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The Institute of Medicine has identified adverse drug events as factors that significantly contribute to increased patient morbidity and mortality. As critically ill patients receive numerous drugs to treat a multitude of complicated health problems, they are at high risk for adverse drug events. Sedation is often a key requirement for the optimal management of critical illness, and propofol, a common sedative, has many desirable characteristics that make it the ideal agent in numerous circumstances. However, over the last decade, increasing numbers of reports have described a potentially fatal adverse effect called propofol-related infusion syndrome. Whether this adverse drug event is preventable is unclear, but recommendations have been proposed to minimize the potential for development of this syndrome. Research is under way to collect data on the use of propofol in intensive care units and on its prevalence. [ABSTRACT FROM AUTHOR]

Osteoporosis is a leading public health threat affecting approximately 44 million people in the United States. Most of the therapies for this disease work to prevent further bone loss, improve bone mineral density, and reduce the risk of fractures. These agents, however, have not been proved to increase bone formation significantly. Therefore, the ideal agent would not only improve bone strength by decreasing bone breakdown, but also promote bone formation in the ultimate quest to prevent fractures. The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become an area of research in the battle against osteoporosis. Two mechanisms for beneficial effects of statins on bones have been proposed, and although in vitro, in vivo, and animal studies have shown positive effects on bone mineralization and reductions in bone resorption, clinical data on surrogate markers and fracture rates are conflicting. The inherent problems with observational studies also must be addressed. Until that time, the use of statins in the prevention of fractures or the treatment of osteoporosis requires further study. [ABSTRACT FROM AUTHOR]

Left ventricular assist devices (LVADs) have revolutionized the care of patients with advanced heart failure, yet still require concomitant medications in order to achieve the best possible clinical outcomes. Since the outset of routine placement of durable, continuous‐flow LVADs, much of the medication management of these patients to date has been based on International Society of Heart and Lung Transplantation (ISHLT) guidance, most recently published in 2013. Since 2013, numerous multidisciplinary pharmacotherapy publications have increased the LVAD community's understanding of best practices with respect to medications. We identified the major domains of LVAD medication management and conducted a comprehensive search of US National Library of Medicine MEDLINE® database using keywords chosen to identify medication‐related publications of significance dated 2013 or later. Trials pertaining to the HeartMate II™ and the HeartMate™ 3 LVADs (Abbott, Chicago, IL) and the HeartWare™ HVAD™ System (Medtronic, Minneapolis, MN) were chosen for inclusion. Highest priority for inclusion was given to prospective, randomized, controlled studies. Absent these, controlled trials (retrospective or prospective observational) were given next‐highest consideration, followed by retrospective uncontrolled studies, and finally case series. Reference lists of qualified publications were reviewed to find any other publications of interest that were not discovered on initial search. Case reports were generally excluded, except where the insight gained was deemed to be uniquely pertinent. This document serves to provide a comprehensive review of the current understanding of optimal medication management in patients with durable, continuous‐flow LVADs. [ABSTRACT FROM AUTHOR]

Evidence‐based management of analgesia and sedation in COVID‐19‐associated acute respiratory distress syndrome remains limited. Non‐guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID‐19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID‐19 patient rooms, marked obesity, altered end‐organ function, and evolving medication shortages, presents numerous short‐ and long‐term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID‐19. [ABSTRACT FROM AUTHOR]

Acute graft‐versus‐host disease remains a devastating complication following hematopoietic cell transplantation, resulting in increased morbidity and mortality. Vast research efforts continue to refine or develop new means of prediction, assessment, prevention, and treatment of this syndrome. Recent updates in acute graft‐versus‐host disease include more definitive guidance and definitions for its grading and diagnosis. Biomarker use is being incorporated into early stages following hematopoietic cell transplantation to aid in the detection and prediction of long‐term outcomes. New preventive strategies under investigation include the use of vedolizumab or tocilizumab as upfront prophylaxis. Finally, although steroids remain the backbone of therapy once treatment is warranted, the efficacy of several agents including vedolizumab, tocilizumab, ruxolitinib, and α1 antitrypsin are being evaluated as potential therapeutic options. [ABSTRACT FROM AUTHOR]

