In a population of patients with respiratory failure, PLUS was fast, highly feasible, and had an acceptable diagnostic accuracy for the diagnosis of cardiogenic pulmonary oedema. Especially the sensitivity of PLUS is high, making it an excellent tool for ruling-out cardiogenic pulmonary oedema, in the case of a PLUS examination with no signs of IS. The specificity was however somewhat lower and not better than the specificity of the clinical assessment. A single prehospital study and several studies conducted in an in-hospital setting have found LUS to have both a high sensitivity and specificity for the diagnosis of cardiogenic pulmonary oedema [
5,
8,
11]. One possible explanation for the lower specificity found in this study might be the relatively high proportion of patients with other conditions which may also cause IS, as reflected by the proportion of patients in which the initial chest x-ray performed in the ED was described with pulmonary fibrosis or possible interstitial lung disease (Appendix, Table 6). Another possible reason for the lower specificity might be the limited level of training in PLUS prior to the study. Studies assessing the learning curve for focused LUS have however found LUS to have a step learning curve for the diagnosis of IS with a high diagnostic accuracy despite limited training [
14,
15]. A third possible explanation may be the gold standard missing patients with cardiogenic pulmonary oedema since chest x-ray often was the only imaging modality used for pulmonary assessment in the patients. Several studies have found focused LUS to have a higher diagnostic accuracy than conventional chest x-ray for the diagnosis of cardiogenic pulmonary oedema [
1,
5]. Additionally, in the time gap between PLUS and initial imaging at the hospital, the patient in most cases would have received treatment and thereby reduce the severity of the cardiogenic pulmonary oedema and thus the changes which could be visualized by chest x-ray in the ED. The transportation times were however relatively short and the diagnostic criteria used for the gold standard did not solely rely on imaging findings. Based on the k value, the agreement between the two auditors was substantial according to Fleiss’ guidelines [
16]. The PLUS diagnostic criteria were based on the international definition of IS, using a definition in which multiple B-lines had to be present in all four scanning zones or in both of the two anterior zones might have improved the PLUS specificity [
1]. As indicated in other studies, such a definition would however also have lead to a decreased sensitivity and thereby also affect PLUS’ utility as an efficient rule-out tool [
17]. The PLUS protocol assessing two zones on each hemithorax was chosen in order to reduce the time used for the ultrasound examination. The median time use of 3 min corresponds to what has been reported using a three zone approach in an intensive care setting and the eight zone approach in an ED setting [
6,
11]. The two zone approach did thus not seem to reduce ultrasound examination time when compared to a three or eight zone approach. This may however be due to fact that relatively experienced or specially trained physicians performed the LUS examinations in the other studies [
6,
11]. A direct comparison of the time used for the different approaches performed by the same physicians is thus needed to assess whether there is a clinical significant time difference or not. When compared to the diagnostic accuracy of the prehospital clinical assessment, the clinical impact of using PLUS as a standard diagnostic test in patients with respiratory failure would be a fast and efficient means of ruling-out cardiogenic pulmonary oedema. This would have clinical important applications regarding several aspects. The use of inhaled bronchodilators in patients with cardiogenic pulmonary oedema is associated with a worse outcome [
18]. In areas with long transportation times to the nearest hospital, PLUS could potentially be used to monitor treatment response during the transportation [
10]. Prehospital ultrasound of trauma patient seems to have a potential effect on prehospital triage and selection of receiving facility [
19]. PLUS could possible in the same manner be used to guide whether the patient should be transferred to a cardiology department or a general emergency department. PLUS may thus potentially improve be prehospital treatment, monitoring and transportation in patients with acute respiratory failure. Depending on how the prehospital and in-hospital systems are organised, PLUS can be used to guide which patients who do not have cardiogenic pulmonary oedema and can thus safely be transported to a general emergency department and to identify patients with a high risk of cardiogenic pulmonary oedema needing initial assessment by a cardiologist.
Limitations
Being a single-MECU study, the results cannot necessarily be applied to other MECUs or other prehospital settings. Being a pilot study with a relatively small sample size, the results has to be interpreted with caution, as also reflected by the relatively wide 95 % CI’s of the results. The study results are however still useful for generating hypotheses for future studies. The physicians performing the examinations only had limited PLUS training, this would however reflect a “real-life-setting” in which the MECU physician does not necessarily have extensive skills and experience in focused ultrasound. In some of the few published LUS learning studies, using LUS to assess whether interstitial syndrome is present or absent, a high diagnostic accuracy could be achieved even after short training as used in the present study [
14,
15,
20]. Even though patients were included prospectively, the study results may have been affected by selection bias. No registration was performed of the patients not included in the study; hence no data are available for the screening process for patient participation in the study. Since patients had to be able to give informed consent in order to participate in the study, patients with very severe respiratory failure who could not give consent was not included. Seen from a study design perspective, ideally all patients with signs of respiratory failure should have been included no matter whether consent could be given or not. Such a design was however not possible in order to obtain approval from the Committee on Biomedical Research Ethics. To what extent patients were not included due to inclusion criteria not being met, due to the treating physician deemed that PLUS would delay life-saving treatment or transportation, or due to patient not being able to give informed consent is not known. Even though all the physicians received the same training prior to the study, differences in ultrasound competencies prior to the study might also have introduced selection bias if more experienced sonographers were more likely to include patients. Based on the average number of MECU activations per year and the relatively common occurrence of patients with respiratory failure one would expect that inclusion of 40 patients to the study could have been completed faster than it did. There is thus a high risk of selection bias being introduced in the patient recruitment process. To what extent this has affected study results are unknown due to the lack of available data.