59

島 根 県 中 病 医 誌 48
5 9頁 〜 6 5頁

症 例 報 告Combination of enzymatic debridement with Nexobridand surgical debridement under intensive carein a patient with massive burn injury: A case report
Sayaka NAKAMURA
Hiroko MATSUMOTO

Shinichi INOUE
and Wataru KAITA

Abstract：A 73-year-old man, critically injured in a burn incident resulting from cooking gas explosion,
was transferred by helicopter ambulance to Shimane Prefectural central hospital. Upon arrival, the patient
was intubated. The Total Burn Surface Area（TBSA）was 84%, mainly with Deep Burns（DB）, and thePrognostic Burn Index（PBI）was 150. We performed enzymatic debridement on the maximum insurance
coverage of 30% Burn Surface Area（BSA）in total with topical agent Nexobrid（Kaken PharmaceuticalCo., Ltd.）, a concentrate of proteolytic enzymes extracted from pineapple stem, launched in Japan in August,2023. Nexobrid only removes nonviable necrotic tissue or eschar in Deep Dermal Burns（DDB）and DB
even in the early period after trauma, when accurate evaluation of burn depth is often challenging. Early
accurate debridement raises the possibility of dermal preservation, which is important for spontaneous
epithelization, and wound bed preparation if skin graft is needed. While the patient died of circulatory failure
4 days after trauma, our experience suggests that Nexobrid is an early, accurate, and less-invasive alternativein debridement, and may assist treatment for burns that aﬀected larger area with surgical debridement
combination. However, additional experiences and follow-ups are required to susbtantiate its beneﬁt.
Key words：burns, enzymatic debridement, Nexobrid

外科手術と壊死組織除去剤ネキソブリッドを併用してデブリドマンを施行した全身熱傷の一例
中村
概

彩芳

井上

真一

松本

紘子

貝田

亘

要： 症例は 73 歳男性， ガスコンロへの引火により全身熱傷（Ⅲ度熱傷， 熱傷面積（Total

Burn Surface Area: TBSA）84％程度，熱傷予後指数（Prognostic Burn Index: PBI）150 程度）を受傷した一例に対して，2023 年８月より日本国内で販売開始となった壊死組織除去剤ネキソブリッドを使用して TBSA 30％の範囲にデブリドマンを施行した．ネキソブリッドは蛋白分解酵素を有するパイ
ナップル茎搾汁精製物を有効成分とする薬剤である．皮膚の壊死部と正常部の境界が不明瞭な受傷
後超早期（12 時間以内）または早期（12-72 時間以内）であっても本剤の熱傷部への塗布により熱傷で生じた壊死組織のみを除去することが可能であり，深達性Ⅱ度熱傷，Ⅲ度熱傷への適応が推奨されている．デブリドマンの高い選択性によって真皮が温存される可能性が高まり，自然な上皮化の促進や植皮の必要面積の縮小などにつながる．本症例の患者は循環不全により死亡したものの，適切な部位に使用し，外科的壊死組織除去と組み合わせることで，将来的により効率の良い熱傷治療を提供できる可能性が示唆された．今後さらなる経験例を増やし，経過を見ていく必要がある．
索引用語：熱傷，化学的デブリドマン，ネキソブリッド

島根県立中央病院

形成外科

Department of Plastic Surgery, Shimane Prefectural
Central Hospital島根県立中央病院医学雑誌

60【Introduction】

第48巻（令和５年）
alone and maintained autonomy in activities of daily living（ADL）.

