Using hyperbaric oxygen therapy in emergency and critical-care practice

It's been used to treat many clinical conditions since the 1930s, but because of a lack of research into its physiological effects, many practitioners were wary of it and of the claims of some who were using it. Only in the last 10 to 15 years has hyperbaric oxygen therapy (HBOT) become widely accepted, based on well-designed and controlled experimental studies in animals.

Clinical reports have found HBOT an excellent adjunctive therapy for a variety of conditions, including severe burns, wounds, osteomylitis, fungal and bacteria infections, especially those that involving anaerobic organisms, carbon-monoxide poisoning and decompression syndrome (the "bends").

In the last few years, HBOT use has been expanded for many conditions involving ischemia in its pathophysiology. These include pancreatitis, bowel ischemia secondary to obstruction, spinal-cord compression, brain injury, stroke, myocardial infarction, crushing injuries and aortic thromboebolism,.

What is HBOT?

It's defined as therapy involving the delivery of supplemental oxygen at higher than atmospheric pressure. In most cases this involves placing the patient into an airtight chamber filled with oxygen and the pressure purposely increased. The patient then is kept in this environment for a specified period (generally 1.0 to 1.5 hours) and receives a therapy session once or twice daily.

The combination of the high concentration of oxygen and its delivery at increased pressure surrounding the body raises plasma and tissue oxygen concentrations three- or four-fold, which has been found to be very supportive of diseased or injured tissue, especially those that are edematous, poorly vascularized and ischemic. The therapy promotes normal cell function and stimulates angiogenesis, stem-cell activation and production healing of ischemic or injured tissue.

There are two types of HBOT delivery methods. The first and most researched in the United States is standard HBOT, in which high-dose oxygen inhalation therapy is achieved by having the patient breathe 100 percent oxygen inside a pressurized hyperbaric chamber where a second or third atmosphere of pressure is achieved (14.7 to 29.4 pounds per square inch). Two types of chambers available commercially are steel-bodied and those made of acrylic or acrylic and metal (Photos 1 and 2).

Photo 1: Sechrist 2500B acrylic and metal hyperbaric chamber (Photo from www.hyperbaricclearinghouse.com).

The second method is what is termed low-pressure HBOT. In this system, supplemental oxygen is provided into a collapsible chamber, and air is added until pressure within is 4-5 psi (approximately another 0.33 atmosphere). This chamber appears as a firm and very rigid structure when pressurized (Photo 3).

Photo 2: A steel-bodied, companion-animal hyperbaric chamber at Central Veterinary Referral Center, Fresno, Calif.

Delivery of enhanced oxygen is greater with the first system.

Photo 3: Oxyhealth hyperbaric chamber used at Pet Emergency Clinics and Specialty Hospital, Thousand Oaks, Calif.

Physiological effects

Pressure of gases is defined as a force per unit area. The pressure of one atmosphere (ATM) is 14.7 pounds per square inch (PSI). This is the weight of the air producing a force on the surface of the Earth. Weathermen usually refer to it as "barometric pressure," measured in inches of mercury (29.9 inches of mercury [Hg] = 760 mm mercury = 1 atmosphere).

The term "atmospheres" refers to atmospheres absolute. Absolute pressure equals the gauge pressure plus the ambient air pressure on the surface at sea level (IE: 1 ATM). For example, if one descends 33 feet in sea water (FSW), one is at an absolute pressure of 2 ATM. This is shown by the fact that water pressure at that depth is equal to a gauged air pressure of 14.7 pounds per square inch as read on the gauge. Absolute pressure equals gauge pressure plus atmospheric pressure (IE: 1 ATM + 1 ATM = 2 ATM)

Gas laws that govern effects

These include Boyle's Law (Table 1), which states that, with pressure constant, the volume of a gas is inversely proportional to the pressure. (P1/P2 = V2/V1). When a chamber is pressurized, the volume of gas in enclosed body areas such as the ears, sinuses, lungs, gastrointestinal tract, etc., responds to increased pressure by contracting. Doubling the pressure reduces the gas volume to about a half and tripling the pressure reduces it by a third.

Table 1: Boyle's law

This is particularly beneficial in the emergency treatment of bowel obstructions, because HBOT, based on Boyle's Law, literally decompresses the distended bowel loops as it "denitrogenates" the gas trapped in the bowel's lumen and substitutes it with oxygen. If a patient suffers gaseous distention of the bowel, compression in the chamber will ease the discomfort, increase bowel-wall and mucosa viability and even continue to remove nitrogen from the distended intestine an hour after the treatment ceases. This is thought to be associated with the envelopment of oxygen in the interstitial tissues during HBOT.

