Adult Sepsis Guidelines
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PANDEM Guidelines for Children and Infants
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The PANDEM guidelines evaluate current practices and provide recommendations for management of pain, agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, ICU environment, and early mobility in critically ill infants and children. Host Margaret M. Parker, MD, MCCM, is joined by Heidi A. B. Smith, MD, MSCI, FAAP, to discuss the guidelines. (Smith HA, et al. Ped Crit Care Med. 2022;23:74-110) Dr. Smith is an assistant professor of pediatric critical care and anesthesiology at the Monroe Carell Jr. Children’s Hospital at Vanderbilt.
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Category: PCCM Podcast
Margaret M. Parker, MD, MCCM: Welcome to the Society of Critical Care Medicine’s iCritical Care Podcast. I’m your host, Dr. Margaret Parker. Today, I will be speaking with Heidi A.B. Smith, MD, MSCI, FAAP, on the article “2022 SCCM Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Considerations of the ICU Environment and Early Mobility.” Pediatric PANDEM guidelines is the nickname. This was published in Pediatric Critical Care Medicine in February 2022. To access the full article, visit pccmjournal.org. Dr. Smith is an associate professor of pediatrics and anesthesiology at the Monroe Carell Jr. Children’s Hospital at Vanderbilt. Welcome, Dr. Smith. Do you have any disclosures to report before we start?
Heidi A.B. Smith, MD, MSCI, FAAP: Thank you, Dr. Parker. It’s a pleasure to be here today. My only disclosures are that I currently have NIH funding through NHLBI for a pediatric-specific sedation study.
Dr. Parker: Thank you. Heidi, would you start by talking about why it’s important to have pediatric guidelines on pain, sedation, and delirium?
Dr. Smith: That’s a great question. I was recently reading an article from one of our pediatric colleagues, struggling with how to move forward on implementation of sedation per se in their ICU. This was just after the PAD guidelines came out for adults through SCCM and an appropriate focus on having patients more awake and interactive while they are on mechanical ventilation for adult patients. This team of clinicians were struggling with that in that their toddlers and preschool-aged children, increasing potentially the risk of device removal, etc., as they were having them more alert, so to speak. What is the right alertness for pediatric patients? The question really began: Where do the PAD and the PADIS guidelines put us as pediatricians and pediatric caregivers?
I think that really highlights just one of the numerous, very specific pediatric questions that only we can answer for ourselves. Our patients have such a wide variance of age and ability to communicate, from language and cognitive understanding to social and emotional health and the involvement of family and how that pertains to our patients as well. That’s just an example of the importance of being able to ask these questions for our patients and looking at outcomes that are more relevant to our patient population as well. So the old adage that children are not just small adults and adults aren’t just big kids is so true and will continue to be true. Collaboration is always important. There are some pieces of literature that will always be able to adapt to our various areas of specialty. I think this is an ongoing legacy and it will continue to be necessary to look at pediatric-specific questions and answers.
Dr. Parker: What specifically in the new guidelines do you think provides new insight for the pediatric critical care clinician?
Dr. Smith: One thing that a lot of adult clinicians may be surprised at is the focus on delirium in the guidelines. To many of them that will be somewhat old news. We’ve been doing this for 20 years now. But I think it’s easy to forget that it’s only been in the last decade that we have been able to create and validate reliable tools for the monitoring of delirium at the bedside, we have had an explosion of delirium-specific medical literature in the last seven years speaking to delirium epidemiology, specifically among pediatric patients. From that, we’ve been able to demonstrate that there are specific risk factors for children to develop delirium. Also, delirium is associated with very important outcomes, such as longer time on ventilation, longer time in the ICU, and even mortality.
So to speak that out into reality, it’s not to point out that pediatric caregivers have had a difficult time rationalizing what is delirium and how does it pertain to my patient, I think the guidelines point out the answers to what delirium is, that you can and should assess for delirium at the bedside and that it does matter. That will—I think surprise may be a little too big of a word—but I think it will be an important foundation for many pediatricians and pediatric-specific caregivers to transition their practice at the bedside.
