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Biomedical subjects

K J Falke

Publications and source records attributed to K J Falke.

At least 37 records · Page 2Linked to original sources
PubMed1997

Global and extended coagulation monitoring during extracorporeal lung assist with heparin-coated systems in ARDS patients.

Heparin-coated systems for extracorporeal lung-assist (ECLA) were developed to reduce hemorrhagic risk by lowering the systemic heparinization, monitored by global tests, e.g. activated coagulation time (ACT) and activated partial thromboplastin time (APTT). Since this strategy gives no insight into procoagulant states, five ARDS patients receiving ECLA with heparin-coated systems were investivated for changes in coagulation using both global and extended tests. During ECLA onset the APTT and ACT were within or near normal ranges, platelets decreased 76.5% within 48 h, fibrinogen decreased 28.7%, thrombin-antithrombin-III complexes were elevated before ECLA (53 micrograms/L), but demonstrated an additional peak (238 micrograms/L), plasminogen-activator-inhibitor-1 increased 12-fold, and the C1-inhibitor dropped 14.1%. In conclusion, after the onset of ECLA from a previous prethrombotic state, the precoagulant, anticoagulant, fibrinolytic and complement systems were activated in a similar way to that reported for non-heparinized systems with high-dose heparin. This was however only monitored by an extended test panel which was unable to predict thromboembolic events during ECLA.

Adult↗
PubMed1996

[Clinical aspects of acute lung failure in adults (ARDS)].

Acute respiratory distress syndrome (ARDS) is rare but beset with a high mortality rate. In recent years, however, a trend towards higher survival rates has been observed. High inspiratory oxygen concentrations, large tidal volumes, and high peak inspiratory airway pressures applied during mechanical ventilation have been identified as harmful to the lung and can contribute to the progression of ARDS. This had led to reconsideration of the sequelae of ventilatory therapy. Mechanical ventilation and other adjunctive strategies in ARDS have changed from the conventional approach aiming at normalisation of physiological ventilatory parameters to an elaborated approach that intends to protect the ventilated lung, prevent oxygen toxicity, recruit the infiltrated atelectatic and consolidated lung and reduce the anatomical and alveolar dead space. This new approach consists of various forms of pressure-controlled mechanical ventilation with PEEP and permissive hypercapnia, body position changes, and inhalation of nitric oxide. Should these procedures fail to improve impaired gas exchange, extracorporeal membrane oxygenation is an additional therapeutic option. None of these therapeutic procedures, however, has been tested against traditional standard treatment in a classical randomised controlled trial. The following review focuses on the latest insights into the pathophysiology, diagnosis, and treatment of ARDS.

Combined Modality Therapy↗
PubMed1996

Evidence of nitric oxide in the exhaled gas of Asian elephants (Elephas maximus).

Nitric oxide (NO) produced in the respiratory tract is released into the respiratory gases of humans, rabbits, guinea-pigs, and rats. We analysed the NO concentrations in the exhaled gas of four awake Asian elephants. Two methods were employed: (1) exhaled gas was sampled from the elephants' trunks with a 1 L syringe and analysed for NO concentrations by chemiluminescence; (2) respiratory gas was continuously aspirated via a thin plastic tube positioned within the trunk and on-line analysed for NO concentrations by chemiluminescence. Syringe sampling (n = 4), when corrected for dilution by ambient air using linear regression analysis, revealed a mean NO concentration of 31 parts per billion (ppb); highest exhalatory concentrations measured during continuous suctioning were 27 and 28 ppb (n = 2). The exhaled NO concentrations in elephants are similar to those found in humans measured with a comparable technique. This supports the hypothesis that a size-independent 'normal value' of endogenous NO is provided in the airways which may contribute to regulation of pulmonary ventilation and perfusion by autoinhalation in some mammals.

Animals↗
PubMed1996

The effects of nitric oxide (NO) on platelet membrane receptor expression during activation with human alpha-thrombin.

