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Take a look at a selection of our recent media coverage:
9th September 2024
Reena Mehta, a consultant pharmacist in critical care at King’s College Hospital, London, UK, has become the first pharmacist appointed as chair of the Intensive Care Society’s Learning division. She talks to Katherine Price about bringing a different perspective to the role, ensuring diverse and multidisciplinary education opportunities for the critical care community in order to deliver the highest quality of care to the sickest of patients in hospitals.
It was the variety of the sector that attracted Reena Mehta to pharmacy, and the team dynamic that led her to settle within the hospital environment. Invited to train as a critical care pharmacist, which at the time there weren’t many of at King’s College Hospital in London, it turned out to be an ideal fit.
‘Within weeks, I found my love for critical care and passion of watching patients recover from being incredibly sick,’ she explains. ‘There are lots of challenges and lots of rewards as well, and you can use your expertise as a pharmacist to think outside the box in a different way around medicines safety and optimising therapy.’
When she started working in critical care at King’s in 2007, it had 32 beds across two intensive care units (ICUs), two pharmacists and a paper-based system. It’s now grown to have 107 beds, a team of 10 pharmacy staff and digital systems.
Reena was promoted to a newly created post as a consultant pharmacist in critical care in 2020 – one of just 10 in the UK. It’s a varied role, she explains, with clinical responsibilities centred around supporting her team and service with complex queries, as well as strategic thinking around delivery of an effective pharmacy service to critically ill patients.
She also has a key role in research, including being a principal investigator on several NIHR Clinical Research Network portfolio studies and supporting colleagues – ‘not just pharmacists, but medical and nursing staff as well’, she clarifies. The role also extends to working collaboratively with local and national stakeholders and acting as a role model, providing specialist input and expert advice in critical care.
Having been a pharmacy representative with the Intensive Care Society since 2019, and chair of its Pharmacy Professional Advisory Group (PAG) for the last three years, despite some apprehension, she put herself forward for chair of the Learning division when the position became vacant earlier this year. She was subsequently elected the first non-medical chair for the Learning division and education committee in the society’s 54-year history.
Reena’s remit includes exploring new training opportunities for the multidisciplinary intensive care community, including organising content for study days. She has already reached out to members for feedback on how these days are run, what they want to see and what could be done differently as study budgets get tighter for attendees.
Her priority is making these events as engaging as possible for a multiprofessional audience and she is keen to work on more collaborative study days with other professional bodies. ‘Critical care is a team sport,’ she explains. ‘Each day you’ll go on ward rounds as part of a multidisciplinary team, so it’s important you work with them inside the four walls, as well as outside.’
Reena is also charged with exploring course accreditation opportunities and chairing the Intensive Care Society’s education committee, ensuring voices from across the intensive care field are heard. And while she may have initially felt like a bit of an outsider, she’s already noticing what her pharmacy perspective can offer by asking diverse questions and proposing different topics and speakers for study days.
‘You have that feeling that everything you know, others will know. You don’t realise what potential you have and what you can give until you work outside your boundary,’ she says.
The Intensive Care Society role is also benefiting Reena professionally, making her think outside of the pharmacy box, establish new relationships and networks, and push herself beyond her comfort zone. ‘And at the end of the day, all of this is to provide critically ill patients the best and optimal care. It’s being able to reach out further than the four walls that you work within all the time,’ she says.
Reena’s term as the chair of the Learning division will depend on whether she is re-elected to the Intensive Care Society council or continues to act as chair of the pharmacy PAG. Longer-term, she is keen to work closely with the Intensive Care Society and, if opportunities arise, to work towards applying for a role on the Trustee Board, ‘because, again, they’ve never had a pharmacist and we bring a different perspective due to our training and skill set’, she says.
Balancing these external leadership roles with her clinical work is a top priority for Reena as being a critical care pharmacist remains her passion. ‘I need to ensure all my other roles are worked around my clinical commitment to the patients. At the end, it all comes down to patient care, it’s what we’re there to do,’ she says. ‘I’m still a clinical pharmacist, that’s one thing I don’t want to lose.’
Since the Covid-19 pandemic, shortages of critical care beds in the UK are high on the national agenda, and Reena is in the process of publishing a paper reviewing the geographical disparities in adult intensive care beds per capita in the NHS in England as part of her recently completed MSc in Health Economics, Policy and Management at the London School of Economics and Political Science.
