This post was inspired by the paper from Zoccali et al. “A randomized multicenter trial on a lung ultrasound–guided treatment strategy in patients on chronic hemodialysis with high cardiovascular risk”, Kidney International 2021 also known as the LUST trial.
This trial showed that in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial.
So POCUS is cool, but is there any hard evidence to support its use?
Although POCUS is a broad bedside tool that helps the physician to answer clinically-focused questions, there is a growing body of evidence of its usefulness in detecting congestion and its superiority when included in the management of the patient (vs traditional signs of volume overload). It is easy to understand how useful this could be in the clinical practice of the nephrologist, as volume overload is a very important risk factor for morbidity and mortality for the whole spectrum of chronic kidney disease patients (CKD).
Most of the evidence comes from the use of lung ultrasound (LUS) to identify and semi-quantify extravascular lung water in heart failure patients, through the detection of lung comets. POCUS can also be used to detect congestion through the use of cardiac ultrasound and the VExUS protocol, but evidence is more limited. Multiple randomized controlled trials show that LUS allows an earlier detection, and faster resolution of congestion, while reducing the admission rate for heart failure decompensations, when compared to usual care.
More recently, the first trials in hemodialysis patients were published, which we will discuss further.
Lung comets? For real?
Yes, for real. This comet tail artifact was described for the first time by Prof. Lichtenstein in 1996 in a series of patients with cardiogenic and non-cardiogenic pulmonary edema, which he named the alveolar-interstitial syndrome.
Nowadays this artifact is most commonly referred as the ultrasound B-line, and is a game-changer in our ability to detect, not only, clinical, but subclinical extravascular lung water when compared to lung auscultation or chest x-ray. A parallel investigation of the LUST trial, the LUST study, revealed a very low sensitivity for lung auscultation and peripheral edema when used for the detection of interstitial lung edema! Also, patients with moderate or severe lung congestion, as assessed by LUS, less than half had audible lung crackles, and less than 20% had peripheral edema. On the other hand, LUS has very high sensitivity and specificity for the diagnosis of acute cardiogenic pulmonary edema.
Another exciting feature of the ultrasound B-lines is that their number decreases in response to any decongestive therapy, in real time even! This makes B-lines useful not only for the diagnosis/detection of congestion, but also for monitoring treatment. For example, LUS could help the nephrologist to determine the optimal dry weight of a patient, hopefully improving their cardiovascular outcomes.
Is it just LUST or was it love at first sight?
With these ideas in mind, Prof. Zoccali and investigators designed the The Lung Water by Ultrasound-Guided Treatment in Hemodialysis Patients trial, more commonly known by the LUST trial. They randomized 363 patients with a “high cardiovascular risk profile”, defined by:
- History of myocardial infarction with or without ST elevation or unstable angina, acute coronary syndrome documented by electrocardiogram recordings, and cardiac troponins;
- Stable angina pectoris with documented coronary artery disease by prior coronary angiography or electrocardiography
- HF with dyspnea class III-IV according to New York Heart Association functional classification
The main study endpoint was a composite of all-cause death, nonfatal myocardial infarction, or decompensated HF. Aproximately 75% of the patients had coronary artery disease and 40% of the patients had HF, mostly HFpEF. The median dialysis vintage was 4-5 years.
Patients were randomized to a LUS treatment protocol or standard-care. The LUS protocol consisted in scanning 28 lung zones and congestion was defined as total B-line count of >15 B-Lines (in all 28 zones).
Patients >15 B-lines were submitted to ultrafiltration (UF) titration, by either lengthening the dialysis sessions or scheduling extra dialysis sessions. This is of extreme importance, showing that the investigators were very alert to the importance of avoiding high UF rates in this population. Afterwards, they were followed once a week with LUS until the treatment goal (<15 US-B lines) was achieved. If this intervention failed to decrease the number of B-Lines, the next step was to optimize or add anti-hypertensive drugs.
At the end of the trial, patients in the intervention arm had less B-lines, were more likely to reach the treatment target of < 15 B-lines, and had less risk of dialysis hypotension. Although this was perceived as a minor finding by the community, this is actually high quality evidence that the use of POCUS makes us better clinicians by allowing a more tailored treatment for our patients!
Warning: bumpy road ahead
Despite the improvement in lung congestion as assessed by LUS, the primary end-point was not met.
After taking into account the results of the heart failure trials referenced previously, that were published while the trial was ongoing, a post-hoc analysis revealed that the intervention group displayed significantly fewer episodes of decompensated HF and recurrent cardiovascular events.
Although this is a post-hoc analysis, there is strong biological plausibility behind this, and it corroborates the findings of the lung ultrasound in heart failure trials. As mentioned by the authors, it is also possible that because the decongestion process is slow and since it was maximized at the end of the trial, it may take a longer time for this process to have an impact on clinical outcomes, as the mean follow-up was just 1.49 +- 0.72 years. Other substudies of the LUST by Loutradis et al. showed this is also an effective tool to guide hypertension treatment in the hemodialysis population, with positive effects in the arterial stiffness and diastolic function of these patients, giving more strength to the post-hoc analysis of the big trial.
Unfortunately, the trial enrolled less patients than what was initially planned (n=500), which could also skew the results. The authors blame the nephrologists, who look like they were not very enthusiastic about ultrasound, and perceived it as a complex and time-consuming tool. The trial was designed before the kick-start of the early-adoption phase of POCUS in Nephrology, so it is understandable that it was harder for this tool to gain traction with the clinicians. Another reason is probably that nephrologists are overconfident in their physical examination skills, unaware of the evidence that the traditional signs of volume overload have really poor sensitivity. I hope that if more Lung Ultrasound trials are designed in the future, more nephrologists are eager to learn this skill and help recruiting patients.
POCUS Crystal ball
So what does the future have in store for the use of lung ultrasound for the detection and treatment guidance of congestion in hemodialysis patients?
I am confident that this will be a commonly used tool in the future, similar to how “we” currently perform auscultation during dialysis rounds. In the trial, a 28 lung-zones method was used, and although it is easy and quick to learn and takes about 5 minutes to perform, you can’t really use it in every patient and in every weekly round you are making. In 2017 I visited one of the study sites in Reggio Calabria and learned their technique. Even if you are experienced with ultrasound, you have to be really fast to do it in 3 minutes as they reported in their research.
28-zone LUS protocol tutorial
In my point of view, for it to become common practice, LUS protocols have to be simplified.
What I usually do in my practice, is to use the 8-zone protocol, as it is much quicker and gives the same “ball figure” as the 28-zone. This was also shown by the trial investigators.
Although we cannot fade that this was a negative trial, it showed that LUS works, allows us to individualize UF orders making dialysis safer and probably reduces the rate of hospitalization due to heart failure decompensation.
As emerging doctors of the 21st century we cannot forget that we have to strive for the tailoring and personalization of our therapies, while reducing harm, and POCUS is a tool that helps us do exactly that.
