Patients
TBLC was conducted in the event of persistent respiratory failure after ongoing lung infection was ruled out or when an alternative diagnosis was suspected based on the patient’s history, clinical and radiologic presentation. The hospital records of all ARDS patients who underwent TBLC from January 2019 to August 2019 in our 26-bed tertiary medical ICU were reviewed. The inclusion criteria were as follows: age ≥ 18 years at the time of TBLC, findings consistent with the Berlin ARDS definition, and ARDS characterized as mild, moderate or severe, as described in the Berlin definition, at the time of diagnosis and biopsy.
TBLC procedure
Five patients with ARDS underwent TBLC (Fig. 1). In four, the procedure was performed at the ICU bedside through an endotracheal tube, with the patient under deep sedation and supported by pressure control ventilation (FiO2 100%, PEEP 0 cmH2O) or combined with extracorporeal membrane oxygenation (ECMO). The fifth patient received TBLC in a hybrid cone beam computed tomography (CBCT) OR. The procedure was conducted by rigid bronchoscopy with the patient under general anesthesia and ventilated by high-frequency jet respirator (FiO2 100%, respiratory rate 60 bpm, tidal volume 500 mL). In the four bedside procedures, flexible bronchoscopes were introduced into the target lobe bronchus through an endotracheal tube, and bronchial blockers were placed at the origin of the target lobe via the nasal tract. Radial probe endobronchial ultrasound (RP-EBUS) (EU-ME1, Olympus, Tokyo, Japan) was used to identify the proper biopsy site (Fig. 1A). Under the guidance of pre-procedure CT images, the bronchoscope was advanced into the potential target bronchi as far as possible and then retracted 1–2 cm. When the surrounding of RP-EBUS showed heterogeneous echo without vascular presentation, the depth of the probe was marked. A 2.4 mm cryoprobe (ERBE, Solingen, Germany) was inserted to the same position (Fig. 1B). Cryobiopsy was performed (freeze time: 4 s) following probe positioning, using carbon dioxide as the cryogen (Fig. 1D). After each biopsy, the bronchial balloon blocker (CRE balloon, Boston Scientific Microvasive, Natick, MA, USA) was immediately filled (0.5-1 atm) to stop bleeding (Fig. 1E). Two to five biopsies were performed in each patient and the sizes of the obtained samples were measured. In the patient who underwent TBLC in the hybrid OR, flexible bronchoscopy and bronchial blocker were inserted through a rigid bronchoscope. Prior to TBLC, CBCT images (Artis Zee III ceiling, Siemens AG, Munich, Germany) were acquired to determine the exact position of the cryoprobe (Fig. 1C2), which was placed under RP-EBUS guidance.
In patients with ECMO, the plan was to stop treatment with unfractionated heparin (UFH) 4 h before TBLC and then monitor the activated clotting time of whole blood (ACT). TBLC was performed when the ACT had decreased to within an acceptable range. After the procedure, the bronchial blocker was not removed until UFH had been reinitiated (Fig. 1F) and the ACT had recovered to the level previously achieved during ECMO and no active bleeding occurred.
Outcomes
Patients routinely underwent a post-procedure chest X-ray to screen for pneumothorax. Bleeding severity was graded on a scale of 4: no bleeding, mild bleeding (requiring suction to clear but no other endoscopic procedures), moderate bleeding (requiring endoscopic procedures such as bronchial occlusion-collapse and/or instillation of ice-cold saline) and severe bleeding (causing hemodynamic or respiratory instability, requiring tamponade or other surgical interventions, transfusions) (14). Other complications, if any, were recorded.
Data on pathological diagnosis, treatment changes after TBLC and survival outcomes were obtained from the patient’s medical records.
Literature search strategy
A literature search of PubMed, EMBASE, ATS meeting abstracts, ERS meeting abstracts, APSR meeting abstract, clinicaltrial.gov, and Google Scholar ending on November 25, 2019 was conducted using the following terms: “acute respiratory distress syndrome” or “ARDS,” and “cryobiopsy” or “cryoprobe,” without restrictions on language or publication year. Then the retrieved papers were read in their entirety to assess their appropriateness for this study of the value of TBLC in ARDS. Data on the characteristics of the TBLC procedure, related complications, pathological diagnosis, treatment changes and patient survival outcomes were extracted and summary proportions were calculated based on individual cases.