The Impact of Early Norepinephrine Administration on Outcomes of Patients With Sepsis-induced Hypotension

Septic shock is defined as sepsis with persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP)≥ 65 mmHg and a serum lactate level of > 2 mmol/L (18 mg/dL) despite sufficient volume resuscitation

. Hypovolemia (both relative and absolute) and reduced vascular tone have a role in determining the severity of hypotension in septic shock

Study Overview

• Status: Completed
• Conditions: Sepsis; Hypotension; Norepinephrine
• Intervention / Treatment: Drug: Crystalloid; Drug: noradrenaline

Detailed Description

Septic shock is defined as sepsis with persistent hypotension requiring vasopressors to maintain mean arterial pressure (MAP)≥ 65 mmHg and a serum lactate level of > 2 mmol/L (18 mg/dL) despite sufficient volume resuscitation . Hypovolemia (both relative and absolute) and reduced vascular tone have a role in determining the severity of hypotension in septic shock

. When mean arterial pressure (MAP) falls below a specific critical level organ blood flow is physiologically dependent on perfusion pressure. Fluid resuscitation and vasopressors have an influence on hypovolemia and the vascular tone in the early phase, as fluid resuscitation aims to correct hypovolemia and vasopressors-norepinephrine (NE)- as a first-line drug aiming to restore vascular tone to assure organ perfusion

. Norepinephrine is both an alpha1- and beta1-agonist so it is able to increase vascular tone and contractility

. Nevertheless, a large amount of fluids will increase the risk of fluid overload, which is a common complication during septic shock resuscitation

• After the early phase, only fifty percent of patients respond to fluid administration, meaning that fluid treatment cannot boost cardiac output (CO) The current data indicate that the time from the onset of septic shock to the initiation of norepinephrine administration is a significant survival predictor; however, a suggestion for the optimal time to provide norepinephrine support was not explicitly expressed

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • El Gharbyia
    • Tanta, El Gharbyia, Egypt, 31111
      • Faculty of medicine, Tanta University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients aged from18 to 65 years old
• had the diagnostic criteria for sepsis as the presence of infection
• systemic manifestations of infection and signs of Hypoperfusion

Exclusion Criteria:

• Acute cerebral vascular event
• Active cardiac conditions
• Valvular heart diseases
• Hypotension suspected to be due to another cause and comorbidities
• Status asthmatics
• Active hemorrhage
• Pregnancy
• Burn injury
• Requirement for immediate surgery
• Advanced-stage cancer
• Refusal to participate in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: A; patients received (30ml /kg) ringer's lactate solution after first presentation then norepinephrine was added when persistent mean arterial pressure (MAP)> 65 mmHg despite adequate fluid resuscitation	Drug: Crystalloid; received (30ml /kg) ringer's lactate solution after first presentation then norepinephrine was added when persistent mean arterial pressure (MAP)> 65 mmHg despite adequate fluid resuscitation; Other Names: late noradrenaline infusion
Active Comparator: B; patients received ( 30ml /kg) ringer's lactate solution after first presentation combined with norepinephrine infusion (0.05 mic/kg/min)	Drug: noradrenaline; received ( 30ml /kg) ringer's lactate solution after first presentation combined with norepinephrine infusion (0.05 mic/kg/min); Other Names: early noradrenaline infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the required duration to achieve the target MAP	time to achieve target mean arterial pressure over or equal to 65 mmHg once the diagnosis of sepsis is confirmed, is the target to stop fluid management.	24 hours since the diagnosis of sepsis

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Study Director: ghada elbarady, MD, tanta university, faculty of medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): March 10, 2023

Study Registration Dates

• First Submitted: March 7, 2023
• First Submitted That Met QC Criteria: March 7, 2023
• First Posted (Actual): March 17, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia; Hypotension; 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: early noradrenaline in sepsis

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