Is there evidence for using ketamine among individuals with dementia?

The aim of this short narrative review was to evaluate the existing literature regarding the clinical use of ketamine among individuals with dementia, especially those with behavioral disturbances. PubMed, Cochrane, and Ovid (Embase, APA PsycINFO, and MEDLINE) databases were searched for abstracts using the search terms "ketamine" AND "dementia." Only articles describing the use of ketamine in individuals with dementia were included. Articles that did not include individuals with dementia, did not use ketamine, were published in a non-English language, primarily described animal studies, or were reviews were excluded. Three case reports met the inclusion criteria. One described the use of subcutaneous ketamine for depression, one described the use of intramuscular ketamine for acute agitation, and one described the use of S-ketamine as anesthesia during electroconvulsive therapy for depression and catatonia. No significant adverse effects were reported in any of the cases. Although the use of ketamine in the treatment of depression and agitation associated with dementia has potential, the current evidence remains limited. High-quality prospective studies are needed to confirm the observations of these case reports before ketamine can be used to treat behavioral disturbances in individuals with dementia.

Correlation Analyses Between Childhood Behavioral Disturbance and Maternal Alexithymia: An Observational Study.

Purpose: Caregivers' responses have an impact on children's emotional and behavioral development. The inability of caregivers to perceive their own emotions affects their responses to children. This study aims to examine the relationship between a mother's difficulties in emotional expression and children's emotional and behavioral disorders. Patient and Methods: A total of 78 cases, aged between 3 and 15 years old, were included in this study. The mothers completed the Taiwan version of the "Toronto Alexithymia Scale" (TAS) and "Children's Behavior Checklist" (CBCL) questionnaires, which served as research tools. TAS consists of three factors: difficulty in distinguishing emotions (Factor 1, F1), difficulty in expressing feelings (Factor 2, F2), and an externally oriented thinking style (Factor 3, F3). CBCL represents a child's behavior profile. The Mann-Whitney test and correlation analyses were used for follow-up analysis. Results: Our analysis revealed that F1, F2, F3, and total scores of TAS (TAS-Total) correlate positively with the somatic complaint subscale of CBCL (F1: p = 0.003; F2: p = 0.002; F3: p = 0.034, TAS-Total p=0.002). Additionally, TAS-F1 was positively correlated with the internalizing problems subscale of CBCL (p = 0.020) and the withdrawn (WD) subscale of CBCL (p = 0.044). We also found a significant association between TAS-F1 and WD of CBCL in boys alone (p = 0.022). However, we observed a negative association between TAS-F3 and the social problems subscale of CBCL in boys alone (p = 0.038). Conclusion: Mothers with alexithymic features are more likely to have children who internalize emotions, leading to withdrawal and somatic expression. Boys tend to exhibit withdrawal traits associated with internalization. This study provides initial evidence of a partial correlation between maternal alexithymia and children's emotional and behavioral disorders, emphasizing the importance of investigating caregivers' emotional traits for a better understanding of children's development in the future.

Reliability and Validity of the Traditional Chinese Version of the Mild Behavioral Impairment - Checklist Among Persons With Mild Cognitive Impairment - A Validation Study.

OBJECTIVE: To evaluate the reliability and validity of the traditional Chinese version of the Mild Behavioral Impairment Checklist (MBI-C) among Hong Kong Chinese with mild cognitive impairment (MCI). METHODS: A total of 172 participants were recruited from 2 community facilities. Cronbach's alpha (α) was calculated to evaluate internal consistency. Intra-class correlation coefficient (ICC) was used to measure 2-week test-retest reliability. Construct validity was evaluated by conducting exploratory factor analysis to identify the internal structure of MBI-C, and assessing the correlation between theoretically related constructs, including objective and subjective cognitive impairment, neurotic personality, social supports, and maladaptive coping. Concurrent validity was assessed by its correlation with Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: The results revealed good internal consistency and test-retest reliability of the MBI-C. Item analysis identified 4 items with low item-to-total correlations. The EFA identified a seven-factor structure. Hypothesis testing identified its significant correlations with subjective cognitive impairment, neurotic personality, social supports, and maladaptive coping. Concurrent validity was supported by its significant correlation with the NPI-Q. CONCLUSIONS: The traditional Chinese version of MBI-C is a valid and reliable outcome measure to assess the severity of neuropsychiatric symptoms of the MCI population.

