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Objectives: To review the current definitions and diagnostic criteria for acute kidney injury (AKI) and type 1 hepatorenal syndrome (HRS) now termed HRS-AKI and discuss the challenges in deciding the most appropriate medication regimens to treat patients with HRS-AKI.Data sources: PubMed (inception to April 2023) with bibliographies of retrieved articles searched for additional articles; organizational websites for clinical practice guidelines (CPGs).Study selection and data extraction: Randomized controlled trials (RCTs) evaluating albumin and vasoconstrictors for HRS-AKI.Data synthesis: A major change in the most recent revision of definitions and diagnostic criteria for HRS-AKI is the elimination of the set cutoff serum creatinine values for AKI. This change should be considered when comparing studies of HRS-AKI over time. Albumin has been administered to both vasoconstrictor treatment and placebo groups in all recent RCTs; however, there has never been a large RCT evaluating a no-albumin group. Most prospective trials comparing a midodrine/octreotide combination or norepinephrine to placebo or terlipressin have enrolled less than 100 patients limiting any conclusions regarding clinically important outcomes. Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events.Relevance to patient care and clinical practice: Type 1 hepatorenal syndrome with acute kidney injury is a potentially life-threatening syndrome with diagnostic and treatment challenges. Albumin plus a vasoconstrictor has become the routine HRS-AKI treatment even though there has not been a large RCT evaluating a no-albumin group. Terlipressin is the vasoconstrictor of choice for HRS-AKI in current CPGs, but it has adverse effect concerns and, until recently, was not available in the United States.Conclusions: In conjunction with changes in the definitions and diagnostic criteria for HRS-AKI, debate continues regarding the optimal therapy for HRS-AKI, particularly considering recent trials demonstrating ischemic and pulmonary adverse events with terlipressin used in combination with albumin.

Monoclonal antibody products are an increasing portion of novel drug approvals. The labeling of initial drug approvals frequently involves body-size-based rather than fixed-dose administration regimens for adults without clear rationale for doing so. This presents challenges when prescribing these products for patients with extremes of body habitus who constitute a small portion of enrollment in pre-approval investigations. Fixed-dose regimens allow for standardized preparation with the potential to reduce the risk of calculation errors, drug waste, and make home administration more practical. Fixed-dose rather than body-size-based monoclonal antibody regimens should serve as the initial approach in early phase 1 clinical trials.

Background: Current critical care pharmacist (CCP) practices and perceptions related to neuromuscular infusion (NMBI) use for acute respiratory distress syndrome (ARDS) maybe different with the COVID-19 pandemic and the publication of 2020 NMBI practice guidelines.Objective: To evaluate CCP practices and perceptions regarding NMBI use for patients with moderate-severe ARDS.Methods: We developed, tested, and electronically administered a questionnaire (7 parent-, 42 sub-questions) to 409 American College of Clinical Pharmacy (ACCP) Critical Care Practice and Research Network members in 12 geographically diverse states. The questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2<150) whose causes of dyssynchrony were addressed. Two reminders were sent at 10-day intervals.Results: Respondents [131/409 (32%)] primarily worked in a medical intensive care unit (ICU) 102 (78%). Compared to COVID-negative(-) ARDS patients, COVID positive(+) ARDS patients were twice as likely to receive a NMBI (34 ± 18 vs.16 ± 17%; P< 0.01). Respondents somewhat/strongly agreed a NMBI should be reserved until after trials of deep sedation (112, 86%) or proning (92, 81%) and that NMBI reduced barotrauma (88, 67%), dyssynchrony (87, 66%), and plateau pressure (79, 60%). Few respondents somewhat/strongly agreed that a NMBI should be initiated at ARDS onset (23, 18%) or that NMBI reduced 90-day mortality (12, 10%). Only 2/14 potential NMBI risks [paralysis awareness (101, 82%) and prolonged muscle weakness (84, 68%)] were frequently reported to be of high/very high concern. Multiple NMBI titration targets were assessed as very/extremely important including arterial pH (109, 88%), dyssynchrony (107, 86%), and PaO2: FiO2ratio (82, 66%). Train-of-four (55, 44%) and BIS monitoring (36, 29%) were deemed less important. Preferred NMBI discontinuation criteria included absence of dysschrony (84, 69%) and use ≥48 hour (72, 59%).Conclusions and Relevance: Current critical care pharmacists believe NMBI for ARDS patients are best reserved until after trials of deep sedation or proning; unique considerations exist in COVID+ patients. Our results should be considered when ICU NMBI protocols are being developed and bedside decisions regarding NMBI use in ARDS are being formulated.

Albumin has only reduced crude mortality in one randomized controlled trial conducted to date. This raises the question as to why potentially beneficial oncotic and pleiotropic properties of albumin do not consistently translate into clinically important outcomes. Four postulated explanations are provided as to why the theoretical advantages of albumin are not apparent in clinical trials: diminished oncotic action due to leakage of albumin from the intravascular compartment, modification of the pleiotropic properties of albumin both in vitro and in vivo, the ability of other plasma proteins to take over the major functions of albumin, and possible adverse effects.

