ADAM KWOK: Well, before the fall, Claude was 77, and he was always a physical person. So despite his age he built a house, and in fact it happens on the day we had tradesmen in the house, and he was too busy showing them what to do, and that’s how the accident happened, and ended up with fracturing of the femoral head. And that’s completely changed his life since then. And that’s why I remember the date, 8th of February 2017. Life has never been the same since then.
MIC CAVAZZINI: That’s Adam Kwok, describing the first dominos in his partner’s descent into delirium. Claude had an operation to pin the femoral fracture but healing was disrupted by an MRSE infection that went undetected for months. When he want back into surgery for a revision it was discovered that a different-sized prosthesis was required, so Claude was kept anaesthetized for longer than intended while a replacement was brought in. This punishing spell in theatre was followed by a night in ICU.
ADAM KWOK: The following day he was transferred to the ward. I went to see him and he was, he was in pain. At first he recognised, he realised what happened, he’s just had a surgery. But then as the day went on, and then he’d doze off, and then he woke up, and then he said to me “I thought we went to a shopping centre. How come I end up being here?” So he was definitely confused, and then I explained to him what happened, and then he took my word for it.
But then after a while, you know, he asked the same questions, and as the day went on, he became more and more agitated. To the point about six o’clock, and I asked to see a doctor, and I said “There’s something not quite right”. But they reassured me he was OK, just go home, and they can handle it. And I went home, and, you know, as soon as I got home, I had a phone call from then saying “He’s a very difficult patient. You have to come back and you have to stay here overnight, otherwise we are going to transfer him to a psychiatric ward”. And that was hard to take, accept, because I did say he had a problem.
Anyway, I got back, and he was agitated, and he would ask me where is he, how did he get here, and he just wanted to leave. And that was my concern at the time, he might fall, and he would damage his leg again. So it was an exhausting night. And they were too scared, really scared to come in, because my partner is quite – he’s six foot four, and so they really, they only came in every four hours to do the observations, and then I think they avoided coming in.
You know, his confusions progressively got worse, and there is one question that will remain in my head, is “Is he having dementia, and is it going to be permanent? And, you know, what’s going on?”. And that was quite frightening, because I didn’t understand what’s happening. Nobody even acknowledged he had an episode of confusions, and the word ‘delirium’ was never ever mentioned, until he has been discharged, and the GP said it was a delirium episode he was experiencing.***
MIC CAVAZZINI: Claude was to go on to have two more episodes of delirium, along with a tortuous clinical journey. But as Adam puts it, the way the delirium was managed by clinical staff and their involvement of him as the primary carer was markedly different at the three hospitals. Over the next two podcasts we’re going to discuss how to reduce such variation in practice. You’re listening to Pomegranate Health, from the Royal Australasian College of Physicians. I’m Mic Cavazzini.
Delirium is an acute disturbance of consciousness, attention, cognition or perception. People sometimes experience hallucinations like crawling ants, or delusions and dread like the feeling that some is someone coming after you. While delirium is more short-lived than chronic psychotic conditions, it should be taken very seriously. It’s associated with an increased risk of falls, dementia and high dependency care, and all of this adds up to higher mortality.
We’ll talk about long-term management of those at risk of delirium in the next episode, but I want to start with the presentations and diagnosis. About a third of patients admitted to ICU experience delirium, but in mechanically-ventilated patients figures up to 80% have been reported. While it can occur even in children, delirium is most common in old or frail patients, like those that Professor Meera Agar and Professor Gideon Caplan look after.
MEERA AGAR: Meera Agar, palliative care physician, I work clinically at Liverpool Hospital in south west Sydney, and I’m an academic at the University of Technology, Sydney.
GIDEON CAPLAN: I’m Gideon Caplan, I’m a geriatrician at Prince of Wales Hospital, and I’ve been researching the pathophysiology of delirium.