Nitric oxide (NO) is known as a regulator of platelet function by its anti-adhesive, anti-aggregating, and disaggregating properties. We investigated the modulating effects of the NO-releasing compound SIN-1 (3-morpholino-sydnonimine) on platelet surface glycoprotein (GP) expression during stimulation with human alpha-thrombin. Analysis was performed with two-color flow cytometry using fluoresceine-isothiocyanate (FITC) and phycoerythrin-(PE)-conjugated monoclonal antibodies (MoAbs) directed against GPIb CD42b), GP IIb-IIIa (CD41), P-selectin (CD62P), and MoAb PAC-1 directed against activated GP IIb-IIIa. Preincubation of platelets with SIN-1 (IC50: 1 microM) significantly decreased expression of both total and activated GP IIb-IIIa, and P-selectin in platelets stimulated with thrombin (ED50: 0.05 U/ml), whereas thrombin-induced downregulation of GP Ib was not attenuated. P-selectin expression increased in thrombin-stimulated platelets over time; in contrast, activated GP-IIb-IIIa decreased after an initial peak, indicating that thrombin-induced GP IIb-IIIa activation is spontaneously reversible. SIN-1 reduced P-selectin expression only when added before or at the same time as thrombin, whereas conformationally changed GP-IIb-IIIa was significantly reversed at up to 60 minutes after stimulation by SIN-1. In conclusion, NO attenuates activation marker expression in a dose and time dependent manner. GP-IIb-IIIa is highly sensitive to NO which not only prevents receptor activation but also promotes reversal of activated GP IIb-IIIa complex.

Blood Platelets↗
PubMed1996

Reduction of platelet trapping in membrane oxygenators by transmembraneous application of gaseous nitric oxide.

Bleeding during extracorporeal circulation (ECC) is often induced and/or aggravated by thrombocytopenia due to platelet-trapping in hollow fiber membrane oxygenators (HFMO). Nitric oxide (NO) has platelet anti-aggregating and dis-aggregating properties. In a paired system we tested whether gaseous NO, added to the gas compartment of one of two parallel running heparin-bonded HFMO attenuated platelet-trapping. Platelet consumption was markedly reduced in the NO-treated HFMO. These data strongly indicate that the application of gaseous NO could prove a new therapeutical approach to reduce bleeding during ECC, serving as a new way of preventing platelet loss, thus reducing the need for high systemic heparinization.

Biocompatible Materials↗
PubMed1995

Extracorporeal membrane oxygenation with heparin-coated systems in a 13-month-old infant with acute hypoxic respiratory failure after correction of tetralogy of Fallot.

Hemorrhagic disorders due to systemic heparinization are frequent during extracorporeal lung support (veno-venous extracorporeal membrane oxygenation: vv-ECMO). The development of heparin-coated systems has reduced the need for high-dose heparinization. Whereas the use of these heparin-coated membrane lungs and tubings has been described in former studies in adults, only few reports exist in children. This case report describes the application of a heparin-coated extracorporeal system for long-term vv-ECMO in a 13-month-old infant suffering from acute hypoxic respiratory failure after correction of tetralogy of Fallot. Only moderately elevated levels of activated clotting time (ACT, 120-160 s) and activated partial thromboplastin time (aPTT, 40-60 s) were necessary to avoid thrombotic events in the extracorporeal system. Thoracotomies were performed twice without bleeding complications by discontinuation of the systemic heparinization. We conclude that the use of heparin-coated membrane lungs in infants may improve the safety of extracorporeal lung support and permits surgical intervention without major risk of bleeding.

Acute Disease↗
PubMed1995

Preliminary evaluation of a new continuous intra-arterial blood gas monitoring device.

