Overview of the PRN

The ACCP Critical Care Practice and Research Network (PRN), founded in 1992, optimizes pharmacotherapy outcomes through promoting excellence and innovation in clinical pharmacy practice, research, and education. Currently, it is home to over 1800 members, including 180 postgraduate trainees and 540 students. The PRN provides members with timely educational updates through continuing education programs, opportunities to participate in multicenter research, and a forum for information sharing across a national community of critical care pharmacists.

PRN Leadership

• Scott T. Benken, Pharm.D., MHPE, FCCP, FCCM, BCCCP, Chair
• Melissa Lynn Thompson Bastin, Pharm.D., PhD, FCCP, FCCM, BCCCP, Chair-Elect
• Payal K. Gurnani, Pharm.D., FCCM, BCCCP, BCPS, Secretary-Treasurer
• Dinesh Yogaratnam, Pharm.D., BCCCP, BCPS, Member-at-Large
• Jenna F. Cox, Pharm.D., FCCM, BCCCP, BCPS, Member-at-Large
• Sandra L. Kane-Gill, Pharm.D., BSPharm, MSc, FCCP, FCCM, Board Liaison
• Zach Smith, Pharm.D., FCCP, FCCM, BCPS, BCCCP, Past-Chair

Opportunities and Resources for Trainee Members

The Critical Care PRN welcomes all trainees (students, residents, and fellows) and encourages activity and engagement in each of its committees: Communications, Membership, Programming, Recognition, Research, Social Media, Trainee Engagement, and Travel Awards. Each committee is led by a chair and chair-elect and consists of trainee members and clinical pharmacists who collaborate throughout the year on various committee charges. One additional opportunity for involvement is serving as the trainee liaison. Each year, 1 trainee member is selected to serve on the Critical Care PRN Steering Committee as a liaison and advocate for other trainee members. Applications for this position typically open in September, so be on the lookout!

The Trainee Engagement Committee provides support in recruiting and maintaining trainee members who now have free membership to join all ACCP PRNs, including the Critical Care PRN. Each year, PGY2 critical care and emergency medicine residency program directors are provided with information on free ACCP membership that can be distributed to their residents. This committee also coordinates an annual feedback survey specifically for trainee members to optimize involvement opportunities, initiatives, and resources throughout the Critical Care PRN. Other initiatives include the Quarterly Trainee Spotlights, which highlight outstanding achievements of selected trainee members; Trainee Poster Practice Sessions, where trainee members can practice their poster presentations and receive feedback before the ACCP Annual Meeting; and “X” Journal Clubs, which are developed and facilitated by trainee members with a mentor. The PRN provides an annual “Keeping Up with the Literature” document aimed at providing strategies and resources for staying current with medical literature and guidelines. To help identify critical care and pharmacy-related conferences for presenting research, the PRN compiles a Conferences and Abstracts Guide with important dates and deadlines to ensure trainee members can plan accordingly.

The Critical Care PRN highly values trainee member engagement within the profession with opportunities including the PGY2 Critical Care Resident Research Grant, which offers financial support for residents conducting innovative critical care pharmacy research. In addition, 2 Critical Care PRN Student Travel Awards and 2 Critical Care PRN Resident/Fellow Travel Awards are available each year to offset the costs of attending and presenting research at the ACCP Annual Meeting. The PRN is active on social media and encourages trainee members to engage in and network through these platforms (X: @accpcritprn; Facebook: ACCP Critical Care PRN; Instagram: @accpcritprn)! The Critical Care PRN also has a mentorship program that pairs first-time attendees with an experienced PRN member to help them get the most from attending the ACCP Annual Meeting.

2026 ACCP Annual Meeting Travel Awards

This year, the Critical Care PRN will be sponsoring 4 travel awards: 2 for students ($1000 per award) and 2 for residents/fellows ($1250 per award). Information on how to apply, eligibility requirements, responsibilities, and deadlines can be found at the following links:

• ACCP - Student Travel Awards
• ACCP - Resident/Fellow Travel Awards

Current Issue: Iloprost for Severe Frostbite

Written by Samuel Yang, Pharm.D. (Critical Care PRN Trainee Liaison)

