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Asthma exacerbations with respiratory failure (AERF) are associated with hospital mortality of 7% to 15%. Extracorporeal membrane oxygenation (ECMO) has been used as salvage therapy for refractory AERF, but controlled studies showing its association with mortality have not been performed.Is treatment with ECMO associated with lower mortality in refractory AERF compared with standard care?This is a retrospective, epidemiologic, observational cohort study using a national, administrative data set from 2010 to 2020 that includes 25% of US hospitalizations. People were included if they were admitted to an ECMO-capable hospital with an asthma exacerbation, and were treated with short-acting bronchodilators, systemic corticosteroids, and invasive ventilation. People were excluded for age 18 years, no ICU stay, nonasthma chronic lung disease, COVID-19, or multiple admissions. The main exposure was ECMO vs No ECMO. The primary outcome was hospital mortality. Key secondary outcomes were ICU length of stay (LOS), hospital LOS, time receiving invasive ventilation, and total hospital costs.The study analyzed 13,714 patients with AERF, including 127 with ECMO and 13,587 with No ECMO. ECMO was associated with reduced mortality in the covariate-adjusted (OR, 0.33; 95% CI, 0.17-0.64; P = .001), propensity score-adjusted (OR, 0.36; 95% CI, 0.16-0.81; P = .01), and propensity score-matched models (OR, 0.48; 95% CI, 0.24-0.98; P = .04) vs No ECMO. Sensitivity analyses showed that mortality reduction related to ECMO ranged from OR 0.34 to 0.61. ECMO was also associated with increased hospital costs in all three models (P .0001 for all) vs No ECMO, but not with decreased ICU LOS, hospital LOS, or time receiving invasive ventilation.ECMO was associated with lower mortality and higher hospital costs, suggesting that it may be an important salvage therapy for refractory AERF following confirmatory clinical trials.

Background. Vasopressin is frequently utilized for a variety of shock states in critically ill patients. Short stability (≤24 hours) after intravenous admixture with current manufacturer labeling requires just in time preparation and may lead to delays in therapy and increased medication waste. We aimed to evaluate vasopressin stability in 0.9% sodium chloride stored in polyvinyl chloride bags and polypropylene syringes for up to 90 days. Additionally, we evaluated the impact of extended stability on the time to administration and cost savings from reduced medical waste at an academic medical center. Methods. Dilutions of vasopressin to concentrations of 0.4 and 1.0 unit/mL were performed under aseptic conditions. The bags and syringes were stored at room temperature (23°C-25°C) or under refrigeration (3°C-5°C). Three samples of each preparation and storage environment were analyzed on days 0, 2, 14, 30, 45, 60, and 90. Physical stability was performed by visual examination. The pH was assessed at each point and upon final degradation evaluation. Sterility of the samples was not assessed. Chemical stability of vasopressin was evaluated using liquid chromatography with tandem mass spectrometry. Samples were considered stable if there was 10% degradation at day 30. Implementation of a batching process resulted in reduced waste ($185 300) and improved time to administration (26 vs 4 minutes). Conclusion. Vasopressin diluted to a concentration of 0.4 units/mL with 0.9% sodium chloride injection is stable for 90 days at room temperature and under refrigeration. When diluted to 1.0 unit/mL with 0.9% sodium chloride injection it is stable for 90 days under refrigeration. Use of extended stability and sterility testing to batch prepare infusions may lead to improved time to administration and cost savings from reduced medication waste.

