Comparison of Weaning Strategies in Patients Receiving Venovenous Extracorporeal Membrane Oxygenation: An Exploratory Retrospective Study.

Venovenous extracorporeal membrane oxygenation (VV ECMO) facilitates the reduction of mechanical ventilation (MV) support in acute respiratory failure. Contrary to increasing evidence regarding its initiation, the optimal timing of VV ECMO weaning in interaction with MV weaning is undetermined. In this retrospective study, 47 patients who received VV ECMO between 2013 and 2021 and survived ≥1 day after ECMO cessation were divided according to their MV status before ECMO removal: 28 patients were classified into an "ECMO weaning during assisted MV/spontaneous breathing" group and 19 into an "ECMO weaning during controlled MV" group. Extracorporeal membrane oxygenation duration was longer in the "assisted MV/spontaneous breathing" group (17 [Interquartile range (IQR) = 11-35] vs. 6 [5-11] days, p < 0.001). These patients had a longer intensive care unit (ICU) stay after ECMO start (48 [29-66] vs. 31 [15-40] days, p = 0.01). No significant differences were found for MV duration after ECMO start (30 [19-45] vs. 19 [12-30] days, p = 0.06) and further ICU survival (86% vs. 89%, p ≥ 0.9). There was a trend toward more patients with mechanical ECMO complications in the "assisted MV/spontaneous breathing" group (57% vs. 32%, p = 0.08). Thus, our results suggest a possible benefit of early ECMO weaning during controlled MV.

Add-On Prostaglandin E1 in Venovenous Extracorporeal Membrane Oxygenation: A Randomized, Double-Blind, Placebo-controlled Pilot Trial.

Rationale: Prostaglandin E1 (alprostadil; PGE1), in addition to low-dose unfractionated heparin, increases the biocompatibility of extracorporeal systems and enhances the efficacy of artificial organs without increasing bleeding risk. Objectives: We investigated the safety and efficacy of PGE1 in adults receiving venovenous extracorporeal membrane oxygenation (ECMO). Methods: This study was a randomized, double-blind, placebo-controlled phase II pilot trial at two medical intensive care units at the Medical University of Vienna, Austria. Adults with venovenous ECMO were randomly assigned to receive an intravenous infusion of 5 ng/kg/min PGE1 or placebo (0.9% saline) in addition to standard anticoagulation with unfractionated heparin. Measurements and Main Results: The primary outcome was the rate of transfused packed red blood cells per ECMO day. Secondary outcomes were the incidence of and time to clinically overt bleeding and thromboembolic events. A post hoc subgroup analysis included only patients with coronavirus disease (COVID-19). Between September 2016 and April 2021, of 133 screened patients, 50 patients were randomized, of whom 48 received the assigned study medication (24 per group). The transfusion rate was similar between groups (0.41 vs. 0.39; P = 0.733). PGE1 was associated with fewer thromboembolic events (7 vs. 16; P = 0.020) and longer thromboembolism-free time (hazard ratio [HR], 0.302; P = 0.01), fewer clinically overt bleeding events (2 vs. 11; P = 0.017), and longer bleeding-free time (HR, 0.213; P = 0.047). In patients with COVID-19 (n = 25), the HRs for clinically overt bleeding and thromboembolism were 0.276 (95% confidence interval, 0.035-2.186) and 0.521 (95% confidence interval, 0.149-1.825), respectively. Conclusions: Add-on treatment with PGE1 was safe but did not meet the primary endpoint of reducing the rate of red blood cell transfusions in patients receiving venovenous ECMO. Larger studies need to evaluate the safety and efficacy of additional PGE1 in ECMO. Clinical trial registered with EudraCT (2015-005014-30) and www.clinicaltrials.gov (NCT02895373).

In Vivo Suction Pressures of Venous Cannulas During Veno-venous Extracorporeal Membrane Oxygenation.

