Our study was conducted to examine how the timing of intubation in COVID-19 patients may have survival benefits. We investigated clinical factors linked to outcomes in critically ill COVID-19 patients with ARDS. We looked at which clinical factors are linked to outcomes in critically ill COVID-19 patients with ARDS. Of the patients, one-third were intubated within 48 hours of ICU admission (early) and one-third after 48 hours of ICU admission (late). Studies on the mortality rate of COVID-19 patients in ICUs reported it to range from 25.7% (
16) to 36.0% (
2), which is lower than our findings. However, because inclusion criteria vary in different studies and some patients in our research had a poor prognosis, the real fatality rate might be more significant.
We found that the NIV failure rate was 66.7% for all the patients. However, it was previously reported to range from 5% to 60% in COPD and acute respiratory failure (ARF) (
17,
18). Besides, Nicolini et al. (
19) reported NIV failure in 20% of community-acquired pneumonia (CAP). Our results showed a high rate of NIV failure compared to previous studies. Also, Menzella et al. (
20) reported the NIV failure rate of 51.9% (41 out of 79), which is close to our reported rate (60 out of 90). However, Mukhtar et al. (
21) reported the NIV failure rate at 26% (13 out of 49 patients) in their study. It should be mentioned that their sample size was smaller than in the present study. Accordingly, NIV failure seems more common in COVID-19 patients than in COPD, CAP, and ARF patients. It should be considered that patients under NIV have different needs that should be addressed properly (
22).
The main findings of this study are aligned with the study of Lee et al. (
4). They advocated that in-hospital mortality did not differ significantly between early- and late-intubated patients. Furthermore, the conclusion of a meta-analysis (
6) indicated that the timing of intubation seems to have no direct effect on mortality or supposed comorbidity. However, it is fair to consider different ways of practicing that can affect the time of intubation and, consequently, the final outcome. Decision-making regarding the insertion of an endotracheal tube should be according to the patient's circumstances and the clinical judgment of the practitioner (
13,
23).
Although we did not find any significant differences (survival benefits) between early- and late-intubated patients, some pieces of evidence and clinician reports are in favor of early intubation (invasive ventilation). First of all, Gattinoni et al. (
10) hypothesized that we could consider an early intubation strategy for P-SILI prevention. Second, it is suggested that early intubation can reduce the risk of contamination to healthcare providers (
7). Thirdly, some criticized late intubation for the supposed dire consequences. Late-intubated patients are reported (
24) to have low lung compliance or more detrimental ventilatory ratios with conceivably higher mortality. It can result from self-induced lung injury or the nature of severe progressive inflammation. In contrast, some papers criticized the liberal use of early intubation. Tobin et al. (
25) believe that PSILI is a new term, and there are no exact definitions for it. They advocated that some severe hypoxemic COVID-19 patients with normal lung compliance did not develop dyspnea. Indeed, this occurs because the amount of hypoxemia is not low enough to elicit increased respiratory motor effort and the concomitant PaCO2 levels dampen the hypoxic response. Although there is insufficient data to advocate late (delayed) intubation, it is a hindsight decision (
11). Undoubtedly, different practices have different effects; thus, early or late intubation may have a different effect on COVID-19 survival, although there is insufficient evidence to advocate either of them. It should be clarified which strategy is used to overcome the other one.
A review (
26) recommended that intubation and mechanical ventilation are multifactorial decisions and thus should not be done according to a single parameter such as decreased oxygen saturation or lung involvement on a CT scan. It is also suggested that patients with moderate to severe hypoxemia should receive supplemental oxygen with HFNC, and an awake prone position for a short trial can be considered.
Our statistical model results in terms of predictors of intubation revealed that APACHE 2 scores, NLR, RR, and history of ischemic heart disease were appropriate predictors of intubation in critical care settings. De Vita et al. (
27) suggested that in COVID-19 patients who needed continuous positive airway pressure (CPAP), higher age, LDH, and change in PaO2/FiO2 ratio after initiating CPAP could be independent predictors of intubation. These results are not controversial and can broaden our horizons to include the prediction of intubation of COVID-19 patients. Mueller et al. (
28) revealed that in COVID-19 inpatients with stable CRP levels, rising CRP levels predicted intubation. As a result, increasing CRP within the first 48 hours of hospitalization predicts respiratory deterioration better than initial CRP levels or ROX indices. However, we did not screen the CRP level of the patients. According to Suliman et al. (
29), the ROX index might be a straightforward, noninvasive approach for predicting the discontinuation of high-flow oxygen treatment and can monitor progress and the risk of intubation in COVID-19 pneumonia patients. The ROX index was found in this study to be one of the most sensitive and competent techniques for predicting intubation. According to Tatum et al. (
30), NLR is a predictor of endotracheal intubation upon hospitalization and an independent predictor of the risk of mortality in SARS-CoV-2 patients on subsequent hospital days. Our findings also showed that NLR could be used as one of the predictors of endotracheal intubation. The SOFA score and the ROX index may both be used to identify patients who are more likely to require intubation (
31), which is consistent with our findings.
APACHE 2 and SOFA scores are two of the most essential prognosis-predicting tools in critical settings. Our study showed that both of these scores are appropriate tools to assess the prognosis of COVID-19 patients who are admitted to ICUs. Han et al. (
32) also proved the importance of these two scores in their research. Also, the findings indicated that respiratory rate and heart rate could be used to evaluate the prognosis of patients. Furthermore, Huang et al. (
33) proposed that an elevated respiratory rate appeared to be related to a patient's prognosis. Creatine phosphokinase has been linked to poor outcomes and can be used as a prognosis factor. This finding is also aligned with Orsucci et al.’s findings (
34).
5.1. Limitations
There are various limitations to our study. This is a prospective study with 30 patients in each group and a medium sample size. As a result, some variables deviated from the normal distribution. The laboratory samples were taken in a critical situation that may have resulted in sampling error or false results. The ventilatory variables such as lung compliance and resistance, tidal volume, and positive end-expiratory pressure were not recorded for mechanically ventilated patients. These variables can help predict liberation (weaning process), complications (like acute kidney injury), and mortality. We followed patients until they were discharged or expired, and we did not consider hospital readmission or in-home mortality. However, our data aligned with previous studies to improve our knowledge of COVID-19 critical care.
5.2. Conclusions
There were no statistically significant differences in total mortality between early- and late-intubated patients. Higher respiratory rates (tachypnea) can indicate early intubation. APACHE 2 scores, NLR, RR, and history of ischemic heart disease are some of the appropriate predictors of intubation. Also, the ROX index is one of the most sensitive and capable tools for predicting intubation. Intubation status, APACHE, and SOFA scores are potent predictors of in-hospital mortality. The intubation strategy for COVID-19 is rather according to clinicians' decision.