The 2018 Clinical Practice Guideline for the Prevention and Management of Pain, Agitation (Sedation), Delirium, Immobility, and Sleep (Disruption) (PADIS) in adult patients in the ICU addresses new management challenges related to pain, agitation, and delirium and offers guidance on two additional topics—rehabilitation/mobility and sleep (1 , 2). The PADIS guidelines build on the 2013 Society of Critical Care Medicine (SCCM) PAD guidelines (3) and incorporate a number of methodological innovations, including critical illness survivor input from start to finish (4–6). The PADIS methods, with an emphasis on those approaches that are novel, are outlined in a separate methods article (7).
If guideline recommendations and statements are to improve ICU clinical practice, effective knowledge translation and implementation science efforts are critical. Although our goal was to provide specific recommendations for each question, we suspect some guideline readers may be discouraged by the conditional nature of many recommendations and daunted by the breadth of topics discussed. The goals of this accompanying article are to stimulate clinician dialogue, guide the interpretation of the PADIS 2018 recommendations and statements, facilitate implementation and quality improvement (QI) efforts, share strategies for effective bedside application, and provide patient scenarios where application of PADIS recommendations and statements may pose challenges.
HOW TO READ THE GUIDELINE
The PADIS guideline represents a wasted effort unless its recommendations can be easily interpreted, understood, and implemented by practicing ICU clinicians. Although the use of GRADE methodology ensures a systematic and transparent approach (8), the basis for determining the strength and quality of evidence inserts uncertainty since the language used is not typically included in our critical care lexicon. Furthermore, critics justifiably express concerns about involving professionals whose very expertise potentially introduces bias, including intellectual conflicts of interest, in the guideline development effort (9).
So, where does a GRADE-naive ICU clinician begin? The recommendations themselves (see PADIS executive summary) (2) are a good starting point. Each actionable question uses a PICO format (i.e., addresses which patients, intervention, comparator, and outcome are being assessed) and is then answered by a recommendation. These recommendations are intentionally brief and direct. (e.g., “We suggest using propofol as compared to benzodiazepines in mechanically ventilated cardiovascular surgery patients.”) They are meant for clinicians looking simply for bottom-line guidance. Although a strong recommendation is more valuable to clinicians than a condition recommendation, practice guidelines, including PADIS, generally contain far more conditional than strong recommendations. The characteristics of conditional and strong recommendations are compared in Table 1 (10).
After reading the recommendations, clinicians may have many important questions. For example, what factors did the panelists consider when generating the specific recommendation? Why was a conditional recommendation issued rather than a strong one? Why does the recommendation only address a specific population? The answer to some of these questions may be found in the “rationale” section which immediately follows each actionable recommendation (1). Relevant factors are described including a brief review of the evidence and strength, the balance of desirable and undesirable outcomes, and any relevant decision-making factors such as costs/resources, feasibility, subgroup considerations, etc. For most clinicians, the recommendation and rationale, taken together, should provide adequate insight and clarity to allow clinical application. The evidence gap sections describe why a question could not be answered unequivocally (i.e., uncertainty remains) and may be especially helpful for those interested in conducting future research. Finally, supplemental materials (1) (e.g., forest plots, evidence summaries, evidence-to-decision frameworks, and voting results) provide all the data that were considered by the guideline writing committee during its deliberations.
POTENTIAL BARRIERS TO INTERPRETING AND IMPLEMENTING PADIS RECOMMENDATIONS
The successful integration of the PADIS guideline into clinical practice will be heavily dependent on the methods used to disseminate (spread) and implement (effectively integrate) the recommendations (11 , 12). Unfortunately, although guidelines often tell us “what” the right things to do are, they do not often describe “how” to integrate them effectively into everyday practice (13). This is particularly true in the critical care setting where well-designed dissemination and implementation science research remains in its infancy (14). Barriers to PADIS adoption can be identified across each of the five domains of the consolidated framework for implementation research (CFIR) (Table 2) (15–20).
