M. Max

Evidence-based medicine in the therapy of the acute respiratory distress syndrome.

In 1972 Cochrane [1] coined the term “evidence-based medicine” (EBM) and suggested that scientific knowledge, especially prospective randomized controlled studies, is superior to personal experience. The principles of EBM were first used by Sackett [2] in 1986 for developing clinical recommendations on the use of antithrombotic agents. He classified five levels of scientific data resulting in three different grades of recommendation:

Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury.

Objective: To investigate a possible additive effect of combined nitric oxide (NO) and almitrine bismesylate (ALM) on pulmonary ventilation-perfusion (V˙.A/Q˙) ratio.¶Design: Prospective, controlled animal study.¶Setting: Animal research facility of a university hospital.¶Interventions: Three conditions were studied in ten female pigs with experimental acute lung injury (ALI) induced by repeated lung lavage: 1) 10 ppm NO, 2) 10 ppm NO with 1 μg/kg per min ALM, 3) 1 μg/kg per min ALM. For each condition, gas exchange, hemodynamics and V˙.A/Q˙ distributions were analyzed using the multiple inert gas elimination technique (MIGET).¶Measurement and results: With NO + ALM, arterial oxygen partial pressure (PaO2) increased from 63 ± 18 mmHg to 202 ± 97 mmHg while intrapulmonary shunt decreased from 50 ± 15 % to 26 ± 12 % and blood flow to regions with a normal V˙.A/Q˙ ratio increased from 49 ± 16 % to 72 ± 15 %. These changes were significant when compared to untreated ALI (p < 0.05) and NO or ALM alone (p < 0.05), although improvements due to NO or ALM also reached statistical significance compared to ALI values (p < 0.05).¶Conclusions: We conclude that NO + ALM results in an additive improvement of pulmonary gas exchange in an experimental model of ALI by diverting additional blood flow from non-ventilated lung regions towards those with normal V˙.A/Q˙ relationships.

Pressure support compared with controlled mechanical ventilation in experimental lung injury.

UNLABELLED It has been suggested that, in acute lung injury (ALI), spontaneous breathing activity may increase oxygenation because of an improvement of ventilation-perfusion distribution. Pressure support ventilation (PSV) is one of the assisted spontaneous breathing modes often used in critical care medicine. We sought to determine the prolonged effects of PSV on gas exchange in experimental ALI. We hypothesized that PSV may increase oxygenation because of an improvement in ventilation-perfusion distribution. Thus, ALI was induced in 20 pigs by using repetitive lung lavage. Thereafter, the animals were randomized to receive either PSV with a pressure level set to achieve a tidal volume >4 mL/kg and a respiratory rate <40 min(-1) (n = 10) or controlled mechanical ventilation (CMV) with a tidal volume of 10 mL/kg and a respiratory rate of 20 min(-1) (n = 10). Positive end-expiratory pressure was set at 10 cm H(2)O in both groups. Blood gas analyses and determination of ventilation-perfusion (.V(A)/.Q) distribution were performed at the onset of ALI and after 2, 4, 8, and 12 h. The main result was an improvement of oxygenation because of a decrease of pulmonary shunt and an increase of areas with normal .V(A)/.Q ratios during PSV (P < 0.005). However, during CMV, a more pronounced reduction of shunt was observed compared with PSV (P < 0.005). We conclude that, in this model of ALI, PSV improves gas exchange because of a reduction of .V(A)/.Q inequality. However, improvements in .V(A)/.Q distribution may be more effective with CMV than with PSV. IMPLICATIONS Assisted spontaneous breathing may have beneficial effects on gas exchange in acute lung injury. We tested this hypothesis for pressure support ventilation in an animal model of acute lung injury. Our results demonstrate that pressure support does not necessarily provide better gas exchange than controlled mechanical ventilation.

Effect of aerosolized prostacyclin and inhaled nitric oxide on experimental hypoxic pulmonary hypertension

Objective: To compare the effect of different concentrations of inhaled nitric oxide and doses of nebulized prostacyclin on hypoxia-induced pulmonary hypertension in pigs.¶Design: Prospective, controlled animal study.¶Setting: Animal research facilities of an university hospital.¶Interventions: After reducing the fraction of inspired oxygen (FIO2) from 1.0 to 0.1, two groups of five pigs each were submitted to inhalation of three concentrations of nitric oxide (5, 10 and 20 ppm) or three doses of prostacyclin (2.5, 5, 10 ng × kg–1× min–1).¶Results: All doses of prostacyclin and concentrations of nitric oxide resulted in a decrease in mean pulmonary arterial pressure and pulmonary vascular resistance when compared to hypoxic ventilation (p < 0.001) which was independent of the dose or concentration of either drug used. While inhalation of nitric oxide caused a reduction in mean pulmonary arterial pressure back to values obtained during ventilation with FIO2 1.0, values achieved with prostacyclin were still significantly higher when compared to measurements prior to the initiation of hypoxic ventilation. However, direct comparison of the effect of 20 ppm nitric oxide and 10 ng × kg–1× min–1 prostacyclin on mean pulmonary arterial pressure revealed no differences between the drugs. All other hemodynamic and gas exchange parameters remained stable throughout the study.¶Conclusions: Inhalation of clinically used concentrations of nitric oxide and doses of prostacyclin can decrease elevated pulmonary arterial pressure in an animal model of hypoxic pulmonary vasoconstriction without impairing systemic hemodynamics or gas exchange.

