Annals of Pharmacotherapy

Acute respiratory distress syndrome (ARDS) management is primarily supportive. Pulmonary vasodilators, such as inhaled epoprostenol (iEPO), have been shown to improve PaO₂:FiO₂ (PF) and are used as adjunctive therapy.

To identify the positive response rate and variables associated with response to iEPO in adults with ARDS. A positive response to iEPO was defined as a 10% improvement in PF within 6 hours.

This retrospective study included adults with ARDS treated with iEPO. The primary endpoint was the variables associated with a positive response to iEPO. Secondary endpoints were positive response rate and the change in PF and SpO₂:FiO₂ within 6 hours. Statistical analysis included multivariable regression.

Three hundred thirty-one patients were included. As baseline PF increased, the odds of responding to iEPO decreased (odds ratio [OR], 0.752, 95% CI, 0.69-0.819, p < 0.001). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related ARDS (OR 0.478, 95% CI, 0.281-0.814, p = 0.007) was associated with decreased odds of a positive response to iEPO. The total population had a 68.3% positive response rate to iEPO. SARS-CoV-2-related ARDS and non-SARS-CoV-2-related ARDS had a 59.5% and 72.7% positive response rate, respectively. iEPO significantly improved PF (71 vs 95, P < 0.001) in the whole population.

iEPO was associated with a positive effect in a majority of moderate-to-severe ARDS patients, including patients with SARS-CoV-2-related ARDS. Lower baseline PF and non-SARS-CoV-2-related ARDS were significantly associated with a positive response to iEPO. The ability to predict which patients will respond to iEPO can facilitate better utilization.

Immune checkpoint inhibitors (ICIs) used in cancer treatment cause immune-related adverse effects (irAEs), including thyroiditis leading to hypothyroidism. The management and outcomes of this irAE are not well established.

The purpose of this analysis is to describe the onset, management, and outcomes of patients experiencing hypothyroidism from ICI.

A retrospective study was conducted of adults receiving ICI therapy at a community cancer center between January 1, 2017, and February 1, 2020. The primary endpoint was to describe onset (timing) of hypothyroidism (thyroid-stimulating hormone [TSH] > 10 µIU/mL). Secondary outcomes included describing hypothyroidism symptoms and levothyroxine use, time to documented disease progression, and occurrence of additional adverse effects (AEs).

Of the 200 patients included in the study, 19% developed clinical hypothyroidism (TSH > 10 µIU/mL, or required initiation of or dose increase in levothyroxine). Median time to TSH higher than 10 µIU/mL was 13.3 weeks and symptoms of hypothyroidism occurred in 34% of patients developing clinical hypothyroidism. The median final daily levothyroxine dose was 88 mcg (0.88 mcg/kg). Time to disease progression was longer in those with clinical hypothyroidism (27.4 months vs. 6.8 months, respectively, P = .015). Additional AEs occurred in 68% of those developing hypothyroidism versus 49% without hypothyroidism (P = .029).

Patients with clinical hypothyroidism during ICI treatment may have improved cancer outcomes, but they also are more likely to develop other AEs. Patients requiring thyroid replacement therapy with levothyroxine may benefit from a starting dose between 50 and 100 mcg/day, approximately 0.88 mcg/kg/day.

Concerns about strategic supplies and quality have increased the scrutiny of the countries where US pharmaceuticals are made.

To examine the locations of manufacturers of brand name, biological, and generic drugs over 10 years.

This longitudinal descriptive study used publicly available data from US government Web sites, including the Food and Drug Administration (FDA) Drug Establishments list, FDA National Drug Code Directory, FDA Orange Book, FDA Purple Book, and the National Institutes of Health DailyMed Drug Labels. These data were collected from 2011 to 2020.

Brand name drug manufacturing in the United States and Europe decreased from 89% in 2011 to 79% in 2020. Biological manufacturing in the United States decreased, while that in Western European countries increased; 100% of biological manufacturing was done in the United States or Europe in 2011 and decreased to 93% by 2020. Generic manufacturing in India increased from 21% to 51%, while US manufacturing decreased from 52% to 35% from 2011 to 2020. These analyses were limited to publicly available data, and the results could be affected by the accuracy and completeness of the data.

Brand name drugs and biologicals are primarily made in the United States and Europe. Generic drugs are increasingly made in India, but the United States remains a major supplier. If the country of origin for pharmaceuticals is important, these findings support supply chain concerns for generic drugs. We recommend that product containers and official labeling prominently include the manufacturer and location for active pharmaceutical ingredients and finished dosage forms.

Multimodal analgesia is a cornerstone of postoperative pain management. Different formulations of local anesthetics are available. Data to support these treatment options are limited.

