maggot therapy is categorised as a debridement for chronic infectious wounds using disinfected live maggots for medical use ( herein referred to as maggots ) .
since the 1930s , maggot debridement therapy ( mdt ) has been conducted mainly in north america . in japan ,
first conducted mdt in 2004 and reported the healing of an ulcerated lesion , leading to the avoidance of major amputation of a limb of a patient with severe cli for whom neither a revascularization procedure nor a transplantation of bone marrow and peripheral mononuclear cells to the lower limb was effective .
wound healing is intractable in most cli patients who have reduced blood flow in the skin ; therefore , revascularization is the most important factor for successful management .
in addition , the debridement of wounds with no sufficient tissue blood flow may deteriorate ischaemic lesions .
treatment decisions are often difficult for cli patients with a reduced cardiac function and surgical intervention or endovascular surgery for revascularization is risky , or not clinically and technically possible .
herein , we report a cli patient with severe cardiac dysfunction for whom highly invasive surgery , such as bypass surgery , was impossible due to a history of fulminant myocarditis , but functional limb salvage was achieved after wound bed preparation ( wbp ) with mdt .
a 73-year - old man consulted our institution for a skin ulcer of the left third toe in september 2014 .
he had a clinical history of fulminant myocarditis , myocardial infarction , acute cardiac failure , chronic renal failure ( undergoing dialysis ) , arteriosclerosis obliterans of the lower limb , hypertension , diabetes and visual disturbance .
he was a non - smoker , living by himself , and he could walk with support .
his notable illness was an episode of fulminant myocarditis and acute cardiac failure in december 2011 , which was treated in the icu for 15 days , and he was discharged from hospital 3 months later . at the time of discharge , he still had significant cardiac functional disorder with an ejection fraction ( ef ) rate of less than 20% . in april 2014 , he developed ulceration of the right toes , diagnosed as arteriosclerosis obliterans of the lower limb at the cardiovascular medicine department and underwent percutaneous transluminal angioplasty ( pta ) . in september 2014 , delayed healing of the ulceration of the skin was noted ; thus , he was referred to the plastic surgery department . upon the first consultation at the plastic surgery department , ischaemic ulcer of the left third toe
biological data on the left limb were examined between the revascularization procedure and surgical management , and blood test and wound culture were examined at the time of surgical management .
ajb : ankle joint nerve block ; crp : c - reactive protein ; mrsa : methicillin - resistant staphylococcus aureus ; pta : percutaneous transluminal angioplasty ; snb : sciatic nerve block ; s. maltophilia : stenotrophomonas maltophilia . 

endovascular surgery was not conducted after october 2016 . in september 2014 , after performing pta for the left lower limb , amputation of the left third toe was conducted . in december 2014 , re - stenosis of the bilateral below - knee arteries and necrosis of the left first toe were noted , thus re - pta was conducted for the bilateral limbs .
subsequently , amputation of the left first toe was performed . in september 2015 , arterial re - stenosis of the lower extremity developed along with necrosis of all the left toes , plantar and dorsum , and
so pta was performed again ; transmetatarsal amputation ( tma ) was also performed in the same month .
however , delayed wound healing , infection and necrosis progressed in the transected surface of the left limb .
therefore , in january 2016 , the first and second toes were amputated at lisfranc s joint , and the other three toes were further amputated at the base of the transmetatarsal bone , and the amputated surface was left as an open wound for wbp and post - operative infection management . at the time of the amputation , extensive arterial contraction and severe arteriosclerosis were noted in the left lower limb ; thus , an additional revascularization procedure by pta could not be performed .
subsequently , cleansing of the wound , topical ointment of sulfadiazine silver , venous drip infusion of an antibiotic agent ( daptomycin ) , and surgical debridement at the bedside were conducted daily , but the yellowish necrosis lesion did not reduce , and his pain aggravated ( figure 1(a ) ) .
( b ) after one session ( 48  h ) of treatment , the reduction of necrotic tissues is seen .
