[Non-invasive Mechanical Ventilation in Acute Respiratory Failure. Clinical Practice Guidelines - on behalf of the German Society of Pneumology and Ventilatory Medicine]. / S2k-Leitlinie Nichtinvasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The guideline update outlines the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.Non-invasive ventilation (NIV) has a high value in therapy of hypercapnic acute respiratory failure, as it significantly reduces the length of ICU stay and hospitalization as well as mortality.Patients with cardiopulmonary edema and acute respiratory failure should be treated with continuous positive airway pressure (CPAP) and oxygen in addition to necessary cardiological interventions. This should be done already prehospital and in the emergency department.In case of other forms of acute hypoxaemic respiratory failure with only mild or moderately disturbed gas exchange (PaO2/FiO2 > 150 mmHg) there is no significant advantage or disadvantage compared to high flow nasal oxygen (HFNO). In severe forms of ARDS NIV is associated with high rates of treatment failure and mortality, especially in cases with NIV-failure and delayed intubation.NIV should be used for preoxygenation before intubation. In patients at risk, NIV is recommended to reduce extubation failure. In the weaning process from invasive ventilation NIV essentially reduces the risk of reintubation in hypercapnic patients. NIV is regarded useful within palliative care for reduction of dyspnea and improving quality of life, but here in concurrence to HFNO, which is regarded as more comfortable. Meanwhile NIV is also recommended in prehospital setting, especially in hypercapnic respiratory failure and pulmonary edema.With appropriate monitoring in an intensive care unit NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency.

Experimental blunt chest trauma--cardiorespiratory effects of different mechanical ventilation strategies with high positive end-expiratory pressure: a randomized controlled study.

BACKGROUND: Uncertainty persists regarding the optimal ventilatory strategy in trauma patients developing acute respiratory distress syndrome (ARDS). This work aims to assess the effects of two mechanical ventilation strategies with high positive end-expiratory pressure (PEEP) in experimental ARDS following blunt chest trauma. METHODS: Twenty-six juvenile pigs were anesthetized, tracheotomized and mechanically ventilated. A contusion was applied to the right chest using a bolt-shot device. Ninety minutes after contusion, animals were randomized to two different ventilation modes, applied for 24 h: Twelve pigs received conventional pressure-controlled ventilation with moderately low tidal volumes (VT, 8 ml/kg) and empirically chosen high external PEEP (16 cmH2O) and are referred to as the HP-CMV-group. The other group (n = 14) underwent high-frequency inverse-ratio pressure-controlled ventilation (HFPPV) involving respiratory rate of 65 breaths · min(-1), inspiratory-to-expiratory-ratio 2:1, development of intrinsic PEEP and recruitment maneuvers, compatible with the rationale of the Open Lung Concept. Hemodynamics, gas exchange and respiratory mechanics were monitored during 24 h. Computed tomography and histology were analyzed in subgroups. RESULTS: Comparing changes which occurred from randomization (90 min after chest trauma) over the 24-h treatment period, groups differed statistically significantly (all P values for group effect <0.001, General Linear Model analysis) for the following parameters (values are mean ± SD for randomization vs. 24-h): PaO2 (100% O2) (HFPPV 186 ± 82 vs. 450 ± 59 mmHg; HP-CMV 249 ± 73 vs. 243 ± 81 mmHg), venous admixture (HFPPV 34 ± 9.8 vs. 11.2 ± 3.7%; HP-CMV 33.9 ± 10.5 vs. 21.8 ± 7.2%), PaCO2 (HFPPV 46.9 ± 6.8 vs. 33.1 ± 2.4 mmHg; HP-CMV 46.3 ± 11.9 vs. 59.7 ± 18.3 mmHg) and normally aerated lung mass (HFPPV 42.8 ± 11.8 vs. 74.6 ± 10.0 %; HP-CMV 40.7 ± 8.6 vs. 53.4 ± 11.6%). Improvements occurring after recruitment in the HFPPV-group persisted throughout the study. Peak airway pressure and VT did not differ significantly. HFPPV animals had lower atelectasis and inflammation scores in gravity-dependent lung areas. CONCLUSIONS: In this model of ARDS following unilateral blunt chest trauma, HFPPV ventilation improved respiratory function and fulfilled relevant ventilation endpoints for trauma patients, i.e. restoration of oxygenation and lung aeration while avoiding hypercapnia and respiratory acidosis.