Extracorporeal lung support includes the risk of hemolysis due to suction pressures. Manufacturers measure the negative suction pressure across drainage cannulas for their products in vitro using water. Clinical experience suggests that hemolysis occurs in vivo already at much lower flow rates. The aim of this study was to analyze the in vivo suction pressure for veno-venous extracorporeal membrane oxygenation (VV-ECMO) cannulas. Prospective, observational study at a tertiary-care intensive care unit: 15 patients on VV-ECMO for severe ARDS were prospectively included. In vitro , the 25 Fr drainage cannula pressure drops below a critical level of around -100 mm Hg at a flow rate of 7.9 L/min, the 23 Fr drainage cannula at 6.6 L/min. In the clinical setting, critical suction pressures were reached at much lower flow rates (5.5 and 4.7 L/min; p < 0.0001, nonlinear regression). The in vitro data largely overestimate the safely achievable flow rates in daily clinical practice by 2.4 L/min (or 44%, 25 Fr) and 1.9 L/min (or 41%, 23 Fr). In vivo measurement of suction pressure of venous drainage cannulas differed significantly from in vitro derived measurements as the latter largely underestimate the resulting suction pressure.

Comparison of Hemostatic Changes in Pump-driven Extracorporeal Carbon Dioxide Removal and Venovenous Extracorporeal Membrane Oxygenation.

Extracorporeal carbon dioxide removal (ECCO 2 R) has gained widespread use as a supposedly less invasive alternative for hypercapnic respiratory failure besides venovenous extracorporeal membrane oxygenation (VV ECMO). Despite technological advances, coagulation-related adverse events remain a major challenge in both therapies. The overlapping operating areas of VV ECMO and pump-driven ECCO 2 R could allow for a device selection targeted at the lowest risk of such complications. This retrospective analysis of 47 consecutive patients compared hemostatic changes between pump-driven ECCO 2 R (n = 23) and VV ECMO (n = 24) by application of linear mixed effect models. A significant decrease in platelet count, increase in D-dimer levels, and decrease of fibrinogen levels were observed. However, except for fibrinogen, the type of extracorporeal support did not have a significant effect on the time course of these parameters. Our findings suggest that in terms of hemocompatibility, pump-driven ECCO 2 R is not significantly different from VV ECMO.

Incidence and Etiology of System Exchanges in Patients Receiving Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) has established as a cornerstone therapy in severe acute respiratory distress syndrome and refractory hemodynamic failure. As circuit integrity is crucial for adequate organ support, component failure may necessitate a system exchange. In this retrospective study, incidence and etiology of system exchanges during applications of venovenous, venoarterial ECMO, and extracorporeal CO2 removal were examined. Sixty-three (44.4%) of 142 patients were affected by one or more exchanges, totaling 105 replaced circuits. The predominant exchange reason was clotting (n = 20), followed by hemolysis (n = 19), systemic coagulation disorders (n = 13), reconfiguration (n = 13), impaired gas exchange (n = 10), mechanical complications (n = 8), bleeding (n = 6), failed weaning (n = 5), prophylactic exchange (n = 3), and undocumented/other (n = 8). Nineteen (18.1%) events were classified as acute and 70 (66.7%) events as elective exchanges. Patients with circuit exchanges more frequently underwent renal replacement therapy at ECMO initiation (49.2% vs. 29.1%; p = 0.023), had a longer ECMO treatment duration (18 vs. 7.5 days, p < 0.001), and lower hospital survival (29.5% vs. 57.1%; p = 0.002). Considering the high occurrence of coagulation complications, further optimization of coagulation management is deemed necessary.

Long-term Respiratory Extracorporeal Membrane Oxygenation and Prognosis: A Retrospective Analysis.

