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Objective: Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs)., Methods: Multicenter, retrospective, observational study in children <18 years who received CI ketamine between 2014 and 2017. Time spent in goal pain/sedation score range and daily cumulative doses of analgesics/sedatives were compared from the 24 hours (H) prior to CI ketamine to the first 24H and 25-48H of the CI. Adverse effects were collected over the first 7 days of CI ketamine., Results: Twenty-four patients from 4 PICUs were included; median (IQR) age 7 (1-13.25) years, 54% female ( n  = 13), 92% intubated ( n  = 22), 25% on CI vasopressors ( n  = 6), and 33% on CI paralytics ( n  = 8). Ketamine indications were analgesia/sedation ( n  = 21, 87.5%) and status epilepticus ( n  = 3, 12.5%). Median starting dose was 0.5 (0.48-0.70) mg/kg/hr and continued for a median of 2.4 (1.3-4.4) days. There was a significant difference in mean proportion of time spent within goal pain score range (24H prior: 74% ± 14%, 0-24H: 85% ± 10%, and 25-48H: 72% ± 20%; p =0.014). A significant reduction in median morphine milligram equivalents (MME) was seen (24H prior: 58 (8-195) mg vs. 0-24H: 4 (0-69) mg and p =0.01), but this was not sustained (25-48H: 24 (2-246) mg and p =0.29). Common AEs were tachycardia (63%), hypotension (54%), secretions/suctioning (29%), and emergence reactions (13%)., Conclusions: Ketamine CI improved time in goal pain score range and significantly reduced MME, but this was not sustained. Larger prospective studies are needed in the pediatric population., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2024 Christine M. Groth et al.)

Background: Half of patients admitted to medicine units report sleep disruption, which increases the risk of sleep deprivation. Non-pharmacological interventions are the first step to improving sleep. However, utilization of sleep aids continues to be prevalent. Limited data are available on sleep aid prescribing practices across transitions of care., Objectives: The aim of this study was to describe the current practices for assessing sleep and prescribing pharmacologic agents to promote sleep in the adult medicine population., Methods: This study was designed as a single-center, retrospective, observational cohort study of all patients discharged by the general medicine teams over a 3-month period (September 2019- November 2019). Prior to admission, inpatient and discharge prescriptions for sleep aids were recorded, and documentation of sleep assessments and non-pharmacological interventions were evaluated., Results: Of 754 patients included, 211 (28%) were prescribed a sleep aid while inpatient. During hospitalization, 124 (16%) patients had at least one documented sleep assessment, and only 22 (3%) were ordered the institutional non-pharmacological sleep promotion order set. The most prescribed sleep aid in inpatients was melatonin (50%), as well as prior to admission (35%) and at discharge (25%). Overall, the relative reduction in sleep aid prescriptions between admission and discharge was 67%., Conclusion: Inpatient sleep aid prescribing is common in medical patients. Despite this, sleep assessments and the standard of care of non-pharmacological interventions are rarely utilized. Future efforts should focus on implementation of strategies to make sleep assessments and non-pharmacological sleep promotion routine and consistent in the inpatient setting., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

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: Critical care pharmacists (CCPs) are essential members of the multidisciplinary critical care team. Professional activities of the CCP are outlined in a 2020 position paper on critical care pharmacy services. This study looks to characterize CCP perspectives for priorities in optimizing pharmacy practice models and professional activities., Methods: This was a cross-sectional survey conducted from July 24 to September 20, 2023. A 41-question survey instrument was developed to assess 7 domains: demographics, CCP resource utilization, patient care, quality improvement, research and scholarship, training and education, and professional development. This voluntary survey was sent to members of the American College of Clinical Pharmacy's Critical Care Practice and Research Network. The survey was open for a total of 6 weeks., Results: There was a response rate of 20.7% (332 of 1,605 invitees), with 66.6% of respondents (n = 221) completing at least 90% of the survey questions. Most respondents were clinical specialists (58.2%) and/or practiced at an academic medical center (58.5%). Direct patient care, quality improvement and medication safety, and teaching and precepting were identified as the CCP activities of highest importance to CCPs. The CCP-to-patient ratios considered ideal were 1:11-15 (selected by 49.8% of respondents) and 1:16-20 (33.9% of respondents). The ideal percentage of time dedicated to direct patient care activities, as identified by survey respondents, was 50% (interquartile range, 40-50)., Conclusion: These findings highlight the professional activities viewed as having the highest priority by CCPs. Future research is needed to define optimal CCP practice models for the delivery of patient care in real-world settings., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Half of patients admitted to medicine units report sleep disruption, which increases the risk of sleep deprivation. Non-pharmacological interventions are the first step to improving sleep. However, utilization of sleep aids continues to be prevalent. Limited data are available on sleep aid prescribing practices across transitions of care., Objectives: The aim of this study was to describe the current practices for assessing sleep and prescribing pharmacologic agents to promote sleep in the adult medicine population., Methods: This study was designed as a single-center, retrospective, observational cohort study of all patients discharged by the general medicine teams over a 3-month period (September 2019- November 2019). Prior to admission, inpatient and discharge prescriptions for sleep aids were recorded, and documentation of sleep assessments and non-pharmacological interventions were evaluated., Results: Of 754 patients included, 211 (28%) were prescribed a sleep aid while inpatient. During hospitalization, 124 (16%) patients had at least one documented sleep assessment, and only 22 (3%) were ordered the institutional non-pharmacological sleep promotion order set. The most prescribed sleep aid in inpatients was melatonin (50%), as well as prior to admission (35%) and at discharge (25%). Overall, the relative reduction in sleep aid prescriptions between admission and discharge was 67%., Conclusion: Inpatient sleep aid prescribing is common in medical patients. Despite this, sleep assessments and the standard of care of non-pharmacological interventions are rarely utilized. Future efforts should focus on implementation of strategies to make sleep assessments and non-pharmacological sleep promotion routine and consistent in the inpatient setting., Competing Interests: Disclosure The authors declare no relevant conflicts of interest or financial relationships., (Copyright © 2024 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: The Society of Critical Care Medicine Clinical Practice Guidelines for Management of Pain, Agitation, Delirium, Immobility, and Sleep recommend protocolized non-pharmacologic sleep improvement. Pharmacologic interventions are frequently initiated to promote sleep but the evidence supporting these strategies remains controversial. Purpose: To systematically search and synthesize evidence evaluating pharmacologic sleep promotion modalities in critically ill adults. Methods: A rapid systematic review protocol was used to search Medline, Cochrane Library, and Embase for reports published through October 2022. We included randomized controlled trials (RCTs) and before-and-after cohort studies evaluating pharmacologic modalities intended to improve sleep in adult intensive care unit (ICU) patients. Sleep-related endpoints were the primary outcome of interest. Study and patient characteristics and relevant safety and non-sleep outcome data were also collected. The Cochrane Collaboration Risk of Bias or Risk of Bias in Non-Randomized Studies of Interventions were used to assess the risk of bias for all included studies. Results: Sixteen studies (75% RCTs) enrolling 2573 patients were included; 1207 patients were allocated to the pharmacologic sleep intervention. Most studies utilized dexmedetomidine (7/16; total n = 505 patients) or a melatonin agonist (6/16; total n = 592 patients). Only half of the studies incorporated a sleep promotion protocol as standard of care. Most (11/16, 68.8%) studies demonstrated a significant improvement in ≥1 sleep endpoint (n = 5 dexmedetomidine, n = 3 melatonin agonists, n = 2 propofol/benzodiazepines). Risk of bias was generally low for RCTs and moderate-severe for cohort studies. Conclusions: Dexmedetomidine and melatonin agonists are the most studied pharmacologic sleep promotion modalities, but current evidence does not support their routine administration in the ICU to improve sleep. Future RCTs evaluating pharmacologic modalities for ICU sleep should consider patients' baseline and ICU risks for disrupted sleep, incorporate a non-pharmacologic sleep improvement protocol, and evaluate the effect of these medication interventions on circadian rhythm, physiologic sleep, patient-perceived sleep quality, and delirium., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.S.H., P.R.L., E.F.G., K.M.L., and D.V. have nothing to report. J.W.D. reports the following: Research funding—NIA, AHRQ, Sedana Medical; Consulting—Trevana Medical, Ceribell Inc., BioExcel Pharma.

