Bilateral Femoral Cannulation Is Associated With Reduced Severe Limb Ischemia-Related Complications Compared With Unilateral Femoral Cannulation in Adult Peripheral Venoarterial Extracorporeal Membrane Oxygenation: Results From the Extracorporeal Life Support Registry.

OBJECTIVES: Peripheral venoarterial extracorporeal membrane oxygenation (ECMO) with femoral access is obtained through unilateral or bilateral groin cannulation. Whether one cannulation strategy is associated with a lower risk for limb ischemia remains unknown. We aim to assess if one strategy is preferable. DESIGN: A retrospective cohort study based on the Extracorporeal Life Support Organization registry. SETTING: ECMO centers worldwide included in the Extracorporeal Life Support Organization registry. PATIENTS: All adult patients (≥ 18 yr) who received peripheral venoarterial ECMO with femoral access and were included from 2014 to 2020. INTERVENTIONS: Unilateral or bilateral femoral cannulation. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the occurrence of limb ischemia defined as a composite endpoint including the need for a distal perfusion cannula (DPC) after 6 hours from implantation, compartment syndrome/fasciotomy, amputation, revascularization, and thrombectomy. Secondary endpoints included bleeding at the peripheral cannulation site, need for vessel repair, vessel repair after decannulation, and in-hospital death. Propensity score matching was performed to account for confounders. Overall, 19,093 patients underwent peripheral venoarterial ECMO through unilateral ( n = 11,965) or bilateral ( n = 7,128) femoral cannulation. Limb ischemia requiring any intervention was not different between both groups (bilateral vs unilateral: odds ratio [OR], 0.92; 95% CI, 0.82-1.02). However, there was a lower rate of compartment syndrome/fasciotomy in the bilateral group (bilateral vs unilateral: OR, 0.80; 95% CI, 0.66-0.97). Bilateral cannulation was also associated with lower odds of cannulation site bleeding (bilateral vs unilateral: OR, 0.87; 95% CI, 0.76-0.99), vessel repair (bilateral vs unilateral: OR, 0.55; 95% CI, 0.38-0.79), and in-hospital mortality (bilateral vs unilateral: OR, 0.85; 95% CI, 0.81-0.91) compared with unilateral cannulation. These findings were unchanged after propensity matching. CONCLUSIONS: This study showed no risk reduction for overall limb ischemia-related events requiring DPC after 6 hours when comparing bilateral to unilateral femoral cannulation in peripheral venoarterial ECMO. However, bilateral cannulation was associated with a reduced risk for compartment syndrome/fasciotomy, lower rates of bleeding and vessel repair during ECMO, and lower in-hospital mortality.

Facial appearance associates with longitudinal multi-organ failure: an ICU cohort study.

BACKGROUND: Facial appearance, whether consciously or subconsciously assessed, may affect clinical assessment and treatment strategies in the Intensive Care Unit (ICU). Nevertheless, the association between objective clinical measurement of facial appearance and multi-organ failure is currently unknown. The objective of this study was to examine whether facial appearance at admission is associated with longitudinal evaluation of multi-organ failure. METHODS: This was a sub-study of the Simple Intensive Care Studies-II, a prospective observational cohort study. All adult patients acutely admitted to the ICU between March 26, 2019, and July 10, 2019, were included. Facial appearance was assessed within three hours of ICU admission using predefined pictograms. The SOFA score was serially measured each day for the first seven days after ICU admission. The association between the extent of eye-opening and facial skin colour with longitudinal Sequential Organ Failure Assessment (SOFA) scores was investigated using generalized estimation equations. RESULTS: SOFA scores were measured in 228 patients. Facial appearance scored by the extent of eye-opening was associated with a higher SOFA score at admission and follow-up (unadjusted 0.7 points per step (95%CI 0.5 to 0.9)). There was no association between facial skin colour and a worse SOFA score over time. However, patients with half-open or closed eyes along with flushed skin had a lower SOFA score than patients with a pale or normal facial skin colour (P-interaction < 0.1). CONCLUSIONS: The scoring of patients' facial cues, primarily the extent of eye-opening and facial colour, provided valuable insights into the disease state and progression of the disease of critically ill patients. The utilization of advanced monitoring techniques that incorporate facial appearance holds promise for enhancing future intensive care support.

High-Sensitivity Cardiac Troponin I and T Kinetics Differ following Coronary Bypass Surgery: A Systematic Review and Meta-Analysis.

