Development, Implementation, and Evaluation of the Pain Management Protocol in the Critical Care Unit

Search strategy

The literature search was conducted in articles published from years 2016-2021. The study used various databases including PubMed, CINAHL, Google Scholar and Scopus. The search was initially conducted in 2018, with the help of librarian Sarah Jewel. This search generated a total of 40 articles that were relevant to the topic of study. The current research was performed in 2021 with the help of librarian Mina Ghajar. 

The search for articles was conducted using key terms including: Mechanical ventilation, Intensive care, CPOT, Intubation and PADIS guidelines. A combination of words was entered in the search engines. Among them include measurement methods, intensive care units, critical care nursing, and pain management among others. This search generated a total of 89 articles that were relevant to the study of interest. PADIS guidelines and mechanical ventilation searches added a total of 63 articles.

The results were narrowed down using inclusion and exclusion criteria. The articles were first filtered using the year of publication. All articles published before the year 2016 were excluded from the study. The articles were further filtered by excluding primary studies that applied an insufficient sample size to attain reliable results for CPOT implementation. The study included peer reviewed articles that paid attention to CPOT and were published in English language. These limitations ensured that the articles information used in this study was recent, easy to understand and was relevant to the topic of study. This process narrowed down the total articles to 50. Further, the end note citation manager was utilized to exclude duplicate articles. The end result was a total of 40 articles. A critical appraisal was conducted and six more articles were excluded based on an insufficient sample size. This study was based on a total of 27 articles.

Evidence synthesis

The literature review incorporated discussion of the selected articles based on various research topics of interest. The research topics adopted by this study includes pain in the intensive care unit, confirmation of pain existence using multiple equipment, analgesia nociceptive index, types of pain assessment tools and vital signs they present, relation of pain and increased ventilation, pain and healthcare financial burden, effects of pain on patient’s quality of life among others. This was achieved by synthesising the selected articles, discussing and comparing the authors’ findings and the criteria for conducting the researches.

The purpose of this topic is therefore to evaluate the development, implementation and evaluation of pain main management protocols in the Critical Care Unit. To achieve this objective, this dissertation will focus on empirical and theoretical literature on the topic of interest. This will include assessment of evidence based materials highlighting pain management protocols in the critical care units. Besides, a theoretical framework will be applied in literature synthesis to obtain a rational perspective towards pain management in critical care units. Literature synthesis will be based on different themes as highlighted in the following sections. 

Pain in the ICU

Several studies have focused on the topic of pain management in the intensive care unit (ICU). A study conducted by Tanios et al., (2019) focused on the analgesic sedation in critical care entities. The study included a randomised controlled trial in a North America. The authors note that pain in the ICU facilities is a limiting factor to the attainment of overall positive outcomes. The authors note that the administration of analgesic is a critical parameter in managing pain on the patients. The study highlights the importance of addressing pain in the intensive care units to avert negative patient’s outcomes such as exacerbations. Considering that the purpose of an intensive care entity is to promote overall patients outcomes, pain management tis a critical part of promoting patients positive outcomes. 

A similar study was conducted by Lucchini et al., (2016) in assessing pain management approaches in an intensive care entity in the United States. The authors note that admission to an intensive care entity is one of the stressful events leading to poor quality of life. This is because patients are subjected to different therapeutic and diagnostic procedures. Therefore, managing such pain in an intensive care entity leads to increase in patients positive outcomes in the long run. The authors conducted a prospective observation study on adult patients admitted in 2 critical care units. The outcomes of the study highlighted the need to address pain management to avert negative consequences leading to patient’s mortality or morbidity. 

 Parcha et al., (2020) have studied the topic of pain in the ICU. The authors assessed the preoperative analgesia pain management techniques. The authors note that pain management in ICU settings leads to reduction in negative health implications for the patients. Besides, the authors note that adoption of analgesic interventions is vital to reduce the burden incurred by healthcare entities in caring for critically ill patients. The study adopted randomised controlled trial to assess the impact of analgesic approaches in postoperative operations in an intensive carte entity. This implies that pain management in an ICU setting is one of the most critical parameter in addressing negative patient parameters. While Parcha et al., (2020) focused on analgesic interventions in managing pin in a critical care facility, Lucchini et al., (2016) highlighted the need to address pain, without specifying key interventionism in an intensive care entity. Despite the interventions adopted by the authors, both studies emphasized the need to manage pain in an intensive entity to avert exacerbations and attain positive patient’s outcomes. 

Pain existence confirmed with multiple equipment 

To address the topic of pain in an inpatient facility, identifying pain is a critical undertaking. This implies that use of different tools is critical towards this perspective. Bradwell et al., (2020), assessed the effectiveness of ABCDE bundle, agitation sedation scale and critical care observational tool in identifying severity of pain during ventilation. The study assessed the effects of implementing these tools to reduce ventilation time and improve pain management. The study was conducted in a teaching hospital with 34 beds in the ICU. This study adopted purposive sampling among patients in an ICU setting to determine the impact of pain assessment tools in managing pain in the critical care units. The study used as retrospective analysis and spread sheet software for data analysis. The findings indicated that use of ABCDE bundle was effective to reduce patient’s time in receiving ventilation and managing pain. 