Acute respiratory distress syndrome (ARDS) presents as an acute inflammatory lung injury characterized by refractory hypoxemia and non-cardiac pulmonary edema. An estimated 10% of patients in the intensive care unit and 25% of those who are mechanically ventilated are diagnosed with ARDS. Increased awareness is warranted as mortality rates remain high and delays in diagnosing ARDS are common. The COVID-19 pandemic highlights the importance of understanding ARDS management. Treatment of ARDS can be challenging due to the complexity of the disease state and conflicting existing evidence. Therefore, it is imperative that pharmacists understand both pharmacologic and non-pharmacologic treatment strategies to optimize patient care. This narrative review provides a critical evaluation of current literature describing management practices for ARDS. A review of treatment modalities and supportive care strategies will be presented., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The workload of healthcare professionals including physicians and nurses in the ICU has an established relationship to patient outcomes, including mortality, length of stay, and other quality indicators; however, the relationship of critical care pharmacist workload to outcomes has not been rigorously evaluated and determined. The objective of our study is to characterize the relationship of critical care pharmacist workload in the ICU as it relates to patient-centered outcomes of critically ill patients., Methods: Optimizing Pharmacist Team-Integration for ICU patient Management is a multicenter, observational cohort study with a target enrollment of 20,000 critically ill patients. Participating critical care pharmacists will enroll patients managed in the ICU. Data collection will consist of two observational phases: prospective and retrospective. During the prospective phase, critical care pharmacists will record daily workload data (e.g., census, number of rounding teams). During the retrospective phase, patient demographics, severity of illness, medication regimen complexity, and outcomes will be recorded. The primary outcome is mortality. Multiple methods will be used to explore the primary outcome including multilevel multiple logistic regression with stepwise variable selection to exclude nonsignificant covariates from the final model, supervised and unsupervised machine learning techniques, and Bayesian analysis., Results: Our protocol describes the processes and methods for an observational study in the ICU., Conclusions: This study seeks to determine the relationship between pharmacist workload, as measured by pharmacist-to-patient ratio and the pharmacist clinical burden index, and patient-centered outcomes, including mortality and length of stay., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Objectives: To provide a concise review of knowledge and practice pertaining to the diagnosis and initial management of unanticipated adult patient disorders of consciousness (DoC) by the general intensivist., Data Sources: Detailed search strategy using PubMed and OVID Medline for English language articles describing adult patient acute DoC diagnostic evaluation and initial management strategies including indications for transfer., Study Selection: Descriptive and interventional studies that address acute adult DoC, their evaluation and initial management, indications for transfer, as well as outcome prognostication., Data Extraction: Relevant descriptions or studies were reviewed, and the following aspects of each manuscript were identified, abstracted, and analyzed: setting, study population, aims, methods, results, and relevant implications for adult critical care practice., Data Synthesis: Acute adult DoC may be categorized by etiology including structural, functional, infectious, inflammatory, and pharmacologic, the understanding of which drives diagnostic investigation, monitoring, acute therapy, and subsequent specialist care decisions including team-based local care as well as intra- and inter-facility transfer., Conclusions: Acute adult DoC may be initially comprehensively addressed by the general intensivist using an etiology-driven and team-based approach. Certain clinical conditions, procedural expertise needs, or resource limitations inform transfer decision-making within a complex care facility or to one with greater complexity. Emerging collaborative science helps improve our current knowledge of acute DoC to better align therapies with underpinning etiologies., Competing Interests: Dr. Chang received funding from the American Board of Internal Medicine, American Board of Psychology and Neurology Neurocritical Care, and Society of Critical Care Medicine (SCCM) for work as Associate Editor of Critical Care Medicine (2021–2023) and a past-President of the Neurocritical Care Society; she disclosed that she is employed by Duke University; and she serves as a Council member and Treasurer for SCCM and is a member of the Board of Rehabilitation Hospital of the Pacific. Dr. Provencio’s institution received funding from SCCM Weil Research Grant; he received funding from Minnetronix; he disclosed that he is an SCCM Council Member and on the Scientific Advisory Board for the Neurocritical Care Society Curing Coma Campaign; and he is a member of the steering committee of the Curing Coma Campaign. Dr. Pascual received funding from multiple medicolegal firms for expert testimony; and he is the Secretary of the SCCM. Dr. Livesay received funding from Stroke Challenges/Lombardi Hill LLC; she disclosed that she is the President of Neurocritical Care Society. Dr. Kaplan received funding from SCCM as President (2020–2021). Dr. Olson is a co-chair of the Neurocritical Care Society’s Neurocritical Care Research Network Subcommittee. Dr. Heavner has disclosed that she does not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Maternal mortality continues to be an issue globally despite advances in technology and pharmacotherapy. Pregnancy can lead to complications that necessitate immediate action to prevent severe morbidity and mortality. Patients may need escalation to the ICU setting for close monitoring and administration of advanced therapies not available elsewhere. Obstetric emergencies are rare but high-stakes events that require clinicians to have prompt identification and management. The purpose of this review is to describe complications of pregnancy and provide a focused resource of pharmacotherapy considerations that clinicians may encounter. For each disease state, the epidemiology, pathophysiology, and management are summarized. Brief descriptions of non-pharmacological (e.g., cesarean or vaginal delivery of the baby) interventions are provided. Mainstays of pharmacotherapy highlighted include oxytocin for obstetric hemorrhage, methotrexate for ectopic pregnancy, magnesium and antihypertensive agents for preeclampsia and eclampsia, eculizumab for atypical hemolytic uremic syndrome, corticosteroids, and immunosuppressive agents for thrombotic thrombocytopenic purpura, diuretics, metoprolol, and anticoagulation for peripartum cardiomyopathy, and pulmonary vasodilators for amniotic fluid embolism., (© 2023 Pharmacotherapy Publications, Inc.)

