Prognostic factors, long-term survival, and outcome of cancer patients receiving chemotherapy in the intensive care unit.

Prognostic factors and outcomes of cancer patients with acute organ failure receiving chemotherapy (CT) in the intensive care unit (ICU) are still incompletely described. We therefore retrospectively studied all patients who received CT in any ICU of our institution between October 2006 and November 2013. Fifty-six patients with hematologic (n = 49; 87.5 %) or solid (n = 7; 12.5 %) malignancies, of which 20 (36 %) were diagnosed in the ICU, were analyzed [m/f ratio, 33:23; median age, 47 years (IQR 32 to 62); Charlson Comorbidity Index (CCI), 3 (2 to 5); Simplified Acute Physiology Score II (SAPS II), 50 (39 to 61)]. The main reasons for admission were acute respiratory failure, acute kidney failure, and septic shock. Mechanical ventilation and vasopressors were employed in 34 patients (61 %) respectively, hemofiltration in 22 (39 %), and extracorporeal life support in 7 (13 %). Twenty-seven patients (48 %) received their first CT in the ICU. Intention of therapy was cure in 46 patients (82 %). Tumor lysis syndrome (TLS) developed in 20 patients (36 %). ICU and hospital survival was 75 and 59 %. Hospital survivors were significantly younger; had lower CCI, SAPS II, and TLS risk scores; presented less often with septic shock; were less likely to develop TLS; and received vasopressors, hemofiltration, and thrombocyte transfusions in lower proportions. After discharge, 88 % continued CT and 69 % of 1-year survivors were in complete remission. Probability of 1- and 2-year survival was 41 and 38 %, respectively. Conclusively, administration of CT in selected ICU cancer patients was feasible and associated with considerable long-term survival as well as long-term disease-free survival.

Extracorporeal membrane oxygenation in adult patients with hematologic malignancies and severe acute respiratory failure.

INTRODUCTION: Acute respiratory failure (ARF) is the main reason for intensive care unit (ICU) admissions in patients with hematologic malignancies (HMs). We report the first series of adult patients with ARF and HMs treated with extracorporeal membrane oxygenation (ECMO). METHODS: This is a retrospective cohort study of 14 patients with HMs (aggressive non-Hodgkin lymphoma (NHL) n = 5; highly aggressive NHL, that is acute lymphoblastic leukemia or Burkitt lymphoma, n = 5; Hodgkin lymphoma, n = 2; acute myeloid leukemia, n = 1; multiple myeloma, n = 1) receiving ECMO support because of ARF (all data as medians and interquartile ranges; age, 32 years (22 to 51 years); simplified acute physiology score II (SAPS II): 51 (42 to 65)). Etiology of ARF was pneumonia (n = 10), thoracic manifestation of NHL (n = 2), sepsis of nonpulmonary origin (n = 1), and transfusion-related acute lung injury (n = 1). Diagnosis of HM was established during ECMO in four patients, and five first received (immuno-) chemotherapy on ECMO. RESULTS: Before ECMO, the PaO2/FiO2 ratio was 60 (53 to 65), (3.3 to 3.7). Three patients received venoarterial ECMO because of acute circulatory failure in addition to ARF; all other patients received venovenous ECMO. All patients needed vasopressors, and five needed hemofiltration. Thrombocytopenia occurred in all patients (lowest platelet count was 20 (11 to 21) G/L). Five major bleeding events were noted. ECMO duration was 8.5 (4 to 16) days. ICU and hospital survival was 50%. All survivors were alive at follow-up (36 (10 to 58) months); five patients were in complete remission, one in partial remission, and one had relapsed. CONCLUSIONS: ECMO therapy is feasible in selected patients with HMs and ARF and can be associated with long-term disease-free survival.

Prognostic factors for intensive care unit admission, intensive care outcome, and post-intensive care survival in patients with de novo acute myeloid leukemia: a single center experience.

