NCT00159510

Studies of Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome

A Controlled Prospective Randomized Open-Label Study of Methylene Blue and Inhaled Nitric Oxide in Patients With Septic Shock and Acute Lung Injury

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Northern State Medical University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Nitric oxide (NO) plays a pivotal role in maintenance of normal vascular tone. However, in sepsis the excessive production of NO results in myocardial depression, vasoplegia, and cytotoxic effects, thus promoting shock and multiple organ dysfunction. A recently completed study from our group showed advantageous cardiovascular effects of continuously infused methylene blue (MB), an inhibitor of NO pathway, in human septic shock. In another investigation, we have found that the combination of inhaled NO and continuously infused MB attenuates endotoxin-induced acute lung injury (ALI) in sheep. Our intention is, in a new study, to test the hypothesis that the combination of MB and NO (MB+NO) improves both cardiovascular and pulmonary functions as well as clinical outcome in patients with septic shock and ALI. Forty mechanically ventilated patients diagnosed with hyperdynamic septic shock and ALI, will be randomized to groups receiving 1. Conventional treatment (control group)(n =10); 2. MB infusion in addition to conventional treatment (n=10); 3. Inhaled NO in addition to conventional treatment (n=10); 4. MB infusion combined with inhaled NO (MB+NO) in addition to conventional treatment (n=10).

Detailed description

The therapy with either MB+NO or NO or MB alone will be prolonged for up to 24 h or until resolution of septic shock, whichever occurs first. MB will be injected as a bolus of 2 mg/kg subsequently followed by dose-titrated infusion. The latter beginning with 0.25 mg/kg/h continuing within the range of from 0.05 to 0.5 mg/kg/h. The goal is to maintain mean arterial pressure within the range of 70-90 mm Hg, with the purpose of reducing any concurrent vasopressor therapy. The NO therapy will be started from 10 ppm and aimed at maintaining the mean pulmonary artery pressure at the lowest possible levels by inhaling NO in concentrations from 1 to 20 ppm.

Conditions

• Sepsis

Interventions

Type	Name	Description
DRUG	Methylene blue	Injection bolus of 2 mg/kg PBW and infusion of 0.2 mg/kg/hr
DRUG	Nitric oxide	An inhalation of NO via ETT at 10 ppm, partially weaned by 72 hrs of therapy
DRUG	Methylene blue & nitric oxide	See the dosage in the previous arms

Timeline

• Start date: 2004-04-01
• Primary completion: 2014-09-01
• Completion: 2014-09-01
• First posted: 2005-09-12
• Last updated: 2015-10-06

Locations

1 site across 1 country: Russia