"Correlation Between PaO2/FiO2 and Lung Ultrasound Score in Patients Admitted to an Intensive Care Unit With Interstitial Syndrome: A Prospective Physiological Study"

JUSTIFICATION FOR THE RESEARCH

Interstitial Syndrome (IS) also known as alveolar-interstitial syndrome, is a diffuse affection of the lung interstitial tissue leading to decreased alveolo-capillary exchange and therefore hypoxemia. Acute conditions such as viral or bacterial pneumonia and pulmonary edema lead to IS. Pulmonary edema can either be haemodynamically induced in acute heart failure (AHF) or secondary to permeability impairment in Acute Respiratory Distress Syndrome (ARDS). In literature, Acute Lung Injury (ALI) is also used to refer to a condition similar to ARDS with less severe hypoxemia. Chronic pathologies as Diffuse Parenchymal Lung Disease (DPLD) also cause IS. Lung Ultrasound (LUS) is a useful tool to diagnose IS. Indeed, LUS is non-invasive, non-irradiating, low cost and easily available at the patient's bedside. The interest of LUS for critically ill patient has been demonstrated5. In ICU, it was shown that LUS reduces number of chest radiography, relative medical costs and radiation exposure without affecting patient outcome. Literature suggests that LUS diagnostic accuracy for IS is higher than the diagnostic accuracy of chest radiography. Chest Computed Tomography is the actual gold standard for IS diagnosis, however not available at patient bedside, irradiating and more expensive. LUS is mostly based on the detection of artefacts created by air-tissue interfaces5. In IS, artefacts have been shown to be related to the presence of extra-vascular water and the water-thickened of interlobular septa. Comet Tail Artefact (CTA) was originally described as dense tapering trail of echoes just distal to a strongly reflective surface whereas Ring Down Artefact (RDA) starts from the point of origin of the ultrasound waves and "ring-down" to the end of the screen without fading. CTA and RDA are created by different mechanisms. Liechtenstein's early work introduced the term CTA to describe artefacts found in IS4. He later introduced the alphabetic nomenclature and assign the term B-lines to those IS artefacts. According to Yue Lee and All, a confusion between CTA and RDA exist in the literature as B-Lines definition correspond to RDA rater then CTA. International recommendations later agreed on the use of the term B-line, to describe artefact found in IS. Presence of multiple B-lines is widely recognised to suggest the presence of IS. Despite poor literature on this topic, IS severity is represented by hypoxemia generally evaluated by the realization of an Arterial Blood Gase (ABG) to obtain Arterial Partial Pressure in Oxygen (PaO2). A study however supported the absence of correlation between PaO2 and long-term mortality for AHF. Another rather recent study, including one-hundred and sixty-five COVID-19 patients that underwent non-invasive ventilation, nevertheless showed a statistically significant difference in PaO2 between survivor and non-survivor at twenty-eight days. According to the Berlin definition, hypoxemia represented by the ratio between PaO2 and the fraction of inspired oxygen (FiO2) is a severity indicator in ARDS. LUS could be an alternative to evaluate severity of IS. The Lung Ultrasound Score (LUSS) was initially developed on an experimental model to assess lung aeration and is based on quantitative assessment of B-lines in six thoracic zones bilaterally. In each zone, a sonographic lung aeration status is determined scoring from zero to four to determine a total score over thirty-six. Literature findings are consistent with LUSS being an efficient tool to measure lung aeration in different intensive care situations: re-aeration antibiotics-induced in Ventilator Associated Pneumonia, assessment of PEEP-induced lung recruitment. LUSS realized during weaning trial has been showed to be able to predict of postextubation distress. In the Intensive Care Unit (ICU), LUSS is efficient to quantify lesions and predict mortality associated with ARDS. During the recent COVID-19 pandemic, numerous trials have demonstrated that LUSS is associated with disease severity and mortality in COVID-19 patients. Recently, a negative linear correlation between PaO2/FiO2 and LUSS was shown three series of patients admitted to Intensive Care Units (ICU) with different aetiologies of IS: one with thirty-three COVID-19 patients, one with thirty-seven ARDS patients and one with seventy-two ALI patients. Lately, this correlation was confirmed in larger series of one-hundred and sixty-two patients admitted the Emergency Departement (ED) suggesting that LUSS could be a tool to evaluate PaO2 and therefore evaluate IS severity regardless of IS' aetiology in patients admitted to ED.

STUDY PROCEDURE

A LUSS will be realized by an investigator trained for Lung UltraSound (LUS) and considering him/herself confident for its use. A five-point Likert scale will be filled. To the statement "I am qualified to realize a LUSS", only emergency doctors answering "I strongly agree" or "I agree" will be eligible for inclusion and added to investigators list using an amendment to this protocol. The ultrasound machines operated for LUS belong to each ED meaning the investigators are familiar to its use. To uniformize the results, settings of the ultrasound machines will be standardized. To allow the exploration of the pulmonary parenchyma a low frequency curvilinear transducer will be used, and evaluation of B-lines will be performed using a depth of at least 12cm as commonly recommended. If patients are isolated for infectious reasons, special precautions will be applied following institutional procedures of ultrasound use on contagious patients. LUS will take place within 10 minutes of ABG analysis. LUS will be performed at the patient's bedside. The investigator will be blinded to any other procedure made by treating physician for diagnostic purposes. The treating physician will be allowed to perform a LUS on its own. The LUSS procedure will be used as validated in a larger number of studies. For that matter, the thorax is virtually divided in six thoracic zones bilaterally, comporting two anterior zones, two lateral zones and two posterior zones. The anterior and lateral zones will be evaluated in strict dorsal decubitus and the posterior zones will be evaluated with a light contro-lateral decubitus allowed, if necessary, because of patient morphotype.

For each zone a score from zero to three will be determined as shown in figure 4: