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)

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