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2. Pengaruh Terapi Oksigen Hiperbarik di bidang Orthopedi-2

PENGARUH TERAPI OKSIGEN HIPERBARIK PADA BIDANG ORTHOPEDI-2

Oleh Dr H Subagyo SpB - SpOT

 

1. Keamanan Terapi Oksigen hiperbarik pada bidang orthopedi

Telah banyak dilakukan penelitian dan dokumentasi tentang efektifitas terapi oksigen hiperbarik pada bidang selular  tubuh. Terapi oksigen hiperbarik juga telah merambah ke bidang orthopedi.Banyak dokter bedah orthopedi dan traumatologist membuat terapi oksigen hiperbarik sebagai terapi adjuvant. Beberapa penyakit orthopedi yang mendapat terapi oksigen hiperbarik sebagai terapi adjuvant adalah:

  1. Luka diabetic pada kaki
  2. Infeksi nekrosis jaringan lunak
  3. Refractory osteomyelitis
  4. Crush injury
  5. Fraktur terbuka

Dengan berkembangnya terapi oksigen hiperbarik pada bidang orthopedi, membuat para peneliti dari Taiwan ingin mengetahui tingkat keamanan terapi tersebut. Pada Oktober 2002 hingga September 2004, Kuo Chin Huang,MD dan rekan-rekannya dari Departemen Ortopedi Rumah Sakit Chang Gung Memorial di Chia Yi, Taiwan membuat evaluasi keamanan terapi oksigen hiperbarik pada pasien orthopedi.

Sebanyak 240 pasien diambil sebagai sampel dengan 4,638 sesi terapi oksigen hiperbarik di pusat pengobatan hiperbarik mereka.Hasilnya adalah sebanyak 1.83% insiden komplikasi tercatat.Lebih dari 94% komplikasi tersebut ringan hingga sedang sehingga digolongkan menjadi komplikasi minor.Kurang dari 6% merupakan komplikasi mayor dimana komplikasi berat atau mengancam nyawa.Insiden toksisitas oksigen pada system saraf pusat terjadi sebanyak 0.109%.Tidak ada mortalitas yang tercatat pada penelitian ini.Sebagai kesimpulan, terapi oksigen hiperbarik pada pasien orthopedi dikatakan sebagai terapi yang aman karena komplikasi yang sangat rendah.

Berikut adalah data dari penelitian di atas :

Komplikasi Jumlah pasien (n= 240) Jumlah sesi terapi  (n=4,638)
Komplikasi Minor
Pandangan kabur yang transien 20 48
Gejalan nonspesifik 13 21
Otitis barotrauma / dibutuhkan timpanostomi 7 7
Nyeri kepala (sinus tertekan) 2 2
Rasa penuh di abdomen dengan/tanpa nausea/vomitus 2 2
Komplikasi Mayor
Kejang tonik klonik 2 3
Kejang parsial kompleks 1 1
Status epileptikus 1 1
Edema pulmoner 0 0
Kematian 0 0
Total 48 85

Karakteristik pasien yang mengalami toksisitias oksigen pada SSP selama terapi dengan oksigen hiperbarik

No Usia (tahun) JK Indikasi terapi oksigen hiperbarik Penyakit yang mendasari Waktu terapi dengan kejang Tipe serangan kejang
1 39 L Necrotizing fasciitis Diabetes mellitus 39 menit Grand mal
2 66 P Luka bermasalah Scleroderma 68 menit Grand mal
3 45 L Refractory osteomyelitis Kanker kolon 54 menit Status epileptikus
4 53 L Refractory osteomyelitis Diabetes mellitus 64 menit Kejang parsial kompleks

2.  Luka Kaki DiabetikKomplikasi kronik dari penyakit  DM  mempengaruhi banyak system organ dan bertanggung jawab terhadap sebagian besar morbiditas dan mortalitas dari penyakit system organ tersebut. Komplikasi kronik dari DM dapat dibagi menjadi komplikasi vascular dan non vascular.  Komplikasi vascular sendiri dibagi lagi menjadi mikrovaskular ( retinopati, neuropati, nefropati ) dan makrovaskular ( penyakit jantung coroner, penyakit arteri perifer, penyakit pembuluh serebral ). Komplikasi non vascular antara lain infeksi, perubahan pada kulit, dan gastroparesis. DM kronik berhubungan dengan hilangnya pendengaran.

   

Diabetes mellitus merupakan penyebab utama amputasi non-trauma ektremitas bawah di Amerika Serikat.Ulkus pada kaki dan infeksi juga merupakan sumber utama morbiditas pada individu dengan DM. meningkatnya insidensi tersebut pada individu dengan DM melibatkan interaksi beberapa factor patogenik yaitu, neuropati, penyakit arteri perifer, dan penyembuhan luka yang buruk.Neuropati sensoris perifer menyebabkan pasien kehilangan mekanisme protektif sehingga individu tidak dapat menyadari trauma pada kaki.Gangguan proprioception menyebabkan tumpuan berat yang abnormal pada kaki ketika berjalan sehingga menimbulkan callus atau ulkus. Neuropati motorik dan sensoris mengarah kepada perubahan struktur pada kaki (hammertoe, deformitas claw toe, sendi Charcot, proksimal metatarsal yang prominen). Neuropati autonom berakibat pada anhidrosis dan perubahan aliran darah superfisial di kaki sehingga kulit menjadi kering dan retak.Penyakit arteri perifer dan buruknya penyembuhan luka memperburuk retakan minor pada kulit sehingga menjadi bertambah luas dan terinfeksi.

   
 

Charcot foot

Clawtoe deformity involves hammer toe deformity associated with

dorsiflexion of metatarsophalangeal joint.

Diperkirakan 15% individu dengan DM tipe 2 mempunyai ulkus kaki ( digiti 1 kaki atau daerah metatarsophalangeal adalah daerah tersering ) dan 14-24% resiko amputasi. Faktor resiko ulkus kaki atau amputasi adalah:

  • Jenis kelamin pria
  • Diabetes > 10 tahun
  • Neuropati perifer
  • Struktur kaki abnormal ( abnormalitas tulang, callus, penebalan kuku )
  • Penyakit arteri perifer
  • Merokok
  • Riwayat ulkus atau amputasi sebelumnya
  • Pengendalian glukosa darah yang buruk
  • Trauma dan sepatu yang tidak tepat

Berdasarkan konsensus ADA, terdapat enam intervensi dalam perawatan luka kaki dibetik:

  1. 1.       Off-loading

Menghindari secara total tumpuan berat badan pada ulkus sehingga trauma mekanik yang menggangu penyembuhan luka terhindari. Berbaring di tempat tidur, peralatan orthotic dapat membatasi tumpuan berat pada luka atau titik tekan.

  1. 2.       Debridement
  2. 3.       Wound dressing

Menggunakan hydrocolloid membantu proses penyembuhan luka dengan menciptakan suasana lembab dan melindungi luka. Agen antiseptic dihindari.Penggunaan antibiotic topical dibatasi penggunaannya.

  1. 4.       Penggunaan antibiotik yang tepat
  2. 5.       Revaskularisasi
  3. 6.       Amputasi terbatas

 

   

Klasifikasi Wagner dan Terapi Ulkus Diabetik  Kaki
Grade Klasifikasi Pengobatan
0 Kaki beresiko terjadinya ulkus. Kulit intact, tetapi deformitas tulang dibawahnya beresiko terhadap pecahnya kulit Memakai alas kaki yang tepat, edukasi pasien, koreksi bedah.
1 Lesi hanya pada kulit Dressing
2 Lesi melibatkan tendon, tulang atau ligament Debridement , rawat inap untuk perawatan luka dan antibiotic intravena. Tujuan terapi ulkus menjadi grade 1
3 Komplikasi ulkus : abses, osteomyelitis, atau sepsis sendi Drainase untuk infeksi akut. Luka dibiarkan terbuka dengan penggantian dreesing hingga penutupan luka atau amputasi dilakukan kemudian
4 Gangrene pada jari-jari kaki Amputasi
5 Seluruh kaki telah menjadi gangrene Amputasi

 

Klasifikasi Rancho Los Amigos oleh Wagner dan Meggitt

 

PROSES PENYEMBUHAN LUKA

 

Proses penyembuhan luka normal mempunyai karakteristik sebagai berikut :

  1. Hemostasis dan inflamasi
  2. Proliferasi
  3. Maturasi dan remodeling

Proses terjadi terjadi tumpang tindih. Semua luka harus melewati semua tahapan proses penyembuhan ini agar terbentuk integritas jaringan yang sempurna.

Luka diklasifikasikan menjadi akut dan kronik.Luka akut menyembuh dalam tahapan dan waktu yang normal dan apabila terdapat komplikasi dapat menyembuh dengan sempurna. Faktor yang mempengaruhi penyembuhan luka adalah :

Sistemik            Lokal
1. Usia 1. Injuri Mekanik
2. Nutrisi 2. Infeksi
3. Trauma 3. Edema
4. Penyakit Metabolic 4. Jaringan nekrosis/ Iskemi
5. Supresi imunitas 5. Agen Topical
6. Gangguan jaringan ikat 6. Radiasi Ionizing
7. Merokok            7. Oksigen Rendah
  8. Benda asing

Epinefrin tidak boleh digunakan pada luka di jari kaki dan tangan, telinga, hidung, atau penis karena resiko nekrosis jaringan akibat vasokonstriksi arteriol terminal pada struktur tersebut.Irigasi luka hanya dilakukan dengan normal saline. Iodine, povidone-iodine, hydrogen peroksida, dan preparat antibacterial menunjukkan merusak proses penyembuhan luka akibat injuri neutrophil dan makrofag luka. Antibiotic digunakan hanya bila terjadi infeksi pada luka.Tanda infeksi yang dapat terlihat adalah eritema, selulitis, edema, cairan purulent.

TERAPI  OKSIGEN HIPERBARIK PADA LUKA KAKI  DIABETIK

Ulkus diabetik pada kaki terjadi pada 1.9% individu dengan diabetes setiap tahunnya dengan angka amputasi 15%-20% pasien dalam 5 tahun.Terapi oksigen hiperbarik pada ulkus yang tidak responsive dengan terapi konvensional dan bedah telah disetujui berdasarkan bukti ilmiah menjadi terapi adjuvant.

Proses penyembuhan luka yang normal mempunyai tahap dimana setelah injuri, proses inflamasi terjadi pada daerah luka, daerah pusat luka mengalami hipoksia dan kadar laktat meningkat sehingga menstimulasi replikasi fibroblast, produksi kolagen, dan pertumbuhan sel endothelial. Stimulasi dan pertumbuhan jaringan tersebut menjadi optimal bila terdapat perpindahan gradient oksigen dari perifer ke daerah hipoksia. Konsentrasi oksigen terlarut yang tinggi  terjadi pada terapi oksigen hiperbarik sehingga mengoptimalkan konsentrasi gradient oksigen dan memfasilitasi perbaikan luka.

Saat konsentrasi oksigen yang tinggi, terdapat stimulasi phagocyte oxidative killing dan meningkatkan modifikasi kolagen.Terapi oksigen hiperbarik secara langsung meningkatkan replikasi fibroblast, aktifasi osteoclast, vascular endothelial growth factor, dan platelet-derived growth factors.Efek persisten setelah administrasi terapi oksigen hiperbarik adalah stimulasi pertumbuhan kapiler.

Pada studi yang dilakukan pada tulang hipovaskular kerusakan akibat radiasi, Marx et al mendemonstrasikan setelah terapi oksigen hiperbarik beberapa sesi, densitas kapiler meningkat hingga 80%.Observasi ini diperhitungkan sebagai mekanisme fisiologis utama pada pengobatan oksigen hiperbarik untuk osteoradionecrosis.Terapi oksigen hiperbarik juga menginduksi pertumbuhan kapiler perifer pada luka yang tidak menyembuh.