Safe and thoughtful medication management of pregnant patients requiring intensive care unit (ICU) level of care is key to optimizing outcomes for both mother and fetus. Pregnancy induces physiologic alterations that closely mirror the changes expected in a critically ill patient. These changes can be predictable depending on the gestational age and trimester and will directly impact the pharmacokinetic profile of medications commonly used in the ICU; examples include decreased gastric emptying, increased blood and plasma volume, increased glomerular filtration, and increased cardiac output. When pregnant patients require ICU care, the resulting impact on drug absorption, distribution, metabolism, and elimination can be difficult to predict. In addition, there are many nuances of medication metabolism and interface with the placental barrier that should be considered when selecting pharmacotherapy for the pregnant patient. Critical care clinicians need to be aware of medication interactions with the placenta and weigh the risk versus benefit profile of medication use in this patient population. Obstetric critical care admissions have increased over the years, especially during the coronavirus waves. Therefore, understanding the interplay between pregnancy and critical illness to optimize pharmacotherapy selection is crucial to improving health outcomes of mother and fetus. This review highlights pharmacotherapy considerations in the pregnant ICU patient for the following topics: physiologic alterations, categorizing medication risk, supportive care, sepsis, cardiogenic shock, acute respiratory distress syndrome, and venous thromboembolism., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Persons living with human immunodeficiency virus (HIV) (PWH) on antiretroviral therapy (ART) are frequently admitted to the intensive care unit (ICU). Persons living with HIV on ART may be at higher risk for potential drug-drug interactions (pDDIs) due to polypharmacy in the ICU. We determined the prevalence of pDDI with ART in critically ill PWH. Objectives: The primary outcome was prevalence of pDDI between ART and ICU medications. Secondary outcomes included pDDI per ICU admission, pDDI severity, ICU, and hospital length of stay (LOS). Methods: A single-center, retrospective cohort evaluating PWH ≥ 18 years old admitted to the ICU for > 24 hours who received ART during ICU admission, between January 2013 and 2015 at a tertiary care hospital in the United States. Each ICU admission was counted as a separate encounter. Medication databases and chart review were used to identify pDDI. Results: We included 77 PWH encounters; mean age was 55 ± 9 years and 65% were male. We identified 208 pDDIs among 53/77 (68.8%), with a mean 4 ± 2 pDDI per ICU admission. Antipsychotics (20%), analgesics (20%), and anti-lipemics (11%) were the most common ICU medications with ART-related pDDI. Of the pDDI, 64% were major, 24% moderate, and 12% contraindicated. Median ICU and hospital LOS were 4 days (IQR: 3-5) and 11 days (IQR: 7-31), respectively. Conclusion: Most PWH had at least one pDDI during ICU admission. Collaborations among pharmacists, intensivists, and infectious disease/HIV specialists to develop effective, actionable strategies, such as electronic health record alerts, could reduce pDDIs for PWH on ART in the ICU.