Evidenzbasierte Medizin des akuten Lungenversagens

ZusammenfassungIn der Behandlung des akuten Lungenversagens (“acute respiratory distress syndrome”, ARDS) wurden in den letzten Jahren verschiedene neue Therapieansätze entwickelt, um die hohe Letalität der Erkrankung zu senken. Vor dem Hintergrund der evidenzbasierten Medizin ist die Bedeutung für den klinischen Alltag jedoch unterschiedlich.Während die Anwendung einer lungenprotektiven Beatmungsstrategie als gesichert gelten kann und auch die Anwendung von positivem endexspiratorischem Druck und Spontanatmung während druckkontrollierter Beatmung einen Platz in der Therapie haben, sind andere Strategien, wie Hochfrequenzbeatmung, partielle Flüssigkeitsbeatmung und die pulmonale Surfactantgabe, noch als experimentelle Therapieformen anzusehen. Bei schweren Fällen von ARDS ist die Bauchlagerung empfehlenswert und bei drohender Hypoxie ist die Anwendung von inhalativem Stickstoffmonoxid und extrakorporaler Membranoxygenierung in speziellen Zentren etabliert. Für den Routineeinsatz dieser drei Therapieformen konnte kein eindeutig verbessertes Outcome gezeigt werden.Bei der medikamentösen Therapie beschränken sich die gesicherten Therapieansätze auf die Gabe von Stressdosen von Kortison und auf die Gabe einer enteralen immunnutritiven Spezialdiät.AbstractDifferent therapeutic approaches have recently been developed for treatment of acute respiratory distress syndrome (ARDS) with the aim of improving the outcome.The clinical significance and success of these therapies is variable with respect to evidencebased medicine.Lung protective ventilation is accepted as a proven therapy and the use of positive end-expiratory pressure as well as spontaneous breathing during controlled ventilation are common therapies. High frequency ventilation, partial liquid ventilation and pulmonary surfactant application are still in the experimental stage.The prone position is recommended for severe cases of ARDS and the application of inhaled nitric oxide and of extracorporeal membrane oxygenation is established in specialized centers for patients with imminent hypoxia. But for the routine use of these three therapies a clear improvement in outcome could not demonstrated.Recommended drug therapy is limited to the administration of stress doses of corticosteroids and a special anti-inflammatory enteral diet.

Combining partial liquid ventilation and prone position in experimental acute lung injury.

BACKGROUND Partial liquid ventilation (PLV) and prone position can improve arterial oxygen tension (PaO2) in acute lung injury (ALI). The authors evaluated additive effects of these techniques in a saline lung lavage model of ALI. METHODS ALI was induced in 20 medium-sized pigs (29.2+/-2.5 kg body weight). Gas exchange and hemodynamic parameters were determined in both supine and prone position in all animals. Thereafter, one group was assigned to PLV with two sequential doses of 15 ml/kg of perfluorocarbon (n = 10); the second group was assigned to gaseous ventilation (n = 10). Gas-exchange and hemodynamic parameters were determined at corresponding time points in both groups in prone and supine position. RESULTS In the PLV group, positioning the animals prone resulted in an increase of PaO2 prior to PLV and during PLV with both doses of perfluorocarbon when compared to ALI. PLV in supine position was only effective if 30 ml/kg of perfluorocarbon was applied. In the gaseous ventilation group, PaO2 increased reproducibly compared with ALI when the animals were turned prone. A significant additive improvement of arterial oxygenation was observed during combined therapy with 30 ml/kg of perfluorocarbon and prone position in the PLV group compared with either therapy alone. CONCLUSIONS The authors conclude that combining PLV with prone position exerts additive effects on pulmonary gas exchange in a saline lung lavage model of ALI in medium-sized pigs.

Changes in pulmonary blood flow during gaseous and partial liquid ventilation in experimental acute lung injury

BackgroundIt has been proposed that partial liquid ventilation (PLV) causes a compression of the pulmonary vasculature by the dense perfluorocarbons and a subsequent redistribution of pulmonary blood flow from dorsal to better-ventilated middle and ventral lung regions, thereby improving arterial oxygenation in situations of acute lung injury. MethodsAfter induction of acute lung injury by repeated lung lavage with saline, 20 pigs were randomly assigned to partial liquid ventilation with two sequential doses of 15 ml/kg perfluorocarbon (PLV group, n = 10) or to continued gaseous ventilation (GV group, n = 10). Single-photon emission computed tomography was used to study regional pulmonary blood flow. Gas exchange, hemodynamics, and pulmonary blood flow were determined in both groups before and after the induction of acute lung injury and at corresponding time points 1 and 2 h after each instillation of perfluorocarbon in the PLV group. ResultsDuring partial liquid ventilation, there were no changes in pulmonary blood flow distribution when compared with values obtained after induction of acute lung injury in the PLV group or to the animals submitted to gaseous ventilation. Arterial oxygenation improved significantly in the PLV group after instillation of the second dose of perfluorocarbon. ConclusionsIn the surfactant washout animal model of acute lung injury, redistribution of pulmonary blood flow does not seem to be a major factor for the observed increase of arterial oxygen tension during partial liquid ventilation.