BACKGROUND: Cardiac troponin I and T are both used for diagnosing myocardial infarction (MI) after coronary artery bypass grafting (CABG), also known as type 5 MI (MI-5). Different MI-5 definitions have been formulated, using multiples of the 99th percentile upper reference limit (10×, 35×, or 70× URL), with or without supporting evidence. These definitions are arbitrarily chosen based on conventional assays and do not differentiate between troponin I and T. We therefore investigated the kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) following CABG. METHODS: A systematic search was applied to MEDLINE and EMBASE databases including the search terms "coronary artery bypass grafting" AND "high-sensitivity cardiac troponin." Studies reporting hs-cTnI or hs-cTnT on at least 2 different time points were included. Troponin concentrations were extracted and normalized to the assay-specific URL. RESULTS: For hs-cTnI and hs-cTnT, 17 (n = 1661 patients) and 15 studies (n = 2646 patients) were included, respectively. Preoperative hs-cTnI was 6.1× URL (95% confidence intervals: 4.9-7.2) and hs-cTnT 1.2× URL (0.9-1.4). Mean peak was reached 6-8 h postoperatively (126× URL, 99-153 and 45× URL, 29-61, respectively). Subanalysis of hs-cTnI illustrated assay-specific peak heights and kinetics, while subanalysis of surgical strategies revealed 3-fold higher hs-cTnI than hs-cTnT for on-pump CABG and 5-fold for off-pump CABG. CONCLUSION: Postoperative hs-cTnI and hs-cTnT following CABG surpass most current diagnostic cutoff values. hs-cTnI was almost 3-fold higher than hs-cTnT, and appeared to be highly dependent on the assay used and surgical strategy. There is a need for assay-specific hs-cTnI and hs-cTnT cutoff values for accurate, timely identification of MI-5.

Serial markers of coagulation and inflammation and the occurrence of clinical pulmonary thromboembolism in mechanically ventilated patients with SARS-CoV-2 infection; the prospective Maastricht intensive care COVID cohort.

BACKGROUND: The incidence of pulmonary thromboembolism is high in SARS-CoV-2 patients admitted to the Intensive Care. Elevated biomarkers of coagulation (fibrinogen and D-dimer) and inflammation (c-reactive protein (CRP) and ferritin) are associated with poor outcome in SARS-CoV-2. Whether the time-course of fibrinogen, D-dimer, CRP and ferritin is associated with the occurrence of pulmonary thromboembolism in SARS-CoV-2 patients is unknown. We hypothesise that patients on mechanical ventilation with SARS-CoV-2 infection and clinical pulmonary thromboembolism have lower concentrations of fibrinogen and higher D-dimer, CRP, and ferritin concentrations over time compared to patients without a clinical pulmonary thromboembolism. METHODS: In a prospective study, fibrinogen, D-dimer, CRP and ferritin were measured daily. Clinical suspected pulmonary thromboembolism was either confirmed or excluded based on computed tomography pulmonary angiography (CTPA) or by transthoracic ultrasound (TTU) (i.e., right-sided cardiac thrombus). In addition, patients who received therapy with recombinant tissue plasminogen activator were included when clinical instability in suspected pulmonary thromboembolism did not allow CTPA. Serial data were analysed using a mixed-effects linear regression model, and models were adjusted for known risk factors (age, sex, APACHE-II score, body mass index), biomarkers of coagulation and inflammation, and anticoagulants. RESULTS: Thirty-one patients were considered to suffer from pulmonary thromboembolism ((positive CTPA (n = 27), TTU positive (n = 1), therapy with recombinant tissue plasminogen activator (n = 3)), and eight patients with negative CTPA were included. After adjustment for known risk factors and anticoagulants, patients with, compared to those without, clinical pulmonary thromboembolism had lower average fibrinogen concentration of - 0.9 g/L (95% CI: - 1.6 - - 0.1) and lower average ferritin concentration of - 1045 µg/L (95% CI: - 1983 - - 106) over time. D-dimer and CRP average concentration did not significantly differ, 561 µg/L (- 6212-7334) and 27 mg/L (- 32-86) respectively. Ferritin lost statistical significance, both in sensitivity analysis and after adjustment for fibrinogen and D-dimer. CONCLUSION: Lower average concentrations of fibrinogen over time were associated with the presence of clinical pulmonary thromboembolism in patients at the Intensive Care, whereas D-dimer, CRP and ferritin were not. Lower concentrations over time may indicate the consumption of fibrinogen related to thrombus formation in the pulmonary vessels.

Nitric Oxide Ventilation Improves Recirculation and Right Ventricular Function During Veno-Venous Extracorporeal Membrane Oxygenation in a COVID-19 Patient.

