Use of Valproic Acid for the Management of Delirium and Agitation in the Intensive Care Unit.

Purpose: Assess the efficacy and safety of valproic acid (VPA) for delirium and agitation in the intensive care unit (ICU) as compared to the use of other antipsychotics. Materials and Methods: This was a retrospective cohort study of patients treated for delirium and agitation in the ICU. Patients were included if they had a Richmond Agitation-Sedation Scale ≥2 and Confusion Assessment Method for the ICU positive. Patients were split into two groups based on their VPA exposure. The primary outcome was delirium free days. Secondary outcomes included agitation free days, ICU length of stay (LOS), mechanical ventilation duration, and mortality. Results: One hundred eight patients were included, 49 patients in the VPA group and 59 patients in the control group. Baseline characteristics were similar between groups. There was no significant difference in the primary outcome (difference -.15, 95% CI: 0.63-.93, P = .70). There were no significant differences in agitation-free days, mortality, mechanical ventilation duration, or ICU LOS. Conclusions: Our findings suggest that VPA is associated with similar delirium and agitation-free days compared to other non-VPA medications, with some adverse effects. Larger prospective studies are needed to validate the routine use of VPA in this setting.

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.

Comparison of clinical outcomes using activated partial thromboplastin time versus antifactor-Xa for monitoring therapeutic unfractionated heparin: A systematic review and meta-analysis.

INTRODUCTION: Continuous intravenous unfractionated heparin (UFH) is a mainstay of therapeutic anticoagulation in the acute setting. The two most common laboratory tests for monitoring UFH are the activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) heparin assay. We reviewed the available evidence to evaluate if the choice of monitoring test for UFH therapy is associated with a difference in the clinical outcomes of bleeding, thrombosis, or mortality. MATERIALS AND METHODS: MEDLINE, Cochrane database, and conference abstracts from the Society of Critical Care Medicine, the American Society of Hematology, and the American College of Clinical Pharmacy were searched for all studies comparing aPTT and anti-Xa monitoring for therapeutic UFH that evaluated outcomes for bleeding, thrombotic events, or mortality. Risk of bias was assessed with the Cochrane Risk of Bias Tool and Newcastle Ottawa Scale. Pooled relative risk ratios were calculated using an inverse variance-weighted random-effects model. RESULTS: Ten studies (n = 6677) were included for analysis. The use of anti-Xa compared to aPTT was not associated with an increased risk of bleeding (RR 1.03; 95% CI 0.8-1.22 I2 = 4%) or an increased risk of thrombotic events (RR 0.99; 95% CI 0.76-1.30, I2 = 3%). There was no difference in mortality within individual studies but the data were not suitable for pooled analysis. CONCLUSIONS: Pooled data comparing aPTT vs. anti-Xa for monitoring therapeutic UFH did not suggest differences in the outcomes of bleeding or thrombosis.

A randomized clinical trial of single dose liposomal bupivacaine versus indwelling analgesic catheter in patients undergoing surgical stabilization of rib fractures.

INTRODUCTION: Locoregional analgesia (LRA) remains underused in patients with chest wall injuries. Surgical stabilization of rib fractures (SSRF) offers an opportunity to deliver surgeon-directed LRA under direct visualization at the site of surgical intervention. We hypothesized that a single-dose liposomal bupivacaine (LB) intercostal nerve block provides comparable analgesia to an indwelling, peripheral nerve plane analgesic catheter with continuous bupivacaine infusion (IC), each placed during SSRF. METHODS: Noninferiority, single-center, randomized clinical trial (2017-2020) was performed. Patients were randomized to receive either IC or LB during SSRF. The IC was tunneled into the surgical field (subscapular space), and LB involved thoracoscopic intercostal blocks of ribs 3 to 8. The primary outcome was the Sequential Clinical Assessment of Respiratory Function score, measured daily for 5 days postoperatively. Secondary outcomes included daily narcotic equivalents and failure of primary LRA, defined as requiring a second LRA modality. RESULTS: Thirty-four patients were enrolled: 16 IC and 18 LB. Age, Injury Severity Score, RibScore, Blunt Pulmonary Contusion Score, and use of nonnarcotic analgesics was similar between groups. Duration of IC was 4.5 days. There were three failures in the IC group versus one in the LB group (p = 0.23). There was no significant difference in Sequential Clinical Assessment of Respiratory Function score between the IC and LB groups. On postoperative days 2 to 4, narcotic requirements were less than half in the LB, as compared with the IC group; however, this difference was not statistically significant. Average wholesale price was US $605 for IC and US $434 for LB. CONCLUSION: In this noninferiority trial, LB provided at least comparable and potentially superior LRA as compared with IC among patients undergoing SSRF. LEVEL OF EVIDENCE: Therapeutic, level II.