Medicines shortages, meanwhile, are ‘probably going to get worse before they get better’, she says, and this is an issue the Intensive Care Society is ‘very aware’ of and is exploring ways to support hospitals, especially smaller hospitals where fewer resources are available. ‘This is adding a lot of pressure on pharmacy staff to source alternatives and we need the Government to help stabilise the situation,’ she says.
Reena also sees opportunities in patient rehabilitation post-critical illness, such as addressing inappropriate medicines continuation and discontinuation. To address such challenges will require a well-resourced, well-trained workforce, and Reena was involved in the NHS Adult Critical Care Pharmacy Workforce Strategy, part of which, she says, was highlighting the importance of the whole critical care pharmacy team and utilising each skill set efficiently.
‘Within the ICU, having the correct skill mix among the workforce will help release nursing time. We need nurses to spend their time at the bedside, having direct patient contact and not putting drugs away, emptying bed pans, ordering medication, et cetera,’ Reena explains. She also emphasises that there are ‘many roles within the pharmacy workforce’ that can support with the shortage of nurses being seen in the UK and elsewhere in Europe.
As for training, the Royal Pharmaceutical Society and UK Clinical Pharmacy Association have published an advanced pharmacist critical care curriculum. And, since April, NHS England is funding training places for pharmacy staff working in adult critical care units. This is something that Reena says will transform patient care for the better.
‘A hundred pharmacists in the country are now enrolled on this first course, which means we will get pharmacists in a year’s time coming out that will all be pretty much trained up to the same level, which is so important, because a big problem we have in critical care pharmacy is a lack of standardised training,’ says Reena. ‘[It’s] making sure we’re able to train the workforce to a certain level so that every patient gets the same care in whichever ICU they are admitted to.’
20th June 2024
Speaking at Hospital Healthcare Europe’s Clinical Excellence in Respiratory Care event, our panel of three experts considered the role of critical care in respiratory medicine. Dr Andrew Chadwick, Jane Scullion and Dr Phyllis Murphie PhD discussed how guidelines and best practice for treating respiratory patients in critical care have changed since the advent of non-invasive ventilation, as well as the lasting impact of the Covid-19 pandemic in this field.
With increasing use of non-invasive ventilation over the past 30 years, not to mention the wide-reaching impact of the Covid-19 pandemic, respiratory critical care has seen its fair share of change in best practice, which three Clinical Excellence event panellists know all too well.
Dr Andrew Chadwick is a respiratory and critical care consultant at Oxford University Hospital NHS Trust, where he is part of the nationally recognised special airways clinic. He reviews over 300 severe asthma, chronic cough and complex breathlessness patients each year and has a vast experience in critical care, as well as a self-professed love of non-invasive ventilation (NIV).
Independent consultant respiratory nurse Jane Scullion spent many years working at Glenfield Hospital, part of the University Hospitals of Leicester NHS Trust, across the TB service, asthma clinics, COPD services and interstitial lung disease clinics. In her early career, she was heavily involved in critical care and NIV on respiratory wards and, more recently, has worked in medical negligence and long Covid clinics.
Dr Phyllis Murphie PhD is an independent respiratory nurse consultant working in Dumfries and Galloway in Scotland. She specialises in sleep medicine and NIV, having introduced the NIV service into her hospital many years ago. In 2020, she led a respiratory nursing team through the Covid-19 pandemic and introduced changes to ensure the effective delivery of respiratory care during this challenging time.
Chaired by Garry McDonald, respiratory pharmacist at University Hospital Crosshouse in Scotland, the panel consider the trajectory of guidelines for managing respiratory failure, their take on ensuring patients respond well to NIV, and key learnings from the Covid-19 pandemic that are still in use at their hospitals today – including the somewhat divisive proning technique.
Dr Chadwick: It is fascinating how our mechanisms of treating respiratory failure have changed or haven’t changed and how we got here. If we wind our brains back, NIV starts getting developed in the late 80s and it starts to be used at home. It was late in the 90s when it exploded onto the scene in hospitals, with the work out of Leeds from Plant showing the staggering effect on COPD exacerbations. Number needed to treat: three to save a life. This is eye watering, it’s fabulous.
Then there is a real push in the early noughties of how far can we push these machines? What can we do? What works and what doesn’t? Then, you start getting a mixed signal in true acute respiratory failure. The narrative starts becoming: are we overusing this? Are we delaying intubation? Are we holding back, holding the patient in a period of risk?
