Valproic acid for agitation in the intensive care unit: an observational study of psychiatric consults.

BACKGROUND: Agitation is a common clinical problem encountered in the intensive care unit (ICU). Treatment options are based on clinical experience and sparse quality literature. AIM: The aim of this study was to describe the effect of valproic acid (VPA) as adjuvant treatment for agitation in the ICU, identify predictors of response to VPA and evaluate the independent effect of VPA on agitation compared to standard of care (SOC). METHOD: This retrospective single center observational study evaluated adult patients admitted to the ICU for whom a psychiatric consultation was requested for agitation management, with agitation defined as a Richmond Agitation Sedation Score of 2 or greater. A descriptive analysis of the proportion of agitation-free patients per day of follow-up, the incidence of agitation-related-events, as well as the evolution of co-medications use over time are presented. A logistic regression model was used to assess predictors of VPA response, defined as being agitation-free on Day 7 and generalized estimating equations were used to evaluate the independent effect of VPA as adjuvant therapy for agitation in the critically ill. RESULTS: One hundred seventy-five patients were included in the study with 78 receiving VPA. The percentage of agitation-free patients on VPA was 6.5% (5/77) on Day 1, 14.1% (11/78) on Day 3 and 39.5% (30/76) on Day 7. Multivariate regression model for clinical and demographic variables identified female gender as predictor of response on Day 7 (OR 6.10 [1.18-31.64], p = 0.03). The independent effect of VPA was non-significant when compared to SOC. CONCLUSION: Although VPA used as adjuvant treatment was associated with a decrease in agitation, its effect when compared to SOC did not yield significant results.

Prevalence and risk factors of emergence agitation among pediatric patients undergo ophthalmic and ENT Surgery: a cross-sectional study.

BACKGROUND: Some studies reported that pediatric patients undergoing otorhinolaryngology (ENT) and ophthalmic surgeries have higher incidences of emergence agitation (EA). Children with EA tend to carry the risk of self-harm, have longer periods of recovery and delayed hospital discharge. Consequently, EA needs to be monitored and risk factors ought to be emphasized to implement preventative measures. The objective of this study was to describe EA and to identify risk factors after pediatric ophthalmic or ENT surgery. METHODS: Between September 2021 and December 2021, a cross-sectional study was conducted in 100 children aged of 0-12 years who underwent ophthalmic or ENT surgery. The Watcha scale was used to observe and record EA, which was defined at levels of 3 or 4 at any time in the post-anesthesia care unit (PACU). The pain intensity was graded with the Face, Legs, Activity, Cry, Consolability (FLACC) Scale after surgery. Patient and surgery-related characteristics, the behavioral criteria of EA, the pharmacologic and non-pharmacologic interventions and recovery outcomes were objectively recorded. A binary logistic regression model was constructed to identify the associated factors of EA. RESULTS: From the 100 analyzed children, 58 were males and 42 were females, and 44 patients received ophthalmic surgery and 56 ENT surgery. The median age was 6 (IQR 4-7) years. The overall incidence of EA among pediatrics was 30% (34.5% for ENT and 24.4% for ophthalmic surgery). High preoperative modified Yale Preoperative Anxiety scale (m-YPAS) grade (OR = 1.19, 95%CI 1.06-1.33, P = 0.003) and high postoperative FLACC score (OR = 3.36, 95%CI 1.88-6.02, P < 0.001) were risk factors for EA. CONCLUSIONS: This study identified that preoperative anxiety and postoperative pain are associated with EA in children after ophthalmic or ENT surgery. Preoperative anxiety assessment and management, and administration of adjunct analgesic treatments should be considered in the routine care.

Clonidine for preventing emergence agitation in infants (PREVENT AGITATION II): Protocol and statistical analysis plan.

