Safety and Efficacy of Flumazenil for Reversal of Iatrogenic Benzodiazepine-Associated Delirium Toxicity During Treatment of Alcohol Withdrawal,a Retrospective Review at One Center

Both alcohol withdrawal syndrome (AWS) and benzodiazepines can cause delirium. Benzodiazepine-associated delirium can complicate AWS and prolong hospitalization. Benzodiazepine delirium can be diagnosed with flumazenil, a GABA-A receptor antagonist. By reversing the effects of benzodiazepines, flumazenil is theorized to exacerbate symptoms of AWS and precludes its use. For patients being treated for alcohol withdrawal, flumazenil can diagnose and treat benzodiazepine delirium without precipitating serious or life-threatening adverse events. Hospital admission records were retrospectively reviewed for patients with the diagnosis of AWS who received both benzodiazepines and flumazenil from December 2006 to June 2012 at a university-affiliated inpatient toxicology center. The day of last alcohol consumption was estimated from available blood alcohol content or subjective history. Corresponding benzodiazepine, flumazenil, and adjunctive sedative pharmacy records were reviewed, as were demographic, clinical course, and outcome data. Eighty-five patients were identified (average age 50.3 years). Alcohol concentrations were detectable for 42 patients with average 261 mg/dL (10–530 mg/dL). Eighty patients were treated with adjunctive agents for alcohol withdrawal including antipsychotics (n = 57), opioids (n = 27), clonidine (n = 35), and phenobarbital (n = 23). Average time of flumazenil administration was 4.7 days (1–11 days) after abstinence, and average dose was 0.5 mg (0.2–1 mg). At the time of flumazenil administration, delirium was described as hypoactive (n = 21), hyperactive (n = 15), mixed (n = 41), or not specified (n = 8). Response was not documented in 11 cases. Sixty-two (72.9 %) patients had significant objective improvement after receiving flumazenil. Fifty-six patients required more than one dose (average 5.6 doses). There were no major adverse events and minor adverse effects included transiently increased anxiety in two patients: 1 patient who received 0.5 mg on abstinence day 2 and another patient who received 0.2 mg flumazenil on abstinence day 11. This is the largest series diagnosing benzodiazepine delirium after AWS in patients receiving flumazenil. During the treatment of AWS, if delirium is present on day 5, a test dose of flumazenil may be considered to establish benzodiazepine delirium. With the limited data set often accompanying patients with AWS, flumazenil diagnosed benzodiazepine delirium during the treatment of AWS and improved impairments in cognition and behavior without serious or life-threatening adverse events in our patients.     

厄他培南致谵妄症状3例并文献复习

<正>厄他培南(ertapenem)是广谱碳青霉烯类抗生素,属于不典型β-内酰胺类抗生素,对于革兰阳性、阴性及厌氧菌有显著抗菌活性^([1,2]),且耐β-内酰胺酶,可用于治疗严重感染。很多研究([1,2]),且耐β-内酰胺酶,可用于治疗严重感染。很多研究^([3,4])报道了其治疗社区获得性肺炎具有很高的有效性及安全性。本文对厄他培南所致精神症状病例进行     

海洛因依赖者脱毒治疗中产生谵妄的临床分析

目的··：探讨海洛因依赖者于脱毒治疗中生产谵妄的影响因素。方法··：总结１９９３年８月至１９９６年８月间首次入我院接受脱毒治疗的１２３例海洛因依赖者的有关资料，并对不同情况下发生谵妄进行比较。结果··：共有５６例产生谵妄，谵妄发生率为４５．５％，以注射方式滥用毒品、健康状况较差的患者谵妄发生率明显高于其他方式滥用者（Ｐ＜０．０１），而使用美沙酮替代方式脱毒较之丁丙诺啡，谵妄发生率明显低（Ｐ＜０．０１）。结论··：海洛因戒断、精神药物的使用、躯体疾患是导致谵妄产生的主要影响因素。     

Delirium during heroin withdrawal with doxepin: A short report

Doxepin was evaluated in a group of 10 patients for its efficacy in decreasing withdrawal symptoms during ambulatory heroin withdrawal. Although no subjective relief was reported by the subjects, during the 10 days trial, four of the patients developed full blown delirium during the trial's first three days. Since delirium is rarely one of the complications of heroin withdrawal the question whether doxepin enhanced or induced its appearance in these patients, remains unanswered. Until this issue is resolved we suggest cessation of doxepin usage in the initial withdrawal phase from heroin.     

