November 16, 2020

An article review from the ESICM Journal Review Club

An article review of the retrospective study of LUS data collected in Israel during first wave of COVID-19

This very interesting paper describes a retrospective study of prospectively collected data on the Lung Ultrasound (LUS) exams performed during the first wave of COVID-19 epidemic in Israel.  Moreover, it investigates the use of (LUS) as a tool for risk stratification and outcome prediction, and may aid management strategies, triage and resource allocation during a pandemic.

Patients that were admitted to the Tel Aviv Medical Center because of COVID-19 infection were examined using a LUS protocol on the first day of hospitalisation. The study population comprised 120 consecutive patients, admitted to the medical ward and Intensive Care Unit, in a time-span of six weeks.

The patients were diagnosed with COVID-19 infection, confirmed by a positive reverse-transcriptase polymerase chain reaction assay for SARS-CoV-2 in a respiratory tract sample. Furthermore, the investigators implemented a prospective programme of performance of LUS on admission and on deterioration for all patients presenting with respiratory illness due to COVID-19 infection, using a pre-defined step-by-step protocol, as part of a routine patient care protocol.

All patients underwent comprehensive LUS combined with bedside echocardiography within 24 hours of admission.  Deteriorating patients were re-examined, using the same protocol.  The study endpoints were: all-cause mortality and a composite of death or new need for mechanical ventilation.  All patients underwent a six-zone examination of each lung, which included a scan of the anterior, antero-lateral, and postero-lateral aspects of the thorax in the supine or semi supine position.

A point-scoring system documented the severity of the LUS image. Zero points were issued for normal A-lines presentation, one point for individual B lines, two points for dense B lines and three points for lung consolidation. A score of 0 was considered normal and 36 was considered highly pathological.  Abnormal pleural appearance (thickened or normal, patchy or homogenous) was also documented.

All precautions and measures were taken to avoid cross- contamination of the patients and personnel.

None of the included patients had normal LUS or homogenous B-lines in all zones.  Most patients had patchy pleural thickening (n = 100; 83%), or patchy sub-pleural consolidations (n = 93; 78%) in at least a single area, while pleural effusion was scarce (n = 9, 8%). The median total lung score was 15.

80 patients (67%) had a baseline LUS score of 0–18 and 40 (33%) had an LUS score of 19–36.  Comorbidities such as hypertension, diabetes and obesity were present in 81% of patients. On admission, the most common symptomatology was from respiratory, followed by fever, chest pain and fatigue.  On chest X-ray, the most common manifestation (39% of patients) were bilateral infiltrates, while pleural effusion and lobar infiltrates were rare (< 15% each).

The optimal cut-off point for LUS score was found to be 18 – using the highest Youden’s index in the ROC analysis for 30-day mortality (AUC 0.76; sensitivity = 62%, specificity = 74%).

Survival was reduced with total LUS score > 18 vs. LUS score ≤ 18 (66 ± 20% vs. 88 ± 11% for 30-day survival; p = 0.01).  The unadjusted hazard ratio of death for total LUS score was 1.08 [1.02–1.16] per point, p = 0.008, while the unadjusted hazard ratio of death for high risk LUS score (> 18) was 2.65 [1.14–6.3], p = 0.02, suggesting a 2.6-fold increase in mortality with high risk, compared to low risk, LUS score.

After the initial LUS, 30 composite events were documented. Pleural thickening and total LUS score were significantly associated with the composite event. The rate of the composite events was increased with total LUS score > 18 vs. LUS score ≤ 18 (43 ± 9% vs. 10.6 ± 3% for thirty days; p = 0.0004).

The unadjusted hazard ratio of the composite event for high risk LUS score (> 18) was 4.24 [2.06–9.1], p < 0.0001 suggesting a 4.2-fold increase in the composite event with high risk versus low risk LUS score

This study documented that:

  1. All admitted patients, even with mild disease, have abnormal LUS at presentation.
  2. For the majority of patients, the most common finding on LUS was patchy pleural thickening or patchy sub-pleural consolidations in at least one zone.
  3. Increased LUS score is associated with worsening disease.
  4. In deteriorating patients, LUS pathology worsens mostly in the anterior lung segments and correlates with PEEP requirements.
  5. Baseline LUS predicts death and/or clinical deterioration and may aid risk stratification and clinical decision-making.
STUDY STRENGTHS & LIMITATIONS

Strengths

  • The results show that a higher LUS score, appearance of pleural thickening and pleural effusion predict the need for mechanical ventilation, mortality and the combination of both. Survival drops significantly with an LUS score above 18. This prediction is independent of chest X-ray findings, making it a stand-alone superior alternative.
  • The predictive ability of LUS score is superior to chest X-ray and O2 saturation as far as the composite outcome of need for invasive mechanical ventilation or death, is concerned.
  • LUS is a reliable bedside imaging study, due to the peripheral distribution of lung infiltrates in COVID-19
  • LUS can be used to predict a good clinical outcome and aid discharge decisions, as patients without any pleural thickening or subpleural consolidations did not experience clinical deterioration
Limitations
  • A single centre study, which included only patients with COVID-19 who were hospitalised for at least 24 hours.
  • This study probably over-estimated the severity of LUS in COVID-19 because only ≈ 7% of patients diagnosed with COVID-19 in Israel are admitted to the hospital.
  • Outcome analysis should be cautiously evaluated due to the limited population of patients.
  • The use of phased-array transducers is acceptable when performing LUS, but its low frequency and high penetrance can compromise pleural evaluation. This was counteracted by placement of focus at the pleura level which enabled reasonable assessment of the pleural line and sub-pleural consolidations.
TAKE HOME MESSAGE

LUS provides risk stratification and prediction of outcomes in COVID-19 and may guide management strategies, triage and resource allocation during a pandemic.

This article review was prepared and submitted by Dr Dimitrios Papadopoulos MD, MSc, PhD, Senior Consultant in Intensive Care Medicine, General Hospital of Larisa, Larisa, Greece, on behalf of the ESICM Journal Review Club.


REFERENCES
Lung ultrasound predicts clinical course and outcomes in COVID-19 patients. Lichter, Y et al. Intensive Care Medicine volume 46, pages1873–1883 (published 28 August 2020)

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