Parallel oxygenators in the same circuit for refractory hypoxemia on veno-venous extracorporeal membrane oxygenation. A 3-patient series.

Extracorporeal membrane oxygenator (ECMO) is a well-established therapy for respiratory failure. Refractory hypoxemia, despite the use of ECMO, remains a challenging problem. The ECMO circuit may not provide enough oxygenation support in the presence of high cardiac output, increased physiologic demand, and impaired gas exchange. Adding a second ECMO oxygenator using the same pump (sometimes needing a second drainage cannula) can improve oxygenation and facilitate lung-protective ventilation in selected patients. We describe a 3-patient series with severe ARDS secondary to SARS-CoV-2 infection and refractory hypoxemia during ECMO support successfully treated with this approach.

Extracorporeal membrane oxygenation for paediatric refractory hypoxic respiratory failure caused by adenovirus in Shanghai: a case series.

BACKGROUND: To assess the outcome of extracorporeal membrane oxygenation (ECMO) for severe adenovirus (Adv) pneumonia with refractory hypoxic respiratory failure (RHRF) in paediatric patients. METHODS: A retrospective observational study was performed in a tertiary paediatric intensive care unit (PICU) in China. Patients with RHRF caused by Adv pneumonia who received ECMO support after mechanical ventilation failed to achieve adequate oxygenation between 2017 and 2020 were included. The outcome variables were the in-hospital survival rate and the effects of ECMO on the survival rate. RESULTS: In total, 18 children with RHRF received ECMO. The median age was 19 (9.5, 39.8) months, and the median ECMO duration was 196 (152, 309) h. The in-hospital survival rate was 72.2% (13/18). Thirteen patients (72.2%) required continuous renal replacement therapy (CRRT) due to fluid imbalance or acute kidney injury (AKI). At ECMO initiation, compared with survivors, nonsurvivors had a lower PaO2/FiO2 ratio [49 (34.5, 62) vs. 63 (56, 71); p = 0.04], higher oxygen index (OI) [41 (34.5, 62) vs. 30 (26.5, 35); p = 0.03], higher vasoactive inotropic score (VIS) [30 (16.3, 80) vs. 100 (60, 142.5); p = 0.04], longer duration from mechanical ventilation to ECMO support [8 (4, 14) vs. 4 (3, 5.5) h, p=0.02], and longer time from confirmed RHRF to ECMO initiation [9 (4.8, 13) vs. 5 (1.3, 5.5) h; p = 0.004]. Patients with PaO2/FiO2 <61 mmHg or an OI >43 and hypoxic respiratory failure for more than 9 days before the initiation of ECMO had worse outcomes. CONCLUSIONS: ECMO seemed to be effective, as severe paediatric Adv pneumonia patients with RHRF had a cumulative survival rate of 72.2% in our study. Our study provides insight into ECMO rescue in children with severe Adv pneumonia.

Prone position in intubated, mechanically ventilated patients with COVID-19: a multi-centric study of more than 1000 patients.

BACKGROUND: Limited data are available on the use of prone position in intubated, invasively ventilated patients with Coronavirus disease-19 (COVID-19). Aim of this study is to investigate the use and effect of prone position in this population during the first 2020 pandemic wave. METHODS: Retrospective, multicentre, national cohort study conducted between February 24 and June 14, 2020, in 24 Italian Intensive Care Units (ICU) on adult patients needing invasive mechanical ventilation for respiratory failure caused by COVID-19. Clinical data were collected on the day of ICU admission. Information regarding the use of prone position was collected daily. Follow-up for patient outcomes was performed on July 15, 2020. The respiratory effects of the first prone position were studied in a subset of 78 patients. Patients were classified as Oxygen Responders if the PaO2/FiO2 ratio increased ≥ 20 mmHg during prone position and as Carbon Dioxide Responders if the ventilatory ratio was reduced during prone position. RESULTS: Of 1057 included patients, mild, moderate and severe ARDS was present in 15, 50 and 35% of patients, respectively, and had a resulting mortality of 25, 33 and 41%. Prone position was applied in 61% of the patients. Patients placed prone had a more severe disease and died significantly more (45% vs. 33%, p < 0.001). Overall, prone position induced a significant increase in PaO2/FiO2 ratio, while no change in respiratory system compliance or ventilatory ratio was observed. Seventy-eight % of the subset of 78 patients were Oxygen Responders. Non-Responders had a more severe respiratory failure and died more often in the ICU (65% vs. 38%, p = 0.047). Forty-seven % of patients were defined as Carbon Dioxide Responders. These patients were older and had more comorbidities; however, no difference in terms of ICU mortality was observed (51% vs. 37%, p = 0.189 for Carbon Dioxide Responders and Non-Responders, respectively). CONCLUSIONS: During the COVID-19 pandemic, prone position has been widely adopted to treat mechanically ventilated patients with respiratory failure. The majority of patients improved their oxygenation during prone position, most likely due to a better ventilation perfusion matching. TRIAL REGISTRATION: clinicaltrials.gov number: NCT04388670.

