# Very late intubation in COVID-19 patients: a forgotten prognosis factor ?

Laurent Camous, Jean-David Pommier, Frederic Martino, Benoît Tressieres, Alexandre Demoule, Marc Valette

► To cite this version:

Laurent Camous, Jean-David Pommier, Frederic Martino, Benoît Tressieres, Alexandre Demoule, et al. Very late intubation in COVID-19 patients: a forgotten prognosis factor?. Critical Care, 2022, 26 (1), pp.89. 10.1186/s13054-022-03966-6. hal-03664838

HAL Id: hal-03664838

https://u-paris.hal.science/hal-03664838

Submitted on 11 May 2022

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
BRIEF REPORT

Open Access

<figure><img src="image_2.png" /></figure>

Check for
updates

# Very late intubation in COVID-19 patients: a forgotten prognosis factor?

Laurent Camous<sup>1,7*</sup>, Jean-David Pommier<sup>1,2</sup>, Frederic Martino<sup>1,3</sup>, Benoît Tressieres<sup>4</sup>, Alexandre Demoule<sup>5,6</sup> and Marc Valette<sup>1</sup>

**Abstract**

Description of all consecutive critically ill COVID 19 patients hospitalized in ICU in University Hospital of Guadeloupe and outcome according to delay between steroid therapy initiation and mechanical ventilation onset. Very late mechanical ventilation defined as intubation after day 7 of dexamethasone therapy was associated with grim prognosis and a high mortality rate of 87%.

**Keywords:** Acute respiratory distress syndrome, Mechanical ventilation, COVID 19, Steroid, High flow nasal oxygen therapy

**Dear Editor,**

After large therapeutic trials, steroid and tocilizumab are now the cornerstones of COVID 19 pneumonia treatment [1, 2]. Outcome in case of respiratory radiological and clinical worsening under immunosuppressive treatment has to our knowledge not been evaluated. For COVID 19 pneumonia, timing and indications of mechanical ventilation are still heavily debated [3]. In these patients, it has been observed that high flow nasal oxygen (HFNO) could reduce the need for mechanical ventilation and associated morbidity [3, 4]. However, delayed intubation could also be harmful due to Patient-Self Induced Lung Injury (P-SILI) [5]. Here, we aimed to describe the characteristics and outcome of COVID-19 patients who were intubated very late after the onset of a severe form of the disease.

We retrospectively analyzed the characteristics and outcome of the 574 consecutive patients with severe acute respiratory failure and laboratory-confirmed SARS-CoV-2 infection admitted to the ICU of the Guadeloupe University hospital, Pointe-à-Pitre, France, between

June 2020 and September 2021. Severe acute respiratory failure was defined as respiratory rate ≥ 25 min⁻<fnref n="1" />, bilateral pulmonary infiltrates on chest X-ray or CT scan and need for standard oxygen ≥ 10 L min⁻<fnref n="1" /> to maintain SpO₂ ≥ 92%. Dexamethasone (DXM) was started for each COVID 19 pneumonia with oxygen requirement. Very late intubation (VLI) was defined as an intubation occurring more than seven days after DXM initiation.

Flowchart is shown in Fig. 1A. Patients were classified based on the time between steroid initiation and intubation. Briefly, sub-groups were similar in term of age, sex-ratio and comorbidities (Table 1). Possibly due to a longer time between DXM start and intubation, VLI patients received more adjunctive therapies (awake prone positioning and Tocilizumab) (Table 1). Noninvasive ventilation (NIV) use was similar between groups. Of the 398 patients intubated in the ICU, 30 (8%) met the criteria for VLI. They were mainly male (n = 17, 59%) with a median age of 63 years (interquartile range 56–66). VLI patients were intubated 9 days (7–13) after DXM start and 5 days (2–7) after HFNO initiation. All patients had pulmonary samples for microbiological analysis at intubation and only 3 (10%) had nosocomial pneumonia at intubation. Within 24 h following intubation, VLI patients had severe hypoxemia (median PaO₂/FiO₂ 86 [70–110] mmHg)

<footnote>*Correspondence: laurent.camous@chu-guadeloupe.fr</footnote>

<footnote n="1">¹ Intensive Care Unit, Guadeloupe University Hospital, Chemin Chauvel, 97139 Les Abymes, Guadeloupe, France</footnote>

<footnote>Full list of author information is available at the end of the article</footnote>
A Chart flow of pulmonary COVID-19 patients admitted in ICU in University Hospital of Guadeloupe

<figure><img src="image_3.png" /></figure>

* All patients had HNFO prior to mechanical ventilation

° HFNO: High nasal flow oxygen

B ICU survival of very late intubated COVID-19 (after 7days) patients compare to early
intubated patients

<figure><img src="image_4.png" /><figcaption>**Fig. 1** A Chart flow of pulmonary COVID 19 patients admitted in ICU in University Hospital of Guadeloupe. B ICU survival of very late intubated COVID-19 (after 7 days) patients compare to early intubated patients. Footnotes: All patients were SARS cov-2 PCR confirmed, p-value was calculated using fisher test, *p* < 0.0001</figcaption></figure>

with very low respiratory system compliance (median 14 [12–20] ml cmH₂O⁻¹) and severe respiratory acidosis (pH < 7.30 mmHg) (55% of them, n=17). ICU mortality was 87% in VLI patients, 49% in those intubated between two and seven day after DXM initiation and 54% in those intubated on the day of DXM initiation (p < 0.001) (Fig. 1B).