 However, this study adopted a small sample size to assess the metrics understudy. Besides, the use of a purposive sampling could have led to bias as the participants could have prior information concerning the study parameters. One of the key limitations of the study is the non-controlled study design that could have led to confounding of variables influencing the outcomes. This implies that the findings of the study cannot be generalised in other ICU’s considering the small sample size that cannot be representative of the entire population. However, the results attained by the authors conform to that by Parcha et al., (2020) on the imperativeness of using pain management tools in addressing pain in a critical care unit.

 Dale et al., (2018) also conducted a study to assess the validation of critical care Pain Observational Tool (CPOT) in detecting oral pharyngeal pain among patients in a critical care entity. This study is among the first to evaluate pain among mechanically ventilated patients. The study used a sample 98 patients in assessing the reliability of CPOT in detecting pain during intubation. The findings illustrate the reliability of CPOT in detecting pain during oral care approaches. These findings are consistent with the findings of Bradwell et al., (2020) despite the two studies adopting different interventions in this perspective. 

Both studies cited that pain assessment tools are vital to enhance management of pain in inpatient settings. However, the adoption of self-reporting approach by Dale et al., (2018) could have led to biased outcomes as it was difficult to determine if the participant gave the true feelings. Besides, it’s possible that the patients exaggerated their pain intensity to get prompt interventions even if there were minimal pain symptoms in the ICU. This factor has also been cited by the authors a key limitation since it would have a significant contribution to results attained. However, the study presented an impetus literature in identifying pain among critically ill patients.

 In comparison of the effectiveness of CPOT and Bispectral Index Scale (BIS) in pain assessment among intubated patients post –operations, the authors found a positive correlation between CPOT and BIS at different baselines. This implies that both assessment tools could be used in pain identification among intubated and sedated patients. The findings also noted that BIS was more sensitive in comparison to CPOT for patients who had undergone cardiac surgery. The study’s methodology was essential in identifying pain among critically ill patients considering the inclusion of a cardiovascular ICU unit. The study also applied a random sampling among the participants to evaluate the study parameters. The findings were significant in highlighting the need to use validated tools in pain assessment for intubated patients in a critical care facility. Also, the evidence presented by the article is good due to adoption of a randomised controlled trial in the study. 

The studies by Kiavar et al., (2016) highlighted the need to adopt reliable pain assessment tools. Both authors agreed that use of CPOT was essential to detect pain among patients in an intensive care facility with significant change in pain levels. However, the study by Kiavar et al., (2016) compared the effectiveness of CPOT and BIS among patients under mechanical ventilation. This study was a retrospective one with an adequate sample of 100 participants although this was less than the original intentions. 

Types of pain assessment tools

Gelinas et al., (2019) conducted a cross sectional study among patients aged 18 years and older admitted to an inpatient cardiac ICU setting. The aim of the study was to determine the effectiveness of CPOT tool in detecting pain among critically ill patients. The study noted that the content validity of the tool was effective in addressing the study parameters. The study found that this tool is more reliable in assessing pain among critically ill patients in a period of 90 minutes. Besides, the authors noted that the utilization of the Behavioural pain scale (BPS) was essential in addressing pain among critical care patients. Barnes-Daly et al., (2017) supported the findings of Gelinas et al., (2019) by noting that the use of ABCDEF and PAD guidelines is essential in assessing pain among critically ill patients. This study adopted a prospective cohort approach among seven community hospitals in California’s health care system. The study incorporated a sample of 5478 in a prospective cohort study. Data collection method incorporated collection of dashboard report of the ABCDEF bundle and comparing this to the outcome dependent variable. The outcome indicated that the application of these tools can be vital to assess the preference of pain among patients in a critical care facility. 

This study was conducted in a community health care facility and therefore, is not a randomised controlled trial. Also, the registered nurses who were involved in data collection were deployed from the same healthcare facility, therefore, increasing the likelihood of biased results. The outcomes of the study illustrated that both ABCDEF tool and the CPOT or BPS can be vital in addressing cases of postoperative pain among patients in a critical care facility. A study by Damico et al., (2018) corroborated the study by Gelinas et al., (2019) considering that the former conducted a retrospective and prospective controlled cohort study to assess the effectiveness of CPOT in identifying among patients admitted to intensive care unit and anaesthesiology units of a Healthcare entity in Italy. However, this study applied a small sample of 70 participants. The outcomes indicated that the application of CPOT was effective to identify pain among the study participants. This study did not apply a randomised control trial and there was lack of appropriate follow up after one year post discharge. The implication of this aspect is that the data obtained cannot be generalized considering that it is a representative of a smaller sample size. However, both studies by Damico et al., (2018) and Barnes-Daly et al., (2017) converged to a proposition that the use of pain assessment tools is critical in attaining and formulating diagnostic criteria based on the pain severity index.