Is Therapeutic Hypothermia for Acute Respiratory Distress Syndrome the Future?

INTRODUCTION: Severe acute respiratory distress syndrome (ARDS) has a high mortality, and there is limited knowledge about management of severe ARDS refractory to standard therapy. Early evidence suggests that therapeutic hypothermia (TH) could be a viable treatment for acute respiratory failure. We present 2 cases where TH was successfully used to manage refractory ARDS on extracorporeal membrane oxygenation (ECMO) and a review of the literature around TH and acute respiratory failure. RESULTS: We present 2 cases of ARDS secondary to H1N1 influenza and human metapneumovirus. Both patients were treated with the current evidence-based therapy for ARDS. Venovenous ECMO was used in both patients for refractory hypoxemia. Therapeutic hypothermia was applied for 24 hours with improved oxygenation. We did a review of the literature summarizing 38 patients in 10 publications where TH was successfully utilized in the treatment of acute respiratory failure. CONCLUSION: Therapeutic hypothermia may be a viable salvage therapy for ARDS refractory to the current evidence-based therapy but needs further evaluation.

Systemic lupus-induced diffuse alveolar hemorrhage treated with extracorporeal membrane oxygenation: a case report and review of the literature.

OBJECTIVES: We report the case of a 28-year-old patient with systemic lupus erythematosus (SLE) with rapid onset of dyspnea and hemoptysis found to have diffuse alveolar hemorrhage (DAH) with refractory hypoxemia successfully treated with venovenous extracorporeal membrane oxygenation (ECMO). The discussion includes clinical presentation, diagnosis, management, outcome, and a review of the available adult literature on the use of ECMO in patients with DAH. DESIGN: Case report. SETTING: Froedtert Hospital and the Medical College of Wisconsin. DATA SOURCES: Data were collected from the patient's electronic medical record and the hospital radiology database. CONCLUSIONS: Diffuse alveolar hemorrhage secondary to SLE is quite rare. The adult literature on the utilization of ECMO for DAH is limited mostly to antineutrophil cytoplasmic antibody (ANCA)-associated alveolar hemorrhage and a few reports of nonvasculitis DAH. Bleeding has been a contraindication to ECMO due to the need for systemic anticoagulation. Our case, along with a review of the literature, indicates that ECMO with anticoagulation can be safely utilized in patients with DAH. To our knowledge, this is the first reported adult case of DAH due to SLE successfully treated with ECMO.

New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report.