There was a bit of controversy about it, and that built. Then, in 2020, a systematic review in JAMA pointed out that there are lots of small studies, put them all together, and what you start getting is a real signal of benefit of delaying intubating, a signal of benefit of saving life, and that helps us go forward.
Then Covid comes. A real challenge came out about are we sure we have got this right? And you had University College London at the start of this – we copied them in Oxford – saying, let’s hold people on continuous positive airway pressure (CPAP), let’s try and avoid incubating. Partly because we were worried we were running out of oxygen and I’m sure a lot of other places were too. And then the trial showed that this really does help to avoid intubating.
And now I think we’re left in a real limbo. I hope that gives a sense of where we are now, as I think where we are now is really interesting. If you were to go into the Berlin ARDS definition of guidelines, I think you’d find NIV spoken of in relatively negative terms in respiratory failure, apart from COPD, pulmonary oedema and cardiogenic shock. But I actually think in the real world, with really good data that I’ve hopefully just pinpointed, you find a much more balanced view and indeed a view that’s increasingly going: I wonder if we should hold, hold, hold off intubation.
If you look at the COPD literature, NIV to treat is unbelievably good compared to almost anything else in medicine. Initial trials using a pH of around 7.3 show significant improvements. I think in treating acute respiratory failure, increasingly, NIV can be a really good adjunct. Intubation is clearly the end of the road.
Ms Scullion: I remember the great big machines that you couldn’t carry around, trying to prop them up next to patients to ventilate them to start with. Now, we have lots of small portable devices, not just in a hospital setting, but people with longer-term conditions are also managing at home, especially with the LSAs [Lung Support Assistants] travelling with it.
It has been life transformative. Things do evolve. The nicest thing that came out of Covid was that respiratory proved that we could do the research, could look after the patients and could get results out of it that will alter as time goes on. We didn’t have enough critical care beds and the ordinary nurses with no respiratory background stepped up and did this, as did the doctors on the wards and pharmacists and physios. We ran almost mini high-dependency units wherever we could run them.
Dr Murphie: It’s remarkable, the evolution of the non-invasive ventilation story. From the days of my first job, I came to the consultant, who had two NIV devices in a cupboard and he didn’t know what to do with them. So, he said, ‘Phyllis, do you think you could arrange some training’, so it started from there.
When these devices were retired, we moved up to the next version, and then the next version, so the whole evolution of the devices that we used in secondary care, particularly during Covid, was a very steep learning curve for a lot of people because we had to do this outside of critical care in the wards.
Covid was the beginning of respiratory support units evolving. We spent hours and hours training all the staff to come in and be able to manage ward-based CPAP and NIV quite safely. For me, NIV really came of age at that point in time in terms of people’s understanding of it, when to use it and when not to use it.
Ms Scullion: It is really difficult when you have a patient in extremis, and you are going to put something onto the face. It is difficult when patients are really ill – you have to have a lot of time to get them to accept things.
I have often thought that as part of pulmonary rehab, especially with COPD patients, we should take these things in before people need them so they can see them and get used to it and feel what it is like because you can’t make a rational decision when you are extremely ill. We know some patients won’t tolerate it although a lot do. It can be uncomfortable, it dries your mucosa and there are all the other side effects. So, it is time and patience.
Dr Murphie: Something that is really important is knowing how to mask fit properly. Being able to make sure they have got the right size mask on, because then you start getting pressure sores and things on the nose. Fitting the masks and making sure that people know how to fit them properly and not do harm is a really important skill to learn as well.
It takes a certain level of skill to acclimatise your patient onto the therapy. You have to be patient, work out the fears and talk them through it. Sometimes, you have to start with the sub-optimal measures to get them comfortable and confident enough to wear the mask. You give them reassurance that this is something that works really well; it could shorten the length of time they are in the hospital and make the other therapies work better as well.
Dr Chadwick: This is one of those times when you really need to add in all your confidence, and you need to get the patient to buy into it. Don’t underestimate the power of reassurance and the power we have as healthcare professionals to do that.
So, coming in, being reassuring and then asking for one hour of NIV and really trying it. Then you can judge the blood gas, and you can go back to them and their family, and say, ‘look, we really tried, but we’re not winning with this, so let’s not’.