Tekanan oksigen pada daerah sekitar luka yang tidak menyembuh dapat diukur dengan elektroda polarografik dalam larutan ionik,  terpisah dari epidermis dengan oxygen-permeable membrane. Oksigen yang terdifusi pada bantalan kapiler dibawah elektroda akan tereduksi oleh katoda sehingga menghasilkan gelombang yang menggambarkan konsentrasi oksigen. Pemeriksaan transcutaneous oxygen concentration(Tcpo2) memberikan parameter objektif yang dapat digunakan untuk mengevaluasi pasien. Pada umumnya, luka tidak menyembuh pada pasien diabetik dengan Tcpo2 > 35 mmHg mempunyai kecenderungan untuk sembuh tanpa terapi adjuvant oksigen hiperbarik.Sebaliknya, bila nilai Tcpo2 < 20 mmHg meningkatkan resiko tidak sembuh sebesar 39 kali. Walaupun tidak terdapat niai pasti Tcpo2 untuk menilai keberhasilan terapi oksigen hiperbarik, pasien dengan  Tcpo2 ≥ 200 mmHg dengan 100% oksigen pada tekanan 2.5 atm cenderung untuk sembuh luka diabetiknya.

Studi retrospektif yang dilakukan oleh Fife et al mengukur Tcpo2  dan penggunaan oksigen hiperbarik pada pasien dengan daerah sekitar luka yang hipoksia. Hasil yang didapatkan adalah pasien dengan Wagner III mempunyai respon sebesar 77%, Wagner IV 64% dan Wagner V 30%.Ratio kesembuhan pada pasien dengan Wagner I dan II adalah sebesar 83%. Hasil tersebut berlawanan dengan percobaan dengan topical recombinant human platelet-derived growth factor BB (becaplermin; Regranex, Ortho-McNeil) sebesar 44% dengan eksklusi luka hipoksia (Tcpo2 < 30 mmHg) dan luka Wagner III,IV,V

Percobaan terkontrol pertama pada luka diabetic ekstremitas bawah dengan terapi oksigen hiperbarik dilakukan sekitar 35 tahun yang lalu.Sejak itu, banyak studi dilakukan untuk menilai efektifitas terapi oksigen hiperbarik pada luka diabetic tidak menyembuh pada ektremitas bawah.

Kessler et al merawat 28 pasien diabetic dengan luka tidak menyembuh kronik.Penyakit makrovaskular tereksklusi pada pasien tersebut.Seluruh pasien diberikan regimen pengendali glukosa, off-loading, dan terapi luka dan dibagi secara acak ke dalam kelompok control dan pasien dengan terapi oksigen hiperbarik.Pada kelompok pasien dengan terapi oksigen hiperbarik, mereka mendapatkan terapi sebanyak dua kali per hari setiap harinya selama 10 hari pada masa 2 minggu perawatan di rumah sakit.Dua minggu berikutnya pasien kelompok tersebut menjalani rawat jalan.Hasil yang didapat adalah kelompok dengan terapi oksigen hiperbarik mempunyai tingkat kesembuhan luka dua kali dibandingkan kelompok control.

Abidia et al melakukan studi acak pada 18 pasien diabetic dengan ulkus iskemik dan mendapatkan terapi oksigen 100% pada tekanan 2.4 atm selama 90 menit setiap harinya untuk 30 kali sesi terapi. Penyembuhan total terjadi setelah 1 tahun terapi pada 5 dari 8 orang pada kelompok hiperbarik dan 1 dari 8 orang pada kelompok control. Hasil dari studi tersebut adalah terdapat penurunan yang signifikan pada daerah luka pada pasien kelompok hiperbarik dibandingkan dengan kelompok control.

Efek terapi oksigen hiperbarik pada penyembuhan luka terbukti dapat bertahan lama. Lebih dari 90% luka tetap tertutup setelah 4 tahun follow up. Studi yang dilakukan oleh Kalani et al, 76% pasien yang diterapi dengan oksigen hiperbarik mempunyai kulit yang intak setelah 3 tahun follow-up, dibandingkan dengan 48% pasien kelompok control. Terdapat reduksi amputasi sebesar 20% pada kelompok yang mendapat terapi oksigen hiperbarik.

Studi yang dilakukan oleh Faglia et al terhadap 68 pasien diabetic dengan luka tidak menyembuh pada ekstremitas bawah untuk melihat efektifitas terapi oksigen hiperbarik pada resiko amputasi.Seluruh individu penelitian mendapatkan perawatan klinis standar dengan evaluasi makrovaskular sebelum mengikuti studi tersebut, sebanyak 35 subjek acak mendapatkan terapi oksigen hiperbarik sebanyak 38.8 sesi. Amputasi yang dilakukan oleh tim bedah terjadi pada 3 dari 35 subjek pada kelompok hiperbarik dan 11 dari 33 subjek pada kelompok control.

Banyak penelitian dan artikel yang menggambarkan hubungan terapi oksigen hiperbarik pada proses penyembuhan luka diabetic. Walaupun demikian, terdapat kontroversi terapi tersebut yang ditulis oleh A.R. Berendt   (2006). Ia berpendapat bahwa seluruh studi yang ada mempunyai kelemahan metodologi dan efek positif dari terapi hiperbarik tersebut tidak terlihat dalam percobaan acak tunggal, sehingga ia berpendapat bahwa terapi oksigen hiperbarik tidak seharusnya disarankan untuk terapi luka kaki diabetic hingga studi dalam sekala besar, terkontrol dan mempunyai tingkat kepercayaan yang besar secara jelas menggambarkan efektifitas dalam penyembuhan ulkus dan pencegahan amputasi besar. Bukti- bukti yang tersedia dari banyak studi yang telah dilakukan dipelajari secara cermat oleh beberapa lembaga termasuk The Cochrane Collaboration dan disimpulkan kualitas studi-studi tersebut buruk dan terdapat bukti yang sedikit untuk mendukung peran terapi oksigen hiperbarik mempercepat proses penyembuhan ulkus. Dari 26 studi tentang terapi hiperbarik oksigen untuk luka kronik, hanya 5 studi yang dinyatakan mempunyai kualitas metodologi yang cukup.4 dari 5 studi tersebut meneliti tentang luka kaki diabetic.Walaupun 4 studi tersebut dinyatakan cukup dalam bidang metodologinya tetapi tidak cukup untuk menjadi bukti ilmiah yang kuat.  Beberapa studi tidak memiliki kelompok placebo dan blinded.

3. Refractory Osteomyelitis

Beberapa system klasifikasi digunakan pada osteomyelitis.Sistem tradisional membagi infeksi tulang berdasarkan durasi gejala, yaitu akut, subakut, dan kronis.Osteomyelitis akut mempunyai onset 7-14 hari.

Infeksi akut sering berhubungan dengan penyebaran infeksi secara  hematogen ke tulang pada anak. Dewasa juga dapat infeksi akut hematogenous terutama pada implant prostesa metal dan alat fiksasi. Subakut osteomyelitis mempunyai durasi beberapa minggu dan beberapa bulan, sedangkan infeksi kronik minimal selama beberapa bulan.

Menurut American College of Hyperbaric Medicine, istilah refractory osteomyelitis adalah penyembuhan yang gagal walaupun mendapatkan terapi antibiotic dan bedah yang adekuat.

Osteomyelitis adalah inflamasi tulang yang disebabkan oleh organisme.Walaupun tulang normalnya resisten terhadap kolonisasi bakteri, keadaan seperti trauma, pembedahan, adanya benda asing, atau prostesa dapat merusak integritas tulang dan mengarahkan kepada infeksi tulang.Osteomyelitis juga dapat disebabkan oleh penyebaran hematogen setelah bacteremia.Ketika sendi prostesa berhubungan dengan infeksi, mikroorganisme tumbuh di biofilm yang melindungi bakteri terhadap terapi antimicrobial dan respon imun tubuh.Terapi dini dan spesifik penting dalam pengobatan osteomyelitis dan identifikasi mikroorganisme penyebab penting dalam terapi antibiotic.Penyebab utama infeksi tulang adalah Staphylococcus aureus.

Diperkirakan 20% kasus osteomyelitis pada dewasa merupakan hematogenous, dan lebih sering terdapat pada pria dengan alasan yang belum diketahui.Insidensi osteomyelitis spinal diperkirakan sebanyak 1 dalam 450.000 pada tahun 2001. Insiden osteomyelitis vertebral terus meningkat diduga karena penggunaan obat intravena, peningkatan usia dalam populasi, peningkatan angka infeksi nosocomial akibat alat intravascular dan instrument lainnya.

SISTEM KLASIFIKASI OSTEOMYELITIS
Sistem Tradisional
Tipe Waktu Onset
Akut ≤ 2 minggu
Subakut Beberapa minggu hingga beberapa bulan
Kronik ≥ 3 bulan
Waldvogel Sistem
Hematogenous osteomyelitis
Focus infeksius osteomyelitis
Osteomyelitis yang berhubungan dengan penyakit vaskular
Kronik osteomyelitis
Cierny – Mader Sistem
Penyebaran infeksi secara anatomis
Medulla saja (akut hematogenous)
Korteks superfisial (penyebaran infeksius atau trauma jaringan lunak)
Local (korteks dan medulla , stabil secara mekanik)
Menyebar rata (korteks dan medulla , stabil secara mekanik)
Berdasarkan status fisiologik pasien
A  Sehat
Bs  Compromised karena factor sistemik
B1 Compromised karena factor sistemik dan lokal
C  Pengobatan lebih buruk dibandingkan penyakit

Sebanyak 47% kasus osteomyelitis disebabkan oleh pasca-trauma. Etiologi osteomyelitis yang lainnya adalah insufisiensi vascular (34% terjadi pada penderita diabetes) dan penyebaran hematogen (19%).

Factor pathogenesis yang berperan penting pada osteomyelitis antara lain:

  • Virulensi organisme
  • Penyakit yang mendasari
  • Status imun penderita
  • Tipe tulang yang terinfeksi
  • Lokasi tulang yang terinfeksi
  • Vaskularisasi tulang yang terinfeksi

Osteomyelitis sering didiagnosa secara klinis dengan gejala nonspesifik seperti demam, menggigil, lesu, lemah, atau rewel. Tanda klasik inflamasi seperti nyeri local, bengkak, atau kulit kemerahan dapat terjadi dan akan menghilang dalam 5-7 hari.

Osteomyelitis kronik pasca trauma memerlukan riwayat anamnesis yang terperinci untuk membuat diagnosis termasuk injuri awal, pengobatan antibiotic sebelumnya dan terapi bedah yang didapat.Ekstremitas yang terkena mengalami gangguan fungsi dan tidak dapat menahan beban tubuh.Riwayat nyeri local, bengkak, eritema, juga dapat ditemukan.

Pada pemeriksaan fisik, dapat ditemukan luka skar atau proses penyembuhan luka yang terganggu dan dapat diikuti oleh tanda cardinal inflamasi. Pada ekstremitas yang terkena juga dapat ditemukan terbatasnya ruang gerak sendi, deformitas, dan tanda rusaknya vaskularitas.

Pemeriksaan kultur darah positif hanya pada 50% kasus osteomyelitis. Bahan kultur harus diambil sebelum atau minimal 48 jam sesudah terapi antibiotik. Biopsy tulang merupakan diagnosis definitive dengan mengisolasi pathogen secara langsung dari lesi tulang.

Biopsy tulang dilakukan melalui jaringan yang tidak terinfeksi dan sebelum terapi antibiotic dimulai atau > 48 jam setelah terapi dihentikan.

