The Role of a Pharmacy Administration and Leadership Rotation within Postgraduate Year Two Critical Care Residency Training.

Introduction: The job of a critical care pharmacy specialist has evolved to include quality improvement and administrative tasks. As such, the American Society of Health-System Pharmacists (ASHP) highlights specific goals and objectives to ensure post-graduate year two (PGY2) critical care residents are sufficiently trained to perform these tasks. The PGY2 critical care pharmacy residency leadership at the University of Kentucky sought to develop a four-week learning experience entitled, "Critical Care Administration / Medication Use Quality & Outcomes," as a unique rotation to capture these requirements and activities. Objectives: The focus of this commentary is to serve as a guide for other residency programs to develop such a rotation, highlight resulting resident contributions to the department, describe perceived benefits of this rotation for residents, and highlight how this rotation impacted graduated residents' early years as practitioners. Conclusions: This learning experience is pivotal to providing a more balanced view of the entire medication use process and the healthcare ecosystem during a specialty residency. PGY2 critical care residents can gain valuable experiences away from the bedside that better prepare them for future tasks in addition to patient care that will be expected of them as clinical pharmacists.

Niche Roles for Dexmedetomidine in the Intensive Care Unit.

OBJECTIVE: Review dexmedetomidine use in critically ill patients for niche indications including sleep, delirium, alcohol withdrawal, sepsis, and immunomodulation. DATA SOURCES: Literature was sought using PubMed (February 2012-November 2022). Search terms included dexmedetomidine AND (hypnotics OR sedatives OR sleep OR delirium OR immunomodulation OR sepsis OR alcohol withdrawal). STUDY SELECTION AND DATA EXTRACTION: Relevant studies conducted in humans ≥18 years published in English were included. Exclusion criteria included systematic reviews, meta-analyses, and studies evaluating oral dexmedetomidine or other alpha-2 agonists. DATA SYNTHESIS: A total of 231 articles were retrieved. After removal of duplicates, title and abstract screening, and application of inclusion criteria, 35 articles were included. Across the clinical conditions included in this review, varying clinical outcomes were seen. Dexmedetomidine may improve morbidity outcomes in delirium, sleep, and alcohol withdrawal syndrome. Due to limited human studies and poor quality of evidence, no conclusions can be drawn regarding the role of dexmedetomidine in immunomodulation or sepsis. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review presents data for potential niche roles of dexmedetomidine aside from sedation in critically ill patients. This may serve as a guide for sedation selection in critically ill patients who may also benefit from the pleiotropic effects of dexmedetomidine due to a clinical condition discussed in this review. CONCLUSION: While further studies are needed, dexmedetomidine may provide benefit in other indications in critically ill patients including delirium, sleep, and alcohol withdrawal. Given the poor quality of evidence of dexmedetomidine use in immunomodulation and sepsis, no conclusions can be drawn.

Comparison of Bivalirudin Versus Unfractionated Heparin for Anticoagulation in Adult Patients on Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) contributes to coagulopathy, necessitating systemic anticoagulation to prevent thrombosis. Traditionally, unfractionated heparin (UFH) has been the anticoagulant of choice, however, due to many inadequacies new evidence suggests benefit with the use of direct thrombin inhibitors. This retrospective cohort sought to evaluate the safety and efficacy of bivalirudin compared to UFH in ECMO patients. Primary endpoints included incidence of bleeding and thrombosis. Percent time in therapeutic range (TR), time to achieve TR and number of dose titrations required to maintain TR were calculated to assess efficacy of institutional protocols. Overall incidence of thrombosis was low, with one event in the bivalirudin group and no events in the UFH group. No difference was found in rates of bleeding between groups (6% vs . 10%, P = 0.44). Bivalirudin yielded higher percent time in TR (86% vs. 33%, P < 0.001), faster time to TR (2 vs . 18 hr, P < 0.001) and required fewer dose adjustments to maintain TR (2 vs . 11, P < 0.001) compared to UFH. These results suggest bivalirudin and UFH are associated with similar rates of bleeding and thrombosis in patients requiring ECMO support. Our results demonstrate the favorable pharmacokinetic profile of bivalirudin, and its ability to consistently maintain TR when compared to UFH.

