Correlation of the Critical Care Pain Observation Tool and Numeric Rating Scale in Intensive Care Unit Patients.

PURPOSE: We sought to determine the correlation between the Numeric Rating Scale (NRS) and Critical-Care Pain Observation Tool (CPOT) to determine whether clinical factors modified the relationship between NRS and CPOT assessments. MATERIALS AND METHODS: We included nonventilated adults admitted to the MICU or SICU who could self-report pain and had at least 3 paired NRS and CPOT assessments. We performed Spearman correlation to assess overall correlation and performed proportional odds logistic regression to evaluate whether the relationship between NRS and CPOT assessments was modified by clinical factors. RESULTS: Nursing staff performed NRS and CPOT assessments every 4 h in 1302 patients, leading to 61,142 matched assessments. We found that the NRS and CPOT have a Spearman correlation coefficient of 0.56 and an intraclass correlation coefficient of 0.32 in intensive care unit patients. Factors that modified the relationship between the NRS and CPOT included the presence of delirium (P < .001) and lower mean daily Richmond Agitation Sedation Scale (<0.001). CONCLUSIONS: The correlation coefficient between the NRS and the CPOT was found to be 0.56. The presence of delirium, decreased level of arousal, modified the relationship between the NRS and CPOT. Self-reported and behavioral pain assessments cannot be used interchangeably in critically ill adults.

Delirium Prevention and Management in Frail Surgical Patients.

Delirium, an acute, fluctuating impairment in cognition and awareness, is one of the most common causes of postoperative brain dysfunction. It is associated with increased hospital length of stay, health care costs, and mortality. There is no FDA-approved treatment of delirium, and management relies on symptomatic control. Several preventative techniques have been proposed, including the choice of anesthetic agent, preoperative testing, and intraoperative monitoring. Frailty, a state of increased vulnerability to adverse events, is an independent and potentially modifiable risk factor for the development of delirium. Diligent preoperative screening techniques and implementation of prevention strategies could help improve outcomes in high-risk patients.

Current Perspectives on the Assessment and Management of Pain in the Intensive Care Unit.

Critical illness is often painful, both from the underlying source of illness, as well as necessary procedures performed for the monitoring and care of these patients. Pain is often under-recognized in the critically ill, especially among those who cannot self-report, so accurate assessment and management continue to be major consideration in their care. Pain management in the intensive care unit (ICU) is an evolving practice, with a focus on accurate and frequent pain assessment, and targeted pharmacologic and non-pharmacologic treatment methods to maximize analgesia and minimize sedation. In this review, we will evaluate several validated methods of pain assessment in the ICU and present management options. We will review the evidence-based recommendations put forth by the largest critical care societies and several high-quality studies related to both the in-hospital approach to pain, as well as the short- and long-term consequences of untreated pain in ICU patients. We conclude with future directions.

Association of Delirium during Critical Illness With Mortality: Multicenter Prospective Cohort Study.

BACKGROUND: The temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year. METHODS: We analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium. RESULTS: Among 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year. CONCLUSIONS: Delirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.

Motoric Subtypes of Delirium and Long-Term Functional and Mental Health Outcomes in Adults After Critical Illness.

OBJECTIVES: Adult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors. DESIGN: Secondary analysis of a prospective multicenter cohort study. SETTING: Academic, community, and Veteran Affairs hospitals. PATIENTS: Adult ICU survivors of respiratory failure and/or shock. INTERVENTIONS: We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes. MEASUREMENTS AND MAIN RESULTS: In our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07-0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder. CONCLUSIONS: Longer duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.

Postoperative Pulmonary Complications' Association with Sugammadex versus Neostigmine: A Retrospective Registry Analysis.

BACKGROUND: Postoperative residual neuromuscular blockade related to nondepolarizing neuromuscular blocking agents may be associated with pulmonary complications. In this study, the authors sought to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications in comparison with neostigmine. METHODS: Adult patients from the Vanderbilt University Medical Center National Surgical Quality Improvement Program database who underwent general anesthesia procedures between January 2010 and July 2019 were included in an observational cohort study. In early 2017, a wholesale switch from neostigmine to sugammadex occurred at Vanderbilt University Medical Center. The authors therefore identified all patients receiving nondepolarizing neuromuscular blockades and reversal with neostigmine or sugammadex. An inverse probability of treatment weighting propensity score analysis approach was applied to control for measured confounding. The primary outcome was postoperative pulmonary complications, determined by retrospective chart review and defined as the composite of the three postoperative respiratory occurrences: pneumonia, prolonged mechanical ventilation, and unplanned intubation. RESULTS: Of 10,491 eligible cases, 7,800 patients received neostigmine, and 2,691 received sugammadex. A total of 575 (5.5%) patients experienced postoperative pulmonary complications (5.9% neostigmine vs. 4.2% sugammadex). Specifically, 306 (2.9%) patients had pneumonia (3.2% vs. 2.1%), 113 (1.1%) prolonged mechanical ventilation (1.1% vs. 1.1%), and 156 (1.5%) unplanned intubation (1.6% vs. 1.0%). After propensity score adjustment, the authors found a lower absolute incidence rate of postoperative pulmonary complications over time (adjusted odds ratio, 0.91 [per year]; 95% CI, 0.87 to 0.96; P < .001). No difference was observed on the odds of postoperative pulmonary complications in patients receiving sugammadex in comparison with neostigmine (adjusted odds ratio, 0.89; 95% CI, 0.65 to 1.22; P = 0.468). CONCLUSIONS: Among 10,491 patients at a single academic tertiary care center, the authors found that switching neuromuscular blockade reversal agents was not associated with the occurrence of postoperative pulmonary complications.

