Veterinary Hyperbaric
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Review of Hyperbaric Medicine

Nathan Slovis DVM, Dipl. ACVIM
Hagyard Equine Medical Institute
McGee Medical Center, 4250 Iron Works Pike, Lexington KY 40511
nmslovis@yahoo.com

Take Home Message:

Hyperbaric oxygen (HBO) therapy proves to be an excellent adjunctive therapy for a variety of medical/surgical disorders because it works through multiple mechanisms of action. HBO appears to be a promising adjunctive medication for a variety of equine disorders.

Introduction:

Hyperbaric oxygen (HBO) is a high dose oxygen inhalation therapy that is achieved by having the patient breathe 100 percent oxygen inside a pressurized hyperbaric chamber. The delivery of oxygen to the tissues is through respiration because there is insufficient absorption of oxygen through the skin.1,2 The principal source of oxygen transport is the red blood cell in the form of oxyhemoglobin (Hbg02). At normal sea level pressure where alveolar oxygen pressure is at 100 mmHg, hemoglobin is about 97% saturated and yields an oxygen content of about 19.8ml of oxygen per dl blood. When alveolar oxygen pressure is at 200 mmHg. hemoglobin becomes fully saturated with oxygen.. After hemoglobin is fully saturated, additional oxygen is carried to the tissues in physical solution in plasma. HBO does not significantly increase hemoglobin’s transport of oxygen, but elevates the capillary plasma oxygen transport.3,4 The benefits of HBO are derived from both the physiological and pharmacological effects of high dose oxygen. HBO is based on two physical factors related to the hyperbaric environment: mechanical effects of pressure and increased oxygenation of tissues. This paper reviews scientific and clinical literature regarding hyperbaric oxygen therapy in lab animals and humans and introduces to the practitioner the potential use of this treatment modality for our equine patient.

History of Hyperbaric Chambers

In 1662, a British clergyman, Henshaw without scientific basis thought it would be a good idea to raise the ambient pressure around a patient for therapeutic purposes. He later built the “domicilium” which was a sealed chamber that could either raise of lower pressure depending on adjustment of the valves. Henshaw reported that acute diseases of all kinds would respond to increased ambient pressure. In the 19th century following Henshaw’s ideology, pneumatic institutes began to sprawl around the European continent. These large chambers where often able to accommodate more than 1 person and could sustain pressures of two or more atmospheres. These pneumatic institutes started to rival the popularity of the mineral water spas.5

It was not until 1879 that semi-scientific efforts where made in regards to the air. A French surgeon names Fontaine built a mobile operating room on wheels that could be pressurized. He performed over 20 surgeries in the unit using nitric oxide as the anesthetic. Dr. Fontaine noted that he could achieve deep surgical anesthesia because it increased the effective percentage of nitrous oxide in the patients body accompanied by a higher oxygen partial pressure (IE: compressed air at two atmospheres given an effective level of 42% inhaled oxygen). Dr. Fontaine also noted that hernias were seen to reduce more easily (Boyle’s law- Pressure volume relationship) and the patients were not their normal cyanotic color when coming out of anesthesia. 5

Compressed air therapy was first introduced into the United States in 1871 by Dr. J.L. Corning . In the early 1900’s Dr. Orville Cunnigham a professor of anesthesia at the University of Kansas noted that patients with heart disease and other circulatory disorders had difficulties acclimating at high altitudes when compared to sea level. With these observations Dr. Cunnigham postulated that increased atmospheric pressure would be beneficial for patients with heart disease. To test his hypothesis (1918) he placed a young resident physician suffering from the flu into a chamber used for animal studies. The physician was successfully oxygenated during his hypoxic crisis when compressed to 2 ATM. Dr. Cunningham realizing that his concepts were sound built a 88-foot- long chamber, 10 feet in diameter in Kansas City and began treating a multitude of diseases, most of them without scientific rationale.5 The AMA and the Cleveland Medical Society, failing to receive any scientific evidence for his rationale, forced him to close his facility in 1930.

