Trending Topics in Health-System Pharmacy
APhA Staff
High-dose dexamethasone for COVID-19 AHRF: Is there a benefit?
Acute hypoxemic respiratory failure (AHRF) is one of the main symptoms of severe COVID-19, leaving clinicians to determine the most appropriate noninvasive respiratory support and the appropriate timing of invasive mechanical ventilation. Low-dose dexamethasone has been the standard of care for patients with severe COVID-19 since the results of the RECOVERY trial, which showed that 6 mg/day of dexamethasone for 10 days reduced 28-day mortality in patients with the most severe COVID-19, was published online in the New England Journal of Medicine in February 2020. But would higher doses be even more effective?
A large group of researchers in France, the COVIDICUS Study Group, studied the effects of high-versus low-dose dexamethasone on 60-day all-cause mortality in patients with COVID-19 and severe AHRF. The multicenter, placebo-controlled randomized clinical trial was conducted in 19 ICUs in France from April 2020 to January 2021. Patients received 6 mg/day dexamethasone for 10 days (or placebo at the beginning of the trial before 6 mg/day dexamethasone become the standard of care) or high-dose dexamethasone (20 mg/day on days 1–5 then 10 mg/day on days 6–10). Patients not requiring invasive mechanical ventilation (IMV) were randomly assigned oxygen support standard of care, CPAP, or high-flow nasal oxygen. All patients were followed-up for 60 days.
Results of the study, published online on July 5, 2022, in JAMA Internal Medicine, showed no difference in 60-day mortality between standard and high-dose dexamethasone groups and no significant difference in the cumulative incidence of IMV criteria at day 28 among oxygen support groups. Interactions between interventions were not significant. ■
Balanced electrolyte solutions versus isotonic saline in adult patients with diabetic ketoacidosis
Isotonic saline is commonly used for treating diabetic ketoacidosis, but could a balanced electrolyte solution, with its lower tendency to cause hyperchloremic metabolic acidosis, be more effective? A new study by researchers at the University of Santo Tomas (Philippines) published in the July 1, 2022, issue of Heart & Lung suggests that the use of a balanced electrolyte solution was associated with faster rates of diabetic ketoacidosis resolution than isotonic saline solution.
The study involved 6 clinical trials that studied the use of balanced electrolyte versus isotonic saline solution for fluid resuscitation in patients with diabetic ketoacidosis. The primary outcome measure was the time to resolution of diabetic ketoacidosis, defined as the mean time (in hours) from diagnosis or treatment to resolution per the ADA 2009 criteria (venous pH > 7.3, serum bicarbonate > 15 mEq/L, blood glucose < 11.1 mmol/L or < 200 mg/dL, and anion gap ≤ 12 mEq/L).
The pooled analysis shows that use of balanced electrolyte solution resulted in faster resolution (in hours) of diabetic ketoacidosis than use of isotonic saline. The authors suggested that time to event analysis for the resolution of diabetic ketoacidosis adjusted for possible confounders such as baseline bicarbonate and volume of I.V. fluids are needed to confirm these preliminary results. ■
Fever treatment or no fever treatment?
Body temperature varies by person and also by the time of day (lower in the morning and higher in the late afternoon and evening) and an oral temperature over 100°F is generally considered a fever. Treating fever in patients admitted to the hospital is commonly standard practice to reduce the patient’s discomfort and to decrease physiological stress. However, a new study by Niklas Nielsen at Lund University, Janus Christian Jakobsen at the University of Southern Denmark, and colleagues suggested that fever therapy may not reduce the risk of death or adverse events.
The study, published online in the BMJ on July 12, 2022, involved a systematic review of randomized clinical trials to investigate the effects of fever therapy compared with no fever therapy in patients diagnosed with fever of any origin. Primary outcomes were all-cause mortality and serious adverse events. Secondary outcomes were quality of life and non-serious adverse events. In total, 42 trials including over 5,000 patients were included, and fever treatment strategies included 11 different antipyretic drugs and physical cooling. Of the participants, ~60% were critically ill.
The researchers concluded that treatment of fever does not seem to affect the risk of death and serious adverse events and found insufficient evidence to confirm or reject the hypothesis that fever treatment influences quality of life or the risk of non-serious adverse events. They conclude that their results suggest little to no difference in effect between treatment of fever or no treatment of fever. Further trials should be conducted to detect smaller and more realistic intervention effects. ■
Is outpatient management appropriate for antibiotic treatment of acute appendicitis?
The recent Comparison of Out-comes of Antibiotic Drugs and Appendectomy (CODA) trial found antibiotics to be noninferior to surgery for acute appendicitis. Approximately half of the participants random-
ized to receive antibiotics were discharged within 24 hours of treatment initiation. In a follow-up cohort analysis, researchers from the CODA Collaborative concluded that outpatient antibiotic management is safe for selected adults with acute appendicitis, with no greater risk of complications or appendectomy than hospital care.
Of the 726 participants, 46% were judged to meet stability criteria (hemodynamically stable, afebrile, oral intake tolerated, pain controlled, and follow-up confirmed) and were discharged within 24 hours. Results of the secondary analysis, published in JAMA Network Open on July 1, 2022, showed that these patients had less than one serious adverse event per 100 participants in the first 7 days of treatment. Serious adverse events and subsequent appendectomies occurred no more frequently in these patients than among hospitalized patients.
The authors concluded that their findings support outpatient antibiotic management for selected adults with acute appendicitis and should be included in shared decision-making discussions of patient preferences for nonoperative and operative care. Such outpatient management could increase convenience for patients and decrease health care use and costs. ■
AHA, ASA release guidelines for DAPT after acute ischemic stroke
In May 2021, the American Heart Association (AHA) and American Stroke Association (ASA) updated their practice guidelines for the use of dual antiplatelet therapy (DAPT) for secondary prevention among patients with minor ischemic stroke, recommending aspirin plus clopidogrel for patients with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 3. A new study published in JAMA Network Open on July 28, 2022, examined the extent to which practice patterns in the U.S. are consistent with these new evidence-based guidelines.
The multicenter retrospective cohort study involved over 132,000 patients from 1,890 hospitals participating in the AHA/ASA Get With The Guidelines–Stroke program. The results showed that 47.0% of patients with minor stroke received DAPT at discharge, as indicated by guidelines, while 42.6% patients with nonminor stroke (NIHSS score > 3), for whom the risks and benefits of DAPT have not been fully established, also received DAPT at discharge. The authors found substantial hospital variation across current practice.
The researchers concluded that adherence to the new DAPT guidelines may be a target for quality improvement in the treatment of patients with ischemic stroke. ■