Risk for Delirium Tremens in Patients with Alcohol Withdrawal Syndrome

To determine the characteristics associated with an increased risk for delirium tremens (DT) we performed a case-control study at the detoxification units of two hospitals. Cases met DSM-IV criteria for DT. For each case (n = 15), 3 controls (n = 45) were chosen. Eligibility criteria were applied equally to cases and controls. Cases were more likely than controls to report a prior complicated withdrawal (DT or alcohol withdrawal seizure) (53 vs. 27%, OR 3.1, 95% CI 0.94–10.55), have a systolic blood pressure greater than 145 mm Hg on admission (60 vs. 27%, OR 4.1, 95% CI 1.21–14.06), and have comorbidity scores of at least 1 (60 vs. 18%, OR 6.9, 95% CI 1.92–25.08). Zero cases (0%) and 15 (33%) controls had no prior complicated withdrawals and no adverse clinical features (systolic blood pressure >145 or comorbidity score >1). Compared to this group, the odds of being a case and having both prior complicated withdrawal and at least 1 adverse clinical feature was 44.8 (95% CI 4.36–460). Elevated blood pressure, prior complicated alcohol withdrawal and medical comorbidity, alone and in combination, are associated with an increased risk of delirium tremens.     

Delirium assessed by Memorial Delirium Assessment Scale in advanced cancer patients admitted to an acute palliative/supportive care unit

Background: Delirium is often unrecognized in cancer patients. The aim of this study was to investigate the prevalence of delirium assessed by the Memorial Delirium Assessment Scale (MDAS) and possible associated factors on admission to an acute palliative/supportive care unit (APSCU). The secondary outcome was to assess changes in MDAS and symptom burden at time of discharge.

Methods: A consecutive sample of advanced cancer patients who were admitted to an APSCU was prospectively assessed for a period of 10 months. Patient demographics, including age, gender, primary diagnosis, Karnofsky status, stage of disease, and educational level were collected. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS were measured at hospital admission and discharge.

Results: A total of 314 patients were surveyed. Of 292 patients with MDAS available at T0, 74 (25.3%) and 24 (8.2%) had a MDAS of 7–12 and ≥13, respectively. At discharge, there was a significant decrease in the number of patients with a MDAS ≥7/30. Higher values of MDAS were associated with age (p?=?.028), a lower Karnofsky status (p?p?=?.04), low level of education (p?=?.002), less awareness of disease (p?p?p?=?.026), hospital stay (p?=?.038) and death (p?p?Conclusion: Delirium is highly prevalent in patients admitted to APSCU, characterized by a low mortality due to early referral. Comprehensive assessment and treatment may allow a decrease in the level of cognitive disorders and symptom burden.     

小儿七氟烷麻醉苏醒期躁动的研究进展

七氟烷是临床常用的吸入麻醉药,具有镇静、镇痛作用,对呼吸和血流动力学影响轻微;其起效迅速,无刺激性等优点被国内外广泛地应用于儿科麻醉,但小儿苏醒期躁动的发生率高于成人.该文概括了七氟烷麻醉在小儿苏醒期躁动的原因及可能机制,重点论述了小儿在七氟烷麻醉苏醒期躁动的预防与治疗,以便为临床应用与研究提供参考.     

心脏外科术后ICU谵妄相关因素调查及对策

目的：探讨心脏外科术后ICU谵妄发生的相关因素,并给与相应护理措施,提高患者生存质量。方法采用方便抽样的方法,观察100例心脏术后的患者,记录患者年龄、性别、血型、手术时间、体外循环时间、阻断时间、机械通气时间及入住ICU时间,利用CAM-ICU量表评估患者是否发生ICU谵妄。并利用SPSS 16.0软件进行统计学处理。结果 ICU谵妄发生率为39%,未发生率为61%。年龄、血型、手术时间、体外循环时间、阻断时间及入住ICU时间均与ICU谵妄发生有关。结论通过统计分析可知,年龄、血型、手术时间、体外循环时间、机械通气时间是ICU谵妄的相关因素,而阻断时间及入住ICU时间均是ICU谵妄发生的危险因素。     

Resistant alcohol withdrawal: Does an unexpectedly large sedative requirement identify these patients early?

