Search

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: The purpose of this article is to discuss how the structural and presumably functional integrity of albumin, as described by the concept of effective albumin concentration (eAlb), has potentially important clinical implications beyond the total albumin concentration (tAlb) routinely reported by clinical laboratories., Summary: Albumin has several functions beyond its oncotic effects, including molecule binding, substance transport, detoxification actions, and serving as an antioxidant. However, there are conformational changes that occur during or following the manufacture of albumin and during its administration to patients with various disease states, such as decompensated liver disease, that often impair these functions. Such impairments are not reflected in tAlb values reported by clinical laboratories and might explain the disconnect often seen between albumin's proposed beneficial mechanistic functions and its less-than-predicted clinical effectiveness as noted in published studies. The concept of eAlb has been introduced to describe albumin with structural and functional integrity. Limited studies have found associations between eAlb values and patient prognostic indicators, but the techniques used to decide these effective concentrations to date are complicated and require specialized equipment and experienced researchers for proper interpretation., Conclusion: Estimation of eAlb may provide valuable information on the functional ability of albumin beyond the tAlb reported by clinical laboratories, but more research is needed to decide how this information is best used in the clinical setting., (© 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.)

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 demonstrate the challenges with current diagnosis and treatment strategies for precipitated opioid withdrawal secondary to naloxone the emergency department (ED) setting and describe the role of the emergency medicine (EM) pharmacist in its management., Summary: There are no standardized criteria to define precipitated opioid withdrawal syndrome, so the diagnosis is typically based on sentinel signs and symptoms and time course. Complicating factors include a positive urine toxicology screen for nonopioid substances, comorbidities and associated medications prior to admission, medications given in the ED, and a fluctuating patient course during the ED stay that likely involves all these issues. Although buprenorphine is frequently recommended as the primary treatment for precipitated withdrawal, its use can be complicated if patients are on methadone maintenance or other long-acting opioids. The EM pharmacist plays a key role in managing patients with precipitated withdrawal., Conclusion: Practice changes related to the diagnosis and treatment of opioid use disorder (OUD) with precipitated withdrawal in the ED are needed. EM pharmacists as part of the interprofessional care team have an important role in the management of patients with OUD, including those patients undergoing possible precipitated withdrawal., (© 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.)

Purpose: The purpose of this review is to discuss important considerations when prescribing buprenorphine for opioid use disorder (OUD) in the intensive care unit (ICU) setting, recognizing the challenges of providing detailed recommendations in the setting of limited available evidence., Summary: Buprenorphine is a partial mu-opioid receptor agonist that is likely to be increasingly prescribed for OUD in the ICU setting due to the relaxation of prescribing regulations. The pharmacology and pharmacokinetics of buprenorphine are complicated by the availability of several formulations that can be given by different administration routes. There is no single optimal dosing strategy for buprenorphine induction, with regimens ranging from very low-dose to high dose regimens. Faster induction with higher doses of buprenorphine has been studied and is frequently utilized in the emergency department. In patients admitted to the ICU who were receiving opioids either medically or illicitly, analgesia will not occur until their baseline opioid requirements are covered when their preadmission opioid is either reversed or interrupted. For patients in the ICU who are not on buprenorphine at the time of admission but have possible OUD, there are no validated tools to diagnose OUD or the severity of opioid withdrawal in critically ill patients unable to provide the subjective components of instruments validated in outpatient settings. When prescribing buprenorphine in the ICU, important issues to consider include dosing, monitoring, pain management, use of adjunctive medications, and considerations to transition to outpatient therapy. Ideally, addiction and pain management specialists would be available when buprenorphine is prescribed for critically ill patients., Conclusion: There are unique challenges when prescribing buprenorphine for OUD in critically ill patients, regardless of whether they were receiving buprenorphine when admitted to the ICU setting for OUD or are under consideration for buprenorphine