Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflurane Anesthesia for Pediatric Liver Surgery.

BACKGROUND We aimed to assess the effect of dexmedetomidine (Dex) combined with remifentanil on emergence agitation (EA) during awakening from sevoflurane anesthesia for pediatric liver surgery. MATERIAL AND METHODS Sixty children who underwent liver surgery in our hospital were prospectively selected and randomly allocated into group A (placebo+remifentanil+sevoflurane) or group B (Dex+remifentanil+sevoflurane). Mean arterial pressure (MAP) and heart rate (HR) at different time points, agitation score during awakening, behavioral status, pain level, and the incidence of postoperative adverse effects were compared in both groups. RESULTS Children in group B had lower HR and MAP levels immediately after tracheal extubation and 5 min after tracheal extubation than those in group A. The Aono's scores, PAED agitation scores, and CHIPP scores at 15 min and 30 min of admission to the PACU were lower in group B than in group A. The incidence of agitation during postoperative anesthesia awakening was lower in group B in contrast to group A. There was no significant difference in postoperative adverse reactions between group A and group B. CONCLUSIONS In pediatric liver surgery, the use of Dex+remifentanil+sevoflurane anesthesia can reduce the incidence of EA during the awakening period, stabilize hemodynamic levels, and relieve postoperative pain, and has fewer postoperative adverse effects, which warrants clinical application.

Effects of different doses of intranasal dexmedetomidine on related complications and parents' satisfaction in anesthetized children: a systematic review.

BACKGROUND: Agitation/delirium is commonly seen in children after anesthesia, and a proper dose of dexmedetomidine can prevent this complication. This study aimed to investigate the effects of different doses of Dexmedetomidine (DEX) on agitation/delirium and other complications in anesthetized children, providing clinical evidence for dose recommendations of DEX. METHODS: This study was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, and EMBASE. Two independent researchers performed literature screening, data extraction, and assessed the methodological quality. Data analysis was conducted using R and STATA 16.0. RESULTS: In the final analysis, 20 randomized controlled trials (RCTs) involving 2521 children were included. The results showed that in comparison to normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX significantly reduced the incidence of post-anesthetic emergence agitation in children with the most effective dose being 2 µg/kg (SUCRA = 0.91). Compared with normal saline, 1 µg/kg, 1.5 µg/kg, and 2 µg/kg intranasal DEX reduced patient's need for postoperative analgesia, with the most effective dose being 1.5 µg/kg (SUCRA = 0.78). However, 1 µg/kg DEX performed the best in reducing Pediatric Anaesthesia Emergence Delirium (PAED) Scale score (SUCRA = 0.88). CONCLUSION: Compared with normal saline, intranasal administration of 2 µg/kg DEX and 1.5 µg/kg DEX are the optimal doses to reduce the incidence of agitation and the need for postoperative pain relief in children under general anesthesia. Given effectiveness and safety, intranasal use of 1 µg/kg DEX appears to be the most effective dosage for anesthetized children.

Effects of cariprazine on reducing symptoms of irritability, hostility, and agitation in patients with manic or mixed episodes of bipolar I disorder.

BACKGROUND: Hostility, irritability, and agitation are common in patients with bipolar I disorder. Post hoc analyses evaluated the effect of cariprazine on these symptoms in patients with bipolar I mania. METHODS: Data were pooled from three randomized, double-blind, placebo-controlled phase 3 cariprazine trials in adults with bipolar I manic/mixed episodes (NCT00488618, NCT01058096, NCT01058668); pooled cariprazine doses (3-12 mg/d) were analyzed. Patients were categorized into hostility/irritability and agitation subgroups by baseline scores: Young Mania Rating Scale (YMRS) irritability and disruptive-aggressive behavior items score ≥ 2; Positive and Negative Syndrome Scale (PANSS) hostility item ≥ 2; PANSS-Excited Component (PANSS-EC) total score ≥ 14 and score ≥ 4 on ≥ 1 individual item. Changes from baseline to week 3 in hostility/irritability- and agitation-related outcomes were evaluated. Adjustments were made for the presence of other manic symptoms, sedation, and akathisia. RESULTS: Most patients met subgroup inclusion criteria (YMRS hostility = 930; PANSS hostility = 841, PANSS-EC agitation = 486). In the YMRS subgroup, least squares mean differences in change from baseline were statistically significant for cariprazine versus placebo on YMRS hostility/irritability-related items (irritability [-0.93], disruptive-aggressive behavior [-0.79], combined [-1.75]; P ≤ 0.001 each), YMRS total score (-5.92, P ≤ 0.0001), and all individual YMRS items (-0.25 to -0.93, P ≤ 0.0001); differences remained significant after adjustment for other manic symptoms, sedation, and akathisia. Differences in PANSS hostility and PANSS-EC subgroups were significant for cariprazine versus placebo (P ≤ 0.001). LIMITATIONS: Post hoc analysis. CONCLUSION: Cariprazine demonstrated specific antihostility/irritability and anti-agitation effects in patients with manic/mixed episodes of bipolar I disorder and baseline hostility, irritability, or agitation.