To determine the efficacy of liposomal bupivacaine compared with bupivacaine or ropivacaine in patients undergoing sternotomy for coronary artery bypass graft (CABG) and/or valve surgery.

Single-center, retrospective, observational study at a community teaching hospital. Patients included were 18 years of age or older undergoing CABG and/or valve surgery via median sternotomy and received either liposomal bupivacaine or an active comparator. The primary outcome was opioid utilization in morphine milligram equivalent (MME) from 0 to 72 hours.

A total of 376 patients were included, 223 in the liposomal bupivacaine arm and 153 in the active comparator arm. There was no difference in the MME use from 0 to 72 hours among patients in the liposomal bupivacaine group compared with the comparator group (114.2 mg [75.55] vs 107.6 mg [68.4], P = 0.38). After Bonferroni correction, there was no difference in pain scores at individual time points. At 24- and 48-hour post-op, pain scores were higher with liposomal bupivacaine at 4.4 (2.7) vs 3.5 (2.8) (P = 0.01) and 3.1 (2.9) vs 2.4 (2.6) (P = 0.02).

Based on these findings and previous studies, liposomal bupivacaine should not be routinely used for CABG and/or valve surgery through a median sternotomy given lack of superiority. This helps inform surgical practice to the role of anesthetics as part of the multimodal analgesia regimen.

Anticoagulation (AC) management of the Impella varies considerably among treatment centers. Published data regarding the management of complications including heparin-induced thrombocytopenia, bleeding and thrombosis are limited.

A multidisciplinary team was assembled to 1) identify baseline knowledge of nurses and pharmacists involved in Impella anticoagulation management; 2) develop an educational tool specific to Impella anticoagulation; 3) reassess knowledge following implementation of the tool.

A team consisting of pharmacists, nurses and a physician developed surveys that were subsequently distributed to 28 nurses and 17 pharmacists. Survey questions measured knowledge in 4 areas of anticoagulation management: product selection, administration, monitoring and therapeutic recommendation. A pocket card containing flow diagrams for Impella anticoagulation management was developed. Following distribution of the card and education on its application, surveys were redistributed to measure the change in knowledge.

The frequency (%) of correct answers for all survey questions for both pharmacists and nurses significantly increased from 38% to 84% (p < 0.00001) and 63% to 93% (p < 0.00001), respectively. Substantial increases in the frequency of correct answers in the majority of question categories were observed for both pharmacists and nurses postintervention.

Using a multidisciplinary approach, an institution-specific pocket card addressing the complexities of Impella anticoagulation was developed. Following dissemination of the card and education on its application, improved knowledge across the scope of Impella anticoagulation management was observed in both pharmacists and nurses.

Proton pump inhibitor (PPI) continuous infusions or intermittent boluses are used for the treatment of upper gastrointestinal bleeding (UGIB). Intermittent boluses are easier to give and are of lower cost without affecting clinical outcomes.

To compare the rate of rebleeding between intermittent bolus and continuous infusion PPI therapy.

We performed a retrospective, multicenter review of patients with UGIB receiving either continuous or intermittent PPI therapy. During the study period, due to drug and supply shortages, each institution implemented policies preferring intermittent PPI bolus therapy. We performed bivariate and multivariable comparisons of the 2 treatment strategies, with the primary outcome of interest being incidence of rebleeding. Additional variables of interest included intensive care unit (ICU) and hospital lengths of stay, discharge disposition, and in-hospital mortality.

Compared with intermittent bolus dosing (n = 209), patients receiving continuous infusion PPI (n = 237) were associated with a higher rate of rebleeding (33.8% vs 23.0%; P = 0.012); however, no difference was detected in multivariable analysis: adjusted odds ratio, 1.50 (95% confidence interval, 0.91-2.50). There was no difference in median hospital or ICU length of stay, discharge disposition, or in-hospital mortality. Correlatively, patients receiving continuous infusion therapy were more likely to have liver disease (29.1% vs 20.1%; P = 0.028), alcohol use disorder (28.3% vs 16.3.%; P = 0.003), history of lower gastrointestinal bleeding (6.4% vs 1.9%; P = 0.021), variceal bleeding (6.3 vs 2.4%, P = 0.045), and be admitted to the ICU (65.0% vs 32.5%, P = 0.00).

Introduction of intermittent PPI bolus UGIB treatment via change in hospital policy was not associated with higher rates of rebleeding. However, continuous PPI therapy may have been perceived as more effective as it was used more commonly in high-risk patients.

Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD).

The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy.

This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration.

A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic.

Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.

