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Considering the COVID-19 pandemic where concomitant occurrence of ARDS and severe acute brain injury (sABI) has increasingly coemerged, we synthesize existing data regarding the simultaneous management of both conditions. Our aim is to provide readers with fundamental principles and concepts for the management of sABI and ARDS, and highlight challenges and conflicts encountered while managing concurrent disease. Up to 40% of patients with sABI can develop ARDS. Although there are trials and guidelines to support the mainstays of treatment for ARDS and sABI independently, guidance on concomitant management is limited. Treatment strategies aimed at managing severe ARDS may at times conflict with the management of sABI. In this narrative review, we discuss the physiological basis and risks involved during simultaneous management of ARDS and sABI, summarize evidence for treatment decisions, and demonstrate these principles using hypothetical case scenarios. Use of invasive or noninvasive monitoring to assess brain and lung physiology may facilitate goal-directed treatment strategies with the potential to improve outcome. Understanding the pathophysiology and key treatment concepts for comanagement of these conditions is critical to optimizing care in this high-acuity patient population.

A 17-year-old previously healthy Taiwanese girl presented with syncope on a background of 1 month of weakness, polyarthritis, and heliotrope rash. Her presentation and investigations, which included an elevated creatine phosphokinase level and diffuse myositis on lower limb MRI, were consistent with juvenile dermatomyositis (JDM).

Background Decannulation from venovenous extracorporeal membrane oxygenation (ECMO) at the earliest and safest possible time may improve outcomes and reduce cost. Yet, no prospective studies have compared weaning strategies for liberation from ECMO. Research Question Is a protocolized daily assessment of readiness to liberate from venovenous ECMO safe and feasible? Study Design and Methods We conducted a prospective, single-arm safety and feasibility study of a protocol for daily assessment of readiness to liberate from venovenous ECMO among consecutive adult patients receiving venovenous ECMO across four ICUs at a single center between June 20, 2020, and November 24, 2020. The ECMO-free protocol included three phases: (1) the safety screening, (2) non-ECMO F io 2 titration, and (3) the ECMO-free trial. Enrollment, interventions, and data collection were performed prospectively by trained study staff. Results Twenty-six patients received the ECMO-free protocol on 385 patient-days. The safety screening was passed during a total of 59 ECMO-free daily assessments (15.3%) among 20 patients. Every passed safety screening proceeded to an ECMO-free trial. Twenty-eight passed ECMO-free trials (47.5%) occurred among 16 patients (61.5%). No missed safety screenings, protocol deviations, or adverse events occurred. Of the 16 patients who passed an ECMO-free trial, 14 patients (87.5%) were decannulated. Among decannulated patients, 12 patients (85.7%) were decannulated on the same day as a passed ECMO-free trial, 6 patients (42.9%) were decannulated on the first day that they passed an ECMO-free trial, and 6 patients (42.9%) passed an ECMO-free trial at least twice consecutively before decannulation. The median time from first passed ECMO-free trial to decannulation was 2 days (interquartile range, 0-3 days). Interpretation The ECMO-free protocol is feasible and may identify patients for decannulation earlier than gradual approaches to weaning.