Association of Hypoactive and Hyperactive Delirium With Cognitive Function After Critical Illness.

OBJECTIVES: Delirium, a heterogenous syndrome, is associated with worse long-term cognition after critical illness. We sought to determine if duration of motoric subtypes of delirium are associated with worse cognition. DESIGN: Secondary analysis of prospective multicenter cohort study. SETTING: Academic, community, and Veteran Affairs hospitals. PATIENTS: Five-hundred eighty-two survivors of respiratory failure or shock. INTERVENTIONS: We assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale daily during hospitalization. We defined a day with hypoactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score less than or equal to 0 and a day with hyperactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score greater than 0. At 3 and 12 months, we assessed global cognition with the Repeatable Battery for the Assessment of Neurologic Status and executive function with the Trail Making Test Part B. We used multivariable regression to examine the associations between days of hypoactive and hyperactive delirium with cognition outcomes. We allowed for interaction between days of hypoactive and hyperactive delirium and adjusted for baseline and in-hospital covariates. MEASUREMENTS AND RESULTS: Hypoactive delirium was more common and persistent than hyperactive delirium (71% vs 17%; median 3 vs 1 d). Longer duration of hypoactive delirium was associated with worse global cognition at 3 (-5.13 [-8.75 to -1.51]; p = 0.03) but not 12 (-5.76 [-9.99 to -1.53]; p = 0.08) months and with worse executive functioning at 3 (-3.61 [-7.48 to 0.26]; p = 0.03) and 12 (-6.22 [-10.12 to -2.33]; p = 0.004) months; these associations were not modified by hyperactive delirium. Hyperactive delirium was not associated with global cognition or executive function in this cohort. CONCLUSIONS: Longer duration of hypoactive delirium was independently associated with worse long-term cognition. Assessing motoric subtypes of delirium in the ICU might aid in prognosis and intervention allocation. Future studies should consider delineating motoric subtypes of delirium.

Association of neuronal repair biomarkers with delirium among survivors of critical illness.

PURPOSE: Delirium is prevalent but with unclear pathogenesis. Neuronal injury repair pathways may be protective. We hypothesized that higher concentrations of neuronal repair biomarkers would be associated with decreased delirium in critically ill patients. MATERIALS AND METHODS: We performed a nested study of hospital survivors within a prospective cohort that enrolled patients within 72 h of respiratory failure or shock. We measured plasma concentrations of ubiquitin carboxyl-terminal-esterase-L1 (UCHL1) and brain-derived neurotrophic factor (BDNF) from blood collected at enrollment. Delirium was assessed twice daily using the CAM-ICU. Multivariable regression was used to examine the associations between biomarkers and delirium prevalence/duration, adjusting for covariates and interactions with age and IL-6 plasma concentration. RESULTS: We included 427 patients with a median age of 59 years (IQR 48-69) and APACHE II score of 25 (IQR 19-30). Higher plasma concentration of UCHL1 on admission was independently associated with lower prevalence of delirium (p = .04) but not associated with duration of delirium (p = .06). BDNF plasma concentration was not associated with prevalence (p = .26) or duration of delirium (p = .36). CONCLUSIONS: During critical illness, higher UCHL1 plasma concentration is associated with lower prevalence of delirium; BDNF plasma concentration is not associated with delirium. Clinical trial number: NCT00392795; https://clinicaltrials.gov/ct2/show/NCT00392795.

Long-term Cognitive and Functional Impairments After Critical Illness.

