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

Study Overview
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Brief Summary
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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

Detailed Description
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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

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

Conditions
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Norepinephrine, Sepsis, Hypotension

Intervention / Treatment
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* Drug: Crystalloid
* Drug: noradrenaline


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: A<br>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<br>* 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<br>* Other names: late noradrenaline infusion;|
| Active Comparator: B<br>patients received ( 30ml /kg) ringer's lactate solution after first presentation combined with norepinephrine infusion (0.05 mic/kg/min) | Drug: noradrenaline<br>* received ( 30ml /kg) ringer's lactate solution after first presentation combined with norepinephrine infusion (0.05 mic/kg/min)<br>* Other names: early noradrenaline infusion;|

What is the study measuring?
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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 |