The duration of extracorporeal membrane oxygenation (ECMO) treatments increases, however, data presented from prolonged support is limited. We retrospectively analyzed all patients during a 4-year period undergoing respiratory ECMO for duration of therapy, demographics, therapy-associated parameters, and outcome according to ECMO duration (<28 days and ≥28 days = long-term ECMO). Out of 55 patients undergoing ECMO for ARDS or during bridging to lung transplantation, 18 were on ECMO for ≥28 days (33%). In the long-term group, median ECMO run time was 40 days (interquartile range 34-54 days). Hospital survival was not significantly different between the groups (54% in short-term and 50% in long-term ECMO patients). There was a significantly higher proportion of patients suffering from malignancy in the group of long-term nonsurvivors. Recovery occurred after more than 40 days on ECMO in 3 patients. The longest ECMO run time in a hospital survivor was 65 days. Duration of ECMO support alone was no prognostic factor and should not represent a basis for decision-making. In patients suffering from malignancy, long-term ECMO support seems to be a factor of adverse prognosis, if not futile.

ECMO without anticoagulation in patients with disease-related severe thrombocytopenia: Feasible but futile?

Severe thrombocytopenia poses a high risk for bleeding thus representing a relative contraindication for anticoagulation and therefore extracorporeal membrane oxygenation (ECMO). We herein report on a series of immunocompromised patients with severe thrombocytopenia undergoing long-term ECMO without systemic anticoagulation. We retrospectively identified seven adult patients with anticoagulation withdrawal for ≥3 days (range 5-317) during venovenous ECMO therapy due to thrombocytopenia < 50 G/L treated in a university-affiliated hospital from January 2013 to April 2017. All ECMO systems used were heparin coated. Overall, 530 ECMO days were observed, 404 (76%) of them without systemic anticoagulation. Platelet count during ECMO treatment was 24 G/L (median, range 1-138), ECMO duration was 35 days (5-317), and ECMO was run without any anticoagulation for 20 days (5-317). Altogether, five clotting events were seen leading to oxygenator exchanges. Bleeding was common including one fatal intracerebral hemorrhage. Altogether, 29 platelet concentrates per patient (7-207) were administered, which correspond to 0.8 per day (0.6-1.3). One patient survived ICU and hospital. In patients with thrombocytopenia, ECMO can be run without anticoagulation even for considerably long periods of time. Bleeding remains common, while clotting events seem to be rare. However, prognosis of this patient population undergoing ECMO support seems grim.

Propofol-based sedation does not negatively influence oxygenator running time compared to midazolam in patients with extracorporeal membrane oxygenation.

OBJECTIVE: Patients on extracorporeal membrane oxygenation are frequently in need for sedation. Use of propofol has been associated with impaired oxygenator function due to adsorption to the membrane as well as lipid load. The aim of our retrospective analysis was to compare two different sedation regimens containing either propofol or midazolam with respect to oxygenator running time. METHODS: Midazolam was used in 73 patients whereas propofol was used in 49 patients, respectively. In the propofol group, veno-arterial-extracorporeal membrane oxygenation was used predominantly (84%), while veno-venous-extracorporeal membrane oxygenation was used more often in the midazolam group (64%). RESULTS: Oxygenator running time until first exchange was 7 days in both groups ( p = 0.759). No statistically significant differences could be observed between the subgroup of patients receiving lipid-free (n = 24) and lipid-containing (n = 31) parenteral nutrition, respectively. Laboratory parameters like triglycerides, free hemoglobin, fibrinogen, platelets, and activated partial thromboplastin time were not significantly different between both sedation regimens ( p = 0.462, p = 0.489, p = 0.960, p = 0.134, and p = 0.843) and were not associated with oxygenator running time. CONCLUSION: The use of propofol as sedative seems suitable in patients undergoing extracorporeal membrane oxygenation therapy.

Parameters associated with therapeutic response using peritoneal dialysis for therapy refractory heart failure and congestive right ventricular dysfunction.

