PMC:7079862 / 28683-41230 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7079862","sourcedb":"PMC","sourceid":"7079862","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7079862","text":"Supportive care\nPatients with severe RVI present typically with pneumonia, acute respiratory distress syndrome (ARDS), decompensated heart failure, or exacerbation of chronic lung disease; leading frequently to acute hypoxemic, and less commonly hypercapnic, respiratory failure. Except for several influenza and novel coronavirus studies noted below, most of the data regarding supportive care strategies come from studies that have not documented specific RVIs. In many ARDS trials, patients with pneumonia constituted a majority of enrolled patients; but detailed description of etiologic pathogens is often lacking. Given the high prevalence of viral pathogens as outlined earlier, it is likely that severe RVIs constitute a considerable proportion. There are general pathophysiologic and clinical similarities between ARDS and pneumonia caused by severe RVIs and those due to other pathogens or etiologies, and therefore, the extrapolation of findings from unselected populations to patients with severe RVIs can be justified in the absence of specific data. At the same time, there are important differences that may lead to heterogeneity in response to treatment.\n\nNon-invasive ventilation\nData on non-invasive ventilation (NIV) in severe RVI are limited. In patients with severe RVI resulting in chronic obstructive pulmonary disease (COPD) exacerbations or cardiogenic pulmonary edema, NIV may be effective in reducing the need of endotracheal intubation and decreasing ventilator-associated complications and mortality [42].\nHowever, NIV in patients with severe RVI causing acute hypoxemic respiratory failure and pneumonia is of uncertain benefit. Observational studies reported variable results for NIV in patients with severe influenza A(H1N1)pdm09 with some reporting NIV failure in up to 85% [43]. In one multicenter observational study of 1898 critically ill patients with acute hypoxemic respiratory failure due to influenza, 806 underwent initial NIV, and 56.8% of them required conversion to invasive ventilation. Patients with SOFA ≥ 5 had a higher risk of NIV failure. Similar to other studies, NIV failure was associated with increased ICU mortality compared with invasive mechanical ventilation [44].\nData from uncontrolled studies suggested that NIV might have been effective and safe in the management of some patients with SARS [45], while others highlighted concerns of increased SARS transmission risk to healthcare workers [46]. In a multicenter cohort of 302 MERS critically ill patients, NIV was used initially in 35% of patients, but the vast majority of them (92.4%) required conversion to invasive mechanical ventilation; however, NIV was not independently associated with 90-day mortality [47].\nA recent single-center RCT in patients with unselected patients with ARDS (n = 83, 45% pneumonia) showed that treatment with helmet NIV resulted in significant reduction of intubation rates and in 90-day mortality [48]. Further studies in patients with severe RVI are needed, as helmet NIV may be more effective than traditional masks and may be associated with less risk of transmission due to aerosol generation.\nBased on available evidence, NIV in severe RVI may be used in selected patients in early stages and milder forms of acute hypoxemic respiratory failure, excluding those in shock or multiorgan failure, with the recognition that for patients who do not show signs of early recovery, NIV may well delay but not avoid invasive ventilation [42].\n\nHigh-flow nasal cannula\nHigh-flow nasal cannula has emerged as an alternative to NIV to prevent intubation in patients with acute hypoxemic respiratory failure. In one trial (n = 310, 72% community-acquired pneumonia), treatment with high-flow oxygen, standard oxygen, or NIV did not result in significantly different intubation rates; however, there was a significant difference in favor of high-flow nasal cannula in 90-day mortality [49]. A small cohort of patients with severe RVI with influenza A(H1N1)pdm09 (n = 25) showed that high-flow nasal cannula was associated with avoidance of intubation in 45% of patients, although almost all patients with higher severity of illness and shock were eventually intubated [50].\n\nInvasive ventilation\nBased on current evidence, patients with ARDS due to severe RVI should be managed with lung-protective strategy with low tidal volumes (6 ml/kg predicted body weight) and plateau pressures \u003c 30 to 35 cmH2O. In adults with acute lung injury or ARDS due to various causes, an individual patient data meta-analysis of 2299 patients from three trials (50% with pneumonia) found that higher positive end-expiratory pressure (PEEP) levels were associated with improved survival among the subgroup of patients with ARDS (defined by PaO2/FiO2 ≤ 200 mmHg) [51]. A recent RCT of over 1000 patients with moderate-to-severe ARDS (55% with pneumonia) demonstrated that prolonged and high-pressure recruitment maneuvers was associated with increased 28-day mortality [52]. Titration of PEEP to achieve optimal oxygenation, perhaps without aggressive recruitment maneuvers, remains a reasonable strategy for most patients.\n\nHigh-frequency oscillatory ventilation (HFOV)\nHFOV ventilates the lung with tidal volumes lower than anatomical dead space while achieving relatively high mean airway pressures [53]. In patients with influenza A(H1N1)pdm09 influenza, HFOV has been used as a rescue therapy for those not responding to conventional ventilation [53]. Two randomized clinical trials showed that HFOV in moderate-to-severe ARDS was not associated with improved outcomes compared to conventional ventilation [54, 55]. However, a meta-analysis of 1552 patients (55% with pneumonia) found that the HFOV treatment effect depended on baseline severity of hypoxemia, with harm among patients with mild-moderate ARDS but possibly decreased mortality in patients with very severe ARDS [56]. Therefore, while HFOV is not recommended for routine use in ARDS, there may still be a role as rescue therapy [53].