Effects of Targets of Blood Pressure on Cerebral Hemodynamics in Septic Shock

Effects of Systemic Blood Pressure Targets on Cerebral Hemodynamics in Septic Shock: a Prospective Study

The sudy objective is to evaluate the cerebral haemodynamic status in different ranges of systemic arterial pressure in patients with septic shock by noninvasive tools, transcranial doppler and intracranial compliance by mechanical sensor (B4C).

Patients participating in the study will be submitted to different levels of arterial pressure, titrated with vasopressor and them their cerebral hemodynamic variables will be evaluated,

Study Overview

• Status: Recruiting
• Conditions: Septic Shock; Cerebral Autoregulation

Detailed Description

Sepsis is the most prevalent cause of admissions to the intensive care unit (ICU) and many of these patients develop septic shock (SC) (need for vasoactive drug, after adequate fluid administration, plus hyperlactatemia). The SC involvement is systemic, so the investigators started to monitor organ dysfunctions and their perfusion windows, including neurological disorders, when is affected, in addition to indicating severity, are also a predictor of worse prognosis.

The principle of cerebral autoregulation (CA) is the basic defense mechanism against pressure oscillations in the most diverse contexts. The SC is a state of vasodilation and consequent drop in mean arterial pressure (MAP), that under normal physiological conditions would be compensated by CA. But it is not known exactly how CA performance at this profile of patients.

The investigators will assess cerebral hemodynamics in SC patients at different MAP targets, in order to identify whether this regulatory variable would be able to generate better parameters of cerebral hemodynamics.

Some smaller studies have shown that liver and heart dysfunction correlate with worsening autoregulation. Another clinical trial showed an inverse relationship between CA and the Sequential Organ Failure Assessment, in addition to the loss of CA in patients with circulatory shock in general. Post-mortem data found generalized ischemic lesions in the brain of septic patients, which translates into a state of reduction at vascular flow. This patient profile has more blood-brain barrier dysfunction, but further studies are needed to correlate CA and CS.

The study will be carried out in the ICU of Hospital São Rafael (HSR), located in the city of Salvador-Ba, Brazil. For the evaluation of cerebral hemodynamics Transcranial Doppler and a Mechanical sensor (B4C) will be used.

Data collection on admission will include the following: demographic characteristics, comorbidities, source of infection, Sequential Organ Failure Assessment (SOFA) at ICU admission, temperature, Glasgow Coma scale (GCE) or Richmond Agitation Sedation Scale (RASS), mechanical ventilation, arterial blood gasses before and after the protocol.

All patients will be monitored with an arterial line, cardioscopy, pulse oximetry and capnography (if unavailable at the time of collection, this will be described). Before starting the monitoring, the proper functioning of the arterial circuit will be confirmed and a blood gas analysis will be collected, as well as at the end.

The investigators will collet data with the patient's baseline pressure for 5 minutes (T0), then through the titration of vasopressors, for another 5 minutes each mean arterial pressure target at 65mmHg (T1), 75 mmHg (T2) and 85 mmHg (T3). After collection, the baseline mean arterial pressure will be restored

• Study Type: Observational
• Enrollment (Anticipated): 40

Contacts and Locations

• Study Contact: Name: Pedro Cury; Phone Number: +5571991950585; Email: pedrovcury@gmail.com
• Study Contact Backup: Name: Juliana Caldas; Phone Number: +55 71 9901-9500; Email: caldas.juliana@gmail.com

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Recruiting
      • São Rafael Hospital
      • Contact: Juliana Caldas; Phone Number: +55 71 99901-9500; Email: caldas.juliana@gmail.com
      • Contact: Pedro Cury; Phone Number: +55 71 991950585; Email: pedrovcury@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with septic shock with less than 48 hours of ICU stay

Description

Inclusion Criteria:

• < 48 hours in the intensive care unit
• Septic shock (sepsis 3.0)

Exclusion Criteria:

