key: cord-0991111-qskg8poq authors: Wilcox, Susan R.; Condella, Anna title: Emergency Department Management of Severe Hypoxemic Respiratory Failure in Adults with COVID-19 date: 2020-12-25 journal: J Emerg Med DOI: 10.1016/j.jemermed.2020.12.014 sha: 1c10d4b935ade6c36e8d50aaede819406abc37b7 doc_id: 991111 cord_uid: qskg8poq Background While emergency physicians are familiar with the management of hypoxemic respiratory failure, management of mechanical ventilation and advanced therapies for oxygenation in the emergency department (ED) have become essential with the pandemic of COVID-19. Objective of the Review: To review current evidence on hypoxemia in COVID-19 and place it in the context of known evidence-based management of hypoxemic respiratory failure in the ED. Discussion COVID-19 causes mortality primarily through the development of acute respiratory distress syndrome (ARDS), with hypoxemia arising from shunt, a mismatch of ventilation and perfusion. Management of patients developing ARDS should focus on mitigating derecruitment and avoiding volutrauma or barotrauma. Conclusions High flow nasal cannula (HFNC) and non-invasive positive pressure ventilation (NIPPV) have a more limited role in COVID-19 due to risk of aerosolization and minimal benefit in severe cases but can be considered. Stable patients who can tolerate repositioning should be placed in prone position while awake. Once intubated, patients should be managed with ventilation strategies appropriate for ARDS, including targeting lung-protective volumes and low pressures. Increasing positive end-expiratory pressure (PEEP) can be beneficial. Inhaled pulmonary vasodilators do not decrease mortality but may be given to improve refractory hypoxemia. Prone positioning of intubated patients is associated with a mortality reduction in ARDS and can be considered for patients with persistent hypoxemia. Neuromuscular blockade should also be administered in patients who remain dyssynchronous with the ventilator despite adequate sedation. Finally, patients with refractory severe hypoxemic respiratory failure in COVID-19 should be considered for veno-venous extracorporeal membrane oxygenation (VV-ECMO). Although management of mechanical ventilation has not been a traditionally significant 48 part of emergency medicine practice (1, 2), it is gaining increased value in emergency medicine 49 (3). With the recent outbreak of COVID-19 and the anticipated need for more frequent and appropriate management of mechanical ventilation in the emergency department is associated 55 with improved outcomes (4, 5). The most common severe complication of COVID-19 appears to 56 be severe hypoxemic respiratory failure from acute respiratory distress syndrome (ARDS) (6-57 8). Mortality in ARDS is strongly impacted by lung protective ventilation (9). Nevertheless, 58 many patients continue to receive suboptimal management. A recent multicentric international 59 observational study of intensive care units (ICUs) from 50 countries found that ARDS is often 60 unrecognized and fewer than 2/3 of patients received appropriate ventilation (10). As such, 61 opportunities remain for emergency physicians to optimize the early management of severe 62 hypoxemia and ARDS, especially in the critical time of an ARDS pandemic. 63 The search strategy for narrative review involved a Pubmed search using combinations of 65 keywords including "COVID-19" "COVID," or "coronavirus" and concepts related to acute 66 hypoxemic respiratory failure, including "acute respiratory distress syndrome," "ARDS," 67 "hypoxemia," "thrombosis," "thromboembolism," "noninvasive ventilation," "high flow 68 oxygen," "high flow nasal cannula," "positive end expiratory pressure," "mechanical 69 ventilation," "ventilator-induced lung injury," "neuromuscular blockade," "cisatracurium," 70 "recruitment," "prone position," "awake prone," "inhaled epoprostenol," "inhaled nitric oxide," 71 "fraction of inspired oxygen," "hyperoxia," "steroids," "dexamethasone," and "ECMO." The 72 original search was conducted April 15 th through May 8 th , 2020, and was updated on November Discussion 84 Physiology of Hypoxemia in COVID-19 85 The pathophysiology of COVID-19 is the subject of intense ongoing research, and 86 several key discussions have emerged. An early observation during the pandemic is that COVID-87 19 patients in severe hypoxemic respiratory failure meet the Berlin criteria for ARDS (12). 