Purpose:Evaluate the stability of isoproterenol hydrochloride injection in 0.9% sodium chloride in polyvinyl chloride bags for up to 90 days. Methods: Dilutions of isoproterenol hydrochloride injection to a concentration of 4 μg/mL were performed under aseptic conditions. The bags were stored in amber ultraviolet light blocking bags at room temperature (23°C-25°C) or under refrigeration (3°C-5°C). Three samples of each preparation and storage environment were analyzed on days 0, 2, 14, 30, 45, 60, and 90. Physical stability was performed by visual examination. The pH was assessed at baseline, each analysis day, and upon final degradation evaluation. Sterility of the samples was not assessed. Chemical stability of isoproterenol hydrochloride was evaluated using liquid chromatography with tandem mass spectrometry. Samples were considered stable if there was

Dalbavancin is a synthetic lipoglycopeptide that exerts its antimicrobial activity through two distinct modes of action, inhibition of cell wall synthesis and an anchoring mechanism. Compared with previous glycopeptide antibiotics, dalbavancin demonstrates improved antibacterial potency against Gram-positive organisms and a long half-life of approximately 1 week, which is longer in tissues (e.g., skin, bone) than plasma. These factors facilitated the development of single-dose or once-weekly dosing regimens to treat acute bacterial skin and skin structure infections (ABSSSI). Dalbavancin exhibits dose-proportional pharmacokinetics and is highly protein bound (93%). Despite being highly protein bound, it has a steady-state volume of distribution10 L and distributes widely into the skin, bone, peritoneal space, and epithelial lining fluid, but not cerebrospinal fluid. Dalbavancin elimination occurs via a combination of renal (approximately 45%) and non-renal clearance, with dose adjustments recommended only in patients with a creatinine clearance30 mL/min not receiving any form of dialysis. The established pharmacokinetic/pharmacodynamic index associated with bacterial kill is free area under the concentration-time curve over the minimum inhibitory concentration (fAUC/MIC), with a goal 24-h fAUC/MIC of at least 27.1 for Staphylococcus aureus infections. Recent data suggest usefulness in the treatment of infections beyond ABSSSI, with convenient dosing and redosing strategies for complicated infections requiring extended treatment durations. Additional studies are needed to confirm these preliminary findings.

Medications are an important part of the management of patients with kidney disease. When used appropriately, pharmacotherapy can slow disease progression and reduce morbidity and mortality. Unfortunately, reduced kidney function can significantly alter the pharmacokinetics and pharmacodynamics of many medications, putting patients at risk for drug toxicity if modifications to therapy are not appropriately managed. Adding complexity to the appropriateness of medication and dosage selection is the difficulty in estimating kidney function and the discordance between the Cockcroft-Gault-derived dosing cut points in most medication package inserts and the estimations of glomerular filtration rate by newer and generally more accurate guideline-recommended equations. This installment of the AJKD Core Curriculum in Nephrology provides recent updates and practical considerations for designing optimal medication regimens. Given the prevalence of abnormal kidney function and its importance in medication selection and dose adjustment, additional focus and specific recommendations are provided for anticoagulant, anti-infective, analgesic, antidiabetic, and antihypertensive agents.

Introduction: Invasive fungal infections (IFIs) remain a significant cause of morbidity and mortality despite significant advancements in currently available therapy. With a flush pipeline of investigational antifungals, the clinician must identify appropriate roles of currently available therapies, potential advantages of emerging antifungals, and shortcomings in the evolving clinical evidence.Areas covered: Standard and developing treatment approaches for IFIs with currently available antifungals are summarized with a focus on invasive candidiasis and invasive aspergillosis. Emerging investigational antifungals are discussed in depth, including mechanisms of action, fungal activity, clinical evidence, and ongoing research. An opinion on the impact and potential role of therapy for emerging antifungals of interest is also provided.Expert opinion: Despite advances and clinical studies optimizing antifungal use, current therapies fall short in preventing IFI morbidity and mortality. Further optimization of currently available antifungals may improve outcomes; however, novel agents are required for historically difficult-to-treat infections, transitions to oral treatment, minimizing adverse drug effects, decreasing drug interactions, and ultimately improving patient quality of life. Emerging antifungals may positively revolutionize the treatment of IFIs.

