Noninvasive ventilation for COVID-19-associated acute hypoxaemic respiratory failure: experience from a single centre
2020; Elsevier BV; Volume: 125; Issue: 4 Linguagem: Inglês
10.1016/j.bja.2020.07.008
ISSN1471-6771
AutoresArjjana Sivaloganathan, Myra Nasim-Mohi, Michael M. Brown, Nabil Abdul, Alexander Jackson, Sophie Fletcher, Sanjay Gupta, Michael P. W. Grocott, Ahilanandan Dushianthan, Sanjay Gupta, Julian Nixon, Michael P. W. Grocott, Denny Levett, Michael Stewart, Ahilanandan Dushianthan, David Sparkes, Robert Chambers, Kathleen Nolan, Suzie J. Tanser, Jonathan Fennell, Michael Celinski, Dominic Richardson, Rebecca Cusack, Benjamin Skinner, Timothy Nicholson-Robert, Mai Wakatsuki, Thomas Ben, François Wessels, Mark G. Jones, Paul Elkington, Tom Wilkinson, Mark C. Allenby, T. Daniels, Paddy Dennison, Anastasios Lekkas, Arjjana Sivaloganathan, David Land, Sophie Fletcher, Wilkinson, Anna Freeman, Hannah Burke, Ahilanandan Dushianthan, Michael Celinski, Saul N. Faust, Gareth J. Thomas, Christopher Kipps,
Tópico(s)Intensive Care Unit Cognitive Disorders
ResumoEditor—In a minority of coronavirus disease 2019 (COVID-19) patients, severe acute hypoxaemic respiratory failure (AHRF) necessitates admission to an ICU for invasive mechanical ventilation with an associated mortality of >50%.1These data arise from the ICNARC Case Mix Programme Database. The Case Mix Programme is the national clinical audit of patient outcomes from adult critical care coordinated by the Intensive Care National Audit & Research Centre (ICNARC). For more information for the representativeness and quality of these data, please contact ICNARC. Available from: https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports (accessed 15 May 2020).Google Scholar, 2Wang D. Hu B. Hu C. et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China.JAMA. 2020; 323: 1061-1069Crossref PubMed Scopus (15355) Google Scholar, 3Bhatraju P.K. Ghassemieh B.J. Nichols M. et al.Covid-19 in critically ill patients in the Seattle Region – case series.N Engl J Med. 2020; 382: 2012-2022Crossref PubMed Scopus (1737) Google Scholar Published cohorts suggest that noninvasive ventilation is a commonly used intervention in COVID-19-related AHRF4Guan W. Ni Z. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (19247) Google Scholar,5Yang X. Yu Y. Xu J. et al.Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.Lancet Respir Med. 2020; 8: 475-481Abstract Full Text Full Text PDF PubMed Scopus (6597) Google Scholar although no formal evaluation has been reported in the setting of a clinical trial. It is uncertain whether noninvasive ventilation is beneficial or harmful for patients with COVID-19. Here, we report a single centre experience of the role of noninvasive ventilation in patients with respiratory failure associated with COVID-19. We report an evaluation of the use of ventilatory support in a single academic medical centre (University Hospital Southampton NHS Foundation Trust) during the early phases of the COVID-19 pandemic within the UK. Ethical approval was obtained as part of the REACT observational study of COVID-19 (a longitudinal cohort study to facilitate better understanding and management of severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] from admission to discharge across all levels of care): REC Reference; 17/NW/0632, SRB Reference Number; SRB0025. Informed consent was waived because of the study design. Consecutive patients diagnosed with COVID-19 based on laboratory reverse transcriptase polymerase chain reaction (RT–PCR) tests and with associated AHRF were assessed from hospital admission to establish suitability for invasive mechanical ventilation, noninvasive