Ateş Karıncasının Mitigator iğnesi ve ısırma tedavisiyle olan tedavisi- Randomize Kontrol Çalışması
Amaç- ticari olarak mevcut olan bir ürünün ateş karıncası ısırmasından sonra ağrıyı azaltmak için Mitigator iğnesi ve ısırma tedavisiyle etkinliğini değerlendirmek.
Yöntem-Yirmi dört gönüllü hususlar her iki ateş karınca sokmalarına maruz bırakıldı. Hususlar 1 kolda Mitigator macunu ve diğer kolda kalamin losyonuna maruz kaldılar. Konular 100 mm vizüel analog skalasında 60 saniye, 20 dakika ve 3 gün maruz kaldıktan sonra bir ağrı kaydedildi. A 2-tailed eşleştirilmiş t testi Mitigatorla tedavi edilen kolla kalamin losyonuyla tedavi edilen kol arasındaki farkı karşılaştırmak için kullanılandı.
Sebepler – 60cı saniyede Mitigator grubunun ortalama görsel analog ağrı skoru 23.9 ve kalamin grubu 24.5 tu. 20ci dakikada Mitigator grubunun puan ortalama skoru 7.6mm idi. 3cü günde, Mitigator grubunun puan ortalamaları ve 2,4 mm ve kalamin grubu için 2,9 mm idi. 60cı saniyede, 20ci dakikada ve ya 3cü günde ortalama analog skorunda hiç bir önemli bir değişiklik olmadı.
Sonuçlar- ateş karıncasının ağrısının azaltılmasında kalamin ve Mitigator arasında hiç bir önemli bir değişiklik olmadı
Giriş
Ateş karıncaları orta-güney ve güneydoğu Birleşik Devletleri boyunca dağıtılmıştır. Ateş karıncasının yılda 1 milyondan çok kişini ısırdığı tahmin ediliyor ve bu ısırmalarla alakalı onbinlerce insan alerji ve infeksiyonlu komplikasyonlarla ilgili tedavi aramaktadır. Isırmaların şiddeti hafif, yerel püstül formasyonundan anafilaksin nadir durumlarına kadar değişebilir. Lokal enflamatuar yanıtı tipikdir ve ve geçici zayıflatmaya neden olabilir. Çok olduğu zaman alerjik ve ya infeksiyoz komplikasyonlar hayati ciddi durumlar yarata bilir.
Yöntemler
Bu çalışma rastgele bir çalışma olmuştur, ateş karıncasının tedavisi için tek denemelik kalamin losyonu vs Mitigator Walgreeens dükkânından alınmıştır. Topikal olarak uygulandığında Mitigator güvenli ve toksinsiz olarak kabul ediliyor. İçeriği su, ceviz kabukları, balmumu NF, pentaerythrityl tetracappryate, izopropil palmitat, ceterearyl alkol, polisorbat 60, sodyum bikarbonat, papain, denatüre alkol, sodyum hidroksit, metilparaben, propilparaben, emülsifiye edici ve fenoksietanol. Bu yazı zamanında Mitigatorun onsı yaklaşık $6 değerinde, kalamin losyonunun ise 6 onsı $2.79 değerindedir. Kurumsal gözden geçirme kurulu onayı çalışmaya başlamadan önce elde edilmiş ve yazılı bilgilendirilmiş onam tüm deneklerden alınmıştır. Gönüllü hususlar halk içinde yayınlanmış teşhir bültenleri kullanılarak alındı. Çalışmaya ilgi gösteren kişiler bir günlük görüşmede hep beraber bir araya geldiler. Denemenin amacını ve tasarımını duyduktan sonra katılmak için istekli olanlara bir sağlık tarama anketi verildi. Tüm kadınlardan denekler katılımı önce idrarda gebelik testi istendi. Aşağıdaki ölçütlere uygun bulunanlar kabul edildiler ve kayıt oldular 18-50 yaş arası ateş karıncası ısırmadan önce, ciddi bir tıbbi durumu olmayanlar, böcek ısırmalarına daha önce alerjisi olmayanlar, astım