Michael Pfeifer

A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia*

Objective:Pump-driven extracorporeal gas exchange systems have been advocated in patients suffering from severe acute respiratory distress syndrome who are at risk for life-threatening hypoxemia and/or hypercapnia. This requires extended technical and staff support. Design:We report retrospectively our experience with a new pumpless extracorporeal interventional lung assist (iLA) establishing an arteriovenous shunt as the driving pressure. Setting:University hospital. Patients:Ninety patients with acute respiratory distress syndrome. Interventions:Interventional lung assist was inserted in 90 patients with acute respiratory distress syndrome. Measurements and Main Results:Oxygenation improvement, carbon dioxide elimination, hemodynamic variables, and the amount of vasopressor substitution were reported before, 2 hrs after, and 24 hrs after implementation of the system. Interventional lung assist led to an acute and moderate increase in arterial oxygenation (Pao2/Fio2 ratio 2 hrs after initiation of iLA [median and interquartile range], 82 mm Hg [64–103]) compared with pre-iLA (58 mm Hg [47–78], p < .05). Oxygenation continued to improve for 24 hrs after implementation (101 mm Hg [74–142], p < .05). Hypercapnia was promptly and markedly reversed by iLA within 2 hrs (Paco2, 36 mm Hg [30–44]) in comparison with before (60 mm Hg [48–80], p < .05], which allowed a less aggressive ventilation. For hemodynamic stability, all patients received continuous norepinephrine infusion. The incidence of complications was 24.4%, mostly due to ischemia in a lower limb. Thirty-seven of 90 patients survived, creating a lower mortality rate than expected from the Sequential Organ Failure Assessment score. Conclusions:Interventional lung assist might provide a sufficient rescue measure with easy handling properties and low cost in patients with severe acute respiratory distress syndrome and persistent hypoxia/hypercapnia.

Development of heart failure following isoproterenol administration in the rat: role of the renin–angiotensin system

OBJECTIVEnHigh dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin-angiotensin system using ramipril.nnnMETHODS AND RESULTSnFollowing the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol + ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins.nnnCONCLUSIONSnIn rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin-angiotensin system.

Evaluation of plasma natriuretic peptides as markers for left ventricular dysfunction

To test the hypothesis that elevated plasma levels of natriuretic peptides may serve to identify patients with left ventricular (LV) dysfunction, we assessed the predictive diagnostic value of natriuretic peptide levels, in addition to clinical and electro-cardiographic risk factors, as noninvasive indicators of cardiac dysfunction. Plasma levels of atrial natriuretic peptide (cANP) (99-126), N-terminal fragment of proANP (nANP) (26-55), nANP(80-96), brain natriuretic peptide (BNP-32), proBNP(22-46), and C-type natriuretic peptide (CNP-22) were measured in 211 subjects before cardiac catheterization. The strongest correlations with parameters of LV function were found for nANP(80-96) (up to r = -0.55, p < 0.0001), whereas there was no significant correlation with proBNP(22-46) or CNP-22. In patients with LV ejection fractions (LVEF) < or = 45% (n = 38) nANP(26-55), nANP(80-96), cANP(99-126), and BNP-32 were significantly increased (p < 0.001). Partition values for elevated versus normal natriuretic peptide levels were obtained from normal controls and used to separate subjects with and without LV dysfunction. Receiver operating characteristic analysis for LVEF < or = 45% indicated a significantly better diagnostic accuracy for high levels of nANP(80-96), nANP(22-56), cANP(99-126), and BNP-32 than for proBNP and CNP-22. Multivariate analysis by logistic regression identified Q waves and bundle branch block in the electrocardiogram as well as elevated plasma levels of cANP, nANP(80-96), and nANP(26-55) as the strongest independent predictors of low ejection fractions. The relative risk of LV dysfunction was raised up to tenfold in subjects with high natriuretic peptide levels (p < 0.001). The addition of nANP(80-96) and nANP(26-55) to the combination of clinical and electrocardiographic risk factors did not further improve the diagnostic sensitivity for the detection of LVEF < or = 45%, but it markedly increased the overall accuracy (59% to 81%, p < 0.001) and specificity (55% to 81%, p < 0.001). Among natriuretic peptides, elevated nANP(80-96) and nANP(26-55) levels have the strongest impact on the detection of LV dysfunction. They add to the diagnostic information contained in clinical and electrocardiographic factors. Plasma levels alone or in combination with clinical factors seem to be of value for a refined identification of abnormal LV function in the individual patient.

Mortality and prognostic factors in patients with obesity-hypoventilation syndrome undergoing noninvasive ventilation.

