Pengobatan Hiperbarik Oksigen dibidang klinik Suyanto Sidik RSAL Dr.Mintohardjo JKT E-mail: suyantosidik@indosat.net.id

Dr.dr.Suyanto Sidik SpPD KGEH SpKL RSAL Dr.Mintohardjo Jakarta Jabatan : Ka Kelompok Ahli RSAL Dr.Mintohardjo Pendidikan: Dokter FK Gadjah Mada Yk 1979 Hyperbaric and under sea Australia 1983 Ahli Peny dalam FK UNAIR Sby 1992 Endoscopy-Gastro intestinal FKUI 1996 Doktor FKUI Jkt 2006 Konsultan Gastro-Hepatologi 2007 Spesiali Kedokteran Kelautan 2009

HISTORY OF HYPERBARIC MEDICINE 1900 Behnke US navy—DCS 1956 Dr I Boerma cardio pulm surg. 1963 Conggres I HBO Proef Boerema 2002 Conggres XIV Cramer & Shefield Sanfransisco, USA 2005 Conggres XV Barcelona Jordi de sola 2008 Conggres XVI Becker & Cramer Beijing

1ST INTERNATIONAL CONGRESS ON HYPERBARIC OXYGENATION, 1963 Australia 9th 1987 Amsterdam 10th 1990 CHINA 11, 16th 1993, 2008 Italy 12th 1996 Japan 13th 1999 America 8,14th 1984, 2002 Spanyol 15th 2005 Beijing 16th 2008

Contraindications Absolute Pneumothorax Relative: Upper Resp Inf Seizure disorders Malignant disease Pregnancy

HBO THERAPEUTIC PROCEDURE 2-3 ATA - 90 I Intermiten O2 Prev O2 toxcicity a. Paul Bert Effect in CNS.  Nausea  Twitching  Convultion b. Lorrain Smith Effect in pulmonal Cough Dyspnea Substernal pain 6

INDICATION HBOT UHMS Air or gas embolism 6 CO poisoning 5 Gas gangrene 8 Crush injury 3 DCS 7 Enhancement of healing 1 Anemia 12 Intracranial absces 13 Necrotizing soft tissue infections 9 Osteomyelitis 4 Delayed radiation injury 2 Skin grafts & flaps 10 Thermal burns 11

Distribution of HBO chambers in the world HBO chambers in Japan, 2004 Hosps: 617 mono: 758 multi: 57 in Europe Textbook of HBO by Jain, 2004 in the world

Specialties of HBO doctor in Japan 172 HBO doctors since 2000

There are eight principal methods in which HBO is capable of affecting tissue: Pressure effects of oxygen Vasoconstrictive effects of oxygen. 100% oxygen concentration effects on the diffusion gradient. Hyperoxygenation of ischemic tissue. Down regulation of inflammatory cytokines. Up-regulation of growth factors. Leukocyte effects. Antibacterial effects.

HBOT should be used to compliment conventional therapies and treatments. HBOT is very cost effective. HBOT is noninvasive. HBOT is safe. HBOT works well with other treatments.

HBOT has five actions which have been used to combat clinical infection: 1.Tissue rendered hypoxic by infection is supported by oxygen. 2.Neutrophils are activated and rendered more efficient. 3.Machrophage activity is enhanced. 4.Bacterial growth is inhibited. 5.The effect of antibiotics is potentiated.

Prinsip Wound Care Social economy Autoimmune Medicine Psychosocial Nutrisi Edema Glucose Lipid Infeksi Trauma Chronic Hematology Disease Social economy Autoimmune Medicine Psychosocial Like a Like Diagnose Everyday Care RA

HBO THERAPY OXYGEN 100%, Pressure 2 – 3 ATA  Hyperbaric Chamber Decompresion sickness tx Tissue damage: wound healing, hipoksia  Fibroblast, synthesis collagen, ratio RNA/DNA,  leucocyte killing, angiogenesis  neovascularisation of the wound  & mikrovasc blood flow, dens cap  iskhaemi – reperfussion  NO 4- 5 X  HBOT 2-3 ATA - 2 hours Healing of tissue damage

ANGIOGENESIS NEOVASKULARISASI

SMITH S. HYPERBARIC TEXT BOOK OF SURGERY PREOPERATIVE CARE, 2002

NITRIT OKSID PRODUCTION eNOS nNOS iNOS FAD + FMD L - ARGININE + n NADPH + O2 CITRULINE + NO + NADP BH4 O 2 NO VASOKONSTRIKSI CO NO VASODILATASI SMITH S. HYPERBARIC TEXT BOOK OF SURGERY PREOPERATIVE CARE, 2002 24