Cisatracurium Continuous Infusion Versus No Neuromuscular Blockade for Acute Respiratory Distress Syndrome on Venovenous Extracorporeal Membrane Oxygenation.

The benefit of continuous infusion neuromuscular blockade concurrently with venovenous (VV) extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome who are receiving mechanical ventilation remains unclear. Adult patients with severe acute respiratory distress syndrome requiring VV ECMO were analyzed in 2 groups: continuous infusion neuromuscular blockade with cisatracurium vs no neuromuscular blockade. Similar mechanical ventilation strategies were used. The primary end point was duration of VV ECMO. This single-center, retrospective observational cohort included a total of 47 patients, 28 of whom received continuous infusion cisatracurium and 19 patients who did not receive neuromuscular blockade. There was no difference in the duration of VV ECMO in patients who received cisatracurium, 226.5 hours (interquartile range, 119-362.3) vs 187.0 hours (interquartile range, 108-374) in the group who did not receive a paralytic (P = .64). There were no differences in secondary outcomes of days in the hospital, days free of organ dysfunction, ECMO survival, or discharged alive. Among patients with severe ARDS who were managed with VV ECMO, patients who received continuous infusion cisatracurium had no difference in the duration of VV ECMO compared to the nonparalytic comparator group.

The effects of propofol on extracorporeal membrane oxygenation oxygenator exchange.

The objective of this study was to determine if propofol administration to veno-venous (VV) extracorporeal membrane oxygenation (ECMO) patients was associated with more incidents of oxygenator failure when compared to patients who did not receive propofol. This was a single center, retrospective cohort study. The primary outcome of the study is oxygenator exchanges per ECMO day in patients who received propofol versus those who did not receive propofol. Patients were 18 years or older on VV-ECMO support between January 1, 2015 and January 31, 2018. Patients were excluded if they required ECMO support for less than 48 h or greater than 21 days. There were five patients in the propofol arm that required oxygenator exchanges and seven patients in the control arm. The total number of oxygenator exchanges per ECMO day was not significantly different between groups (p = 0.50). When comparing those who required an oxygenator exchange and those who did not, there was no difference in the cumulative dose of propofol received per ECMO hour (0.64 mg/kg/h vs 0.96 mg/kg/h; p = 0.16). Propofol use in patients on VV-ECMO does not appear to increase the number of oxygenator exchanges.

Ascorbic Acid in the Acute Care Setting.

Ascorbic acid (AA) is an essential nutrient with many physiologic roles not limited to the prevention of scurvy. Beyond its role as a supplement, it has gained popularity in the acute care setting as an inexpensive medication for a variety of conditions. Because of limitations with absorption of oral formulations and reduced serum concentrations observed in acute illness, intravenous (IV) administration, and higher doses, may be needed to produce the desired serum concentrations for a particular indication. Following a PubMed search, we reviewed published studies relevant to AA in the acute care setting and summarized the results in a narrative review. In the acute care setting, AA may be used for improved wound healing, improved organ function in sepsis and acute respiratory distress syndrome, faster resolution of vasoplegic shock after cardiac surgery, reduction of resuscitative fluids in severe burn injury, and as an adjunctive analgesic, among other uses. Each indication differs in its level of evidence supporting exogenous administration of AA, but overall, AA was not commonly associated with adverse effects in the identified studies. Use of AA remains an active area of clinical investigation for various indications in the acute care patient population.

Comparison of Low- Versus High-Dose Four-Factor Prothrombin Complex Concentrate (4F-PCC) for Factor Xa Inhibitor-Associated Bleeding: A Retrospective Study.

