[Computed tomographic criteria as expected effect to inhaled nitric oxide in patients with severe acute respiratory distress syndrome]. / Computertomographische Kriterien für den zu erwartenden Effekt von inhaliertem Stickstoffmonoxid bei Patienten mit schwerem akutem Lungenversagen.

PURPOSE: Inhaled nitric oxide (iNO) is an effective therapy for severe hypoxemia in most patients with acute respiratory distress syndrome (ARDS). For unknown reason, a subset of ARDS patients does not respond favorably to iNO therapy. We hypothesized that radiological manifestation of lung injury may be related to iNO response. MATERIALS AND METHODS: We retrospectively analyzed data from n = 25 ARDS patients who received iNO, and underwent chest CT within 72 h prior to inhaled treatment. The morphology of coherently pathologic lung tissue was characterized by the length of the borderline between consolidated, infiltrated and atelectatic lung tissue and radiologically normal lung tissue. This quantity was expressed as relative fraction of the visceral pleural circumference and averaged over all CT slices. Furthermore we semiquantitatively determined the total volume of consolidated lung tissue as part of the whole lung. RESULTS: In n = 6 non-responders to iNO (DeltaPaO2 < 10 %), we determined a short relative borderline between normal and consolidated lung tissue due to the presence of large and coherently consolidated lung regions. In n = 19 iNO responders (DeltaPaO2 > 10 %), we found significantly less coherently consolidated lung tissue evidenced by an increased relative borderline when compared to iNO non-responders (0.09 +/- 0.02 vs. 0.1 +/- 0.01; P < 0.05). Moreover, there was a moderate and significant correlation between DeltaPaO2 induced by iNO and the relative borderline in all patients studied (R = 0.59; P < 0.05). Total fraction of consolidated lung tissue volume was not different between iNO non-responders and responders (60 +/- 3 % vs. 54 +/- 2 % n. s.). CONCLUSION: Our data demonstrate that the gross morphological distribution of pathological lung tissue influences iNO response in ARDS. Inhaled NO was most beneficial in injured lungs characterized by many small consolidated areas surrounded by normal lung tissue. The increased borderline between pathologic and normal lung tissue offers additional possibility for iNO to divert blood flow from shunt areas to ventilated lung regions, which consequently improves arterial oxygenation.

[Inhaled nitric oxide for the treatment of ARDS]. / Stellenwert von inhaliertem Stickstoffmonoxid bei der Behandlung des schweren akuten Lungenversagens.

Acute respiratory distress syndrome (ARDS) is characterized by perfusion in favor of non-ventilated areas of the lungs as the main cause of intrapulmonary right-to-left shunt and hypoxemia. Therapeutic interventions to selectively influence pulmonary perfusion in ARDS became possible with the introduction of inhaled nitric oxide (iNO), which provided a way not only to reduce pulmonary hypertension, but also to acutely improve ventilation-perfusion mismatch, and thus to treat severe hypoxemia. Clinical studies in ARDS demonstrated that the combination of iNO with other interventions, such as positive end-expiratory pressure (PEEP) and prone positioning, yielded beneficial and additive effects on arterial oxygenation. Although randomized controlled trials of this concept have up to now failed to show an improved outcome, iNO is a valuable option for the treatment of severe refractory hypoxemia in ARDS patients.

"Ideal PEEP" is superior to high dose partial liquid ventilation with low PEEP in experimental acute lung injury.

