Retrospective Review of Critically Ill Patients Experiencing Alcohol Withdrawal: Dexmedetomidine Versus Propofol and/or Lorazepam Continuous Infusions

Background:

Alcohol withdrawal symptoms can be difficult to manage and may lead to an intensive care unit (ICU) admission. Patients experiencing severe alcohol withdrawal often require high doses of sedatives, which can lead to respiratory depression and the need for endotracheal intubation. Dexmedetomidine, an alpha-2 adrenoreceptor agonist, provides adequate sedation with little effect on respiratory function when compared to other sedatives.

Objective:

To evaluate sedation with a continuous infusion of dexmedetomidine versus propofol and/or lorazepam in critically ill patients experiencing alcohol withdrawal.

Methods:

A retrospective chart review was conducted on ICU admissions between March 2002 and April 2009 for alcohol withdrawal patients who necessitated treatment with a continuous infusion of dexmedetomidine, propofol, and/or lorazepam. Primary outcomes included the incidence of mechanical ventilation, length of mechanical ventilation (if applicable), and ICU and hospital length of stay.

Results:

Fifteen patients were treated with a continuous infusion of dexmedetomidine, and 17 were treated with an infusion of propofol and/or lorazepam. Two patients (13.3%) required intubation and mechanical ventilation in the dexmedetomidine group versus 10 (58.8%) in the propofol and/or lorazepam group (P = .006). Length of stay in the ICU was 53 hours for patients treated with dexmedetomidine versus 114.9 hours in the propofol and/or lorazepam group (P = .016). Hospital length of stay was less for the dexmedetomidine group, 135.8 hours versus 241.1 hours in the propofol and/or lorazepam group (P = .008).

Conclusions:

Dexmedetomidine use was associated with a decrease in the incidence of endotracheal intubation when used to sedate patients experiencing alcohol withdrawal. Patients transferred to a lower level of care faster and were discharged from the hospital sooner when treated with dexmedetomidine.Key Words: alcohol, dexmedetomidine, lorazepam, propofol, withdrawalThere are approximately 18.3 million people in the United States dependent on or abusing alcohol and 2.9 million people requiring treatment for problems related to alcohol use.¹ The impact of alcohol withdrawal syndrome can be devastating, both physically and neurologically. The syndrome can include headache, anxiety, hallucinations, nausea and vomiting, sweating, seizures, irritability, and the most severe form of alcohol withdrawal, delirium tremens. Patients experiencing delirium tremens have a mortality rate of up to 5%.² The American Society of Addiction Medicine guidelines for the management of alcohol withdrawal delirium recommend sedative-hypnotic drugs, such as benzodiazepines, as the primary agents for managing alcohol withdrawal syndrome.³The goal of alcohol withdrawal treatment is to relieve the patients’ agitation and prevent the further development of more severe symptoms. Some patients may experience symptoms such as increased levels of anxiety, hallucinations, and delirium tremens. In these severe cases, escalating benzodiazepine doses (to include initiation of a continuous infusion) or initiation of another sedative, such as propofol or phenobarbital, becomes necessary to control agitation. The use of sedatives can cause a decrease in respiratory drive, which can lead to patients requiring transfer to a higher level of care with the potential for intubation and mechanical ventilator support.At North Colorado Medical Center (NCMC), patients undergoing alcohol withdrawal are initially treated with benzodiazepines. If escalating doses of benzodiazepines are unable to control agitation and other alcohol withdrawal symptoms, patients are evaluated by the physician for transfer to the intensive care unit (ICU). In the past, the standard of care in the NCMC ICU for patients experiencing severe alcohol withdrawal not controlled by intermittent benzodiazepines was the initiation of a benzodiazepine and/or propofol infusion based on the physician’s assessment and preference. Often these patients required intubation and mechanical ventilation. Recently, however, the sedation of patients experiencing severe alcohol withdrawal is increasingly being managed with dexmedetomidine in the ICU at NCMC.Clonidine has historically been used for treatment and prophylaxis of the symptoms of alcohol withdrawal.^3–9 Dexmedetomidine is a centrally acting, relatively selective, alpha2-adrenergic agonist similar to clonidine with sedative and analgesic properties. Dexmedetomidine reduces the stress response, decreases norepinephrine and epinephrine levels, and attenuates increases in heart rate and blood pressure without depressing the respiratory drive.^10,11The use of dexmedetomidine has been noted in multiple case reports, case series, and one small randomized controlled trial as a possibly effective agent for the management of alcohol withdrawal.^12–19 The case reports and case series primarily reported on safety, reduced benzodiazepine doses, and reduced delirium scores in the use of dexmedetomidine in alcohol withdrawal patients. The one randomized, blinded, placebo-controlled trial published to date by Mueller et al compared dexmedetomidine to placebo in patients with severe alcohol withdrawal. The primary endpoint was benzodiazepine requirements in the first 24 hours and cumulative dose over the first 7 days of hospitalization. They reported a reduced 24-hour benzodiazepine dose in the dexmedetomidine group and no difference in the 7-day cumulative dose between groups.¹²One of the main advantages of dexmedetomidine is that it does not cause respiratory depression.¹¹ This is especially important in patients admitted to the ICU for severe alcohol withdrawal. Studies have demonstrated that patients admitted to the ICU with severe alcohol withdrawal have a high rate of intubation, reportedly 22% to 65%.²⁰ Ventilator-associated pneumonia (VAP) can occur in 10% to 20% of patients receiving greater than 48 hours of mechanical ventilation. Patients who contract VAP have increased hospital costs of more than $10,000 per day, increased ICU length of stay by 5 to 7 days, and, in some reports, increased mortality.²¹ Furthermore, intubation and mechanical ventilation on ICU day 1 has been recognized as a predictor of a longer length of hospital stay.²²Assessment and documentation of the effectiveness of dexmedetomidine for treatment of alcohol withdrawal, while growing rapidly, is still lacking in the medical literature. The purpose of this retrospective observational study was to evaluate the incidence and duration of mechanical ventilation and the length of ICU and hospital stay in alcohol withdrawal patients treated with dexmedetomidine, propofol, and/or lorazepam continuous infusions.     

