Diagnosing and Treating Delirium in the ICU

Podcast Transcript

Raed Dweik, MD:

Hello and welcome to the Respiratory Exchange Podcast, I'm Raed Dweik, Chairman of the Respiratory Institute at Cleveland Clinic. This podcast series of short, digestible episodes is intended for healthcare providers and covers topics related to respiratory health and disease. My colleagues and I will be interviewing experts about timely and timeless topics in the areas of pulmonary, clinical care, sleep, infectious disease, and related disciplines. We will share information that will help you take better care of your patients today as well as the patients of tomorrow. I hope you enjoy today's episode.

Abhijit Duggal, MD:

Welcome to our podcast, I am Dr. Abhijit Duggal. I'm the vice chair for the department of clinical care and the vice chair for research for the department of pulmonary clinical care, infectious disease in the Integrated Hospital Care Institute at the Cleveland Clinic. My guest today is Dr. Heather Torbic and she will be talking about delirium with us. Dr. Torbic?

Heather Torbic, PharmD:

Thank you for having me. I'm Heather Torbic, I am a medical ICU pharmacist at the Cleveland Clinic. I'm also the program director for our PGY2 Critical Care Pharmacy Residency Program and I'm excited to talk about delirium today.

Abhijit Duggal, MD:

Thank you so much Dr. Torbic. Dr Torbic, what is delirium?

Heather Torbic, PharmD:

So it's a little complicated. Essentially, it's fluctuating state of confusion in ICU patients or floor patients, but according to The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, or the DSM-5, it's an acute mental disorder associated with fluctuating changes in cognition and attention and is likely a consequence of another medical condition. And so when we think about delirium in patients, particularly in the ICU, there's different subtypes of delirium. So we have hyperactive, which is typically the most recognized type of delirium, because patients are agitated, they're restless, they're having hallucinations, their sleep-wake cycle is disturbed. So it's the most easy one for us to identify because patients are very disoriented, typically.

We also have hypoactive delirium, which is actually the most common type of delirium, but unfortunately is often unrecognized, because it's actually patients who are more withdrawn, less responsive, still having disturbances in their sleep-wake cycle, but typically goes unrecognized because they're not that agitated patient where you feel like you need to do something about that patient. And then of course, there's always a mixed picture as well, so patients can also have both periods of hyper and hypoactive delirium. So it is a little challenging to diagnose, but ultimately, it's confusion.

Abhijit Duggal, MD:

Thank you so much for that detailed explanation. How common is delirium in our hospitalized and ICU patients?

Heather Torbic, PharmD:

So as I previously mentioned, it is challenging for us to diagnose, especially when you're thinking about the different subtypes of delirium. So the actual incidence ranges from 45 to 87 percent, but the range is so wide because, again, difficulty in diagnosing, evaluating only at specific times of the day, different ICU subtypes. So different ICUs are probably going to have different incidences of delirium because of differing severity of illness across ICUs, so there's often misdiagnosis, and it's important for us to understand the correlation between severity of illness and the incidence of delirium. Understanding that patients who are more sick are probably more likely to develop delirium.

Abhijit Duggal, MD:

Thank you so much for that answer Dr. Torbic. So, Dr. Torbic, you explained very nicely that, you know, this is a difficult disease condition to diagnose, and because of that, you know, our understanding in terms of the prevalence of this disease process is very limited. In contemporary medical circles, what is the prevailing thought in terms of pathogenesis of delirium?

Heather Torbic, PharmD:

Yeah. (laughs) This was a difficult question to answer, but I think, ultimately, we believe that there are alterations in inflammation, particularly neurotransmitters and overall modifications or disruptions in neuromodulation across brain patterns. There have been a number of inflammatory markers that have evaluated in this disease state trying to identify if there are patients who have higher inflammatory markers or lower. And there is some signal that maybe there is an increased inflammatory process that occurs in patients with delirium, but it's difficult to tease out because we know that there are many inflammatory disease states that may put patients at a greater risk for delirium so it's challenging to distinguish whether that hyperinflammation is from delirium itself or some of the disease processes that may be predisposing patients to delirium. And then we've also had studies evaluating neurotransmitters, so things like dopamine and serotonin and trying to distinguish whether there's alterations in those bubbles, which has lead us to study certain medications in this disease state, because we are trying to work on altering the neuromodulation that we believe is occurring the state of delirium.

Abhijit Duggal, MD:

That's very good to know. Now you brought up the fact that delirium usually is a consequence of underlying medical problems, and also in your discussion about the pathogenesis, you again brought up the factor around inflammatory conditions kind of really causing things. What are the risk factors associated with delirium?

