Agitation, Delirium, Guidelines, PAD, Sedation



  1. Jablonski, Juliane DNP, RN, CCRN, CCNS
  2. Gray, Jaime PharmD, BCPS
  3. Miano, Todd PharmD, MSCE
  4. Redline, Gretchen PharmD, BCPS
  5. Teufel, Heather PharmD, BCPS
  6. Collins, Tara ACNP, RN
  7. Pascual-Lopez, Jose MD, PhD, FACS
  8. Sylvia, Martha PhD, MBA, RN
  9. Martin, Niels D. MD, FACS, FCCM


Background: Societal guidelines exist for the management of pain, agitation, and delirium (PAD) in critically ill patients. This contemporary practice aims for a more awake and interactive patient. Institutions are challenged to translate the interrelated multivariable concepts of PAD into daily clinical practice and to demonstrate improvement in quality outcomes. An interdisciplinary goal-directed approach shows outcomes in high-acuity surgical critical care during the early stages of implementation.


Methods: This study was a prospective preintervention and postintervention design. A formal PAD clinical practice guideline targeting standardized assessment and "light" levels of sedation was instituted. All mechanically ventilated patients admitted to a 24-bed surgical intensive care unit (ICU) at an academic medical center during a 6-month period were included (3 months before and 3 months after implementation). Sedation and agitation were measured using the Richmond Agitation Sedation Scale (RASS), pain measured using a Behavioral or Numeric Pain Scale (NPS/BPS), and delirium using the Confusion Assessment Method for the Intensive Care Unit. Total ventilator days with exposure to continuous opioid or sedative infusions and total ICU days where the patient received a physical activity session exercising out of bed were recorded.


Results: There were 106 patients (54 at preintervention and 52 at postintervention). Mean percentage of RASS scores between 0 to -1 increased from 38% to 50% postintervention (P < .02). Mean percentage of NPS/BPS scores within the goal range (<5 for BPS and <3 for NPS) remained stable, 86% to 83% (P = .16). There was a decrease in use of continuous narcotic infusions for mechanically ventilated patients. This was reported as mean percentage of total ventilator days with a continuous opioid infusing: 65% before implementation versus 47% after implementation (P < .01). Mean percentage of ICU days with physical activity sessions increased from 24% to 41% (P < .001). Overall mean ventilator-free days and ICU length of stay were 5.4 to 4.5 days (P = .29) and 11.75 to 9.5 days (P = .20), respectively.


Conclusion: Measureable patient outcomes are achievable in the early stages of PAD guideline initiatives and can inform future systems-level organizational change. Pain, agitation, and delirium assessment tools form the foundation for clinical implementation and evaluation. High-acuity surgical critical care patients can achieve more time at goal RASS, decreased ventilator days, and less exposure to continuous opioid infusions, all while maintaining stable analgesia.


Article Content

Sedatives and analgesics are among the most commonly administered medications in mechanically ventilated intensive care unit (ICU) patients.1 The compassionate intent is to ensure comfort and reduce anxiety, while supporting ventilator synchrony.1-3 Continuous intravenous sedative use in the United States has increased from 39.7% of ICU patients in 2001 to 66.7% in 2007. Although this may be related to increasing acuity levels, gaps in care exist as ICU survey data suggest an overall lack of standardization in methods of assessing and determining optimal daily sedation targets in ICUs across the United States. In addition, there is a reported tendency toward deeper levels of sedation for ventilated patient.4,5 Recent literature has demonstrated that maintaining a deep level of sedation is associated with a longer duration of mechanical ventilation, longer ICU length of stay (LOS), and increased acquired weakness from immobility.6-10 Contemporary guidelines, therefore, aim for lighter sedation targets as they have now been associated with improved patient outcomes.11


Patient sedation needs are closely associated with pain, agitation, and delirium (PAD), and oversedated patients may suffer from delayed diagnosis of these closely associated processes.1,5,12 Poorly controlled pain and delirium in critically ill patients can cause patient suffering and agitation.11-13 Pain has been shown to be a risk factor for the development of delirium.11,12 Delirium may not only prolong ICU stay but also increase the incidence of post-ICU syndrome and posttraumatic stress disorder up to 1 year after hospital discharge.14-18 Delirium has also been shown to be associated with an increased risk of mortality.19,20