ve ya diğer reaktif havayolu hastalıkları olmayanlar ve cevize karşı alerjisi olmayanlar. Ayrıca, katılmak isteyenler 3 gün sonra bir takip oturumuna katılacaklarını sağlamak zorundaydılar. Hamile olanlar veya düzenli oral kortikosteroid, anti-inflamatuar ajan, veya antihistaminik kullananlar konu dışı bırakıldı. Yirmi dört kayıtlı hususlar (7 [% 28] kadın ve 17 [% 68] erkek) 10 canlı traş olmuş kol üstünde küçük bir kapda ateş karıncaları ısırmalarına maruz bırakıldı. Isırma 10 saniyelik oldu. Standart bir prosedur olarak karıncaları ısırdıktan sonra kaldırıldı. 1 dakikada tüm hususlara vücut bölgesi göstermek için ‘L’ (sol) ve ‘R’ (sağ) etiketli kart verildi. Kartlar uzunluğu 100 mm olan “en çok acı” ve “en az acı” etiketli görsel analog skalası içeriyordu. Hususlardan her kartta tedavi öncesi ağrı düzeyini gösteren görsel analog skalası çizmeleri istendi. Isırmalardan 90 saniye sonra Mitigator pastası kol üstünün zehirlenme bölgelerinin farklı yerlerine ve kalamin losyonunun 0,5 onsu alternatif kola uygulandı. Bu sürede hususların gözleri kapatıldı. Tedavi randomu tura ile belirlendi. Macun veya losyon kuvvetlice 2-3 dakika etkilenen bölgeye sürüldü, 10 dakika o şekilde kaldı ve daha sonra Mitigator için paket talimatlarına göre durulandı. 20 dakikada hususlardan tekrar ağrıyı derecelendirilmeleri istendi. Hususlar daha sonra görevden alındı ve bir sonraki 72 saat içinde ısırmaları istedikleri gibi tedavi etmelerine izin verildi. 72ci saatte hususlar takip için çalışma araştırmacılarının yanına döndüler ve kartların üçüncü setini tamamladılar. Yanıtlar kayd edildi ve statiksel analizler örnek için hazırlandı. Eşleştirilmiş t-testi ve Wilcoxon
Sonuçlar
Mitigator 8 kişide sol kolda ve 16 kişide sağ kolda yerleştirildi ve her bir kişide diğer kola kalamin losyonu uygulandı. Tedaviye hiçbir sistematik tepki olmadı. 60cı saniyede ya da 3cü günde gruplar arasında hiçbir fark görülmedi. Sadece 3 kişi ev tedavisine kayıt oldular 1ci gün ve 2 takip 2 kişi oral difenhidramin ve aspirin aldı
Netice
Mitigator ve kalamin losyonu tedavisi arasında ani veya gecikmeli ağrı gösterilebilir fark yoktu. Bu zehirlenmeler potansiyel hastalık kaynağı olarak kalıyor ve tedavisi için daha fazla araştırma gerekmektedir.
Wilderness and Environmental Medicine, 17, 21 25 (2006)
ORIGINAL RESEARCH
Treatment of Imported Fire Ant Stings With Mitigator
Sting and Bite Treatment—A Randomized Control Study
David C. Hile, MD; Troy P. Coon, MD; Carl G. Skinner, MD; Lisa M. Hile, MD; Phillip Levy, MD;
Manish M. Patel, MD; Michael A. Miller, MD
From Darnall Army Community Hospital, Fort Hood, TX (Drs Hile, Coon, Skinner, Levy, Hile, and Miller); Wayne State University–Detroit
Receiving Hospital, Detroit, MI (Dr Levy); and Emory University, Atlanta, GA (Dr Patel).
Objective.—To evaluate the efficacy of the commercially available product Mitigator Sting and
Bite Treatment in reducing the pain after imported fire ant stings.
Methods.—Twenty-four volunteer subjects were exposed to imported fire ant stings on both forearms.
