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Pain related to maggot debridement therapy

l objective: to summarise our experience with maggot debridement therapy (MDt) in relation to pain observed in patients treated in 16 departments and units of the Hadassah Hospital in Jerusalem, Israel.l Method: A secondary analysis of data from 435 patients. Maggots were either placed directly on the wound using a cage-like dressing (DA), or they were applied to the wound encased in a previously prepared hermetic tea-bag like pouch (tBA). During each treatment, patients were asked whether they felt any difference in the level of pain before and during MDt treatment.l results: overall, 165 patients (38%) reported increased pain during MDt. seventeen patients (41%), who were treated with the tBA technique, and 148 patients (38%), who were treated with the DA technique, reported increased pain and were treated with analgesics before or during MDt. In five patients, the treatment had to be discontinued due to uncontrolled pain during MDt. Pain control measures were undertaken in patients who were already in intense pain prior to the initiation of MDt and in those patients who reported intense pain during DA treatment. the measures included shorter periods of application of maggots, use of the tBA rather than DA technique, and applying relatively small maggots as well as a smaller number of maggots during an MDt session. In patients who continued reporting intense pain, systemic analgesic medications and peripheral nerve blocks were used.l conclusion: since a full debridement requires an average of 2–3 maggot cycles, which last 3–5 days, and since a large percentage of patients treated with MDt complain of pain that may last throughout the therapy period, it is deemed worthwhile and even essential to titrate analgesics as needed and be prepared to treat patients even with potent analgesics, such as opioids. In cases when pain is intense and uncontrolled with systemic medications, peripheral nerve blocks should be considered.l declaration of interest: there were no external sources of funding for this study. the authors have no conflicts of interest to declare.

Lucilia sericata; maggot debridement therapy; side-effects; pain; peripheral nerve blocks

Maggot debridement therapy (MDT), also called larva therapy, is the intentional treatment of suppura-tive skin infections with the larvae of calliphorid flies. First introduced

by Baer in 1931,1 this method was used extensively in the 1930s and early 1940s in over 300 hospitals in the USA alone.2–4 However, MDT was abandoned with the introduction of antibiotics and the use of aggressive surgical debridement.

Between 1950 and 1980, MDT was used only occasionally as salvage therapy for skin and soft tissue wounds that did not respond to surgery or antibiotics.5–8 In 1989, MDT was re-introduced for the treatment of intractable wounds in the USA,9–11 and since the mid 1990s it has also been used in Israel,12–14 the United Kingdom,15,16 Sweden,17 and Germany.18 MDT practice is currently estimated to involve over 3000 doctors, clinics and hospitals, in over 24  countries. In 2008, approximately 50 000 treatments were administered to more than 10 000 patients.19 Today, 20 years after its reintroduction, we estimate that more than 80 000  patients have been treated by MDT.

MDT is used as an adjunct therapy in necrotic and infected wounds when antibiotic treatment, surgi-cal debridement, high tech advanced dressings, drainage and other conventional methods do not halt or reverse the progressive tissue destruction. MDT has been shown to achieve debridement of necrotic wounds significantly faster than most con-ventional treatment methods.18,20,21

MDT usually employs sterile maggots of the green bottle fly, Lucilia sericata, and is used for any kind of purulent, sloughy wound on the skin, independent of the underlying disease or the location on the body, for ambulatory as well as for hospitalised patients. In 80–95% of the cases, a complete or significant debri-dement of the wound is achieved by MDT.21

Although many patients do not report major dis-comfort during MDT, maggots can induce, or inten-sify, wound pain and at the surrounding tissues, espe-cially in patients with superficial wounds and those who were in pain prior to the initiation of MDT. The pain related to MDT at times may be severe enough to necessitate discontinuation of treatment.21

In a separate study, the authors’ experience with MDT, in the setting of a modern hospital in Israel, and

K.Y. Mumcuoglu,1 PhD;e. davidson,2 MD;a. avidan,2 MD;l. Gilead,3 MD, PhD;1 Department of Microbiology and Molecular genetics, the Kuvin Center for the study of Infectious and tropical Diseases, Hadassah Medical school, the Hebrew university, Jerusalem, Israel; 2 Department of Anesthesia and CCM, Hadassah university Hospital, Jerusalem, Israel; 3 Department of Dermatology and venereology, Hadassah university Hospital, Jerusalem, Israel.Email: kostam@ cc.huji.ac.il

