Hello, my name is Neelima Marupudi. I'm an assistant professor of pediatrics within the Division of Pediatric Critical Care at Comer Children's Hospital at the University of Chicago. I'm very excited to talk to you all about Thrive and the ABCDEF bundle today. I have no disclosures. Every year, millions of Americans survive critical illness, but despite the efforts of their ICU, many are left with ongoing problems. Thrive is the Society of Critical Care Medicine's initiative to provide resources and education for ICU patient survivors and their families related to post-intensive care syndrome. Thrive offers education, resources, and a community to help patient survivors and their families after the ICU so they can better understand how to thrive after a stay in the ICU. The objectives of this presentation are twofold. First, to describe the ABCDEF bundle and its applications in the pediatric intensive care unit, and second, to summarize the current evidence supporting each component of the ABCDEF bundle in pediatrics specifically. We're now at a point where the mortality rate is quite low for patients who get admitted to a pediatric ICU, about four percent, and so we're able to turn from a sole focus on survival to emphasis on this concept of survivorship or how the patient and their family fare not only during their time in the ICU but after discharge as well. This is where the concept of post-intensive care syndrome stems, identifying acquired morbidities in the domains of physical, cognitive, emotional, and social health of the child as well as the family, the parents, and the siblings of the patient. Post-intensive care syndrome occurs in both adults and pediatric patients, but in pediatrics there are almost always primary caregivers who are intimately involved in the patient's care. The experience of hospitalization has a strong impact on the entire family union, including parents and siblings as well as other family members, and any or all of these individuals can experience impacts on their physical, cognitive, emotional, or social health. In order to address the risk of post-intensive care syndrome for patients while they're admitted to the ICU, SCCM created this ABCDEF bundle with each letter standing for a specific step. We'll go through each step in the following slides. As we learn more about the concepts of survivorship and post-intensive care syndrome and their impact on outcomes, we've continued to add more letters to the bundle. So now most people refer to it as the ICU Liberation Collaborative rather than the Alphabet Bundle. ICUliberation.org also has a lot of in-depth information about each of these steps. There's a lot of evidence for each component in adult patients. This slide shows a recent study that had some very impressive results. This was a quality improvement collaborative that looked at the ABCDEF bundle in 15,000 adult patients that were admitted to the ICU. For nearly every outcome, there was a statistically significant improvement when the ABCDEF bundle was implemented. That includes things like decreases in mechanical ventilation duration, incidence of coma, restraint use, pain, delirium, and ICU readmission, as well as overall mortality. But what about in pediatrics? It would be incredible to be able to replicate this study in our patient population, but there's a lot of heterogeneity in pediatric patients in terms of age, development, and diagnosis. ICU units are often mixed. There's typically no separate medical and surgical pediatric ICU. These are all things we need to consider when using the bundle in pediatric populations. So jumping into the actual bundle, the A in the ABCDEF bundle stands for assessment and management of pain. This is the SCCM pain care bundle in adults, and as you read through this slide, you'll see that pretty much all of these things are relevant in pediatrics, but in pediatrics, the pain scale correlates are different. Here we see some of the commonly used validated pain scales for PICU patients. The most important thing isn't which scale you use, but that you choose one that is validated for younger patients. This is a survey from 2014 of PICU clinicians looking at what was generally being done for mechanically ventilated patients, and about 85% of clinicians said that they used a combination of an opioid and a benzodiazepine in these patients, with fentanyl being the most commonly used medication in the United States. What is the issue with opioid use in the PICU? This study looked at opioid analgesia in PICU patients to try to determine which factors influenced excessive opioid use. You can see here that midazolam use was a significant factor for doubling opioid use in pediatric patients. There was also a slight tendency toward using less opioid if using morphine over fentanyl. Our common practice is to start a narcotic infusion, and if the patient is not comfortable, to add in a sedative such as a benzodiazepine. However, looking deeper into the reasons for discomfort may allow us to use other modalities. For example, there are adjuncts that can be used in these patients, including sub-anesthetic ketamine for pain management. Epidurals can be useful in certain groups of patients, such as children with extensive burns or localized post-operative pain. And there are also non-pharmacologic options, such as music therapy, that are being explored. Is there a role for patient-controlled analgesia? In certain patients, absolutely. Adding a PCA as an option for older mechanically ventilated pediatric patients, or even ones