Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes.

Use of a Standardized Dalbavancin Approach to Facilitate Earlier Hospital Discharge for Vulnerable Patients Receiving Prolonged Inpatient Antibiotic Therapy.

Twenty-seven patients receiving prolonged inpatient antibiotic therapy for a serious bacterial infection received a single dose of dalbavancin 7-10 days before the planned end date to facilitate earlier hospital discharge. Eighty-one percent met criteria for clinical success, 7% experienced a potential adverse event, and 182 hospital days were averted.

A randomized, double-blind pilot study of dexmedetomidine versus midazolam for intensive care unit sedation: patient recall of their experiences and short-term psychological outcomes.

INTRODUCTION: Sedation with dexmedetomidine may facilitate ventilator liberation and limit the occurrence of delirium. No trial has assessed patient recall or the development of psychological outcomes after dexmedetomidine sedation. This pilot study evaluated whether transitioning benzodiazepine sedation to dexmedetomidine alters patient recall and the incidence of anxiety, depression, or acute stress disorder (ASD). METHODS: This investigation was a randomized, double-blind, single-center study. Existing continuous benzodiazepine sedation was converted to dexmedetomidine or midazolam when patients qualified for daily awakenings. Sedation was titrated to achieve Riker sedation agitation scores of 3 to 4. The intensive care unit (ICU) Stressful Experiences Questionnaire, hospital anxiety and depression scale, and the impact of event scale-revised were administered before hospital discharge to assess recall, anxiety, depression, and manifestations of ASD. RESULTS: A total of 11 patients received dexmedetomidine, and 12 patients received midazolam. Median dosing was 0.61 µg/kg/h for 3.5 days for dexmedetomidine and 3.7 mg/h for 3 days for midazolam. Attainment of goal sedation and analgesia was similar; however, more dexmedetomidine patients experienced agitation and pain. The median duration of mechanical ventilation from study drug initiation to extubation was 3.4 days in dexmedetomidine patients and 2.9 days in midazolam patients. Dexmedetomidine patients remembered 18.5 experiences compared with 8.5 in midazolam patients (P = .015). Rates of anxiety and depression were similar. In all, 5 (62.5%) dexmedetomidine patients and 1 (12.5%) midazolam patient manifested ASD (P = .063), and 1 dexmedetomidine patient and 5 midazolam patients developed new-onset delirium (P = .07). Hypotension occurred in 10 (90.9%) dexmedotomidine patients and 6 (50%) midazolam patients (P = .069). CONCLUSIONS: Transitioning benzodiazepine sedation to dexmedetomidine when patients qualify for daily awakenings may reduce the development of delirium and facilitate remembrance of ICU experiences but may lead to manifestations of ASD. Monitoring hypotension is required for both the sedatives. Additional comparative studies focusing on the long-term impact of ICU recall and psychological outcomes are needed.

A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal.

OBJECTIVES: To evaluate dexmedetomidine as adjunctive therapy to lorazepam for severe alcohol withdrawal. DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: Single center; medical ICU. PATIENTS: Twenty-four adult patients with a Clinical Institute Withdrawal Assessment score greater than or equal to 15 despite greater than or equal to 16 mg of lorazepam over a 4-hour period. INTERVENTIONS: Patients received a symptom-triggered Clinical Institute Withdrawal Assessment protocol with lorazepam and were randomized to dexmedetomidine 1.2 µg/kg/hr (high dose), 0.4 µg/kg/hr (low dose), or placebo as adjunctive therapy for up to 5 days or resolution of withdrawal symptoms. MEASUREMENT AND MAIN RESULTS: High-dose and low-dose groups were combined as a single dexmedetomidine group for primary analysis with secondary analysis exploring a dose-response relationship. The difference in 24-hour lorazepam requirements after versus before study drug was greater in the dexmedetomidine group compared with the placebo group (-56 mg vs -8 mg, p = 0.037). Median differences were similar for high dose and low dose. The 7-day cumulative lorazepam requirements were not statistically different between dexmedetomidine and placebo (159 mg vs 181 mg). Clinical Institute Withdrawal Assessment or Riker sedation-agitation scale scores representing severe agitation (13% vs 25%) or moderate agitation (27% vs 22%) within 24 hours of initiating study drug were similar for dexmedetomidine and placebo groups, respectively. Bradycardia occurred more frequently in the dexmedetomidine group versus placebo group (25% vs 0%, p = not significant), with the majority of bradycardia occurring in the high-dose group (37.5%). Study drug rate adjustments occurred more often in the dexmedetomidine group compared with the placebo group (50% vs 0%, p = 0.02). Neither endotracheal intubation nor seizure occurred in any group while on study drug. CONCLUSIONS: Adjunctive dexmedetomidine for severe alcohol withdrawal maintains symptom control and reduces lorazepam exposure in the short term, but not long term, when using a symptom-triggered protocol. Monitoring for bradycardia is needed with dexmedetomidine but the occurrence may be lessened with low dose. Further study is needed to evaluate the clinical impact of dexmedetomidine.

