Interrater Agreement between Bedside and Video Raters Using the CPOT-Neuro for Pain Assessment in Critically Ill Patients with a Brain Injury.

This study aimed to examine the interrater agreement of Critical-Care Pain Observation Tool-Neuro (CPOT-Neuro) scores as a newly developed tool for pain assessment in patients with critical illness and brain injury between raters using two methods of rating (bedside versus video) during standard care procedures (i.e., non-invasive blood pressure and turning). The bedside raters were research staff, and the two video raters had different backgrounds (health and non-health disciplines). Raters received standardized 45 min training by the principal investigator. Video recordings of 56 patient participants with a brain injury at different levels of consciousness were included. Interrater agreement was supported with an Intraclass Correlation Coefficient (ICC) > 0.65 for all pairs of raters and for each procedure. Interrater agreement was highest during turning in the conscious group, with ICCs ranging from 0.79 to 0.90. The use of video recordings was challenging for the observation of some behaviors (i.e., tearing, face flushing), which were influenced by factors such as lighting and the angle of the camera. Ventilator alarms were also challenging to distinguish from other sources for the video rater from a non-health discipline. Following standardized training, video technology was useful in achieving an acceptable interrater agreement of CPOT-Neuro scores between bedside and video raters for research purposes.

Acceptability and Feasibility of a Patient-Oriented Music Intervention to Reduce Pain in the Intensive Care Unit: Protocol for a Crossover Pilot Randomized Controlled Trial.

BACKGROUND: Many patients experience pain in the intensive care unit (ICU) despite receiving pain medication. Research has shown that music can help reduce pain. Music interventions studied so far have not used music streaming to generate playlists based on patient preferences while incorporating recommended tempo and duration. Previous research has focused on postoperative ICU patients able to self-report, which is underrepresentative of the ICU population that might benefit from a music intervention for pain management. We developed a new patient-oriented music intervention (POMI) that incorporates features based on theoretical, empirical, and experiential data intended to be used in the ICU. Such a music intervention should consider the expertise of ICU patients, family members, and nursing staff, as well as the practicality of the intervention when used in practice. OBJECTIVE: The primary objectives of this study are to (1) evaluate the acceptability and feasibility of the POMI to reduce pain in ICU patients and (2) evaluate the feasibility of conducting a crossover pilot randomized controlled trial (RCT) for intervention testing in the ICU. A secondary objective is to examine the preliminary efficacy of the POMI to reduce pain in ICU patients. METHODS: A single-blind 2×2 crossover pilot RCT will be conducted. Patients will undergo 1 sequence of 2 interventions: the POMI which delivers music based on patients' preferences via headphones or music pillow for 20-30 minutes and the control intervention (headphones or pillow without music). The sequence of the interventions will be inverted with a 4-hour washout period. Timing of the interventions will be before a planned bed turning procedure. Each patient will undergo 1 session of music. Twenty-four patients will be recruited. Patients able to self-report (n=12), family members of patients unable to self-report (n=12), and nursing staff (n=12) involved in the bed turning procedure will be invited to complete a short questionnaire on the POMI acceptability. Data will be collected on the feasibility of the intervention delivery (ie, time spent creating a playlist, any issue related to headphones/pillow or music delivery, environmental noises, and intervention interruptions) and research methods (ie, number of patients screened, recruited, randomized, and included in the analysis). Pain scores will be obtained before and after intervention delivery. RESULTS: Recruitment and data collection began in March 2022. As of July 5, 2022, in total, 22 patients, 12 family members, and 11 nurses were recruited. CONCLUSIONS: Methodological limitations and strengths are discussed. Study limitations include the lack of blinding for patients able to self-report. Strengths include collecting data from various sources, getting a comprehensive evaluation of the intervention, and using a crossover pilot RCT design, where participants act as their own control, thus reducing confounding factors. TRIAL REGISTRATION: ClinicalTrials.gov NCT05320224; https://clinicaltrials.gov/ct2/show/NCT05320224. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40760.

Description of the validity of the Analgesia Nociception Index (ANI) and Nociception Level Index (NOL) for nociception assessment in anesthetized patients undergoing surgery: a systematized review.