Short-term effects of noisy pressure support ventilation in patients with acute hypoxemic respiratory failure.

INTRODUCTION: This study aims at comparing the very short-term effects of conventional and noisy (variable) pressure support ventilation (PSV) in mechanically ventilated patients with acute hypoxemic respiratory failure. METHODS: Thirteen mechanically ventilated patients with acute hypoxemic respiratory failure were enrolled in this monocentric, randomized crossover study. Patients were mechanically ventilated with conventional and noisy PSV, for one hour each, in random sequence. Pressure support was titrated to reach tidal volumes approximately 8 mL/kg in both modes. The level of positive end-expiratory pressure and fraction of inspired oxygen were kept unchanged in both modes. The coefficient of variation of pressure support during noisy PSV was set at 30%. Gas exchange, hemodynamics, lung functional parameters, distribution of ventilation by electrical impedance tomography, breathing patterns and patient-ventilator synchrony were analyzed. RESULTS: Noisy PSV was not associated with any adverse event, and was well tolerated by all patients. Gas exchange, hemodynamics, respiratory mechanics and spatial distribution of ventilation did not differ significantly between conventional and noisy PSV. Noisy PSV increased the variability of tidal volume (24.4 ± 7.8% vs. 13.7 ± 9.1%, P <0.05) and was associated with a reduced number of asynchrony events compared to conventional PSV (5 (0 to 15)/30 min vs. 10 (1 to 37)/30 min, P <0.05). CONCLUSIONS: In the very short term, noisy PSV proved safe and feasible in patients with acute hypoxemic respiratory failure. Compared to conventional PSV, noisy PSV increased the variability of tidal volumes, and was associated with improved patient-ventilator synchrony, at comparable levels of gas exchange. TRIAL REGISTRATION: ClinicialTrials.gov, NCT00786292.

Bedside estimation of nonaerated lung tissue using blood gas analysis.

OBJECTIVES: Studies correlating the arterial partial pressure of oxygen to the fraction of nonaerated lung assessed by CT shunt yielded inconsistent results. We systematically analyzed this relationship and scrutinized key methodological factors that may compromise it. We hypothesized that both physiological shunt and the ratio between PaO2 and the fraction of inspired oxygen enable estimation of CT shunt at the bedside. DESIGN: : Prospective observational clinical and laboratory animal investigations. SETTING: ICUs (University Hospital Leipzig, Germany) and Experimental Pulmonology Laboratory (University of São Paulo, Brazil). PATIENTS, SUBJECTS AND INTERVENTIONS: Whole-lung CT and arterial blood gases were acquired simultaneously in 77 patients mechanically ventilated with pure oxygen. A subgroup of 28 patients was submitted to different Fio2. We also studied 19 patients who underwent repeat CT. Furthermore we studied ten pigs with acute lung injury at multiple airway pressures, as well as a theoretical model relating PaO2 and physiological shunt. We logarithmically transformed the PaO2/Fio2 to change this nonlinear relationship into a linear regression problem. MEASUREMENTS AND MAIN RESULTS: We observed strong linear correlations between Riley's approximation of physiological shunt and CT shunt (R = 0.84) and between logarithmically transformed PaO2/Fio2 and CT shunt (R = 0.86), allowing us to construct a look-up table with prediction intervals. Strong linear correlations were also demonstrated within-patients (R = 0.95). Correlations were significantly improved by the following methodological issues: measurement of PaO2/Fio2 during pure oxygen ventilation, use of logarithmically transformed PaO2/Fio2 instead of the "raw" PaO2/Fio2, quantification of nonaerated lung as percentage of total lung mass and definition of nonaerated lung by the [-200 to +100] Hounsfield Units interval, which includes shunting units within less opacified lung regions. CONCLUSION: During pure oxygen ventilation, logarithmically transformed PaO2/Fio2 allows estimation of CT shunt and its changes in patients during systemic inflammation. Relevant intrapulmonary shunting seems to occur in lung regions with CT numbers between [-200 and +100] Hounsfield Units.

