Translating Clinical Decision-Making Skills From a Critical Care Pharmacy Elective to the Required Curriculum.

OBJECTIVE: To examine the impact of a critical care pharmacy elective (CCPE) on student performance in other courses in the Doctor of Pharmacy curriculum that emphasize clinical reasoning and decision making. METHODS: This is a retrospective, cohort study including all students from the 2019-2021 graduating classes enrolled in required courses, Pharmacotherapy and Integrated Patient Cases (IPCs). Students were divided for comparison based on completion of the CCPE. The primary outcome was outstanding performance, defined by a final course grade ≥90%, in Pharmacotherapy and IPC. Baseline characteristics and outcomes were analyzed using descriptive statistics and the χ2 test or two-sided t test for categorical and continuous variables, respectively. Binary logistic regression models were constructed to identify variables associated with the primary outcome. RESULTS: Of 377 students included, 129 (34%) completed the CCPE. Baseline characteristics were similar between both groups, except more females completed the CCPE. Students that completed the CCPE were not more likely to demonstrate outstanding performance in Pharmacotherapy III (20% vs 30%) or Pharmacotherapy IV (27% vs 24%), but were more likely in IPC (34% vs 23%). In the adjusted analysis, CCPE students were almost twice as likely to exhibit outstanding performance in IPC. CONCLUSION: Students that completed the CCPE were more likely to demonstrate outstanding performance in IPC, but not in either of the Pharmacotherapy courses. Students may benefit from practicing clinical reasoning earlier in the curriculum to build-up to effective and efficient clinical decision-making. Implications of course structure on student performance should be further explored.

Caring for two in the ICU: Pharmacologic management of pregnancy-related complications.

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

Controlling cleaning agent residues in pharmaceutical manufacturing: A harmonized scientific strategy.

This paper proposes a scientifically justified and harmonized strategy to control cleaning agent ingredients' (CAIs) residues in pharmaceutical manufacturing. Firstly, we demonstrate that worst-case cleaning validation calculations on CAI residues with representative GMP standard cleaning limits (SCLs) are enough to control CAI residues of low concern to safe levels. Secondly, a new harmonized strategy for the toxicological assessment of CAI residues is presented and validated. The results establish a framework applicable to cleaning agent mixtures based on hazard and exposure considerations. This framework is primarily based on the hierarchy of a single CAI's critical effect, where the lowest resulting limit may become the driver of the cleaning validation process. The six critical effect groups are: (1) CAIs of low concern based on safe exposure reasoning; (2) CAIs of low concern based on the mode of action reasoning; (3) CAIs with local concentration-dependent critical effects; (4) CAIs with dose-dependent systemic critical effects for which a route-specific PDE should be calculated; (5) poorly characterized CAIs with unknown critical effect for which a default value of 100 µg/day is proposed; (6) poorly characterized CAIs which should be avoided because of potential mutagenicity and/or potency.

Caring for two in the ICU: Pharmacotherapy in the critically ill pregnant patient.

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

Sedative Choice: The Chilling Confounder to Targeted Temperature Management.

Targeted temperature management (TTM) is a technique used in adults who lack a meaningful response after the return of spontaneous circulation following cardiac arrest (CA). The implementation of TTM is believed to improve neurological outcomes by decreasing cerebral metabolism, reducing apoptosis, and lowering oxygen demand. While this technique is recommended as a part of advanced cardiovascular life support (ACLS), there is a lack of consistency regarding drug choice and depth of sedation in TTM. In this report, the authors provide a review of the myriad of regimens outlined in research protocols and current guidelines to stimulate discussion and promote further studies pertaining to sedation strategies in TTM. Through this call to action, the ultimate goal is to develop a uniform approach to bedside practice.

Effects of Propofol on Hemodynamic Profile in Adults Receiving Targeted Temperature Management.