Pengobatan antibiotic harus berdasarkan jenis pathogen yang didapat pada hasil kultur tulang terapi antibiotic parenteral dini dapat dilakukan hingga hasil kultur keluar. Setelah hasil kultur didapat, terapi dapat dimodifikasi sesuai organisme pada kultur. Umumnya lama terapi antibiotic pada osteomyelitis 4 – 6 minggu.Antibiotic oral yang terbukti efektif termasuk klindamisin, rifampin, trimethoprim-sulfamethoxazole, dan fluoroquinolone.

Tindakan pembedahan diindikasikan bagi penderita yang tidak ada respon terhadap terapi antimikroba. Berdasarkan klasifikasi Cierny-Mader, kategori 1 dan 2 umumnya tidak membutuhkan terapi bedah, kategori 3 dan 4 mempunyai respon yang baik terhadap terapi bedah. Tindakan bedah sendiri meliputi drainase yang adekuat, debridemen jaringan neksrosis, penutupan jaringan lunak yang adekuat, mengembalikan supply darah.Apabila infeksi terjadi pada alat penopang dalam tulang, alat dikeluarkan dan digunakan fiksasi eksternal.

Pada pemeriksaan penunjang radiologi konvesional, dapat terlihat penebalan atau elevasi  periosteal, penebalan korteks tulang, sclerosis, dan irregularitas. Perubahan yang lain yang dapat dilihat adalah hilangnya arsitektur trabekula, osteolisis, dan pembentukan tulang yang baru. Perubahan tersebut tidak tampak nyata hingga hari ke 5-7 pada anak dan 10-14 hari pada dewasa.Pada foto polos dapat ditemukan perubahan lytic sesudah minimal 5—75% matriks tulang rusak. Dengan demikian, hasil radiologi yang negative tidak dapat menyingkirkan diagnose osteomyelitis akut. Gambaran penyembuhan fraktur, kanker, dan tumor jinak tulang juga dapat mempunyai gambaran radiologi yang sama pada foto polos.

 

Kronik oteomyelitis pada calcaneum. Tampak udara pada jaringan lunak

Osteomyelitis T10

Komplikasi tersering pada anak dengan osteomyelitis adalah rekurensi infeksi tulang.Infeksi kronik dapat terjadi pada 5-10% pasien dengan pengobatan yang tepat. Komplikasi umum pada anak dengan usia kurang dari 18 bulan adalah destruksi tulang, osteomyelitis kronik, pertumbuhan tulang yang terganggu terutama bila lempeng pertumbuhan terinfeksi. Walaupun jarang, destruksi tulang yang hebat atau penipisan korteks dapat mengakibatkan fraktur patologis.

Terapi yang tidak adekuat dapat berakibat pada infeksi yang relapse dan infeksi kronik.Avaskularitas tulang menyebabkan kronik osteomyelitis hanya dapat diterapi dengan reseksi radikal atau amputasi.

Pemeriksaan CT digunakan dalam penuntun biopsi pada infeksi tertutup dan untuk perencanaan perioperative dalam mendeteksi abnormalitas tulang, benda asing, atau tulang nekrotik dan jaringan lunak.Pemeriksaan osteomyelitis dengan modalitas MRI mempunyai tingkat sensitifitas yang tinggi sehingga mendukung tingkat kesuksesan terapi.Lokasi osteomyelitis dan daerah yang terkena didemonstrasikan bersama dengan perubahan patologi pada sumsum tulang dan jaringan lunak.

Pemeriksaan ultrasound juga dapat digunakan dalam pemeriksaan osteomyelitis dengan gambaran kumpulan cairan sekitar tulang tanpa menggangu jaringan lunak sekitar , periosteum yang menebal dan elevasi.


Kronik osteomyelitis. T1 dan T2 MRI sagittal menunjukkan edema pada sumsum tulang L1 dan kerusakan ruang diskus antara L1 dan L2

Terapi oksigen hiperbarik pada osteomyelitis

Terapi oksigen hiperbarik biasanya digunakan pada osteomyelitis akut, kronik, atau refraktori.Terapi oksigen hiperbarik digunakan hanya sebagai terapi adjuvant osteomyelitis dan harus dilaksanakan bersama dengan antibiotic parenteral, debridement, dukungan nutrisi, dan bedah rekonstruksi.Karena osteomyelitis dapat kambuh walaupun telah bertahun-tahun hasil terapi sukses, evaluasi minimal 2-5 tahun direkomendasikan.

Tekanan oksigen dalam tulang osteomyelitik rendah, jarang melebihi 25 mmHg. Mader et al, melakukan percobaan dengan hewan dan hasil penelitian menunjukkan tekanan oksigen pada tulang yang normal maupun yang terinfeksi meningkat pada terapi oksigen hiperbarik.

Pada keadaan tanpa oksigen hiperbarik, tekanan oksigen pada tulang normal adalah 45 mmHg sedangkan di tulang osteomyelitik adalah 23 mmHg.Dengan terapi oksigen hiperbarik, tekanan oksigen dinaikkan menjadi 104 mmHg pada tulang osteomyelitik dan 322 mmHg pada tulang normal.

Sel PMN merupakan sel yang bertanggung jawab terhadap perlawanan infeksi bakteri. Dengan menggunakan model S.aureus, Mader menunjukkan hubungan proporsional antara tekanan oksigen dan kemampuan fagosit. Meningkatkan oksigen hingga 150 mmHg dan 760 mmHg membunuh sebagian besar S.aureus.Penelitian menunjukkan hasil terapi osteomyelitis staphylokokus membaik dengan terapi adjuvant oksigen hiperbarik.

Fibroblast tidak dapat mensintesa kolagen atau migrasi ke daerah terinfeksi apabila tekanan oksigen kurang dari 20 mmHg.Meningkatkan tekanan oksigen di atas 200 mmHg mengembalikan aktifitas fibroblastik ke dalam fungsi normal.

Barth et al mendemonstrasikan efek menguntungkan dari terapi oksigen hiperbarik pada penyembuhan tulang dengan menunjukkan defek metafisis pada korteks femur di tikus percobaan membaik dengan osifikasi primer ketika tikus tersebut diterapi dengan oksigen hiperbarik sehari sekali selama 90 menit dalam tekanan 2 atmosfer.

Vankomisin, kuinolon, sulfonamide, dan kelas antibiotic aminoglikosida lainnya menunjukkan aktifitas yang rendah pada keadaan hipoksia.Mader menunjukkan bahwa terapi oksigen hiperbarik, meningkatkan aktifitas bakterisidal pada golongan aminoglikosida.

Penelitian yang dilakukan oleh M.Kawahima dkk di Rumah Sakit Orthopedi Kawashima, Nakatsu, Jepang pada  256 kasus osteomyelitis tanpa terapi oksigen hiperbarik (hanya dilakukan debridement pada daerah infeksi dengan irigasi tertutup). Hasil yang didapat adalah sebanyak 226 kasus (88.3%) menunjukkan hasil yang bagus, 7 kasus (2.7%) hasil yang sedang, dan sebanyak 23 kasus (9.0%) menunjukkan hasil yang jelek. Pada 433 kasus osteomyelitis yang diterapi dengan oksigen hiperbarik, 398 kasus (91.9%) menunjukkan hasil yang bagus, hasil sedang pada 10 kasus (2.3%), dan hasil yang buruk sebanyak 25 kasus (5.8%). Kesimpulan dari penelitian ini adalah hasil terapi dengan oksigen hiperbarik lebih baik dibandingkan tidak mendapatkan terapi oksigen hiperbarik (p<0.01).

 

Hasil Terapi 668 Kasus Osteomyelitis
  Tidak mendapatkan terapi oksigen hiperbarik Mendapatkan terapi oksigen hiperbarik
Baik 226 (88.3%) 398 (91.9%)
Sedang 7 (2.7%) 10 (2.3%)
Buruk 23 (9.0%) 25 (5.8%)
Total 256 433
P<0.01

Perbandingan Terapi Oksigen Hiperbarik dengan Ozonized Oxygen  Sebagai Terapi Adjuvant Pada Osteomyelitis :  Osteomyelitis merupakan diagnosis yang serius dalam bidang trauma dan bedah tulang. Pengobatan osteomyelitis kompleks dan sulit dan membutuhkan pendekatan multidisiplin.Walaupun operasi debridemen dan pengobatan dengan antibiotic telah dilakukan, terapi membutuhkan waktu yang lama dan hasil akhirnya dapat tidak sesuai dengan harapan. Kegagalan terapi pada osteomyelitis mempunyai berbagai macam factor antara lain yang berperan adalah aliran darah yang berkurang, hipoksia, dan iskemia jaringan. Oleh karena itu, akhir-akhir ini dikembangkan terapi adjuvant untuk terapi osteomyelitis .terapi oksigen hiperbarik adalah salah satu terapi adjuvant yang paling potensial dan yang tersering digunakan sebagai adjuvant pada terapi osteomyelitis. Studi eksperimental dan klinis telah membuktikan bahwa terapi oksigen hiperbarik efektif dalam pengobatan osteomyelitis.Rendahnya tingkat oksigen pada daerah osteomyelitis ditingkatkan secara signifikan oleh inhalasi oksigen 100% dalam kondisi hiperbarik.

Campuran gas ozone/oksigen (O3/O2)yang digunakan dalam bidang kesehatan juga dikenal dengan istilah terapi O3 medis, akhir-akhir ini mendapatkan perhatian dalam komunitas medis. O3 dan O2 merupakan oksidan paling potensial.Pada bidang farmakologi yang baru, O3 sendiri digolongkan sebagai obat yang dalam dosis non toksik dapat menginduksi jalur biokimia.Kondisi iskemia merupakan contoh yang baik dalam konteks ini.campuran O3 dan O2 juga mempunyai efek terhadap system imunitas tubuh seperti modulasi aktifitas fagosit. Studi klinis hingga sejauh ini telah menunjukkan terapi O3 mempunyai keuntungan dalam pengobatan penyakit termasuk peritonitis, luka yang terinfeksi, ulkus kulit kronik, gangrene tahap awal, luka bakar, dan penyakit iskemia tahap lanjut.

Ozonized O2 telah digunakan sebagai disinfekstan air minum dan peralatan karena efek bakterisidalnya.O3 juga digunakan sebagai terapi eksperimental pada infeksi tulang dasar cranium.

Pada tahun 2010, Erbil Oguz dkk melakukan evaluasi dan perbandingan efek terapi oksigen hiperbarik dan ozonized oxygen dalam terapi adjuvant pada tikus percobaan yang telah diinduksi dengan methicillin-resistant Staphylococcus aureus pada tulangnya. Hasil yang didapat adalah ozone merupakan senyawa oxidative kuat dan sangat bakterisidal terhadap methicillin-resistant Staphylococcus aureus.Penelitian mereka menyimpulkan bahwa administrasi O3 lebih efektif dibandingkan dengan administrasi oksigen pada kondisi hiperbarik, tetapi kedua modalitas dapat digunakan sebagai terapi adjuvant dalam osteomyelitis.

Hal ini didukung oleh dokumentasi Yamayoshi dan Tatsumi bahwa tipe Staphylococcus aureus yang resisten, sensitive terhadap O3. Steinhart et al menggunakan radiologi klinis dan analisa mikrobiologi, menemukan bahwa tulang osteomyelitis yang telah diaplikasikan dengan terapi O3 , terapi antibiotic, dan pembedahan menunjukkan hasil yang memuaskan.

Beberapa studi menunjukkan O3 dalam konsentrasi sangat tinggi mempunyai potensi sebagai anti viral dan bacterial dalam plasma ex vivo, mengindikasikan kemungkinan dalam in vivo.

Bertolak belakang dengan penelitian-penelitian sebelumnya, Torossian et al menginvestigasi efek O3 dosis tinggi pada tikus.Hasilnya adalah angka survival pada tikus yang mendapat terapi O3 dosis tinggi lebih rendah dibandingkan kelompok control.