that aren't intubated, gives them a sense of control, and it can be a very good option when the goal is to minimize sedation and keep those kids awake during the day, so hopefully they sleep better at night. It's useful in specific populations, and you can collaborate with your pain team to make sure that you target the right patients. And it's all along the general recommendations of an analgo-sedation approach for most of our patients that come into the ICU, where we treat their pain first and then only give them sedation if needed. And we find that oftentimes these patients require far less sedation or even no sedation if their pain is well controlled. In summary, for the letter A in our bundle, assessing pain is the key. For intubated kids, we need to focus on treating the noxious stimuli of the endotracheal tube first, and we no longer assume that every intubated patient needs to be sedated. Typically, these patients do need some type of pain control. Moving on to B in the bundle, it refers to the concept of spontaneous breathing. This slide shows a typical schematic for what a spontaneous breathing trial or extubation readiness protocol looks like. You see if they meet the criteria for an assessment of extubation readiness, and if they do, you perform the test or the screening tool. If they pass, you consult with your team and consider extubation. If they don't pass, you continue ventilatory support until the next screening, and the process continues. Ideally, if the patient doesn't pass, the team will discuss the reasons for failure and may adjust the care plan to optimize the patient for the next screen with the goal of reaching extubation at the earliest possible time. What are the barriers to breathing trials? The staff may have concerns about workload and productivity. For instance, how shift changes can affect the timing of SBTs. There are concerns about patient discomfort and inadvertent extubation during the test, as well as self-extubation when sedation is decreased and a patient becomes more awake and alert. Here it is important to note that studies have shown that decreased sedation and allowing wakefulness and increased mobility of patients has not led to an increased number of accidental extubations. It's also not uncommon for providers to decide to wait one more day or delay the test because of concerns that there might not be adequate coverage during a night shift. At least by having a systematic approach to performing the SBTs, we can try to be on the same page about extubation readiness assessments as a team. This is a secondary analysis coming from the RESTORE trial that focused on the accuracy of extubation readiness tests on the patients enrolled in the trial. These are specific patients with lower respiratory tract disease and what the study found was that patients who had a successful ERT or extubation readiness test had a very high rate of successful extubation without the need to re-intubate. Based on those results, the study recommended that in patients with acute respiratory failure from lower respiratory tract disease, the ERT should be considered at least on a daily basis when the oxygenation index is less than or equal to six. This is another study that looked at ERTs and their potential effect on extubation failures. In this study, the authors found that they could decrease extubation failure rates by three percent without increasing the duration of mechanical ventilation when an ERT protocol was used. The key here, as you can see in the conclusion, is that the initiative needs to be developed by an interprofessional team in order to achieve the greatest success rates and the greatest ease in implementation when used in these PICU patients. To sum up the letter B, these are the key aspects that need to be considered in order to achieve success in extubation. As we just noted, extubation takes a team approach and it's something that we need to talk about on a daily basis, especially in terms of timing. It's also important to have a dedicated respiratory therapist available during rounds so they can review the case, give their opinion, and discuss concerns with other team members. It can be helpful to have extubation rates posted so that all team members are held accountable for their roles in the breathing trials and extubation protocols. Next up is the letter C, which stands for a choice of analgesia and sedation. The goal here is to develop a medication regimen that's minimal and safe, while still effective for managing pain and agitation. This can be hard for a diverse patient population of different ages and behavioral needs. Oversedation can lead to negative consequences like dependence on the sedating drugs, hypersensitivity to pain, increased agitation, delirium, and sleep disturbances, increased time on mechanical ventilation, interference with early mobilization initiatives, and even increases in morbidity and mortality. We started recognizing these effects and discussing them at the patient level more often with increased focus on treating pain first and then addressing sedation if needed. With this approach, centers have shown less use of sedatives, specifically benzodiazepines, which have a direct causal relationship with the development of delirium. The key is to implement goal-directed sedation using a validated tool instead of simply giving these drugs while we wait for the illness to resolve. To do this, we need to have an all-team members on the same page with regard to the sedation goals for each individual patient. In the U.S., the