Apathy as a Predictor for Conversion From Mild Cognitive Impairment to Dementia: A Systematic Review and Meta-Analysis of Longitudinal Studies.

BACKGROUND: Apathy is one of the most prevalent neurobehavioral manifestations in mild cognitive impairment (MCI) and is included among the behavioral and psychological symptoms of dementia (BPSD). Studies suggest that the presence of apathy could be associated with increased dementia risk. The role of apathy in conversion from MCI to dementia, and whether apathy could be a relevant predictor for dementia progression, are still matters of investigation. AIM: To study the relationship between apathy and progression to dementia in individuals with MCI. METHODS: A systematic literature search in Medline, Embase, Cochrane Library, Epistemonikos, PsychINFO, and CINAHL was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search included longitudinal studies reporting on the association between apathy and dementia. RESULTS: The main outcome was pooled unadjusted hazard ratios (HR) of apathy in dementia conversion and included 11 studies with 9504 individuals. There was a significant association between apathy and dementia conversion, HR = 1.54; 95% CI, 1.29, 1.84. Subgroup analysis showed a significant association between apathy and progression to AD. CONCLUSION: Apathy was associated with an increased risk of conversion to AD and all-cause dementia in patients with MCI. The role of apathy as a marker for incident dementia needs to be investigated in large, high-quality studies.

Possible association of limbic tau pathology with psychosis or behavioral disturbances: Studies of two autopsied psychiatric patients.

Tauopathies, including Alzheimer's disease and primary age-related tauopathy (PART), present heterogeneous clinico-pathological phenotypes that include dementia, aphasia, motor neuron diseases, and psychiatric symptoms. PART is neuropathologically characterized by the presence of neurofibrillary tangles in limbic regions without significant Aß deposition, but its clinical features have not yet been fully established. Here, we present two patients with distinct psychosis and behavioral symptoms. At autopsy, these patients showed tau pathologies that could not be classified as typical PART, although PART-like neurofibrillary tangles were present in limbic regions. Clinically, both patients were admitted to mental hospitals due to severe delusions or other neuropsychiatric/behavioral symptoms. The first case presented with hallucination, delusion, and apathy at age 70, and died of pancreatic cancer at age 75. He had neuronal cytoplasmic inclusions with selective accumulation of 3Rtau in the striatum and thorn-shaped astrocytes in the amygdala. The second case, who presented with abnormal behaviors such as wandering, agitation and disinhibition, exhibited limbic neurodegeneration with massive 4R tau-positive oligodendroglial inclusions in the medial temporal white matter. His age at onset was 73, and the duration of disease was 15 years. These findings support the notion that distinct limbic tau pathology with concomitant degeneration of the related neural circuits might induce specific psychosis and behavioral symptoms. This underlines the importance of neuropathological evaluation for both clinical education and practice in the fields of neuropathology and neuropsychiatry.

Stewardship applied to antipsychotics: Development of an antipsychotic stewardship program in inpatient settings for monitoring and optimizing outcomes.

