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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Injection bolus of 2 mg/kg PBW and infusion of 0.2 mg/kg/hr
An inhalation of NO via ETT at 10 ppm, partially weaned by 72 hrs of therapy
See the dosage in the previous arms
University Hospital #1
Arkhangelsk, Russia, Russia
Mortality
Mortality rate by Day 28
Time frame: 28
Duration of inotropic and vasopressor support
Duration of vasopressor and/or inotrope suppor
Time frame: 7 Days
Severity of organ dysfunction
Number of organ-specific dysfunctions
Time frame: 7 Days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.