Intracranial hemorrhage in a large cohort of patients supported with veno-venous ECMO. A retrospective single-center analysis

Background Intracranial bleeding (ICB) is a serious complication during veno-venous extracorporeal membrane oxygenation (V-V ECMO), with potentially fatal consequences. Purpose This study aimed to evaluate the incidence, time of detection of ICB among patients treated with V-V ECMO and potential risk factors for developing ICB during V-V ECMO. Methods Five hundred fifty six patients were included in this retrospective single center analysis. Results Median time on V-V ECMO was 9 (IQR 6-15) days. Intracranial bleeding during V-V ECMO was detected in 10.9% of all patients (61 patients with ICB). Only 17 patients with ICB presented obvious clinical symptoms. Intracranial bleeding was detected on cerebral imaging in median after 5 days (IQR 1-14) after starting V-V ECMO. Overall survival to hospital discharge was 63.7% (ICB: 29.5%). Risk factors of ICB before starting V-V ECMO in univariable analysis were platelets 1.5mg/dl (OR: 1.98), norepinephrine >2.5mg/h (OR: 2.5), ASAT >80U/L (OR: 1.86), blood-urea >100mg/dl (OR: 1.81) and LDH >550u/L (OR: 2.07). Factors associated with cannulation were rapid decrease in paCO2 >35mmHg (OR: 2.56) and rapid decrease in norepinephrine >1mg/h (OR: 2.53). Multivariable analysis revealed low platelets, high paCO2 before ECMO, and rapid drop in paCO2 after V-V ECMO initiation as significant risk factors for ICB. Conclusion The results emphasize that ICB is a frequent complication during V-V ECMO. Many bleedings were incidental findings, therefore screening for ICB is advisable. The univariate risk factors reflect the underlying disease severity, coagulation disorders and peri-cannulation factors, and may help to identify patients at risk

Validation of Prognostic Scores in Extracorporeal Life Support: A Multi-Centric Retrospective Study

Multiple prognostic scores have been developed for both veno-arterial (VA) and veno-venous (VV) extracorporeal membrane oxygenation (ECMO), mostly in single-center cohorts. The aim of this study was to compare and validate different prediction scores in a large multicenter ECMO-population. Methods: Data from five ECMO centers included 300 patients on VA and 329 on VV ECMO support (March 2008 to November 2016). Different prognostic scores were compared between survivors and non-survivors: APACHE II, SOFA, SAPS II in all patients; SAVE, modified SAVE and MELD-XI in VA ECMO; RESP, PRESET, ROCH and PRESERVE in VV ECMO. Model performance was compared using receiver-operating-curve analysis and assessment of model calibration. Survival was assessed at intensive care unit discharge. Results: The main indication for VA ECMO was cardiogenic shock; overall survival was 51%. ICU survivors had higher Glasgow Coma Scale scores and pH, required cardiopulmonary resuscitation (CPR) less frequently, had lower lactate levels and shorter ventilation time pre-ECMO at baseline. The best discrimination between survivors and non-survivors was observed with the SAPS II score (area under the curve [AUC] of 0.73 (95% CI 0.67–0.78)). The main indication for VV ECMO was pneumonia; overall survival was 60%. Lower PaCO2, higher pH, lower lactate and lesser need for CPR were observed among survivors. The best discrimination between survivors and non-survivors was observed with the PRESET score (AUC 0.66 (95% CI 0.60–0.72)). Conclusion: The prognostic performance of most scores was moderate in ECMO patients. The use of such scores to decide about ECMO implementation in potential candidates should be discouraged

The effects of nitric oxide on coagulation and inflammation in ex vivo models of extracorporeal membrane oxygenation and cardiopulmonary bypass

Background Extracorporeal life support (ECLS) has extensive applications in managing patients with acute cardiac and pulmonary failure. Two primary modalities of ECLS, cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), include several similarities in their composition, complications, and patient outcomes. Both CPB and ECMO pose a high risk of thrombus formation and platelet activation due to the large surface area of the devices and bleeding due to system anticoagulation. Therefore, novel methods of anticoagulation are needed to reduce the morbidity and mortality associated with extracorporeal support. Nitric oxide (NO) has potent antiplatelet properties and presents a promising alternative or addition to anticoagulation with heparin during extracorporeal support. Methods We developed two ex vivo models of CPB and ECMO to investigate NO effects on anticoagulation and inflammation in these systems. Results Sole addition of NO as an anticoagulant was not successful in preventing thrombus formation in the ex vivo setups, therefore a combination of low-level heparin with NO was used. Antiplatelet effects were observed in the ex vivo ECMO model when NO was delivered at 80 ppm. Platelet count was preserved after 480 min when NO was delivered at 30 ppm. Conclusion Combined delivery of NO and heparin did not improve haemocompatibility in either ex vivo model of CPB and ECMO. Anti-inflammatory effects of NO in ECMO systems have to be evaluated further

