Selasa, 08 April 2014

HYPERBARIC OXYGEN THERAPY from "JAMA" "The Journal of the American Medical Association"

     Hyperbaric oxygen  therapy  involves  intermittent  inhalation of
     100% oxygen under a pressure greater than 1 atm. Despite  over  a
     century  of  use in medical settings, hyperbaric oxygen remains a
     controversial therapy.
     The last 20 years have  seen  a clarification of the mechanism of
     action of hyperbaric therapy and a greater understanding  of  its
     potential benefit. However, despite the substantial evidence that
     hyperbaric  oxygen  may  have  a  therapeutic  effect  in certain
     carefully  defined  disease  states,  many  practitioners  remain
     unaware of these findings or are concerned about using hyperbaric
     therapy because of the controversy it has engendered. This review
     examines the  indications  currently  considered  appropriate for
     hyperbaric oxygen and briefly evaluates animal and clinical  data
     substantiating these indications. Areas in which the mechanism of
     action of hyperbaric oxygen is still not well understood, as well
     as possible new areas of applications, are discussed.
     HYPERBARIC  oxygen (HBO) therapy involves intermittent inhalation
     of 100% oxygen under a pressure greater than 1 atm. [1]
     Both therapeutic and toxic  effects  result  from two features of
     treatment: mechanical effects of  increased  pressure  and
      physiologic effects of hyperoxia.
     Hyperbaric  oxygen  therapy  has  long been accepted as a primary
     treatment for decompression sickness [2]; however, other proposed
     indications have been controversial.  During  the 1960s there was
     widespread enthusiasm  for  hyperbaric  treatment  of  myocardial
     infarction,  stroke, senility, and cancer. Enthusiasm waned after
     results of clinical trials  (and direct experience) showed little
     benefit for these diseases.  The  overzealous  claims  about  the
     effectiveness  of  HBO  therapy  have left a legacy of skepticism
     among physicians. [3]  However,  animal studies, clinical trials,
     and greater clinical experience over the last  two  decades  have
     produced  a  set  of  indications  for  which HBO therapy appears
     beneficial. These clinical conditions are substantially different
     from those  in  the  1960s.  However,  there  has  been no recent
     interdisciplinary review of HBO therapy delineating these current
     indications, despite their broad applications.
     Thus, while substantial evidence supports use of HBO  therapy  in
     certain  carefully  de  fined  settings,  many patients who might
     benefit go untreated  because  of  their physician's unfamilarity
     with recent research and overall uncertainty about the legitimacy
     of HBO as therapy. We discuss the  mechanism  of  action  of  HBO
     therapy  and the commonly accepted clinical indications (Table 1)
     as delineated by the Undersea and Hyperbaric Medical Society, [1]
     the  professional  association  of  physicians  administering HBO
     therapy, and  we  briefly  review  the  data  supporting  current
     In  disease  such as air embolism and decompression sickness, the
     therapeutic  effect  of  HBO  therapy  is  achieved  through  the
     mechanical reduction in bubble size  brought on by an increase in
     ambient pressure. A 5 atm a bubble  is  reduced  to  20%  of  its
     original volume and 60% of its original diameter.
     Increasing   pressure  in  HBO  therapy  is  often  expressed  in
     multiples of atmospheric pressure absolute  (ATA); 1 ATA equals 1
     kg/c[m.sup.2] or 735.5 mm Hg. Most HBO treatments  are  performed
     at  2 to 3 ATA. In air embolism and decompression sickness, where
     pressure is crucial to  therapeutic effect, treatments frequently
     start at 6 ATA.
     This additional pressure, when  associated  with  inspiration  of
     high  levels  of  oxygen,  substantially  increases  the level of
     oxygen dissolved into blood plasma. This state of serum hyperoxia
     is the second beneficial effect of hyperbaric oxygen therapy.
     Hyperoxia: Life Without Blood
     At  sea  level  in  room  air,  hemoglobin  is  approximately 97%
     saturated with oxygen (19.5 vol% oxygen, of  which  approximately
     5.8  vol% is extracted by tissue). The amount of oxygen dissolved
     into plasma  is  0.32  vol%.  An  increase  in  P[O.sub.2]  has a
     negligible impact on total hemoglobin oxygen content; however, it
     does result in an increase  in  the  amount  of  oxygen  dissolve
     directly  into  plasma.  With  100% inspired oxygen the amount of
     plasma oxygen increases to  2.09  vol%.  At 3 ATA plasma contains
     6.8 vol%  oxygen,  a  level  equivalent  to  the  average  tissue
     requirements  for  oxygen.  Thus,  HBO  treatment  could  and has
     sustained life without hemoglobin. [4]
     The immune  system,  wound  healing,  and  vascular  tone are all
     affected  by  oxygen  supply.  Oxygen  alone  has  little  direct
     antimicrobial  effect,  even  for  most  anaerobes  [5];  it  is,
     however, a crucial factor in immune function.