Continuous intra-arterial blood gas monitoring is a new technique, possibly offering therapeutic advantages through improved monitoring in patients prone to hypoxaemia, hypercapnia and/or respiratory acidosis. Therefore, we studied the clinical applicability, reliability, precision and side effect of long-term continuous intra-arterial blood gas monitoring in patients suffering from severe acute respiratory distress syndrome. In 10 patients continuous intra-arterial blood gas monitoring based on fluorescent optodes technique was performed. At 4 h intervals, arterial blood samples for in vitro blood gas analyses were drawn, stored in ice, and analysed within 3 min. Evaluation of data retrieved from the continuous intra-arterial blood gas monitoring and in vitro blood gas analysis was based on 596 data points using 10 catheters. Average length of insertion was 281 +/- 215 h, max. lengths of stay was 750 h. Arterial blood gas data obtained in vivo were compared to the mean of in vivo and in vitro arterial blood gases. Inter-catheter bias, expressed as percent difference between continuous intra-arterial blood gas and mean in vitro blood gas analysis was 0.19 +/- 0.23% for pH. 1.1 +/- 5.2% for PaCO2 and 1.6 +/- 5.7% for PaO2. No significant gas partial pressure dependent change in precision was demonstrable. There was no significant time dependent drift in sensor precision over the study period. No negative side-effects related to IABG monitoring were observed. We conclude that long-term use of this new device is possible in patients and represents a reliable alternative to conventional in vitro arterial blood gas analysis, when continuous monitoring of blood gases and/or acid-base balance is critical.

Acid-Base Equilibrium↗
PubMed1995

Influence of mixed venous PO2 and inspired O2 fraction on intrapulmonary shunt in patients with severe ARDS.

In 12 patients undergoing extracorporeal membrane oxygenation for treatment of severe acute respiratory distress syndrome (ARDS), we examined the effects of independent variations in mixed venous oxygen tension (PvO2) and inspired oxygen fraction (FIO2) on the distribution of ventilation and perfusion as assessed by the multiple inert gas elimination technique. Reducing the oxygen concentration of the constant gas stream through the membrane lungs allowed us to decrease the PvO2 by approximately 20 Torr independently of variations in cardiac output and FIO2 as well as to augment FIO2 without influencing PvO2. The interventions did not induce any change in heart rate or systemic or pulmonary hemodynamics. In general, neither during mechanical ventilation at FIO2 of 0.6 nor during mechanical ventilation at FIO2 of 1.0 did the reduced PvO2 cause variations in the distribution of pulmonary blood flow in our patients with severe ARDS. Nevertheless, in individual patients, decreasing PvO2 or ventilation at FIO2 of 1.0 was associated with changes in intrapulmonary shunt. Therefore, we conclude that it is not possible to predict the influence of such interventions in pulmonary gas exchange in the individual patient suffering from ARDS. Differences in the regulation of the local distribution of blood flow caused by the disease itself might explain this phenomenon.

Acute Disease↗
PubMed1995

Incidence, severity, and mortality of acute respiratory failure in Berlin, Germany.

A prospective multicenter study was carried out from October 1 to November 30, 1991, to determine the incidence, severity, and mortality of acute respiratory failure (ARF) in Berlin, Germany, a metropolis with a population of 3.44 million. Adult patients from 72 intensive care units (ICUs) were evaluated. ARF was defined as: (1) intubation and mechanical ventilation (I+MV) > or = 24 h; age > or = 14 yr. Incidence of ARF was assessed as the number of patients fulfilling ARF criteria within the 2-mo study period. Severity of ARF was defined as "no lung injury" (NLI), "mild-to-moderate lung injury" (MMLI), and "severe lung injury" (SLI) according to Murray and coworkers' proposals. Mortality was assessed as number of patients with ARF dying during ICU stay. During the study period, 508 patients were diagnosed as having ARF, representing an incidence of ARF of 88.6 per 100,000/yr. Twenty-four h after I+MV, MMLI occurred in 94% and SLI in 3.6% of the ARF patients. Overall mortality rate was 42.7%. Mortality rate in the NLI group was 36.4%; in patients with MMLI, 40.8%; and in patients with SLI, 58.8%. Our data offer novel information on incidence, severity, and mortality of ARF in a major urban population.