88 Patients with COVID-19-associated respiratory failure present with a spectrum of disease, 89 leading to doubts that ARDS is the underlying pathophysiology of the severe form. An early 90 letter to the editor noted that in 16 patients, the shunt fraction was disproportionately low as 91 compared to the compliance (13). However, the compliance in that letter, 50.2 ± 14.3 92 ml/cmH2O, is not substantially different than the compliance in earlier works on ARDS (14). 93 The compliance noted in other reports of COVID-19 patients (15) also aligns with reported 94 values in ARDS (16), and direct comparisons of patients with and without COVID-19 ARDS 95 have found similar pulmonary mechanics (17). While some studies have found the compliance to 96 be slightly higher in COVID-19 ARDS, the differences are not clinically significant (18). 97 Editorials have hypothesized that COVID-19 ARDS is notable for two phenotypes (19). 98 However, different sub-phenotypes of ARDS have long been recognized, indicating that this is 99 not a new or unique finding (11, (20) (21) (22) . The pathophysiology of all ARDS includes microthrombi and macrothrombi formation in When atelectasis occurs on a large scale, it results in the functional closure of lung units, 125 leading to derecruitment(37). Derecruitment produces a large shunt and is a common cause of 126 hypoxemia. Edematous lungs are at particular high risk of derecruitment, and this appears to be a 127 driving factor for the severe hypoxemia seen in some patients with COVID-19(18). When a 128 patient presents to the ED in respiratory distress, he or she is often sitting upright, using 129 J o u r n a l P r e -p r o o f accessory muscles to maintain adequate negative intrathoracic pressure, and thereby stenting 130 open the distal airways. When the patient is laid down and relaxed for rapid sequence intubation, 131 the pressure from the chest wall, intra-abdominal contents, and even the weight of the lungs 132 themselves can lead to worsening derecruitment (38). Consequently, lying patients flat before 133 intubation can lead to rapid desaturation (39). Mortality from ARDS is due to multi-organ system failure rather than from the 135 hypoxemia itself (40). This is because ARDS is a syndrome of diffuse inflammatory response, is less than 25 cmH 2 O, and the patient continues to have significant respiratory acidosis, the tidal 246 volume can be increased up to a total of 8 ml/kg. The driving pressure, or the pressure to distend alveoli, has also been strongly correlated 248 with outcomes in ARDS (80), even in patients receiving otherwise lung-protective ventilation. The driving pressure is the difference between the plateau pressure and PEEP (79). Driving 250 pressure should be targeted to less than 15cmH2O (55, 81). However, a much larger randomized controlled trial of NMB in 1006 patients found no 306 difference in 90-day mortality (42.5% in the intervention group vs. 42.8% in the controls) (94). As such, NMB has no evidence of benefit nor of harm. NMB has been shown to prevent 308 ventilator dyssynchrony from breath stacking, thereby reducing the risk of additional ventilator-309 associated lung injury and allowing lung-protective ventilation (95) . In the subset of patients who 310 are well-sedated yet remain dyssynchronous with the ventilator, NMB should be given. There have been therefore appropriate concerns regarding the safety of recruitment 334 maneuvers, in terms of hemodynamics or worsening lung injury. However, it seems that the 335 major deleterious effects arise from the rapid rise in pressure, as opposed to a more gentle, Additionally, vasodilation helps the right ventricle by decreasing the right ventricular afterload. Right ventricular dysfunction is strongly associated with poor outcomes in ARDS (106). Academic emergency medicine physicians' knowledge of 480 mechanical ventilation Invasive Mechanical Ventilation in California Over Examining the Impact of an Emergency Department Mechanical Ventilator Protocol on 486 Clinical Outcomes and Lung-Protective Ventilation in Acute Respiratory Distress 487 Lung-Protective Ventilation Emergency Department (LOV-ED): A Quasi-Experimental, Before-After Trial Clinical Characteristics of 138 Hospitalized Patients with 494 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China Care for Critically Ill Patients With COVID-19 Prone position in