RESUMO
Pulmonary hypertension (PH) can be diagnosed in the context of connective tissue diseases (CTD) as well as in elderly patients with multiple comorbidities. A correct clinical differential diagnosis and classification is essential before adequate therapeutic decisions can be made. Differential diagnosis of PH in CTD comprises associated pulmonary arterial hypertension (APAH), group 2 or 3 PH (PH arising from left heart or chronic lung disease), chronic thromboembolic PH (PH) and group 5 (e.âg. in the context of terminal renal insufficiency). This is also true of elderly patients in whom the decision has to be made if the increasing number of coincident diseases lead to PH or have to be interpreted as comorbidities. In this manuscript, the differential diagnosis of PH is elucidated, focusing on CTD, in the context of left heart disease and chronic lung disease. Furthermore, criteria are presented facilitating an objective approach in this context.
Assuntos
Diagnóstico Diferencial , Cardiopatias , Hipertensão Pulmonar , Pneumopatias/diagnóstico , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Cardiopatias/diagnóstico , Humanos , Hipertensão Pulmonar/diagnósticoRESUMO
At the 6th World Symposium on Pulmonary Hypertension (WSPH), which took place from February 27 until March 1, 2018 in Nice, scientific progress over the past 5 years in the field of pulmonary hypertension (PH) was presented by 13 working groups. The results of the discussion were published as proceedings towards the end of 2018.âOne of the major changes suggested by the WSPH was the lowering of the diagnostic threshold for PH from ≥â25 to >â20âmmHg mean pulmonary arterial pressure, measured by right heart catheterization at rest. In addition, the pulmonary vascular resistance was introduced into the definition of PH, which underlines the importance of cardiac output determination at the diagnostic right heart catheterization.In this article, we discuss the rationale and possible consequences of a changed PH definition in the context of the current literature. Further, we provide a current overview on non-invasive and invasive methods for diagnosis, differential diagnosis, and prognosis of PH, including exercise tests.
Assuntos
Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Guias de Prática Clínica como Assunto/normas , Cateterismo Cardíaco , HumanosRESUMO
Riociguat is the first clinically available soluble Guanylate-cyclase stimulator (sGC) and representative of a completely new class of drugs. Riociguat is approved for pulmonary arterial hypertension (PAH) and non-operable or recurrent/persistent chronic thromboembolic pulmonary hypertension (CTEPH). Moreover, Riociguat is currently under investigation for a wider spectrum of diseases. This article focusses on its mode of action and clinical trial data. Finally, based on these data, the status of approval, as well as the costs a proposal is given how Riociguat can be integrated in the current treatment of PAH and CTEPH.
Assuntos
Guanilato Ciclase/metabolismo , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/metabolismo , Pirazóis/administração & dosagem , Pirimidinas/administração & dosagem , Receptores Citoplasmáticos e Nucleares/metabolismo , Anti-Hipertensivos/administração & dosagem , Doença Crônica , Fibrinolíticos/administração & dosagem , Humanos , Hipertensão Pulmonar/complicações , Embolia Pulmonar/complicações , Pirazóis/farmacocinética , Pirimidinas/farmacocinética , Receptores Citoplasmáticos e Nucleares/agonistas , Guanilil Ciclase Solúvel , Resultado do TratamentoRESUMO
An 87-year-old woman presented with a left-sided pleural effusion. The milky aspirate fulfilled the criteria of a chylothorax. Thorax computed tomography (CT) showed characteristic multiple cysts and consequently the rare diagnosis of post-menopausal pulmonary lymphangioleiomyomatosis was made. In the diagnostic work-up of pleural effusion the determination of triglycerides should be considered to confirm the diagnosis of chylothorax. In the presence of a chylothorax the differential diagnosis of lymphangioleiomyomatosis should be included even in advanced age.