Dalton's Law: Total pressure exerted by a mixture of gases is equal to the sum of the pressure of each of the different gases making up the mixture (PO2=Ptot X FiO2), where FiO2 is the fractional concentration of oxygen expressed as a decimal.

Using Dalton's Law we are be able to determine that the PO2 in mmHg in the chamber while breathing 100 percent oxygen at 33 feet of sea-water pressure = 2 absolute atmospheres and PO2=Ptot X FiO2, PO2=760(2) X 1.0, which totals 1520 mmHg.

Henry's Law: Gas in solution. The amount of gas dissolved in a liquid is directly proportional to the partial pressure of the dissolved gas.

An animal breathing air at sea-level pressure has only 1.5 percent of the oxygen physically dissolved in plasma. Oxygen transport by plasma is the key to hyperbaric oxygen therapy, for even poorly perfused tissue can receive oxygen as the hyperoxygenated plasma seeps across it.

Plasma in edematous tissues flows through narrowed capillaries better than blood. As the chamber is pressurized, the elevated alveolar oxygen tension in the lungs drives oxygen into the plasma of the pulmonary circulation and its subsequent transport throughout the body. Unlike hemoglobin saturation, which has an S-shaped curve, the amount of dissolved oxygen increases linearly as PO2 increases 0.4.

Oxygen solubility is defined by Henry's Law, which looks at the relative quantity of gas entering solution as related to the PAO2, but does not define the absolute amount of gas in solution. That varies with different fluids and is determined by the solubility coefficient of gas in fluids, which is temperature-dependent.

Oxygen solubility in whole blood at 37 degrees C is 0.0031 ml of oxygen per deciliter (dl) of blood per mmHg PAO2. Breathing air at sea level, arterial oxygen tension is about 100 mmHg. Therefore the blood carries about 0.31 ml of dissolved oxygen per dl whole blood. When breathing 100 percent oxygen at sea level ,the amount of dissolved oxygen increases to about 2.1 ml of O2 per dl blood. Breathing 100 percent oxygen at 2 ATA results in a PAO2 of 1,433 mmHg (4.4 ml of dissolved oxygen per dl of blood). Three ATA provides a PA O2 of about 2,200 mmHg and adds about 6.8 ml O2 to each dl of blood.

A healthy animal at rest uses about 6 ml of oxygen per dl of circulating blood. Thus HBOT at 3 ATA provides sufficient plasma oxygen to exceed the body's total metabolic requirement. The dissolved content of 6ml oxygen per dl of blood is equivalent to the sea-level oxygen capacity of 5 grams of hemoglobin. This phenomenon is the reason Dr. Boerma was able to sustain a pig's life without blood in his study "Life Without Blood."

Gas exchange and oxygen diffusion

An increase in oxygen tension causes oxygen to diffuse further from the functioning capillaries. Tissue oxygen content depends on three factors: distance from the functioning capillaries, oxygen demand of the tissue and the oxygen tension of the capillary.

Using the Krogh Erlang mathematical model, when breathing air at 1 ATA, oxygen diffuses about 64 micrometers (about the thickness of a sheet of typing paper) at the arterial end of the capillary. Breathing at 2 ATA, oxygen diffuses about 160 micrometers (about the thickness of two sheets of typing paper).

In a hypoxic environment, HBOT may be able to restore PO2 to normal or slightly elevated levels (depending on the severity of the injury). It enhances epithelization, collagen deposition, fibroplasia, angiogenesis and bacterial killing. In the presence of tissue hypoxia, some or all of these processes are impaired. Fibroblasts can survive in 3 mm Hg, but cannot migrate in < 10 mm Hg. Fibroblasts also do not divide in < 22 mm Hg and do not form collagen in < 28 mm Hg.

It has been reported that if oxygen tension is held continuously at 290-560 mm Hg, fibroblastic replication is halted. When oxygen tension is returned to normal, the replication continues. Therefore daily high doses are needed to correct the hypoxic environment but must be delivered in an intermittent pattern to avoid possible side effects in the cells.

Therapeutic effects of HBOT include: reverse hypoxia, altered ischemic effect, influence on vascular reactivity, reduced edema. Hyperoxygenation will cause vasoconstriction, but despite that more oxygen is delivered to the tissues.

HBOT modulates nitric oxide (NO) production. An NO increase leads to vasodilation, while a decrease leads to vasoconstriction. Carbon dioxide increases NO production and oxygen decreases NO production by the endothelial cells.