Safety and Effectiveness of Dexmedetomidine in the Pediatric Intensive Care Unit (SAD–PICU)

Background:

Critically ill children require sedation for comfort and to facilitate mechanical ventilation and interventions. Dexmedetomidine is a newer sedative with little safety data in pediatrics, particularly for therapy lasting longer than 48 h.

Objective:

To quantify the frequency of adverse events and withdrawal syndromes associated with dexmedetomidine and to describe the use of this drug for continuous sedation in critically ill children.

Methods:

In this retrospective study of patients who received dexmedetomidine for sedation in the pediatric intensive care unit, adverse events were assessed with the Naranjo scale to determine the likelihood of association with dexmedetomidine. Interventions in response to adverse events were also recorded.

Results:

One hundred and forty-four patients (median age 34 months, range 0 – 17.7 years) who underwent a total of 153 treatment courses were included. The mean infusion rate of dexmedetomidine was 0.42 μg/kg per hour (standard deviation 0.17 μg/kg per hour, range 0.05–2 μg/kg per hour). The median duration of therapy was 20.50 h (range 0.75–854.75 h), and 70 infusions (46%) lasted more than 24 h. At least one adverse event was observed in 115 (75%) of the treatment courses. Hypotension (81 [53%]) and bradycardia (38 [25%]) were the most common adverse events and were deemed “probably” attributable to dexmedetomidine in 17 (11%) and 9 (6%) of the treatment courses, respectively. In 55 of the 66 treatment courses with infusions lasting longer than 24 h for which post-infusion data were available, at least one withdrawal symptom was observed; agitation (41 [62%]) and hypertension (22 [33%]) were the most common withdrawal symptoms.

Conclusions:

Dexmedetomidine was commonly administered for longer than 24 h in the authors’ institution. Dexmedetomidine was generally well tolerated; however, the majority of patients experienced withdrawal symptoms. Patients receiving dexmedetomidine for more than 24 h should be monitored for withdrawal following discontinuation, and interventions should be provided if needed. Prospective, controlled studies are needed to characterize the safety of long-term dexmedetomidine therapy in critically ill children.     

Retrospective Analysis of Levetiracetam Compared to Phenytoin for Seizure Prophylaxis in Adults with Traumatic Brain Injury

Background:

Phenytoin is standard of care for seizure prophylaxis following traumatic brain injury (TBI). Levetiracetam, an alternative antiepileptic drug, is utilized for seizure prophylaxis despite limited data supporting its use.