Dr. Parker: There’s been a lot of focus on the use of antipsychotics in the treatment of delirium. How do the guidelines address this in children?
Dr. Smith: This is a really big question. I think this pertains not just to haloperidol and atypical antipsychotics alone but also to the treatment of delirium. I think we all would love to have a magic drug that allows us to sedate as we would need to sedate, to protect a child, to provide adequate ventilation and yet have none of the risks that are associated with those sedatives, including the development and duration of delirium, but that’s not the case. So there has been a lot of focus on use of these drug classes to help decrease those risks and exacerbate acute brain dysfunction. But I think we have to first acknowledge that there have been no significant RCTs for the use of haloperidol or atypical antipsychotics for the management of delirium in pediatric patients.
Furthermore, there’s no FDA approval currently for use of these agents for delirium in pediatric patients. While there’s obviously adult literature from the New England Journal of Medicine, where Gerard and colleagues demonstrated that there was not a significant difference in delirium duration in adult patients with delirium who received haloperidol or ziprasidone versus placebo, it still comes around, and the guidelines at least address to some extent: Is there a place for these medications in pediatrics?
Although there is some literature regarding safety in that there are case reports and case series, some retrospective studies and also some smaller prospective studies in pediatrics using atypical antipsychotics and haloperidol with delirium manifestations, we believe that use of these drugs should be limited to those patients with severe manifestations. What do I mean by that? When we speak about patients with delirium, all patients with delirium will have those core features. Specifically, you hear us talk about inattention and acute fluctuation or change from baseline mental status, but each patient may differ with how they manifest acute brain dysfunction depending on if their excitatory or their inhibitory neurotransmitter systems are more dysregulated. That’s why you see patients who might have hyperactive delirium or seem more agitated or combative versus patients with hypoactive delirium who may seem more somnolent or just not quite engaged with family as normal.
These are the patients where the parents will say, This child is just not my child, something is not quite right, but we don’t see that as being abnormal. It is really more of those manifestations when they become severe on those continuums, where we are thinking about use potentially, in particular, of some atypical antipsychotics. There are also a lot of reports specifically using these drugs as a means to improve sleep-wake cycle disturbances that also can exacerbate delirium. Also, is there a place to use those drugs, particularly when, let’s say, the agitation, that manifestation of delirium, is requiring something in order to prevent further harm, like a child pulling their breathing tube out.
So if you’re going to have to use something, is it better to use, let’s say, haloperidol versus a sedative. I know I’m kind of hem-hawing around the answer—but the guidelines at least provide some construct to say, look, when there are severe manifestations of delirium, we think that this is still an important consideration to think of this drug class, recognizing that just further sedating these patients may actually make their delirium and thus their agitation even worse. But there clearly has to be much more research in this area and therefore the guidelines can’t provide much more direction than that at this time.
Dr. Parker: The ICU Liberation Bundle is geared toward the implementation of the A-to-F Bundle that helps engage the medical team to discuss sedation and pain management in the setting of weaning ventilation, avoiding delirium, mobilizing patients, and involving family. What are some issues regarding sedation that these guidelines address?
Dr. Smith: I think that the guidelines in many ways pointed out to many of us what we didn’t know. We recognize that there’s a need to provide anxiolysis and comfort to our patients. That’s a necessity, right? But the time of sedating in this belief that it alone prevents trauma or prevents memories of the ICU experience, that time has really come to a close. So, this is where it is in between where we think that there is a goal. There is a focus on allowing these patients to be more awake, more alert, decreasing that exposure to sedation with risks of obviously delirium. But on the flip side, we still have to figure out, how do we best get them there, these questions of, where is my patient now? Where do I want them to go? And then how do I get them there? I think the guidelines do a good job of pulling us back to basics and saying, We can ask all these questions, including choice of drug, but because there is not some magic drug out there that we can give without concern of risk, we have to get back to assessing the patient.