OBJECTIVE: To determine the effects of a high dose partial liquid ventilation (PLV) approximating the amount of the functional residual capacity (FRC) with low levels of positive end-expiratory pressure (PEEP) compared to a lung-protective strategy with volume-controlled mechanical ventilation (vcMV) with a PEEP level above the lower inflection point (LIP) on pulmonary gas exchange, haemodynamics, respiratory mechanics and lung injury in an experimental model of acute lung injury (ALI). DESIGN: Prospective, randomised, controlled study. METHODS: Twenty-four anaesthetised, tracheotomised and mechanically ventilated (FIO(2) 1.0) pigs underwent induction of ALI by repeated saline wash-out of surfactant. Animals were randomly assigned to receive either PLV ( PLV, n=8) with 30 ml/kg of perfluorocarbons (PF 5080, 3 M, Germany) and a PEEP level of 5 cmH(2)O, to receive vcMV with a PEEP level of 1 cmH(2)O above the LIP ( (ideal) PEEP, n=8), or to receive vcMV with a PEEP level of 5 cmH(2)O ( Controls, n=8). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange, respiratory mechanics and haemodynamics were performed hourly for a 6 h period. In the (ideal) PEEP group, intra-pulmonary shunt (Qs/Qt) decreased from 55+/-5% after induction of ALI to 10+/-3% ( p<0.05 versus Controls and versus PLV) and PaO(2) increased from 52+/-4 to 566+/-19 mmHg after 6 h of treatment ( p<0.05 versus Controls and versus PLV). In the PLV group, Qs/Qt decreased from 50+/-5% after induction of ALI to 24+/-3% ( p<0.05 versus Controls) and PaO(2) increased from 59+/-5 to 306+/-35 mmHg after 6 h of treatment ( p<0.05 versus Controls). In the PLV group and in Controls, mean pulmonary artery pressure (MPAP) was significantly increased from 27+/-2 to 38+/-2 mmHg and from 29+/-1 to 40+/-1 mmHg, respectively, 6 h after induction of ALI ( p<0.05 versus (ideal) PEEP), while in the (ideal) PEEP group, MPAP was maintained between 26+/-1 and 31+/-2 mmHg for 6 h after ALI. Cardiac output (CO) decreased significantly in the (ideal) PEEP group compared to Controls ( p<0.05), while CO did not change in the PLV group and in Controls. The compliance of the respiratory system (C(RS)) increased in the (ideal) PEEP group after induction of ALI from 11+/-2 to 22+/-5 ml/mbar ( p<0.05 versus Controls and versus PLV) and in the PLV group from 10+/-2 to 13+/-3 ml/mbar after 6 h of treatment ( p<0.05 versus Controls). On histological examination, the highest total injury scores were found in animals of the PLV group ( p<0.05 versus Controls and versus (ideal) PEEP), while the lowest total lung injury score was found in the dependent lung regions of the (ideal) PEEP group ( p<0.05 versus Controls). CONCLUSION: In this porcine model of ALI, vcMV with a PEEP level of 1 cmH(2)O above the LIP was superior to high dose PLV with a PEEP of 5 cmH(2)O in improving gas exchange and lung mechanics. In terms of lung damage, the treatment in the (ideal) PEEP group resulted in the lowest total lung injury scores.

Small dose of exogenous surfactant combined with partial liquid ventilation in experimental acute lung injury: effects on gas exchange, haemodynamics, lung mechanics, and lung pathology.

A combination of exogenous surfactant and partial liquid ventilation (PLV) with perfluorocarbons should enhance gas exchange, improve respiratory mechanics and reduce tissue damage of the lung in acute lung injury (ALI). We used a small dose of exogenous surfactant with and without PLV in an experimental model of ALI and studied the effects on gas exchange, haemodynamics, lung mechanics, and lung pathology. ALI was induced by repeated lavages (PaO2/FIO2 less than 13 kPa) in 24 anaesthesized, tracheotomized and mechanically ventilated (FIO2 1.0) juvenile pigs. They were treated randomly with either a single intratracheal dose of surfactant (50 mg kg(-1), Curosurf, Serono AG, München, Germany) (SURF-group, n=8), a single intratracheal dose of surfactant (50 mg kg(-1), Curosurf) followed by PLV with 30 ml kg(-1) of perfluorocarbon (PF 5080, 3M, Germany) (SURF-PLV-group, n=8) or no further intervention (controls, n=8). Pulmonary gas exchange, respiratory mechanics, and haemodynamics were measured hourly for a 6 h period. In the SURF-group, the intrapulmonary right-to-left shunt (QS/QT) decreased significantly from mean 51 (SEM 5)% after lavage to 12 (2)%, and PaO2 increased significantly from 8.1 (0.7) to 61.2 (4.7) kPa compared with controls and compared with the SURF-PLV-group (P<0.05). In the SURF-PLV-group, QS/QT decreased significantly from 54 (3)% after induction of ALI to 26 (3)% and PaO2 increased significantly from 7.2 (0.5) to 30.8 (5.0) kPa compared with controls (P<0.05). Static compliance of the respiratory system (C(RS)), significantly improved in the SURF-PLV-group compared with controls (P<0.05). Upon histological examination, the SURF-group revealed the lowest total injury score compared with controls and the SURF-PLV-group (P<0.05). We conclude that in this experimental model of ALI, treatment with a small dose of exogenous surfactant improves pulmonary gas exchange and reduces the lung injury more effectively than the combined treatment of a small dose of exogenous surfactant and PLV.

Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury.

OBJECTIVES: To study the effects of an inhaled endothelin A (ET(A)) receptor antagonist on hemodynamics and pulmonary gas exchange in experimental acute lung injury (ALI). DESIGN AND SETTING: Prospective, randomized, and controlled study in a university laboratory. PARTICIPANTS AND INTERVENTIONS: Sixteen pigs were ventilated in a volume controlled mode during general anesthesia. ALI was induced by surfactant depletion using repetitive lung lavages until the PaO2/FIO2 ratio was below 100 mmHg. The animals were then randomly assigned to receive either a nebulized ET(A) receptor antagonist (LU-135252, 3 mg/kg, inhaled over 1 h; LU group) or nebulization of saline (5-10 ml inhaled over 1 h) with no further intervention (controls). MEASUREMENTS AND RESULTS: Parameters of hemodynamics and gas exchange were measured for 6 h after induction of ALI. In the LU group intrapulmonary right-left shunting (QS/QT) decreased from 58 +/- 8% at the onset of ALI to 27 +/- 12% 3 h and 24 +/- 9% 6 h after ALI (p < 0.05); PaO2 increased from 55 +/- 12 to 257 +/- 148 mmHg 3 h and 270 +/- 136 mmHg 6 h after ALI. (p < 0.05), whereas in controls QS/QT and PaO2 did not improve over the 6 h after onset of ALI. In the LU group mean pulmonary artery pressure was stable for 6 h after ALI (26-29 mmHg), while in controls it increased from 28 +/- 2 to 41 +/- 2 mmHg (p < 0.05). Inhaled LU-135252 reduced cardiac output by 31 +/- 11% (p < 0.05) and increased systemic vascular resistance by 60 +/- 29 % (p < 0.05), while these parameters remained stable in controls. CONCLUSION: In this porcine model of ALI the inhalation of an ET(A) receptor antagonist improved arterial oxygenation and maintained a stable pulmonary artery pressure without inducing systemic vasodilatation.

A case of septicemia with Pediococcus acidilactici after long-term antibiotic treatment.

Presented here is a case of septicemia caused by an uncommon, multiresistant, gram-positive microorganism (Pediococcus acidilactici) after long-term antibiotic treatment. Pediococcus spp. are rarely cultivated from clinical specimens, and species differentiation is difficult due to the paucity of phenotypic traits. In this case, a polyphasic approach consisting of phenotypic and molecular genetic analyses was used, and the identification of Pediococcus acidilactici was conclusive. Precise identification and antimicrobial susceptibility testing of rarely isolated bacteria are required in order to provide adequate treatment to infected patients and to determine the pathogenic role of these organisms.

Low nitric oxide concentrations in exhaled gas and nasal airways of mammals without paranasal sinuses.

To investigate whether relevant levels of nasal nitric oxide (NO) are produced in the absence of paranasal sinuses, we studied 17 healthy baboons, mammals without any paranasal sinuses. The animals were anesthetized with ketamine hydrochloride and breathed spontaneously. While the baboons breathed through a face mask (mouths closed) connected to a respirator, NO concentrations in exhaled gas were sampled from the expiratory limb and analyzed by chemiluminescence. While the animals were breathing ambient air, nasal gas was sampled via a thin plastic tube and analyzed for NO concentrations by chemiluminescence. Mean NO concentration in the exhaled gas was 1.00 +/- 0.59 parts/billion, and NO release was 4.28 +/- 2.72 nl/min. A NO concentration of 4.79 +/- 2.08 parts/billion was found in the nasal gas (NO release: 7.18 +/- 3.13 nl/min). An age-dependent increase in nasal NO levels was not observed. Exhaled and nasal NO concentrations in baboons were markedly lower than in mammals with paranasal sinuses, suggesting that paranasal sinuses might be an anatomic requirement for production of relevant nasal NO levels.