Objective:

Our primary outcome was post-TBI seizure activity measured by electroencephalogram (EEG) for levetiracetam versus phenytoin. Secondary outcomes were length of intensive care unit (ICU) stay, requirement for additional antiepileptic drugs (AED), and drug and monitoring costs.

Methods:

A retrospective review was performed of patients admitted to neurosurgical or surgical trauma ICU. Adult patients with at least 1 day of EEG monitoring were included. Patients were excluded if they had history of epilepsy, prior TBI, less than 48 hours of AED therapy, or additional AED prior to EEG monitoring.

Results:

A total 90 patients met inclusion criteria, with 18 receiving levetiracetam and 72 receiving phenytoin. Prevalence of EEG-confirmed seizure activity was similar between the levetiracetam and phenytoin groups (28% vs 29%; P = .99). ICU length of stay (13 vs 18 days; P = .28), time to EEG-confirmed seizure activity (4 vs 6 days; P = .24), and duration of seizure prophylaxis (9 vs 14 days; P = .18) were also similar. The median daily cost of levetiracetam therapy was $43 compared to $55 for phenytoin therapy and monitoring (P = .08). When all anticonvulsant therapy and monitoring were included, costs were lower for the levetiracetam group ($45 vs $83; P = .02).

Conclusion:

Levetiracetam may provide an alternative treatment option for seizure prevention in TBI patients in the ICU. Total antiepileptic drug and monitoring costs were lower for levetiracetam patients.     

右美托咪定和咪达唑仑复合芬太尼对ICU术后机械通气患者镇静的影响

目的观察右美托咪定和咪达唑仑复合芬太尼用于ICU术后机械通气患者的镇静效果及安全性。方法选取150例ICU术后机械通气患者,采用信封法随机分为右美托咪定组和咪达唑仑组,每组75例,两组患者均给予芬太尼持续泵入。右美托咪定组采用右美托咪定0.2～0.6μg/(kg·h)持续泵入。咪达唑仑组采用0.08～0.10 mg/(kg·h)咪达唑仑持续泵入。采用Ramsay分级标准对两组患者镇静效果进行分级评分,观察两组患者的镇静效果。详细记录两组患者芬太尼用量、达到理想镇静所需的时间、停药后苏醒时间、镇静期间呼吸及循环系统功能的变化及其他不反应发生情况。结果右美托咪定组镇静满意率为97.33%,咪达唑仑组镇静满意率为96.00%,两组镇静满意率比较差异无统计学意义(P>0.05)。右美托咪定组芬太尼用量明显低于咪达唑仑组(P<0.05),达到理想镇静所需时间及停药后苏醒时间明显短于咪达唑仑组(P<0.05)。两组患者呼吸抑制、平均动脉压下降、SpO2下降及恶心发生率比较差异无统计学意义,但右美托咪定组谵妄发生率明显低于咪达唑仑组,两组比较差异有统计学意义(P<0.05)。结论右美托咪定复合芬太尼用于ICU术后机械通气患者的镇静治疗,镇静效果满意,可以达到理想镇静时间及易唤醒时间短,谵妄发生率低,可减少芬太尼用量,而且对患者呼吸及循环系统影响小,是一种较为理想的ICU镇静剂。     

右美托咪啶对重症治疗室患者镇静效果研究

目的观察盐酸右美托咪啶对重症治疗室患者的镇静效果及安全性。方法将50例重症创伤而需要机械通气的ICU患者随机分为两组;A咪达唑仑组（n=25）和B盐酸右美托咪啶组（n=25）。记录镇静前的APACHEⅡ评分、Ramsay评分。分别观察镇静中4、8、12h的心率,平均动脉血压,呼吸频率,氧饱和度等基本生命体征及用药后两药起效时间,恢复时间,镇静满意度,Ramsay评分和谵妄发生率等。结果B组血压、心率有明显下降但停药后马上恢复,而对呼吸氧饱和度影响均小于A组,安全性良好;且比较单纯咪达唑仑用量、调整泵速至镇静满意时间、镇静满意程度、恢复时间等,B组均明显少于A组（P〈0．05）。结论右美托咪啶用于重症治疗室患者镇静安全性好,能够提供良好的镇静。     

