Introduction

Over a short period in early 2020, the World Health Organization by their authorities announced Coronavirus disease-2019 (COVID-19) as a global outbreak (1). Coronavirus started as an isolated epidemic in China before rapidly spreading to other countries worldwide (1). COVID-19 is characterized by causing respiratory manifestations, which eventually may lead to the development of serious complications such as severe hypoxemia and acute respiratory distress syndrome (ARDS) (2). From the initial period of the pandemic, a study from China showed that there was an increased in mortality in COVID-19 patients who were older than 65, patients with comorbidities, and patients who develop ARDS (3). Therefore, invasive procedures such as mechanical ventilation or intubation were needed (2, 4). The practice of utilizing mechanical ventilation was changed, especially when COVID-19 was at its peak, because it was considered to prevent the transmission of infection among healthcare workers (5). Moreover, many physicians around the world have been compelled to manage critically ill COVID-19 patients in the absence of practice driven by evidence-based data (6). Therefore, the best time to introduce mechanical ventilation, whether early intubation in the Emergency Department or late in the intensive care unit (ICU), was a matter of debate (7, 8). At that time, physicians' clinical judgment was the primary determinant role in this dilemma of the best intubation time (9).

After several months of treating COVID-19 patients who were critically ill, ARDS guidelines recommended that patients with ARDS should be recognized early because they require immediate Intubation, as delayed Intubation showed increased mortality (10, 11). It was noted that COVID-19 patients can tolerate a severe level of hypoxia even without experiencing respiratory symptoms. Additionally, the shortage of ventilators and ICU rooms resulted in some of the COVID-19 patients having Intubation delayed or completely omitted, which ultimately helped to avoid potential adverse effects such as ventilator-induced lung injury (VILI) and ventilator-associated pneumonia (VAP) (12, 13). Despite all the previous studies, according to a recent meta-analysis that involved more than 8,000 patients, the timing of Intubation does not affect the mortality of critically ill COVID-19 patients, whether they were intubated early or late (14).

The effect of endotracheal Intubation on the mortality of COVID-19 patients remains a topic of ongoing research and debate (7, 8). Therefore, this study aimed to comprehend the impact of endotracheal Intubation and compare its mortality on COVID-19 patients.

Methodology

This single-center retrospective cohort study was conducted in the Emergency and Intensive Care Unit Departments of King Abdulaziz Medical City, Jeddah, Saudi Arabia. The study recognized all patients with COVID-19 positive who were intubated from early 2020 to January 2023. Those discharged from the ER or not hospitalized were excluded from the study. The data of Forty-seven intubated patients with confirmed COVID-19 were collected from the electronic database. The study was conducted and approved by the King Abdullah International Medical Research Center (KAIMRC) of the Ministry of National Guard - Health Affairs with an IRB number SP21J/063/03. Roasoft calculator was used to estimate the sample size with a confidence interval of 95%; nevertheless, a non-probability consecutive sampling technique was considered; thus, all patients who met the inclusion criteria were included from the specified period.

This study retrieved demographic data such as age, gender, patient characteristics, clinical manifestations, and past medical history. Additionally, the study presented findings on chest X-rays, characteristics of intubation including sedatives and muscle relaxant agents, procedural complications and outcomes of study participants, including length of stay in hospital and intubation, whether the patient was discharged or deceased.

The data was collected, cleaned, and checked for completeness. Then, the data was entered and analyzed using JMP Statistical Software version 15.2.0 (SAS Institute, Cary, NC, USA; a subsidiary of the SAS Institute). Categorical variables were presented as frequency (%) while mean and standard deviation were used for continuous variables. A logistic regression was performed to identify predictors of mortality. Variables tested included length of hospital stay, hypotension after intubation, and hypoxemia after intubation. A P-value of <0.05 was considered for significance with 95% confidence interval (CI).

Results

A total of 47 COVID-19 intubated patients were included out of 2867 COVID-19 patients. Males constituted more than half of targeted included patients, 30 (63.83%). The mean age was 73.44 ±13.22. There were 34 (72.34%) patients with history of hypertension and 33 (70.21%) with diabetes. Regarding respiratory system, only 3 (6.38%) patients had history of asthma. Shortness of breath, cough, and fever were the common reported clinical presentations among 38 (80.85%), 36 (76.60%), 28 (59.57%) of patients, respectively. Upon chest x-ray findings, the majority of patients, 28 (59.57%) had opacifications while 7 (14.89%) had lung infiltrations (Table 1).