Heather Torbic, PharmD:

When I think about risk factors for delirium, I think about patient-specific risk factors. So there are patients who are presenting already with risk factors that are known to be associated with an increased risk of delirium. So things like having dementia at baseline, older patients, history of hypertension or alcoholism or other history of using illicit substances, those are automatically going to predispose patients to increased risk of delirium. But then we also know that patients have increased risk of delirium by certain medical conditions that they're now experiencing. So patients who are experiencing respiratory failure and have lower oxygen levels, patients who have sepsis or an infection, patients with just an overall higher severity of illness, as I mentioned previously, are going to be at a greater risk of delirium. And then of course, medications in and of themselves, so some of our sedative medications, benzodiazepines, these medications are going to predispose patients to increased risk of delirium. But on the flip side of things, if patients are using medications at home, there can also be withdrawal of these substances that also predispose patients to delirium as well.

Abhijit Duggal, MD:

Thank you so much. Dr. Torbic, how do we diagnose delirium in our patients?

Heather Torbic, PharmD:

So we actually have a few validated bedside tools. So the Intensive Care Delirium Screening Checklist and the Confusion Assessment Method for the ICU are two validated scores that we have available. The nurses or clinicians at the bedside will typically use these tools every eight to 12 hours in patients. And the challenge with using these tools is that we're just getting a snapshot at that time of whether the patient is delirious or not, and as I mentioned previously, it's a waxing and waning state of confusion. So I think that's another reason why the incidence of delirium is so variable, because we're only capturing small time periods where patients are being evaluated for delirium in the ICU. Of course, as I mentioned previously, hyperactive delirium is going to be much more recognizable to clinicians, and so we may place a greater emphasis on evaluating those patients, whereas the patients with hypoactive delirium may be just more withdrawn and we may be less likely to evaluate those patients, often missing a delirium diagnosis. And I think that that ultimately can lead to long-term consequences, particularly in those patients with hypoactive delirium.

Abhijit Duggal, MD:

Thank you so much. Dr. Torbic, given that we have such a high prevalence of delirium, and, you know, we have a lot of risk factors that you just described that are existing in a lot of our patients, both patient-centered and iatrogenic or things that we are doing to them, how can we prevent delirium in our patients?

Heather Torbic, PharmD:

That's a great question. Although data is limited, there actually have been a number of studies that have looked at medications to prevent delirium. These studies have primarily focused on looking at both first- and second-generation antipsychotics, which, again as I mentioned, these medications are of interest because we believe that there's alterations in neurotransmitters, like dopamine and serotonin and histamine. And so, the thought process behind these studies was that if we use antipsychotics in this setting, we can alter neurotransmitter levels in these patients and potentially prevent delirium before it even occurs. Unfortunately, the data was largely negative, these medications did not actually prevent delirium, and in fact they're associated with many adverse effects and downstream effects of continuing these medications if not intended to be continued. And so, ultimately, we rely on guidelines from The Society of Critical Care Medicine, which has evaluated this data that we do have available and they recommend against the initiation of pharmacologic management to prevent delirium.

So, I think the greatest tool that we have available to us now is nonpharmacologic intervention. So making sure that we're evaluating patients' medication lists while they're in the ICU, minimizing medications that we know can increase the risk of delirium, lightening sedation, decreasing exposure to sedation within the ICU, trying to keep patients on a normal sleep-wake cycle, getting physical therapy involved early and working with physical therapy to early mobilize our patients. Also, trying to reorient the patient using hearing aids and eyeglasses if that's something the patients use at baseline, those should be the things that we prioritize to prevent delirium in our patients, rather than pharmacologic interventions.

Abhijit Duggal, MD:

That's good to know. So Dr. Torbic, you gave a very good explanation in terms of why nonpharmacologic interventions perhaps are the most important things for the prevention of delirium. How about our patients that have a redeveloped delirium? How do we treat those patients?

Heather Torbic, PharmD:

So, again, nonpharmacologic interventions are still going to be the number one thing that we use for treatment of delirium as well. Again, as I mentioned previously, there are studies that have looked at antipsychotics for prevention of delirium, but there are also studies that have looked at antipsychotics for treatment of delirium, and in fact we have more studies looking at treatment of delirium and larger studies looking at treatment of delirium. Although there is still limited data, a recent meta-analysis looking at five randomized control trials and almost 2,000 patients found that antipsychotics do not decrease the duration of delirium or duration of mechanical ventilation, ICU and hospital length of stay, or impact mortality compared to placebo. And as I mentioned previously, we know that these medications can be associated with adverse effects, and so there are consequences of giving these medications and in this setting we know that they're not really providing a benefit in terms of treatment.

So, it's best to really avoid these medications. The Society of Critical Care Medicine, as I mentioned previously, really only recommends using these medications if patients truly are a danger to either themselves or to ICU staff. The concern with adding these medications are things like extrapyramidal effects, QTC prolongation, hemodynamic effects. And then we also know that patients also are inadvertently continued on these medications after they leave the ICU, which further predisposes them to consequences. It's been estimated that up to 47 to 80 percent of patients leave the ICU still on an antipsychotic if it was started in the ICU to treat delirium, and 20 to 30 percent of patients are still on that medication at hospital discharge, which I think is often not what was intended by adding these medications in the acute setting.