Introduction: Aminoglycoside antibiotics such as gentamicin are bactericidal and effective against gram negative organisms and act synergistically against gram positive organisms, including S taphylococcus aureus. However, they have serious adverse effects such as nephrotoxicity and ototoxicity. Gentamicin ototoxicity may occur after a single dose and results in decreased vestibular function, which is frequently debilitating and often permanent. Objective: To emphasize the risk of gentamicin ototoxicity and suggest alternative antibiotics in penicillin-allergic patients undergoing surgery. Case Summary: We present a case of a woman with preexisting Meniere’s Disease who received gentamicin 400 mg perioperatively for a sigmoidectomy due to a penicillin allergy listed in the patient’s medical record. The patient developed severe ototoxicity preventing her from working or driving. Physical examination was remarkable for a broad-based gait requiring assistance to walk and bilateral corrective saccades. Vestibular testing revealed high-grade bilateral vestibular loss associated with all semicircular canals, a considerable decline compared to her function 3 years prior. Discussion: Gentamicin is indicated for surgical prophylaxis when a patient has a true allergy to penicillins and cannot receive cephalosporins, though alternatives exist. True allergies include IgE-mediated illness (anaphylaxis, bronchospasm, or urticaria 30-60 minutes after administration) or exfoliative reactions (Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis). The authors encourage more prudent use of gentamicin, especially in patients susceptible for debilitating otologic insults, and offer recommendations for alternative agents prior to using gentamicin.

In recent years, vasopressin has been increasingly used as an early treatment of vasopressor-refractory septic shock. In this article, we describe 2 episodes of transient diabetes insipidus after vasopressin for the treatment of septic shock was discontinued, which adds to a modest number of case studies reporting the same phenomenon. With the anticipated continued use of vasopressin in intensive care units, it can be expected that this adverse effect will occur with some frequency. Awareness and early recognition of this phenomenon can lead to prompt diagnosis and treatment.

Background Management of alcohol withdrawal syndrome (AWS) requires bedside assessments of symptom severity to guide therapies. Commonly used assessment tools are the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the modified Minnesota Detoxification Scale (mMINDS) and the Severity of Ethanol Withdrawal Scale (SEWS). Objective To determine strength of correlation between the CIWA-Ar, mMINDS, and SEWS for bedside assessment of severe AWS and to survey nurses regarding ease of use of each tool. Methods A single-center prospective correlation study of the three assessment tools performed by bedside nurses on patients with AWS followed by a questionnaire assessing ease of use of each tool (1 being the easiest and 9 being the hardest). Results A total of 66 correlation assessments were performed by 49 nurses in 21 patients with AWS. Bedside CIWA-Ar, mMINDS, and SEWS were 14 ± 8.3, 13.9 ± 6.5, and 10.1 ± 4.5, respectively. The Pearson correlation coefficients were 0.814 (95% CI, 0.714-0.881) between CIWA-Ar and mMINDS; 0.722 (95% CI, 0.585-0.820) between CIWA-Ar and SEWS; and 0.658 (95% CI, 0.498-0.775) between SEWS and mMINDS. Nurse ratings for ease of use were 4 ± 2.3 for CIWA-Ar, 2.9 ± 2 for mMINDS (p=0.0044 vs. CIWA-Ar), and 4.8 ± 2.1 for SEWS (p=0.036 vs. CIWA-Ar, pConclusion Correlations between the three scoring tools in severe AWS are robust. Only mMINDS was considered easy to use by nurses. It was the preferred tool.