Or you can say, ‘Actually, look, we have really made a big progress; our pH has jumped from 7.1 to 7.15, so that’s a huge difference’. Then suddenly, you are in a new conversation saying, ‘well, actually, I’ve got physiological proof that this works for you, so work with me. This is going to be brilliant’.
Dr Murphie: Having outreach teams is really important. Making sure that we can talk to the teams in, say, the combined assessment unit. They want to see patients early. If they are starting to struggle, and you can see that their blood gases are going off, then we want to know early on.
Getting in early and trying to work with the patient to reassure them that there is something worth trying to see if they can feel better. They can turn a clock back very quickly and start to see improvements if it is applied early enough and not too late.
Dr Chadwick: You just jumped onto one of my pet peeves. Number needed to treat is unbelievably good – better than almost everything else in medicine. Increasingly, what you are seeing is drift in all of us, in every clinical practice, we are just holding it back later when the patient is sicker. Early is better. You get in there early and stop the hypercapnia, if that’s what you’re doing with NIV. It’s much easier than coming in when they are really down the line. It’s a real pet peeve of mine: what are we doing holding back? There is a kind of odd culture of holding NIV back.
Ms Scullion: The acceptance of patients is better if they are not confused and not fighting it and not agitated and not desperately ill. That has to be the best option to do it as soon as possible.
We want to do the best for the patients in front of us, and sometimes NIV is the best treatment that you can give, and it stops a lot of other things. Our patients nowadays do get fully ventilated and do get off ventilators, but not in great numbers.
A lot of them do poorly, and it is not a terribly nice prognosis at the end for the family to cope with. So, NIV, for me, is a nicer option because the patient is still in the room with their loved ones.
Ms Scullion: I was so proud of the respiratory community during Covid because we had to get on with it. A lot of the decisions were made by clinicians. We did for patients what we could and everybody – across the board, pharmacists, physios, put their shoulder to the wheel and did it. Even in patients when we were proning, and things like that, you know there were 10 or 12 people proning a patient.
I mean, proning was something where, if you can say, good came out of Covid because it worked. It’s probably quite an old technique. I’ve seen the pictures of the old machines where people were turned in the machines and had a mirror so they could see up or a mirror that could see down. So, it has been around for a long time and often, just because it’s old, doesn’t mean it’s not good.
Dr Chadwick: It is perceived as an old trial. I was working out in Paris briefly on a long placement and they, honestly, were flabbergasted pre-Covid that we don’t just prone everybody. And in England, the problem is – and this is common across units and there’s no judgement because these are world-class British units – but we would always say things like, ‘oh, it’s not safe, you might dislodge, you might do something’. And you’re absolutely right, Covid put that all to the wind.
Work done by people like UCL really nudged the needle back to say, ‘come on now, prone them, it really works. It buys you space to ventilate them kindly and keep within those safe parameters’. So, you’re absolutely right, Jane, it’s another fabulous example of where real positives came out of Covid and essentially just reset that needle and how we treat acute respiratory failure.
Dr Murphie: We had the Army logistics teams come in and they basically organised and changed the flow of the hospital. Dumfries and Galloway is a brand new hospital with all single rooms, which was fantastic. The air changes in each single room six times per hour, so we actually really didn’t have a huge amount of in hospital transmission.
We moved the respiratory ward right along to the other end of the hospital so we were very close to the combined assessment unit. When patients were being moved, there was a green flow and we had a red flow. The green flow was the clean way to go and the red for the contaminated way. So, that really changed the way in which we actually managed patients in the hospital and we had a command control structure that did work really, really well in that environment and it served a purpose at that particular time and helped us to think about how we carry on and give safe care in the really, really difficult place that we were all working.
And that brings me to the point about MDT working. It was fantastic. Every morning, at nine o’clock on the ward, we would have a huddle and every single discipline was there to actually be involved in everything that we needed to do that day with the patients.
For me, the shining stars were the physios and the occupational therapists (OTs). They were so good at trying to get people on their feet. Anybody who had been in critical care and had been ventilated, they’d lost so much of their muscle tone, health, you name it. And the physios and the OTs got them back on their feet and got them home again and it really did shine a light on how great our MDT colleagues are.
Dr Chadwick: We had loads of colleagues, like our vascular surgeons, who came and said, ‘we’re here to help’. The way our respiratory MDT started setting up was that we gave them a physio to lead them as a proning team. There’s this wonderful image of Annika who’s an amazing physio and quite a petite lady, and these six quite bulky vascular surgeons turning this patient. But they learned very quickly that the rules were you just do what Anika says to the letter. It was serious because you’re turning someone on a ventilator – you can really muck it up – but it was really wonderful to watch.