Objectives The purpose of this article is to summarize the results of major randomized controlled trials (RCTs) comparing clinical outcomes of critically ill patients treated with normal saline (NS) or balanced salt solutions (BSSs), address discordant results of these studies, and provide direction for future investigations.Data Sources PubMed (2011 to January 2022) with bibliographies of retrieved articles searched for additional articles.Study Selection and Data Extraction RCTs comparing NS and BSSs in critically ill adult patients.Data Synthesis Recently published large RCTs comparing NS with BSSs in heterogeneous populations of intensive care unit patients did not find significant differences in mortality, despite positive findings in some end points in prior RCTs. However, there were a number of methodologic issues common to the RCTs including: varying study designs and end points, clinician discretion for the majority or all treatments other than the primary intervention fluid, heterogeneous patients with varying levels of acuity, and lack of power to investigate potential subgroup differences. In addition, there were problematic issues related to blinding and use of nonstudy fluids.Relevance to Patient Care and Clinical Practice Intravenous fluids are a mainstay of supportive care for critically ill patients. Similar to the so-called crystalloid-colloid debate, there has been a long-standing debate among critical care clinicians and researchers concerning the preferred crystalloid solution, NS versus one of the available BSSs.Conclusions Despite the recent publication of large multicenter RCTs, the preferred resuscitation fluid, NS or a BSS, for critically ill patients is still open for debate, although the available investigations do provide some direction for clinicians and for future investigations.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.annemergmed.2009.12.017 Byline: Asad E. Patanwala (a), Terri L. Warholak (a), Arthur B. Sanders (b), Brian L. Erstad (a) Abstract: We determine the rate and severity of medication errors, as well as factors associated with error occurrence in the emergency department (ED). Author Affiliation: (a) Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona, Tucson, AZ (b) Department of Emergency Medicine, University of Arizona, Tucson, AZ Article History: Received 23 October 2009; Revised 18 November 2009; Accepted 11 December 2009 Article Note: (footnote) Please see page 523 for the Editor's Capsule Summary of this article., Supervising editor: Robert L. Wears, MD, MS, Author contributions: AEP, TLW, ABS, and BLE conceived and designed the study. AEP performed all data collection. AEP and BLE conducted data analysis and drafted the article. TLW and ABS contributed substantially to its revision. AEP takes responsibility for the paper as a whole., Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. This research was supported by a junior investigator grant from the American Society of Health-System Pharmacists Foundation., Reprints not available from the authors., Publication date: Available online January 15, 2010.

To describe an evaluation of a generative language model tool to write examination questions for a new elective course focused on the interpretation of common clinical laboratory results being developed as an elective for students in a Bachelor of Science in Pharmaceutical Sciences program.

Objectives: To review the clinical usefulness of the biomarker TIMP-2•IGFBP7 in adult, general medical-surgical intensive care unit (ICU) settings.Data Sources: PubMed (1946 to mid-February 2021) and EMBASE (1947 to mid-February 2021) with bibliographies of retrieved articles reviewed for additional articles.Study Selection and Data Extraction: Studies evaluating use of the urinary TIMP-2•IGFBP7 assay in adult patients in ICU settings.Data Synthesis: Studies published after investigations leading to TIMP-2•IGFBP7 assay approval confirm the appropriateness of considerations discussed in product labeling, such as use of the test within 12 hours of assessment, use of a dichotomous 0.3 (ng/mL)2/1000 cutoff, and use only in combination with other assessments of acute kidney injury (AKI). However, as a biomarker routinely used for early identification of patients at risk for AKI in mixed ICU populations, the additional resources required for TIMP-2•IGFBP monitoring are difficult to justify because of limited data demonstrating usefulness in preventing or ameliorating AKI and its attendant complications.Relevance to Patient Care and Clinical Practice: Biomarkers are potentially useful not only for assessment and diagnosis of AKI, but also for practitioners involved in the management of nephrotoxic medications and medications needing adjustment for decreased kidney function.Conclusions: Although there is evidence to suggest that the urinary TIMP-2•IGFBP7 biomarker is helpful in predicting AKI progression in general medical-surgical ICU patients when used within 12 hours of patient assessment in combination with routine testing, including serum creatinine and urine output, there is little evidence that its use leads to improvements in clinically important patient outcomes.

Objectives: To discuss methods for the assessment of creatinine clearance (Clcr) when serum creatinine (SCr) is not at steady state in order to estimate kidney function and apply the estimate to kidney function staging for clinical assessment or drug dosing.Data Sources: A PubMed search was conducted from 1976 to mid-January 2021 with other articles identified through review of bibliographies of retrieved articles and citations in Scopus.Study Selection and Data Extraction: Articles assessing Clcrunder non–steady-state conditions and studies evaluating predictive equations were selected.Data Synthesis: When SCr is systematically changing (ie, trending up or down), kinetic methods to estimate Clcrare appropriate. Estimates from kinetic methods should be individual based and not indexed to body surface area, and careful monitoring is required to confirm predictions as the situation evolves. Standard methods intended for steady-state conditions should not be used to estimate Clcrin patients with unstable SCr.Relevance to Patient Care and Clinical Practice: Creatinine continues to be a monitoring parameter of choice and is an important variable in all the commonly used equations for estimating Clcrand most important for estimating glomerular filtration rate. However, standard methods of estimating Clcrfor medication dosing are not accurate under non–steady-state conditions.Conclusion: The methods for kinetic clearance estimation and standards methods for clearance estimation, such as the Cockcroft-Gault equation, are mutually exclusive. There are no benefits of using the kinetic method in patients with stable SCr concentrations, and standard equations are not appropriate with unstable SCr concentrations.

AbstractBackgroundWith the increasing occurrence of infectious diseases in lower-and-middle-income countries (LMICs), emergency preparedness is essential for rapid response and mitigation. Economic evaluations of mitigation technologies and strategies have been recommended for inclusion in emergency preparedness plans. We aimed to perform an economic evaluation using dynamic transition modeling of ebola virus disease (EVD) vaccination in a hypothetical community of 1,000 persons in the Democratic Republic of Congo (DRC).MethodUsing a modified SEIR (Susceptible, Exposed, Infectious, Recovered, with Death added [SEIR-D]) model that accounted for death and epidemiological data from an EVD outbreak in the DRC, we modeled the transmission of EVD in a hypothetical population of 1,000. With our model, we estimated the cost-effectiveness of an EVD vaccine and an EVD vaccination intervention.ResultsThe results showed vaccinating 50% of the population at risk prevented 670 cases, 538 deaths, and 22,022 disability-adjusted life years (DALYs). The vaccine was found to be cost-effective with an incremental cost-effectiveness ratio (ICER) of $95.63 per DALY averted. We also determined the minimum required vaccination coverage for cost-effectiveness to be 40%. Sensitivity analysis showed our model to be fairly robust, assuring relatively consistent results even with variations in such input parameters as cost of screening, as well as transmission, infection, incubation, and case fatality rates.ConclusionEVD vaccination in our hypothetical population was found to be cost-effective from the payer perspective. Our model presents an efficient and reliable approach for conducting economic evaluations of infectious disease interventions as part of an emergency preparedness plan.

