Antipsychotics,Delirium, and Acute Respiratory Distress Syndrome: What Is the Link?

Acute respiratory distress syndrome (ARDS) is an acute inflammatory process that impairs the ability of the lungs to oxygenate and ultimately leads to respiratory failure. Patients who develop ARDS often have prolonged and complicated hospital courses putting them at risk for intensive care unit (ICU) delirium. Patients with ICU delirium often need chemical sedation, mechanical ventilation, prolonged duration of ICU and hospital stays, and they experience long‐term cognitive impairment and increased mortality. In a patient with ARDS, ICU delirium further complicates the hospital course and increases the risk of morbidity and mortality. Antipsychotics are prescribed to decrease the severity and duration of ICU delirium, thus potentially decreasing their risk of morbidity and mortality. However, antipsychotics are associated with many adverse effects including respiratory failure. Given the long‐term sequelae associated with the development of ICU delirium and the risks associated with antipsychotic use, clinicians must weigh the risks and benefits of antipsychotic use. This review investigates the interrelationship between ARDS, delirium, and antipsychotic use. In addition to discussing relevant studies evaluating antipsychotics for the prevention and treatment of delirium, we investigate safety concerns with the use of antipsychotics, especially as they relate to ARDS. Using the data compiled in this review, clinicians can make an informed decision about the use of antipsychotics for the prevention or treatment of delirium, with special consideration for their patients with ARDS. Future studies are needed to critically evaluate antipsychotic timing, dose, and duration for the prevention and treatment of ICU delirium and specifically evaluate the impact in special populations, particularly patients with ARDS.     

Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

Study Objective

Serotonergic adverse drug events (ADEs) are caused by enhanced intrasynaptic concentrations of 5‐hydroxytryptamine (5‐HT). No systematic process currently exists for evaluating cumulative 5‐HT and off‐target toxicity of serotonergic drugs. The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) by using a molecular bioinformatics, polypharmacologic approach for assessment of the participation of individual 5‐HT drugs in serotonin syndrome (SS) reports.

Data Sources

Publicly available databases including the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), ChEMBL, DrugBank, PubChem, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were queried for computational and pharmacologic data.

Design

An in‐house bioinformatics TargetSearch program ( http://dxulab.org/software ) was used to characterize 71 serotonergic drugs interacting at 13 serotonin receptor subtypes and serotonin reuptake transporter protein (SERT). In addition, off‐target interactions at norepinephrine transporter (NET), monoamine oxidase (MAO), and muscarinic receptors were included to define seven polypharmacological drug cohorts. Serotonin syndrome reports for each serotonergic drug were extracted from FAERS by using the Sternbach and Hunter criteria.

Measurements and Main Results

A proportional reporting adverse drug reaction (ADR) ratio (PRR) was calculated from each drug's total ADEs and SS case reports and aggregated by drug bioactivity cohorts. Triple‐receptor interactions had a disproportionately higher number of SS cases using both the Hunter criteria (mean PRR 1.72, 95% CI 1.05–2.39) and Sternbach (mean PRR 1.54, 95% CI 1.29–1.79). 5‐Hydroxytryptamine agonists were associated with a significantly lower proportion of SS cases using the Hunter and Sternbach criteria, respectively (mean PRR 0.49, 95% CI 0.17–0.81 and mean PRR 0.49, 95% CI 0.15–0.83). Drugs with disproportionately higher participation in SS vary considerably between the two diagnostic criteria.

Conclusion

The SEBM model suggests a possible polypharmacological role in SS. Although further research is needed, off‐target receptor activity may help explain differences in severity of toxicity and clinical presentation.     

Changes in cognitive function after a 12-week exercise intervention in adults with Down syndrome

Background

Between 250,000 and 400,000 individuals in the United States are diagnosed with Down syndrome (DS). Nearly all adults with DS will develop Alzheimer's disease pathology starting in their thirties. Recent studies suggest that increased physical activity (PA) may be important for maintaining components of cognition, including memory.

The motivational process for physical activity in young adults with autism spectrum disorder

Background

Many young adults, specifically those with a diagnosis of autism spectrum disorder (ASD), do not meet the national physical activity (PA) guidelines. One way to address this problem may be to examine the factors that motivate individuals to engage in PA. However, the majority of current literature does not consider the unique characteristics of individuals with ASD, which may influence their motivation.