BACKGROUND: Although andexanet alfa was recently approved as a specific reversal agent for apixaban and rivaroxaban, some providers still elect to administer 4-factor prothrombin complex concentrate (4F-PCC) instead, due to concerns surrounding efficacy, thrombotic risk, administration logistics, availability, and cost. Previous studies have described success with 4F-PCC doses ranging from 25 to 35 U/kg, with some guidelines recommending 50 U/kg. OBJECTIVES: The purpose of this study was to compare hemostasis between patients receiving low- (20-34 U/kg) versus high-dose (35-50 U/kg) 4F-PCC for the urgent reversal of apixaban and rivaroxaban. PATIENTS/METHODS: We performed a retrospective cohort study at a level one trauma center and comprehensive stroke center between January 2015 and December 2018. Main exclusion criteria included patients receiving less than 20 U/kg or if postreversal imaging were unavailable. Outcomes assessed included hemostasis for critical bleeding associated with apixaban or rivaroxaban and postoperative bleeding for reversal for emergent procedures. RESULTS: The low-dose strategy was administered to n = 57 (57.6%) patients at a mean dose of 26.6 U/kg. The high-dose strategy was used in n = 42 (42.4%) patients at a mean dose of 47.6 U/kg. There was no difference in hemostasis by dosing strategy (75.4% vs 78.6%, P = .715) or hospital mortality (19.3% vs 35.7%, P = .067). No difference was found for secondary end points, including thrombotic events (5.3% vs 2.4%, P = .635) and hospital length of stay (11.3 vs 12.5 days, P = .070). CONCLUSIONS: Our comparison addresses a gap in the literature surrounding optimal dosing and supports a similar efficacy profile between dosing low- versus high-dose treatment.

Comparison of Venous Thromboembolism Prophylactic Measures Post Coronary Artery Bypass Graft Surgery.

BACKGROUND: There is considerable debate surrounding venous thromboembolism (VTE) prophylaxis in patients post coronary artery bypass grafting (CABG) procedures. The American College of Chest Physicians guidelines report weak recommendations for starting VTE prophylaxis, but provide no specific guidance regarding timing or preferred prophylactic agent. METHODS: This retrospective cohort study was designed to compare outcomes of post-cardiac surgery patients admitted to the cardiovascular intensive care unit (ICU) who received subcutaneous unfractionated heparin (UFH), with those who received subcutaneous enoxaparin for VTE prophylaxis. Between January 2013 and September 2017, 1085 patients were identified, and, after propensity score matching, 850 patients were selected for analysis. The primary outcomes were postoperative VTE and the occurrence of bleeding events up to 30 days postoperatively. Secondary outcomes included chest tube output, days mechanically ventilated, ICU length of stay, total hospital length of stay, and 30-day readmission rates. RESULTS: During the study period, rates of 2.03% for VTE events and 1.38% for bleeding events were reported in the entire cohort. After matching, the rates of VTE events (2.12% vs. 1.41%, p = 0.43) and bleeding events (1.18% vs. 0.94%, p = 1.00) were more frequent in the heparin group versus the enoxaparin group; these differences were not statistically significant. However, we did find a statistically significant increase in several secondary endpoints, including chest tube output, days mechanically ventilated, ICU length of stay, and total hospital length of stay, within the heparin cohort. Bleeding rates were similar to those previously published, despite the early initiation of VTE prophylaxis. CONCLUSIONS: We report no statistical difference in the rates of VTE or bleeding between chemical agents, but our results suggest enoxaparin may be a preferred agent over UFH.

Overview of Pharmacological Considerations in Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation has become more widely used in recent years. Although this technology has proven to be lifesaving, it is not devoid of complications contributing to significant morbidity and mortality. Nurses who care for patients receiving extracorporeal membrane oxygenation should further their understanding of changes in medication profiles due to complex interactions with the extracorporeal membrane oxygenation circuitry. The aim of this comprehensive review is to give nurses a better understanding of analgesic, sedative, anti-infective, and anticoagulation medications that are frequently used to treat patients receiving extracorporeal membrane oxygenation.

Moderate-Intensity Insulin Therapy Is Associated With Reduced Length of Stay in Critically Ill Patients With Diabetic Ketoacidosis and Hyperosmolar Hyperglycemic State.