     Neutrophils require molecular oxygen as a substrate for microbial
     killing.  The  oxidative  burst   seen   in   neutrophils   after
     phagocytosis  of  bacteria  involves  a 10-to 15-fold increase in
     oxygen consumption. [6] Here oxygen  serves as a substrate in the
     formation of free radicals, which directly or indirectly initiate
     phagocytic killing. [7] This endogenous  antimicrobial  system
     virtually  ceases  functioning under conditions of hypoxia. A
     tissue [PO.sub.2] of at least  30  mm  Hg of oxygen is considered
     necessary for normal oxidative  function  to  occur.  [8]  Oxygen
     partial  pressures  below  this  are  often  seen  in damaged and
     infected tissues. Increasing the oxygen  level in this tissue can
     allow restoration of white blood  cell  function  and  return  of
     adequate  antimicrobial action. [9] The cardiovascular effects of
     hyperbaric oxygen include  a  generalized  vasoconstriction and a
     small reduction in  cardiac  output.  [10]  This  ultimately  may
     decrease  the  overall blood supply to a region, but the increase
     in serum oxygen content results  in  an overall gain in delivered
     oxygen. In conditions such as burns, cerebral  edema,  and  crush
     injuries, this vasoconstriction may be beneficial, reducing edema
     and tissue swelling while main taining tissue oxygenation. [11]
     Usual  complications  of  HBO therapy are listed in Table 2. They
     are a result  of  either  barometric  pressure  changes or oxygen
     toxicity. The most common complications involve cavity trauma due
     to change in pressure. [12] Any  air-filled  cavity  that  cannot
     equilibrate  with  ambient  pressure, such as the middle ear when
     the eustachian  tube  is  blocked,  is  subject  to deformity and
     barotrauma during pressure changes in HBO therapy.
     Pneumothorax is a  rare  complication  of  HBO  treatment,
     usually occurring only in patients with severe lung disease.
     Air  embolism,  presumably  resulting from a small tear in
     the pulmonary vasculature, is another rare complication. [13] One
     hundred percent oxygen under high  pressure is neurotoxic and can
     lower the seizure threshold and  affect  central  nervous  system
     control  of  respiration. However, neurotoxicity is rare with the
     low-pressure, short-duration  treatments  used  clinically in HBO
     therapy. In one series the incidence was reported as 1.3 seizures
     per 10 000 treatments. [14]
     Pulmonary oxygen toxic reactions can  occur  with  100%  inspired
     oxygen  at  less  than  1 ATA with prolonged exposure. Almost all
     patients will show pulmonary toxicity after 6 continuous hours of
     inspired oxygen at 2 ATA.  [15] No clinical HBO protocol requires
     this length of continuous exposure to 100% oxygen.  However,  HBO
     treatments  may  contribute to the pulmonary oxygen toxicity seen
     in critically ill  patients  who  receive  high concentrations of
     inspired oxygen between hyperbaric treatments.
     Although a concern in premature newborns, retrolental fibroplasia
     has not been noted in infants, children, or adults undergoing HBO
     therapy. [16] Development  of  cataracts  has  been  reported  in
     patients receiving more than 150 HBO treatments. [17]
     Hyperbaric oxygen can be administered in either a multiplace or a
     monoplace chamber.
     Multiplace Chamber
     Multiplace  chambers are large tanks accommodating 2 to 14 people
     (Fig 1). They are usually built  to achieve pressures up to 6 atm
     and have a chamber lock-entry system  that  allows  personnel  to
     pass  through without altering the pressure of the inner chamber.
     Patients can be directly  cared  for  by medical staff within the
     chamber. The chamber is  filled  with  compressed  air;  patients
     breathe   100%   oxygen  through  a  face  mask,  head  hood,  or
     endotracheal tube.  Although  fire  hazards  restrict  the use of
     certain electronic equipment, some monitors and ventilators  with
     solid-state  circuitry  can  be used within the chamber, allowing
     intensive care of  critically  ill  patients. [18] The multiplace
     chamber's ability to maintain pressures of 6 atm or  more,  makes
     it  the  chamber  of  choice  for  decompression sickness and air
     Monoplace Chamber
     Monoplace chambers (Fig 2) are  far less costly than their larger
     counterparts and have allowed hospitals to institute HBO programs
     without prohibitive capital outlays. Most chambers are  sized  to
     allow  a single patient to lie supine under a transparent acrylic
     dome or viewing  port.  The  internal  environment of a monoplace
     chamber is maintained at 100% oxygen; thus, the patient does  not
     wear  a mask. This high concentration of oxygen precludes the use
     of any electronic  equipment  in  the chamber. However, specially
     adapted ventilators and monitoring systems do allow treatment  of
     critically ill patients.
     Acute Conditions
     Decompression Sickness:
     Although occasionally seen in aviators, decompression sickness is
     generally  a  disease  of  divers.  During  a  dive, the diver is
     exposed to pressures greater  than  1  atm,  and tissue uptake of
     nitrogen increases according to the principles  of  Henry's  law.