Background: Crystalloids, nonprotein colloids (NPCs), and albumin are used for many indications. The use of the least costly agent in situations where these products are clinically interchangeable can reduce health care costs. Objectives: To characterize the prescribing of albumin and NPC. To evaluate the appropriateness and cost implications of their use. Methods: An observational study conducted in 15 academic health centers from April 11 through May 6, 1994, to assess the appropriateness of albumin and NPC use, based on 'model' consensus-derived indication guidelines. Results: A total of 969 case report forms were evaluated. Albumin and NPCs were administered in 83% and 17% of the cases, respectively. Albumin and NPCs were administered mostly in the intensive care (50%) or operating room (31%) settings. The most common prescribers of these products were surgeons (45%) and anesthesiologists (20%). In 87% of cases, albumin or NPC was administered to reach a defined end point (eg, to achieve a target physiological state or to resolve a pathophysiological condition). Only one albumin recipient experienced an adverse event; no adverse events were noted with NPC administration. Approximately $203 000 was spent on albumin and NPC therapy for the 969 cases; $49 702 (24%) was spent on appropriate administrations, $124939 (62%) on inappropriate administrations, and $28014 (14%) on unevaluated indications. Conclusions: Evaluated against model guidelines, most of the albumin and NPC use in the study was found to be inappropriate. The need for institutions to define and implement guidelines that focus on the cost-efficient use of these agents is recommended in an increasingly cost-conscious health care environment. (Arch Intern Med. 1995;155:2450-2455)

Objective: To develop contemporary, comprehensive guidelines for the appropriate and efficient use of albumin, nonprotein colloid, and crystalloid solutions. Design: A systematic, literature-based, consensus exercise employing a modified Delphi method. Participants: Thirty-one medical and allied health professionals from 26 University Hospital Consortium (Oak Brook, Ill) member institutions were initially chosen to participate. Participants were selected on the basis of their recognized research in the use of albumin, nonprotein colloid, and crystalloid solutions, and/or experience in the review of appropriateness of such use. A total of 24 participants completed the exercise. Main Outcome Measures: Group responses were statistically analyzed in an iterative consensus development process. Five separate questionnaire rounds were designed to establish criteria for the appropriate use of albumin, nonprotein colloid, and crystalloid solutions. Results: Consensus guidelines were developed outlining the appropriate use of these products for 12 clinical indications, including hemorrhagic shock, nonhemorrhagic (maldistributive) shock, hepatic resection, thermal injury, cerebral ischemia, nutritional intervention, cardiac surgery, hyperbilirubinemia of the newborn, cirrhosis and paracentesis, nephrotic syndrome, organ transplantation, and plasmapheresis. Conclusion: The Delphi method, a systematic, literature-based consensus process, was shown to be useful in the development of complex clinical practice guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. It is anticipated that the guidelines will assist health care providers to develop local institutional policies and procedures for the appropriate and efficient use of albumin and albumin alternatives. Institutions reviewing and updating existing local guidelines may use the University Hospital Consortium guidelines as a model for comparison.

A review is presented of the medical literature concerning the clinical uses of albumin, a protein normally found in the blood. These include giving albumin as a supplement in transfusions for people with serious injuries or who are undergoing surgery. It may be administered until an optimal level in the blood is reached, or according to empirical formulas, to normalize hemodynamic variables such as arterial blood pressure. Albumin has also been used to treat patients with pulmonary insufficiency (a condition in which the lungs do not oxygenate the blood sufficiently); during open-heart surgery; for treating burn patients; and for treating patients with cirrhosis (a chronic liver disease) or nephrosis (a degenerative kidney disorder). Albumin has been administered as a nutritive supplement to patients undergoing enteral feeding (by means of a tube) or total parenteral nutrition (intravenous feeding). Other uses are also discussed. In summary, the clinical use of albumin is controversial; it is expensive but offers the advantage over blood products of not carrying viral contaminants. Albumin does not appear to be more effective than crystalloid solutions (which diffuse across membranes) as a transfusion agent in many circumstances, but it may be beneficial for the elderly who cannot be given the larger fluid volumes used for crystalloid solutions. More research is needed to compare the effectiveness of albumin with that of crystalloid solutions; the latter are relatively inexpensive. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objectives The purpose of this critical narrative review is to discuss common indications for ordering serum albumin levels in adult critically ill patients, evaluate the literature supporting these indications, and provide recommendations for the appropriate ordering of serum albumin levels.Data Sources PubMed (1966 to August 2020), Cochrane Library, and current clinical practice guidelines were used, and bibliographies of retrieved articles were searched for additional articles.Study Selection and Data Extraction Current clinical practice guidelines were the preferred source of recommendations regarding serum albumin levels for guiding albumin administration and for nutritional monitoring. When current comprehensive reviews were available, they served as a baseline information with supplementation by subsequent studies.Data Synthesis Serum albumin is a general marker of severity of illness, and hypoalbuminemia is associated with poor patient outcome, but albumin is an acute phase protein, so levels vacillate in critically ill patients in conjunction with illness fluctuations. The most common reasons for ordering serum albumin levels in intensive care unit (ICU) settings are to guide albumin administration, to estimate free phenytoin or calcium levels, for nutritional monitoring, and for severity-of-illness assessment.Relevance to Patient Care and Clinical Practice Because hypoalbuminemia is common in the ICU setting, inappropriate ordering of serum albumin levels may lead to unnecessary albumin administration or excessive macronutrient administration in nutritional regimens, leading to possible adverse effects and added costs.Conclusions With the exception of the need to order serum albumin levels as a component of selected severity-of-illness scoring systems, there is little evidence or justification for routinely ordering levels in critically ill patients.