OBJECTIVES: Insulin infusion therapy is commonly used in the hospital setting to manage diabetic ketoacidosis and hyperosmolar hyperglycemic state. Clinical evidence suggests both hypoglycemia and glycemic variability negatively impact patient outcomes. The hypothesis of this study was that moderate-intensity insulin therapy decreases hospital length of stay and prevalence of hypoglycemia in patients with diabetic ketoacidosis and hyperosmolar hyperglycemic state. DESIGN: Pre-post study. SETTING: Large academic medical center in the United States. PATIENTS: Two-hundred one consecutive, nonpregnant, adult patients admitted for diabetic ketoacidosis and hyperosmolar hyperglycemic state between October 2010 and December 2014. INTERVENTIONS: High-intensity insulin therapy versus moderate-intensity insulin therapy. High-intensity insulin therapy was designed to rapidly normalize blood glucose levels with bolus doses of insulin and rapid insulin titration. Moderate-intensity insulin therapy was designed to mitigate glycemic variability and hypoglycemia through avoidance of bolus dosing, a liberalized blood glucose target, and gradual insulin titration. MEASUREMENTS AND MAIN RESULTS: Hospital and ICU length of stay were reduced by 23.6% and 38%, respectively. The relative risk of remaining in the hospital at day 7 (0.51; p = 0.022) and day 14 (0.28; p = 0.044) were significantly reduced by the moderate-intensity insulin therapy strategy. The relative risk of remaining in the ICU at 48 hours was significantly lower in the moderate-intensity insulin therapy cohort (0.34; p = 0.0048). The prevalence (35% vs 1%; p = 0.0003) and relative risk (0.028; p = 0.0004) of hypoglycemia were significantly lower in the moderate-intensity insulin therapy cohort. Glycemic variability decreased by 28.6% (p < 0.0001). There was no difference in the time to anion gap closure (p = 0.123). CONCLUSIONS: Moderate-intensity insulin therapy for diabetic ketoacidosis and hyperosmolar hyperglycemic state resulted in improvements in hospital and ICU length of stay, which appeared to be associated with decreased glycemic variability.

Enteral Guanfacine to Treat Severe Anxiety and Agitation Complicating Critical Care After Cardiac Surgery.

This article is the first reported case describing the off-label use of enteral immediate-release guanfacine, a long-acting α-2 adrenergic agonist most commonly used in the treatment of attention-deficit hyperactivity disorder, for sedation in a patient with severe anxiety and agitation limiting mechanical ventilation weaning several days after cardiac surgery. In this case, after several days of unsuccessful attempts to control his agitation and anxiety with conventional therapies, guanfacine therapy was initiated, and the patient was rapidly weaned from all other sedatives and mechanical ventilation shortly thereafter. The patient was weaned from guanfacine therapy without evidence of bradycardia, hypotension, or rebound syndrome. Enteral guanfacine therapy should be further studied as a potentially useful and cost-effective sedative therapy for patients with severe anxiety and/or agitation in the intensive care unit following cardiac and thoracic surgical procedures.

Factor VIIa administration in orthotopic heart transplant recipients and its impact on thromboembolic events and post-transplant outcomes.

Recombinant, activated factor VIIa (rFVIIa) is used during cardiac surgeries to mitigate refractory coagulopathic bleeding. The purpose of this study was to examine whether rFVIIa use in orthotopic heart transplant (OHT) recipients was associated with a higher incidence of thromboembolic (TE) events compared to patients who did not. A single-center, retrospective, cohort study was performed on OHT recipients who received rFVIIa for refractory coagulopathic bleeding from January 2013 to December 2015. Patients were evaluated for up to 6 months after transplantation and assessed for TE events, rejection, readmissions, graft survival, and patient survival. Categorical variables were analyzed using the Chi square test while student's t or ANOVA testing was utilized for continuous variables. Of the 62 patients who met inclusion criteria, 27 patients received rFVIIa, and 35 patients were selected for the control group. The overall incidence of TE events was not significantly different between patients who received rFVIIa compared to patients in the control group (14.8% vs 11.4%) (p = 0.69). Within 14 days, 14.81% of rFVIIa patients suffered a TE event compared to 5.7% of the control group (p = 0.23). Rejection, readmissions, graft survival, and patient survival were not significantly different at any time points. Use of rFVIIa in heart transplantation showed no difference in the overall rate of TE events, however, there was a nonsignificant trend toward higher risk of early TE development in the rFVIIa group compared to the control group.

Evaluating the impact of obesity on safety and efficacy of weight-based norepinephrine dosing in septic shock: A single-center, retrospective study.

