Participants
The study was prospectively registered at chictr.org.cn-ChiCTR2000032311, and is reported according to CONSORT guidelines. From April 2020 to December 2020, the active tuberculosis patients diagnosed with respiratory failure and treated in ICU of Beijing Chest Hospital, were enrolled in the study. The research protocol was approved by the Human Ethics Committee of Beijing Chest Hospital (2019-clinic-64) and the study was carried out based on the Declaration of Helsinki 1964. Informed consent was obtained from all participants.
Included criteria: (1) diagnosed with pulmonary tuberculosis according to medical history, tests for Mycobacterium tuberculosis, and chest radiography, (2) respiratory rate > 30 breaths/min, (3) tidal volume < 6 mL/kg, (4) artery pressure of oxygen (PaO2) < 60 mm Hg, (5) arterial carbon dioxide partial pressure (PaCO2) > 50 mm Hg, and (6) oxygenation index (PaO2/FiO2) < 300 mm Hg.
Exclusion criteria: (1) diagnosed with tuberculosis in central nervous system, (2) with severely damaged lung and probably to be ventilator dependent, (3) with lung cancer or cachexia, (4) acute physiology and chronic health evaluation II (APACHE II) score > 16 [10], (5) with multiple organ dysfunction and risk of ventilator dependent, (6) with stress ulcer-induced gastrointestinal bleeding or gastrointestinal perforation, and (7) with facial deformity and unable to receive non-invasive MV.
Treatment Protocol
All patients were randomly divided into sequential MV (SMV) group and conventional MV (CMV) group. At beginning, patients in both groups received invasive positive pressure ventilation (IPPV) using following ventilation modality: synchronized intermittent mandatory ventilation (SIMV) + pressure support ventilation (PSV) + positive end expiratory pressure (PEEP). Subjects were ventilated with a pressure support level targeting an expired tidal volume of 6–8 mL/kg and a respiratory rate of < 30 breaths/min. FiO2 was adjusted to maintain peripheral oxygen saturation (SpO2) at > 92% with PEEP of at least 5 cm H2O (1 cm H2O = 0.098 kPa). SIMV was set at 10–12 breaths/min and PSV was adjusted to 10–12 breaths/min.
When the patients' conditions were basically relieved, the ventilation modality in SMV group was switched to oronasal face continuous positive airway pressure (CPAP) until weaning. The indication for non-invasive MV included a stable blood pressure with FiO2 ≤ 55%, SpO2 ≥ 95%, respiratory rate ≤ 30 breaths/min and tidal volume ≥ 6 mL/kg. The patients in CMV group received persistent IPPV until weaning.
During the study, all patients received routine treatment of active tuberculosis and mixed infections with fluid therapy and nutritional supports. The vital signs of patients were carefully monitored during the ventilation and any necessary management was placed for symptomatic treatment.
Data Collection
The basic characteristics of all patients were collected, including: age, gender, body mass index (BMI), APACHE II score, medical history and chest radiography.
The primary end point of this study was assessed by detecting respiratory parameters (including respiratory rate, heart rate, oxygenation index, alveolo-arterial oxygen partial pressure difference (A-aDO2), PaCO2 and blood pH), and inflammatory parameters (white blood cells (WBC), percentage of neutrophil (NEU) and C-reactive protein (CRP)). The respiratory parameters were recorded before treatment (baseline) and in every 8 hrs during the treatment. And the inflammatory parameters were detected at baseline and in every 24 hrs. The data in baseline and after treatment (defined as the point when FiO2 reduced to 50%) were analyzed and compared between the two groups.
The secondary end-point was evaluated by comparing in-hospital outcomes between the two groups, including ventilation time, invasive mechanical ventilation time, the length of ICU stay, visual analogue scale (VAS) score, total cost (RMB), ventilator-associated pneumonia (VAP) and atelectasis. VAS score was evaluated by doctors and nurses with a scale of 0–10 (0: no pain, 10: utmost pain), and the mean VAS score during the study was calculated and recorded.
Statistical analysis
Data analysis was performed using SPSS 23.0 (IBM Corp., Armonk, NY, USA). Continuous variables such as age, BMI, respiratory and inflammatory parameters were presented as mean ± standard deviation (SD). Categorical variables such as gender were presented as number (percentage). Significance was analyzed using student’s t test for continuous variables and Chi-square test for categorical variables. As for in-hospital outcomes, mean difference (MD) and relative ratio (RR) with 95% confidence interval (CI) were calculated for continuous variables and categorical variables, respectively. Two sided P < 0.05 was considered to be statistically significant.