Host Kyle Enfield, MD, FCCM, welcomes Adriano Targa, PhD, to discuss the article, “Sleep and Circadian Health of Critical Survivors: A 12-Month Follow-Up Study,” published open access in the August 2024 issue of Critical Care Medicine (Henríquez-Beltrán M, et al. Crit Care Med. 2024;52:1206-1217). They will discuss the prevalence of sleep disturbances and circadian rhythm fragmentation in critical survivors, the impact of factors such as invasive mechanical ventilation and hospitalization duration, and associations among sleep quality, mental health, and respiratory function one year post-discharge.
Dr. Targa is a researcher at the Center for Biomedical Research Network - CIBER in Madrid, Spain.
Find more expert-developed articles from Critical Care Medicine at ccmjournal.org.
Transcript:
Dr. Enfield: Hello and welcome to the Society of Critical Care Medicine podcast. I’m your host, Kyle Enfield. Today I’m speaking with Dr. Adriano Targa, PhD, about the article “Sleep and Circadian Health of Critical Survivors: A 12-Month Follow-Up Study,” published in the August 2024 issue of Critical Care Medicine. To access the full article, visit ccmjournal.org.
Dr. Targa is a researcher at the Center for Biomedical Research Network - CIBER in Madrid, Spain. Welcome, Dr. Targa, and thanks for taking time out of your day to meet with me and talk about this article. I’m really excited about our conversation. Before we dig in to the work that you’ve done, do you have any disclosures you’d like to report?
Dr. Targa: I have no disclosures. Thank you for a nice presentation.
Dr. Enfield: Recovery from critical illness is definitely something that has been obtaining a lot of importance in our work. Tell me a little bit about what got you and your research group interested in looking at the sleep patterns of people who have survived critical illness and what led you to start this study.
Dr. Targa: Actually, this study started with the COVID-19 pandemic. I work in a group of sleep researchers and pneumologists. The idea was to perform a follow-up of these patients, more in terms of respiratory function, but we also decided to take advantage of this situation to study the sleep of these patients because the data, the literature at the moment, were subjective data in terms of sleep health, and also only one question, for example, asking whether the patient felt like his or her sleep was disturbed.
We wanted to dig deeper on this matter and start a more complete evaluation. So the idea started with the pandemic, and that was because our project was focused on critical patients due to COVID-19. We started the project at that moment, and we decided to perform subjective and objective evaluations because that was also not present in the literature at the moment, so the idea started with that. Now, of course, we have more projects ongoing to evaluate this matter on critical patients due to causes other than COVID-19.
Dr. Enfield: I wonder if we could back up just a little bit and ask, what got you interested in sleep chronobiology? Why should critical care and health practitioners in general be interested in this subject? Why did you get interested in it and why is it important to us as a healthcare provider community?
Dr. Targa: Sleep is a really important factor for overall quality of life. If we don’t have good sleep health, we will have lots of problems in the short term in terms of quality of life, attention, consolidation of memories, and daytime somnolence, for example. That’s one thing and maybe that’s not the most important thing if we’re thinking about critical survivors because they have lots of other problems in the short term, but then, for complete recovery of these patients, sleep health is very, very important because we can see, like the studies indicate, we do have evidence of a close relationship between sleep health and immune function, for example.
So if you want complete recovery, we have to think about the relationship between sleep and immune function and also the role of sleeping, especially the circadian rhythm on respiratory function. So if we are thinking about a critical patient, of course, the benefits of good sleep health can be seen at short term in terms of quality of life, but maybe we can see that clearly because of other situations, conditions that the patient is suffering at that moment.
But especially in the long term, if you want to have complete recovery of these patients, we have to think, in really, really good circadian health in terms of the outcomes associated with poor sleep health in the long term, the development of a lot of conditions due to poor sleep health. So I think it’s a matter that is very important, obviously, if we look at the short term, but even more when we look at the long term.