The advent of the use of hyperbaric oxygen in modern clinical medicine began in 1955 with the work of Churchhill-Davis, who helped to attenuate the effects of radiation therapy in cancer patients using high oxygen environments. That same year Dr.Ite Boerma, a professor of Surgery at the University of Amsterdam in Holland, proposed using hyperbaric oxygen (HBO) in cardiac surgery to help prolong the patient’s tolerance to circulatory arrest. He conducted surgical operations under pressure including surgical corrections of transposition of the great vessels, tetralogy of Fallot and pulmonic stenosis. In 1960 Dr. Boerma published a study on “life without blood”. The study involved exsanguinating pigs and removing their erythrocytes before exposing them to 3 ATM of HBO. These pigs were noted to have sufficient oxygen in the plasma to sustain life when they where given HBO at 3 ata.6

It is frequently been said that the history of “hyperbaric oxygenation” goes back “over 300 years” probably referring to the work of Henshaw. This is incorrect, as oxygen was not discovered until 1775 by Priestly. All the early chambers were pressurized with compressed air, and oxygen was not a consideration. Clinical hyperbaric oxygen goes back only about 50 years, beginning with the work of Churchill-Davidson and Boerma.5

In 1967 the Undersea Medical Society (UMS) was founded by six U.S. Navy Diving and Submarine medical officers as an organization dedicated to diving and undersea medicine. The UMS was later renamed Undersea and Hyperbaric Medical Society(UHMS) in 1986. This professional society was established for those practicing hyperbaric medicine or diving medicine. They are responsible for publishing approved indication for HBO treatments.

The American Board of Preventative Medicine started to offer board certification in Undersea and Hyperbaric Medicine in 1999 which was later co-sponsored by the American Board of Emergency Medicine in 2001. The National Board on Diving and Hyperbaric Medical Technology offers board certification in Hyperbaric Technology in 1991 and for hyperbaric nursing in 1995.

There are currently numerous fellowships available in the United States in Clinical Hyperbaric Medicine.

Physiological Effects

Pressure of gases is defined as a force per unit area. The pressure of one atmosphere (ATM) is equal to 14.7 pounds per square inch(PSI). This pressure results from the weight of the air producing a force on the surface of the earth. Weathermen usually refer to this pressure as “barometric pressure” which is measured in inches of mercury (29.9 inches of mercury = 760 mm mercury = 1 atmosphere). The term “atmosphere’s” when used 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 exampled by the fact that 33 feet is equal to a gauge 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)7

 

ABSOLUTE PRESSURES
GAUGE PRESSURES
ATA mmHg
1 760
2 1520
3 2280
4 3040
FSW PSA
0 0
33 14.7
66 29.4
99 44.1

 

Terms applicable to hyperbaric exposures 8

  1. Surface: The normal atmospheric pressure from which a hyperbaric exposure begins. (IE: Ground level or sea level)
  2. Dive: any exposure to hyperbaric pressure, either in water or in a chamber
  3. Descent: Increase pressure, either by going down under water or by adding pressure to a chamber. May be referred to as compression
  4. Depth: The maximum pressure achieved during a hyperbaric exposure. Typically measured in ATA, feet of sea water (fsw) or pounds per square inch (psi) Also referred as treatment pressure
  5. Ascend: Decrease in pressure. May be referred to as decompression

Gas Laws

Boyle’s Law (Table 1) – Pressure-volume relationship. With pressure constant , the volume of 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 and etc. respond to increase 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

Pressure (psi)

Feet sea water

Atmospheres Absolute

Relative Volume

mmHg

14.7

sea level

1 ATA

1

760

29.4

33 fsw

2 ATA

1/2

1520

44.1

66 fsw

3 ATA

1/3

2280

58.8

99 fsw

4 ATA

1/4

3040

73.5

132 fsw

5 ATA

1/5

3800

 

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 Fi02 is the fractional concentration of oxygen expressed as a decimal

Using Daltons law we would be able to determine the PO2 in mmHg in the chamber while breathing 100% oxygen at 66 fsw.
66 fsw = 3 absolute atmospheres

PO2=Ptot X FiO2
PO2=760(3) X 1.0
PO2=2280 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 (P1/P2=A1/A2)

If a carbonated drink contains 20cc of dissolved gas at 2 ATA, How much gas remains in solution when the beverage reaches sea level?