BACKGROUND: Emergence agitation is a common clinical condition in children. Symptoms pertaining to the spectrum of early postoperative negative behavior typically occur upon emergence from anesthesia. Clonidine is an effective adjunctive agent for the prevention of emergence agitation in children, but evidence in the smallest age groups is sparse We aim to investigate the efficacy and safety of an intraoperative bolus of intravenous clonidine for preventing emergence agitation in children 3-12 months of age. METHODS: This is a randomized, placebo-controlled, double-blind trial. We will enroll 320 patients aged 3-12 months who have been scheduled for general anesthesia maintained with sevoflurane and opioid. The randomization is parallel and stratified by age group, sex, and site. The investigational medicinal product will be administered intravenously ~20 min before the anticipated end of the surgical procedure. The intervention is clonidine 3 µg/kg and placebo is isotonic saline in a corresponding volume. RESULTS: The primary outcome is the incidence of emergence agitation as assessed on the Watcha scale, that is, any Watcha score >2 during participants' stay in the postanesthetic care unit. Secondary outcomes are the proportion of participants with postoperative pain, with postoperative nausea and vomiting, and a composite safety outcome. Statistical analysis will be conducted according to the Statistical Analysis Plan with the intention-to-treat population for our primary analyses. CONCLUSION: The PREVENT AGITATION II trial will contribute valuable knowledge on efficacy for the prevention of emergence agitation and safety in infants.

Effect of a repeated verbal reminder of orientation on emergence agitation after general anaesthesia for minimally invasive abdominal surgery: a randomised controlled trial.

BACKGROUND: An orientation strategy providing repeated verbal reminders of time, place, and person has been widely used for the non-pharmacological management of delirium. We hypothesised that using this strategy could reduce emergence agitation and improve recovery profiles. METHODS: This prospective observer-blinded RCT included male and female patients aged 18-70 yr undergoing minimally invasive abdominal surgery. During emergence from general anaesthesia, subjects in the orientation group (n=57) were provided a repeated reminder, including orientation: '(Patient's name), you are now recovering from general anaesthesia after surgery at Seoul National University Hospital, open your eyes!' via noise-cancelling headphones, whereas those in the control group (n=57) only heard their name: '(Patient's name), open your eyes!'. The primary outcome was the incidence of emergence agitation (Riker sedation agitation scale [SAS] ≥5). The incidence of dangerous agitation (SAS=7), maximal SAS score in the operating room, and recovery profile until 24 h postoperatively were evaluated as secondary outcomes. RESULTS: The incidence of emergence agitation in the operating room was significantly lower in the orientation group than in the control group (16/57 [28.1%] vs 38/57 [66.7%]; relative risk [95% confidence interval], 0.5 [0.3-0.7]; P<0.001). The incidence of dangerous agitation (0 [0.0%] vs 10 [17.5%], P=0.001) and the median maximal SAS score (4 [4-5] vs 5 [4-6], P<0.001) were also lower in the orientation group. Secondary outcomes, other than agitation-related variables, were comparable between the two groups. CONCLUSIONS: Repeated verbal stimulation of orientation may serve as a simple and easily applicable strategy to reduce emergence agitation after general anaesthesia. CLINICAL TRIAL REGISTRATION: NCT05105178.

Clinical and Sociodemographic Profile of Psychomotor Agitation in Mental Health Hospitalisation: A Multicentre Study.

Psychomotor agitation is characterised by an increase in psychomotor activity, restlessness and irritability. People with psychomotor agitation respond by over-reacting to both intrinsic and extrinsic stimuli, experiencing stress and/or altered cognition. The objective of this study is to assess the clinical and sociodemographic profile of psychomotor agitation in patients with severe mental disorders. The study was carried out in Spain by means of multicentre cross-sectional convenience sampling involving 140 patients who had been admitted to psychiatric hospital units and had experienced an episode of psychomotor agitation between 2018 and 2021.Corrigan's Agitated Behaviour Scale was used to assess psychomotor agitation. The results show that the predominant characteristic in psychomotor agitation is aggressiveness, which is also the most reported factor in patients with severe mental disorder. Patients who also have anxiety develop psychomotor agitation symptoms of moderate/severe intensity. The clinical and sociodemographic profile found in our study is consistent with other studies on the prevalence of psychomotor agitation.

Efficacy of different doses of intranasal dexmedetomidine in preventing emergence agitation in children with inhalational anaesthesia: A prospective randomised trial.