Background: Sleep and circadian disruption (SCD) is common and severe in the ICU. On the basis of rigorous evidence in non-ICU populations and emerging evidence in ICU populations, SCD is likely to have a profound negative impact on patient outcomes. Thus, it is urgent that we establish research priorities to advance understanding of ICU SCD. Methods: We convened a multidisciplinary group with relevant expertise to participate in an American Thoracic Society Workshop. Workshop objectives included identifying ICU SCD subtopics of interest, key knowledge gaps, and research priorities. Members attended remote sessions from March to November 2021. Recorded presentations were prepared and viewed by members before Workshop sessions. Workshop discussion focused on key gaps and related research priorities. The priorities listed herein were selected on the basis of rank as established by a series of anonymous surveys. Results: We identified the following research priorities: establish an ICU SCD definition, further develop rigorous and feasible ICU SCD measures, test associations between ICU SCD domains and outcomes, promote the inclusion of mechanistic and patient-centered outcomes within large clinical studies, leverage implementation science strategies to maximize intervention fidelity and sustainability, and collaborate among investigators to harmonize methods and promote multisite investigation. Conclusions: ICU SCD is a complex and compelling potential target for improving ICU outcomes. Given the influence on all other research priorities, further development of rigorous, feasible ICU SCD measurement is a key next step in advancing the field.

Purpose: Targeted temperature management (TTM), including normothermia and therapeutic hypothermia, is used primarily for comatose patients with return of spontaneous circulation after cardiac arrest or following neurological injury. Despite the potential benefits of TTM, risks associated with physiological alterations, including electrolyte shifts, may require intervention., Summary: This review describes the normal physiological balance of electrolytes and temperature-related alterations as well as the impact of derangements on patient outcomes, providing general recommendations for repletion and monitoring of key electrolytes, including potassium, phosphate, and magnesium., Conclusion: Frequent monitoring and consideration of patient variables such as renal function and other risk factors for adverse effects are important areas of awareness for clinicians caring for patients undergoing TTM., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population., Design: This was a multicenter, observational cohort study., Setting: Twenty-eight ICUs in the United States., Patients: Adult ICU patients., Interventions: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively., Measurements and Main Results: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (β coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (β coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (β coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (β coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (β coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (β coefficient, -0.05; 95% CI, -0.09 to -0.01)., Conclusions: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes., Competing Interests: Dr. Newsome has received research funding through the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers UL1TR002378 and KL2TR002381. Dr. Rech’s institution received funding from Spero Pharmaceuticals; she received funding from Harm Reduction Therapeutics. Dr. DePriest received funding from Baxter. Dr. Flannery’s institution received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the American Society of Nephrology, and La Jolla Pharmaceutical Company. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: The bispectral index (BIS) is an attractive approach for monitoring level of consciousness in critically ill patients, particularly during paralysis, when commonly used sedation scales cannot be used., Objectives: As a first step toward establishing the utility of BIS during paralysis, this review examines the strength of correlation between BIS and clinical sedation scales in a broad population of non-paralyzed, critically ill adults., Methods: We included studies evaluating the strength of correlation between concurrent assessments of BIS and Richmond Agitation Sedation Scale (RASS), Ramsay Sedation Scale (RSS), or Sedation Agitation Scale (SAS) in critically ill adult patients. Studies involving assessment of depth sedation periperative or procedural time periods, and those reporting BIS and sedation scale assessments conducted >5 min apart or while neuromuscular blocking agents (NMBA) were administered, were excluded. Data were abstracted on sedation scale, correlation coefficients, setting, patient characteristics, and BIS assessment characteristics that could impact the quality of the studies., Results: Twenty-four studies which enrolled 1235 patients met inclusion criteria. The correlation between BIS and RASS, RSS, and SAS overall was 0.68 (95% confidence interval, 0.61-0.74, Ƭ 2  = 0.06 I 2  = 71.26%). Subgroup analysis by sedation scale indicated that the correlation between BIS and RASS, RSS, and SAS were 0.66 (95% confidence interval 0.58-0.73, Ƭ 2  = 0.01 I 2  = 30.20%), 0.76 (95% confidence interval 0.69-0.82, Ƭ 2  = 0.04 I 2  = 67.15%), and 0.53 (95% confidence interval 0.42-0.63, Ƭ 2  = 0.01 I 2  = 26.59%), respectively. Factors associated with significant heterogeneity included comparator clinical sedation scale, neurologic injury, and the type of intensive care unit (ICU) population., Conclusions: BIS demonstrated moderate to strong correlation with clinical sedation scales in adult ICU patients, providing preliminary evidence for the validity of BIS as a measure of sedation intensity when clinical scales cannot be used. Future studies should determine whether BIS monitoring is safe and effective in improving outcomes in patients receiving NMBA treatment., (© 2022 Pharmacotherapy Publications, Inc.)