Zhai et al., (2018) conducted a meta-analysis and systematic review to assess the accuracy off critical care in observation tool in patients in intensive care unit. The authors engaged in a database search 25 materials published between 2006 and 2020 focusing on the topic of interest. After applying the inclusion criteria, a sample of 25 articles was included in the study. The outcome indicated that CPOT pain assessment tool had a moderate diagnostic parameter suggesting that it is not an excellent tool for pain management. These results conflicted with those of Barnes-Daly et al., (2017) concerning the validity and reliability of CPOT in assessing pain in critical care unit. The increased variation between the two studies can be attributed to inclusion of articles published in Chinese by Zhai et al., (2020). Also, it is evident from the disclosures that the study was supported by different stakeholders including clinical research entities from China who could have influenced the outcomes of the study. The article attained a limitation considering that most of the studies included had high risk of bias attributed to sample selection, timing and flow. Some of the studies were also done by the research nurses who could have influenced their outcomes of the study.

Untreated pain and if negative consequences

 According to Rijkenberg et al., (2017), pain is the fifth vital sign and experience can contribute to psychological and other physiological responses in critically ill patients. The authors indicate that the high increase in pain among patients in ICU contributes to increased mortality and morbidity and can be linked to vital sign leading to immobilization. This implies that untreated pain in the intensive care entities is a threat to the overall health outcome of the patients. Besides, the Healthcare facilities incur significant amounts of resources in taking care of untreated pain considering the adverse health outcomes. According to the authors, pain assessment is a critical parameter in pain management. The aspect leads to identification of untreated pain and, therefore, adopting effective interventions to improve the patient's overall health outcomes. 

Luchini at all (2016) also indicates that untreated pain in an ICU setting is a stressful event considering that the fundamental reasons for admission in this unit are life-threatening conditions. The author supports the argument by Rijkenberg et al., (2017) indicating that patients in a critical care unit are at high risk of experiencing untreated pain considering that they are unable to communicate due to various factors such as the sedation, alteration in mental functioning or intubation. The study indicates that untreated and persistent pain contributes to altered functions on the patient's cardiovascular, neurologic, endocrine, skeletal and muscular systems. Also, untreated pain is associated with increased mortality and morbidity. The authors indicated that development of untreated pain could lead to chronic pain in the long term. This complication incorporates developing anxiety depression, post-traumatic stress disorder and reduction in the overall quality of life. Therefore, untreated pain in the critical care facilities contribute to negative health consequences on quality of life location

Dale et al (2018) indicate that untreated pain is one of the most significant problems for patients in the intensive care unit. This notion is attributed to inability of patients in critical care unit to express themselves or portray signs of pain. Untreated pain leads to increase in use of mechanical ventilation, increasing treatment cost, infections during hospitalization, mortality rate and increase in length of patients in the critical care facilities. These conditions contribute to deterioration in actual physical condition of a patient and may lead to adverse health effects such comorbidities and exacerbation. These finding are in harmony with the findings of other authors that untreated pain leads to reduced quality of life and negative health implications for the patient. Therefore, it is fundamental to apply appropriate pain assessment tools untreatable and improve patience quality of life.

CPOT Psychometric properties

 A study by Barzanji et al. (2019), aimed at assessing the symmetric properties of behavioural pain scale among intubated patient in intensive care unit. The study specifically focused on assessing the psychometric properties of CPOT behavioural pain assessment tool among cardiac surgery patients. The authors included 47 articles in the discussion of validity and reliability, specificity and responsiveness of each tool. The study found that CPOT is among the most reliable tools in assessing the extent of pain in post-cardiac surgery patients. Besides, the authors noted that the use of BPS tool was essential in assessing short term pain. The results attained from this study are reliable considering the large sample size used by the researchers. Besides, all the articles included in the study were descriptive, cross sectional and chart review. While this study failed to include randomised controlled trials, the evidence presented was good to warrant the use of CPOT in identifying pain in clinical settings. 

Zhai et al., (2020) conducted a systematic study to evaluate the accuracy of the CPOT tool in assessing pain among the inpatients in an ICU setting. The study by the authors incorporated reviewing articles published from 2006 to 2020. A total sample of 25 articles was included in the study with 16 of them written in English. The outcomes indicated that COPT was a fair tool in diagnosing pain experienced by patients with mechanical ventilation. The study however included articles written more than 10 years ago, which questions the validity and reliability of the results attained. 

Pain and increased ventilation

A study by Luchini et al, (2016) addresses the relationship between levels of pain and respiratory care guidelines during tracheal suctioning to patients in intensive care unit. The authors argue that nursing interventions on factors that increase patients’ discomfort during ventilation can significantly reduce pain symptoms. This is attributed to the nature of endotracheal sanctioning to cause distress to the patient, which has been cited to provoke barotrauma, hypoxemia, bronchospasm, hemodynamic instability and direct mechanical trauma. The increase in CPOT score with increased suctioning passes imply that there is a positive relationship between increased pain and increased ventilation 

The study results conform to AARC tracheal suction guidelines for decreasing procedural pain during ventilation (Luchini et al., 2016). Additionally, provision of analgesia based on the CPOT score proved to be an effective intervention for pain relief. This study was more relevant to our study objectives because it was carried out in an intensive care unit. Conversely, the study was based on a small number of respondents which cannot be efficiently used to represent the large population of intensive care unit patients. Additionally, CPOT scale as a tool for assessing pain is challenged in quantification of the intensity of pain. 