Exactly as you describe, Phyllis, it was fabulous MDT working. And that’s actually stayed with us in Oxford: to this day: we do a lot more proning and our physios still run our proning teams, not our doctors. We’ve decided that they do a better job, and therefore that’s very much left with them. Whoever’s there doing the proning, be that a consultant or whoever it is, that doesn’t matter as in that moment, the physio is in charge. We listen to them, we do what we’re told and we prone very safely.
I think acute respiratory failure is just a lovely example of a bit of medicine where the MDT does make it all work. If you took any one cog away, all of it falls away.
25th May 2023
Stephen Taylor PhD is a critical care and research dietitian based in the ICU department at Southmead Hospital, North Bristol NHS Trust. He has spent many years exploring the use of enteral feeding and more recently on optimising the insertion of feeding tubes, which he stresses should be deemed a specialist rather than routine procedure based on the associated high level of risk.
With around 6% of hospital patients requiring invasive nutritional support, particularly with nasogastric feeding, tube insertion has become a relatively common intervention.
This, according to Stephen Taylor PhD, critical care and research dietitian at Southmead Hospital, North Bristol NHS Trust, means that the procedure is deemed to be of low risk, which is simply not the case. ‘Most people don’t realise that placing a nasogastric tube, the easiest to do, has about the same morbidity and mortality as a tracheotomy,’ he says.
Dr Taylor believes that in an ideal world, there should be small teams and who are ‘expertly trained in guided tube placements, either electromagnetic, direct vision or both.’
Interestingly, he cites published data showing that centres with a low use of electromagnetic tube placement have ‘a worse rate of undetected misplacement than blind placement’. However, the overall use of guided-tube placement results in a lower incidence of pneumothorax than blind placement. This is because in most cases misplacement is detected during placement, when most complications occur.
Unfortunately, regulatory bodies only permit pH and X-ray as the end-of-procedure checks. Despite the success of guided-tube placement, these methods are really only perceived as acceptable ‘add-ons’ that increase the overall procedural costs. But, as Dr Taylor explains, this serves only to discourage clinicians from using them even though these are the only techniques that ‘prevent those lung complications and oesophageal misplacements that would otherwise happen and would only be detected at the very end.’
Evidence from studies where these more sophisticated techniques have been used by untrained hands, ‘has led to major complications’, says Dr Taylor. As a result, rather than mandating high quality training, regulatory authorities have simply suggested that these techniques cannot be relied upon.
So, how does a clinician know if they have inserted a tube correctly? Dr Taylor first highlights the importance of tube tracking. After all, once it ‘hits the greater curvature of the stomach it could then coil back towards the oesophagus’, he says. Hence, without some means of tracking, it is impossible to know the precise location of a tube.
While it seems intuitive and rather obvious that some form of tube tracking is required, Dr Taylor describes how ‘more than 95% of tubes in most centres are placed blindly’ – that is to say, unguided. Once a tube is placed beyond the mouth or nose, ‘you no longer know where the tube is’, Dr Taylor explains. He adds that although sophisticated tracking devices are available, ‘such devices are used in less than 5% of all the tubes that are placed’.
Although a patient’s response, such as coughing, quickly alerts a clinician that a tube may be traveling down the respiratory tract, there remains uncertainty over the precise location of the tube. In the absence of a tracking system, several end-of-procedure checks are used to help identify tube misplacements, for instance, if a tube has inadvertently entered the thorax, by which time a pneumothorax may have occurred or, at the least, the tube must be re-positioned and re-confirmed,’ Dr Taylor says.
One check, for example, relies on determining the pH of the surrounding fluid. A small amount of fluid is aspirated and the pH checked with the acceptable range – set s anywhere between a pH of 4.0 and 5.5. At his own centre, Dr Taylor and his team use a pH of 4.0 simply because this indicates that the tube is more likely to be within the stomach and not the distal oesophagus where, in practice, the pH might be above 4.0.
An alternative end of procedure check is the use of X-rays, which are deemed the gold standard. Sometimes, clinicians will also use a mid-procedure X-ray check, which allows the operator to identify whether the tube has become lodged in the respiratory tract rather than the alimentary canal.