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in the treatment of hospitalised and ambulatory patients with intractable, chronic wounds was inves-tigated.22 During the years 1996–2009, 723 wounds of 435 patients were treated by MDT in 16 departments and units of the Hadassah Hospital in Jerusalem. In 82.1% of the wounds complete debridement was achieved, while in 16.8% of the wounds the debride-ment was partial and in 1.1% ineffective.22

The aim of this report is a secondary analysis of the data, to summarise our experience with MDT in relation to pain observed in the above-mentioned 435 patients.

MethodMaggots and their applicationSterile maggots of the green bottle fly, Lucilia serica-ta, were cultured according to previously described methods.13 Maggots were either placed directly on the wound using a cage-like dressing, which pre-vents them from escaping but allows air to reach the maggots and facilitates the drainage of liquefied necrotic tissue through the top of the dressing (direct application, DA), or the maggots were applied to the wound encased in a previously pre-pared hermetic tea-bag like pouch composed of two 0.5mm-thick layers of polyvinyl alcohol netting, which were sealed together with a head-sealer (Mer-cier Corp.) over a small cube of a spacer material (tea-bag application [TBA] method). The maggots are thus able to feed through the netting and their secretions reach the wound bed in order to digest the necrotic tissue extra-corporeally.

PatientsFrom 1996 to 2009, details of all MDT treatments were collected and documented. For each patient a standardised protocol was filled in and the number of treatments, number of maggots applied, pain, treat-ing physician and outcomes were all documented in this protocol, for the entire treatment period.

In total, 723 wounds of 435 patients (180 females and 255  males) were treated with MDT in 16  departments and units of the Hadassah Hospital in Jerusalem, Israel. Overall, 261 patients were treated during hospitalisation, while 174  were treated as ambulatory patients. In 91% of the patients, the wounds were located on the leg, but only 48% had diabetic foot ulcers. The wound duration ranged from 1 to 240 months (mean=8.9 months; median=4 months; Table 1). In 91% of the cases the DA and in 9.4% of the cases the TBA methods were used. The number of treatments ranged from 1 to  48 (mean=3.0; median=2) and the duration of the treatment varied from 1–81  days (mean=4.7  days; median=3  days). In 357  patients (82%) complete debridement of the wound was achieved, while in 73  patients (17%) the debridement was partial and in five (1.1%) it was ineffective.22

All treatments were conducted by one of the authors (KYM), who is a parasitologist and biothera-pist. Written informed consent was obtained from all patients or their custodians, as well as from the responsible physician. The treatments were carried out in the form of an open study and approved by the institutional review board.

Pain assessmentAll patients treated with MDT in the study period were assessed daily by our team. During the visit, they were asked whether they felt any difference in the level of pain before and during MDT treatment. Specifically, they were asked whether they felt that MDT caused them increased pain, and whether pain

Table 1. demographics and general medical background of patients treated with maggot debridement therapy

no. of patients 435

Sex

l Male 255 (58.6%)l Female 180 (41.4%)

age (years) 66.3l Median 68 (19–100)

Place of treatment

l Hospitalised 261 (60.0%)l Ambulatory 174 (40.0%)

department

l Dermatology 243 (63.1%)l vascular surgery 38 (9.6%)l Internal medicine 37 (9.6%)l orthopaedics 31 (8.1%)l other 86 (9.6%)

no. of wounds 725l Mean no. per patient 1.6l Median no. per patient 1

location of the wounds

l legs 656 (90.5%)l sacrum 58 (8.0%)l Hands 11 (1.5%)

wound duration (months) 1–240l Mean 8.9l Median 4

Background disease

l Diabetes 209 (48.0%)l venous stasis 74 (17.0%)l vascular stasis 48 (11.0%)l other 104 (24.0%)

Results given as n (%), unless otherwise specified

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was slightly, moderately or significantly higher than before the initiation of MDT. Patients were not assessed specifically for neuropathic pain, and no records were taken of the different types of pain; however, the severity of pain was recorded.

