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Biomedical subjects

R Dembinski

Publications and source records attributed to R Dembinski.

At least 19 recordsLinked to original sources

[Pulmonary hypertension].

Pulmonary hypertension can arise in the presence of acute cardiopulmonary decompensation or develop as a chronic and progressive disease in association with connective tissue diseases, infectious diseases, or metabolic diseases, or in the form of idiopathic pulmonary hypertension. Impaired regulation of endogenous vasoactive mediators, growth factors, and thrombotic factors leads to pulmonary artery vasoconstriction, endothelial and epithelial proliferation, and thrombotic vascular obstruction, with resulting right heart failure. There is no curative treatment for chronic pulmonary hypertension, and the immediate objective of palliative treatment is to relieve right heart stress by reducing pulmonary arterial pressure with the aid of pulmonary vasodilators. Depending on the severity of the illness, perioperative mortality is high, which must be borne in mind by both anesthetists and intensivists. Chronic medical treatment for these patients must be optimized before any surgery is undertaken. In the perioperative period, it is essential that anything that could lead to worsening of pulmonary hypertension is avoided, or at least recognized and treated at an early stage. Intraoperatively, imminent acute right heart decompensation is treated by improving right-ventricular contractility and reducing right-ventricular afterload. In the postoperative period, monitoring and optimization of the cardiopulmonary status, adequate analgesia and sedation, and careful anticoagulation must be ensured.

Anesthesia↗

Role of extracorporeal lung assist in the treatment of acute respiratory failure.

For patients with most severe acute respiratory distress syndrome (ARDS) conservative treatment with lung protective ventilation is often not sufficient to prevent life-threatening hypoxemia and additional strategies are necessary. Extracorporeal lung assist (ECLA) or extracorporeal membrane oxygenation (ECMO) using capillary membrane oxygenators can provide sufficient gas exchange and lung rest. In 2 randomized trials mortality was unchanged for ECMO. Today an technically enhanced ECMO is used for most severe ARDS using clinical algorithm and different case studies demonstrated a survival rate about 56%. Today miniaturized ECMO with optimized blood pumps and oxygenators are available and could enhance safety and clinical management. Another approach is an arterio-venous pumpless interventional lung assist (ILA) with a low resistance oxygenator. Advantages seem a simplified clinical management and less blood trauma. At present new devices are developed for chronic respiratory failure or bridge to lung transplant. Oxygenators with even less flow resistance could be implanted paracorporeal using the right ventricle as driving force. An intravascular oxygenator has been developed using the combination of a miniaturized blood pump and an oxygenator for implantation in the vena cava. Well designed clinical trials are necessary to demonstrate a clinical benefit for these experimental devices.

Acute Disease↗

Cardiopulmonary effects of iloprost in experimental acute lung injury.

Iloprost, a prostacyclin analogue with a prolonged plasma half-life has beneficial effects in chronic pulmonary hypertension, whereas the effects in acute lung injury (ALI) are unknown. The present study was performed to evaluate the cardiopulmonary effects of iloprost in experimental ALI. ALI was induced in 18 pigs by repeated lung lavage. Animals were randomised to controls, i.v. or inhaled iloprost for 15 min. Haemodynamics, gas exchange and ventilation-perfusion distribution were measured at the end of iloprost application and after 1 and 2 h. As a short-term effect, both i.v. and inhaled iloprost significantly decreased pulmonary artery pressure without major effects on gas exchange or systemic haemodynamics. After 1 and 2 h, a reduction of pulmonary hypertension was no longer present. As a long-term effect, inhaled, but not i.v., iloprost decreased pulmonary shunt and significantly improved gas exchange after 1 and 2 h. In conclusion, the single application of iloprost revealed short-term pulmonary vasodilation without other major cardiopulmonary effects. However, inhaled iloprost improved gas exchange due to a decrease of pulmonary shunt as a long-term effect, possibly as a result of a reduction of lung oedema formation.

Acute Disease↗

Artificial lung and extracorporeal gas exchange.