Although this mid-procedure x-ray has some value, Dr Taylor thinks that a downside to these additional checks, which require movement of the patient to the X-ray room and a slightly higher exposure to radiation, is that it will delay the medication and feeding by hours, sometimes a day.
Another increasingly used mid-procedure check relies on the measurement of carbon dioxide. After insertion of the tube by only 30-35cm, the tube is aspirated to check for CO2 with either colorimetric paper or a meter. If the CO2 reading is high, this is a clear indication that the tube is within the respiratory tract, allowing the operator to withdraw the tube.
Electromagnetic tracking can also be used. This more sophisticated technique allows the operator to visualise the path followed by the tube on a computer screen. Additionally, several direct visual methods are also available.
Currently, pH and chest X-ray checks are the standard practice to prevent undetected misplacements, Dr Taylor confirms.
End-of-procedure checks designed to ensure that a feeding tube has reached its intended location are the only checks mandated and endorsed by regulatory authorities.
Nevertheless, Dr Taylor feels that the focus on detection of tube misplacements ignores a more important problem: the damage that might occur during blind tube placement. ‘Undetected misplacements occurs in only 0.015% of tube placements,’ says Dr Taylor. While these can result in a pneumothorax, pneumonia and even death, they represent a small proportion of tube-related respiratory complications. The current end-of-procedure checks fail to recognise any direct damage from respiratory placement.
Bu comparison, ‘some 1.6% of tubes enter the respiratory tract resulting in 0.49% causing a pneumothorax,’ Dr Taylor says, ‘so 97% of tube-related major complications and/or death. These cannot be prevented by using an end-of-procedure – pH or X-ray – checks because they have already occurred before checking.’ In other words, end-of-procedure checks only ensure that food, water or medications are delivered to the correct location. Such checks cannot identify any trauma caused by insertion of the tube.
Dr Taylor airs concern that in reality most of the risks to patients arise from tube insertion and ‘none of the major bodies have addressed this in their guidelines’.
There is still a need to reduce the level of misplacements, but Dr Taylor believes this will only occur if regulatory bodies accept that risks arise not only from undetected misplacement but also from trauma during respiratory tract misplacement and oesophageal misplacement that pH can fail to detect.
Regulatory authorities need to sanction the use of guided placement by an expert, says Dr Taylor. But this, he adds, would require the regulator to ‘nationally mandate evidence-based guidance and training to attain expertise in guided methods’.
He is hopeful that in future the mid-procedure CO2 screening will become standard, and that guided tube placement will become more common. Drawing a parallel with the insertion of coronary artery stents, which is a guided procedure, he thinks it nonsensical for feeding tubes to be routinely inserted without any such guidance. His hope is for the development of a system that enables direct vision of the tube combined with a tracking system showing the tube’s path.
Though electromagnetic tracking and direct vision have been available for many years, it remains expensive. Dr Taylor thinks that the technology is under-used because the focus of guidelines is on reducing undetected misplacements and not on complications. Nevertheless, while guided techniques are expensive, the costs associated with complications such as a pneumothorax are even higher, and this must be considered.
Finally, Dr Taylor reflects on how for too long the insertion of feeding tubes has become seen as a routine rather than specialist procedure. Consequently, clinical staff remain largely ignorant of the potential risks and complications associated with the procedure and there is an urgent need to change this mindset.
16th January 2023
A diagnostic aid based on polymerase chain reactions (PCR) that uses a 52-pathogen custom array card, has been found to provide both rapid (compared to blood culture) and reliable information on respiratory infections in critically ill, mechanically ventilated children, according to a study by UK researchers.
Respiratory tract infections are responsible for a large number of admissions to paediatric intensive care units. Moreover, an intensive care unit is unique environment and for which clinicians often make decisions to use antibiotics with some degree of diagnostic uncertainty.
This was clearly illustrated in one study of paediatric intensive care unit children, where despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed.
While in many cases respiratory infections are viral in nature, it is necessary to utilise methods such as quantitative PCR, as a diagnostic aid to identify the presenting pathogens.
In fact, a recent study in adults found that multiplex bacterial PCR examination of bronchoalveolar lavage, reduced the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and who were at risk of Gram-negative infection.
In the current study, researchers made use of the TaqMan Array Card (TAC) as a diagnostic aid, which is a microfluidic quantitative PCR system comprising of 384 wells containing pre-aliquoted customised primer and probe combinations.