MIC CAVAZZINI: OK. So I’ve got no less than five pages of questions, hopefully we’ll manage to get through. From my point of view it was interesting to go over the different manifestations of delirium in various settings, and then we’ll pick through the medical and environmental triggers afterwards. So a prospective study of general admissions to four Australian hospitals showed a delirium prevalence of 17% amongst patients over 70. Does that tell you anything about how well managed delirium is in our hospital system?
MEERA AGAR: I think the ballpark, the easy to remember ballpark is one in five. If you’ve seen five patients today in an admitted setting and you haven’t found the one person with delirium, go back and have a look. And also to remember it is an adjustable figure, and that if we have better delirium care and prevention in place we all have opportunity to reduce that figure in our units, even where the prevalence is naturally high because of the clinical risks of that population.
MIC CAVAZZINI: In that Australian study published in 2013, patients who went into hospital with delirium already were five times more likely to die in hospital than those without. And if the delirium came on during their stay in hospital, the mortality risk was 30 times higher. But it’s not so much that the delirium itself is killing them, it’s a waving red flag that these are sick people and are deteriorating quite rapidly.
MEERA AGAR: It’s actually the delirium itself. So you can have people in ICU with similar comorbidity, similar acute illness scores, and there’s something about having delirium above and beyond all of those other physiological and clinical parameters that is dangerous in itself. And so if you have a hip fracture and pneumonia and don’t get delirium, you’re going to be better off than if you have the same hip fracture and pneumonia with delirium. And we don’t know exactly what drives the additional mortality, but it is an independent factor. And so even if you’re acutely unwell, if you can prevent them getting delirium as well, that can impact on the mortality of what’s already a seriously ill patient. And that seems to hold true even in the palliative care setting, and in people with dementia where they’re already quite unwell and at risk of dying.
MIC CAVAZZINI: OK, so it’s not just a marker, it’s another system that’s shutting down?
GIDEON CAPLAN: Well, when people get adverse events from delirium, like dying, they don’t die because their brain shuts down, but my take on it is that that exposes them to all sorts of other problems. So for example they can pull out their drips or their nasogastric tubes more easily when they’re delirious. Most of the injurious falls that happen in hospital are on people with delirium, almost every single one of them. So it predisposes you to have accidents because you can’t think clearly. It makes it harder for you to cooperate with health preserving treatments, and just simple things like physiotherapy and other therapies that we need to give patents in hospital. I can impair their swallowing, so they might get aspiration of their food into their lungs, get aspiration pneumonia, because the rest of the body doesn’t work properly when you’ve got delirium, so they don’t walk as well, they don’t swallow as well, everything is worse.
But for a long time it was thought to be just a marker of acute illness. I mean, we’ve known about delirium for over 2,500 years, it’s described very clearly by Hippocrates. For most of that time it’s been thought to be just an epiphenomenon of serious illness or injury, and so people didn’t take it as seriously as perhaps they should have.
MIC CAVAZZINI: The way I had understood it, so of course we all experience hallucinations when we dream, when the brain lets down its guard of normal cognitive and attentional processes. But if a person has dementia, there is less cognitive reserve, even during waking hours. Is that a good way to think about the greater emergence of delirium in those with dementia?
GIDEON CAPLAN: That’s very true, cognitive reserve protects you against developing delirium, not absolutely, but is a relatively protective phenomenon. But professors at university, judges of the High Court, can still get delirium if they get sick enough. So no one is immune from delirium.
MEERA AGAR: And we don’t really understand what the brain changes are driving that predisposition. Is it central information, is it some change in metabolic process, and so that’s where I think a lot of interest in the research is.
MIC CAVAZZINI: And yes, we don’t have time to go into the pathophysiology, but it is a distinct neurological process to dementia and neurodegeneration and so forth. And while the stereotype of delirium is the agitated patient, perhaps aggressive or frantically roaming the hospital corridors, it can also manifest as a hypoactive presentation. What does this look like, and how common is it?