右美托咪定用于ICU机械通气患者的镇静作用观察

目的研究右美托咪定用于ICU机械通气患者的镇静作用。方法对40例机械通气患者给予右美托咪定镇静,维持Ramsay评分3-4分,观察并记录各项指标。结果右美托咪定的镇静满意度为（91．3±8．4）％,镇静期间平均输注速度为（0．42±0．15）μg／（kg·h）,镇静12h时停止右美托咪定输注后恢复时间为（23．6±8．2）s,镇静期间生命体征基本平稳。结论右美托咪定可有效应用于ICU机械通气患者。     

右美托咪定在重症监护患者镇静中的临床观察

目的研究右美托咪定在重症监护患者镇静中的效果及安全性。方法将2011年1月至2012年4月本院重症监护病房收治的需要镇静的60例患者随机分为右美托咪定组(30例)和咪达唑仑组(30例)。调整药物剂量使Ramsay评分控制在3～4分,分别记录镇静起效的时间、停用镇静药物后苏醒时间、谵妄发生率、机械通气时间、ICU留住时间及不良反应的发生率。结果与咪达唑仑组比较,右美托咪定组起效迅速,唤醒所需时间短,谵妄发生率低,治疗剂量内不诱发临床意义的呼吸抑制。两组患者的机械通气时间,ICU留住时间,血流动力学影响发生率相似。结论右美托咪定在重症监护病房是一种较为理想的镇静剂。     

右美托咪定用于重症监护病房正颌外科术后留置气管插管患者的镇静

目的探讨右美托咪定用于重症监护病房(ICU)正颌外科术后留置气管插管患者镇静作用的有效性和安全性。方法 40例正颌外科术后入ICU留置气管插管患者,随机分为右美托咪定组和咪达唑仑组,每组20例。右美托咪定组予右美托咪定0.4μg·kg~(-1)·h~(-1)微泵静注,调整范围0.2～0.7μg·kg~(-1)·h~(-1);咪达唑仑组予咪达唑仑0.1 mg·kg~(-1)·h~(-1)微泵静注,调整范围0.05～0.2 mg·kg~(-1)·h~(-1)。采用Ramsay镇静深度评分系统,以Ramsay评分2～4分级为镇静目标,进行注射剂量的调整。记录用药前,用药后1、2、3、4、6、8、12、16 h的血压、心率、呼吸、脉搏血氧饱和度,观察镇静效果及不良反应。结果 2组患者用药后均可获得满意的镇静效果,Ramsay评分维持在2～4分级,良好耐受气管插管。2组用药前心率、平均动脉压(MAP)无显著差异(P>0.05),用药后心率和血压均有所下降,右美托咪定组各时点心率均低于咪达唑仑组(P<0.05),用药后1、2、3、4 h MAP低于咪达唑仑组(P<0.05)。2组呼吸频率、脉搏血氧饱和度无显著差异(P>0.05)。右美托咪定组需剂量调整的次数(2例1次)较咪达唑仑组(3例1次,4例2次)低。右美托咪定组发生2例心动过缓,予以阿托品治疗好转,2组均无严重不良反应发生。结论右美托咪定0.4μg·kg~(-1)·h~(-1)可安全用于ICU正颌外科术后留置气管插管患者的镇静,剂量调整发生率低于咪达唑仑。     

两种镇痛药用于重症监护室术后机械通气患者的疗效探讨

目的：评估两种镇静药物右旋美托咪啶和咪达唑仑分别用于ICU机械通气患者的镇痛疗效。方法：选取2014年6月～2015年6月我院ICU收治的术后机械通气患者75例,根据随机抽样原则将入组患者分成观察组38例和对照组37例。观察组采用右旋美托咪啶持续静脉泵注镇痛,对照组采用咪达唑仑持续静脉泵注镇痛。记录两组镇痛起效时间、唤醒时间、镇静-躁动评分、机械通气时长、临时应用镇痛药次数、住院时长。此外,记录患者出现的不良反应。结果：两组患者镇痛起效时间、镇静-躁动评分、机械通气时长对比差异无统计学意义（P>0.05）;观察组麻醉唤醒时间、ICU住院时长显著短于对照组（P<0.05）,镇静过程中临时应用镇痛药的次数显著少于对照组（P<0.05）;观察组镇静后心动过缓、谵妄、呼吸抑制发生率显著低于对照组（P<0.05）。结论：应用右旋美托咪啶对ICU中行机械通气的患者进行镇痛,有效性和安全性较高,可临床推广。     

Cost–Consequence Analysis of Nitisinone for Treatment of Tyrosinemia Type I

Background:

Tyrosinemia type I is a rare but severe genetic metabolic disorder. Nitisinone combined with a diet low in tyrosine and phenylalanine became first-line therapy in 1994.

