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• W2414894688 abstract "Assembled by the American College of Critical Care Medicine and well collaborated over six years, a 20-person task force with expertise developed updated guidelines for management of pain, agitation and delirium (PAD) in adult critically ill patients via reviewing, evaluating, and summarizing over 19 000 references.1 Beyond the regular revision of the “Clinical Practice Guidelines for the Sustained Use of Sedatives and Analgesics in the Critically Ill Adult” published in Critical Care Medicine in 2002,2 PAD guidelines generated valuable changes such as the analgesia-first concept, the light levels of sedation target, and early mobility for delirium prevention. Consequently, it exerted a tremendous effect on ICU physicians who had a thirst for bridging the knowledge gaps in management of PAD, the current highly concerning issues in the clinical practice of analgesia and sedation for critical ill patients. However, it was noted that satisfied answer was not always provided for each of critical questions due to lack of sound evidences. Notably, some statements and recommendations (developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as indicated in PAD guidelines)1 remained controversial because some pivotal supporting trials were inadequately powered and shared significant limitations, which have been considered critically important to reduce the generalizability and the universal adoption of the related interventions.3–5 Therefore, we briefly summarized the valuable contributions and provided our perspective on these controversies in this article. Contribution of PAD guidelines PAD guidelines have developed 32 recommendations and 22 summary statements in four parts related to pain and analgesia, agitation and sedation, delirium, and the related clinical outcomes in adult ICU patients. It was recognized that PAD guidelines determined the problems we currently face, and provide an evidence-based framework for preventing and treating pain, agitation, and delirium in critically ill patients.6 First, it emphasized the fact of that “adult medical, surgical, and trauma ICU patients routinely experience pain, both at rest and with routine ICU care”. Notably, the procedure pain, which should be preemptively treated, was prevalent in adult ICU patients regardless the admission diagnosis. Therefore, routine pain assessment with the most valid and reliable pain scales, the Behavioral Pain Scale (BPS) and the Critical Care Pain Observation Tool (CPOT), was recommended for ICU adult patients who are unable to self-report. Furthermore, PAD guidelines strengthened the analgesia-first concept of our routine sedation practice. On the issue of agitation and sedation, a significant renovation defined maintaining light levels of sedation (Richmond Agitation Sedation Scale (RASS) -2 to 0) in adult ICU patients. This was mainly based on the evidence of a light sedation strategy that prevented mechanically ventilated patients from undergoing unnecessary deep sedation, and was associated with improved clinical outcomes (e.g., shorter duration of mechanical ventilation and a shorter ICU length of stay). A light sedation target is a big step forward to optimize current sedation practice. In addition, compared to “the 2002 guidelines”, delirium was heavily weighted in the PAD guidelines because growing evidence identified delirium as a major health problem that can affect most mechanically ventilated adult ICU patients. It is recommended that early mobility and sleep hygiene will contribute to delirium prevention. And finally, to improve the ICU care quality and patient outcome, it was recommended that “using an interdisciplinary ICU team approach that includes provider education, preprinted and/or computerized protocols and order forms, and quality ICU rounds checklists facilitated the use of PAD management guidelines or protocols in adult ICUs (+1B)”. Overall, PAD guidelines brought new light to there cognition and management of pain, agitation, and delirium.6 Numerous questions, but limited answers in PAD guidelines Based on reviewing and analyzing mountains of references, PAD guidelines raised numerous questions about clinical sedation practice. However, the paired answers were not systematically offered. A big gap between the questions and the answers could be the greatest barrier to PAD guidelines implementation. For pain management, it is well stated that pain is prevalent and routine pain assessment is essential for adequate analgesic treatment in adult ICU patients. However, all current available assessment methods are subjective and depend on patient consciousness. No objective bedside tool has yet been developed for precise pain assessment. Despite their superiority over other tools,7,8 the BPS and CPOT, which were recommended by PAD guidelines, have been identified with marked heterogeneity in their validity and reliability of pain assessment for