So, I drew the short straw, Brenda Punn couldn't be here today, unfortunately, and I will be speaking to you and doing my best Brenda Punn imitation about ICU delirium in the wake of the COVID-19 pandemic. I have no financial conflicts of interest to disclose and all photos of VA patients were obtained with permission. By the end of this talk, you should have a better understanding of the current prevalence and impacts of ICU delirium, effective management strategies to prevent and treat ICU delirium, and how to overcome barriers to manage delirium in your ICUs. As a refresher, ICU delirium is a clinical syndrome, underlying syndrome, characterized by a change or fluctuation in baseline mental status, inattention, and either disorganized thinking or an altered level of consciousness. The clinical presentation of ICU delirium can vary within and between patients over time. There are three recognized subtypes of ICU delirium, hyperactive, hypoactive, and mixed. Hyperactive delirium is easier to detect since these patients tend to be agitated. By contrast, hypoactive delirium is typically characterized by confusion, lethargy, and apathy, and is often overlooked in critically ill patients. This distinction is important because hypoactive delirium is associated with worse clinical outcomes in patients. The causes of ICU delirium are multifactorial and not well understood, but probable mechanisms include susceptibility of the aging brain, neuroinflammation, hypoxia, neuronal myocondrial dysfunction, systemic inflammation, and neurotransmitter dysregulation. Pre-existing risk factors for ICU delirium include age, hypertension, severity of illness, baseline neurologic dysfunction, and substance abuse. Multiple delirium risk factors include pain, sedative use, especially benzodiazepines, deep sedation, mechanical ventilation, sleep deprivation, immobility, restraint use, and social isolation. ICU delirium is associated with an increase in ICU and hospital length of stay, an increased risk of PICS in ICU survivors, the need for institutionalization on discharge, and increased hospital and long-term mortality. And all of these bad outcomes are associated with higher healthcare and societal costs. Nearly two decades ago, when Wes Ely and colleagues published their seminal article in JAMA to raise awareness about the ICU delirium epidemic, the incidence of ICU delirium in mechanically ventilated patients was greater than 80% and was estimated to be between 20% and 50% in non-mechanically ventilated patients. With increasing utilization of the ICU liberation bundle practices prior to the pandemic, the incidence of ICU delirium in mechanically ventilated patients had decreased to less than 50% in many ICUs. But the onslaught of the pandemic brought a catastrophic reduction in delirium monitoring, prevention, and patient care in the ICU due to organizational issues, a lack of personnel, increased use of benzodiazepines for sedation, and restricted family visitation. This resulted in large numbers of critically ill patients, including both COVID and non-COVID ICU patients, who were deeply sedated, lightly monitored, and cared for in understaffed ICUs where delirium monitoring and prevention became a very low priority. Critically ill COVID-19 patients are at particularly high risk of delirium due to a combination of systemic inflammation, neuroinflammation, and thrombosis related to COVID infections, and the effects of deep sedation strategies, benzodiazepine use, prolonged mechanical ventilation, restraint use, and social isolation in these patients. Estimates of delirium in critically ill COVID patients range from 55% to 84%. COVID patients are also more likely to manifest hyperactive delirium, up to 69%, as compared to non-COVID ICU patients. A study by Brenda Punn and colleagues of over 2,000 adult ICU patients with COVID-19 showed that over 90% of these patients required mechanical ventilation, and 64% of these patients received benzodiazepine infusions for an average of seven days. Over 80% of these patients were in a coma for an average of 10 days, and over 50% were delirious for an average of three days, for a total period of acute brain dysfunction of nearly two weeks. Delirium in compliance with the ICU liberation bundle was also adversely affected. They found that non-benzodiazepine sedation was associated with a 41% lower risk of delirium than with benzodiazepine sedation. Family visitation was associated with a 27% lower risk of delirium, although family visitation, either in person or virtually, occurred only 17% of the time. And bundle compliance across all elements occurred on only one out of every three days for these patients. So what can we do to improve ICU delirium management and outcomes for our patients? We know that routine use of either the CAM ICU or the ICDSC assessment tools improves delirium detection and management in patients. The CAM ICU tool is the most commonly used delirium assessment tool and assesses patients for the three cardinal features of delirium, mental status changes, inattention, and either altered level of consciousness or disorganized thinking. It's important to remember that before you can assess a patient with the CAM ICU tool that you must first assess their sedation level using the RAS tool. If a patient's RAS score is either minus 4 or minus 5, then you're unable to assess that patient for delirium. If patients have all three features of delirium, then they're considered CAM positive for ICU delirium. Traditionally, ICU delirium has been managed with a variety of medications, including sedatives and antipsychotics, along with physical restraints. But we now know from the multicenter MIND-USA trial that antipsychotics don't prevent or treat ICU delirium. They only help to manage the symptoms of delirium. And sedatives, both sedative type and exposure, are actually a risk factor for ICU delirium. Shahabi and colleagues showed that any sedation in the first 48 hours of admission to the ICU increases the risk for subsequent delirium. And the deeper the level of sedation, the higher the risk. For every one-point increase in sedation intensity, the risk of patients subsequently developing ICU delirium