MEERA AGAR: So they’re the patients that we all think are the ones that are not causing us trouble today, or we can see last on the ward round because they’re not acutely unwell, and the nurses haven’t rushed up and said “You have to see Mrs So and So first”. No, often they’re just quiet, withdrawn, maybe not so talkative to you, and they’re the ones that the delirium can be really often missed. And so sleeping in the day and being awake at night is sometimes a clue, or “I just don’t feel well”. And those patients can still have hallucinations. And so often families will say “Mum is not quite herself today”, and those are the little clues that really you have to pick up on to pick up a hypoactive delirium.
GIDEON CAPLAN: And the hypoactive delirium illustrates how dangerous delirium is, because it’s often missed. It actually has a worse prognosis than hyperactive delirium, as it doesn’t get investigated and appropriately treated.
MIC CAVAZZINI: And yeah, it’s reported that a third of people in end of life care are affected by delirium. Meera, does this tend towards, more towards one subtype or another of delirium?
MEERA AGAR: Yes, so there’s been some really good studies that have done prevalence of a whole palliative care unit, and up to two thirds can have the hypoactive presentation. And again, the assumption that that’s just the normal cognitive change that’s part of the process of deterioration with a palliative diagnosis is a problem.
We treat delirium as a problem that needs to be fixed when it manifests. If we thought of maintaining cognitive wellbeing for all our patients in hospital as a proactive positive thing, then the distinction wouldn’t really matter, because we’d be looking for cognitive change and people not quite being themselves in their thinking and their memory, and trying to do something positive to improve that, and it wouldn’t matter if they weren’t jumping up and down and causing havoc on the ward, we would be thinking it was an important thing for us to invest time in managing and treating.***
MIC CAVAZZINI: Hypoactive or not, delirium is notoriously underdiagnosed. One illustration comes from a 2010 study in which the researchers followed acute general admissions of patients over 70 to a London Hospital. Within 3 days of admission they were all screened properly by the researchers, and it turns out that 72% of confirmed delirium cases had been missed by the admissions team. A similar study from a Montreal emergency room found a non-detection rate of 65%. Some older papers suggest that the detection rate is better in general medicine wards , perhaps because there’s more time for a careful diagnosis.
There are a several different screening algorithms that can take anything from 30 seconds to five minutes to complete. The well-known Confusion Assessment method, or CAM, starts with assessment of the cardinal signs; 1) acute onset and 2) inattention. If both of these are present, along with either 3) disorganised thinking or 4) altered level of consciousness, then a positive diagnosis of delirium can be made. The full version of the CAM also considers 5) disorientation, 6) memory impairment, 7) perceptual disturbances, 8) psychomotor agitation or retardation and 9) altered sleep-wake cycle. But as Meera Agar says, some of these signs are hard to recognise even for experienced clinicians.
MEERA AGAR: And it doesn’t matter if it’s a senior doctor, a junior doctor, it doesn’t matter what discipline, even if you work in disciplines that are specialising in older people’s care, the rates of under-detection are quite high, unless out of a whole of system it’s both valued, and that there is structure in place to screen people with proper and validated assessments. It’s not at the end of the bed that we can just say “Oh, yes, that person’s delirious, that person isn’t.” It’s something you have to actually do a formal clinical assessment regardless of how experienced and senior and trained you are. And it’s not just in medical disciplines, it’s in nursing, it’s an interdisciplinary problem.
GIDEON CAPLAN: The rate of delirium detection has been increasing over recent years. So a lot of geriatric teams and emergency departments now screen for delirium. But we do need ongoing screening through the admission, because delirium is not only present at admission it may develop after admission.
MIC CAVAZZINI: So yes, there are several different clinical assessment tools around. For hospitalised older the patients, the Confusion Assessment Method is reported to have a sensitivity of around 94%, and a specificity of 89%. The 4AT and Delirium Observation Screening Scale are both around 90% for sensitivity, although the latter of those has the best specificity of the three. There are another couple used in triage scenarios or intensive care. What do our listeners need to know about all these different screens, and are they appropriate to different settings, do they stand up for different subtypes of delirium?