Maintaining optimum analgesia in anesthetized patients is challenging due to the inability to self-report pain or exhibit pain-related behaviours. The Analgesia Nociception Index (ANI) (based on heart rate variability [HRV]) and the Nociception Level Index (NOL) (based on HRV, photoplethysmography, skin conductance, and temperature) both include HRV and provide continuous index monitoring for nociception assessment. The research question was: "What are the validation strategies of the NOL and ANI for nociception assessment in anesthetized patients?". The objectives were to describe and analyze the validation strategies and results. A systematized review was conducted using a comprehensive search with keywords under three concepts (nociception/pain, ANI/NOL, and validity) in four databases. A quality assessment using an adapted GRADE approach for measurement tools, and a risk of bias assessment using QUADAS-2 tool were performed by two reviewers. Out of 525 results, 15 validation studies were included. Strategies included hypothesis testing, discriminative, and criterion validation. Significant changes in ANI/NOL values were found in response to nociceptive stimuli at different opioid concentrations (hypothesis testing). Higher ANI/NOL values were observed during nociceptive stimuli (discriminative). AUCs ranging from 0.83 to 0.99 were obtained to detect nociceptive stimuli (criterion). Both technologies performed superiorly in detecting nociceptive stimuli compared to individual monitoring of HR and blood pressure. Although the aforementioned validation strategies are deemed appropriate, in the absence of a gold standard, criterion validation findings should be interpreted with caution. Moreover, reliability could be examined using test-retest with consistent ANI/NOL values during a stable time-interval.

Exploration of a Multi-Parameter Technology for Pain Assessment in Postoperative Patients After Cardiac Surgery in the Intensive Care Unit: The Nociception Level Index (NOL)TM.

INTRODUCTION: The aim of this study was to explore the use of a multi-parameter technology, the Nociception Level (NOL) index (Medasense Biometrics Ltd, Ramat Gan, Israel), for pain assessment in postoperative awake patients after cardiac surgery during non-nociceptive and nociceptive procedures in the intensive care unit (ICU). MATERIALS AND METHODS: A prospective cohort repeated-measures design was used. Patients were included if they were in the ICU after undergoing cardiac surgery and if they could self-report their pain. A non-invasive probe was placed on the patient's finger for the continuous monitoring of the NOL index. Patients' self-reports of pain and anxiety (0-10 Numeric Rating Scale or NRS), and behavioral scores with the Critical-Care Pain Observation Tool (CPOT) were obtained before and during a non-nociceptive procedure (ie, non-invasive blood pressure [NIBP] using cuff inflation), and before, during and after a nociceptive procedure (ie, chest tube removal [CTR]) for a total of five time points. Non-parametric tests were used to compare scores at different time points, and receiver operating characteristic curve analysis was performed. RESULTS: Fifty-four patients were included in the analysis. The NOL index, pain and anxiety scores were significantly higher during CTR compared to rest and NIBP (p < 0.001). During CTR, the NOL was associated with self-reported pain intensity and unpleasantness but not with anxiety and CPOT scores. The NOL showed a modest performance in detecting pain (NRS ≥1 and ≥5) in this sample with sensitivity and specificity ranging from 61% to 85%. CONCLUSION: The NOL index was able to discriminate between a non-nociceptive and a nociceptive procedure and was associated with self-reported pain. Further validation testing of the NOL is necessary in a heterogeneous sample of ICU patients.

Validation of the Critical-Care Pain Observation Tool-Neuro in brain-injured adults in the intensive care unit: a prospective cohort study.