increased by 25%. The MENDS and CEDCOM trials both demonstrated that the risk of ICU delirium is higher with benzodiazepine sedation versus non-benzodiazepine sedation, specifically using either propofol or dexamethamidine. Only one large study, the MENDS 2 trial, has compared delirium prevalence with propofol versus dex for sedation, and they found no difference between two groups. A recent systematic review and meta-analysis by Hibati and colleagues did demonstrate a lower incidence of delirium with dex than propofol, but only in cardiothoracic surgery patients. Stevens and colleagues showed that in the COVID CED study, that mechanically ventilated ICU patients with COVID were much more likely to receive benzodiazepines and other sedatives at much higher doses than non-COVID patients. Rusulo and colleagues demonstrated that this approach to sedation in mechanically ventilated COVID ICU patients is associated with over a tenfold increased risk of these patients subsequently developing delirium. Restraints are commonly used to keep delirious patients from pulling out their lines and tubes, but restraints themselves actually increase the incidence of ICU delirium. A variety of other non-pharmacologic evidence-based strategies can significantly reduce the risk of ICU delirium without the need for restraints. These include effective pain management, minimizing sedative use, avoiding delirogenic medications, discontinuing mechanical ventilation as soon as it's feasible, mobilizing patients, including mechanically ventilated patients, and getting them out of bed, removing invasive lines and tubes when they're no longer needed, avoiding restraint use, actively reorienting patients, eliminating sleep, and engaging patients and family members in care processes. The pandemic created a number of unique barriers to performing the ICU liberation bundle and preventing and managing ICU delirium in patients in particular. Work environment barriers included contagion precautions and the use of PPE, increased workload, staffing shortages, and the use of providers with limited critical care training. Social distancing that precludes interprofessional team rounds from occurring at the bedside hampers team communication and reduces family visitation. And drug shortages that lead to the increased use of benzos for sedation. Patient care barriers included reduced pain, sedation, and delirium assessment in these patients, the use of deep sedation, high dose opioids, restraints and paralysis due to fears of isolated patients becoming agitated and pulling out lines and tubes, limited AT and SPT trial, mobilization efforts, and reorienting patients to keep staff out of the room. Severe sleep disruption and social isolation of these patients ensued. In other words, it was the perfect storm of delirogenic conditions for patients. Even as the pandemic is now becoming endemic and COVID related risks to staff and visitors have decreased, many of these delirium management barriers still exist in ICUs. A recent interprofessional survey of SCCM members of their current ICU liberation practices demonstrated that overall compliance with the ICU liberation bundle has significantly decreased since the pandemic. Persistent barriers to bundle implementation include staffing shortages, a lack of bundle education, a lack of staff and leadership buy-in and support for the bundle, and poor team communication. Respondents were also asked where their ICUs currently were with implementing best practices for each bundle element. Only 17% of ICUs had fully implemented delirium management practices. About 40% had partially implemented delirium management practices but had remaining challenges. And 30% hadn't implemented any delirium management practices yet. So how do we overcome these barriers to ICU delirium management? During the pandemic, John Devlin and colleagues published specific strategies for performing the bundle in COVID ICU patients. General strategies included having intensivist-led teams of non-intensivists with just-in-time bundle education for team members, cross-training staff to perform various bundle elements like pad assessments and reorientation mobility efforts, conducting virtual IPT rounds and using bundle scripts and checklists, and involving families virtually in these rounds. Delirium management strategies included recognition that delirium is present in most COVID ICU patients, reassessing the need for deep sedation and paralysis on a daily basis, prioritizing CAM ICU assessments and reorienting patients whenever they're awake, identifying and mitigating delirium risk factors for patients every day, minimizing sleep disruptions at night by clustering patient care activities, and using antipsychotics only to treat the symptoms of delirium. Several organizational characteristics can also improve bundle performance. The most important of these have been shown to be strong leadership at the C-suite level, a robust safety culture, a collaborative work environment, daily interprofessional ICU team rounding using checklists and goal sheets, and integration of the bundle into the electronic health record. So what are some realistic strategies for preventing and treating ICU delirium in the future? Significant progress is being made towards developing reliable, continuous brain function monitors to detect pain, depth of sedation, and delirium in critically ill patients. Personalized sedation strategies are also being developed to mitigate the risk of over-sedation in patients. ICU redesign that focuses on sleep preservation, mobility, and patient and family interactions. And of course, making sure that the ICU liberation bundle is delivered to every single ICU patient every day. We know that ICU liberation can significantly reduce ICU delirium, improve lives, and reduce healthcare costs for our sickest patients. The COVID-19 pandemic has caused major setbacks to bundle performance in ICUs worldwide. But going forward, I am confident that we can accelerate bundle performance in the near future to prevent and treat ICU delirium more effectively. Thank you for your time and attention.

ICU delirium

COVID-19 pandemic

delirium management

sedation

bundle performance