     With  ascent,  a  pressure gradient develops, and nitrogen leaves
     the tissue, dissolving into the  blood  and passing to the lungs,
     where it is exhaled. With rapid ascent a steep pressure  gradient
     develops  and intravascular nitrogen gas bubbles form. [19] These
     can  be  detected  in  asymptomatic  divers.  [20]  With  greater
     pressure gradients, the nitrogen  bubbles become large enough and
     prevalent enough to mechanically deform tissue and obstruct blood
     vessels. The gas-fluid interface also interacts with blood cells,
     platelets, and proteins, causing disruption of the  intravascular
     coagulation system. [21] Decompression sickness results.
     Divers  can  experience  decompression  sickness  as  pain  only,
     usually  as  a  "deep  and  dull  ache"  in the extremities. More
     serious  cases  can  present   as  paraplegia  or  cardiovascular
     collapse due to embolization  of  bubbles  into  the  cardiac  or
     central nervous system.
     Hyperbaric  oxygen therapy mechanically decreases the size of the
     bubbles, oxygenates  ischemic  tissue,  and  reduces the nitrogen
     gradient. Any  patient  with  decompression  sickness  should  be
     transferred  immediately  to  the  nearest  HBO facility with the
     capacity to decompress to 3 to  6  ATA, as this has been shown in
     numerous series to be the most reliable and effective  treatment.
     [22,23]  The  Duke  University  Divers  Alert Network maintains a
     24-hour emergency consultation  telephone number, (919) 684-9111,
     and can identify the closest available HBO facility.
     Air Embolism.
     Air embolism can be a  complication  of  uncontrolled  ascent  in
     diving  but  more  frequently  is  seen  medically  in iatrogenic
     misadventures. Bubbles can  embolize  to  the cerebral or cardiac
     circulation,  producing  either  severe  neurologic  symptoms  or
     sudden  death.  Hyperbaric  oxygen  therapy  has  been  part   of
     successful  treatment  of  air  embolism  due  to  cardiovascular
     procedures,  [24,25]  lung  biopsies, [26] hemodialysis, [27] and
     central line placement.  [28]  Presumably,  HBO therapy decreases
     the volume of the embolism and oxygenates local tissues.
      Treatment involves immediate descent to  6  ATA  for  15  to  30
     minutes  on  air, followed by decompression to 2.8 ATA, where the
     patient  receives  prolonged  oxygen  treatment.  Carbon Monoxide
     Poisoning.—Carbon monoxide poisoning accounts  for  half  of  all
     fatal poisonings in the United States. Multiple series have shown
     that  patients  with  carbon  monoxide poisoning improve markedly
     following treatment with HBO. [29-31] However, both the mechanism
     of carbon monoxide toxicity and the therapeutic effect of HBO are
     poorly understood. Carbon monoxide  toxicity  was long thought to
     be due to anoxia alone; [32] however, there is evidence that  the
     pathophysiologic  effects  occur  with carbon monoxide binding to
     the   cytochrome-oxidase   system,    causing   anoxia   at   the
     mitochondrial level. [33] In either case, HBO therapy is the most
     rapid way of displacing carbon monoxide bound to  hemoglobin  and
     cytochromes.   The   serum   half-life  of  carboxyhemoglobin  is
     decreased from 5 hours  20  minutes  with  room air to 80 minutes
     with 100% oxygen and 23 minutes with 100% oxygen at 3  ATA.  [34]
     In  treating  patients  with  carbon  monoxide  poisoning,  it is
     important to remember that serum carboxyhemoglobin levels do no t
     reflect tissue levels  of  carboxyhemoglobin  and, therefore, may
     not correlate with the degree of toxicity. Accompanying signs and
     symptoms are  as  important  to  guiding  therapy  as  the  serum
     carboxyhemoglobin  level.  [35]  Although HBO therapy remains the
     preferred treatment for  significant  exposure  (Table 3), only a
     few controlled  human  studies  with  inconclusive  results  have
     compared HBO with 100% oxygen at 1 atm. [36,37]
     Clostridial Myonecrosis.
     Clostridial  myonecrosis occurs when a hypoxic environment within
     a  necrotic  wound  allows   clostridial  spores  to  convert  to
     vegetative organisms.  These  organisms  produce  exotoxins  that
     destroy red blood cells, cause tissue necrosis, and abolish local
     host  defenses.  The  most  important  exotoxin is alpha toxin. A
     tissue [PO.sub.2] of 250 mm  Hg  inhibits the production of alpha
     toxin by Clostridium. [38]
     Hyperbaric oxygen is commonly  used  as  an  adjunct  therapy  in
     clostridial   infections.   In  vivo  studies  have  demonstrated
     decreased mortality rates and  diminished tissue loss in infected
     mice. [39,40] In a study by DeMello et al, [41] using a dog model
     of clinical Clostridium infection, 100% of infected control  dogs
     and  dogs randomized to either HBO therapy or surgery died. Fifty
     percent of the dogs  that  received  antibiotics survived, 70% of
     the  dogs  that  received  antibiotics  and   underwent   surgery
     survived,  and  95% of the dogs that received antibiotics and HBO
     therapy and underwent surgery survived.
