Tanezumab: Therapy targeting nerve growth factor in pain pathogenesis.

In recent years, nerve growth factor (NGF) and the NGF receptor have become potential therapeutic targets in the treatment of acute and chronic pain states. NGF is a neurotrophin involved in regulating the function of sensory and sympathetic neurons during development. Numerous pain states have been linked to elevated levels of NGF and its role in increasing the perception of pain. Tanezumab, a recombinant humanized monoclonal antibody (IgG), was developed to target NGF, binding both circulating and local tissue NGF preventing interaction with the tropomyosin-related kinase-A and p75 receptors. Recent clinical studies with tanezumab in different patient populations to date, including osteoarthritis, low back pain, and diabetic peripheral neuropathy, demonstrate efficacy with few side effects, including transient arthralgias, paresthesias, hypoesthesia, and rarely, osteonecrosis. Anti-NGF antibodies are a novel therapy in pain management and have shown promise in the treatment of certain pain conditions, which at present are poorly treated. Tanezumab offers an exciting new class of analgesics that has the potential to change the treatment of pain.

Low-Dose Ketamine in Chronic Critical Illness.

We report a case series on the observed effects of low-dose ketamine infusions in 4 critically ill patients with varying complications related to prolonged critical illness. Doses of ketamine infusion ranged from 0.5 to 4 µg/kg/min. A low-dose ketamine infusion was used to reduce agitation in a patient requiring high doses of sedatives and analgesics. In a second patient, ketamine improved depression and anxiety symptoms. In a third patient, ketamine may have facilitated liberation from mechanical ventilation. In a fourth patient, ketamine was used for palliation to avoid lethargy. Ketamine may be considered to help decrease agitation, manage pain, facilitate opioid and benzodiazepine withdrawal, prevent respiratory depression, and potentially manage depression and anxiety in chronically critically ill patients.

A pharmacist's guide to mitigating sleep dysfunction and promoting good sleep in the intensive care unit.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To review causes, risk factors, and consequences of sleep disruption in critically ill patients; evaluate the role of nonpharmacological and pharmacological therapies for management of sleep in the intensive care unit (ICU); and discuss the role of pharmacists in implementation of sleep bundles. SUMMARY: Critically ill patients often have disrupted sleep and circadian rhythm alterations that cause anxiety, stress, and traumatic memories. This can be caused by factors such as critical illness, environmental factors, mechanical ventilation, and medications. Methods to evaluate sleep, including polysomnography and questionnaires, have limitations that should be considered. Multicomponent sleep bundles with a focus on nonpharmacological therapy aiming to reduce nocturnal noise, light, and unnecessary patient care may improve sleep disorders in critically ill patients. While pharmacological agents are often used to facilitate sleep in critically ill patients, evidence supporting their use is often of low quality, which limits use to patients who have sleep disruption refractory to nonpharmacological therapy. Dedicated interprofessional teams are needed for implementation of sleep bundles in the ICU. Extensive pharmacotherapeutic training and participation in daily patient care rounds make pharmacists vital members of the team who can help with all components of the bundle. This narrative review discusses evidence for elements of the multicomponent sleep bundle and provides guidance on how pharmacists can help with implementation of nonpharmacological therapies and management of neuroactive medications to facilitate sleep. CONCLUSION: Sleep bundles are necessary for patients in the ICU, and dedicated interprofessional teams that include pharmacists are vital for their successful creation and implementation.

Rethinking the Drug Distribution and Medication Management Model: How a New York City Hospital Pharmacy Department Responded to COVID-19.

Beginning in March 2020, New York City began the fight against coronavirus disease 2019. Health care workers were faced with a disease that led to significant morbidity and mortality with no proven therapies. As hospitals became inundated with patients and underwent rapid expansion of capacity, resources such as drugs, protective and medical equipment, and hospital staff became limited. Pharmacists played a critical role in the management of clinical care and drug delivery during the pandemic. As members of the department of pharmacy within NewYork-Presbyterian Hospital, we describe our experiences and processes to overcome challenges faced during the pandemic. Strict inventory management through the use of daily usage reports, frequent communication, and minimization of waste was critical for the management of drug shortages. The creation of guidelines, protocols, and restrictions were not only used to mitigate drug shortages, but also helped educate health care providers and guided medication use. Managing technology through setting up new automatic dispensing cabinets to address hospital expansions and modifying the electronic order entry system to include new protocols and drug shortage information were also vital. Additional key pharmacist functions included provision of investigational drug service support and training of pharmacists, prescribers, nurses, and respiratory therapists to educate and standardize medication use. Through implementation of operational and clinical processes, pharmacists managed critical drug inventory and guided patient treatment. As the pandemic continues, pharmacists will remain vital members of the multidisciplinary team dedicated to the fight against the virus.

