HBO: What It Is & How It Works

Objectives Enhance physician education regarding the scientific foundation of HBO as an adjunctive tool in advanced wound care. Provide information to physicians on the proper patient selection and risk management associated with safe, effective HBO delivery.

What is HBO Therapy? Hyperbaric oxygen (HBO) is a medical treatment in which the patient is entirely enclosed in a pressure chamber breathing 100% oxygen at greater than one atmosphere pressure.

What is not HBO?

What is this ?

How HBO Works

How it works: The Mechanical Effects of HBO 1. Direct Pressure - Reduces bubble size 2. Hyperoxygenation - Delivery of oxygen to hypo-perfused tissues - Promotes angiogenesis & neovascularization 3. Enhanced Antimicrobial Activity - Aids in oxygen-dependent killing of bacteria - Facilitates oxygen dependent transport of antibiotics 4. Vasoconstriction - Limits leukocyte adhesion (reduces effects of reperfusion injury) - Decreases tissue edema

Direct Pressure: Boyle's Law For more than a century this mechanism has formed the basis for hyperbaric oxygen therapy as the standard of care for (DCS) decompression sickness and cerebral arterial gas embolism (AGE). Robert Boyle 1627-1691

Hyperoxygenation: Physiology Cardiopulmonary - Increase in PaO2 - Hgb 97% saturated at atmospheric pressure - Maximization does not significantly increase O2 delivery - Increase in dissolved O2 -Using 100% FiO2 at 3 atm increases up to 2000 mmHg -Increases O2 from 3 ml/L blood to 60 ml/L -20 times more O2 circulating in plasma

Hyperoxygenation: Physiology (The Start) Dr. Ite Boerema

Hyperoxygenation: Physiology (The Start) The Chamber The Pig (24 hrs post tx)

Like all good experiments, Dr Like all good experiments, Dr. Boerema has been replicated many times with like results.

Hyperoxygenation: Physiology Cardiopulmonary - Dissolved O2 diffuses into RBC impassible areas - May also deliver O2 in absence of functional Hgb - 100% O2 at 3.0 atm; effects at capillary beds > Doubles distance of venous diffusion. >Quadruples distance of arterioal diffusion

Hyperoxygenation: Physiology Tissue & Cellular Levels - Tissue PO2 is 55 mmHg at atmospheric pressure. > Tissue PO2 > 40 mmHg is needed to initiate healing. - Using FiO2 100% at 3 atm it increases to 500 mmHg: > Almost 10 fold increase in tissue oxygen tension. - Increased activation of fibroblasts & osteoblasts. - Promotes angiogenesis & neovascularization.

Oxygen diffusion distances: 36 microns- Patient breathing room air 21% oxygen 280 microns- Patient breathing 100% oxygen at 2.0 ATA At 2.0 ata breathing 100% O2 arterial blood PO2 can achieve levels greater than 1500mmHg. This high PO2 value allows for a greatly expanded radius of diffusion of O2. This also creates a steep oxygen gradient from open capillaries to the edge of the wound. As a result, tissues with borderline ischemia or hypoxia can be intermittently supplied with oxygen in quantities sufficient to accelerate wound healing, and enhance leukocyte microbiocidal function, and stave off necrosis.

Diffusing distance of O2 from functioning capillaries: Capillary blood flow Capillary blood flow Wound Margins 36 Microns @ 1 ata with 21% O2 280 Microns @ 2 ata with 100% O2 Note: Increasing the diffusing distance of oxygen, improves oxygenation of tissue with borderline ischemia by increasing the ability of capillary beds to overlap one another.

Neovascularization & Angiogenesis: Represents an indirect and delayed response to serial HBOT. Collagen forms a basement membrane that provides structure support for these budding vessels. Capillaries then grow into hypoxic areas. HBOT increases the amount of oxygen reaching advancing cells. HBOT enables this new vascular supply to advance quickly, ensuring faster wound closure.

O2 and fibroblast replication / collagen synthesis: Fibroblast replication is normal within the range of 40-60 mmHg PO2. Any degree of hypoxia below this range slows it and reduces the potential for collagen synthesis. The maximum rate of collagen production is at approximately 250 mmHg which is beyond the normal oxygen tension in a wound. At this level 90% of fibroblast are functioning at full capacity at 2.0 ata. Fibroblasts cannot synthesize or deposit collagen in the absence of molecular oxygen or in a BGL > 200 mg/dL.

Wound Care & Hyperbaric Medicine. Blood Glucose Levels Published in Wound Care & Hyperbaric Medicine. 2012; 3 (3): 13-17. HBO patients with an average daily BGL of < 200 mg/dL during HBO had a 89% healing rate. Patients that had an average BGL of >200 mg/dL, only had a 24% healing rate.

Enhanced Antimicrobial Activity: Bacteriostatic / Bactericide Generation of oxygen free radicals Bacterial replication inhibited. Toxin production inhibited Protentiation of antimicrobial agents. Enhanced White Cell Function Phagocytic killing requires a minimum of 30 mmHg of oxygen. Phagocytic killing increases as the partial pressure of oxygen increases.