The aim of this study was to synthesize evidence available on continuous infusion ketamine versus nonketamine regimens for analgosedation in critically ill patients.

A search of MEDLINE, EMBASE, CINAHL, CDSR, and ClinicalTrials.gov was performed from database establishment to November 2021 using the following search terms: critical care, ICU, ketamine, sedation, and anesthesia. All studies included the primary outcome of interest: daily opioid and/or sedative consumption.

Relevant human studies were considered. Randomized controlled trials (RCT), quasi-experimental studies, and observational cohort studies were eligible. Two reviewers independently screened articles, extracted data, and appraised studies using the Cochrane RoB and ROBINS-I tools.

A total of 13 RCTs, 5 retrospective, and 1 prospective cohort study were included (2255 participants). The primary analysis of six RCTs demonstrated reduced opioid consumption with ketamine regimens (n = 494 participants, −13.19 µg kg⁻¹ h⁻¹ morphine equivalents, 95% CI −22.10 to −4.28, P = 0.004). No significant difference was observed in sedative consumption, duration of mechanical ventilation (MV), ICU or hospital length of stay (LOS), intracranial pressure, and mortality. Small sample size of studies may have limited ability to detect true differences between groups.

This meta-analysis examining ketamine use in critically ill patients is the first restricting analysis to RCTs and includes up-to-date publication of trials. Findings may guide clinicians in consideration and dosing of ketamine for multimodal analgosedation.

Results suggest ketamine as an adjunct analgosedative has the potential to reduce opioid exposure in postoperative and MV patients in the ICU. More RCTs are required before recommending routine use of ketamine in select populations.

A literature review of antiplatelet agents for primary and secondary stroke prevention, including mechanism of action, cost, and reasons for lack of benefit.

Articles were gathered from MEDLINE, Cochrane Reviews, and PubMed databases (1980-2021). Abstracts from scientific meetings were considered. Search terms included ischemic stroke, aspirin, clopidogrel, dipyridamole, ticagrelor, cilostazol, prasugrel, glycoprotein IIb/IIIa inhibitors.

English-language original and review articles were evaluated. Guidelines from multiple countries were reviewed. Articles were evaluated independently by 2 authors.

An abundance of evidence supports aspirin and clopidogrel use for secondary stroke prevention. In the acute phase (first 21 days postinitial stroke), these medications have higher efficacy for preventing further stroke when combined, but long-term combination therapy is associated with higher hemorrhage rates. Antiplatelet treatment failure is influenced by poor adherence and genetic polymorphisms. Antiplatelet agents such as cilostazol may provide extra benefit over clopidogrel and aspirin, in certain racial groups, but further research in more diverse ethnic populations is needed.

This review presents the data available on the use of different antiplatelet agents poststroke. Dual therapy, recurrence after initiation of secondary preventative therapy, and areas for future research are discussed.

Although good evidence exists for the use of certain antiplatelet agents postischemic stroke, there are considerable opportunities for future research to investigate personalized therapies. These include screening patients for platelet polymorphisms that confer antiplatelet resistance and for randomized trials including more racially diverse populations.

The aim of this study is to review the available data on efficacy and tolerability of tazarotene 0.045% lotion.

A literature search of MEDLINE (PubMed) and EMBASE databases was completed in November 2021.

Articles that discussed efficacy, tolerability, and pharmacology of tazarotene 0.045% lotion, written in English and published before mid-November 2021, were assessed.

In two, 12-week phase III clinical trials, tazarotene 0.045% lotion had higher rates of treatment success (study 1: 25.5% and study 2: 29.6%) than individuals who received the vehicle (study 1: 13.0% and study 2: 17.3%) (both Ps < 0.001). Participants treated with tazarotene 0.045% lotion had greater least squares mean reduction in inflammatory (study 1: 55.5% and study 2: 59.5%) and noninflammatory (study 1: 51.4% and study 2: 60%) acne lesions when compared with vehicle (inflammatory acne lesions, study 1: 45.7% and study 2:49%; noninflammatory acne lesions, study 1: 41.5% and study 2: 41.6%) (P < 0.001 for studies 1 and 2). Tazarotene 0.045% lotion was well tolerated.

Retinoids are first-line therapy in the treatment of acne vulgaris. However, many patients experience cutaneous irritation, which can decrease patient adherence and efficacy. Tazarotene 0.045% lotion is the first retinoid to utilize polymeric emulsion technology (PET) to efficiently distribute the medication across the skin, decreasing adverse effects while maintaining efficacy.

Tazarotene 0.045% lotion is an effective and well-tolerated retinoid recently approved by the US Food and Drug Administration (FDA) for treating acne vulgaris in individuals 9 years of age and older.