ResultsOverall, 165 patients (38%) reported increased pain during MDT. Seventeen out of 41  patients (41%) treated with the TBA technique, and 148  out of 394 patients (38%) treated with the DA technique, reported increased pain and were treated with anal-gesics before or during MDT. Five patients request-ed to discontinue the MDT treatment due to an unbearable increase in pain, unrelieved with systemic analgesic medication.

Preemptive pain control measures were taken for patients with a previous history indicating a signifi-cant risk for pain that may interfere with MDT, such as those reporting continuous consumption of anal-gesic medication, sleep deprivation due to wound pain, and patients who received recurrent MDT treat-ments and were known to have suffered increased discomfort and pain during the treatment.

Pain control measures were selected to be more potent than the ones previously used by the patient, or according to the degree of discomfort reported by the patient. These included, in the milder cases, oral paracetamol and dipyrone, and in moderate cases potent opioids, such as slow and immediate release oxycodone HCl, tramadol HCl or a fentanyl patch. In severe cases, when extreme pain was pre-dicted or already encountered by patients in past or present treatment, a continuous peripheral nerve block was introduced prior to treatment initiation (depending on the anatomical region of the wound a sciatic, femoral or brachial plexus block), and continuous pain control was maintained through-out the MDT course.

Nineteen continuous peripheral blocks (12 female and 7  male patients, aged 41–91  years [median 71 years]) were inserted for periods of 2–8 days. The majority (n=17) were continuous sciatic blocks inserted at the popliteal or gluteal region. Peripheral nerve blocks were performed with the aid of a nerve stimulator (Polystim II; Temena Group). Catheters for administration of local anaesthetics (continuous administration bupivacaine 0.1–0.2% 4–6ml/hour; bolus injection bupivacaine 10–25ml 3–4 times dai-ly) were inserted using an insulated needle (Con-tiplex Tuohy; B. Braun).

Catheters were observed daily by the acute pain service. If any signs of local infection were observed, the catheters were removed. No complications, such as nerve injury or severe or deep infection, were observed in patients treated with continuous blocks.

These measures resulted in a considerable reduc-tion in pain associated with MDT, as reported by the

patients during their daily assessments, and thus enabling the patients to complete the full treatment and benefit from its significant advantage over alter-native methods, saving both time and suffering.23

DiscussionIn the present study, 38% of the patients reported increased pain during treatment with maggots. In earlier studies,14,21 we reported that approximately 20–25% of patients with superficial, painful wounds complained of increased pain during treatment with maggots, and were treated with analgesics.

Similar results were published by Sherman et al.,24 who reported that, during MDT, the most common patient complaint was the physical discomfort. Although treatment-associated pain has been reported in only 6% of nursing home patients (n=113), pain was reported in 38.1% (n=21) of ambulatory patients.

Wollina et al.25 used MDT to debride the wounds of 30 patients with chronic leg ulcers of mixed ori-gin. Twelve patients (40%) reported temporary pain, but only two needed analgesic treatment.

Wolff and Hansson17 treated 74  patients with necrotic or sloughy chronic ulcers of different aeti-ologies and found that maggots effectively debrided 86% of the necrotic ulcers, and a single application was clinically beneficial in two-thirds of the patients. One-quarter of the study group experienced less pain during treatment, while 41% felt no difference in pain, and, although 34% noted an increase in pain, most of these patients wanted to continue the treatment because of subjective and objective visual improvement in wound debridement.

Steenvoorde et al.26 determined pain levels in patients treated with MDT using a visual analogue scale. Paracetamol (1g/3×daily) and fentanyl patch (25μg/hour every 3 days and 50μg/hour a day, before the maggot challenge) were administered for pain relief in the outpatient clinic. Diabetic patients expe-rienced the same amount of pain before and during MDT, while 8 out of 20 non-diabetic patients experi-enced more pain during MDT than before. The differ-ence between diabetic and non-diabetic patients was statistically significant for all applications combined. In 78% (n=37) of patients, pain was adequately treat-ed with analgesic therapy. The authors came to the conclusion that a standardised but individually tailored pain management protocol is mandatory.