• No window for DTC
• Hepatic or uremic encephalopathy
• Pregnancy
• Acute or prior structural neurological insult
• Exogenous intoxication
• Dementia
• Chronic Obstructive Pulmonary Disease
• Instability for acute arrhythmia
• Extracorporeal support by modifying the pulse wave form (intra aortic balloon pump and Extracorporeal membrane oxygenation
• Extreme severity, with imminent risk of death

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

ALL PATIENTS; All patients are monitored with the transcranial Doppler helmet and the 2Hz probe in one of the middle cerebral hemispheres and the Brain 4 care on the other side. Necessary monitoring: arterial line, electrocardiographic monitor, pulse oximetry, temperature. ETCO2 monitoring whenever possible. Step 1: Test arterial line circuit, ensure proper temperature, arterial blood gases Step 2: Record data with the patient's baseline pressure (data from the monitor, transcranial doppler and brain4care), for 5 min Step 3: Vasopressor titrant for 3 MAP targets (65, 75 and 85 mmHg) , record data with the patient's baseline pressure (data from the monitor, transcranial doppler and brain4care), each target record for 3 minutes Step 4: Arterial blood gases, gradually restore PAM to baseline value

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The primary objective is to evaluate the effects of cerebral haemodynamic in patients with septic shock in different targets of MAP, through ARI (by Transcranial Doppler), and intracranial compliance by mechanical sensor (B4C)	This outcome will be analyzed by transcranial Doppler (ARI, PI) and B4C (intracranial compliance) index). Data will be obtained at the time of collection (mean arterial pressure targets) and subsequently analyzed	Data will be obtained at the time of collection (mean arterial pressure targets) and subsequently analyzed

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess factors that influence cerebral autoregulation (by ARI) and intracranial compliance (B4C)	To verify clinical factors that influence cerebral autoregulation (CA) and intracranial compliance of septic patients	Data will be obtained at the time of collection (mean arterial pressure targets) and subsequently analyzed
Evaluate the correlation between CA by TDC and B4C index.	Report the similarity between the two indices	Data will be obtained at the time of collection (mean arterial pressure targets) and subsequently analyzed
Correlate mechanical ventilation time with perfusion pressure value	Observation that there is a correlation between the duration of mechanical ventilation and the patient's baseline perfusion pressure	Mechanical ventilation time up to 28 days
Explore the correlation between incidence of brain dysfunction	Brain dysfunction will be considered as: Glasgow Coma Scale score < 15 or when disorientation, altered thinking or agitation was reported by the attending physician, independently of the use of sedatives/analgesics and in the absence of previous neurological diseases (i.e., dementia, cerebrovascular disease, brain tumors, previous traumatic brain injury) with DTC and B4C index.	Until 28º day

Collaborators and Investigators

• Sponsor: D'Or Institute for Research and Education
• Investigators: Principal Investigator: Juliana Caldas, Phd, D'Or Institute for Research and Education (IDOR), Hospital São Rafael; Study Chair: Pedro Cury, D'Or Institute for Research and Education (IDOR), Hospital São Rafael

Publications and helpful links

Helpful Links

• The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)
• Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021
• Cerebral dysfunctions caused by sepsis during ageing
• Cerebral autoregulation
• Dynamic Autoregulation is Impaired in Circulatory Shock
• Impaired cerebral autoregulation is associated with brain dysfunction in patients with sepsis
• Waveform Morphology as a Surrogate for ICP Monitoring: A Comparison Between an Invasive and a Noninvasive Method
• Noninvasive intracranial pressure waveforms for estimation of intracranial hypertension and outcome prediction in acute brain-injured patients
• Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors
• POCUS, how can we include the brain? An overview
• A Novel Noninvasive Technique for Intracranial Pressure Waveform Monitoring in Critical Care
• Daily blood pressure variability in relation to neurological functional outcomes after acute ischemic stroke

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): July 7, 2024

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: April 17, 2023
• First Posted (Actual): April 27, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 17, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Septic Shock; Cerebral autoregulation; Cerebral hemodynamics
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: 28134720.1.0000.0048

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We don't have that plan, but if the data is useful for larger research, no problem.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No