Yoonsun Mo

Role of Dexmedetomidine for the Prevention and Treatment of Delirium in Intensive Care Unit Patients

OBJECTIVE: To review recent clinical studies regarding the role of dexmedetomidine for prevention and treatment of delirium in intensive care unit (ICU) patients. DATA SOURCES: MEDLINE and PubMed searches (1988-Feburary 2013) were conducted, using the key words delirium, dexmedetomidine, Precedex, agitation, α-2 agonists, critical care, and intensive care. References from relevant articles were reviewed for additional information. STUDY SELECTION AND DATA EXTRACTION: Clinical trials comparing dexmedetomidine with other sedatives/analgesics or with antipsychotics for delirium were selected. Studies that evaluated the use of dexmedetomidine for sedation for more than 6 hours were included in this review. DATA SYNTHESIS: Dexmedetomidine is a highly selective α-2 receptor agonist that provides sedation, anxiolysis, and modest analgesia with minimal respiratory depression. Its mechanism of action is unique compared with that of traditional sedatives because it does not act on γ-aminobutyric acid receptors. In addition, dexmedetomidine lacks anticholinergic activity and promotes a natural sleep pattern. These pharmacologic characteristics may explain the possible antidelirium effects of dexmedetomidine. Eight clinical trials, including 5 double-blind randomized trials, were reviewed to evaluate the impact of dexmedetomidine on ICU delirium. CONCLUSIONS: Currently available evidence suggests that dexmedetomidine is a promising agent, not only for prevention but also for treatment of ICU-associated delirium. However, larger, well-designed trials are warranted to define the role of dexmedetomidine in preventing and treating delirium in the ICU.

Recent Advances in the Development of Specific Antidotes for Target-Specific Oral Anticoagulants

Warfarin, a vitamin K antagonist, has been the only orally available anticoagulant for > 60 years. During the past decade, the U.S. Food and Drug Administration has approved several target‐specific oral anticoagulants (TSOACs) for the prophylaxis and treatment of arterial and venous thromboembolism and stroke prevention in patients with nonvalvular atrial fibrillation. These new agents have several advantages over warfarin including more predictable pharmacokinetics and pharmacodynamics, fewer food and drug interactions, and lack of need for routine coagulation monitoring. However, unlike warfarin, currently no antidotes are available to reverse the anticoagulant effect of TSOACs. Specific antidotes for TSOACs may not be needed in most situations due to their short half‐life, yet the absence of antidotes for these agents is a concern, especially in emergent situations such as life‐threatening major bleeding or nonelective major surgery. Several specific antidotes for TSOACs including idarucizumab, andexanet alfa, and aripazine have been developed and have shown promise in early clinical trials evaluating their efficacy and safety. In this narrative review, the progress made in developing specific antidotes for TSOACs is summarized based on the latest available preclinical and clinical data.

Emerging Role of Melatonin and Melatonin Receptor Agonists in Sleep and Delirium in Intensive Care Unit Patients

Delirium, an acute state of mental confusion, can lead to many adverse sequelae in intensive care unit (ICU) patients. Although the etiology of ICU delirium is often multifactorial, and at times not fully understood, sleep deprivation is considered to be a major contributing factor to its development. It has been postulated that administration of exogenous melatonin and melatonin receptor agonists such as ramelteon may prevent delirium by promoting nocturnal sleep in ICU patients. The purpose of this review is to summarize the pharmacology of melatonin and melatonin receptor agonists and investigate their potential roles in sleep promotion and delirium prevention in ICU patients. Although few studies evaluating the impact of melatonergic agents on sleep and delirium in the ICU have been completed, some data suggest their potential positive effects on sleep and delirium. However, large-scale randomized controlled trials are warranted to determine the optimal role of melatonergic agents in the prevention of ICU delirium.