The interrelated concepts of pain, agitation, and delirium confirm the need for a bundled approach to identification and treatment. Published ICU sedation protocols can be used to maintain patient comfort while decreasing practice variation and cumulative sedative exposure.20-24 Furthermore, by using validated and targeted scales in a systematic, integrated, and stepwise fashion with an analgesia-first approach, the judicious use of benzodiazepine sedatives, reduction of continuous infusions, and the promotion of early physical therapy lighter sedation can be successfully achieved.11 However, surveys of ICU providers have reported challenges of low adherence, inconsistent use, and gaps in communication between caregivers.2,3 Institutions are challenged to translate individual components of the evidence-based PAD guidelines into daily practice. Determining early and long-term success metrics contributes to the complexity of the implementation process.



In our high-acuity surgical critical care population, opportunity existed for sedation minimization in mechanically ventilated patients. The stated problem of oversedation is based on clinical expertise and opinion of the interdisciplinary team. Preimplementation sedation practice in the surgical ICU (SICU) did not include delirium screening, standardized physician orders, daily discussion of targets for Richmond Agitation Sedation Scale (RASS) goals, or daily spontaneous awakening trials (SATs). Propofol was the first line of sedation therapy for the first 24 hours of mechanical ventilation, with transition to benzodiazepine boluses every hour to "keep the patient calm." The behavioral pain scale and the RASS had limited use during the preimplementation period. Physical and occupational therapy was performed on a physician consult-only basis.


The aim of our work in instituting a PAD guideline in surgical critical care is to increase percentage of ventilator days with lighter sedation scores without negatively impacting pain control or agitation. In addition, the study was also to demonstrate that lighter sedation will be associated with improvements in patient participation in care as measured by the number of physical therapy sessions during ICU care and less days of delirium. Lastly, we hypothesize that markers of ICU care including ventilator-free days and LOS will improve.



This is a prospective, observational quality improvement initiative capturing data before and after implementation of a PAD guideline. The setting is a 24-bed SICU at a large, urban, academic medical center with a provider structure of surgical critical care intensivists, advanced practice providers, and house staff. The study was performed over an 11-month period (May 2013 to March 2014) where initial data were collected for 3 months, followed by a 5-month gap during implementation, and finally postimplementation data were collected during the last 3 months. All patients who were mechanically intubated were included with the exception of the following: age younger than 18 or older than 90 years, intubation lasting less than 24 hours, need for a continuous neuromuscular blocker, active management of intracranial pressure, chronic ventilator dependence, alcohol withdrawal syndrome, uncontrolled seizures, an unstable airway, or patients transferred in from another ICU after being intubated for more than 24 hours (Figure 1). The performance improvement study was reviewed and approved by our institutional review board.

Figure 1 - Click to enlarge in new windowFigure 1. Patient inclusion/exclusion criteria.

A multidisciplinary team including critical care physicians, nurses, advanced practice providers, pharmacists, physical therapists, and respiratory care therapists was assembled to review current sedation practices and to protocolize the guideline specific to our ICU. This included recommended pharmacologic agents, titration practices, and standardized nursing assessments. Enhanced provider communication was facilitated by use of a common language of evidence-based assessment tools including the RASS, Behavioral Pain Scale (BPS), Numeric Pain Scale (NPS), and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU).


Under the protocol, RASS and BPS/NPS were assessed at minimum every 4 hours and CAM-ICU every 12 hours. An analgesia-first approach was taken, with a goal BPS of 3 to 5 and a goal NPS of less than 3. Next, light sedation was targeted by a goal RASS of 0 to -1. Pharmacological treatment preferences included the use of propofol for initial sedation, the use of intermittent dosing of sedatives and analgesics before beginning continuous infusions, and judicious use of benzodiazepines unless clinically indicated. If propofol was used for sedation, it was turned off once a shift for an SAT. For patients with delirium, nonpharmacologic management was preferred; however, patients could receive haloperidol or an atypical antipsychotic for hyperactive delirium. See Figure 2 for agitation/sedation algorithm.

Figure 2 - Click to enlarge in new windowFigure 2. Agitation-sedation algorithm. This is the algorithm used for the implementation of the PAD guidelines. Pain and delirium algorithms were also created to assist with clinical treatment decisions for pain and delirium.