SBS, or state behavioral scale, score is most commonly used for mechanically ventilated patients, while in Europe, the comfort scale is more common. RAS, or the Richmond agitation and sedation scale, is another very commonly used tool that can be used in all patients, not just those who are mechanically ventilated. Again, the important point here is it doesn't necessarily matter which tool you use, just to be sure to use one that's validated and use it consistently. Why is goal-directed sedation important? First, it allows us to use a common language to measure the level of sedation objectively, which minimizes the risk of both under- or over-sedation. By decreasing the risk of over-sedation, we can also potentially reduce the patient's ventilator days, delirium, and other morbidities, and we can facilitate things like early mobilization. By minimizing the risk of under-sedating a patient, we can avoid things like higher energy expenditure, problems with immunomodulation, and the risk of PTSD. In an analgo-sedation strategy, we want to address pain and discomfort first before administering sedatives. Once the patient is sedated, it's going to be more difficult to assess their pain level. Whenever we can, we aim to use one drug to accomplish both pain management and sedation, if appropriate. Opioids and benzodiazepines might be the most commonly used analgo-sedatives in PICU patients, but we try to use them judiciously because of the side effects. One of the biggest problems with using these drugs is that they interfere with sleep patterns and sleep quality, which can have a major bearing on kids' health. For instance, benzodiazepines may help patients fall asleep faster, but the quality of that sleep is severely diminished. Benzodiazepines also are an independent risk factor for the development of PTSD. Benzodiazepines are also an independent risk factor for the development of delirium in kids, as well as adults. Current evidence suggests that alpha-agonists can be very good at replicating natural sleep patterns, which means that patients who take alpha-agonists are potentially more likely to achieve restful, higher quality, more restorative sleep that they need during their recovery. This is a study that looked at alpha-agonists' use for sedation in PICU patients. As you can see on the plots on the right, it favored alpha-agonists in terms of opioid reduction. The top group, or A, is clonidine, and the bottom plot is dexmedetomidine. Both decreased opioid use significantly in these patients. This may also be in part due to their analgesic effects in addition to their sedative effects. Restore trial is the largest randomized trial of sedation in PICU patients. When Restore was initiated, midazolam was still the standard of care, so that's important to note. At the end of the study, they found there was actually no difference between protocolized sedation and usual care in terms of the duration of mechanical ventilation, which was their primary outcome. However, there are some interesting things to take away from this trial. Specifically, when a sedation protocol was used, patients were exposed to opioids for less time, which is very important. They also received fewer different classes of sedatives, so the level of polypharmacy decreased significantly. That's also important for reducing the risk of neurotoxicity that can occur with some of these medications, especially when they're used together. The sandwich trial was a long-awaited multicenter trial in the UK that was just published in August 2021. The objective was to determine if a sedation and ventilator liberation intervention can reduce duration of invasive mechanical ventilation. This was a multicenter stepped wedge randomized clinical trial that included 17 hospital sites and over 8,000 critically ill infants and children who were anticipated to require prolonged mechanical ventilation. The results show that there was a significantly shorter median time to successful extubation for the protocol intervention compared to usual care. However, the difference was between 64.8 hours and 66.2 hours, so the clinical significance of this finding is a bit uncertain. To summarize letter C, we want to use a validated sedation scoring tool to set our daytime and nighttime goals on a patient-by-patient basis, with those goals changing as the patient's health and other needs change. We want to make sure all of our team members are using the same tool and understanding how to use the tool. We aim to treat pain first before targeting sedation for the patient, minimizing or even avoiding benzodiazepines, especially with continuous infusions. Finally, when it comes to dosing, start low and go slow. Next up is D for delirium. Delirium is defined as an acute neurologic dysfunction manifested as an abrupt onset of inattention and other cognitive dysfunction. Inattention is defined here as the inability to direct, sustain, and shift attention. Delirium also causes a decrease in the patient's awareness of their environment and a change in cognition or perception, which includes things like hallucinations, short-term memory problems, or problems with speech and auditory processes. Patients may also have delusions and emotional lability, including increased anxiety levels. This is a flowchart that shows how to assess pediatric patients for delirium. It looks a little complicated, but as we see at the first step, if there's no acute change or fluctuating course of mental status, then we don't need to go any further because that is the key characteristic