Fig. 2. Factors in the intensive care setting that may obstruct the nitrate-nitrite-nitric oxide pathway. Several important steps in nitrate-nitrite-nitric oxide (NO) pathway may be negatively affected in patients treated in the intensive care unit (ICU). The normal dietary intake of nitrate (NO3−, mostly from vegetables) will be almost abolished because both enteral and parenteral feeding formulas contain extremely low concentrations of nitrate and nitrite (NO2−). A patient on full enteral or parenteral feeding is subjected to nitrate/nitrite starvation. Nitrate reduction to nitrite in the oral cavity depends on saliva production and active oral commensal bacteria. Intubated and sedated patients have poor saliva production and are often treated with broad-spectrum antibiotics, which will inhibit this part of the pathway. Normally, swallowed salivary nitrite will immediately be reduced to nitric oxide in the acidic stomach, and this nitric oxide may be involved in host defense and upholding gastric mucosal integrity. ICU patients often have problems swallowing saliva due to sedation and intubation, and their gastric pH is often increased, sometimes pharmacologically, to prevent gastric ulceration. This may partly explain high incidence of gastric ulceration and bacterial colonization found in ICU patients. Finally, many conditions in the ICU are associated with increased oxidative stress in which reactive oxygen species can scavenge nitric oxide, thereby reducing nitric oxide bioactivity.