The assessment I think is what you’ll see driven throughout the guidelines. Assessment of pain, assessment of sedation, assessment of delirium, assessment of iatrogenic withdrawal syndrome, etc. It is really truly pulling back to being willing to assess the patient, point out what my target level of sedation should be, then trying to lessen drug exposure through those mechanisms. Because again we’re not at the point where we have all of these other creative ways in which to provide anxiolysis without the use of some degree of pharmacologic intervention. The guidelines also, I think, focus on choice of sedation. It’s been highlighted in part due to the work on delirium.
The studies have been at least association studies where we have demonstrated that there’s greater exposure to benzodiazepines associated with delirium. Yet not every patient who receives a benzodiazepine develops delirium. So again there’s this component of risk, risk factors, and thinking about patient-specific therapies, patient-specific sedation. Not every level is right for each patient each day, that will change. So, again, targeting that depth of sedation and then also choice. The guidelines also do support the preferential use of dexmedetomidine as a sedative choice, being safe and efficacious, particularly for postoperative cardiac patients and those undergoing early extubation from operative procedures.
Again, more work needs to be done on, not just dexmedetomidine, but other sedatives as well. One drug doesn’t fit every patient, and that will continue to be an issue for our pediatric patients. Finally, specifically talking about sedation, we try to focus on nonpharmacologic interventions as well, and they may prove to be even more of a benefit in improving satisfaction among our families and family caregivers. I believe there is so much more to the efficacy of nonpharmacologic interventions than either what we’ve studied so far. But I also think it just takes a little bit more effort and sometimes, between the severity of illness, the other issues going on in the ICU, patients coming and going, focusing on those nonpharmacologic pieces can be very difficult. Institutions that implement these strategies in a functional way I think will provide all of us a huge light in being able to, again, combine this nonpharmacologic and pharmacologic balance beam that we have to be on for our pediatric patients.
Dr. Parker: What new approaches to pain management for pediatric patients are addressed in the guidelines?
Dr. Smith: To some degree, the evidence that we are able to talk about in the guidelines focuses on things that we already know we should do but maybe that we don’t always do. That focus is on the nonsteroidal antiinflammatory agents being used as consistent adjuncts for analgesia. Even when you step outside of the ICU, even in the postoperative areas, those combinations of acetaminophen and ibuprofen or ketorolac and opioid, I think again we’re trying to reinitiate those conversations of how do we best provide analgesic regimens that provide great pain control and yet at the same time decrease that overall opioid exposure. The guidelines do focus on that as well. There’s also somewhat of a highlight on, again, sedation and delirium, and that inadequate pain control can manifest obviously often as agitation. If we think of agitation as a symptom, agitation can be a symptom of anxiety, it can be a symptom of pain, and it can be a symptom of delirium. If we think, how are we going to tease those things out, at the end of the day, we always want to make sure that we are treating pain.
Hence we’re coming back around to this reassessment. Assessment of pain on a consistent basis, treatment, and then reassessment, and that reassessment piece is so difficult. I would just take a moment to step back and think about, because these guidelines focus so much on assessment, assessment, assessment, and knowing your patient, it comes back to the bedside nurse. They hold such an important role in patient care and patient throughput and patient outcomes. And yet they are inundated with so many responsibilities at the bedside, from communication to documentation, and then at the end of the day, also trying to take care of the patient. I continue to believe, even though the guidelines obviously don’t specifically touch on this, how important it is to support the nursing role at the bedside and how, as we move forward as a community, that finding ways to better support them in doing either less documentation or having support for other people to document or using more electronic medical record documentation, to where our nurses can spend more time physically at the bedside with the patient, becomes so important. Quickly I had to get that in there.
Dr. Parker: I couldn’t agree with you more.