BACKGROUND: Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome (HPS) after liver transplant (LT), this case adds information and experience on this issue along with a treatment with positive outcomes. HPS is a complication of end-stage liver disease, with a 10%-30% incidence in cirrhotic patients. LT can reverse the physiopathology of this process and restore normal oxygenation. However, in some cases, refractory hypoxemia persists, and extracorporeal membrane oxygenation (ECMO) can be used as a rescue therapy with good results. CASE SUMMARY: A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS. He had good liver function (Model for End-Stage Liver Disease score 12, Child-Pugh class B7). He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%. The macroaggregated albumin test result was > 30. Spirometry demon strated a forced expiratory volume in one second (FEV1) of 78%, forced vital capacity (FVC) of 74%, FEV1/FVC ratio of 81%, diffusion capacity for carbon monoxide of 42%, and carbon monoxide transfer coefficient of 57%. He required domiciliary oxygen at 2 L/min (16 h/d). The patient was admitted to the intensive care unit (ICU) and extubated in the first 24 h, needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards. Reintubation was needed after 72 h. Due to the non-response to supportive therapies, installation of ECMO was decided with progressive recovery after 9 d. Extubation was possible on the tenth day, maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h. He was discharged from ICU on postoperative day (POD) 20 with a 90%-92% oxygen saturation. Steroid recycling was needed twice for acute rejection. The patient was discharged from hospital on POD 27 with no symptoms, with an 89%-90% oxygen saturation. CONCLUSION: Due to the favorable results observed, ECMO could become the central axis of treatment of HPS and refractory hypoxemia after LT.

Characteristics and risk factors associated with mortality during the first cycle of prone secondary to ARDS due to SARS-CoV-2 pneumonia.

OBJECTIVE: To analyze characteristics, changes in oxygenation, and pulmonary mechanics, in mechanically ventilated patients with ARDS due to SARS-CoV-2 treated with prone position and evaluate the response to this maneuver. DESIGN: Cohort study including patients with PaO2/FiO2 <150mmHg requiring prone position over 18 months. We classified patients according to PaO2/FiO2 changes from basal to 24h after the first prone cycle as: 1) no increase 2) increase <25%, 3) 25%-50% increase 4) increase >50%. SETTING: 33-bed medical-surgical Intensive Care Unit (ICU) in Argentina. PATIENTS: 273 patients. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Epidemiological characteristics, respiratory mechanics and oxygenation were compared between survivors and non-survivors. Independent factors associated with in-hospital mortality were identified. RESULTS: Baseline PaO2/FiO2 was 116 [97-135]mmHg (115 [94-136] in survivors vs. 117 [98-134] in non-survivors; p=0.50). After prone positioning, 22 patients (8%) had similar PaO2/FiO2 values; 46(16%) increased PaO2/FiO2 ≤25%; 55 (21%) increased it 25%-50%; and 150 (55%), >50%. Mortality was 86%, 87%, 72% and 50% respectively (p<0.001). Baseline PaO2/FiO2, <100mmHg did not imply that patients were refractory to prone position. Factors independently associated with mortality were age, percentage increase in PaO2/FiO2 after 24h being in prone, and number of prone cycles. CONCLUSIONS: Older patients unable to improve PaO2/FiO2 after 24h in prone position and who require >1 cycle might early receive additional treatments for refractory hypoxemia. After the first 24h in the prone position, a low percentage of PaO2/FiO2 increase over baseline, beyond the initial value, was independently associated with higher mortality.

Right-to-Left Intra-cardiac Shunt in a COVID-19 Patient Leading to Stroke and Poor Prognosis: A Case Report and Review of the Literature.

Coronavirus disease 2019 (COVID-19) often presents with a wide range of complications, including respiratory distress, acute respiratory distress syndrome (ARDS), and hypercoagulable states with resultant cerebrovascular incidents. Intra- and extra-pulmonological shunts can further complicate patient courses, leading to persistent hypoxemia and paradoxical emboli, resulting in potentially life-threatening consequences, necessitating a comprehensive, multidisciplinary approach to patient care. Here we present the case of a 73-year-old male who experienced severe persistent hypoxemic respiratory failure, superimposed methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, and stroke with a previously undiagnosed patent foramen ovale (PFO) contributing to his clinical presentation.

Comparison of Serial and Parallel Connections of Membrane Lungs against Refractory Hypoxemia in a Mock Circuit.