BACKGROUND: Acute myeloid leukemia is a life-threatening disease associated with high mortality rates. A substantial number of patients require intensive care. This investigation analyzes risk factors predicting admission to the intensive care unit in patients with acute myeloid leukemia eligible for induction chemotherapy, the outcome of these patients, and prognostic factors predicting their survival. DESIGN AND METHODS: A total of 406 consecutive patients with de novo acute myeloid leukemia (15-89 years) were analyzed retrospectively. Markers recorded at the time of diagnosis included karyotype, fibrinogen, C-reactive protein, and Charlson comorbidity index. In patients requiring critical care, the value of the Simplified Acute Physiology Score II, the need for mechanical ventilation, and vasopressor support were recorded at the time of intensive care unit admission. The independent prognostic relevance of the parameters was tested by multivariate analysis. RESULTS: Sixty-two patients (15.3%) required intensive care, primarily due to respiratory failure (50.0%) or life-threatening bleeding (22.6%). Independent risk factors predicting intensive care unit admission were lower fibrinogen concentration, the presence of an infection, and comorbidity. The survival rate was 45%, with the Simplified Acute Physiology Score II being the only independent prognostic parameter (P<0.05). Survival was inferior in intensive care patients compared to patients not admitted to an intensive care unit. However, no difference between intensive care and non-intensive care patients was found concerning continuous complete remission at 6 years or survival at 6 years in patients who survived the first 30 days after diagnosis (non-intensive care patients: 28%; intensive care patients: 20%, P>0.05). CONCLUSIONS: Ongoing infections, low fibrinogen and comorbidity are predictive for intensive care unit admission in acute myeloid leukemia. Although admission was a risk factor for survival, continuous complete remission and survival of patients alive at day 30 were similar in patients who were admitted or not admitted to an intensive care unit.

Short-term effects of combining upright and prone positions in patients with ARDS: a prospective randomized study.

INTRODUCTION: Prone position is known to improve oxygenation in patients with acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). Supine upright (semirecumbent) position also exerts beneficial effects on gas exchange in this group of patients. We evaluated the effect of combining upright and prone position on oxygenation and respiratory mechanics in patients with ALI or ARDS in a prospective randomized cross-over study. METHODS: After turning them prone from a supine position, we randomized the patients to a prone position or combined prone and upright position. After 2 hours, the position was changed to the other one for another 6 hours. The gas exchange and static compliance of the respiratory system, lungs, and chest wall were assessed in the supine position as well as every hour in the prone position. RESULTS: Twenty patients were enrolled in the study. The PaO2/FiO2 ratio improved significantly from the supine to the prone position and further significantly increased with additional upright position. Fourteen (70%) patients were classified as responders to the prone position, whereas 17 (85%) patients responded to the prone plus upright position compared with the supine position (P = n.s.). No statistically significant changes were found with respect to compliance. CONCLUSIONS: Combining the prone position with the upright position in patients with ALI or ARDS leads to further improvement of oxygenation. TRIAL REGISTRATION: Clinical Trials No. NCT00753129.

Continuous lateral rotation therapy to prevent ventilator-associated pneumonia.