Background Weaning from venovenous extracorporeal membrane oxygenation (VV-ECMO) has not been not well studied. VV-ECMO can be discontinued when patients tolerate noninjurious mechanical ventilation (MV) during a sweep gas-off trial (SGOT). However, predictors of safe liberation are unknown. Research Question Can safe liberation from VV-ECMO be predicted at the bedside? Study Design and Methods Two observational studies of adults weaned from VV-ECMO for severe ARDS at Toronto General Hospital were conducted. MV settings, respiratory mechanics, and clinical variables were analyzed to predict safe liberation from VV-ECMO, defined a priori as avoida7ce of ECMO recannulation, increased MV support, need for rescue therapy, or hemodynamic instability developed within 48 h following decannulation. Results During both studies, 83 patients were weaned from VV-ECMO, 21 (25%) of whom did not meet the criteria for safe liberation. In the retrospective study, higher tidal volume per predicted body weight (OR, 1.58; 95% CI, 1.05-2.40; P = .03) and heart rate (OR, 1.07; 95% CI, 1.022-1.15; P = .01) at the end of SGOT were significantly associated with increased odds of unsafe liberation when adjusted for age (OR, 1.02; 95% CI, 0.95-1.09; P = .63) and sequential organ failure assessment score (OR, 1.16; 95% CI, 0.86-1.56; P = .34). Change in ventilatory ratio had an imprecise association (OR, 2.7; 95% CI, 0.94-7.95; P = .06) with unsafe liberation when adjusted for age (OR, 1.03; 95% CI, 0.96-1.10; P = .42), sequential organ failure assessment score (OR, 1.11; 95% CI, 0.81-1.51; P = .52), and heart rate (OR, 1.07; 95% CI, 1.01-1.13; P = .02). In the prospective study, patients who had unsafe liberation from VV-ECMO also had significantly higher inspiratory efforts (esophageal pressure swings, 9 [7-13] vs 18 [7-25] cm H2O; P = .03) and worse outcomes (longer MV duration, ICU and hospital length of stay). Interpretation Patients with higher tidal volume, heart rate, ventilatory ratio, and esophageal pressures swings during SGOT were less likely to achieve safe liberation from VV-ECMO.

Case Presentation A 57-year-old man who had been intubated and placed on venovenous extracorporeal membrane oxygenation for hypoxemic respiratory failure due to COVID-19 pneumonia was transferred to our facility. He underwent anticoagulation with IV heparin titrated to an anti-Factor Xa goal of 0.1 to 0.3 international unit/mL. Over extracorporeal membrane oxygenation days 13 to 17, his WBC count rose from 17,500 to 47,000 cells/μL. He simultaneously experienced the development of fluid-refractory shock that required multiple vasopressors and received stress-dose hydrocortisone when his WBC was 30,000 cells/μL. He remained afebrile and was started on broad-spectrum antimicrobials that included antifungal and anthelminthic therapy.

Case Presentation A 47-year-old Hispanic woman presented to a pulmonology clinic with 2 weeks of cough productive of white sputum and worsening dyspnea on exertion, requiring increasing supplemental oxygen. In addition, she reported fatigue, night sweats, diffuse myalgias, and extremity weakness. She denied hemoptysis, fevers, chills, weight loss, or rash. Her medical history is significant for undifferentiated rapidly progressive hypoxemic respiratory failure 2 years before her current presentation. At that time, she presented to the ED with 3 weeks of progressive shortness of breath and cough. Chest CT imaging showed bilateral infiltrates concerning for infection, and she was treated empirically for community-acquired pneumonia. She developed worsening hypoxemic respiratory failure despite broadening of her antibiotics and subsequently required intubation. Her course was further complicated by pulseless electrical activity arrest with return of spontaneous circulation and development of shock requiring multiple vasopressors. Because of difficulty with oxygenation, she was referred to our center for extracorporeal membrane oxygenation evaluation and was ultimately started on venous-arterial extracorporeal membrane oxygenation. Bronchoscopy with BAL was negative for bacterial, viral, and fungal origins, and initial autoimmune evaluation (antinuclear antibody and rheumatoid factor) was negative, except an elevated creatine kinase (CK) to 3,000. Her course was complicated by heparin-induced thrombocytopenia, and as a result she suffered limb ischemia requiring amputation of her left lower extremity. Elevated CK at that time was attributed to compartment syndrome before amputation. The patient recovered clinically with supportive care and was ultimately discharged on 2 L supplemental oxygen, with a diagnosis of acute respiratory failure of unclear origin. The patient had stability in her clinical symptoms until this current presentation.

Severe pulmonary edema, secondary to left ventricular afterload increment, is a common problem occurring in patients receiving venoarterial extracorporeal membrane oxygenation. No consensus is currently available for its management, but several devices/procedures have been described, including an Impella device (Abiomed), balloon atrial septostomy, intraaortic balloon counterpulsation, or an additional venous cannula, as possible adjuncts. We report the feasibility and efficacy of the atrial flow regulator device (Occlutech) for left ventricular unloading in a 58-year-old patient receiving extracorporeal membrane oxygenation. However, the benefits of this device relative to simple balloon atrial septostomy need to be further investigated.