ventilation, or both in the event of severe respiratory failure. Indications for escalation of care to noninvasive ventilation/invasive mechanical ventilation were based on respiratory distress, gas exchange, other organ dysfunction, and the rate of change in their clinical condition. Patients who were candidates for escalation to invasive mechanical ventilation were admitted to the general ICU (Cohort 1). Patients in whom noninvasive ventilation was defined as the ceiling of ventilation care were admitted to a Level 2 area (Cohort 2). Data were collected from existing electronic hospital records, from the index patient (March 6, 2020) until 16.00 on May 14, 2020. For descriptive statistics, data were presented as median (25th–75th centiles) as variables were found to be non-normally distributed when assessed by the Kolmogorov–Smirnov test. A comparison of proportions was performed using the χ2 test. Unadjusted univariate logistic regression was performed to obtain non-adjusted odds ratios and 95% confidence intervals for important variables. A total of 586 confirmed COVID-19-positive patients were hospitalised during the study period, of whom 103 (17.6%) required noninvasive ventilation or invasive mechanical ventilation. Of these, 79 were admitted to the ICU to receive noninvasive ventilation or invasive mechanical ventilation (Cohort 1), and 24 were admitted to a separate Level 2 area for noninvasive ventilation support as a ceiling of ventilatory care (Cohort 2). Cohort 2 patients were older (median age 67 yr), more frail (median Rockwood clinical frailty scale of 6),6 had more comorbidities (median Charlson comorbidity index of 4),7 and were more hypoxic when care was escalated to noninvasive ventilation (Table 1).Table 1Patient characteristics and outcomes of all patients who received noninvasive and invasive ventilation. Data are presented as median (25th–75th centiles). All variables and scoring were performed at the time of the ICU admission. APACHE II, Acute Physiology and Chronic Health Evaluation II; ECMO, extracorporeal membrane oxygenation; IMV, invasive mechanical ventilation; INR, international normalised ratio; NIV, noninvasive ventilation; PaO2/FiO2, partial pressure of arterial oxygen to fraction of inspired oxygen ratio; SOFA, sequential organ failure assessment.Patient characteristics and outcomesCohort 1 NIV only group (n=31)Cohort 1 NIV+IMV group (n=27)Cohort 1 IMV only group (n=21)Cohort 2 NIV ceiling group (n=24)Age (yr)50 (45–60)57 (50–64)61 (18–65)66 (54–72)Female:Male1:21:0.81:3.21:1.4Symptomatic days before hospitalisation7 (6–10)9 (6.5–13)5 (3–10)4 (3–8)Rockwood clinical frailty scale6Rockwood K. Song X. MacKnight C. et al.A global clinical measure of fitness and frailty in elderly people.CMAJ. 2005; 173: 489-495Crossref PubMed Scopus (4892) Google Scholar2 (1–2)2 (1–2.5)2 (2–3)6 (5–7)Charlson comorbidity index7Charlson M.E. Pompei P. Ales K.L. MacKenzie C.R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chronic Dis. 1987; 40: 373-383Abstract Full Text PDF PubMed Scopus (36283) Google Scholar1 (0–2.5)2 (1–3)3 (1–3)4 (3–7)BMI>30 kg m−2 (%)45412953APACHE II11 (8–12.5)18 (13.0–24.5)22 (15–25)18 (16–20)SOFA score3 (4–3)4 (3–6)6 (4–8)5 (4.5–6)Worse PaO2/FiO2 ratio at 24 h17 (14.3–20.4)13.9 (12.8–16.8)15.3 (12.7–18.1)10.1 (8.2–13.9)Time (h) from hospitalisation to noninvasive ventilation initiation or intubation18 (5–54)1 (0–13)1 (0–7)26 (8–94)Total noninvasive ventilation time (h)72 (41–132)17 (4–31)N/A44 (18–103)Biochemical markersCreatinine (mM)67 (60–90)60 (48–91)89 (74–142)75 (57–125)Bilirubin (mM)11 (9–12.5)13 (9–18)9 (7–16)11 (8–19)White cell count (109 L−1)6.3 (5.3–10.8)7.9 (5.7–13.4)10.6 (8.1–12.6)7 (4.6–9.9)Lymphocytes (109 L−1)1 (0.8–1.4)0.8 (0.6–1.0)0.7 (0.6–1.1)0.9 (0.5–1.0)C-reactive protein (mg L−1)120 (91–164)158 (113–220)179 (154–276)118 (45–160)INR1.2 (1.1–1.2)1.2 (1.1–1.3)1.2 (1.1–1.4)1.2 (1.1–1.3)Ferritin (mg L−1)1093 (451–2243)1014 (542–1380)754 (609–965)326 (111–993)Lactate dehydrogenase (U L−1)888 (695–1332)900 (752–1179)1607 (1186–1884)830 (488–1192)Troponin (ng L−1)9 (6–15)13 (8–37)64 (27–249)18 (6–102)D-Dimer (mg L−1)420 (263–655)540 (333–1057)1677 (682–2884)635 (364–1029)Creatine kinase (U L−1)242 (94–412)109 (83–242)247 (116–420)91 (38–235)Outcome (n [%])•Died0 (0)3 (11.1)6 (28.6)20 (83.3)•Home29 (93.5)8 (29.6)8 (38.1)4 (16.7)•Hospitalised (ICU)2 (6.5)9 (33.3)5 (23.8)0 (0)•Hospitalised (ward)0 (0)5 (18.5)2 (9.5)0 (0)•Transferred for ECMO0 (0)2 (7.4)0 (0)0 (0) Open table in a new tab Among Cohort 1 patients, 58/79 (73%) had an initial trial of noninvasive ventilation whilst 21/79 (27%) underwent immediate tracheal intubation (Group IMV alone). Among those patients who had an initial trial of noninvasive ventilation, 27/58 progressed to invasive mechanical ventilation (Group NIV+IMV) whereas 31/58 did not require subsequent invasive mechanical ventilation (Group NIV alone). Of note, 29/31 (94%) patients in Group NIV alone were discharged from hospital alive with the remaining 2/31 (6%) being alive in the ICU at the time of data collection. Of Cohort 2 patients, 4/24 (17%) were discharged from hospital alive whereas 20/24 (83%) died in hospital. In Group NIV+IMV, the median time to invasive mechanical ventilation was 17 h (4–31) and 55% failed within the first 24 h. For Group NIV alone, the median noninvasive ventilation duration was 3 days. The median age for patients in Group NIV alone was 50 yr compared with 57 yr in Group NIV+IMV. The clinical frailty scale, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score were similar between these two groups. The only variable associated with risk of intubation was the admission SOFA score. In all patients who underwent a trial of noninvasive ventilation (Group NIV alone and Group NIV+IMV), univariate unadjusted logistic regression analysis showed increased SOFA scores on admission were associated with increased risk of tracheal intubation (odds ratio 2.4, 95% confidence interval 1.34–4.38, P<0.0001). Among the patients eligible for escalation to invasive mechanical ventilation, the overall mortality was 9/61 (14%) patients with completed ICU episodes and 9/79 (11%) of all admitted patients including those remaining in the ICU. Overall, 23 patients (30%) remained hospitalised either in the ICU (20%) or on medical wards (10%), and 45 patients (57%) had been successfully discharged home. Two patients were transferred to another tertiary hospital for extracorporeal membrane oxygenation. Substantially higher mortality (83%) was noted among those patients who received noninvasive ventilation as ceiling of care. Comparisons with published national critical care data for England, Wales, and Northern Ireland from the Intensive Care National Audit and Research Centre (ICNARC) provide interesting context to our data. It is important to emphasise that such comparisons are limited by the absence of comprehensive matching of the characteristics of our patients with those within the ICNARC dataset. APACHE-II and PaO2/FiO2 ratios for Cohort 1 (eligible for escalation to invasive mechanical ventilation) were similar to the ICNARC cohort. However, the use of basic respiratory support (noninvasive ventilation) was more common (73.4% for Cohort 1 vs 56.7% ICNARC).1 In comparison with ICNARC mortality from completed episodes (discharged from hospital or dead) (3139/6860; 45.8%), there was a smaller proportion