initiation. There is a critical need for more research in this area., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The purpose of this review is to discuss infectious disease-related adverse effects associated with long-term proton pump inhibitor (PPI) therapy in patients with cirrhosis and to provide recommendations for appropriate use and choice of PPI when such therapy is indicated., Summary: Long-term PPI therapy in patients with cirrhosis increases the risk of infections, with infections in turn increasing the risk of mortality in this patient population. Expert recommendations include restricting long-term PPI use in cirrhosis to patients with appropriate gastrointestinal indications, using a PPI for the shortest possible duration and at the lowest possible dose, and avoiding PPIs with unfavorable pharmacogenetic properties., Conclusion: Long-term PPI use in patients with cirrhosis has been associated with increased infections. The risk of adverse effects in observational studies, including decompensation, severe infection (especially spontaneous bacterial peritonitis), and increased mortality, appears to increase as the dose and duration of PPI increase., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Creatinine-based estimates of glomerular filtration rate (GFR) have been the standard for classifying kidney function and guiding drug dosing for over 5 decades. There have been many efforts to compare and improve different methods to estimate GFR. The National Kidney Foundation recently updated the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations without race for creatinine (CKD-EPIcr&#95;R) and creatinine and cystatin C (CKD-EPIcr-cys&#95;R), and the 2012 CKD-EPI equation based on cystatin C (CKD-EPIcys) remains. The focus of this review is to highlight the importance of muscle atrophy as a cause for overestimation of GFR when using creatinine-based methods., Summary: Patients with liver disease, protein malnutrition, inactivity, denervation, or extensive weight loss may exhibit markedly lower creatinine excretion and serum creatinine concentration, leading to overestimation of GFR or creatinine clearance when using the Cockcroft-Gault equation or CKD-EPIcr (deindexed). In some cases, estimated GFR appears to exceed the physiological normal range (eg, >150 mL/min/1.73 m2). Use of cystatin C is recommended when low muscle mass is suspected. One would expect discordance between the estimates such that CKD-EPIcys < CKD-EPIcr-cys < CKD-EPIcr ≈ Cockcroft-Gault creatinine clearance. Clinical evaluation can then occur to determine which estimate is likely accurate and should be used for drug dosing., Conclusion: In the setting of significant muscle atrophy and stable serum creatinine levels, use of cystatin C is recommended, and the resulting estimate can be used to calibrate interpretation of future serum creatinine measurements., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Echinocandins are favored drugs for the treatment of fungal infections. There is growing evidence that obese patients treated with echinocandins have lower exposures due to pharmacokinetic (PK) alterations. We conducted a scoping review to characterize, evaluate, and summarize the available evidence on echinocandins exposures in obese patients., Summary: A comprehensive search of PubMed, Embase, and Cochrane Library for studies on echinocandins published from database inception to October 28, 2022, was conducted using PRISMA-ScR methodology. A total of 25 studies comprising more than 3,174 subjects (8 micafungin studies, 7 caspofungin studies, 9 anidulafungin studies, and 1 rezafungin study) were included in this review. Seventeen studies reported lower echinocandins exposures in overweight and obese individuals compared with normal-weight individuals; the authors of these studies recommended dose adjustments. Conversely, 8 studies did not find significant differences in echinocandin exposure among subjects in varying body weight categories. Clinicians may consider dose adjustments of echinocandins in obese patients; however, there is limited evidence on the ideal dose adjustment strategy to overcome the low echinocandins exposures in obese patients., Conclusion: This scoping review shed light on a growing body of evidence indicating that obese patients have lower echinocandin exposures relative to targeted PK indices, which may lead to negative therapeutic implications. Currently, a lack of high-quality evidence impedes reaching consensus on recommendations for echinocandin dosing adjustment in obese patients. Future research evaluating the optimal echinocandin dosing strategy for obese patients is needed., (© American Society of Health-System Pharmacists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are often recommended as opioid-sparing agents. The objective of this scoping review was to conduct a thorough search of the current literature to determine whether in adult critically ill patients there is an association between exposure to NSAIDs vs no NSAIDs and the subsequent development of serious adverse events, particularly gastrointestinal bleeding and acute kidney injury (AKI)., Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews was utilized as a guideline for reporting. Searches were performed in PubMed (National Library of Medicine), Cochrane Library (Wiley), EMBASE (Elsevier), Stat!Ref (Teton), and Access Pharmacy (McGraw Hill) for articles published from January 2016 to August 2022., Results: Of the 3,062 citations and titles identified in the search, 2,737 titles remained after removal of duplicates, 2,588 were excluded at title and abstract screening, and 149 articles remained for full-text review. None of the studies involved heterogeneous groups of critically ill patients in nonspecialty intensive care unit settings. Most studies evaluated were conducted in the perioperative setting and had limited adverse events reporting, particularly with respect to serious NSAID-related adverse effects of concern in critically ill patients., Conclusion: In published studies primarily involving perioperative patients, there is insufficient detail concerning the definitions and reporting of NSAID-related serious adverse events such as bleeding and AKI. These events are of particular concern in heterogeneous critically ill patient populations predisposed to such complications. In most (if not all) critically ill patients, sustained dosing of NSAIDs should be avoided regardless of COX-1 selectivity due to the paucity of safety data., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To review the evidence cited in recent consensus documents providing recommendations for drug dosing for venous thromboembolism (VTE) prophylaxis in obese trauma patients., Summary: Recent publications from the American Association for the Surgery of Trauma and the American College of Surgeons provide recommendations for VTE prophylaxis in trauma. These documents address key aspects of pharmacologic prophylaxis, one of which is drug dosing in obesity. Both documents provide recommendations for obese patients, but they were not formulated using Grading of Recommendations Assessment, Development and Evaluation methodology, which has become the standard approach for guideline development. We reviewed and critiqued the literature cited in recently published consensus documents along with identifying additional studies retrieved from a PubMed search pertaining to drug dosing for VTE prophylaxis in obesity. The overall body of evidence was reviewed, and caveats for application in the clinical setting are provided. Dosing strategies for obese trauma patients are largely extrapolated from studies conducted in nonobese patients. Studies evaluating clinical outcomes are limited as most rely on anti-factor Xa concentrations versus VTE occurrence., Conclusion: The strength of the evidence surrounding dosing recommendations for VTE prophylaxis in obese trauma patients is low. Further research efforts should be directed towards this subset of trauma patients., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To assess the quality of critical care clinical practice guidelines (CPGs) involving pharmacotherapy recommendations., Methods: A systematic electronic search was performed using PubMed, MEDLINE, and Embase for critical care CPGs published between 2012 and 2022 and involving pharmacotherapy recommendations. The Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument was employed to appraise CPG quality through independent assessment by 2 appraisers., Results: Twenty-one CPGs were evaluated. The number of recommendations in each guideline ranged from 2 to 250, with a total of 1,604 recommendations. The number of strong (vs weak) recommendations in each guideline ranged from 0 to 31, with a total of 116 strong recommendations, or 7.23% of the total number of recommendations. There was at least 1 pharmacist author for 9 (43%) of the guidelines. The AGREE II domains for which mean quality scores of evaluated guidelines were highest were scope and purpose (0.88; 95% CI, 0.85-0.92), rigor of development (0.80; 95% CI, 0.77-0.83), clarity of presentation (0.84; 95% CI, 0.81-0.87), and editorial independence (0.86; 95% CI, 0.79-0.94), while those for which mean scores were lowest were stakeholder involvement (0.69; 95% CI, 0.63-0.75) and applicability (0.49; 95% CI, 0.43-0.55). Involvement of a pharmacist in CPG development was associated with significantly higher scoring for stakeholder involvement (P = 0.0356)., Conclusion: Strong recommendations accounted for less than 10% of the recommendations in the evaluated CPGs. Moreover, there are concerns related to guideline applicability (ie, advice or tools for putting recommendations into practice) and stakeholder involvement (ie, inclusion of individuals from all relevant groups). It is important to involve pharmacists in CPGs with pharmacotherapy recommendations., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Several studies have shown hydrocortisone to be beneficial in the treatment of vasopressor-refractory septic shock, but there are minimal data evaluating the efficacy of this fixed dosing regimen in overweight and obese patients. The purpose of this study was to compare the effects of fixed-dose hydrocortisone on vasopressor dose and mean arterial pressure in obese and nonobese patients with septic shock