ABSTRACTBackground:The risk of immune-related(ir)-hypothyroidism in older patients with advanced melanoma treated with anti-CTLA4 or anti-PD1 therapies is poorly understood, especially in the real-world setting.Research design and methods:We identified older patients (≥65 years) diagnosed with advanced melanoma between 2011-2015 and treated with anti-CTLA4 or anti-PD1 agents in the SEER-Medicare database. Applying probability-of-treatment-weighting for confounder adjustment and proportional hazards models, we estimated the risk of ir-hypothyroidism between treatment initiation and up to 90 days from last dose between anti-PD1 and anti-CTLA4 users.Results:Of 210 older patients with advanced melanoma identified, 164 received anti-CTLA4 (ipilimumab) and 46 anti-PD1 agents (11 nivolumab, 35 pembrolizumab). There was no statistically significant difference in ir-hypothyroidism risk between anti-PD1 and anti-CTLA4 users (HR=2.15, 95%CI=0.83-5.53). Pairwise medication comparisons showed a lower risk among ipilimumab versus nivolumab (HR=0.15, 95%CI=0.06-0.40) and pembrolizumab versus nivolumab users (HR=0.13, 95%CI=0.03-0.55). Sensitivity analyses using an all-stages melanoma cohort did not show a difference in ir-hypothyroidism risk between medication classes and individual medications.Conclusions:This retrospective claims data analysis revealed no statistically significant difference in ir-hypothyroidism risk between anti-CTLA4 or anti-PD1 users. However, patients with advanced melanoma treated with ipilimumab or pembrolizumab may have a lower ir-hypothyroidism risk compared to nivolumab users.

We provide recommendations for stocking of antidotes used in emergency departments (EDs). An expert panel representing diverse perspectives (clinical pharmacology, medical toxicology, critical care medicine, hematology/oncology, hospital pharmacy, emergency medicine, emergency medical services, pediatric emergency medicine, pediatric critical care medicine, poison centers, hospital administration, and public health) was formed to create recommendations for antidote stocking. Using a standardized summary of the medical literature, the primary reviewer for each antidote proposed guidelines for antidote stocking to the full panel. The panel used a formal iterative process to reach their recommendation for both the quantity of antidote that should be stocked and the acceptable timeframe for its delivery. The panel recommended consideration of 45 antidotes; 44 were recommended for stocking, of which 23 should be immediately available. In most hospitals, this timeframe requires that the antidote be stocked in a location that allows immediate availability. Another 14 antidotes were recommended for availability within 1 hour of the decision to administer, allowing the antidote to be stocked in the hospital pharmacy if the hospital has a mechanism for prompt delivery of antidotes. The panel recommended that each hospital perform a formal antidote hazard vulnerability assessment to determine its specific need for antidote stocking. Antidote administration is an important part of emergency care. These expert recommendations provide a tool for hospitals that offer emergency care to provide appropriate care of poisoned patients.

The removal of the X-waiver in the Mainstreaming Addiction Treatment (MAT) Act of 2023 has substantial implications for buprenorphine prescribing as one of the options to treat opioid use disorder. The purpose of this commentary is to discuss the unanswered questions regarding buprenorphine in the intensive care unit (ICU) including how the passage of the MAT Act will affect ICU providers, which patients should receive buprenorphine, what is the most appropriate route of administration and dose of buprenorphine, what medications interact with buprenorphine, and how can transitions of care be optimized for these patients.

The potential uses of artificial intelligence have extended into the fields of health care delivery and education. However, challenges are associated with introducing innovative technologies into health care, particularly with respect to information quality.

Since 2020, there have been changes in Food and Drug Administration guidance and in recommendations by national organizations with a focus on kidney diseases pertaining to the choice of equations used to estimate creatinine clearance and glomerular filtration rate in patients with renal impairment. This includes a recommendation by the National Kidney Foundation to avoid the use of the Cockcroft-Gault equation for drug dosing in patients with renal impairment. This commentary provides an overview of recent recommendations concerning kidney function assessment that have important implications for drug dosing in patients with renal impairment and provides suggestions for implementing these recommendations.

There are unique challenges associated with the evaluation of faculty in pharmacy departments or divisions that have a mix of non-tenure-track and tenure-track faculty members. Such evaluations are intended to provide feedback on performance and personal growth but have the potential to demotivate faculty and add to existing stress if improperly performed. The purpose of this commentary is to suggest best practices for department chairs involved in performing evaluations of faculty in pharmacy departments or divisions that have a mix of non-tenure-track and tenure-track faculty members. The paper is intended to help ensure these evaluations not only capture the quality and quantity of each faculty member’s full range of activities and responsibilities but also are conducted in a supportive and constructive fashion. This commentary is targeted for new department chairs, new faculty members unfamiliar with academic evaluation processes, and departments contemplating changes in their existing evaluation procedures.

Amiodarone is a drug used to manage life-threatening ventricular tachyarrhythmias, where the heart beats wildly and irregularly. Phenytoin is normally used for the treatment of seizures, yet it seems to have some effectiveness in treating some ventricular arrhythmias as well. There is evidence that the levels of phenytoin are greater in patients also taking amiodarone; this has been confirmed in healthy volunteers. Furthermore, research has shown that this is because the amiodarone inhibits the metabolism of phenytoin, so that it is broken down more slowly. In order to determine the effect this would have on patients taking phenytoin on a daily basis, the steady-state blood levels of phenytoin were measured in healthy volunteers over a period of two weeks. The subjects received two to four milligrams of phenytoin per kilogram of body weight each day; the calculated dose was rounded off to the nearest 100 milligram capsule. After six days, 200 milligrams of amiodarone were added to the drug regimen. The serum concentration of phenytoin increased, and a concomitant decrease was seen in the urinary excretion of phenytoin metabolites. The increase in phenytoin was sufficiently large to recommend that for patients on phenytoin, the dose be reduced between 25 and 30 percent if amiodarone is to be added to the therapeutic regimen. (Consumer Summary produced by Reliance Medical Information, Inc.)