Introduction Left ventricular (LV) thrombus is a complication of acute endomyocardial injury and chronic ventricular wall hypokinesis (e.g. dilated cardiomyopathy), resulting in increased risk of thromboembolic complications. Historically, observational studies support the general safety and efficacy of warfarin for this indication. To date, limited data exists regarding the use of the direct oral anticoagulants (DOACs) for LV thrombus. Methods A retrospective cohort study utilizing electronic medical records was conducted from September 2012 - October 2018 at the University of Colorado Hospital System. Patients were included if they had any diagnosis of LV thrombus and received either a DOAC or warfarin within 90 days of diagnosis. The primary outcome was to determine the incidence of thromboembolic stroke in patients receiving a DOAC compared to warfarin. Secondary outcomes consisted of the composite incidence of thromboembolic events (stroke and systemic embolism), bleeding rates defined by the The Global Use of Strategies to Open Occluded Arteries (GUSTO) criteria, and blood product administration. Chi square test was used to analyze categorical variables and the student's t-test and Wilcoxon Rank Sum test for continuous data. All statistical analyses were conducted using SAS. Results A total of 949 patients met inclusion, of whom 180 (19%) received a DOAC and 769 (81%) warfarin. Of the DOAC cohort, 77 (41.6%) received rivaroxaban, 79 (42.7%) apixaban, and 29 (15.7%) dabigatran. For baseline demographic information, see table 1. For the primary endpoint of new onset thromboembolic stroke on or within 90 days of LV thrombus diagnosis, no difference existed between treatment groups (DOAC: 7.8% vs warfarin: 11.7%, p=0.524). When compared to warfarin, no difference existed in the composite of thromboembolic events (33.1% vs 30.6%, P=0.524, respectively) or in GUSTO bleeding (11.1% vs 7.8%, p=0.397, for DOAC vs. warfarin, respectively). However, more patients on warfarin received blood products compared to those taking a DOAC (25.8% vs 13.9%, p Conclusions Compared to warfarin, DOACs may be safe and efficacious for the treatment of LV thrombus, however further studies are warranted.

There is minimal literature to support the appropriate dosing for the initiation of IV regular insulin therapy in DKA patients. A 0.1 unit/kg bolus followed by 0.1 units/kg/hour or 0.14 units/kg/hour is commonly utilized and recommended in guidelines.We sought to assess clinical and safety outcomes associated with various insulin infusion starting doses in patients diagnosed with DKA in the emergency department in an effort to help guide prescribing.A retrospective cohort study was conducted within an academic emergency department and included patients who received continuous infusion regular insulin with an ICD-10 code for DKA between January 2016 and January 2019. A predictive regression model was applied to test if predefined lab values influenced the starting insulin infusion rates. Clinical and safety outcomes were evaluated by starting insulin infusion rate. Data was analyzed based on starting insulin infusion rates.347 patients met inclusion criteria with 92 (26.5%) patients receiving0.07 units/kg/hr, 123 (35.4%) patients receiving 0.07 to 0.099 units/kg/hr, 123 (35.4%) patients receiving 0.10 to 0.139 units/kg/hr, and 9 (2.6%) patients receiving ≥0.14 units/kg/hr. After adjusting for baseline labs, glucose was the only significant predictor of the initial infusion rate (p0.001). For every 100 mg/dL increase in the baseline glucose value, the initial infusion rate increased by 0.005 units/kg/hr. There was no difference between insulin starting infusion rates and length of stay, rates of hypoglycemia, hypokalemia, or dysrhythmias.Glucose levels significantly influenced the insulin starting infusion rate, with no identified differences in adverse effects or clinical outcomes.

INTRODUCTION: Heart failure hospitalization is a hallmark of disease progression associated with increased morbidity and mortality. Benefits of multidisciplinary clinics have been established in the care of heart failure patients and can be particularly impactful post-hospital discharge. OBJECTIVE: This study aimed to investigate the impact of a clinical pharmacist-integrated model of care within a Heart Failure Bridge Clinic (HFBC) at a large tertiary care referral center. METHODS: In this single-center retrospective study, patients with left ventricular ejection fraction (LVEF) ≤40% discharged from Mission Hospital (Asheville, North Carolina) between August 2018 and July 2019 were screened. Patients in the HFBC arm had a clinic visit inclusive of a clinical pharmacist within 30 days of hospital discharge and were compared with a control group of patients with a usual care provider clinic visit. The HFBC provided clinical assessment, detailed heart failure education, and medication reconciliation and adjustment with an emphasis on optimization of Guideline Directed Medical Therapy (GDMT). Patients were followed for 90 days for the primary end point of hospitalization, emergency department (ED) visit, or death. RESULTS: A total of 1463 patients (HFBC, n = 307; control, n = 1156) comprised our final cohort. After accounting for baseline variables, 90-day cumulative probability of hospitalization, ED visit, or death favored HFBC patients (26% vs 32%, P = .0275). Comprehensive review of medications prior to and after HFBC appointment demonstrated significant alterations to therapies (30% GDMT addition, 27% GDMT titration, 7.2% discontinuation of medications associated with worsening heart failure, and 28% loop diuretic adjustment). CONCLUSION: Clinical pharmacist-integrated HFBC allows for focused medication review and optimization and is associated with a 19% relative risk reduction in hospitalization, ED visit, or death at 90 days.