Over the last years, several observational studies have suggested that extracorporeal lung assist (ECLA) may be an important contribution to clinical algorithms for the treatment of most severe acute respiratory distress syndrome (ARDS). Today ECLA is used only as a rescue therapy in life threatening gas exchange disorders if maximal conventional therapy fails to prevent from hypoxemia. With subsequent reduction of complications and improvement of biocompability, extracorporeal membrane oxygentation (ECMO) indications may be extendend to treat patients earlier and not only in rescue situations along the original idea to buy the lung some time to heal by avoiding further ventilator associated lung injury. Veno-venous ECMO therapy at present is an important therapeutic option in severe ARDS with persisiting life threatening gas exchange disorder as a rescue therapy. The development of smaller, less complex and more secure ECMO or pumpless veno-arterial ECLA systems has the potential to perform controlled studies of its use in ARDS and potentially expand indications.

Animals↗

[Extracorporeal membrane oxygenation by acute respiratory distress syndrome].

After 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 ultimate ratio but to less severe ARDS to enable lung protective, less invasive mechanical ventilation.

Anticoagulants↗

[Treatment of acute respiratory distress syndrome in a treatment center. Success is dependent on risk factors].

SUBJECT: Mortality rates remain high for the acute respiratory distress syndrome (ARDS) despite standardised treatment algorithms. Little is known about prognostic factors and exclusion criteria for advanced treatment including extracorporeal membrane oxygenation (ECMO). METHODS: In an observational study design a cohort of 93 patients with severe ARDS admitted to a referral centre were analysed according to ventilatory and vital parameters. RESULTS: Overall survival rate was 70% and in patients who received ECMO treatment it was 67%. In patients exhibiting relevant co-morbidity the odds ratio for fatal outcome increased to 4.7 (95% CI: 3.3-24.9), and patients with multiple organ failure had a 7.5-fold increase (95% CI: 2.3-25.2) for risk of death. Survivors demonstrated a more pronounced improvement in oxygenation ( p<0.05) and CO(2) removal ( p<0.05) than non-survivors. CONCLUSIONS: Advanced treatment of ARDS including ECMO represents a therapeutic option if none of the currently considered contraindications are present. An improvement in gas exchange parameters, but not a defined value per se may be useful as a prognostic factor for favourable outcome.

Adult↗

Modulating the pulmonary circulation: an update.

Pulmonary hypertension is a common finding in pulmonary circulatory disorders of different origin. Chronic pulmonary hypertension may develop due to either cardiopulmonary or systemic diseases whereas acute and acute-on-chronic pulmonary hypertension often occur in the course of cardiothoracic surgery. Right heart failure is the major risk particularly in the course of acute pulmonary hypertension. Thus, besides basic treatment of the underlying disease the use of vasodilators is a valuable therapeutic option to decrease right ventricular afterload, but intravenous vasodilators may provoke systemic arterial hypotension and impair gas exchange due to vasodilation of pulmonary shunt areas. Therefore, inhaled vasodilators such as nitric oxide and prostacyclin have been suggested for the treatment of pulmonary hypertension especially when concomitant hypoxemia is present due to a ventilation-perfusion mismatch. However, randomised controlled trials performed to evaluate long-term effects revealed different results: thus, in chronic pulmonary hypertension inhaled vasodilators improved outcome whereas the results for the treatment of the acute respiratory distress syndrome revealed beneficial effects only when used as a rescue and/or bridging therapy in severe hypoxemia. In cardiothoracic surgery, inhaled vasodilators have been shown to improve pulmonary circulation when severe pulmonary hypertension is present. Although effective in experimental studies no clear recommendation can be made in view to the use of other vasodilators such as phosphodiesterase inhibitors or endothelin antagonists. Likewise, the combination of different vasodilators merit further investigations to prove efficacy in randomised controlled trials.

Humans↗

Anesthetic considerations in patients with chronic pulmonary diseases.

AIM: Increasing age and co-morbidities of patients admitted for surgery impose new challenges on the anesthesiologist. METHODS: Review of current literature regarding the perioperative management of patients with chronic pulmonary disease. RESULTS: If patients are treated adequately, surgery can be safely performed under regional and general anaesthesia. Major risk factors include type of surgery, type and duration of anesthesia, general health status and smoking history, but not certain lung function parameters. Regional anesthesia remains the first choice for intra- and postoperative care, and if general anesthesia is necessary, early extubation should be achieved. Non-invasive ventilation could be a possible alternative in weaning failure. CONCLUSION: Assessing the functional status of patients admitted to surgery remains a difficult task, and in patients identified at risk by clinical examination additional spirometry and blood gases may be helpful. If there are signs of respiratory failure, the anaesthetist should monitor the patient closely and invasively, yet there is no reason to deny any patient a substantially beneficial operation.