P1/P2=A1/A2

2/1=20/A2

2A2=20

A2= 10cc

Mechanical Effects

Bubbles and gas-containing cavities within the body are subject to the mechanical effects of changing pressure which follows Boyle’s law. Volume is changed in a geometric progression related to pressure change; large reductions take place near the surface, with subsequent reductions becoming smaller at higher pressure (Table 1). These mechanical effects are responsible for unwanted barotraumas that may result in middle-ear squeeze, sinus squeeze, and burst of lung if the patient holds their breath during decompression. If a patient is suffering from gaseous distention of the bowel, compression in the chamber will ease the discomfort while the inhalation of oxygen will form a high gradient for the removal of nitrogen from the distended gut. Gas trapped in the bowel decreases by approximately 50% when a patient breathes oxygen over a 6 hour period at 2 ATM. 3,9,10

Oxygen Solubility

As chamber pressure increases, PO2 in the breathing media also increases. For instance, Using Dalton’s Law , air at sea level pressure (760mm Hg) contains 21% oxygen with a PO2 of 160 mmHg. When the chamber is pressurized with air to 3 ATA PO2 is 479 mmHg which is equivalent of breathing 63% oxygen at sea level. As the chamber is pressurized with air to 5 ATA, PO2 exceeds 798 mm Hg, which is greater oxygen pressure than can be attained breathing 100% oxygen at sea level!


Oxygen is transported by the blood from the lungs into the tissue by two methods: Bound to hemoglobin, and physically dissolved in the plasma. At normal sea level pressure where alveolar oxygen pressure is about 100 mm Hg, hemoglobin is already 97% saturated (Oxyhemoglobin) and yields an oxygen content of about 19.8 ml of oxygen per dl blood. When PAO2 (alveolar oxygen partial pressure) reaches 200mmHg, hemoglobin then becomes fully saturated with oxygen. Therefore further increases in pressure will not increase the amount of oxyhemoglobin, thus oxygen transport via hemoglobin is not improved with hyperbaric oxygen therapy. Instead oxygen is dissolved into the plasma and carried to the tissues in physical solution. A person breathing air at sea level pressure has only 1.5% 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 across4 it. As the chamber is pressurized, the elevated alveolar oxygen tension in the lungs drives oxygen into the plasma of the pulmonary circulation and it’s subsequent transport throughout the body. Unlike hemoglobin saturation, which has an S-shaped curve, the amount of dissolved oxygen increases linearly as PO2 increases.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. The absolute amount of gas varies with different fluids and is determined by the solubility coefficient of gas in fluids, which is temperature dependent. Oxygoen solubility in whole blood at 37oC is 0.0031 ml of O2 per dl 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% 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 1433 mmHg ( 4.4 ml of dissolved oxygen per dl of blood). At 3 ATA provides a PAO2 of about 2200 mmHg and adds about 6.8 ml O2 to each dl of blood. A healthy adult human at rest uses about 6ml of oxygen per dl of circulating blood. Thus HBO 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 pigs life without blood in his study “Life Without Blood”.4,6

Gas Exchange and Oxygen Diffusion

An increase in oxygen tension causes oxygen to diffuse further from the functioning capillaries. Tissue oxygen content depends on 3 factors:

  1. Distance from the functioning capillaries
  2. Oxygen demand of the tissue
  3. he oxygen tension of the capillary

Using the Krogh Erlang mathematical model breathing air at 1 ATA, oxygen diffuses about 64 micrometers (about the thickness of 1 sheet of typing paper) at the arterial end of the capillary. During oxygen breathing at 3 ATA, oxygen diffuses about 250 micrometers (about the thickness of 3 sheets of typing paper).4,11,12,13 In a hypoxic environment HBO may be able to restore P02 to normal or slightly elevated levels (Depends 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. Human 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. Interestingly it has been reported that if oxygen tension is held continuously at 290-560 mm Hg fibroblastic replication was halted.4 When oxygen tension was returned to normal. The replication process continued. Therefore daily high doses is needed to correct the hypoxic environment but must be delivered in an intermittent pattern to avoid possible side effects of the cells.

Therapeutic Effects of HBO

  1. Reverse Hypoxia14
  2. Alter ischemic effect
  3. Influence vascular reactivity
  4. Reduce edema15,16
  • Hyperoxygenation will cause vasoconstriction. Although vasoconstriction may be present there is more oxygen delivered to the tissues.
  1. Modulate nitric oxide production4,17,18
  • An increase of nitric oxide leads to vasodilation while a decrease of nitric oxide (NO) leads to vasoconstriction. Carbon dioxide increases NO production and oxygen decreases NO production by the endothelial cells.
  1. Modify growth factors and cytokine effect by regulating their levels and/or receptors19,20
  • 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 thereby stimulating more rapid development of capillary budding and granulation formation within the wound bed
  1. Induce changes in membrane proteins affecting ion exchange and gaiting mechanisms
  2. Promote cellular proliferation2, 4, 11,12,13
  3. Accelerate collagen deposition
  4. Stimulate capillary budding and arborization
  5. Accelerate microbial oxidative killing
  6. Improve select antibiotic exchange across membranes21,22,23
    1. Anoxia decreases the activity of several antibiotics (aminoglycosides, sulfonamides, fluoroquinolone). By raising the pO2 of ischemic tissue to normoxic levels, may normalize the activity of these antimicrobials. In addition, HBO may potentiate the activity of certain antimicrobials by inhibiting biosynthetic reactions in bacteria.
  7. Interfere with bacterial disease propagation by denaturing toxins
  8. Modulate the immune system response
  9. Enhance oxygen radical scavengers thereby decreasing ischemia-reperfusion injury.24,25
    1. HBOT increases the amount and activity of the free radical scavenger superoxide dismutase
    2. 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. HBO reversibly inhibits the ß2 Integrins therefore inhibiting the neutrophil-endothelial adhesion