BACKGROUND: Emergence agitation is a common paediatric complication after inhalational anaesthesia. Intranasal dexmedetomidine can prevent emergence agitation effectively, but the optimal dose is uncertain. OBJECTIVE: The aim of our study was to investigate the 95% effective dose (ED 95 ) of intranasal dexmedetomidine for the prevention of emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery. DESIGN: A prospective, randomised, placebo-controlled, double-blind, clinical trial. SETTING: The study was conducted in Guangzhou Women and Children's Medical Center in China from August 2017 to December 2018. PATIENTS: Three hundred and eighteen children scheduled for ambulatory surgery were enrolled into two age groups of less than 3 years and at least 3 years. INTERVENTIONS: The children in each age group were randomised into five equal subgroups to receive either intranasal dexmedetomidine 0.5, 1.0, 1.5 or 2.0 µg kg -1 (Groups D 0.5 , D 1.0 , D 1.5 and D 2.0 ), or intranasal isotonic saline (group C) after induction. MAIN OUTCOME MEASURES: The primary outcome was the ED 95 dose of intranasal dexmedetomidine for preventing emergence agitation after inhalational anaesthesia for paediatric ambulatory surgery. RESULTS: The incidences of emergence agitation for Groups C, D 0.5 , D 1.0 , D 1.5 and D 2.0 were 63, 40, 23, 13 and 3% in children less than 3 years, and 43, 27, 17, 7 and 3% in children at least 3 years. The ED 95 of intranasal dexmedetomidine for preventing emergence agitation was 1.99 µg kg -1 [95% confidence interval (CI), 1.83 to 3.80 µg kg -1 ] in children less than 3 years, and 1.78  µg kg -1 (95% CI, 0.93 to 4.29 µg kg -1 ) in children at least 3 years. LMA removal time for groups D 1.5 and D 2.0 was 9.6 ±â€Š2.2 and 9.7 ±â€Š2.5 min, respectively, for children less than 3 years, and 9.4 ±â€Š2.0 and 9.9 ±â€Š2.7 min in children at least 3 years, respectively. Length of stay in the postanaesthesia care unit for Groups D 1.5 and D 2.0 was 34.3 ±â€Š9.6 and 37.1 ±â€Š11.2 min, respectively, in children less than 3 years, and 34.7 ±â€Š10.2 and 37.3 ±â€Š8.3 min in children at least 3 years, respectively. These times were longer in the D 1.5 and D 2.0 subgroups than in the control subgroup in the two age groups of less than 3 years and at least 3 years, respectively: 7.2 ±â€Š1.9 min in children less than 3 years and 7.3 ±â€Š2.5 min in children at least 3 years for LMA removal time, 22.2 ±â€Š7.9 min in children less than 3 years and 22.0 ±â€Š7.7 min in children at least 3 years for PACU stay time in control subgroup, respectively ( P  < 0.05). CONCLUSION: Intranasal dexmedetomidine prevented emergence agitation after paediatric surgery in a dose-dependent manner. The optimal dose of intranasal dexmedetomidine for preventing emergence agitation was higher in younger children. TRIAL REGISTRY: chictr.org.cn: ChiCTR-IOR-17012415.

Epidemiological and Psychopharmacological Study About Off-Label Treatment in Child and Adolescent Psychiatric Emergencies: A Tertiary/Single Center Experience.

OBJECTIVE: The study used an epidemiological and pharmacological description of child and adolescent psychiatric emergencies (CAPEs), during which psychotropic medications are frequently administered as off-label therapies. METHODS: We retrospectively describe CAPE in 190 patients (mean age, 14.7 years) referring in the emergency department of a single tertiary center, from June 2016 to June 2018, focusing on off-label administration rate, most of all in emergency setting. RESULTS: An intrinsic fragility was observed in this population, where 28.4% of patients present a history of self-harm, 24.7% a concomitant neurodevelopmental disorder, and 17.3% a history of substance abuse. Psychomotor agitation was the most frequent referral reason, and it represents an unspecified clinical presentation of several conditions, while self-harm showed a stronger association with depressive disorders (55.2%).Globally, 811 medications were administered both as baseline therapy (67.8% of off-label rate) and/or in the emergency setting, where the off-label rate raised to 78.3%. Benzodiazepines had the highest rate of off-label use (98.2% as baseline therapy, 92.9% in acute context). Nevertheless, in 83.5% cases of acute administrations, a singular oral benzodiazepine (mostly lorazepam) guaranteed psychomotor agitation resolution, with a lower rate of adverse effects in contrast with atypical antipsychotics. CONCLUSIONS: Off-label drug use in CAPEs is a recurrent clinical practice. An international agreement about off-label drugs is crucial to obtain standard long-term pharmacoepidemiological, safety, and efficacy data. Pharmacological pediatric trials and international guidelines are also required to regulate pharmacological treatments of CAPEs, most of all in emergency settings.