5 Crush Injury dan Compartment Syndrome

Iskemi perifer traumatic akut merupakan kategori untuk cedera yang disebabkan oleh trauma dan berakibat pada iskemia jaringan dan edema. Pada kategori tersebut crush injury dan compartment syndrome termasuk di dalamnya.

Crush injury terjadi ketika bagian tubuh terkena tekanan atau  dengan derajat tinggi, umumnya setelah terjepit diantara dua objek yang berat atau tak bergerak. Compartment syndrome merupakan keadaan dimana peningkatan tekanan diantara ruang tertutup (tekanan kompartemen) melebihi tekanan perfusi kapiler, yang berakibat pada terganggunya mikrovaskular sehingga terjadi kematian sel akibat kekurangan oksigen. Compartment syndrome dapat terjadi setelah fraktur, kompresi tungkai, olahraga yang berlebihan, atau luka bakar. Istilah crush syndrome didefinisikan sebagai manifestasi sistemik kerusakan sel otot akibat tekanan atau himpitan disertai atau tidak disertai dengan compartment syndrome.

Crush injury dapat terjadi pada keadaan individual (kecelakaan pada tempat kerja yang berhubungan dengan mesin atau kendaraan) atau bencana alam seperti gempa bumi. Crush injury sering terjadi pada ekstremitas karena injuri pada badan atau kepala dan leher sangat fatal. Crush injury umumnya mempunyai prognosa yang buruk karena usaha tubuh untuk menangani cedera primer, menyebabkan tubuh menghasilkan lebih banyak cedera akibat respon reperfusi.

  

Penyebab umum compartment syndrome

Orthopedic  Fraktur tibia
Fraktur antebrachii
Vascular  Injuri iskemik-reperfusi
Perdarahan
Iatrogenic  Tusukan vascular pada pasien dalam keadaan antikoagulasi
Injeksi obat intravena atau intraarterial
Injuri jaringan lunak   Kompresi tungkai lama
Crush injury
Luka bakar
 
Crush injuries merupakan cedera iskemia yang traumatik yang menyebabkan kerusakan hebat pada jaringan sehingga angka survival jaringan dipertanyakan, biasanya, dua atau lebih jaringan mengalami injury hebat sehingga survival jaringan tersebut tidak dapat dipastikan.

Edema akibat hipoksia jaringan mempunyai efek merusak pada proses penyembuhan luka dan pemantauan infeksi. Hal tersebut berhubungan dengan ketersediaan oksigen dalam sel-sel yang dalam keadaan membutuhkan oksigen yang banyak daripada biasanya. Efek merusak lain dari edema adalah kapiler yang collapse. Cairan edema meningkatkan tekanan interstitial di sekitar kapiler. Ketika tekanan cairan interstitial meningkat dibandingkan tekanan perfusi kapiler dalam ruang tertutup, capillary bed collapses sehingga aliran mikrosirkulasi terhenti. 

Bakteri berkembang biak dengan baik apabila sirkulasi terganggu pada lokasi injuri. Pasokan darah yang terganggu atau rusak, antibiotic tidak dapat mencapai area injuri atau infeksi.

Pada lingkungan hipoksia, neutrophil kehilangan daya untuk menghasilkan sel oksigen reaktif yang membunuh bakteri-bakteri tersebut. Selain area yang kehilangan pasokan darah dan tidak adanya daya untuk melawan infeksi, permasalahan yang lain pada lokasi injuri tersebut adalah terganggunya proses penyembuhan luka. Sebuah luka tidak akan sembuh apabila tidak terdapat konsentrasi oksigen yang memadai agar fibroblast dapat berfungsi, tekanan oksigen jaringan yang dibutuhkan fibroblast bermobilisasi dan menghasilkan matriks kolagen untuk neovaskularisasi dan penyembuhan luka adalah 300 mmHg.

40% compartment syndrome terjadi pada tibia dan fibula. Tungkai bawah mempunyai empat kompartemen yaitu anterior, lateral, posterior superfisial, posterior dalam.Tungkai atas mempunyai tiga kompartemen yaitu anterior, posterior dan medial.Ekstremitas atas bagian antebrachii merupakan bagian yang sangat beresiko tinggi dalam pembentukan compartment syndrome.Bagian tersebut mempunyai tiga kompartemen yaitu flexor, ekstensor dan mobile wad.

Trauma pada otot berakibat pada peningkatan konsentrasi  ion kalsium di ekstraseluler. Dengan bertambahnya cedera dan  kematian sel, potassium, fosfat, myoglobin, kreatinine kinase, dan urate terkandung banyak di dalam sirkulasi darah. Serum haptoglobin mengikat myoglobin tetapi  tersaturasi ketika 100 gram jaringan otot mati. Myoglobin yang bersirkulasi mempunyai dampak yang buruk terhadap ginjal.Kerusakan membrane pada sel otot dan edotel kapiler sistemik berakibat pada kehilangan volume vascular dan hipovolemia.Hyperkalemia dan hipokalsemia menyebabkan aritmia dan henti jantung.Asidosis metabolic akibat hipovolemik dan syok toksik memperberat aritmia. Gagal ginjal merupakan komplikasi serius pada crush syndrome. Pathogenesis kegagalan ginjal tersebut mempunyai banyak factor termasuk sistemik hipoperfusi, nefrotoksik dari myoglobin, kandungan urate dan fosfat yang tinggi pada tubulus distal. Kandungan urate dan fosfat yang tinggi dieksaserbasi oleh rendahnya pH urine  dan volume urine. Myoglobin juga secara tidak langsung mempunyai efek nefrotoksik melalui induksi lipid peroksidase dan produksi oksigen radikal bebas.

Tekanan normal kompartemen otot adalah < 15 mmHg. Setelah crush injury, edema seluler terjadi sehingga menghasilkan peningkatan tekanan pada kompartemen yang mempunyai volume yang tetap tersebut. Tekanan > 30 mmHg menghasilkan iskemia otot, kerusakan irreversible saraf dan kerusakan otot, terjadi setelah 4 hingga 6 jam.

Compartment syndrome umumnya memiliki gejala klinis 5P :

  • Pain

          Nyeri yang dirasakan terus menerus dan merata, diperparah dengan gerakan, sentuhan, atau tekanan.

  • Paresthesia (atau anesthesia)
  • Passive stretch

          Nyeri hebat ketika otot dalam kompartemen yang terkena ditarik

  • Pressure

          Palpasi pada kompartemen yang terkena didapatkan kesan keras, kencang dan kadang hangat.

  • Pulselessness

          Tanda tersebut kurang dapat diandalkan karena baru terjadi pada tahap lanjut.Pemeriksaan denyut nadi kurang dapat

          diandalkan karena compartment syndrome melibatkan mikrovaskular sehingga pembuluh darah utama umumnya tidak

          terlibat.

Kontraktur iskemik Volkmann merupakan akibat compartment syndrome yang akut dimana jaringan fibrosa digantikan dengan otot yang mati.

Diagnosa compartment syndrome dipastikan dengan pemeriksaan tekanan kompartemen.Tekanan > 30 mmHg umumnya dimasukkan ke dalam hasil yang positif. Pemeriksaan dapat dilakukan dengan alat pengukur tekanan kompartemen atau dengan memasukkan jarum yang telah diisi oleh saline yang terhubung dengan system pengukuran tekanan intravascular (seperti alat pengukur tekanan sentral vena atau arteri) ke dalam kompartemen.


Forearm extensor compartment


Forearm flexor compartment


Mobile wad compartment

Tatalaksana pada crush injury adalah resusitasi cairan dengan normal saline 1 – 2 liter bolus menggunakan dua jalur IV yang besar. Analgetik juga diberikan pada pasien tersebut. Apabila pasien mengalami entrapment dalam durasi yang panjang, bicarbonate 1 ampul/ jam harus dipikirkan. Kadar potassium serum harus dipantau secara serial.Pasien dirawat di dalam ruangan unit intensif untuk pemantauan administrasi cairan dan status elektrolit.Keluaran urine harus sebesar 200 hingga 300 ml/jam untuk dewasa.Alkalinisasi urine dapat diberikan dengan tujuan pH urine pH > 6 dengan menggunakan bicarbonate.Apabila metabolic alkalosis terjadi, acetazolamide dapat diberikan sebanyak 500 mg IV.Hemodialysis darurat dapat diberikan pada pasien dengan anuria, hyperkalemia, atau kelebihan cairan.

Pada keadaan bencana alam akibat gempa bumi, prosedur fasciotomy kebanyakan dilakukan > 12 jam setelah trauma. Peninjauan ulang dari kasus- kasus berikut, didapatkan tingkat infeksi yang tinggi, mortalitas dan amputasi yang meningkat dengan hasil akhir yang buruk. Berdasarkan hasil tersebut, fasciotomy diindikasikan pada korban yang dapat ditangani dalam waktu 6 jam tetapi kurang dari 12 jam setelah trauma. Apabila paralisis terjadi pada tungkai yang terkena, fasciotomy tidak diindikasikan.Fasciotomy yang dilakukan pada kompartemen yang awalnya normal tetapi kemudian berkembang menjadi compartment syndrome, angka infeksi dilaporkan tinggi dan memanjang, perdarahan local yang hebat juga dapat terjadi.

 

Volar Arm Fasciotomy

   

  

Terapi Oksigen Hiperbarik pada Compartment Syndrome

Terapi oksigen hiperbarik mempunyai efek langsung pada compartment syndromeyaitu :

  • Meningkatkan kandungan oksigen pada tingkat jaringan
  • Meningkatkan distribusi oksigen per unit aliran darah
  • Reduksi edema

Efek jangka panjangnya adalah :

  • Meningkatkan penyembuhan luka setelah fasciotomy
  • Mengurangi angka infeksi
  • Meningkatkan hasil skin grafts

Vasokonstriksi merupakan efek sekunder dari terapi oksigen hiperbarik.Efek tersebut menyebabkan berkurangnya edema pada lokasi injuri. Pada area yang terpapar dengan oksigen hiperbarik,  akan terjadi pengurangan aliran darah sebanyak 20%. Dengan berkurangnya aliran darah, ekstravasasi cairan di daerah injuri berkurang sehingga edema berkurang.Pengurangan edema sebesar 20% atau lebih setelah terapi oksigen hiperbarik telah dipelajari dalam penelitian-penelitian ahli.Kandungan oksigen yang meningkat dalam sirkulasi pada terapi oksigen hiperbarik mengkompensasi aliran sirkulasi yang berkurang akibat vasokonstriksi.Terlebih lagi, aliran mikrosirkulasi ditingkatkan di saat berkurangnya edema dan tekanan eksternal sekitar mikrosirkulasi.Cedera reperfusi dihilangkan pada terapi oksigen hiperbarik karena dihasilkannya pembasmi oksigen radikal.

Terapi oksigen hiperbarik juga mengurangi jumlah otot skeletal yang mengalami nekrosis. Terapi oksigen hiperbarik pada kasus crush injury harus dimulai sedini mungkin, idealnya dalam waktu 4-6 jam setelah cedera. Setelah intervensi pembedahan darurat, pasien diberikan terapi oksigen hiperbarik dengan tekanan 2 – 2.5 atm selama 60-90 menit.Untuk 2-3 hari berikutnya, terapi oksigen hiperbarik dilakukan tiga kali sehari setiap harinya kemudian dua kali sehari setiap harinya selama 2-3 hari, lalu setiap hari selama 2-3 hari berikutnya.

