The effect of music therapy on delirium in patients receiving mechanical ventilatory support in the Intensive Care Unit: A protocol for systematic review and meta-analysis.

BACKGROUND: Delirium is a very common sick syndrome in patients receiving mechanical ventilatory support in the Intensive Care Unit (ICU). Music therapy is a promising non-pharmacological intervention. However, its effect on the duration, incidence and severity of delirium is unknown. So we will perform a systematic review and meta-analysis to evaluate the effect of music therapy on delirium in patients receiving mechanical ventilatory support in the ICU. METHODS: This systematic review was registered in the PROSPERO. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-analysis Protocol to accomplish the systematic review protocol. Searches of PubMed, EMbase, the Cochrane library, CBM, CNKI and Wanfang databases will be conducted through computer to collect randomized controlled trials (RCTs) on the effects of music therapy on delirium in patients receiving mechanical ventilatory support in the ICU. The search time will be all from database establishment to April 2023. Two evaluators will independently screen the literature, extract information and evaluate the risk of bias of included studies, then data analysis will be performed using Stata 14.0 software. RESULTS: The results of this systematic review and meta-analysis will be publicly available and published in a peer-reviewed journal. CONCLUSION: This study will provide evidence-based medical evidence for music therapy to control delirium in patients receiving mechanical ventilatory support in the ICU.

Safety of baclofen versus tizanidine for older adults with musculoskeletal pain.

BACKGROUND: Baclofen and tizanidine are both muscle relaxants that carry the risk for neuropsychiatric events in older adults but there is a lack of data directly comparing their safety. This study aimed to investigate the relative risk between these two medications in causing injury and delirium in older adults. METHODS: This was a retrospective cohort study that was completed in an integrated healthcare system in the United States and included patients aged 65 years or older who started baclofen or tizanidine for the treatment of musculoskeletal pain from January 2016 through December 2018. Outcomes included new incidence of injury (concussion, contusion, dislocation, fall, fracture, or other injuries) and delirium. The cohort was followed from the initiation of therapy until the first occurrence of any of the following events: end of the index drug exposure, end of health plan membership, death, or the study end date of December 31st, 2019. Descriptive statistics were used to compare baseline patient characteristics between baclofen and tizanidine treatment groups. Cox proportional hazards model was used to calculate adjusted hazard ratios (HRs) with 95% confidence intervals. RESULTS: The final study cohort included 12,101 and 6,027 older adults in the baclofen and tizanidine group respectively (mean age 72.2 ± 6.2 years old, 59% female). Older adults newly started on baclofen had a greater risk of injury (HR = 1.54, 95% CI = 1.21-1.96, P = < 0.001) and delirium (HR = 3.33, 95% CI = 2.11-5.26, p = <0.001) compared to those started on tizanidine. CONCLUSION: The results of this study suggest that baclofen is associated with higher incidences of injury and delirium compared to tizanidine when used for the treatment of musculoskeletal pain. Future studies should investigate if these risks are dose-related and include a comparison group not exposed to either drug.

2022 Society of Critical Care Medicine Clinical Practice Guidelines on Prevention and Management of Pain, Agitation, Neuromuscular Blockade, and Delirium in Critically Ill Pediatric Patients With Consideration of the ICU Environment and Early Mobility.