Introduction

While most patients with alcohol withdrawal (AW) respond to standard treatment that includes doses of benzo-diazepines, nutrition and good supportive care (non resistant alcohol withdrawal-NRAW), a subgroup may resist therapy (resistant alcohol withdrawal-RAW). This study describes a distinct group of AW patients, their sedative requirements, and hospital courses.

Methods

Over a period of 6 months, AW patients requiring 50 mg diazepam IV in the first hour were followed. We recorded admission indices and diazepam doses with vital signs at 1, 2, 3, 6, 12, and 24 hours. Patients were considered to have RAW if they required additional sedatives for control of symptoms and/or were having persistent abnormal vital signs despite the physicians’ choices of therapy.

Results

Nineteen patients were enrolled; all had similar admission indices. While the 4 NRAW had normal vital signs within 3 hours, all 15 RAW patients had abnormal vital signs; 15 RAW patients required escalating diazepam doses — 14 required barbiturates, 7 were intubated, and 5 had hypotension. Comparing groups: interval and total diazepam doses were not different at 1, 2, and 3 hours; interval doses at 6 and 12 hours, and total doses at 6, 12, and 24 hours were significantly different.

Conclusions

RAW patients require large doses of benzodiazepine administration, additional sedatives, and undergo complicated hospitalizations.     

Dexmedetomidine in the prevention of postoperative delirium in elderly patients following non-cardiac surgery: A systematic review and meta-analysis

The efficacy of dexmedetomidine in the prevention of postoperative delirium (POD) remains ambiguous, however, it has been used to reduce the incidence of delirium in elderly patients. Here, we conducted a meta-analysis study for assessing the effects of dexmedetomidine on POD among elderly patients following non-cardiac surgery. A systematic literature search was performed against the PubMed, EMBASE, Cochrane Library, and Web of Science databases, and all relevant literature published till November 30, 2019, were considered. Our analysis included 16 randomised controlled trials conducted with 4534 patients for exploring the effects of dexmedetomidine on POD in elderly patients following non-cardiac surgery. It was observed that the overall incidence of POD was significantly lower in the dexmedetomidine group than in the control group (risk ratio [RR] 0.51, 95% confidence interval [CI] 0.43–0.61, P < .01). Similar results were obtained from subgroup analysis upon comparison of the placebo (RR 0.52, 95% CI 0.41–0.66, P < .01, moderate quality of evidence), propofol-treated (RR 0.55, 95% CI 0.38–0.78, P < .01, low quality of evidence), and midazolam-treated (RR 0.38, 95% CI 0.20–0.71, P < .01, low quality of evidence) groups. Trial sequential analysis revealed that the cumulative z-value superseded the monitoring boundary and reached the required information size. However, patients who received dexmedetomidine had a higher incidence of bradycardia and hypotension. In conclusion, the meta-analysis revealed that dexmedetomidine appears to decrease the risk of POD in elderly patients following non-cardiac surgery. However, as some of the studies were heterogeneous and of low quality, high-quality trials are necessary for drawing more definitive conclusions.     

Risk for delirium tremens in patients with alcohol withdrawal syndrome 1

To determine the characteristics associated with an increased risk for delirium tremens (DT) we performed a case‐control study at the detoxification units of two hospitals. Cases met DSM‐IV criteria for DT. For each case (n = 15), 3 controls (n = 45) were chosen. Eligibility criteria were applied equally to cases and controls. Cases were more likely than controls to report a prior complicated withdrawal (DT or alcohol withdrawal seizure) (53 vs. 27%, OR 3.1, 95% CI 0.94–10.55), have a systolic blood pressure greater than 145 mm Hg on admission (60 vs. 27%, OR 4.1, 95% CI 1.21–14.06), and have comorbidity scores of at least 1 (60 vs. 18%, OR 6.9, 95% CI 1.92–25.08). Zero cases (0%) and 15 (33%) controls had no prior complicated withdrawals and no adverse clinical features (systolic blood pressure >145 or comorbidity score >1). Compared to this group, the odds of being a case and having both prior complicated withdrawal and at least 1 adverse clinical feature was 44.8 (95% CI4.36–460). Elevated blood pressure, prior complicated alcohol withdrawal and medical comorbidity, alone and in combination, are associated with an increased risk of delirium tremens.     