Objectives:

To estimate the direct medical costs of health care services related to the treatment of tyrosinemia type I, taking into consideration the real-life efficacy of nitisinone.

Methods:

A cost–consequence analysis was performed for all children with a confirmed diagnosis of tyrosinemia type I who were treated in Quebec between January 1, 1984, and January 1, 2009. The costs of care were compared for 3 consecutive historical groups: no nitisinone (1984 to 1994), late intervention with nitisinone (first dose received between 1994 and 1997), and early intervention with nitisinone (first dose received between 1997 and 2008). Data were derived from patient charts, hospital databases, and the Régie de l’assurance maladie du Québec and MED-ÉCHO administrative databases. Costs were reported in 2008 Canadian dollars.

Results:

Nitisinone treatment was associated with significant reductions in the number and duration of hospital admissions, the number of admissions to a pediatric intensive care unit, and the number of liver transplants. The cost of hospitalization per person-year was significantly lower in the 2 groups treated with nitisinone: $673 and $5 590 for the early-intervention and late-intervention groups, respectively, as compared to $12 980 for the no-nitisinone group (p < 0.001). Hospital costs per person-year for liver transplant were $3 198 for the late-intervention group and $5 044 for the no-nitisinone group: there were no transplants in the early-intervention group. The cost of nitisinone per person-year was $51 493 for the early-intervention group and $64 895 for the late-intervention group.

Conclusions:

Nitisinone treatment significantly improved the outcomes of patients with tyrosinemia type I, while decreasing utilization of health care resources, liver transplants, and associated costs.     

Economic Impact of Converting from Pen and 10-mL Vial to 3-mL Vial for Insulin Delivery in a Hospital Setting

Purpose:

To compare the impact on acquisition cost and purchased volume of rapid- and short-acting insulins following conversion from 3-mL disposable pens and 10-mL vials to 3-mL vials for individual patient supply (IPS) in a hospital setting.

Methods:

On February 1, 2010, St. Joseph’s Hospital and Medical Center of Dignity Health in Phoenix, Arizona, converted from pens to 3-mL vials for IPS subcutaneous (SC) injection and from 10-mL short-acting insulin vials to 3-mL vials for intravenous (IV) preparation. Pharmacy purchasing data were analyzed over 6-month periods before and after conversion (March 1 through August 31, 2009, and March 1 through August 31, 2010).

Results:

Before conversion, acquisition costs were $27,866 for 5,335 mL of rapid-acting insulins and $53,336 for 26,310 mL of short-acting insulins. After conversion, insulin acquisition costs were $24,211 for 5,850 mL of rapid-acting insulins (13.1% decrease in costs, 9.7% rise in volume), with cost reduction attributable to the lower cost of 3-mL vials. Acquisition costs were $17,395 for 14,700 mL of short-acting insulins after conversion (67.4% decrease in costs, 44.1% reduction in volume), with cost reduction attributable to lower cost of 3-mL vials versus pens for IPS SC injections and 10-mL vials for IV preparation. The reduction in purchased volumes of short-acting insulins may be partly due to decreased insulin use in IV preparation.

Conclusion:

Conversion from pens and 10-mL vials to 3-mL vials for rapid-and short-acting insulins resulted in reduced acquisition costs and decreased use of short-acting insulin in IV preparations.     

右美托咪定对机械通气患者睡眠情况及谵妄发生率的影响

目的探讨右美托咪定镇静效应及其对机械通气患者的睡眠情况及谵妄发生率的影响。方法对2011年1月至2012年12月进入我院重症加强护理病房（intensivecareunit,ICU）的60例术后需机械通气患者,分别应用右美托咪定及咪唑安定（各30例）联合舒芬太尼实施镇静镇痛,依据Ramsay评分标准,维持适当的镇静深度。比较两组患者术后留置气管插管时间、机械通气时间和人住ICU的天数,镇静镇痛药物的总量,用药后不同时间段的Ramsay分值、疼痛视觉模拟评分（visualanalogueseale,VAS）、ICU谵妄诊断的意识模糊评估法（confusionassessmentmethodforthediagnosisofdeliriumintheICU,CAM—ICU）。结果A、B两组术后留置气管插管时间、机械通气的时间和人住ICU的天数存在统计学差异（P〈0．01）,阿森斯失眠量表评分及谵妄发生率也有非常显著的统计学差异（P〈0．01）。结论右美托咪定能较好地改善机械通气患者的睡眠情况,降低谵妄发生率。     