Objective: To review evidence for intensive care unit (ICU) sleep improvement bundle use, identify preferred sleep bundle components and implementation strategies, and highlight the role for pharmacists in developing and evaluating bundle efforts., Data Sources: Multiple databases were searched from January 1, 1990, to September 1, 2021, using the MeSH terms sleep , intensive care or critical care , protocol or bundle to identify comparative studies evaluating ICU sleep bundle implementation., Study Selection and Data Extraction: Study screening, data extraction, and risk-of-bias evaluation were conducted in tandem. The ICU quality improvement literature and Institute for Healthcare Improvement bundle improvement guidance were also reviewed to identify recommended strategies for successful sleep bundle use., Data Synthesis: Nine studies (3 randomized, 1 quasi-experimental, 5 before-and-after) were identified. Bundle elements varied and were primarily focused on nonpharmacological interventions designed to be performed during either the day or night; only 2 studies included a medication-based strategy. Five studies were associated with reduced delirium; 2 studies were associated with improved total sleep time and 2 with improved patient-perceived sleep. Pharmacists were involved directly in 4 studies., Relevance to Patient Care and Clinical Practice: Sleep improvement bundles are recommended for use in all critically ill adults; specific bundle elements and ICU team member roles should be individualized at the institution/ICU level. Pharmacists can help lead bundle development efforts and routinely deliver key elements., Conclusions: Pharmacists can play an important role in the development and implementation of ICU sleep bundles. Further research regarding the relative benefit of individual bundle elements on relevant patient outcomes is needed.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established., Objectives: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium., Design Setting and Participants: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients receiving CI ketamine between January 2014 and December 2017., Main Outcomes and Measures: Chart review evaluating institutional and patient demographics, ketamine indication, dose, administration, and adverse effects. Pain/sedation scores, cumulative doses of sedatives and analgesics, and delirium screenings in the 24 hours prior to ketamine were compared with those at 0-24 hours and 25-48 hours after., Results: A total of 390 patients were included (median age, 54.5 yr; interquartile range, 39-65 yr; 61% males). Primary ICU types were medical (35.3%), surgical (23.3%), and trauma (17.7%). Most common indications were analgesia/sedation ( n = 357, 91.5%). Starting doses were 0.2 mg/kg/hr (0.1-0.5 mg/kg/hr) and continued for 1.6 days (0.6-2.9 d). Hemodynamics in the first 4 hours after ketamine were variable (hypertension 24.0%, hypotension 23.5%, tachycardia 19.5%, bradycardia 2.3%); other adverse effects were minimal. Compared with 24 hours prior, there was a significant increase in proportion of time spent within goal pain score after ketamine initiation (24 hr prior: 68.9% [66.7-72.6%], 0-24 hr: 78.6% [74.3-82.5%], 25-48 hr: 80.3% [74.6-84.3%]; p < 0.001) and time spent within goal sedation score (24 hr prior: 57.1% [52.5-60.0%], 0-24 hr: 64.1% [60.7-67.2%], 25-48 hr: 68.9% [65.5-79.5%]; p < 0.001). There was also a significant reduction in IV morphine (mg) equivalents (24 hr prior: 120 [25-400], 0-24 hr: 118 [10-363], 25-48 hr: 80 [5-328]; p < 0.005), midazolam (mg) equivalents (24 hr prior: 11 [4-67], 0-24 hr: 6 [0-68], 25-48 hr: 3 [0-57]; p < 0.001), propofol (mg) (24 hr prior: 942 [223-4,018], 0-24 hr: 160 [0-2,776], 25-48 hr: 0 [0-1,859]; p < 0.001), and dexmedetomidine (µg) (24 hr prior: 1,025 [276-1,925], 0-24 hr: 285 [0-1,283], 25-48 hr: 0 [0-826]; p < 0.001). There was no difference in proportion of time spent positive for delirium (24 hr prior: 43.0% [17.0-47.0%], 0-24 hr: 39.5% [27.0-43.8%], 25-48 hr: 0% [0-43.7%]; p = 0.233). Limitations to these data include lack of a comparator group, potential for confounders and selection bias, and varying pain and sedation practices that may have changed since completion of the study., Conclusions and Relevance: There is variability in the use of CI ketamine. Hemodynamic instability was the most common adverse effect. In the 48 hours after ketamine initiation compared with the 24 hours prior, proportion of time spent in goal pain/sedation score range increased and exposure to other analgesics/sedatives decreased., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS., (© 2021 Pharmacotherapy Publications, Inc.)

Men and women have fundamental anatomic and physiologic differences. A myriad of studies has shown that these distinctions can result in significant differences in the way certain drugs affect each sex and vice versa. This article provides an overview of sex differences in drug pharmacokinetics, with a focus on pharmacology in respiratory disease and in critical illness, as well as differences in pharmacokinetics throughout the female life cycle, with regard to pregnancy and menopause., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Opioids are one of the high-risk medication classes that are administered to critically ill patients during their intensive care unit (ICU) stay. However, little attention has been given to inpatient opioid prescribing practices, especially in critically ill patients. The purpose of our study was to characterize opioid prescribing practices across 2 transitions of care during an inpatient hospital stay: medical ICU (MICU)/intermediate care unit (IMC) to floor and floor to hospital discharge and identify potential patient-specific factors that impact opioid continuation., Methods: This is a retrospective cohort study evaluating opioid-naive adult patients with new opioid therapy initiated in MICU/IMC at a tertiary care academic medical center from December 1, 2016, to November 30, 2017. Opioid continuation rate was assessed twice: transition 1 (MICU/IMC to floor) and transition 2 (floor to hospital discharge)., Results: In total, 112 opioid-naive patients with initial opioid administration in the MICU/IMC were included. Opioid therapy was continued in 56.1% (37/66) at transition 1 and 56.8% of patients (21/37) at transition 2. Patients with opioids continued at transition 1 had a longer hospital length of stay compared to those not continued on opioids, 22 (interquartile range [IQR] 11-36) vs 8 (IQR 6-14; P = .0004). Among the patients continued on opioids at hospital discharge, intubation during hospital stay and cumulative opioid dosage were greater than those not continued on opioids (17 [80.9%] vs 7 [43.8%], P = .019; and 3482 mcg [IQR 1690-9530] vs 732.5 mcg [IQR 187.5-1360.9], P = .0018, respectively)., Conclusions: Opioid-naive patients receiving opioid therapy in the MICU/IMC had a continuation rate of >56% during transitions of care, including hospital discharge. Factors that contributed to the continuation of opioids at transitions of care included longer hospital length of stay, intubation, and cumulative hospital opioid dosage. These findings may help to provide health systems with guidance on targeted opioid stewardship programs.

Vasodilatory shock is a serious medical condition that increases the morbidity and mortality of perioperative and critically ill patients. Norepinephrine is an established first-line therapy for this condition, but at high doses, it may lead to diminishing returns. Oftentimes, secondary noncatecholamine agents are required in those whose hypotension persists. Angiotensin II and vasopressin are both noncatecholamine agents available for the treatment of hypotension in vasodilatory shock. They have distinct modes of action and unique pharmacologic properties when compared to norepinephrine. Angiotensin II and vasopressin have shown promise in certain subsets of the population, such as those with acute kidney injury, high Acute Physiology and Chronic Health Evaluation II scores, or those receiving cardiac surgery. Any benefit from these drugs must be weighed against the risks, as overall mortality has not been shown to decrease mortality in the general population. The aims of this narrative review are to provide insight into the historical use of noncatecholamine vasopressors and to compare and contrast their unique modes of action, physiologic rationale for administration, efficacy, and safety profiles.