medical, postoperative, and trauma ICU patients.9,10 Moreover, suggestions and recommendations for pain treatment were characterized with weak (three recommendations with “no recommendation” and three recommendations with grade “2B” or “2C” among all of 11 recommendations), based on low quality of evidence (no evidence for 1, ranked “C” evidences for five, ranked “B” evidences for three and ranked “A” evidences for only two out of all 11 recommendations in pain treatment) and specific rather than global. Additionally, those recommendations with ranked “A” evidences were not adapted for the majority of the ICU population (“item vi. We recommend that either enterally administered gabapentin or carbamazepine, in addition to IV opioids, be considered for treatment of neuropathic pain (+1A)” and “item viii. We provide no recommendation for using a lumbar epidural over parenteral opioids for postoperative analgesia in patients undergoing abdominal aortic aneurysm surgery, due to a lack of benefit of epidural over parenteral opioids in this patient population (0, A)”).1 On the other hand, items from i to v, which are more commonly used analgesic interventions, and provide global rather than specific practical instruction on pain treatment, were inadequately powered (only supported with ranked “C” evidences) due to lack of reliable data from large scale randomized control trials (RCTs). There are numerous suggestions and recommendations, but they are based on low quality evidences, indicating that valid and reliable analgesic regimens remain under developed. A light sedation target was considered as the predominant contribution of PAD guidelines. As previously reported, mechanically ventilated patients were commonly over sedated because of insufficient monitoring of the depth of sedation, frequently non-protocolized administration of sedatives, and even a shortage of nurses.11,12 PAD guidelines strongly recommend maintaining a light rather than a deep level of sedation in adult ICU patients (+1B), which has been associated with improved clinical outcomes.13–15 However, several questions remain to be answered. First, PAD guidelines do not help to determine the indications for light sedation (i.e who would benefit from this strategy). In a report from a current RCT, only 38 (10.8%) out of 352 consecutive admissions with mechanical ventilation were qualified to be assigned into the arm receiving a goal directed light sedation strategy (RASS -2 to +1).16 It implied that a light sedation strategy was only preferred by a specific population of patients such as cases receiving mechanical ventilation with a moderate to low level of ventilator settings, or patients during weaning.15 Another important question is the safety of a light sedation strategy, which remains underinvestigated. Successful implementation of light sedation is highly depended on timely and precise monitoring and adjusting the depth of sedation. However, monitoring the depth of sedation has not been well implemented in our clinical practice, and this is especially true in developing countries with a serious shortage of nurses.17,18 A light sedation strategy could bring about new problems if it was used in an inappropriate way, such as the wrong indications and lack of tight monitoring of the depth of sedation. For instance, Shehabi19 previously reported that delirium was diagnosed in 228 of 354 of patients (64.4%) who were maintained at a target of RASS -2 to +1. A significantly increased duration of mechanical ventilation, length of ICU stay, and mortality were also found in patients with delirium in this prospective, multicenter, cohort study. A protocol of no sedation, an extreme case reported by Stromin in 2010, also showed that the rate of delirium was not reduced, but significantly increased in patients with a no sedation protocol in comparison with patients routinely receiving sedatives (20% vs. 7%, P <0.05).20 In another Shehabi trial comparing early goal directed sedation vs. standard care sedation,16 self-extubation was reported in 2/21 cases receiving early goal-directed sedation, but none in the patients with standard sedation (0/16). We previously reported that over 90% of cases with light sedation or no sedation recalled extreme physical discomfort during their ICU stay after one week being transferred to the wards.17 Inappropriate or suboptimal use of light sedation accounts for at least some of those reported harmful effects. Up to now, however, the incidence, causes, and consequences of inappropriate or suboptimal use of light sedation have not been well investigated. Importantly, little is known about the detrimental effects secondary to inappropriate or suboptimal light sedation induced adverse events such as stress responses. Clarifying this issue will be the cornerstone of successful implementation of light sedation strategies. It is noteworthy that PAD guidelines suggest that sedation strategies using nonbenzodiazepine sedatives (either propofol or