Nexobrid（Kaken Pharmaceutical Co., Ltd.）, launched
in Japan in August 2023, is a concentrate of proteolytic
enzymes extracted from pineapple stem and is designed toInitial burn assessment: Burn Surface Area (BSA) %and burn depth

remove nonviable necrotic tissue or eschar in deep dermal1）. Initial assessment ofburns（DDB）and deep burns（DB）

Face and neck4 + 5 % （DDB + DB）

as it is diﬃcult to visually

Chest and abdomen

3 + 15 % （DDB + DB）

distinguish vital from necrotic tissue at early period after

Back and buttocks

1 + 5 % （DDB + DB）

trauma, which may result in unnecessary surgery or

Right side of the upper limb

8 % （DB）

damage to the vital dermis. In contrast, a high selectivity

Left side of the upper limb

9 % （DB）

of debridement at early hours after trauma using Nexobrid

Right side of the lower limb

4 + 12 % （DDB + DB）

may potentially facilitate dermal preservation and an early

Left side of the lower limb

2 + 16 % （DDB + DB）

burn depth is often inaccurate

2,3）

accurate burn depth evaluation may help determine theappropriate treatment 2,4-6）. Following its recent approval in

After admission, immediate skin-incision on theJapan, only few domestic reports on Nexobrid exist, andlower abdomen and bilaterally in the lower limb forreport about its application on massively burned patient

decompression (Figure 1a, c) was made at the emergency

with severe systemic state remains scarce. Herein, weroom to prevent compartment syndrome. A life-saving

report a case of severe-burn patient treated with Nexobrid,

emergency burn surgery for 3 h over around 20% Burnalong with a literature review.

Surface Area（BSA）was scheduled. Surgical debridement【Case Presentation】

and skin graft under general anesthesia were performed
11 hours after trauma. The patient was ﬁrst placed in

A 73-year-old man with critically-ill burn was

the left lateral position, and split-thickness skin grafts

transferred through a helicopter ambulance to Shimane（STSG）were harvested from the right lateral back using

Prefectural Central Hospital. The patient was involved ina mechanical dermatome set to 0.2 mm thickness. The

cooking gas explosion at 5:00 am on that day. Althoughpatient was subsequently placed in the supine position,

the patient was initially transported to another hospital,

and a debridement using electrocautery on the neck, chest,

the hospital could not deal with the case and the patient

abdomen and the anterior surface of bilateral thigh was

was transferred to our hospital. On arrival at 11:03, theperformed mainly over DB. Full-thickness debridement

patient was mechanically ventilated with mild spontaneous

was performed in the sequential excision manner down

breathing, and was receiving midazolam infusion forto bleeding, visually vital fat tissue (Figure 2a). Part ofsedation. The Glasgow Coma Scale（GCS）was E1VTM1.

the harvested STSG were placed into a skin graft mesher

The vital signs were as follows: low blood pressure andand expanded to a ratio of 1:6. We applied the unmeshedheart rate, which were not able to be measured, and SpO2

STSG（sheet grafts）on the neck, and the meshed grafts

by pulse oximetry 99%（FiO2 0.6, mechanically ventilated.

on the chest and abdomen (Figure 2b). Staples were

The Total Burn Surface Area （TBSA） was 84%, withused to ﬁx the STSG to the wound bed, and tie-overmost part of DB and partial DDB combination aﬀecting

dressing was applied to secure its immobilization. As

the entire body (Figure 1a–c). The burn index（BI）was

the surface area that needs to be covered was larger than

77 %, and the prognostic BI（PBI）was 150. The patient

the available donor sites, we applied dermal substitutehas a history of rheumatoid arthritis and cerebral infarction

matrix （PELNAC

with left-sided hemiparesis. Daily medication includedLtd.）to the anterior surface of bilateral thigh for dermal

methotrexate, folate, and biaspirin. The patient was living

wound bed preparation. Delayed sequential skin grafting®

Bilayer Wound Matrix, Gunze Co.,

Combination of enzymatic debridement with Nexobrid and surgical debridement under intensive carein a patient with massive burn injury: A case report

Figure 1. Patient with burn caused by cooking gas explosion（before the initial surgery）. Upon arrival, immediateskin-incision for decompression on the lower abdomen and the lower limb bilaterally was performed（arrows）.（a）Partial Deep Dermal Burns（DDB）and Deep Burns（DB）on most part of the chest and abdomen.（b）DB on thebilateral forearms.（c）DDB and DB on the bilateral lower limb.