( d ) after six sessions of treatment , debridement was conducted to the deep portion from the ulcerated base , and favourable granulation can be seen on the amputated surface .
the patient strongly desired to save his limb and refused to undergo major amputation of the limb .
surgical management under general anaesthesia ( such as bypass surgery ) or extensive and highly invasive debridement for a long time was also considered unacceptable , because the patient fulfilled three items of the revised cardiac risk index ( history of cardiac failure , insulin - dependent diabetes and renal failure ) , had ef of 18.4% and had a constantly high level of b - type natriuretic peptide ( over 2000  pg / ml ) . as conventional treatment methods
were considered difficult for the patient to tolerate , mdt was started from february 2016 .
second instar larvae of maggots were placed on the surface of the skin ulcer at six larvae per 1  cm , covered by a mesh sheet and dressing was performed .
the maggots were removed when they grew to third instar larvae and were replaced by second instar larvae . by defining a 48-h duration as one session , a total of six sessions were conducted . for pain control ,
the oral administration of nsaids was performed and he could tolerate the pain , although it remained to a certain extent .
subsequently , compared with the conventional treatment , the reduction of necrotic tissues at the ulceration site was noted each time the maggots were replaced , and favourable granulation was observed .
mdt was particularly effective in the portion where the margin between the granulation and necrosis was unclear , and the deep portion of the ulceration where manual debridement was difficult ( figure 1(b  d ) ) .
intraoperative and post - operative views are shown in figure 2(a , b ) . under sciatic nerve block , additional debridement and partial simple reefing suture
were done , and skin graft with a split thickness of 20/1000 inches was conducted , harvesting the graft from his left inguinal region .
the operation took 1  h and 40  min , and the amount of bleeding was 140  ml .
after conducting partial simple reefing , split thickness skin graft of 20/1000 inches was used .
post - operatively , about 70% of the grafted skin was taken , although it was unstable for 2 weeks , and his pre - operative pain markedly reduced .
although some raw surface remained , the range was relatively small , and additional surgical management was unnecessary .
after rehabilitation exercise , as of one post - operative months , he became able to stand with assistance when moving from a wheelchair , walk using a four - point walker , and his barthel index improved to a score of 80 ( figure 3(b ) ) .
the barthel index improved from a score of 45 to 80 , and the patient started to walk using a four - point walker .
in patients with cli , debridement may deteriorate necrosis by inducing ischaemia of normal tissues . therefore , blood flow evaluation and the revascularization procedure are important before conducting debridement . however , clinically or technically , up to ( maximum ) 14% of cli patients are unable to undergo surgical management or endovascular surgery for angioplasty . also , soga et  al . reported a vascular re - stenosis rate of 86.0% and re - occlusion rate of 52.8% in cli patients who underwent endovascular management . in our patient , although the preoperative ankle brachial index and skin perfusion pressure were relatively maintained , arterial restenosis of the lower extremity was seen before healing , and pta was conducted three times . in addition , vascular reconstruction by additional pta was difficult after october 2016 .
some cli patients are unable to undergo highly invasive surgery because of a reduced cardiac function .
reported that 15.6% of their cli patients had an ef rate of less than 50% and 41.1% had coronary artery disease ( cad ) .
in addition , a mortality rate of less than 25% has been reported within a year for cli patients .
physiologic classification of the american society of anesthesiologists ( asa ) reports perioperative mortality rate of class - iii patients ( angina , old myocardial infarction , and insulin - dependent diabetes ) and class - iv patients ( unstable angina ) of 1.8% and 7.8% , respectively .
the revised cardiac risk index , which is commonly used to predict cardiovascular events during a perioperative period , defines six risk factors : ischaemic cardiac disease , history of cardiac failure , cerebrovascular disease , insulin - dependent diabetes , renal failure and high - risk surgical management .
if a patient has three or more of these risk factors , when conducting non - cardiac surgery , the average cardiovascular complication rate is reported to be 9.1% and mortality due to cardiovascular disease is 3.6% .
our patient had three of these risk factors , suggesting a high risk during the perioperative period .
adjuvant therapies for ischaemic ulcer , other than mdt , include hyperbaric oxygen therapy , cell therapy , gene therapy ( intravascular growth factor )   and ldl apheresis .
however , these therapies require special equipment and qualification as a specialist ; thus , they are difficult to perform flexibly depending on the needs of a particular situation . on the other hand
, mdt can be conducted less problematically in ordinary hospitals or outpatient clinics , although it is categorised as a private practice in japan and thus not covered by the japanese national health insurance system .
four debridement methods are considered for the selective removal of necrotic tissues : ( 1 ) surgical debridement , ( 2 ) enzymatic debridement , ( 3 ) autolytic debridement and ( 4 ) biological debridement .
surgical debridement removes necrotic tissues with scissors or a scalpel , which entails bleeding and pain of patients , as well as damage to peripheral intact tissues to some extent .
enzymatic debridement uses chemical agents for liquefaction of necrotic tissues and is also called chemical debridement .