To these CFIR items, we added three others chosen after reflecting on the discordances in local practices reflected by our regional, national, and international guideline expert members. These potential barriers should be proactively discussed at both the hospital/health system and ICU level prior to the initiation of formal implementation efforts. These often difficult and impassioned conversations should involve all key stakeholders (Table 3) and may be enhanced by using a variety of information gathering techniques (one-on-one meetings, anonymous surveys, and facilitated group discussions) (19).
The priority outcomes chosen for each question, many of which occur after ICU discharge (e.g., longer term cognitive dysfunction), may not immediately resonate with ICU clinicians who focus on more traditional outcomes like duration of mechanical ventilation and ICU mortality. In this situation, it may be helpful for those involved in PADIS implementation efforts to initially focus their teaching on the prevalence and consequences of postintensive care syndrome and the importance of family-centered care both during and after the ICU stay (21–23). Institutional buy-in is also important to establish performance metrics and provide needed resources and training to reach and maintain QI goals (including those involving clinical outcomes after discharge) (24 , 25).
OPTIMIZING IMPLEMENTATION SCIENCE STRATEGIES TO MAKE PRACTICE CHANGE
The release of the PADIS guideline will catalyze the integration of the recommendations into clinical practice in many ICUs with different resources, patient populations, and otherwise varied local characteristics. Although many different implementation science strategies can support better recognition of PADIS-related symptoms, clinical bundle development, care reorganization, improved educational efforts, and new financial incentives (26 , 27), none have been shown to be effective for a “holistic” PADIS approach. The Plan-Do-Study-Act model (20) has been successful in delirium and may help accelerate PADIS recommendation adoption (16). Prior large-scale QI efforts (28 , 29) have also found engagement (i.e., attracting and involving appropriate individuals in the implementation process) (17) to be one of the most important predictors of success. Whether comparators of granular data across ICUs to drive and maintain “quality competition” (30), learning frameworks (31), or international knowledge sharing platforms (32) help deliver better quality PADIS-related care remains to be tested.
Implementation leaders may want to begin their efforts by using adoption strategies highlighted in the prior PAD guideline (3) by assessing current practice through walking rounds, case reviews, and staff interviews; reviewing existing PADIS-related policies and procedures; identifying those committees that should be involved in change; performing a gap analysis (what should be done vs what is already being done); evaluating the electronic health record to see what PADIS-related documentation is already in place; and exploring the ICU’s culture to identify why current practice is the way it is (18 , 33). They may also want to consider contacting external change agents such as experts in the field of PADIS, including guideline authors, and the SCCM ICU liberation committee (http://www.iculiberation.org/Pages/default.aspx) with questions they have regarding interpretation or application of the guideline.
Next, both ICU “opinion leaders” (i.e., individuals in the organization who have formal or informal influence on the attitudes and beliefs of their colleagues) and potential PADIS “champions” (individuals who dedicate themselves to supporting, marketing, and leading implementation and overcoming indifference or resistance that the PADIS adoption may provoke in an organization) (17) should be identified and asked if they are willing to take part in the process. If institutional protocols and care bundles exist, these too can be updated and/or built upon to accommodate the new guideline recommendations. It is important to note that there really is no need to “reinvent the wheel.” Many organizations and healthcare systems can provide protocols that address many of the PADIS recommendations. Finally, an implementation plan and methods to monitor progress should be developed. This plan should include the planning, implementation, and evaluation strategies that heighten the likelihood that guideline implementation efforts will be successful (Table 4) (34). Sustaining practice changes over time can be challenging. Benchmark data, continuously collected and publicly posted in the ICU, can be effective (35). The use of daily rounding checklists, goal setting, and clinician prompting should also be considered (36).
APPLICATION OF PADIS RECOMMENDATIONS COMMON ICU PATIENT SCENARIOS NOT EXPLICITLY ADDRESSED IN THE GUIDELINE
Clinical practice guidelines are often criticized because they do not clearly offer management options for common clinical conditions, and if they do, those suggestions are usually vague and lack unequivocal direction. From a guideline development point of view, this is entirely appropriate for topics that are not well studied or have conflicting data reported in the literature. As a result, many clinical scenarios have no proven or even preferred choices to guide management decisions. This section identifies clinical questions specific to each of the five components of the PADIS guideline; they are not meant to be exhaustive in nature. Rather, they are examples of pedagogical problem-solving (37) and should be used by critical care clinicians as examples to further discussion, debate, and application of the guideline recommendations to real-life clinical scenarios.