Preoperative Intrathecal Morphine is Associated With Reduced Postoperative Pain, Agitation, and Delirium In Living Donor Kidney Transplantation Recipients.

BACKGROUND: Postoperative delirium after organ transplantation can lead to increased length of hospital stay and mortality. Because pain is an important risk factor for delirium, perioperative analgesia with intrathecal morphine (ITM) may mitigate postoperative delirium development. We evaluated if ITM reduces postoperative delirium incidence in living donor kidney transplant (LDKT) recipients. METHODS: Two hundred ninety-six patients who received LDKT between 2014 and 2018 at our hospital were retrospectively analyzed. Recipients who received preoperative ITM (ITM group) were compared with those who did not (control group). The primary outcome was postoperative delirium based on the Confusion Assessment Method for Intensive Care Unit results during the first 4 postoperative days. RESULTS: Delirium occurred in 2.6% (4/154) and 7.0% (10/142) of the ITM and control groups, respectively. Multivariable analysis showed age (odds ratio [OR]: 1.07, 95% CI: 1.01-1.14; P = .031), recent smoking (OR: 7.87, 95% CI: 1.43-43.31; P = .018), preoperative psychotropics (OR: 23.01, 95% CI: 3.22-164.66; P = .002) were risk factors, whereas ITM was a protective factor (OR: 0.23, 95% CI: 0.06-0.89; P = .033). CONCLUSIONS: Preoperative ITM showed an independent association with reduced post-LDKT delirium. Further studies and the development of regional analgesia for delirium prevention may enhance the postoperative recovery of transplant recipients.

Approach to acute agitation in the pediatric emergency department.

PURPOSE OF REVIEW: The complexity of pediatric mental and behavioral health (MBH) complaints presenting to emergency departments (EDs) is increasing at an alarming rate. Children may present with agitation or develop agitation during the ED visit. This causes significant distress and may lead to injury of the child, caregivers, or medical staff. This review will focus on providing safe, patient-centered care to children with acute agitation in the ED. RECENT FINDINGS: Approaching a child with acute agitation in the ED requires elucidation on the cause and potential triggers of agitation for optimal management. The first step in a patient-centered approach is to use the least restrictive means with behavioral and environmental strategies. Restraint use (pharmacologic or physical restraint) should be reserved where these modifications do not result in adequate de-escalation. The provider should proceed with medications first, using the child's medication history as a guide. The use of physical restraint is a last resort to assure the safety concerns of the child, family, or staff, with a goal of minimizing restraint time. SUMMARY: Children are increasingly presenting to EDs with acute agitation. By focusing primarily on behavioral de-escalation and medication strategies, clinicians can provide safe, patient-centered care around these events.

Alternative Approaches for Addressing Acute Agitation in Schizophrenia and Bipolar Disorder.

Importance: The prompt effective treatment of acute agitation among patients with schizophrenia or bipolar disorder can alleviate distressing symptoms for the patient and decrease the risk of escalation to aggression and the potential for serious harm to the patient, health care providers, and others.Observations: A commonly used approach for the management of acute agitation has been the intramuscular administration of antipsychotic medications and/or benzodiazepines. However, US Food and Drug Administration-approved treatments with alternative routes of delivery now include inhaled loxapine powder and, more recently, dexmedetomidine sublingual film. Two formulations of intranasal olanzapine for acute agitation are in development.Conclusions and Relevance: Intranasal formulations offer the potential for favorable pharmacokinetics and onset of action combined with ease of delivery obviating the need for injections and are thus consistent with patient-centered factors such as preference and self-administration. In this review, alternative methods of medication delivery are discussed, with an emphasis on the potential for intranasal administration to treat acute agitation in adult patients with schizophrenia or bipolar disorder.Prim Care Companion CNS Disord 2024;26(1):23nr03596. Author affiliations are listed at the end of this article.

Agony of akathisia: a case of sodium valproate-induced akathisia.

Akathisia is a subjective feeling of restlessness that often results in a compulsion to move. Drug-related causes are the most common aetiologies. It can often be confused with restless legs syndrome (RLS). We describe a case of valproate-induced akathisia that improved with drug cessation. This case reports a rare but treatable adverse effect of sodium valproate and highlights the importance of differentiating akathisia from RLS.