中性粒细胞与淋巴细胞比值和急性冠状动脉综合征的相关性及其对急性心肌梗死的诊断价值

目的 探讨中性粒细胞与淋巴细胞比值（NLR）与急性冠状动脉综合征（ACS）患者冠脉严重程度之间的关 系,并分析NLR对急性心肌梗死的诊断价值。方法 回顾性分析2016年11月—2017年3月于我院行冠状动脉造影 检查的259例ACS患者的临床资料,其中不稳定型心绞痛组（UA组）148例、急性非ST段抬高型心肌梗死组（NSTEMI组）46例、急性ST段抬高型心肌梗死组（STEMI组）65例。比较3组的白细胞计数（WBC）、中性粒细胞计数（N）、淋巴细胞计数（L）、NLR、高敏C反应蛋白（hs-CRP）、心肌酶谱、血脂、血糖、肝功能等指标的差异。根据冠状动脉造影结果将患者按照冠状动脉病变支数分为单支病变组（70例）、双支病变组（70例）和三支病变组（119例）,比较不同病变支数组间炎性细胞的差异。同时绘制NLR的受试者工作特征（ROC）曲线,评价NLR对急性心肌梗死的预测价值。结果 UA组、NSTEMI组及STEMI组间WBC、N、NLR、hs-CRP、cTnT、CK、CK-MB水平依次升高,STEMI组L值低于UA组,差异有统计学意义（P＜0.05）;WBC、NLR随冠状动脉病变支数的增加而呈上升趋势,但仅三支病变组与单支病变组间差异有统计学意义;NLR诊断急性心肌梗死的ROC曲线下面积（AUC）为0.865（95%CI：0.814~0.916）。当NLR=4.22时,其对急性心肌梗死的诊断效能最高,敏感度为72.1％,特异度为95.3％。结论 NLR水平与ACS患者病情严重程度呈正相关,并对诊断急性心肌梗死具有较高的诊断价值,可作为ACS患者病情的预测因素。     

急性呼吸窘迫综合征存活者长期结局研究进展

随着重症医学的发展和急性呼吸窘迫综合征（ARDS）呼吸支持手段的进步,ARDS短期病死率大大下降,存活者越来越多,存活者的长期结局越来越受到关注。ARDS存活者肺功能恢复比较完全,但可遗留多种后遗症,包括生理功能（肌无力、活动能力受限）、认知功能和精神心理（焦虑、抑郁、创伤后应激障碍）障碍,被称为重症监护后综合征,可持续到ARDS后5年,导致生命质量下降,增加了家庭负担和医疗资源消耗。ARDS患者患病前的健康情况（如并存病、肥胖、自理能力、精神状况）、生活方式（如吸烟）以及重症监护病房（ICU）期间相关变量（如谵妄、皮质 激素、阿片类药物、获得性肌无力、低氧血症）对存活者的长期结局有重要影响。发现ARDS长期结局不良的高危患者及可改变的危险因素,并及时采取干预措施,对减少ARDS后的功能障碍有重要意义。ICU内及ICU后干预措施是否可有效改善ARDS存活者的长期结局,还需要进一步研究和验证。     

鹿瓜多肽致Kounis综合征一例

鹿瓜多肽主要用于关节炎、强直性脊柱炎、各种类型骨折及腰腿疼痛等疾病,已广泛应用于临床。鹿瓜多肽引发过敏性心肌缺血综合征（Kounis综合征）的报道罕见。本文中患者既往无冠心病病史,因骨性关节炎使用鹿瓜多肽,静脉滴注1 min后出现Kounis综合征,经抗过敏及急性心肌缺血处理后痊愈出院。鹿瓜多肽作为临床常用药物,在使用时如出现急性心肌缺血表现,应警惕Kounis综合征可能,妥善处理。     

基因突变检测在骨髓增生异常综合征诊疗中的应用

骨髓增生异常综合征 （MDS） 是一种由遗传学异常驱动的克隆性造血干细胞或祖细胞性疾病, 通常表现为全血细胞减少、 病态造血及向白血病转化的高风险。细胞形态学和细胞遗传学异常是目前确立MDS诊断的主要参数。近年来, 随着基因测序技术, 尤其是二代测序技术的快速发展和广泛应用, 大多数MDS患者可检出基因突变。本文就基因突变在MDS诊断、 分型、 危险度分层和治疗中的应用作一评述。     

Pharmacological modulation of C‐X‐C motif chemokine receptor 4 influences development of acute respiratory distress syndrome after lung ischaemia–reperfusion injury

Activation of C‐X‐C motif chemokine receptor 4 (CXCR4) has been reported to result in lung protective effects in various experimental models. The effects of pharmacological CXCR4 modulation on the development of acute respiratory distress syndrome (ARDS) after lung injury, however, are unknown. Thus, we studied whether blockade and activation of CXCR4 influences development of ARDS in a unilateral lung ischaemia–reperfusion injury rat model. Anaesthetized, mechanically ventilated animals underwent right lung ischaemia (series 1, 30 minutes; series 2, 60 minutes) followed by reperfusion for 300 minutes. In series 1, animals were treated with vehicle or 0.7 μmol/kg of AMD3100 (CXCR4 antagonist) and in series 2 with vehicle, 0.7 or 3.5 μmol/kg ubiquitin (non‐cognate CXCR4 agonist) within 5 minutes of reperfusion. AMD3100 significantly reduced PaO₂/FiO₂ ratios, converted mild ARDS with vehicle treatment into moderate ARDS (PaO₂/FiO₂ ratio<200) and increased histological lung injury. Ubiquitin dose‐dependently increased PaO₂/FiO₂ ratios, converted moderate‐to‐severe into mild‐to‐moderate ARDS and reduced protein content of bronchoalveolar lavage fluid (BALF). Measurements of cytokine levels (TNFα, IL‐6, IL‐10) in lung homogenates and BALF showed that AMD3100 reduced IL‐10 levels in homogenates from post‐ischaemic lungs, whereas ubiquitin dose‐dependently increased IL‐10 levels in BALF from post‐ischaemic lungs. Our findings establish a cause‐effect relationship for the effects of pharmacological CXCR4 modulation on the development of ARDS after lung ischaemia–reperfusion injury. These data further suggest CXCR4 as a new drug target to reduce the incidence and attenuate the severity of ARDS after lung injury.