refractory to adequate fluid resuscitation and vasopressor administration., Methods: In this multicenter, retrospective study, we included adult patients with a confirmed or suspected diagnosis of septic shock who received hydrocortisone (200 mg/day). Patients were divided into 4 study groups based on admission body mass index (BMI; defined as BMI of <25 kg/m2, 25-29.9 kg/m2, 30-34.9 kg/m2, and ≥35 kg/m2). The primary outcomes analyzed were change in norepinephrine equivalent dose requirements and mean arterial pressure (MAP) at 6, 12, and 24 hours after initiating hydrocortisone., Results: Between October 1, 2017, and September 30, 2020, 431 patients were screened of whom 219 met inclusion criteria. Baseline characteristics were comparable among the groups. Mean vasopressor requirements (in μg/min) at 6, 12, and 24 hours were as follows: BMI of <25 kg/m2: 28.8, 24.8, and 20; BMI of 25-29.9 kg/m2: 34.1, 33.5, and 24.8; BMI of 30-34.9 kg/m2: 29.5, 33.5, and 24.8; and BMI of ≥35 kg/m2: 32, 25.7 and, 21.2 (P = 0.75, 0.41, and 0.61, respectively). Mean MAP (in mm Hg) at 6, 12, and 24 hours was as follows: BMI of <25 kg/m2: 73.5, 73.6, and 74; BMI of 25-29.9 kg/m2: 71.6, 73.8, and 71.9; BMI of 30-34.9 kg/m2: 72.2, 70, and 72.7; and BMI of ≥35 kg/m2: 70.7, 73.5, and 71.4 (P = 0.56, 0.15, and 0.62, respectively)., Conclusion: BMI does not appear to impact the effects of fixed-dose hydrocortisone on vasopressor dose or blood pressure in patients with septic shock. Fixed-dose hydrocortisone should continue to be used for vasopressor-refractory septic shock in obese patients., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To discuss the potential implications of obesity for drug administration and absorption from subcutaneous (SC) and intramuscular (IM) injection sites., Summary: The SC and IM routes are useful for the parenteral administration of medications to optimize pharmacokinetic properties such as time to onset and duration of effect, for cost considerations, or for ease of administration, such as when intravenous access is unavailable. The choice of SC or IM injection depends on the specific medication, with SC administration preferred for products such as insulin where a slower and more sustained response is desirable, while IM administration is usually preferred for products such as vaccines where more rapid absorption leads to a more rapid antibody response. Obesity has the potential to influence the rate and extent of absorption, as well as adverse effects, of medications administered by the SC or IM route through changes in SC tissue composition and depth or by inadvertent administration of IM medications into SC tissue because of improper needle length. Potential adverse effects associated with IM or SC injections in addition to pain, bruising, and hematoma formation include sciatic nerve injury, particularly with IM injection in the upper outer quadrant of the buttock; bone contusion or rarely osteonecrosis if the IM injection is excessively deep; and granulomas, fat necrosis, and calcification with SC injection., Conclusion: Issues related to medication absorption in obese patients are likely to become more prominent in the future with increasing approvals of a wide range of biotherapeutic agents administered by SC injection. Studies should be directed toward these and other agents to assist with dosing decisions in this challenging population., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To evaluate potential differences in days on mechanical ventilation for patients with coronavirus disease 2019 (COVID-19) based on route of administration of analgesic and sedative medications: intravenous (IV) alone vs IV + enteral (EN)., Summary: This institutional review board-approved study evaluated ventilation time and fentanyl or midazolam requirements with or without concurrent EN hydromorphone and lorazepam. Patients were included in the study if they were 18 to 89 years old and were admitted to the intensive care unit with a positive severe acute respiratory syndrome coronavirus 2 reverse transcription and polymerase chain reaction or antigen test and respiratory failure requiring invasive mechanical ventilation for more than 72 hours. In total, 100 patients were evaluated, 60 in the IV-only group and 40 in the IV + EN group. There was not a significant difference in ventilation time between the groups (mean [SD], 19.6 [12.8] days for IV + EN vs 15.6 [11.2] days for IV only; P = 0.104). However, fentanyl (2,064 [847] μg vs 2,443 [779] μg; P < 0.001) and midazolam (137 [72] mg vs 158 [70] mg; P = 0.004) requirements on day 3 were significantly higher in the IV-only group, and the increase in fentanyl requirements from day 1 to day 3 was greater in the IV-only group than in the IV + EN group (378 [625] μg vs 34 [971] μg; P = 0.033)., Conclusion: Addition of EN analgesic and sedative medications to those administered by the IV route did not change the duration of mechanical ventilation in patients with COVID-19, but the combination may reduce IV opioid requirements, decreasing the impact of IV medication shortages., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Cost-avoidance studies are common in pharmacy