Background

Frostbite is a form of soft tissue injury resulting from exposure to extreme cold, affecting a diverse range of wilderness activity, military, and unhoused populations.¹ This condition can lead to limb amputation with few options for medical management to preserve limb structure and function. Analysis of a national database reported 2600 yearly admissions for frostbite, with an associated 20% amputation rate at initial presentation.² Digital amputations may cause significant and prolonged psychological consequences, as well as reduce patient-reported quality of life and functional status.^3,4 When compared with isolated extremity thermal burn injuries, patients with frostbite were found to have longer hospital stays (8.1 vs 4 days) and higher treatment costs ($43,400 vs $15,600).⁵ Frostbite is a highly morbid condition that disproportionately affects populations at high risk, such as patients experiencing homelessness, and can be associated with devastating consequences.

Frostbite typically affects the extremities and can present with waxy skin, numbness, swelling, pain, and black eschars.⁶ Two distinct pathophysiologic stages lead to microvascular damage progressing to limb ischemia.^1,7 During the cooling-supercooling-freezing stage, the normal physiologic response is peripheral vasoconstriction. When exposure is prolonged or at sufficiently low temperatures, ice crystals form, causing direct tissue injury and cellular death. In the vascular stage, thawing microcirculation is exposed to a secondary ischemic reperfusion injury from fluid shifts caused by endothelial dysfunction and inflammatory responses. One method of injury classification differentiates tissue depth similar to thermal burns, ordered as superficial (first), dermal (second), full-thickness (third), and subdermal tissue including muscle and bone (fourth).¹ An alternative grading classification has historically been applied to treatment strategies according to extent of initial lesion involvement and progression on day 2, ordered by location as none (grade 1), distal phalanx (grade 2), middle and proximal phalanx (grade 3), and carpal or tarsal (grade 4).

The Wilderness Medical Society endorses prevention through education and recognition as a key management strategy.⁸ Treatment recommendations differ depending on setting and resource availability. Field management includes thawing, hydration, correction of hypothermia, dressings and protection, and NSAIDs. In a resource-limited setting, the goal is to prevent further injury until the patient reaches a higher level of care at a field clinic or hospital. Definitive care at these settings focuses on restoring perfusion and mitigating damage from inflammatory activation at the site of injury.

Common pharmacologic therapies for frostbite target key inflammatory mediators of platelet and erythrocyte aggregation, such iloprost for prostaglandin F_2α and NSAIDs (aspirin or ibuprofen) for thromboxane A₂. Heparin and thrombolytics are also commonly used for severe frostbite to dissolve or reduce clot burden, improving microvasculature perfusion. Except for iloprost, all other drugs studied for frostbite have an off-label indication.

Iloprost

AURLUMYN (iloprost) was approved by the FDA in February 2024 to treat severe frostbite in adults to reduce the risk of finger or toe amputation.¹¹ Iloprost is a synthetic analog of prostacyclin I₂, which has vasodilating and platelet inhibition properties that target the primary pathophysiologic mediators of secondary ischemic injury.¹² This drug is administered as an intravenous infusion for 6 hours daily up to 8 days. Before the approval of AURLUMYN, intravenous iloprost was only available in Europe for other indications such as Raynaud disease, peripheral artery disease, and critical leg ischemia. In the United States, inhaled iloprost is approved for pulmonary artery hypertension, but is not currently available.¹³ Iloprost is primarily cleared by the kidneys after hepatic metabolism. There are no known pharmacokinetic drug interactions. Like other prostacyclin analogs, common adverse reactions include flushing, hypotension, nausea, and headache. Given the drug’s average wholesale price of $5500 per 100-μg/mL vial, an 8-day course of AURLUMYN for a patient of average weight may cost $44,000.¹⁴

Use of iloprost for frostbite is determined by the grade of frostbite and time of presentation from initial injury. For grade 3 and 4 frostbite, the Wilderness Medical Society issues strong recommendations for iloprost within 48 to 72 hours after rewarming and alteplase within 24 hours of injury.⁸ Other treatment strategies include the Helsinki protocol for grade 3 and 4 frostbite, combining alteplase, papaverine, and heparin within 48 hours of injury with iloprost as a second-line therapy.¹⁵ The Yukon protocol uses iloprost at grades 2 through 4 within 72 hours of rewarming with the addition of alteplase and heparin in early presentation of grade 4 frostbite.¹⁶ Most established protocols use iloprost and/or alteplase for higher grades of frostbite that present relatively early after initial injury.