Pain Section Clinical Questions
How do we evaluate pain when all the components of Behavioral Pain Scales (Critical Care Pain Observation Tool [CPOT] and Behavioral Pain Score [BPS]) are not available for assessment? What guides the choice of pharmacologic and nonpharmacologic pain management interventions in a patient who may not tolerate opioid therapy?
The PADIS guideline advocates that analgesia must take priority over sedation, both to control pain and to avoid sedative overuse. Use of validated behavioral pain tools is preferred to assess pain in ICU patients unable to communicate. Occasionally, patients may be unable to self-report pain and have conditions such as weakness or joint deformations that do not allow assessment of limb movement or muscle tension. As a result, validated tools (BPS or CPOT) cannot be “strictly” applied. In this situation, clinicians may still want to consider facial expression as an indicator of pain. Any changes in behavior or vital signs observed during painful procedures (e.g., suctioning, turning) should also be considered, even if they are not used in recommended tools. Furthermore, physical examinations should be diligently performed to detect and treat complications (e.g., peritonitis, compartment syndrome) before escalating analgesia or sedation.
Although opioids are regarded as the first-line management option for ICU pain in the PADIS guideline, some patients will never require them (38). Although the guidelines conditionally suggest the use of a multimodal approach with adjunctive nonopioids like acetaminophen, low-dose ketamine, or nefopam in an effort to limit opioid exposure and potential adverse events, the evidence to support these recommendations was generally weak, and many ICU subpopulations were not well represented in studies. Conversely, an agent for which there was also sparse evidence but that is part of clinical practice in some centers, IV lidocaine, received a recommendation against its use as safety concerns were highlighted. Choice of adjunctive analgesics will thus depend on availability/cost and the potential for individualized safety concerns: acetaminophen (e.g., hepatotoxicity), ketamine (e.g., hallucinations), nefopam (e.g., tachycardia). Nonpharmacologic interventions (e.g., massage, music therapy) can also be used in a “multimodal approach.” Cold therapy, conditionally recommended before chest tube removal, may also prove useful as a pain reduction strategy for other painful procedures.
Sedation Section Clinical Question
What guides the choice of pharmacotherapy when treating agitation in a patient who is hemodynamically unstable?
Although the PADIS guidelines make specific recommendations regarding sedative approaches and choices, it does not distinguish between pharmacologic treatment options for agitation in hemodynamically stable versus hypotensive patients. Three potential options exist: 1) aggressive analgosedation with synthetic opioids such as fentanyl relieves discomfort and facilitates ambivalence to the environment. Since fentanyl does not cause histamine release, hypotension, should it occur, is likely related to a diminished stress response. High-dose fentanyl carries the risk of serotonin syndrome especially if other serotoninergic agents are administered (39); 2) if greater sedation is required, intermittently administered benzodiazepines on an “as needed” basis may suffice. It should be noted that the association between benzodiazepine use and delirium occurrence is strongest with continuous infusion administration when administered doses are usually greater (40); and 3) sometimes these strategies are not effective, and alternative approaches such as continuously infused propofol or dexmedetomidine may be necessary albeit with clear concern for their adverse effects. Newer use of older agents such as phenobarbital and valproate can be considered in select patients (41).
Delirium Section Clinical Question
What guides the choice of pharmacotherapy for the symptomatic treatment of agitated and nonagitated delirium and do these interventions affect delirium severity and duration?
The PADIS guideline suggests that many critically ill adults screen positive for delirium, but does not provide guidance on pharmacologic treatment options other than haloperidol, an atypical antipsychotic, or a HMG-CoA reductase inhibitor (i.e., a statin) should not be routinely used. Among the sequelae of delirium (1), distress experienced by patients, families, and care providers is one of the most important. Unfortunately, there is a dearth of data on the topic, and as a result, the best pharmacologic intervention to reduce patient stress due to delirium remains unclear (42). In addition, no pharmacologic management option has demonstrated an effect on delirium-related outcomes such as long-term cognitive impairment prevalence, duration of ICU and hospital stay, discharge disposition, or physical and psychologic functionality after hospital discharge.
