Corticosteroids in critically ill patients: A narrative review.

Corticosteroids have been utilized in modern medicine for decades. Many indications have been investigated across various treatment settings with both benefit and harm observed. Given the instability of critically ill patients, the increased risk of corticosteroid-related complications, and the pervasive comorbidities, patients who receive corticosteroids must be carefully managed. Common critical care disease states in which corticosteroids have been studied and are routinely utilized include acute respiratory distress syndrome, adrenal insufficiency, angioedema, asthma, chronic obstructive pulmonary disease, community-acquired pneumonia, coronavirus disease 2019, septic shock, and spinal cord injury. Benefits of corticosteroids include an improvement in disease state-specific outcomes, decreased hospital length of stay, decreased mechanical ventilatory support, and decreased mortality. The harm of corticosteroids is well documented through adverse effects that include, but are not limited to, hyperglycemia, tachycardia, hypertension, agitation, delirium, anxiety, immunosuppression, gastrointestinal bleeding, fluid retention, and muscle weakness. Furthermore, corticosteroids are associated with increased health care costs through adverse effects as well as drug acquisition and administration costs. Given the assortment of agents, dosing, benefits, risks, and utilization in the critical care setting, there may be difficulty with identifying the appropriate places for use of corticosteroids in therapy. There currently exists no comprehensive report detailing the use of corticosteroids in the aforementioned disease states within the critical care setting. This narrative review sets out to describe these in detail.

Efficacy and safety of factor Xa inhibitors in low body weight patients.

STUDY OBJECTIVE: The purpose of this study is to provide evidence for the safety and efficacy of factor Xa inhibitors in patients with a weight ≤60 kg or BMI < 18.5 kg/m2 . DESIGN: Multicenter, retrospective, cohort study. SETTING: Twenty-two Ascension Health hospitals. PATIENTS: Low-body-weight adult patients (weight ≤ 60 kg or BMI < 18.5 kg/m2 ) receiving treatment for atrial fibrillation or venous thromboembolism. INTERVENTION: Factor Xa inhibitors (apixaban or rivaroxaban) or warfarin. MEASUREMENTS AND MAIN RESULTS: This study included 2538 patients between the factor Xa inhibitors (n = 1695) and warfarin (n = 843) groups with a mean weight of 53.5 ± 5.5 kg and BMI of 20.7 ± 3.1 kg/m2 . No significant difference in time to major bleeding was noted after controlling for potential confounders (HR 1.03, 95% CI 0.70-1.53, p = 0.87); similar results were seen following propensity score matching. Thromboembolism (5.3% vs. 6.2%, p = 0.38), composite major + clinically relevant nonmajor bleeding (9.8% vs. 11.5%, p = 0.18), and all-cause mortality (10.7% vs. 12.8%, p = 0.12) were similar between patients receiving factor Xa inhibitors versus warfarin. CONCLUSION: No differences in safety or effectiveness were noted between factor Xa inhibitors versus warfarin. These findings provide encouraging evidence to support the use of factor Xa inhibitors in low-body-weight patients.

Hydrocortisone versus vasopressin for the management of adult patients with septic shock refractory to norepinephrine: A multicenter retrospective study.

STUDY OBJECTIVE: Significant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating doses of norepinephrine. The goal of this study was to assess differences in clinical outcomes between these two agents. DESIGN: Multicenter, retrospective, observational study. SETTING: Ten Ascension Health hospitals. PATIENTS: Adult patients with presumed septic shock receiving norepinephrine prior to study drug initiation between December 2015 and August 2021. INTERVENTION: Vasopressin (0.03-0.04 units/min) or hydrocortisone (200-300 mg/day). MEASUREMENTS AND MAIN RESULTS: A total of 768 patients were included with a median (interquartile range) SOFA score of 10 (8-13), norepinephrine dose of 0.3 mcg/kg/min (0.1-0.5 mcg/kg/min), and lactate of 3.8 mmol/L (2.4-7.0 mmol/L) at initiation of the study drug. A significant difference in 28-day mortality was noted favoring hydrocortisone as an adjunct to norepinephrine after controlling for potential confounding factors (OR 0.46 [95% CI, 0.32-0.66]); similar results were seen following propensity score matching. Compared to vasopressin, hydrocortisone initiation was also associated with a higher rate of hemodynamic responsiveness (91.9% vs. 68.2%, p < 0.01), improved resolution of shock (68.8% vs. 31.5%, p < 0.01), and reduced recurrence of shock within 72 h (8.7% vs. 20.7%, p < 0.01). CONCLUSIONS: Addition of hydrocortisone to norepinephrine was associated with a lower 28-day mortality in patients with septic shock, compared to the addition of vasopressin.

Conducting Multicenter Residency Research.

PURPOSE: Conducting well designed pharmacy resident research projects has inherent challenges including inadequate sample size, a lack of time, decreased generalizability, and inadequate research support. A way to overcome these barriers is through conducting multicenter research projects. However, this approach may also bring new challenges. Therefore, the purpose of this article is to provide a general approach for pharmacy preceptors and leaders on implementation of multicenter residency research. SUMMARY: This article includes a general approach to conducting multicenter research from experienced individuals based upon their successes and failures. A timeline-based format is presented to lay the groundwork for implementation of this approach. Key topics in this paper include establishing a research overview committee, research question development, Institutional Review Board considerations, site recruitment, authorship discussions, resident coordination, protocol development, data collection, manuscript development, and considerations after residency. The approach maintains a critical focus on the individual residents ability to achieve American Society of Health-System Pharmacists accreditation standards for conducting research while operating in a collaborative manner. CONCLUSION: Conducting multicenter residency research projects requires a team-based approach and advanced planning. This approach has the potential to improve pharmacy resident project quality.