Background: Propofol is a key component for the management of sedation and shivering during targeted temperature management (TTM) following cardiac arrest. The cardiac depressant effects of propofol have not been described during TTM and may be especially relevant given the stress to the myocardium following cardiac arrest. The purpose of this study is to describe hemodynamic changes associated with propofol administration during TTM. Methods: This single center, retrospective cohort study evaluated adult patients who received a propofol infusion for at least 30 minutes during TTM. The primary outcome was the change in cardiovascular Sequential Organ Failure Assessment (cvSOFA) score 30 minutes after propofol initiation. Secondary outcomes included change in systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and vasopressor requirements (VR) expressed as norepinephrine equivalents at 30, 60, 120, 180, and 240 minutes after propofol initiation. A multivariate regression was performed to assess the influence of propofol and body temperature on MAP, while controlling for vasopressor dose and cardiac arrest hospital prognosis (CAHP) score. Results: The cohort included 40 patients with a median CAHP score of 197. The goal temperature of 33°C was achieved for all patients. The median cvSOFA score was 1 at baseline and 0.5 at 30 minutes, with a non-significant change after propofol initiation (P = .96). SBP and MAP reductions were the greatest at 60 minutes (17 and 8 mmHg; P < .05 for both). The median change in HR at 120 minutes was -9 beats/minute from baseline. This reduction was sustained through 240 minutes (P < .05). No change in VR were seen at any time point. In multivariate regression, body temperature was the only characteristic independently associated with changes in MAP (coefficient 4.95, 95% CI 1.6-8.3). Conclusion: Administration of propofol during TTM did not affect cvSOFA score. The reductions in SBP, MAP, and HR did not have a corresponding change in vasopressor requirements and are likely not clinically meaningful. Propofol appears to be a safe choice for sedation in patients receiving targeted temperature management after cardiac arrest.

Putting midodrine on the MAP: An approach to liberation from intravenous vasopressors in vasodilatory shock.

PURPOSE: Prolonged duration of intravenous (IV) vasopressor dependence in critically ill adult patients with vasodilatory shock results in increased length of stay in both the intensive care unit (ICU) and hospital, translating to higher risk of infection, delirium, immobility, and cost. Acceleration of vasopressor liberation can aid in reducing these risks. Midodrine is an oral α 1-adrenergic receptor agonist that offers a potential means of liberating patients from IV vasopressor therapy. This clinical review summarizes primary literature and proposes a clinical application for midodrine in the recovery phase of vasodilatory shock. SUMMARY: Five studies with a total of over 1,000 patients conducted between 2011 and 2021 were identified. In observational studies, midodrine administration was demonstrated to lead to faster time to liberation from IV vasopressor therapy and shorter ICU length of stay in patients recovering from vasodilatory shock. These findings were not replicated in a prospective, multicenter, randomized controlled trial. In this review, literature evaluating midodrine use for IV vasopressor liberation is summarized and study limitations are discussed. CONCLUSION: On the basis of this review of current literature, recommendations are provided on selecting appropriate candidates for adjunctive midodrine in the recovery phase of vasodilatory shock and considerations are discussed for safely and effectively initiating, titrating, and discontinuing therapy.

PDE concept for controlling cleaning agent residues in pharmaceuticals- A critical analysis.

Cleaning agents (CAs) are used in multipurpose facilities to control carryover contamination of active pharmaceutical ingredients (APIs) to scientifically justified limits. While this is often done with the PDE methodology used for API impurities, it is unclear if it is justifiable and necessary for cleaning agents, which generally represent a comparatively lower health risk. Comparing calculated oral PDE values for CA ingredients (CAIs) from four companies with PDEs of a selected number of small-molecule APIs showed that the toxicity of CAIs is several orders of magnitude lower. Furthermore, a critical review of the toxicity and everyday exposure to the general population of the main CAIs functional groups showed that the expected health risks are generally negligible. This is particularly true if the associated mode of actions cause local toxicity that is usually irrelevant at the concentration of potential residue carryover. This work points towards alternative approaches to the PDE concept to control CAIs' contamination and provides some guidance on grouping and identifying compounds with lower health risks based on exposure and mode of action reasoning. In addition, this work supports the concept that limit values should only be set for CAIs of toxicological concern.

From theory to bedside: Implementation of fluid stewardship in a medical ICU pharmacy practice.

