Which anti-inflammatory agent is best to treat frostbite, aspirin or NSAID?

Report By: Marianne Gauthier - PGY4 emergency medicine
Search checked by Maude St-Onge - Critical Care Physician and Emergency Physician
Institution: Université Laval, Canada
Date Submitted: 8th October 2015
Last Modified: 8th October 2015
Status: Blue (submitted but not checked)

Three Part Question

In [patients suffering from frostbite], which [anti-inflammatory agent is better between aspirin and NSAID] to [reduce tissue loss]?

Clinical Scenario

A 33 years-old itinerant comes to the emergency department after a long winter night outside. He has clear blisters on three of his right fingers. You diagnose moderate frostbite and you start a rewarming process. Then, you wonder what to give him to reduce the inflammatory cascade. Should you use aspirin or a non-steroidal-anti-inflammatory drug?

Search Strategy

Search conducted on September 9th , 2015

A. The website clinicaltrials.gov was searched for an ongoing trial on the topic.
1) None
B. Cochrane review
1) None
C. MEDLINE (PubMed)
1) frostbite[MeSH Terms] = 1800
2) frostbite = 2107
3) (agents, nonsteroidal antiinflammatory[MeSH Terms]) OR (aspirin[MeSH Terms]) OR antiinflammatory agents[MeSH Terms]) OR ibuprofen[MeSH Terms]) OR naprosyn[MeSH Terms]) OR ketorolac[MeSH Terms]) OR indomethacin[MeSH Terms]) OR diclofenac[MeSH Terms]) OR acetylsalicylic acid[MeSH Terms]) OR acid, salicylic[MeSH Terms]) OR diclofenac[MeSH Terms]))) = 187197
4) ((((((((NSAID) OR nonsteroidal antiinflammatory agents) OR (aspirin OR asa OR salicylic acid)) OR ibuprofen) OR naprosyn) OR diclofenac) OR ketorolac) OR indomethacin) OR acetylsalicylic acid = 256289
5) 1 AND 2 = 2107
6) 3 AND 4 = 304344
7) 5 AND 6 = 31
8) After abstract review = 1 article selected
9) After reading reviews and their references = 0 new article relevant

D. EMBASE
1) 'frostbite'/exp OR 'frostbite' AND ('antiinflammation agent'/exp OR 'antiinflammation agent' OR 'aspirin'/exp OR 'aspirin' OR 'ibuprocin'/exp OR 'ibuprocin' OR 'salicyclic acid'/exp OR 'salicyclic acid' OR 'naproxen'/exp OR 'naproxen' OR 'ketorolac'/exp OR 'ketorolac' OR 'diclofenac'/exp OR 'diclofenac' OR 'indometacine'/exp OR 'indometacine') = 94
2) After abstract review = 1 new article selected
3) After reading reviews and their references = 0 new article relevant

Search Outcome

2 relevant articles

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Heggers JP, Robson MC, Manavalen K, et al 1987 USA	154 patients with frostbite injuries admitted at Detroit Receiving Hospital from 1982 to 1985. Group 1 (56 patients): treated with the frostbite protocol including Ibuprofen (12 mg/kg PO per day), aloe vera and penicillin prophylaxis Group 2 (98 patients): treated with a variety of therapeutic modalities but no medication other than topical antibiotics	Control trial	Tissue loss	25% for protocol group vs 34,6% (p<0,01), RR =0,48, NNT=2,8	Allocation biais (No randomization) Sampling biais (only admitted patient) Selection biais Confusion biais (no rando) Not blinded
			Amputation	7% for protocole group vs 32,7% (p<0,01), RR=0,22, NNT=3,9
			Hospital length of stay	Acute injury : 8,5 days for protocol group vs 17,5 days Subacute injury : 14,9 days for protocol group vs 19 days
McCauley RL, Hing DN, Robson MC, Heggers JP 1983 USA	38 consecutive patients with frostbite injuries admitted to The University of Chicago Burn Center in January 1982	Observationnal study	Tissue loss	No major tissue loss (one patient with tissue loss but no reconstruction needed)	No control group No randomization Selection biais Small population
McCauley RL, Hing DN, Robson MC, Heggers JP 1983 USA		Observationnal study	Hospital length of stay	Acute injury : 5,6 days Subacute injury : 6,9 days

Comment(s)

In terms of pathophysiology, it makes sense that aspirin or NSAID would help prevent further ischemia in frostbite by blocking the inflammatory cascade. They are given all around the world, but there is only one old study with multiples biais that shows benefits to give ibuprofen (with aloe vera and penicillin). The other study noted that patients treated with aspirin, also with aloe vera and penicillin, dit not have major tissue loss, but there was no control group. Finally, there is no study that compare directly aspirin and NSAID for frostbite treatment.

Clinical Bottom Line

Ibuprofen, along with aloe vera and penicillin prophylaxis, should be considered to treat frostbite. There is poor evidence that aspirin, also with aloe vera and penicillin prophylaxis, could have a benefit. Nevertheless there is no evidence that compare anti-inflammatory agents.

References

Heggers JP, Robson MC, Manavalen K, et al. Experimental and clinical observations on frostbite Ann Emerg Med 1987;16:1056–1062
McCauley RL, Hing DN, Robson MC, Heggers JP Frostbite injuries: a rational approach based on the pathophysiology J. Trauma 1983; 23:143Y7