OBJECTIVE: To investigate the impact of prophylactic continuous lateral rotation therapy on the prevalence of ventilator-associated pneumonia, duration of mechanical ventilation, length of stay, and mortality in critically ill medical patients. DESIGN: Prospective, randomized, clinical study. SETTING: Three medical intensive care units of an university tertiary care hospital. PATIENTS: Patients were randomized to continuous lateral rotation therapy or standard care if they were mechanically ventilated for <48 hrs and free from pneumonia. Primary study end point was development of ventilator-associated pneumonia. Ventilator-associated pneumonia was defined as infiltrate on the chest radiograph plus newly developed purulent tracheal secretion plus increasing signs of inflammation. The diagnosis had to be confirmed microbiologically and required the growth of a pathogen >10(4) colony-forming units/mL in bronchoalveolar lavage. Radiologists were blinded to randomization whereas clinical outcome assessors were not. INTERVENTIONS: Rotation therapy was performed continuously in a specially designed bed over an arc of 90 degrees. Additional measures to prevent ventilator-associated pneumonia were equally standardized in both groups including semirecumbent position. MEASUREMENTS AND MAIN RESULTS: Ventilator-associated pneumonia frequency during the intensive care unit stay was 11% in the rotation group and 23% in the control group (p = .048), respectively. Duration of ventilation (8 +/- 5 vs. 14 +/- 23 days, p = .02) and length of stay (25 +/- 22 days vs. 39 +/- 45 days, p = .01) were significantly shorter in the rotation group. In a forward stepwise logistic regression model including the continuous lateral rotation therapy, gender, Lung Injury Score, and Simplified Acute Physiology Score II, continuous lateral rotation therapy just failed to reach statistical significance with respect to development of ventilator-associated pneumonia (p = .08). Intolerance to continuous lateral rotation therapy during the weaning phase was observed in 29 patients (39%). Mortality was comparable in both groups. CONCLUSIONS: Ventilator-associated pneumonia prevalence was significantly reduced by continuous lateral rotation therapy. Continuous lateral rotation therapy led to shorter ventilation time and length of stay. Continuous lateral rotation therapy should be considered in ventilated patients at risk for ventilator-associated pneumonia as a feasible method exerting additive effects to other preventive measures.

Don't drink and chill: Effects of alcohol on subjective and physiological reactions during music listening and their relationships with personality and listening habits.

Recent research indicates that favorite music can induce chills and alters physiological reactions. People frequently listen to music when they drink alcohol, for example in bars or discotheques. Alcohol has numerous effects on emotions, peripheral physiological and neural reactions. We investigated whether alcohol intake influences chill experiences and physiological reactions during music listening. 39 participants took part in the study and were tested twice: Once in a sober condition and once when they had drunken alcohol. Participants listened to two pieces of music in each of the two conditions: A favorite self-selected song and a control-song that was selected by the research group. Participants had to indicate when they experienced a chill and electrodermal activity and heart rate were measured during music listening. In addition, participants filled out questionnaires concerning the big five personality dimensions, music listening habits and general chill experiences. Results indicate that participants experienced most chills when they were sober and listened to their self-selected song. Electrodermal activity was highest when participants were sober. In addition, alcohol intake led to a dedifferentiation in heart rate activity. After alcohol intake, participants had similar heart rates, no matter whether they listened to their self-selected song or to the control-song. Extraversion was negatively related with physiological reactions, while openness to experiences was positively related with physiological reactions. Music listening habits also showed various relationships with chill experiences and physiological reactions, while general chill experiences did not. We conclude that alcohol intake reduces subjective chill experiences during music listening and alters the physiological reactions to music. Music listening habits and personality seem to influence these effects.

Prolonged lateral steep position impairs respiratory mechanics during continuous lateral rotation therapy in respiratory failure.

OBJECTIVE: To establish whether prolonged lateral steep position during continuous rotation therapy leads to improvement on pulmonary gas exchange, respiratory mechanics and hemodynamics. DESIGN: Prospective observational study. SETTING: Intensive care unit of a university hospital. PATIENTS: Twelve consecutive patients suffering from acute lung injury or adult respiratory distress syndrome undergoing continuous rotation therapy. INTERVENTIONS: Blood gas analysis, static lung compliance, blood pressure, cardiac index and pulmonary shunt fraction were measured in supine as well as in left and right lateral steep position at 62 degrees during continuous rotation therapy (phase I). Rotation was then stopped for 30 min with the patients in supine position, left and right lateral steep position, and the same measurements were performed every 10 min (phase II). MEASUREMENTS AND RESULTS: Phase I and II revealed no significant changes in PaO(2)/FiO(2) ratio, mean arterial blood pressure, pulmonary shunt fraction, or cardiac index. Significantly lower static compliance was observed in lateral steep position than in supine position (p<0.001). Concomitantly, PaCO(2) was significantly lower in supine position than in left and right lateral steep position (p<0.01). CONCLUSIONS: Lateral steep positioning impairs the compliance of the respiratory system. Prolonged lateral steep position does not lead to benefits with respect to oxygenation or hemodynamics. Individual response to the different positions is unpredictable. The pauses in "extreme" positions should be as short as possible.