A study by Kobayashi et al., (2017) on assessment of ventilator associated events in critically ill patients with prolonged mechanical ventilation was conducted in an intensive care unit indicated an increase in infection related ventilator exacerbation with increased ventilations. The author suggests that the increased complications are directly related to increased hospital mortality hazards. However, this study did not provide sufficient information regarding causes of the ventilator associated events; hence the results are not reliable for this study. Additionally, the study was conducted in a single facility which further complicates comparability to suit the larger intensive care unit population.

Healthcare financial burden

Kramer et al., (2017) assessed the financial implications of mortality in intensive care unit settings attributed to pain. The authors argue that pain management has significant cost implications due to increase in mortality rate. The authors adopted a retrospective cohort study to evaluate the parameters of interest. A sample of 26 ICU facilities in 13 healthcare entities in United States was applied. Data was analysed by the application of multivariable regression model to evaluate cost implications attributed to pain in ICU settings. The study found that individuals with a prolonged length of stay in the ICU facility experienced pain leading to increased mortality rates. This study adopted a sufficient sample size in different healthcare facilities. Additionally, the data analysis procedures allowed for control of outliers. This implies that the results attained can be generalized due to increased reliability and validity. However, there was some limitations including lack of data coding and the impact of adverse events such as hospital acquired infections on mortality rate. Therefore, it was difficult to ascertain if the financial implications recorded was attributed to pain management or other comorbidities resulting from prolonged stay in an inpatient setting. These findings are consistent with the outcomes by Kainji et al., (2016), who found that pain management has significant financial implications to the healthcare facilities and the patients. The authors conducted a prospective cohort study in two ICUs in a Canadian healthcare centre. In comparison to the study by Kramer et al., (2017), the authors adopted a larger sample size. In this regard, these results are more likely to be a true representative of the implications of pain management to the financial burden of the healthcare facilities and the patients. 

Impact of pain to the patient’s quality of life

According to Joffe et al., (2016), pain in the intensive care unit is a critical parameter of medication, considering that it contributes to improvement in a patient's quality of life. It is the reason why individuals in an inpatient setting seek further interventions in addition to psychological and physiological malfunction. The authors indicate that critically ill patients experience various distressing symptoms during hospitalization as a result of the pain. In most cases, the symptoms attributed to pain are often managed by keeping the patient overly sedated. In some cases, the caretakers keep the patient socially isolated and immobilized to manage the pain symptoms and other symptoms such as agitation. According to Joffe et al., (2016), how the healthcare professionals manage pain symptoms in patients determines the overall health outcomes. For example, the authors note that keeping the patient sedated for a long time may contribute to biological and neurological dysfunction.

Dale et al (2018) on the other hand argue that increase the symptoms of pain may contribute to psychological stress to the patient in the cuticle care facility. The authors argue that patients may experience pain during insertion of instruments in situ. For example, carrying out routine or procedure extubation may contribute to exhibition of pain resulting from tube movement. The process may lead to increase in patient stress and therefore, result in patient resistance to further medical procedure. The end result of this undertaking is reduced quality of life of the patient. Dale et al (2018) corroborate the proposition of Joffe et al., (2016) that pain contributes to delayed recovery and quality of life for the patient in the critical care unit.

ORDER THE DISSERTATION LITERATURE REVIEW ASSIGNMENT HERE

Devlin et al., (2018) conducted study to evaluate the impact of pain management on quality of life. The authors indicate that pain is a noxious experience that contributes to deterioration of other aspects of life such as physiological function and mood of a patient. The study indicates that pin contributed to a significant financial burden not only to the patient but also to the healthcare facility. This aspect arises from the fact that individuals with pain are more likely to stay at an in-patient facility for a long time in comparison to those without pain. During this time, the productivity is reduced significantly. Frandsen et al., (2016) also cited that pain has a profound and universal negative effect on quality of life of patients in critical care considering that they require assistance in virtually all activities due to the mobility or intubation. Frandsen et al., (2016), however, opine that it is important to address symptoms of pain to improve the patient quality of life by application of reliable assessment tools or administration of analgesia. The difference between this study and other studies that have focused on the impact of pain on patient quality of life is the orientation of the authors to the identification of significant symptoms of pain by the use of validated tools and analgesia for pain management. However, this study agree with  previous studies that pain contributes to adverse health outcomes on the patients in intensive care and may lead to other comorbidities or exacerbation.

TABLE OF EVIDENCE (TOE)

EBQ: In the ICU, will the implementation of evidence-based pain management protocol with CPOT improve quality of effective pain assessment and management among mechanically ventilated patients.

