K Falke

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.

Abstract Objective: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). Design: Uncontrolled prospective trial. Setting: One university hospital intensive care department. Patients and participants: 122 patients with ARDS, consecutively admitted to the ICU. Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) group (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Measurements and results: The groups differed in both APACHE II (16 ± 5 vs 18 ± 5 points, p = 0.01) and Murray scores (3.2 ± 0.3 vs 3.4 ± 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 ± 9 vs 13 ± 9 days, p = 0.0151), and length of ICU stay in Berlin (31 ± 17 vs 50 ± 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 ± 27 mm Hg in AT-sine-ECMO patients that improved to 165 ± 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 ± 28 mm Hg and improvement to 160 ± 102 mm Hg was not reached until ICU day 13. Q˙S/Q˙T was significantly higher in the ECMO-treated group and exceeded 50 % during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75 %. Survival rates were 89 % in the AT-sine ECMO group and 55 % in the ECMO treatment group (p = 0.0000). Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.

Postoperative tracheal extubation after orthotopic liver transplantation

Background: The duration of postoperative mechanical ventilation and its influence on pulmonary function in liver transplant recipients is still debated controversially.

Incidence and indications for reintubation during postoperative care following orthotopic liver transplantation

STUDY OBJECTIVE To analyze the incidence and indications for reintubation during postoperative care following orthotopic liver transplantation (OLT). DESIGN Retrospective chart review. SETTING Large metropolitan teaching hospital. PATIENTS 546 adult liver transplant recipients. MEASUREMENTS AND MAIN RESULTS The medical charts of 546 patients who underwent OLT at our institution between January 1992 and September 1996 were reviewed for the incidence and indications of reintubation throughout primary hospitalization. Eighty-one of 546 patients (14.8%) required one or more episodes of reintubation after OLT. In the majority of cases, reintubation was performed for pulmonary complications (44.6%), followed by cerebral (19.1%) and surgical (14.5%) complications. Cardiac (9.1%) and peripheral neurologic (2.7%) complications were less frequent reasons for reintubation. Overall patient survival, according to the Kaplan-Meier estimates, was 89.9%, 87.5%, 86.5%, and 82.2% after 1, 2, 3, and 5 years, respectively. In patients with one or more episodes of reintubation, overall survival decreased to 62.5% after 1, 2, and 3 years, and to 56.4% after 5 years (p < 0.001). CONCLUSIONS The main indications for reintubation after OLT were pulmonary, cerebral, and surgical complications. These reintubation events had a considerable influence on the patients postoperative recovery, and were associated with a significantly higher rate of mortality, than for OLT patients who did not undo reintubation.

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.

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 μg · 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 μg · 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 ≥ 8.0 μg · kg–1· min–1 did not improve pulmonary gas exchange compared to controls. When compared to low doses of Alm < 4.0 μg · kg–1· min–1, high doses ≥ 8.0 μg · 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.

The relevance of perioperative coagulation parameters to indications for blood transfusion. Analysis of 300 liver transplantations

Zusammenfassung. Ein Problem bei der Analyse von Transfusionsdaten ist die uneinheitliche Indikationsstellung: der geschätzte Blutverlust, perioperative Labordaten und/oder hämodynamische Parameter werden hierbei je nach Ausbildung des Anästhesisten und seiner persönlichen Bewertung herangezogen. Bei orthotopen Lebertransplantationen, die sich durch massive Entgleisungen des Gerinnungssystems und einen hohen Transfusionsbedarf auszeichnen, scheint diesbezüglich die Tendenz zu bestehen, durch ein zunehmend perfektioniertes perioperatives Monitoring der Gerinnung die Indikation zu Transfusionen nach Labordaten und weniger nach der Klinik des Patienten zu richten. Die aktuellen medizinischen, ethisch-rechtlichen und nicht zuletzt auch finanziellen Aspekte bei der Übertragung von Fremdblut ließen eine diesbezügliche Studie sinnvoll erscheinen. Nach 300 Lebertransplantationen, bei denen zur Indikation von Bluttransfusionen hämodynamische Parameter, Diurese und Hämoglobin herangezogen wurden, wurde festgestellt, daß 1) die perioperativen Gerinnungsparameter nicht mit dem Transfusionsbedarf korrelierten, 2) der Transfusionsbedarf vergleichsweise niedrig gehalten werden konnte, und 3) auch postoperativ kein erhöhter Transfusionsbedarf entstand. Die Relevanz perioperativer Gerinnungsdaten für die Indikation von Bluttransfusionen bei Lebertransplantationen muß daher auch weiterhin als fraglich eingeschätzt werden.Abstract. 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.