Pharmacologic Considerations Surrounding Sedation, Delirium, and Sleep in Critically Ill Adults: A Narrative Review.

INTRODUCTION: Agitation, delirium, and sleep dysfunction in the intensive care unit (ICU) are common occurrences that result in negative patient outcomes. With the recent publication of the 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU (PAD-IS), several areas are of particular interest due to emerging literature or conflicting results of research. OBJECTIVE: To highlight areas where emerging literature or variable study results exist and to provide the clinician with recommendations regarding patient management. METHODS: The 2018 PAD-IS guidelines were reviewed, and areas of emerging literature or lack of consensus of included investigations surrounding pharmacologic management of sedation, delirium, and sleep in the ICU were identified. A review and appraisal of the literature was conducted specifically to address the identified areas. Prospective, randomized trials were included in this narrative review. RESULTS: Four areas with emerging data or conflicting evidence were identified and included: use of propofol or dexmedetomidine for sedation, pharmacologic prevention of delirium, treatment of delirium, and pharmacologic strategies to improve sleep. CONCLUSION: A comprehensive approach to the prevention and management of delirium, sedation, and sleep in the ICU is necessary to optimize patient outcomes.

Major publications in the critical care pharmacotherapy literature: January-December 2017.

PURPOSE: To summarize selected meta-analyses and trials related to critical care pharmacotherapy published in 2017. The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 32 journals monthly for impactful articles and reviewed 115 during 2017. Two meta-analyses and eight original research trials were reviewed here from those included in the monthly CCPLU. Meta-analyses on early, goal-directed therapy for septic shock and statin therapy for acute respiratory distress syndrome were summarized. Original research trials that were included evaluate thrombolytic therapy in severe stroke, hyperoxia and hypertonic saline in septic shock, intraoperative ketamine for prevention of post-operative delirium, intravenous ketorolac dosing regimens for acute pain, angiotensin II for vasodilatory shock, dabigatran reversal with idarucizumab, bivalirudin versus heparin monotherapy for myocardial infarction, and balanced crystalloids versus saline fluid resuscitation. CONCLUSION: This clinical review provides perspectives on impactful critical care pharmacotherapy publications in 2017.

Major publications in the critical care pharmacotherapy literature: January-December 2014.

PURPOSE: Nine recently published articles and one guideline with important implications for critical care pharmacy practice are summarized. SUMMARY: The Critical Care Pharmacotherapy Literature Update (CCPLU) group includes more than 40 experienced critical care pharmacists across the United States. Group members monitor 29 peer-reviewed journals on an ongoing basis to identify literature relevant to pharmacy practice in the critical care setting. After evaluation by CCPLU group members, selected articles are chosen for summarization and distribution to group members nationwide based on applicability to practice, relevance, and study design and strength. Hundreds of relevant articles were evaluated by the group in 2014, of which 114 were summarized and disseminated to CCPLU group members. From among those 114 publications, 10 deemed to be of particularly high utility to the critical care practitioner were selected for inclusion in this review for their potential to change practice or reinforce current evidence-based practice. One of the selected articles presents updated recommendations on the management of patients with atrial fibrillation (AF); the other 9 address topics such as albumin replacement in patients with severe sepsis, use of enteral statins for acute respiratory distress syndrome, fibrinolysis for patients with intermediate-risk pulmonary embolism, the use of unfractionated heparin versus bivalirudin for primary percutaneous coronary intervention, and early protocol-based care for septic shock. CONCLUSION: There were many important additions to the critical care pharmacotherapy literature in 2014, including a joint guideline for the management of AF and reports of clinical trials.