\n\nProne positioning\nA multicenter RCT (n = 474, 60% with pneumonia) demonstrated that early application of prone positioning (at least 16 h per session) in patients with severe ARDS (PaO2/FiO2 \u003c 150 mmHg, with an FiO2 ≥ 0.6, PEEP of ≥ 5 cmH2O, and a tidal volume close to 6 ml/kg predicted body weight) resulted in decreased mortality [57]. Prone positioning in patients with avian A(H7N9) influenza-related severe ARDS has been associated with improved oxygenation, sustained after returning to a supine position, and with decreased carbon dioxide retention [58].\n\nNeuromuscular blockers\nIn patients with severe ARDS, in one trial (n = 339, 38% community-acquired pneumonia), early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness [59]. However, in a recent larger trial that enrolled patients with moderate-to-severe ARDS (n = 1006, 59% pneumonia), treated with a strategy involving high PEEP, there was no significant difference in mortality at 90 days between patients who received an early, continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets [60]. Specific data on neuromuscular blockade in severe RVI are lacking.\n\nExtracorporeal membrane oxygenation (ECMO)\nThe latest RCT for ECMO (EOLIA) included 249 patients with severe ARDS, 18% with viral etiologies, and found that ECMO did not reduce mortality at day 60 [61]. Yet, a post hoc Bayesian analysis found that the interpretation of benefit versus no benefit in this trial is critically dependent upon the range of prior assumptions reflecting varying degrees of skepticism and enthusiasm of previous evidence for the benefit of ECMO—clinicians with more enthusiasm for the benefit of ECMO may be justified in considering it for certain patients [62].\nIndeed, observational studies reported lower hospital mortality among patients with ARDS related to influenza A(H1N1)pdm09 with transfer to an ECMO center compared with matched non-ECMO-referred patients [63]. A case–control study also suggested survival benefit for ECMO in patients with severe MERS [64]. ECMO is likely to be associated with better outcomes when used among patients with limited organ failures and good premorbid functional status, and should be considered for patients who fail other evidence-based oxygenation strategies according to individual patient characteristics and a potential risk–benefit determination.\n\nCardiovascular management\nTimely adequate fluid resuscitation is an essential element of the management of patients with severe RVI and shock. However, in those with ARDS (n = 1000, 47% pneumonia), a conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation without increasing non-pulmonary-organ failures [65]. In addition, aggressive fluid administration may worsen ventricular function. This may be particularly relevant for patients with severe RVI. Myocardial involvement is not uncommon with severe influenza A or B virus infection, and multiple studies have shown an association between influenza and acute myocardial infection and myocarditis [66–68]. Echocardiographic findings often include right- and left-ventricular dysfunction [66]. Therefore, clinical assessment of fluid responsiveness is important along with quantification of right- and left-ventricular size and function using echocardiography and/or dynamic minimally invasive cardiovascular monitoring, if available. Myocarditis has associated with longer duration of vasoactive agents and mortality and may sometimes require ECMO or other types of supportive care [69, 70].\n\nInfection prevention and control\nTable 2 summarizes infection control precautions for different RVIs as recommended by the Centers for Disease Control and Prevention (please refer to Table 2 footnote for CDC references). In patients presenting with severe RVIs, contact plus droplet precautions are recommended; droplet precautions may be discontinued when adenovirus and influenza have been ruled out. For patients with a history of recent travel (10–21 days) to countries with active outbreaks of SARS, MERS, or avian influenza, airborne plus contact precautions and eye protection are recommended.\nAerosol-generating procedures, such as bronchoscopy, endotracheal intubation, and open suctioning of the respiratory tract, tracheotomy, manual ventilation before intubation, nebulizer treatment, high-flow nasal cannula, non-invasive ventilation, and chest compressions, have been implicated with transmission of infectious agents to healthcare personnel. However, these findings were identified from limited studies, mainly during the SARS outbreak [71]. Nevertheless, it is recommended during aerosol-generating procedures on patients with suspected or proven infections transmitted by aerosols (for example influenza, MERS, SARS) to wear a fit-tested N95 mask in addition to gloves, gown, and face/eye protection. Closed-circuit suctioning may reduce the exposure to aerosols. Performing these procedures in an airborne isolation room when feasible is recommended.\nRCTs comparing N95 respirators to medical masks in health care personnel working in outpatient and ward settings have not shown significant differences in protection from laboratory-confirmed influenza or other RVIs [72, 73]. The relevance of these observations to the ICU setting is uncertain, given the frequent use of aerosol-generating procedures in critically ill patients. Cloth masks are clearly inferior to medical masks in protecting HCWs from RVIs [74]. Other aspects of prevention strategies to prevent transmission when caring for patients with severe RVIs include annual influenza vaccination of healthcare workers, adherence to standard precautions, including hand hygiene, during the care of any patient and appropriate management of ill healthcare workers (please refer to Table 2 footnote for CDC references). Recently, antiseptic hand rubbing using ethanol-based disinfectants (EBDs) was found to be less effective than hand washing with running water in inactivating influenza virus in undried mucus under experimental conditions; [75] also nonenveloped viruses like adenovirus which are not easily inactivated by EBDs. The implications of these observations for clinical practice remain to be determined but hand washing with soap and water or hand rubbing with EBD for longer than 30 s may be 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