HBOT modifies growth factors and cytokine effect by regulating their levels and/or receptors. Vascular endothelial growth factor (VEGF) is important for the growth and survival of endothelial cells, and is found in plasma, serum and wound exudates. Under normobaric conditions, VEGF is stimulated by hypoxia, lactate, nitric oxide and nicotinamide adenine dinucleotide (NAD). HBO induces production of VEGF, stimulating more rapid development of capillary budding and granulation formation within the wound bed.

Other therapeutic effects include: inducing changes in membrane proteins affecting ion exchange and gaiting mechanisms, promoting cellular proliferation, accelerating collagen deposition, stimulatingcapillary budding and arborization, accelerating microbial oxidative killing, improving select antibiotic exchange across membranes.

Anoxia decreases the activity of several antibiotics (aminoglycosides, sulfonamides, fluoroquinolone). Raising the pO2 of ischemic tissue to normoxic levels may normalize the activity of these antimicrobials. In addition, HBOT may potentiate the activity of certain antimicrobials by inhibiting biosynthetic reactions in bacteria.

HBOT also interferes with bacterial disease propagation by denaturing toxins, modulates immune-system response, enhances oxygen radical scavengers, thereby decreasing ischemia-reperfusion injury.

It increases the amount and activity of the free radical scavenger superoxide dismutase.

Decreased neutrophil adhesion and subsequent release of free radicals is an important early event leading to endothelial damage and microcirculatory failure associated with I-R injury. HBOT reversibly inhibits the ß2 integrins, therefore inhibiting the neutrophil-endothelial adhesion.

Complications, side effects and contraindications

These have been rare in my experience. Although any therapeutic application of hyperbaric oxygenation is associated intrinsically with the potential for producing mild to severe side effects, the appropriate use of hyperoxia is one of the safest therapeutics available.

CNS oxygen toxicity can occur at levels of 2.2 ATA for one to two hours in dogs. Signs include convulsions, vomiting, muscle twitching and acting in a confused state.

Therefore I always recommend staying at 2 ATA or below for all treatments.

Pulmonary oxygen toxicity can occur, but usually is associated only with prolonged HBOT (> 4-6 hours at 2.0 ATA).

Look for clinical signs of difficult breathing, and difficulties inhaling. Possible causes for pulmonary toxicity include thickening of the alveolar membrane and pulmonary surfactant changes. Prevention of side effects includes the maintaining of the pressures below 2.2 ATA and no 100 percent oxygen at pressures greater than 3 ATA.

Contraindications for HBOT are unknown for animals, but may include untreated and un-resolving pneumothorax, high fevers (predisposed to oxygen toxicity), emphysema and upper airway occlusions.

Accepted indications for HBOT: Air or gas embolism; carbon monoxide poisoning; clostridial myositis and myonecrosis; crush injury, compartment syndrome and other acute ischemias; decompression sickness; enhancement of healing in selected wounds; exceptional anemia; intracranial abscess; necrotizing soft-tissue infections; refractory osteomyelitis; delayed radiation injury (soft-tissue and bony necrosis); skin grafts and flaps; thermal burns.

These are all the indications that are "accepted by insurance" in human medicine.

Use of HBOT in veterinary medicine is in its infancy. Veterinary clinics have treated more than 10,000 patients in hyperbaric oxygen chambers.

Patients included pregnant animals as well as neonatal foals, puppies and kittens, dogs and cats, horses, cattle, sheep, pigs, rabbits and other non-domestic animals, birds, geese and ducks, with no adverse effects noted. Patients have been pressurized from 1.4 to 2 ATA and received 40 percent to 100 percent oxygen, with treatment times ranging from 45 to 90 minutes at treatment pressure (depth).

I have used HBO as adjunctive therapy for severe wounds, burns, septic cellulitis, necrotizing fasciitis, obstructive biliary disease, peritonitis, fungal disease (pneumonia), thermal burns, carbon monoxide, smoke inhalation; closed head injuries, ileus; CNS edema from acute disc rupture, spinal-cord injury, fibrocartilagenous embolism, perinatal asphyxia, post-delivery cerebral palsy, peripheral neuropathies, sports injuries (tendon injury, fractures, joint injuries), post-operative swelling, cellulitis, poisonous snake-bite envenomation, spider bite, compartment syndrome, ischemic injuries, sepsis, pancreatitis, bowel obstruction, thrombo-embolism, severe wound infections, gas gangrene, clostridial cellulitis, post cardiac arrest and resuscitation, clostridial pneumonia, periostitis, osteomylitis, aspergellosis, coccidiomycosis, delayed fracture healing.