BACKGROUND: Pain assessment in brain-injured patients in the intensive care unit (ICU) is challenging and existing scales may not be representative of behavioral reactions expressed by this specific group. This study aimed to validate the French-Canadian and English revised versions of the Critical-Care Pain Observation Tool (CPOT-Neuro) for brain-injured ICU patients. METHODS: A prospective cohort study was conducted in three Canadian and one American sites. Patients with a traumatic or a non-traumatic brain injury were assessed with the CPOT-Neuro by trained raters (i.e., research staff and ICU nurses) before, during, and after nociceptive procedures (i.e., turning and other) and non-nociceptive procedures (i.e., non-invasive blood pressure, soft touch). Patients who were conscious and delirium-free were asked to provide their self-report of pain intensity (0-10). A first data set was completed for all participants (n = 226), and a second data set (n = 87) was obtained when a change in the level of consciousness (LOC) was observed after study enrollment. Three LOC groups were included: (a) unconscious (Glasgow Coma Scale or GCS 4-8); (b) altered LOC (GCS 9-12); and (c) conscious (GCS 13-15). RESULTS: Higher CPOT-Neuro scores were found during nociceptive procedures compared to rest and non-nociceptive procedures in both data sets (p < 0.001). CPOT-Neuro scores were not different across LOC groups. Moderate correlations between CPOT-Neuro and self-reported pain intensity scores were found at rest and during nociceptive procedures (Spearman rho > 0.40 and > 0.60, respectively). CPOT-Neuro cut-off scores ≥ 2 and ≥ 3 were found to adequately classify mild to severe self-reported pain ≥ 1 and moderate to severe self-reported pain ≥ 5, respectively. Interrater reliability of raters' CPOT-Neuro scores was supported with intraclass correlation coefficients > 0.69. CONCLUSIONS: The CPOT-Neuro was found to be valid in this multi-site sample of brain-injured ICU patients at various LOC. Implementation studies are necessary to evaluate the tool's performance in clinical practice.

Exploration of the Nociception Level (NOL™) Index for Pain Assessment during Endotracheal Suctioning in Mechanically Ventilated Patients in the Intensive Care Unit: An Observational and Feasibility Study.

BACKGROUND: Many patients in the intensive care unit (ICU) suffer from pain and are non-communicative. Therefore, alternative pain measures are necessary. Although behavioral pain measures are available, physiological measures are lacking. The Nociception Level index (NOL™) provides a value from combination of multiple physiological parameters to measure pain and its use in the ICU is new. AIM: To explore the use of a multiple physiological parameter measure for pain assessment, the NOL™ index, in mechanically ventilated patients able to self-report pain in the ICU. METHODS: A prospective cohort study was performed. Data were collected before, during, and 15 minutes after a non-nociceptive procedure (noninvasive blood pressure using cuff inflation) and a nociceptive procedure (endotracheal suctioning). NOL index, 0 to 10 pain intensity, and Critical-Care Pain Observation Tool (CPOT) scores were also obtained. Data were analyzed using Friedman and Mann-Whitney tests. Feasibility of study procedures was described. RESULTS: Out of 28 patients who consented, 17 remained eligible and data were analyzed for 15. Technical issues prevented obtaining a NOL signal in 2 patients. NOL values were higher during endotracheal suctioning (median = 41.6) compared with before (median = 11.2) and after the procedure (median = 11.8) and compared with cuff inflation (median = 15.1; Friedman test, p < .001). NOL values were associated with pain intensity and CPOT scores (Mann-Whitney tests, p < .05). CONCLUSIONS: The study procedures with the NOL were found feasible; NOL values could discriminate between nociceptive and non-nociceptive procedures, and values were associated with reference pain measures. Further NOL testing is required in other ICU patient groups and procedures.

The Effect of Music on Pain in the Adult Intensive Care Unit: A Systematic Review of Randomized Controlled Trials.