GIDEON CAPLAN: Well, I don’t think there’s evidence that one is better in a particular setting, but there is evidence that people need to be trained in using these tools, and you can’t just stick it in the EMR and just tell the nurses to go off and do it without explaining, instructing them how to do it.
MIC CAVAZZINI: Is there one that’s de rigueur in Australian hospitals?
MEERA AGAR: I’d probably think the 4AT and the CAM are the most common instruments across Australia and New Zealand. And I think especially for junior doctors it’s important that we try and be consistent. If they’re moving between hospitals, and it’s interdisciplinary communications, and we need to be talking about the same thing, and so if we’re all using the same instrument and talking about it in the same way, that’s probably more important than the exact instrument. Now, I think the tricky feature is inattention, that’s something that is hard to teach people about, and hard for people to learn how to assess, because it’s a real nuanced clinical skill.
MIC CAVAZZINI: So there’s a great review from 2018 titled ‘Responding to 10 Common Delirium Misconceptions with Best Evidence’. The first misconception they point to is that if someone can orient to person, place and time, that means they’ve got their wits about them and they can’t be delirious. And the authors of that review suggested an assessment be carried out at least once per nursing shift. Is that desirable and practical?
GIDEON CAPLAN: So they need probably an initial assessment when they’re admitted, but then they can be assessed three times a day on every drug round, or on every change of nursing shift, with a very brief, ultra-brief screening instrument that takes only a few seconds, that can be used every shift. Some people advocate doing it on the drug round. And then if that’s positive, they need another test like the CAM or the 4AT to drill down a bit more.
But despite knowing about delirium for 2500 years we have no blood test for delirium, we have no imaging study that can diagnose delirium, it’s purely a clinical diagnosis, and it’s a condition that fluctuates. So people can be very delirious for part of the day, and at other parts of the day can appear close to or completely normal, or what we perceive to be normal for that patient. It may not be actually normal, but we may perceive that it’s normal for that patient.
So it’s essential to know what the patient was like beforehand, so it’s very difficult to do those assessments if you haven’t met the patient. But if the nurses have been seeing the patient, and it’s really helpful to ask their family, because there’s a whole range of patients who come into hospital and a key question is what are they like compared to normal.***
MIC CAVAZZINI: The varying intensity of delirium symptoms over the day makes it hard to recognise, especially with the frequent changes in staff on the wards. It can be helpful for nurses and doctors to record the time of day that they’ve observed a worrying behaviour and what cues preceded it. But the issue of screening for delirium on every shift can have unintended consequences, according to Professor Sharon Inouye of Harvard Medical School. She designed the CAM diagnostic tool, as well as a multi-component intervention that’s been adopted around the world. Speaking on the GeriPal podcast she described how about 5 years ago in the Netherlands, it became mandatory to perform an assessment for delirium on every nursing shift. As thorough as this sounds, it was accompanied by a 4 to 5-fold increase in the prescribing of antipsychotics. [After these findings were presented at an IAGG conference, they’ve not been published more widely to date, despite Prof Inouye’s inquiries; personal communication]. The moral of the story is that screening alone isn’t enough. You have to build a culture in your health service of prevention in order to make real gains in patient wellbeing. We’ll talk about this, and the overreliance on pharmacological management in the next episode. Spoiler alert, there’s isn’t enough evidence to date to support the indication of any drug for the treatment of delirium.
Let’s go back to Adam’s story. As we heard his partner Claude first experienced delirium in February 2017 thanks to a cocktail of infection, anaesthesia and post-surgical sedation. After three operations to sort out his femoral fracture, more diagnostics revealed an enlarged aorta which needed replacement along with the aortic valve. In May 2018, Claude went back into theatre but again there were complications. Spongy tissue around the valve made for difficult surgery, and Claude was kept in an induced coma until the morning.