of deaths in all groups except for Cohort 2 (noninvasive ventilation as limit of ventilatory care): overall mortality 29/85 (34.1%); Cohort 1 mortality 9/61 (14.6%).1These data arise from the ICNARC Case Mix Programme Database. The Case Mix Programme is the national clinical audit of patient outcomes from adult critical care coordinated by the Intensive Care National Audit & Research Centre (ICNARC). For more information for the representativeness and quality of these data, please contact ICNARC. Available from: https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports (accessed 15 May 2020).Google Scholar Despite the widespread use of noninvasive ventilation for the treatment of AHRF and acute respiratory distress syndrome, its utility in COVID-19 lung disease remains controversial.4Guan W. Ni Z. Hu Y. et al.Clinical characteristics of coronavirus disease 2019 in China.N Engl J Med. 2020; 382: 1708-1720Crossref PubMed Scopus (19247) Google Scholar,5Yang X. Yu Y. Xu J. et al.Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study.Lancet Respir Med. 2020; 8: 475-481Abstract Full Text Full Text PDF PubMed Scopus (6597) Google Scholar,8Bellani G. Laffey J.G. Pham T. et al.Noninvasive ventilation of patients with acute respiratory distress syndrome. Insights from the LUNG SAFE study.Am J Resp Crit Care Med. 2017; 195: 67-77Crossref PubMed Scopus (381) Google Scholar We report on 103 critically-ill patients with COVID-19 and moderate–severe hypoxaemic respiratory failure, including 24 patients who were offered noninvasive ventilation as a ceiling of ventilatory care. More than half of the patients eligible for escalation to invasive mechanical ventilation tolerated noninvasive ventilation well and avoided tracheal intubation at any time. Unsurprisingly, the mortality and clinical outcome of these patients were better than those patients who were subsequently intubated. In conclusion, noninvasive ventilation is a safe, feasible, and useful ventilatory strategy that may avoid the complications of tracheal intubation and ventilation in selected patients with COVID-19-associated respiratory failure. Our data from a single centre suggest that noninvasive ventilation has a role in the management of COVID-19-associated respiratory failure, but clarification of the nature of this role await the results of large RCTs. Patient selection, defining appropriate limits of care, and effective team working between critical care and respiratory specialists are important in the effective delivery of an integrated clinical ventilation strategy for COVID-19-associated respiratory failure. Conception and design: AD, MG, SG, SF Data collection: AS, MN, MB, NA Manuscript preparation: AS, MB, AD, MG Critical revision of manuscript: all authors The authors declare that they have no conflicts of interest. UHS Critical Care Clinical Team Dr Sanjay Gupta Dr Julian Nixon Professor Michael P. W. Grocott Professor Denny ZH Levett Dr Michael Stewart Dr Ahilanadan Dushianthan Dr David Sparkes Dr Robert Chambers Dr Kathleen Nolan Dr Suzie Tanser Dr Jonathan Fennell Dr Michael Celinski Dr Dominic Richardson Dr Rebecca Cusack Dr Benjamin Skinner Dr Timothy Nicholson-Robert Dr Mai Wakatsuki Dr Ben Thomas Dr Francois Wessels UHS Respiratory Clinical Team Dr Mark Jones Prof Paul Elkington Prof Tom Wilkinson Dr Mark Allenby Dr Thomas Daniels Dr Paddy Dennison Dr Anastasios Lekkas Dr Arjjana Sivaloganathan Dr David Land Dr Sophie Fletcher REACT Investigators Professor Tom Wilkinson Dr Anna Freeman Dr Hannah Burke Dr Ahilanadan Dushianthan Dr Michael Celinski Professor Saul Faust Professor Gareth Thomas Professor Christopher Kipps
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