Oksigen hiperbarik juga digunakan sebagai terapi tambahan pada manajemen compartment syndromes dan iskemi perifer traumatic akut lainnya. Terapi oksigen hiperbarik tidak direkomendasikan untuk compartment syndrome dalam tahap suspek (compartment syndrome belum terlihat tetapi mungkin dalam tahap impending). Terapi oksigen hiperbarik bermanfaat ketika compartment syndrome sudah dalam tahap impending yaitu tanda objektif terlihat (nyeri, kelemahan, nyeri saat regangan pasif, kompartemen yang tegang). Dengan tanda-tanda tersebut, walaupun terapi pembedahan tidak dipilih akibat tekanan kompartemen atau stabilitas pasien, terapi oksigen hiperbarik menjadi indikasi.Apabila pasien telah menjalankan fasiotomi, terapi oksigen hiperbarik dapat digunakan untuk mengurangi morbiditas.

4.6 Infeksi Nekrosis Jaringan Lunak

Infeksi nekrosis jaringan lunak dibagi atas necrotizing fasciitis dan necrotizing myositis. Necrotizing fasciitis merupakan infeksi jaringan lunak subkutan dan jaringan fasia yang jarang tetapi sangat agresif dan  mengancam nyawa, biasanya ditemukan pada pasien diabetik. Jaringan otot biasanya tidak terinfeksi. Pada pemeriksaan klinis,kulit tampak eritema, kadang-kadang terdapat beberapa bula kecil, pada region luka tusuk. Indurasi local sering ditemukan, kadang-kadang krepitasi subkutan yang disebabkan oleh gas pada jaringan lunak dapat ditemukan.Udara dalam jaringan lunak umumnya dapat terlihat pada pemeriksaan radiologi sederhana pada infeksi gas-producing clostridial.Pemeriksaan serial diperlukan untuk mencari tahu sumber infeksi, yang mengalami progress cepat mengikuti alur drainase vena. Debridement darurat pada jaringan non vital (kadang diperlukan amputasi) diikuti dengan antibiotic diperlukan untuk mencegah mortalitas.

 

Gambar MRI menunjukkan inflamasi pada daerah subkutan

tetapi jaringan otot tidak menunjukkan inflamasi

Lokasi tersering necrotizing fasciitis adalah genitalia eksternal, perineum, ekstremitas, dan dinding abdomen. Kuman pathogen yang sering ditemukan pada pasien dengan infeksi nekrosis jaringan lunak adalah organisme gram positif; streptococci group A, enterococci, Staphylococcus aureus, Staphylococcus epidermis, dan Clostridium. Organisme gram negative yang sering dihubungkan dengan infeksi nekrosis adalah Escherichia coli, Enterobacter, Pseudomonas.Pada kasus infeksi nekrosis, infeksi polimikrobial lebih sering terjadi dibandingkan organisme tunggal.

Faktor resiko pada necrotizing fasciitis tipe I adalah:

  1. Diabetes mellitus
  2. Arteriosklerosis berat
  3. Penggunaan obat intravena
  4. Ulkus dekubitus
  5. Malnutrisi
  6. Obesitas
  7. Alkoholisme kronik
  8. Penyakit vascular perifer yang berat
  9. Pasien post operasi atau pasien dengan trauma penetrasi
  10. Penggunaan steroid
  11. Sirosis
  12. Abses pada  traktus genital wanita    

Faktor resiko pada necrotizing fasciitis tipe II adalah:

  1. Diabetes mellitus
  2. Penyakit vascular perifer yang berat
  3. Trauma
  4. Strain otot
  5. Varisela
  6. Wanita yang baru saja partus

Injuri awal yang tersering menyebabkan infeksi adalah trauma minor (80% kasus), luka operasi, dan ulkus decubitus. Presentasi kasus biasanya akut atau subakut, 3-14 hari setelah injuri. Pada beberapa kasus, terutama yang berhubungan dengan infeksi group A streptococcus, onset mendadak, kondisi dapat berjalan secara dramatis dari abrasi kecil hingga syok septik, dengan nekrosis subkutan massif dalam 24 jam. Pada infeksi group A Streptococcus, lebih dari 50% pasien tidak memiliki penyakit yang mendasari dan dalam kondisi kesehatan yang baik.

Setelah invasi bakteri awal, infeksi menyebar sepanjang fascia dan lemak subkutan, jaringan yang iskemik memfasilitasi penyebaran nekrosis.Pada tahap awal, pemeriksaan histologi biopsy kulit tidak menunjukkan kelainan.Akan tetapi lemak subkutan dan fascia menunjukkan reaksi inflamasi nonspesifik dengan arteriolitis fibrinoid, thrombosis pembuluh darah dan pada akhirnya nekrosis. Jika kondisi tersebut tidak diterapi, kulit yang melapisinya akan menjadi nekrosis akibat oklusi thrombosis vena dan arteri yang memperdarahinya.

Etiologi dan Patofisiologi

Necrotizing fasciitis dapat disebabkan oleh infeksi sinergis polibakterial dimana paling sedikit satu organisme anaerobic (umumnya Bacteroides, Peptostreptococcus, atau Peptococcus) terisolasi dengan kombinasi satu atau lebih organisme facultative (umumnya Streptococci, E.coli, Klebsiella, S.aureus) atau dapat juga disebabkan oleh organisme tunggal, biasanya S.pyogenes. Pada kebanyakan kasus yang disebabkan oleh polimikrobial, organisme multiple dapat ditemukan dengan rata-rata tiga atau empat mikroba dalam satu pasien.

2. Necrotizing fasciitis tipe I

  • Necrotizing fasciitis tipe
          Infeksi polimikrobial oleh bakteri aerobic dan anaerobic
          Hingga 15 patogen terisolasi pada luka tungga
          Rata-rata 5 jenis pathogen pada setiap luka
  • Orgamisme tersering
          Non-group A streptococci
          Enterobacteriaceae organisme
          Bacteroides
          Peptostreptococcus
  • Varian air asin
          Trauma penetrasi atau luka terbuka terkontaminasi di dalam air asin
          Disebabkan oleh vibrio laut, dengan virulensi tertinggi Vibrio vulnificus
2. Necrotizing fasciitis tipe II
  • Umumnya disebabkan oleh infeksi monomikroba; Streptococcus pyogenes
  • Dapat berkombinasi dengan Staphylococcus aureus

Tanda dan Gejala Klinis

Terdapat riwayat injuri sebelumnya dan onset gejala dimulai beberapa jam atau hari sesudahnya dengan keluhan nyeri dan bengkak yang disertai demam dan tubuh yang menggigil.

Nyeri berjalan progresif, terus menerus, dan berat, seringkali dirasakan melebihi apa yang tampak pada pemeriksaan fisik.

Terdapat daerah eritema pucat pada daerah yang terkena. Progresi yang cepat dari eritema menjadi bullae, ekimosis, dan necrosis atau gangrene. Perubahan warna kulit menjadi coklat kebiruan akan terjadi pada tahap lanjut. Apabila kondisi tersebut dibiarkan, gangrene kulit dapat terlihat.

Nyeri secara bertahap akan digantikan dengan rasa baal atau analgesia akibat kompresi dan rusaknya saraf kulit. Hyperesthesia daerah yang terkena dapat menjadi tanda perjalanan penyakit terus berlanjut.

Edema ditemukan pada kebanyakan pasien.Edema dapat ditemukan jauh dari batas eritema kulit.

Krepitasi tidak umum ditemukan tetapi dapat ditemukan pada pasien dengan tahap lanjut perjalanan penyakit.

Vesikel-vesikel dapat ditemukan pada daerah yang eritema, seringkali diikuti langsung oleh gangrene kulit yang nyata.

Toksisitas sistemik dengan disorientasi umumnya buruk.Terjadi pergeseran cairan ekstrasel yang banyak, hipotensi syok, dan jaundice mengikuti. Apabila penemuan tersebut akibat infeksi group A streptococci, istilah streptococcal toxic shock syndrome digunakan.

Tidak ada respon terhadap terapi empiris antimikroba

Necrotizing fasciitis pada tungkai bawah. Tampak eritema yang dusky , dengan vesikel dan gangrene kulit
 

Hasil post operasi pada gambar atas. Seluruh jaringan nekrosis subkutan dieksisi


Necrotizing fasciitis dengan bullae pada daerah terinfeksi

Perubahan warna kulit kaki pada pasien dengan necrotizing fasciitis

 

Necrotizing fasciitis dengan gangrene.

Diagnosa Banding
1. Selulitis
Infeksi akut meluas pada kulit dan jaringan lunak yang ditandai dengan eritema, edema, nyeri, dan kalor.Perjalanan penyakit yang terus berjalan walaupun telah diberikan antibiotic, terjadi toksisitas sistemik, nyeri hebat, nekrosis kulit mengarahkan kepada diagnosa necrotizing fasciitis dibandingkan selulitis.
2. Pyomyositis
Supurasi pada otot skeletal.Nyeri terlokalisir pada kelompok otot yang spesifik dan tidak terjadi toksisitas sistemik.Pemeriksaan radiologi otot mengkonfirmasi diagnosa.
3. Erythema induratum
Nyeri pada penekanan, nodul eritema subkutan terjadi pada tungkai bawah terutama bagian cruris.Tidak ada demam, toksisitas sistemik, dan nekrosis kulit mengarahkan kepada eritema induratum daripada necrotizing fasciitis.Lesi pada erythema induratum dapat berjalan secara kronis, rekurensi, dan pasien memiliki riwayat tuberculosis.
4. Clostridial myonecrosis
Infeksi nekrosis akut pada jaringan otot disebabkan oleh organisme clostridial. Eksplorasi bedah dan pemeriksaan kultur diperlukan untuk membedakannya dengan necrotizing fasciitis.
5. Streptococcal or staphylococcal toxic shock syndrome
Respon inflamasi sistemik terhadap bakteri penghasil toksin.Ditandai dengan demam, hipotensi, erythroderma generalisata, myalgia, dan keterlibatan organ multisystem.Necrotizing fasciitis dapat terjadi sebagai bagian dari toxic shock syndrome.

Managemen

Sebelum terapi antimicrobial dimulai, pengambilan bahan kultur dan pemeriksaan Gram dilakukan dengan aspirasi jarum langsung pada daerah yang terkena. Dengan mengeksisi kecil kulit atau melalui drainase, dapat terlihat proses necrotizing fasciitis yang terjadi dibawah kulit. Biopsy kulit dapat membantu diagnose.

Prinsip managemen pada necrotizing fasciitis adalah menjaga keadaan umum tetap baik, administrasi antimicrobial, tindakan pembedahan. Digunakan pengawasan melalui vena sentral dan kateter arteria, administrasi cairan intravena untuk mengkoreksi dehidrasi, menjaga oksigenasi yang adekuat, terapi penyakit yang mendasari (seperti koreksi ketoasidosis atau gagal jantung kongestif), dan memperhatikan status nutrisi pasien. Nutrisi yang adekuat dibutuhkan setelah post operasi untuk peningkatan kebutuhan nitrogen yang  besar dalam proses perbaikan jaringan, hipertermia, sepsis, dan kebutuhan organ vital.

Pemilihan antibiotika berdasarkan hasil pewarnaan Gram.Apabila pemeriksaan mikrobiologi spesifik tidak ada, penggunaan antibiotika spectrum luas digunakan, termasuk menjangkau organisme anaerob. Aminoglikosida (gentamisin atau tobramisin) 3 – 5 mg/kg sehari dalam 3 dosis terbagi atau 5-7 mg/kg dosis tunggal, ditambahkan klindamisin 1200 – 2400 mg/hari dalam 3-4 dosis terbagi, adalah terapi awal yang adekuat.