ADAM KWOK: And then when he woke up from the surgery, he was in really good spirits, and he was winking at me, and I thought “God, the surgery must have gone well,” he was coherent, I could talk to him and he would respond. Little I know, a couple of hours later he started looking for his pants, so I got a bit concerned. And so I spoke to the doctor on duty, and the doctor went and talked to him, and came back and said “He seems to be pretty good to me, but if you can detect something wrong with him, how about we put him on a very light dosage of sedative, just in case, to keep him calm”.
And except in a couple of hours later he had a really full-on episode of delirium. He was hallucinating, all the doctors and nurses, they were hippies, and he could hear them talking in Italian, because my partner is Italian in descent. And he could hear them plotting to murder him in Italian, and he was trying to hide himself and trying to run away. He was still strong enough, and he’s trying to pull his tubes out, and he was trying to get off the bed, and we tried to hold him down, and he screamed for police.
And that went on for quite a while. And during that time they increased the dosage of sedatives. But his arms were still waving in the air, and he was still mumbling and calling for police. It was really, it was heart-wrenching to watch him, and I couldn’t do anything. And he was expecting me to help him, but I actually had to restrain him, because he was going to do damage to himself. So he started being verbally abusive to me, in a very personal way, like any other couple, things that they said in the spur of the moment, or in anger, things that were quite hurtful, and you sometimes wonder whether that’s in his subconscious.
I actually had to leave the ICU, and I went outside and had a good cry. And even after the episode, I really felt quite hurt by those abuse, and because it was about our relationship, and so I didn’t talk to anyone about it. But then it’s always been in the back of my mind. So I happened to spend a bit of time with Meera in the car, and in fact Meera said actually that’s quite common, and sometimes it actually destroys that relationship, and it became irreparable. And explained to me that because when they are having the delusions, someone’s trying to murder them, and they turn to their loved ones to rescue them, but then I was one of the accomplices. So the hurt to him is a lot worse than someone he didn’t know. And when Meera told me, it was such a relief, I can almost physically I can feel the relief on my shoulder.***
MIC CAVAZZINI: Claudes’s reaction to the insults of cardiac surgery is not surprising. Perioperative hypotension and hypoxia are two common precipitants of delirium. Other conditions that can increase risk are acute MI, endocrine dysfunction or metabolic disturbances like hypercalcaemica. And of course alcohol withdrawal gets it own flavour known delirium tremens. There’s a good chart summarising potential causes of delirium and appropriate investigations in a NSW Health handbook called Assessment and Management of People with BPSD.
But to quote Canadian geriatrician Professor Kenneth Rockwood, the most common triggers of delirium are, in this order, drugs, drugs, drugs, infection, infection and drugs, other. I asked Meera Agar and Gideon Caplan to unpack this in more detail, starting with the medications that impair cognition directly.
MEERA AGAR: I think opioids, benzodiazepines, antidepressants, anticonvulsants, I think anything that has a psychoactive effect can contribute.
GIDEON CAPLAN: Many drugs that you don’t think of as psychoactive have anticholinergic effects, and anticholinergic burden of the collection of drugs that people are on is more common in people with delirium, so it’s worth thinking about that as well.
MIC CAVAZZINI: Anticholinergics were next on my list. What are the more common anticholinergics you encounter, and how do you manage when they all start building up?
GIDEON CAPLAN: I mean, there’s a long list of anticholinergic drugs, antihistamines, some antipsychotics, some antidepressants, even common drugs, diuretics, can have a big anticholinergic effect, digoxin, cimetidine, things like that, some that we don’t use very much. But you can see older patients have been on these drugs for years and relatively stable, but then another straw will break the camel’s back, or some other illness will be the straw that breaks the camel’s back, but they’re all adding to the burden of insults to the brain. Now the average patient that comes to geriatrics is on more than five or more drugs.
MEERA AGAR: Yeah, and someone’s put on morphine to control their bone pain, no one realises that they’re also now constipated because they didn’t give them advice about laxatives, and they feel nauseous, so someone adds something else. And then they become a bit confused at night, so someone gives them a sleeping tablet, and then…
MIC CAVAZZINI: The spider-inside-her.