BACKGROUND: In patients with refractory heart failure (HF) peritoneal dialysis (PD) is associated with improved functional status and decrease in hospitalization. However, previous studies did not focus on right ventricular dysfunction as an important pathophysiologic component of cardiorenal syndrome. METHODS: In a prospective cohort study PD was started in 40 patients with refractory right HF (with/without left HF). Refractoriness to conservative therapy was defined as persistent right heart congestion/ascites with intensified diuretic treatment and/or ≥2 hospitalizations within 6 months because of cardiac decompensation despite optimal medical treatment, and/or acute renal failure during intensified conservative treatment of cardiac decompensations. RESULTS: Patient survival was 55.0% at 1 year, 35.0% at 2 years and 27.5% at 3 years. The number of hospitalization days declined after initiation of PD for both cardiac [13 (IQR 1-53) days before vs. 1 (IQR 0-12) days after start of PD, p<0.001] and unplanned reasons [12 (IQR 3-44) days before vs. 1 (IQR 0-33) days after start of PD, p = 0.007]. Using a combined endpoint including survival time of ≥1 year and either improvement in quality of life or decline in hospitalizations we found that patients with extended ascites, higher systolic pulmonary artery pressure, more marked impairment of right ventricular function and tricuspid valve insufficiency, higher residual renal function as well as those who could perform PD without assistance have benefited most from this therapy. CONCLUSIONS: Patients with more pronounced backward failure, less marked residual renal functional impairment and those not depending on assistance for therapy are likely to profit most from PD.

Supraclavicular Approach to the Subclavian Vein as an Alternative Venous Access Site for ECMO Cannulae? A Retrospective Comparison.

Venous reperfusion and double-lumen cannulae for extracorporeal membrane oxygenation (ECMO) are usually inserted via the right internal jugular vein. The supraclavicular approach to the right or left subclavian vein could serve as a possible alternative. The aim of this analysis was to compare feasibility, complications, and performance of supraclavicular and jugular cannulation. We retrospectively analyzed charts and registry data of patients undergoing venovenous ECMO. Twenty-four patients underwent jugular cannulation, and 11 patients underwent supraclavicular cannulation. Ten patients underwent femoro-jugular, and five patients underwent femoro-supraclavicular ECMO. Double-lumen cannulae were inserted via the jugular approach in 14 patients and via the supraclavicular approach in 6 patients. No cannulation-associated complications but for a single minor bleeding from the insertion site of a supraclavicular double-lumen cannula were recorded. Performance of the extracorporeal circuit was comparable between jugular and supraclavicular groups but for a more pronounced oxygenation effect in the supraclavicular double-lumen group caused by higher blood flows via larger (24 F) cannulae. The supraclavicular approach seems safe and equivalent to jugular cannulation and could serve as a valid alternative.

Successful weaning from 65-day extracorporeal membrane oxygenation therapy in influenza-associated acute respiratory distress syndrome.

INTRODUCTION: Data on prolonged extracorporeal membrane oxygenation (ECMO) usage in influenza associated acute respiratory distress syndrome (ARDS) are lacking. Furthermore, no consensus exists on when to terminate ECMO treatment in refractory cases. This report highlights additional treatment measures and complications in prolonged ECMO therapy and discusses associated ethical burdens. CASE REPORT: We report on a 64-year-old man with confirmed H1N1 influenza virus infection who was successfully weaned from 65-day ECMO treatment with an excellent outcome. CONCLUSIONS: Our experience suggests that prolonged ECMO therapy may be provided as long as only 1-organ failure exists and no lung fibrosis occurs. Active physical therapy, facilitated by ECMO treatment, is crucial and should be performed as early as possible.

Incidence of intensive care unit admission, outcome and post intensive care survival in patients with diffuse large B-cell lymphoma.

Some patients with diffuse large B-cell lymphoma (DLBCL) require intensive care unit (ICU) admission prior to or during chemotherapy. We analyzed all unscheduled ICU admissions in 331 consecutive patients (18-93 years) with newly diagnosed DLBCL. Thirty-seven patients (11.2%) required ICU treatment primarily due to hemodynamic (37.8%) or respiratory failure (24.3%). Bulky disease and high IPI score were predictive of ICU admission in the early course. ICU and hospital survival was 75.7% and 70.3%, respectively. Overall survival in ICU patients with newly diagnosed DLBCL was worse compared to non-ICU-patients (40.7% vs. 72.7% at two years). However, survival of high-risk patients (IPI 3-5), continuous complete remission, and disease-free survival did not differ. Post-ICU survival was poor in patients with relapsed/refractory DLBCL (0.1-10 months). Our observations favor unrestricted ICU support in DLBCL patients undergoing first-line therapy. ICU referral of patients with refractory/relapsed disease must be evaluated in the context of the hematologic prognosis.