The 5-month gap between preimplementation and postimplementation data collection was dedicated to dissemination of the unit-based PAD guidelines from the Society of Critical Care Medicine.11 The clinical nurse specialist for the SICU was the team leader. Surveys were administered to the clinical nurses to identify knowledge gaps and obstacles to implementation. The interdisciplinary team met biweekly to address stakeholder concerns. The clinical nurse specialist attended physician faculty, pharmacy, and physical rehabilitation group meetings to gain support for the PAD guideline. Clinical practice algorithms were laminated and distributed to all stakeholders and posted on computers. Education to the clinical nurses included PowerPoint presentations, self-learning packets, and posttest evaluation.


For the purposes of this study, sedation and agitation were measured by mean percentage of RASS scores at goal, pain by mean percentage of NPS/BPS at goal, and delirium by CAM-ICU scores. Patient participation in care was measured by the number of successful physical therapy sessions. A physical therapy session was defined as ambulating, sitting on the edge of the bed, standing in place, pivoting to a chair, or using a mechanical lift to sit in bedside chair and perform range-of-motion activities. Patient demographics, diagnosis, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, accidental extubation, falls, and percentage of ventilator days spent on a continuous opioid or sedative infusion were also recorded. The APACHE II is an acuity score used to predict mortality. The tool is based on end-organ failure, vital signs, laboratory results, and demographics. An APACHE II score ranges from 0 to 71 and with a higher score associated with a higher risk of mortality.


Data were collected for the entire ICU LOS to a maximum of 28 days to limit the effect of outliers. Statistical analysis was performed using IBM SPSS Statistics for Macintosh version 21.0 (IBM Corp, Armonk, New York) [chi]2 Tests were used for categorical data, and t tests were used for continuous data to compare the preintervention and postintervention groups. Normality assumptions were examined, and normal distribution confirmed; [chi]2/Fisher exact and t tests were used as appropriate for categorical and continuous variables.



There were a total of 54 patients in the preintervention group and 52 patients in the postintervention group, cumulatively equaling 634.5 ICU patient days in the preintervention group and 498.3 ICU patient days in the postintervention group. There were a total of 3337 individual RASS scores reported (1833 at preintervention and 1504 at postintervention), 3291 BPS/NPS scores (1799 at preintervention and 1492 at postintervention), and 1270 CAM-ICU scores (679 at preintervention and 591 at postintervention). There were no statistically significant differences between the groups in the areas of patient demographics, APACHE scores, or admitting diagnosis (Tables 1 and 2).

Table 1 - Click to enlarge in new windowTABLE 1 Comparison of Patient Characteristics in Preintervention to and Postintervention Groups
Table 2 - Click to enlarge in new windowTABLE 2 Comparison of Admission Diagnosis as a Single Variable in the Preintervention and Postintervention Groups

Mean percentage of total scores at goal RASS (0 to -1) showed a statistically significant increase from 38% at preintervention to 50% at postintervention (P < .02) (Figure 3). Mean percentage of total scores at goal BPS/NPS (3-5 for BPS and <3 for NPS) remained stable from 86% to 83% (P = .16). There were no statistically significant differences in the mean percentage of positive CAM-ICU scores, 31% to 29% (P = .68). The mean percentage of total ventilator days with patients receiving a continuous opioid infusion had a statistically significant decrease from 65% to 47% (P < .01); however, there was no statistically significant differences in the mean percentage of ventilator days where the patient was receiving a continuous sedative infusion, 44% to 45% (P = .86) (Table 3).

Figure 3 - Click to enlarge in new windowFigure 3. Distribution of mean RASS scores during time on mechanical ventilation.
Table 3 - Click to enlarge in new windowTABLE 3 Patient Outcomes in Preintervention and Postintervention Groups

There was a statistically significant increase in the mean percentage of ICU days with physical therapy sessions from 24% to 41% (P < .001), but no statistically significant differences in the mean number of days from ICU admission to the day of the patient receiving the first physical therapy session (5.85 days to 4.75 days [P = .31]). Mean ventilator-free days decreased from 5.4 days to 4.5 days (P = .29), and mean ICU LOS decreased from 11.75 days to 9.5 days (P = .20), in the preintervention and postintervention groups, respectively. The average ICU LOS being greater than 1 week reflects the high acuity and the fact that only mechanically ventilated patients were included in this study. The health care institution does not have a progressive level of care to accommodate complete ventilator liberation. One incidental patient removal of the endotracheal tube was encountered in both the preintervention and postintervention groups during the study period. One patient fall was encountered in both the preintervention and postintervention groups.