Dumville et al.27 reported that the mean ulcer-related pain scores (for the 24 hours before removal of first debridement treatment) for the larvae groups were about double those of the hydrogel group, when comparing loose larvae or bagged larvae with hydrogel.

In our patient cohort, in general, increased pain prior to the treatment was a risk factor for signifi-cant pain associated with MDT. Although the TBA

references1 Baer, W.s. the treatment of chronic osteomyelitis with the maggot (larva of the blow fly). J Bone Joint surg. 1931; 13: 438–475.2 McKeever, D.C. Maggots in treatment of osteomyelitis. J Bone Joint surg. 1933; 15: 85–93. 3 Robinson, W., norwood, v.H. the role of surgical maggots in the disinfection of osteomyelitis and other infected wounds. J Bone Joint surg. 1933; 15: 409–412. 4 sherman, R.A., Pechter, E.A. Maggot therapy: a review of the therapeutic application of fly larvae in human medicine, especially for treating osteomyelitis. Med vet Entomol. 1988; 2: 3, 225–230.5 Horn, K.l., Cobb, A.H. Jnr., gates, g.A. Maggot therapy for subacute mastoiditis. Arch otolaryngol. 1976; 102: 6, 377–379.6 Pechter, E.A., sherman, R.A. Maggot therapy: the surgical metamorphosis. Plast Reconstr surg. 1983; 72: 4, 567–570.7 Bunkis, J., gherini, s., Walton, R.l. Maggot therapy revisited. West J Med. 1985; 142: 4, 554–556.8 teich, s., Myers, R.A.M. Maggot therapy for severe skin infections. south Med J. 1986; 79: 9, 1153–1155.

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technique showed a slightly higher percentage of increased pain compared with DA, this technique was initially selected in those patients who reported significant pain before MDT was applied. Neverthe-less, it is our clinical impression that the TBA tech-nique causes less pain then the DA technique.

It should be taken into consideration that pain is also a subjective symptom. Before treatment patients were informed about the possibility that MDT might cause pain or increase the level of exist-ing pain. This might have influenced some of the patients in experiencing more pain during MDT.

We did not check the patients for other causes of pain, such as neuropathic pain, as the patients included in our report were all coherent and were specifically asked for MDT-associated pain. There were no significant differences noted in pain report-ing by patients with diabetes compared with the rest of the patient population.

MDT-associated pain is likely the result of mag-gots’ movements on the wound surface, especially as they use their two mouth hooks to pull their body forwards, and because the cuticular layer of their body is covered with thorn-like hairs. In addi-tion, the secretion/excretion products of the mag-gots, which include proteolytic enzymes, might have an influence on the exposed nerves and nerve endings of an open wound.28

Several measures were taken in order to try to prevent the induction of additional pain by MDT, mainly to patients already suffering from intense pain before initiation of therapy. The pain reduction measures used included application of the maggots for shorter periods of time, such as 6–8 hours, mainly during the daytime hours, use of the TBA rather than the DA technique, and the application of smaller maggots as well as a smaller number of maggots.

During early MDT treatments, our clinical impres-sion was that in cases where a smaller number of mag-gots was used the debridement was slower and patients reported less severe pain. This observation was later reinforced during the following years of MDT. Another observation was that TBA causes less pain than DA and, therefore, as mentioned previous-ly, in patients suffering from intense pain before the initiation of MDT, the TBA rather than the DA tech-nique was used. We believe that in this manner of application, the maggots do not irritate the exposed nerves and nerve endings with their mouth hooks, skin scales and hairs and, therefore, it is less painful.

limitationsThe present study had a number of limitations. As the patients were treated in an open clinical study, the level of pain was not routinely measured and quantified before and during MDT, and the inter-ventions for pain reduction were decided on sepa-rately for each patient, without a predetermined set of possible interventions.

