Microcirculation After MAP Increase in Septic Shock Patients With Previous Hypertension

The optimal levels of mean arterial pressure that must be achieved in septic shock are subject of debate. Studies tried to correlate blood pressure increase in patients with septic shock with microcirculation. However, there are few studies that specifically assessed septic shock patients with previous arterial hypertension. The main objective of this study is to evaluate the effect of increased blood pressure level in the microcirculation of these patients and compare them with patients without arterial hypertension.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Drug: norepinephrine

Detailed Description

Hypothesis: After a rise in mean arterial pressure, microcirculation improvement will occur only in the previously hypertensive patients.

Study design: Prospective clinical trial Setting: Intensive care units of the Anesthesiology Department at the Federal University of Sao Paulo and the intensive care unit of Kidney Hospital.

Studied population: Forty patients will be included, being 20 without known history of systemic arterial hypertension and 20 with this diagnosis for at least 2 years and already with clinical or subclinical organ damage.

Inclusion criteria: age over than 18 years old, norepinephrine drug use for at least 12 hours and for less than 72 hours, sedation level equal or deeper than Ramsay 4, blood pressure stable for the last 30 minutes prior to inclusion, central venous catheter in place and signed informed consent.

Exclusion criteria: pregnancy, cirrhosis, systemic sclerosis, and need to maintain mean arterial pressure above 65mmHg for others conditions.

Intervention: noradrenaline dose will be risen to obtain a mean arterial pressure of 85-90 mmHg.

Assessments and outcome: Systemic hemodynamic (central venous oxygen saturation, cardiac output, heart rate, central venous pressure) and sublingual microcirculation variables (microcirculatory flow index, total vascular density, proportion of perfused vessels, perfused vascular density) will be measured before and after the rise in mean arterial pressure. Sidestream darkfield will be used to assess microcirculation. The variation between those variables before and after the intervention will be compared.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 04024-003
    • Hospital São Paulo - Universidade Federal de São Paulo

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• age over than 18 years old,
• norepinephrine drug use for at least 12 hours and for less than 72 hours,
• sedation level equal or deeper than Ramsay 4,
• blood pressure stable for the last 30 minutes prior to inclusion,
• central venous catheter in place and
• signed informed consent.

Exclusion Criteria:

• pregnancy,
• cirrhosis,
• systemic sclerosis, and
• need to maintain mean arterial pressure above 65mmHg for others conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Norepinephrine; Noradrenaline continuous infusion IV	Drug: norepinephrine; Increase in mean arterial pressure using norepinephrine; Other Names: noradrenaline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microcirculatory flow index (MIF) measured by sidestream darkfield after rising the mean arterial pressure with norepinephrine	MIF will be measured in points varying from 0 to 4	after 20 min

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total vascular density (TVD) measured by sidestream darkfield after rising the mean arterial pressure with norepinephrine	TVD will be measured in mm/mm2	after 20 min
Perfused vascular density (PVD) measured by sidestream darkfield after rising the mean arterial pressure with norepinephrine	PVD will be measured in mm/mm2	after 20 min
Proportional perfused vessels (PPV) measured by sidestream darkfield after rising the mean arterial pressure with norepinephrine	PPV will be measured in percentage	after 20 min

Collaborators and Investigators

• Sponsor: Federal University of São Paulo
• Investigators: Study Chair: Flavia Machado, PhD, Federal University of São Paulo

Publications and helpful links

General Publications

• Dubin A, Pozo MO, Casabella CA, Palizas F Jr, Murias G, Moseinco MC, Kanoore Edul VS, Palizas F, Estenssoro E, Ince C. Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study. Crit Care. 2009;13(3):R92. doi: 10.1186/cc7922. Epub 2009 Jun 17.
• Leone M, Asfar P, Radermacher P, Vincent JL, Martin C. Optimizing mean arterial pressure in septic shock: a critical reappraisal of the literature. Crit Care. 2015 Mar 10;19(1):101. doi: 10.1186/s13054-015-0794-z.
• Correa TD, Vuda M, Takala J, Djafarzadeh S, Silva E, Jakob SM. Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function. Crit Care. 2013 Jan 30;17(1):R21. doi: 10.1186/cc12495.
• Xu JY, Ma SQ, Pan C, He HL, Cai SX, Hu SL, Liu AR, Liu L, Huang YZ, Guo FM, Yang Y, Qiu HB. A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study. Crit Care. 2015 Mar 30;19(1):130. doi: 10.1186/s13054-015-0866-0.
• Fiorese Coimbra KT, de Freitas FGR, Bafi AT, Pinheiro TT, Nunes NF, de Azevedo LCP, Machado FR. Effect of Increasing Blood Pressure With Noradrenaline on the Microcirculation of Patients With Septic Shock and Previous Arterial Hypertension. Crit Care Med. 2019 Aug;47(8):1033-1040. doi: 10.1097/CCM.0000000000003795.

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: July 28, 2015
• First Submitted That Met QC Criteria: August 6, 2015
• First Posted (Estimate): August 11, 2015

Study Record Updates

• Last Update Posted (Actual): April 4, 2017
• Last Update Submitted That Met QC Criteria: April 2, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Hypertension; Shock, Septic; Shock; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympathomimetics; Vasoconstrictor Agents; Norepinephrine
• Other Study ID Numbers: CEP173.166

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: undecided