A pilot trial of quetiapine for the treatment of patients with delirium

Twenty-two Korean inpatients with delirium were administered prospectively a flexible dose of quetiapine. The delirium rating scale-revised-severity 98 (DRS-R-98) and clinical global impression scale-severity (CGI-s) scores were assessed at the time of pre- and post-treatment. The DRS-R-98 and CGI-s scores were significantly reduced by 57.3% and 55.1%, respectively. Quetiapine was effective and safe for the treatment of patients with delirium, and could be a useful alternative agent to classical antipsychotics in the treatment of delirium.     

Challenges of Delirium Management in Patients with Traumatic Brain Injury: From Pathophysiology to Clinical Practice

Traumatic brain injury (TBI) can initiate a very complex disease of the central nervous system (CNS), starting with the primary pathology of the inciting trauma and subsequent inflammatory and CNS tissue response. Delirium has long been regarded as an almost inevitable consequence of moderate to severe TBI, but more recently has been recognized as an organ dysfunction syndrome with potentially mitigating interventions. The diagnosis of delirium is independently associated with prolonged hospitalization, increased mortality and worse cognitive outcome across critically ill populations. Investigation of the unique problems and management challenges of TBI patients is needed to reduce the burden of delirium in this population.In this narrative review, possible etiologic mechanisms behind post-traumatic delirium are discussed, including primary injury to structures mediating arousal and attention and secondary injury due to progressive inflammatory destruction of the brain parenchyma. Other potential etiologic contributors include dysregulation of neurotransmission due to intravenous sedatives, seizures, organ failure, sleep cycle disruption or other delirium risk factors. Delirium screening can be accomplished in TBI patients and the presence of delirium portends worse outcomes.There is evidence that multi-component care bundles including an analgesia-prioritized sedation algorithm, regular spontaneous awakening and breathing trials, protocolized delirium assessment, early mobility and family engagement can reduce the burden of ICU delirium. The aim of this review is to summarize the approach to delirium in TBI patients with an emphasis on pathogenesis and management. Emerging CNS-active drug therapies that show promise in preclinical studies are highlighted.     

右美托咪定对胸腔镜老年肺癌根治术后患者谵妄发生率的影响

目的探讨右美托咪定对胸腔镜老年肺癌根治术后患者谵妄发生率的影响。方法选取2016年1月至2019年1月咸阳市第一人民医院的胸腔镜肺癌根治术后老年患者56例,随机分为右美托咪啶组和0.9%氯化钠溶液组,各28例。比较2组患者谵妄发生率、重度谵妄发生率、谵妄持续时间、不良反应发生率、睡眠质量评分和术后疼痛视觉模拟评分。结果右美托咪啶组和0.9%氯化钠溶液组患者在谵妄发生率(7.1%和28.6%)、重度谵妄发生率(0.0%和14.3%)、谵妄持续时间[(1.5±0.7)d和(2.8±0.4)d]、不良反应发生率(0.0%和21.4%)、睡眠质量评分[(3.2±1.3)分和(6.4±2.7)分]及术后疼痛数字评分[(3.3±2.2)分和(5.4±1.8)分]方面,应用右美托咪啶组结果优于对照组,差异有统计学意义(均P<0.05)。结论老年患者全身麻醉下行胸腔镜肺癌根治术,麻醉时应用右美托咪啶可降低谵妄和重度谵妄的发生率,缩短谵妄的持续时间。     

