In this predefined secondary analysis of the InventCOVID trial evaluating the correlation between four existing LUS scores and EVLWi in COVID-19 ARDS patients, the main findings were: (1) the global LUS score, the LUS-ARDS score and the anterior-lateral score correlated well with EVLWi, (2) the LUS-ARDS score showed the highest diagnostic accuracy for severe pulmonary edema at baseline, (3) the B-line count score did not correlate with EVLWi and (4) changes in the 12- and 8-region scores were correlated to changes in EVLWi over time.
The 12- and 8-region scores examined in this study performed well in quantifying PiCCO-derived pulmonary edema measurements in COVID-19 ARDS. Combined with previous studies21,22,35, our results underline the value of LUS for the assessment of pulmonary edema in patients with COVID-19 ARDS. In a second notable finding, the 8-region anterior-lateral score showed a similar correlation with EVLWi compared to the 12-region scores. The limited LUS score was examined with the rationale that invasively ventilated patients frequently show a loss of aeration in the dorsal lung regions due to compression atelectasis and accumulation of pulmonary edema in the supine position36. Moreover, a score that requires less time to perform remains clinically attractive, as LUS is a bedside tool. Our data suggests that quantification of EVLW with the 8-region anterior-lateral score may be an alternative to the more extended 12-region protocols.
The correlation of the LUS-ARDS score with EVLWi and its good diagnostic accuracy for severe pulmonary edema are promising for comprehensive assessment of COVID-19 ARDS patients. Notably, this score was developed and validated for ARDS diagnosis and not to predict pulmonary edema22. Yet, it showed the highest diagnostic accuracy. The difference between the LUS-ARDS and other LUS aeration scores is that the presence of pleural abnormalities contributes to the final score. Presumably, in ARDS patients, taking into account pleural morphology increases diagnostic accuracy for EVLW because pleural abnormalities are highly specific for noncardiogenic interstitial syndromes such as ARDS21. Moreover, they may represent a surrogate of ARDS severity, which is associated with the degree of pulmonary edema37. In combination with its recently reported high accuracy for ARDS diagnosis22, our findings provide further support that the LUS-ARDS score may be a useful adjunct to improve assessment of ARDS patients. Validation in a non-COVID-19 ARDS cohort is needed to extrapolate our findings to the broader ARDS population.
A remark about scoring LUS aeration patterns is that the degree of aeration does not directly translate to the degree of pulmonary edema. This is a strength, as LUS can quantify disease processes other than edema and provide clinically valuable information about the nature and location of underlying pathologies and inform about lung morphology38. Thereby, it offers what a PiCCO monitoring device cannot. A potential risk of using LUS is under- or overestimation of pulmonary edema based on aeration patterns. An increase in A-patterns may for instance arise from overdistension due to higher positive end-expiratory pressure (PEEP) levels5 and a C-pattern may represent atelectasis39–41. Thus, the clinical context has to be taken into account to inform interpretation of LUS aeration patterns.
It follows that a LUS score based solely on the number of B-lines may be more appropriate for the focused quantification of pulmonary edema. Enghard and colleagues found an excellent correlation of a simplified 4-region B-line count score with EVLWi in a mixed ICU population (r = 0.91, p < 0.001)24. However, of the 50 patients, only 6 were classified as ARDS, considerably limiting the validity of their findings for the ARDS population. One study examined the same score in 26 ARDS patients and described a significant correlation (r = 0.66), however it found that changes in B-line score could not predict variations in EVLWi7. In the current study, we found no significant correlation of the B-line count score with EVLWi nor with ∆EVLWi. Considering these discrepancies, it is questionable whether B-line counting is suitable for scoring pulmonary edema in ARDS patients. Reasons for the inconsistent performance of the score may be that abnormal pleural morphology in ARDS hampers reliable counting of individual B-lines, and that the choice of transducer and ultimately the interpretation of the sonographer affect reproducibility of this method42.
Aside from ARDS diagnosis and the assessment of severity, monitoring changes in pulmonary edema and lung aeration would be useful to evaluate treatment response. A change in global LUS score and the anterior-lateral LUS score between time points 1 and 2 was significantly associated with ∆EVLWi and ∆LUS-ARDS score was positively associated with ∆EVLWi, despite not reaching statistical significance. Possibly, the global and anterior-lateral LUS scores are better suited to monitor pulmonary edema over time. A reason may be that the LUS-ARDS score considers pleural abnormalities, which may not be as sensitive to changes in EVLW as aeration patterns are. However, considering the similarity in correlation coefficients (r = 0.49 vs. r = 0.43), it is unclear whether this reflects a clinically relevant difference. Based on our findings and previous studies43,44, LUS aeration scores seem useful to evaluate a change in EVLW in (COVID-19) ARDS. To validate this conclusion, a future study may include measurements at multiple time points and later stages of ARDS.
Strengths and limitations
The study has several strengths. First, the prospectively included population was exclusively comprised of patients with COVID-19 ARDS, making this a population with a single pulmonary etiology and thus providing a rare degree of relative homogeneity. Second, the availability of two time points of measurement allowed us to investigate the correlation of ∆LUS and ∆EVLWi, allowing for assessment of the value of LUS for monitoring pulmonary edema. Third, to our knowledge this is the first study to compare and contrast four previously proposed LUS scores that differ in terms of examined regions and/or means of score aggregation. This enabled us to contribute to the ongoing effort to identify the optimal LUS method for semi-quantifying pulmonary edema.
Some limitations should be acknowledged. The inclusion of COVID-19 ARDS patients with moderate-to-severe illness may reduce the external validity of its findings to ARDS populations with a different underlying etiology or milder disease severity. Second, the study only included invasively ventilated patients, not patients receiving non-invasive modes such as high-flow nasal oxygen. Therefore, we cannot draw conclusions about the accuracy of LUS to quantify pulmonary edema in a group that would particularly benefit from quantifying it, as these patients may face (impending) onset of ARDS45,46 and may benefit from early intervention. Lastly, the number of missing regions decreased the sample size and excluding patients with ≥ 4 missing regions may have induced a degree of selection bias.
Implications
Our findings show that LUS may represent a viable alternative to PiCCO-derived EVLWi measurement. Based on this, one can speculate that bedside quantification of pulmonary edema by LUS may be used to guide adherence to a restrictive fluid balance25, which has shown to improve outcomes in patients with (COVID-19) ARDS47,48,49. A randomized-controlled trial examining this question is currently ongoing (ClinicalTrials.gov Identifier: NCT05188092). In addition, the use of LUS to monitor patients at risk of progressing to severe pulmonary edema could prevent invasive diagnostic and monitoring measures such as CT scanning or the insertion of a PiCCO catheter. It should be acknowledged that the direct clinical implications of this study are limited due to the scarce use of PiCCO to monitor ARDS patients.