this can be done without anaesthesia and is relatively simple to perform with little risk of bleeding ; however , it is a time - consuming procedure and thus not suitable for situations requiring more immediate results .
autolytic debridement involves the application of wound dressing materials such as ointments or hydrocolloid materials , making it suitable for wounds that locate near the body surface or autonomic healing power of the wound is maintained .
there are three major benefits of wbp by mdt for cli patients [ 1921 ] .
first , selective and efficient debridement can be performed . even for wounds with unclear margins with the surrounding normal tissues
, maggots selectively englobe and liquefy only necrotic tissues . in addition , as maggots naturally favour darker environments ( negative phototaxis ) , maggots reach to the deep portions of a wound where surgical debridement is difficult .
pain associated with mdt can be controlled with oral analgesics or by controlling the number of applied maggots , making local or surface anaesthesia unnecessary .
further , the technique for mdt is relatively straightforward and easily learned , so a certain efficacy can be obtained irrespective of the proficiency of each surgeon . even for patients of advanced age , with dementia , or unfavourable systemic conditions , for whom surgical debridement is problematic , mdt can be utilised .
maggots have a sterilising effect both in vivo and in vitro . in the body ,
maggots eliminate bacteria through a digesting process in their foregut , midgut and hindgut . in an extracorporeal ( in vitro )
study , antibacterial peptide contained in maggots secretion was shown to be effective against gram - positive bacterium , including methicillin - resistant staphylococcus aureus ( mrsa ) .
thus , mdt is considered suitable for cli patients who likely face the presence of multiple drug - resistant bacteria at high incidence , because of relative immune deficiency and long - term hospitalisation .
harmful bacteria including mrsa were not detected in wound cultures of our patient in the months of january and february 2016 , while mdt was being conducted , suggesting effective antibacterial action of the maggots secretions .
such processes include activation of fibroblast migration , angiogenesis ( the formation of new blood vessels from pre - existing vessels ) within the wound bed and an enhanced production of growth factors within the wound environment .
these are believed to have been part of the success of wbp with our patient although his skin perfusion pressure ( spp ) in the dorsum of the foot was only 15  mmhg before mdt .
a recent case report also indicated the possibility of mdt to improve blood flow , in addition to supporting its effectiveness for debridement , showing the increased skin perfusion pressure by 42  mmhg in the dorsum and 27  mmhg in the plantar .
nevertheless , the number of published articles on this aspect is limited , and thus further investigation will be necessary before clear determination can be made .
our case presented with five problematic conditions : ( 1 ) delayed wbp due to circulation failure , ( 2 ) difficulty of angioplasty after re - stenosis , ( 3 ) contraindication of highly invasive treatment , ( 4 ) infection by mrsa and ( 5 ) pain . to cope with these difficulties
, mdt provided the benefits of the following : ( 1 ) capability of wbp by removing necrotic tissues with unclear margins , ( 2 ) possibility of improving blood flow , ( 3 ) effective debridement with low invasiveness , ( 4 ) antibiotic effect on mrsa and ( 5 ) capability of pain control using analgesics , adjusting the number of maggots and duration of treatment .
the barthel index at the time of discharge from the hospital was a score of 80 ; thus , we considered that functionally meaningful limb salvage could be pursued . from these facts ,
mdt is believed to be an effective method to improve the wound surface with delayed healing , under the condition that a certain revascularization procedure is performed .
mdt is one of the promising adjuvant treatments for patients with an unfavourable systemic condition and difficulty in undergoing highly invasive surgery .
in conclusion , we could achieve functionally meaningful lower limb salvage by wbp with mdt for an ulcerated lower limb lesion in a cli patient who had a severe cardiac disorder , delayed healing of the wound surface and difficulty in undergoing a revascularization procedure after arterial restenosis .
mdt is considered one of the adjuvant treatment strategies even for patients with cli , provided it is performed appropriately .
the authors certify that there is no actual or potential conflict of interest in relation to this article .
none of the authors received any financial support in association with this study and have no relationships that may pose an actual or potential conflict of interest .
 abstractischaemic skin ulcer occurred on the foot of a 73-year - old man who had a history of fulminant myocarditis with severe cardiac dysfunction . 
 we attempted wound bed preparation by maggot debridement therapy and salvaged his limb . 
 it can be one of the adjuvant treatment strategies for critical limb ischaemia . 
Introduction
Case report
Discussion
Conclusions
Disclosure statement