PURPOSE: Intravenous fluids are the most commonly prescribed medication in the intensive care unit (ICU) and can have a negative impact on patient outcomes if not utilized properly. Fluid stewardship aims to heighten awareness and improve practice in fluid therapy. This report describes a practical construct for implementation of fluid stewardship services and characterizes the pharmacist's role in fluid stewardship practice. SUMMARY: Fluid stewardship services were integrated into an adult medical ICU at a large community hospital. Data characterizing these services over a 2-year span are reported and categorized based on the 4 rights (right patient, right drug, right route, right dose) and the ROSE (rescue, optimization, stabilization, evacuation) model of fluid administration. The review encompassed 305 patients totaling 905 patient days for whom 2,597 pharmacist recommendations were made, 19% of which were related to fluid stewardship. This corresponded to an average of 1.52 fluid stewardship recommendations per patient. Within the construct of the 4 rights, 39% of recommendations were related to the right patient, 33% were related to the right route, 17% were related to the right drug, and 11% were related to the right dose. By the ROSE model, 1% of recommendations were related to the rescue phase, 3% were related to optimization, 79% were related to stabilization, and 17% were related to evacuation. CONCLUSION: Implementation of fluid stewardship pharmacy services in a community hospital medical ICU is feasible. Integration of this practice contributed to 19% of pharmacy recommendations. The most common recommendations involved evaluation of the patient for the appropriateness of fluid therapy during the stabilization phase. The impact of fluid stewardship on patient outcomes needs to be explored.

Fluid Stewardship of Maintenance Intravenous Fluids.

Despite the frequent use of maintenance intravenous fluids (mIVF) in critically ill patients, limited guidance is available. Notably, fluid overload secondary to mIVF mismanagement is associated with significant adverse patient outcomes. The Four Rights (right drug, right dose, right duration, right patient) construct of fluid stewardship has been proposed for the safe evaluation and use of fluids. The purpose of this evidence-based review is to offer practical insights for the clinician regarding mIVF selection, dosing, and duration in line with the Four Rights of Fluid Stewardship.

Scholastic synergy: A team prototype for pharmacy faculty engagement in education, research, and service.

INTRODUCTION: Many clinical faculty members are challenged by competing factors of scholarly productivity, education, service obligations, and patient care. A team-based approach has the potential to synergistically increase productivity and mitigate factors associated with burnout. METHODS: The purpose of this report is to discuss a prototype for a small, team-based, practice-oriented collaborative approach to advancing critical care pharmacy practice through research and education. Productivity was evaluated in the areas of scholarship and teaching. RESULTS: This team was formed in 2017 and includes five critical care faculty across four campuses from a single academic institution. This collaborative has published peer-reviewed articles, secured grant funding, and developed novel teaching modalities. CONCLUSIONS: Challenges encountered include timeline adherence, development of uniform data collection processes, clarifying roles and expectations for different projects, and authorship. This team may act as a prototype for clinical faculty teams to enhance engagement and scholarship productivity in a practice-based setting.

Low Prevalence of Thrombosis Prophylaxis Dose Adjustments Highlights Implications for Patient Safety.

Background: Pharmacologic thromboprophylaxis (PTP) is the mainstay prevention strategy for venous thromboembolism (VTE). PTP agents traditionally dosed, like unfractionated heparin (UFH) and enoxaparin (ENOX), are associated with failure and bleeding in obese and underweight patients, respectively. Objectives: This study aimed to describe the prevalence of unadjusted ENOX and UFH dosing for PTP based on anthropometric measures. Patients/Methods:This was a post-hoc, multicenter, cross-sectional analysis of critically ill adults receiving PTP with ENOX or UFH. The primary outcome was the prevalence of unadjusted PTP based on body mass index (BMI) and total body weight (TBW). Definitions for dose adjustments were developed based on existing literature. A secondary outcome was to identify factors associated with unadjusted dosing per BMI and TBW using multivariable generalized linear mixed-effect models. Results: The nested cohort included 172 patients (ENOX=46, UFH=126). Unadjusted PTP was observed in 118 patients (68.6%) based on BMI and 74 (43%) per TBW. When comparing UFH to ENOX, more patients who received UFH had doses unadjusted by BMI (78.6% vs. 41.3%, p<0.05) but not TBW (43.7% vs. 41.3%). Factors independently associated with unadjusted PTP per BMI were receipt of UFH (OR 6.93, 95% CI 1.06-8.77) or a BMI underweight or overweight/obese (OR 10.45, 95% CI 4.38-24.92). Having a TBW <50kg or >100kg (OR 4.85, 95% CI 2.15-10.96) were independently associated with unadjusted PTP based on TBW. Conclusions: Unadjusted dosing of PTP occurs frequently in critically ill adults receiving ENOX or UFH. This was seen in body size extremes by both BMI and TBW.

Association of hidden fluid administration with development of fluid overload reveals opportunities for targeted fluid minimization.