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction.

INTRODUCTION: Quantitative computed tomography (qCT)-based assessment of total lung weight (Mlung) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI. METHODS: In this prospective observational study, Mlung was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for Mlung was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges. RESULTS: The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference Mlung value was 885 (771 to 973) g, and the reference interval for Mlung was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median Mlung value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had Mlung values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days. CONCLUSIONS: Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.

[Case report: sepsis and multi organ dysfunction syndrome in a patient returning from holiday on the Canary Islands: a difficult diagnosis]. / Kasuistik interaktiv: Lanzarote-Urlauber mit Sepsis und Multiorganversagen - Ein langer Weg bis zur richtigen Diagnose.

UNLABELLED: A forty-five year old male tourist suffers a febrile illness, delirium and severe abdominal pain on the fifth day of his holiday trip to the Canary Islands (Spain). After hospitalization he presents a surgical abdomen which requires emergency laparotomy however without detectable pathology. Progressing critical illness and septic shock leads to multiple organ failure, but focus identification is not possible. Well after return to Germany diagnostic uncertainty persists due to recurrent fever and possible travel-associated infections. Finally, besides a simple pararectal abscess, manifestation of acute intermittent porphyria is diagnosed. CONCLUSION: Clinicians should consider acute intermittent porphyria as a rare cause of a surgical abdomen. Its clinical presentation include abdominal pain, life-threatening neurovisceral, neurological and psychiatric symptoms, hypertension, tachycardia, hyponatriemia and reddish urine.

Evidence and consensus-based German guidelines for the management of analgesia, sedation and delirium in intensive care--short version.

Targeted monitoring of analgesia, sedation and delirium, as well as their appropriate management in critically ill patients is a standard of care in intensive care medicine. With the undisputed advantages of goal-oriented therapy established, there was a need to develop our own guidelines on analgesia and sedation in intensive care in Germany and these were published as 2(nd) Generation Guidelines in 2005. Through the dissemination of these guidelines in 2006, use of monitoring was shown to have improved from 8 to 51% and the use of protocol-based approaches increased to 46% (from 21%). Between 2006-2009, the existing guidelines from the DGAI (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin) and DIVI (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin) were developed into 3(rd) Generation Guidelines for the securing and optimization of quality of analgesia, sedation and delirium management in the intensive care unit (ICU). In collaboration with another 10 professional societies, the literature has been reviewed using the criteria of the Oxford Center of Evidence Based Medicine. Using data from 671 reference works, text, diagrams and recommendations were drawn up. In the recommendations, Grade "A" (very strong recommendation), Grade "B" (strong recommendation) and Grade "0" (open recommendation) were agreed. As a result of this process we now have an interdisciplinary and consensus-based set of 3(rd) Generation Guidelines that take into account all critically illness patient populations. The use of protocols for analgesia, sedation and treatment of delirium are repeatedly demonstrated. These guidelines offer treatment recommendations for the ICU team. The implementation of scores and protocols into routine ICU practice is necessary for their success.

[Intra-abdominal hypertension and abdominal compartment syndrome--basic knowledge and anesthesiological aspects]. / Intraabdominelle Hypertonie und abdominelles Kompartmentsyndrom--Basiswissen und anästhesiologische Aspekte.

The increase in intra-abdominal pressure may be followed by a renal, gut, respiratory and cardial dysfunction and an increase in intra-cranial pressure. The review focuses risk factors and pathophysiological consequences of intra-abdominal hypertension and of abdominal compartment syndrome. Patients with intra-abdominal hypertension and abdominal compartment syndrome are critical ill and need special anesthesiological care due to risk of pulmonary aspiration, hemodynamic disturbances and difficult mechanical ventilation.

[The significance of perioperative immunonutrition]. / Stellenwert der perioperativen Immunonutrition.

Perioperative immunonutrition is aiming at modulating altered immunological and metabolic functions in the context of major surgery. It is defined as the supplementation of constitutionally essential substrates such as glutamine, arginine, omega-3-fatty acids or nucleotides. The application of such formula is recommended for patients undergoing major abdominal-surgical procedures and tumour surgery in the head neck area. The substitution should be given 5-7 days before and after the intervention.