Pressure and Flow Properties of Cannulae for Extracorporeal Membrane Oxygenation I: Return (Arterial) Cannulae

Adequate extracorporeal membrane oxygenation support in the adult requires cannulae permitting blood flows up to 6-8 L/minute. In accordance with Poiseuille's law, flow is proportional to the fourth power of cannula inner diameter and inversely proportional to its length. Poiseuille's law can be applied to obtain the pressure drop of an incompressible, Newtonian fluid (such as water) flowing in a cylindrical tube. However, as blood is a pseudoplastic non-Newtonian fluid, the validity of Poiseuille's law is questionable for prediction of cannula properties in clinical practice. Pressure-flow charts with non-Newtonian fluids, such as blood, are typically not provided by the manufacturers. A standardized laboratory test of return (arterial) cannulae for extracorporeal membrane oxygenation was performed. The aim was to determine pressure-flow data with human whole blood in addition to manufacturers' water tests to facilitate an appropriate choice of cannula for the desired flow range. In total, 14 cannulae from three manufacturers were tested. Data concerning design, characteristics, and performance were graphically presented for each tested cannula. Measured blood flows were in most cases 3-21% lower than those provided by manufacturers. This was most pronounced in the narrow cannulae (15-17 Fr) where the reduction ranged from 27% to 40% at low flows and 5-15% in the upper flow range. These differences were less apparent with increasing cannula diameter. There was a marked disparity between manufacturers. Based on the measured results, testing of cannulae including whole blood flows in a standardized bench test would be recommended.info:eu-repo/semantics/publishedVersio

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Impact of gastroesophageal reflux disease symptoms on the quality of life in pregnant women

Objective Pregnant women often suffer from gastroesophageal reflux disease (GERD). GERD symptoms are known to influence the quality of life; however, there is a lack of data in pregnant women. The aim of this study was to establish the impact of GERD symptoms on health-related quality of life (HRQOL) during pregnancy. Participants and methods A prospective longitudinal cohort study to investigate the impact of GERD symptoms on the HRQOL was carried out in 510 pregnant women and 330 nonpregnant women as controls. Two validated questionnaires, the Reflux Disease Questionnaire and the Quality of Life in Reflux and Dyspepsia Questionnaire, were used. Results The study showed a significant negative impact on HRQOL in pregnant women with GERD symptoms. All five areas, emotional distress, sleep disturbance, vitality, food/drink problems, and physical/social functioning, were significantly reduced, but the most significant impact was on sleep (Quality of Life in Reflux and Dyspepsia Questionnaire score - 35%). Overall, quality of life in women with GERD worsened throughout pregnancy. Conclusion GERD is frequently seen in pregnant women and has a negative impact on HRQOL, especially in late pregnancy. Therefore, there is a need for adequate therapy of GERD in pregnant women and HRQOL could be an adequate monitoring tool in this population. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved

Whom are we treating with adaptive servo-ventilation? A clinical post hoc analysis

Background Recent evidence has shown that adaptive servo-ventilation (ASV) is contraindicated in patients with predominant central sleep apnea (CSA) and reduced left ventricular ejection fraction (LVEF <= 45%). The objective of this study was to assess the clinical usage of ASV in patients at the time-point of the release of a safety warning by type of SDB, breathing pattern and LVEF. Methods Patients of a cardiac and a respirology sleep center, both in Germany, who received ASV therapy were contacted between May and October 2015. Retrospective analyses included diagnostic polysomnography, polysomnography with continuous positive airway pressure prior to ASV initiation and echocardiography. Treatment emergent CSA was diagnosed after an appropriate treatment period on CPAP. Results 285 patients receiving ASV therapy (91 in the cardiac and 194 in the respirology setting) underwent diagnostic polysomnography. 233 (82%) patients had severe SDB, 94 (33%) predominant CSA, and 185 (65%) periodic breathing. 20% (n = 52) of patients had an LVEF of <= 45%. The most common indications for ASV were CSA in heart failure (41%) in the cardiac setting and treatment emergent CSA (80%) diagnosed after an appropriate period on CPAP in the respirology setting. The proportion of patients in whom ASV was contraindicated (CSA and LVEF <= 45%) was 16% in the cardiac setting and 9% in the respirology setting. Conclusion Clinical usage of ASV changed for a small subgroup of patients after release of the SERVE-HF results. Nevertheless, ASV treatment should be monitored and evaluated with diligence in the reminder indications