Extracorporeal membrane oxygenation (ECMO) is an important rescue therapy method for the treatment of severe hypoxic lung injury. In some cases, oxygen saturation and oxygen partial pressure in the arterial blood are low despite ECMO therapy. There are case reports in which patients with such instances of refractory hypoxemia received a second membrane lung, either in series or in parallel, to overcome the hypoxemia. It remains unclear whether the parallel or serial connection is more effective. Therefore, we used an improved version of our full-flow ECMO mock circuit to test this. The measurements were performed under conditions in which the membrane lungs were unable to completely oxygenate the blood. As a result, only the photometric pre- and post-oxygenator saturations, blood flow and hemoglobin concentration were required for the calculation of oxygen transfer rates. The results showed that for a pre-oxygenator saturation of 45% and a total blood flow of 10 L/min, the serial connection of two identical 5 L rated oxygenators is 17% more effective in terms of oxygen transfer than the parallel connection. Although the idea of using a second membrane lung if refractory hypoxia occurs is intriguing from a physiological point of view, due to the invasiveness of the solution, further investigations are needed before this should be used in a wider clinical setting.

Shunting Across a Latent Patent Foramen Ovale (PFO) in a Patient With Right Ventricular (RV) Infarction Improved With Impella.

The right-to-left shunt (RTLS) through a latent patent foramen ovale (PFO) is a rare complication of right ventricle myocardial infarction (MI). Though a rare complication, the development of refractory hypoxemia after right ventricular MI should always alert clinicians to consider the possibility of shunting across PFO. Right-sided Impella (Impella RP) can be considered in such patients, which helps to decrease the elevated right heart pressure reducing the shunt, thereby providing a bridge to recovery.

A Chest Pain Conundrum: Dapsone-Induced Methemoglobinemia in a Heart Transplant Patient.

We present the case of a 39-year-old male with a past medical history of orthotopic heart transplantation who presented with chest pain and dyspnea on exertion. He was diagnosed with dapsone-induced methemoglobinemia toward the end of his hospital course, and his condition clinically improved with the discontinuation of the offending agent. This case highlights the importance of medication review and history-taking. Clinicians should be mindful of dapsone-induced methemoglobinemia, especially when encountering patients with dyspnea and a history of dapsone intake.

Management of refractory hypoxemia using recruitment maneuvers and rescue therapies: A comprehensive review.

Refractory hypoxemia in patients with acute respiratory distress syndrome treated with mechanical ventilation is one of the most challenging conditions in human and veterinary intensive care units. When a conventional lung protective approach fails to restore adequate oxygenation to the patient, the use of recruitment maneuvers and positive end-expiratory pressure to maximize alveolar recruitment, improve gas exchange and respiratory mechanics, while reducing the risk of ventilator-induced lung injury has been suggested in people as the open lung approach. Although the proposed physiological rationale of opening and keeping open previously collapsed or obstructed airways is sound, the technique for doing so, as well as the potential benefits regarding patient outcome are highly controversial in light of recent randomized controlled trials. Moreover, a variety of alternative therapies that provide even less robust evidence have been investigated, including prone positioning, neuromuscular blockade, inhaled pulmonary vasodilators, extracorporeal membrane oxygenation, and unconventional ventilatory modes such as airway pressure release ventilation. With the exception of prone positioning, these modalities are limited by their own balance of risks and benefits, which can be significantly influenced by the practitioner's experience. This review explores the rationale, evidence, advantages and disadvantages of each of these therapies as well as available methods to identify suitable candidates for recruitment maneuvers, with a summary on their application in veterinary medicine. Undoubtedly, the heterogeneous and evolving nature of acute respiratory distress syndrome and individual lung phenotypes call for a personalized approach using new non-invasive bedside assessment tools, such as electrical impedance tomography, lung ultrasound, and the recruitment-to-inflation ratio to assess lung recruitability. Data available in human medicine provide valuable insights that could, and should, be used to improve the management of veterinary patients with severe respiratory failure with respect to their intrinsic anatomy and physiology.

The role of dexmedetomidine in ARDS: an approach to non-intensive care sedation.