RATIONALE: A guideline that both evaluates current practice and provides recommendations to address sedation, pain, and delirium management with regard for neuromuscular blockade and withdrawal is not currently available. OBJECTIVE: To develop comprehensive clinical practice guidelines for critically ill infants and children, with specific attention to seven domains of care including pain, sedation/agitation, iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment, and early mobility. DESIGN: The Society of Critical Care Medicine Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility Guideline Taskforce was comprised of 29 national experts who collaborated from 2009 to 2021 via teleconference and/or e-mail at least monthly for planning, literature review, and guideline development, revision, and approval. The full taskforce gathered annually in-person during the Society of Critical Care Medicine Congress for progress reports and further strategizing with the final face-to-face meeting occurring in February 2020. Throughout this process, the Society of Critical Care Medicine standard operating procedures Manual for Guidelines development was adhered to. METHODS: Taskforce content experts separated into subgroups addressing pain/analgesia, sedation, tolerance/iatrogenic withdrawal, neuromuscular blockade, delirium, PICU environment (family presence and sleep hygiene), and early mobility. Subgroups created descriptive and actionable Population, Intervention, Comparison, and Outcome questions. An experienced medical information specialist developed search strategies to identify relevant literature between January 1990 and January 2020. Subgroups reviewed literature, determined quality of evidence, and formulated recommendations classified as "strong" with "we recommend" or "conditional" with "we suggest." Good practice statements were used when indirect evidence supported benefit with no or minimal risk. Evidence gaps were noted. Initial recommendations were reviewed by each subgroup and revised as deemed necessary prior to being disseminated for voting by the full taskforce. Individuals who had an overt or potential conflict of interest abstained from relevant votes. Expert opinion alone was not used in substitution for a lack of evidence. RESULTS: The Pediatric Pain, Agitation, Neuromuscular Blockade, and Delirium in critically ill pediatric patients with consideration of the PICU Environment and Early Mobility taskforce issued 44 recommendations (14 strong and 30 conditional) and five good practice statements. CONCLUSIONS: The current guidelines represent a comprehensive list of practical clinical recommendations for the assessment, prevention, and management of key aspects for the comprehensive critical care of infants and children. Main areas of focus included 1) need for the routine monitoring of pain, agitation, withdrawal, and delirium using validated tools, 2) enhanced use of protocolized sedation and analgesia, and 3) recognition of the importance of nonpharmacologic interventions for enhancing patient comfort and comprehensive care provision.

Use of a combination of dexmedetomidine and magnesium sulfate as a multimodal approach to the treatment of alcoholic delirium.

INTRODUCTION: The search for an effective sedation schedule in managing delirium tremens that would ensure an adequate sedation level and good safety profile is an urgent problem of modern intensive care medicine. In this respect, the use of dexmedetomidine combined with magnesium preparations seems to be promising. MATERIAL AND METHODS: A quasi-randomized prospective observational study was conducted on 80 patients with alcoholic delirium, who were divided into 4 groups. Assessment parameters were delirium duration, mean arterial pressure and heart rate, and plasma magnesium, urea, creatinine, transaminase, cortisol, and serotonin levels. The control-group patients underwent standard sedation therapy with benzodiazepines. In group 1, standard sedation was supplemented by magnesium sulphate. In group 2, dexmedetomidine infusion was used. In group 3, dexmedetomidine was supplemented by the correction of hypomagnesemia. RESULTS: The duration of delirium proved to be significantly shorter in all study groups (3.4 ± 0.6 days in group 1; 1.55 ± 0.61 days in group 2) as compared to the control (5.4 ± 1.48 days), P < 0.001, being the shortest in group 3 (1.1 ± 0.18 days), P < 0.001. Cases of hypotension were detected only in the control group (2 cases [10%]) and group 1 (4 cases [20%]). The patients of groups 2 and 3 showed significant improvement in plasma levels of cortisol (16.7 ± 2.25 nmol L-1; 15.62 ± 1.63 nmol L-1) compared with the control (18.77 ± 2.76 nmol L-1), P = 0.019; P = 0.003. Serotonin level was higher in the experimental group 3 (87.8 ± 7.32 ng mL-1) as compared to the control (62.81 ± 9.81ng mL-1) and group 2 (71.73 ± 9.61 ng mL-1), P < 0.001. CONCLUSIONS: Dexmedetomidine infusion combined with magnesium sulphate proved to be effective in the treatment of patients with alcohol delirium.

Delirium in Critical Illness Patients and the Potential Role of Thiamine Therapy in Prevention and Treatment: Findings from a Scoping Review with Implications for Evidence-Based Practice.