Respiratory failure after stem cell transplantation: improved outcome with non-invasive ventilation.

We retrospectively analyzed the efficacy of non-invasive ventilation in 35 patients with acute hypoxemic respiratory failure after autologous or allogeneic stem cell transplantation (SCT). Non-invasive ventilation was delivered by a standard face mask or helmet. Decisions to intubate were made according to standard criteria. Between 1993 and 2003, 836 patients underwent an autologous or allogeneic bone marrow or SCT. Eighty-two patients developed respiratory failure. Of these, 47 patients were initially intubated and mechanically ventilated. None of these patients survived. Thirty-five patients initially underwent non-invasive ventilation at the bone marrow transplant unit. Seven of these patients survived and were discharged from the hospital (20%). Eleven of the 35 (31%) patients improved within the first 4 h of non-invasive ventilation with respect to oxygenation and were regarded as responders. Seven of these patients survived to hospital discharge (64%), while all non-responders died (P<0.001). In all survivors, the partial pressure of arterial oxygen (PaO2) improved after the initiation of non-invasive ventilation. In non-survivors, PaO2 improved in only 4 of 28 patients (17%) (P<0.0001). Non-invasive ventilation in patients with acute respiratory failure after SCT could improve prognosis in a carefully selected group of patients.

Unilateral chronic thromboembolic pulmonary disease associated with combined inherited thrombophilia.

Chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be an extreme variant of pulmonary thromboembolism. The underlying mechanisms for the failure of thrombus resolution are still unclear. In looking for inherited thrombophilia, an association with a lupus anticoagulant has been described repeatedly, and single cases of anticoagulant deficiencies (ie, antithrombin [AT], protein C, and protein S) have been reported. We describe a young patient with type I AT deficiency, the heterozygous prothrombin G20210A mutation, and unilateral chronic thromboembolic pulmonary disease presenting after a single thrombotic event. Pulmonary vascular patency was restored successfully by surgical pulmonary thromboendarterectomy. This case is unique because unilateral CTEPH is extremely uncommon, and it illustrates the severe clinical sequelae of the cosegregation of inherited thrombophilic defects.

Comparison of three severity scores for critically ill cancer patients.

OBJECTIVE: To compare three scoring systems, the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS) II and a modified Mortality Probability Model II (ICU cancer mortality model, ICMM) for their prognostic value for mortality during hospital stay in a group of cancer patients admitted to a medical ICU. DESIGN: Prospective cohort study. SETTING: Medical ICU of a tertiary care hospital. PATIENTS: Two hundred forty-two consecutive cancer patients admitted to the ICU. MEASUREMENTS AND RESULTS: Variables included in APACHE II, SAPS II and the ICMM scores as well as demographic data were assessed during the first 24 h of stay in the ICU. Hospital mortality was measured; it was 44%. Calibration for all three scoring systems was acceptable, SAPS II yielded a significantly superior discrimination between survivors and non-survivors. The areas under the receiver operating characteristic curves were 0.776 for APACHE II, 0.825 for SAPS II and 0.698 for the ICMM. CONCLUSION: The SAPS II was superior to APACHE II and ICMM. The newly developed ICMM does not improve mortality prediction in critically ill cancer patients.

Major bleeding complications in cardiopulmonary resuscitation: the place of thrombolytic therapy in cardiac arrest due to massive pulmonary embolism.