The removal or reversal of inciting factors remains the mainstay of delirium management in the ICU. For example, benzodiazepines, if they are required, are associated with a dose-dependent increase in a positive delirium screening result; simply reducing exposure may be all that is needed (40). Some intensivists may choose to treat delirium with an antipsychotic, particularly when agitation, not related to pain, is present (43). Antipsychotic choice is guided by patient factors (e.g., gastrointestinal tract accessibility, side effects such as QTc prolongation, etc.). It should be emphasized that there are few supportive data on ICU antipsychotic use and that the initiation of psychoactive medications during critical illness often results their inappropriate continuation after ICU discharge (44 , 45).
Rehabilitation/Mobilization Section Clinical Question
What criteria exist for commencing rehabilitation/mobilization and how should this intervention be safely initiated in complicated critically ill patients who may be hemodynamically unstable and/or delirious?
As conditionally recommended in the PADIS guidelines, rehabilitation/mobilization commenced within a few days of initiating mechanical ventilation (vs later) is safe, feasible, and beneficial (46–49). Mechanical ventilation via an oral endotracheal tube is not a contraindication to rehabilitation/mobilization; indeed, waiting for clinician judgment that the patient is “ready” delays mobilization for up to 5 days and may worsen recovery probability. Patients’ pain, agitation/sedation, and delirium status, as well as cardiovascular and pulmonary status, complete the assessment for rehabilitation/mobilization. Assessing the patient’s capability for in-bed movement after an evaluation of appropriate function, position, and securement of the medical devices such as the endotracheal tube, vascular access, and drains helps guide subsequent rehabilitation/mobilization goals. Communication within the clinical team is important in planning and conducting rehabilitation/mobilization interventions (50). After conducting the above assessments, it may be decided to sit patients on the edge of the bed for 10 minutes to demonstrate stability of their cardiovascular, respiratory, and neurologic systems. Thereafter, patients can be asked to stand next to the bed for around 6 minutes; if they tire, they can be transferred into a bedside chair. The duration of rehabilitation/mobilization interventions should be based upon ongoing patient monitoring given the lack of existing evidence regarding the optimal duration of rehabilitation/mobilization.
Sleep Section Clinical Question
What is the best strategy to encourage sleep in mechanically ventilated patients and is it appropriate to reinitiate home sleeping medications in the ICU, particularly if delirium is present?
As outlined in the guideline, patients who use sleep aids at home are known to be at risk for poor sleep in the ICU; however, many sleep aids such as the benzodiazepine-receptor agonists confer risk in critically ill patients and have not been tested for efficacy in this context (51). The relationship between delirium and poor sleep in the ICU is complex and remains poorly understood (52). All efforts should be made to minimize disruptive interruptions and to create a safe, quiet environment at night conducive to sleep. Delirium management should proceed according to the PADIS guideline. If a sedative infusion is necessary, dexmedetomidine may be preferred from the standpoint of sleep architecture, but evidence suggesting a corresponding improvement in sleep outcomes (e.g., patient-reported sleep quality) is lacking. As noted in the guideline, melatonin is an unproven, low-risk, low-cost option for patients with accessible and functional gastrointestinal tracts. For other sleep disorders such as restless legs syndrome, treatment would have to be considered on a case-by-case basis since both the untreated syndrome and its medical management with dopamine agonists may contribute to agitation. As recommended in the PADIS guideline, nonpharmacologic sleep interventions should be instituted in all ICU patients.
The 2018 PADIS guideline provides the multiprofessional ICU team with important new guidance on how to manage pain, agitation, delirium, immobility, and disrupted sleep in critically ill adults from a patient-centric perspective. It should inspire clinicians to reflect on current practices, identify gaps, and use proven QI strategies to enhance care for critically ill patients. Although the guideline cannot provide definitive answers on all topics judged important by experts and patients/families, it can serve as a comprehensive foundation for discussions on clinical issues that have immediate relevance to patient care. Uncertainties inherent to individual care management should not interfere with QI initiatives that focus on all PADIS domains since they have the potential to enhance the care of the critically ill.
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