Image reconstruction affects computer tomographic assessment of lung hyperinflation.

OBJECTIVES: Lung hyperinflation may be assessed by computed tomography (CT). As shown for patients with emphysema, however, CT image reconstruction affects quantification of hyperinflation. We studied the impact of reconstruction parameters on hyperinflation measurements in mechanically ventilated (MV) patients. DESIGN: Observational analysis. SETTING: A University hospital-affiliated research Unit. PATIENTS: The patients were MV patients with injured (n = 5) or normal lungs (n = 6), and spontaneously breathing patients (n = 5). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Eight image series involving 3, 5, 7, and 10 mm slices and standard and sharp filters were reconstructed from identical CT raw data. Hyperinflated (V(hyper)), normally (V(normal)), poorly (V(poor)), and nonaerated (V(non)) volumes were calculated by densitometry as percentage of total lung volume (V(total)). V(hyper) obtained with the sharp filter systematically exceeded that with the standard filter showing a median (interquartile range) increment of 138 (62-272) ml corresponding to approximately 4% of V(total). In contrast, sharp filtering minimally affected the other subvolumes (V(normal), V(poor), V(non), and V(total)). Decreasing slice thickness also increased V(hyper) significantly. When changing from 10 to 3 mm thickness, V(hyper) increased by a median value of 107 (49-252) ml in parallel with a small and inconsistent increment in V(non) of 12 (7-16) ml. CONCLUSIONS: Reconstruction parameters significantly affect quantitative CT assessment of V(hyper) in MV patients. Our observations suggest that sharp filters are inappropriate for this purpose. Thin slices combined with standard filters and more appropriate thresholds (e.g., -950 HU in normal lungs) might improve the detection of V(hyper). Different studies on V(hyper) can only be compared if identical reconstruction parameters were used.

Successful emergency reversal of phenprocoumon anticoagulation with prothrombin complex concentrate: a prospective clinical study.

The present prospective study was designed to evaluate the effectiveness and safety of prothrombin complex concentrate (PCC) for emergency reversal of oral anticoagulation with phenprocoumon, a long-acting coumarin. Patients were eligible for study entry if they required emergency reversal of phenprocoumon anticoagulation because they needed invasive surgical or diagnostic procedures or were actively bleeding. Patients received one or more infusions of pasteurized nanofiltered PCC (Beriplex P/N). Primary study endpoints were changes in International Normalized Ratio, Quick value, factors II, VII, IX and X, and protein C 10, 30 and 60 min following PCC infusion. Eight adult patients were enrolled, seven requiring urgent invasive procedures and one experiencing intracranial bleeding. In the first infusion, patients received a median 3600 IU PCC at median infusion rate 17.0 ml/min. Mean (SD) baseline International Normalized Ratio was 3.4 (1.2). The International Normalized Ratio 10 min after PCC infusion declined to 1.3 or less in seven of eight patients and to 1.4 in one patient. After PCC infusion, the Quick value increased by a mean of 57% [confidence interval (CI), 45-69%], circulating factor II concentration by 85% (CI, 68-103%), factor VII by 51% (CI, 40-62%), factor IX by 61% (CI, 47-76%), factor X by 115% (CI, 95-135%) and protein C by 100% (CI, 82-117%). Clinical effectiveness of PCC treatment was rated 'very good' in seven patients and 'satisfactory' in one. No thromboembolic or other adverse events occurred. PCC treatment rapidly, effectively and safely reversed phenprocoumon anticoagulation in patients undergoing urgent invasive procedures or actively bleeding.

Early recovery from post-traumatic acute respiratory distress syndrome.