A randomized controlled trial (RCT) conducted between 1996 and 2008 in France examined a total of 47 patients with severe frostbite randomized to receive one of three 8-day treatment regimens after an initial dose of intravenous aspirin 250 mg and intravenous buflomedil 400 mg (α-blocker)^17-19:

1. Intravenous buflomedil 400 mg daily and intravenous aspirin 250 mg daily
2. Intravenous iloprost 0.5 to 2 ng/kg/min for 6 hours daily and intravenous aspirin 250 mg daily
3. Intravenous alteplase 100 mg on day 1, intravenous iloprost 2 ng/kg/min for 6 hours daily, and intravenous aspirin 250 mg daily

The study sample was primarily young (mean age 33 years), male (94%), and free of medical or surgical comorbidities who acquired severe frostbite from high-altitude sports activities (96%). Patients were noted to have received this regimen directly after mountain rescue. At the participant level, amputations were significantly less common in the iloprost group (0%) and iloprost plus alteplase group (19%) than in the buflomedil group (60%). Similar findings were observed across the 407 frostbitten digits; significantly fewer digits were amputated in the iloprost group (0%) and iloprost plus alteplase group (3%) than in the buflomedil group (40%). Adverse effects included flushing (55%), nausea (25%), palpitations (15%), and vomiting (5%). A subgroup analysis found that the risk of amputation was significantly lower in participants who received any treatment within 12 hours compared with later treatment (4.8% vs 25% amputated digits, P < .001). The authors concluded that intravenous aspirin and iloprost should be used in the treatment of severe frostbite after rapid rewarming with the addition of alteplase on a case-by-case basis.

A review from 2023 identified 20 iloprost studies including 254 patients and more than 1000 frostbitten digits.²⁰ Most data included men in their 40s who developed frostbite from high-altitude sports. Classification methods and use of radiography to define frostbite severity were inconsistent across studies. Although most studies used the suggested dosing strategy from the AURLUMYN package insert, some cases also reported treatment duration ranging from 1 to 56 days. In addition, almost all studies reported the use of concomitant therapies with iloprost, the most common of which was NSAIDs followed by alteplase. This review suggests that iloprost use is associated with reduced amputation rates, though most of the data are from case series and reports.

Conclusion

Iloprost currently has a limited evidence base for severe frostbite, mostly consisting of retrospective data in a specific patient population. This is further supported by the package insert, which states that “[effectiveness] was established in young, healthy adults who suffered frostbite at high altitudes.”¹² Furthermore, the study protocol from the RCT included medications (intravenous aspirin and buflomedil) that are not available in the United States.¹⁸ Given the familiarity and efficacy of alteplase for different indications such as acute ischemic stroke, a trial comparing alteplase and iloprost may help elucidate each drug’s place in therapy. An ongoing trial from Finland began in 2018 to compare the 2 drugs; however, no updates are available.²¹ No robust data exist to compare alteplase and iloprost for this indication. Furthermore, there are no pharmacoeconomic analyses that compare iloprost with other frostbite treatments. Additional studies that may better inform the usefulness of this agent include large, multicenter retrospective cohorts or surveys describing institutional use.

Iloprost is a promising therapy to reduce digital amputation risk from severe frostbite but is limited by scarce literature and high cost. Pharmacists practicing at hospitals treating higher volumes of frostbite injuries should discuss the role of this medication in their institutional formulary and develop local guidelines in collaboration with other necessary providers (eg, surgeons). Education and other standard therapies for frostbite, such as supportive care, remain crucial in the hospital and field settings.