Background: Published bundles to reduce Clostridioides difficile Infection (CDI) frequently lack information on compliance with individual elements. We piloted a computerized clinical decision support-based intervention bundle and conducted detailed evaluation of several intervention-related measures., Methods: A quasi-experimental study of a bundled intervention was performed at 2 acute care community hospitals in Maryland. The bundle had five components: (1) timely placement in enteric precautions, (2) appropriate CDI testing, (3) reducing proton-pump inhibitor (PPI) use, (4) reducing high-CDI risk antibiotic use, and (5) optimizing use of a sporicidal agent for environmental cleaning. Chi-square and Kruskal-Wallis tests were used to compare measure differences. An interrupted time series analysis was used to evaluate impact on hospital-onset (HO)-CDI., Results: Placement of CDI suspects in enteric precautions before test results did not change. Only hospital B decreased the frequency of CDI testing and reduced inappropriate testing related to laxative use. Both hospitals reduced the use of PPI and high-risk antibiotics. A 75% decrease in HO-CDI immediately postimplementation was observed for hospital B only., Conclusion: A CDI reduction bundle showed variable impact on relevant measures. Hospital-specific differential uptake of bundle elements may explain differences in effectiveness, and emphasizes the importance of measuring processes and intermediate outcomes., (Copyright © 2020 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

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., (© 2020 Pharmacotherapy Publications, Inc.)

Purpose: Although guidelines recommend dexmedetomidine (DEX) or propofol (PRO) as preferred sedatives in critically ill adults, comparisons in neurocritical care (NCC) are limited. We aimed to evaluate the clinical utility and safety of DEX compared with PRO in NCC setting., Materials and Methods: This retrospective, multicenter, observational cohort study conducted at three tertiary academic hospitals with Level 1 Trauma Center and Comprehensive Stroke Center designations, compared the clinical indication and safety of DEX vs PRO in patients in NCC setting., Results: 179 patients were included (94 DEX and 85 PRO), median age of 58, 49% were male (DEX) and 58% were male (PRO). PRO was more commonly used to manage agitation. DEX was more commonly used for facilitating extubation, alcohol withdrawal, and sedation during frequent neurologic assessments. Mean Glasgow Coma Scale scores were higher in DEX group (11 vs. 9; p = .04). The duration of either infusions, mechanical ventilation, and lengths of stay were similar. No difference was observed in hypotension or bradycardia rates. Death was significantly higher with PRO (DEX 10% vs. PRO 22%; p = .02)., Conclusions: DEX and PRO were used for distinct indications in our cohort. Adverse effect profiles and clinical outcome, in the cohorts are largely similar., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Maximal dosing of early antimicrobials with high loading and maintenance doses may optimize pharmacokinetic parameters to achieve and maintain therapeutic concentrations at the site of infection in septic shock. Little is known about the current practice of early antimicrobial dosing in septic shock. Objective: To characterize early antimicrobial dosing in patients in the resuscitation phase of septic shock. Methods: This retrospective cohort study included patients admitted to the medical intensive care unit (ICU) with septic shock. The primary outcome was the percentage of early antibiotic orders that were maximal or conservative during the resuscitation (0 to 48 hours) phase based on predefined dosing criteria. The secondary outcomes were the correlations of different dosing strategies on hospital length of stay (LOS), ICU LOS, and hospital mortality. Results: This study evaluated 161 patients and 692 antibiotic orders; 504 (72.8%) of the orders during the resuscitation phase were conservative. There were no differences in mortality (odds ratio = 0.66; 95% confidence interval = 0.35-1.25; P = .20), hospital LOS (median = 20 [interquartile range (IQR) = 10-34] vs 19 [IQR = 11-32] days; P = .93), or ICU LOS (median = 8 [IQR = 5-16] vs 9 [IQR = 5-15] days; P = .63) between maximal and conservative dosing groups, respectively, in the resuscitation phase. Limitations of this study included the use of institution-specific antimicrobial dosing guidelines and its retrospective nature. Conclusions: Early antibiotic dosing is conservative for a majority of patients in septic shock. Future studies are needed to evaluate the impact of dosing strategy on patient-centered outcomes in septic shock., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic., (© 2020 Pharmacotherapy Publications, Inc.)

Objective: We describe a multicenter descriptive case series of six patients admitted with synthetic cannabinoid (SC) intoxication displaying similar symptoms and sequelae, all resulting in multiple organ failure., Methods: Patients were included in this report if they presented with known SC use and experienced multiple organ failure between March 1, 2016, and July 19, 2016, to the intensive care units of three hospitals in Maryland. Patients were followed to either discharge or death, and complications related to SC were documented., Results: All six patients presented with altered mental status and severe rhabdomyolysis, with a peak creatine phosphokinase ranging from 4000 to >320,000 units/L. The majority of patients (five of six) presented with acute kidney injury, with most (four of six) requiring continuous renal replacement therapy. Most patients experienced fever (five of six) and myocardial injury, as evidenced by a troponin elevation (three of six). Seizures occurred in half of patients (three of six patients). Two patients required emergent fasciotomies of the bilateral lower extremities for acute compartment syndrome. Two patients developed fulminant hepatic failure that necessitated liver transplant evaluation, one requiring Molecular Adsorbent Recirculating System (MARS) therapy as a bridge to successful transplant, while the patient without it did not survive. Delirium, severe rhabdomyolysis, acute kidney injury, and fever are common in patients with synthetic cannabinoid intoxication., Conclusions: Given the growing abuse of these substances, clinicians should consider their use in the differential of such patient presentations. To our knowledge, only a few published case reports discuss multiple organ failure associated with SC toxicity, and only two have described an associated acute liver failure. Our report describes the first case of SC-associated acute liver failure requiring organ transplantation. Clinicians should be aware of life-threatening complications and consider SC ingestion in the differential diagnosis of patients presenting with multiple organ failure., (© 2019 Pharmacotherapy Publications, Inc.)