     Multiple series  have  evaluated  the  effect  of  HBO therapy on
     clostridial infections in humans.  [42,43]  Surgeons  experienced
     with  its use emphasize that early HBO treatment reduces systemic
     toxic reactions so that  patients  in  shock seem more stable and
     better able to tolerate surgery, and there is clearer demarcation
     of viable and nonviable tissue.  There  have,  however,  been  no
     randomized, controlled studies.
     Hyperbaric  oxygen  therapy has been recommended for treatment of
     necrotizing fasciitis, since  anaerobic  bacteria  play a role in
     the  disease.  [44,45]  The  diversity  of  clinical  states   in
     retrospective  studies  and the paucity of experimental data make
     it  difficult  to  demonstrate  the  effect  of  HBO  therapy  on
     nonclostridial   soft-tissue   infection.   Although  necrotizing
     fasciitis is an accepted indication  for  HBO,  the  benefit  HBO
     therapy  may  provide  is  still  poorly  understood, and surgery
     remains the cornerstone of therapy. [46]
     Acute Traumatic  Ischemia.
     Acute crush injury to  an  extremity  may  cause severe edema and
     ischemia in tissue and capillary beds not relieved by restoration
     of arterial perfusion. Hyperbaric oxygen therapy may aid  salvage
     during  the  acute  stages of revascularization by reducing edema
     via vasoconstriction and  increasing  oxygen  delivery via plasma
     flow. [47] Investigators have used HBO therapy successfully as an
     adjunct to surgery in crush injuries. [48,49] Additional evidence
     has demonstrate d that HBO therapy may also serve as  an  adjunct
     therapy in the compartment syndrome. [50]
     Irradiated Tissue.
     Radiation  therapy,  in  addition to its therapeutic effects, can
     damage normal adjacent tissue.  The initial pathologic process is
     a progressive obliterative endarteritis, resulting  in  areas  of
     tissue  hypoxia  and  eventual  cell  death.  [51] Large areas of
     hypocellular, hypovascular, and  hypoxic  tissue are created that
     are devoid of functioning fibroblasts and osteoblasts. [52]
     Hyperbaric oxygen therapy appears to  assist  in  salvaging  such
     tissue   by  stimulating  angioneogenesis  in  marginally  viable
     tissue.  [53]  Marx   and   Johnson   [54]   emphasize  that,  in
     reconstructive  surgery  involving  recently  irradiated  tissue,
     presurgical HBO treatment can help  promote  a  well-vascularized
     wound  bed that will enhance reconstruction and graft take. Using
     a  specific  HBO   protocol   of   presurgical  and  postsurgical
     treatments, they demonstrated a satisfactory surgical outcome  in
     92% of their patients and a complication rate of 9%.
     In osteoradionecrosis, tissue destruction progresses to breakdown
     of  overlying  tissues and symptomatic destruction of bone. Prior
     to the introduction of HBO  therapy,  only  5% to 30% of patients
     who developed  osteoradionecrosis  could  expect  remission  with
     conservative  therapy. [55] In a protocol developed by Marx, [56]
     a series  of  58  patients  received  an  initial  series  of HBO
     treatments, followed by debridement and further HBO treatment, as
     dictated by their clinical course. All 58  patients  studied  had
     resolution  of  symptoms of osteoradionecrosis, with good results
     on  long-term  follow  up.  These  impressive  results  have been
     corroborated by others. [57,58] Successful results have also been
     demonstrated  for  radiation-induced  cystitis  [59]  and   other
     radiation-damaged  soft tissue. [60] Hyperbaric oxygen therapy is
     beneficial  for  patients   at   risk   for  the  development  of
     osteoradionecrosis, such as irradiated patients  requiring  tooth
     extraction.  In  a  randomized trial comparing HBO and penicillin
     therapy  in  74  pr  eviously  irradiated  patients,  30%  of the
     patients who received  penicillin  developed  osteoradionecrosis,
     while   5.4%   of   the   patients  who  received  HBO  developed
     osteoradionecrosis.  [61]  Similar  results  have  been  reported
     elsewhere. [62]
     Refractory Osteomyelitis.
     Hyperbaric  oxygen  is  currently  being  used  as  an adjunctive
     therapy with debridement and antibiotics  in  osteomyelitis  that
     has  remained refractory to standard therapy. Animal studies have
     demonstrated that  HBO  therapy  used  in  experimental models of
     osteomyelitis has increased  osseous  repair  [63]  and  promoted
     callus formation, [64] possibly by promoting osteoclast activity.
     [65]  Human  studies  involve series of patients in whom standard
     treatment  regimens   have   failed.   Multiple  clinical  series
     demonstrate  substantial  success  with  HBO  therapy  in   these
     patients.  [66-68] However, to date there have been no randomized
     Problem Wounds.