practice literature. This scoping review summarizes, critiques, and identifies current limitations of the methods that have been used to determine cost avoidance associated with pharmacists' interventions in acute care settings., Methods: An Embase and MEDLINE search was conducted to identify studies that estimated cost avoidance from pharmacist interventions in acute care settings. We included studies with human participants and articles published in English from July 2010 to January 2021, with the intent of summarizing the evidence most relevant to contemporary practice., Results: The database search retrieved 129 articles, of which 39 were included. Among these publications, less than half (18 of 39) mentioned whether the researchers assigned a probability for the occurrence of a harmful consequence in the absence of an intervention; thus, a 100% probability of a harmful consequence was assumed. Eleven of the 39 articles identified the specific harm that would occur in the absence of intervention. No clear methods of estimating cost avoidance could be identified for 7 studies. Among all 39 included articles, only 1 attributed both a probability to the potential harm and identified the cost specific to that harm., Conclusion: Cost-avoidance studies of pharmacists' interventions in acute care settings over the last decade have common flaws and provide estimates that are likely to be inflated. There is a need for guidance on consistent methodology for such investigations for reporting of results and to confirm the validity of their economic implications., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Cost-avoidance studies of pharmacist interventions are common and often the first type of study conducted by investigators to quantify the economic impact of clinical pharmacy services. The purpose of this primer is to provide guidance for conducting cost-avoidance studies pertaining to clinical pharmacy practice., Summary: Cost-avoidance studies represent a paradigm conceptually different from traditional pharmacoeconomic analysis. A cost-avoidance study reports on cost savings from a given intervention, where the savings is estimated based on a counterfactual scenario. Investigators need to determine what specifically would have happened to the patient if the intervention did not occur. This assessment can be fundamentally flawed, depending on underlying assumptions regarding the pharmacists' action and the patient trajectory. It requires careful identification of the potential consequence of nonaction, as well as probability and cost assessment. Given the uncertainty of assumptions, sensitivity analyses should be performed. A step-by-step methodology, formula for calculations, and best practice guidance is provided., Conclusions: Cost-avoidance studies focused on pharmacist interventions should be considered low-level evidence. These studies are acceptable to provide pilot data for the planning of future clinical trials. The guidance provided in this article should be followed to improve the quality and validity of such investigations., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The need for high-quality research during disaster responses has been well described in the literature, and such research is supported by efforts at the federal level through the National Institutes of Health Disaster Research Response (DR2) Program. This article describes the fourth DR2 workshop with a specific focus on opportunities for pharmacists to get involved with disaster research efforts., Summary: Pharmacists have historically played a significant role in disaster planning and response, and there are a number of opportunities for pharmacists to bring their unique perspective, positioning, and skills to disaster research response (ie, onsite and other research on the medical and public health aspects of disasters and public health emergencies). In February 2019, the fourth DR2 workshop was held in Tucson, AZ, in conjunction with the University of Arizona College of Medicine-Tucson, the university's Mel and Enid Zuckerman College of Public Health, University of Arizona College of Pharmacy, and the university's Bio5 Institute to explore clinical and population-based research in a simulated disaster setting. This article describes the workshop and discusses several opportunities for pharmacists to design, lead, and support research efforts during disaster scenarios through involvement in research areas including clinical, operational, educational, and logistic aspects of pharmacy practice., Conclusion: Due to their positioning throughout health systems, unique perspective, training, and skills, pharmacists are uniquely situated to play an important role in disaster research response., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Medication product labeling was reviewed to determine if sufficient information is available to appropriately calculate dosing regimens for special intensive care unit (ICU) populations, including patients at extremes of body habitus and patients receiving hemodialysis, continuous renal replacement therapy (CRRT), or extracorporeal membrane oxygenation (ECMO)., Methods: The labeling of the 100 most