Article #	Author & Date	Evidence Type	Sample, sample size, & setting	Study findings that help answer the EBP Question	Limitations	Evidence Level & Quality
	Balas et al., 2018.	Clinical guideline interpretation	Sample size N/A, Setting adult ICU	The article ensured that CPOT as one of the valid tools for vented adult ICU patients. Well written guidance to identify site readiness for change before QI project implementation. Suggests the use of multimodal analgesia use to manage pain together with non- pharmacological measures	This article was pure step by step approach for QI project implementation based on the original clinical guideline of the 2018 Pain, Agitation/sedation, Delirium, Mobility, and sleep disruption. This was not a research article and it did not include complete systematic review and research strategies to identify the EBP.	Non-research Level VI, Good quality data
	Bradwell et al., 2020	Pre and post quasi experimental study	Patients age 18 year- old or older, who were intubated in the field, during their admission or unable to self-report pain.  34 ICU bed hospital with medical, neurosurgical, and surgical setting at Longview, Texas	The study found 76.5% compliance with ABCDE bundle after implementation, mean ventilation days significantly reduced (50%, P<0.05). Sedation days reduced 50% as well with no statistical significance.	Small simple size Non RCT study	Level III, Good quality
	Barnes-Daly, et al., 2017	Prospective cohort study	Vented and nonverbal adult patients >18 years old, average age of 63.1 from mixed ICU setting N=6,064 n= 586 died before discharge n=5,478completed the full study. Daily dashboard reports on the ABCDEF bundle compliance compared to the outcome- dependent variable. Reports collected 12 months from seven community hospitals within California, USA	Independent variable compliance with the bundle was total- 89%-95% CI, partial 95% CI. 10% increase in compliance increased the chance of hospital survival by 7%, and 10% increase in ABCDEF bundle increased the hospital survival by 15% A in the bundle states assess, prevent, and manage pain performed with CPOT or BPS. The tools had used as part of the bundle. ABCDEF bundle utilized to improve PAD guideline compliance and implementation.	The study performed in the community hospitals. The study is not a RCT. The RNs who collected the reports were form same facility which might increase bias towards the data	Research  Level III, B: Good quality
	Barzanji et al., 2019	Systematic review	Systematic literature review of n= 47 articles from Ovid, Science Direct, Scopus, PubMed, CINHAL, Google scholar, Persian resources Sid, Marigram, Iran doc, IranMedex Five behavioral pain assessment tools validity and reliability among cardiac surgery patients. Included studies until 2017.  Patients age of >18 years old, in English and Persian, including both qualitative and quantitative articles. COSMIN checklist used to evaluate the quality of methodology.	Initial result of 1216 narrowed down to 47 articles related to the 5 pain assessment tools. 22 articles were associated to the CPOT and 2 papers with FLACC scale. The results from these 2 tool findings considered to answer clinical question. The CPOT reliability in 18 studies yielded Spearman correlation coefficient of 0.81-0.93, interrater consistency was 0.31-0.81among 10 studies, one study had 0.95. Good discriminant validity observed in 11 studies. Validity evaluated in 17 studies found to be moderate Spearman Correlation coefficient, feasibility tested in 2 studies where 90% nurses found the tool feasible and 72.7% recommend the tool. The FLACC also had high correlation, reliability, and validity. The FLACC was limited form 2 studies in total	All the articles were cross sectional, cohort studies, descriptive studies, and chart reviews. The was no RCT studies in the article	Non- Research Level IV, Good quality
	Dale et al., 2018.	Cross sectional study-prospective observational study	Mechanically vented adult ICU patients >18 years old admitted >24 hr, < 4 weeks. Mean age of 61.2, with mean LOS 6.6 days N=96 The study conducted in 2 ICUs, one in a mixed medical -surgical, trauma ICU and second in a cardiovascular surgery ICU at Sunnybrook Health Science Center in tertiary academic center in Toronto, Canada.	The participants’ CPOT score >2 was documented the highest (42.9%) during the oral suctioning. Criterion validation confirmed with numeric rating scale >4 (NRS) among 46 participants (GCS 13-15), AUC=0.80 during tooth brushing and AUC=0.72 while suctioning.  Inter-reliability was high in body movement domain (ICC=0.86-0.88).  Discriminate validity indicated that CPOT accurately identified the pain during painful nursing procedures compared to less stimulation activities. Also, CPOT was lower among patient who received analgesics before the procedures.	Inability to blind the raters to each other	Research Level III, good quality
	Damico et al., 2018	Retrospective and prospective controlled cohort study	Patients 18-year-old or older who admitted to the ICU >48 hours and were unable to report their pain, who were in mechanical ventilation, required sedation and analgesia. Retrospective data collected from 2011- 2015 with 370 participants. Prospective study from 2015-2016 (217 patients). Study conducted among patients admitted to the Anesthesiology and Critical Care Services of Lecco Hospital in Italy.	The study found statistically significant reduction in memory of pain between pre and post implementation in one year after discharge (χ2=4.31, p=0.37). There was 70.5% increase in analgesic administration based on the CPOT score of 4 or higher.  The study found significant decrease in sedative use and significant increase multimodal analgesia use in post intervention group.	Non RCT study. There was 15% follow up loss after year 12-month post discharge. There was no inter-reliability study.	Level III, Good quality
	Devlin et al., 2018	GRADE clinical guideline was created and updated by 32 international experts, 4 methodologist and 4 critical illness survivors.	Society of Critical Care Medicine recommendations	The document issued on the PAIN Agitation/Sedation, Delirium, Immobility and Sleep disruption effect on the ICU population heath. There are 3 strong, 34 conditional recommendations, and 32 ungraded statements. 37 recommendations priority level were build based on the GRADE principals. The document can support the background of the project deeply. Also strongly recommends the CPOT use for vented and nonverbal adult ICU population.	There is no RCT data to support the recommendations.	Non-research Level IV, High quality
	Frandsen et al., 2016	Retrospective cohort study	Patients age of 18 years age or older who require mechanical ventilation.  The patients were included >24 hours of hospitalization, 7 day per week. n= 56 pre-implementation group compared to the n= 79 post-implementation group after implementing the 2013 PAD guideline recommendation of analgo- sedation. The study conducted in 24 bed medical ICU unit at Taxes health Presbyterian a large teaching, community Hospital in Dallas.	The recognizing the pain appropriately with CPOT scale and practicing the analgo-sedation protocol showed the deduction on sedation score (RASS -2.57 vs-1.25, P=0.001) significantly. The CPOT score decreased from 2 to 1.5 after the implementation. There was average of 45.5 fewer mechanical ventilation hours (P<0.001), there was 50.8 median hours of LOS in the ICU. Pre and post intervention groups had similar 28 ventilation free days. There were significantly reduce of propofol (92.3%) use, and the increase amount of analgesia (fentanyl) used.	The study focused on the MICU not generalizable to SICU, CCU, or trauma ICU.	Level III, B: Good quality