OBJECTIVE: Thrombolytic therapy in patients with massive pulmonary embolism (MPE) and prolonged cardiopulmonary resuscitation (CPR) is subject to debate. This study was performed to determine whether (1) thrombolytic treatment increases the risk of bleeding complications, (2) if the risk of bleeding is influenced by the duration of CPR and if (3) thrombolytic therapy improves outcome. DESIGN: Retrospective cohort study. SETTING: Emergency department of a tertiary care university hospital. PATIENTS AND METHODS: Sixty-six patients with cardiac arrest (CA) due to MPE admitted between July 1993 and December 2001. Thirty-six patients received thrombolysis (TL) and were compared with 30 patients without thrombolytic therapy. Bleeding complications were assessed by clinical evidence or autopsy. RESULTS: Major bleeding complications appear to occur more frequently in patients treated with thrombolytics (9/36 (25%) vs. 3/30 (10%)) even though the difference was statistically not significant (P=0.15). It appears that CPR duration >10 min has no adverse impact on major bleeding complications. No difference in the rate of major bleeding complications between thrombolyzed patients who had a CPR duration of 10 min could be observed (2/8 (25%) vs. 7/28 (25%), P=0.99). In thrombolyzed patients a return of spontaneous circulation could be achieved more frequently (24/36 (67%) vs.13/30 (43%) in controls, P=0.06) and survival after 24 h was higher (19/36 (53%) vs. 7/30 (23%), P=0.01). Survival to discharge was also higher in the TL group (7/36 (19%) vs. 2/30 (7%)), but not statistically significant (P=0.15). CONCLUSION: Although severe bleeding complications tend to occur more frequently in patients undergoing TL, the benefit of this treatment might outweigh the risk of bleeding.

Endothelial cell activation and blood coagulation in critically ill patients with lung injury.

INTRODUCTION: Adult respiratory distress syndrome is a life-threatening disease that requires respiratory assistance. It is associated with endothelial cell damage, coagulation activation, and intravascular fibrin deposition. This prospective study was conducted to determine whether the plasma levels of specific markers of endothelial cell function and coagulation activation are related to the degree of pulmonary disturbance. PATIENTS AND METHODS: Fourteen patients (8 male, 6 female, median age 69 years), admitted to a medical intensive care unit with various stages of lung injury needing mechanical ventilation, were compared with 16 healthy age- and sex-matched control subjects. RESULTS: Markers of endothelial cell damage and coagulation activation were significantly elevated in patients with lung injury compared with controls: von Willebrand factor (vWF) 4.12 vs. 1.25 U/ml, p < 0.0001; F VIII 4.40 vs. 1.88 U/ml, p = 0.0001; tissue-type plasminogen activator (tPA) 11.6 vs. 8.7 ng/ml, p = 0.02; plasminogen activator inhibitor-1 (PAI) 48.9 vs. 14.6 ng/ml, p < 0.0001; D-dimer 2.9 vs. 0.6 microgram/ml, p < 0.0001; thrombin-antithrombin III complex (TAT) 7.9 vs. 2.2 ng/ml, p < 0.0001 (median values; Mann-Whitney U-test). vWF, tPA, PAI and D-Dimer were significantly correlated with the PaO2/FiO2 ratio (p = 0.0003, 0.003, 0.04, 0.02, respectively; Spearman's rank correlation). CONCLUSION: These findings suggest that the endothelial cell disturbance and the activation of the coagulation system in patients with lung injury are related to the degree of pulmonary dysfunction.

Bedside exclusion of clinically significant recirculation volume during venovenous ECMO using conventional blood gas analyses.