     The  rationale  for  HBO   therapy   in   problem  wounds  is  to
     intermittently increase the tissue  oxygen  tension  to  optimize
     fibroblast  proliferation  [69]  and  white  blood  cell  killing
     capacity  [70]  during  periods  of  hyperoxia  and  to stimulate
     angioneogenesis during periods  of  relative hypoxia. [71] Series
     have been published showing improved healing with HBO therapy  in
     problem  wounds  refractory to standard therapy. [72,73] Patients
     in whom  increased  oxygenation  of  wounds  can  be demonstrated
     following HBO therapy are the most likely  to  benefit.  However,
     unlike  osteoradionecrosis, where a well-defined clinical problem
     has been shown  to  improve  with  a  carefully designed protocol
     incorporating HBO therapy, treatment of problem wounds remains an
     ill-defined field, and HBO data often  consist  of  small  series
     without standardized patient populations or treatment schedules.
     Hyperbaric   oxygen   therapy   cannot  substitute  for  surgical
     revascularization in advanced  arterial  insufficiency and cannot
     reverse inadequate  microvascular  circulation.  [74]  Hyperbaric
     oxygen  therapy  may  serve  as  an  adjunct  in the treatment of
     certain problem wounds,  but  it  cannot replace meticulous local
     care based on sound physiologic principles.
     Special Considerations
     Certain animal data indicate that HBO  therapy  may  improve  the
     outcome of moderate and severe burns. [75] Few centers use HBO as
     standard  therapy, but recent publications of patient series have
     demonstrated good response.  [76-78] Broad-based justification of
     the use of HBO  in  burns,  however,  will  depend  on  favorable
     results of randomized clinical trials.
     Hyperbaric oxygen therapy is a safe and effective primary therapy
     when  administered  for  decompression sickness and air embolism.
     The role of HBO  as  an  adjunctive  therapy in the treatment and
     prevention   of   osteoradionecrosis   has   been    impressively
     documented.  Its  contribution  to  the  treatment of clostridial
     myonecrosis has  been  substantiated  by  both  animal models and
     clinical experience. The role of HBO  therapy  in  recovery  from
     carbon  monoxide poisoning, while probably significant, is poorly
     understood and awaits clarification of the mechanism of action of
     both carbon  monoxide  poisoning  and  the  beneficial effects of
     oxygen therapy.
     Hyperbaric oxygen therapy  is  clearly  of  value  for  carefully
     defined  indications.  Successful  extension  of its use in other
     situations  will  be  predicated   on   in   vitro  and  in  vivo
     experimental evidence and  appropriate  well-controlled  clinical
     [1.] Hyperbaric Oxygen Therapy: A Committee Report. Bethesda, Md:
     Undersea and Hyperbaric Medical Society; 1986.
     [2.]  Francis  TJ,  Dutka  AJ,  Hallenbeck JM. Pathophysiology of
     decompression  sickness.  In:  Bove  AA,  Davis  JC,  eds. Diving
     Medicine. Philadelphia, Pa: WB Saunders Co; 1990:170-187.
     [3.] Gabb G, Robin ED. Hyperbaric oxygen: a therapy in search  of
     diseases. Chest. 1987;92:1074-1082.
     [4.]  Boerema  I,  Meyne  NG, Brummelkamp WK, et al. Life without
     blood: a study of the  influence of high atmospheric pressure and
     hypothermia  on   dilution   of   blood.   J   Cardiovasc   Surg.
     [5.]  Tally  FP,  Stewart  PR,  Sutter  VL, Rosenblatt JE. Oxygen
     tolerance of fresh clinical anaerobic bacteria. J Clin Microbiol.
     [6.] Badwey  JA,  Karnovsky  ML.  Active  oxygen  species and the
     functions   of   phagocytic   leukocytes.   Ann   Rev    Biochem.
     [7.]  Forman  HJ,  Thomas MJ. Oxidant production and bactericidal
     activity of phagocytes. Ann Rev Physiol. 1986;48:669-680.
     [8.] Hohn DC,  MacKay  RD,  Halliday  B,  Hunt  TK. The effect of
     [O.sub.2] tension on the microbicidal function of  leukocytes  in
     wounds and in vitro. Surg Forum. 1976;27:18-20.
     [9.]  Knighton  DR, Halliday B, Hunt TK. Oxygen as an antibiotic:
     the  effect  of   inspired   oxygen   on  infection.  Arch  Surg.
     [10.] Risber J, Tyssebotn I.  Hyperbaric  exposure  to  a  5  ATA
     He-[N.sub.2]-[O.sub.2]  atmosphere  affects  the cardiac function
     and organ blood flow distribution in awake trained rats. Undersea
     Biomed Res. 1986;13:77-90.
     [11.] Nylander G, Lewis D,  Nordstrom  H, Larsson J. Reduction of
     postischemic edema with hyperbaric oxygen. Plast  Reconstr  Surg.