Clinical Trajectories of Neuropsychiatric Symptoms in Mild-Moderate to Advanced Dementia.

BACKGROUND: There is high prevalence of neuropsychiatric symptoms (NPS) among dementia patients. NPS are correlated with dementia progression, functional decline, early institutionalization, and death. There is scarce evidence on the progression of NPS in the latest stages of dementia. OBJECTIVE: To describe the prevalence of NPS in mild-moderate to severe dementia and to reveal the progression of each NPS over time. METHODS: We studied 317 patients (77.3% female, average age: 81.5 years) with a DSM-IV-TR diagnosis of dementia. This is a cross-sectional, and a prospective longitudinal study with 78-month follow-up. We assessed cognitive status (Mini-Mental State Examination and Severe Mini-Mental State Examination), dementia severity (Global Deterioration Scale and Clinical Dementia Rating), and psychopathological measures (Neuropsychiatric Inventory, APADEM-Nursing Home, Apathy Inventory, Cornell Scale for Depression in Dementia, and Cohen-Mansfield Agitation Inventory). RESULTS: Overall prevalence of NPS was 94.6%, being apathy the most prevalent (66.7%) and the one whose severity increased the most with progression of dementia. Agitation/aggression, irritability, and sleeping and eating disorders also increased over time. Delusions and depressive symptoms decreased in severity with disease progression. In severe dementia, female displayed more depressive symptoms and eating disorders, while male displayed more agitation/aggression and sleep disturbances. CONCLUSION: NPS in dementia follow a heterogeneous course. Apathy is the most prevalent NPS and the one that worsens most significantly over time. The course of some NPS differs between sexes. Further research is required to understand the evolution of NPS at advanced stages of dementia.

The course of neuropsychiatric symptoms and psychotropic drug use in Dutch nursing home patients with dementia during the first wave of COVID-19: A longitudinal cohort study.

OBJECTIVE: To describe the course of neuropsychiatric symptoms in nursing home residents with dementia during the step-by-step lifting of restrictions after the first wave of the COVID-19 pandemic in the Netherlands, and to describe psychotropic drug use (PDU) throughout the whole first wave. METHODS: Longitudinal cohort study of nursing home residents with dementia. We measured neuropsychiatric symptoms using the Neuropsychiatric Inventory-Questionnaire (NPI-Q). From May to August 2020, the NPI-Q was filled in monthly. Psychotropic drug use was retrieved from the electronic prescription system, retrospectively for the months February to April and prospectively for the months May to August. RESULTS: We followed 252 residents with dementia in 19 Dutch nursing homes. Agitation was the most prevalent type of neuropsychiatric symptom at each assessment. Overall, the prevalence and severity of agitation and depression significantly decreased over time. When considering more in detail, we observed that in some residents specific neuropsychiatric symptoms resolved (resolution) while in others specific neuropsychiatric symptoms developed (incidence) during the study period. For the majority of the residents, neuropsychiatric symptoms persisted over time. Psychotropic drug use remained stable over time throughout the whole first wave of the pandemic. CONCLUSIONS: At group level, lifting the measures appeared to have beneficial effects on the prevalence and severity of agitation and depression in residents with dementia. Nevertheless, on an individual level we observed high heterogeneity in the course of neuropsychiatric symptoms over time. Despite the pressure of the pandemic and the restrictions in social contact imposed, PDU remained stable.

Effects of preoperative nasal spray esketamine on separation anxiety and emergence agitation in pediatric strabismus surgery: A randomized clinical trial.

OBJECTIVE: To investigate the effects of preoperative nasal spray esketamine on separation anxiety and postoperative emergence agitation in pediatric strabismus surgery. METHOD: Ninety children aged 3 to 6 years who underwent elective strabismus surgery were randomly divided into 3 groups that received 0.5 mg/kg (group S1), 1 mg/kg of esketamine (group S2), and the same volume of normal saline (group C) by nasal spray 10 minutes before surgery. The observation indicators of this test include the Ramsay sedation score, separation anxiety score, mask induction score, and the incidences of postoperative emergence agitation. Patient's heart rate, blood oxygen, post anesthesia care unit stay time, and any adverse events were recorded. RESULTS: The Ramsay sedation score was significantly lower in group C than those in groups S1 and S2 (P < .001). The separation anxiety scores and the mask induction scores were significantly higher in group C than those in groups S1 and S2 (P < .001). The incidences of emergence agitation in groups S1 and S2 were significantly lower than that in C group (P < .001). No obvious clinical complication was observed. CONCLUSION: Preoperative nasal spray esketamine reduced the preoperative separation anxiety and decrease emergence agitation in pediatric strabismus surgery.