STUDY OBJECTIVE: To investigate prospectively whether blood gas samples drawn from extracorporeal membrane oxygenation (ECMO) cannulae help to exclude at least clinically significant recirculation volumes in patients with acute respiratory failure. DESIGN: Feasibility study. SETTING: Intensive care unit at a university-affiliated hospital. PATIENTS: Ten consecutive adult patients suffering from severe respiratory failure and undergoing ECMO. INTERVENTIONS: The drawing (venous) ECMO cannula was placed into the inferior vena cava via a femoral vein, and the oxygenated blood was returned via the right subclavian vein by supraclavicular access directly into the right atrium. Blood gas samples were obtained from both cannulae. MEASUREMENTS AND MAIN RESULTS: The median arterial oxygen tension (PaO(2)) obtained from the arterial cannula was 537 mmHg (range, 366 to 625 mmHg), the median mixed venous oxygen tension (PvO(2)) drawn from the venous cannula was 42 mmHg (range, 25 to 54 mmHg), which was less than 10% of that observed in the arterial cannula, and also within the physiologic range of PvO(2). The ECMO flow necessary to maintain patients' oxygen saturation above 90% (4.1 L/min; range, 1.95 to 5.8 L/min) was significantly lower than the patients' cardiac output (CO; 6.2 L/min; range, 4.1 to 7.9 L/min; p < 0.001). CONSLUSIONS; We recommend obtaining blood gas samples-immediately after initiation of ECMO-from both cannulae. A PvO(2) within physiologic range and below 10% of PaO(2) rules out any clinically relevant recirculation volume.

Influence of different oxygenator types on changing frequency, infection incidence, and mortality in ARDS patients on veno-venous ECMO.

PURPOSE: Veno-venous extracorporeal membrane oxygenation (vv-ECMO) is pivotal in the treatment of patients suffering from acute respiratory distress syndrome (ARDS). Comparative data with different oxygenator models have not yet been reported. The aim of this retrospective investigation was therefore to assess whether different oxygenator types might influence changing frequency, infection incidence, and mortality in patients on vv-ECMO. METHODS: 42 patients undergoing vv-ECMO between 1998 and 2009 were identified. In 20 out of these patients, a polypropylene (PP) microporous hollow fiber membrane oxygenator, and in 22 patients a nonmicroporous polymethylpentene (PMP) diffusion membrane oxygenator was used. Infection incidence, changing frequency, and mortality were documented. RESULTS: In the PMP group, an oxygenator change was necessary less often than in the PP group (p<0.001). The incidence of bacterial, viral, or fungal growth was similar in the groups, thus independent of the frequency of oxygenator change. Irrespective of the groups, the occurrence of Candida sp. tended to correlate with death (p = 0.06). In general, there was a trend towards a higher infection incidence in the subgroup with pulmonary ARDS (p = 0.07). Moreover, infection incidence was associated with a longer ICU stay (p = 0.03) and longer ECMO therapy (p = 0.03). ICU mortality was lower in the PMP group than in the PP group, although not statistically significant (p = 0.10). CONCLUSIONS: The PMP oxygenator membranes showed benefits with regards to changing frequency, but not infection incidence, length of ICU stay, and length of ECMO therapy. There was a trend towards a lower ICU mortality in patients with PMP oxygenators.

"Il flauto magico" still works: Mozart's secret of ventilation.

BACKGROUND: Synchronisation/coupling between respiratory patterns and musical structure. METHODS: Healthy professional musicians and members of the audience were studied during a performance of W.A. Mozart's Piano Concerto KV 449. Electrocardiogram (ECG)/Heart Rate Variability (HRV) data recording (Schiller: Medilog®AR12, ECG-channels: 3, sampling rate: 4096 Hz, 16 Bit) was carried out and a simultaneous synchronized high definition video/audio recording was made. The breathing-specific data were subsequently extracted using Electrocardiogram-derived respiration (EDR; Software: Schiller medilog®DARWIN) from the HRV data and overlaid at the same time onto the musical score using FINALE 2011 notation software and the GIMP 2.0 graphics programme. The musical score was graphically modified graphically so that the time code of the breathing signals coincided exactly with the notated musical elements. Thus a direct relationship could be produced between the musicians' breathing activity and the musical texture. In parallel with the medical/technical analysis, a music analysis of the score was conducted with regard to the style and formal shaping of the composition. RESULTS: It was found that there are two archetypes of ideally typical breathing behaviour in professional musicians that either drive the musical creation, performance and experience or are driven by the musical structure itself. These archetypes also give rise to various states of synchronisation and regulation between performers, audience and the musical structure. CONCLUSIONS: There are two archetypes of musically-induced breathing which not only represent the identity of music and human physiology but also offer new approaches for multidisciplinary respiratory medicine.