Background The relative distribution of cefazolin into the cerebrospinal fluid (CSF) remains debated. Determining the distribution of cefazolin into the CSF in noninfected adults may allow for further treatment applications of cefazolin. This prospective pharmacokinetic study aimed to determine the pharmacokinetic parameters of cefazolin in serum and CSF from external ventricular drains (EVDs) in neurologically injured adults. Methods Blood and CSF were collected, using a biologic waste protocol, for cefazolin quantification and trapezoidal rule–based pharmacokinetic analysis in a total of 15 critically ill adults receiving 2000 mg intravenously every 8 hours or the renal dose equivalent for EVD prophylaxis. Results A median (range) of 3 (2–4) blood and 3 (2–5) CSF samples were collected for each patient. The most common admitting diagnosis was subarachnoid hemorrhage (66.7%). The median calculated cefazolin CSF Cmax and Cmin values (interquartile range [IQR]) were 2.97 (1.76–8.56) mg/L and 1.59 (0.77–2.17) mg/L, respectively. The median (IQR) CSF to serum area under the curve ratio was 6.7% (3.7%–10.6%), with time-matched estimates providing a similar estimate (8.4%). Of those receiving cefazolin every 8 hours, the median and minimum directly measured CSF cefazolin concentration ≥4 hours following administration were 1.87 and 0.78 mg/L, respectively. Conclusions Cefazolin dosed for EVD prophylaxis achieved CSF concentrations suggesting viability as a therapeutic option for patients with meningitis or ventriculitis due to susceptible bacteria such as methicillin-susceptible Staphylococcus aureus. Further clinical trials are required to confirm a role in therapy for cefazolin. Population-based pharmacokinetic–pharmacodynamic modeling may suggest an optimal cefazolin regimen for the treatment of central nervous system infections., D/C/F/TAF is the reference for combination therapy based on protease inhibitors but has not been compared with regimens containing integrase inhibitors as initial ART. We could not demonstrate D/C/F/TAF noninferiority relative to DTG/ABC/3TC, although both regimens were similarly well tolerated.

Patients with COVID-19 are at higher risk of thrombosis due to the inflammatory nature of their disease. A higher-intensity approach to pharmacologic thromboprophylaxis may be warranted. The objective of this retrospective cohort study was to determine if a patient specific, targeted-intensity pharmacologic thromboprophylaxis protocol incorporating severity of illness, weight, and biomarkers decreased incidence of thrombosis in hospitalized patients with COVID-19. Included patients were hospitalized with COVID-19 and received thromboprophylaxis within 48 h of admission. Exclusion criteria included receipt of therapeutic anticoagulation prior to or within 24 h of admission, history of heparin-induced thrombocytopenia, extracorporeal membrane oxygenation, pregnancy, or incarceration. Per-protocol patients received thromboprophylaxis according to institutional protocol involving escalated doses of anticoagulants based upon severity of illness, total body weight, and biomarker thresholds. The primary outcome was thrombosis. Secondary outcomes included major bleeding, mortality, and identification of risk factors for thrombosis. Of 1189 patients screened, 803 were included in the final analysis. The median age was 54 (42–65) and 446 (55.5%) were male. Patients in the per-protocol group experienced significantly fewer thrombotic events (4.4% vs. 10.7%, p = 0.002), less major bleeding (3.1% vs. 9.6%, p