Developmental multi-trajectory of irritability, anxiety, and hyperactivity as psychological markers of heterogeneity in childhood aggression.

BACKGROUND: A growing body of evidence suggests that child aggression is likely to be driven by multiple developmental pathways. However, little is known about the complex interactions between developmental trajectories of child psychological factors (such as anxiety, irritability, and hyperactivity/impulsivity dimensions) and their associations with aggression from childhood to adolescence. Therefore, the current study aimed to identify clusters of individuals with different developmental multi-trajectory, investigate their early risk factors, and describe their longitudinal associations with physical aggression. METHOD: The sample comprised 4898 children derived from the Fragile Families and Child Wellbeing Study. A parallel process growth mixture model was used to identify developmental multi-trajectory groups at 5, 9 and 15 years old. Associations between multi-trajectory group membership and physical aggression were examined with Generalized Estimating Equations models. Finally, multinomial logistic regression was performed to assess perinatal and early risk factors for multi-trajectory groups. RESULTS: Multi-trajectory groups differed in the magnitude of risk for exhibiting physical aggression, compared to typically developing children. The risk for physical aggression was the most prominent in children who were hyperactive/impulsive and irritable [odds ratio (OR) 6.47; 95% confidence interval (CI) 5.44-7.70] and hyperactive/impulsive, irritable, and anxious (OR 7.68; CI 6.62-8.91). Furthermore, maternal cigarette and alcohol use during pregnancy and maternal depression consistently predicted multi-trajectory groups characterized by problematic levels of at least two co-occurrent psychological symptoms. CONCLUSIONS: Identified combinations of developmental trajectories of psychological characteristics were associated with different magnitude in risk for exhibiting physical aggression. These results may highlight the heterogeneity of developmental trajectories associated with childhood aggression.

Agitation and Restraint in a Pediatric Psychiatric Emergency Program: Clinical Characteristics and Diagnostic Correlates.

OBJECTIVES: Agitation and restraint among pediatric psychiatric patients are a frequent, yet little studied, source of morbidity and, rarely, mortality in the emergency department (ED). This study examined agitation and restraint among youth patients in a specialized pediatric psychiatric ED, considering clinical and sociodemographic characteristics of those who required restraint to determine the clinical correlates of agitation and restraint in this population. METHODS: This descriptive study was a 6-year retrospective chart review of all patients restrained for acute agitation. Demographics, clinical characteristics, diagnoses, and reasons for restraint were collected. Relationships between sociodemographic and clinical variables to types of restraints used were examined, along with change over the study period in rate of and mean time in restraint. RESULTS: The average restraint rate was 1.94%, which remained fairly consistent throughout study period, although average time in restraint decreased significantly. Restraints were more common in males. Adolescents were overrepresented in the ED population, and after controlling for this, restraint rates were similar in adolescents and younger children. Physical aggression was the most frequent precipitant, although among adolescents verbal aggression was also a precipitant (more so than in younger children). Disruptive behavior disorder diagnoses were most frequently associated with restraint. CONCLUSIONS: A lower rate of restraint is reported here than has been seen in programs where youths are treated in medical or adult psychiatric EDs. Hospitals without specialized pediatric psychiatric emergency programs should invest in staff training in deescalation techniques and in access to pediatric psychiatric treatment. The finding that, of youth restrained, a significant proportion were under 12 years old and/or carried diagnoses not typically associated with aggressive behavior, indicates that crisis prevention, management, and treatment should include younger populations and diverse diagnostic groups, rather than focusing narrowly on older patients with psychotic or substance use disorders.

Factor Analysis of the Short-Form Cohen-Mansfield Agitation Inventory and the Measurement Invariance by Gender.