Furthermore, the most administered sedative agents for intubations were fentanyl in 46 (97.87%) of patients and midazolam in 43 (91.49%) of patients. Also, for muscle relaxant agents, cisatracurium and rocuronium were administered to 16 (33.04%) and 13 (27.66%), respectively. Moreover, 15 (31.91%) patients had hypotension and 6 (12.77%) patients had hypoxemia after intubations. Also, only 3 (6.38%) patients had endotracheal intubation (Table 2).

Table 1. Demographics and Characteristics of Patients
Item	N (%)
Age, Mean ± SD	73.44 ±13.22
Gender Male Female	30 (63.83%) 17 (36.17%)
Symptoms Shortness of breath Cough Fever Sputum production Chest Pain Vomiting Nausea Chill Confusion Decreased oral intake. Fatigue Diarrhea Edema	38 (80.85%) 36 (76.60%) 28 (59.57%) 16 (34.04%) 14 (29.79%) 8 (17.02%) 7 (14.89%) 5 (10.64%) 3 (6.38%) 2 (4.25%) 2 (4.25%) 2 (4.25%) 1 (2.12%)
Past History Hypertension Diabetes Ischemic Heart Disease Asthma	34 (72.34%) 33 (70.21%) 15 (31.91%) 3 (6.38%)
Chest X-Ray Findings Opacification Infiltration Effusion Atelectasis Congestion Pulmonary edema Consolidation	28 (59.57%) 7 (14.89%) 5 (10.64%) 4 (8.51%) 2 (4.25%) 3 (6.38%) 2 (4.25%)
Sedatives Fentanyl Midazolam Propofol Etomidate Ketamine	46 (97.87%) 43 (91.49%) 9 (19.15%) 7 (14.89%) 3 (6.38%)
Muscle Relaxants Cisatracurium Recuronium Dexmedetomidine Succinylcholine	16 (34.04%) 13 (27.66%) 3 (6.38%) 4 (8.51%)

Table 2. Characteristics of Intubations
Item	N (%)
Sedatives Fentanyl Midazolam Propofol Etomidate Ketamine	46 (97.87%) 43 (91.49%) 9 (19.15%) 7 (14.89%) 3 (6.38%)
Muscle Relaxants Cisatracurium Recuronium Dexmedetomidine Succinylcholine	16 (34.04%) 13 (27.66%) 3 (6.38%) 4 (8.51%)
Procedural Complication Hypotension Hypoxemia Endotracheal Intubation Pneumothorax Gastric Aspiration	15 (31.91%) 6 (12.77%) 3 (6.38%) 3 (6.38%) 1 (2.12%)

Table 3. Outcomes of study participants
Item	N (%)
Total length of Stay in Hospital Less than/ equal 30 Days More than 30 Days	30 (63.83%) 17 (36.17%)
Length of Intubation Less than/ equal 30 Days More than 30 Days	37 (78.72%) 10 (21.28%)
Outcome of patient Deceased Discharged Home	29 (61.70%) 18 (38.30%)
Deceased patient While patient on intubation After patient was extubated	28 (96.55%) 1 (3.44%)

Among the 47 intubated patients, 30 (63.83%) were male. Although more male patients died (18 out of 29 deceased), logistic regression showed no statistically significant association between gender and mortality (OR = 1.46, 95% CI: 0.39–5.49, p = 0.5698). Due to lack of statistical significance, gender was excluded from the final multivariable model. A logistic regression was computed predicting mortality based on length of stay in hospital, hypotension, and hypoxemia after

intubation. Characteristics were noted by regression analysis as follows: hospitalized more than 30 days (OR= 2.55; 95% CI= 9.96-0.65; P= 0.1777), hypotension (OR= 3.18; 95% CI= 18.45-9.55; P= 0.1956), and hypoxemia (OR= 2.05; 95% CI= 31.21-0.55; P= 0.6024), had reported higher possibility to be deceased, nevertheless, no significant differences were found (Table 4).

Table 4. Logistic regression of study participants’ mortality
Item	Odds ratio	Upper 95% CI	Lower 95% CI	P
Length of stay in hospital < 30 Days > 30 Days	0.39 2.55	1.53 9.96	0.10 0.65	0.1777
Hypotension after intubation Yes No	3.18 0.31	18.45 1.81	0.55 0.05	0.1956
Hypoxemia after intubation Yes No	2.05 0.48	31.21 7.35	0.13 0.03	0.6024

Discussion

The impact of intubation on patient mortality has been a subject of ongoing research, with varying results reported in literature and factors such as timing, patient characteristics, and management practices contributing to the complexity of understanding these outcomes (6, 14). Recognizing the need for a comprehensive analysis, this study aims to investigate the effects of endotracheal intubation on COVID-19 patients and report patients’ mortality.

