It remains unclear if intubation and ventilation earlier in the disease course confers a survival advantage in acute respiratory distress syndrome. Our objective was to determine whether patients with COVID-19 who died following mechanical ventilation were more advanced in their disease compared to survivors. Forty-seven patients admitted directly to our centre received ventilation, of who 26 (57%) patients died. The rate of fall in SpO2:FiO2 ratio (p = 0.478) and increasing respiratory rate (p = 0.948) prior to IMV were similar between survivors and non-survivors. Our data support a trial of continuous positive airway pressure prior to IMV in patients with moderate-to-severe COVID-19 ARDS

Arulkumaran, N

Bonnici, T

Green, J

Khan, A

Longobardo, A

Singer, M

English

UCL Discovery

  Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website.  Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.  Journal of Critical Care 62 (2021) 289–291Contents lists available at ScienceDirectJournal of Critical Carej ourna l homepage: www. journa ls .e lsev ie r .com/ journa l -o f -c r i t i ca l -ca reInfluence of respiratory and inflammatoryparameters preceding intubation on survival ofpatients with COVID-19 ARDS– A single centreretrospective analysisKeywords:Acute respiratory distress syndromeLung injuryMechanical ventilationContinuous positive airway pressureto IMV (p = 0.398), respiratory rate (p = 0.704) and SpO2:FiO2ratio (p = 0.066) immediately prior to IMV and use of CPAPDear Editor:The relative harm of lung injury induced by prolonged trials ofspontaneous breathing with assisted non-invasive support (patientself-inflicted lung injury; p-SILI) versus early mechanical ventilation-induced lung injury (VILI) has engendered vigorous debate [1,2]. It re-mains unclear if intubation and IMV earlier in the disease course con-fers a survival advantage in acute respiratory distress syndrome(ARDS). Our objective was to determine whether patients withCOVID-19 pneumonia who died following invasive mechanical ventila-tion (IMV)were more advanced in their disease compared to survivors.We conducted a single-centre retrospective cohort study of me-chanically ventilated COVID-19 patients treated at University CollegeLondonHospital (UCLH) between 1March and 30 June 2020. Our strat-egy, adopted from the outset, was to utilize continuous positive air-ways pressure (CPAP) in patients deteriorating with facemask oxygenalone in either the intensive care unit (ICU) or a newly-established re-spiratory high dependency unit (HDU). Patients proceeded to IMV ifthey showed a trajectory of worsening hypoxaemia and/or increasingrespiratory effort/fatigue.Data were extracted from electronic healthcare records on patientdemographics, clinical features (duration of symptoms, timing of intu-bation, daily peak temperature, and daily median SpO2, FiO2 and respi-ratory rate), and routine biochemistry (C-reactive protein (CRP),neutrophil count). Respiratory and inflammatory variables were col-lected three days preceding IMV requirement. Continuous and cate-gorical variables are reported as median (interquartile range) and n(%), respectively. For comparison of continuous variables, Mann Whit-ney U test for comparison between 2 groups. The change in continu-ous variables over time between survivors and non-survivors wasassessed using two-way ANOVA. Categorical data were comparedusing the chi-squared test. Statistical analysis was performed, andgraphs constructed using Prism (GraphPad Software, Version 5.0d,San Diego, California, US).Abbreviations: ARDS, acute respiratory distress syndrome; CPAP, continuous positiveairway pressure; CRP, C-reactive protein; ICU, Intensive Care Unit; IMV, Invasivemechan-ical ventilation; p-SILI, patient self-inflicted lung injury; SpO2:FiO2, Oxygen saturation:fraction of inspired oxygen ratio; VILI, ventilation-induced lung injury.https://doi.org/10.1016/j.jcrc.2021.01.0010883-9441/© 2021 Elsevier Inc. All rights reserved.Ninety-nine patients received IMV. Fifty-two (52%) patients trans-ferred from other hospitals were excluded as complete clinical dataprior to IMV were unavailable. Forty-seven patients admitted directlyto UCLH received IMV, of who 26 (57%) patients died in hospital. Sixpatients were intubated shortly after hospital admission. Of the re-maining 40 patients, 39 (98%) received CPAP. Duration from symp-tom onset to hospitalisation (p = 0.436), days from hospitalisation(p = 0.119) were similar between survivors and non-survivors. Atrajectory of falling SpO2:FiO2 ratio (p = 0.056) and increasingtachypnoea (p < 0.001) prior to intubation was noted in all patients.However, the rate of change of SpO2:FiO2 ratio (p = 0.478) and in-creasing respiratory rate (p = 0.948) prior to IMV were similar be-tween survivors and non-survivors. The change in inflammatoryparameters preceding IMV were similar between survivors andnon-survivors (Fig. 1).Consistent with international expert consensus recommendationson airway management in COVID-19, we intubated patients in their in-dividual pathology and pathophysiology, the acute trajectory of their ill-ness, in addition to their responsiveness to trials of noninvasive airwaymanagement [3]. On IMV initiation, 61% of patients fulfilled the Berlincriteria for severe ARDS. This contrasts with 39% in the first 24 h ofICU admission in the UK national database [4]. Despite this higher pro-portion, the mortality rate was comparable for patients mechanicallyventilatedwithin the first 24 h [4].While cognisant of the potential det-rimental effects of p-SILI, this does not appear to have had any attribut-able impact on mortality. Furthermore, a