     [12.]  Bassett  BE,  Bennett PB. Introduction to the physical and
     physiological bases of hyperbaric therapy. In: Davis JC, Hunt TK,
     eds.  Hyperbaric  Oxygen  Therapy.  Bethesda,  Md:  Undersea  and
     Hyperbaric Medical Society; 1977:11-24.
     [13.] Bond GF. Arterial  gas  embolism.  In:  Davis JC, Hunt, TK,
     eds.  Hyperbaric  Oxygen  Therapy.  Bethesda,  Md:  Undersea  and
     Hyperbaric Medical Society; 1977:141-152.
     [14.] Davis  JC,  Dunn  JM,  Heimbach  RD.  Hyperbaric  medicine:
     patient  selection,  treatment  procedures, and side effects. In:
     Davis JC, Hunt TK, eds.  Problem  Wounds: The Role of Oxygen. New
     York, NY: Elsevier Science Publishing Co Inc; 1988;225-235.
     [15.] Clark JM,  Lambertson  CJ.  Pulmonary  oxygen  toxicity:  a
     review. Pharmacol Rev. 1971;23:37-133.
     [16.] Nichols CW, Lambertsen CJ. Effects of high oxygen pressures
     on the eye. N Engl J Med. 1969;291:25-30.
     [17.]  Palmquist  BM, Phillipson B, Barr PO. Nuclear cataract and
     myopia  during  hyperbaric  oxygen   therapy.  Br  J  Ophthalmol.
     [18.]  Kindwall  EP,  Goldman   RW,   eds.   Hyperbaric   Medical
     Procedures. Milwaukee, Wis: Saint Lukes Medical Center; 1988.
     [19.]  Lynch  PR, Brigham M, Tuma R, Wiedeman MP. Origin and time
     course  of  gas  bubbles  following  rapid  decompression  in the
     hamster. Undersea Biomed Res. 1985;12:105-114.
     [20.] Whitecraft DD, Karas  S.  Air  embolism  and  decompression
     sickness in scuba divers. JACEP. 1976;5:355-361.
     [21.]  Tanoue  K,  Mano  Y,  Kuroiwa  K,  Suzuki  H, Shibayama M,
     Yamazaki H. Consumption of platelets in decompression sickness of
     rabbits. J Appl Physiol. 1987;62:1772-1779.
     [22.] Kizer KW. Delayed  treatment  of dysbarism: a retrospective
     review of 50 cases. JAMA. 1982;247:2555-2558.
     [23.] Green RD, Leitch DR. Twenty years of treating decompression
     sickness. Aviat Space Environ Med. 1987;58:362-366.
     [24.] Thomatis L, Nemiroff M, Riahi M, et  al.  Massive  arterial
     air   embolism   due  to  rupture  of  pulsatile  assist  device:
     successful treatment in the  hyperbaric chamber. Ann Thorac Surg.
     [25.] Peirce EC II. Specific therapy for arterial  air  embolism.
     Ann Thorac Surg. 1980;29:300-303.
     [26.]  Cianci  P,  Posin JP, Shimshak RR, Singzon J. Air embolism
     complicating percutaneous  thin  needle  biopsy  of  lung. Chest.
     [27.] Baskin  FE,  Wozniak  RL.  Hyperbaric  oxygenation  in  the
     treatment  of hemodialysis associated air embolism. N Engl J Med.
     [28.] Murphy BP, Hartford  FJ,  Cramer  FS. Cerebral air embolism
     resulting  from  invasive  medical  procedures:  treatment   with
     hyperbaric oxygen. Ann Surg. 1985;201:242-245.
     [29.]  Myers  RAM,  Snyder  SK,  Linberg  S,  Cowley RA. Value of
     hyperbaric oxygen in  suspected  carbon monoxide poisoning. JAMA.
     [30.] Norkool DM,  Kirkpatrick  JN.  Treatment  of  acute  carbon
     monoxide poisoning with hyperbaric oxygen: a review of 115 cases.
     Ann Emerg Med. 1985;14:1168-1171.
     [31.]  Goldbaum LR, Ramirez RG, Absalom KB. What is the mechanism
     of  carbon   monoxide   toxicity?   Aviat   Space   Environ  Med.
     [32.] Jackson DL, Menges H. Accidental carbon monoxide poisoning.
     JAMA. 1980;243:772-774.
     [33.]  Kindwall  EP.  Carbon  monoxide  poisoning  treated   with
     hyperbaric oxygen. Respir Ther. 1975;5:29-33.
     [34.]  Peterson  JE,  Stewart  RD.  Absorption and elimination of
     carbon monoxide  by  inactive  young  men.  Arch  Environ Health.
     [35.] Kindwall EP. Carbon monoxide  and  cyanide  poisoning.  In:
     Davis  JC,  Hunt TK, eds. Problem Wounds: The Role of Oxygen. New
     York, NY: Elsevier Science Publishing Co Inc; 1988:177-190.