OBJECTIVE: Norepinephrine is the first-line vasopressor recommended for patients in septic shock. Weight-based dosing may increase drug exposure and the risk of adverse effects in obese patients. The objective was to evaluate the safety and efficacy of weight-based norepinephrine dosing using actual body weight in the morbidly obese compared with normal weight patients. METHODS: This was a single centre, retrospective study of adult patients admitted with septic shock requiring norepinephrine for at least 12hours. The primary endpoint was the incidence of tachycardia within 48hours after norepinephrine initiation. Secondary endpoints included timing and dosing of norepinephrine when adjunctive agents were added. RESULTS: The incidence of tachycardia was similar between groups. Total norepinephrine exposure was significantly greater in obese patients on day 1 (p=0.02). Obese patients were more likely to be started on vasopressin (p<0.001) and steroids at a lower weight-based norepinephrine dose (p=0.016). CONCLUSIONS: Weight-based norepinephrine dosing using actual body weight did not result in more tachycardia in the morbidly obese compared to normal weight patients, despite greater total exposure. These results were limited by the low doses used and a small cohort. However, use of actual body weight in morbidly obese patients appears to be safe.

Managing the Rising Costs and High Drug Expenditures in Critical Care Pharmacy Practice.

Pharmaceutical costs for patients in the intensive care unit (ICU) constitute a large portion of hospital drug budgets. Unfortunately, prices for medications commonly used in the ICU are on the rise for a variety of reasons. In particular, the U.S. Food and Drug Administration's Unapproved Drugs Initiative, generic manufacturers cornering the marketplace, drug shortages, and regulatory device changes are major drivers of pharmaceutical price escalation affecting costs in the ICU. Furthermore, traditional high acquisition cost items still pose challenges to controlling costs. To offer strategies to mitigate the rising costs of pharmaceuticals in the ICU setting, we searched the PubMed/Medline and International Pharmaceutical Abstracts databases and other related sources to identify published cost-saving protocols concerning specific medications that are affected by rising prices or have traditional high acquisition costs. In the absence of specific protocols, we offer possible cost-saving initiatives based on published literature regarding specific agents or based on our own diverse set of experiences. Finally, we review suggested clinical and operational activities at an institutional level to address these rising drug costs in the ICU setting.

Inadequate Sedation During Therapeutic Paralysis: Use of Bispectral Index in Critically Ill Patients.

BACKGROUND: Patients receiving therapeutic paralysis may experience inadequate sedation due to intrinsic limitations of behavioral sedation assessment. Bispectral index (BIS™) provides an objective measure of sedation; however, the role of BIS™ is not well defined in intensive care unit (ICU) patients on neuromuscular blocking agents (NMBA). OBJECTIVE: The aim of this study was to delineate the relationship between BIS™ and level of sedation for critically ill patients during therapeutic paralysis. METHODS: This was a retrospective observational study conducted in ICU patients receiving continuous infusion NMBA and BIS™ monitoring. The primary endpoint was the correlation of BIS™ <60 during therapeutic paralysis with a Richmond Agitation Sedation Score (RASS) of -4 to -5 (i.e., deep or unarousable sedation) at the time of emergence from therapeutic paralysis. RESULTS: Thirty-one patients were included in the analysis. Three of these patients (9.6 %) were inadequately sedated upon emergence from paralysis; that is, restless or agitated (RASS +1 to +2). We did not observe a correlation between BIS™ and RASS upon emergence from paralysis (r = 0.27, p = 0.14). The sensitivity of BIS™ <60 in predicting deep sedation (RASS -5 to -4) was 100 % (95 % confidence interval [CI] 0-100) with a positive predictive value of 35.7 %. The sensitivity and positive predictive value of BIS™ <60 in predicting light sedation or deeper (RASS -5 to -2) was 92.9 % (95 %CI 83.3-100) and 92.9 %, respectively. CONCLUSION: These results suggest that 1 in 10 critically ill patients receiving therapeutic paralysis may be inadequately sedated. BIS™ monitoring may serve as a useful adjunctive measure of sedation in critically ill patients receiving therapeutic paralysis.