Barbiturates for the treatment of alcohol withdrawal syndrome: A systematic review of clinical trials

PURPOSE To perform a systematic review of the clinical trials concerning the use of barbiturates for the treatment of acute alcohol withdrawal syndrome (AWS). MATERIALS AND METHODS A literature search of MEDLINE, EMBASE, and the Cochrane Library, together with a manual citation review was conducted. We selected English-language clinical trials (controlled and observational studies) evaluating the efficacy and safety of barbiturates compared with benzodiazepine (BZD) therapy for the treatment of AWS in the acute care setting. Data extracted from the included trials were duration of delirium, number of seizures, length of intensive care unit and hospital stay, cumulated doses of barbiturates and BZDs, and respiratory or cardiac complications. RESULTS Seven studies consisting of 4 prospective controlled and 3 retrospective trials were identified. Results from all the included studies suggest that barbiturates alone or in combination with BZDs are at least as effective as BZDs in the treatment of AWS. Furthermore, barbiturates appear to have acceptable tolerability and safety profiles, which were similar to those of BZDs in patients with AWS. CONCLUSIONS Although the evidence is limited, based on our findings, adding phenobarbital to a BZD-based regimen is a reasonable option, particularly in patients with BZD-refractory AWS.

Practice Patterns and Opinions on Current Clinical Practice Guidelines Regarding the Management of Delirium in the Intensive Care Unit.

Objective: The aim of this study was to determine current delirium practices in the intensive care unit (ICU) setting and evaluate awareness and adoption of the 2013 Pain, Agitation, and Delirium (PAD) guidelines with emphasis on delirium management. Design, Setting, and Participants: A large-scale, multidisciplinary, online survey was administered to physician, pharmacist, nurse, and mid-level practitioner members of the Society of Critical Care Medicine (SCCM) between September 2014 and October 2014. A total of 635 respondents completed the survey. Measurements and Main Results: Nonpharmacologic interventions such as early mobilization were used in most ICUs (83%) for prevention of delirium. A majority of respondents (97%) reported using pharmacologic agents to treat hyperactive delirium. Ninety percent of the respondents answered that they were aware of the 2013 PAD guidelines, and 75% of respondents felt that their delirium practices have been changed as a result of the new guidelines. In addition, logistic regression analysis of this study showed that respondents who use delirium screening tools were twice more likely to be fully aware of key components of the updated guidelines (odds ratio [OR] = 2.07, 95% confidence interval [CI] = 1.20-3.60). Conclusions: Most critical care practitioners are fully aware and knowledgeable of key recommendations in the new guidelines and have changed their delirium practices accordingly.

Rational Use of Second-Generation Antipsychotics for the Treatment of ICU Delirium: A Neuropharmacological Approach

Delirium, described as an acute neuropsychiatric syndrome, occurs commonly in critically ill patients and leads to many negative outcomes including increased mortality and long-term cognitive deficits. Despite the lack of clinical data supporting the use of antipsychotics for the management of intensive care unit (ICU) delirium, pharmacological interventions are often needed to control acutely agitated patients. Given that the most current guidelines do not advocate the use of haloperidol for either the prevention or treatment of ICU delirium due to a lack of evidence, second-generation antipsychotics (SGAs) have been commonly used as alternatives to haloperidol for ICU patients with delirium. Nonetheless, the evidence supporting the use of SGAs to treat ICU delirium remains limited. This review is designed to assess the available clinical evidence and highlights the different neuropharmacological and safety properties of SGAs in order to guide the rational use of SGAs for the treatment of ICU delirium.

Continuous Lidocaine Infusion as Adjunctive Analgesia in Intensive Care Unit Patients

Despite a paucity of data, the role of intravenous lidocaine (IVLI) as adjunctive analgesia in the intensive care unit (ICU) seems promising due to a low potential to contribute to respiratory depression. A retrospective chart review was conducted to evaluate the safety and effectiveness of IVLI for the treatment of pain in ICU patients with varying degrees of organ dysfunction from March 2014 to March 2016. The primary outcomes included the time to a ≥20% reduction in pain scores after the initiation of IVLI and the difference in opioid requirements as well as pain scores prior to and during IVLI therapy. Other variables included the presence of IVLI‐related adverse events and the dosage and duration of IVLI. A total of 21 ICU patients were included from 2 different hospitals. The mean time to a ≥20% reduction in pain scores from the start of IVLI was 3.3 hours (SD = 2.2). The median morphine dose equivalents required during 6, 12, and 24 hours pre‐IVLI were significantly higher compared to the same time periods after IVLI (18.3 vs 10 mg, P = .002; 41.8 vs 18.3 mg, P = .002; 93.5 vs 30.5 mg, P = .037). Neurological adverse effects of lidocaine were noted in 3 patients, but the effects were reversed on IVLI discontinuation. This report suggests that IVLI as an adjunctive agent in the treatment of acute pain may be a potential option in ICU patients who are refractory to opioids or those in whom opioid‐induced respiratory depression is a concern.