INTRODUCTION: Thiamine is a water-soluble vitamin and is necessary for energy metabolism. Critically ill patients are at particular risk of developing thiamine deficiency and related complications. One of the complications that can occur is delirium. Delirium is a disorder that affects the body's response to treatment, length of stay in the ward, mortality, long-term cognitive impairment, and significantly increases treatment costs. In addition, studies show that delirium medication is more effective in preventing than in treating delirium. Given its low cost, availability, and minimal risk of side effects, thiamine supplementation could prove to be a relevant strategy in the prevention and treatment of delirium. METHODS: PubMed, Cochrane Library, Ovid, and ClinicalTrials.gov databases were searched using relevant keywords that focus on the use of thiamine to prevent or treat delirium in critically ill patients. RESULTS: Seven articles were included in the analysis. CONCLUSION: The small number of studies and considerable heterogeneity prevent conclusions supporting the use of thiamine as an adjuvant in the prevention and treatment of delirium among critically ill patients. There is a need for high-quality, large-scale randomized clinical trials to confirm the beneficial effects of thiamine in the prevention and treatment of delirium.

Statistical analysis plan for the Prophylactic Melatonin for Delirium in Intensive Care (ProMEDIC): a randomised controlled trial.

RATIONALE: Delirium is defined as acute organic brain dysfunction characterised by inattention and disturbance of cognition. It is common in the intensive care unit and is associated with poorer outcomes. Good quality sleep is important in the prevention and management of delirium. Melatonin is a natural hormone secreted by the pineal gland which helps in the regulation of the sleep-wake cycle. It is possible that melatonin supplementation in intensive care improves sleep and prevents delirium. METHODS AND DESIGN: The 'Prophylactic Melatonin for Delirium in Intensive Care' study is a multi-centre, randomised, double-blinded, placebo-controlled trial. The primary objective of this study is to determine whether melatonin given prophylactically decreases delirium in critically ill patients. A total of 850 ICU patients have been randomised (1:1) to receive either melatonin or a placebo. Participants were monitored twice daily for symptoms of delirium. RESULTS: This paper and the attached additional files describe the statistical analysis plan (SAP) for the trial. The SAP has been developed and submitted for publication before the database has been locked and before the treatment allocation has been unblinded. The SAP contains details of analyses to be undertaken, which will be reported in the primary and secondary publications. DISCUSSION: The SAP details the analyses that will be done to avoid bias coming from knowledge of the results in advance. This trial will determine whether prophylactic melatonin administered to intensive care unit patients helps decrease the rate and the severity of delirium. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry (ANZCTR) ACTRN1261600043647 , registration date: 06 April 2016. WHO Trial Number - U1111-1175-1814.

Yokukansan for Treatment of Preoperative Anxiety and Prevention of Postoperative Delirium in Cancer Patients Undergoing Highly Invasive Surgery. J-SUPPORT 1605 (ProD Study): A Randomized, Double-Blind, Placebo-Controlled Trial.

CONTEXT: No standard preventive or therapeutic methods have been established for preoperative anxiety and postoperative delirium in patients with cancer. OBJECTIVES: To clarify the therapeutic effect of yokukansan for perioperative psychiatric symptoms in patients with cancer as well as to confirm its safety profile. METHODS: This is a randomized, double-blind, and placebo-controlled trial conducted at a single center in Tokyo, Japan. About 195 patients with cancer scheduled to undergo tumor resection took one packet of the study drug, which was administered orally. Coprimary outcomes were change in preoperative anxiety assessed with the Hospital Anxiety and Depression Scale-Anxiety and incidence of postoperative delirium assessed with the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Interim analysis was performed with one-third (n = 74) of the target number of registered patients. RESULTS: Because this trial was canceled based on the results of the interim analysis and the protocol treatment was discontinued in patients who were already registered, conclusions were based on the full analysis set of 160 participants. There were no significant differences between groups in the change of mean Hospital Anxiety and Depression Scale-Anxiety score (intervention group [SD] 0.4 [3.0] vs. placebo group 0.5 [3.0]; P = 0.796) or the incidence of postoperative delirium (32% vs. 30%; P = 0.798). There were no serious adverse events in either group. CONCLUSION: In patients with cancer undergoing highly invasive surgeries, yokukansan demonstrated no significant efficacy for the treatment of preoperative anxiety or the prevention of postoperative delirium. Yokukansan is already used in daily practice in Japan, but we should be careful with its future use.