Background: Many alcohol withdrawal scoring tools are used in hospitalized patients to assess the severity of alcohol withdrawal and guide treatment. The revised Clinical Institute Withdrawal Assessment (CIWA-Ar) and the modified Minnesota Detoxification Scale (mMINDS) are commonly used but have never been correlated., Objective: To determine the strength of correlation between the CIWA-Ar and mMINDS scoring tools in patients with alcohol withdrawal syndrome., Methods: A single-center, prospective correlation study conducted at a large academic medical center. Patients treated for alcohol withdrawal syndrome according to the Yale Alcohol Withdrawal Protocol were identified daily, and both the CIWA-Ar and mMINDS were administered at each time point required by the protocol. Clinical data were obtained from the electronic medical records., Results: A total of 185 CIWA-Ar and mMINDS scores were collected in 30 patients. The Pearson correlation coefficient across all scores was 0.82, indicating a strong correlation. The Pearson correlation coefficient was 0.87 for CIWA-Ar scores of 10 or less and 0.52 for CIWA-Ar scores above 10. Strong correlations were also shown for tremor (0.98), agitation (0.84), and orientation (0.87)., Conclusions: The correlation between the CIWA-Ar and mMINDS tools is strong and appears to be most robust in patients with CIWA-Ar scores of 10 or less., (©2018 American Association of Critical-Care Nurses.)

Study Objective: Alcohol use disorders are prevalent and put patients at risk for developing alcohol withdrawal syndrome (AWS). Treatment of AWS with a symptom-triggered protocol standardizes management and may avoid AWS-related complications. The objective of this study was to evaluate whether implementation of a specific intensive care unit (ICU) symptom-triggered protocol for the management of AWS was associated with improved clinical outcomes and, in particular, would reduce the risk of patients with AWS requiring mechanical ventilation., Design: Retrospective pre- and postprotocol implementation study., Setting: A 36-bed closed medical ICU (MICU) at a large tertiary care teaching hospital in an urban setting., Patients: A total of 233 adults admitted to the MICU with any diagnosis of alcohol use disorders based on International Classification of Diseases, Ninth Revision codes and who received at least one dose of any benzodiazepine; of these patients, 139 were in the preprotocol era (August 2009-January 2010 and August 2010-January 2011), and 94 were in the postprotocol era (August 2012-January 2013) after implementation of the Yale Alcohol Withdrawal Protocol (YAWP) in April 2012., Measurements and Main Results: The YAWP pairs a modified Minnesota Detoxification Scale with an order set that includes benzodiazepine dosing regimens and suggests adjuvant therapies. AWS was the primary reason for ICU admission (107/233 patients [45.9%]) and did not significantly vary between study eras (p=0.2). Of the 233 patients included, 81.1% were male and 67.0% were white, which did not significantly differ by study era. Severity of illness at MICU admission did not significantly differ between patients in the preprotocol and postprotocol eras (Acute Physiology and Chronic Health Evaluation [APACHE] II median scores of 12 [interquartile range (IQR) 9-17] and 12.5 [IQR 7-16], respectively, p=0.4). Median lorazepam-equivalent dose per MICU day, duration of benzodiazepine infusion, and use of adjuvant therapy were not significantly different between eras. MICU intubation was less common in the postprotocol era (36/139 patients [25.9%] preprotocol vs 8/94 patients [8.5%] postprotocol, p=0.0009). ICU-related pneumonia was also decreased in the postprotocol era (30/139 patients [21.6%] preprotocol vs 10/94 patients [10.6%] postprotocol, p=0.03). After adjusting for demographics, adjuvant therapies, and APACHE II scores, protocol implementation was associated with a decreased odds of MICU intubation (odds ratio 0.13, 95% confidence interval 0.04-0.39)., Conclusion: Implementation of YAWP was associated with a decreased risk of MICU intubation in patients at risk for AWS., (© 2018 Pharmacotherapy Publications, Inc.)

Objectives: To determine if adding a clinical pharmacist to the cardiac arrest team in a documenter role improves completeness of documentation and quality of advanced cardiovascular life support (ACLS)., Setting: A 1541-bed, tertiary care, academic medical center with an integrated clinical pharmacy practice model., Practice Description: In 2012, we identified documentation of resuscitation activities during cardiac arrest events and compliance with published ACLS guidelines as opportunities for systematic quality improvement at our tertiary care academic medical center. Although clinical pharmacists provided pharmacotherapy support through active participation on multidisciplinary patient care rounds, pharmacists were not routinely accountable for care provided during cardiac arrest events., Practice Innovation: We integrated pharmacists on the cardiac arrest team in the unique role of documenter and pharmacotherapy consultant. The pharmacist documenter was responsible for recording all activities (e.g., medication administered, endotracheal intubation, vital signs), providing real-time quality assurance during the event, and assisting with any clinical or operational needs of the team. Participating pharmacists received didactic lectures, practical assessments, and a written examination to ensure baseline competency in ACLS and teamwork principles., Evaluation: Using a before-and-after study design, we conducted a retrospective chart review to evaluate our pilot program. All cardiac arrest events requiring activation of the cardiac arrest team from January 2012 through December 2013 were included (n = 80)., Results: Pharmacists attended all cardiac arrest team events in the postintervention period during the scheduled coverage hours. The percentage of forms with all documentation components complete increased from 0% at baseline to 28% postintervention (P = 0.002). ACLS compliance also increased from 8% preintervention to 31% postintervention (P = 0.024)., Conclusion: Implementation of a dedicated pharmacist for documentation and pharmacotherapy consultation during cardiac arrest events is associated with improved documentation completeness and ACLS compliance. This was achieved without funding or additional pharmacist resources., (Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: We provide an overview of antimicrobials that are considered last resort for the treatment of resistant gram-negative infections in adult critically ill patients. The role in therapy, pharmacodynamic (PD) goals, and pharmacokinetic (PK) changes in critical illness for aminoglycosides, polymyxins, tigecycline, fosfomycin, and fluoroquinolones are summarized., Recent Findings: Altered PK in septic patients in the intensive care unit (ICU) is observed with many of our agents of last resort. Based on the available literature, dosage adjustments may be required to optimize PK parameters and meet PD targets for most effective bacterial killing. Data is limited, studies are conducted in heterogeneous patient populations, and conclusions are frequently conflicting. Strategic dosing regimens such as high-dose extended interval dosing of aminoglycosides or loading doses with colistin and polymyxin B are examples of ways to optimize antibiotic PK in critically ill patients. Benefits of these strategies must be balanced with risks of increased toxicity. Patients with resistant gram-negative infections may present with septic shock in the ICU. Sepsis can significantly alter the PK of antibiotics and require dosage adjustments to attain optimal drug levels. An understanding of PK and PD properties of these agents of last resort will help to maximize therapeutic efficacy while minimizing toxic effects.