CONTEXT: Multimodal analgesic approaches are recommended for intensive care unit (ICU) pain management. Although music is known to reduce pain in acute and chronic care settings, less is known about its effectiveness in the adult ICU. OBJECTIVES: Determine the effects of music interventions on pain in the adult ICU, compared with standard care or noise reduction. METHODS: This review was registered on PROSPERO (CRD42018106889). Databases were searched for randomized controlled trials of music interventions in the adult ICU, with the search terms ["music*" and ("critical care" or "intensive care")]. Pain scores (i.e., self-report rating scales or behavioral scores) were the main outcomes of this review. Data were analyzed using a DerSimonian-Laird random-effects method with standardized mean difference (SMD) of pain scores. Statistical heterogeneity was determined as I2 > 50% and explored via subgroup analyses and meta-regression. RESULTS: Eighteen randomized controlled trials with a total of 1173 participants (60% males; mean age 60 years) were identified. Ten of these studies were included in the meta-analysis based on risk of bias assessment (n = 706). Music was efficacious in reducing pain (SMD -0.63 [95% CI -1.02, -0.24; n = 10]; I2 = 87%). Music interventions of 20-30 minutes were associated with a larger decrease in pain scores (SMD -0.66 [95% CI -0.94, -0.37; n = 5]; I2 = 30%) compared with interventions of less than 20 minutes (SMD 0.10 [95% CI -0.10, 0.29; n = 4]; I2 = 0%). On a 0-10 scale, 20-30 minutes of music resulted in an average decrease in pain scores of 1.06 points (95% CI -1.56, -0.56). CONCLUSION: Music interventions of 20-30 minutes are efficacious to reduce pain in adult ICU patients able to self-report.

Vital signs fluctuations and their relationship with pain in the brain-injured adult critically ill - A repeated-measures descriptive-correlational study.

OBJECTIVES: To evaluate the use of vital signs for pain detection in brain-injured patients in the intensive care unit. DESIGN: A repeated-measures descriptive-correlational study. SETTING: Two neurological intensive care units in Montréal, Canada. A total of 101 brain-injured patients were included. MAIN OUTCOME MEASURES: This study examined the fluctuations in systolic and diastolic blood pressure, heart and respiratory rates, and oxygen saturation in brain-injured critically ill patients before, during, and 15 minutes after turning and soft touch using a data collection computer. When possible, patients' pain self-reports were obtained using a 0-10 Faces Pain Thermometer. RESULTS: The heart and respiratory rates were higher during turning than soft touch and higher during the procedure compared to prior (p < 0.05), but their fluctuation was modest. The systolic blood pressure increased during both turning and soft touch by 2 mmHg, but was 26.6 mmHg higher for those who reported pain versus no pain (Mann-Whitney = 25.00, p = 0.008, n = 28). A moderate correlation was observed between the systolic blood pressure (Spearman's rho = 0.617, p = 0.004, n = 24) and self-reported pain intensity during turning. No significant effects were observed for diastolic blood pressure and oxygen saturation. CONCLUSION: Only increases in systolic blood pressure were positively associated with pain in this sample and replication studies with larger samples is needed.

Role of Family Members in Pain Management in Adult Critical Care.

This review describes family member involvement in intensive care unit pain assessment and management and generates implications for clinical practice, education, and future research. A literature review was performed in MEDLINE, PubMed, EMBASE, Cochrane, and CINAHL databases from their inception until April 30, 2019. Only 11 studies addressing the topic were identified, and the current quality of evidence is low. Family members can be involved in pain assessment by describing patients' pain behaviors and in pain management by selecting and delivering nonpharmacological interventions tailored to patients' needs, if the family members feel comfortable with this role. More-rigorous research is required to describe the role of family members in patients' pain assessment and management. Advancing knowledge in this field could improve patients' and family members' experiences with pain assessment and management in the intensive care unit.

Family members' perceptions of pain behaviors and pain management of adult patients unable to self-report in the intensive care unit: A qualitative descriptive study.

BACKGROUND: Current guidelines suggest that family members be consulted in the pain assessment process of patients unable to self-report. However, little is known regarding family members' perceptions of their loved one's pain behaviors and pain management. AIMS: This qualitative descriptive study aimed to describe family members' perceptions of pain behaviors and pain management in critically ill hospitalized patients admitted to an intensive care unit and unable to self-report. METHODS: A qualitative descriptive design was used. This study was conducted in a medical-surgical intensive care unit in Canada. Family members of nonverbal adult patients participated in a semistructured interview regarding their perceptions of pain behaviors and pain management in the intensive care unit. RESULTS: Ten family members with a nonverbal loved one admitted to the intensive care unit participated. Family members agreed on the presence of pain in the intensive care unit and reported being proactive and applying nonpharmacological interventions to help palliate pain of their loved one. Although family members identified behavioral indicators such as grimace, limb movement, and verbal complaints to assess pain in their loved one, the majority were unsure of their ability to detect pain. CONCLUSIONS: Family members have intimate knowledge of their loved one and could be invited to share their perceptions of their loved one's pain when they feel confident to do so.

