Refractory circulatory failure in COVID-19 patients treated with veno-arterial ECMO: A retrospective single-center experience

Objectives: Data about COVID-19 patients treated with veno-arterial-ECMO (VA-ECMO) is limited. Reported survival rates range from 27.9% to 77.8%, depending on VA-ECMO indication. A subgroup of patients suffers from circulatory failure due to a COVID-19 associated hyperinflammatory state (CovHI). In these patients, differentiation between inflammation and sepsis is difficult but important. In this retrospective case series, differential diagnoses of COVID-19 associated refractory circulatory failure and survival rates in different indications for VA-ECMO are investigated. Method(s): Retrospective analysis of 28 consecutive COVID-19 patients requiring VA-ECMO at the University Hospital Regensburg between March 2020 and May 2022. Specific treatment for COVID-19 was in accordance with respective guidelines. Mycotic infections were either invasive or met current definitions of COVID19-associated-pulmonary aspergillosis. Result(s): At VA-ECMO initiation, median age was 57.3 years (IQR: 51.4 - 61.8), SOFA score 16 (IQR: 13 - 17) and norepinephrine dosing 0.53mug/kg/min (IQR: 0.32 - 0.78). Virus-variants were: 61% wild-type, 14% Alpha, 18% Delta and 7% Omicron. Survival to hospital discharge was 39%. 17 patients were primarily supported with VA-ECMO only (survival 42%), 3 patients were switched from VV to VA-ECMO (survival 0%), and 8 patients were converted from VA to VAV or VV-ECMO (survival 50%). Indications for VA-ECMO support were pulmonary embolism (PE) (n=5, survival 80%), right heart failure due to secondary pulmonary hypertension (n=5, survival 20%), cardiac arrest (n=4, survival 25%), acute left heart failure (ALHF) (n=11, survival 36%) and refractory vasoplegia (n=3, survival 0%). Inflammatory markers at VA-ECMO initiation were higher in patients with ALHF or vasoplegia;in these patients a higher rate of invasive fungal infections (10/14, 71% vs. 4/14, 29%;p=0.023) compared to the other patients was found. Conclusion(s): Survival on VA-ECMO in COVID-19 depends on VA-ECMO indication, which should be considered in further studies and clinical decisions making. Circulatory failure due to vasoplegia should be considered very carefully as indication for VA-ECMO. A high rate of mycotic infections mandates an intense microbiological workup of these patients and must be considered as an important differential diagnosis to CovHI.

Angiotensin in shock

Angiotensin II is a potent vasoconstrictor agent, but until recently there has been little interest in using it as a therapeutic agent in hypotensive conditions. In an ovine model of sepsis with acute kidney injury, we demonstrated that angiotensin II restored arterial pressure and improved renal function, without adverse effects. Importantly, unlike noradrenaline, angiotensin II did not worsen sepsis-induced renal medullary hypoxia. Following these preclinical studies, angiotensin II was developed as a treatment (Giapreza®) for vasodilatory shock. The safety and efficacy of angiotensin II have been examined in numerous clinical trials that indicate it effectively restores arterial pressure in patients with sepsis, COVID-19, and postoperative vasoplegia. In the ATHOS-3 trial, in those patients who received renal replacement therapy, 28-day survival was greater with earlier liberation from renal replacement therapy. In those patients with increased plasma renin concentrations, mortality was reduced, and release from renal replacement therapy and ICU discharge occurred earlier. Thus, angiotensin II appears to be an effective treatment for vasodilatory shock, and further examination of its efficacy as a primary vasopressor and optimization of the choice of patient based on renin levels is warranted. © 2023 Elsevier Inc. All rights reserved.

Methylene blue and hydroxocobalamin in a severely vasoplegic lung transplant recipient

INTRODUCTION: Vasoplegia is defined as a refractory shock state with profound hypotension in the setting of reduced systemic vascular resistance and high cardiac output. Lung transplantation is an arduous surgery often requiring cardiopulmonary bypass, which ultimately predisposes to vasoplegia. We detail the treatment of a patient with end-stage lung disease secondary to COVID-19 pneumonia undergoing lung transplant who developed vasoplegia. DESCRIPTION: The patient is a 36-year-old female who was admitted with profound hypoxemic respiratory failure secondary to COVID-19 pneumonia. Despite initial therapy, she remained ventilator-dependent with need for extracorporeal membrane oxygenation (ECMO) support. Given her single organ failure status - lungs being solely affected - she was promptly considered for lung transplant evaluation upon resolution of her active SARS-CoV-2 infection. She was ultimately deemed appropriate for listing and underwent subsequent transplant. The surgery required the use of cardiopulmonary bypass, given the extensive adhesions of the native COVID-19-infected lungs. The lungs were, unfortunately, quite necrotic, with multiple purulent pockets. She was profoundly hypotensive throughout the surgery and required massive fluid resuscitation, as well as multiple vasopressors. In the setting of this vasoplegia, she received multiple doses of methylene blue at 2 mg/kg, with only marginal improvement in blood pressure. Decision was made to add high-dose (5 g) hydroxocobalamin in an attempt to synergistically stabilize blood pressure. Intraoperatively, her blood pressure stabilized within hours;she remained on ECMO support and was transferred to the ICU postoperatively. Eventually, she was slowly weaned from her vasopressors, with stable blood pressure. DISCUSSION: Methylene blue mechanistically inhibits inducible nitric oxide synthase and guanylyl cyclase, while hydroxycobalamin acts as a nitric oxide scavenger. Both agents have been used independently to treat vasoplegia during cardiopulmonary bypass. Together, they may be used as a salvage therapy to improve blood pressure in refractory cases of shock seemingly exacerbated by the cytokine milieu promoted by recent SARS-CoV-2 infection.