Dr. Smith: Finally, just as we talked about with sedation, is the importance of nonpharmacologic intervention. Here, we do highlight music therapy and nonnutritive sucking as pieces or adjuncts to pain control or analgesia in our pediatric patients. Obviously our neonatal ICUs have been utilizing nonnutritive sucking for a long time, but once they get to the pediatric ICU, we have so many different age ranges, it may not be a focus for us, but particularly in the cardiac ICU, a huge percentage of those patients are going to be our neonates and our young infants. Again, pulling those normal things that we would normally do for our children if they were at home, it doesn’t matter if they’re at home, they’re sick, they’re in the ICU, or they’re anywhere else, those very native manners in which we provide self-soothing become important. The guidelines do touch on that.
Dr. Parker: We’ve talked about sedation and analgesia, but the management of these often requires the use of opioids and sometimes benzodiazepines, leading to iatrogenic withdrawal. What are the ways in which we can optimize monitoring and or management of iatrogenic withdrawal syndrome?
Dr. Smith: One of the things that came to light as part of our literature reviews and the discussions that the subcommittees had on the task force was a realization during this decade-long journey we had we saw the initiation and the ramped-up use of dexmedetomidine in the ICU. During that time, literature changed, particularly in the withdrawal area, because I think we thought that the use of dexmedetomidine would decrease iatrogenic withdrawal. What we instead saw were patients reported receiving not just benzodiazepines, not just opioids, but also dexmedetomidine. And that it wasn’t “use one, now we don’t have to use the others.” That makes sense, obviously, because each of those drugs has a different reason for using them.
But on the flip side, part of this became the culture and the way we utilize all of these drugs. Withdrawal, even from dexmedetomidine, which I think many of us thought would never cause withdrawal, we began seeing reports of this in the literature, some symptoms very similar to what you would see with opioids or benzodiazepines and would be picked up to some degree using scales such as the WAT-1 as you’re assessing for withdrawal of opiates or benzodiazepines but yet very important distinct features such as hypertension or tachycardia.
Yet another example of how, if we don’t begin to consider tying in choice of drug with the way we use it, our depth of sedation, the question of targeting sedation, if we continue to use any drug in high doses, high exposure, we create a truly iatrogenic complication that we would hope we could begin to influence or change down the road. The guidelines demonstrate and talk about the importance of identifying withdrawal, routinely monitoring for that, particularly in patients who have received opioids, benzodiazepines, among other drug classes, for over a certain period of time or a certain drug exposure. Also, further work needs to be done to recognize whether or not current tools such as the WAT-1 are the best tools to assess for, particularly, alpha-2 agonist withdrawal, such as dexmedetomidine. It really highlights assessment, reassessment, alternating the way in which you utilize sedatives and opiates, and the need to study and validate tools to assess for withdrawal, specifically from dexmedetomidine.
Dr. Parker: The PADIS adult guidelines touched on sleep and immobility. What are some highlights from the optimization of the PICU environment in the pediatric guidelines?
Dr. Smith: One area we were relatively surprised at the lack of pediatric literature was in regard to the optimal use of the family to decrease whatever, meaning decreased need for analgesia, decreased need for sedation, optimizing the sleep-wake cycle, better communication with the medical team, decreased time on mechanical ventilation. We actually thought that there would be more literature out there to support what we already innately felt was a really important piece to pediatric care. We also kind of giggled because when the PAD guidelines for adults initially came out and they talked about the A-to-F bundle, F obviously being family involvement, I think most pediatric caregivers were saying, yeah, of course that’s important.
Yet when you look at the literature, you would think we didn’t already know that. So I think, again, coming back around to—and this was somewhat of the story throughout the guidelines and the work that the task force did—that we, as pediatric caregivers, do so many wonderful things. What we haven’t done consistently, I think, is publish what we’re doing and asking questions in a very strategic way and working together, and it’s gotten better, and it’s getting better.
