Characteristics of delirium and its association with sedation and in-hospital mortality in patients with COVID-19 on veno-venous extracorporeal membrane oxygenation.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods: We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU (CAM-ICU) when patients scored-3 or above on the Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence and duration in the proportion of days on VV-ECMO. Results: Of 47 patients (median age = 51), 6 were in a persistent coma and 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n = 21) and non-survivors (n = 26) was first detected at a similar time point (VV-ECMO day 9.5(5,14) vs. 8.5(5,21), p = 0.56) with similar total delirium days on VV-ECMO (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3] days, p = 0.43). Non-survivors had numerically lower RASS scores on VV-ECMO days (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p = 0.06) and significantly prolonged delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0(6,23), p = 0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p = 0.04). The proportion of delirium-present days correlated with RASS (r = 0.64, p < 0.001), the proportions of days on VV-ECMO with a neuromuscular blocker (r = -0.59, p = 0.001), and with delirium-unassessable exams (r = -0.69, p < 0.001) but not with overall ECMO duration (r = 0.01, p = 0.96). The average daily dosage of delirium-related medications on ECMO days did not differ significantly. On an exploratory multivariable logistic regression, the proportion of delirium days was not associated with mortality. Conclusion: Longer duration of delirium was associated with lighter sedation and shorter paralysis, but it did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

A case series evaluating the effect of esmolol therapy to treat hypoxemia in COVID-19 patients on VV-ECMO.

When COVID-19 ARDS abolishes pulmonary function, VV-ECMO can provide gas exchange. If oxygenation remains insufficient despite maximal VV-ECMO support, the addition of esmolol has been proposed. Conflict exists, however, as to the oxygenation level which should trigger beta-blocker initiation. We evaluated the effect of esmolol therapy on oxygenation and oxygen delivery in patients with negligible native lung function and various degrees of hypoxemia despite maximal VV-ECMO support. We found that, in COVID-19 patients with negligible pulmonary gas exchange, the generalized use of esmolol administration to raise arterial oxygenation by slowing heart rate and thereby match native cardiac output to maximal attainable VV ECMO flows actually reduces systemic oxygen delivery in many cases.

Rising Mortality in Coronavirus-19 Patients Supported With Extracorporeal Membrane Oxygenation.

We aimed to describe practice patterns and outcomes in patients with extracorporeal membrane oxygenation (ECMO) support throughout the coronavirus 2019 (COVID-19) pandemic, with the hypothesis that mortality would improve as we accumulated knowledge and experience. We included 48 patients supported on veno-venous ECMO (VV-ECMO) at a single institution between April 2020 and December 2021. Patients were categorized into three waves based on cannulation date, corresponding to the wild-type (wave 1), alpha (wave 2), and delta (wave 3) variants. One hundred percent of patients in waves 2 and 3 received glucocorticoids, compared with 29% in wave 1 ( p < 0.01), and the majority received remdesivir (84% and 92% in waves 2 and 3, vs . 35% in wave 1; p < 0.01). Duration of pre-ECMO noninvasive ventilation was longer in waves 2 and 3 (mean 8.8 days and 3.9 days, vs . 0.7 days in wave 1; p < 0.01), as was time to cannulation (mean 17.2 and 14.6 days vs . 8.8 days in wave 1; p < 0.01) and ECMO duration (mean 55.7 days and 43.0 days vs . 28.4 days in wave 1; p = 0.02). Mortality in wave 1 was 35%, compared with 63% and 75% in waves 2 and 3 ( p = 0.05). These results suggest an increased prevalence of medically refractory disease and rising mortality in later variants of COVID-19.

Translational design for limited resource settings as demonstrated by Vent-Lock, a 3D-printed ventilator multiplexer.

BACKGROUND: Mechanical ventilators are essential to patients who become critically ill with acute respiratory distress syndrome (ARDS), and shortages have been reported due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We utilized 3D printing (3DP) technology to rapidly prototype and test critical components for a novel ventilator multiplexer system, Vent-Lock, to split one ventilator or anesthesia gas machine between two patients. FloRest, a novel 3DP flow restrictor, provides clinicians control of tidal volumes and positive end expiratory pressure (PEEP), using the 3DP manometer adaptor to monitor pressures. We tested the ventilator splitter circuit in simulation centers between artificial lungs and used an anesthesia gas machine to successfully ventilate two swine. RESULTS: As one of the first studies to demonstrate splitting one anesthesia gas machine between two swine, we present proof-of-concept of a de novo, closed, multiplexing system, with flow restriction for potential individualized patient therapy. CONCLUSIONS: While possible, due to the complexity, need for experienced operators, and associated risks, ventilator multiplexing should only be reserved for urgent situations with no other alternatives. Our report underscores the initial design and engineering considerations required for rapid medical device prototyping via 3D printing in limited resource environments, including considerations for design, material selection, production, and distribution. We note that optimization of engineering may minimize 3D printing production risks but may not address the inherent risks of the device or change its indications. Thus, our case report provides insights to inform future rapid prototyping of medical devices.