Objectives.u2002 The incidence of obesity‐hypoventilation syndrome (OHS) has greatly increased over time, but data on long‐term outcome are limited. We investigated survival and prognostic factors in these patients undergoing noninvasive positive pressure ventilation (NPPV).

Smoking and cancer-related gene expression in bronchial epithelium and non-small-cell lung cancers.

Tobacco smoking is the leading cause of lung cancer worldwide. Gene expression in surgically resected and microdissected samples of non‐small‐cell lung cancers (18 squamous cell carcinomas and nine adenocarcinomas), matched normal bronchial epithelium, and peripheral lung tissue from both smokers (n = 22) and non‐smokers (n = 5) was studied using the Affymetrix U133A array. A subset of 15 differentially regulated genes was validated by real‐time PCR or immunohistochemistry. Hierarchical cluster analysis clearly distinguished between benign and malignant tissue and between squamous cell carcinomas and adenocarcinomas. The bronchial epithelium and adenocarcinomas could be divided into the two subgroups of smokers and non‐smokers. By comparison of the gene expression profiles in the bronchial epithelium of non‐smokers, smokers, and matched cancer tissues, it was possible to identify a signature of 23 differentially expressed genes, which might reflect early cigarette smoke‐induced and cancer‐relevant molecular lesions in the central bronchial epithelium of smokers. Ten of these genes are involved in xenobiotic metabolism and redox stress (eg AKR1B10, AKR1C1, and MT1K). One gene is a tumour suppressor gene (HLF); two genes act as oncogenes (FGFR3 and LMO3); two genes are involved in matrix degradation (MMP12 and PTHLH); three genes are related to cell differentiation (SPRR1B, RTN1, and MUC7); and five genes have not been well characterized to date. By comparison of the tobacco‐exposed peripheral alveolar lung tissue of smokers with non‐smokers and with adenocarcinomas from smokers, it was possible to identify a signature of 27 other differentially expressed genes. These genes are involved in the metabolism of xenobiotics (eg GPX2 and FMO3) and may represent cigarette smoke‐induced, cancer‐related molecular targets that may be utilized to identify smokers with increased risk for lung cancer. Copyright

Pumpless extracorporeal lung assist and adult respiratory distress syndrome

We report use of a pumpless extracorporeal lung assist-a safe and effective method in the management of severe acute respiratory failure that allows an extracorporal gas-exchange without the use of a pump.

Sleep Apnea is an Independent Correlate of Erectile and Sexual Dysfunction

INTRODUCTIONnObstructive sleep apnea (OSA) has been linked with erectile dysfunction (ED), but it is unknown whether this association is maintained in the presence of other risk factors for ED.nnnAIMnThe aim of this study was to evaluate the relationship between ED/sexual dysfunction and polysomnographic measures of sleep apnea in patients with known risk factors for ED.nnnMETHODSnProspective cross-sectional analysis of 401 male patients undergoing in-lab polysomnography for suspected OSA. Erectile (EF) and sexual function were assessed by the 15-item International Index of Erectile Function (IIEF-15) questionnaire.nnnMAIN OUTCOME MEASURESnSeverity of OSA via apnea-hypopnea index (AHI) and mean/lowest nocturnal oxygen saturation (SaO(2)). The IIEF-15 including the sexual domains: EF, intercourse satisfaction, orgasmic function, sexual desire, and overall satisfaction.nnnRESULTSnOSA (AHI > 5/h) was diagnosed in 92% of patients. ED (EF subdomain < or = 25) was present in 69% of patients with, and 34% of patients without OSA (P < 0.001). Multivariate stepwise regression analyses including known risk factors for ED, such as age, obesity, coronary heart disease, peripheral occlusive disease, hypertension, diabetes, prostate surgery, and beta-blocker treatment, and measures of sleep apnea identified mean nocturnal SaO(2) as independently associated with ED (P = 0.002; mean [95% CI] normalized slope 0.126 [0.047; 0.205]). Age (P < 0.001), peripheral occlusive disease (P = 0.001), prostate surgery (P = 0.018), and hypertension (P = 0.021) were confirmed as risk factors for ED, but did not abolish the sleep apnea-associated risk. Similar results were obtained for sexual dysfunction. Logistic regression analysis using the diagnosis of ED (EF subdomain < or = 25) as binary dependent variable confirmed that mean nocturnal SaO(2) (P = 0.012), as well as age (P < 0.001) were independently associated with ED.nnnCONCLUSIONSnED and overall sexual dysfunction were highly prevalent in patients with suspected OSA. Irrespective of known risk factors, mean nocturnal SaO(2) was an additional, independent correlate of these dysfunctions, suggesting that OSA-related intermittent nocturnal hypoxemia specifically contributes to their development.