Apabila mikroba batang gram positif dalam jumlah banyak ditemukan atau group A streptococcus dicurigai, penisilin G ditambahkan 20-24 juta U/hari dalam dosis terbagi. Kombinasi klindamisin dan penisilin diperkirakan sebagai terapi pilihan pada infeksi berat jaringan lunak akibat group A streptococcus. Penggunaan immunoglobulin intravena 0.4 g/kg/hari selama 4-5 hari atau 2 g/kg dosis tunggal dengan dosis berulang dalam 48 jam merupakan terapi tambahan pada pasien dengan streptococcal toxic shock syndrome.

Untuk necrotizing fasciitis tipe I, regimen awal antibiotic harus mencakup gram positif, negative dan organisme anaerob. Regimen lini pertama adalah:

  • Ampicillin-sulbactam plus clindamycin plus ciprofloxacin.
  • Piperacillin-tazobactam plus clindamycin plus ciprofloxacin.
  • Carbapenem monotherapy (imipenem/cilastin atau meropenem atau ertapenem).
  • Cefotaxime plus metronidazole.
  • Cefotaxime plus clindamycin.

Necrotizing fasciitis tipe II memerlukan regimen antibiotic penisilin dan klindamisin.Adanya Staphylococcus aureus memerlukan regimen penicillinase-resistant penicillin atau generasi pertama sefalosporin generasi pertama.Apabila ditemukan methicillin-resistant Staphylococcus aureus, vankomisin digunakan sebagai pengobatan.

Managemen utama adalah eksplorasi bedah, debridement, dan drainase yang harus dilakukan segera.Diperlukan debridemen dan eksisi jaringan adipose subkutan dan fascia yang telah nekrosis.Luka dibiarkan terbuka.Eksplorasi harian dalam anestesi umum diperlukan pada infeksi di daerah perianal dan trunkus dan untuk seluruh pasien yang dalam keadaan toksik.Penggantian balutan dilakukan sesering mungkin hingga jaringan granulasi sehat tumbuh.Mungkin diperlukan tindakan amputasi untuk mengontrol penyakit.

Pemeriksaan Penunjang

  • Pemeriksaan laboratorium rutin tidak menunjukkan hal yang spesifik
  • Pemeriksaan kultur terbaik diambil dari jaringan yang dalam.
  • Radiologi standar kecil nilainya kecuali terdapat udara dalam jaringan
  • MRI dapat melihat peluasan penyakit tetapi terapi pembedahan tidak boleh ditunda.
  • Biopsy
  • Penampakan umum ditemukan fascia yang bengkak, berwarna abu gelap dengan daerah yang nekrosis
  • Nekrosis pada fascia dan jaringan lemak menghasilkan pus yang berair dan sangat bau.
  • Histologi menunjukkan nekrosis jaringan lemak subkutan, vasculitis, dan perdarahan local.

Prognosis

Tingkat mortalitas sebesar 20% - 47% walaupun terapi yang agresif dan terbaru.Diagnosis dini dan terapi dapat menurunkan tingkat mortalitas hingga 12%.Usia di atas 50 tahun, diabetes, dan gagalnya debridement yang adekuat berhubungan dengan tingkat mortalitas.

Terapi Oksigen Hiperbarik pada Necrotizing Fasciitis

Studi terbaru menunjukkan penurunan morbiditas sebanyak 50% dan mortalitas sebanyak 34% pada penggunaan hiperbarik pada pasien dengan necrotizing fasciitis.

Oksigen hiperbarik menunjukkan peningkatan aktifitas bakterisidal neutrophil dan mengurangi edema jaringan.

Riesman melaporkan tingkat mortalitas sebesar 66% pada pasien necrotizing fasciitis yang tidak diterapi dengan oksigen hiperbarik dan 23% pada pasien yang mendapatkan terapi oksigen hiperbarik.

Studi klinis multiple yang dilakukan berdasarkan studi kasus, studi retrospektif dan prospektif, dan percobaan klinis non randomized menunjukkan bahwa terapi oksigen hiperbarik menurunkan angka mortalitas dan morbitas pada pasien dengan necrotizing fasciitis. Pada 2 studi yang dilakukan, angka mortalitas menurun sebesar 11,9% dibandingkan dengan kasus yang tidak diterapi dengan oksigen hiperbarik (34%). Pada kelompok studi yang lain, kelompok yang mendapatkan terapi oksigen hiperbarik mempunyai kondisi klinis diabetes, syok, dan tetap menunjukkan penurunan angka mortalitas sebesar 23% dibandingkan kelompok control (66%).

Terapi oksigen hiperbarik merupakan terapi adjuvant pada necrotizing fasciitis.Terapi utama tetap debridement yang agresif.Insisi dini yang luas pada kulit dan jaringan subkutan hingga menjangkau jaringan yang sehat, diikuti dengan eksisi seluruh fasia nekrosis, kulit dan jaringan subkutan yang sudah nekrosis diperlukan.Terapi antibiotic merupakan manajemen penting dalam kasus necrotizing fasciitis tetapi kedudukannya hanya sebagai adjuvant terapi juga.

Beberapa studi juga menunjukkan bahwa oksigen hiperbarik mempunyai reaksi toksik terhadap bakteria anaerob, meningkatkan fungsi polimorfonuklear dan bakterisida.Oksigen hiperbarik juga mengurangi adhesi neutrophil berdasarkan fungsi inhibisi beta-2 integrin.Pada necrotizing fasciitis yang disebabkan oleh organisme clostridial, oksigen hiperbarik dapat menghentikan kerja toksin alfa yang dikeluarkan oleh organisme tersebut.Bukti yang terbatas menunjukkan bahwa oksigen hiperbarik dapat memfasilitasi penetrasi antibiotic atau kerja beberapa kelas antibiotic termasuk aminoglikosida, sefalosporin, sulfonamide dan amphotericin.

Mader dan Thom membuat ketentuan rasional dalam penggunaan oksigen hiperbarik sebagai terapi adjuvant necrotizing fasciitis. Tujuan utama adalah:

  • Memperbaiki tekanan oksigen jaringan
  • Meningkatkan fungsi fagosittik melalui stimulai mekanisme oxygen-dependent killing
  • Menghilangkan edema dan meningkatkan sirkulasi pada daerah yang terinfeksi

Secara keseluruhan, terapi oksigen hiperbarik menstimulasi mekanisme pertahanan tubuh dan mekanisme perbaikan sel melalui sintesa kolagen dan angiogenesis.

Terapi oksigen hiperbarik awal dilakukan secara agresif dua kali per hari diimbangi dengan debridement.Umumnya tekanan 2.0 – 2.5 atm adekuat pada terapi necrotizing fasciitis.

7  Fraktur Terbuka

Fraktur atau patah tulang adalah terputusnya kontinuitas jaringan tulang dan/atau tulang rawan yang umumnya disebabkan oleh rudapaksa.

Fraktur terbuka merupakan fraktur yang berhubungan dengan injuri jaringan lunak diatasnya, terdapat komunikasi antara lokasi fraktur dengan kulit.Istilah fraktur terbuka tidak hanya digunakan pada tulang yang terekspose di luar tetapi digunakan pula pada luka tusuk yang mempunyai kedalaman hingga ke lokasi fraktur yang mendasari.Luka tusuk tersebut dapat dihasilkan oleh tekanan eksternal atau oleh fragmen tukang yang tajam yang secara transien menembus kulit kemudian kembali lagi ke bawah lapisan kulit.

Komplikasi utama fraktur terbuka adalah osteomyelitis.Apabila telah terjadi osteomyelitis, nyeri dapat dirasakan hingga beberapa bulan hingga tahun, menyebabkan disabilitas, memerlukan terapi medis dan prosedur pembedahan, hingga pada beberapa kasus memerlukan amputasi.

Klasifikasi fraktur terbuka umumnya berdasarkan tingkat keparahan, ukuran laserasi, luasnya jaringan yang rusak, hilangnya pelindung tulang, energy kinetic yang menyebabkan fraktur, dan bukti adanya kontaminasi.

Klasifikasi Gustilo dan Anderson

Klasifikasi Deskripsi
I Luka < 1 cm, kontaminasi minimal, cimminution, kerusakan jaringan lunak
II Luka > 1 cm, kerusakan jaringan lunak moderat dan minimal periosteal stripping
III Perlukaan disertai kerusakan luas pada jaringan lain seperti kerusakan kulit, otot, dan neurovascular atau fraktur comminutif berat atau segmental tanpa melihat besarnya perlukaan.
III A Kontaminasi, kerusakan jaringan lunak yang parah tetapi masih dapat menutupi fraktur, biasanya karena trauma dengan energy tinggi
III B Kontaminasi, periosteal stripping, kerusakan jaringan lunak yang parah, penutupan fraktur yang tidak adekuat
III C Fraktur terbuka yang disertai injuri arterial yang memerlukan tindakan perbaikan.

Tanda dan Gejala

  1. Nyeri terus menerus dan bertambah beratnya sampai fragmen tulang diimobilisasi. Spasme Otot yang menyertai fraktur merupakan bentuk alamiah yang dirancang untuk meminimalkan gerakan antar fragmen tulang.
  2. Deformitas dapat disebabkan pergeseran fragmen pada ekstremitas. Deformitas dapat diketahui dengan membandingkan dengan ekstremitas normal. Ekstremitas tidak dapat berfungsi dengan baik karena fungsi normal otot bergantung pada integritas tulang tempat melekatnya otot.
  3. Pemendekan tulang, karena kontraksi otot yang melekat diatas dan dibawah tempat fraktur. Fragmen sering saling melengkapi satu sama lain sampai 2,5 sampai 5,5 cm.
  4. Krepitasi yaitu pada saat ekstremitas diperiksa dengan tangan, teraba adanya derik tulang. Krepitasi yang teraba akibat gesekan antar fragmen satu dengan lainnya.
  5. Pembengkakan dan perubahan warna lokal pada kulit terjadi akibat trauma dan perdarahan yang mengikuti fraktur. Tanda ini baru terjadi setelah beberapa jam atau beberapa hari setelah cedera.

Manajemen Fraktur Terbuka

Kebanyakan pasien dengan fraktur terbuka mengalami injuri multiple dan syok berat.Luka harus ditutup dengan dressing yang tepat dan steril.Profilaksis tetanus diberikan.Semua fraktur terbuka dianggap terkontaminasi. 4 pilar manajemen fraktur terbuka adalah :

  1. Debridemen luka
  2. Profilaksis antibiotic / anti tetanus
  3. Stabilisasi fraktur
  4. Menutup luka agar tidak terekspose dengan lingkungan

Komplikasi Lokal pada Fraktur

Segera Moderate Beberapa minggu kemudian
Injuri visceral lokal Blister Delayed union
Injuri vascular Ulserasi akibat tekanan Malunion
Injuri saraf Terjepitnya saraf Non-union
Compartment syndrome Injuri ligament Avascular necrosis
Haemarthrosis Lesi tendon Kontraktur otot
Infeksi Kekakuan sendi Tidak seimbangnya sendi
Gas gangrene   Osteoarthritis

 

Proses Penyembuhan Tulang

Penyembuhan fraktur dibagi menjadi penyembuhan primer dan sekunder. Pada penyembuhan primer, korteks tulang mencoba membangun kembali komponennya tanpa formasi callus (penyembuhan osteonal atau haversian). Proses ini terjadi apabila fraktur secara anatomis berkurang, supply darah terjaga, dan fraktur difiksasi dengan internal fixation. Penyembuhan sekunder merupakan hasil dari formasi callus dan keikutsertaan periosteum dan jaringan lunak eksternal.Respon penyembuhan ini diperkuat oleh gerakan dan dihambat oleh fiksasi ketat.