The aid has been previously shown to be of value in supporting ventilator-associated pneumonia (VAP) diagnosis in adults. Nevertheless, it has not been examined in critically ill children and therefore, the aim of the present study was to assess the utility of TAC to identify bacterial and fungal respiratory pathogens in critically ill children with suspected community acquired pneumonia or VAP.
The study recruited children ≤ 18 years of age who were mechanically ventilated and had commenced or were commencing antimicrobial therapy for a lower respiratory tract infection.
The researchers determined the sensitivity and specificity of TAC to detect bacterial and fungal pathogens causing lower respiratory tract infections and the time to a result provided by TAC compared to standard microbiology cultures.
Secondary objectives included a description of the micro-organisms detected by TAC but not by microbiology culture as well as the impact of TAC on antimicrobial decision-making.
A total of 100 children with a median age of 1.2 years (58% male) were included in the study, of whom 80 had suspected community acquired pneumonia and the remainder had hospital acquired pneumonia.
Bacteria were detected more frequently on TAC compared to microbiology cultures (57% vs 18%, p < 0.001)) and In addition, TAC also identified more fungi (17% vs 2%, p < 0.001).
For the detection of bacterial and fungal species, TAC had a sensitivity of 89.5% (95% CI 66.9 – 98.7) and a specificity of 97.9% (95% CI 97.2 – 98.5).
The median time to obtain a result for the diagnostic aid was 25.8 hours compared to 110.4 hours for microbiological cultures and overall, TAC was significantly quicker for both positive and negative results (p < 0.001).
Finally, consultants reported a change of prescription in 47% of cases based upon TAC results. Antimicrobial therapy duration was reduced or stopped in 26% of children, extended in 16% and the spectrum of treatment was broadened in 17% of cases and reduced in 17%.
The authors concluded that as a diagnostic aid, TAC can be used to reliably detect pathogens quicker than routine culture in critically ill children with suspected lower respiratory tract infections. They also called for future studies to incorporate antimicrobial decision support and economic analysis.
Citation
Clark JA et al. The rapid detection of respiratory pathogens in critically ill children. Crit Care, 2023.
12th December 2022
Increased acetylcholinesterase activity in critically ill patients is associated with an increased risk of being delirious but this does lead to subsequent cognitive impairment following discharge from hospital according to the findings of a prospective study by US researchers.
Delirium is defined as a disturbance of consciousness and cognition that develops over a short period of time (hours to days) and fluctuates over time. Furthermore, it is a common manifestation of acute brain dysfunction in critically ill patients with prevalence as high as 75%. However, more troublesome is the finding from a meta-analysis of 24 studies, which showed how delirium was significantly associated with long-term cognitive decline in both surgical and nonsurgical patients. The causes of delirium remain uncertain although several pro-inflammatory markers have been found to be elevated in critical ill patients with delirium. A widely held hypothesis has proposed that this inflammatory response seen in critically ill patients is regulated by the cholinergic system, resulting from a deficit of acetylcholine (ACh). The cholinesterase enzyme, acetylcholinesterase (AChE), is found primarily found in synapses and red blood cell membranes and cleaves ACh in the synaptic cleft, terminating the transmission of a stimulus. Although the primary neurotransmitter of the cholinergic system is acetylcholine, this cannot be measured directly in clinical settings but the activity of two enzymes, AChE and butyrylcholinesterase (BChE) can be assessed with a decreased activity of the latter, seen in patients with systemic inflammation.
Researchers therefore set out to establish whether there was an association between acute brain dysfunction (i.e., delirium and coma) during critical illness and the activity of these two enzymes as well as if enzyme activity levels were predictive of long-term cognitive impairment, disability, and health-related quality of life in survivors of critical illness. Blood samples were taken on days 1 (study enrolment), 3, 5 and 7 while in the hospital to measure the activity of both enzymes. In addition, patients were assessed for delirium and/or coma twice daily until discharged from the intensive care unit IICU) and then once daily after ICU discharge.
Cholinesterase activity, delirium and cognitive impairment
A total of 272 patients with a median age of 56 (56% male) and a median Sequential Organ Failure Assessment score at enrolment of 8, were included in the analysis. Overall, 15% of the cohort died within the hospital and 23% within 90 days of enrolment.