	Gelinas et al., 2019	Systematic review	ICU patients age 18 years or older who speak English and French. Search performed with search terms of pain assessment, pain measurement.  The CINAHL, PubMed, MEDLINE, and Embase databases used and 54 articles selected to review the psychometric proprieties of 9 pain measurements which used in the ICU. The articles’ quality of evidence measured by GRADE recommendations.	Cited that 59 studies conducted using CPOT. There were 35 new researched since 2013. The tool is studied in 21 countries and available in 17 languages. Among other 9 pain assessment tools CPOT had the highest psychometric scores. CPOT was validated in 47 studies among 3966 patients. Internal consistency – Cronbach α (>0.70). Interrater reliability was κ>0.60 (ICC>80) in 30 studies. Criterion validity was r>0.60 with gold standard measures. Sensitivity 67-93%, specificity 46%-90% Feasibility confirmed with high quality of evidence in 14 studies	No RCT studies	Level IV, Good quality
	Joffe et al., 2016	Prospective cohort study	Patients 18- year- old or older admitted to neurosurgery ICU with brain injury with GCS>4, >2 days or <4 weeks of admission period. N=79 Patients average age of 50 years old with brain injury. Study conducted in the Neuroscience Intensive Care Unit of the Harborview Medical Center in Seattle, WA, USA.	The study found the CPOT is reliable tool during nociceptive stimuli. There muscle tension was absent 67% of the patients who has brain injury. 28 patients were conscious and able self-report pain. 19 had pain and the self-report were moderately positively correlated with CPOT scores (P<0.05). Inter-reliability while painful stimuli 0.75 (95% ICC, 0.57-0.83). Sensitivity were 0.90 and specificity 0.67 among patients with brain injury.	No RCT, small sample size, not generalizable to other ICU population	Level III, Good quality
	Kobayashi et al., 2017	Single center retrospective cohort study	Patients age>18 years old, who required mechanical ventilation >4 days n=407 20 bed general ICU academic hospital in Tokyo, Japan	The electronic chart reviews showed that there was infection- related ventilator complications independently association with hospital mortality (hazard ratio 2.42, 95%CI 1.39-4.20, P=0.02). The ventilator associated complications also have shown the similar result (hazard ratio 1.45, 95% CI 0.97-2.18, P=.07). Ventilator associated pneumonia did not increased the hazards of hospital mortality (hazards ratio 1.08, 95% CI 0.44-2.66, P=.87). This information supports the background significance.	Ventilator associated event causes unclear, the study was performed in one facility and the study was performed retrospectively. The study was performed out of USA, therefore population differences expected.	Level III, Low Quality
	Kramer et al., 2017	Retrospective Cohort Study	The data collected from the electronic MAR. The study included 26 ICUs in 13 hospitals in the USA. N=60,784 n=58,344 admissions to the ICU unit in past for years.	Predicted cost in ICU among non- survivors were significantly costly then the survivors. Mechanical ventilation increased the cost by 26.3 % the first day. Surgical ICU costs were more expensive than other ICU units. For the project the cost of vented patients in day 2 $10, 317 further increased to $19, 627 in day 5, compared to the no vented ICU patient stay $6,709 in day 2, and $13,816 in day 5 clearly mirror the need to early extubating.	Total hospital cost calculated instead of categories of the cost. The study included only 13 hospitals	Level III,  Good quality
	Kiavar et al., 2016	Prospective observational study	Patients age >18 years old who admitted to the ICU post cardiac surgery, who was mechanically ventilated. Target sample size N=100 n= 91 Study conducted in university of cardiovascular, medical and research center at Tehran, Iran	There was high level of agreement (κ=0.787) between the CPOT and the Face Expression among conscious patients.  The CPOT and FE showed weak to no agreement during painful stimuli, 30 min, 60 min, 90, min and 120 mins after assessment.  The CPOT showed significant association of score with SBP change, where FE did not. There was no other significant correlation between the CPOT score with HR and DBP	Sample size adequate, less than originally intended. The study generalizable for cardiac patients only.  Study performed outside the US, population difference.	Level III,  Good quality
	Lucchini et al., 2016	Prospective observational study,	Patients age >18 years old who admitted to the ICU, who was mechanically ventilated and sedated. n= 47. study conducted at 2 ICU district hospital in Italy	There was significant increase in the CPOT score during tracheal suctioning (CPOT>3, P<0.001). There was increased pain with increases passes of the suctioning. The study related to decreasing the procedural pain based on the American association of Respiratory Care guideline. Also, provision of analgesia based on the CPOT score suggested eliminating additional pain.	Population difference, small sample size	Level III, High quality
	Parcha et al., 2020	Retrospective analysis	The analysis of the National Center for health Statistics’ nationwide mortality data conducted to assess the acute respiratory failure (ARF) and acute respiratory distress syndrome (ARDS) related mortality trends. Data collected from 2014-2018	The study found 1,434,349 death related to the ARF and 52,958 death related to the ARDS in 5-year period with age adjusted mortality rate (per 100,000 people) of 81.1(95% CI, 80.9-81.2) and 3.1 (95% CI, 3.0-3.1).  The death rate was highest among men age 65 or older, Hispanic, Black people, and people who live in nonmetropolitan area.  Increase ARF related death per year estimated 3.4%.	The study is broad and misses the other cofactors of the morbidity and its association with appropriate treatments.	Level III,  Good quality
	Tanios et al., 2019	Randomized control trial	N=160, n=90 was eligible, participants age >18 years old, mechanically ventilated > 48 hours, patients who is receiving continues IV midazolam, propofol, and fentanyl. The daily screening conducted 3 months. RCT conducted in a 36- bed medical, surgical ICU at Memorial Care Long Beach Medical Center, a 420-bed community teaching hospital in Long Beach, CA	The group characteristics were similar. There were 3 groups: analgesic first sedation, protocol directed sedation, and protocol directed sedation with daily sedation interruptions. The study did not show any significant difference in length of stay, ventilation time, or in spontaneous breathing trials. However, there was high adherence to all 3 practice, high to similar goal CPOT <2 and RASS -2-0 observed. This study reflects the length of stay and mechanical ventilation time likely being long term outcomes, and the nurses’ adherence to the guideline and reaching the CPOT goal of <2, and RASS score -2-0 being the short the outcomes.	The midazolam used in the study not a common practice in other hospitals as sedation. The frequent injection of fentanyl infusion side effects and adverse events not evaluated appropriately. More RCT studies need to test the analgesia first then sedation phenomena. The groups not blinded to each other.	Level II, Good quality
	Zhai et al., 2020	Systematic review and Meta-analysis	Literature search conducted following databases: PubMed, Medline, CINAHL, ProQuest, EMBASE, Cochrane Library, CNKI, Wanfang, COVIP, CBM.  The key words used include: “CPOT”, “validation” English and Chinese languages included in the search from 2006- February 2020 An inclusion criterion was patients 18-year-old or older who hospitalized to the ICU and experience delirium. QUADAS-2 and STARD 2015 checklists used to extract the articles	Total of 370 articles found, after duplicates removed, exclusion of non-full text articles, and reading the articles 25 studies left to review in this systematic review.  16 articles were in English, 8 in Chinese and one in Korean. All articles were prospective and descriptive studies. The studies were in good quality in applicability. The studies had moderate heterogeneity with DOR effect size of 57.1% (P<0.001) 24 articles adopted the gold standard yes/ no to identify the presence of pain with CPOT. The results of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnosis of odds ration stayed stable after removal of any solitary test during meta-analysis. Literature analyses found CPOT as an adequate assessment tool for nonverbal patients with score of 2 or 3 indicating presence of pain.	No randomized control studies found	Level III, Good quality