Neurological Complications in COVID-19 Patients With ECMO Support: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with Coronavirus disease 2019 (COVID-19)-related acute respiratory disease (ARDS) increasingly receive extracorporeal membrane oxygenation (ECMO) support. While ECMO has been shown to increase risk of stroke, few studies have examined this association in COVID-19 patients. OBJECTIVE: We conducted a systematic review to characterise neurological events during ECMO support in COVID-19 patients. DESIGN: Systematic review of cohort and large case series of COVID-19 patients who received ECMO support. DATA SOURCES: Studies retrieved from PubMed, EMBASE, Cochrane, Cochrane COVID-19 Study Register, Web of Science, Scopus, Clinicaltrials.gov, and medRχiv from inception to November 11, 2020. ELIGIBILITY CRITERIA: Inclusion criteria were a) Adult population (>18 year old); b) Positive PCR test for SARS-CoV-2 with active COVID-19 disease; c) ECMO therapy due to COVID-19 ARDS; and d) Neurological events and outcome described while on ECMO support. We excluded articles when no details of neurologic events were available. RESULTS: 1,322 patients from 12 case series and retrospective cohort studies were included in our study. The median age was 49.2, and 75% (n=985) of the patients were male. Diabetes mellitus and dyslipidaemia were the most common comorbidities (24% and 20%, respectively). Most (95%, n=1,241) patients were on venovenous ECMO with a median P:F ratio at the time of ECMO cannulation of 69.1. The prevalence of intracranial haemorrhage (ICH), ischaemic stroke, and hypoxic ischaemic brain injury (HIBI) was 5.9% (n=78), 1.1% (n=15), and 0.3% (n=4), respectively. The overall mortality of the 1,296 ECMO patients in the 10 studies that reported death was 36% (n=477), and the mortality of the subset of patients who had a neurological event was 92%. CONCLUSIONS: Neurological injury is a concern for COVID-19 patients who receive ECMO. Further research is required to explore how neuromonitoring protocols can inform tailored anticoagulation management and improve survival in COVID-19 patients with ECMO support.

Assessing the SAfety and FEasibility of bedside portable low-field brain Magnetic Resonance Imaging in patients on ECMO (SAFE-MRI ECMO study): study protocol and first case series experience.

BACKGROUND: To assess the safety and feasibility of imaging of the brain with a point-of-care (POC) magnetic resonance imaging (MRI) system in patients on extracorporeal membrane oxygenation (ECMO). Early detection of acute brain injury (ABI) is critical in improving survival for patients with ECMO support. METHODS: Patients from a single tertiary academic ECMO center who underwent head CT (HCT), followed by POC brain MRI examinations within 24 h following HCT while on ECMO. Primary outcomes were safety and feasibility, defined as completion of MRI examination without serious adverse events (SAEs). Secondary outcome was the quality of MR images in assessing ABIs. RESULTS: We report 3 consecutive adult patients (median age 47 years; 67% male) with veno-arterial (n = 1) and veno-venous ECMO (n = 2) (VA- and VV-ECMO) support. All patients were imaged successfully without SAEs. Times to complete POC brain MRI examinations were 34, 40, and 43 min. Two patients had ECMO suction events, resolved with fluid and repositioning. Two patients were found to have an unsuspected acute stroke, well visualized with MRI. CONCLUSIONS: Adult patients with VA- or VV-ECMO support can be safely imaged with low-field POC brain MRI in the intensive care unit, allowing for the assessment of presence and timing of ABI.

Patient Trajectories Among Persons Hospitalized for COVID-19 : A Cohort Study.

BACKGROUND: Risk factors for progression of coronavirus disease 2019 (COVID-19) to severe disease or death are underexplored in U.S. cohorts. OBJECTIVE: To determine the factors on hospital admission that are predictive of severe disease or death from COVID-19. DESIGN: Retrospective cohort analysis. SETTING: Five hospitals in the Maryland and Washington, DC, area. PATIENTS: 832 consecutive COVID-19 admissions from 4 March to 24 April 2020, with follow-up through 27 June 2020. MEASUREMENTS: Patient trajectories and outcomes, categorized by using the World Health Organization COVID-19 disease severity scale. Primary outcomes were death and a composite of severe disease or death. RESULTS: Median patient age was 64 years (range, 1 to 108 years); 47% were women, 40% were Black, 16% were Latinx, and 21% were nursing home residents. Among all patients, 131 (16%) died and 694 (83%) were discharged (523 [63%] had mild to moderate disease and 171 [20%] had severe disease). Of deaths, 66 (50%) were nursing home residents. Of 787 patients admitted with mild to moderate disease, 302 (38%) progressed to severe disease or death: 181 (60%) by day 2 and 238 (79%) by day 4. Patients had markedly different probabilities of disease progression on the basis of age, nursing home residence, comorbid conditions, obesity, respiratory symptoms, respiratory rate, fever, absolute lymphocyte count, hypoalbuminemia, troponin level, and C-reactive protein level and the interactions among these factors. Using only factors present on admission, a model to predict in-hospital disease progression had an area under the curve of 0.85, 0.79, and 0.79 at days 2, 4, and 7, respectively. LIMITATION: The study was done in a single health care system. CONCLUSION: A combination of demographic and clinical variables is strongly associated with severe COVID-19 disease or death and their early onset. The COVID-19 Inpatient Risk Calculator (CIRC), using factors present on admission, can inform clinical and resource allocation decisions. PRIMARY FUNDING SOURCE: Hopkins inHealth and COVID-19 Administrative Supplement for the HHS Region 3 Treatment Center from the Office of the Assistant Secretary for Preparedness and Response.