Effects of a single bolus of hydroxocobalamin on hemodynamics in vasodilatory shock.

PURPOSE: Hydroxocobalamin has been observed to cause transient hypertension in healthy subjects, but rigorous studies examining its efficacy are lacking. MATERIALS AND METHODS: Adults in shock who received hydroxocobalamin from 2017 to 2021 were analyzed retrospectively. Hourly hemodynamics from 24 h before and after treatment were collected, and the difference and hourly change of mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), and norepinephrine-equivalent dose (NED) were examined in mixed-effects models. RESULTS: This study included 3992 hemodynamic data points from 35 patients and is the largest case series to date. In the mixed effects model, there was no difference in MAP 24-h after hydroxocobalamin administration (estimated fixed effect [EFE] -0.2 mmHg, p = 0.89). A two-piecewise mixed model found that the hourly change in MAP was not different from zero in either the pre-administration (EFE 0.0 mmHg/h, p = 0.80) or post-administration segments (EFE 0.0 mmHg/h, p = 0.55). Analysis of the SBP, DBP, and NED also found similar insignificant results. CONCLUSIONS: Although hydroxocobalamin has been observed to cause hypertension in healthy subjects, our results suggest that in patients with shock, hydroxocobalamin may not be effective in improving hemodynamics at 24 h after administration.

COVID-19: What Iodine Maps From Perfusion CT can reveal-A Prospective Cohort Study.

BACKGROUND: Subtraction CT angiography (sCTA) is a technique used to evaluate pulmonary perfusion based on iodine distribution maps. The aim of this study is to assess lung perfusion changes with sCTA seen in patients with COVID-19 pneumonia and correlate them with clinical outcomes. MATERIAL AND METHODS: A prospective cohort study was carried out with 45 RT-PCR-confirmed COVID-19 patients that required hospitalization at three different hospitals, between April and May 2020. In all cases, a basic clinical and demographic profile was obtained. Lung perfusion was assessed using sCTA. Evaluated imaging features included: Pattern predominance of injured lung parenchyma in both lungs (ground-glass opacities, consolidation and mixed pattern) and anatomical extension; predominant type of perfusion abnormality (increased perfusion or hypoperfusion), perfusion abnormality distribution (focal or diffuse), extension of perfusion abnormalities (mild, moderate and severe involvement); presence of vascular dilatation and vascular tortuosity. All participants were followed-up until hospital discharge searching for the development of any of the study endpoints. These endpoints included intensive-care unit (ICU) admission, initiation of invasive mechanical ventilation (IMV) and death. RESULTS: Forty-one patients (55.2 ± 16.5 years, 22 men) with RT-PCR-confirmed SARS-CoV-2 infection and an interpretable iodine map were included. Patients with perfusion anomalies on sCTA in morphologically normal lung parenchyma showed lower Pa/Fi values (294 ± 111.3 vs. 397 ± 37.7, p = 0.035), and higher D-dimer levels (1156 ± 1018 vs. 378 ± 60.2, p < 0.01). The main common patterns seen in lung CT scans were ground-glass opacities, mixed pattern with predominant ground-glass opacities and mixed pattern with predominant consolidation in 56.1%, 24.4% and 19.5% respectively. Perfusion abnormalities were common (36 patients, 87.8%), mainly hypoperfusion in areas of apparently healthy lung. Patients with severe hypoperfusion in areas of apparently healthy lung parenchyma had an increased probability of being admitted to ICU and to initiate IMV (HR of 11.9 (95% CI 1.55-91.9) and HR 7.8 (95% CI 1.05-61.1), respectively). CONCLUSION: Perfusion abnormalities evidenced in iodine maps obtained by sCTA are associated with increased admission to ICU and initiation of IMV in COVID-19 patients.