There is no consensus on which weight clinicians should use for weight-based dosing of neuromuscular blocking agents (NMBAs), as exemplified by differing or absent recommendations in clinical practice guidelines. The purpose of this paper is to review studies that evaluated various size descriptors for weight-based dosing of succinylcholine and non-depolarising NMBAs, and to provide recommendations for the descriptors of choice for the weight-based dosing of these agents in patients with obesity. All of the studies conducted to date involving depolarising and non-depolarising NMBAs in patients with obesity have assessed single doses or short-term infusions conducted in perioperative settings. Recognising that any final dosing regimen must take into account patient-specific considerations, the available evidence suggests that actual body weight is the size descriptor of choice for weight-based dosing of succinylcholine and that ideal body weight, or an adjusted (or lean) body weight, is the size descriptor of choice for weight-based dosing of non-depolarising NMBAs.

Background: Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use.Objective: To evaluate the clinical and economic impact of a clinical pharmacist–led intervention strategy targeting inappropriate albumin use in general ward patients.Methods: A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist–led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods.Results: A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (P< 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; P< 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (P< 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use.Conclusion and Relevance: Clinical pharmacist–led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients.

Objectives: To discuss the evidence and caveats associated with estimated and measured creatinine clearance (eClCr and mClCr) and glomerular filtration rate (eGFR and mGFR) assessments of kidney function in patients with more extreme forms of obesity.Data Sources: PubMed (1976 to mid-May 2020) was used, with bibliographies of retrieved articles searched for additional articles.Study Selection and Data Extraction: Articles using gold standard mGFR to evaluate eClCr, mClCr, and eGFR assessments of kidney function in patients with more extreme forms of obesity were included.Data Synthesis: The overestimation of GFR by mClCr is well established, but mClCr is an alternative to mGFR assessments for determining medication dosing in patients with extremes of body size or muscle mass, or in patients receiving narrow therapeutic index medications when eGFR is likely to be inaccurate. The vast majority of studies comparing eGFR assessments with gold standard indicators of kidney function were attempts to validate eGFR equations for diagnosing and staging chronic kidney disease (CKD).Relevance to Patient Care and Clinical Practice: For dosing medications in patients with stable kidney function and extreme obesity, a deindexed 4-variable Modification of Diet in Renal Disease or CKD Epidemiology Collaboration equation is an alternative to Cockcroft-Gault. Consistent use of the same equation by provider and between providers within any given setting is of paramount importance.Conclusions: In patients with extreme obesity and stable kidney function, eClCr or eGFR using deindexed values provides estimates of function for dosing adjustments of medications with elimination by the kidneys, but more research is needed with respect to the best size descriptor to use with estimating equations.

Critical drug shortages have been widely documented during the coronavirus disease 2019 (COVID-19) pandemic, particularly for IV sedatives used to facilitate mechanical ventilation. Surges in volume of patients requiring mechanical ventilation coupled with prolonged ventilator days and the high sedative dosing requirements observed quickly led to the depletion of “just-in-time” inventories typically maintained by institutions. This manuscript describes drug shortages in the context of global, manufacturing, regional and institutional perspectives in times of a worldwide crisis such as a pandemic. We describe etiologic factors that lead to drug shortages including issues related to supply (eg, manufacturing difficulties, supply chain breakdowns) and variables that influence demand (eg, volatile prescribing practices, anecdotal or low-level data, hoarding). In addition, we describe methods to mitigate drug shortages as well as conservation strategies for sedatives, analgesics and neuromuscular blockers that could readily be applied at the bedside. The COVID-19 pandemic has accentuated the need for a coordinated, multi-pronged approach to optimize medication availability as individual or unilateral efforts are unlikely to be successful.

AbstractAimsSix Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The six dimensions have been described separately: (δ1) cost-effectiveness analysis and cost-utility analysis-based pricing; (δ2) willingness-to-pay-based pricing; (δ3) reference-based pricing; (δ4) safety-based pricing; (δ5) risk of efficacy failure-based pricing; and (δ6) adherence-based pricing. The final step is to integrate the various dimension-specific pricing estimates into a composite estimate termed the All-Dimensional Price (ADP). We describe the methodology for this integration and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib.Materials and methodsFor better accuracy in estimating the ADP, we used the prices generated from the six dimensions at scenario levels, not at the dimension-specific price (DSP) level. We pooled the price estimates and performed Monte Carlo Simulations (MCS) for the price scenarios generated by the six dimensions. We used the results of the proof-of-concept exercise involving osimertinib in NSCLC with EGFR mutation to estimate the ADP in two hypothetical contracts: 1-year (2019–2020) and 2-year contract (2019–2021).ResultsThe average of the 30-day prescription estimates from the six dimensions averaged $10,819 (SD=$8,486) for the 1-year contract and $10,730 (SD=$8,500) for the 2-year contract. MCS yielded for the 1-year contract an ADP of $10,959 (or −25.02% the 2018 WAC price) and an ADP for the 2-year contract was $10,788 (or −26.19% the 2018 WAC price).ConclusionsWe demonstrated that the integration of the prices from the six dimensions of the Six Delta platform and market conditions is feasible and yields multidimensional prices estimates to support outcome-based pricing/contracting.