Assuntos
Quilotórax/diagnóstico , Quilotórax/etiologia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico , Linfangioleiomiomatose/complicações , Linfangioleiomiomatose/diagnóstico , Idoso de 80 Anos ou mais , Quilotórax/terapia , Diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Neoplasias Pulmonares/terapia , Linfangioleiomiomatose/terapia , Pós-MenopausaRESUMO
The aim of this study was to assess fractional exhaled nitric oxide (FeNO) for the early diagnosis of bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTX). 611 FeNO measurements in 166 consecutive patients were classified depending on BOS stage at the time of assessment and course during minimum follow-up of 3 months: (1) stable non-BOS, (2) unstable non-BOS, (3) stable BOS and (4) unstable BOS. Unstable course was defined as new onset of BOS≥1 or progression of BOS. FeNO before unstable course was significantly increased in comparison to their stable counterparts (non-BOS: 28.9 ± 1.2 ppb, n = 40 vs. 16.4 ± 0.8 ppb, n = 131 and BOS: 32.5 ± 1.3 ppb, n = 35 vs. 15.3 ± 0.8 ppb, n = 26; p = 0.01 each). Average time from FeNO reading to onset of deterioration was 117 ± 9 days in non-BOS and 136 ± 9 days in BOS patients. The positive and negative predictive value of FeNO >20 ppb for BOS was 69.0% and 96.9%, respectively. Serial measurements demonstrated significantly lower mean individual variation in stable recipients as compared to stable patients switching to unstable course (3.2 ± 0.3 ppb vs. 12.7 ± 1.4 ppb, p = 0.02). In particular, the excellent negative predictive value of persistently low FeNO readings for future BOS make FeNO assessments a useful tool for continuous risk stratification after LTX.
Assuntos
Bronquiolite Obliterante/diagnóstico , Transplante de Pulmão , Óxido Nítrico , Expiração , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RiscoRESUMO
Pulmonary hypertension (PH) leads to an increased right ventricular workload, cardiac failure and death. In idiopathic pulmonary arterial hypertension (PAH) the vasodilating vasoactive intestinal peptide (aviptadil) is deficient. The aim of the present study was to test the acute effects on haemodynamics and blood gases, and the safety, of a single dose of inhaled aviptadil in chronic PH. A total of 20 patients with PH (PAH in nine, PH in lung disease in eight and chronic thromboembolic PH in three) inhaled a single 100-microg dose of aviptadil during right-heart catheterisation. Haemodynamics and blood gases were measured. Aviptadil aerosol caused a small and temporary but significant selective pulmonary vasodilation, an improved stroke volume and mixed venous oxygen saturation. Overall, six patients experienced a pulmonary vascular resistance reduction of >20%. In patients with significant lung disease, aviptadil tended to improve oxygenation. The pulmonary vasodilating effect of aviptadil aerosol was modest and short-lived, did not cause any side-effects and led to a reduced workload of the right ventricle without affecting systemic blood pressure. Aviptadil inhalation tended to improve oxygenation in patients with significant lung disease. Further studies are needed to evaluate the full therapeutic potential of aviptadil aerosol, including higher doses and chronic treatment.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Fentolamina/administração & dosagem , Peptídeo Intestinal Vasoativo/administração & dosagem , Peptídeo Intestinal Vasoativo/metabolismo , Adulto , Aerossóis , Idoso , Pressão Sanguínea , Combinação de Medicamentos , Feminino , Insuficiência Cardíaca/patologia , Ventrículos do Coração/patologia , Humanos , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismoRESUMO
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed information about the diagnosis of pulmonary hypertension, and furthermore provide novel recommendations for risk stratification and follow-up assessments. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to risk stratification and follow-up assessment of patients with PAH. This manuscript summarizes the results and recommendations of this working group.
Assuntos
Determinação da Pressão Arterial/normas , Cardiologia/normas , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/terapia , Guias de Prática Clínica como Assunto , Pneumologia/normas , Alemanha , Humanos , Hipertensão Pulmonar/classificação , Prognóstico , Medição de Risco/normas , Resultado do TratamentoRESUMO
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. The guidelines contain detailed recommendations for the targeted treatment of pulmonary arterial hypertension (PAH). However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to the targeted therapy of PAH. This article summarizes the results and recommendations of the working group on targeted treatment of PAH.