References

Balas, M. C., Weinhouse, G. L., Denehy, L., Chanques, G., Rochwerg, B., Misak, C. J., Skrobik, Y., Devlin, J. W., & Fraser, G. L. (2018). Interpreting and Implementing the 2018 Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption Clinical Practice Guideline. Critical care medicine, 46(9), 1464–1470. https://doi.org/10.1097/CCM.0000000000003307 

Bradwell, J., Brimmer, S., Davis, W. (2020). Implementing the ABCDE Bundle, Critical Care Observation Tool, and Richmond Agitation-Sedation Scale to Reduce Ventilation Time. AACN Advanced Critical Care, 31(1) 16-21. http://doi.org/10.4037/aacnacc2020451 

Barnes-Daly, M. A., Phillips, G., & Ely, E. W. (2017). Improving Hospital Survival and Reducing Brain Dysfunction at Seven California Community Hospitals: Implementing PAD Guidelines Via the ABCDEF Bundle in 6,064 Patients. Critical care medicine, 45(2), 171–178. https://doi.org/10.1097/CCM.0000000000002149 

Barzanji, A., Zareiyan, A., Nezamzadeh, M., & Mazhari, M. S. (2019). Evaluation of Observational and Behavioural Pain Assessment Tools in Nonverbal Intubated Critically Adult Patients after Open - Heart Surgery: A Systematic Review. Open access Macedonian journal of medical sciences, 7(3), 446–457. https://doi.org/10.3889/oamjms.2019.103

Dale, C. M., Prendergast, V., Gélinas, C., & Rose, L. (2018). Validation of The Critical-care Pain Observation Tool (CPOT) for the detection of oral-pharyngeal pain in critically ill adults. Journal of critical care, 48, 334–338. https://doi.org/10.1016/j.jcrc.2018.09.024 