Anesthesia↗

Breathing pattern and workload during automatic tube compensation, pressure support and T-piece trials in weaning patients.

BACKGROUND AND OBJECTIVE: Automatic tube compensation has been designed as a new ventilatory mode to compensate for the non-linear resistance of the endotracheal tube. The study investigated the effects of automatic tube compensation compared with breathing through a T-piece or pressure support during a trial of spontaneous breathing used for weaning patients from mechanical ventilation of the lungs. METHODS: Twelve patients were studied who were ready for weaning after prolonged mechanical ventilation (10.2 +/- 8.4 days) due to acute respiratory failure. Patients with chronic obstructive pulmonary disease were excluded. Thirty minutes of automatic tube compensation were compared with 30 min periods of 7 cmH2O pressure support and T-piece breathing. Breathing patterns and workload indices were measured at the end of each study period. RESULTS: During T-piece breathing, the peak inspiratory flow rate (0.65 +/- 0.20 L s(-1)) and minute ventilation (8.9 +/- 2.7L min(-1)) were lower than during either pressure support (peak inspiratory flow rate 0.81 +/- 0.25 L s(-1) minute ventilation 10.2 +/- 2.3 L min(-1), respectively) or automatic tube compensation (peak inspiratory flow rate 0.75 +/- 0.26L s(-1); minute ventilation 10.8 +/- 2.7 L min(-1)). The pressure-time product as well as patients' work of breathing were comparable during automatic tube compensation (pressure-time product 214.5 +/- 104.6 cmH2O s(-1) min(-1), patient work of breathing 1.1 +/- 0.4 J L(-1)) and T-piece breathing (pressure-time product 208.3 +/- 121.6 cmH2O s(-1) min(-1), patient work of breathing 1.1 +/- 0.4 J L(-1)), whereas pressure support resulted in a significant decrease in workload indices (pressure-time product 121.2 +/- 64.1 cmH2O s(-1) min(-1), patient work of breathing 0.7 +/- 0.4 J L(-1)). CONCLUSIONS: In weaning from mechanical lung ventilation, patients' work of breathing during spontaneous breathing trials is clearly reduced by the application of pressure support 7 cmH2O, whereas the workload during automatic tube compensation corresponded closely to the values during trials of breathing through a T-piece.

Adult↗

Effects of combined high-dose partial liquid ventilation and almitrine on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury.

OBJECTIVES: To determine possible additive effects of combined high-dose partial liquid ventilation (PLV) and almitrine bismesylate (ALM) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN AND SETTING: Prospective, controlled animal study in an animal research facility of a university hospital. INTERVENTIONS: ALI was induced in 12 anesthetized and mechanically ventilated pigs by repeated wash-out of surfactant. After initiation of PLV with 30 ml/kg perfluorocarbon the animals were randomly assigned to receive either accumulating doses of ALM (0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 micrograms/kg per minute) for 30 min each (n = 6) or the solvent malic acid (n = 6). MEASUREMENT AND RESULTS: Pulmonary gas exchange and hemodynamics were measured at the end of each infusion period. Compared to ALI, PLV alone significantly increased arterial oxygen partial pressure (PaO2) and decreased venous admixture (QVA/QT) and mean pulmonary artery pressure (MPAP). Administration of ALM did not result in a further improvement in PaO2, QVA/QT or MPAP compared to PLV alone but decreased PaO2 and increased QVA/QT and MPAP when 16 micrograms/kg per min ALM was compared to PLV alone. CONCLUSIONS: In an animal model of surfactant depletion induced ALI the combined treatment of PLV and ALM induced no significant improvement in pulmonary gas exchange or hemodynamics when compared to PLV alone. Moreover, high-dose ALM significantly impaired gas exchange and pulmonary hemodynamics.

Almitrine↗

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

BACKGROUND: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. METHODS: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 ng.kg(-1).min(-1) inhaled prostacyclin alone, 1 microg.kg(-1).min(-1) almitrine alone, 25 ng.kg(-1).min(-1) inhaled prostacyclin in combination with 1 microg.kg(-1).min(-1) almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. RESULTS: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution. CONCLUSIONS: The authors conclude that, in this experimental model of ALI, the combination of 25 ng.kg(-1).min(-1) prostacyclin and 1 microg.kg(-1).min(-1) almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.