Nonetheless, I think those things still need to come to the forefront, which is why the guidelines also specifically focus on every single section. From pain to delirium to early mobility, they focus on those questions that we were not able to answer because of the lack of literature. While there is some evidence that family presence does decrease the amount of analgesia and sedation required, it’s still not as robust to be able to give very strong recommendations of the how and in what way to best implement their presence.
The other thing that we wish we could have spoken of more specifically—I think many studies will focus on this moving forward in pediatrics—is the effect and impact of sedation or pain management on, not just delirium, but long-term outcomes such as posttraumatic stress symptoms, both in the child and the family. We’ve had some great data already, but those questions were not focused on in the guidelines. I think the entire task force still feels like those are areas for future consideration.
You asked about sleep and immobility. Coming back around to early mobility and sleep hygiene, I think those are hugely important areas for our ongoing research and study and to utilize those in the ICU. The guidelines were able to at least highlight feasibility and efficacy of early mobility programs in the guidelines, but there are still not enough data to drive a lot of strong recommendations for early mobility as of yet. That’s the same for sleep hygiene. But as a pediatrician, I can only think of nutrition as being as important as exercise and good sleep in healthy children. If that is the case at home, then how can it not impact these patients when they are sick? I think this will become a major frontier and turning point for the ICU environment and how it pertains to our pediatric patients moving forward as well.
Dr. Parker: What recommendations do you have for units or institutions that want to implement the guidelines?
Dr. Smith: We have a very close relationship with the ICU Liberation committee and that initiative through SCCM, trying to operationalize the A-to-F bundle and how different pieces of the guidelines support those specific bundle elements. SCCM has provided a very in-depth and explanatory website, including a specific part for ICU Liberation, which includes both adults and pediatrics. It will identify the areas where there is pediatric-specific support for the various bundle elements, the PANDEM guidelines themselves. We also created a figure that helps to pull in the focus on: How do I assess for each one of these things? In what way should I manage these things? What would be first step, second step? What parts of these have strong versus conditional recommendations? The PANDEM guidelines themselves have some easy way to reflect on the recommendations, and the ICU Liberation website provides an extreme amount of both education and tools in order to implement many of these recommendations from pediatric PANDEM.
Dr. Parker: Thank you very much, Heidi. You’ve given a great overview of the guidelines and the important work that has been done and that has yet to be done. Do you have any final comments you’d like to make?
Dr. Smith: I so appreciate being part of this process. I appreciate all of the hard work that our colleagues did on the task force, those who were able to stay until the end and those who were there for the conception of this guidelines task force. I would continue to encourage people to continue to think about how important assessment and knowing your patient are. I think we all felt that, throughout these guidelines, truly knowing where your patient is now, knowing where you want them to go, and then discussing how to get them there with a very diverse and interdisciplinary team by far will get us down the road farther and get our patients liberated from both mechanical ventilation and the ICU, so keep on keeping on. I so appreciate you all listening today.
Dr. Parker: Thank you very much. This concludes another edition of the iCritical Care Podcast. For the iCritical Care Podcast, I’m Dr. Margaret Parker.
Margaret M. Parker, MD, MCCM, is professor emeritus of pediatrics at Stony Brook University in New York, and is the director of the pediatric intensive care unit (ICU) at Stony Brook University Medical Center. She is a former president of the Society of Critical Care Medicine and currently serves as associate editor of Critical Care Medicine and senior associate editor of Pediatric Critical Care Medicine (PCCM). In her role as associate editor, Dr. Parker conducts interviews with authors of PCCM articles and other pediatric critical care experts. Dr. Parker received her bachelor of science and medical degrees from Brown University. She trained in internal medicine at Roger Williams General Hospital in Providence, Rhode Island, USA, and in critical care at the National Institutes of Health (NIH) in Bethesda, Maryland, USA. She spent 11 years in the Critical Care Medicine Department at the NIH where she was head of the Critical Care Section. In 1991, she accepted a position in the pediatric ICU at Stony Brook University and became the director of the unit, where she served for 27 years.
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