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.

Tenecteplase utility in acute ischemic stroke patients: A clinical review of current evidence.

INTRODUCTION: Acute ischemic stroke is a leading cause of disability in the United States. Treatment is aimed at reducing impact of cerebral clot burden and life-long disability. Traditional fibrinolytic treatment with recombinant tissue plasminogen activator (tPA) has shown to be effective but at high risk of major bleeding. Multiple studies have evaluated tenecteplase as an alternative to tPA. OBJECTIVE: This review evaluates literature and utility of tenecteplase for treatment of acute ischemic stroke. DISCUSSION: Tenecteplase is modified, third generation fibrinolytic with greater specificity for fibrin bound clots. Current data in acute myocardial infarction suggest decreased bleeding events compared to alteplase. Multiple trials have investigated superiority of tenecteplase compared to tPA for treatment of acute ischemic stroke. Current guidelines designate tenecteplase as an alternative treatment for mild acute ischemic stroke patients based on recent literature. CONCLUSION: Recent emerging literature and limited recommendation guidance from governing medical societies leave many emergency medicine providers to weigh benefit versus risk of fibrinolytic therapy and tenecteplase's place in therapy. This review evaluates the available literature regarding tenecteplase and its utility in the treatment of acute ischemic stroke patients.

A double-blind, randomized controlled trial of gabapentin vs. placebo for acute pain management in critically ill patients with rib fractures.

INTRODUCTION: Achieving adequate pain control for rib fractures remains challenging; prescription of alternatives to narcotics is imperative to curtail the current opioid epidemic. Although gabapentin has shown promise following elective thoracic procedures, its efficacy in patients with rib fractures remains unstudied. We hypothesized that gabapentin, as compared to placebo, would both improve acute pain control and decrease narcotic use among critically ill patients with rib fractures. MATERIALS AND METHODS: Adult patients admitted to the trauma surgery service from November 2016 - November 2017 at an urban, Level I trauma center with one or more rib fractures were randomized to either gabapentin 300 mg thrice daily or placebo for one month following their injury. Daily numeric pain scores, opioid consumption, oxygen requirement, respiratory rate, and incentive spirometry recordings during the index admission, as well as and one-month quality of life survey data were abstracted. RESULTS: Forty patients were randomized. The groups were well matched with respect to age, gender, prior narcotic use, tobacco use, and prior respiratory disease. Although the median RibScore did not differ between groups, the gabapentin group had a higher median number of ribs fractured as compared to the placebo group (7 vs. 5, respectively). Degree of pulmonary contusion and injury severity score were similar between groups. Use of loco-regional anesthetic modalities did not differ between groups. Daily numeric pain scores, opioid consumption, oxygen requirement, respiratory rate, and incentive spirometry recordings were similar between both groups. No benefit was observed when adding gabapentin to a multi-modal analgesic regimen for rib fractures. There were no instances of pneumonia, respiratory failure, or mortality in either group. Hospital and intensive care unit length of stay were similar between groups. Both overall and chest-specific quality of life was equivalent between groups at one month follow-up. CONCLUSIONS: In this group of critically ill patients with rib fractures, gabapentin did not improve acute outcomes for up to one month of treatment.

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.