Pharmacist contributions as members of the multidisciplinary ICU team.

Critical care pharmacy services in the ICU have expanded from traditional dispensing responsibilities to being recognized as an essential component of multidisciplinary care for critically ill patients. Augmented by technology and resource utilization, this shift in roles has allowed pharmacists to provide valuable services in the form of assisting physicians and clinicians with pharmacotherapy decision-making, reducing medication errors, and improving medication safety systems to optimize patient outcomes. Documented improvements in the management of infections, anticoagulation therapy, sedation, and analgesia for patients receiving mechanical ventilation and in emergency response help to justify the need for clinical pharmacy services for critically ill patients. Contributions to quality improvement initiatives, scholarly and research activities, and the education and training of interdisciplinary personnel are also valued services offered by clinical pharmacists. Partnering with physician and nursing champions can garner support from hospital administrators for the addition of clinical pharmacy critical care services. The addition of a pharmacist to an interprofessional critical care team should be encouraged as health-care systems focus on improving the quality and efficiency of care delivered to improve patient outcomes.

Stability of dexmedetomidine in polyvinyl chloride bags containing 0.9% sodium chloride injection.

PURPOSE: The stability of dexmedetomidine in polyvinyl chloride (PVC) bags containing 0.9% sodium chloride injection was studied. METHODS: Dexmedetomidine solutions (4, 8, 12, and 20 µg/mL; n = 6 for each) were prepared by removing 2, 4, 6, and 10 mL of 0.9% sodium chloride injection, respectively, from 50-mL PVC bags and injecting 2, 4, 6, and 10 mL of dexmedetomidine 100 µg/mL, respectively. To ensure a homogeneous mixture, the contents of each bag was manually mixed initially and before each sample was removed. All compounding was conducted by a single pharmacist using aseptic technique in a horizontal-laminar-airflow hood at 25 °C. Forced-degradation studies were conducted at 70 ± 1 °C. Stability samples were analyzed using high-performance liquid chromatography electrospray ionization-tandem mass spectrometry (LC/MS-MS) and high-performance liquid chromatography-ultraviolet-light (HPLC/UV) absorbance. Forced-degradation samples were monitored using LC/MS-MS, HPLC/UV, and gas chromatography-MS. RESULTS: Dexmedetomidine solutions were very stable at 23 ± 2 °C at all four concentrations over the 48-hour testing period. As determined via LC/MS-MS and HPLC/UV methods, over 97% of the initial concentration of dexmedetomidine remained after 48 hours. Extensive HPLC/UV active degradation products could be observed in basic conditions; only minor UV active degradation products were observed in acidic, oxidative, and photochemical conditions. CONCLUSION: Dexmedetomidine hydrochloride 4, 8, 12, and 20 µg/mL stored in PVC bags at 23 ± 2 °C was stable for 48 hours, despite a slight decrease in solution pH seen with increasing dexmedetomidine concentrations.