Assuntos
Anti-Hipertensivos/administração & dosagem , Cardiologia/normas , Hipertensão Pulmonar/terapia , Terapia de Alvo Molecular/normas , Guias de Prática Clínica como Assunto , Pneumologia/normas , Alemanha , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/genética , Técnicas de Diagnóstico Molecular/normasRESUMO
In suspected acute pulmonary embolism, the measurement of the d-dimer is now an established screening method. Further diagnostic measures include the electrocardiogram, echocardiography and conventional chest radiography, as well as the analysis of blood gases. The specific demonstration of a pulmonary embolism is achieved with a helical CT of the thorax, pulmonary angiography and ventilation/perfusion scanning. Apart from continuous (infusion) of unfractionated heparin, the low molecular weight heparins also are of potential value in the treatment of pulmonary embolism. A larger percentage of patients benefit from the use of fibrinolytic agents than was previously thought, so that the indication for fibrinolytic therapy should not be made dependent on the presence of hemodynamic instability.
Assuntos
Emergências , Heparina/administração & dosagem , Embolia Pulmonar/tratamento farmacológico , Terapia Trombolítica , Árvores de Decisões , Diagnóstico por Imagem , Eletrocardiografia , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Valor Preditivo dos Testes , Embolia Pulmonar/diagnóstico , Reprodutibilidade dos TestesAssuntos
Anti-Hipertensivos/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/administração & dosagem , Vasodilatadores/administração & dosagem , Administração por Inalação , Adulto , Feminino , Doença de Gaucher/complicações , Humanos , Hipertensão Pulmonar/complicaçõesRESUMO
The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension (PH) have been adopted for Germany. Invasive hemodynamic data obtained by right heart catheterization are essential to confirm the diagnosis, test vasoreactivity, assess severity and guide therapy in PH patients. The definition of PH is resting on a mean pulmonary artery pressure ≥ 25 mm Hg obtained by right heart catheterization. Furthermore, a pulmonary capillary wedge pressure > 15 mm Hg excludes pre-capillary PH. Vasoreactivity testing is part of the diagnostic work-up in pulmonary arterial hypertension. Recent data on the use of inhaled iloprost update these guidelines and are of special importance due to the frequent diagnostic use of iloprost in Germany. Other aspects of invasive hemodynamic data in certain PH subgroups as well as their measurement and interpretation in children are discussed. Several aspects of right heart catheterization in PH justify a detailed commentary, and in some areas an update already appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Paediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups were initiated, one of which was specifically addressing the invasive hemodynamic evaluation of patients with PH. This commentary summarizes the results and recommendations of this working group.
Assuntos
Medicina Baseada em Evidências , Hemodinâmica/fisiologia , Hipertensão Pulmonar/diagnóstico , Administração por Inalação , Cateterismo de Swan-Ganz , Criança , Alemanha , Humanos , Hipertensão Pulmonar/fisiopatologia , Iloprosta , Pressão Propulsora Pulmonar/fisiologia , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , VasodilatadoresRESUMO
The 2009 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension have been adopted for Germany. The guidelines contain detailed recommendations for the diagnosis of pulmonary hypertension. However, the practical implementation of the European Guidelines in Germany requires the consideration of several country-specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update y appears necessary. In June 2010, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, a number of working groups was initiated, one of which was specifically dedicated to non-invasive diagnosis of PH. This commentary summarizes the results and recommendations of the working group on treatment of PAH.