Dr. Enfield: So as you guys approached this study, what were sort of the big things that you found, sort of the key findings, and maybe what were some of the findings that surprised you and your research team?
Dr. Targa: We observed that there’s a high prevalence of poor sleep quality. The study that we are commenting on is the third study because if you are talking about the COVID-19 pandemic, we started with a three-month follow-up, then we performed a six-month assessment, then a 12-month follow-up. And we can see that, for example, there’s a high prevalence of poor sleep quality at three-month follow-up, around 60% of patients reporting poor sleep quality. Then we have a slight improvement in terms of sleep quality at 12-month follow-up. That’s interesting because the values are quite similar to the general population with indirect comparisons, obviously.
But I think an interesting point is that circadian health doesn’t change, so we have a higher fragmentation of the rhythm in a group of patients that remains the same. Fragmentation of the rhythm remains the same along the 12-month follow-up, so we do not see an improvement in 12-month follow-up. There are a lot of other things obviously, but we can see some markers, predictors of this high fragmentation at 12-month follow-up, like days of hospitalization or invasive mechanical ventilation.
Dr. Enfield: Maybe for some of us not as in tune with chronobiology and sleep, can you speak briefly about the normal circadian patterns that you would expect to see in, say, a normal person, and then compare that a little bit to the changes you see in these critically ill patients?
Dr. Targa: Well, in a healthy person, we expect to see a really stable rhythm with some kind of routing in terms of activity of sleep time or time of awakening, for example. We expect to see some kind of stability along the days during the week. And we also expect to see a high amplitude of the rhythm. That means that we expect to see higher activity during the active phase and lower activity during the rest phase. We also expect to have a good pattern. For example, you expect to see a continuous pattern of activity during the active phase and a continuous pattern of lower activity during the rest phase.
What we are seeing in critical survivors due to COVID-19 is that this continuous pattern of activity during the active phase and this continual pattern of low activity during the rest phase are not observed. We can see a lot of fragmentation of this rhythm, so we can see a lot of periods of inactivity during the active phase and periods of activity during the rest phase.
This is something that you would expect of a person who has a lot of naps, for example, or a person who has some kind of disturbance that makes him or her remain active during the night. So we don’t know exactly the reasons why a critical patient has a lot of fragmentation of the rhythm, but this is what’s happening and this is what is unexpected at 12-month follow-up. You would expect that at three-month follow-up, for example, but at 12-month follow-up, that’s a lot of time.
Dr. Enfield: So obviously you guys are still doing research, but any thoughts about what might be steps that clinicians can take for their recovering patients to help with this? Are there known strategies or known thoughts right now in your field about what we might be recommending to our patients who are surviving critical illness right now?
Dr. Targa: Well, with our study, I think it’s important to highlight this, we can’t establish relationships of causality because it’s an observational study, but we know some factors that might increase the fragmentation of the rhythm, which are like the constant exposure to artificial light or mistiming exposure to artificial light, interruptions during the ICU stay, the noise of the equipment or the personnel, interventions that are necessary most of the time but we can try to adjust that, also the lack of exposure to sunlight. So there are a lot of factors that could increase fragmentation of the rhythms. In terms of the ICU stay, what we can do is try to avoid these factors whenever it’s possible.
Also we have ICUs with windows in which the patient can be exposed to some kind of natural light. We have some places that we can adjust the timing, exposure to artificial light or noise. So there are some things that we can do, but this is not a behavior or an attitude that we can do as a clinician, for example. It’s impossible to do that alone. This is a situation that needs to be adjusted as a group in an organized context.
These are factors that could be avoided or adjusted to try to decrease this fragmentation of the rhythm. Also, even if we can do that in terms of an attempt to decrease fragmentation of the rhythm, we can see these factors like time and duration of the ICU stay or time spent in the ICU or duration of invasive mechanical ventilation as markers of this increase in fragmentation.
