Postextubation Stridor in Severe COVID-19

Ethics

Anonymized data were collected after ethical approval (Ethical Committee CESRLF 20–42) provided by ethics committee of the French Intensive Care Society, Paris, France, on May 8, 2020. If the subjects were unable to provide informed consent at inclusion, investigators sought consent for participation from surrogates. If the surrogates chose not to give consent, the patients were not included. Written consent was then requested from all included subjects as soon as they regained competence. For the historical cohort, all subjects received an informative letter. The trial was investigator-initiated and received no industry support.

Study Population

We included consecutive subjects admitted between March–June 2020 (first COVID-19 wave in France) and between July–December 2020 (second COVID-19 wave) to the medical-surgical ICU of the Versailles Hospital (France) with reverse-transcriptase polymerase chain reaction (RT-PCR) assays of nasopharyngeal or tracheal samples positive for SARS-CoV-2 and a requirement for mechanical ventilation. We compared these subjects to historical controls who were admitted consecutively to the same ICU between 2016–2019 without COVID-19 and who required mechanical ventilation for > 48 h. We excluded patients who died before extubation.

Study Outcome

The primary outcome was a stridor audible to the naked ear within 2 h after extubation and requiring a curative medical treatment.

Study Setting and ICU Management

During the first wave, the 28 beds in our ICU were managed by intensivists, and 15 beds created in operating rooms were managed by anesthesiologists with the same COVID care protocol. All 43 beds were occupied by patients with COVID-19. During the second wave, 22 ICU beds were reserved for COVID-19 subjects. The management of ARDS complicating COVID-19 followed the French Intensive Care Society guidelines.¹⁴ During the first wave, specific therapeutic interventions such as rescue corticosteroid therapy were discussed by the medical team for patients with moderate-to-severe ARDS whose P_aO2/F_IO2 was below 150 despite neuromuscular-blocking agents and prone positioning and whose pulmonary compliance was below 30 mL/cm H₂O. When deemed indicated, we gave intravenous dexamethasone, 20 mg once daily from day 1 to day 5, then 10 mg once daily from day 6 to day 10.¹⁵ During the second wave, all patients with severe COVID-19 received 6 mg of dexamethasone per d for 10 d.¹⁶ All intubations were performed by experienced prehospital emergency physicians or intensivists. The use of videolaryngoscopy with a hyper-angulated stylet or bougie and the tracheal tube diameter was at the discretion of the intubating physician; however, the maximum tube size was 8, with subglottic suction. During the ICU stay, cuff pressures were routinely checked every 4 h and maintained between 25–30 cm H₂O. Extubation was decided by the bedside physician according to current guidelines¹⁷ after a successful 1-h spontaneous breathing trial with minimal pressure support and no PEEP.¹⁸ The decision to perform a cuff leak test was at the discretion of the physician. A positive cuff leak test was defined as < 110 mL of leakage after tube balloon deflation just before extubation.^18,19 PES prevention was at the discretion of the bedside physician; when performed, it consisted in preextubation intravenous methylpredni-solone, 80 mg over 12 h.²⁰ The nasogastric tube was removed and the trachea and mouth were carefully suctioned. The cuff was then deflated and the trachea suctioned again. Treatment for PES consisted of nebulized epinephrine with or without intravenous steroids, depending on the decision of the medical team. Extubation failure was defined as the need to re-intubate within 48 h after extubation, irrespective of the reason.

Data Collection

Data were collected from the electronic medical records using a standardized data collection form. PES occurrence was searched directly in nurses, physiotherapists, and medical records or indirectly through prescribed treatments such as postextubation systemic steroids and epinephrin or steroid nebulization. For each subject, we recorded age, sex, body mass index, medical history, clinical signs, microbiological findings, characteristics of intubation (prehospital or in the ICU, intubation difficulties), severity score assessed with Simplified Acute Physiology Score II expanded (SAPS II), mechanical ventilation duration (from intubation to first planned extubation), and prolonged intubation, defined as ≥ 7 d of invasive ventilation. In subjects with respiratory distress requiring immediate re-intubation but without PES, mechanical ventilation duration was counted from the first intubation to the second extubation. We also recorded endotracheal tube (ETT) diameter and the ratio of the subject’s height to the tracheal tube diameter (in millimeters), whether accidental extubation occurred, the number of intubations during the ICU stay before the last extubation, and the reasons for re-intubation (extubation failure or tube obstruction). Difficult intubation was defined as intubation after > 2 laryngoscopies performed by a trained physician with a Cormack-Lehane grade 3 or 4 or a need for rescue oxygenation.²¹ We recorded whether subjects received steroids before extubation and specially within the 48 h before extubation and the reason for steroid administration (septic shock, persistent severe ARDS, bronchospasm, or preventive or curative treatment of PES). Finally, we collected the results of RT-PCR assays for SARS-CoV-2 on tracheal samples done each week and within 48 h before extubation. A positive RT-PCR for SARS-CoV-2 was expressed in cycle thresholds. The cycle threshold value was the number of cycles it takes for the PCR test to detect the virus; the threshold was 40 cycles. If the virus was found in a low number of cycle thresholds, it meant that the sample contained a large amount of virus, thus a higher viral load.

Statistical Analysis

Quantitative parameters were described as median (interquartile range [IQR]) and qualitative parameters as number (percentage). We compared categorical variables using Fisher exact tests and continuous variables using Wilcoxon rank-sum tests. All tests were 2 sided, and P values < .05 were considered significant.

To assess risk factors for PES, we compared subjects with versus without PES by building a multivariate model using variables associated with P values < .15 by univariate analysis and variables deemed clinically relevant. We adjust our multivariate model on severity based on SAPS II. All continuous variables were checked for log-linearity. Non-log-linear variables were transformed into dummy variables using the median value as the cutoff. The following variables were included into the multivariate model: female sex, body mass index, difficult intubation, COVID-19 status, tube mobilization or re-intubation or prone positioning, prolonged mechanical ventilation, and subject height/tube diameter. We used a backward stepwise multivariate approach, and we chose the final model according to the best Hosmer-Lemeshow goodness-of-fit test and area under the receiver operating characteristic curve estimated by the C statistic. Associations of factors with PES were reported as odds ratios with their 95% CIs.

To test the robustness of the comparison of the frequency of PES in the COVID-19 subjects and controls, we conducted an exploratory analysis using a propensity score based on 1:1 exact matching on each score variable, with no replacement, using a prespecified caliper width of 0.2. This matching process based on propensity score was used to equalize potential risk factors of PES in both groups. The variables included in the propensity score were demographic and baseline characteristics associated with PES with P < .05 by multivariate logistic regression and data about prolonged mechanical ventilation. These variables were COVID-19 status, female sex, and tube mobilization or re-intubation or prone positioning. Each of 65 COVID-19 subjects was matched on the propensity score to a control.

Finally, we sought to identify COVID-19-specific risk factors for PES during the first wave to avoid a potential effect of routine corticosteroid therapy. Bonferroni correction was applied to adjust for multiple comparisons. We also compared the main characteristics of the subjects between the first and second COVID-19 waves. All analyses were performed using R version 4.1 (R Foundation for Statistical Computing, Vienna, Austria).