BACKGROUND: Fluid overload is associated with poor outcomes, but mitigating its occurrence poses significant challenges. OBJECTIVE: This study sought to assess the impact of hidden fluid volume on fluid overload. METHODS: This study was a multi-center, retrospective evaluation of adults admitted to a medical or surgical intensive care unit for at least 72 h. Patients were divided into tertiles (low, moderate, and high) based on the hidden fluid volume received. Hidden fluids were defined as intravenous medications, line flushes, blood products, and enteral nutrition. The primary outcome was the incidence of fluid overload at intensive care unit (day 3). Secondary outcomes included mechanical-ventilation free days and association of hidden fluid volume with fluid overload, length of stay, and mortality. RESULTS: A total of 219 (73 per tertile) were included, with hidden fluid volume comprising ⩽2500, 2501-4400, and >4400 mL in the low, moderate, and high tertiles, respectively. Incidence of fluid overload was significantly different across groups (low: 3%, moderate: 14%, high: 25%; p < 0.001). No difference existed in mechanical-ventilation free days or in-hospital mortality across tertiles. In binary logistic regression, hidden fluid volume received at 3 days was independently associated with fluid overload (odds ratio = 1.40, 95% confidence interval = 1.15-1.70). CONCLUSION: The volume of hidden fluid volume administered by intensive care unit day 3 independently predicted development of fluid overload.

Teaching research skills to student pharmacists: A multi-campus, multi-semester applied critical care research elective.

BACKGROUND AND PURPOSE: Research electives are commonly offered in doctor of pharmacy programs but are typically limited to one faculty member mentoring individual students at a single site for a semester long self-study experience. The purpose of this paper is to describe pharmacy student experiences and perceptions of the research process after completing a multi-campus, multi-investigator critical care research elective. EDUCATIONAL ACTIVITY AND SETTING: The Research in Critical Care Pharmacotherapy elective was launched in spring 2019 and implemented a novel approach to the pharmacy research elective that promoted collaborative research across four campuses that may be continued for up to four semesters of credit. FINDINGS: Six second- and third-year doctor of pharmacy students enrolled in the course during the first offering. Three students were located on the main campus with one student on each of the extended campuses. Students completed a median of five unique research activities with at least one student participating in 15 of the 19 activities evaluated. Students were asked to complete a pre- and post-course survey assessing perceived research abilities using the Dreyfus model. There was a significant decrease in the number of novice responses in the post-course survey (pre- 10 vs. post- 2, p = 0.043). SUMMARY: A multi-campus, multi-investigator critical care research elective provided broad research experiences and increased student confidence related to numerous research skills.

Fluid Stewardship During Critical Illness: A Call to Action.

Intravenous fluids (IVFs) are the most common drugs administered in the intensive care unit. Despite the ubiquitous use, IVFs are not benign and carry significant risks associated with under- or overadministration. Hypovolemia is associated with decreased organ perfusion, ischemia, and multi-organ failure. Hypervolemia and volume overload are associated with organ dysfunction, delayed liberation from mechanical ventilation, and increased mortality. Despite appropriate provision of IVF, adverse drug effects such as electrolyte abnormalities and acid-base disturbances may occur. The management of volume status in critically ill patients is both dynamic and tenuous, a process that requires frequent monitoring and high clinical acumen. Because patient-specific considerations for fluid therapy evolve across the continuum of critical illness, a standard approach to the assessment of fluid needs and prescription of IVF therapy is necessary. We propose the principle of "fluid stewardship," guided by 4 rights of medication safety: right patient, right drug, right route, and right dose. The successful implementation of fluid stewardship will aid pharmacists in making decisions regarding IVF therapy to optimize hemodynamic management and improve patient outcomes. Additionally, we highlight several areas of focus for future research, guided by the 4 rights construct of fluid stewardship.

Twelve Tips for Synergistic Delivery of Remote Advanced Pharmacy Practice Experience Rotations.

This article was migrated. The article was marked as recommended. In response to the COVID-19 pandemic, many institutions changed their staffing models to incorporate remote work which created a need for pharmacy faculty and preceptors to also shift their rotation experience to a remote format. While initially this may be a daunting task, remote experiences have the potential to equip students with unique skillsets while offering a mutually beneficial effort towards patient care and/or other responsibilities. In addition, these remote experiences can offer students a more customized rotation and a behind the scenes look at the preceptor's career. This article provides 12 tips for developing a remote learning experience.