This is seemingly the first report of COVID-19
patients intubated very late after DXM initiation.

Although VLI was uncommon (8% of the intubated
patients in our study), it was associated with high
mortality. In most studies on timing of intubation in
COVID, patients with delayed intubation were actually
intubated only 2 days after ICU admission [3, 4] with-
out report on time between DXM start and intubation.
The extreme respiratory severity of VLI patients sug-
gests that severe lung damage unrelated to nosocomial
bacterial pneumonia occurs prior to intubation. P-SILI
<table><caption>**Table 1** Characteristics and outcome of COVID 19 patients hospitalized in ICU with delayed intubation 7 days after dexamethasone treatment (≥ 7 days) versus other patients admitted in the same ICU</caption><thead><tr><th></th><th>All patients (n = 556)</th><th>HNFO only (n = 152)</th><th>Intubation ≤ 1 day<br>after DXM initiation<br>(n = 196)</th><th>Intubation 2 to<br>7 days after DXM<br>initiation (n = 178)</th><th>Intubation > 7 days<br>after DXM initiation<br>(n = 30)</th><th>p</th></tr></thead><tbody><tr><td><strong>Patient's characteristics</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Age, years</td><td>59 (50–66)</td><td>58 (46–66)</td><td>60 (50–66)</td><td>59 (52–65)</td><td>63 (57–66)</td><td>0.56</td></tr><tr><td>Gender male, n (%)</td><td>336 (60)</td><td>97 (64)</td><td>110 (56)</td><td>112 (63)</td><td>17 (57)</td><td>0.55</td></tr><tr><td>SOFA</td><td>4 (3–7)</td><td>3 (2–4)</td><td>7 (4–9)</td><td>5 (3–7)</td><td>5 (3–7)</td><td>&lt;0.01</td></tr><tr><td>ROX score on day<br>of HFNO onset,<br>min<sup>-1</sup></td><td>4.2 (3.0–6.0)</td><td>6.7 (4.8–8.6)</td><td>3.0 (2.2–4.0)</td><td>4.2 (3.3–5.2)</td><td>6.0 (4.0–7.5)</td><td>&lt;0.01</td></tr><tr><td>ROX score at intu-<br>bation, min<sup>-1</sup></td><td>2.2 (2.0–2.7)</td><td>NA</td><td>2.2 (2.0–2.8)</td><td>2.3 (2.0–2.8)</td><td>2.0 (2.0–2.1)</td><td>0.45</td></tr><tr><td><strong>Comorbidities</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Arterial hyperten-<br>sion, n (%)</td><td>293 (53)</td><td>67 (44)</td><td>107 (55)</td><td>99 (56)</td><td>20 (67)</td><td>0.38</td></tr><tr><td>Diabetes, n (%)</td><td>209 (38)</td><td>49 (32)</td><td>78 (40)</td><td>72 (40)</td><td>10 (33)</td><td>0.18</td></tr><tr><td>IMC > 30 kg m<sup>-2</sup>,<br>n (%)</td><td>291 (52)</td><td>71 (47)</td><td>116 (59)</td><td>89 (50)</td><td>15 (50)</td><td>0.08</td></tr><tr><td><strong>Biology</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>White blood cells,<br>G L<sup>-1</sup></td><td>8.6 (6.3–11.3)</td><td>8.4 (6.4–10.5)</td><td>9.1 (6.8–11.2)</td><td>8.7 (1.0–11.5)</td><td>8.7 (6.0–11.8)</td><td>0.757</td></tr><tr><td>D-dimers, ng mL<sup>-1</sup></td><td>1.4 (1.0–2.5)</td><td>1.5 (0.9–2.8)</td><td>1.2 (0.8–2.6)</td><td>1.6 (0.9–2.4)</td><td>1.4 (1.0–2.1)</td><td>0.93</td></tr><tr><td><strong>Adjunctive therapies</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Noninvasive venti-<br>lation, n (%)</td><td>120 (22)</td><td>24 (16)</td><td>45 (23)</td><td>43 (24)</td><td>8 (27)</td><td>0.66</td></tr><tr><td>Awake prone posi-<br>tioning, n (%)</td><td>154 (27)</td><td>71 (50)</td><td>18 (9)</td><td>53 (30)</td><td>12 (40)</td><td>&lt;0.01</td></tr><tr><td>Tocilizumab, n (%)</td><td>66 (12)</td><td>33 (22)</td><td>5 (3)</td><td>19 (11)</td><td>9 (30)</td><td>&lt;0.01</td></tr><tr><td><strong>Outcome</strong></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>ICU mortality, n (%)</td><td>219 (39)</td><td>0 (0)</td><td>105 (54)</td><td>88 (49)</td><td>26 (87)</td><td>&lt;0.01</td></tr></tbody></table>

