Overview of the Critical Care PRN

The Critical Care PRN is made up of pharmacists practicing in a variety of settings across the world, but primarily in ICUs and EDs. The PRN has a rich history. Since its establishment as one of the 2 original PRNs in 1992, its membership has grown to include 1530 active members, including 108 residents, 4 research fellows, and 212 students. Most days, there is an active discussion on the PRN email list (eg, Communities) regarding new evidence published on the care of critically ill patients, sharing of best practices between institutions, and weighing in of experts on the clinical controversies that members face in their practices.

Opportunities and Resources

The ACCP Critical Care PRN welcomes all student, resident, and fellow (SRF) members and encourages activity and engagement in each of its committees: Communications, Membership, Programming, Recognition, Research, Social Media, Trainee Engagement, and Travel Awards.

The PRN supports registration for or travel to the ACCP Annual Meeting for 2 residents and 2 student members. SRFs serve on each of the committees and have an active voice within the PRN. In addition, networking opportunities are plentiful, both through online interactions and in person at the PRN business meeting. The PRN also provides several resident research grants, and residents receiving these awards present their findings at the Critical Care PRN Business Meeting and Networking Session held each year at the ACCP Annual Meeting.

The Critical Care PRN is active on social media (X: @accpcritprn and Facebook: ACCP Critical Care PRN), highlighting member achievements—specifically highlighting 2 trainee spotlights each quarter!

Current Issue: Overcoming Loop Diuretic Resistance in Acute Decompensated Heart Failure

By: Abigail Rath, Pharm.D., PGY2 Critical Care Resident and ACCP Critical Care PRN SRF Liaison

Acute decompensated heart failure (ADHF) caused by left ventricular dysfunction is represented by sodium and water retention that contributes to symptoms such as shortness of breath and edema. The onset of ADHF can occur gradually, typically over days.¹ First-line treatment recommended by evidence-based guidelines to remove fluid and provide decongestion for patients with heart failure who are normotensive is to administer intravenous loop diuretics. If patients are nonresponsive to the initial dosing of an intravenous loop diuretic, increasing the dose of it or adding a second diuretic with a different mechanism is recommended.^1,2 There is no universally accepted definition of diuretic resistance, and proposed definitions have been widely variable. Examples of these include a failure to excrete at least 90 mEq/L of sodium within 72 hours of 160-mg twice-daily furosemide, persistent congestion after oral furosemide dosing above 80 mg per day, less than 2 L of urine output in 12 hours while receiving at least 24 mg/d of furosemide equivalents, or practically less than 20% the amount of sodium excreted as a percentage of filtered load.^3,4 Diuretic resistance in decompensated heart failure can be attributed to intestinal edema, leading to decreased oral diuretic absorption among some of the loop diuretics; or decreased renal perfusion, leading to reduced filtration leading to decreased delivery of loop diuretics to the nephron.³ Given the many patients who experience volume overload despite loop diuretic therapy, alternative treatments have been investigated.

Trials such as DOSE and REALITY-AHF have explored loop diuretic dosing strategies to optimize outcomes in patients presenting with ADHF. The DOSE trial was a 2 × 2 factorial designed trial that looked at a patient’s home dose compared with a 2.5 times dose and whether an intravenous bolus or intravenous continuous infusion was superior at providing decongestion at 72 hours. These investigators found that patients in the high-dose arm had improved decongestion, weight loss, and total diuresis. There was no difference with respect to administering loop diuretics as an intravenous bolus or intravenous continuous infusion.⁵ The REALITY-AHF trial looked at early (defined as less than 60 minutes) versus late (more than 60 minutes) administration of loop diuretics from hospital admission and found that early loop diuretic administration had a significantly lower in-hospital mortality.⁶

One of the key adverse effects that can be observed in patients undergoing significant diuresis is contraction alkalosis. In a patient with heart failure and volume overload that is refractory to loop diuretics, several adjunct diuretic approaches exist including thiazides, carbonic anhydrase inhibitors (CAIs), SGLT2 (sodium-glucose cotransporter-2) inhibitors, and potassium-sparing diuretics. The CAI acetazolamide has gained attention over the years because of its theoretical ability to treat or prevent the contraction alkalosis seen in patients undergoing aggressive diuresis with loop diuretics.

The ADVOR trial, published in 2022, aimed to determine whether adding acetazolamide to standardized intravenous loop diuretic therapy would improve the incidence of successful decongestion among patients hospitalized with ADHF.⁷ This was a multicenter, parallel-group, double-blind randomized, placebo-controlled trial that compared patients receiving either acetazolamide 500 mg intravenously once daily or placebo added with patients receiving standardized intravenous loop diuretics. The primary outcome was successful decongestion, defined as the absence of signs of volume overload (ie, no more than trace edema, no residual pleural effusion, and no residual ascites) as assessed by a cardiologist trained in completion of the congestion score, within 3 days after randomization without an indication for escalation of decongestive therapy. The primary outcome was statistically significant, occurring in 42.2% of patients in the acetazolamide group compared with 30.5% of patients in the placebo group (P < .001). A subgroup analysis found that patients with an ejection fraction of 40% or less, who identified as female, had an estimated GFR of 39 mL/min/1.73 m² or greater; those receiving higher maintenance doses of loop diuretics (greater than 60 mg of furosemide equivalents) had less benefit from acetazolamide. No differences were observed in secondary outcomes, including duration of hospital stay or death from any cause or rehospitalization for heart failure, during 3 months of follow-up. Furthermore, there was no difference in the safety outcomes evaluated, which included severe metabolic acidosis, hypokalemia, hypotension, or cardiovascular adverse events.⁷

Overall, the authors concluded that adding acetazolamide to standardized intravenous loop diuretic therapy in hospitalized patients with ADHF led to a higher incidence of successful decongestion.⁷ This trial lays the framework for future trials to investigate optimal combination diuretic decongestion strategies in ADHF. The ADVOR trial adds to the limited literature surrounding successful decongestion strategies in ADHF.

References

1. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure [published correction appears in Eur Heart J. 2021;42(48):4901. https://doi.org/10.1093/eurheartj/ehab670]. Eur Heart J. 2021;42(36):3599-3726. https://doi.org/10.1093/eurheartj/ehab368
2. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022;145(18):e1033. https://doi.org/10.1161/CIR.0000000000001073]. Circulation. 2022;145(18):e895-e1032. https://doi.org/10.1161/CIR.0000000000001063
3. Wilcox CS, Testani JM, Pitt B. Pathophysiology of diuretic resistance and its implications for the management of chronic heart failure. Hypertension. 2020;76(4):1045-1054. https://doi.org/10.1161/HYPERTENSIONAHA.120.15205
4. ter Maaten JM, Valente MA, Damman K, Hillege HL, Navis G, Voors AA. Diuretic response in acute heart failure-pathophysiology, evaluation, and therapy. Nat Rev Cardiol. 2015;12(3):184-192. https://doi.org/10.1038/nrcardio.2014.215
5. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797-805. https://doi.org/10.1056/NEJMoa1005419
6. Matsue Y, Damman K, Voors AA, et al. Time-to-furosemide treatment and mortality in patients hospitalized with acute heart failure. J Am Coll Cardiol. 2017;69(25):3042-3051. https://doi.org/10.1016/j.jacc.2017.04.042
7. Mullens W, Dauw J, Martens P, et al. Acetazolamide in acute decompensated heart failure with volume overload. N Engl J Med. 2022;387(13):1185-1195. https://doi.org/10.1056/NEJMoa2203094