Incidence and Risk Factors for Cannula-Related Venous Thrombosis After Venovenous Extracorporeal Membrane Oxygenation in Adult Patients With Acute Respiratory Failure

Objectives: Venovenous extracorporeal membrane oxygenation is indicated in patients with severe refractory acute respiratory failure. Venous thrombosis due to indwelling catheters is a frequent complication. The aim of this study was to analyze the incidence of cannula-related thrombosis and its risk factors after venovenous extracorporeal membrane oxygenation. Design: Retrospective observational study. Setting: A medical ICU at the University Hospital Regensburg. Patients: We analyzed consecutive patients with severe respiratory failure (Pao 2 /Fio 2 < 85 mm Hg and/or respiratory acidosis with pH < 7.25) who were successfully treated with venovenous extracorporeal membrane oxygenation in a medical ICU between 2010 and 2017. Intervention: None. Measurements and Main Results: After extracorporeal membrane oxygenation weaning, duplex sonography or CT was conducted to detect cannula-related thrombosis. Thrombosis was classified as a large thrombosis by vein occlusion of greater than 50%. The incidence of thrombosis was correlated with risk factors such as coagulation variables (mean activated partial thromboplastin time = 50 s, international normalized ratio antithrombin III, fibrinogen, plasma-free hemoglobin, platelets, and decline in D-dimer = 50% the day after decannulation), cannula size, time on venovenous extracorporeal membrane oxygenation, renal failure, and underlying malignant disease. Data cut-off points were identified by receiver operating characteristic analysis. One-hundred seventy-two of 197 patients (87%) were screened. One-hundred six patients (62%) showed thrombosis that was considered large in 48 of 172 (28%). The incidence of thrombosis was higher in patients with a mean aPTT of less than or equal to 50 seconds (odds ratio, 1.02; p = 0.013) and in patients with a decline in D-dimer less than or equal to 50% (odds ratio, 2.76; p = 0.041) the day after decannulation following adjustment for risk factors. Conclusions: The incidence of cannula-related venous thrombosis after venovenous extracorporeal membrane oxygenation is high. Reduced systemic anticoagulation may enhance the risk of thrombosis. Sustained elevation of D-dimer after decannulation may indicate thrombosis. Patients should undergo routine duplex sonography after extracorporeal membrane oxygenation to detect thrombosis formation in the cannulated vessel

Hemostatic Changes During Extracorporeal Membrane Oxygenation

Objective: Extracorporeal membrane oxygenation is a rescue therapy for patients with severe lung failure. Major complications caused by extracorporeal membrane oxygenation are bleeding, thrombosis, and hemolysis. The aim of this study was to compare the impact of different extracorporeal membrane oxygenation systems on blood hemostasis in adults during veno-venous extracorporeal membrane oxygenation therapy. Design: Single center prospective randomized study. Setting: University Hospital Regensburg, Germany. Patients: Adult patients with severe acute respiratory distress syndrome requiring veno-venous extracorporeal membrane oxygenation therapy. Interventions: None. Measurements and Main Results: Three different extracorporeal membrane oxygenation systems: the Cardiohelp system (Maquet Cardiopulmonary AG), the Dideco ECC.O5 (Sorin Group), and the Deltastream system with Hilite 7000 LT + DP3 pumphead (Medos Medizintechnik AG) were compared. Therefore hemostasis, anticoagulation, hemolysis, and inflammatory parameters were monitored. Of the 54 patients included in the study, 18 patients each were randomly assigned to the three different extracorporeal membrane oxygenation systems. Exclusion criteria were acute renal failure, trauma, and surgery within 2 days. The median time on veno-venous extracorporeal membrane oxygenation support was 13.5 days (4-70 d). Median platelet count had dropped from 220.5 G/L before extracorporeal membrane oxygenation therapy to a minimum of 133 G/L by the last day of extracorporeal membrane oxygenation support. During the first 5 days of extracorporeal membrane oxygenation therapy, prothrombin fragment 1.2 (F1.2) (1.36-2.4 mu M), thrombin-antithrombin complex (14.5-50 mu g/L), and D-dimers (6.00-27.0 mg/L) increased, whereas fibrinogen values dropped from 5.8 to 4.1 g/L. The three different extracorporeal membrane oxygenation systems did not show any differences with regard to hemostasis, anticoagulation, hemolysis, and inflammatory parameters within the first 5 days of extracorporeal membrane oxygenation therapy. Conclusions: Over time, miniaturized veno-venous extracorporeal membrane oxygenation therapy increasingly activates coagulation. The different types of membrane oxygenators and pumps did not significantly alter hemostasis