of delirium. The second step looks for any sign of inattention, which can be more difficult to assess in many patients. Again, if the patient is assessed and inattention is not present, then we can stop. The key points are to use a validated tool like PCAM or CAPD, score objectively, so score as you see the patient not making adjustments for baseline status, and consistently score and discuss those scores every day. This slide shows the CAPD, which is another screening tool that's used in many pediatric ICUs. In the CAPD study, 111 patients were assessed for delirium, showing a prevalence of about 20% in this one center, and the CAPD screening tool showed a very high level of sensitivity at 94% with a specificity of 79% when compared to the gold standard of a psychiatric evaluation. These are some of the risk factors for pediatric delirium from one of the first studies that looked at these factors. They include younger age, mechanical ventilation, developmental delays, and higher levels of sedation. The study also showed the prevalence of delirium in PICU populations is about 25% at any given time. This is a different study that found benzodiazepines were associated with longer duration of delirium and a lower likelihood of ICU discharge in a group of preschool-aged children. Benzodiazepines were also associated with an increased use of mechanical ventilation. There's been a lot of research published over the last few years on pediatric delirium. Here are two incredible studies, one published in 2020 and one in 2021, that show links to health outcomes and development of delirium in the hospitalized child. These studies show that delirium during the ICU stay is associated with a decline in health-related quality of life from baseline to post-discharge follow-up. This is significant because it shows that delirium is a strong contributor to the development of PICS-P. So what do we know so far about delirium in PICU patients? We know delirium is prevalent in children of all ages, including infants and neonates, and the risk factors include younger age, benzodiazepine use, use of physical restraints, and mechanical ventilation. We also know delirium has a negative effect on outcomes in these patients, and we know that pediatric delirium can be very expensive to treat and to deal with in the pediatric ICU setting. We also know that it's important to screen for delirium, not just to diagnose it and treat it, but also because a new diagnosis of delirium often is an indicator that this patient will have a worsening condition in the near future. For example, a new diagnosis of delirium could indicate that the child is developing a serious infection or sepsis. In some ways, delirium may be thought of almost as a fifth vital sign rather than simply a sign that the patient needs additional medication. When it comes to diagnosing delirium, there are several barriers we need to overcome. They include things like workflow, tolerance of a hypoactive state without recognizing it as delirium, an absence of screening, and difficulty establishing an analgo-sedation strategy. Are we using protocols? Are we using consistent language? There also may be a lack of protocol in terms of what to do if the screening is positive. How do we prevent delirium in these patients? We start by focusing on sleep promotion as the primary non-pharmacologic approach. That means optimizing patients' day-night cycles to better support health and better outcomes. Sleep promotion is low-cost, it's easy to implement, and it's necessary for a child's developing brain. What do we do when we have a positive delirium screen? First, we address the possible cause of the delirium. That means we need to consider the differential diagnosis, and to do that we have a couple of well-known mnemonics. Dr. Dre is a really easy one, and it stands for diseases, drug removal, and environmental modifications, all things you should be considering when treating delirium. We want to minimize the risk factors for delirium, which means minimizing the use of benzodiazepines and other medications known to cause delirium, improving the sleep-wake cycle with good sleep hygiene, and performing those extubation readiness tests. We need to collaborate and work as a team consulting with other specialists. There's no strong data supporting the use of an antipsychotic medication to treat pediatric delirium, but studies show that it is relatively safe and can be considered in certain cases when there is extreme agitation or the patient is unsafe. There's less evidence to support its use in hypoactive delirium currently, and more evidence is needed. Moving on to E. Early mobilization is the E part of the ABCDEF bundle. What do we know about the benefits of early mobilization? We know that in general being mobile is good for us, and being immobile is bad, both for physical health and for our emotional state. We also know that early mobilization studies have shown a lot of promising results in terms of lowering length of stay, lowering costs, and improving or maintaining strength. Ideally, we want to transition from a culture of immobility to a culture of early mobility. One of the top barriers to achieving early mobilization is multidisciplinary engagement. Nursing staff and therapists worry that getting children out of bed will be labor-intensive, and there's often not a lot of direction on how to accomplish early mobilization safely. One of the reasons why early mobilization is important is because we know that weak patients tend to have worse outcomes. Studies