Management challenges at end-of-life in a patient with agitated delirium and benzodiazepine withdrawal at comprehensive cancer care center.

Most people have some idea of how they want to live their life; however, an estimated two-thirds of Americans have not completed their advance directives. This becomes an issue when up to 90% of patients develop delirium during their final days of life, at which point we depend on advance directives or surrogate decision-makers. Here, we present a case of terminal delirium in a patient with advanced cancer and a history of alprazolam abuse who had not discussed his end-of-life wishes with the medical team or with his estranged family. Treatment was provided to address reversible causes of delirium, including correcting electrolyte imbalances, urinary retention, and administered antibiotics for purulent otitis media. Hyperactive delirium was managed aggressively with intravenous neuroleptics and benzodiazepine, while keeping a balance between somnolence and control of agitative symptoms. Without knowing the patient's wishes, the family continued to struggle with decision making. However, with multidisciplinary team approach patients and caregivers' symptoms were better managed. Family then requested us to transfer him to a local hospice facility. The patient eventually passed away peacefully surrounded by his family members. This case highlights the importance of advance care planning, addressing emotional distress in estranged family members regarding symptom burden, and developing the appropriate treatment regimen for a delirious patient with a history of benzodiazepine abuse. Our case serves as a reminder of the support, guidance, and impact that inpatient palliative care teams can offer to both the patient and caregivers.

Parenteral thiamine for prevention and treatment of delirium in critically ill adults: a systematic review protocol.

BACKGROUND: Delirium is an acute confusional state, common in critical illness and associated with cognitive decline. There is no effective pharmacotherapy to prevent or treat delirium, although it is scientifically plausible that thiamine could be effective. Thiamine studies in dementia patients are inconclusive. Aside from small numbers, all used oral administration: bioavailability of thiamine is poor; parenteral thiamine bypasses this. In the UK, parenteral thiamine is administered as a compound vitamin B and C solution (Pabrinex®). The aim of this review is to evaluate the effectiveness of parenteral thiamine (alone or in a compound solution) in preventing or treating delirium in critical illness. METHODS: We will search for studies in electronic databases (MEDLINE (Pro-Quest), EMBASE, CINAHL, LILACS, CNKI, AMED, and Cochrane CENTRAL), clinical trials registries (WHO International Clinical Trials Registry, ClinicalTrials.gov, and Controlled-trials.com), and grey literature (Google Scholar, conference proceedings, and Index to Theses). We will perform complementary searches of reference lists of included studies, relevant reviews, clinical practice guidelines, or other pertinent documents (e.g. official documents and government reports). We will consider quasi-randomised or randomised controlled trials in critically ill adults. We will include studies that evaluate parenteral thiamine versus standard of care, placebo, or any other non-pharmacological or pharmacological interventions. The primary outcomes will be the delirium core outcome set, including incidence and severity of delirium and cognition. Secondary outcomes are adapted from the ventilation core outcome set: duration of mechanical ventilation, length of stay, and adverse events incidence. Screening, data extraction, and risk of bias assessment will be undertaken independently by two reviewers. If data permits, we will conduct meta-analyses using a random effects model and, where appropriate, sensitivity and subgroup analyses to explore sources of heterogeneity. DISCUSSION: This review will provide evidence for the effectiveness of parental thiamine in the prevention or treatment of delirium in critical care. Findings will contribute to establishing the need for a multicentre study of parenteral thiamine in the prevention and treatment of critical care delirium. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019118808.

Experimental analysis of the onset mechanism of TdP reported in an LQT3 patient during pharmacological treatment with serotonin-dopamine antagonists against insomnia and nocturnal delirium.