Background Fraction unbound has been used as a surrogate for antimicrobial sieving coefficient (SC) to predict extracorporeal clearance in critically ill patients on continuous renal replacement therapy (CRRT), but this is based largely on expert opinion. Objectives To examine relationships between package insert-derived fraction unbound (Fu-P), study-specific fraction unbound (Fu-S), and SC in critically ill patients receiving CRRT. Methods English-language studies containing patient-specific in vivo pharmacokinetic parameters for antimicrobials in critically ill patients requiring CRRT were included. The primary outcome included correlations between Fu-S, Fu-P, and SC. Secondary outcomes included correlations across protein binding quartiles, serum albumin, and predicted in-hospital mortality, and identification of predictors for SC through multivariable analysis. Results Eighty-nine studies including 32 antimicrobials were included for analysis. SC was moderately correlated to Fu-S (R2 = 0.55, P 92%) quartiles of fraction unbound and above median albumin concentrations of 24.5 g/L (R2 = 0.71, P = 0.07). Conversely, correlation was weaker in patients with mortality estimates greater than the median of 55% (R2 = 0.06, P = 0.84). SC and Fu-P were also best correlated in the first quartile of antimicrobial fraction unbound (R2 = 0.66, P Conclusions Fu-S and Fu-P were both reasonably correlated to SC. Caution should be taken when using Fu-S to calculate extracorporeal clearance in antimicrobials with 69%–92% fraction unbound or with >55% estimated in-hospital patient mortality. Fu-P may serve as a rudimentary surrogate for SC when Fu-S is unavailable.

The parenterally administered direct thrombin inhibitors (DTIs) argatroban and bivalirudin are effective anticoagulants for acute heparin-induced thrombocytopenia (HIT) treatment. The activated partial thromboplastin time (aPTT) has classically been used as the monitoring test to assess degree of anticoagulation, however concerns exist with using aPTT to monitor DTI therapy. In this observational study plasma samples from DTI treated patients were analyzed by aPTT, dilute thrombin time (dTT) and ecarin chromogenic assay (ECA) to delineate results into concordant and discordant groups. Discordant samples were further analyzed via liquid chromatography with tandem mass spectrometry (LC MS/MS). In total 101 patients with 198 samples were evaluated. Discordance between tests were frequent (59% of DTI treated patients). Bivalirudin aPTT vs dTT discordance was observed in 45% (57/126) of samples. Amongst bivalirudin samples with test discordance dTT results were more likely to be concordant with LC MS/MS than the aPTT (77% vs 9%, p

Cancer increases risk for venous thromboembolism. Incident thrombocytopenia increases hemorrhagic risk. Hospitalized adults with a cancer diagnosis who received subcutaneous dalteparin in doses adjusted according to platelet count were retrospectively evaluated. Outcomes of interest included nadir platelet counts, transfusions, thromboembolism, and hemorrhage. During a 2-year period of observation, 1854 cancer patients received individualized inpatient treatment with dalteparin. Transfusion was required in 38 of 77 (49.4%) patients with nadir platelet counts 50 × 109 cells/L (RR − 8.07; 95% CI − 4.79 to − 13.59, p 50 × 109 cells/L, respectively (p > 0.9 for all comparisons). Acute blood loss or major bleeding was documented in 10.5%, 12.5%, and 15.6% of patients with platelet counts of 50 × 109 cells/L, respectively (p > 0.9 for all comparisons). Among hospitalized cancer patients who received individualized dalteparin treatment, transfusion requirements varied inversely with platelet count. Irrespective of platelet counts, occurrence rates for venous thromboembolism and acute hemorrhage were similar across all treatment groups. Individualized dalteparin treatment provided a consistent pattern of safety and effectiveness.

This book is an alphabetical directory of drugs, listed by generic name. Thus, the book will have 26 chapters - one chapter per letter (chapter 1 will have all drugs starting with the letter "A", chapter 2 with drugs starting with letter "B", etc.).