The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge. Guidelines have delineated how best to diagnose and manage patients with PE. However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms. Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care. The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis. The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects. This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19.

Background Pulmonary arterial hypertension (PAH) is a progressive disease associated with significant morbidity and mortality. Despite the negative impact of PAH on quality of life and survival, data on use of specialty palliative care services (PCS) is scarce. Research Question We sought to evaluate the inpatient use of PCS in patients with PAH. Study Design and Methods Using the National (Nationwide) Inpatient Sample, 30,495 admissions with a primary diagnosis of PAH were identified from 2001 through 2017. The primary outcome of interest was temporal trends and predictors of inpatient PCS use in patients with PAH. Results The inpatient use of PCS was low (2.2%), but increased during the study period from 0.5% in 2001 to 7.6% in 2017, with a significant increase starting in 2009. White race, private insurance, higher socioeconomic status, hospital-specific factors, higher comorbidity burden (Charlson Comorbidity Index), cardiac and noncardiac organ failure, and use of extracorporeal membrane oxygenation and noninvasive mechanical ventilation were independent predictors of increased PCS use. PCS use was associated with a higher prevalence of do-not-resuscitate status, a longer length of stay, higher hospitalization costs, and increased in-hospital mortality with less frequent discharges to home, likely because these patients were also sicker (higher comorbidity index and illness acuity). Interpretation The inpatient use of PCS in patients with PAH is low, but has been increasing over recent years. Despite increased PCS use over time, patient- and hospital-specific disparities in PCS use continue. Further studies evaluating these disparities and the role of PCS in the comprehensive care of PAH patients are warranted.

ARDS is a lethal form of acute respiratory failure, and because no specific treatments exist, supportive care remains the primary management strategy in these patients. Extracorporeal membrane oxygenation (ECMO) has emerged as an intervention in patients with severe ARDS to facilitate gas exchange and the delivery of more lung protective ventilation. Over the past 20 years, improvements in ECMO technology have increased its safety and transportability, making it far more available to this patient population globally. Deciding which patients with ARDS should be initiated on ECMO remains a challenging question. Numerous clinical and laboratory markers have been investigated, and multiple risk scores developed, to aid physicians in this decision-making process. However, they are still imperfect, and the choice is often based on institutional guidelines and the clinical impression of the treating physician. Given the potential risks and resource implications for this intervention, patient selection is critical and it is important to provide ECMO only to patients who have a reasonable chance for recovery or bridge to transplantation. In patients undergoing ECMO where there is no potential for recovery or transplant, the only option may be withdrawal of ECMO and palliation. These patients may be awake and interactive, which is often a very challenging scenario for patients, families, and the clinical team. In this article, we present a more controversial case and a review of the literature regarding the selection of patients with ARDS who should receive ECMO.

Health systems confronting the coronavirus disease 2019 (COVID-19) pandemic must plan for surges in ICU demand and equitably distribute resources to maximize benefit for critically ill patients and the public during periods of resource scarcity. For example, morbidity and mortality could be mitigated by a proactive regional plan for the triage of mechanical ventilators. Extracorporeal membrane oxygenation (ECMO), a resource-intensive and potentially life-saving modality in severe respiratory failure, has generally not been included in proactive disaster preparedness until recently. This paper explores underlying assumptions and triage principles that could guide the integration of ECMO resources into existing disaster planning. Drawing from a collaborative framework developed by one US metropolitan area with multiple adult and pediatric extracorporeal life support centers, this paper aims to inform decision-making around ECMO use during a pandemic such as COVID-19. It also addresses the ethical and practical aspects of not continuing to offer ECMO during a disaster.