AbstractAimsSix Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The sixth dimension (δ6) estimates prices on the basis of adherence to the prescribed regimen, whereby manufacturers provide payers with adherence-enhancing programs and whereby payers implement these programs and provide adherence data to the manufacturer. We describe this dimension’s methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib.Materials and methodsWe propose two paybacks based on adherence: in-advance (based on clinical trial data) and in-arrear (based on real-world data). The risk of efficacy failure pricing dimension utilizes a 7-step method: 1) defining efficacy endpoints; 2) extracting data; 3) predicting models; 4) estimating in-advance and in-arrear paybacks; 5) suggesting ranges for in-advance and in-arrear paybacks; 6) adjusting for medical inflation; and 7) performing Monte Carlo Simulation (MCS) to estimate the DSPAdherence. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019–2020) and 2-year (2019–2021). The 2018 wholesale acquisition cost (WAC) for a 30-day prescription was used and inflated as needed. Herein, the DSPAdherenceis estimated exclusively in terms of in-advance payback because real-world data about osimertinib are not yet available and thus the in-arrear payback cannot yet be estimated.ResultsFor the 1-year contract, the average price for osimertinib was $13,798 (SD=$1,265) and the DSPAdherencewas $13,785 (or −5.69% of the 2018 WAC) for a 30-day prescription. For the 2-year contract, the average price was $12,555 (SD=$2,847) and the DSPAdherencewas $12,582 (or −13.92% of the 2018 WAC).ConclusionsWe demonstrated that adherence-based pricing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting. The proof-of-concept exercise needs to be expanded with the in-arrear pricing method based on real world data to be secured.

AbstractAimsSix Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fifth dimension (δ5) estimates prices on the basis of the risk of efficacy failure of a drug. We describe this dimension’s methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib.Materials and methodsThe risk of efficacy failure pricing dimension utilizes a seven-step method: (1) defining risk; (2) extracting data; (3) predicting models; (4) performing Monte Carlo Simulation (MCS) to estimate risk of efficacy failure; 5) estimating ranges for a payback; (6) adjusting for medical inflation; and (7) performing Monte Carlo Simulation (MCS) to estimate the DSPRisk of efficacy failure. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019–2020) and 2-year (2019–2021). We estimated the risk of efficacy failure for osimertinib in terms of overall and progression-free survival versus standard of care. We used the estimated risk to estimate the price reduction on the wholesale acquisition cost (WAC) for the two hypothetical contracts: a 1-year (2019–2020) and 2-year contract (2019–2021). From this we estimated the DSPRisk of efficacy failure.ResultsBased on the risk of OS and PFS efficacy failure for osimertinib in OS and PFS, in the 1-year contract, the DSPRisk of efficacy failurewas estimated at $12,652 (or −13.44% the 2018 WAC) for a 30-day prescription. For the 2-year contract (2019–2021), the DSPRisk of efficacy failurewas estimated at $13,019 (or −10.93% the 2018 WAC).ConclusionsWe demonstrated that pricing methods based on risk of efficacy failure methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

AbstractAimsSix Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The second dimension (δ2) estimates prices on the basis of four willingness-to-pay (WTP) thresholds. We describe this dimension’s methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib.Materials and methodsEight WTP scenarios based on four levels of real gross domestic product per capita (<1GDP/capita, 1 × GDP/capita, 3 × GDP/capita, and >3 × GDP/capita) and two market conditions (monopolistic versus competitive) were assumed. The incremental cost-utility ratio (ICUR) was applied to differently to both markets. In the monopolistic market, assuming no competitors, the cost/QALY ratio for a drug was used; whereas in the competitive market, assuming competitors, the incremental cost-utility ratio (ICUR) was applied. One-way sensitivity analyses were performed and predictive equations were specified to estimate the prices of treatment for the resulting eight WTP scenarios; for which subsequently the average and standard deviation were calculated. A gamma distribution was specified and Monte Carlo Simulation (MCS) was applied to estimate the dimension-specific price based on WTP (DSPWTP). A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019–2020) and 2-year (2019–2021). The 2018 wholesale acquisition cost (WAC) of $14,616 (30-day prescription) was used to estimate the DSPWTPfor each contract.ResultsThe 1-year estimates averaged $4,654 (SD=$6,462) and the MCS yielded a DSPWTPof $4,547 or −68.89% of the 2018 WAC for a 30-day prescription. The 2-year estimates averaged $4,7667 (SD=$6,480) with the MCS generating a DSPWTPof $4,704 or −67.82% of the WAC.ConclusionsWe demonstrated that WTP-based methods that include various WTP thresholds and market conditions generate price estimates across these thresholds and market conditions that can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

AbstractAimsSix Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The fourth dimension (δ4) estimates prices on the basis of assessments of the safety of the drug using an ex anteanalysis based on clinical trial data. We describe this dimension’s methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib.Materials and methodsThe safety-based pricing dimension utilizes a four-step method: 1) pooling adverse events (AE), standardizing, estimating 95%Cis, and adjusting for time; 2) estimating correction factors and corrected probabilities of AEs; 3) estimating the probability of at least one adverse event (AE) occurring and leading to treatment discontinuation; and 4) estimating ranges for payback percentages and performing Monte Carlo Simulation to estimate a DSPSafety. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019–2020) and 2-year (2019–2021). We estimated the DSPSafetybased on the grade 3/4 AEs observed for osimertinib and standard of care. The 2018 wholesale acquisition cost (WAC) of osimertinib at $14,616 for a 30-day prescription was used.ResultsAEs3/4 were retrieved from the FLAURA trial. In the 1-year contract, the DSPSafetyof osimertinib was estimated at $14,627 (or +0.08% the 2018 WAC) for a 30-day prescription. In the 2-year contract, the DSPSafetyof osimertinib was estimated at $14,516 (or −0.68% the 2018 WAC) for a 30-day prescription.ConclusionsWe demonstrated that ex antepricing methods-based paybacks for safety issues leading to treatment discontinuation can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