acute respiratory distress syndrome Use of Prone Positioning in Nonintubated Patients 617 With COVID-19 and Hypoxemic Acute Respiratory Failure Prone positioning improves oxygenation in 619 spontaneously breathing nonintubated patients with hypoxemic acute respiratory failure: 620 A retrospective study Early Self-Proning in Awake Awake prone positioning in COVID-19 625 hypoxemic respiratory failure: exploratory findings in a single-center retrospective cohort 626 study Awake prone positioning for COVID-19 629 hypoxemic respiratory failure: A rapid review Can High-flow Nasal Cannula Reduce the Rate of 632 Endotracheal Intubation in Adult Patients With Acute Respiratory Failure Compared With 633 Conventional Oxygen Therapy and Noninvasive Positive Pressure Ventilation?: A 634 Systematic Review and Meta-analysis The effect of high-flow nasal cannula in reducing the mortality the rate of endotracheal intubation when used before mechanical ventilation compared 638 with conventional oxygen therapy and noninvasive positive pressure ventilation. A 639 systematic review and meta-analysis High-Flow Nasal Cannula Versus 642 Conventional Oxygen Therapy in Emergency Department Patients With Cardiogenic 643 Pulmonary Edema: A Randomized Controlled Trial Clinical management of severe acute respiratory infection when COVID-19 is suspected 647 High-flow oxygen through nasal cannula in acute 651 hypoxemic respiratory failure Treatment for severe acute respiratory distress 654 syndrome from COVID-19 High-flow nasal therapy in adults with severe acute 657 respiratory infection. A cohort study in patients with 2009 influenza A/H1N1v Practical recommendations for critical care and anesthesiology for novel coronavirus (2019-nCoV) patients Noninvasive ventilation for 662 COVID-19-associated acute hypoxaemic respiratory failure: experience from a single 663 centre High-flow nasal cannula may be no safer than non-666 invasive positive pressure ventilation for COVID-19 patients Exhaled air dispersion during high-flow nasal cannula 670 therapy versus CPAP via different masks Assessment of the potential for pathogen 672 dispersal during high-flow nasal therapy High-flow nasal cannula for COVID-19 patients: low risk of 674 bio-aerosol dispersion High-flow nasal cannula for acute hypoxemic 677 respiratory failure in patients with COVID-19: systematic reviews of effectiveness and its 678 risks of aerosolization, dispersion, and infection transmission Critically ill patients with 2009 influenza 681 A(H1N1) infection in Canada Risk factors for noninvasive ventilation failure ill subjects with confirmed influenza infection Outcome of non-invasive ventilation in COVID-19 686 critically ill patients: A Retrospective observational Study Consensus statement: Safe Airway Society principles of airway management and tracheal 690 intubation specific to the COVID-19 adult patient group | Management of COVID-19 Respiratory Distress Caution about early intubation and mechanical ventilation 698 in COVID-19 Rethinking the early intubation paradigm of COVID-701 19: Time to change gears? Presenting Characteristics, Comorbidities, 704 and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City 705 Ventilated Patients with COVID-19: A Cohort Study ICU and Ventilator Mortality among 710 Critically Ill Adults with Coronavirus Disease Timing of Intubation and Its Implications on 714 Outcomes in Critically Ill Patients With Coronavirus Disease Available from: 716 /pmc/articles/PMC7587415/?report=abstract 717 75 Noninvasive ventilation improves 722 preoxygenation before intubation of hypoxic patients Compared Efficacy of Four Preoxygenation 726 Methods for Intubation in the ICU: Retrospective Analysis of McGrath Mac 727 Videolaryngoscope Versus Macintosh Laryngoscope (MACMAN) Trial Data Respiratory support techniques to avoid 731 desaturation in critically ill patients requiring endotracheal intubation: A systematic 732 review and meta-analysis Higher versus Lower Positive End-Expiratory Pressures in Patients with the Acute 734 Respiratory Distress Syndrome Effect of driving pressure on mortality in ARDS 737 patients during lung protective mechanical ventilation in two randomized controlled trials 738 Driving Pressure and Survival in the Acute 741 Respiratory Distress Syndrome Re-examining Permissive Hypercapnia in ARDS: A 744 Narrative Review Initial mechanical ventilator settings and lung 747 protective