Dexmedetomidine and ST-91 analgesia in the formalin model is mediated by alpha2A-adrenoceptors: a mechanism of action distinct from morphine

Background and purpose:

Intrathecal administration of α₂-adrenoceptor agonists produces potent analgesia. This study addressed the subtype of spinal α₂-adrenoceptor responsible for the analgesic effects of i.t. dexmedetomidine and ST-91 in the formalin behavioural model and their effects on primary afferent substance P (SP) release and spinal Fos activation.

Experimental approach:

The analgesic effects of i.t. dexmedetomidine and ST-91 (α₂ agonists) were tested on the formalin behavioural model. To determine the subtype of α₂-adrenoceptor involved in the analgesia, i.t. BRL44408 (α_2A antagonist) or ARC239 (α_2B/C antagonist) were given before dexmedetomidine or ST-91. Moreover, the ability of dexmedetomidine and ST-91 to inhibit formalin-induced release of SP from primary afferent terminals was measured by the internalization of neurokinin₁ (NK₁) receptors. Finally, the effects of dexmedetomidine on formalin-induced Fos expression were assessed in the dorsal horn.

Key results:

Intrathecal administration of dexmedetomidine or ST-91 dose-dependently reduced the formalin-induced paw-flinching behaviour in rats. BRL44408 dose-dependently blocked, whereas ARC239 had no effect on the analgesic actions of dexmedetomidine and ST-91. Dexmedetomidine and ST-91 had no effect on the formalin-induced NK₁ receptor internalization, while morphine significantly reduced the NK₁ receptor internalization. On the other hand, both dexmedetomidine and morphine diminished the formalin-induced Fos activation. The effect of dexmedetomidine on formalin-induced Fos activation was reversed by BRL44408, but not ARC239.

Conclusion and implications:

These findings suggest that α_2A-adrenoceptors mediate dexmedetomidine and ST-91 analgesia. This effect could be through a mechanism postsynaptic to primary afferent terminals, distinct from that of morphine.     

右美托咪啶用于重症监护病房镇静的效果评价

目的观察右美托咪啶用于重症监护病房（ICU）镇静的效果及安全性。方法选择全身麻醉腹部手术后带气管插管转入ICU患者40例,随机分为右美托咪啶组（D组）和丙泊酚组（P组）各20例。D组予右美托咪啶负荷量1μg／kg20min内静脉泵入,每1h依据Ramsay评分调整药物泵入剂量为0．2～0．7μg／（kg·h）;P组予丙泊酚负荷剂量lmg／kg静脉注射,根据不同镇静程度维持剂量为O．5～3mg／（kg·h）。每2h进行数字疼痛评分（NRS）,当NRS评分大于4分时给予芬太尼1μg／kg;达到拔管备件者拔出气管导管。结果与P组比较,D组镇静效率明显较高（P〈0．05）,芬太尼用量明显减少（P〈0．05）,停药后苏醒、拔管时间明显缩短（P〈0．05）;用药期间两组心血管事件发生率有显著性差异（P〈0．05）,术后谵妄发生率无显著性差异（P〉0．05）。结论右美托咪啶用于ICU的镇静、镇痛效果好,苏醒快,可缩短拔管时间,血流动力学稳定,谵妄发生率低,是ICU理想的镇静剂。     

Adverse Events Associated With Procedural Sedation in Pediatric Patients in the Emergency Department

Purpose:

To determine the agents used by emergency medicine (EM) physicians in pediatric procedural sedation and the associated adverse events (AEs) and to provide recommendations for optimizing drug therapy in pediatric patients.

