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).

Estimating the age of p.(Phe508del) with family studies of geographically distinct European populations and the early spread of cystic fibrosis.

The high incidence of cystic fibrosis (CF) is due to the frequency of the c.1521_1523delCTT variant in the cystic fibrosis transmembrane conductance regulator (CFTR), but its age and origin are uncertain. This gap limits attempts to shed light on the presumed heterozygote selective advantage that accounts for the variant's high prevalence among Caucasian Europeans and Europe-derived populations. In addition, explaining the nature of heterozygosity to screened individuals with one c.1521_1523delCTT variant is challenging when families raise questions about these issues. To address this gap, we obtained DNA samples from 190 patients bearing c.1521_1523delCTT and their parents residing in geographically distinct European populations plus a Germany-derived population in the USA. We identified microsatellites spanning CFTR and reconstructed haplotypes at 10 loci to estimate the time/age of the most recent common ancestor (tMRCA) with the Estiage program. We found that the age estimates differ between northwestern populations, where the mean tMRCA values vary between 4600 and 4725 years, and the southeastern populations where c.1521_1523delCTT seems to have been introduced only about 1000 years ago. The tMRCA values of Central Europeans were intermediate. Thus, our data resolve a controversy by establishing an early Bronze Age origin of the c.1521_1523delCTT allele and demonstrating its likely spread from northwest to southeast during ancient migrations. Moreover, taking the archeological record into account, our results introduce a novel concept by suggesting that Bell Beaker folk were the probable migrating population responsible for the early dissemination of c.1521_1523delCTT in prehistoric Europe.

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.

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.

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.

Intraoperative complications have a negative impact on postoperative outcomes after rectal cancer surgery.

PURPOSE: The impact of intraoperative complications on the postoperative outcome in rectal cancer surgery is only poorly studied in literature. Thus, the aim of the present study was to assess the frequency of intraoperative complications during rectal resections for malignancies and its influence on the short term outcome. MATERIAL AND METHODS: We analyzed 605 consecutive patients, who had operations for rectal cancer at a single institution between 1995 and 2010. Retrospective data from the surgical procedure and postoperative course were obtained from the institutional colorectal database and individual chart reviews. Intraoperative complications were recorded and its influence on postoperative course was investigated. RESULTS: Intraoperative complications occurred in 66 (10.9%) patients, with injury to the spleen (n = 35 of 66, 53%) being the most frequent complication. Patients with intraoperative complications had a significant longer hospital stay (median: 13 days, range 7-92) compared to patients without complications (median: 12 days, range 2-135; p = 0.0102). In addition, intraoperative complications showed a tendency towards an increased risk for postoperative surgical complications (p = 0.0536), whereas no impact on postoperative medical complications could be found (p = 0.8043). Pulmonary disorders were the only predictive marker for intraoperative complications (p = 0.0247) by univariate analysis. CONCLUSION: We found that intraoperative complications during rectal cancer surgery significantly prolonged hospital length stay. The overall morbidity rate was not affected.

First experience with a new miniaturized pump-driven venovenous extracorporeal CO2 removal system (iLA Activve): a retrospective data analysis.

iLA Activve is a new minimally invasive device for extracorporeal CO2 removal (ECCO2-R) using a miniaturized pump, a special gas exchange membrane, and a double-lumen cannula. We retrospectively analyzed our experiences in 12 patients with hypercapnic respiratory failure undergoing ECCO2-R. Indication for ECCO2-R was hypercapnia due to terminal lung failure during bridging to lung transplantation, pneumonia, and chronic obstructive lung disease or asthma. The median duration of ECCO2-R was 8 days (range 2-30). Seven patients were successfully weaned and five died. Patients with primarily hypoxic lung failure were significantly longer ventilated before ECCO2-R and had a higher mortality rate. Complications were retroperitoneal hematoma after cannulation in one patient and repeated system changes because of clotting in two patients. We observed effective CO2 removal in all patients, with significant reduction in ventilation pressures and minute volumes at median blood flow rates of 1.2-1.4 L/min. The iLA Activve system using venous double-lumen cannulas proved to be an effective method for ECCO2-R. Invasiveness of ventilation could be reduced. Additional severe impairment of oxygenation and prolonged mechanical ventilation before ECCO2-R are factors of adverse prognosis. The use of ECCO2-R should be thoroughly reconsidered in these cases.

Pelvic organ function and quality of life after anastomotic leakage following rectal cancer surgery.

INTRODUCTION: There is a paucity of studies assessing the influence of anastomotic leakage after rectal cancer surgery on pelvic organ function and quality of life. METHODS: Between 1995 and 2006, 500 patients underwent rectal resection for malignancies at a single institution. Thirty-six patients (7.2%) developed an anastomotic leakage postoperatively. Fifteen of these patients (41.6%) died during the follow-up period. A self-administering questionnaire including the International Index of Erectile Function, Female Sexual Function Index, Short Form-12 Health Survey, International Prostatic Symptom Score, International Consultation on Incontinence Questionnaire-Short Form, Vaizey Incontinence Score and Wexner Constipation Score was sent to all 21 alive patients. Patients with rectal cancer resection without leakage served as controls for each case and were matched by sex, age (±5 years), type of resection, and neoadjuvant therapy (yes/no). RESULTS: Sixteen patients (76.2%) were available and were included in the analysis. The median follow-up time was 106.8 months (32.4-170.4). Fecal incontinence, constipation, and sexual function did not differ significantly between patients and controls (p = 0.1973, 0.1189, 0.8519, respectively). By contrast, urinary continence was impaired significantly in the leakage group (p = 0.0430) but not in control patients. The Quality of Life assessing Short Form-12 Health Survey reached no significant difference between both groups (p = 1.0000 and 0.1973). CONCLUSION: Anastomotic leakage following anterior resection negatively aggravates urinary function but not fecal incontinence, constipation or sexual functions. The data indicate that patients experiencing anastomotic leakages can be relieved from the fear of gross pelvic floor function disturbances.