As critical illness survivorship increases, patients and health care providers are faced with management of long-term sequelae including cognitive and functional impairment. Longitudinal studies have demonstrated impairments persisting at least 1-5 years after hospitalization for critical illness. Cognitive domains impacted include memory, attention, and processing speed. Functional impairments include physical weakness, reduced endurance, and dependence on others for basic tasks of daily living such as bathing or feeding. In characterizing the trajectory of long-term recovery, multiple risk factors have been identified for subsequent impairment, including increased severity of illness and severe sepsis, prolonged mechanical ventilation, and delirium. Preadmission status including frailty, high level of preexisting comorbidities, and baseline cognitive dysfunction are also associated with impairment after critical illness. Development of cognitive and functional impairment is likely multifactorial, and multiple mechanistic theories have been proposed. Neuroinflammation, disruption of the blood-brain barrier, and structural alterations in the brain have all been observed in patients with long-term cognitive dysfunction. Systemic inflammation has also been associated with alterations in muscle integrity and function, which is associated with intensive care unit-acquired weakness and prolonged functional impairment. Efforts to ease the burden of long-term impairments include prevention strategies and rehabilitation interventions after discharge. Delirium is a well-established risk factor for long-term cognitive dysfunction, and using delirium-prevention strategies may be important for cognitive protection. Current evidence favors minimizing overall sedation exposure, careful selection of sedation agents including avoidance of benzodiazepines, and targeted sedation goals to avoid oversedation. Daily awakening and spontaneous breathing trials and early mobilization have shown benefit in both cognitive and functional outcomes. Multifactorial prevention bundles are useful tools in improving care provided to patients in the intensive care unit. Data regarding cognitive rehabilitation are limited, while studies on functional rehabilitation have conflicting results. Continued investigation and implementation of prevention strategies and rehabilitation interventions will hopefully improve the quality of life for the ever-increasing population of critical illness survivors.

Delirium's Arousal Subtypes and Their Relationship with 6-Month Functional Status and Cognition.

OBJECTIVE: We sought to determine how delirium subtyped by arousal affected 6-month function and cognition in acutely ill older patients. METHODS: This was secondary analysis of a prospective cohort study which enrolled hospitalized patients ≥65 years old. Delirium and arousal were ascertained daily in the emergency department and the first 7 days of hospitalization using the modified Brief Confusion Assessment Method and Richmond Agitation Sedation Scale, respectively. For each day, patients were categorized as having no delirium, delirium with normal arousal, delirium with decreased arousal, or delirium with increased arousal. Preillness and 6-month functional status were determined using the Older American Resources and Services activities of daily living scale which ranges from 0 (completely dependent) to 28 (completely independent). Preillness and 6-month cognition were determined using the Informant Questionnaire on Cognitive Decline in the Elderly which ranges from 1 (markedly improved cognition) to 5 (severe cognitive impairment). Multiple linear regression was performed adjusted for preillness Older American Resources and Services activities of daily living and Informant Questionnaire on Cognitive Decline in the Elderly and other relevant confounders. RESULTS: In 228 older patients, delirium with normal arousal was the only subtype independently associated with poorer 6-month function and cognition. For every day spent in this subtype, the 6-month Older American Resources and Services activities of daily living decreased by 0.84 points (95% confidence interval: -1.59 to -0.09) and the patient's 6-month Informant Questionnaire on Cognitive Decline in the Elderly significantly increased by 0.14 points (95% confidence interval: 0.06-0.23). CONCLUSIONS: Delirium with normal arousal, as opposed to delirium with decreased or increased arousal, was the only arousal subtype significantly associated with worsening 6-month function and cognition. Subtyping delirium by arousal may have important prognostic value.

Pain and Its Long-term Interference of Daily Life After Critical Illness.

BACKGROUND: Persistent pain likely interferes with quality of life in survivors of critical illness, but data are limited on its prevalence and risk factors. We sought to determine the prevalence of persistent pain after critical illness and its interference with daily life. Additionally, we sought to determine if intensive care unit (ICU) opioid exposure is a risk factor for its development. METHODS: In a cohort of adult medical and surgical ICU survivors, we used the brief pain inventory (BPI) to assess pain intensity and pain interference of daily life at 3 and 12 months after hospital discharge. We used proportional odds logistic regression with Bonferroni correction to evaluate the independent association of ICU opioid exposure with BPI scores, adjusting for potential confounders including age, preadmission opioid use, frailty, surgery, severity of illness, and durations of delirium and sepsis while in the ICU. RESULTS: We obtained BPI outcomes in 295 patients overall. At 3 and 12 months, 77% and 74% of patients reported persistent pain symptoms, respectively. The median (interquartile range) pain intensity score was 3 (1, 5) at both 3 and 12 months. Pain interference with daily life was reported in 59% and 62% of patients at 3 and 12 months, respectively. The median overall pain interference score was 2 (0, 5) at both 3 and 12 months. ICU opioid exposure was not associated with increased pain intensity at 3 months (odds ratio [OR; 95% confidence interval], 2.12 [0.92-4.93]; P = .18) or 12 months (OR, 2.58 [1.26-5.29]; P = .04). ICU opioid exposure was not associated with increased pain interference of daily life at 3 months (OR, 1.48 [0.65-3.38]; P = .64) or 12 months (OR, 1.46 [0.72-2.96]; P = .58). CONCLUSIONS: Persistent pain is prevalent after critical illness and frequently interferes with daily life. Increased ICU opioid exposure was not associated with worse pain symptoms. Further studies are needed to identify modifiable risk factors for persistent pain in the critically ill and the effects of ICU opioids on patients with and without chronic pain.