The subjects received Mitigator paste on 1 arm and calamine lotion on the opposite arm, in a
blinded manner, from 90 seconds to 10 minutes after exposure. Subjects recorded pain on a 100-mm
visual analog scale 60 seconds, 20 minutes, and 3 days after exposure. A 2-tailed paired t test was
used to compare the difference in reduction of pain over time between the Mitigator-treated arms and
the calamine-treated arms.
Results.—At 60 seconds, the mean visual analog scale pain score was 23.9 mm for the Mitigator
group and 24.5 mm for the calamine group. At 20 minutes, the mean score was 7.6 mm (_ _ 16.3)
for the Mitigator group and 12.7 mm (_ _ 11.8) for the calamine group. At 3 days, the mean score
was 2.4 mm (_ _ 21.5) for the Mitigator group and 2.9 mm (_ _ 21.6) for the calamine group.
There was no significant difference between groups for change in visual analog scale pain score at
60 seconds, 20 minutes (P _ .256), or 3 days (P _ .64).
Conclusions.—There was no significant difference in pain relief between calamine and Mitigator
for imported fire ant stings.
Key words: imported fire ant, Hymenoptera, calamine lotion, insect bites and stings, therapeutic techniques
and equipment, pain management, analgesia, Mitigator
Introduction
Imported fire ants (IFAs) are widely distributed across
the south-central and southeastern United States, having
been introduced from their native habitat in sub-Amazonian
South America many decades ago. By far, the
most common and widely distributed species is Solenopsis
invicta, the red IFA. In recent years, red IFAs
have also been discovered in New Mexico, in California,
and on many Caribbean islands, as well as in Australia
and New Zealand.1
This abstract was presented at the annual conference of the Society
for Academic Emergency Medicine, May 22 to 25, 2005, in New York,
NY.
There was no funding in the production of the above manuscript.
Mitigator product was provided courtesy of Mr Pat Kennedy of
www.mitigator.net. We are not aware of any conflicts of interest.
Corresponding author: David Hile, MD, 2014 Lakefront Dr, Harker
Heights, TX 76548 (e-mail: hile_16@yahoo.com).
It is estimated that IFAs sting more than 1 million
people in the United States annually, and tens of thousands
of people will seek medical treatment for allergic
and infectious complications related to these stings.2 The
severity of the stings can range from mild, local pustule
formation to rare cases of anaphylaxis in predisposed
individuals.3,4 Development of a local inflammatory response
is typical and may result in temporary debilitation.
In the wilderness, allergic or infectious complications
may create a potentially life-threatening situation.
Efforts to diminish the duration and severity of symptoms
once a person has been stung have not yielded
positive results.5–7 Mitigator Sting and Bite Treatment
(American Natural Technology Sciences, Rogers, AR) is
a recently developed paste that targets the local inflammatory
reaction associated with IFA stings. Mitigator is
hypothesized to work by rendering the IFA venom ineffective,
possibly by protein denaturation. Although anecdotal
evidence of successful IFA treatment with Mit22
Hile et al
Sting technique.
igator exists, no randomized trials have been conducted.
This study was therefore designed to investigate the clinical
benefit of Mitigator through comparison with a common
standard therapy.
Methods
This study was designed as a randomized, single-blind
comparison trial of IFA sting treatment with Mitigator
vs calamine lotion purchased from a Walgreens store.
Mitigator is considered safe and nontoxic when applied
topically. The main ingredients are water, walnut shells,
emulsifying wax NF, pentaerythrityl tetracappryate, isopropyl
palmitate, ceterearyl alcohol, polysorbate 60, sodium
bicarbonate, papain, alcohol denatured, sodium hydroxide,
methylparaben, propylparaben, and phenoxyethanol.
At the time of this writing, Mitigator costs approximately
$6 for 1 ounce of scrub in comparison with
$2.79 for 6 ounces of calamine lotion. Institutional review
board approval was obtained before study initiation,
and written informed consent was obtained from
all subjects.
Volunteer subjects were recruited by using publicly
displayed bulletins. Individuals who expressed interest
in the study were gathered at a single-day event. After
hearing an explanation of the intent and design of the
trial, those who were willing to participate were given a
health-screening questionnaire. All female subjects were
required to take a urine pregnancy test before participation.