Figure 2. After surgical debridement and split-thickness skin graft.（a）Full-thickness debridement was done in thesequential excision manner down to bleeding, visually vital fat tissue.（b）Part of the harvested STSGs expanded
to a ratio of 1:6 was applied on the chest and abdomen. Unmeshed STSGs（sheet grafts）were applied on the neck.
Staples were used to ﬁx the STSG to the wound bed. Due to the shortage of STSGs, we applied dermal substitutematrix（PELNAC® Bilayer Wound Matrix, Gunze Co., Ltd. ）to the anterior surface of bilateral thigh for dermal
wound bed preparation（arrow heads）
.

61

62

島根県立中央病院医学雑誌

第48巻（令和５年）

using cultured epidermal autograft（JACE ®, Japan Tissue

Following the instruction and adding some arrangements,

Engineering Co., Ltd.）, was planned. Prior to surgery, aNexobrid was applied in three consecutive steps including

small part of healthy skin tissue was harvested from the

preparation, application and removal1）.

patient on day 2 for culturing epidermal cells. The patientmaintained a low blood pressure that lasted after the initial■ Preparation

surgery, which required careful monitoring and blood

The wound was thoroughly cleaned with normal salinepressure management with continuous norepinephrine

to remove blisters（keratin layer of the epidermis）andinfusion. Further decrease in blood pressure was observed

other unnecessary tissues, followed by 2 h occlusion of theeven at postural changes during daily wound care atburned area with gauze soaked with normal saline.

the bedside. Under this critically-ill state with unstable
hemodynamics, we decided not to conduct another■ Application

debridement surgery for the remaining aﬀected surface

The surrounding skin area around the targeted woundarea, and perform enzymatic debridement using Nexobrid

surface was covered with semipermeable waterproof ﬁlm

instead. Enzymatic debridement was performed on the（Multi Fix-Roll®, ALCARE Co., Ltd）to avoid Nexobrid

maximum insurance coverage of 30% BSA in two diﬀerent

leakage. Nexobrid was applied to the targeted woundsessions with 15% BSA each. On day 2, Nexobrid（15%surface and was covered with a gauze, which is also sealed

BSA in total）was applied to the right and left side of thewith Multi Fix-Roll® at the side of contact with the wound.

upper limb, at 32 h and 27 h after trauma, respectively

The wound was left in place for hours after it was dressed(Figure 3a-c). On day 3, 60 h after trauma, Nexobrid waswith loose, thick, and ﬂuﬀy gauze with bandage.

applied to the bilateral lower limbs in a same manner,which corresponds to another 15 % BSA (Figure 3d, e).

Figure 3．Enzymatic debridement with Nexobrid®（Note that left upper and lower limbs are not shown above）.
（a）Right upper limb before the treatment（32 h after trauma）.（b）After the removal of Nexobrid® on the rightside of the upper limb, 4 h after its application.（c）Enlarged view of the image（b）.（d）Left lower limb before thetreatment（60 h after trauma）.（e）After the removal of Nexobrid® on the left side of the lower limb, 4 h after its
application.

Combination of enzymatic debridement with Nexobrid and surgical debridement under intensive carein a patient with massive burn injury: A case report■ Removal

63

In previous studies, advantages of debridement withThe dressing was released, and the treated area was

Nexobrid include high preservability of dermis owing torubbed by a gauze soaked with saline to remove theits distinguished selectivity in debridement 2, 4-6）, reduction

Nexobrid and other remnants of necrotic tissue. The area

in procedural blood loss5, 6） and shortening the duration

was wiped until the clear dermis or subcutaneous tissueof debridement 5）. Kreiger et al. found that only 28.6% ofappears.

the area thought to be DB at the initial assessment wereAn ointment（Bucladesine Sodium + Sucrose, Povidone-

indeed burned to this depth3）. This indicates the diﬃculty

Iodine mixed）was applied to the treated area and wrappedin distinguishing vital from necrotic tissue on inspection

with gauze and bandage.

at early period after trauma, which can result in further
excision surgery with damage on preservable dermis 2）.