third of our patients initiatedon CPAP improved without needing IMV [5].The mortality among COVID-19 ARDS patients not initiated on IMVwithin the first 24 h of admission to UK ICUs was lower than later initi-ation of IMV, supporting our observation [4]. Furthermore, a 21% im-provement in UK ICU mortality rates over the course of the COVIDpandemic mirrors an equivalent reduction in use of IMV, including a42% reduction in IMV within the first 24 h, despite unchanged PaO2:FiO2 ratios [6]. Recent data from the second surge show this trend iscontinuing [7].Advancing age was associated with mortality consistent with UKdata [4]. Inflammatory parameters including CRP and neutrophil: lym-phocyte ratio predict survival among hospitalised patients withCOVID-19 [8,9]. We therefore explored the trajectory of inflammatoryvariables among COVID-19 patients receiving invasive mechanical ven-tilation but found no difference in neutrophil count, temperature, norCRP change prior to IMV between survivors and non-survivors.As with all retrospective analyses, we acknowledge residual con-founding, and that results are associative. Furthermore, the small sam-ple size limits generalisability. Nonetheless, these data support a trialof CPAP prior to IMV in patients with moderate-to-severe COVID-19Fig. 1. Trajectory of respiratory rate and SpO2: FiO2 ratio and inflammatory variables over the three days preceding invasive mechanical ventilation. (a-b). An increase in respiratory rate(p < 0.001) and fall in SpO2: FiO2 ratio (p = 0.056) occur over time but with no difference in the rate in change over time between patients who survive or die. No difference is seen ininflammatory parameters; c). neutrophils, d). peak daily temperature, or e). Box and whisker plots represent median (horizontal line), interquartile range (box) and 95% confidenceintervals (whiskers). Two- way ANOVA comparing change over time between survivors and non-survivors.N. Arulkumaran, J. Green, A. Khan et al. Journal of Critical Care 62 (2021) 289–291ARDS, especially in a resource- limited setting. Randomised controlledtrials evaluating timing of IMV in ARDS are imperative.Ethics approvalEthics to report observational data on critical care patients at UCLH iscovered by the National Research Ethics Service (14/LO/103).Consent for publicationN/A.Availability of data and materialsUpon reasonable request.FundingNone.Authors' contributionsStudy design (NA), data collection (AL, TB, AK, JG), Statistics (NA),Drafting manuscript (NA). All authors read and approved the finalmanuscript.Declaration of Competing InterestNone.290AcknowledgementsUCLH Intensive Care.References[1] Gattinoni L, Marini JJ, Camporota L. The respiratory drive: an overlooked tile ofCOVID-19 pathophysiology. Am J Respir Crit Care Med 2020;202(8):1079–80.[2] Tobin MJ, Jubran A, Laghi F. Hypoxaemia does not necessitate tracheal intubation inCOVID-19 patients. Br J Anaes 2020 Nov 16. https://doi.org/10.1016/j.bja.2020.11.007 [S0007-0912(20)30922-3; In press].[3] Wei H, Jiang B, Behringer EC, Hofmeyr R, Myatra SM, Wong DT, et al. Controversies inairway management of COVID-19 patients: updated information and internationalexpert consensus recommendations. Br J Anaes 2020 Nov 6 S0007-0912(20)30896-5.[4] Richards-Belle A, Orzechowska I, Gould DW, Thomas K, Doidge JC, Mouncey PR, et al.COVID-19 in critical care: epidemiology of the first epidemic wave across England,Wales and Northern, Ireland. Am J Respir Crit Care Med 2020 Dec 11.[5] Arina P, Baso B, Moro V, Patel H, Ambler G, Group, U. C. L, UCL Critical Care COVID-19Research Group. Critical Care COVID-19 Research. Discriminating between CPAP suc-cess and failure in COVID-19 patients with severe respiratory failure. Intensive CareMed 2020 Nov 16:1–3 [In press].[6] Doidge, JC, Mouncey, PR, Thomas, K, Gould DW, Ferrando- Vivas, P, Shankar-Hari, M,et al. Trends in intensive care for patients with COVID-19 in England, Wales andNorthern Ireland.[7] ICNARC report on COVID-19 in critcal care: England, Wales and Northern Ireland.https://www.icnarc.org/Our-Audit/Audits/Cmp/Reports. (Accessed 6th Nov 2020).[8] Manson JJ, Crooks C, Naja M, Ledlie A, Goulden B, Liddle T, et al. COVID-19-associatedhyperinflammation and escalation of patient care: a retrospective longitudinal cohortstudy. Lancet Rheumatol 2020;2(10):e594–602.[9] Liao D, Zhou F, Luo L, Xu M, Wang H, Xia J, et al. Haematological characteristics andrisk factors in the classification and prognosis evaluation of COVID-19: a retrospectivecohort study. Lancet Haematol 2020;7(9):e671–8.N. ArulkumaranBloomsbury Institute of Intensive CareMedicine, University College London,UKE-mail address: nisharulkumaran@doctors.org.ukN. Arulkumaran, J. Green, A. Khan et al. Journal of Critical Care 62 (2021) 289–291J. GreenBloomsbury Institute of Intensive CareMedicine, University College London,UKA. KhanBloomsbury Institute of Intensive CareMedicine, University College London,UKT. BonniciBloomsbury Institute of Intensive CareMedicine, University College London,UK291A. LongobardoBloomsbury Institute of Intensive CareMedicine, University College London,UKM. SingerBloomsbury Institute of Intensive CareMedicine, University College London,UKAvailable online xxxx

Influence of respiratory and inflammatory parameters preceding intubation on survival of patients with COVID-19 ARDS- A single centre retrospective analysis

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Influence of respiratory and inflammatory parameters preceding intubation on survival of patients with COVID-19 ARDS- A single centre retrospective analysis

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