     [36.] Raphael JC, Elkharrat  D,  Jars-Guincestre MC, et al. Trial
     of normobaric and hyperbaric oxygen  for  acute  carbon  monoxide
     intoxication. Lancet. 1989;2:414-419.
     [37.]  Goulon  M,  Barois  A,  Rapin  M, Nouailhat F, Grosbuis S,
     Labrousse  J.  Carbon  monoxide  poisoning  and  acute  anoxia. J
     Hyperbar Med. 1986;1:23-41.
     [38.]  Van  Unnik  AJM.  Inhibition  of   toxin   production   in
     Clostridium  perfringens  in  vitro by hyperbaric oxygen. Antonie
     von Leeuwenhoek. 1965;31:181-186.
     [39.] Holland JA, Hill  GB,  Wolfe  WG, Osterhout S, Saltzman HA,
     Brown IW. Experimental and clinical  experience  with  hyperbaric
     oxygen  in  the  treatment  of  clostridial myonecrosis. Surgery.
     [40.] Hill GB,  Osterhout  S.  Experimental effects of hyperbaric
     oxygen on selected clostridial species, II: in  vivo  studies  in
     mice. J Infect Dis. 1972;125:26-35.
     [41.]  DeMello  FJ, Haglin JJ, Hitchcock CR. Comparative study of
     experimental Clostridium  perfringens  infection  in dogs treated
     with  antibiotic,  surgery,  and  hyperbaric   oxygen.   Surgery.
     [42.]  Gibson  A,  Davis  FM.  Hyperbaric  oxygen  therapy in the
     management of  Clostridium  perfringens  infections.  N  Z Med J.
     [43.] Hart GB, Lamb RC, Strauss MB. Gas gangrene, II:  a  15-year
     experience with hyperbaric oxygen. J Trauma. 1983;23:995-1000.
     [44.]  Schreiner  A,  Tonjum  S,  Digranes  A.  Hyperbaric oxygen
     therapy in Bacteroides infections. Acta Chir Scand. 1974;140:73-76.
     [45.] Bakker DJ. Necrotizing  soft  tissue infections. J Hyperbar
     Med. 1987;2:161-169.
     [46.] Miller JD. The  importance  of early diagnosis and surgical
     treatment   of   necrotizing   faciitis.   Surg  Gynecol  Obstet.
     [47.] Davis JC, Heckman  JD.  Compromised soft tissue wounds. In:
     Davis JC, Hunt TK, eds. Problem Wounds: The Role of  Oxygen.  New
     York, NY: Elsevier Science Publishing Co Inc; 1988:125-142.
     [48.]  Loder RE. Hyperbaric oxygen therapy in acute trauma. Ann R
     Coll Surg Engl. 1979;61:472-473.
     [49.] Monies-Chass I, Hashmonai  M,  Hoerer D, Kaufman T, Steiner
     E,  Schramek  A.  Hyperbaric  oxygen  treatment as an adjuvant to
     reconstructive    vascular    surgery    in    trauma.    Injury.
     [50.] Strauss MB, Hargens  AR,  Gershuni  DH, et al. Reduction of
     skeletal  muscle necrosis using intermittent hyperbaric oxygen in
     a  model   compartment   syndrome.   J   Bone   Joint   Surg  Am.
     [51.] Ewing J.  Radiation osteitis.  Acta Radiol.
     [52.]  Marx  RE.  Osteoradionecrosis:  s  new  concept   of   its
     pathophysiology. J Oral Maxillofac Surg. 1983;41:283-288.
     [53.] Hunt TK, Dai MP.  The  effect  of  varying  ambient  oxygen
     tensions on wound metabolism and collagen synthesis. Surg Gynecol
     Obstet. 1972;135:561-567.
     [54.]   Marx   RE,   Johnson  RP.  Problem  wounds  in  oral  and
     maxillofacial surgery: the role  of  hyperbaric  oxygen. In: Davis JC,
     Hunt TK, eds. Problem Wounds:  The  Role  of  Oxygen.  New  York,  NY:
     Elsevier Science Publishing Co Inc; 1988;65-124.
     [55.]  Obwegesser  HB,  Sailer  HF.  Experience  with  intra-oral
     resection    and    immediate    reconstruction   in   cases   of
     radio-osteomyelitis  of   the   mandible.   J   Maxillofac  Surg.
     [56.]  Marx   RE.   A   new   concept   in   the   treatment   of
     osteoradionecrosis. J Oral Maxillofac Surg. 1983;41:351-357.
     [57.] Farmer JC Jr, Sheldon  DL, Angelillo JD, Bennett PD, Hudson
     WR. Treatment of radiation-induced tissue  injury  by  hyperbaric
     oxygen. Ann Otol Rhinol Laryngol. 1978;87:707-715.
     [58.]  Davis  JC,  Dunn  JM,  Gates  GA,  Heimbach RD. Hyperbaric
     oxygen: a new adjunct  in  the  management of radiation necrosis. Arch
     Otolaryngol Head Neck Surg. 1979;105:58-61.