Enhanced Antimicrobial Activity: Oxygen Consumption and Infected Wounds Not only are infection potentiated by hypoxia, but infections further impair wound healing by increasing hypoxia. The more leukocytes and bacteria there are in a wound, the higher the oxygen consumption and the lower the local tissue PO2. Oxygen consumption by leukocytes rises approximately 50 fold in the process of killing bacteria.

Vasoconstriction: Vasoconstriction occurs during hyperbaric oxygen therapy without component hypoxia. This is helpful in managing intermediate compartment syndrome and other acute ischemias in injured extremities, and reducing interstitial edema in grafted tissue. Hyperbaric oxygen reduces edema by increasing diffusion of oxygen. The resulting vasoconstriction reduces inflow by approximately 20% while maintaining outflow, thereby, reducing edema by (20%) thru the reabsorption of tissue fluids.

Ischemia-Reperfusion Injury: Most of the damage associated with reperfusion is brought about by the inappropriate activation of leukocytes. I-R injury results from two components: 1. Direct irreversible injury component from hypoxia. 2. Indirect injury which is largely mediated by the inappropriate activation of leukocytes. HBOT reduces the indirect component of the injury by preventing the down regulation of leukocyte receptor sites. Basically HBO inhibits leukocyte endothelial intravascular adhesions for ≈ 8 hours post-treatment. The net effect is the preservation of marginal tissues.

Treatment Protocols: Oxygen, under increased pressure, is a potent drug. HBO can produce noticeable toxic effects if administered indiscriminately. Safe time-dose limits have been established for HBO exposure, and these profiles form the basis for all TT. In those cases for which angiogenesis is the primary goal, ≈ 20 to 30 treatments may be necessary. The precise number of treatments depends upon clinical response of each pt. Treatments may be given once, twice or occasionally three times daily and may last up to 120 minutes.

Cycling: We know that tissue hyperoxia lasts longer than the actual exposure (2 to 4 hours) depending on the type of tissue. Many researchers have suggested that this effect may last as long as 6 to 8 hours post-treatment in some tissues. The effects on bacterial killing, angiogenesis, collagen deposition, are cumulative and will last beyond the exposure time. For instance, since bacteria are killed during exposure, the bacterial count cannot bounce back to pre-treatment levels immediately. Nitric oxide production also rises temporarily, leading to increased perfusion.

The PO2 Wave: Base-line tcpO2 25 mmHg After 16-20 treatments the base-line tcpO2 level starts to move up. Increased tissue pO2 last 2-8 hrs 1400 mmHg The base-line level will continue moving up to within 80% of normal tissue/post HBO. Level required for normal wound healing 40 mmHg Tx # 1 Tx # 2 Tx # 16-20 20 mmHg HBO Tx. 90-120 mins. Tissue pO2 levels 6-8 hrs post therapy. Approximately 8 -18 hrs until next treatment.

Indication for HBO Therapy

Undersea and Hyperbaric Medical Society: Hyperbaric Oxygen Therapy Indications 12th Ed. “As each year goes by, the body of scientific evidence to support the use of hyperbaric oxygen therapy builds…”

Indications Approved for Hyperbaric Oxygen Therapy Severe Anemia Intracranial Abscess Necrotizing Soft Tissue Infections Refractory Osteomyelitis Delayed Radiation Injuries (Soft Tissue and Bony Necrosis) Compromised Grafts and Flaps Acute Thermal Burn Injury Idiopathic Sudden Sensorineural Hearing Loss Air or Gas Embolism Carbon Monoxide Poisoning Clostridial Myonecrosis (Gas Gangrene) Crush Injuries/Compartment Syndromes Decompression Sickness Central Retinal Artery Occlusion* Enhancement of Healing in Selected Problem Wounds Acute Sensory-Neural Hearing Loss

Air or Gas Embolism: Gas bubbles introduced into vascular system a. venous b. Arterial Can be decompression or iatrogenically induced. Can affect any organ. Symptoms may mimic MI or stroke. Direct Pressure Hyperoxygenation Vasoconstriction Treatment of choice is HBO. DCS CPG: H03.02 (US Navy TT6A or TT6)

Effect of HBO on Outcome after AGE 100 Full Recovery Residual 80 Death 60 % Patients 40 20 HBO No Recompression N = 288 Dutka, 1991 N = 411

U. S. Navy Treatment Table 6

Carbon Monoxide/Cyanide Poisoning: Carbon monoxide displaces oxygen on hemoglobin. Symptoms can range from mild to severe. (COHb > 20%) Treatment of choice is HBO. Hyperoxygenation Vasoconstriction DCS CPG: H03.04 (2.5-3.0 ata or US Navy TT5) Notes: 1. Fetal COHb > 10-15% higher than maternal level. 2. Neurologic status.