Torsade de pointes (TdP) occurred in a long QT syndrome type 3 (LQT3) patient after switching perospirone to blonanserin. We studied how their electropharmacological effects had induced TdP in the LQT3 patient. Perospirone hydrochloride (n = 4) or blonanserin (n = 4) of 0.01, 0.1, and 1 mg/kg, i.v. was cumulatively administered to the halothane-anesthetized dogs over 10 min. The low dose of perospirone decreased total peripheral vascular resistance, but increased heart rate and cardiac output, facilitated atrioventricular conduction, and prolonged J-Tpeakc. The middle dose decreased mean blood pressure and prolonged repolarization period, in addition to those observed after the low dose. The high dose further decreased mean blood pressure with the reduction of total peripheral vascular resistance; however, it did not increase heart rate or cardiac output. It tended to delay atrioventricular conduction and further delayed repolarization with the prolongation of Tpeak-Tend, whereas J-Tpeakc returned to its baseline level. Meanwhile, each dose of blonanserin decreased total peripheral vascular resistance, but increased heart rate, cardiac output and cardiac contractility in a dose-related manner. J-Tpeakc was prolonged by each dose, but Tpeak-Tend was shortened by the middle and high doses. These results indicate that perospirone and blonanserin may cause the hypotension-induced, reflex-mediated increase of sympathetic tone, leading to the increase of inward Ca2+ current in the heart except that the high dose of perospirone reversed them. Thus, blonanserin may have more potential to produce intracellular Ca2+ overload triggering early afterdepolarization than perospirone, which might explain the onset of TdP in the LQT3 patient.

Co-ultraPEALut: Role in Preclinical and Clinical Delirium Manifestations.

BACKGROUND: Delirium is a disorder in awareness, attention and cognition. Pathophysiologically it is a response to stress. Postoperative delirium (POD) is a usual complication in aged patients following hip fracture surgery. Neuroinflammation is an important factor linked with the progress of POD. Though there are no efficient cures for delirium the endocannabinoid system may have a role in neuropsychiatric disorders. OBJECTIVE: Therefore, we examined the effects of co-ultramicronized PEALut (co-ultraPEALut) in the LPS murine model of delirium and in elderly hip fractured patients. METHODS: In the preclinical study, mice were injected intraperitoneally (i.p.) with Escherichia coli LPS (10 mg/kg). Co-ultraPEALut (1 mg/kg o.s.) was administered 1h before LPS injection or 1h and 6h after LPS injection or 1h before LPS injection and 1h and 6h after LPS. In the clinical study, the effects of Glialia® (co-ultramicronized 700 mg PEA + 70 mg luteolin) administration was evaluated in elderly hip fractured patients with an interventional, randomized, single-blind, monocentric study. RESULTS: Administration of co-ultraPEALut to LPS-challenged mice ameliorated cognitive dysfunctions and locomotor activity; moreover, it reduced inflammation and apoptosis, while stimulating antioxidant response and limiting the loss of neurotrophins. In the clinical study, the results obtained demonstrated that administration of Glialia® to these surgical patients prevented the onset of POD and attenuated symptom intensity and their duration. CONCLUSION: Therefore, the results obtained enhanced the idea that co-ultraPEALut may be a potential treatment to control cognitive impairment and the inflammatory and oxidative processes associated with delirium.

In a Model of Neuroinflammation Designed to Mimic Delirium, Quetiapine Reduces Cortisol Secretion and Preserves Reversal Learning in the Attentional Set Shifting Task.