Introduction: Severe COVID-19 is a life-threatening condition characterized by complications such as interstitial pneumonia, hypoxic respiratory failure, and acute respiratory distress syndrome (ARDS). Non-pharmacological intervention with mechanical ventilation plays a key role in treating COVID-19-related ARDS but is influenced by a high risk of failure in more severe patients. Dexmedetomidine is a new generation highly selective α2-adrenergic receptor (α2-AR) agonist that provides sedative effects with preservation of respiratory function. The aim of this study is to assess how dexmedetomidine influences gas exchange during non-invasive ventilation (NIV) and high-flow nasal cannula (HFNC) in moderate to severe ARDS caused by COVID-19 in a non-intensive care setting. Methods: This is a single center retrospective cohort study. We included patients who showed moderate to severe respiratory distress. All included subjects had indication to NIV and were suitable for a non-intensive setting of care. A total of 170 patients were included, divided in a control group (n = 71) and a treatment group (DEX group, n = 99). Results: A total of 170 patients were hospitalized for moderate to severe ARDS and COVID-19. The median age was 71 years, 29% females. The median Charlson comorbidity index (CCI) was 2.5. Obesity affected 21% of the study population. The median pO2/FiO2 was 82 mmHg before treatment. After treatment, the increase of pO2/FiO2 ratio was clinically and statistically significant in the DEX group compared to the controls (125 mmHg [97-152] versus 94 mmHg [75-122]; ***p < 0.0001). A significative reduction of NIV duration was observed in DEX group (10 [7-16] days vs. 13 [10-17] days; *p < 0.02). Twenty four patients required IMV in control group (n = 71) and 16 patients in DEX group (n = 99) with a reduction of endotracheal intubation of 62% (OR 0.38; **p < 0.008). A higher incidence of sinus bradycardia was observed in the DEX group. Conclusion: Dexmedetomidine provides a "calm and arousal" status which allows spontaneous ventilation in awake patients treated with NIV and HFNC. The adjunctive therapy with dexmedetomidine is associated with a higher pO2/FiO2, lower duration of NIV, and a lower risk of NIV failure. A higher incidence of sinus bradycardia needs to be considered.

Intraperitoneal oxygen microbubble therapy: A novel approach to enhance systemic oxygenation in a smoke inhalation model of acute hypoxic respiratory failure.

Background: Patients suffering from severe acute respiratory distress syndrome (ARDS) face limited therapeutic options and alarmingly high mortality rates. Refractory hypoxemia, a hallmark of ARDS, often necessitates invasive and high-risk treatments. Oxygen microbubbles (OMB) present a promising approach for extrapulmonary oxygenation, potentially augmenting systemic oxygen levels without exposing patients to significant risks. Methods: Rats with severe, acute hypoxemia secondary to wood smoke inhalation (SI) received intraperitoneal (IP) bolus injections of escalating weight-by-volume (BW/V) OMB doses or normal saline to determine optimal dosage and treatment efficacy. Subsequently, a 10 % BW/V OMB bolus or saline was administered to a group of SI rats and a control group of healthy rats (SHAM). Imaging, vital signs, and laboratory studies were compared at baseline, post-smoke inhalation, and post-treatment. Histological examination and lung tissue wet/dry weight ratios were assessed at study conclusion. Results: Treatment with various OMB doses in SI-induced acute hypoxemia revealed that a 10 % BW/V OMB dose significantly augmented systemic oxygen levels while minimizing dose volume. The second set of studies demonstrated a significant increase in partial pressure of arterial oxygen (PaO2) and normalization of heart rate with OMB treatment in the SI group compared to saline treatment or control group treatment. Conclusions: This study highlights the successful augmentation of systemic oxygenation following OMB treatment in a small animal model of severe hypoxemia. OMB therapy emerges as a novel and promising treatment modality with immense translational potential for oxygenation support in acute care settings.

The Impact of a Standardized Refractory Hypoxemia Protocol on Outcome of Subjects Receiving Venovenous Extracorporeal Membrane Oxygenation.