Subjects who met the following inclusion criteria
were consented and enrolled: age 18 to 50 years with
prior exposure to IFA stings, absence of a serious medical
condition, absence of previous IFA stings or allergic
reactions to insect bites or stings, absence of asthma or
other reactive airway diseases, and absence of a known
allergy to walnuts. In addition, those willing to participate
had to ensure ability to attend a follow-up session
3 days later. Subjects who were pregnant or were regularly
using oral corticosteroids, anti-inflammatory
agents, or antihistamines were excluded.
Twenty-four enrolled subjects (7 [28%] women and
17 [68%] men) were exposed to IFA stings on a small
shaved area of both forearms with a small cup containing
10 live IFAs (Figure). Sting exposure was for 10
seconds, based on a rough estimation of time for a typical
IFA encounter. After exposure, the subjects were
allowed to remove the ants, as would be standard procedure
for a reasonable person. At 1 minute, all subjects
were given cards labeled ‘L’ (left) and ‘R’ (right) to indicate
body site. The cards contained a visual analog
scale (VAS), 100 mm in length, with ends labeled ‘‘most
pain’’ and ‘‘least pain.’’ The subjects were asked to draw
a line through the VAS indicating pain level before treatment
on each card, with response for each arm considered
independently. At 90 seconds after the stings, treatment
with 0.5 ounces of Mitigator paste was applied to
a randomly selected envenomation site (left or right forearm),
and standard 0.5 ounces of calamine lotion was
applied to the alternative arm. Subjects were blinded to
treatment allocation. Treatment randomization (right or
left) was predetermined by a coin flip. The paste or lotion
was vigorously rubbed into the affected area for 2
to 3 minutes, left in place for 10 minutes, and then rinsed
off as per the package instructions for Mitigator. At 20
minutes poststing, subjects were asked to repeat the pain
rating on another pair of 100-mm VAS cards labeled
‘‘L’’ and ‘‘R’’ without seeing their initial responses. Subjects
were then dismissed and allowed to treat the stings
as desired for the next 72 hours. At 72 hours, the subjects
returned for direct follow-up with study investigators
and completed a third set of VAS cards.
Baseline VAS responses were recorded and statistical
analysis was performed for the self-pairing study sample.
A 2-tailed paired t test (parametric) and the Wilcoxon
signed rank test (nonparametric) were used to compare
differences in pain-score change from 60 seconds
to 20 minutes and from 60 seconds to 3 days for grouped
data of the Mitigator- and calamine-treated arms. By using
13 mm as the statistically significant difference in
change of pain over time between groups, with a power
of 80% and a 2-tailed alpha of 0.05, we determined that
a minimum of 21 subjects would be needed. We also
used a random-effects repeated-measures analysis of
variance and found similar results as with the paired t
test (results not reported).
Results
Mitigator was placed on the left arm in 8 subjects and
on the right arm in 16 subjects, with calamine lotion
Treatment of Imported Fire Ant Stings 23
Table 1. Perceived pain (in millimeters) by individual subjects on the visual analog scale
Subject
Mitigator
60 s 20 min 3 d
Calamine
60 s 20 min 3 d
1
2
3
4
5
6
7
8
9
10
11
12
22
57
67
17
2
3
19
32
33
7
11
51
4
11
42
3
0
0
7
1
15
2
0
32
0
2
9
0
8
0
0
0
10
2
0
14
10
32
58
15
5
3
23
9
24
4
5
64
4
11
17
13
4
0
6
6
21
21
12
14
0
0
9
4
28
0
0
0
4
2
0
3
13
14
15
16
17
18
19
20
21
22
23
24
17
26
7
2
27
16
22
27
49
48
8
4
1
0
0
2
24
9
0
19
5
6
0
0
0
0
6
0
0
1
2
4
0
0
14
0
74
27
19
1
32
17
23
8
49
52
30
4
25
0
7
3
10
6
9
0
57
35
25
0
1
0
0
0
0
0
0
1
3
4
11
0
Table 2. Mean perceived pain (in millimeters) by each subject
as recorded on the visual analog scale
Time
Mean pain
Calamine Mitigator
Difference
(95% CI) P value
60 s
20 min
3 d
24.5
12.8
2.92
23.9
7.63
2.42
0.583 (_6.22, 7.39)
5.13 (_1.94, 12.2)
0.500 (_1.88, 2.88)
.861
.147
.668
applied to the opposite respective arm in each individual.