Our aim was to review the efficacy, safety, and pharmacology of brexanolone (Zulresso), a new antidepressant with a novel mechanism of action, in the treatment of postpartum depression (PPD). Pertinent data and information were obtained via PubMed (1993 to August 2018). Articles published in English that evaluated the safety and efficacy of brexanolone and other off‐label PPD treatments were included. Literature regarding epidemiology and pathophysiology of PPD was also selected. Brexanolone, administered as an intravenous infusion over 60 hours, produced a statistically significant and clinically meaningful reduction in Hamilton Depression Rating Scale (HAM‐D) scores compared with placebo at both 60 and 90 μg/kg/hour in patients with moderate to severe PPD. Brexanolone groups had higher response and remission rates compared with placebo. Common adverse effects were somnolence, dizziness, and headache. A small percentage (4%) of patients required cessation of therapy due to excessive sedation or loss of consciousness. Although the evidence for brexanolone as a novel treatment for PPD looks promising, a Risk Evaluation and Mitigation Strategies (REMS) program requirement and the logistics of prolonged infusions serve as barriers to treatment. A discussion of these obstacles as well as pharmacokinetics, monitoring, and dosing is provided. Brexanolone is a novel antidepressant indicated for the treatment of PPD. Clinical trials demonstrated that brexanolone significantly reduces depression scores in women with moderate to severe PPD. Due to risk of oversedation and loss of consciousness, a REMS program will be put in place to mitigate the risk of adverse events. [ABSTRACT FROM AUTHOR]

Optimal blood pressure (BP) management is controversial in neurocritically ill patients due to conflicting concerns of worsening ischemia with decreased BP versus cerebral edema and increased intracranial pressure with elevated BP. In addition, high‐quality evidence is lacking regarding optimal BP goals in patients with most of these conditions. This review summarizes guideline recommendations and examines the literature for BP management in patients with ischemic stroke, intracerebral hemorrhage, aneurysmal subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury. [ABSTRACT FROM AUTHOR]

Traditional first‐line therapy in the prehospital setting for the acutely agitated patient includes an antipsychotic in combination with a benzodiazepine. Recently, interest has grown regarding the use of ketamine in the prehospital setting as an attempt to overcome the limitations of the traditional medications and provide a more safe and effective therapy. This review provides an overview of the pharmacology of ketamine, evaluates the literature regarding ketamine use for prehospital agitation, and proposes an algorithm that may be used within the prehospital setting. A literature review was conducted to identify articles utilizing ketamine in the prehospital setting. The review was limited to English‐language articles identified in Embase (1988–June 2017) and the U.S. National Library of Medicine (1970–June 2017). References of all pertinent articles were also reviewed. Ten articles were identified including 418 patients receiving ketamine for agitation. The most commonly utilized route for administration was intramuscular (IM), with five of the seven IM administration studies using a ketamine dose of 5 mg/kg. Ketamine administered in this fashion was efficacious to achieve proper sedation during transport and did not require repeat dosing. Three studies applied a ketamine protocol to outline dosing and the management of ketamine adverse events. The most common adverse events identified were respiratory‐related events and hypersalivation. Ketamine has a role for agitation management in the prehospital setting; however, emergency personnel education and ketamine protocols should be utilized to aid in safe and effective pharmacotherapy and provide guidance on the management of adverse events. Future prospective comparative studies, with protocolized standard ketamine regimens, are needed to further delineate the role of ketamine in agitation management and identify accurate adverse event incidence rates. [ABSTRACT FROM AUTHOR]

Objective To compare succinylcholine and rocuronium regarding mortality in patients with traumatic brain injury ( TBI) who are intubated in the emergency department ( ED). Methods This was a retrospective cohort study conducted in an academic ED in the United States. Adult patients with TBI who underwent rapid sequence intubation ( RSI) in the ED with rocuronium or succinylcholine between October 2010 and October 2014 were included. The main outcome of interest was in-hospital mortality. Subjects were stratified based on severity of injury using head abbreviated injury scores. The high-severity group had a severe or critical head injury (score 4 or higher); the low-severity group had a less than severe head injury (score lower than 4). Main Results The final study cohort included 233 patients who were underwent RSI with succinylcholine (149 patients) or rocuronium (84 patients). In patients who received rocuronium, mortality was 22% (12/54) and 23% (7/30) in the low-severity and high-severity categories, respectively (difference 1%, 95% confidence interval [ CI] −18% to 20%). In patients who received succinylcholine, mortality was 14% (14/103) and 44% (20/46) in the low-severity and high-severity categories, respectively (difference 30%, 95% CI 14-46). In the multivariate analysis after adjusting for important confounders, there was no significant association between succinylcholine and mortality in the low-severity category (odds ratio [ OR] 0.75, 95% CI 0.29-1.92). However, in patients in the high-severity category, succinylcholine was associated with increased mortality compared with rocuronium ( OR 4.10, 95% CI 1.18-14.12). Conclusions In severely brain-injured patients undergoing RSI in the ED, succinylcholine was associated with increased mortality compared with rocuronium. [ABSTRACT FROM AUTHOR]