Complications and Side effects26

Although any therapeutic application of hyperbaric oxygenation is intrinsically associated with the potential for producing mild to severe side effects, the appropriate use of hyperoxia is one of the safest therapeutics available to the practitioner. CNS oxygen toxicity can occur at levels of 3 ata for 1-2 hours. Signs in humans include convulsions, nausea, dizziness, muscle twitching, anxiety and confusion. Pulmonary oxygen toxicity is usually associated with prolonged exposure to HBO. Onset of symptoms has been noted to occur 4-6 hours at 2.0 ata. Symptoms include dyspnea, shortness of breath, chest tightness and difficulties inhaling a deep breath. Possible causes for pulmonary toxicity include thickening of the alveolar membrane and pulmonary surfactant changes. Prevention of side effects includes removal from the oxygen source when first signs occur and no 100% oxygen at pressures greater than 3 ata.

Contraindications for HBO therapy are unknown for horses but may include untreated pneumothorax, high fevers (predispose to oxygen toxicity), emphysema and upper airway occlusions.

Accepted Indications for HBOT in humans1

  1. Air or gas Embolism
  2. Carbon Monoxide poisoning
  3. Clostridial myositis and myonecrosis
  4. Crush injury, compartment syndrome, and other acute ischemias
  5. Decompression sickness
  6. Enhancement of healing in selected wounds
  7. Exceptional anemia
  8. Intracranial abscess
  9. Necrotizing soft tissue infections
  10. Refractory Osteomyelitis
  11. Delayed radiation injury (soft tissue and bony necrosis)
  12. Skin grafts and flaps
  13. Thermal burns

The use of HBO and veterinary medicine is in its infancy. Our clinic has currently treated more than 100 patients in our hyperbaric oxygen chamber. Patients included pregnant animals as well as neonatal foals with no adverse effects noted. Patients have been pressurized from 2 to 3 ata ranging from 60-90 minutes at treatment pressure (depth). We have used HBO as adjunctive therapy for:

  • Fungal disease (Fungal Pneumonia)
  • Thermal burns, carbon monoxide, smoke inhalation
  • Closed head injuries
  • Ileus
  • CNS edema/perinatal asphyxia
  • Peripheral neuropathies
  • Sports injuries (Exertional rhabdomyolysis)
  • Cellulitis, compartment syndrome
  • Ischemic injuries (Laminitis)

In carefully selected patients, the addition of HBO therapy to standard measures may improve clinical outcomes. Further research is needed in the field of equine HBO medicine.

The current cost for HBO is $400-500 per treatment. For example an osteomyelitis case may take 20-25 treatments while an exertional rhabdomyolysis may take only 2 or 3 treatments.

References:

  1. Feldmeier JJ. Hyperbaric Oxygen Therapy 2003: Indications & Results. The Hyperbaric Oxygen Therapy Committee Report. Kensington, MD: Undersea & Hyperbaric Medical Society, 2003
  2. Gimbel ML, Hunt TK. Wound healing and hyperbaric oxygenation. In EP Kindwall (ed), Hyperbaric Medicine Practice. Flagstaff, AZ: Best Publishing (2002); pp 169-204
  3. Hammarlund, C. The Physiologic effects of hyperbaric oxygen. In EP Kindwall (ed), Hyperbaric Medicine Practice. Flagstaff, AZ: Best Publishing (2002); pp 37-68
  4. Sheffield PJ, Smith AP. Physiological and pharmacological basis of hyperbaric oxygen therapy. In DJ Bakker (ed) Hyperbaric Surgery: Perioperative Care. Flagstaff, AZ: Best Publishing (2002); pp 63-110
  5. Kindwall EP. A History of hyperbaric medicine. In EP Kindwall (ed), Hyperbaric Medicine Practice. Flagstaff, AZ: Best Publishing (2002); pp 1-20
  6. Boerma I, Meyne NG, Brummelkamp WH, et al. Life without blood: A study of the influence of high atmospheric pressure and hypothermia on dilution of blood. J Cardiovascular Surgery 1960; 1:133-146
  7. Sheffield PJ. Measuring Tissue Oxygenation. In Davis JC, Hunt TK Problem Wounds: Role of Oxygen, New York: Elsevier, 1988; 17-51
  8. Sheffield PJ. Tissue oxygen measurements with respect to soft tissue wound healing with normobaric and hyperbaric oxygen. Hyperbaric Oxygen Review 1985; 6 (1): 18-46
  9. Cross FS. Effects of increased atmospheric pressures and the inhalation of 95% oxygen and helium oxygen mixtures on the viability of the bowel wall and the absorption of gas in closed loop obstructions. Surgery. 1954;36:1001-1026
  10. Cross FS, Wangensteen OH. Effect of increased atmospheric pressures on the viability of the bowel wall and the absorption of gas in closed loop obstructions. Surg Forum. 1952;3:111-116
  11. Hunt TK, MP Pai . Effect of varying ambient oxygen tensions on wound metabolism and collagen synthesis. Surgery, Gynecol. And Obstet. 1977; 135:561-567
  12. Hunt TK, J Niinikoski, BH Zederfeldt. Oxygen in wound healing enhancement: Cellular effects of Oxygen, In Hyper Baric Therapy JC Davis and TK Hunt (eds) Bethesda: The Undersea Medical Society, 1977; 111-122
  13. Niinikoski J. Effect of oxygen supply on wound healing and formation of experimental granulation tissue. Acta Physiol Scand Suppl 1969; 334:1
  14. Bouachour G, Cronier P, Gouello JP et al. Hyperbaric oxygen therapy in the management of crush injuries: a randomized double blind placebo-controlled clinical trial. J. Trauma. 1996;41:333-339
  15. Nylander G, Nordstrom H and Eriksson E. Effects of hyperbaric oxygen on edema formation after a scald burn. Burns, 1984:10(3): 193-196
  16. Nylander G, Lewis DH, Nordstrom H. R. Reduction of post ischemic edema with hyperbaric oxygen. Plast. Reconstr. Surg. 1985;76: 596-601
  17. Elayan, Ikram M, Milton J. Effect of hyperbaric oxygen treatment on nitric oxide and oxygen free radicals in rat brain. J Neurophysiology. 2000; 83: 2022-2029
  18. Oury TD, Ho Y, Piantadosi CA. Extracellular superoxide dismutase, nitric oxide, and central nervous system O2 toxicity. Proceedings of the National Academy of Sciences 1992;89:9715-9719
  19. Zhao LL, Davidson JD, Wee SC. Effect of hyperbaric oxygen and growth factors on rabbit ear ischemic ulcers. Int J Radiat Oncol Biol Phys 1998 Jan 1; 40(1): 189-196
  20. Wang X, Ding I, Xie H. Hyperbaric oxygen and basic fibroblast growth factor promote growth of irradiated bone. Growth Factors 1995;12(1): 29-35
  21. Pakman LM. Inhibition of Pseudomonas aeruginosa by hyperbaric oxygen. I. Sulfonamide activity enhancement and reversal. Infect Immun. 1971;4:479-487
  22. Park MK, Muhvich KH, Myers RAM. Hyperoxia prolongs the aminoglycoside-induced post antibiotic effect in pseudomonas aeruginosa. Antimicrob Agents Chemother. 1991;35:691-695
  23. Park MK. Effects of hyperbaric oxygen in infectious diseases. Basic Mechanisms. In EP Kindwall (ed), Hyperbaric Medicine Practice. Flagstaff, AZ: Best Publishing (2002); pp 205-244
  24. Thom SR, Mendiguren I, Hardy K, Bolotin T. Inhibition of human neutrophil beta2-integrin-dependent adherence by hyperbaric O2. Am J Physiol. 1997;26:82-86
  25. Zamboni WA, Wong HP. Effect of hyperbaric oxygen on neutrophil concentration and pulmonary sequestration in reperfusion injury. Arch Surg 1996;131:756-760
  26. Sheffield JC, Sheffield PJ, Ziemba AL. Complications rates of HBO treatments: a 21-year analysis. Proceedings of XIV International Congress on Hyperbaric Medicine, Flagstaff, AZ: Best Publishing, 2002

 

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