References

1. Sheridan RL, Goverman JM, Walker TG. Diagnosis and treatment of frostbite. N Engl J Med. 2022;386(23):2213-2220. https://doi.org/10.1056/NEJMra1800868

2. Endorf FW, Nygaard RM. Social determinants of poor outcomes following frostbite injury: a study of the national inpatient sample. J Burn Care Res. 2021;42(6):1261-1265. https://doi.org/10.1093/jbcr/irab115

3. Skoff H, Skoff H. The psychological and somatic consequences of digital amputation. Plast Reconstr Surg Glob Open. 2022;10(6):e4387. https://doi.org/10.1097/GOX.0000000000004387

4. Chung KC, Yoon AP, Malay S, et al. Patient-reported and functional outcomes after revision amputation and replantation of digit amputations: the FRANCHISE multicenter international retrospective cohort study. JAMA Surg. 2019;154(7):637-646. https://doi.org/10.1001/jamasurg.2019.0418

5. Nygaard RM, Endorf FW. Frostbite vs burns: increased cost of care and use of hospital resources. J Burn Care Res. 2018;39(5):676-679. https://doi.org/10.1093/jbcr/iry033

6. Torpy JM, Lynm C, Golub RM. JAMA patient page. Frostbite. JAMA. 2011;306(23):2633. https://doi.org/10.1001/jama.2011.1799

7. Mohr WJ, Jenabzadeh K, Ahrenholz DH. Cold injury. Hand Clin. 2009;25(4):481-496. https://doi.org/10.1016/j.hcl.2009.06.004

8. McIntosh SE, Freer L, Grissom CK, et al. Wilderness Medical Society clinical practice guidelines for the prevention and treatment of frostbite: 2024 update. Wilderness Environ Med. 2024;35(2):183-197. https://doi.org/10.1177/10806032231222359

9. Handford C, Buxton P, Russell K, et al. Frostbite: a practical approach to hospital management. Extrem Physiol Med. 2014;3:7. https://doi.org/10.1186/2046-7648-3-7

10. Imray C, Grieve A, Dhillon S; Caudwell Xtreme Everest Research Group. Cold damage to the extremities: frostbite and non-freezing cold injuries. Postgrad Med J. 2009;85(1007):481-488. https://doi.org/10.1136/pgmj.2008.068635

11. US Food and Drug Administration. Press release. FDA approves first medication to treat severe frostbite. US Food and Drug Administration; February 16, 2024. Accessed May 28, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-treat-severe-frostbite

12. AURLUMYN (iloprost). Prescribing information. SERB Pharmaceuticals; 2025. Accessed June 25, 2026. https://aurlumyn.com/sites/aurlumyn-library/files/2025-09/Aurlumyn_iloprost_label_Jan_2025.pdf

13. Drug shortage detail: iloprost inhalation solution (Ventavis). Accessed June 10, 2026. https://www.ashp.org/Drug-Shortages/Current-Shortages/Drug-Shortage-Detail.aspx?id=1008

14. SERB Pharmaceuticals. AURLUMYN ordering, pricing, and distribution product fact sheet. Published online November 2025. https://www.aurlumyn.com/documents/aurlumyn-pricing-ordering-distribution-fact-sheet.pdf

15. Lindford A, Valtonen J, Hult M, et al. The evolution of the Helsinki frostbite management protocol. Burns. 2017;43(7):1455-1463. https://doi.org/10.1016/j.burns.2017.04.016

16. Poole A, Gauthier J, MacLennan M. Management of severe frostbite with iloprost, alteplase and heparin: a Yukon case series. CMAJ Open. 2021;9(2):E585-E591. https://doi.org/10.9778/cmajo.20200214

17. Lorentzen AK, Davis C, Penninga L. Interventions for frostbite injuries. Cochrane Database Syst Rev. 2020;12(12):CD012980. https://doi.org/10.1002/14651858.CD012980.pub2

18. Cauchy E, Cheguillaume B, Chetaille E. A controlled trial of a prostacyclin and rt-PA in the treatment of severe frostbite. N Engl J Med. 2011;364(2):189-190. https://doi.org/10.1056/NEJMc1000538

19. Cheguillaume B. Essai Contrôlé de l’iloprost et Du Rt-PA Dans Le Traitement Des Gelures Graves. Master’s thesis. 2011. https://dumas.ccsd.cnrs.fr/dumas-00618697

20. Gauthier J, Morris-Janzen D, Poole A. Iloprost for the treatment of frostbite: a scoping review. Int J Circumpolar Health. 2023;82(1):2189552. https://doi.org/10.1080/22423982.2023.2189552

21. Study on frostbite treatment for severe cases using alteplase and iloprost. European Clinical Trials Information Network. Accessed June 5, 2026. https://clinicaltrials.eu/trial/study-on-frostbite-treatment-for-severe-cases-using-alteplase-and-iloprost/