Outcome of conservative management vs. assist device implantation in patients with advanced refractory heart failure.

BACKGROUND: In patients with advanced refractory heart failure (HF) cardiac transplantation (HTX), conservative medical management and the implantation of a ventricular assist device (VAD) represent valuable options. The determination of the best therapeutic destination strategy for the individual patient remains a challenge. The aim of this study was to assess the clinical outcome in advanced refractory HF patients either managed conservatively receiving optimal contemporary medical therapy ('conservative'), or who who underwent pulsatile flow VAD ('pVAD') or continuous-flow VAD ('contVAD') implantation. MATERIALS AND METHODS: A total of 118 patients with INTERMACS profile >1 at baseline, who died, or fully completed a 24-month follow-up free from HTX were included into this retrospective analysis. All-cause mortality at 24 months was assessed and compared between the three groups. RESULTS: Fifty (42%) patients were managed conservatively, 25 (21%) received a pVAD and 43 (36%) a contVAD. NT-proBNP values were comparable between the three groups (median 4402 (IQR 2730-13390) pg/mL, 3580 (1602-6312) pg/mL and 3693 (2679-8065) pg/mL, P = 0·256). Mean survival was 18·6 (95% CI 16·2-21·0) months for patients managed conservatively, 7·0 (3·9-10·0) for pVAD and 20·5 (18·2-22·8) for contVAD (overall log-rank test P < 0·001). Conservatively managed patients spent a mean of 22·4 (95% CI 22·1-22·8), pVAD 17·7 (15·4-20·1) and contVAD 21·6 (21·2-22·1) months out of hospital (conservative vs. pVAD P < 0·001; conservative vs. contVAD P = 0·015; pVAD vs. contVAD P < 0·001). CONCLUSIONS: In accordance with the literature, contVAD resulted in a significantly better clinical outcome than pVAD implantation. However, conservative management with current optimal medical therapy appears to remain a valuable option for patients with advanced HF.

A novel pump-driven veno-venous gas exchange system during extracorporeal CO2-removal.

PURPOSE: Pump-driven veno-venous extracorporeal CO2-removal (ECCO2-R) increasingly takes root in hypercapnic lung failure to minimize ventilation invasiveness or to avoid intubation. A recently developed device (iLA activve(®), Novalung, Germany) allows effective decarboxylation via a 22 French double lumen cannula. To assess determinants of gas exchange, we prospectively evaluated the performance of ECCO2-R in ten patients receiving iLA activve(®) due to hypercapnic respiratory failure. METHODS: Sweep gas flow was increased in steps from 1 to 14 L/min at constant blood flow (phase 1). Similarly, blood flow was gradually increased at constant sweep gas flow (phase 2). At each step gas transfer via the membrane as well as arterial blood gas samples were analyzed. RESULTS: During phase 1, we observed a significant increase in CO2 transfer together with a decrease in PaCO2 levels from a median of 66 mmHg (range 46-85) to 49 (31-65) mmHg from 1 to 14 L/min sweep gas flow (p < 0.0001), while arterial oxygenation deteriorated with high sweep gas flow rates. During phase 2, oxygen transfer significantly increased leading to an increase in PaO2 from 67 (49-87) at 0.5 L/min to 117 (66-305) mmHg at 2.0 L/min (p < 0.0001). Higher blood flows also significantly enhanced decarboxylation (p < 0.0001). CONCLUSIONS: Increasing sweep gas flow results in effective CO2-removal, which can be further reinforced by raising blood flow. The clinically relevant oxygenation effect in this setting could broaden the range of indications of the system and help to set up an individually tailored configuration.