In this study, we found that lighter, targeted levels of sedation are achievable with the implementation of a PAD guideline. In the postintervention period, more time was spent at goal RASS (0 to -1), indicating lighter sedation without compromising pain and agitation. This was achieved with less continuous opioid infusions and no change in patient perceived pain control in terms of BPS/NPS. These findings supported the published goal of PAD guidelines, which include the concept of patients being comfortable, pain-free, and being spontaneously arousable. This is evidence of effecting outcomes even in the beginning phases of project implementation.


Although RASS scores rose to being at goal of 0 to -1, 50% of the time postintervention, there is likely still room for improvement. In a SICU, there is an expected lower RASS score, indicating deeper sedation in the immediate postoperative recovery period. Others have published similar time at goal RASS rates; Mansouri et al25 published work showing a 9-month implementation and achieved a goal 0 to -1 RASS 65% of the time in mechanically ventilated patients. Similarly, they also achieved excellent patient perceived pain control.


Pain, agitation, and delirium guidelines supporting light levels of sedation evolved in part from the multitude of trials involving SATs.6-10 Operationally, these include a practice of holding continuous sedative (including continuous opioids) infusions once a day and evaluating patient response and readiness for extubation. In these studies, patients often were maintained at a deeply sedated RASS score of -3 to -5, supporting the SAT intervention. Our improvement study excluded patients who met criteria for therapeutic deep sedation. Therefore, SATs were not part of our ICU practice except in holding propofol infusions daily. Our goal was to achieve consistent light levels of sedation throughout the ICU LOS, negating the need to spontaneously awaken. Research findings supporting the Society of Critical Care Medicine PAD guidelines support multiple strategies including analagosedation, targeted overall light levels of sedation, and SATs.11


Continuous opioid infusions decreased after intervention, but continuous sedative infusion rates were not different. Other studies of PAD bundles have shown decreases in both such as Hager et al,26 who showed a 74% to 33% opioid reduction and a 70% to 22% sedative reduction for continuous infusion rates. The reason for our ICU showing no difference in sedative infusions is likely because propofol is the continuous sedative of choice in our SICU. Benzodiazepines have been associated with increased risk of transitioning to delirium, and therefore the PAD guideline recommends against first-line use as a sedative.27-29 Because propofol is administered as a continuous infusion, the mean percentage of time with a continuous sedative infusion did not change in the preintervention versus and postintervention groups. Although the use of continuous propofol infusions did not change, it is possible that the cumulative doses were less and contributed to the greater percentage of patients within the target RASS goal, but these data were not readily available. Of note, dexmedetomidine was not utilized during this study.


In this study, we found more ICU days with patients participating in physical therapy sessions. There was no increase in physical or occupational therapy staff throughout our data collection period. Early mobilization in the ICU setting can be achieved only when patients have lighter sedation levels. Early mobilization and participation in physical therapy, even in mechanically ventilated patients, have been shown to be safe and have resulted in more ventilator-free days and less delirium in the ICU.10,30-33 For this reason, early mobilization is a component in PAD guidelines including the one used in the present study.11 It is also a component of the recently published ABCDE trial (Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Exercise) by Balas et al,34 where the authors showed an 18% increase in patient's mobilization out of bed after implementation. Not only are patients able to get more physical therapy sessions, but also they can start them at an earlier time point.


Although not the primary focus of our study, both ventilator-free days and total ICU LOS trended downward but did not show a significant difference. Bryczkowski et al35 did show more ventilator-free days, shorter ICU LOS, lower total opioid requirement, and less time spent in pain in a postintervention group. Bryczkowski et al used hourly RASS assessments by the clinical nurses to evaluate hours deeply sedated beyond RASS of -2 during mechanical ventilation therapy in a preintervention and postintervention study, noting a decrease from 35 hours to 12 hours per patient ICU stay.


