Impact of Time to Intubation on Mortality and Pulmonary Sequelae in Critically Ill Patients With COVID-19

A Prospective Cohort Study

Jessica González; Iván D. Benítez; David de Gonzalo-Calvo; Gerard Torres; Jordi de Batlle; Silvia Gómez; Anna Moncusí-Moix; Paola Carmona; Sally Santisteve; Aida Monge; Clara Gort-Paniello; María Zuil; Ramón Cabo-Gambín; Carlos Manzano Senra; José Javier Vengoechea Aragoncillo; Rafaela Vaca; Olga Minguez; María Aguilar; Ricard Ferrer; Adrián Ceccato; Laia Fernández; Ana Motos; Jordi Riera; Rosario Menéndez; Darío Garcia-Gasulla; Oscar Peñuelas; Gonzalo Labarca; Jesús Caballero; Carme Barberà; Antoni Torres; Ferran Barbé


Crit Care. 2022;26(18) 

In This Article

Abstract and Introduction


Question: We evaluated whether the time between first respiratory support and intubation of patients receiving invasive mechanical ventilation (IMV) due to COVID-19 was associated with mortality or pulmonary sequelae.

Materials and Methods: Prospective cohort of critical COVID-19 patients on IMV. Patients were classified as early intubation if they were intubated within the first 48 h from the first respiratory support or delayed intubation if they were intubated later. Surviving patients were evaluated after hospital discharge.

Results: We included 205 patients (140 with early IMV and 65 with delayed IMV). The median [p25;p75] age was 63 [56.0; 70.0] years, and 74.1% were male. The survival analysis showed a significant increase in the risk of mortality in the delayed group with an adjusted hazard ratio (HR) of 2.45 (95% CI 1.29–4.65). The continuous predictor time to IMV showed a nonlinear association with the risk of in-hospital mortality. A multivariate mortality model showed that delay of IMV was a factor associated with mortality (HR of 2.40; 95% CI 1.42–4.1). During follow-up, patients in the delayed group showed a worse DLCO (mean difference of − 10.77 (95% CI − 18.40 to − 3.15), with a greater number of affected lobes (+ 1.51 [95% CI 0.89–2.13]) and a greater TSS (+ 4.35 [95% CI 2.41–6.27]) in the chest CT scan.

Conclusions: Among critically ill patients with COVID-19 who required IMV, the delay in intubation from the first respiratory support was associated with an increase in hospital mortality and worse pulmonary sequelae during follow-up.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in December 2019 as the cause of coronavirus disease 2019 (COVID-19).[1] A far from negligible proportion of hospitalized patients (20–67%) may develop a more severe disease, resulting in acute respiratory distress syndrome (ARDS).[2,3] ARDS has generated a surge of patients who require respiratory support with invasive or noninvasive mechanical ventilation (IMV and NIMV).[3,4] The highest mortality rates are associated with IMV in patients with COVID-19, ranging from 16.7 to 88–97%.[5] Furthermore, respiratory impairment is very common in surviving critically ill patients with COVID-19 and well described.[6–9] After hospital discharge, the most frequent respiratory function abnormality (up to 82%) is an impairment in the carbon monoxide diffusing capacity (DLCO).[6] Additionally, a higher proportion of patients (up to 70%) present a reticular or fibrotic pattern on chest CT scans at follow-up.[6]

COVID-19-induced ARDS (CARDS) has been proposed as an "atypical ARDS" due to the dissociation of relatively well-preserved lung mechanics and the severity of hypoxemia.[10,11] The management of CARDS has changed over time. At the beginning of the COVID-19 pandemic, most clinicians followed the recommendations of international guidelines for the treatment of CARDS using either standard oxygen therapy (SOT) or early IMV.[12] As the pandemic progressed, hospitals were overloaded and the number of ventilators was limited; thus, the trend to use noninvasive techniques such as NIMV or high-flow oxygen therapy by nasal cannula (HFNC) increased. Moreover, the strategy for using these techniques outside the ICU is even more widely accepted.[13] To date, the effectiveness and optimal respiratory support strategy for CARDS are still unknown.

The high mortality rate associated with CARDS appears to be decreasing;[14,15] however, the inconsistent results have been emerged.[16] This discrepancy could be explained by many factors, but the decision on the management of respiratory support might play an important role. While some experts advocate for early intubation to combat patient self-inflicted lung injury (P-SILI),[10,17–19] others defend exhausting noninvasive options before IMV.[19–23] Wendel Garcia et al.[24] recently published an important study conducted in the ICU showing that NIV was associated with higher mortality rates (HR: 2.67; 1.14–6.25; p < 0.001) than other respiratory support strategies.

Our study consists of a prospective cohort of ICU patients who needed to be intubated due to CARDS. With the aim of assessing the effect of early respiratory strategy, we compared in-hospital mortality and pulmonary sequelae in patients who were intubated within the first 48 h from the first ventilatory support (HFNC or NIV) and those intubated later (> 48 h). Pulmonary sequelae were evaluated at follow-up including pulmonary function tests (spirometry, lung volumes and DLCO), exercise tests (6MWT) and chest CT scans.