commonly used injectable medications in the adult ICUs of an academic medical center in Arizona were evaluated. Any information related to adult weight-based dosing, weight descriptors, dosing of patients at extremes of weight (body mass index of <18.5 or >40 kg/m2), and dosing of patients receiving hemodialysis, CRRT, or ECMO was extracted from Food and Drug Administration-approved product labeling. Information was ranked for dosing usefulness on a scale of 0 to 3; an information usefulness score of 2 or greater was considered minimally adequate for dosing special ICU populations., Results: Among the 100 medications evaluated, the labeling of 47 provided information on weight-based dosing, with the labeling of 30% referring to a specific weight descriptor. The labeling of 15 medications had information on dosing for patients at extremes of body habitus: underweight (3 medications), obesity (12 medications), and extreme obesity (2 medications), with the labeling of 8 medications receiving an information usefulness score of ≥2 (2, 6, and 1 medication in the respective categories). Among the 42 medications whose labeling provided hemodialysis-related dosing information, the labeled information of 52% was assigned a usefulness score of ≥2; among the 3 medications with CRRT-related dosing information, the labeling of 1 received a score of ≥2. ECMO-related dosing information was available for 2 medications, with 1 score of ≥2 assigned., Conclusion: Information in the product labeling of injectable medications commonly used in the ICU is limited and generally inadequate for calculating an appropriate dose for special ICU populations., (© American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The development of the Critical Care Pharmacotherapy Trials Network (CCPTN) as a model for practice-based pharmacotherapy research is described., Summary: The CCPTN was formed in 2010 as a collaborative research network dedicated to scientific investigation in the field of critical care pharmacotherapy. The CCPTN organizational structure is consistent with many professional pharmacy and interdisciplinary organizations and organized into 3 primary domains: executive committee, working committees, and network membership. The network membership consists of critical care investigators dedicated to the mission and vision of the CCPTN and is open to anyone expressing an interest in contributing to high-level research. Network member sites represent the breadth of U.S. critical care practice environments. In addition, network members include individuals with demonstrated expertise in patient safety, administration, research design, grantsmanship, database management, peer review, and scientific writing. In 2015, there were more than 100 site investigators from around the United States and Canada. Projects to date have yielded numerous abstracts, platform presentations, and peer-reviewed publications in high-impact journals. The CCPTN has expanded to form collaborations with researchers in the United Kingdom, Australia, and New Zealand. The CCPTN has identified new potential partnerships and field-based areas for inquiry. Numerous opportunities for continued growth and scientific inquiry in the field of critical care pharmacotherapy research exist for the CCPTN to foster in the coming years., Conclusion: The CCPTN has been a successful model for practice-based pharmacotherapy research and assists its members in expanding critical care pharmacotherapy knowledge., (Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

Purpose: Pharmacists' impact in reducing the time interval from intubation to sedative and analgesic use during trauma patient resuscitations is investigated., Methods: A retrospective cohort study was conducted at a level 1 trauma center to compare medication-use outcomes in consecutive cases in which trauma patients underwent rocuronium-assisted rapid-sequence intubation (RSI) and subsequent sedation and analgesia with or without a pharmacist's participation on the resuscitation team. The primary and secondary outcomes were, respectively, the time to sedative provision and the time to analgesic provision after intubation., Results: Relative to resuscitation cases not involving a pharmacist, the presence of the pharmacist during RSI was associated with decreased mean times to provision of postintubation sedation (9 minutes versus 28 minutes, p = 0.007) and analgesia (21 minutes versus 44 minutes, p = 0.057). The cumulative proportions of patients receiving appropriate sedation 5, 10, and 15 minutes after intubation were 11%, 26%, and 41% in the pharmacist-absent group and 33%, 53%, and 63% in the pharmacist-present group (p = 0.009, 0.008, and 0.045, respectively); for postintubation analgesic use, the corresponding figures were 9%, 14%, and 23% in the pharmacist-absent group and 17%, 30%, and 43% in the pharmacist-present group (p = 0.236, 0.066, and 0.039, respectively)., Conclusion: The presence of a pharmacist during RSI procedures was associated with decreased times to postintubation sedative and analgesic use, indicating that pharmacist participation in trauma-resuscitation responses can facilitate appropriate drug therapy.