BACKGROUND: To present and discuss the rationale and possible benefits of timely alveolar recruitment in early post-traumatic acute respiratory distress syndrome. METHODS: A 17-year-old patient who had sustained blunt thoracic trauma presented with severe hypoxaemia on admission and whole body computed tomography showed pulmonary contusion and substantial bilateral atelectasis. Oxygenation and lung mechanics did not improve with low tidal volume ventilation using high positive end-expiratory pressures (PEEPs). Therefore we applied an alveolar recruitment manoeuvre 7 h after admission. After alveolar recruitment, PEEP was titrated to the lowest level which prevented alveolar derecruitment. RESULTS: Oxygenation and lung compliance improved rapidly and aeration of the entire lung was confirmed by computed tomography 27 h after the recruitment manoeuvre. The patient recovered completely and was discharged after 17 days. CONCLUSION: Although robust evidence is still lacking, several lines of evidence suggest potential benefits of timely alveolar recruitment. Patients with early post-traumatic respiratory failure seem to most readily respond to alveolar recruitment manoeuvres and could thus benefit from the gain in functional lung volume and oxygenation. Moreover the probability of ventilator associated complications may be reduced.

Impact of age on in-hospital mortality of surgical patients in a German university hospital.

Although the frequency of major surgical procedures in elderly patients is increasing, the impact of age as an independent factor on in-hospital mortality and capacity planning is uncertain. Therefore, we analyzed how age, gender, number of diagnoses, and number of operations per patient are reflecting the demographic changes going on in the last decade. Furthermore, we analyzed the influence of age, main diagnoses, and comorbidities on in-hospital mortality, and cost factors, like duration of in-hospital stay, number of operations, and stay at the intensive care unit using multiple regression analysis. One thousand four hundred and sixty-nine patients hospitalized in 1990, and 5,718 patients hospitalized during 1998-2000 at the surgical department of a German university hospital were recruited. The average age of the patients increased significantly from the year 1990 to 1999 (by 4 years). The overall in-hospital mortality of the elderly patients (above 70 years of age) declined from 18.6% in 1990 to 7.6% in 2000. The number of diagnoses increased from 1.27 to 3.5 per patient. Age is a significant, independent risk factor for in-hospital mortality (odd's ratio (OR), 2.2), prolonged stay at intensive care unit (OR, 1.8), reoperation (OR, 1.3), and prolonged hospitalization (OR, 1.8). Nevertheless, oncologic diseases and pre-existing comorbidities are also significant independent factors for the clinical course and costs resulting from treating elderly patients. We conclude that decisions for surgical treatment should not be solely based on patient's age. The demographic changes in Europe result in an over-proportional increase in expenditures, which should be included when planning the capacities of a surgical department.

Alveolar recruitment in combination with sufficient positive end-expiratory pressure increases oxygenation and lung aeration in patients with severe chest trauma.

OBJECTIVE: Investigation of oxygenation and lung aeration during mechanical ventilation according to the open lung concept in patients with acute lung injury or acute respiratory distress syndrome. DESIGN: Retrospective analysis. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: We retrospectively identified 17 patients with acute lung injury/acute respiratory distress syndrome due to pulmonary contusion who had thoracic helical computed tomography scans before and after ventilation with the open lung concept. INTERVENTIONS: Baseline ventilation consisted of low tidal volumes (< or =6 mL/kg) and positive end-expiratory pressure (PEEP; 5-17 cm H2O). We briefly applied high inspiratory pressures for opening up collapsed alveoli. External PEEP and intrinsic PEEP were combined to keep recruited lung units open. We generated intrinsic PEEP by pressure-cycled high-frequency inverse ratio ventilation (80 min, inspiratory/expiratory ratio 2:1) and maintained our ventilatory strategy for 24 hrs. Then, after reducing total PEEP by decreasing respiratory rate, Pao2/Fio2 ratio was reevaluated. If it remained >300 mm Hg, weaning was started. If not, previous ventilator settings were resumed for another 24 hrs after recruiting the lungs once again. MEASUREMENTS AND MAIN RESULTS: Physiologic variables and ventilator settings were obtained from routine charts. Data from computed tomography before and after the open lung concept were analyzed for volumetric quantification of lung aeration and collapse. All results are presented as median and range. During baseline ventilation, PEEP was 10 (range, 5-17) cm H2O and after recruitment 21 (range, 18-26) cm H2O. Opening pressures were 65 (range, 50-80) cm H2O. After recruitment, Pao2/Fio2 ratio was higher in all patients. Total lung volume increased from 2915 (range, 1952-4941) to 4247 (range, 2285-6355) mL and normally aerated volume from 1742 (range, 774-2941) to 2971 (range, 1270-5232) mL. Atelectasis decreased significantly from 604 (range, 147-1538) to 106 (range, 0-736) mL. Hyperinflation increased significantly from 5 (range, 0-188) to 62 (range, 1-424) mL, whereas poor aeration did not change substantially from 649 (range, 302-1292) to 757 (range, 350-1613) mL. No hemodynamic problems occurred. CONCLUSIONS: Lung recruitment increased arterial oxygenation, normally aerated lung volume, and total lung volume while decreasing the amount of collapsed tissue. These results indicate that the open lung concept is a reasonable mode of ventilation for patients with severe chest trauma.