COLLAGENIZATION

SMITH S. HYPERBARIC TEXT BOOK OF SURGERY PREOPERATIVE CARE, 2002

OHB & IMMUNOHUMORAL B IgG OHB + - + + - + + STRESSOR IFN Ƴ IL 10 APC CD4+ TCR + APC MHC II Th1 CD4+ TCR Th2 CD4+ TCR - IFN Ƴ IL 10 + + B CD8+ TCR - + + APC SP MHC I IgG

OHB & IMMUNOSUPRESI IgG IgE B - OHB + IFN Ƴ IL 4 STRESSOR APC Th1 Th2 CD4+ TCR APC MHC II + IgG IgE - B IFN Ƴ IL 4 Th1 CD4+ TCR Th2 CD4+ TCR

HBOT FOR ANTI-INFLAMATORY Sumen G, Cimsit M, Eroglu L. HBOT reduces carrageenan-induced acute inflammation in rats. Eur J Pharmacoln2001: 431; 265-8. Haapaniemi T, Nylander G, Sirsyo A et al. Hyperbaric oxygen reduces ischemia-induced skeletal muscle injury. Plast Reconstr Surg 1996: 97: 602-7. Waisman d, Brod V, Wolf R et al.Effects hyperoxia on local and remote circulatory inflammatory response alter splanchnic ischemia and reperfusion. Am J Physiol Heart Circ Physiol 2003:285: H 643-52.

HBO for Treatment RA Mc Carty 1981, Warren et al 1979, Shakbazylan et al 1988 HBOT 1.5 – 3 ATA: 1,5 – 3 times development clinical early state Kamada 1985 SOD ↑, Lipid peroxide activity decrease, ESR loxubury index ↓ Salkovsky et al 1986 HBOT of 20 RA Lukich et al 1991 HBOT 21 Pres1.7 ATA 40 minut supres T lymphocyt.

2.The curative and obcious rate is high. 1995 Proceding ICHM-11th HBOT in treating RA in Europe and Asia Rui-Chang Cured 24.4% Obvious effect 51.4% Improvement 16.2% No effect 8.1% Effective HBOT RA 91,9% 1.The repercusision of the joint is fast, the effect of analgesia is good. 2.The curative and obcious rate is high.

HBO tratmen2-2,5 ATAfor 60 - 90mnt Use coal stoves CO poisoning ↑ COHb ↑ HBO tratmen2-2,5 ATAfor 60 - 90mnt Risk neuropsychological deficit ↓ Mild poisoning  1 sesion Moderate poisoning  2 sesion

RADIASI PELVIS KARSINOMA PROKTITIS RADIASI LASHNER GILINSKY TERGANTUNG : DOSIS FRAKSINASI LUAS TEKNIK RADIASI GEJALA ESL : ~ ESA + LEBIH BERAT DIARE LENDIR + DARAH GEJALA ESA : SAKIT PERUT TENESMUS HEMATOCHEZIA KARSINOMA PROKTITIS RADIASI ESA : 50 – 70 % ESL : 2,5 – 25 % 33

Treatment of Radiation Proctitis and Enteritis Author Type of Report NCl Grade Clinical Eviden Comments Bouachour (1990)59 Charneau (1991)60 Nakada (1993)61 Feldmeier (1995)63 Feldmeier (1996)63 Woo (1997)64 Case Series-8 patients Single case report Animal study Case series-8 patients: 7 proctitis/colitis; 1 enteritis Case series-18 patients 3ii Not clinical Likely to be Benefical Positive Case Unknown Effectiveness Single Positive Case Not clinical but Positive Study Likely to be Beneficial 6 of 8 patients with hemorrhagic proctitis resolved Single patient with succesful treatment of hemorrhagic proctitis Reduced fibrosis and reduced gross appereance of enteritis in murine ileum 4 of 7 proctitis/colitis resolved; 1 enteritis did not resolve 2 patient had complete resolution; 8 partial and no change in 8 34