MEERA AGAR: …you’re set for a disaster. And so I think the prescriber of any new medicine has that responsibility to think about the cognitive impacts of their prescribing, and when review should happen. Because I think sometimes we prescribe things and then the review point’s not set, or who’s going to do that, because the medication that was useful a month ago may need to be a lower dose, or a different type of medication because the circumstances have changed.
It’s often cumulative, or when the physiological clearance or metabolism of that drug has changed. And so you may have someone who has been stable on that medication, and someone adds something else, or changes the dose or their renal function or hepatic function changes and that medication becomes a problem.
MIC CAVAZZINI: So yes, are kidney function tests and liver function tests up there in your arsenal?
GIDEON CAPLAN: Mm. Well, if someone presents with delirium, you need to do a broad screen of tests to look for causes of delirium.
MIC CAVAZZINI: It’s first line diagnostics, OK. You’ve already mentioned constipation—constipation is often overlooked. Is it fair to say that in your patients, urinary tract or respiratory tract infections would be the main culprits?
GIDEON CAPLAN: A common culprit, they’re definitely common. When we have done studies, we find most people have at least two causes of delirium that we can identify—and often they’re linked. So it might be that they get a urine infection, and then they stop drinking because they don’t like to pass urine so often, they get dehydrated, and then they might get acute kidney injury, and they get on to a spiral, it’s like dominoes. The first domino then knocks over a whole line of other dominoes, and you have to intervene at multiple points to pick the patient up.
MIC CAVAZZINI: Now, in older patients you might assume stroke to be an obvious medical cause of delirium, but the Society for Geriatric Medicine guidelines, and also the Scottish ones that you pointed me to Meera, say that acute neurological causes are rare, and that brain scans shouldn’t be routinely used to investigate delirium. What are the exceptions to this rule? What presentations would make you consider scans and so on?
MEERA AGAR: So I think if someone has neurological features on their examination, or very specific neurological symptoms that are localising, or they’ve developed a new onset headache, or people who have had cerebrovascular problems before, a history of head trauma. And in the cancer setting, brain metastases is something that we probably think about more commonly, and may have a lower threshold to undertake a scan. And there’s probably another rarer group who have had seizures, I think that probably is the other group that a scan might happen earlier rather than later.
GIDEON CAPLAN: The other group I like to scan is where you can’t identify a cause. If you’ve done the full screen, history, examination, investigations, you can’t find anything else, it’s always worthwhile to do a brain scan.
MEERA AGAR: Often there’s three, four, five precipitants in the one patient, and so once you’ve found the first one you don’t stop looking, you keep looking. And in palliative care it’s always the opioid that gets blamed, and they might be on a stable pain regimen for months, nothing’s changed, their renal function hasn’t changed, but everyone says it’s the opioid caused their delirium. But actually they’re hypercalcemic, and they’ve got new brain metastases, and that gets all missed, because everyone just hones in on “Oh, delirium, that’s caused by that, so we’ll just blame that”.
MIC CAVAZZINI: It’s the go-to answer.
MEERA AGAR: It’s like being a detective. Delirium requires really astute clinicians who don’t go in with assumptions, who do a head to toe assessment, and listen to the clues that a good history and examination with some tailored investigations can provide.***
MIC CAVAZZINI: Many thanks to Meera Agar and Gideon Caplan for guiding me through this story. And most sincerely to Adam Kwok for sharing his experience as a learning tool. We’ll hear how his and Claude’s journey progressed in the next episode, as well as advice on best practice prevention and management of delirium. I’m also very grateful to all the members of the Pomegranate Health editorial group who helped me polish this podcast up for you. They’ve been credited by name at our website, along with all the composers responsible for the great music here. Please go to racp.edu.au/podcast to find piles of supporting material to read, listen and watch. I’m Mic Cavazzini. Until next time.