Purpose: Product information and pivotal studies on newly marketed injectable medications were reviewed to determine whether a weight descriptor was included and if information was provided for dosing patients with extremes of body weight., Methods: Products with new drug applications approved by the Food and Drug Administration between January 1, 2004, and January 30, 2009, were evaluated. Any information related to weight descriptors or dosing of patients with extremes of weight (body mass index of <18.5 or >40 kg/m(2)) relative to age and height was extracted from the product labeling or pivotal studies. Pharmaceutical companies were contacted if pivotal studies had not been published. The information was evaluated with a dosing usefulness score of 0-3; a score of 2 or greater was considered minimally adequate for dosing patients with extremes of weight., Results: Of the 84 medications evaluated, some reference to weight descriptors was found for 23 (27%). None had a calculated usefulness score of 2 or above based on information from product information or pivotal trials. conclusion: Information from product labeling and pivotal studies involving newly marketed injectable medications is inadequate for dosing patients with extremes of weight.

Purpose: The use of hypertonic saline injection in trauma patients is discussed., Summary: Patients with hemorrhage, burns, and traumatic brain injury (TBI) may develop hypovolemic shock and require resuscitation. Compared with conventional isotonic crystalloids, hypertonic saline has several advantages, including hemodynamic, immune-modulating, and antiinflammatory effects, for use in trauma patients for resuscitation. In addition, hypertonic saline is also used in patients with TBI to reduce intracranial pressure (ICP). Overall, studies have not shown a difference in mortality or other clinically important outcomes with the use of hypertonic saline for resuscitation in trauma patients; however, most of these studies were not adequately powered to show significant differences. A recent Cochrane review concluded that there is no evidence that hypertonic crystalloids are better than isotonic or near-isotonic crystalloids for fluid resuscitation in trauma patients. Two recent trials that were adequately powered to investigate a mortality endpoint were halted for futility. A few small randomized controlled studies found that hypertonic saline was more effective than mannitol as a hyperosmolar agent for ICP reduction. Recent guidelines from the American Burn Association have suggested that hypertonic saline may be used for burn shock resuscitation by experienced providers with close monitoring to avoid excessive hypernatremia. One of the main concerns with the use of hypertonic saline is its potential to cause central pontine myelinolysis due to a rapid increase in serum sodium levels., Conclusion: There is no evidence that hypertonic saline provides any additional benefit over isotonic crystalloid solutions for trauma resuscitation. Hypertonic saline may be more effective than mannitol at reducing ICP in patients with TBI.

Purpose: The cost implications of and potential adverse events prevented by the interventions of a critical care pharmacist were studied., Methods: A decentralized clinical pharmacist assigned to a surgical intensive care unit (ICU) documented all interventions made from mid-October 2003 through February 2004 using a standardized written form. The data were retrospectively evaluated and the following information was extracted: amount of time spent performing various clinical activities, how drug-related problems were identified (e.g., order entry versus chart review), and a general description of the interventions. The interventions were independently reviewed by two other clinical pharmacists to determine whether an actual or potential adverse drug event (ADE) would have occurred without the intervention, the probability that an ADE would have occurred without the intervention, the type of intervention, and potential cost avoidance of the intervention. Once the evaluations were completed, the data obtained from order entry and verification activities were compared with the data obtained during other clinical functions., Results: A total of 129 interventions were documented over 4.5 months. The majority of interventions were identified during chart review (40%) and patient care rounds (39%). The potential cost avoidance of the documented interventions was $205,919-$280,421. Interventions identified during patient care rounds and chart review were most likely to achieve the greatest impact on cost avoidance., Conclusion: Among the interventions performed and documented by a clinical pharmacist in an ICU, patient care rounds and chart-review activities were associated with the greatest number of interventions and the greatest potential cost avoidance.