Damico, V., Cazzaniga, F., Murano, L., Ciceri, R., Nattino, G., & Dal Molin, A. (2018). Impact of a Clinical Therapeutic Intervention on Pain Assessment, Management, and Nursing Practices in an Intensive Care Unit: A before-and-after Study. Pain management nursing : official journal of the American Society of Pain Management Nurses, 19(3), 256–266. https://doi.org/10.1016/j.pmn.2018.01.007 

Devlin, J. W., Skrobik, Y., Gélinas, C., Needham, D. M., Slooter, A., Pandharipande, P. P., Watson, P. L., Weinhouse, G. L., Nunnally, M. E., Rochwerg, B., Balas, M. C., van den Boogaard, M., Bosma, K. J., Brummel, N. E., Chanques, G., Denehy, L., Drouot, X., Fraser, G. L., Harris, J. E., Joffe, A. M., … Alhazzani, W. (2018). Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU. Critical care medicine, 46(9), e825–e873. https://doi.org/10.1097/CCM.0000000000003299 

Frandsen, J. B., O'Reilly Poulsen, K. S., Laerkner, E., & Stroem, T. (2016). Validation of the Danish version of the Critical Care Pain Observation Tool. Acta anaesthesiologica Scandinavica, 60(9), 1314–1322. https://doi.org/10.1111/aas.12770 

Gélinas, C., Fillion, L., Puntillo, K. A., Viens, C., & Fortier, M. (2006). Validation of the critical-care pain observation tool in adult patients. American journal of critical care: an official publication, American Association of Critical-Care Nurses, 15(4), 420–427.

Gélinas, C., Harel, F., Fillion, L., Puntillo, K. A., & Johnston, C. C. (2009). Sensitivity and specificity of the critical-care pain observation tool for the detection of pain in intubated adults after cardiac surgery. Journal of Pain and Symptom Management, 37(1), 58-67

Gélinas, C., Joffe, A. M., Szumita, P. M., Payen, J. F., Bérubé, M., Shahiri T, S., Boitor, M., Chanques, G., & Puntillo, K. A. (2019). A Psychometric Analysis Update of Behavioral Pain Assessment Tools for Noncommunicative, Critically Ill Adults. AACN advanced critical care, 30(4), 365–387. https://doi.org/10.4037/aacnacc2019952

Joffe, A. M., McNulty, B., Boitor, M., Marsh, R., & Gélinas, C. (2016). Validation of the Critical-Care Pain Observation Tool in brain-injured critically ill adults. Journal of critical care, 36, 76–80. https://doi.org/10.1016/j.jcrc.2016.05.011 

Kobayashi, H., Uchino, S., Takinami, M., & Uezono, S. (2017). The impact of ventilator- associated events in critically ill subjects with prolonged mechanical ventilation. Respiratory Care, 62(11), 1379-1386. http://doi/10.4187/respcare.05073

Kramer, A. A., Dasta, J. F., & Kane-Gill, S. C. (2017). The impact of mortality on total costs within the ICU. Critical Care Medicine, 45(9), 1457-1463. doi:10.1097/CCM.0000000000002563 

Kiavar, M., Azarfarin, R., Totonchi, Z., Tavakoli, F., Alizadehasl, A., & Teymouri, M. (2016). Comparison of Two Pain Assessment Tools, "Facial Expression" and "Critical Care Pain Observation Tool" in Intubated Patients After Cardiac Surgery. Anesthesia Pain Medicine, 6(1), e33434. http://10.5812/aapm.33434 

Lucchini, A., Canesi, M., Robustelli, G., Fumagalli, R., & Bambi, S. (2016). An Association Between Pain and American Association of Respiratory Care 2010 Guidelines During Tracheal Suctioning. Dimensions of critical care nursing : DCCN, 35(5), 283–290. https://doi.org/10.1097/DCC.0000000000000200

Parcha, V., Kalra, R., Bhatt., S, Berra, L., Arora, G., Arora, P. (2020). Trends and geographic variation in Acute Respiratory Failure and ARDS Mortality in the United States. American College of Chest Physicians, http://doi.org/10.1016/j.chest.2020.10.042 

Rijkenberg, S., Stilma, W., Bosman, R. J., van der Meer, N. J., & van der Voort, P. H. J. (2017). Pain measurement in mechanically ventilated patients after cardiac surgery: Comparison of the Behavioral Pain Scale (BPS) and the Critical-Care Pain Observation Tool 

(CPOT). Journal of Cardiothoracic and Vascular Anesthesia, 31(4), 1227-1234.

doi: 10.1053/j.jvca.2017.03.013.

Tanios, M., Nguyen, H. M., Park, H., Mehta, S., Epstein, S. K., Youssef, F., Beltran, A., Flores, G., Sidhom, R., Sehgal, A., Leo, J., & Devlin, J. W. (2019). Analgesia-first sedation in critically ill adults: A U.S. pilot, randomized controlled trial. Journal of critical care, 53, 107–113. https://doi.org/10.1016/j.jcrc.2019.06.008 

Zhai, Y., Cai, S., & Zhang, Y. (2020). The Diagnostic Accuracy of Critical Care Pain Observation Tool (CPOT) in ICU Patients: A Systematic Review and Meta-Analysis. Journal of pain and symptom management, 60(4), 847–856.e13.