitted to ICUs at Hvidovre and Bispebjerg Hospital, respectively.

Description

Inclusion Criteria:

• Suspected or documented infection
• Need for vasopressors to maintain mean arterial blood pressure (MAP) ≥65 mmHg
• Serum lactate levels >2 mmol/L
• Norepinephrine infusion of > 0.2 mcg/kg/min

Exclusion Criteria:

• Absolute contraindication for esophageal doppler or urinary catheter insertion as noted in the patients' charts.
• Severe valvular pathology and cardiac arrhythmias resulting in severe hemodynamic instability.
• Lithium treatment
• Treatment with other vasopressor or inotropic drugs.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Septic Shock; Adult patients with septic shock, admitted to ICUs at Hvidovre and Bispebjerg Hospital, respectively. Sedated and mechanically ventilated adult patients (>18 years).

Drug: Hemodynamic measurements during reduction in Norepinephrine and fluid boli.; Extended monitoring equipment will be connected to the patient. Clinical and biochemical parameters will be collected for a baseline before the next step. A Safety check will be performed to ensure correct patient data, correct equipment function and safety measures are meet. A passive leg raise test will be performed to predict fluid responsiveness, in case of a positive test, a fluid challenge will be administered.; A stepwise reduction of the NE infusion rate from baseline while monitoring stroke volume (SV) to elucidate changes in SV and potential preloadresponsiveness. The reduction will occur in steps of 3-5 minute until either discontinuation of the norepinephrine infusion, a 50% reduction in SV or MAP<40.; While maintaining the NE infusion rate from the previous step 2, a fluid challenge will be administrated, until additional fluid does not increase SV>10%.; As in step 2, a stepwise increase in NE infusion rate to the baseline infusion level or the baseline BP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Preload responsiveness defined as stroke volume increase > 10%, measured by continuous arterial waveform analysis.	The number of patients who were preload responsive after down-titration of NE.	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac output response measured by lithium indicator dilution and Doppler ultrasound.	The effect on cardiac output after fluid bolus and subsequent up-titration of NE to the pre-intervention blood pressure target.	Through study completion, an average of 1 year
Microcirculation/perfusion measures during intervention.	The effect of the intervention on measures of tissue perfusion. Different topical sites (Brain, Muscle, Finger, Urethra, Sublingual) by minimal- or noninvasive methods.	Through study completion, an average of 1 year
CO measurement method	Assess the correlation between indirect measurements of CO and lithium dilution measured CO during NE titration.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Copenhagen University Hospital, Hvidovre
• Collaborators: University Hospital Bispebjerg and Frederiksberg

Study record dates

Study Major Dates

• Study Start (Actual): March 8, 2022
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 12, 2022
• First Submitted That Met QC Criteria: January 26, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Hemodynamic; Septic Shock; Norepinephrine; Intensive Care; Microcirculation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Shock, Septic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Neurotransmitter Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: HW-NA-Fluid-Measurements

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No