35 Author Type of Report NCl Grade Clinical Eviden Comments Warren (1997)65 Bredfelt (1998)66 Feldmeier (1998)67 Carl (1998)68 Gouello (1999)69 Bem (2000)70 Meyer (2001)52 Boyle (2002)71 Case series-14 patients Case series-19 patients Animal study Case Series-2 patients Case series-36 patients Case series-2 patients Case series – 10patients Case series- 19 patients 3ii Not clinical Likely to be Benefical Not clinical but positive study 7 patients complete resolution; 2 improved 5 patient non-responder Complete resolution in 47%; 37% improved 16% non-responder Quantitative morphometry showed decreased Collagen in Bowel Wall One patient completely rsolved;the other stopped at 38 treatments without improvement 2/3’s patients followed long term were improved or cured; 1/3 failed to improved Both patients with anorectal ulcers resolved 5 of 5 with rectal bleeding resolved; Statistically significant decrease in late morbidity score 13 of 19 patients had major resolution of symptoms at completion of hyperbaric 35

PERBAIKAN STRUKTUR JARINGAN KERANGKA TEORI OHBT 4 2 3 6 7 8 1 PENYEMBUHAN LUKA PERBAIKAN STRUKTUR JARINGAN AGREGASI TROMBOSIT EPITEL SEL ENDOTEL LISIS KOLAGEN SINTESIS MAKROFAG GRANULOSIT V A S O D I L T 9 5 VASOKONTR KS Keterangan : - NOS = Nitric oxide syntethase - Lingkaran – lingkaran kuning menunjukan tempat-tempat kerja OHB 1.Vasokonstriksi. 2. Peningkatan kemampuan sel endotel 3. Peningkatan VEGF 4. Peningkatan reseptor epitel vaskular 5. Pengurangan inflamasi 6. Kolagen sintesis. 7. Kolagen lisis 8. Perbaikan struktur jaringan. 9. Penyembuhan luka 36

METODE DAN ALUR PENELITIAN 03 y P R S Kontrol Eksperimen 01 X 02 04 Keterangan P = Seleksi Pasien Penelitian R = Randominasi S = Sampel Penelitian 01 = Pretes pok pasien tanpa perlakuan sbg kontrol 02 = Postes pok pasien tanpa perlakuan sbg kontrol 03 = Pretes pok pasien dgn perlakuan 04 = Postes pok pasien dgn perlakuan 37

Tabel 7. Variabel penelitian pada pemeriksaan pertama Data deskriptif variabel penelitian yg akan di analisis dpt dilihat pada tabel 7. Tabel 7. Variabel penelitian pada pemeriksaan pertama VARIABEL KELOMPOK OHBT RERATA + SD KONTROL RERATA + SD K-1 73,8 ± 6,0 74,6 ± 8,3 Lent-1 7,7 ± 2,0 6,8 ± 2,3 MVD-1 7,8 ± 3,9 9,3 ± 3,4 Keterangan : K ; karnofsky Lent : LENT-SOMA MVD : MICRO VASCULER DENSITY 38

Ratio beda pemeriksaan sebelum perlakuan s/d bulan ke-6 setelah perlakuan yang dinyatakan dalam persen. Tabel 8. VARIABEL KELOMPOK OHBT KONTROL Δ K 2-1 (%) 19,67 ± 9,64 4,53 + 10,74 Δ K 3-1 (%) 15,27 + 14,74 2,47 + 16,11 Δ Lent 1-2 (%) 44,12 + 28,22 0,71 + 30,16 Δ Lent 1-3 (%) 33,64 + 57,64 -19,69 + 69,44 Prevalensi proktitis 6 ( 13% ) 11 ( 23,9% ) P < 0,001 0,007 0,008 0,026 Keterangan : ΔK 21 = Perbedaan kualitas hidup seblm perlakuan & segera setelah perlakuan ΔK 31 = Perbedaan kualitas hidup seblm perlakuan & bulan ke-6 setelah perlakuan ΔLent 12 = Perbedaan efek samping seblm perlakuan & segera setelah perlakuan ΔLent 13 = Perbedaan efek samping seblm perlakuan & segera bulan ke-6 setelah perlakuan) 39

HUBUNGAN OHBT DGN PREVALENSI PROKTITIS RADIASI Tabel 9. Hasil analisis statistik chi-square untuk kejadian proktitis radiasi pada kelompok OHBT dan kontrol pada bulan ke-6 perlakuan Kelompok Angka Kejadian Proktitis (%) Total P Ya Tidak OHBT (%) 6 (13%) 20 (43,5%) 26 (56.5%) 0.026 Kontrol (%) 11 (23,9%) 9 (19,6%) Total (%) 17 (37%) 29 (63%) 46 (100%) Keterangan : OHBT = Oksigen Hiperbarik Terapi 40