Purpose: The adequacy of end-of-procedure free cefazolin concentrations after administration for the prevention of surgical-site infection (SSI) and compliance with national guidelines for antimicrobial prophylaxis for SSI were assessed., Methods: Patients undergoing elective surgery and receiving cefazolin for perioperative antimicrobial prophylaxis were prospectively enrolled. Antibiotic administration was controlled by the surgeon and usage was recorded. For each patient, a single blood sample for cefazolin serum free and total concentrations was obtained within 15 minutes of wound closure. A free serum concentration threshold of 4 microg/mL was arbitrarily chosen based on the minimum inhibitory concentration required to inhibit 90% of strains of methicillin-susceptible Staphylococcus aureus and Escherichia coli., Results: Fifty-seven subjects were enrolled, and noncompliance with published guidelines was observed for 26% of patients. Forty-six subjects had serum samples available for assay, 21.7% of whom had end-of-procedure free cefazolin concentrations of <4 microg/mL. Results of multivariate regression and population pharmacokinetic analysis revealed the importance of age and lean body weight in cefazolin clearance. Younger and taller patients had a greater risk of achieving below-threshold end-of-procedure concentrations. Of the patients for whom published guidelines were not followed, 67% had end-of-procedure free cefazolin concentrations below the threshold concentration (4 microg/mL). In contrast, less than 15% of cases where SSI prophylaxis complied with the published guidelines had below-threshold concentrations at the end of surgery., Conclusion: Noncompliance with antimicrobial prophylaxis guidelines was associated with low end-of-procedure antibiotic levels. Compliance with guidelines did not guarantee adequate levels.

Purpose: The implications of recent studies for guidelines that pertain to stress ulcer prophylaxis in the postoperative period are discussed., Summary: The therapeutic guidelines on stress ulcer prophylaxis published by the American Society of Health-System Pharmacists (ASHP) provided clinicians with recommendations regarding appropriate candidates for stress ulcer prophylaxis and selection of a pharmacologic agent. Since these guidelines were published in 1999, additional research has been completed to resolve some of the controversial issues surrounding stress ulcer prophylaxis. The frequency of stress-induced bleeding in recent investigations continues to be highly variable, depending on the definition used to describe bleeding. In general, investigations that evaluate overt bleeding or bleeding without hemodynamic changes or blood transfusion report higher frequencies of bleeding than those that evaluate clinically important bleeding. Similar to that reported in the initial ASHP guidelines, the frequency of clinically important bleeding in recent investigations is low. In addition, the majority of recently published prospective studies and a meta-analysis have been unable to demonstrate a reduction in clinically important bleeding with pharmacologic agents. As a result, some experts have suggested that advances in critical care are more influential in the development of stress-induced bleeding than the use of pharmacologic agents. Recently published investigations support the effectiveness of institution-specific guidelines to help clinicians identify appropriate candidates for stress ulcer prophylaxis. The selection of an optimal pharmacologic agent for stress ulcer prophylaxis continues to be debated. The majority of recent studies have involved the administration of proton-pump inhibitors (PPIs). In general, these studies have demonstrated that PPIs are at least as effective as histamine H2-receptor antagonists at increasing gastric pH, but adequately powered studies investigating the endpoint of clinically important bleeding are needed. Similar to the initial ASHP guidelines, the development of institution-specific guidelines is recommended to identify the most appropriate pharmacologic treatment., Conclusion: The frequency of clinically important bleeding reported in recent studies is low. The majority of recently published prospective studies and meta-analyses found little significant reduction in bleeding with pharmacologic prophylaxis.

The implications of prion-induced diseases for the use of medications that theoretically could harbor the infectious pathogens are discussed. Prions have been identified as protein particles that lack nucleic acids. There is evidence that prions cause the transmissible neurodegenerative diseases known as transmissible spongiform encephalopathies. Of these diseases, bovine spongiform encephalopathy (BSE) and the human spongiform encephalopathy to which it has been linked, new variant Creutzfeldt-Jakob disease (CJD), have generated the most attention. The first cases of new variant CJD appeared in Britain in the mid-1990s. Ingestion of prion-infected beef remains the only known cause of new variant CJD. No cases of BSE or new variant CJD have been documented in the United States. The time from exposure to the development of clinical sequelae appears to be about 10 years. The median duration of illness is 14 months, and the outcome is invariably death. There is no treatment; currently the only available approach is prevention. There is no reliable method of predicting the number of new cases that might occur because of lack of definitive information on the efficiency of transmission from animals to humans and the number of people currently infected and at risk for infection. The infectivity of medications and plasma fractionation products containing material from cattle with BSE is unknown, but the risk is believed to be very low. No cases of such transmission have been identified. Guidelines to keep the risk of transmission via medications low have been promulgated by FDA, and further research is warranted. There have been no reports of medications or plasma fractionation products being contaminated with the prions that cause new variant CJD. Ongoing vigilance and research are appropriate, however.