Patients with coronavirus disease 2019 (COVID-19) are prone to pulmonary artery hypertension (PAH) and right ventricular pressure overload due to severe bilateral infiltrates, high ventilation pressures, persistent hypoxemia, pulmonary fibrosis, and/or pulmonary embolism. In patients on extracorporeal membrane oxygenation (ECMO), this potentially leads to increased recirculation. In the current report, the authors present a case in which continuous inhaled nitric oxide (iNO)-enriched ventilation was effective in terms of PAH and recirculation reduction in a COVID-19 patient on veno-venous ECMO.

The impact of Centre's heart transplant status and volume on in-hospital outcomes following extracorporeal membrane oxygenation for refractory post-cardiotomy cardiogenic shock: a meta-analysis.

BACKGROUND: Postcardiotomy cardiogenic shock (PCS) that is refractory to inotropic support remains a major concern in cardiac surgery and is almost universally fatal unless treated with mechanical support. While reported mortality rates on ECMO vary from center to center, aim of the current report is assess if the outcomes differ between centres according to volume and heart transplantation status. METHODS: A systematic search was performed according to PRISMA statement using PubMed/Medline databases between 2010 and 2018. Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and heart transplantation status of the centre. Paediatric and congenital heart surgery-related studies along with those conducted in the setting of veno-venous ECMO for respiratory distress syndrome were excluded. Differences were assessed by means of subgroup meta-analysis and meta-regression. RESULTS: Fifty-four studies enrolling N = 4421 ECMO patients were included. Of those, 6 series were performed in non-HTx centres (204 pts.;4.6%). Overall 30-day survival (95% Confidence Intervals) was 35.3% (32.5-38.2%) and did not statistically differ between non-HTx: 33.3% (26.8-40.4%) and HTx centres: 35.7% (32.7-38.8%); Pinteraction = 0.531. There was no impact of centre volume on survival as well: ßcoef = 0.0006; P = 0.833. No statistical differences were seen between HTx and non-HTx with respect to ECMO duration, limb complications, reoperations for bleeding, kidney injury and sepsis. There were however significantly less neurological complications in the HTx as compared to non-HTx centres: 11.9% vs 19.5% respectively; P = 0.009; an inverse relationship was seen for neurologic complications in centres performing more ECMOs annually ßcoef = - 0.0066; P = 0.031. Weaning rates and bridging to HTx and/or VADs were higher in HTx facilities. CONCLUSIONS: There was no apparent difference in survival after ECMO implantation for refractory PCS according to centre's ECMO volume and transplantation status. Potentially different risk profiles of patients in these centres must be taken account for before definite conclusions are drawn.

Baseline surgical status and short-term mortality after extracorporeal membrane oxygenation for post-cardiotomy shock: a meta-analysis.

OBJECTIVE: While reported mortality rates on post-cardiotomy extracorporeal membrane oxygenation vary from center to center, impact of baseline surgical status (elective/urgent/emergency/salvage) on mortality is still unknown. METHODS: A systematic search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement using PubMed/Medline databases until March 2018 using the keywords "postcardiotomy," "cardiogenic shock," "extracorporeal membrane oxygenation," and "extracorporeal life support." Relevant articles were scrutinized and included in the meta-analysis only if reporting in-hospital/30-day mortality and baseline surgical status. The correlations between mortality and percentage of elective/urgent/emergency cases were investigated. Inference analysis of baseline status and extracorporeal membrane oxygenation complications was conducted as well. RESULTS: Twenty-two studies (conducted between 1993 and 2017) enrolling N = 2,235 post-cardiotomy extracorporeal membrane oxygenation patients were found. Patients were mostly of non-emergency status (65.2%). Overall in-hospital/30-day mortality event rate (95% confidence intervals) was 66.7% (63.3-69.9%). There were no differences in in-hospital/30-day mortality with respect to baseline surgical status in the subgroup analysis (test for subgroup differences; p = 0.406). Similarly, no differences between mortality in studies enrolling <50 versus ⩾50% of emergency/salvage cases was found: respective event rates were 66.9% (63.1-70.4%) versus 64.4% (57.3-70.8%); p = 0.525. Yet, there was a significant positive association between increasing percentage of emergency/salvage cases and rates of neurological complications (p < 0.001), limb complications (p < 0.001), and bleeding (p = 0.051). Incidence of brain death (p = 0.099) and sepsis (p = 0.134) was increased as well. CONCLUSION: Other factors than baseline surgical status may, to a higher degree, influence the mortality in patients treated with extracorporeal membrane oxygenation for post-cardiotomy cardiogenic shock. Baseline status, however, strongly influences the complication occurrence while on extracorporeal membrane oxygenation.

Protracted aortic valve closure during peripheral veno-arterial extracorporeal life support: is intra-aortic balloon pump an effective solution?