Ratio beda pemeriksaan sebelum perlakuan dan setelah perlakuan yang dinyatakan dalam prosen. VARIABEL KELOMPOK Sebelum OHB Sesudah OHB CD 31( 30pasien ) 7,83±3,91 10,03±5,29 P < 0,001 Keterangan : CD31 =Cluster define 31 OHB = Oksigen hiperbarik 41

Hubungan korelasi efek samping dengan MVD pada OHB Tabel Korelasi ESA radiasi dengan MVD 12 pada OHB Mean Standar Deviasi N Korelasi Pearson P ESA Lent21 3,5 1,8 32 0,550** 0,002 MVD21 7,3 29 Keterangan : ESA Lent21 = Efek samping akut menurut LENT SOMA segera setelah perlakuan dibanding sebelum perlakuan MVD21 = Densitas vaskuler segera setelah perlakuan dibanding sebelum perlakuan 42

Published Report of Hyperbaric Oxygen for Prevention of Mandibular Necrosis Author Type of Report AHA Grade NCI Clinical Evidence Comments Marx (1985) RCT-74 patient 1B 1ii Beneficial 5.4% ORN in HBO Group 29.9% in non-HBO Group Vudiniabola (1999) Case Series-37 patients 4 3ii Likely to be beneficial 1 of 29 HBO and 7 of 8 non-HBO developed ORN David (2001) Case Series-24 patients 5 1 of 24 developed ORN 43

Published Report of Hyperbaric Oxygen as Treatment for Mandibular Necrosis Author Type of Report AHA Grade NCI Grade Clinical Evidence Comments Mounsey (1993) Case Series-41 patients 5 3ii Likely to be Beneficial 34 of 41 had significant improvement Van Merkestey (1995) Case Series-29 patients 20 of 29 patients resolved Maier (2000) 3 2 Not Beneficial A negative trial of hyperbaric compared o historic controls;13 of 20 HBO resolved Curi (2000) Case Series-18 patients 14 of 18 resolved David (2001) Case Series-51 patients 48 of 51 showed improvement 44

Hyperbaric Oxygen as Treatment for Soft Tissue Radiation Injury of the Head and Neck Author Type of Report AHA Grade NCI Grade Clinical Evidence Comments Neovius (1997) Case Series-15 patients compared to historical control group 4 3ii Likely to be Beneficial Healing in 12 of 15 patients; 2 improved; 1 non-healing; compared to 7 of 5 healed in the control group with 1 fatal bleed Marx (1999) Prospective controlled but not randomized study of 160 patients 3 2 Stat signfcnt reduct in wound infection, dehiscience & delayed healing in HBO group Filintisis (2000) Case Series-18 patients with laryngeal necrosis 5 13 of 18 had major improvement Nazrozny (2001) Case Series-2 patients soft tissue necrosis including larynx and pharynx Resolution in both patients 45

Hyperbaric Oxygen as Treatment for Radiation Cystitis Author Type of Report AHA Grade NCI Grade Clinical Evidence Comments Bevers (1995) Prspctive non-rndmized trial of 40 patients 5 3ii Likely to be Beneficial 37 of 40 resolved Del Pizzo (1998) Case Series-11 patients Not Likely to be Beneficial 3 of 11 resolved Weiss (1998) Case Series-29 patients 7 of 10 resolved Mathews (1999) Case Series-17 patients 11 of 17 resolved Mayer (2001) Case Series-8 patients 6 of 8 resolved Hendicks (2000) Case Series-20 patients 14 of 20 resolved 46

Hyperbaric Oxygen as Treatment for Radiation Injury of the Chest Wall and Breast Author Type of Report AHA Grade NCI Grade Clinical Evidence Comments Feldmeier (1995) Case Series-23 patients softtissue-15 bone+soft tissue necrosis of chest wall 5 3ii Likely to be Beneficial 6 of 8 soft tissue resolved 8 of resolved 15 tissue+bone resolved Carl (1998) Case Report Single Positive case No category for single case report Resolution of breast edema and pain Carl (2001) Case Series-44 patients 32 received HBO; 12 control 4 2 Statistically significant improvement in pain, erythema and edema of breast in HBO group compared to control 47

Hyperbaric Oxygen as Treatment for Radiation Injuries of the Extremities Author Type of Report AHA Grade NCI Clinical Evidence Comments Farmer (1978) Single Case Report 5 3ii Unknown 1 of 1 failed to respond Effectiveness Single Negative Case Feldmeier (2000) Case Series-17 patients Likely to be Beneficial 11 of 17 resolved; 11 of 13 if those lost to follow up or with active cancer are excluded 48