BACKGROUND AND PURPOSE: The Cohen-Mansfield Agitation Inventory (CMAI) is a widely used measure of agitation. The purpose of this study was to test the internal consistency, reliability, and validity of short-form CMAI in a sample of nursing home residents with cognitive impairment and examine if it is invariant across gender. METHODS: This study utilized baseline data from a randomized trial including 553 residents from 55 nursing homes. Data was analyzed using structural equation modeling. RESULTS: Confirmatory factory analysis supported the three-factor structure including aggressive (α = .794), physically nonaggressive (α = .617), and verbally agitated (α = .718) behaviors. Invariance testing confirmed that the shortened measure is invariant across gender. CONCLUSIONS: Findings provide validity evidence of short-form CMAI to assess agitation and gender differences in agitation in nursing home population.

Agitated Behaviors following Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prevalence by Post-Traumatic Amnesia Status, Hospital Setting, and Agitated Behavior Type.

Agitation is a common behavioral problem following traumatic brain injury (TBI); however, the precise proportion of patients who experience agitation in the early stages of recovery is unknown. The aim of this systematic review and meta-analysis was to evaluate the prevalence of agitation in TBI patients undergoing inpatient care, and whether this prevalence differed by post-traumatic amnesia (PTA) status and setting (acute and rehabilitation). We also aimed to describe the prevalence of sub-types of agitated behavior (disinhibited, aggressive, and emotionally labile). We searched five databases and one clinical trials register, with additional review of websites and key journals to identify any relevant records up to July 2020. We included studies describing the proportion of hospitalized TBI patients age 16 years or older demonstrating agitated behavior. We included comparative studies with and without concurrent controls, randomized controlled trials, pseudo-randomized controlled trials, and case series. Methodological quality was critically appraised using a Joanna Briggs Institute checklist. Sixteen studies met eligibility criteria, with a total of 5592 participants. The pooled prevalence of agitation was 31.73% (95% confidence interval [CI], 25.25%-39.00%) during inpatient care (acute and rehabilitation), 32.23% (95% CI, 27.13%-37.80%) during rehabilitative care and 44.06% (95% CI, 36.15%-52.28%) for inpatients in PTA specifically. Disinhibited behaviors were the most common. There was substantial heterogeneity between studies. Additional high-quality research featuring large samples, frequent and long-term measurement of agitation, use of validated scales, and consideration of variables such as PTA status will further improve estimates of agitation prevalence following TBI.

Childhood neurodevelopmental markers and risk of premature mortality: Follow-up to age 60-65 years in the Aberdeen Children of the 1950s study.

BACKGROUND: Individual neurodevelopmental disorders are associated with premature mortality. Little is known about the association between multiple neurodevelopmental markers and premature mortality at a population level. The ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations) approach considers multiple neurodevelopmental parameters, assessing several markers in parallel that cluster, rather than considering individual diagnostic categories in isolation. OBJECTIVES: To determine whether childhood neurodevelopmental markers, including reduced intellectual functioning, are associated with all-cause premature mortality. METHODS AND PROCEDURES: In a general population cohort study (n = 12,150) with longitudinal follow up from childhood to middle age, Cox proportional hazard models were used to study the associations between childhood neurodevelopmental markers (Rutter B scale and IQ) and premature all-cause mortality. OUTCOMES AND RESULTS: The cognitive measures and 21 of the 26 Rutter B items were significantly associated with premature mortality in bivariate analyses with hazard ratios from 1.24 (95% CI 1.05-1.47) to 2.25 (95% CI 1.78-2.90). In the final adjusted model, neurodevelopmental markers suggestive of several domains including hyperactivity, conduct problems and intellectual impairment were positively associated with premature mortality and improved prediction of premature mortality. CONCLUSIONS: A wide range of neurodevelopmental markers, including childhood IQ, were found to predict premature mortality in a large general population cohort with longitudinal follow up to 60-65 years of age. IMPLICATIONS: These findings highlight the importance of a holistic assessment of children with neurodevelopmental markers that addresses a range of neurodevelopmental conditions. Our findings could open the door to a shift in child public mental health focus, where multiple and/or cumulative markers of neurodevelopmental conditions alert clinicians to the need for early intervention. This could lead to a reduction in the risk of broad health outcomes at a population level.

Impact of agitation in long-term care residents with dementia in the United States.