Assuntos
Medicina Baseada em Evidências , Hipertensão Pulmonar/diagnóstico , Algoritmos , Alemanha , Humanos , Hipertensão Pulmonar/etiologia , Valor Preditivo dos Testes , Sociedades MédicasAssuntos
Comportamento Cooperativo , Hipertensão Pulmonar/tratamento farmacológico , Comunicação Interdisciplinar , Terapia de Alvo Molecular/métodos , Adulto , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Terapia Combinada , Aprovação de Drogas , Quimioterapia Combinada , Antagonistas dos Receptores de Endotelina/efeitos adversos , Antagonistas dos Receptores de Endotelina/uso terapêutico , Medicina Baseada em Evidências , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/mortalidade , Inibidores da Fosfodiesterase 5/efeitos adversos , Inibidores da Fosfodiesterase 5/uso terapêutico , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Addition of inhaled iloprost to bosentan may have beneficial effects in patients with idiopathic pulmonary arterial hypertension (IPAH). A multicentre, open, randomised, controlled trial was performed to assess the safety and efficacy of inhaled iloprost in patients with IPAH who had already been treated with bosentan. The trial was terminated early after a futility analysis predicted failure with respect to the predetermined sample size. At that time, 40 patients were randomised to receive either bosentan alone (control group) or bosentan plus inhaled iloprost (combination group) for a 12-week period. The primary end-point, change in 6-min walking distance, was not met (mean changes +1 m and -9 m in the control and combination group, respectively). These results may have been skewed by three outliers in the iloprost group who presented with severe clinical worsening. None of the secondary end-points including functional class, peak oxygen uptake, and time to clinical worsening differed significantly between groups. The current study failed to show a positive effect of adding inhaled iloprost to bosentan in idiopathic pulmonary arterial hypertension patients. Further studies involving larger sample sizes and long-term follow-up are needed to determine the efficacy of adding inhaled iloprost to bosentan in patients with idiopathic pulmonary arterial hypertension.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/uso terapêutico , Sulfonamidas/uso terapêutico , Vasodilatadores/uso terapêutico , Administração por Inalação , Adulto , Idoso , Bosentana , Quimioterapia Combinada , Teste de Esforço , Feminino , Humanos , Iloprosta/administração & dosagem , Iloprosta/efeitos adversos , Masculino , Pessoa de Meia-Idade , Vasodilatadores/administração & dosagem , Vasodilatadores/efeitos adversosAssuntos
Cateterismo Cardíaco/métodos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Diagnóstico Diferencial , Hemodinâmica/fisiologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Oxigênio/sangue , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Pressão Propulsora Pulmonar/fisiologia , Resistência Vascular/fisiologiaRESUMO
Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS.
Assuntos
Bronquiolite Obliterante/mortalidade , Líquido da Lavagem Broncoalveolar/virologia , Herpesvirus Humano 6 , Transplante de Pulmão/mortalidade , Infecções por Roseolovirus/mortalidade , Infecções por Adenoviridae/mortalidade , Adulto , Bronquiolite Obliterante/virologia , Estudos de Coortes , Infecções por Citomegalovirus/mortalidade , DNA Viral/análise , Infecções por Vírus Epstein-Barr/mortalidade , Feminino , Herpes Simples/mortalidade , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Herpesvirus Humano 6/genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/virologia , Fatores de RiscoRESUMO
The antioxidant glutathione (GSH) is increased in the epithelial lining fluid (ELF) of chronic smokers. The rate-limiting enzyme in GSH synthesis is glutamate-cysteine ligase (GCL), also known as gamma-glutamylcysteine synthetase, consisting of a heavy, catalytic (GCLC) and a light, modulatory (GCLM) subunit. To determine the contribution of bronchoalveolar lavage (BAL) cells to GSH levels in ELF, BAL was performed in eight smokers and eight never-smokers. Intra- and extracellular total glutathione (GSHt) levels and GCL subunit expression were assessed. GSHt was increased in ELF from smokers (1,090.1 +/- 163.0 microM versus 559.2 +/- 48.2 microM). GSHt content of BAL cells (nmol x mg protein(-1)) was decreased in smokers without differences reaching statistical significance (8.0 +/- 1.4 versus 12.4 +/- 2.6). GCLM expression was also reduced in smokers (0.6 +/- 0.1 versus 2.8 +/- 0.4) and correlated with intracellular GSHt content. There was no significant difference in GCLC expression and in differential cell counts in BAL fluid. The authors conclude that smoking does increase glutathione levels in the epithelial lining fluid but not intracellular levels in bronchoalveolar lavage cells. The data suggest that the intracellular glutathione concentration of bronchoalveolar lavage cells (predominately alveolar macrophages) is regulated by the modulatory glutamate-cysteine ligase subunit rather than the catalytic subunit.