Is there a place for thyroidectomy in older patients with thyrotoxic storm and cardiorespiratory failure?

Early thyroidectomy is the treatment of choice for thyrotoxic storm in patients with thyroid autonomy often induced by iodine. However, older patients who are mostly affected by this condition often have underlying chronic cardiopulmonary diseases, apparently contradicting surgical intervention. The published evidence for suitable treatment strategies in these patients is limited. We report the outcome of a series of older critically ill patients who were treated by thyroidectomy because of thyrotoxic storm. We retrospectively analyzed the outcome of 10 patients (4 males, 6 females; 70 years of age, range, 54-79, Burch-Wartofsky point scale, 61; range, 40-85) with thyrotoxic storm, thyroid autonomy, and severe cardiorespiratory and renal failure with cardiac arrhythmia, coronary artery or chronic obstructive pulmonary disease, or acute inflammation. Thyroidectomy was performed for the following reasons: symptoms of thyrotoxic storm deteriorated or did not improve within 24-48 hours despite intensive medical treatment, or patients developed thionamide-induced agranulocytosis or severe thrombocytopenia. All patients with severe accompanying diseases survived thyroidectomy (early post-operative mortality, 0%). The two oldest patients died 2-3 weeks after thyroidectomy because of myocardial infarction or respiratory failure (late postoperative mortality, 20%). In contrast, in the few previous reports of patients who underwent thyroidectomy for thyrotoxic storm and severe accompanying diseases (n = 7), late postoperative mortality was 43%. The overall mortality for all reported patients including our own, who underwent thyroidectomy for thyrotoxic storm with and without severe accompanying disease (n = 49) was 10%. Our results suggest that early total thyroidectomy should be considered as the method of choice for older, chronically ill patients with thyrotoxic storm complicated by cardiorespiratory and renal failure, especially if high-dose thionamide treatment, iopanoic acid, glucocorticoids, and intensive care fail to improve the patient's conditions within 12-24 hours.

Efficacy and safety of a prothrombin complex concentrate with two virus-inactivation steps in patients with severe liver damage.

OBJECTIVE: To evaluate the efficacy and safety of intravenous infusions of an improved prothrombin complex concentrate (PCC) formulation. PATIENTS AND METHODS: Twenty-two adults with haemostatic defects due to severe liver disease (Quick's test 50%), which required rapid haemostasis because of bleeding or before urgent surgery or invasive intervention. Laboratory follow-up, including the response and in-vivo recovery of the substituted coagulation factors II, VII, IX and X and protein C took place before, then 10 min, 30 min and 60 min after PCC substitution. Clinical efficacy (avoidance or cessation of bleeding) was assessed using a scale ranging from 'very good' to 'none'. RESULTS: Patients received a median PCC dose of 25.7 IU/kg. The response of factor IX and protein C was 1.2-1.4 (IU/dl)/(IU/kg), the in-vivo recovery was 49.7-57.4%, and the Quick's test increased from 39% to a maximum of 65%. Levels of activation markers of the coagulation system factor VIIa, prothrombin fragment 1 + 2 and thrombin antithrombin complex (TAT) increased, but without evidence of any thromboembolic events. Clinical efficacy was judged as 'very good' in 76% of patients after the first (n = 21) treatment. There were no changes in serological status regarding transmission of HIV, hepatitis A virus, hepatitis B virus and hepatitis C virus. No PCC-related adverse reactions occurred. CONCLUSIONS: The infusion of pasteurized, nanometre-filtered PCC is an effective, well-tolerated method of correcting prothrombin complex deficiency in patients with severe liver disease with haemorrhage, or before an urgent surgical or invasive diagnostic intervention.