ConclusionMDT proved to be an effective method in debriding and disinfecting chronic wounds, as well as initiating granulation. It is a simple, efficient, safe and cost-effective tool for the treatment of wounds and ulcers which do not respond to conventional treatments and surgical interventions. A full debridement is achieved with 2–3 MDT cycles, which last 3–5 days. It is therefore worthwhile having a setup that is prepared to treat patients experiencing pain with potent analgesics such as opioids, and in extreme cases of severe unrelieved pain by continuous periph-eral nerve blocks, as conventional methods would take much longer to achieve the same result. n

9 stoddard, s.R., sherman, R.M., Mason, B.A. et al. Maggot debridement therapy: an alternative treatment for nonhealing ulcers. J Amer Podiatr Med Ass. 1995; 85: 4, 218–221.10 sherman, R.A., Wyle, F., vulpe, M. Maggot therapy for treating pressure ulcers in spinal cord injury patients. J spinal Cord Med. 1996; 18: 2, 71–74.11 sherman, R.A., tran, J.M., sullivan, R. Maggot therapy for venous stasis ulcers. Arch Dermatol. 1996; 132: 3, 254–256.12 Mumcuoglu, K.Y., lipo, M., Ioffe-uspensky, I. et al. Maggot therapy for gangrene and osteomyelitis [in Hebrew]. Harefuah. 1997; 132: 5, 323–325.13 Mumcuoglu, K.Y., Ingber, A., gilead, l. et al. Maggot therapy for the treatment of diabetic foot ulcers. Diabetes Care. 1998; 21: 11, 2030–2031.

14 Mumcuoglu, K.Y., Ingber, A., gilead, l. et al. Maggot therapy for the treatment of intractable wounds. Int J Dermatol. 1999; 38: 8, 623–637.15 thomas, s., Jones, M., shutler, s., Jones, s. using larvae in modern wound management. J Wound Care. 1996; 5: 2, 60–69.16 thomas, s., Jones, M., shutler, s., Andrews, A. Making friends with maggots. nurs times. 1996; 92: 46, 76–82.17 Wolff, H., Hannson, C. larval therapy for a leg ulcer with methicillin-resistant Staphylococcus aureus. Acta Derm venereol. 1999; 79: 4, 320–321.18 Fleischmann, W., grassberger, M., sherman, R. Maggot therapy: A Handbook of Maggot-Assisted Wound Healing. thieme, 2004.19 BtER Foundation. c2011. Homepage on the internet: http://www.bterfoundation.org/home.

20 sherman, R.A., Hall, M.J., thomas, s. Medicinal maggots: an ancient remedy for some contemporary afflictions. Annu Rev Entomol. 2000; 45: 55–81.21 Mumcuoglu, K.Y. Clinical applications for maggots in wound care. Am J Clin Dermatol. 2001; 2: 4, 219–227.22 gilead, l., Mumcuoglu, K.Y., Ingber, A. the use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients. J Wound Care. 2012; 21: 2, 78–85.23 sherman, R.A. Maggot therapy for treating diabetic foot ulcers unresponsive to conventional therapy. Diabetes Care. 2003; 26: 2, 446–451. 24 sherman, R. A., sherman, J., gilead, l., lipo, M., Mumcuoglu, K.Y. Maggot débridement therapy in outpatients. Arch Phys Med Rehabil. 2001; 82: 1226–1229.

25 Wollina, u., liebold, K., schmidt, W.D. et al. Biosurgery supports granulation and debridement in chronic wounds—clinical data and remittance spectroscopy measurement. Int J Dermatol. 2002; 41: 10, 635–639.26 steenvoorde, P., Budding, t., oskam, J. Determining pain levels in patients treated with maggot debridement therapy. J Wound Care. 2005; 4: 10, 485–458. Erratum in: J Wound Care. 2006; 15: 2, 71.27 Dumville, J.C., Worthy, g., Bland, J.M. et al. larval therapy for leg ulcers (venus II): randomised controlled trial. BMJ. 2009; 338: b773.28 Chambers, l., Woodrow, s., Brown, A.P. et al. Degradation of extracellular matrix components by defined proteinases from the greenbottle larva Lucilia sericata used for the clinical debridement of non-healing wounds. Br J Dermatol. 2003; 148: 1, 14–23.