Antipsychotic (AP) medications are prescribed for various psychiatric diagnoses that require routine monitoring to ensure optimal use, effectiveness, adherence, and for potentially severe adverse effects. There is currently no comprehensive protocol for institutional supervision of prescribing and monitoring AP. Antibiotics (ABX) are commonly associated with stewardship programs aimed at optimizing use and mitigating harm. These programs have proven to result in positive outcomes in both safety and efficacy parameters for numerous institutions. Given that AP are also associated with significant adverse effects and often misused, the concept of stewardship can be applied to this class of agents to optimize their use and improve overall patient outcomes. The objective of this paper is to provide guidance for the implementation of antipsychotic stewardship programs (APSP) in the inpatient setting. The development of this APSP was designed based on ABX stewardship programs and the Centers for Disease Control and Prevention, Agency for Healthcare Research and Quality, and the American Psychiatric Association practice guidelines on the treatment of patients with schizophrenia. In conclusion, APSPs have the potential to enhance and standardize institutional supervision of prescribing and monitoring practices of AP, leading to improved clinical outcomes and the reduction of adverse effects. APSP teams should be multidisciplinary, consisting of clinicians and administrators, working in conjunction with patients and patient advocates to design individualized recovery plans that consider the individual patient's history and desired outcomes. Monitoring, stewardship interventions, and outcomes should be documented on both an individual and deidentified institutional basis, analyzed, and summarized periodically as measures for quality improvement.

The Twilight Zone: Oxybutynin Overuse Exacerbating Delirium.

Anticholinergic medications, such as oxybutynin, are first-line pharmacologic therapies in overactive bladder. However, the cognitive adverse effect profiles of frequently used anticholinergic medications are extensive and limit their use in older patients. Additionally, many older patients continue on anticholinergic therapy if adverse effects are not self-reported by the patient or detected by the provider.Here, we present a case of a 73-year-old male with a history of major neurocognitive disorder, in which unreported oxybutynin overuse led to repeated delirious states, erratic driving, and subsequent psychiatric hospitalizations. During his hospitalizations, he displayed progressively more linear thought processes and improved insight without clear etiology. After a more thorough history of his medication use was obtained, he disclosed that he would often take additional doses of oxybutynin to prevent incontinence during car rides and had done so prior to recent hospitalizations.Our example highlights the importance of thorough history taking, medication review, reducing polypharmacy, careful patient education about medications with psychiatric adverse effects, and, importantly, the avoidance of anticholinergic medication prescription in older patients.

An Integrative Review of Behavioral Disturbances in Veterans With Dementia and PTSD.

OBJECTIVE: Both posttraumatic stress disorder (PTSD) and dementia have been associated with a variety of behavioral changes; however, little is known about the behavioral consequences of comorbid PTSD and dementia. An integrative review was conducted to identify and examine studies reporting on behavioral disturbances in Veterans with PTSD and dementia. METHODS: PubMed and PsychINFO databases were searched for articles on behavioral disturbances in Veterans with comorbid PTSD and dementia. RESULTS: Seven studies met inclusion for this review, sampling a total of 822 Veterans. Preliminary findings suggest that though Veterans with dementia and comorbid PTSD may present with more difficult behavioral symptoms, they do not typically display increased levels of aggression. CONCLUSION: Given the limited study inventory, the key finding from this review highlights the lack of methodologically rigorous empirical studies on this topic. A research agenda is proposed to encourage future studies to address gaps in the literature.

Treatment and Management of Sexual Disinhibition in Elderly Patients With Neurocognitive Disorders.

Sexual disinhibition is uncommon but challenging symptom to address in elderly patients with neurocognitive disorders. Due to the lack of large-scale studies, there is no gold standard treatment for sexual disinhibition, and treatment is largely left up to the discretion of the provider based on the severity and onset of the patient's symptoms. A review was conducted to investigate the non-pharmacological and pharmacological interventions for treating this condition. Articles that discussed treatments were screened for the type of treatment and possible side effects of medication if applicable. Thorough patient history should be taken prior to starting any drug therapy to rule out possible behavioral changes due to an existing medication side effect, delirium, or past mental or sexual health history. Non-pharmacological treatment has been generally recommended as first-line therapy over pharmacological treatment. Distraction/diversion of the patient when inappropriate sexual behaviors occur was the most common non-pharmacological intervention. Antidepressants were generally recommended as the first line of pharmacological treatment after attempting all possible non-pharmacological interventions. Several other categories of interventions are discussed as well in addition to the ethical implications of treating a patient for this condition.