Possible Hepatotoxicity Associated With Daptomycin: A Case Report and Literature Review.

Purpose To report a case of isolated daptomycin-induced acute liver injury without elevations in creatine kinase (CK) levels or kidney dysfunction. Summary A 49-year-old female with a history of pancreatitis, lupus, diabetes, congestive heart failure, hypertension, and chronic pain syndrome presented to the emergency department with alteration in mental status and acute liver failure. The patient had been treated with daptomycin for methicillin-resistant Staphylococcus aureus (MRSA) endocarditis for 3 weeks. After ruling out other possible etiologies, daptomycin was suspected as a cause of acute liver failure. Her liver failure resolved gradually following withdrawal of daptomycin. Conclusion Although hepatic abnormalities caused by daptomycin are rare, a handful of cases with daptomycin-induced liver injury have been reported in the literature. Of note, in most cases, patients on daptomycin therapy developed liver damage with elevations in CK levels. Our case report suggests possible severe liver injury associated with high-dose and long-term daptomycin treatment in the absence of rhabdomyolysis. Future research is warranted to further investigate the relationship between daptomycin use and liver injury, yet it is reasonable to monitor liver function tests at baseline and weekly thereafter along with CK levels, especially in patients requiring long-term daptomycin therapy.

Effect of Modafinil on Cognitive Function in Intensive Care Unit Patients: A Retrospective Cohort Study

Modafinil therapy, a nonamphetamine cognition‐enhancing agent, holds the potential to improve recovery from cognitive impairment after intensive care unit (ICU) admission. To date, however, there is a paucity of data on modafinil use in the ICU setting. The purpose of this study was to explore the role of modafinil for improvement in cognition in ICU patients. This retrospective cohort study evaluated a total of 60 ICU patients with any ventilatory support who started on modafinil during their ICU stay from January 1, 2010, to March 19, 2016. The requirements of opioids and sedatives, as well as the lowest and average scores of the Glasgow Coma Scale (GCS) and Riker Sedation‐Agitation Scale (SAS), were recorded during 48 hours before and after the start of modafinil therapy in 6‐hour periods. The average daily modafinil dose of 170 mg was given for a median duration of 9 days. Modafinil administration was associated with a small, nonsignificant increase in GCS by 0.34 points after controlling for age, baseline severity of illness, and changes in sedation and analgesia over time (95%CI, −0.34 to 0.73 points; P = .0743). No major modafinil‐associated adverse effects were observed. Modafinil administration did not significantly improve cognitive function in ICU patients within 48 hours of initiation. However, because of lack of robust evidence, the impact of modafinil on overall patient outcomes in the ICU remains unclear and needs further investigation.

Evaluation of Potential Drug–Drug Interactions With Direct Oral Anticoagulants in a Large Urban Hospital

Objective: The aim of this study is to assess patterns of potential drug–drug interactions (DDIs) with direct oral anticoagulants (DOACs) in an inpatient hospital setting. Methods: A retrospective chart review was conducted at the Brookdale University Hospital and Medical Center (BUHMC) from January 2014 to November 2016. All adult patients admitted to the BUHMC who were treated with a DOAC for at least 3 days were screened. Among them, those who received selected interacting drugs at any time during the course of DOAC therapy were included in this study. Results: This study included 165 patients with an average of 73 years (standard deviation [SD] = 12.3) and 233 cases. The most commonly used concomitant drug with a DOAC was aspirin (58%), followed by amiodarone (16%) and P2Y12 inhibitors (11%). The combined use of dual antiplatelet therapy and a DOAC was identified in 18 (6%) cases. Approximately one-third of the cases encountered were classified as the “avoidance” category. Conclusions: Despite computerized DDI alerts, potentially significant DDIs with DOACs still occur. While the present study provides insight into the current patterns of DDIs, further studies are needed to evaluate clinical outcomes of the potential DDIs with DOACs in practice.