R. Kuhlen

Comparison of electrical velocimetry and thermodilution techniques for the measurement of cardiac output

Aim:  To compare a new method of non‐invasive determination of cardiac output based on electrical velocimetry (EV‐CO) with invasive thermodilution methods.

Procalcitonin serum levels after out-of-hospital cardiac arrest.

The time course of Procalcitonin (PCT) serum levels was assessed in cardiac arrest survivors and compared with S-100 serum levels concerning their predictive values for neurological outcome. PCT and S-100 serum levels were analyzed serially on admission and during the following 3 days after hospitalization in 23 patients successfully resuscitated from out-of-hospital cardiac arrest. At day 14 patients were divided into groups according to the Glasgow-Outcome-Scale (GOS): one group with bad neurological outcome (GOS 1-3) and one group with good neurological outcome (GOS 4-5). Group comparisons were performed with the Mann-Whitney U-Test. The diagnostic performance of PCT and S-100 levels was analyzed using receiver operating characteristics (ROC). Patients with a bad neurological outcome had significantly higher S-100 levels than those with a good neurological outcome at all investigated time points and significantly elevated PCT levels at days 1-3. Highest levels for S-100 were found immediately after hospitalization (3.4 +/- 3.8 vs. 0.7 +/- 0.3 microg/l, P=0.003), and for PCT at day 1 (37 +/- 103 vs. 0.2 +/- 0.2 microg/l, P=0.0002). The results show that PCT serum levels are possibly elevated in patients with bad neurological outcome after cardiac arrest, without signs of severe infection or concomitant sepsis. Based on this observation, studies on larger numbers of patients should prove the predictive value of PCT in those patients.

Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury

IntroductionAtelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchangeMethodsIn eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung.ResultsNonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve.ConclusionA recruitment maneuver by repeatedly hyperinflating the lungs led to an increase of poorly aerated and a decrease of nonaerated lung mainly. Changes in aerated and nonaerated lung volumes were adequately represented by respiratory compliance but not by changes in oxygenation or shunt.

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.

Clinical practice guideline: non-invasive mechanical ventilation as treatment of acute respiratory failure.

INTRODUCTION Non-invasive mechanical ventilation (NIV) has been used to treat acute respiratory failure (ARF) for approximately 20 years. This guideline addresses the indications for, and limitations of, NIV as treatment for ARF according to evidence-based criteria. METHODS A panel of experts from 12 scientific medical societies reviewed circa 2900 publications. The panel judged the clinical relevance of these studies and assessed the evidence presented in each, then held two interdisciplinary consensus conferences to formulate guideline recommendations and algorithms. RESULTS Whenever possible, NIV should be preferred to invasive mechanical ventilation, in order to avoid the risk of ventilator and tube-associated complications such as nosocomial pneumonia (grade of recommendation A). Particularly in patients with hypercapnic ARF, NIV reduces the rate of hospital-acquired pneumonia, the length of hospital stay and mortality in the intensive care unit and in the hospital (grade of recommendation A). NIV (or continuous positive airway pressure) is also recommended in cardiogenic pulmonary edema (grade of recommendation A), as treatment for ARF in immunocompromised patients (grade of recommendation A), to prevent postextubation failure, to facilitate weaning in patients with hypercapnic ARF (grade of recommendation A), and to improve dyspnea in palliative care (grade of recommendation C). NIV is not generally recommended in patients with hypoxic ARF because of its high failure rate of 30% to over 50% in such patients. DISCUSSION Although evidence indicates that NIV can be used as the treatment of first choice for several indications, it is still underutilized in the acute setting. These guidelines provide evidence-based information about the indications for, and limitations of, NIV in the treatment of ARF.

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.

Changes in diffusion parameters, energy-related metabolites and glutamate in the rat cortex after transient hypoxia/ischemia

It has been shown that global anoxia leads to dramatic changes in the diffusion properties of the extracellular space (ECS). In this study, we investigated how changes in ECS volume and geometry in the rat somatosensory cortex during and after transient hypoxia/ischemia correlate with extracellular concentrations of energy-related metabolites and glutamate. Adult male Wistar rats (n = 12) were anesthetized and subjected to hypoxia/ischemia for 30 min (ventilation with 10% oxygen and unilateral carotid artery occlusion). The ECS diffusion parameters, volume fraction and tortuosity, were determined from concentration-time profiles of tetramethylammonium applied by iontophoresis. Concentrations of lactate, glucose, pyruvate and glutamate in the extracellular fluid (ECF) were monitored by microdialysis (n = 9). During hypoxia/ischemia, the ECS volume fraction decreased from initial values of 0.19 +/- 0.03 (mean +/- S.E.M.) to 0.07 +/- 0.01 and tortuosity increased from 1.57 +/- 0.01 to 1.88 +/- 0.03. During reperfusion the volume fraction returned to control values within 20 min and then increased to 0.23 +/- 0.01, while tortuosity only returned to original values (1.53 +/- 0.06). The concentrations of lactate and glutamate, and the lactate/pyruvate ratio, substantially increased during hypoxia/ischemia, followed by continuous recovery during reperfusion. The glucose concentration decreased rapidly during hypoxia/ischemia with a subsequent return to control values within 20 min of reperfusion. We conclude that transient hypoxia/ischemia causes similar changes in ECS diffusion parameters as does global anoxia and that the time course of the reduction in ECS volume fraction correlates with the increase of extracellular concentration of glutamate. The decrease in the ECS volume fraction can therefore contribute to an increased accumulation of toxic metabolites, which may aggravate functional deficits and lead to damage of the central nervous system (CNS).