OBJECTIVES: To describe characteristics and compare clinical outcomes including falls, fractures, infections, and neuropsychiatric symptoms (NPS) among long-term care residents with dementia with and without agitation. METHODS: A cross-sectional secondary analysis of administrative healthcare data was conducted whereby residents with dementia residing in a long-term care facility for ≥12 months were identified from the AnalytiCare LLC database (10/2010-06/2014) and were classified into mutually exclusive cohorts (Agitation Cohort or No-Agitation Cohort) based on available agitation-related symptoms. Entropy balancing was used to balance demographic and clinical characteristics between the two cohorts. The impact of agitation on clinical outcomes was compared between balanced cohorts using weighted logistic regression models. RESULTS: The study included 6,265 long-term care residents with dementia among whom, 3,313 were included in the Agitation Cohort and 2,952 in the No-Agitation Cohort. Prior to balancing, residents in the Agitation Cohort had greater dementia-related cognitive impairment and clinical manifestations compared to the No-Agitation Cohort. After balancing, residents with and without agitation, respectively, received a median of five and four distinct types of medications (including antipsychotics). Further, compared to residents without agitation, those with agitation were significantly more likely to have a recorded fall (OR = 1.58), fracture (OR = 1.29), infection (OR = 1.18), and other NPS (OR = 2.11). CONCLUSIONS: Agitation in long-term care residents with dementia was associated with numerically higher medication use and an increased likelihood of experiencing falls, fractures, infections, and additional NPS compared to residents without agitation, highlighting the unmet need for effective management of agitation symptoms in this population.

Admission Features Associated With Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: A Case-Control Study.

OBJECTIVES: Paroxysmal sympathetic hyperactivity occurs in a subset of critically ill traumatic brain injury patients and has been associated with worse outcomes after traumatic brain injury. The goal of this study was to identify admission risk factors for the development of paroxysmal sympathetic hyperactivity in traumatic brain injury patients. DESIGN: Retrospective case-control study of age- and Glasgow Coma Scale-matched traumatic brain injury patients. SETTING: Neurotrauma ICU at the R. Adams Cowley Shock Trauma Center of the University of Maryland Medical System, January 2016 to July 2018. PATIENTS: Critically ill adult traumatic brain injury patients who underwent inpatient monitoring for at least 14 days were included. Cases were identified based on treatment for paroxysmal sympathetic hyperactivity with institutional first-line therapies and were confirmed by retrospective tabulation of established paroxysmal sympathetic hyperactivity diagnostic and severity criteria. Cases were matched 1:1 by age and Glasgow Coma Scale to nonparoxysmal sympathetic hyperactivity traumatic brain injury controls, yielding 77 patients in each group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission characteristics independently predictive of paroxysmal sympathetic hyperactivity included male sex, higher admission systolic blood pressure, and initial CT evidence of diffuse axonal injury, intraventricular hemorrhage/subarachnoid hemorrhage, complete cisternal effacement, and absence of contusion. Paroxysmal sympathetic hyperactivity cases demonstrated significantly worse neurologic outcomes upon hospital discharge despite being matched for injury severity at admission. CONCLUSIONS: Several anatomical, epidemiologic, and physiologic risk factors for clinically relevant paroxysmal sympathetic hyperactivity can be identified on ICU admission. These features help characterize paroxysmal sympathetic hyperactivity as a clinical-pathophysiologic phenotype associated with worse outcomes after traumatic brain injury.

A Prospective Study of Intramuscular Droperidol or Olanzapine for Acute Agitation in the Emergency Department: A Natural Experiment Owing to Drug Shortages.

STUDY OBJECTIVE: Intramuscular medications are commonly used to treat agitation in the emergency department (ED). The purpose of this study is to compare intramuscular droperidol and olanzapine for treating agitation. METHODS: This was a prospective observational study of ED patients receiving intramuscular droperidol or olanzapine for acute agitation. The treating physician determined the medication and dose; however, over time drug shortages made either olanzapine (July to September 2019) or droperidol (November 2019 to March 2020) unavailable, creating a natural experiment. The primary outcome was time to adequate sedation, assessed by the Altered Mental Status Scale (AMSS), defined as time to AMSS score less than or equal to 0. RESULTS: We analyzed 1,257 patients (median age 42 years; 73% men); 538 received droperidol (median dose 5 mg) and 719 received olanzapine (median dose 10 mg). The majority of patients (1,086; 86%) had agitation owing to alcohol intoxication. Time to adequate sedation was 16 minutes (interquartile range 10 to 30 minutes) for droperidol and 17.5 minutes (interquartile range 10 to 30 minutes) for olanzapine (absolute difference -0.7 minutes; 95% confidence interval -2.1 to 0.5 minutes). Adjusted Cox proportional hazard model analysis revealed no difference between groups in time to sedation (hazard ratio for adequate sedation for droperidol compared with olanzapine 1.12; 95% confidence interval 1.00 to 1.25). Patients receiving olanzapine were more likely to receive additional medications for sedation (droperidol 17%; olanzapine 24%; absolute difference -8% [95% confidence interval -12% to -3%]). We observed no difference between drugs regarding adverse effects except for extrapyramidal adverse effects, which were more common with droperidol (n=6; 1%) than olanzapine (n=1; 0.1%). CONCLUSION: We found no difference in time to adequate sedation between intramuscular droperidol and olanzapine.