BACKGROUND: Current mechanical ventilation practice and the use of treatment adjuncts in patients requiring extracorporeal membrane oxygenation (ECMO) for refractory hypoxemia (RH) vary widely and their impact on outcomes remains unclear. In 2015, we implemented a standardized approach to protocolized ventilator settings and guide the escalation of adjunct therapies in patients with RH. This study aimed to investigate ICU mortality, its associated risk factors, and mechanical ventilation practice before and after the implementation of a standardized RH guideline in patients requiring venovenous ECMO (VV-ECMO). METHODS: This was a single-center, retrospective cohort study of patients undergoing VV-ECMO due to RH respiratory failure between January 2008 and March 2015 (before RH protocol implementation) and between April 2015 and October 2019 (after RH protocol implementation). RESULTS: A total of 103 subjects receiving VV-ECMO for RH were analyzed. After implementation of the RH protocol, more subjects received prone positioning (6.7% vs 23.3%, P = .02), and fewer received high-frequency oscillatory ventilation than before launching the RH protocol (0% vs 13.3%, P = .01). Plateau pressure was also lower before initiation of ECMO (P = .04) and at day 1 during ECMO (P = .045). Driving pressure was consistently lower at days 1, 2, and 3 after ECMO initiation: median 13.0 (interquartile range [IQR] 10.6-18.0) vs 16.0 (IQR 14.0-20.0) cm H2O at day 1 (P = .003); 13.0 (IQR 11.0-15.9) vs 15.5 (IQR 12.0-20.0) cm H2O at day 2 (P = .03); and 12.0 (IQR 10.0-14.5) vs 15.0 (IQR 12.0-19.0) cm H2O at day 3 (P = .005). CONCLUSIONS: The implementation of a standardized RH guideline improved compliance with a lung-protective ventilation strategy and utilization of the prone position and was associated with lower driving pressure during the first 3 days after ECMO initiation in subjects with refractory hypoxemia.

Diffuse Alveolar Hemorrhage in the Setting of Cytarabine Therapy in a Critically Ill Patient.

Diffuse alveolar hemorrhage (DAH) is a potentially life-threatening pulmonary condition characterized by hypoxemia with progression to respiratory failure, rapid onset of dyspnea, and blood loss anemia. While hemoptysis may be present and corroborates the diagnosis, it is absent in about half of the cases, resulting in a diagnostic challenge with variable presenting symptoms. Imaging findings on chest x-ray or computed tomography (CT) scans are also non-specific, often showing diffuse bilateral alveolar opacities. Because DAH is an under-recognized diagnosis, physicians should maintain a degree of clinical suspicion for DAH in patients with unexplained airspace opacities and no signs of an infectious etiology. This is especially important in higher-risk populations such as patients with hematological malignancies, who have a propensity for thrombocytopenia and coagulopathy compounded by the use of anticoagulants. Patients with hematological malignancies, namely acute myeloid leukemia (AML), are also at risk for drug-induced DAH due to the use of cytotoxic medications like cytarabine. Here, we present the case of a 48-year-old male with a past medical history of AML and myeloid sarcoma who developed shortness of breath after receiving cytarabine chemotherapy. Chest radiography revealed diffuse bilateral infiltrates. He was intubated and underwent flexible bronchoscopy, which resulted in a bloody effluent consistent with DAH. After ruling out infectious etiologies, we reached a final diagnosis of DAH and started the patient on corticosteroid therapy.

The Clinical Effect of an Early, Protocolized Approach to Mechanical Ventilation for Severe and Refractory Hypoxemia.

BACKGROUND: ARDS remains a source of significant morbidity and mortality in the critically ill patient. The mainstay of therapy entails invasive mechanical ventilation utilizing a lung-protective strategy designed to limit lung injury associated with excessive stress and strain while the underlying etiology of respiratory failure is identified and treated. Less is understood about what to do once conventional ventilation parameters have been optimized but the patient's respiratory status remains unchanged or worsens. In 2015, a protocolized, stepwise approach to mechanical ventilation with partially automated and clearly defined thresholds for management changes was implemented at our institution. We hypothesized that, by identifying appropriate patients earlier, time-to-escalation and rescue therapy implementation would be shortened. METHODS: Subjects with severe ARDS, treated with prone positioning based on our institution's protocolized approach from December 2013 to August 2016 were included. Their baseline characteristics, severity of illness scores, and mechanical ventilation parameters were collected and analyzed. RESULTS: Baseline characteristics, tidal volumes, PaO2 /FIO2 , duration of ventilation after proning, and mortality were similar in both groups. Median (interquartile range [IQR]) PEEP at the time of proning was higher after the protocol implementation (12.5 cm H2O [IQR 6.5-19.4] vs 18 cm H2O [IQR 10-22], P = .386), and mean (IQR) respiratory system driving pressure was lower (16 cm H2O [IQR 13-36.2] vs 12 cm H2O [IQR 9-19.6], P = .029). Median (IQR) time from refractory hypoxemia identification to proning was shorter after protocol implementation (42.2 h [IQR 6.83-347.2] vs 16.3 h [IQR 1-99.7], I = .02), and PaO2 /FIO2 at 1 h after proning was higher. ICU and hospital LOS were shorter after the protocol implementation. CONCLUSIONS: Following the implementation of an early, evidence-based, protocolized approach to optimizing mechanical ventilation, subjects with true refractory hypoxemia were identified earlier and time to proning was significantly shorter. Despite improvement in the evaluation and management of refractory hypoxemia as well as time to initiation of prone positioning, mortality was unchanged and there was variation in the duration of the position.

Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019.

OBJECTIVES: The objectives of this study were to evaluate the efficacy and safety of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. PATIENTS: Thirty-eight adult critically ill patients with coronavirus disease 2019 and refractory hypoxemia treated with either inhaled epoprostenol or inhaled nitric oxide for at least 1 hour between March 1, 2020, and June 30, 2020. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Of 93 patients screened, 38 were included in the analysis, with mild (4, 10.5%), moderate (24, 63.2%), or severe (10, 26.3%), with acute respiratory distress syndrome. All patients were initiated on inhaled epoprostenol as the initial pulmonary vasodilator and the median time from intubation to initiation was 137 hours (68-228 h). The median change in Pao2/Fio2 was 0 (-12.8 to 31.6) immediately following administration of inhaled epoprostenol. Sixteen patients were classified as responders (increase Pao2/Fio2 > 10%) to inhaled epoprostenol, with a median increase in Pao2/Fio2 of 34.1 (24.3-53.9). The mean change in Pao2 and Spo2 was -0.55 ± 41.8 and -0.6 ± 4.7, respectively. Eleven patients transitioned to inhaled nitric oxide with a median change of 11 (3.6-24.8) in Pao2/Fio2. A logistic regression analysis did not identify any differences in outcomes or characteristics between the responders and the nonresponders. Minimal adverse events were seen in patients who received either inhaled epoprostenol or inhaled nitric oxide. CONCLUSIONS: We found that the initiation of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019, on average, did not produce significant increases in oxygenation metrics. However, a group of patients had significant improvement with inhaled epoprostenol and inhaled nitric oxide. Administration of inhaled epoprostenol or inhaled nitric oxide may be considered in patients with severe respiratory failure secondary to coronavirus disease 2019.

Pulmonary vascular endothelial injury and acute pulmonary hypertension caused by COVID-19: the fundamental cause of refractory hypoxemia?

Coronavirus disease (COVID-19) is a severe infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that binds to the cells; angiotensin converting enzyme 2 (ACE2) receptor. In the first severe case of COVID-19 in Shenzhen city, we found that in addition to the typical clinical manifestations, our patient presented hemoptysis, refractory hypoxemia and pulmonary fibrosis-like changes on computed tomography (CT) involving alveoli and pulmonary interstitium in the early stage and acute pulmonary hypertension and right heart failure in the later stage, which were not completely justified by myocarditis, acute respiratory distress syndrome (ARDS), pulmonary fibrosis and high PEEP level. The lung compliance deterioration of this patient was not as serious as we expected, indicating classic ARDS was not existed. Simultaneously, the first autopsy report of COVID-19 in China showed normal-structured alveoli and massive thick excretion in the airway. Then, we speculated that the virus not only attacked alveolar epithelial cells, but also affected pulmonary vascular endothelial cells. Imbalance in the ACE2-RAAS- bradykinin axis and the cytokine storm could be an important mechanism leading to pathophysiological changes in pulmonary vascular and secondary refractory hypoxemia. Pulmonary vasculitis or capillaritis associated to immune damage and an inflammatory storm could exist in COVID-19 because of ground-glass opacities in the subpleural area, which are similar to connective tissue disease associated interstitial lung disease (CTD-ILD). Thus, this case elucidates new treatment measures for COVID-19.