Antibody-drug conjugates ( ADCs) combine highly specific monoclonal antibodies with potent cytotoxic drugs. Their synergy allows for targeted delivery of toxic drugs to cancer cells while sparing systemic exposure. In this review, we focus on the history and clinical applications of ADCs approved by the U.S. Food and Drug Administration ( FDA) for the treatment of cancer and highlight new ADCs in the drug development pipeline. Three ADCs have received FDA approval thus far. Gemtuzumab ozogamicin, although withdrawn from the U.S. market, may still be an effective treatment modality in subsets of patients with acute myeloid leukemia. Brentuximab vedotin and ado-trastuzumab emtansine have shown improved efficacy and safety data compared with standard chemotherapy for the treatment of advanced lymphoma and breast cancer, respectively. With a number of ADCs with promising preliminary data in the clinical trial pipeline, cancer therapy is moving forward from traditional chemotherapy to targeted treatment modalities driven by the specificity of monoclonal antibodies and advancing biotechnology. [ABSTRACT FROM AUTHOR]

Continuous-flow left ventricular assist devices reduce short-term mortality and improve quality of life in patients with end-stage heart failure. Unfortunately, device-related complications remain common, with many patients experiencing adverse events within the first year. New literature suggests that rates of device-related thrombosis may be increasing since 2011, which is particularly troublesome given that this pathology can result in a disabling stroke, organ damage, and death. In 2013, a group of practitioners in the field of mechanical circulatory support published a treatment algorithm based on their expert opinion. However, a comprehensive review of the pharmacotherapy of this condition is lacking. A search of the literature revealed 20 separate publications of case reports or case series describing outcomes associated with the use of drug therapy for suspected pump thrombosis. Each of these experiences was limited by small sample size, nonrandomized treatment allocation, and nonstandardized medication dosing. Data describing the outcomes of surgical versus medical management of device thrombosis are also sparse, with only three published reports identified. Based on the review of this limited literature, surgical management appears to be the preferred treatment modality, especially in those with organ hypoperfusion or hemodynamic instability. In patients ineligible for surgery, pharmacotherapy options remain limited. Use of all drug classes described in the literature for the HeartMate II device-fibrinolytics, glycoprotein IIb/ IIIa inhibitors, and direct thrombin inhibitors-was hindered by either marginal efficacy or bleeding. Based on historical experience with unfractionated heparin in patients under HeartMate II support, we recommend this agent as a possible option for those with suspected pump thrombosis in lieu of surgical device exchange. For the HeartWare HVAD, limited data suggest that direct intraventricular administration of alteplase may be an acceptable treatment alternative. Additional research is clearly needed to further delineate the role of pharmacotherapy and to identify the optimal agent for managing this potentially life-threatening condition. [ABSTRACT FROM AUTHOR]

Study Objective To determine the natremic response of a single 20-mg bolus dose of conivaptan, an arginine vasopressin antagonist, in hyponatremic neurosurgical patients with the syndrome of inappropriate antidiuretic hormone secretion ( SIADH). Design Retrospective medical record review. Setting Neurosurgical intensive care unit of a tertiary care referral hospital. Patients Thirty-two hyponatremic patients with SIADH who were admitted to the neurosurgical intensive care unit and received a single 20-mg bolus dose of conivaptan between January and December 2011. Measurements and Main Results Each patient's natremic response over 48 hours was determined. The primary end point was an increase in serum sodium level of 4 mEq/L or greater over the first 24 hours. The mean ± SD baseline serum sodium level was 129.8 ± 3.4 mEq/L, which increased to 133.1 ± 3.2 mEq/L at 6 hours after administration of the bolus dose of conivaptan. The serum sodium level at 24 hours was 134.2 ± 3.2 mEq/L, indicating a 24-hour natremic response of 4.3 ± 2.6 mEq/L (range 1-13 mEq/L) from baseline (p<0.001). Eighteen patients (56%) met the primary end point. The mean ± SD fluid balance over the first 24 hours was -783 ± 440 ml. The mean ± SD change in serum sodium level from 24 to 48 hours was 0.5 ± 1.3 mEq/L. No adverse effects or injection-site reactions were noted. The patients who failed to reach the primary end point were treated with repeated doses of conivaptan plus other agents. Conclusion We recommend a single 20-mg dose of conivaptan as the preferred initial approach to treating patients with SIADH who are in the neurosurgical intensive care unit. The 24-hour natremic response should then dictate whether additional doses of conivaptan or other therapeutic interventions are required. We believe that such an approach is safe and will result in a controlled and predictable increase in the serum sodium concentration. [ABSTRACT FROM AUTHOR]