Measurement showed that a higher AChE enzyme activity level was associated with a higher odd of delirious status on the same day (p = 0.045), but not comatose mental status (p = 0.13). When examining delirium, patients with AChE activity at the 75th percentile compared to those with values at the 25th percentile example, had 64% increased odds of developing delirium (odds ratio, OR = 1.64, 95% CI 1.11 – 2.43, p = 0.045). However, when AChE levels were normalised per gram of haemoglobin (since AChE is found in synapses and on red blood cell membranes), this relationship was no longer significant (OR = 1.20, 95% CI 0.95 – 1.52, P = 0.21).
A further finding was how patients in the 75th percentile of BChE activity, had 44% higher odds of having more days alive without delirium or coma, i.e., indicating less brain dysfunction (OR = 1.44, 95% CI 1.06 – 1.94, p = 0.05). Finally, there was no significant association between any of the cholinesterase enzymes with cognitive impairment, disability, or quality of life after discharge.
The authors concluded that plasma cholinesterase activity was predictive of acute brain dysfunction during critical illness but not long-term impairments. They suggested that future studies need to examine whether cholinergic modulation in selected patients identified by plasma cholinesterase activity, could reduce acute brain dysfunction.
Citation
Hughes CG et al. Association between cholinesterase activity and critical illness brain dysfunction. Crit Care 202
16th September 2022
Vitamin D administration to critical care patients leads to a significant reduction in mortality, the length of stay in critical care and the need for mechanical ventilation according to the findings of a systematic review and meta-analysis by European and Canadian researchers.
Except for rare circumstances such as the complete absence of UV radiation, the human body can synthesise vitamin D. Whilst the vitamin is known to play a role in the regulation of calcium and phosphate levels in circulation, the active metabolite of vitamin D, calcitriol, has been found in vitro to up-regulate different anti-inflammatory pathways.
Furthermore, as dysregulated host immune responses to infection often occur, leading to sepsis, multiple organ failure, and death, vitamin D deficiency appears to be associated with an increased susceptibility of sepsis. In fact, a 2020 meta-analysis suggested that severe vitamin D deficiency may be independently associated with increased mortality in adult patients with sepsis.
Nevertheless, based on the currently available evidence, it seems that correction of a deficiency, through high dose vitamin D administration to critically ill patients does not reduce hospital length of stay, hospital mortality, or 6-month mortality compared to placebo, unless patients had severe deficiency of the vitamin. Despite this, one small trial in 36 patients with COVID-19, did find that high dose (300,000 IU) vitamin D administration to intensive care patients, decreased the length of stay and duration of mechanical ventilation.
Given this uncertainty, for the present study, researchers undertook a systematic review and meta-analysis of clinical outcomes in critically ill patients given vitamin D. They focused on randomised trials that included adults treated within an intensive care unit and for whom vitamin D administration or its metabolite, was provided via either an enteral or parenteral route.
Studies were also required to have a comparator group who received standard care and which reported on the outcomes of interest, i.e., mortality, length of intensive care unit (ICU) and hospital stay or the duration of mechanical ventilation. The primary outcome of interest was overall mortality, whereas secondary outcomes were hospital and ICU length of stay and the duration of mechanical ventilation.
Vitamin D administration and critical care outcomes
A total of 16 studies with 2449 patients were included in the analysis. Only 12 studies included vitamin D deficient patients (i.e., < 30 ng/mL) whereas the remaining 4 studies did not specify a threshold.
In terms of mortality, vitamin D administration was associated with a 22% reduced risk of death compared to placebo (risk ratio, RR = 0.78, 95% CI 0.62 – 0.97, p = 0.03). With respect to ICU length of stay, vitamin D supplementation lead to a mean difference in length of stay (compared to placebo) of 3.13 days (95% CI -5.36 to – 0.89, p = 0.006).
Based on 7 studies, the length of hospital stay was no different to placebo. Finally, vitamin D administration was significantly associated with a reduction in the number days for which patients required mechanical ventilation (mean difference = -5.07 days, 95% CI -7.42 to -2.73, p < 0.0001). There was also an important effect of the route of administration, with parenteral having a more significant effect on mortality compared to the enteral route.
The authors concluded that vitamin D administration may be associated with a lower mortality among critically ill patients. However, they added that since several smaller and inconsistent studies with an inherent risk of bias were included, larger and more definitive trials were needed to support the findings regarding the type of supplementation and specific populations that achieve the greatest benefit.
Citation
Menger J et al. Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials Crit Care 2022
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