Association between a low-risk COVID-19 extracorporeal membrane oxygenation criteria and mortality: A retrospective study.

OBJECTIVE: Our study aimed to compare the outcomes of COVID-19 patients who met a low-risk inclusion criteria for veno-venous extra corporeal membrane oxygenation (VV ECMO) with those who did not meet criteria due to higher risk but were subsequently cannulated. METHODS: This was a retrospective observational cohort study that included adult patients who were placed on VV ECMO for COVID-19 related acute respiratory distress syndrome (ARDS) at a tertiary care academic medical center. The primary outcome was the association between the low-risk criteria and mortality. The patients met the criteria if they met EOLIA severe ARDS criteria, no absolute contraindications (age > 60 years, BMI > 55 kg/m2, mechanical ventilation (MV) duration >7 days, irreversible neurologic damage, chronic lung disease, active malignancy, or advanced multiorgan dysfunction), and had three or less relative contraindications (age > 50 years, BMI > 45 kg/m2, comorbidities, MV duration > 4 days, acute kidney injury, receiving vasopressors, hospital LOS > 14 days, or COVID-19 diagnosis > 4 weeks). RESULTS: Sixty-five patients were included from March 2020 through March 2022. Patients were stratified into low-risk or high-risk categories. The median Sequential Organ Failure Assessment score was 7 and the median PaO2/FiO2 ratio was 44 at the time of ECMO cannulation. The in-hospital mortality was 47.8% in the low-risk group and 69.0% in the high-risk group (p = 0.096). CONCLUSION: There was not a statistically significant difference in survival between low-risk patients and high-risk patients; however, there was a trend toward higher survival in the lower-risk group.

Evaluation of Cangrelor Use After Percutaneous Coronary Intervention in Patients With Mechanical Circulatory Support.

OBJECTIVES: To describe cangrelor use in patients on concurrent mechanical circulatory support who underwent postpercutaneous coronary intervention. DESIGN: A single-center, retrospective, cohort study. SETTING: At a quaternary teaching hospital. PARTICIPANTS: Included patients were ≥18 years old, admitted to the intensive care unit, underwent percutaneous coronary intervention with stent placement, initiated on mechanical circulatory support, and received cangrelor in the postpercutaneous coronary intervention period. INTERVENTIONS: Retrospectively analyzed cangrelor use in patients on mechanical circulatory support. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the incidence of thrombosis and bleeding events during cangrelor administration. Additional outcomes included initial cangrelor dose, number of cangrelor dose adjustments per patient, survival from mechanical circulatory support, and mortality within 30 days. Overall, 19 patients were included in this study. In total, 14 patients (74%) experienced a bleeding event; however, 93% were classified as a minor bleed. There was 1 major bleeding event. There were no thrombotic events observed during cangrelor administration. The median initial cangrelor dose was 0.5 µg/kg/min. There were 10 patients who underwent dose adjustment, with the majority being dose reductions based on antiplatelet monitoring (VerifyNow assay). Survival from mechanical circulatory support occurred in 17 patients (89%), and 30-day mortality occurred in 8 patients (42%). CONCLUSIONS: For patients receiving cangrelor as a bridge to oral P2Y12 inhibitor therapy on mechanical circulatory support, the authors observed a low rate of major bleeding and no episodes of thrombosis. Lower starting doses appear feasible with no observed increased risk of thrombotic complications. Future studies are needed to confirm these observations.

Angiotensin II in Patients With Shock on Mechanical Circulatory Support: A Single-Center Retrospective Case Series.

OBJECTIVES: To describe angiotensin II (ANGII) use in patients on mechanical circulatory support (MCS). To evaluate the efficacy and safety of ANGII in patients with shock on MCS. DESIGN: Retrospective cohort study. SETTING: A single-center, quaternary care academic medical center. PARTICIPANTS: The study comprised critically ill patients on MCS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fourteen patients were included in this retrospective analysis. The median age was 54 years (44.8, 68.3) and 78.6% were men. Six patients were receiving venoarterial extracorporeal membrane oxygenation support, 4 patients were receiving venovenous extracorporeal membrane oxygenation support, and 4 patients were on left ventricular assist devices. Five patients (36%) achieved hemodynamic response to ANGII at 3 hours, defined as a mean arterial pressure (MAP) of ≥65 mmHg or a 10-mmHg increase in MAP with a decrease or no change in total vasopressor dose. Overall, the median MAP increased from 61 mmHg (51, 73) at baseline to 66 mmHg (58, 71) at 3 hours, and the median norepinephrine dose decreased from 0.45 µg/kg/min (0.28, 0.6) at baseline to 0.2 µg/kg/min (0.18, 0.32) at 3 hours. The in-hospital mortality rate was 78.6%. Two patients experienced severe adverse drug events and 1 patient had a sentinel thrombotic event. CONCLUSIONS: This study suggested that ANGII may provide a salvage treatment option in patients on MCS with refractory vasodilatory shock. There are several safety considerations with the use of ANGII in these patients. Prospective randomized controlled trials are needed to evaluate the safety and efficacy of ANGII in patients on MCS.

ECMO for Adults with Severe Respiratory Failure.

