What Should be the Next Vasopressor for Severe Septic Shock? Methylene Blue or Terlipressin

Study Overview
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Brief Summary
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The ICU mortality rate of patients with septic shock was still high upto 54.1%.In first 6 hours of resuscitation, the goals of resuscitation in sepsis shock after adequate fluid resuscitation is MAP ≥65 mmHg. In refractory septic shock patient, prolong shock correlate with poor outcome due to multiple organ failure. Alternative vasopressor in septic shock with catecholamine resistance has been studied such as terlipressin, methylene blue Terlipressin (TP) mediate vasoconstriction via V1 receptors coupled to phospholipase C, and increases intracellular Ca2+ concentration Methylene blue (MB) directly inhibits nitric oxide synthase (NOS) by inhibit the enzyme guanylate cyclase (GC)

Official Title
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What Should be the Next Vasopressor for Severe Septic Shock Patients? Methylene Blue or Terlipressin

Conditions
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Septic Shock, Refractory Shock

Intervention / Treatment
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* Drug: Methylene Blue
* Drug: Terlipressin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >15 years old Diagnosis septic shock as SCCM/ACCP Refractory septic shock defined as hypotension although adequate fluid resuscitate and high dose vasopressor(NE >0.5 mcg/kg/min) Concent form Exclusion Criteria: Known case G6PD deficiency Acute respiratory distress syndrome (ARDS) Hx of drug allergy MB, NE, terlipressin Hx of Raynaud's phenomenon, systemic sclerosis, PHT Known case coronary heart disease without treatment Current drug use serotonin reuptake inhibitors (SSRI), Serotonin and norepinephrine reuptake inhibitors (SNRIs) Reject to join project

Ages Eligible for Study
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Minimum Age: 15 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: A<br>standard care septic shock according sepsis bundles | |
| Experimental: B<br>after defined refractory shock (adequate fluid resuscitation + add NE>0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care) | Drug: Methylene Blue<br>* after defined refractory shock (need NE>0.5 mcg/kg/min) add Methylene blue 1 mg/kg iv drip then 2 hr later drip 0.5 mg/kg/hr*4 hr (intervention add on to standard care)<br>|
| Experimental: C<br>after defined refractory shock (adequate fluid resuscitation + add NE>0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care) | Drug: Terlipressin<br>* after defined refractory shock (need NE>0.5 mcg/kg/min) add terlipressin 1 mg IV then repeated dose 20 min later if unstable BP (intervention add on to standard care)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mortality rate |  | 7 days | 
| time to wean of vasopressor |  | through complete weaning off vasopressor, an average of 24 hours | 
| ICU duration |  | through out off indication need ICU care, an average of 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hemodynamic parameter: Mean arterial pressure (mmHg) | mmHg, A-line monitoring | every 30 min after start protocol up to 6 hr then every 1 hr up to 24 hours | 
| hemodynamic parameter: lactate (mmol/l) | mmol/l | every 2 hr until 6 hr then every 4 hr until wean off vasopressor up to 24 hours | 
| hemodynamic parameter: urine output (ml) | ml | every 2 hr until wean off vasopressor up to 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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refractory septic shock, catecholamine resistance septic shock, terlipressin, methylene blue