So, even though I can’t establish a causal relationship, if I know that a patient who received invasive mechanical ventilation or who spent a lot of days in the ICU will have a high probability to have fragmentation of the rhythm, I can try to adjust the follow-up of this patient and attempt to decrease this fragmentation. So these are some of the factors.
We also observed some kind of correlation between respiratory function and fragmentation of the rhythm at 12-month follow-up. This also could be a marker of a patient with probability of having high fragmentation of the rhythm. It’s interesting to highlight, as previously mentioned, that we can’t infer if there is causality here, but it’s important to see these factors as markers of possible fragmentation of the rhythm and then provide appropriate follow-up for patients.
Dr. Enfield: You said you guys are doing some additional studies now because obviously this is a population enriched for COVID-19. Do you expect to see the same findings in other critically ill patients or do you think this is unique to that population of patients?
Dr. Targa: This is exactly what we are doing right now. We have a project that we are recruiting patients for, of course it is other than COVID-19, to see whether these alterations that we observed with critical COVID-19 patients are also true for critical patients in general, because we hypothesize that the effects that we are observing are due to the ICU stay or invasive mechanical ventilation but we can’t prove that yet. So we are trying to observe that with other critical patients to see if we can replicate the results or if the prevalence of poor sleep quality or the prevalence of higher fragmentation of the rhythm is different compared to COVID-19 patients.
We hypothesize that the effects we have are due to the ICU stay or this environment of the ICU and not due to the disease itself. Because if we look at other indicators, severity of disease, even though in the article, invasive mechanical ventilation is used as a marker of severity of disease, if we look at other markers, we don’t see any relationship with fragmentation of the rhythm, for example, so we hypothesize that this is more related to the context of the ICU than to the disease itself.
Dr. Enfield: I think a lot of us are looking forward to seeing that. I think we all share that hypothesis and we’re excited to see your results. Before we wrap up, are there any questions I should have asked or things that you wanted to share with the audience?
Dr. Targa: Maybe it would be interesting to talk about some articles, the follow-up articles of this one, because now we have a 24-month follow-up article, which is the last one of this study, obviously. It’s interesting because we thought, when we were observing the results of the 12-month follow-up, that the sleep quality was almost normal, because you can see a slight improvement close to the prevalence of the general population. But what we are seeing in this final article is that there are patients who require 24 months to recover their sleep health.
This is interesting because now we can see that there are two groups of patients, for example, one group that starts with good sleep quality at three-month follow-up and remains with good sleep quality during the follow-up. But there is another group that starts with poor sleep quality at the three-month follow-up and this poor sleep quality is recovered, well, it changes and it gets to the point of good sleep quality similar to the other group. In terms of the circadian function, we don’t have the results yet, but in terms of sleep, it is interesting.
The most interesting part in terms of sleep specifically is that it doesn’t correlate with anything, with the baseline characteristics or invasive mechanical ventilation or the ICU state but with mental health. The curves of improvement or the evolution of mental health are really, really similar to the evolution of sleep health for both groups, the ones with poor sleep quality at three-month follow-up and the ones with good sleep quality at three-month follow-up.
But these results will not be the same for the circadian rhythms probably, because what we saw during all the studies during this investigation is that sleep health is mostly associated with mental health in general and the circadian rhythms are more related to the ICU or invasive mechanical ventilation. So the focus, in terms of critical care, would be more related to circadian rhythms than to sleep quality in this specific population.
Dr. Enfield: That’s fascinating. Thank you so much for sharing those early results for your 24-month study, and we’ll look forward to seeing the circadian health data as well. This is going to conclude another episode of the Society of Critical Care Medicine podcast. If you like what you heard, consider rating and reviewing us. For the Society of Critical Care Medicine, I’m your host, Dr. Kyle Enfield. Have a great day.
Announcer: Kyle B. Enfield, MD, is an associate professor of medicine in the Division of Pulmonary and Critical Care at the University of Virginia. He received his undergraduate degree from the University of Oklahoma.
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