Methods:

We conducted a prospective study at Stanford Hospital’s pediatric emergency department (ED) from April 2007 to April 2008 to determine the medications most frequently used in pediatric procedural sedation as well as their effectiveness and AEs. Patients, 18 years old or younger, who required procedural sedation in the pediatric ED were eligible for the study. The data collected included medical record number, sex, age, height, weight, procedure type and length, physician, and agents used. For each agent, the dose, route, time from administration to onset of sedation, duration of sedation, AEs, and sedation score were recorded. Use of supplemental oxygen and interventions during procedural sedation were also recorded.

Results:

We found that in a convenience sample of 196 children (202 procedures) receiving procedural sedation in a university-based ED, 8 different medications were used (ketamine, etomidate, fentanyl, hydromorphone, methohexital, midazolam, pentobarbital, and thiopental). Ketamine was the most frequently used medication (88%), regardless of the procedure. Only twice in the study was the medication that was initially used for procedural sedation changed completely. Fracture reduction was the most frequently performed procedure (41%), followed by laceration/suture repair (32%). There were no serious AEs reported.

Conclusion:

EM-trained physicians can safely perform pediatric procedural sedation in the ED. In the pediatric ED, the most common procedure requiring conscious sedation is fracture reduction, with ketamine as the preferred agent.     

High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without ��2 adrenoceptor activation

BACKGROUND AND PURPOSE

Dexmedetomidine, an α₂-adrenoceptor agonist, exhibits anti-nociceptive actions at the spinal cord and enhances the effect of local anaesthetics in the peripheral nervous system. Although the latter action may be attributed in part to inhibition of nerve conduction produced by dexmedetomidine, this has not been fully examined yet.

EXPERIMENTAL APPROACH

We examined the effects of various adrenoceptor agonists including dexmedetomidine, and tetracaine, a local anaesthetic, on compound action potentials (CAPs) recorded from the frog sciatic nerve, using the air-gap method.

KEY RESULTS

Dexmedetomidine reversibly and concentration-dependently reduced the peak amplitude of CAPs (IC₅₀ = 0.40 mmol·L⁻¹). This action was not antagonized by two α₂-adrenoceptor antagonists, yohimbine and atipamezole; the latter antagonist itself reduced CAP peak amplitude. Clonidine and oxymetazoline, two other α₂-adrenoceptor agonists, also inhibited CAPs; the maximum effect of clonidine was only 20%, while oxymetazoline was less potent (IC₅₀ = 1.5 mmol·L⁻¹) than dexmedetomidine. On the other hand, (±)-adrenaline, (±)-noradrenaline, α₁-adrenoceptor agonist (-)-phenylephrine and β-adrenoceptor agonist (-)-isoprenaline (each 1 mmol·L⁻¹) had no effect on CAPs. Tetracaine reversibly reduced CAP peak amplitude (IC₅₀ of 0.014 mmol·L⁻¹).

CONCLUSIONS AND IMPLICATIONS

Dexmedetomidine reduced CAP peak amplitude without α₂-adrenoceptor activation (at concentrations >1000-fold higher than those used as α₂ adrenoceptor agonist), with a lower potency than tetracaine. CAPs were inhibited by other α₂ adrenoceptor agonists, oxymetazoline and clonidine, and also an α₂ adrenoceptor antagonist atipamezole. Thus, some drugs acting on α₂ adrenoceptors are able to block nerve conduction.     

Economic Impact of Pharmacy Graduates on a Regional Economy

Objectives

To analyze the impact of recent pharmacy graduates on a local economy.

Methods

Input-output analysis was applied to data from Spokane County, Washington, in 2006 and the findings were reviewed and conclusions were drawn.

Results

The local college of pharmacy added nearly $1 million (in 2006) directly to the local economy. New pharmacists added nearly $400,000 in direct value. However, because the graduates alleviated a shortage of pharmacists in the area, thereby avoiding both the tangible and intangible (eg, human health) economic costs of a continued shortage, the true economic impact may have been even greater.

Conclusions

Doctor of pharmacy (PharmD) graduates entering the workforce add substantial value, both to the local retail pharmacy industry specifically and the local economy in general. Thus, the economic impact of the pharmacy practice program training these students is also substantial.     