Contexte: Les lignes directrices actuelles suggèrent que les membres de la famille soient consultés lors du processus d'évaluation de la douleur des patients incapables de fournir une auto-évaluation. Toutefois, on sait peu de choses au sujet de perceptions des membres de la famille au sujet des comportements de leur proche relativement à la douleur et à la prise en charge de la douleur.But: Cette étude descriptive qualitative avait pour but de décrire la perception des membres de la famille des comportements relatifs à la douleur et à la prise en charge de la douleur chez des patients en état critique de santé admis dans une unité de soins intensifs et incapables de fournir une auto-évaluation.Méthodes: Un devis descriptif qualitatif a été utilisé. Cette étude a été menée dans une unité de soins intensifs médicale-chirurgicale au Canada. Les membres de la famille de patients adultes non verbaux ont participé à une entrevue semi-structurée concernant leur perception des comportements relatifs à la douleur et à la prise en charge de la douleur à l'unité des soins intensifs.Résultats: Dix membres de famille ayant un proche non verbal admis à l'unité des soins intensifs ont participé. Les membres de famille étaient d'accord pour dire que la douleur était présente dans l'unité des soins intensifs. Ils ont aussi dit être proactifs et appliquer des interventions non pharmacologiques pour aider à soulager la douleur de leur proche. Bien que les membres de la famille ont identifié des indicateurs comportementaux comme une grimace, le mouvement d'un membre ou des plaintes verbales pour évaluer la douleur de leur proche, la majorité d'entre eux n'étaient pas certains de leur capacité à détecter la douleur.Conclusions: Les membres de la famille ont une connaissance intime de leur proche et pourraient être invités à partager leur perception de la douleur ressentie par leur proche lorsqu'ils se sentent à l'aise de le faire.

Content validation of behaviours and autonomic responses for the assessment of pain in critically ill adults with a brain injury.

BACKGROUND: The evidence shows that brain-injured patients express behaviours that are related to their level of consciousness (LOC), and different from other patients in the intensive care unit (ICU). Therefore, existing behavioural scales should be revised to enhance their content and validity for use in these patients. OBJECTIVES: The aim was to evaluate the content relevance of behaviours and autonomic responses for pain assessment of brain-injured ICU patients from the perspective of critical care clinicians. METHODS: A total of 77 clinicians from four adult neuroscience ICUs (three from Canada and one from the United States) participated in this descriptive study. A physician/nurse ratio of 21% (13/61) was reached in this quota sample, and three physiotherapists also participated. They completed a content validation questionnaire of 19 items rated on clarity and relevance based on the patient's LOC. Item Content Validity Index (I-CVI), and modified kappa (κ*) were calculated. Values higher than 0.78 and 0.75 respectively were considered excellent. RESULTS: Regardless of the patient's LOC, brow lowering, grimacing, and trying to reach the pain site were rated as the most relevant behaviours by clinicians, with excellent values of I-CVI>0.78 and κ*>0.75. Eyes tightly closed, moaning and verbal complaints of pain also obtained excellent values in altered LOC and conscious patients. Eye weeping obtained excellent values only in conscious patients. Other items showed fair (0.40-0.59) to good (0.60-0.74) values, while blinking and coughing showed poor values (<0.40) at various LOC. CONCLUSIONS: Facial expressions, movements towards the pain site, and vocalisation of pain were the most relevant pain-related behaviours rated by critical care clinicians. The relevance of some behaviours (e.g., moaning and verbal complaints of pain) varied across LOCs, thereby calling forth adaptations of behavioural pain scales to allow for interpretation in the context of a patient's LOC and ability to express specific behaviours.