Adult↗
PubMed1994

Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx.

Exogenous nitric oxide (NO) reduces pulmonary vascular resistance after low-dose inhalation in patients. To estimate endogenous NO synthesis in the upper respiratory tract, we measured inhaled and exhaled NO in volunteers and patients during spontaneous or controlled ventilation, respectively. 20.3 nmol per min NO was synthesised in the nasopharynx of non-smoking volunteers, leading to autoinhalation of 0.07-0.13 NO parts per million during inspiration; smokers had reduced NO synthesis. In volunteers, 50-70% of the NO was resorbed by the lungs; ventilated patients were deprived of NO autoinhalation. Bacteria in the nose may take part in endogenous NO synthesis.

Adolescent↗
PubMed1994

[The relevance of perioperative coagulation parameters to indications for blood transfusion. A retrospective analysis of 300 liver transplantations].

In the present study, a retrospective statistical analysis of laboratory data, clinical data, and perioperative blood requirements from 300 primary orthotopic liver transplantations (OLT) is described. METHODS. OLT was performed using established surgical techniques and total IV anaesthesia. Volume was substituted with red blood cells (RBC) and fresh frozen plasma (FFP) according to haemodynamic data, haemoglobin, and diuresis. Platelet counts, prothrombin time, activated partial thromboplastin time (aPTT), thrombin time, fibrinogen, and antithrombin III were registered but not used as indications for transfusions. Statistics were performed using regression analysis and analysis of variance. RESULTS. The mean intraoperative fluid requirement was 793 ml balanced salt solution, 7.1 units RBC, and 8.4 units FFP; pooled random donor platelets were given only once. During 24 h postoperatively, an average of 1.8 units RBC and 4.6 units FFP had to be transfused. Currently, 278 of the 300 patients (92.7%) are alive. There was no significant correlation between clotting data and intraoperative blood use; for postoperative transfusion rates, the preoperative aPTT and postoperative platelet counts had a significant correlation. Reviewing the basic diseases of the patients, there were significant differences in coagulation status, but no differences in transfusion rates. CONCLUSION. According to the data presented, indications for transfusions in OLT according to clotting data are not valid, since these data do not correlate with the blood requirement. In addition, strategies for pretreatment of patients such as preoperative plasmapheresis are no longer justified with respect to possible side effects.

Adult↗
PubMed1994

Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome.

In 12 patients with severe adult respiratory distress syndrome (ARDS), pulmonary gas exchange and hemodynamics were evaluated before, during, and after a 2-h period of pressure-controlled mechanical ventilation with the patient in the prone position. Ventilation-perfusion relationships (VA/Q) were assessed by a multiple inert gas elimination technique. Pressure-controlled mechanical ventilation in the prone position resulted in an overall increase (p < or = 0.05) of arterial oxygenation after 120 min (98.4 +/- 50.3 to 146.2 +/- 94.9 mm Hg). Whereas eight patients revealed an improvement of PaO2 of more than 10 mm Hg after 30 min in the prone position (responders), four patients reacted to positional changes with a deterioration of arterial oxygenation (nonresponders). Data about the continuous distribution of ventilation-perfusion ratios revealed that in the responder group positioning caused a decrease of shunt perfusion of 11 +/- 5% and a concomitant increase of normal VA/Q by 12 +/- 4% after 30 min. There was no change demonstrable within low VA/Q areas. Returning the patient to the supine position reversed the improvement in gas exchange. The nonresponder group did not show any significant alteration in the distribution of VA/Q during the study. We concluded that improvement of oxygenation during pressure-controlled mechanical ventilation in the prone position is due to a shift of blood flow away from shunt regions, thus increasing areas with normal VA/Q. This redistribution of blood flow is most likely caused by a recruitment of previously ateletatic but nondiseased areas induced by altered gravitational forces.

Adolescent↗