Pharmacotherapy Considerations for the Management of Advanced Cardiac Life Support.

Health care providers should be aware of the pharmacotherapy considerations in the American Heart Association's guidelines for advanced cardiac life support (ACLS). Current evidence does not suggest a reduction in mortality with ACLS medications; however, these medications can improve return of spontaneous circulation. Proper agent selection and dosing are imperative to maximize benefit and minimize harm. The latest guideline update included major changes to the ventricular fibrillation/pulseless ventricular tachycardia and pulseless electrical activity/asystole algorithms, which providers should adopt. It is critical that providers be prepared for post-code management. Health care professionals should remain abreast of changing evidence and guidelines.

Cell line modeling to study biomarker panel in prostate cancer.

BACKGROUND: African-American men with prostate cancer (PCa) present with higher-grade and -stage tumors compared to Caucasians. While the disparity may result from multiple factors, a biological basis is often strongly suspected. Currently, few well-characterized experimental model systems are available to study the biological basis of racial disparity in PCa. We report a validated in vitro cell line model system that could be used for the purpose. METHODS: We assembled a PCa cell line model that included currently available African-American PCa cell lines and LNCaP (androgen-dependent) and C4-2 (castration-resistant) Caucasian PCa cells. The utility of the cell lines in studying the biological basis of variance in a malignant phenotype was explored using a multiplex biomarker panel consisting of proteins that have been proven to play a role in the progression of PCa. The panel expression was evaluated by Western blot and RT-PCR in cell lines and validated in human PCa tissues by RT-PCR. As proof-of-principle to demonstrate the utility of our model in functional studies, we performed MTS viability assays and molecular studies. RESULTS: The dysregulation of the multiplex biomarker panel in primary African-American cell line (E006AA) was similar to metastatic Caucasian cell lines, which would suggest that the cell line model could be used to study an inherent aggressive phenotype in African-American men with PCa. We had previously demonstrated that Protein kinase D1 (PKD1) is a novel kinase that is down regulated in advanced prostate cancer. We established the functional relevance by over expressing PKD1, which resulted in decreased proliferation and epithelial mesenchymal transition (EMT) in PCa cells. Moreover, we established the feasibility of studying the expression of the multiplex biomarker panel in archived human PCa tissue from African-Americans and Caucasians as a prelude to future translational studies. CONCLUSION: We have characterized a novel in vitro cell line model that could be used to study the biological basis of disparity in PCa between African-Americans and Caucasians.

Prescriber Compliance with a New Computerized Insulin Guideline for Noncritically Ill Adults.

BACKGROUND: In March 2008, the University of California, Davis Medical Center (UCDMC), implemented a guideline for the inpatient management of diabetes in noncritically ill adults. In accordance with national guidelines, all patients with type 2 diabetes are prescribed basal, nutritional, and correctional insulin. The guideline was added to the electronic medical record as a standardized physician order set in April 2008 and provider training on the insulin guideline occurred in May 2008. OBJECTIVE: To evaluate provider compliance with a new electronic standardized insulin order set in a hospital setting. METHODS: All patients with insulin orders admitted to the general internal medicine service between June 1, 2008, and November 1, 2008, were evaluated in this single-center retrospective chart review at UCDMC in Sacramento. Patients older than 18 years with a history of type 2 diabetes were included in the analysis. Insulin orders were categorized as preferred (followed the guideline) or nonpreferred regimens (did not follow all components of the guideline). RESULTS: A total of 265 patients were identified during the study period. The preferred regimen was ordered in 82 (30.9%) of the evaluated patient admissions. Of the 183 (69.1%) nonpreferred regimens, more than half (54.6%) contained correctional insulin alone; 84.2% of patient admissions prescribed nonpreferred regimens lacked nutritional insulin. Average admission blood glucose readings were higher in the preferred versus nonpreferred regimen group (224.4 vs 164.8 mg/dL, p < 0.001). CONCLUSIONS: The preferred regimen was not prescribed for the majority of patients admitted with a history of type 2 diabetes, despite computerized decision support. Nutritional insulin was the most common missing component in the nonpreferred regimens. Baseline clinical factors, educational modalities, and guideline content may have influenced prescribing patterns.