Management of Venous Thromboembolism in Morbid Obesity With Rivaroxaban or Warfarin.

BACKGROUND: Rivaroxaban is a first-line option for the management of venous thromboembolism (VTE). However, limited data are available regarding its effectiveness in morbidly obese patients. OBJECTIVE: To evaluate rates of thrombosis and bleeding in morbidly obese patients receiving rivaroxaban or warfarin for VTE. METHODS: A multicenter, retrospective cohort study was conducted to compare rates of bleeding and thrombosis in patients receiving rivaroxaban versus warfarin for acute VTE. Patients were included if they were older than 18 years and had a body mass index (BMI) greater than 40 kg/m2 or weight greater than 120 kg. The primary effectiveness outcome was hazard of VTE recurrence; the primary safety outcome was hazard of major bleeding. Patients were followed for up to 12 months. RESULTS: A total of 1281 patients were identified for acute VTE and were included in this study with 487 patients receiving rivaroxaban and 785 receiving warfarin. The average cohort age was 57.6 ± 14.6 years, and the average weight was 136.4 ± 27.2 kg. After controlling for confounding factors, the use of rivaroxaban was not associated with an increased hazard of VTE events when compared with warfarin (hazard ratio [HR] = 0.69, 95% confidence interval [CI]: 0.42-1.08, P = 0.12) or major bleeding (HR = 1.29, 95% CI: 0.66-2.30, P = 0.52). CONCLUSION AND RELEVANCE: No difference was observed in obese patients with weight >120 kg or BMI >40 kg/m2 receiving rivaroxaban or warfarin for VTE treatment in hazard of VTE or major bleeding. Either agent may be considered an appropriate treatment option in this population.

Monitoring and Dosing of Argatroban in a Patient With Antiphospholipid Syndrome.

Background: This case reports outlines argatroban dosing and necessary dose adjustments in a 56 year-old male with a past medical history of antiphospholipid syndrome and heparin-induced thrombocytopenia. Method: Argatroban was initiated as a fixed dose of 0.5 µg/kg/min with all initial aPTTs above goal. Argatroban was held for a procedure and re-initiated at 0.25 µg/kg/min. The dose was increased or decreased by 25% from the current rate based on supratherapeutic and subtherapeutic aPTTs, respectively. Results: The patient remained on argatroban for 6 total days, while achieving goal aPTT levels with no VTE or bleeding events. Conclusion: Our patient represents the first reported case of monitoring argatroban with aPTTs in an individual with APS.

Efficacy and Safety of Vasopressin as First-Line Treatment of Distributive and Hemorrhagic Shock States.

Background: Norepinephrine remains the first-line option to manage patients with circulatory shock. Limited evidence exists evaluating noncatecholamine compounds as first-line monotherapy for managing noncardiogenic shock. Objective: To compare vasopressin monotherapy with norepinephrine monotherapy for reversal of distributive and hemorrhagic shock. Methods: This was a retrospective cohort study including adult patients who were diagnosed with hypovolemic or septic shock, received fluids, and received norepinephrine or vasopressin monotherapy for at least 1 hour. Patients excluded lacked a clear diagnosis, were initiated on 2 or more vasopressors at once, or underwent cardiac surgery. The primary outcome was time to shock reversal. Secondary outcomes included mortality, lengths of stay, and safety end points. A multivariable Cox proportional hazards model was performed incorporating baseline and treatment variables. Results: A total of 85 and 160 patients were treated with vasopressin and norepinephrine, respectively. A decrease in time to shock reversal was observed in the vasopressin group (58.32 hours [95% CI, 50.88-66.00] vs 74.64 hours [95% CI, 60.96-88.32], P = 0.004). Mortality was lower in the vasopressin group (25% vs 41%, P = 0.01), and intensive care unit length of stay was longer (13 days [interquartile range, IQR = 7-19] vs 7 days [IQR = 5-9], P = 0.006). Remaining secondary outcomes were similar. The multivariable analysis revealed no difference in time to shock reversal. Conclusion and Relevance: First-line vasopressin exhibited faster time to distributive shock reversal in the unadjusted analysis but failed to maintain this difference in the multivariable analysis. These findings support safe use of vasopressin as first-line therapy or as an alternative to norepinephrine in distributive shock.

Increased Enoxaparin Dosing Requirements for Treatment of Deep Vein Thrombosis in a Severely Burned Patient: Case Report and Literature Review.

Dosing of enoxaparin for deep vein thrombosis (DVT) prophylaxis in acutely burned patients has been shown to result in anti-Xa levels below target range. We describe the first case report, to our knowledge, of a severely burned patient who, despite prophylactic dosing of enoxaparin 30 mg subcutaneously twice daily, developed an acute DVT that required high-dose enoxaparin (100 mg [1.5 mg/kg] subcutaneously every 8 hours) to maintain anti-Xa levels within the therapeutic range (0.6-1 IU/ml). Pharmacokinetic evaluations were performed using anti-Xa levels measured throughout the patient's hospital stay to validate the appropriateness of this high-dose regimen based on established therapeutic anti-Xa level ranges. These results suggest that routine anti-Xa level monitoring, regardless of enoxaparin dosing, is necessary for burn patients who are receiving enoxaparin given their hypermetabolic state following injury.