Successful allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia during respiratory failure and invasive mechanical ventilation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment option for various hematologic disorders. However, life-threatening adverse events resulting from treatment-related toxicity, severe infections, and/or graft-versus-host disease (GvHD) can occur. We report on a 64-year-old patient suffering from secondary acute myeloid leukemia (AML) who underwent successful allogeneic HSCT while on invasive mandatory ventilation (IMV). The patient received reduced intensity conditioning (RIC) according to the FLAMSA-protocol. Acute respiratory failure occurred one day before scheduled HSCT. Following emergency endotracheal intubation the patient was transferred to the intensive care unit (ICU). Because of respiratory deterioration, stem cell infusion was postponed. After stabilization of respiratory parameters, HSCT was performed during IMV which was continued for seven days. Following hematopoietic regeneration the patient was discharged in good condition on day 35 after HSCT. This case illustrates that intubation and mechanical ventilation do not necessarily exclude leukemic patients from HSCT.

A surge of flu-associated adult respiratory distress syndrome in an Austrian tertiary care hospital during the 2009/2010 Influenza A H1N1v pandemic.

We report on 17 patients with influenza A H1N1v-associated Adult Respiratory Distress Syndrome who were admitted to the intensive care unit (ICU) between June 11th 2009 and August 10th 2010 (f/m: 8/9; age: median 39 (IQR 29-54) years; SAPS II: 35 (29-48)). Body mass index was 26 (24-35), 24% were overweight and 29% obese. The Charlson Comorbidity Index was 1 (0-2) and all but one patient had comorbid conditions. The median time between onset of the first symptom and admission to the ICU was 5 days (range 0-14). None of the patients had received vaccination against H1N1v. Nine patients received oseltamivir, only two of them within 48 hours of symptom onset. All patients developed severe ARDS (PaO(2)/FiO(2)-Ratio 60 (55-92); lung injury score 3.8 (3.3-4.0)), were mechanically ventilated and on vasopressor support. Fourteen patients received corticosteroids, 7 patients underwent hemofiltration, and 10 patients needed extracorporeal membrane-oxygenation (ECMO; 8 patients veno-venous, 2 patients veno-arterial), three patients Interventional Lung Assist (ILA) and two patients pump driven extracorporeal low-flow CO(2)-elimination (ECCO(2)-R). Seven of 17 patients (41%) died in the ICU (4 patients due to bleeding, 3 patients due to multi-organ failure), while all other patients survived the hospital (59%). ECMO mortality was 50%. The median ICU length-of-stay was 26 (19-44) vs. 21 (17-25) days (survivors vs. nonsurvivors), days on the ventilator were 18 (14-35) vs. 20 (17-24), and ECMO duration was 10 (8-25) vs. 13 (11-16) days, respectively (all p = n.s.). Compared to a control group of 241 adult intensive care unit patients without H1N1v, length of stay in the ICU, rate of mechanical ventilation, days on the ventilator, and TISS 28 scores were significantly higher in patients with H1N1v. The ICU survival tended to be higher in control patients (79 vs. 59%; p = 0.06). Patients with H1N1v admitted to either of our ICUs were young, overproportionally obese and almost all with existing comorbidities. All patients developed severe ARDS, which could only be treated with extracorporeal gas exchange in an unexpectedly high proportion. Patients with H1N1v had more complicated courses compared to control patients.

Catastrophic graft-versus-host disease after lung transplantation proven by PCR-based chimerism analysis.

Acute graft-versus-host disease (GvHD) is a rare complication after solid organ transplantation. We describe a 52-year-old female developing neutropenia and fever 48 days after single lung transplantation for chronic obstructive pulmonary disease. Bone marrow (BM) biopsy suggested drug-induced marrow failure, so immunosuppression was reduced. Five days later a maculopapular skin rash was observed, progressing to a generalized erythema with desquamation. Skin biopsy was suspectable for GvHD, so immunosuppression was re-initiated. PCR-based chimerism analysis of BM revealed 78% donor cells. Intensified immunosuppression resulted in temporary improvement, but BM aplasia recurred and the patient experienced severe GvHD of gut and liver. Despite extensive immunosuppression the patient died from multi-organ failure 99 days after transplantation. This report describes the occurrence of neutropenia as an early presenting sign of acute GvHD after lung transplantation. We therefore recommend incorporating GvHD in the differential diagnosis of neutropenia after solid organ transplantation, calling for early chimerism analyses.