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 48h, fibrinogen decreased 28.7%, thrombin-antithrombin-III complexes were elevated before ECLA (53 μg/L), but demonstrated an additional peak (238 μg/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.

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise.

Objective: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers.¶Design: Prospective observational study.¶Setting: University laboratory.¶Participants: Fourteen healthy adult volunteers.¶Interventions: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min.¶Measurement and results: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 ± 89 nl/min for non-smokers and 261 ± 142 nl/min for smokers (mean ± SD, n. s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 ± 21 nl/min versus 23 ± 14 nl/min, p < 0.05; smokers: 41 ± 8 nl/min versus 22 ± 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 ± 3.1 ppb at rest and this decreased to 9.3 ± 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 ± 2 to 21 ± 3 l/min.¶Conclusion: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.

Klinische Aspekte des akuten Lungenversagens des Erwachsenen (ARDS)

ZusammenfassungDas akute Lungenversagen des Erwachsenen ist selten, aber auch heute noch mit einer sehr hohen Letalität belastet, wenngleich sich in den letzten Jahren ein Trend zu verbesserten Überlebensraten abzuzeichnen beginnt. Neuere Studien haben gezeigt, daß die bis vor kurzem noch in der Behandlung des ARDS angewendete Beatmungstherapie mit großen Atemzugvolumina, hohen Beatmungsdrücken und hohen inspiratorischen Sauerstoffkonzentrationen die erkrankte Lunge weiter schädigen kann. Diese Erkenntnisse haben zu einem Umdenken in der Behandlung geführt. Vorrangiges Ziel ist heute nicht mehr, die Wiederherstellung und Aufrechterhaltung physiologischer Normwerte für Sauerstoff- und Kohlendioxidpartialdrücke sowie arteriellen pH zu erreichen, sondern die Lunge vor beatmungsinduzierten Schäden zu schützen.Hierzu hat sich ein erweitertes Behandlungskonzept, bestehend aus verschiedenen Formen der drucklimitierten Beatmung mit PEEP und permissiver Hyperkapnie, Lagerungsmaßnahmen, Inhalation von Stickstoffmonoxid und – zumindest in Europa – extrakorporaler Membranoxygenierung als erfolgreich erwiesen, ohne daß die Effizienz jeder einzelnen Methode in kontrollierten randomisierten Studien bewiesen worden wäre. In dem vorliegenden Übersichtsartikel werden die neuesten Entwicklungen aufgezeigt, diskutiert und im Hinblick auf ihre klinische Effizienz bewertet.AbstractAcute 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.

Morphological changes in chest radiographs of patients with acute respiratory distress syndrome (ARDS)

Objective: To determine whether the quality of infiltrations in chest radiographs can accurately predict the histological extent of fibrotic change in patients with acute respiratory distress syndrome (ARDS). Design: Retrospective clinical investigation. Setting: Intensive care unit (ICU) of a university teaching hospital. Patients and methods: Of 47 patients treated with extracorporeal membrane oxygenation (ECMO) for severe ARDS over a 5-year period, 23 patients underwent open lung biopsy at thoracotomy for treatment, mostly of pneumothorax. Chest films obtained by portable chest roentgenography preceding the operation were reviewed retrospectively and compared to the histomorphological results of the lung specimen. Results: Chest radiographs displayed mixed alveolar-reticular opacification in 60.2 %, alveolar patterns in 22.9 % and reticular opacities in 10.5 %. In 0.4 % there were no infiltrates, 6 % could not be evaluated because of insufficient quality. There was no relevant difference between the right and left lungs. Subdividing patients into two groups according to the histological results of either absent or mild (1) or severe (2) lung fibrosis, we found an alveolar haziness in 12.3 % in group 1 compared with 28.2 % in group 2, while reticular characteristics were identified in 13 % and 11 %, respectively. Conclusions: The most common opacity in chest radiographs of patients with severe ARDS treated with ECMO is mixed alveolar-reticular opacification. Severe lung fibrosis is not positively correlated with a reticular radiographic pattern. ECMO does not lead to specific radiological changes in conventional radiograms, contrary to clinical findings that treatment with ECMO might induce pleural or pulmonic haemorrhage, especially in the earlier days when systemic heparinization had to be used instead of the heparin-coated tube-surfacing.