     [59.]   Weiss  JP,  Boland  FP,  Mori  H,  et  al.  Treatment  of
     radiation-induced  cystitis  with   hyperbaric  oxygen.  J  Urol.
     [60.] Ferguson BJ, Hudson WR, Farmer JC Jr. Hyperbaric oxygen for
     laryngeal radionecrosis. Ann Otol Rhinol Laryngol. 1987;96:1-6.
     [61.]  Marx   RE,   Johnson   RP,   Kline   SN.   Prevention   of
     osteoradionecrosis:   a   randomized  prospective  clinical  trial  of
     hyperbaric oxygen versus penicillin. J Am Dent Assoc. 1985;111:49-54.
     [62.]   Kraut   RA.   Prophylactic  hyperbaric  oxygen  to  avoid
     osteoradionecrosis when  extractions  follow  radiation necrosis.
     Arch Otolaryngol Head Neck Surg. 1985;7:17-20.
     [63.]  Triplett  RG,   Branham   GB,   Gillmore   JD,  Lorber  M.
     Experimental mandibular osteomyelitis:  therapeutic  trials  with
     hyperbaric oxygen. J Oral Maxillofac Surg. 1982;40:640-646.
     [64.] Niinikoski J, Penttinen R, Kulonen E. Effect of  hyperbaric
     oxygen  on  fracture  healing  in  the  rat: a biochemical study.
     Calcif Tissue Res. 1970;4(suppl):115-116.
     [65.] Mader JT,  Brown  GL,  Guskian  JC.  A  mechanism  for  the
     amelioration  by hyperbaric oxygen of experimental Staphylococcus
     osteomyelitis in rabbits. J Infect Dis. 1980;142:915-922.
     [66.] Davis JC,  Heckman  JD,  DeLee  JC,  Buckwold  FJ.  Chronic
     nonhematogenous  osteomyelitis  treated  with adjuvant hyperbaric
     oxygen. J Bone Joint Surg Am. 1986;66:1210-1217.
     [67.] Strauss MB.  Refractory osteomyelitis.  J Hyperbar Med.
     [68.]  Herman  DS.  Hyperbaric oxygen therapy and its role in the
     treatment  of  chronic   osteomylelitis:   a  preliminary  report
     involving refractory osteomyelitis in  the  foot.  J  Foot  Surg.
     [69.]  Silver  IA.  Local  and  systemic factors which affect the
     proliferation of fibroblasts. In:  Kulonen E, Pikkarainen J, eds.
     The Biology of Fibroblast.  Orlando,  Fla:  Academic  Press  Inc;
     [70.] Hohn DC, Ponce B, Burton RW, Hunt TK. Antimicrobial systems
     of the surgical wound, I: a comparison  of  oxidative  metabolism
     and  microbicidal  capacity  of  phagocytes  from wounds and from
     periferal blood. Am J Surg. 1977;133:597-600.
     [71.]  Kighton  D, Silver I, Hunt TK. Regulation of wound healing
     angiogenesis: effect  of  oxygen  gradients  and  inspired oxygen
     concentration. Surgery. 1981;90:262-270.
     [72.] Wyrick WJ, Mader JT, Butler E, Hulet WH. Hyperbaric  oxygen
     in    treatment    of    pyoderma    gangrenosum.    Arch    Dermatol.
     [73.] Bass BH. The treatment of varicose leg ulcers by hyperbaric
     oxygen. Postgrad Med. 1970;46:407-408.
     [74.]  Davis  JC,  Buckley  CJ,  Barr PO. Compromised soft tissue
     wounds: correction of wound hypoxia.  In: Davis JC, Hunt TK, eds.
     Problem Wounds: The  Role  of  Oxygen.  New  York,  NY:  Elsevier
     Science Publishing Co Inc; 1988:143-152.
     [75.]  Korn HN, Wheeler ES, Miller T. Effect of hyperbaric oxygen
     on second-degree burn wound healing. Arch Surg. 1977;112:732-737.
     [76.]  Cianci  P,  Lueders H, Lee H, et al. Adjunctive hyperbaric
     oxygen reduces the need for  surgery  in 40-80% burns. J Hyperbar
     Med. 1988;3:97-101.
     [77.] Wiseman DH, Grossman AR. Hyperbaric oxygen in the treatment of burns. Crit Care Clin. 1985;1:129-145.
     [78.] Niu AKC, Yang C, Lee  HC,  Chen SH, Chang LP. Burns treated with adjunctive hyperbaric oxygen therapy: a comparative study in humans. J Hyperbar Med. 1987;2:75-85.

sumber :
Hyperbaric Oxygen Therapy 
from "JAMA" 
"The Journal of the American Medical Association" 
April 25, 1990 v263 n16 p2216(5) 
by Grim, Pamela S.; Gottlieb, Lawrence J.; 
Boddie, Allyn; Batson, Eric