Debridement quality of eschar and other necrotic

As the dermis is important for epithelization, dermal

tissue appeared to be prominent than we had expected.

preservation with Nexobrid after debridement enables anSome areas appeared to be intact immediately after theincrease in surface area that can spontaneously epithelize,

debridement, which was easily dissolved with rubbing.

and therefore decreases the surface area that needs skin

However, debridement of the areas where the epidermis

grafts 2, 5,6）. A study has shown that Nexobrid reduces theremained before the application of Nexobrid were

number of surgical excisions needed up to one third, andinsuﬃcient.

the surface area that needs surgical excision up to one

Although most part of the wound appeared to be DB atquarter 5）.

the initial assessment, dermis was preserved in some areas,

As the number of blood transfusion has been reported

which raises the possibility to epithelize spontaneously, or

to be associated with mortality and infectious episodes

may at least reduce surface area that needs skin graft. In

in major burn patients7）, reduction in procedural bloodother areas, fat tissues were exposed. The wound was thenloss prevents needless blood transfusion. According to a®

dressed with gauze soaked with ZALKONIN SOLUTION

study, the average time for complete debridement utilizing

0.025 （Benzalkonium Chloride, Kenei Pharmaceutical

Neobrid is 2.2 days, which is far below 8.7 days inCo., Ltd.,）. Daily wound care was done with conservative

surgical debridement 5）.

treatment with ointment（Bucladesine Sodium + Sucrose,
Povidone-Iodine mixed） to the area where dermis was

In terms of insurance coverage, the use of Nexobrid ispreserved. Applying STSG in the scheduled surgery forpossible with up to 15% BSA per session and must notanterior thigh was planned for the area where fat tissue

exceed 30% BSA in total under sequential use8）. Therewas expose. Due to the worsening of circulatory failure,is a lack of appropriate evidence on the eﬀectiveness or

the patient died 4 days after admission.

safety of Nexobrid applying to the BSA larger than 30%;
however, the use of Nexobrid over 30% BSA has been

【Discussion】

reported in other countries6, 9）. There were two case reports

Enzymatic debridement with Nexobrid is indicated1）

about a partial Nexobrid use over 80% TBSA patient,for patients with DB and DDB . Contraindications are

similar to the presented case6, 9）. In one case, the patient

described for patients with a known hypersensitivity todied due to systemic failure after successful enzymatic1）

bromelain, pineapples, papayas, and papain . It can be

debridement9 ）, and in another case, the patient wasapplied even at markedly early （within 12 h） to early

resuscitated with successful skin graft after surgical and4）（between 12-72 h）timing after trauma.

enzymatic debridement combination6）. Although the lattercase showed successful result, a major part of the patientOver the last few years, enzymatic debridement withwas DDB6）, which cannot be directly compared with or

Nexobrid has become popular in countries outside Japan.

applied to our case. In case the wound area needed for島根県立中央病院医学雑誌

64

第48巻（令和５年）

debridement is larger than 30% BSA, a combination of

fat is exposed, it is regarded as full-thickness tissue

6）

enzymatic and surgical debridement would be necessary .

loss, which can highly be an indication for skin graft 6）.

At this point, we should consider which part of the wound

Regarding the timing of skin graft, at least two days after

Nexobrid should be applied. Previous studies demonstrated

enzymatic debridement is recommended by the Europeanthat facial and hand burns can be good indications

2-4, 10, 11）.

consensus guidelines4）, and ﬁve days by Bowers et al 6）.

Due to its morphologically ununiform surface, surgicaldebridement is often challenging in face, and even a small

Pain management is another important factor in2）

loss of tissue has a large impact on change in appearance .

debridement with Nexobrid 4,6,8 ）. In the domesticThus, dermal preservation that promotes less scaring is

clinical trial, opioids, analgesics, and nonsteroidal anti-

2）

necessary . Schulz et al. reported 77% of facial burninﬂammatory drugs were used 8 ）. Additionally, use ofwounds treated enzymatically appeared more superﬁciallylocal anesthesia and regional blocks has been reported in2）burned than initially assessed . Hand burns, as anotherprevious literature6）. A combination of ReCell® （Avita

good indication, have shown good outcomes both inmedical, inc.） spray （cultured autologous cell product）