ventilation in the ED Duration of mechanical ventilation in the 749 Emergency Department Emergency Department Blood Gas 751 Utilization and Changes in Ventilator Settings The effect of emergency department crowding on 753 lung-protective ventilation utilization for critically ill patients Ventilation Strategy Using Low Tidal Volumes Recruitment Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung 758 Injury and Acute Respiratory Distress Syndrome Positive end-expiratory pressure. When more may not be better Association Between Hyperoxia and Mortality After Stroke Emergency department hyperoxia is 767 associated with increased mortality in mechanically ventilated patients: a cohort study 768 Neuromuscular blocking agents decrease 771 inflammatory response in patients presenting with acute respiratory distress syndrome* 772 Attenuates Lung Injury by Inhibition of Nicotinic Acetylcholine Receptor-α1 Neuromuscular blockers in early acute 779 respiratory distress syndrome Early neuromuscular blockade in the acute 781 respiratory distress syndrome Quantifying unintended exposure to high tidal 786 volumes from breath stacking dyssynchrony in ARDS: the BREATHE criteria How large is the lung recruitability in early 790 acute respiratory distress syndrome: a prospective case series of patients monitored by 791 computed tomography Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients 795 With Acute Respiratory Distress Syndrome Complications from recruitment maneuvers in 799 patients with acute lung injury: Secondary analysis from the lung open ventilation study Efficacy and safety of recruitment maneuvers in 802 acute respiratory distress syndrome Reversibility of Lung Collapse and Hypoxemia in Early Acute Respiratory Distress Syndrome Effects of alveolar recruitment 810 maneuvers on clinical outcomes in patients with acute respiratory distress syndrome: a 811 systematic review and meta-analysis Prone Positioning in Patients With Moderate and Severe Acute Respiratory Distress Syndrome Prone Position for Acute Respiratory 818 Distress Syndrome. A Systematic Review and Meta-Analysis Inhaled epoprostenol improves oxygenation in 824 severe hypoxemia Right heart function during acute respiratory distress 827 syndrome Severity of Hypoxemia and Other Factors That 830 Influence the Response to Aerosolized Prostacyclin in ARDS Nitric Oxide for the Treatment of ARDS Inhaled epoprostenol vs inhaled nitric oxide for 837 refractory hypoxemia in critically ill patients The role of inhaled prostacyclin in treating 841 acute respiratory distress syndrome The Importance of Ground Critical Care 844 J o u r n a l P r e -p r o o f Transport: A Case Series and Literature Review Successful aeromedical transport using inhaled 846 prostacyclin for a patient with life-threatening hypoxemia Remdesivir in adults with severe COVID-19: a 848 randomised, double-blind, placebo-controlled, multicentre trial Effect of Remdesivir vs Standard Care on 852 Clinical Status at 11 Days in Patients with Moderate COVID-19: A Randomized Clinical 853 Remdesivir for the Treatment of Covid-19 -856 Final Report Anticoagulation, Bleeding, Mortality, and 859 Pathology in Hospitalized Patients With COVID-19 Scientific and Standardization Committee 863 communication: Clinical guidance on the diagnosis, prevention, and treatment of venous 864 thromboembolism in hospitalized patients with COVID-19 ISTH interim guidance on recognition and 868 management of coagulopathy in COVID-19 Extracorporeal membrane oxygenation for critically 871 ill adults Inter-hospital transports on extracorporeal membrane oxygenation in 874 different health-care systems Improved Oxygenation after Transport in Patients 876 with Hypoxemic Respiratory Failure Interhospital transport of ARDS patients on 878 extracorporeal membrane oxygenation Referral to an extracorporeal membrane 881 oxygenation center and mortality among patients with severe 2009 influenza A(H1N1) Extracorporeal Membrane Oxygenation for 884 Severe Acute Respiratory Distress Syndrome Failure in Adults with COVID-19" 899 1) Why is this topic important? 900During the global pandemic of COVID-19, there has been an incredible outpouring of research and 901 collaboration among emergency physicians to share their evolving knowledge of managing the 902 disease. A current review helps to focus this information and place it in context for practicing 903 emergency physicians.