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.

Extrakorporale Membranoxygenierung beim akuten Lungenversagen

ZusammenfassungDie extrakorporale Membranoxygenierung (ECMO) stellt heute im Rahmen klinischer Algorithmen einen wichtigen Baustein in der Therapie des schweren akuten Lungenversagens (ARDS) dar, nachdem sich in observationellen Studien der Wert dieses Verfahrens für die ARDS-Therapie trotz fehlender positiver kontrollierter Studien gezeigt hat. In spezialisierten Zentren wird bei Patienten mit drohender Hypoxie nach Anwendung verschiedener konservativer Therapieverfahren die ECMO unter Integration von Blutpumpen und künstlichen Membranlungen (Oxygenatoren) als Lungenersatzverfahren angewandt. Die Neuentwicklung von Oberflächenbeschichtungen, optimierten Oxygenatoren und miniaturisierten Blutpumpen sollte in der Zukunft sowohl die Hämokompatibilität steigern als auch die klinische Anwendung vereinfachen und komplikationsärmer machen. Die Entwicklung von Oxygenatoren mit deutlich niedrigeren Strömungswiderständen ermöglicht dabei die klinische Anwendung als pumpenloses, durch die arteriovenöse Druckdifferenz getriebenes Lungenunterstützungsverfahren (ECLA). Diese Neuentwicklungen könnten in der Zukunft zur Anwendung der ECMO nicht mehr nur als „ultima ratio“, sondern auch bei weniger schwerem ARDS führen, um lungenprotektivere, weniger invasive Beatmungsformen zu ermöglichen.AbstractAfter various observational studies demonstrated a benefit of extracorporeal membrane oxygenation (ECMO) in the therapy of severe acute respiratory distress syndrome (ARDS), ECMO now represents an important contribution for ARDS therapy using clinical algorithms despite a lack of positive controlled studies. In specialized centers patients with severe ARDS and imminent hypoxia despite intensive conventional therapy, are treated with ECMO using blood pumps and artificial membrane lungs (oxygenators) for extracorporeal lung assist. The development of new surface modifications, optimized oxygenators and miniaturized blood pumps should increase hemocompatibility and lead to simplified treatment as well as less complications. New oxygenators with significantly decreased blood resistance allow the clinical application of pumpless arteriovenous extracorporeal lung assist (ECLA). After these new developments indications for ECMO could be extended from use not only as ultima ratio but to less severe ARDS to enable lung protective, less invasive mechanical ventilation.

[Non-invasive ventilation as treatment for acute respiratory insufficiency. Essentials from the new S3 guidelines].

BACKGROUND Scientific evidence is accumulating that non-invasive ventilation (NIV) may be beneficial for different patient groups with acute respiratory insufficiency (ARI). The aim of the new S3 guidelines is to propagate evidence-based knowledge about the indications and limitations of NIV in clinical practice. METHODS A total of 28 experts from 12 German medical societies were involved in the process of development of the present guidelines. These experts systematically analyzed approximately 2,900 publications. Finally, the recommendations were discussed and approved in two consensus conferences. RESULTS In hypercapnic ARI, NIV reduces the length of stay and mortality during intensive care treatment [grade A recommendation (A)]. Patients with cardiopulmonary edema should be treated with continuous positive airway pressure (CPAP) or NIV (A). For immunocompromized patients with ARI, NIV reduces the mortality (A). In patients with postextubation respiratory failure and during weaning from mechanical ventilation, NIV reduces the risk of reintubation (A). For patients who decline to be ventilated invasively, NIV may be an acceptable alternative (B). Non-invasive ventilation can also successfully be used in pediatric patients with ARI caused by different reasons (C). In acute respiratory distress syndrome (ARDS) NIV cannot generally be recommended because the failure rate is relatively high. CONCLUSION Non-invasive ventilation is still not as widely implemented in clinical medicine as would be expected on the basis of the scientific literature. The aim of the present guidelines is to further propagate NIV for the treatment of ARI.