3, 4, 10, 11 ）. Hands are markedly

and xenograft or allograft is also recommended to reduce

vulnerable with its complex anatomical structures packed

pain during dressing changes6）. In the presented case, thein limited space10）. Intricate components such as nerves,patient was continuously administered with intravenous

vessels, and tendons are prone to be easily damaged by

sedative agent under critically-ill state, which excluded

function and appearance

11 ）, which directly associates with

the need for additional pain control. However, strong pain

functional loss. Early and highly selective debridement

is induced immediately after the application of Nexobrid,with Nexobrid is therefore beneﬁcial, with skin-graftedand during its removal 8）. Preparation of pain medication isareas reduced by 37% compared to the initial assessment

needed when patients are awake.

surgical debridement11）

in a study .

While our observation period with this patient was
Conversely, according to the European consensus

remarkably short to conclusively demonstrate theguidelines, debridement with Nexobrid is not

eﬀectiveness of Nexobrid, we advocate for its use in burnrecommended in the truncus and extremity with establishedpatients. This aligns with the recommendation of Bowers

4）compartment syndrome . Under such state, immediate

et al. who propose that facilities initiating enzymatic

decompression is essential, which is only achievable bydebridement should commence with a small area andsurgical debridement. Similar to the presented case, forprogressively gain experience in managing extensively

decompression, we performed immediately upon arrival

burned patients6）.

a skin-incision on the lower abdomen and the lower limb
bilaterally, which appeared to be ischemic.

【Conclusion】
Our experience suggests that Nexobrid can be an early,

Decision on whether the wound needs skin grafts or

accurate, and less-invasive alternative in debridement.

other procedures after the enzymatic debridement with

The potential for treating larger areas aﬀected by burns

4）

Nexorid is challenging and remains controversial . The

may be enhanced if enzymatic debridement with Nexobrid

European consensus guidelines suggest skin graft should

is combined with surgical debridement. However,be considered after 21 days if there is no signiﬁcant

additional experiences and longer follow ups are needed to

4）process in epithelization , whereas Bowers et al. suggested

substantiate the beneﬁt of this approach.

6）

to wait at least 14 days before decision . The presence ofadequate dermis in the wound, is assessed as indicative ofa potential to heal spontaneously 6）. However, if subdermal【References】
１）Vericel Corporation: NexoBrid （anacaulase-bcdb ）,Combination of enzymatic debridement with Nexobrid and surgical debridement under intensive carein a patient with massive burn injury: A case reportsite intended for U.S. healthcare professionals, https://www.nexobrid-us.com/ cited on 2023.9.19.
２）Schulz A, Fuchs PC, Rothermundt I, et al. Enzymatic
debridement of deeply burned faces: Healing and65７）Palmieri TL, Caruso DM, Foster KN, et al.: Eﬀect ofblood transfusion on outcome after major burn injury:
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early scarring based on tissue preservation compared

８）Kaken Pharmaceutical Co.,Ltd.: NexoBrid ®

to traditional surgical debridement. Burns, 2017; 43（Kaken Pharmaceutical Co., Ltd.）, site intended for（6）: 1233-1243.

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2023.9.19ne.
９）Krauss S, Bender D, Rothenberger J, et al.: Delayed
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debridement （Nexobrid ） in burns: European

10）Schulz A, Perbix W, Shoham Y, et al.: Our initialconsensus guidelines update. Burns, 2020; 46（4）:learning curve in the enzymatic debridement of

782-796.

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５）Rosenberg L, Krieger Y, Bogdanov-Berezovski

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11）Cordts T, Horter J, Vogelpohl J, et al.: Enzymatic６）Bowers C, Randawa A, Sloan B, et al. Enzymatic

debridement for the treatment of severely burned

debridement in critically injured burn patients - Ourupper extremities - early single center experiences.

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（受付日：2023年10月24日，掲載決定日：2023年12月27日）