右美托咪定在慢性阻塞性肺疾病需机械通气患者镇静中的应用

目的探讨右美托咪定用于慢性阻塞性肺疾病(COPD)需机械通气患者镇静的有效性及安全性。方法 COPD急性发作期需机械通气患者50例,随机分为2组,每组25例。右美托咪定组负荷剂量右美托咪定1μg·kg~(-1),维持量0.2～0.7μg·kg~(-1)·h~(-1);丙泊酚组负荷剂量丙泊酚1 mg·kg~(-1),维持量0.5～4.0 mg·kg~(-1)·h~(-1)。根据Riker镇静-躁动评分(SAS)调整镇静药物剂量,记录SAS、达SAS 2～3分时间和苏醒时间,并比较2组重症监护病房(ICU)住院时间、机械通气时间,呼吸抑制、心动过缓和谵妄发生率。结果右美托咪定与丙泊酚都能使患者达到镇静目标评分且达标时间无显著差异(P>0.05),右美托咪定组患者更易唤醒并保持安静。右美托咪定组ICU住院时间和机械通气时间[(6.4±1.2)d和(3.2±1.0)d]均短于丙泊酚组[(8.3±1.4)d和(5.1±2.3)d,P<0.05],呼吸抑制和谵妄发生率(4%和4%)低于丙泊酚组(32%和28%),差异有显著意义(P<0.05)。2组心动过缓发生率无显著差异(P>0.05)。结论右美托咪定用于COPD需机械通气患者镇静效果满意,可缩短ICU住院及机械通气时间,且安全性高。     

Dexmedetomidine blocks thermal hyperalgesia and spinal glial activation in rat model of monoarthritis

Aim:

To investigate the effect of systemic administration dexmedetomidine, a selective alpha 2 adrenergic receptor (α₂AR) agonist, on thermal hyperalgesia and spinal glial activation evoked by monoarthritis (MA).

Methods:

MA was induced by an intra-articular injection of complete Freund''s adjuvant (CFA). Thermal hyperalgesia was measured by Hargreaves'' test. The spinal glial activation status was analyzed by GFAP (an astrocytic marker) and Iba-1 (a microglial marker) immunohistochemistry or immunoblotting.

Results:

Unilateral intra-articular injection of CFA produced a robust glial activation of astrocytes and microglia in the spinal cord, which was associated with the development and maintenance of thermal hyperalgesia. Intraperitoneal (ip) injection of dexmedetomidine (2.5 and 10 μg/kg) was repeatedly given once daily for 5 days with the first injection 60 min before intra-articular CFA. At the dose of 10 μg/kg, dexmedetomidine significantly attenuated MA-induced ipsilateral hyperalgesia from day 2 to day 5. MA-induced up-regulation of GFAP expression on both sides of the spinal dorsal horn was significantly suppressed by day 5 post-MA following dexmedetomidine application, whereas MA-induced Iba-1 up-regulation was only partially suppressed.

Conclusion:

Systemic dexmedetomidine inhibits the activation of spinal glia, which is possibly associated with its antihyperalgesia in monoarthritic rats.     

Implementation of the glucommander method of adjusting insulin infusions in critically ill patients

Background:

Intensive glycemic control has been associated with reduced morbidity and mortality in critically ill patients. Web-based, patient-specific insulin nomograms may facilitate improved glucose control.

Objective:

To compare 2 algorithms for individualizing insulin infusion therapy (a web-based system [Glucommander method] and a standard paper-based nomogram) in a cardiovascular surgery intensive care unit (ICU).

Methods:

In this prospective, before–after cohort study, measures of glycemic control for 50 patients receiving insulin according to the Glucommander system were compared with a control group (n = 50) who received insulin according to the standard paper-based nomogram used in the cardiovascular surgery ICU.

Results:

There was no significant difference between the 2 groups with respect to time to target blood glucose (5.1–8.0 mmol/L), percentage of time within the target range, or mean amplitude of glucose excursion. Patients in the intervention group spent less time above the target range (p = 0.007) and more time below the target range (p < 0.001), and the mean glucose was lower in this group compared with the control group (7.9 versus 8.6 mmol/L, p = 0.002). The percentage of blood glucose measurements below 4 mmol/L was higher in the intervention group than in the control group (3.7% versus 1.4%, p = 0.003). Satisfaction surveys revealed that the program was well accepted by the nursing staff in the cardiovascular surgery ICU.

Conclusions:

A web-based insulin nomogram was an easy-to-use instrument for achieving tighter glucose control for patients in the cardiovascular surgery ICU. Use of the Glucommander system led to lower mean blood glucose but an increase in episodes of hypoglycemia.