There were no systemic reactions to IFA stings or adverse
reactions to treatment. Within-group baseline VAS
scores (Table 1) were generally similar, with the exception
of subject No. 13. There were no significant between-
group differences in mean VAS scores at baseline,
60 seconds, or 3 days (Table 2). Mean change in VAS
scores over time was statistically equivalent between
groups (Table 3). Only 3 of the subjects described the
use of any at-home therapy between day 1 and their
follow-up visit: 2 subjects used oral diphenhydramine
and 1 subject used oral aspirin and topical 1% hydrocortisone
cream on both arms. Subject No. 9 sought
medical care for her IFA stings, which had resulted in
bilateral arm hives when she went to work at a local
hospital 1 hour after her participation. She was treated
with diphenhydramine orally and a 5-day prescription
for prednisone. She had no complications at her 3-day
follow-up visit.
Discussion
Although fewer than 20% of those who seek medical
attention for IFA envenomation (1% of all who receive
IFA stings) will require an intervention such as treatment
of local infection or systemic reaction,8,9 identification
of effective treatment for IFA stings is important. Venom
from IFAs is composed of a mixture of allergens and
alkaloids, which shares some similarities to other Hymenoptera
species.3,10,11 The humoral responses invoked
by the envenomation include neurogenic inflammation
and cytokine cascade initiation as well as the generation
of humoral antibodies.11,12 Adverse local reactions may
occur as a result, and there have been several case reports
of IgE-mediated anaphylaxis.4,10 Immunotherapy
24 Hile et al
Table 3. Mitigator vs calamine lotion mean decrease in pain (in millimeters) from the visual analog scale
Time Mitigator Calamine Difference (95% CI) P value
60 s to 20 min
20 min to 3 d
60 s to 3 d
16.3
5.21
21.5
11.8
9.83
21.6
4.54 (_3.53, 12.6)
_4.625 (_11.4, 2.12)
_0.083 (_7.00, 6.83)
.256
.150
.640
has emerged as a potential therapy for people with severe
allergic reactions, but no advances have been made
regarding treatment of local pain and inflammation. Multiple
cellular processes are involved in the pain response,
and once initiated, pharmacotherapeutic intervention is
difficult. Although prophylactic treatment may effectively
block similar processes, as demonstrated in a recent
trial involving Chrysaora fuscescens and Chiropsalmus
quadrumanus (jellyfish) envenomations,13 this is not a
practical approach for IFA stings, as exposure is rarely
anticipated. Consequently, interventions directed at minimizing
pain are needed.
Available data on the treatment of IFA envenomations
are limited, and the manner of appropriate management
is uncertain. We believe this study is the first to address
the treatment of IFA stings through a randomized clinical
trial. We chose to investigate a commercially available
product (Mitigator) in an attempt to substantiate
subjective reports of its efficacy. However, we were unable
to demonstrate any statistical difference in relief of
pain when Mitigator was compared with a standardized
regimen with calamine treatment, and the situation remains
unresolved.