Treatment of adult patients with sepsis-induced coagulopathy and purpura fulminans using a plasma-derived protein C concentrate (Ceprotin).

BACKGROUND AND OBJECTIVES: The aim of this study was to document the effects of supplementation with a plasma-derived protein C concentrate in adult patients with infectious purpura fulminans. MATERIALS AND METHODS: We report the effect of the administration of a human protein C concentrate (Ceprotin, Baxter, Vienna, Austria) in eight adult patients with purpura fulminans. Five patients received the concentrate as level-adjusted continuous infusion (10 U/kg/h, target protein C activity 100%) and three patients received the concentrate as bolus infusions (100 U/kg every 6 h) in addition to standard sepsis therapy. Heparin, fresh-frozen plasma, antithrombin- and fibrinogen concentrates, low-dose rtPA, and platelet transfusions were given when appropriate. RESULTS: Six patients had overt disseminated intravascular coagulation: platelets, 19 g/l; fibrinogen, 60 mg/dl; antithrombin, 47%; prothrombin time, 32%; activated partial thromboplastin time (APTT), 88 s; d-dimer, 66 microg/ml; protein C activity, 29% (medians). Five patients had septic shock, six renal failure and four respiratory failure. Patients received between 5000 and 77,000 U of protein C concentrate over 2.5 days (median); the protein C activity increased to 184% (median) and coagulopathy resolved within 3 days in seven of the eight patients. Six patients survived, one died early from fulminant sepsis, and one died after 14 days from candida sepsis. CONCLUSIONS: Our data suggest that treatment with a plasma-derived protein C zymogen concentrate might be a useful support in adult patients with purpura fulminans.

Frequent development of lupus anticoagulants in critically ill patients treated under intensive care conditions.

OBJECTIVE: To investigate how often a prolongation of the activated partial thromboplastin time in critically ill patients is caused by lupus anticoagulants and to identify possible triggering events. DESIGN: Prospective study. SETTING: Internal medicine intensive care unit (University Hospital of Vienna, Vienna, Austria). PATIENTS: Fifty-one critically ill patients without severe coagulopathy, hepatopathy, or anticoagulant treatment (35 male, 16 female, median age 60 yrs, range: 22-85 yrs). INTERVENTIONS: All patients were screened daily for lupus anticoagulants with the activated partial thromboplastin time STA assay. MEASUREMENTS AND MAIN RESULTS: Diluted Russell's viper venom time, plasma mixing studies, and confirmation assays were used to identify lupus anticoagulants at the time of an unexplained prolongation of the activated partial thromboplastin time. The influence of heparin was excluded by determination of thrombin clotting time and anti-Xa activity. In 27 of 51 patients (52.9 %) lupus anticoagulants were found after a median stay of 13 days. None of the patients had concomitant immune thrombocytopenia, hypoprothrombinemia, bleeding, or thromboembolic complications. Sepsis (p =.006) and/or catecholamine treatment (p =.002) were significantly associated with the development of lupus anticoagulants. Extracorporeal circulation, transfusion of blood products, or surgery did not increase this risk. Lupus anticoagulants resolved spontaneously in 63% of the patients after a median stay of 17 days. CONCLUSIONS: Lupus anticoagulants are frequent in critically ill patients and associated with sepsis syndrome and/or catecholamine treatment. The prolonged activated partial thromboplastin time does not warrant the administration of coagulation factors or the cessation of anticoagulant therapy or prophylaxis, inasmuch as this phenomenon is not associated with bleeding or thromboembolic complications.