Extracorporeal CO2 removal as bridge to lung transplantation in life-threatening hypercapnia.

In patients awaiting lung transplantation (LTX), adequate gas exchange may not be sufficiently achieved by mechanical ventilation alone if acute respiratory decompensation arises. We report on 20 patients with life-threatening hypercapnia who received extracorporeal CO2 removal (ECCO2-R) by means of the interventional lung assist (ILA®, Novalung) as bridge to LTX. The most common underlying diagnoses were bronchiolitis obliterans syndrome, cystic fibrosis, and idiopathic pulmonary fibrosis, respectively. The type of ILA was pumpless arteriovenous or pump-driven venovenous (ILA activve®, Novalung) in 10 patients each. ILA bridging was initiated in 15 invasively ventilated and five noninvasively ventilated patients, of whom one had to be intubated prior to LTX. Hypercapnia and acidosis were effectively corrected in all patients within the first 12 h of ILA therapy: PaCO2 declined from 109 (70-146) to 57 (45-64) mmHg, P < 0.0001; pH increased from 7.20 (7.06-7.28) to 7.39 (7.35-7.49), P < 0.0001. Four patients were switched to extracorporeal membrane oxygenation due to progressive hypoxia or circulatory failure. Nineteen patients (95%) were successfully transplanted. Hospital and 1-year survival was 75 and 72%, respectively. Bridging to LTX with ECCO2-R delivered by arteriovenous pumpless or venovenous pump-driven ILA is feasible and associated with high transplantation and survival rates.

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.

Hepatic dysfunction contributes to coagulation disturbances in patients undergoing whole body hyperthermia by use of extracorporeal circulation.

PURPOSE: This phase I study was performed to evaluate coagulation alterations during extracorporeal circulation (ECC) induced whole body hyperthermia (WBHT) in 12 patients with advanced soft tissue sarcomas. METHODS: To distinguish between effects of normothermic ECC and ECC-WBHT, blood samples were drawn at different time points: at baseline, after 30 min on normothermic ECC, at the end of the heating period, and 24 h and 7 days thereafter. Standard coagulation tests, coagulation factors, thrombelastography,platelets and reticulated platelets, liver enzymes, and scintigraphic platelet imaging were performed. RESULTS: Normothermic ECC resulted in coagulation alterations most likely due to systemic anticoagulation. Induction of hyperthermia caused thrombocytopenia, increased fibrin degradation products,prolonged clotting times, alteration in coagulation factors, and increased liver enzymes. The majority of these effects was most pronounced 24 h after ECC-WBHT. In addition, late liver sequestration of platelets was demonstrated in scintigraphic imaging at that time point. CONCLUSIONS: Temporal correlation between hemostatic alterations and elevation in liver enzymes leads to the assumption that liver impairment might play a crucial role in coagulation disturbances observed during ECC-WBHT and thereafter, thus strongly supported by liver sequestration of platelets.Therefore a close monitoring of hepatic derived coagulation alterations in patients undergoing extracorporeal whole body hypothermia is warranted.

Acute hemodynamic effects of riociguat in patients with pulmonary hypertension associated with diastolic heart failure (DILATE-1): a randomized, double-blind, placebo-controlled, single-dose study.

BACKGROUND: Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF. METHODS: Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction > 50%, mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg, and pulmonary arterial wedge pressure (PAWP) > 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics. RESULTS: There was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11, P = .6). However, riociguat 2 mg significantly increased stroke volume (+9 mL [95% CI, 0.4-17]; P = .04) and decreased systolic BP (-12 mm Hg [95% CI, -22 to -1]; P = .03) and right ventricular end-diastolic area (-5.6 cm2 [95% CI, -11 to -0.3]; P = .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated. CONCLUSIONS: In patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01172756; URL: www.clinicaltrials.gov.

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.