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

Overview

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 Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Treatment
  • Masking: Double (Participant, Outcomes Assessor)
• Study Primary Completion Date: February 1, 2023

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 vascular tone in the early phase, as fluid resuscitation aiming 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 indicates 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

Interventions

• 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
• Drug: noradrenaline
  • received ( 30ml /kg) ringer’s lactate solution after first presentation combined with norepinephrine infusion (0.05 mic/kg/min)

Arms, Groups and Cohorts

• 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
• Active Comparator: B
  • patients received ( 30ml /kg) ringer’s lactate solution after first presentation combined with norepinephrine infusion (0.05 mic/kg/min)

Clinical Trial Outcome Measures

Primary Measures

• time to achieve target mean arterial pressure (≥ 65 mmHg).
  • Time Frame: 24 hours since the diagnosis of sepsis
  • once the diagnosis of sepsis is confirmed, time to achieve target mean arterial pressure (≥ 65 mmHg) is the target to stop fluid management.

Participating in This Clinical Trial

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:

1- Acute cerebral vascular event 2. Active cardiac conditions 3. Valvular heart diseases 4. Hypotension suspected to be due to another cause and comorbidities 5. Status asthmatics 6. Active hemorrhage 7. Pregnancy 8.Burn injury 9. Requirement for immediate surgery 10. Advanced-stage cancer 11. Refusal to participate in the study

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 65 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Tanta University
• Provider of Information About this Clinical Study
  • Principal Investigator: tarek abdel hay mostafa, principle investigator – Tanta University
• Overall Official(s)
  • ghada elbarady, MD, Study Director, tanta university, faculty of medicine