Memantine for the Treatment of Behavioral Disturbance in Unspecified Major Neurocognitive Disorder.

In this case report, we aimed to examine how the use of memantine in an elderly gentleman with unspecified major neurocognitive disorder (NCD) led to significant clinical improvement in his behavioral disturbances. After presenting to the psychiatric ward due to aggressive behavior at his assisted living facility, the patient continued to exhibit numerous disruptive and confrontational behaviors while hospitalized. Memantine was started at 5 mg daily with gradual titration up to 10 mg twice daily over the course of four weeks, with marked improvement in behavior as well as an increase in Montreal Cognitive Assessment (MoCA) score by five points after seven weeks of treatment. Given our experience and the safety profile of memantine, we conclude that memantine may have a role in the treatment of behavioral disturbances in patients with unspecified major NCD, though further research will be necessary to define this role.

Biochemical and Clinical Effects of Vitamin E Supplementation in Hungarian Smith-Lemli-Opitz Syndrome Patients.

Smith-Lemli-Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7-dehydrocholesterol (7-DHC) levels. 7-DHC-derived oxysterols likely contribute to disease pathophysiology, and thus antioxidant treatment might be beneficial because of high oxidative stress. In a three-year prospective study, we investigated the effects of vitamin E supplementation in six SLOS patients already receiving dietary cholesterol treatment. Plasma vitamin A and E concentrations were determined by the high-performance liquid chromatography (HPLC) method. At baseline, plasma 7-DHC, 8-dehydrocholesterol (8-DHC) and cholesterol levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The clinical effect of the supplementation was assessed by performing structured parental interviews. At baseline, patients were characterized by low or low-normal plasma vitamin E concentrations (7.19-15.68 µmol/L), while vitamin A concentrations were found to be normal or high (1.26-2.68 µmol/L). Vitamin E supplementation resulted in correction or significant elevation of plasma vitamin E concentration in all patients. We observed reduced aggression, self-injury, irritability, hyperactivity, attention deficit, repetitive behavior, sleep disturbance, skin photosensitivity and/or eczema in 3/6 patients, with notable individual variability. Clinical response to therapy was associated with a low baseline 7-DHC + 8-DHC/cholesterol ratio (0.2-0.4). We suggest that determination of vitamin E status is important in SLOS patients. Supplementation of vitamin E should be considered and might be beneficial.

Medications in Patients with Dementia and Behavioral Disturbance.

BACKGROUND: Behavioral disturbance (BD) is common in dementia patients, with no FDA approved medications for this condition. Little data exists on the real-world medication use in this population. OBJECTIVE: To describe real-world medications use in this population. METHODS: A cross-sectional study was conducted using the MarketScan database for outpatient medications and the Cerner database for inpatient medications. The study period was Oct 2015-Jun 2018. Patients with dementia and BD were identified through ICD-10-CM. We examined outpatient medications prescribed during 6-month before or after BD event date, and inpatient medications during inpatient visits, especially on central nervous systems (CNS) drugs including antidementia drugs, antidepressants, antipsychotics, anxiolytics, and anticonvulsants. RESULTS: A total of 56,544 outpatients and 34,245 patient hospitalizations were assessed separately. Among outpatients, patients filled more medications after a BD event. The use of the five CNS drug classes generally increased after a BD event, and the largest increase was seen in antipsychotics (23%to 33%). Among inpatients, the median number of medications used in each hospitalization was 14. The use of antipsychotics was particularly high (64%), followed by anxiolytics (51%). A list of 60 unique medications were suggested to be the commonly used drugs in dementia patients with BD. CONCLUSION: In dementia patients with BD, anti-dementia medications, antidepressants, anticonvulsants, hypnotics and antipsychotics were the most used drug classes. Antidepressants and antipsychotics use were more frequent after a BD event, which suggests a need for safe drugs targeting BD in dementia patients.