Effect of PEEP and inhaled nitric oxide on pulmonary gas exchange during gaseous and partial liquid ventilation with small volumes of perfluorocarbon

Background: Partial liquid ventilation, positive end‐expiratory pressure (PEEP) and inhaled nitric oxide (NO) can improve ventilation/perfusion mismatch in acute lung injury (ALI). The aim of the present study was to compare gas exchange and hemodynamics in experimental ALI during gaseous and partial liquid ventilation at two different levels of PEEP, with and without the inhalation of nitric oxide.

The necessity of performing transesophageal echocardiography in patients with acute respiratory distress syndrome.

Sir: The acute respiratory distress syndrome (ARDS) is a severe disorder of pulmonary gas exchange, mainly due to inflammatory processes and noncardiogenic pulmonary edema. There are direct and indirect causes of ARDS, e. g. trauma, sepsis, pneumonia, aspiration, and toxic inhalation. ARDS is characterized by acute onset, an arterial oxgentension/fractional inspired oxygen ratio (PaO2/FiO2) £ 200 mmHg, bilateral infiltrates shown radiologically, and pulmonary capillary wedge pressure (PCWP) £ 18 mmHg [1]. However, patients may exist who have an undiagnosed, persisting cardiac disease which has caused structural changes of lung parenchyma where the clinical situation advances to ARDS according to the above findings. We present two patients who were referred to our center for advanced treatment of ARDS. In neither of them had the diagnosis of severe valvular damage been suspected beforehand. Both patients were mechanically ventilated for 9 and 12 days, respectively, both requiring an FIO2 of 1.0 to achive a PaO2 of 51 and 85 mmHg, respectively. In one patient transthoracic echocardiography (TTE) had been performed in the referring hospital. It demonstrated a slight mitral insufficiency but seemed to exclude a cardiac cause for the gas exchange disturbance. In both patients, neither auscultation nor electrocardiography (ECG) hinted at valvular dysfunction. On admission to our intensive care unit (ICU), mean pulmonary artery pressure was 38 and 35 mmHg, respectively, and wedge pressure 14 and 12 mmHg, respectively. In neither patient was a large Vwave observed when a pulmonary artery line was put into wedge position. Cardiac output was observed to be normal. However, when transesophageal echocardiography (TEE) was performed on the 2nd and 3rd day, respectively, after admission to our ICU, severe, excentric insufficiency of the mitral valve because of infective endocarditis (IE) was shown in both patients: additionally, one had a leakage between the aortic valve and the left atrium. Despite short-term improvement of the respiratory situation after emergency open heart surgery, both patients died due to multiple organ failure following the prolonged course of the disease. In these two cases TEE has proven to be a valuable diagnostic tool and supplement to pulmonary artery catheterization, which may become unreliable under conditions regularly encountered in the critically ill [2]. Data collected with the pulmonary artery catheter over 2 and 3 days, respectively, never gave rise to the suspicion of an underlying cardiac problem; during this time PCWP was below 18 mmHg, there was no large V-wave and cardiac output remained normal. Also, auscultatory and ECG findings did not indicate any valvular damage. The reason for the lack of sensivity of the data gained from the pulmonary artery catheter may be the dehydration strategy in ARDS treatment. Since TEE is accepted as the leading method of cardiac imaging to diagnose the presence of vegetation [3] and the diagnostic accuracy of TTE is limited in patients who are being mechanically ventilated with high positive end-expiratory pressure due to poor image quality, we suggest that performing a TEE should be obligatory in suspected ARDS in order to avoid a misdiagnosis in patients suffering from IE.

Nitric oxide inhalation in pulmonary hypertension and severe respiratory failure.

Inhalation of nitric oxide (NO) can cause selective pulmonary vasodilation in aerated lung regions; thus, it may be of benefit in the treatment of various forms of pulmonary hypertension and respiratory distress due to a mismatch of pulmonary ventilation and perfusion. The specific characteristics of inhaled NO exclude long-term treatment, but NO has been successfully used as a test substance to screen patients for response to oral vasodilators. Furthermore, inhalation of NO has been shown to improve gas exchange and right ventricular performance and to reduce the need for other, more invasive therapies in various settings of acute pulmonary hypertension. However, the improvement of arterial oxygenation seen in patients with the acute respiratory distress syndrome does not result in increased survival, questioning the future importance of inhaled NO in the treatment of this pulmonary disorder.