Results are number n (percentage) of for categorical variables and median (q1-q3) for continuous variables. P values were obtained using Kruskal-Wallis for continuous variables, and Chi2 or fisher test when appropriate for categorical variables

HFNO—high flow nasal oxygen, DXM—dexamethasone, ICU—intensive care unit, SOFA—Sepsis-related Organ Failure Assessment

[5] and/or a rapid pulmonary fibrotic evolution despite DXM treatment could explain this rapid and severe worsening. Deleterious effect of NIV before intubation on the prognosis of COVID-19 patients has been raised recently [6]. In our study, by definition, VLI patients were exposed to NIV and/or HFNO during a longer period of time, which could have contributed to the generation of P-SILI.

The retrospective and monocentric design without control group of the present study are its main limitations and results should be thus confirmed by other large cohorts.

Based on the grim prognosis of VLI in COVID 19 patients, our study highlights the need for criteria predicting steroid and NIV/HFNO failures in order to avoid delayed intubation.

**Abbreviations**

HFNO: High flow nasal oxygen; NIV: Noninvasive ventilation; ICU: Intensive care unit); DXM: Dexamethasone; VLI: Very late intubation.

**Acknowledgments**

None.

**Author contributions**

LC, JDP, FM and MV designed the study. JDP, LC, AD and BT conducted the analyses. All authors significantly contributed to the research, discussed the results of the analyses, edited the draft manuscript, and approved the submitted version. All authors read and approved the final manuscript.

**Funding**

None.

**Availability of data and materials**

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
# Declarations

## Ethics approval and consent to participate

This retrospective study was approved by the ethics committee of the Guadeloupe University Hospital under the number LJ-1002, which waived the need for informed consent from individual patients due to the retrospective nature of the study.

## Consent for publication

Not applicable.

## Competing interests

None.

## Author details

¹Intensive Care Unit, Guadeloupe University Hospital, Chemin Chauvel, 97139 Les Abymes, Guadeloupe, France. ²Institut Pasteur de la Guadeloupe, Morne Jolivière, 97183 Abymes, France. ³INSERM UMR S 1134, Biologie Intégrée du Globule Rouge, Antilles-Guyane University, 97157 Pointe-à-Pitre, France. ⁴Antilles-Guyane Clinical Investigation Center, Inserm CIC 1424, Guadeloupe University Hospital, 97139 Les Abymes, Guadeloupe, France.

⁵AP-HP, Groupe Hospitalier Universitaire APHP-Sorbonne Université, site Pitié-Salpétrière, Service de Médecine Intensive - Réanimation (Département R3S), Paris, France. ⁶INSERM, UMRS1158 Neurophysiologie Respiratoire Expérimentale et Clinique, Sorbonne Université, 75005 Paris, France. ⁷Reanimation Médicale et Chirurgicale, Centre Hospitalier Universitaire de Pointe À Pitre, Chemin Chauvel, 97139 Les Abymes, Guadeloupe, France.

Received: 10 January 2022 Accepted: 27 March 2022

Published online: 02 April 2022

## References

1. The RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693-704.

2. Hermine O, Mariette X, Tharaux P-L, Resche-Rigon M, Porcher R, Ravaud P, et al. Effect of tocilizumab vs usual care in adults hospitalized with COVID-19 and moderate or severe pneumonia: a randomized clinical trial. JAMA Intern Med. 2021;181(1):32.

3. Vera M, Kattan E, Born P, Rivas E, Amthauer M, Nesvadba A, et al. Intubation timing as determinant of outcome in patients with acute respiratory distress syndrome by SARS-CoV-2 infection. J Crit Care. 2021;65:164-9.

4. Azoulay E, Bartoukh M, Darmon M, Géri G, Voiriot G, Dupont T, et al. Increased mortality in patients with severe SARS-CoV-2 infection admitted within seven days of disease onset. Intensive Care Med. 2020;46(9):1714-22.

5. Battaglini D, Robba C, Ball L, Silva PL, Cruz FF, Pelosi P, et al. Noninvasive respiratory support and patient self-inflicted lung injury in COVID-19: a narrative review. Br J Anaesth. 2021;127(3):353-64.

6. Karagiannidis C, Hentschker C, Westhoff M, Weber-Carstens S, Janssens U, Kluge S, et al. Observational study of changes in utilization and outcomes in mechanical ventilation in COVID-19. PLOS ONE. 2022;17(1):e0262315.

# Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Ready to submit your research? Choose BMC and benefit from:

* fast, convenient online submission

* thorough peer review by experienced researchers in your field

* rapid publication on acceptance

* support for research data, including large and complex data types

* gold Open Access which fosters wider collaboration and increased citations

* maximum visibility for your research: over 100M website views per year

At BMC, research is always in progress.

Learn more biomedcentral.com/submissions

<figure><img src="image_5.png" /></figure>