Reduction and prevention of agitation in persons with neurocognitive disorders: an international psychogeriatric association consensus algorithm.

OBJECTIVES: To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA). DESIGN: Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion. SETTING: IPA Agitation Workgroup. PARTICIPANTS: IPA panel of international experts on agitation. INTERVENTION: Integration of available information into a comprehensive algorithm. MEASUREMENTS: None. RESULTS: The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues-home, nursing home, emergency department, hospice-and adjustments to the therapeutic approach are presented. CONCLUSIONS: The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.

Dexmedetomidine Sublingual Film: A New Treatment to Reduce Agitation in Schizophrenia and Bipolar Disorders.

OBJECTIVE: The objective of this study was to review the available literature for dexmedetomidine sublingual film use in the treatment of acute agitation associated with schizophrenia and bipolar disorders. DATA SOURCES: A literature search of PubMed (January 2017-March 2023) and EMBASE (January 2017-March 2023) was performed using the terms: Igalmi, dexmedetomidine, schizophrenia, bipolar disorder, and agitation. Additional information sources include ClinicalTrials.gov, scientific posters, and articles identified through review of references from clinical trials publications. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language articles conducted in humans were considered, with a preference for phase 3 clinical trials. Trial analyses and articles discussing pharmacology, pharmacokinetics, efficacy, and safety were also evaluated. DATA SYNTHESIS: Dexmedetomidine sublingual film was evaluated for use in schizophrenia in the SERENITY 1 pivotal trial and for bipolar disorders in the SERENITY 2 pivotal trial. Both studies found treatment of mild to moderate agitation with dexmedetomidine sublingual film 180 and 120 µg to be superior to placebo in reducing the severity of agitation. Treatment effect was seen as early as 20 minutes. Somnolence was the most common adverse effect in both studies. Cardiovascular adverse effects were mild and transient in most cases. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Dexmedetomidine sublingual film is a new and novel treatment for agitation and gives clinicians an alternative to antipsychotic and benzodiazepine use. It has advantageous properties including its noninvasive route of administration, fast absorption, and rapid onset of effect. Cost may limit its use. CONCLUSION: Dexmedetomidine sublingual film provides an alternative approach to treatment of acute agitation in adults with schizophrenia and bipolar disorders based on both mechanism of action and route of administration.

Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: shared neuronal mechanisms?

Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent preclinical experimental data in rodents, we provide a coherent and unifying neurobiological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.

A Novel Approach to Monitoring Cognitive Adverse Events for Interventional Studies Involving Advanced Dementia Patients: Insights From the Electroconvulsive Therapy for Agitation in Dementia Study.

OBJECTIVE: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study). METHODS: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study. RESULTS: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change. CONCLUSIONS: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia.

Optimal strategies for assessing and managing pain, agitation, and delirium in the critically ill surgical patient: What you need to know.

ABSTRACT: Pain, agitation, and delirium (PAD) are primary drivers of outcome in the ICU, and expertise in managing these entities successfully is crucial to the intensivist's toolbox. In addition, there are unique aspects of surgical patients that impact assessment and management of PAD. In this review, we address the continuous spectrum of assessment, and management of critically ill surgical patients, with a focus on limiting PAD, particularly incorporating mobility as an anchor to ICU liberation. Finally, we touch on the impact of PAD in specific populations, including opioid use disorder, traumatic brain injury, pregnancy, obesity, alcohol withdrawal, and geriatric patients. The goal of the review is to provide rapid access to information regarding PAD and tools to assess and manage these important elements of critical care of surgical patients.

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.

Enhancing management of agitation after traumatic brain injury: Psychiatric perspectives and quantitative assessments.

BACKGROUND: Post-traumatic agitation is a common and problematic complication after traumatic brain injury. It may present with features consistent with psychiatric disorders, which may provide clues as to management. OBJECTIVE: This is a narrative review of pertinent literature and a description of a collaborative clinical approach utilizing psychiatric and brain injury rehabilitation strategies to optimize outcomes in the management of post-traumatic agitation. METHODS: Describe and provide evidence for a transdisciplinary clinical approach supported by existing literature and clinical experience. RESULTS: Given the heterogeneity of the problem and limitations in the current literature there is no standardized approach to manage post-traumatic agitation; nevertheless, a strategy is proposed that clinicians may utilize to guide treatment and assess efficacy of the chosen intervention(s). CONCLUSION: A clinical approach that uses quantitative assessment of targeted behavior to objectively evaluate pharmacological interventions that are generated by a collaborative approach may yield improved outcomes for managing post-traumatic agitation.