There may be multiple etiologies for the lack of statistically
significant differences in this study. Although
our study population was small, the number needed to
show a clinical difference on our VAS was sufficient. In
a study of this type, one would expect a curvilinear decrease
in pain, with the greatest difference in treatment
effect initially. Although there was a ‘‘trend’’ toward a
decrease in the Mitigator-treated arm at 20 minutes, the
difference was not significant. We acknowledge that subject
No. 13 in our study had a wide variability in pain
at onset between the calamine- and Mitigator-treated
arms. However, excluding this subject from the database
and recalculating the data still failed to demonstrate a
significant difference between the 2 treatments. Among
the multiple possible reasons for this is the inability of
the clinical setting to adequately reproduce the natural
environment. As those who have been stung will recall,
IFAs frequently ‘‘attack’’ in unison, and a person may
easily receive 10 to 20 stings before the ants can be
removed. Although approximately 10 ants were present
in each container in this study, many subjects experienced
just 2 or 3 stings. Furthermore, it is likely that the
ants expended their venom during the collection process
and therefore may have had less venom available during
the study than in the natural environment. This may have
led to decreased initial pain in the study population, thus
decreasing the apparent treatment effect. Because the
initial pain described by the subjects was low, demonstration
of therapeutic benefit from Mitigator, if it exists,
may require more volunteers than this study enrolled.
Future studies may benefit from attempts to increase initial
pain levels either by increasing the total number of
stings or by ‘‘resting’’ the IFAs for a number of days to
ensure that high levels of venom are present in the study
ants.
Conclusion
There was no demonstrable difference in immediate or
delayed pain relief between Mitigator and calamine lotion
therapy for IFA stings. These envenomations remain
a source of potential morbidity, and further investigation
into appropriate treatment is needed.
Acknowledgments
We thank the Brooke Army Medical Center Institutional
Review Board for reviewing and approving this study.
Mitigator Sting and Bite Treatment was provided upon
request for this study by Mr Pat Kennedy and American
Natural Technology Sciences, Rogers, AR; however, no
financial relationship exists between the investigators
and the manufacturer or distributors of Mitigator Sting
and Bite Treatment.
References
1. Morrison LW, Porter SD, Daniels E, Korzukhin MD. Potential
global range expansion of the invasive fire ant, Solenopsis
invicta. Biol Invasions. 2004;6:183–191.
2. Caldwell ST, Schuman SH, Simpson WM Jr. Fire ants: a
continuing community health threat in South Carolina. J
S C Med Assoc. 1999;95:231–235.
3. Freeman TM, Hylander R, Ortiz A, Martin ME. Imported
fire ant immunotherapy: effectiveness of whole body extracts.
J Allergy Clin Immunol. 1992;90:210–215.
Treatment of Imported Fire Ant Stings 25
4. Caplan EL, Ford JL, Young PF, Owenby DR. Fire ants
represent an important risk for anaphylaxis among residents
of an endemic region. J Allergy Clin Imunol. 2003;
111:1274–1277.
5. Ross EV, Badame AJ, Dale SE. Meat tenderizer in the
acute treatment of imported fire ant stings. J Am Acad
Dermatol. 1987;16:1189–1192.
6. Bruce S, Tschen EH, Smith EB. Topical aluminum sulfate
for fire ant stings. Int J Dermatol. 1984;23:211.
7. Parrino J, Kandawalla NM, Lockey RF. Treatment of local
skin response to imported fire ant sting. South Med J.
1981;74:1361–1364.
8. Yeager W. Frequency of fire ant stinging in Lowndes
County, Georgia. J Med Assoc Ga. 1978;67:101–102.
9. Adams CT, Lofgren CS. Incidence of stings or bites of the
red imported fire ant (Hymenoptera: Formicidae) and other
arthropods among patients at Ft. Stewart, Georgia, USA.
J Med Entomol. 1982;19:366–370.
10. Stafford CT. Hypersensitivity to fire and venom. Ann Allergy
Asthma Immunol. 1996;77:87–97.
11. Minton SA, Bechtel HB, Erickson TB. North American
arthropod envenomation and parasitism. In: Auerbach PS,
ed. Wilderness Medicine. 4th ed. St Louis, Mo: Mosby;
2001:863–887.
12. Freeman TM. Hymenoptera hypersensitivity in an imported
fire ant endemic area. Ann Allergy Asthma Immunol.
1997;78:369–372.
13. Kimball AB, Arambula KZ, Stauffer AR, et al. Efficacy
of a jellyfish sting inhibitor in preventing jellyfish stings
in normal volunteers. Wilderness Environ Med. 2004;15:
102–108.