Cariprazine and akathisia, restlessness, and extrapyramidal symptoms in patients with bipolar depression.

BACKGROUND: Akathisia is a neuropsychiatric syndrome that is commonly related to the use of dopamine receptor antagonists/partial agonists. The characteristics of cariprazine-related akathisia, restlessness, and extrapyramidal symptoms (EPS) were investigated in patients with bipolar I depression. METHODS: Akathisia-related data from 3 fixed-dose clinical studies of cariprazine 1.5 mg/d and 3 mg/d in bipolar depression were evaluated in pooled post hoc analyses. Outcomes related to treatment-emergent adverse events (TEAEs) included incidence, time to onset, time to resolution, severity, discontinuations, and rescue medication use. RESULTS: The incidence of akathisia was 7.6% for overall cariprazine (1.5 mg/d=5.5%; 3 mg/d=9.6%) and 2.1% for placebo; acute EPS occurred in 4.5% of cariprazine-treated (1.5 mg/d=3.8%; 3 mg/d=5.1%) and 2.1% of placebo-treated patients. Findings were similar for restlessness. Most TEAEs were mild/moderate (>95%), occurred during the first 3 weeks of cariprazine initiation or dose increase, and resulted in few discontinuations (<3%); median time to resolution of an akathisia or EPS TEAE after the last dose of cariprazine was ~1 week. Rescue medication was used by <3% of patients to manage akathisia/EPS events. LIMITATIONS: Post hoc analyses; no active comparator. CONCLUSIONS: In patients with bipolar depression, the incidence of cariprazine-related akathisia was higher than acute EPS or restlessness, with lower cariprazine doses associated with lower incidences of events. Akathisia and EPS TEAEs occurred early in treatment and were mild/moderate in severity. Few patients with akathisia or acute EPS discontinued treatment. Cariprazine-related akathisia and EPS can be minimized with conservative dosing and titration strategies. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT01396447, NCT02670538, NCT02670551.

Effect of ketamine on emergence agitation following septoplasty: a randomized clinical trial.

BACKGROUND AND OBJECTIVES: The risk of emergence agitation (EA) is high in patients undergoing nasal surgery. The aim of the present study was to investigate the incidence of EA in adults undergoing septoplasty and the effect of ketamine on EA. METHODS: In this randomized study, a total of 102 ASA I-II patients who underwent septoplasty between July 2018 and April 2019 were divided into two groups: ketamine (Group-K, n=52) and saline (Group-S, n=50). After anesthesia induction, Group-K was intravenously administered 20mL of saline containing 1mgkg-1 ketamine, whereas Group-S was administered 20mL of saline. Sedation and agitation scores at emergence from anesthesia, incidence of cough, emergence time, and response to verbal stimuli time were recorded. The sedation/agitation and pain levels were recorded for 30minutes in the recovery unit. RESULTS: There was no significant difference between the groups in terms of the incidence of EA (Group-K: 15.4%, Group-S: 24%). The incidence of cough during emergence was higher in Group-S than in Group-K, but the response time to verbal stimuli and emergence time were shorter in Group-S. The sedation and agitation scores were similar after surgery. Pain scores were higher in Group-S at the time of admission to the recovery unit and were similar between groups in the other time points. CONCLUSION: Administration of 1mgkg-1 ketamine after anesthesia induction does not affect the incidence of EA in patients undergoing septoplasty, but it prolongs the emergence and response time to verbal stimuli and reduces the incidence of cough.