Improving the pharmacotherapeutic treatment of agitation associated with bipolar disorder.

INTRODUCTION: Agitation is commonly encountered in people with bipolar disorder, particularly when experiencing a manic episode. The number of approved pharmacological agents to manage acute episodes of agitation in this population is limited. AREAS COVERED: A search was conducted using the US National Library of Medicine PubMed.gov resource for English-language papers of clinical trials and reviews/meta-analyses, using the text words 'bipolar disorder' AND 'agitation,' as well as any papers with both two text words in the title, without any date restrictions. EXPERT OPINION: Existing pharmacologic options approved by regulatory authorities for the treatment of acute episodes of agitation associated with bipolar disorder have similar degrees of efficacy but differ in their tolerability profiles and ease of use, giving clinicians an opportunity to individualize treatment. The goal is to treat mild-moderate agitation before it evolves into severe agitation, encouraging noninvasive pharmacologic treatment options. Inhaled loxapine and sublingual dexmedetomidine are newer options with rapid onset of action and may be preferable for patients willing to cooperate with treatment.

Factors influencing agitation, de-escalation, and physical restraint at a children's hospital.

BACKGROUND: Children hospitalized in medical hospitals are at risk of agitation. Physical restraint may be used to maintain patient and staff safety during de-escalation, but physical restraint use is associated with physical and psychological adverse events. OBJECTIVE: We sought to better understand which work system factors help clinicians prevent patient agitation, improve de-escalation, and avoid physical restraint. DESIGN, SETTING, AND PARTICIPANTS: We used directed content analysis to extend the Systems Engineering Initiative for Patient Safety model to clinicians working with children at risk for agitation at a freestanding children's hospital. INTERVENTION, MAIN OUTCOME, AND MEASURES: We conducted semistructured interviews to examine how five clinician work system factors affected patient agitation, de-escalation, and restraint: person, environment, tasks, technology and tools, and organization. Interviews were recorded, transcribed, and analyzed until saturation. RESULTS: Forty clinicians participated in this study, including 21 nurses, 15 psychiatric technicians, 2 pediatric physicians, 1 psychologist, and 1 behavior analyst. Work system factors that contributed to patient agitation were medical tasks like vital signs and the hospital environment including bright lights and neighboring patients' noises. Supports that helped clinicians de-escalate patients included adequate staffing and accessible toys and activities. Participants indicated that organizational factors were integral to team de-escalation, drawing connections between units' teamwork and communication cultures and their likelihood of successful de-escalation without the use of physical restraint. CONCLUSION: Clinicians perceived that medical tasks, hospital environmental factors, clinician attributes, and team communication influenced patients' agitation, de-escalation, and physical restraint. These work system factors provide opportunities for future multi-disciplinary interventions to reduce physical restraint use.

Ketamine: A Practical Review for the Consultation-Liaison Psychiatrist.

BACKGROUND: Ketamine is a noncompetitive N-methyl-D-aspartate-receptor antagonist often used for sedation and management of acute agitation in general hospital settings. Many hospitals now include ketamine as part of their standard agitation protocol, and consultation-liaison psychiatrists frequently find themselves treating patients who have received ketamine, despite lack of clear recommendations for management. OBJECTIVE: Conduct a nonsystematic narrative review regarding the use of ketamine for agitation and continuous sedation, including benefits and adverse psychiatric effects. Compare ketamine to more traditional agents of agitation control. Provide consultation-liaison psychiatrists with a summary of available knowledge and recommendations for managing patients receiving ketamine. METHODS: A literature review was performed using PubMed, querying published articles from inception to March 2023 for articles related to use of ketamine for agitation or continuous sedation and side effects including psychosis and catatonia. RESULTS: A total of 37 articles were included. Ketamine was found to have multiple benefits, including shorter time to adequate sedation for agitated patients when compared to haloperidol ± benzodiazepines and unique advantages for continuous sedation. However, ketamine carries significant medical risks including high rates of intubation. Ketamine appears to induce a syndrome that mimics schizophrenia in healthy controls, and such effects are more pronounced and longer-lasting in patients with schizophrenia. Evidence regarding rates of delirium with ketamine for continuous sedation is mixed and requires further investigation before the agent is widely adopted for this purpose. Finally, the diagnosis of "excited delirium syndrome" and use of ketamine to treat this controversial syndrome warrants critical evaluation. CONCLUSIONS: Ketamine carries many potential benefits and can be an appropriate medication for patients with profound undifferentiated agitation. However, intubation rates remain high, and ketamine may worsen underlying psychotic disorders. It is essential that consultation-liaison psychiatrists understand the advantages, disadvantages, biased administration, and areas of limited knowledge regarding ketamine.