The Effect of Massage on Acute Postoperative Pain in Critically and Acutely Ill Adults Post-thoracic Surgery: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Critical care practice guidelines identify a lack of clear evidence on the effectiveness of massage for pain control. To assess the effect of massage on acute pain in critically and acutely ill adults post-thoracic surgery. Medline, Embase, CINAHL, PsychInfo, Web of Science, Scopus and Cochrane Library databases were searched. Eligible studies were randomized controlled trials (RCTs) evaluating the effect of massage compared to attention control/sham massage or standard care alone on acute pain intensity post-thoracic surgery. Twelve RCTs were included. Of these, nine evaluated massage in addition to standard analgesia, including 2 that compared massage to attention control/sham massage in the intensive care unit (ICU), 6 that compared massage to standard analgesia alone early post-ICU discharge, and 1 that compared massage to both attention control and standard care in the ICU. Patients receiving massage with analgesia reported less pain (0-10 scale) compared to attention control/sham massage (3 RCTs; N = 462; mean difference -0.80, 95% confidence interval [CI] -1.25 to -0.35; p < 0.001; I2 = 13%) and standard care (7 RCTs; N = 1087; mean difference -0.85, 95% CI -1.28 to -0.42; p < 0.001; I2 = 70%). Massage, in addition to pharmacological analgesia, reduces acute post-cardiac surgery pain intensity.

Conformational dynamics of Kir3.1/Kir3.2 channel activation via δ-opioid receptors.

This study assessed how conformational information encoded by ligand binding to δ-opioid receptors (DORs) is transmitted to Kir3.1/Kir3.2 channels. Human embryonic kidney 293 cells were transfected with bioluminescence resonance energy transfer (BRET) donor/acceptor pairs that allowed us to evaluate independently reciprocal interactions among signaling partners. These and coimmunoprecipitation studies indicated that DORs, Gßγ, and Kir3 subunits constitutively interacted with one another. GαoA associated with DORs and Gßγ, but despite being part of the complex, no evidence of its direct association with the channel was obtained. DOR activation by different ligands left DOR-Kir3 interactions unmodified but modulated BRET between DOR-GαoA, DOR-Gßγ, GαoA-Gßγ, and Gßγ-Kir3 interfaces. Ligand-induced BRET changes assessing Gßγ-Kir3.1 subunit interaction 1) followed similar kinetics to those monitoring the GαoA-Gßγ interface, 2) displayed the same order of efficacy as those observed at the DOR-Gßγ interface, 3) were sensitive to pertussis toxin, and 4) were predictive of whether a ligand could evoke channel currents. Conformational changes at the Gßγ/Kir3 interface were lost when Kir3.1 subunits were replaced by a mutant lacking essential sites for Gßγ-mediated activation. Thus, conformational information encoded by agonist binding to the receptor is relayed to the channel via structural rearrangements that involve repositioning of Gßγ with respect to DORs, GαoA, and channel subunits. Further, the fact that BRET changes at the Gßγ-Kir3 interface are predictive of a ligand's ability to induce channel currents points to these conformational biosensors as screening tools for identifying GPCR ligands that induce Kir3 channel activation.

[Functional selectivity of opioid receptors ligands]. / Sélectivité fonctionnelle des ligands des récepteurs opiacés.

Opiates are the most effective analgesics available for the treatment of severe pain. However, their clinical use is restricted by unwanted side effects such as tolerance, physical dependence and respiratory depression. The strategy to develop new opiates with reduced side effects has mainly focused on the study and production of ligands that specifically bind to different opiate receptors subtypes. However, this strategy has not allowed the production of novel therapeutic ligands with a better side effects profile. Thus, other research strategies need to be explored. One which is receiving increasing attention is the possibility of exploiting ligand ability to stabilize different receptor conformations with distinct signalling profiles. This newly described property, termed functional selectivity, provides a potential means of directing the stimulus generated by an activated receptor towards a specific cellular response. Here we summarize evidence supporting the existence of ligand-specific active conformations for two opioid receptors subtypes (delta and mu), and analyze how functional selectivity may contribute in the production of longer lasting, better tolerated opiate analgesics. double dagger.