Background Adjunctive strategies are an important part of the management of ARDS. However, their application in clinical practice remains inconsistent. Research Question We wished to determine the frequency and patterns of use of adjunctive strategies in patients with moderate to severe ARDS (Pa o 2/F io 2 [P/F ratio] Study Design and Methods The LUNG SAFE study was an international, multicenter, prospective cohort study of patients with severe respiratory failure, conducted in 2014 in 459 ICUs from 50 countries. The primary objective of this substudy was to determine the frequency of use of widely available (neuromuscular blockade, prone position) adjuncts vs adjuncts requiring specialized equipment (extracorporeal membrane oxygenation, inhaled vasodilators, high-frequency ventilation) in patients in the first 48 h of moderate to severe ARDS (P/F ratio Results Of 1,146 patients on invasive ventilation with moderate to severe ARDS, 811 patients (71%) received no adjunct within 48 h of ARDS onset. Of 335 (29%) that received adjunctive strategies, 252 (75%) received a single strategy, and 83 (25%) receiving more than one adjunct. Of ARDS nonsurvivors, 67% did not receive any adjunctive strategy in the first 48 h. Most patients (67%) receiving specialized adjuncts did not receive prone positioning or neuromuscular blockade. Patients that received adjuncts were more likely to have their ARDS recognized, be younger and sicker, have pneumonia, be more difficult to ventilate, and be in a European high-income country than those that did not receive adjuncts. Interpretation Three in 10 patients with moderate to severe ARDS, and only one-third of nonsurvivors, received adjunctive strategies over the first 48 h of ARDS. A more consistent and evidence-driven approach to adjunct use may reduce costs and improve outcomes in patients with moderate to severe ARDS. Trial Registry ClinicalTrials.gov; No.: NCT02010073 ; URL: www.clinicaltrials.gov

Venoarterial extracorporeal membrane oxygenation therapy (VA-ECMO) after refractory cardiogenic shock or cardiac arrest has significant morbidity and mortality. Early outcome prediction is crucial in this setting, but data on neuroprognostication are limited. We examined the prognostic value of clinical neurologic examination, using an automated device for the quantitative measurement of pupillary light reactivity.An observational cohort of sedated, mechanically ventilated VA-ECMO patients was analyzed during the early phase after ECMO insertion (first 72 h). Using the NPi-200 automated infrared pupillometer, pupillary light reactivity was assessed repeatedly (every 12 h) by calculating the Neurological Pupil index (NPi). Trends of NPi over time were correlated to 90-day mortality, and the prognostic performance of the NPi, alone and in combination with the 12-h PREDICT VA-ECMO score, was evaluated.One hundred consecutive patients were studied (51 with refractory cardiogenic shock and 49 with refractory cardiac arrest; 12-h PREDICT VA-ECMO, 40%; observed 90-day survival, 43%). Nonsurvivors (n = 57) had significantly lower NPi than did survivors at all time points (all P .01). Abnormal NPi (3, at any time from 24 to 72 h) was 100% specific for 90-day mortality, with 0% false positives. Adding the 12-h PREDICT VA-ECMO score to the NPi provided the best prognostic performance (specificity, 100% [95% CI, 92%-100%]; sensitivity, 60% [95% CI, 46%-72%]; area under the receiver operating characteristic curve, 0.82).Quantitative NPi alone had excellent ability to predict a poor outcome from day 1 after VA-ECMO insertion, with no false positives. Combining NPi and 12-h PREDICT-VA ECMO score increased the sensitivity of outcome prediction, while maintaining 100% specificity.

Patients with COVID-19 report severe respiratory symptoms consistent with ARDS. The clinical presentation of ARDS in COVID-19 is often atypical, as patients with COVID-19 exhibit a disproportionate hypoxemia compared with relatively preserved lung mechanics. This pattern is more similar to neonatal respiratory distress syndrome secondary to surfactant deficiency, which has been shown to benefit from exogenous surfactant. We present our experience with exogenous surfactant treatment in a patient with COVID-19 experiencing COVID-19-related ARDS. The patient responded with improved oxygenation, and we believe surfactant was the catalyst for the successful extubation and clinical improvement of the patient.