So really, we should be focusing, again, on nonpharmacologic interventions — maintaining a sleep-wake cycle, reorienting the patient, and using the A-F Bundle that The Society of Critical Care Medicine recommends to make sure that we're appropriately assessing pain for patients, using spontaneous breathing trials daily, selectively picking our choice of analgesic and sedative for patients, making sure that they're patient-specific and appropriate for the patient, and using as little of it as possible. Thinking about delirium, early mobility, and engaging the family to help reorient the patient and be at the bedside to help combat delirium.

Abhijit Duggal, MD:

That's a very detailed discussion about the treatment options available for these patients. So Dr. Torbic, you mentioned the A-F Bundle. You know that there's a lot of thought that different societies have put in in terms of the impact of delirium on our patients. Is it because of the acute changes that happen in the hospital that this is such a big problem or do we need to be worried about any long-term consequences in these patients too?

Heather Torbic, PharmD:

Yeah, unfortunately the dangers and the outcomes of delirium extend beyond the hospital stay and beyond the ICU stay. So we know that patients who develop ICU delirium have a need for more sedation, a longer duration of mechanical ventilation, they spend more time in the ICU and the hospital, and actually have higher mortality and increased likelihood of long-term cognitive impairment. We know that the estimated hospital length of stay for a patient who has delirium is about ten days longer than a patient who doesn't develop delirium and we also know that delirium is independently associated with a threefold increase in six-month mortality. So there's really serious consequences associated with the development of delirium. Patients go on to need additional support following an ICU stay, especially with the long-term cognitive impairment, increased risk of dementia and decreased functional status, so often requiring more support or need for a long-term care facility. And ultimately this creates a bigger financial burden for the healthcare system with a longer hospital length of stay and need for more support following ICU discharge.

Abhijit Duggal, MD:

Thank you so much for that explanation. So, as you've talked about the fact that, you know, delirium is difficult disease to diagnose, the prevalence is really unknown. We don't have any good mechanisms for either prevention or treatment for this disease process. What is the direction in terms of future research or other priorities for this disease process at this point in time?

Heather Torbic, PharmD:

You've made delirium sound incredibly negative. But I think ultimately, we need a better understanding of delirium pathophysiology and its association with long-term cognitive impairment. You know, we have some leads with neurotransmitter modulation, inflammatory markers being elevated, but I think we still truly don't know some of the true etiology and pathophysiology of delirium and it'd be important for us to be able to, one, better prevent delirium if we had more understanding in this area, and two, potentially look at medications that might be better equipped to manage delirium if we can better understand the pathophysiology. I think we need more objective tools for screening and it would be helpful if we had laboratory values like biomarkers as well that we could send off to better understand a patient's risk of delirium as well their trajectory once they do have delirium.

I think it's also really important to develop phenotyping models for patients with delirium, that way we can create more personalized interventions. We know that there's a number of different pathways that delirium may occur through, and so not all patients may experience the same delirium or the same phenotype of delirium, and so we may be able to better provide personalized care if we have a better understanding of the different types of delirium. And I think ultimately we need large randomized clinical trials in critically ill patients to look at our effects of sleep optimization, physical training, alternating safety practices, early mobility, family engagement. These are things that we believe to play a role, but again, the data has not been as rigorously studied and I think it would be helpful if we had larger trials with more rigorously evaluated interventions to help us truly identify the best way to manage these patients.

Abhijit Duggal, MD:

That's great. So Dr. Torbic, this was an extremely informative session and you talked about the significant burden that delirium places on our patients. I think it's really important for us to be mindful so that we can both prevent the occurrence of this disease process and also help our patients who develop using the nonpharmacological interventions that you really detailed very well. As we've discussed about all of these aspects about delirium and the impact that it has on our patients, any other thoughts that you think that healthcare providers should always be thinking about when they are taking care of these patients?

Heather Torbic, PharmD:

I think the first step is, one, thinking about things to minimize the risk of delirium before it even occurs, identifying who your high-risk patients are, and start implementing prevention strategies early to even prevent the occurrence of delirium. The next step is making sure that we're carefully screening patients for delirium. As I mentioned, our hypoactive delirium patients often go unrecognized, so making sure that we are using our validated tools at a frequency that makes sense to capture patients who have delirium. And then finally, implement strategies to treat delirium once it occurs, and trying to minimize as much as possible and avoiding pharmacologic agents if possible to manage delirium in patients if it unfortunately develops. And I think ultimately, too, educating patients and their families about delirium, I think it's something that can be really challenging for patients and families to experience. And so helping them understand how to work through the process and empowering families at the bedside to help be a tool for us to manage delirium.

Abhijit Duggal, MD:

Thank you so much. So again, our speaker today was Dr. Heather Torbic, and she discussed the prevalence and incidence of delirium and discussed other options in terms of both prevention and treatment of delirium in ICU and hospitalized patients. Thank you so much Dr. Torbic for a very informative session.

Heather Torbic, PharmD:

Thank you for having me.

Raed Dweik, MD:

Thank you for listening to this episode of the Respiratory Exchange Podcast. For more stories and information from the Cleveland Clinic Respiratory Institute, you can follow me on Twitter at Raed Dweik, MD.