Almitrine↗

Time-dependency of improvements in arterial oxygenation during partial liquid ventilation in experimental acute respiratory distress syndrome.

BACKGROUND: The mechanisms by which partial liquid ventilation (PLV) can improve gas exchange in acute lung injury are still unclear. Therefore, we examined the time- and dose-dependency of the improvements in arterial oxygen tension (PaO2) due to PLV in eight pigs with experimental lung injury, in order to discriminate increases due to oxygen dissolved in perfluorocarbon before its intrapulmonary instillation from a persistent diffusion of the respiratory gas through the liquid column. RESULTS: Application of four sequential doses of perfluorocarbon resulted in a dose-dependent increase in PaO2. Comparison of measurements 5 and 30 min after instillation of each dose revealed a time-dependent decrease in PaO2 for doses that approximated the functional residual capacity of the animals. CONCLUSION: Although oxygen dissolved in perfluorocarbon at the onset of PLV can cause a short-term improvement in arterial oxygenation, diffusion of oxygen through the liquid may not be sufficient to maintain the initially observed increase in PaO2.

Analysis of Variance↗

Effect of inhaled nitric oxide 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 microg/kg per min ALM, 3) 1 microg/ 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.

Administration, Inhalation↗

Dose-dependent effects of almitrine on hemodynamics and gas exchange in an animal model of acute lung injury.

OBJECTIVE: To determine the dose-response relationship of almitrine (Alm) on pulmonary gas exchange and hemodynamics in an animal model of acute lung injury (ALI). DESIGN: Prospective, randomized, controlled study. METHODS: Twenty anesthetized, tracheotomized and mechanically ventilated (FIO2 1.0) pigs underwent induction of ALI by repeated saline washout of surfactant. Animals were randomly assigned to either receive cumulating doses of Alm intravenously (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 micrograms.kg-1.min-1) for 30 min each (treatment; n = 10) or to receive the solvent malic acid (controls; n = 10). MEASUREMENTS AND RESULTS: Measurements of pulmonary gas exchange and hemodynamics were performed at the end of each infusion period. Alm < 4.0 micrograms.kg-1.min-1 improved arterial oxygen pressure (PaO2) (105 +/- 9 mmHg for Alm 1.0 vs 59 +/- 5 mmHg) and decreased intrapulmonary shunt (Qs/Qt) (32 +/- 4% for Alm 1.0 vs 46 +/- 4%) (P < 0.05). Alm > or = 8.0 micrograms.kg-1.min-1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 micrograms.kg-1.min-1, high doses > or = 8.0 micrograms.kg1.min-1 decreased PaO2 (58 +/- 11 mmHg for Alm 16.0) and increased Qs/Qt (67 +/- 10% for Alm 16.0) (P < 0.05). CONCLUSIONS: In experimental ALI, effects of almitrine on oxygenation are dose-dependent. Almitrine is most effective when used at low doses known to mimic hypoxic pulmonary vasoconstriction.

Almitrine↗

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. METHODS: Seven pigs (24+/-2 kg BW) were surfactant-depleted by repeated lung lavage with saline. Gas exchange and hemodynamic parameters were assessed in all animals during gaseous and subsequent partial liquid ventilation at two levels of PEEP (5 and 15 cmH2O) and intermittent inhalation of 10 ppm NO. RESULTS: Arterial oxygenation increased significantly with a simultaneous decrease in cardiac output when PEEP 15 cmH2O was applied during gaseous and partial liquid ventilation. All other hemodynamic parameters revealed no relevant changes. Inhalation of NO and instillation of perfluorocarbon had no additive effects on pulmonary gas exchange when compared to PEEP 15 cmH2O alone. CONCLUSION: In experimental lung injury, improvements in gas exchange are most distinct during mechanical ventilation with PEEP 15 cmH2O without significantly impairing hemodynamics. Partial liquid ventilation and inhaled NO did not cause an additive increase of PaO2.

Administration, Inhalation↗

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

BACKGROUND: It 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. METHODS: After 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. RESULTS: During 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. CONCLUSIONS: In 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.

Animals↗