With all of these conditions, if treated within the period noted before cell death and necrosis have occurred, recovery has been enhanced. It was noted in these patients, numbering more than 2,000, that apparent pain relief is one of the first effects observed, followed by decreased edema in those conditions where outward swelling is observed (e.g., snake-bite envenomation and postoperatively following stifle surgery).

Further research is needed in veterinary medicine to see if the routine addition of HBOT to standard measures may improve clinical outcomes.

Basic treatment protocol

First the patient is examined to ensure the animal does not have a pneumothorax, IV catheters are flushed and wrapped securely and all collars are removed. Then the patient is placed into the chamber, the door is closed and the high-flow oxygen is begun with the evacuation ports open.

After the specified time to fill the chamber with oxygen, the evaluation port is closed and oxygen infusion into the chamber continues until the specified pressure is reached. This usually is between 1.3 ATA (4.5 psi) and 2 ATA (14.7 psi).

During the next 45 to 90 minutes, oxygen flow continues at a slower rate to maintain the desired pressure yet allow enough effluent flow to prevent CO2 build-up (generally noted to be the same amount to prevent water vapor steaming on the inside viewing port of the chamber).

When the treatment time is up, the evacuation port is opened widely. the oxygen supply turned off. allowing pressure to fall back to normal and the chamber door is opened.

For most conditions, a small series of treatments is ideal, but even one or two treatment sessions is preferable to none at all.

Equipment costs, fees

The current cost for a low-pressure soft chamber, 25 to 33 inches in diameter and 7 feet long, plus the oxygen generator and air compressors needed for filling, is about $20,000 new and at least several thousand dollars if used.

High-pressure (standard HBOT) chambers are made of metal or metal and acrylic and cost $45,000 to $100,000 or more new and $25,000 to $35,000 used. They are 25 to 36 inches in diameter and 4 to 7 feet long.

HBOT chambers also are available for horses.

A single hour-long HBOT session averages $400 to $500 per treatment for horses and $100 to $150 per treatment for small animals.

The number of treatments and the expense depends on the disease and how long it was present.

For example, a severe case of osteomyelitis might require 20 treatments, while a snake-bite envenomation and early necrosis may take only two treatments. Most cases show clinical improvement after only one or two treatments.

HBOT has been judged beneficial in 85 percent of patients. For almost all disease processes, a course of two to eight treatments is ideal to set in motion the healing and reparative effects of the HBOT.

For suppliers and installers of of hyperbaric chambers in the veterinary market, please check the DVM Newsmagazine Web site, www.dvm360.com.

Closing statement

I cannot think of any ischemic disease or injury that will not benefit from the use of either low- or high-pressure hyperbaric oxygen therapy.

In Russia they typically use low pressure, and one physician-therapist from Moscow told me, "You in the United States are using too much pressure." She said there are physiological effects of just the pressure on tissues that make a significant effect on all injured or diseased tissues, and that is principally due to its effect on one of the effects of inflammation, that of edema.

I took her words seriously and have now treated more than 2,000 animals with the low-pressure chamber alone. The results have been phenomenal.

His includes its use even in such severe conditions as spinal-cord injury with a resultant fracture luxation at L2-L3; the patient had no deep-pain sensation 24 hours post-injury.

The patient, a Jack Russell Terrier that was stuck by an SUV, received multiple treatments over four days after its spine was decompressed and stabilized with two plates at the time of his admission (the day following the trauma).

It made a complete neurological recovery.

I highly encourage all colleagues to consider adding HBOT to their hospitals. The low-pressure chambers can be set up easily at less cost. The high-pressure ones require more set-up and expense, but provide exceptional therapy for ischemic injury or disease. Even the parvovirus puppy responds dramatically with one treatment (probably because the hyperbaric oxygen decreases edema within the intestinal tract and enhances viral clearance by a variety of mechanisms that are associated with HBOT).

For more information, visit www.dvm360.com. (In the July 2007 issue of DVM Newsmagazine, see the article, "Use of hyperbaric oxygen therapy in small-animal medicine.")

Also, visit the Veterinary Hyperbaric Medicine Society at www.vet.utk.edu/vhms/ or get information via a CD Powerpoint presentation and manuscript on my Web site, www.dtimcrowe.com.

For a history of hyperbaric oxygen therapy, a list of suggested readings and names of some suppliers, go to www.dvm360.com and search for HBOT.

Dr. Crowe is chief of staff at Pet Emergency Clinics and Specialty Hospital, Ventura, Calif.