Early Use of Norepinephrine in Septic Shock Resuscitation

Study Overview
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Brief Summary
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Current septic shock guideline recommends fluid resuscitation as the first treatment. Vasopressors, including norepinephrine is recommended to start after achieve adequate fluid therapy. This can cause a certain duration of systemic hypotension before vasopressor is commenced. Initiation of norepinephrine together with fluid therapy soon after diagnosis of septic shock may increase blood pressure quicker than start treatment with intravenous fluid alone. The rapid restoration of perfusion pressure may improve septic shock outcome.

Detailed Description
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We will include severe infection patient who had evidence of organ dysfunction and hypotension and randomize into 2 groups as following: Control group. The patient will receive treatment according to septic shock guideline 2013, which start with intravenous fluid replacement until achieve target central venous pressure (CVP) or pulmonary capillary wedge pressure (PCWP) or other fluid responsive test goal. If the patient's mean arterial blood pressure still lower than 65 mmHg, then norepinephrine or dopamine will initiate to rise blood pressure. The patient will receive 5% dextrose water as the placebo of norepinephrine. Early norepinephrine group. The patient will receive fluid therapy together with low dose of norepinephrine (0.05 mcg/kg/min). If after titrate intravenous fluid therapy until achieve goal CVP or PCWP or other fluid responsive test, but the mean blood pressure still lower than 65 mmHg, then additional titrate dose of norepinephrine will be given to the patient according to standard septic shock guideline.

Official Title
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The Comparison Between Early Norepinephrine Use and Standard Treatment During Severe Sepsis and Septic Shock Resuscitation.

Conditions
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Septic Shock, Severe Sepsis

Intervention / Treatment
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* Drug: Early norepinephrine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > or = 18 years old Diagnosed severe sepsis or septic shock according to survival sepsis campaign 2013 Mean arterial pressure < 65 mmHg Exclusion Criteria: Pregnancy Severe underlying condition that unexpected to survive more than 48 hours Severe peripheral vascular disease Patient who required major surgery within 24 hours

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Early norepinephrine<br>Norepinephrine 4 mg in 5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour, adjusted according to patient's body weight to achieve norepinephrine 0.05microgram/kg/min Continuous drip for 48 hours. | Drug: Early norepinephrine<br>* Initiation of norepinephrine, a strong vasoconstrictor, at the initiation of septic shock management, together with fluid resuscitation.<br>* Other names: Early vasopressor therapy;|
| Placebo Comparator: Placebo<br>5% dextrose water 250 ml Intravenous infusion rate range from 8 to 15 ml/hour. Adjust rate of infusion according to patient's body weight to achieve dosage of norepinephrine comparable to 0.05 microgram/kg/min Continuous drip for 48 hours. | Drug: Placebo<br>* 5% dextrose water intravenous drip in the same rate of calculated norepinephrine for the patient's body weight<br>* Other names: 5%D/W infusion as the placebo of norepinephrine.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic goal achievement | Therapeutic goal including Mean arterial blood pressure > or = 65 mmHg Evidence of adequate tissue perfusion which include continuation of urine output > or = 0.5 ml/kg/hour for 2 hours or decreasing of serum lactate > or = 10 percent in 1 to 2 hours. | 6 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rate |  | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Septic shock, Severe sepsis, Norepinephrine