BACKGROUND: Left ventricular (LV) afterload increase with protracted aortic valve (AV) closure may represent a complication of veno-arterial extracorporeal membrane oxygenation (V-A ECMO). The aim of the present study was to assess the effects of an intra-aortic balloon pump (IABP) to overcome such a hemodynamic shortcoming in patients submitted to peripheral V-A ECMO. METHODS: Among 184 adult patients who were treated with peripheral V-A ECMO support at Medical University Center Maastricht Hospital between 2007 and 2018, patients submitted to IABP implant for protracted AV closure after V-A ECMO implant were retrospectively identified. All clinical and hemodynamic data, including echocardiographic monitoring, were collected and analyzed. RESULTS: During the study period, 10 subjects (mean age 60 years old, 80% males) underwent IABP implant after peripheral V-A ECMO positioning due to the diagnosis of protracted AV closure and inefficient LV unloading as assessed by echocardiography and an absence of pulsation in the arterial pressure wave. Recovery of blood pressure pulsatility and enhanced LV unloading were observed in 8 patients after IABP placement, with no significant differences in the main hemodynamic parameters, inotropic therapy or in the ECMO flow (p=0.48). The weaning rate in this patient subgroup (mean ECMO duration 8 days), however, was only 10%, with another patient finally transplanted, leading to a 20% survival-to-hospital discharge. CONCLUSION: IABP placement was an effective solution in order to reverse the protracted AV closure and impaired LV unloading observed during peripheral V-A ECMO support. However, the impact on the weaning rate and survival needs further investigations.

Hypertrophic remodelling in cardiac regulatory myosin light chain (MYL2) founder mutation carriers.

AIMS: Phenotypic heterogeneity and incomplete penetrance are common in patients with hypertrophic cardiomyopathy (HCM). We aim to improve the understanding in genotype-phenotype correlations in HCM, particularly the contribution of an MYL2 founder mutation and risk factors to left ventricular hypertrophic remodelling. METHODS AND RESULTS: We analysed 14 HCM families of whom 38 family members share the MYL2 c.64G > A [p.(Glu22Lys)] mutation and a common founder haplotype. In this unique cohort, we investigated factors influencing phenotypic outcome in addition to the primary mutation. The mutation alone showed benign disease manifestation with low penetrance. The co-presence of additional risk factors for hypertrophy such as hypertension, obesity, or other sarcomeric gene mutation increased disease penetrance substantially and caused HCM in 89% of MYL2 mutation carriers (P = 0.0005). The most prominent risk factor was hypertension, observed in 71% of mutation carriers with HCM and an additional risk factor. CONCLUSION: The MYL2 mutation c.64G > A on its own is incapable of triggering clinical HCM in most carriers. However, the presence of an additional risk factor for hypertrophy, particularly hypertension, adds to the development of HCM. Early diagnosis of risk factors is important for early treatment of MYL2 mutation carriers and close monitoring should be guaranteed in this case. Our findings also suggest that the presence of hypertension or another risk factor for hypertrophy should not be an exclusion criterion for genetic studies.

Rotational thromboelastometry as a biomarker for mortality - The Maastricht Intensive Care COVID cohort.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID-19) present with persisting hypercoagulability, hypofibrinolysis and prolonged clot initiation as measured with viscoelastic assays. The objective of this study was to investigate the trajectories of traditional assays of hemostasis, routine and tissue plasminogen activator (tPA) rotational thromboelastometry (ROTEM) in COVID-19 patients and to study their association with mortality. METHODS: Patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included. Traditional assays of hemostasis (prothrombin time; PT, fibrinogen and D-dimer) were measured daily and ROTEM EXTEM, FIBTEM and tPA assays were performed weekly. Trajectories of these biomarkers were analyzed over time for survivors and non-survivors using linear mixed-effects models. Additional Fine and Gray competing risk survival analysis was performed for the first available measurement after intubation. RESULTS: Of the 138 included patients, 57 (41 %) died in the intensive care unit (ICU). Over 450, 400 and 1900 individual measurements were available for analysis of routine, tPA ROTEM and traditional assays of hemostasis, respectively, with a median [IQR] follow-up of 15 [8-24] days. Non-survivors on average had prolonged CT (clotting time) and increased fibrinogen compared to survivors. MCF (maximum clot firmness), LOT (lysis onset time), LT (lysis time) and PT measurements increased more over time in non-survivors compared to survivors. Associations persisted after adjustment for demographics and disease severity. EXTEM and FIBTEM CT at intubation were associated with increased 45-day ICU mortality. CONCLUSIONS: ROTEM measurements demonstrate a further increase of hypercoagulability and (hypo)fibrinolysis parameters in non-survivors throughout ICU admission. Furthermore, prolonged CT at intubation was associated with higher 45-day ICU mortality.