Inhaled carbon monoxide protects time-dependently from loss of hypoxic pulmonary vasoconstriction in endotoxemic mice.

BACKGROUND: Inhaled carbon monoxide (CO) appears to have beneficial effects on endotoxemia-induced impairment of hypoxic pulmonary vasoconstriction (HPV). This study aims to specify correct timing of CO application, it's biochemical mechanisms and effects on inflammatory reactions. METHODS: Mice (C57BL/6; n = 86) received lipopolysaccharide (LPS, 30 mg/kg) intraperitoneally and subsequently breathed 50 ppm CO continuously during defined intervals of 3, 6, 12 or 18 h. Two control groups received saline intraperitoneally and additionally either air or CO, and one control group received LPS but breathed air only. In an isolated lung perfusion model vasoconstrictor response to hypoxia (FiO2 = 0.01) was quantified by measurements of pulmonary artery pressure. Pulmonary capillary pressure was estimated by double occlusion technique. Further, inflammatory plasma cytokines and lung tissue mRNA of nitric-oxide-synthase-2 (NOS-2) and heme oxygenase-1 (HO-1) were measured. RESULTS: HPV was impaired after LPS-challenge (p < 0.01). CO exposure restored HPV-responsiveness if administered continuously for full 18 h, for the first 6 h and if given in the interval between the 3(rd) and 6(th) hour after LPS-challenge (p < 0.05). Preserved HPV was attributable to recovered arterial resistance and associated with significant reduction in NOS-2 mRNA when compared to controls (p < 0.05). We found no effects on inflammatory plasma cytokines. CONCLUSION: Low-dose CO prevented LPS-induced impairment of HPV in a time-dependent manner, associated with a decreased NOS-2 expression.

Restrictive transfusion practice during extracorporeal membrane oxygenation therapy for severe acute respiratory distress syndrome.

Recommendations concerning the management of hemoglobin levels and hematocrit in patients on extracorporeal membrane oxygenation (ECMO) still advise maintenance of a normal hematocrit. In contrast, current transfusion guidelines for critically ill patients support restrictive transfusion practice. We report on a series of patients receiving venovenous ECMO (vvECMO) for acute respiratory distress syndrome (ARDS) treated according to the restrictive transfusion regimen recommended for critically ill patients. We retrospectively analyzed 18 patients receiving vvECMO due to severe ARDS. Hemoglobin concentrations were kept between 7 and 9 g/dL with a transfusion trigger at 7 g/dL or when physiological transfusion triggers were apparent. We assessed baseline data, hospital mortality, time on ECMO, hemoglobin levels, hematocrit, quantities of packed red blood cells received, and lactate concentrations and compared survivors and nonsurvivors. The overall mortality of all patients on vvECMO was 38.9%. Mean hemoglobin concentration over all patients and ECMO days was 8.30 ± 0.51 g/dL, and hematocrit was 0.25 ± 0.01, with no difference between survivors and nonsurvivors. Mean numbers of given PRBCs showed a trend towards higher quantities in the group of nonsurvivors, but the difference was not significant (1.97 ± 1.47 vs. 0.96 ± 0.76 units; P = 0.07). Mean lactate clearance from the first to the third day was 45.4 ± 28.3%, with no significant difference between survivors and nonsurvivors (P = 0.19). In our cohort of patients treated with ECMO due to severe ARDS, the application of a restrictive transfusion protocol did not result in an increased mortality. Safety and feasibility of the application of a restrictive transfusion protocol in patients on ECMO must further be evaluated in randomized controlled trials.