Quetiapine, an atypical antipsychotic medication has lacked pre-clinical validation for its purported benefits in the treatment of delirium. This laboratory investigation examined the effects of quetiapine on the attentional set shifting task (ASST), a measure of cognitive flexibility and executive functioning, in a rodent model of lipopolysaccharide (LPS) mediated neuroinflammation. 19 Sprague Dawley female rats were randomly selected to receive intraperitoneal placebo (N = 5), LPS and placebo (N = 7) or LPS and quetiapine (n = 7) and performed the ASST. We measured trials to criterion, errors, non-locomotion episodes and latency to criterion, serum cortisol and tumor necrosis factor alpha (TNF-α) levels. TNF-α levels were not different between groups at 24 h. Cortisol levels in the LPS + Quetiapine group were reduced compared to LPS + Placebo (P < 0.001) and did not differ from the placebo group (P = 0.15). Analysis between LPS + Quetiapine and LPS + Placebo treated rats demonstrated improvement in the compound discrimination reversal (CD Rev1) (P = 0.016) and the intra-dimensional reversal (ID Rev2) (P = 0.007) discriminations on trials to criterion. LPS + Quetiapine treated rats had fewer errors than LPS + Placebo treated animals in the compound discrimination (CD) (P = 0.007), CD Rev1 (P = 0.005), ID Rev2 (P < 0.001) discriminations. There was no difference in non-locomotion frequency or latency to criterion between the three groups in all discriminations (P > 0.0167). We demonstrated preserved reversal learning, no effect on attentional set shifting and normalized cortisol levels in quetiapine-treated rats in this neuroinflammatory model of delirium. This suggests that quetiapine's beneficial effects in delirium may be related to the preservation of reversal learning and potential downstream effects related to reduction in cortisol production. Graphical Abstract.

Factors Associated With Delirium in Surgical Intensive Care Unit Patients Treated With Supplemental Melatonin: A Case-Cohort Study.

OBJECTIVES: Intensive care unit (ICU) delirium is a common neuropsychiatric syndrome that confers significant morbidity and mortality. Melatonin is an endogenous neurohormone involved with regulating sleep-wake cycles and has been found to be disturbed in ICU delirium. We hypothesized that there are independent factors that predict delirium in a cohort of patients on melatonin in the surgical ICU (SICU). METHODS: A retrospective, observational case-cohort analysis of adult SICU patients was conducted. Cases were defined by testing positive on the Confusion Assessment Method for the ICU (CAM-ICU). Delirioprotective and deliriogenic factors were assessed prior to the studied melatonin administration. RESULTS: Forty-one CAM-ICU-positive cases and 59 CAM-ICU-negative controls were included. Higher mean Acute Physiology and Chronic Health Evaluation II scores were associated with delirium in univariable analysis. Stratified analysis found a higher incidence of delirium in baseline CAM-ICU-positive patients who experienced emergency surgery within 24 hours of admission compared with baseline CAM-ICU-negative patients after melatonin administration. CONCLUSIONS: This study describes the use of melatonin in the SICU and characterizes the patients who receive it. Further research is needed to determine the role of melatonin in deliriogenesis and to clarify its utility as a delirioprotectant for postsurgical, critical care patients.

Multiprofessional care for delirium patients in intensive care: integrative review. / Cuidados multiprofissionais para pacientes em delirium em terapia intensiva: revisão integrativa.

OBJECTIVE: To describe the multiprofessional care for the management of critical patients in delirium in the ICU from the evidences found in the literature. METHODS: This integrative review was carried out in the period from February 1 to June 30, 2016 through searches on PubMed, Scopus, Web of Science, and CINAHL, with the following descriptors: delirium, critical care e intensive care units, which brought up 17 original papers. RESULTS: A bundle and a guideline, two systematic reviews, evidence 1a and four clinical trials, evidence 1b and 2b, cohort and observational studies were found. The multiprofessional care was presented to better understand the diagnosis of delirium, sedation pause, early mobilization, pain, agitation and delirium guidelines, psychomotor agitation, cognitive orientation, sleep promotion, environment and family participation. CONCLUSION: The care for delirium is wide and not specific, which determines its multifactorial aspect.

[Therapeutic effect of ginkgo biloba extract on postoperative delirium in aged patients].