Hypercalcemia Associated with Extramammary Paget's Disease.

Hypercalcemia of malignancy occurs in up to one third of patients at some point during the course of their advanced stage. The majority of them is caused by humoral hypercalcemia of malignancy due to systemic secretion of parathyroid hormone-related protein (PTHrP) by tumor cells. Extramammary Paget's disease is a slow-growing cutaneous malignancy commonly limited to the epidermis of the anogenital region, but rarely becomes invasive and metastatic to distant sites. Herein, we report a 70-year-old male patient with metastatic extramammary Paget's disease. He consulted our hospital with altered consciousness and tumor in his genital area. Physical examination revealed erythematous plaque with a tumor on the scrotum and perineum. It was diagnosed as extramammary Paget's disease (multiple liver metastases and multiple lymph node metastases by skin biopsy and image examination). Increases in serum-corrected calcium and PTHrP-intact levels (15.3 mg/dL and 66.1 pg/L, respectively) were confirmed. PTHrP immunohistochemistry showed positive staining in the tumor cells. We diagnosed humoral hypercalcemia of malignancy. We treated hypercalcemia with saline, furosemide, zoledronic acid, and elcatonin. Regarding the local control of the tumor, 30 Gy/10 Fr electron beam therapy was performed. However, treatment with zoledronic acid was only temporally effective to correct hypercalcemia, and an increased serum calcium level developed again. Concurrently, the liver metastases were rapidly enlarged, and his general condition gradually deteriorated. The patient died on day 55. When patients with extramammary Paget's disease show unconsciousness, serum calcium level should be measured and PTHrP-producing tumor distinguished.

Identification of a Rare PSEN1 Mutation (Thr119Ile) in Late-Onset Alzheimer's Disease With Early Presentation of Behavioral Disturbance.

Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. In this study, whole genome sequencing identifies one rare and likely pathogenic mutation in the presenilin 1 (PSEN1) gene (c.356C > T, p.T119I) associated with a frontal variant of AD. Affected individuals in the kindred developed late-onset cognitive decline accompanied with early presentation of psychiatric symptoms. Positive amyloid PiB PET tracing suggested presence of pathophysiological biomarker for AD. Whole genome sequencing analysis evaluated rare coding mutations in susceptible genes for various types of dementia and supported the role of PSEN1 as a causal gene. Identification of this T119I variant in PSEN1 might broaden the spectrum of genetic basis and clinical diversity of familial AD.

Sorting nexin 27 (SNX27) variants associated with seizures, developmental delay, behavioral disturbance, and subcortical brain abnormalities.

Sorting nexin 27 (SNX27) influences the composition of the cellular membrane via regulation of selective endosomal recycling. Molecular analysis indicates that SNX27 regulates numerous cellular processes through promiscuous interactions with its receptor cargos. SNX27 deficient (Snx27 -/- ) mice exhibit reduced embryonic survival, marked postnatal growth restriction and lethality. Haploinsufficient mice (Snx27 +/- ) show a less severe phenotype, with deficits in learning, memory, synaptic transmission and neuronal plasticity. One family previously reported with a homozygous SNX27 frameshift variant (c.515_516del;p.His172Argfs*6), exhibited infantile intractable myoclonic epilepsy, axial hypotonia, startle-like movements, cardiac septal defects, global developmental delay, failure to thrive, recurrent chest infections, persistent hypoxemia and early death secondary to respiratory failure. Here, we report two additional patients with compound heterozygous SNX27 variants, that are predicted to be damaging: (a) c.510C>G;p.Tyr170* and c.1295G>A;p.Cys432Tyr, and (b) c.782dupT;p.Leu262Profs*6 and c.989G>A;p.Arg330His. They exhibit global developmental delay, behavioral disturbance, epilepsy, some dysmorphic features and subcortical white matter abnormalities. In addition, possible connective tissue involvement was noted. Epilepsy, developmental delays and subcortical white matter abnormalities appear to be core features of SNX27-related disorders. We correlate the observed phenotype with available in vitro, in vivo and proteomic data and suggest additional possible molecular mediators of SNX27-related pathology.