Penyembuhan fraktur dibagi berdasarkan 4 tahapan yang terjadi (menurut AO):

  1. Inflamasi
  2. Formasi soft callus
  3. Formasi hard callus
  4. Bone remodeling

 

1.  Inflamasi

Setelah fraktur terjadi, proses inflamasi terjadi dengan cepat dan berakhir hingga jaringan fibrosa, kartilago, atau formasi tulang  dimulai (1-7 hari setelah fraktur). Awalnya terbentuk hematoma dan eksudate inflamasi dari pembuluh darah yang rupture.Nekrosis tulang terlihat pada ujung fragmen tulang yang fraktur.Injuri pada jaringan lunak dan degranulasi platelets menghasilkan cytokines.Cytokines menghasilkan reaksi inflamasi seperti vasodilatasi, hyperemi, migrasi dan proliferasi polimorfonuklear neutrophil, makrofag, dan lainnya.Di dalam hematoma, terdapat anyaman fibrin, reticulin fibrils, dan fibrils kolagen.Hematoma fraktur secara bertahap digantikan oleh jaringan granulasi.Osteoclast menghancurkan tulang yang telah nekrosis pada ujung fragmen.

2.  Formasi soft callus

Nyeri dan edema berkurang dan pembentukan soft callus dimulai. Proses ini terjadi saat fragmen tulang sudah tidak dapat bergerak bebas lagi, kurang lebih 2-3 minggu setelah fraktur.

 

Osifikasi intramembranosa.Jaringan granulasi digantikan dengan jaringan fibrin dan kartilago dan pembentukan pembuluh darah ke dalam callus yang terkalsifikasi. Proses ini dimulai pada bagian perifer dan bergerak  kearah tengah.

 

Hasil akhir pembentukan callus adalah stabilitas sehingga pemendekan tulang terhindar walaupun pergeseran sudut mungkin masih dapat terjadi pada lokasi fraktur.

Tahap pembentukan soft callus ditandai dengan pertumbuhan callus.Sel progenitor pada cambial layer periosteum dan endosteum distimulasi dan menjadi osteoblast.Pembentukan tulang intramembranosa dimulai pada lapisan periosteum dan endosteum dengan arah menjauhi fracture gap, membentuk woven bone periosteally dan mengisi intramedullary canal. Pada proses ini juga terjadi pertumbuhan kapiler di dalam callus sehingga vaskularisasi meningkat. Daerah dekat fracture gap, sel mesenkimal progenitor proliferasi dan mingrasi melalui callus, berdiferensiasi menjadi fibroblast atau kondrosit dan secara perlahan menggantikan hematoma.

3.  Formasi hard callus

Ketika ujung fraktur telah dihubungkan dengan soft callus, tahap hard callus dimulai dan berakhir saat fragmen telah bersatu dengan kuat oleh tulang yang baru (3-4 bulan). Saat formasi tulang intramembranosa berlanjut, jaringan lunak diantara fragmen mengalami osifikasi endochondral dan callus dikonversi menjadi jaringan keras yang terkalsifikasi (woven bone). Pertumbuhan callus tulang dimulai pada daerah perifer lokasi fraktur, dimana regangan paling rendah. Formasi hard callus dimulai dari arah perifer dan secara progresif bergerak kea rah pusat fraktur dan fracture gap. Jaringan lunak pada fracture gap digantikan dengan woven bone pada proses osifikasi endochondral.

4.  Remodeling

Tahap ini dimulai apabila fraktur telah disatukan dengan solid oleh woven bone. Woven bone kemudian secara perlahan digantikan oleh lamellar bone melalui erosi lapisan dan osteonal remodeling. Tahap ini berlangsung dalam beberapa bulan hingga tahun, berakhir ketika tulang telah kembali seutuhnya pada morfologi awal.

 

Terapi Oksigen Hiperbarik pada Fraktur Terbuka

Pada fraktur terbuka, terjadi keadaan hipoksia local yang diikuti oleh iskemia jaringan, lesi vaskuler, nekrosis ujung fragmen tulang yang patah dan gangguan proses metabolisme seluler. Kejadian tersebut akan mengakibatkan gangguan perfusi dan oksigenasi jaringan lunak dan tulang.

HBO adalah tekanan oksigen lebih dari 1 atmosfer yang menyebabkan tekanan oksigen pada jaringan juga meningkat , sehingga gradient difusi oksigen kedalam sel akan meningkat . Erythrocyt akan lebih mudah menyesuaikan bentuk dengan dinding kapiler yang telah rusak sehingga dapat dilaluinya dan turut membantu tranportasi oksigen ke daerah fraktur .

Oksigen yang larut tersebut akan masuk ke ekstravaskuler dan ruang intraselluler dengan cara difusi dan kemudian dapat dipergunakan oleh sel-sel yang mengalami hipoksia oleh karena fraktur terbuka. Selanjutnya akan meningkatkan metabolisme enzimatik dalam sel serta aktifitas metabolic dari fungsi osteogenesis.

Mekanisme Terapi Oksigen Hiperbarik pada Fraktur Terbuka

1.  Tekanan Oksigen

Tekanan oksigen pada daerah fraktur biasanya menurun dan jarang melebihi 25 mmHg.Penelitian binatang oleh Hunt, Kivisaari dan Mader menunjukan P O2 pada fraktur terbuka tidak lebih dari 23 mmHg,  pada tulang normal 40 mmHg. HBO (O2 100%, 2 ATA) dapat meningkatkan P O2 sampai 104 mmHg pada fraktur terbuka,  pada tulang normal 322 mmHg.  Hipoperfusi dan inflamasi sekunder terjadi akibat tekanan oksigen  yang rendah menimbulkan peningkatan tekanan intramedular pada fraktur terbuka yang kemungkinan mengalami infeksi, dimana pus dan debris mengisi system Havers dan medullary canal.

2.  Mekanisme pertahanan selular tubuh

Mekanisme pertahanan selular tubuh yang pertama adalah polymorphonuclear (PMN) merupakan respons pertama yang memerangi infeksi bakteri pada fraktur terbuka. Phagositic killing pada kuman aerob menurun pada tekanan oksigen yang rendah (Mader). Dengan HBO tekanan oksigen pada fraktur terbuka mencapai 109 mmHg, kondisi ini dapat memberikan fungsi fagosit bakteri. Mader juga membuktikan, dengan peningkatan tekanan oksigen sampai 150 mmHg dan 760 mmHg dapat membunuh kuman Staphylococcus aureus dalam jumlah besar.

3.  Superokside dismutase dan catalase

Seperoxide dismutase dan catalase merupakan mekanisme enzimatik yang digunakan oleh bakteri aerob untuk menurunkan toksik radikal oksigen pada fraktur terbuka yang terinfeksi.Pada Anaerobic organisme dan organisme mikroaerofilik kurang kemampuannya untuk memproduksi enzim ini.Kuman Anaerob sangat sensitif terhadap radikal oksigen pada intraselular dan ekstraselular selama terapi HBO.

4.  Menghambat alpha toksin

Terapi HBO akan menghambat alpha toxin dari organisme clostridial yang  merusak membran sel dan meningkatkan permeabilitas kapilar pada fraktur terbuka yang terinfeksi. HBO merupakan bakterisidal pada sebagian besar spesies clostridial.Pada penelitian in vitro HBO mempunyai mekanisme membunuh secara tidak langsung pada bacteri clostridium perfringen melalui lekosit PMN mekanisme.

5.  Merangsang aktifitas fibroblast

Fibroblast tidak dapat mensintesis kolagen dalam membentuk callus pada daerah fraktur terbuka yang terinfeksi saat tekanan oksigen kurang dari 20 mmHg. Peningkatan oksigen sampai 200 mmHg menghasilkan  fungsi yang normal.

6.  Meningkatkan daya serap aminoglikosida

Antibiotika ini tidak dapat melakukan mempenetrasi  pada daerah fraktur terbuka yang terinfeksi sehingga aktivitasnya menurun sebagai akibat dari tekanan oksigen yang rendah. Dengan HBO akan meningkatkan aktivitas Bakterisidal dari antibiotika tersebut.

7.  Efek Oksigen Hiperbarik pada Proses Penyembuhan Fraktur

Pada percobaan yang dilakukan oleh Dong Wu, Malda, Crawford, dan Yin pada tahun 2007, didapatkan hasil bahwa oksigen hiperbarik menstimulasi proliferasi osteoblast. Oksigen hiperbarik juga meningkatkan biomineralisasi dengan peningkatan formasi bone nodule, deposit kalsium, dan aktifitas alkaline fosfatase. Data tersebut memperkirakan terpaparnya osteoblast dengan oksigen hiperbarik meningkatkan diferensiasi kepada osteogenik.Bukti ilmiah tersebut mempunyai potensi terhadap penerapan terapi oksigen hiperbarik dalam penyembuhan fraktur dan regenerasi tulang.

Sejak tahun 1966, terapi oksigen hiperbarik telah disarankan untuk menunjang proses penyembuhan fraktur terutama pada non-union fraktur. Pada percobaan dengan binatang, oksigen hiperbarik menunjukkan peningkatan generasi tulang dan pengangkatan tulang yang telah mati atau abnormal. Pada studi yang lain dengan menggunakan kucing sebagai subjek, oksigen hiperbarik menunjukkan formasi tulang yang meningkat tetapi tidak memperbaiki vaskularisasi, gambaran radiologis atau gambaran histologi (Kerwin 2000). Oleh karena itu, penggunaan oksigen hiperbarik pada pasien dengan fraktur masih kontroversial.

8.  Rheumatoid Arthritis

Istilah gangguan rheumatic meliputi berbagai penyakit yang menyebabkan nyeri kronik, kekakuan, dan bengkak sekitar sendi dan tendon.Rheumatoid arthritis merupakan penyebab tersering penyakit kronik inflamasi sendi. Tanda klinis tersering adalah polyarthritis yang simetris dan tenosynovitis, kekakuan pada pagi hari, peningkatan laju endap darah dan pemeriksaan serum anti-IgG globulins (rheumatoid factor) yang positif.

Prevalensi rheumatoid arthritis adalah 1-3% dengan insiden tertinggi pada usia dekade empat atau lima. Perempuan terserang lebih sering 3-4 kali dibanding pria.

Penyebab rheumatoid arthritis masih belum dimengerti sepenuhnya. Faktor-faktor penting yang diketahui memiliki peranan dalam perkembangan rheumatoid arthritis adalah:

  1. Kecenderungan genetik
  2. Reaksi imunologi, mungkin melibatkan antigen asing, terutama yang menargetkan jaringan synovial
  3. Reaksi inflamasi pada sendi dan serat tendon
  4. Adanya  anti-IgG antibodi (rheumatoid factor) pada darah dan cairan synovial
  5. Proses inflamasi yang berjalan terus menerus
  6. Destruksi kartilago articular

Patogenesis Rheumatoid Arthritis

Rheumatoid arthritis mengenai jaringan synovial dan kartilago dan tulang yang mendasarinya.Membrane synovial, serat tendon dan bursae merupakan lapisan tipis jaringan ikat.Pada sendi, lapisan tersebut menyatukan permukaan tulang yang saling berhadapan.Tanda khas pada RA adalah inflamasi synovial dan proliferasi synovial, erosi tulang, penipisan kartilago articular. Inflamasi kronik menyebabkan hiperplasia lapisan synovial dan formasi pannus (jaringan granulasi fibrovaskular yang menebal dan menginvasi kartilago dan tulang).

Kerusakan structural dari kartilago yang termineralisasi dan tulang subchondral dimediasi oleh osteoclast.Lesi kerusakan secara topikal berlokasi pada membrane synovial yang memasuki permukaan periosteal pada sisi tepi tulang yang dekat dengan kartilago articular dan pada daerah melekatnya ligament dan serat tendon.  Proses ini menjelaskan mengapa erosi tulang biasanya terbentuk pada sisi radial sendi metacarpal.