dexmedetomidine) may be preferred over sedation with benzodiazepines (either midazolam or lorazepam) to improve clinical outcomes in mechanically ventilated adult ICU patients (+2B, +2 represents weak, “B” means that the quality of evidences for supporting this recommendation is moderate). Inspite of weak recommendation (“2B” means that further research is likely to have an important impact on the confidence in the estimate of the effect and may change the estimate), its influence on ICU physicians has been far beyond the suggestion with grade “+2B”, because it implied against the use benzodiazepine, and particularly midazolam, the most commonly used sedatives for mechanical ventilation. One of the key references driving this suggestion was a trial comparing the impact of lorazepam and propofol on clinical outcomes in mechanically ventilated adult ICU patients.21 In fact, evidence from the lorazepam study has little clinical significance due to its infrequent prescription (not even available in China). The most powerful evidence is the results from the prospective, double-blind, randomized trial conducted in 68 centers comparing the safety and efficacy of dexmedetomidine with midazolam, published by Riker et al in JAMA, 2009.22 This study demonstrated that dexmedetomidine treated patients spent less time on the ventilator, experienced less delirium, and developed fewer adverse effects. As indicated by the results, there was no difference in the percentage of time within the target RASS range (77.3% for the dexmedetomidine group vs. 75.1% for the midazolam group, P=0.18). However, it was noted that open-label midazolam was administered to more dexmedetomidine treated patients on the first study day (105/244 (43%) vs. 37/122 (30%) P=0.02) and during the entire double-blind treatment period (153/244 (63%) vs. 60/122 (49%) P=0.02). Based on these data (the authors did not provide the detailed distribution on the depth of sedation in each arm of this trial), it is a fair bet that 22.7% of the time patients were out of the target RASS range sedation was likely to be lighter than RASS +1 in the dexmedetomidine treated patients, but 24.9% of the time patients were out of the target RASS range sedation was likely to be deeper than RASS -2 in the midazolamtreated patients. In fact, determined by their pharmacological properties, dexmedetomidine based sedation is apt to be light, but midazolam often deeply sedates patients in settings without tight monitoring.23 Therefore, the different depth of sedation could confound the effect of different types of sedatives on the outcomes in this trial. In addition, a meta-analysis that served for this PAD guideline also concluded that benzodiazepines increase the ICU length of stay. However, Riker's data were highly weighted in this meta-analysis. If Riker's data were excluded because of the limitation mentioned above, the pooled effect on the ICU length of stay did not favor the non-benzodiazepines patients. Thus, it is the crucial that the limitations as well as the positive evidence provided by the supporting trials need to be systematically analyzed in order to objectively understand the guidelines. Still worse, the guidelines were incorrectly considered as prescriptive instructions for implementation by a few doctors, specially by those in developing countries. Reasonably, a grade “2B” suggestion indicates that physicians should be cautious about implementing this intervention. Thus, further developments should be considered before the implementation of this intervention. Increasing evidence demonstrates that delirium is closely linked with worse outcomes in critical ill patients.12,19 PAD guidelines systematically state the prevalence, the related risk factors, and the impact on outcome of delirium and report the expert's concerns on this issue to ICU physicians. However, the mechanisms still remain unclear although current research demonstrates that delirium is associated with inflammatory mediator-induced brain injury.24 In addition, nothing has been proven to be effective for the treatment of delirium.25,26 Therefore, suggestions are focused on prevention much more, but less on specific treatments. Conclusions PAD guidelines provide information on management of PAD, which are the biggest challenges in our clinical sedation practice. Almost certainly, they will greatly promote the ICU physician's awareness about the issues in clinical management of analgesia and sedation. However, more answers for questions raised by PAD guidelines are needed to help ICU physicians practice sedation and analgesia better in the future." @default.
• W2414894688 created "2016-06-24" @default.
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• W2414894688 date "2014-12-20" @default.
• W2414894688 modified "2023-09-30" @default.
• W2414894688 title "Questions on the pain, agitation, and delirium practice guidelines for adult critically ill patients" @default.
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