A Prospective Study of the Safety and Effectiveness of Droperidol in Children for Prehospital Acute Behavioral Disturbance.

Study objective: Although uncommon, children (<16 years) with acute behavioral disturbance are a significant issue for emergency medical service providers. In this study, we aimed to investigate the safety and effectiveness of droperidol in children with prehospital acute behavioral disturbance. Methods: This was a prospective observational study over 1 year investigating the use of droperidol (0.1-0.2 mg/kg) for children (< 16 years) with acute behavioral disturbance. Inclusion criteria for acute behavioral disturbance were defined by a sedation assessment tool score of ≥2 determined by the attending paramedic. The primary outcome was the proportion of adverse effects (need for airway intervention, oxygen saturation <90% and/or respiratory rate <12, systolic blood pressure <90 mmHg, sedation assessment tool score of -3 and dystonic reactions). Secondary outcomes included time to sedation (sedation assessment tool score decreased by 2 or more, or a score of zero), requirement for additional sedation, failure to sedate and proportion of sedation success defined as the number of patients successfully sedated who did not suffer any adverse events or receive additional sedation. Results: There were 96 patients (males 51 [53%], median age 14 years [range 7-15 years]) who presented on 102 occasions over the one year study period. Self-harm and/or harm to others was the commonest (74/105 [70%]) cause of acute behavioral disturbance followed by alcohol (16/105 [15%]). There were 9 adverse events in 8 patients (8/102 [8%]; 95% confidence intervals [CI]: 3-13%) Five patients had hypotension, all asymptomatic and only one required treatment; 2 dystonic reactions managed with benztropine and one patient with respiratory depression. Median time to sedation was 14 min (interquartile range (IQR): 10-20 min; range: 3-85 min). There was no requirement for prehospital additional sedation (0/102 [0%]; 95% CI: 0-4%) and additional sedation in the first hour of arrival to hospital was required by 4 patients (4/102 [4%]; 95% CI: 1-10%). Overall successful sedation was achieved in 89 (87%) patients. Conclusions: The use of droperidol in children for acute behavioral disturbance in the prehospital setting is both safe and effective.

The effect of an immersive virtual reality tour of the operating theater on emergence delirium in children undergoing general anesthesia: A randomized controlled trial.

BACKGROUND AND AIMS: An immersive virtual reality tour of the operating theater could reduce preoperative anxiety. This study was designed to determine whether a preoperative immersive virtual reality tour demonstrates a reduction in emergence delirium through reducing the preoperative anxiety in children undergoing general anesthesia. METHODS: Eighty-six children were randomly allocated into either the control or virtual reality group. The control group received conventional education regarding the perioperative process. The virtual reality group watched a 4-minute virtual reality video showing the operating theater and explaining the perioperative process. Incidence and severity of emergence delirium were the main outcomes. Secondary outcomes included preoperative anxiety using modified Yale Preoperative Anxiety Scale and postoperative behavioral disturbance. RESULTS: Eighty children completed the final analysis (control group = 39, virtual reality group = 41). The incidence (risk ratio [95% CI]: 1.1 [0.5-2.8], P = 0.773) and severity of emergence delirium (mean difference [95% CI]: -0.2 [-2.7 to 2.2], P = 0.791) were similar in the two groups. After the intervention, children in the virtual reality group had a significantly lower modified Yale Preoperative Anxiety score than those in the control group (mean difference [95% CI]: 9.2 [0.3-18.2], P = 0.022). No difference was observed regarding postoperative behavioral disturbance between the two groups at postoperative 1 day (mean difference [95% CI]: -0.1 [-0.3 to 0.1], P = 0.671) and 14 day (mean difference [95% CI]: -0.0 [-0.1 to 0.0], P = 0.329). CONCLUSION: Preoperative immersive virtual reality tour of the operating theater did not reduce the incidence and severity of emergence delirium, although it was effective in alleviating preoperative anxiety in children.

Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia.

BACKGROUND: Agitation is a common neuropsychiatric symptom of Alzheimer disease (AD). Data are scarce regarding agitation prevalence among community-dwelling patients with AD. OBJECTIVE: To estimate agitation prevalence in a sample of US patients with AD/dementia overall and by AD/dementia disease severity, using data from electronic health records (EHR). METHODS: This retrospective database study examined community-dwelling patients with ≥1 EHR record indicating AD/dementia from January 2008 to June 2015 and no evidence of non-Alzheimer dementia during the 12-month preindex and postindex periods. Agitation was identified using diagnosis codes for dementia with behavioral disturbance and EHR abstracted notes records indicating agitation symptoms compiled from the International Psychogeriatric Association provisional consensus definition. RESULTS: Of 320 886 eligible patients (mean age, 76.4 y, 64.7% female), 143 160 (44.6%) had evidence of agitation during the observation period. Less than 5% of patients with agitation had a diagnosis code for behavioral disturbance. The most prevalent symptom categories among patients with agitation, preindex and postindex, were agitation (31.4% and 41.3%), falling (22.6% and 21.7%), and restlessness (18.3% and 23.3%). Among the 78 827 patients (24.6%) with known AD/dementia severity, agitation prevalence was 61.3%. Agitation during the observation period was most prevalent for moderate-to-severe and severe AD/dementia (74.6% and 68.3%, respectively) and lowest for mild AD/dementia (56.4%). CONCLUSIONS: Agitation prevalence was 44.6% overall and 61.3% among patients with staged AD/dementia. Behavioral disturbance appeared to be underdiagnosed. While agitation has previously been shown to be highly prevalent in the long-term care setting, this study indicates that it is also common among community-dwelling patients.

Ketamine for Rapid Sedation of Agitated Patients in the Prehospital and Emergency Department Settings: A Systematic Review and Proportional Meta-Analysis.

BACKGROUND: Rapid tranquilization of agitated patients can prevent injuries and expedite care. Whereas antipsychotics and benzodiazepines are commonly used for this purpose, ketamine has been suggested as an alternative. OBJECTIVE: The aim of this systematic review is to determine the safety and effectiveness of ketamine to sedate prehospital and emergency department (ED) patients with undifferentiated agitation. METHODS: Studies and case series of patients receiving ketamine for agitation were included. Studies were excluded if ketamine was used for analgesia, procedural sedation, asthma, or induction. Information sources included traditional and gray literature. RESULTS: The initial search yielded 1176 results from 14 databases. After review of titles and abstracts, 32 studies were reviewed and 18 were included in the analysis, representing 650 patient encounters. The mean dose of ketamine was 315 mg (SD 52) given intramuscularly, with adequate sedation achieved in 7.2 min (SD 6.2, range 2-500). Intubation occurred in 30.5% of patients (95% confidence interval [CI] 27.0-34.1%). In the majority of those patients, ketamine was administered by paramedics during ground transport and the patient was intubated on ED arrival. When ketamine was administered in the ED, the intubation rate was 1.8% (95% CI 0.0-4.4%); in air medical transport, the rate was 4.9% (95% CI 0.0-10.3%). Other reported side effects included: vomiting, 5.2% (2.3-8.1%); hypertension, 12.1% (5.7-18.6%); emergence reactions, 3.5% (1.4-5.6%); transient hypoxia, 1.8% (0.1-3.6%) and laryngospasm, 1.3% (0.3-2.3%). CONCLUSIONS: Ketamine provides rapid sedation for undifferentiated agitated patients and is associated with higher intubation rates when used by ground Emergency Medical Services paramedics, compared with ED or air medical transport patients. Other side effects are common but usually self-limiting.