show weak adult patients have longer durations of mechanical ventilation and longer hospital and ICU stays, and they're less likely to go home after their hospitalization. They're more likely to need to be re-intubated and to have delays in rehabilitation, and they have a higher rate of hospital mortality. They also tend to have a prolonged impairment in their quality of life and physical function. This is the Pick You Up Study Protocol for Early Rehabilitation and Progressive Mobility. It's a multidisciplinary structured program that's integrated into the patient's routine care, and its goal is to get everyone on the same page in terms of what do we need to do to increase a patient's mobility levels. A key point is that mobility is a spectrum, so different patients will have different goals based on their premorbid condition and their critical illness. So patients can be included in the early stages of their illness and participate more and more as they recover from their critical illness. The aims of the Pick You Up Protocol are to provide a standardized mechanism that can be used to increase a patient's activity level and to improve patient outcomes in terms of decreasing duration of mechanical ventilation, decreasing mobility associated complications, and decreasing ICU and hospital length of stay. These are the results of the Pick You Up Study, and you can see that over 737 pick you ICU days, there were zero adverse events and endotracheal tube ambulation increased from zero to 10%. The investigators have demonstrated the safety and feasibility of the Pick You Up Mobility Program, which integrates sleep promotion, delirium prevention, sedation optimization as a bundle to increase mobilization. However, the generalizability and broader impact on patient and family centered outcomes is still unknown, and that is the aim of the next step, which is a multicenter stepped wedge trial that is getting underway. The overall objective of this research is to determine the impact of a multidisciplinary and multifaceted early mobility program on clinical outcomes and ICU acquired morbidities in critically ill children. Additionally, the investigators will also look at barriers and facilitators to high performance bundle adoption. To summarize the E part of ABCDEF, early mobility is safe and feasible in the Pick You setting. We need to remember that mobility is a spectrum and the goal should be established based on individual patient factors. Early mobility is multidisciplinary, and we need to engage the physical therapists, occupational therapists early on. We also need to optimize those day night cycles to make sure patients are getting the rest they need so they can be more mobile during the day. Finally, early mobility in Pick You populations is still relatively new, which means we're still looking at outcomes in these patients. Finally, the F of the ABCDEF bundle is the family component. The goal of patient and family centered care is to keep the patient and the family members informed, to involve them in decision-making, and to keep them actively involved in self-management. We want to be sure to give them physical and emotional support and to make sure we have a clear understanding of the patient's and family's concepts of illness, as well as their cultural beliefs. These are some simple ways to increase family engagement in the Pick You. We need to provide brochures or other materials and resources to help family members understand how they can help the patient. Some of the things they can do include talking quietly and calmly with the patient, bringing in sensory aids like glasses or hearing aids if the patient uses them, helping to reorient the patient, participating in mobilizing the patient, decorating the room with objects that remind the patient of home, and talking to the patient about family members. ICU diaries can also play an important role in family engagement. In adult studies, ICU diaries have helped decrease the incidence of PTSD following an ICU stay by 60%. Diaries can contain things like photographs of the patient, the care team, and the ICU itself, notes about significant milestones, entries by staff and family members, and other information that can help provide both patients and their families with an ongoing record of the ICU stay. You can develop your own templates or find templates online and download them. To sum up, there are still a lot of barriers to pulling together the ABCDEF bundle in the pediatric ICU, but the first step is to gather the team members to talk about what's working, what's not, and what goals need to be set for improvement. It's got to be a multidisciplinary effort. We need to make sure that all of our team members are speaking the same language before we can really optimize patient care. It's important to start slowly and build our effort over time, pushing the envelope safely with that multidisciplinary team buy-in. Right before this recording, a pediatric guideline task force released the 2022 Society of Critical Care Medicine clinical practice guidelines on prevention and management of pain, agitation, neuromuscular blockade, and delirium in critically ill pediatric patients with consideration of the ICU environment and early mobility. I hope you'll all take time to read this published guideline and implement it into your daily patient care. Thank you so much for your time.

Thrive initiative

ABCDEF bundle

pediatric intensive care

post-intensive care syndrome

pain management

family engagement

multidisciplinary collaboration