异丙酚对小儿七氟醚全麻苏醒期躁动的预防作用

目的观察异丙酚对小儿七氟醚全麻苏醒期躁动的预防作用。方法选择择期行腺样体切除或伴有扁桃体切除,年龄2⁷岁,ASA(American society of anesthesiologists)分级Ⅰ级的患儿60例。将患儿按随机数字法分为3组(P 1.0组,P 0.5组,NS组),每组20例,于手术结束时,分别静注异丙酚1.0 mg/kg、异丙酚0.5 mg/kg及盐水0.1 m L/kg。患儿入室后评估基础情绪,记录基础血压、心率、血氧饱和度、静脉穿刺抵抗情况;所有患儿采用七氟醚复合50%笑气面罩吸入诱导,七氟醚及50%笑气、50%氧气维持,记录患儿面罩诱导抵抗情况。术中监测血压、心率、血氧饱和度、MAC、呼气末二氧化碳;并记录手术时间、拔管时间、苏醒时间。躁动的严重程度采用PAED评分,疼痛严重程度采用m-CHEOPS评分。结果 P 1.0组及P 0.5组在各个时间点的PAED评分均低于NS组(P<0.05);P 1.0组与P 0.5组的PAED评分在各个时间点差异无统计学意义(P>0.05)。P 1.0组的苏醒时间及拔管时间长于NS组(P<0.05),P 0.5组的苏醒时间及拔管时间与NS组比较差异无统计学意义(P>0.05)。结论手术结束时单次给予异丙酚1.0 mg/kg和0.5 mg/kg对小儿苏醒期躁动均有预防作用,而在苏醒及拔管时间方面,采用0.5 mg/kg的剂量优于1.0 mg/kg。     

Iodine-induced delirium

A case of delirium that was believed to have been caused by disinfectant iodoform is reported. The delirium began on the seventh day following filling with iodoform gauze, and approximately one month later, the patient entered a semi-comatose state. The patient began to recover roughly seven days after filling was discontinued. At that time, there were indications that the serum-iodine levels was five times higher than normal. From the above, it is believed that the case of the delirium was the iodine absorbed from the filling gauze.     

主动脉夹层术后谵妄的临床特点和相关危险因素研究

目的 研究主动脉夹层术后谵妄的发生率、临床特点以及相关危险因素.方法 以2013年1-12月北京安贞医院主动脉夹层术后患者为研究对象,以意识错乱评估方法作为谵妄诊断工具,分析术后谵妄的发生率和危险因素.结果 共有84例患者纳入研究,发生术后谵妄28例,发生率为33.3％.21例（75.0％）为一过性谵妄（＜24 h）;7例（25.0％）为持续性谵妄.术后谵妄最常见的表现是精神运动性兴奋（23例,82.1％）;其次是睡眠-觉醒周期紊乱（21例,75.0％）;多数患者有思维紊乱或者不连贯、定向力障碍、意识水平改变.将术后谵妄的危险因素分为术前、术中和术后危险因素,并对其进行单因素分析和多因素回归分析.与谵妄发生有关的术前危险因素包括左心室射血分数≤30％[P=0.023,比值比（OR）=1.99,95％置信区间（CI）：1.29～3.31]、脑梗死（P=0.002,OR=2.86,95％ CI：1.43 ～ 5.72）;术中危险因素包括手术持续时间（P=0.023,OR =0.90,95％ CI：0.49 ～ 1.67）、深低温停循环时间（P =0.019,OR=1.18,95％ CI：1.06 ～2.97）;术后危险因素包括机械通气时间（P =0.043,OR=1.17,95％ CI：1.00 ～1.37）、血氧饱和度（P=0.001,OR=2.77,95％ CI：1.51 ～5.11）、重症监护病房时间（P=0.036,OR=1.10,95％ CI：1.10～1.21）,上述各因素对术后谵妄的影响差异有统计学意义（P＜0.05）.Logistic多因素回归分析结果表明脑梗死（P=0.017,OR=1.48,95％ CI：1.07 ～2.04）、深低温停循环时间（P=0.002,OR=2.86,95％ CI：1.43 ～5.72）、重症监护病房时间（P=0.030,OR =2.18,95％ CI：1.07 ～4.44）是术后谵妄的独立危险因素.结论 既往脑梗死、深低温停循环时间、重症监护病房持续时间是术后谵妄的独立危险因素.