Objective: To observe whether Ginkgo biloba extract (EGb761) can improve postoperative delirium in elderly patients. Methods: Eighty elderly patients undergoing tumor surgery at Zhejiang Cancer Hospital and complicated with postoperative delirium(POD) between June 2013 and July 2016 were randomly divided into treatment group (group A) and control group (group B) according to the random number table method. Patients in group A received ginkgo biloba extract (EGb761) drops oral treatment (3 times/d, 80 mg each time) in addition to oxygen inhalation and appeasement treatment. Patients in group B underwent routine oxygen inhalation and appeasement treatment. POD assessment was performed twice between the hours of 8: 00 am and 8: 00 pm daily after the diagnosis of POD. Observed indicators include sex ratio, age, body mass index (BMI), educated level, type of surgery, anesthesia method, duration of surgery, intraoperative mean arterial blood pressure, intraoperative blood loss, type of POD, visual analogue scale (VAS) scores when diagnosis of POD, the onset time of POD, initial RASS scores, duration of POD. Results: A total of 80 patients with POD were enrolled, 23 patients were excluded for did not cooperate with the tests of POD or refused to participate in the study. Finally, 57 elderly patients completed the study, 29 patients in the medication group (A group) and 28 patients in the control group (B group). There was no significant difference in sex ratio, age, BMI, education level, operation type, anesthesia method, operation duration, intraoperative mean arterial pressure, intraoperative blood loss, POD type and VAS score (all P>0.05). There was no significant difference between the two groups in POD onset time and initial RASS score (all P>0.05). The duration of POD in group A and group B was 16 (16)h and 48 (35) h respectively, the difference was statistically significant (U=161.500, P<0.001). Conclusion: Ginkgo biloba extract (EGb761) can shorten the course of POD in elderly patients.

Haloperidol for delirium in critically ill patients - protocol for a systematic review.

BACKGROUND: In the intensive care unit, the prevalence of delirium is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer intensive care unit stay, increased long-term mortality, and cognitive impairment. Thus, the burden of delirium for patients, relatives, and societies is considerable. The objective of this systematic review was to critically access the evidence of randomised clinical trials on the effects of haloperidol vs. placebo or any other agents for delirium in critically ill patients. METHODS: We will search for randomised clinical trials in the following databases: Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, and Allied and Complementary Medicine Database. Two authors will independently screen and select references for inclusion using Covidence, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager, STATA 15, and Trial Sequential. ANALYSIS: The aim of this study was to assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. DISCUSSION: Our ambition with this systematic review is to provide reliable and powered evidence to better inform decision makers on the use of or future trials with haloperidol for the management of delirium in critically ill patients.

Continuous palliative sedation for patients with advanced cancer at a tertiary care cancer center.

BACKGROUND: Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely worldwide. The aim of our study was to evaluate the frequency, clinical indications and outcomes of PS in advanced cancer patients admitted to our tertiary comprehensive cancer center. METHODS: We retrospectively studied the use of PS in advanced cancer patients who died between March 1st, 2012 and December 31st, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms in the end of life. This study was approved by the Research Ethics Committee of our institution (project number 2481-15). RESULTS: During the study period, 552 cancer patients died at the institution and 374 met the inclusion criteria for this study. Main reason for exclusion was death in the Intensive Care Unit. Among all included patients, 54.2% (n = 203) received PS. Patients who received PS as compared to those not sedated were younger (67.8 vs. 76.4 years-old, p < 0.001) and more likely to have a diagnosis of lung cancer (23% vs. 14%, p = 0.028). The most common indications for sedation were dyspnea (55%) and delirium (19.7%) and the most common drugs used were midazolam (52.7%) or midazolam and a neuroleptic (39.4%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range - IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Patient survival (length of hospital stay from admission to death) of those who had PS was more than the double of those who did not (33.6 days vs 16 days, p < 0.001). The palliative care team was involved in the care of 12% (n = 25) of sedated patients. CONCLUSIONS: PS is a relatively common practice in the end-of-life of cancer patients at our hospital and it is not associated with shortening of hospital stay. Involvement of a dedicated palliative care team is strongly recommended if this procedure is being considered. Further research is needed to identify factors that may affect the frequency and outcomes associated with PS.