Pumpless extracorporeal lung assist – experience with the first 20 cases

OBJECTIVEnLong-term extracorporeal lung assist is limited by a significant mechanical blood trauma resulting in bleeding and hemolysis. To reduce the drawbacks of extracorporeal lung assist a new technique has been developed, by which the driving force for the extracorporeal circuit derives from the patients arterio-venous pressure gradient (pumpless extracorporeal lung assist). The aim of this clinical study was to test the feasibilty and effectiveness of pumpless extracorporeal lung assist in patients with acute respiratory distress syndrome.nnnMETHODSnTwenty patients (41+/-16 years) with acute respiratory distress syndrome of various causes and failing respirator therapy were enrolled. The minimum hemodynamic requirements included a cardiac output (CO) >6 l/min and mean arterial pressure (MAP) >70 mmHg. Pumpless extracorporeal lung assist was established using a short circuit arterio-venous shunt including a special designed low-resistance membrane oxygenator which was placed between the patients legs.nnnRESULTSnAt the time of inclusion FiO(2) in all patients was 1.0 (paO(2) 45.9+/-7 mmHg, paCO(2) 58.9+/-17 mmHg). After 24 h of pumpless extracorporeal lung assist FiO(2) was reduced to 0.8+/-0.1. A significant improvement in oxygenation (paO(2) 84.1+/-21 mmHg, P<0.05) and CO(2) removal (paCO(2) 32.7+/-5 mmHg, P<0.05) was notable. The mean extracorporeal flow was 2.6+/-0.6 l/min, which represented approximately 25% of the patients mean CO (10.8+/-2 l/min). The median assist time was 12+/-8 (1-32) days. Fifteen out of twenty patients were weaned off pumpless extracorporeal lung assist. Five out of twenty patients died while on the system (four sepsis, one ventricular fibrillation). Three out of twenty patients died after successful weaning on day 8, 30, and 50, respectively. Twelve out of twenty patients were discharged in a healthy state (overall survival 60%). Technical problems included thrombosis of the venous cannula (n=5), thrombus formation within the membrane oxygenator (n=2), membrane oxygenator plasma leakage (n=2), and membrane oxygenator contamination with Candida albicans. No bleeding complication was observed.nnnCONCLUSIONnPumpless extracorporeal lung assist is feasible and effective in a selected group of patients with acute respiratory distress syndrome but preserved hemodynamic function. By eliminating the pump and reducing the tubing length blood trauma can be minimized. Being very simple the system entails fewer risks of technical complications and also facilitates nursing care.

Extracorporeal pumpless interventional lung assist in clinical practice: determinants of efficacy

Respiratory acidosis can become a serious problem during protective ventilation of severe lung failure. A pumpless arteriovenous interventional lung assist (iLA) for extracorporeal carbon dioxide removal has been used increasingly to control critical respiratory situations. The present study sought to evaluate the factors determining the efficacy of iLA and calculate its contribution to gas exchange. In a cohort of 96 patients with severe acute respiratory distress syndrome, haemodynamic parameters, oxygen consumption and carbon dioxide production as well as gas transfer through the iLA were analysed. The measurements demonstrated a significant dependency of blood flow via the iLA device on cannula size (mean±sd 1.59±0.52u2005L·min−1 for 15u2005French (Fr), 1.94±0.35u2005L·min−1 for 17u2005Fr, and 2.22 ±0.45u2005L·min−1 for 19u2005Fr) and on mean arterial pressure. Oxygen transfer capacity averaged 41.7±20.8u2005mL·min−1, carbon dioxide removal was 148.0±63.4u2005mL·min−1. Within two hours of iLA treatment, arterial oxygen partial pressure/inspired oxygen fraction ratio increased significantly and a fast improvement in arterial carbon dioxide partial pressure and pH was observed. Interventional lung assist eliminates ∼50% of calculated total carbon dioxide production with rapid normalisation of respiratory acidosis. Despite limited contribution to oxygen transfer it may allow a more protective ventilation in severe respiratory failure.

Impact of right ventricular reserve on exercise capacity and survival in patients with pulmonary hypertension.

Pulmonary hypertension is a clinical syndrome characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are key subgroups of this disorder with comparable clinical and pathological findings. Resting pulmonary haemodynamics correlate only moderately with functional parameters and do not predict prognosis in these patients sufficiently accurately. We therefore correlated exercise haemodynamics with peak oxygen uptake (peakVO2) and determined their prognostic significance.