AbstractAimsSix Delta is a six-dimensional independent platform for outcome-based pricing/contracting. The third dimension (δ3) estimates prices on the basis of international drug price referencing methods. We describe this dimension’s methodology and present a proof-of-concept application to the treatment of non-small cell lung cancer (NSCLC) with EGFR mutation with osimertinib.Materials and methodsThe reference-based pricing dimension utilizes a six-step method: (1) selecting foreign countries based on a set of four criteria (drug is available in the foreign country, price information is available in the foreign country, foreign countries are members within the organization for Economic Co-operation and Development, pricing methods in the foreign countries involve value assessment); (2) adjusting for exchange rates; (3) generating reference price (RP) scenarios; (4) adjusting with the medical inflation rate; (5) pooling all generated RP scenarios and calculating average and standard deviation (SD); (6) and Monte Carlo Simulation (MCS) to estimate the dimension-specific DSPReference. A proof-of-concept exercise with osimertinib in NSCLC was performed for two hypothetical outcome-based contracts: 1-year (2019–2020) and 2-year (2019–2021).ResultsThe United Kingdom and Canada met the four criteria. For the osimertinib 1-year contract price, the average of eight RP scenarios, adjusted for inflation by 0.44%, was $8,892 (SD = $2,606) for a 30-day prescription. MCS yielded a DSPReferenceestimate of $9,395 or −35.72% of the wholesale acquisition cost (WAC) of $14,616. For the 2-year contract, the average, adjusted for inflation by 0.72%, was $8,928 (SD = $2,610). MCS yielded a DSPReferenceestimate of $9,442 or −35.40% of the WAC of $14,616.ConclusionsWe demonstrated that international price referencing methods can be integrated into our proposed Six Delta platform for outcome-based pricing/contracting.

Objectives:The purpose of this critical narrative review is to discuss the revised Starling equation for microvascular fluid exchange and the associated implications for intravenous fluid administration. Data Sources:PubMed (1946 to December 2019) and EMBASE (1947 to December 2019) were used, and bibliographies of retrieved articles were searched for additional articles. Study Selection and Data Extraction:Articles pertaining to the revised Starling equation and microvascular fluid exchange. Additionally, prospective human studies involving the disposition and oncotic action of radiolabeled albumin and large randomized trials comparing fluid requirements associated with isotonic crystalloid and albumin administration were included. Data Synthesis:In the revised Starling equation, oncotic forces act across the endothelial cell layer, more specifically between the fluid in the vessel lumen and the protein-sparse subglycocalyx space. The revised Starling equation and radiolabeled investigations of albumin necessitate a reconsideration of conventional views of the plasma-expanding properties of exogenous albumin. Large clinical trials demonstrate that the administration of iso-oncotic or hyper-oncotic albumin solutions in patients undergoing resuscitation does not have the reductions in fluid requirements anticipated from a traditional understanding of the oncotic actions of albumin. Relevance to Patient Care and Clinical Practice:When used as a resuscitation fluid, albumin does not have the degree of plasma expansion or intravascular retention commonly used to justify its use. Conclusions:The principles underlying the revised Starling equation in conjunction with data from radiolabeled studies of albumin and large clinical trials demonstrate that albumin does not have the perceived degree of plasma expansion or duration of intravascular retention beyond crystalloid solutions predicted by the classic Starling equation.

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This study aims to quantify the extent of electrolyte (potassium, magnesium, and phosphorus) and blood glucose changes during targeted temperature management (TTM), with insight on electrolyte replacements and insulin administration. This was a 3-year retrospective study of patients who underwent TTM via Arctic Sun. Electrolyte and blood glucose values in addition to electrolyte replacements and insulin administrations were collected before, during, and post-TTM. The primary analysis assessed changes in electrolyte and blood glucose values during and after TTM, and the secondary analysis assessed changes before and during, and before and after TTM. The secondary analysis also incorporated amount of electrolyte replacements and insulin administrations patients received before, during, and post-TTM. Sixty patients were included for analysis. Comparing levels during to after TTM, there was a significant increase in potassium (3.7 [0.7]–4.4 [0.7] mmol/L, p< 0.001) and decrease in blood glucose (192 [135]–134 [55] mg/dL, p= 0.001). Comparing levels before to during TTM, there was a significant decrease in potassium (4.3 [0.7]–3.7 [0.7] mmol/L, p< 0.001) and phosphorus (4.8 [3.2]–3.4 [1.5] mg/dL, p= 0.003). Comparing levels before to after TTM, there was a significant decrease in phosphorus (4.5 [2.9]–3.3 [1.2] mmol/L, p= 0.026) and blood glucose (219 [35]–134 [55] mg/dL, p< 0.001). Patients received on average potassium 102 mEq, magnesium 1.9 g, phosphorus 9 mmol, and insulin 94 units. Potassium significantly decreased during and significantly increased after TTM. Phosphorus significantly decreased during TTM and blood glucose significantly decreased after TTM. There were no significant changes in magnesium during the defined time period.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective:To evaluate the clinical and economic impact of a clinical pharmacist–led intervention strategy targeting inappropriate albumin in the ICU. Methods:A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results:A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use (P< 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively (P< 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance:Clinical pharmacist–led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.

Evaluation of clinical faculty involves an assessment of the quality of their publications in addition to quantity (number) of publications. In contrast to assessing quantity, assessing quality is difficult. The purpose of this paper is to discuss practical considerations and provide recommendations related to quality of publications that clinical faculty members should bear in mind as part of their overall scholarship activity. College and schools of pharmacy may not provide written criteria for assessing quality of publications, so it is important that clinical faculty members seek guidance from their department chair or direct supervisor, experienced colleagues, and formal or informal mentors or advisers. One criterion for assessing quality is whether a publication was evaluated through a peer-review process although there are other considerations including dissemination of the paper via search engines such as PubMed. Clinical faculty also need to consider authorship order on their papers and potential journals for submission.

Faculty retention is an issue of concern to schools and colleges of pharmacy. The reasons why faculty leave are multifactorial but often involve a breach of unwritten contract obligations between the faculty member and the organization. This article provides strategies for retaining faculty based on published literature that include perceived breaches of unwritten contracts and our own perspectives as departmental and university administrators and senior faculty members who have been involved in devising and implementing institutional change. Retention begins with recruitment but then needs to be nurtured during onboarding and as part of the overall enculturation process for new faculty members. Particular attention to the factors that influence the retention of underrepresented minorities must be incorporated to help ensure that pharmacy educators reflect the diversity of the US population.