Purpose of Review: Beta-lactam antibiotics are commonly prescribed in critically ill patients for a variety of infectious conditions. Our understanding of how critical illness alters beta-lactam pharmacokinetics/pharmacodynamics (PK/PD) is rapidly evolving., Recent Findings: There is a growing body of literature in adult patients demonstrating that physiological alterations occurring in critically ill patients may limit our ability to optimally dose beta-lactam antibiotics to reach these PK/PD targets. These alterations include changes in volume of distribution and renal clearance with multiple, often overlapping causative pathways, including hypoalbuminemia, renal replacement therapy, and extracorporeal membrane oxygenation. Strategies to overcome these PK alterations include extended infusions and therapeutic drug monitoring. Combined data has demonstrated a possible survival benefit associated with extending beta-lactam infusions in critically ill adult patients. This review highlights research on physiological derangements affecting beta-lactam concentrations and strategies to optimize beta-lactam PK/PD in critically ill adults.

Pregnant women are at high risk for venous thromboembolism, including pulmonary embolism (PE), given expected changes in coagulation, fibrinolysis, and venous blood flow. In fact, PE is the leading cause of maternal death in the United States. Nonpregnant patients who develop PE with hypotension or show signs of deterioration after anticoagulation receive thrombolytics as a standard of care. Pregnant women, however, have been excluded from clinical trials with thrombolytics, and all data available in this population are published as case reports or case series. We reviewed all reports of thrombolytics, systemic or catheter directed, used in pregnant patients with massive PE. This article summarizes the risks for thromboembolism in pregnancy, compares and contrasts thrombolytic agents in this setting, and provides a recommendation for management of massive PE in this special population. Overall, reports suggest that the use of these agents is associated with beneficial outcomes and a relatively low risk of complications. The quality of this evidence is low, and clinical judgment is required to assess individual patients for risks versus benefits of thrombolysis., (© 2017 Pharmacotherapy Publications, Inc.)

Purpose: The implementation and outcomes of a pharmacist career ladder program (PCLP) at a tertiary care, academic medical center are described., Summary: A PCLP was developed at Yale-New Haven Hospital to guide career development, motivate staff to perform beyond their daily tasks and responsibilities, and recognize and retain high performers through professional advancement. The PCLP advancement criteria include specific requirements for excellence in five categories: level of training and experience, pharmacy practice, drug information, education and scholarship, and leadership. The PCLP is designed with four distinct tiers: clinical pharmacist, clinical pharmacist II, clinical pharmacy specialist, and clinical pharmacy specialist II. The specific criteria are increasingly challenging to achieve when moving up the ladder. Pharmacists may apply voluntarily each year for advancement. A PCLP review committee consisting of pharmacist peers and managers meets annually to discuss and vote on career advancement decisions. Since PCLP implementation, we have observed an increasing success rate for advancement (50% in 2013, 85% in 2014, and 100% in 2015) and a considerable increase in pharmacist participation in clinical and process improvement projects, as well as intervention and medication-use variance documentation., Conclusion: The implementation of a PCLP at a tertiary care, academic medical center provided an opportunity for frontline pharmacists to advance professionally and increased their participation and leadership in clinical and process improvement projects and drug-use policy and medication safety initiatives; the program also increased the number of pharmacists with specialty board certification and peer-reviewed publications., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: The safety of converting kidney transplant recipients on brand-name tacrolimus to generic tacrolimus during hospitalization was evaluated., Methods: A single-center observational study compared tacrolimus dosages and trough tacrolimus levels in kidney transplant recipients who had a kidney transplant more than 90 days before hospital admission. Patients in the "brand" group were maintained on brand-name tacrolimus throughout the entire study period. Patients in the generic group were maintained on brand-name tacrolimus before hospital admission, converted to the generic formulation during hospitalization, and returned to the brand-name product at discharge. Tacrolimus dosages were converted on a milligram-per-milligram basis and adjusted, if needed. Outcomes evaluated included the percentage of patients requiring a dosage change, absolute change in average tacrolimus trough level, and frequency of biopsy-proven acute rejection within six months of discharge., Results: A total of 100 patients were evaluated for inclusion in the brand group, with 42 meeting study criteria; 98 patients were evaluated in the generic group, with 36 qualifying for the study. There were no significant differences between the brand and generic groups with respect to dosage adjustments required or trough tacrolimus levels at any point in the transition of care. Mean trough concentrations were similar between groups during all periods of care. The only occurrence of new-onset acute rejection within six months after admission occurred in the brand group., Conclusion: Substitution of a generic formulation of tacrolimus for the innovator product during hospitalization of kidney transplant recipients was safely implemented. Tacrolimus dosage adjustments were common throughout the transitions of care, regardless of the formulation used.