 

Proses Patologi Pada Sendi dan Tendon

  • Tahap 1 : synovitis

Perubahan awal adalah kongesti vascular, proliferasi synoviocytes dan infiltrasi lapisan subsynovial oleh sel plasma, limfosit dan polimorfonuklear.Terjadi penebalan struktur kapsular, formasi villous synovium dan efusi cairan yang mengandung banyak sel pada sendi dan serat tendon.Keluhan pada tahap ini adalah nyeri, bengkak dan nyeri pada penekanan. Walaupun demikian, struktur masih intact dan dapat digerakkan (mobile), dan gangguan tersebut masih reversible.

  • Tahap 2 : destruksi

      Synovitis yang persisten menyebabkan destruksi sendi dan tendon.Kartilago articular mengalami erosi oleh enzim proteolitik dan invasi kartilago oleh jaringan granulasi yang berada di atas permukaan articular.Pada tepi – tepi sendi, tulang mengalami erosi oleh invasi jaringan granulasi dan resorpsi osteoclastic.

      Bukti terbaru menyatakan erosi tulang merupakan akibat hyperplasia synovial disbanding inflamasi (Kirwan, 1997). Perubahan yang sama terjadi pada serat tendon sehingga menyebabkan tenosynovitis sehingga pada akhirnya terjadi rupture tendon sebagian atau seluruhnya.

Efusi synovial seringkali mengandung bahan fibrinoid yang melimpah sehingga menghasilkan pembengkakan pada sendi dan tendon.

  • Tahap 3 : deformitas

Kombinasi dari destruksi articular, peregangan kapsular, dan rupture tendon menghasilkan instabilitas sendi dan deformitas sendi.Pada tahap ini, reaksi inflamasi telah mereda.

Mekanisme pathogen dari inflamasi synovial disebabkan oleh factor lingkungan, genetic, dan faktor imunologi.Ketiga faktor tersebut meyebabkan disregulasi sistem imunitas.Hal yang mencetuskan dan bagaimana genetic dan lingkungan dapat merusak system imunitas masih belum terjawab.

 

Gejala dan Tanda Klinis

 Insiden rheumatoid arthritis meningkat pada usia antara 25 tahun dan 55 tahun, kemudian garis kurva mendatar hingga usia 75 tahun kemudian menurun setelah usia tersebut.

Gejala yang timbul pada rheumatoid arthritis merupakan hasil dari inflamasi pada sendi, tendon dan bursae. Pasien sering mengeluhkan kaku sendi pada pagi hari yang berlangsung selama 1 jam dan membaik dengan aktifitas fisik. Sendi yang terlibat pertama kali adalah sendi-sendi kecil pada tangan dan kaki. Keterlibatan sendi dapat monoarticular, oligoarticular (≤ 4 sendi) atau poliarticular (> 5 sendi), biasanya simetris.

Sendi pergelangan tangan, metacarpophalangeal, dan proximal interphalangeal merupakan sendi yang tersering pada rheumatoid arthritis.Flexor tendon tenosynovitis merupakan tanda khas pada rheumatoid arthritis dan menyebabkan berkurangnya gerakan sendi, berkurangnya kekuatan menjepit.Destruksi progresif pada sendi dan jaringan lunak menyebabkan deformitas kronik yang irreversible.

   

Metacarpophalangeal dan proximal interphalangeal yang membengkak pada rheumatoid arthritis

 

Z-line deformity

 

Swan Neck Deformity

Kriteria Rheumatoid Arthritis ACR-EULAR 2010

  Skor
Keterlibatan sendi 1 sendi besar (bahu, siku , panggul, lutut, mata kaki) 0
  2-10 sendi besar 1
  1-3 sendi kecil (MCP, PIP,interphalangeal digiti I manus,MTP, pergelangan tangan) 2
  4-10        sendi kecil 3
  >10 sendi (paling sedikit 1 sendi kecil) 5
Serologi Rheumatoid factor (-) 0
  Positif rendah RF atau anti-CCP antibodies (≤ 3 kali batas atas normal) 2
  Positif tinggi RF atau anti-CCP antibodies (> 3 kali batas atas normal) 3
Fase akut reaktan LED dan CRP normal 0
  LED dan CRP abnormal 1
Durasi gejala < 6 minggu 0
  ≥ 6 minggu 1

*Skor ≥ 6 : rheumatoid arthritis definite.

Serum IgM RF ditemukan positif pada 75-80% pasien dengan rheumatoid arthritis sehingga hasil yang negative tidak menyingkirkan diagnose RA. Hasil yang postif juga ditemukan pada penyakit jaringan ikat yang lain seperti SLE. Serum RF juga dapat ditemukan positif pada 1-5% populasi individu sehat.

Serum anti-CCP antibodies mempunyai sensitifitas yang sama dengan serum RF untuk mendiagnosa RA. Namun demikian, spesifisitasnya mendekati 95% sehingga hasil yang positif mempunyai nilai penting dalam mendiagnosa RA dengan penyakit arthritis lain. Tidak semua individu dengan rheumatoid arthritis mempunyai nilai anti-CCP antibodies yang positif dan tidak semua penderita RA dengan rheumatoid factor positif mempunyai nilai positif pada anti-CCP antibodies.Individu yang memiliki nilai anti-CCP antibodies positif memiliki prognosis yang lebih buruk dibandingkan yang tidak.

Analisis cairan synovial pada penderita RA menggambarkan keadaan inflamasi.Hitung sel darah putih dalam cairan synovial pada RA 5000 – 50.000 sel/ µ3 dibandingkan pada kondisi non inflamasi < 2000 sel/ µ3 seperti osteoarthritis.

Pemeriksaan Radiologi

Pemeriksaan sendi dengan modalitas radiologi digunakan untuk mendiagnosa RA dan menilai progresi kerusakan sendi.Foto polos merupakan modalitas tersering yang digunakan tetapi mempunyai kekurangan yaitu tidak dapat melihat struktur tulang dengan jelas dan kerusakan kartilago articular.Pemeriksaan dengan MRI dan ultrasound dapat menilai perubahan pada jaringan lunak seperti synovitis, tenosynovitis, dan efusi dan dapat melihat abnormalitas tulang.

 

Foto X-ray menunjukkan erosi pada sendi proximal interphalangeal

Terapi Oksigen Hiperbarik Pada Rheumatoid Arthritis

Terapi oksigen hiperbarik telah banyak digunakan sebagai terapi adjuvant pada penderita rheumatoid arthritis tanpa adanya data komplikasi akibat penggunaan modalitas oksigen hiperbarik.Bukti terbaru menyatakan oksigen hiperbarik menginhibisi kerja beberapa cytokins, bekerja sebagai imunomodulator, dan memperbaiki disfungsi kognitif.

D.J. Wallace, Silverman, Goldstein, dan D.Hughes  melakukan studi  efek terapi oksigen hiperbarik pada penyakit arthritis. Hasil yang didapat adalah oksigen hiperbarik mempunyai efek immunisuppresive.

Proses inflamasi pada  rheumatoid  arthritis menyebabkan jaringan sekitar menjadi edema dan mengganggu sirkulasi darah sehingga jaringan menjadi hipoksia dan metabolism sel menjadi rendah. Hipoksia pada rheumatoid arthritis selain disebabkan oleh edema jaringan juga disebabkan oleh kebutuhan oksigen yang banyak pada jaringan yang mengalami inflamasi. Studi menemukan bahwa terapi oksigen hiperbarik memperbaiki reperfusi jaringan, menurunkan reaksi radang dan mensupresi reaksi imunologi sehingga proses destruksi sendi oleh mediator imun terhenti.

Pada tahun 1995, Proceedings of the Eleventh International Congress on Hyperbaric Medicine mempublikasikan hasil dari studi tentang efek hiperbarik pada rheumatoid arthritis, dengan hasil sebagai berikut :

  • sembuh                             23.4%
  • efek yang terlihat  jelas       51.4%
  • terdapat perbaikan klinis     16.2%
  • tidak ada efek                      8.1%

Efektifitas total terapi oksigen hiperbarik pada RA adalah sebesar 91.9%

 

KESIMPULAN

Therapy oksigen hyperbarik mempunyai peran penting dalam manajemen terapi bidang orthopaedi. Efektifitasnya telah banyak diuji oleh para peneliti dan terbukti mempunyai peran dalam proses penyembuhan luka, mengurangi proses inflamasi, membantu proses unifikasi fracture tulang, dan peran penting lainnya.

Pada kasus penyembuhan luka kaki diabetik, oksigen hyperbarik mengoptimalkan konsentrasi gradient oksigen sehingga menstimulasi dan mendorong pertumbuhan jaringan pada pusat luka yang mengalami hypoxia.Terapi oksigen hyperbarik secara langsung meningkatkan replikasi fibroblast, aktifasi osteoclast, vascular endothelial growth factor, dan platelet-derived growth factors.Efek persisten setelah administrasi terapi oksigen hyperbarik adalah stimulasi pertumbuhan capiler.

Therapy oksigen hyperbarik digunakan hanya sebagai terapi adjuvant osteomyelitis dan harus dilaksanakan bersama dengan antibiotic parenteral, debridement, dukungan nutrisi, dan bedah rekonstruksi.Pada keadaan tanpa oksigen hyperbarik, tekanan oksigen pada tulang normal adalah 45 mmHg sedangkan di tulang osteomyelitis adalah 23 mmHg.Dengan terapi oksigen hyperbarik, tekanan oksigen dinaikkan menjadi 104 mmHg pada tulang osteomyelitis dan 322 mmHg pada tulang normal.Meningkatkan oksigen hingga 150 mmHg dan 760 mmHg juga membunuh sebagian besar S.aureus yang merupakan salah satu kuman pathogen dalam osteomyelitis.Selain itu, hyperbarik juga meningkatkan aktifitas fibroblast dan meningkatkan aktifitas bacterisidal pada golongan aminoglikosida.

Terapi hiperbarik juga membantu proses terapi crush injury dan compartemen syndrome antara lain dengan efek secundernya yaitu vasoconstriksi. Efek tersebut menyebabkan berkurangnya edema pada lokasi injury.Kandungan oksigen yang meningkat dalam sirkulasi pada terapi oksigen hyperbarik mengkompensasi aliran sirculasi yang berkurang akibat vasoconstriksi.Terapi oksigen hyperbarik juga mengurangi jumlah otot skeletal yang mengalami nekrosis. Terapi oksigen hyperbarik pada kasus crush injury harus dimulai sedini mungkin, idealnya dalam waktu 4-6 jam setelah cedera.

Studi terbaru menunjukkan penurunan morbiditas sebanyak 50% dan mortalitas sebanyak 34% pada penggunaan hyperbarik pada pasien dengan necrotizing fasciitis. Terapi oksigen hyperbarik merupakan terapi adjuvant pada necrotizing fasciitis.Terapi utama tetap debridement yang agresif.Secara keseluruhan, therapy oksigen hyperbarik menstimulasi mekanisme pertahanan tubuh dan mekanisme perbaikan sel melalui synthesa kolagen dan angiogenesis.

Oksigen hyperbarik juga mempunyai peran dalam proses penyembuham fracture terbuka dengan meningkatkan tekanan oksigen pada daerah fracture, meningkatkan fungsi phagosit bakteri, membentuk radikal oksigen yang dapat membunuh kuman anerob, menghambat alpha toxin, merangsang aktifitas fibroblast, dan meningkatkan daya serap amoinoglikosida.

Hypoxia pada rheumatoid arthritis selain disebabkan oleh edema jaringan juga disebabkan oleh kebutuhan oksigen yang banyak pada jaringan yang mengalami inflamasi. Studi menemukan bahwa therapy oksigen hyperbarik memperbaiki reperfusi jaringan, menurunkan reaksi radang dan mensupresi reaksi imunologi sehingga proses destruksi sendioleh mediator immun terhenti.  Efektifitas total therapy oksigen hyperbarik pada RA adalah sebesar 91.9%

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