Limitations to this study include the small sample size and the single ICU setting. Another limitation is that cumulative dosing of opioids, sedatives, and medications given outside the ICU (operating room) was not included in data analysis. Being a clinical implementation study, availability of data is obtained from actual bedside clinicians caring for the patients. This creates the limitation of data through the medical record and the possibility of inconsistencies in the accuracy of the assessments. In efforts to combat this issue, the clinical nurse specialist on the critical care unit validated the results of the assessments on dayshift, Monday through Friday.


Assessment and documentation of RASS, BPS/NPS, and CAM-ICU scores are important as these become necessary metrics in evaluating outcomes related to PAD bundle implementation. Stakeholder adherence to unit-based sedation guidelines can be an obstacle to outcome evaluation. Measuring adherence is important in the early stages of project implementation. A descriptive study including the distribution of surveys to 41 North American Hospitals and the American Thoracic Society e-mail database showed that 80% use validated sedation assessment tools, and only 50% use delirium-screening tools. Research by Shehabi et al20 showed that despite the use of validated sedation tools clinicians typically prescribe target sedation goals only 24.9% of the time. Balas et al34 reported similar clinical nurse adherence rates for performing the CAM-ICU at 50% adherence. Furthermore, Swan36 demonstrated that clinical nurses frequently use "unable to assess" ratings when performing CAM-ICU assessments on mechanically ventilated ICU patients. More research is needed to identify barriers to performing the CAM-ICU assessment and how this impacts treatment and days of delirium for the critical care patient. In our quality improvement study, adherence of CAM-ICU scores was only 56% in the preintervention group and 63% in the postintervention group; it is therefore inappropriate to conclude on impact of the PAD bundle on days of delirium. Nursing adherence to assessment and documentation of RASS and BPS/NPS scores every 4 hours was 81% in the preintervention group and 91% in the postintervention group.


Future directions in sedation algorithms should focus both on optimizing the use of relevant metrics such as RASS and CAM-ICU by all critical care providers and using them effectively to titrate participation in care. As these metrics are more easily obtained electronically, perhaps long-term sustainable use can be realized. In addition, these metrics can be used to drive production of future evidence-based guidelines.37 Recent work by Walsh et al38 introduces process control methodology in the evaluation of PAD guideline implementation. Although a SICU was the setting for this study, this implementation process and metrics are translatable and may provide a framework for other ICUs to implement an ICU PAD guideline in their organizations.



Implementation of a PAD guideline is feasible through interdisciplinary team processes. It is possible to pilot PAD protocols and achieve results over a short period. During the pilot period, it is important to create attention to establishing standardized PAD assessments, adherence to the assessments, team discussions, and the determination of success metrics. Even over a short period, a PAD guideline can improve time spent at goal RASS and decrease continuous opioid infusions, all while not effecting pain control. Furthermore, physical therapy sessions increased, and ICU LOS and ventilator days trended lower. Early success can engage interdisciplinary teams and drive organizational-level change. The results of this work created a foundation to drive systems-level practice standardization in a very large academic center. Implementation of a PAD guideline should be considered in all ICU settings.


PAD Guidelines

Use valid, reliable tools and establish a standard frequency for the assessment of pain, agitation, and delirium.


Always treat pain first.


Use PRN doses before beginning continuous infusions or increasing infusion rates.


Titrate continuous infusions according to a team-established goal using a standardized tool, for example, RASS of 0 to -1.


Create a culture that not all mechanically ventilated ICU patients require deep sedation.


Limit deep sedation levels only to patients who meet clinical criteria.


Use caution with benzodiazepines use except for seizures, alcohol withdrawal, or benzodiazepine withdrawal syndrome.


Where to Begin

Form a dedicated team of engaged interdisciplinary critical care specialists.


Determine a team leader.


Compare current pain, agitation, delirium assessment practices to evidence-based PAD guidelines.


Establish a standard of practice that includes valid and reliable assessment tools with targeted goals.


Develop an algorithm to guide clinical decision making for mechanically ventilated patients.


Determine an agreed-upon standard sedation level for the majority of typical ICU patients receiving mechanical ventilation.


Use easy wins to model the algorithm in actual practice.


Measure adherence to assessment practices through auditing and feedback.




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