Carbon Monoxide Poisoning

Clostridial Myonecrosis: (Gas Gangrene) Signs and symptoms include rapid, fulminating, life and limb threatening infection. Most commonly caused by Clostridium perfingens. HBO is adjunctive to aggressive surgical debridement. Hyperoxygenation. Enhanced Antimicrobial Activity. Vasoconstriction Halt production of alpha toxin. DCS CPG: H02.08

Gas Gangrene:

Crush Injuries Compartment Syndromes and Other Acute Traumatic Ischemias: Blood flow to extremity is impeded. May be diffused crush or disruption of arterial flow. HBO used in conjunction with surgery (fasciotomy). Hyperoxygenation Vasoconstriction DCS CPG: H02.03

Crush Injuries & Compartment Syndromes

Decompression Sickness: Formation of inert gas bubbles in bloodstream and tissue during decompression. Occludes blood vessels and can compress nerves. Symptoms can be subtle and diverse. Treatment of choice is HBO. Direct pressure Hyperoxygenation Vasoconstriction DCS CPG: H03.03 (US Navy TT5 or TT6)

Decompression Sickness:

Decompression Sickness:

Central Retinal Artery Occlusion: Symptoms are sudden and painless: loss of vision Occlusion of the retinal artery. Ophthalmic emergency The retina has the highest rate of oxygen consumption of any organ in the body at 13ml/100g/min. Treatment of choice is HBO. Hyperoxygenation. DCS CPG: H04.01

Classic Example of CRAO Cherry Red Spot classically occur after CRAO. There is also edema present.

Enhancement of Healing in Selected Problem Wounds: Re-establish wound oxygen gradient. Prepare for definitive coverage or surgery. Hyperoxygenation Vasoconstriction Enhanced Antimicrobial Activity. DCS CPG: H02.01A Diabetic Lower Extremity H02.01B Critical Limb Ischemia- Arterial Insufficiency Ulcers.

Diabetic Wound of the Lower Extremity Pre-HBO Post HBO

Severe Anemia: Increases physically dissolved oxygen concentrations. Hyperoxygenation CPG: H03.01 The hand of a woman with severe anemia (right) is comparison to the normal hand of her husband (left)

Intracranial Abscess: Relieves hypoxia and augment treatment of concomitant skull necrosis. Reduces peri-focal brain edema and enhance host defenses and augment treatment of anaerobic flora. Hyperoxygenation Vasoconstriction. Enhanced Antimicrobial Activity CPG: H03.05 (pending)

Intracranial Abscess

Necrotizing Soft Tissue Infections: Mixed flora infections (including Fungal) Hypoxic wounds in host compromised patients. Primary treatment is surgery and antibiotics, with HBO used adjunctively. Demarcate potentially viable from non-viable tissue, pre-operatively. Hyperoxygenation Enhanced Antimicrobial Activity Vasoconstriction CPG: H02.07

Necrotizing Soft Tissue Infections:

Refractory Osteomyelitis: Chronic infection in bone which has failed to heal with conventional therapy. (surgery/antibiotics). HBO is used adjunctively. Hyperoxygenation Enhanced Antimicrobial Activity Vasoconstriction DCS CPG: H02.06

Refractory Osteomyelitis:

Delayed Radiation Injuries (Soft Tissue and Bony Necrosis): Soft tissue radionecrosis (STRN) or osteoradionecrosis (ORN). Progressive obliterative endarteritis. HBO essential in overall treatment plan. Hyperoxygenation Enhanced Antimicrobial Activity. Vasoconstriction CPG: H02.05

ORN of the Mandible: Pre-HBO Post HBO (30 txs)

STRN and Failing Flap: Pre-HBO Post HBO

Radiation Proctitis: Pre-HBO 60 Days Post HBO (30 txs)

Radiation Cystitis: Cystoscopy Pre-HBO

Radiation Cystitis: Cystoscopy Post 60 HBOT

Compromised Grafts and Flaps: Supports marginally perfused or oxygenated tissue and improves development of granulation tissue while supporting marginally perfused tissue. Accelerates angiogenesis Hyperoxygenation Vasoconstriction Enhanced Antimicrobial Activity CPG: H02.02

Failing Graft Treated with HBO: Pre-HBO Post HBO

Acute Thermal Burn Injury: Burns are dynamic. Difficulties include circulatory damage, edema, fluid loss, secondary infection and slow healing. Limits tissue fluid loss. Limits burn wound extension and conversion. HBO used adjunctive to standard burn care. Hyperoxygenation Vasoconstriction Enhanced Antimicrobial Activity CPG: H02.04

Acute Thermal Burn 23-year old white female with facial burns from flaming gasoline, 12 hours post injury. 24 hrs later (36 hours post injury) after two HBO treatment. 72 hours later (84 hours post injury) after six HBO treatments. Shortly before discharge.

One year post facial burns Acute Thermal Burn 24-year old white female One year post facial burns

Miscellaneous other HBO Indications: Bisphosphonate Osteonecrosis Actinomycoses Brown recluse envenomation when progressive necrosis is present. Frostbite Ulcers associated with calciphylaxis Sickle cell ulcers No other off label use of HBO is allowed without approval of the Chief Medical Officer of Healogics.