This study’s findings indicate that most intubated patients were elderly (mean age 73.44 ± 13.22) and male (63.83%). The predominance of elderly and male patients in this study aligns with previous research conducted by Richardson et al. in New York City Area, which included 5700 patient and reported that older age and male gender are associated with a higher risk of severe COVID-19 infection and poorer outcomes (2). The high prevalence of hypertension and diabetes among intubated patients is consistent with prior studies in Wuhan China, conducted by Yang et al., who included 52 patients and Zhou et al., who included 191 patients, supported those comorbidities identified as significant risk factors for severe COVID-19 and poorer prognosis (3, 4). Regarding the presence of opacifications on chest x-ray findings, this study is consistent with previous research conducted by Chamorro et al. which reported that airspace opacities are the most common radiologic findings in COVID-19 patients. The uncommon findings, such as lobar consolidation and pleural effusion, match what was reported in our study, as only a minority of patients had these chest x-ray findings (15). Like a previous study, a published review in Medscape by Cennimo et al. supported that the most common clinical presentations were shortness of breath and cough, followed by fever, as these symptoms were found to be part of severe illness and mortality caused by COVID-19 (16).

Moreover, this study highlighted the adherence to the current guidelines and practices for managing critically ill patients, specifically regarding the commonly administered sedative intubation agents (5). Nevertheless, there was a relatively high rate of hypotension and hypoxemia after intubation. Midazolam, for example, causes excessive sedation, a decrease in respiratory drive, and hemodynamic instability, which explains the hypotension and hypoxemia observed in our patients (17). Moreover, fentanyl can cause chest wall stiffness which affects lung compliance and the ventilation process (18).

Furthermore, 61.70% of included patients in our study did not survive compared to a study conducted in 15 hospitals under the armed forces in Saudi Arabia by Alsayer et al., who reported that of the 71.6% of COVID-19 patients who were hospitalized, among them, 0.65% did not survive (19). Another study by Aljaber et al., that included 656 patients, reported that mortality in ICU was 27.8% compared to 7.8% in non-ICU (20). A systematic review analyzed data collected from 12 studies regarding the effect of early intubation vs. late intubation on mortality. They included 8944 critically ill patients with COVID-19 and showed no statistically detectable difference in all-cause mortality between patients undergoing early versus late intubation 45.4% versus 39.1%; (p = 0.08). Thus, they concluded that the timing of intubation, whether early or late, did not affect the mortality or morbidity of the targeted patients included. Therefore, they recommended following the approach of waiting and seeing, which may contribute to fewer intubations (14).

Similar to other studies, the logistic regression analysis of this study did not identify any statistically significant predictors of mortality (19, 21). The observed trends in our study suggest that longer stay in hospital, post-intubation hypotension and hypoxemia may be associated with higher odds of mortality. These findings can help inform future research and contribute to developing targeted interventions for intubated COVID-19 patients.

Limitations and recommendations

This study had certain limitations as it included a small sample size and the fact that it is the experience of only a single tertiary center, which may limit the generalizability of findings. However, this study provides valuable insights into the clinical characteristics, management, and mortality of intubated COVID-19 patients which helps to warrant further research for a better understating the effect of intubations in such patients.

Conclusion

This study revealed a noteworthy alignment with existing protocols governing the management of critically ill patients, with a particular emphasis on using sedative agents in intubation procedures. However, a large number of patients did not survive, which constituted 61.70% of the intubated COVID-19 patients included. While multivariate analysis revealed that demographic factors, including gender and age, as well as clinical variables such as intubation duration and post-intubation hypoxemia and hypotension, exhibited higher odds of contributing to mortality, nevertheless, it was found to be statistically not significant.

Disclosure

Authors contributions

MJ, BA, AA, RM, RB, and FA conducted the study. BA, AA, RM, RB, and FA were responsible for data collection. BA provided statistical advice and study design and analyzed the data. BA, AA, RM, RB, and FA drafted the manuscript. MJ took responsibility and supervision of the study as a whole. All the authors reviewed the study. All authors have read and approved the final version of the manuscript and have agreed to be accountable for all aspects of the work.

Ethical statement

The study was conducted and approved by the King Abdullah International Medical Research Center (KAIMRC) of Ministry of National Guard - Health Affairs with an IRB number of SP21J/063/03.

Consent for publication

Not applicable.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Conflict of interests

The authors declare that they have no competing interests.

Funding

This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgments

Not applicable.