The technology to provide Extracorporeal Life Support (ELS) has existed for over four decades. Its use has increased markedly in the last decade, initially in response to severe Acute Respiratory Distress Syndrome (ARDS) in adults during the 2009 H1N1 influenza epidemic and continuing with the increasing acceptance of Extracorporeal Membrane Oxygenation (ECMO) for the treatment of severe respiratory failure in adults from other causes.1 We highlight the use of ECMO, particularly at our institution.

Safety of intensivist-led bedside decannulation of internal jugular bi-caval dual-lumen veno-venous extracorporeal membrane oxygenation cannulas and report of technique.

BACKGROUND: In the past decade, the rate and utilization of veno-venous extracorporeal membrane oxygenation (VV-ECMO) has increased dramatically. A single catheter technique has recently come into favour for providing VV-ECMO. Although it has been shown that intensivists can safely place these catheters, the safety of decannulation by intensivists has not been reported in the literature. OBJECTIVE: We describe a technique for safely decannulating the Avalon Elite VV-ECMO catheter at the bedside and assess the safety of this technique, as compared with the standard technique of decannulation in the operating room by a surgeon. METHODS: This was a retrospective cohort design conducted at a tertiary care cardiovascular intensive care unit at an academic medical centre. All patients who underwent VV-ECMO from 2009 to 2014 were included in the study except for those who had been decannulated for withdrawal of care. Complication rates from decannulation were compared between patients who were decannulated by surgeons in the operating room and those decannulated by intensivists in the intensive care unit (ICU). RESULTS: Twenty-eight patients were included in this study, of whom twenty-three patients (82%) were decannulated by intensivists, board certified in Critical Care Medicine through the American Board of Anesthesiology, while five (18%) the patients were decannulated by a surgeon. There was no significant difference in the complications rates between the surgeons (0) and intensivists (1) (P = 1.00). There were no major complications requiring operative intervention associated with decannulation identified in this study. CONCLUSIONS: It is safe for intensivists to decannulate the Avalon Elite VV-ECMO cannula in the ICU using our purse-string suture technique. Performing these decannulations at the bedside compared to operating room may have positive clinical ramifications that include improved patient safety, timely patient care and reduced operating room costs.

Inhibition of glutamatergic activation of extracellular signal-regulated protein kinases in hippocampal neurons by the intravenous anesthetic propofol.

BACKGROUND: Intravenous anesthetics cause amnesia, but the underlying molecular mechanisms are poorly understood. Recent studies reveal a significant role of extracellular signal-regulated protein kinases (ERKs) in controlling synaptic plasticity and memory formation. As a major synapse-to-nucleus superhighway, ERK transmits N-methyl-D-aspartate (NMDA) receptor signals to inducible transcriptional events essential for NMDA receptor-dependent forms of synaptic plasticity and memory. This study investigated the role of the widely used intravenous anesthetic propofol in regulating NMDA receptor-dependent ERK phosphorylation. METHODS: The possible effect of propofol on NMDA receptor-mediated ERK phosphorylation was detected in cultured rat hippocampal neurons with Western blot analysis. RESULTS: The authors found that propofol at clinical relevant concentrations (1-10 microm) reduced NMDA receptor-mediated ERK phosphorylation. This reduction was independent of gamma-aminobutyric acid transmission. The inhibition of the NMDA receptor seems to contribute to the effect of propofol on NMDA-stimulated ERK phosphorylation, because propofol reduced constitutive NMDA receptor NR1 subunit phosphorylation and impaired NMDA receptor-mediated Ca influx. Furthermore, by inhibiting the ERK pathway, propofol blocked NMDA receptor-dependent activation of two key transcription factors, Elk-1 and cyclic adenosine monophosphate response element-binding protein (CREB), and, as a result, attenuated Elk-1/CREB-dependent reporter gene (c-Fos) expression. CONCLUSIONS: These results suggest that propofol possesses the ability to inhibit NMDA receptor activation of the ERK pathway and subsequent transcriptional activities in hippocampal neurons. These findings indicate a new avenue to explore a transcription-dependent mechanism that may underlie anesthetic interference with synaptic plasticity related to amnesic properties of intravenous anesthetics.

A signaling mechanism from G alpha q-protein-coupled metabotropic glutamate receptors to gene expression: role of the c-Jun N-terminal kinase pathway.

Galphaq-protein-coupled group I metabotropic glutamate receptors (mGluRs) are densely expressed in brain neurons and are actively involved in various cellular activities. In this study, we investigated the role of group I mGluRs in regulating the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase in cultured neurons. We found that selective activation of mGluR5 induced a rapid and transient phosphorylation of JNK. In a series of studies to determine the mechanisms, we found that the conventional mGluR5-associated signaling pathways (inositol-1,4,5-triphosphate-mediated Ca2+ release and activation of protein kinase C) were not involved in the mGluR5 regulation. Instead, ligand stimulation of mGluR5 caused a dynamic transactivation of the epidermal growth factor (EGF) receptor, which in turn triggered a downstream signaling pathway to upregulate JNK phosphorylation. Furthermore, the mGluR5-dependent JNK activation specifically activated c-Jun, but not activating transcription factor-2 or JunD, and increased activator protein-1 (AP-1)-mediated endogenous transcriptional activity. Together, we identified a novel mGluR5-to-nucleus communication through the EGF/JNK pathway, which functions to regulate AP-1-mediated transcription.