Objective:To discuss why opioids have been considered the long-standing first-line therapy for treating acute, severe nociceptive pain in critically ill patients and discuss considerations for limiting opioid overuse in the intensive care unit setting. Data Sources:Articles were identified through searches of PubMed and EMBASE from database inception until December 2018. Additional references were located through a review of the bibliographies of articles and clinical practice guidelines. Study Selection and Data Extraction:Original research articles excluding case reports were included if they concerned nonopioid agents for pain management in critically ill patients. The focus was on studies not included in the most recent pain management guidelines. Data Synthesis:Ten studies were retrieved. Nonopioid therapies or opioid-sparing therapies have been touted as possible alternatives for critically ill patients, but they have particular adverse effects concerns in critically ill patients, often lack parenteral dosage forms, and frequently require dose adjustment or avoidance in patients with renal or hepatic dysfunction. Relevance to Patient Care and Clinical Practice:There is a well-recognized opioid epidemic that has been the subject of much discussion. Attempts to control the epidemic have focused on limiting opioid prescribing and using nonopioid alternatives, but there are special considerations when treating severe pain in critically ill patients that often preclude nonopioid analgesics. Conclusions:There continues to be an unmet need for medications that are as effective as opioids for severe nociceptive pain in critically ill patients but without the adverse effect and abuse concerns. Until such medications are available, clinicians need to optimize prescribing of opioid and nonopioid analgesics.

The transition of patients from the intensive care unit (ICU) to the ward is a complicated process and patients may be at risk of increased levels of pain.

Background:Acute kidney injury (AKI) commonly occurs in patients with sepsis. Acetaminophen (APAP) has been shown to inhibit lipid peroxidation and, thus, may be renal protective in patients with sepsis. Objective: The objective of this study was to determine the effect of APAP on AKI in patients with sepsis. Methods:This was a retrospective cohort study conducted at 2 affiliated academic medical centers in the United States. Adult patients who were admitted to the intensive care unit with a diagnosis of severe sepsis were included. Patients were categorized based on whether APAP was received within the first 7 days of hospitalization (APAP or no APAP groups). The primary outcome measure was occurrence or increase in AKI stage from admission. Multivariate logistic regression analyses were used to adjust for potential confounders. Results:There were 238 patients who were included in the study cohort. Of these, 122 received APAP and 116 did not receive APAP. AKI or exacerbation occurred in 16.4% (n = 20) of patients in the APAP group and 19.8% (n = 23) of patients in the no APAP group (P= 0.505). After adjusting for the most important confounders, there was no significant association between APAP use and AKI (odds ratio = 1.2; 95% CI = 0.6-2.4; P= 0.639). Conclusion:APAP use in critically ill patients with sepsis may not reduce the occurrence or exacerbation of AKI.

The purpose of this commentary is to discuss the qualifications, responsibilities, and keys to success for pharmacy faculty considering a department (or division) chair (head) or dean (including assistant or associate dean) position. The perspectives are those of a department chair, vice dean, and past dean of colleges of pharmacy with extensive experience in pharmacy administration. The qualifications for these administrative positions vary by institution, particularly with respect to the institution’s focus on research. Because the dean is the chief executive officer of a college of pharmacy, previous administrative experience is almost always a basic requirement for the position. For associate/assistant deans and department chairs, previous experience as a faculty member is a typical minimum requirement and may include experience as a department vice chair or director of a unit within the department or division. The dean has a fiduciary duty to university administration, as well as to other external and internal stakeholders, to educate and graduate competent pharmacists and to operate within budget. Associate/assistant deans often have responsibility for specific functions of the college, such as student or professional affairs, and it is common for deans to delegate authority, responsibility, and accountability to associate/assistant deans. Department chairs have a unique perspective with respect to college activities because they must not only think about the “big picture” when considering issues with other college administrators but must oversee the implementation and monitoring of strategic initiatives through the faculty and staff who report to them.

Critical care clinicians are likely to see an increasing number of patients admitted to the ICU who are receiving Food and Drug Administration-approved medications for opioid use disorder (MOUDs) given the well-documented benefits of these agents. Oral methadone, multiple formulations of buprenorphine, and extended-release naltrexone are the three types of MOUD most likely to be encountered by ICU clinicians; however, these drugs vary with respect to formulations, pharmacokinetics, and adverse effects.

Despite the availability of multiple nonheparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT), few data are available comparing the cost-effectiveness of these agents. This analysis is particularly important when considering differences in the risk of adverse effects, routes of administration, requirements for phlebotomy and laboratory monitoring, and overall drug costs. We conducted a cost-effectiveness analysis of argatroban, bivalirudin, and fondaparinux for the treatment of suspected HIT from the institutional perspective. A 3-arm decision-tree model was developed that employs standard practices for anticoagulation monitoring. We incorporated published data on drug efficacy and probability of HIT-related thromboembolism and major bleeding. We considered both institutional costs and average wholesale price (AWP) and performed probabilistic sensitivity analyses (PSA) to address any uncertainty in model parameters. Using institutional costs, fondaparinux prevailed over both argatroban and bivalirudin in terms of cost ($151 vs $1250 and $1466, respectively) and adverse events averted (0.9989 vs 0.9957 and 0.9947, respectively). Results were consistent when AWP was used, with fondaparinux being less expensive ($555 vs $3081 and $2187, respectively) and more effective in terms of adverse events averted (0.9989 vs 0.9957 and 0.9947, respectively). The PSA confirmed our findings using both institutional costs and AWP. In conclusion, fondaparinux subcutaneous injection afforded significant advantages in terms of cost savings and adverse events averted compared with IV argatroban or bivalirudin infusions. Our data strongly suggest potential cost savings with fondaparinux and underscore the critical need for larger clinical studies of fondaparinux in the treatment of suspected HIT.

The purpose of this narrative review is to provide practical and useful guidance for clinicians considering the use of intravenous ketamine for its analgosedative properties in adult, critically ill patients.