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Glutamato-Cisteína Ligase/metabolismo , Macrófagos Alveolares/metabolismo , Fumar/metabolismo , Adulto , Líquido da Lavagem Broncoalveolar/citologia , Domínio Catalítico , Contagem de Células , Feminino , Glutationa/metabolismo , Humanos , Masculino , Testes de Função Respiratória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estatísticas não ParamétricasRESUMO
Inhalation of aerosolized prostacyclin (PGI(2)) exerts selective pulmonary vasodilation, but its effect is rapidly lost after termination of nebulization. Amplification of the vasodilatory response to inhaled PGI(2) might be achieved by phosphodiesterase (PDE) inhibitors to stabilize its second messenger, cAMP. We established stable pulmonary hypertension in perfused rabbit lungs by continuous infusion of U-46619. Short-term (10-min) aerosolization maneuvers of PGI(2) effected a rapid, moderate decrease in pulmonary arterial pressure, with post-PGI(2) vasorelaxation being lost within 10-15 min, accompanied by a marginal reduction in shunt flow. Preceding administration of subthreshold doses of the PDE inhibitors theophylline, dipyridamole, and pentoxifylline via the intravascular or inhalational route, which per se did not influence pulmonary hemodynamics, caused more than doubling of the immediate pulmonary arterial pressure drop in response to PGI(2) and marked prolongation of the post-PGI(2) vasorelaxation to >60 min (all PDE inhibitors via both routes of application). This was accompanied by a reduction in shunt flow in the case of aerosolized theophylline (27.5%), pentoxifylline (30.5%), and dipyridamole (33.4%). Coaerosolization of PGI(2) and PDE inhibitors may be considered as a therapeutic strategy in pulmonary hypertension.
Assuntos
Anti-Hipertensivos/farmacologia , Epoprostenol/farmacologia , Hipertensão Pulmonar/tratamento farmacológico , Inibidores de Fosfodiesterase/farmacologia , Teofilina/farmacologia , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Administração por Inalação , Animais , AMP Cíclico/metabolismo , Dipiridamol/farmacologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Nebulizadores e Vaporizadores , Pentoxifilina/farmacologia , Pressão , Troca Gasosa Pulmonar/efeitos dos fármacos , Coelhos , Vasoconstritores/farmacologia , Relação Ventilação-Perfusão/efeitos dos fármacosRESUMO
The aim of the present study was to investigate the feasibility and efficacy of bronchoscopic surfactant administration in a noncontrolled multicentre study in five university centres. A total number of 27 patients, suffering from severe acute respiratory distress syndrome (mean+/-SEM lung injury score: 3.15+/-0.06) and septic shock (Acute Physiology and Chronic Health Evaluation (APACHE) II score at study entry 33.2+/-1.3, lactate 4.3+/-0.6 mmol x L(-1)) were studied. The patients were ventilated with a mean tidal volume of 11.0+/-0.5 mL x kg(-1) body weight (bw), either volume or pressure controlled, with 16.3+/-2.8 cmH2O positive end-expiratory pressure, for an average of 3.5+/-0.3 days at study entry. A natural bovine surfactant extract (300 mg x kg(-1) bw Alveofact; mean total volume 378 mL) was delivered in divided doses to each segment of the lungs via flexible bronchoscope within approximately 45 min. No untoward effects on gas exchange, lung mechanics and haemodynamics were noted during the procedure of surfactant administration. Within 12 h the oxygen tension in arterial blood/inspiratory oxygen fraction increased from a mean of 109+/-8 mmHg to 210+/-20 mmHg (p<0.001). In seven patients, in whom gas exchange again deteriorated with further progression of the disease, a second surfactant dose of 200 mg x kg(-1) was administered 18-24 h after the first application, again improving arterial oxygenation. A total of 15 patients survived the 28-day study period (mortality rate 44.4%, compared to a calculated risk of death for the given APACHE II scores of 74.0+/-3.5%), with all causes of death being nonrespiratory. The bronchoscopic application of a high dose of natural surfactant in patients with severe acute respiratory distress syndrome and septic shock is both feasible and safe, resulting in a pronounced improvement in gas exchange.