HBO and burns

Historical development

The potential beneficial effects of HBO in the treatment of patients, who are suffering from burns, has been first recognized by Ikeda et al. [1] in1968 when he treated several patients after a coal-mining accident suffering from carbon monoxide poisoning (CO-intox) and thermal burns. Patients suffering from CO-intoxication and thermal burns where treated with adjunctive HBO treatment. Although they were basically more severely injured than the patients injured at the same accident but did not have a CO-intox the “HBO-group” had markedly faster wound healing and less length of hospital stay (LHOS). Several animal studies were carried out showing faster wound healing after HBO treatment than the controls. In 1960 Gruber et al. [2] could proof that the tissue around full thickness burns is hypoxic and that by administering HBO the oxygen partial pressure could be raised. In 1988, the Committee on Hyperbaric Oxygenation of the Undersea and Hyperbaric Medical Society removed thermal burn from a special considerations category and recommended that hyperbaric oxygen treatment of patients with thermal burns should be reimbursed by third-party carriers. Since then several case reports and cohort-studies have been published, most of them showing faster wound healing, less edema and less operations and shorter LHOS. However an adequately powered prospect-

Marc G. Jeschke et al. (eds.), Handbook of Burns

ive randomized controlled study as requested by EBM is still missing [3].

Scientific background supporting the use of HBO in thermal burns

The mechanism of action of HBO is very simple. As the ambient pressure limits the maximal partial pressure of a gas the maximal O2 pressure in normobaric conditions is 1 bar (760 mmHg). By increasing the ambient pressure up to a maximum of 3 bars (2 280 mmHg) the arterial O2 partial is increased in a way that only every fourth capillary is needed to provide sufficient tissue oxygen partial pressure (Figs. 1 and 2).

Therefore the theoretical background for using hyperbaric oxygen in thermal burns is to provide the oxygen necessary to maintain viability in critically perfused zones. Moreover it has been assumed to maintain microvascular integrity and minimize edema. The mechanisms suggested include the preservation of ATP in cell membranes, as first demonstrated by Nylander et al. [4] and confirmed by Yamaguchi et al. [5].

In summary as traditional mechanism of action for HBO has been postulated that it improves the physiological state of hypoperfused, hypoxic tissues by providing metabolic substrate and by limiting edema formation due to hyperoxic vasoconstriction. These assumptions have been supported by controlled animal studies showing a reduction of 30 per-

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Fig. 1. Due to the increase from 1 to 3bar the diffusion rate is increased and the diffusion distance within the tissue is xtended. The oxygen-diffusion distance in the tissue (Krogh cylinder model) increases through this up to the 4-fold radius and reaches a multiple of the normal tissue volume. Subsequently can also maintain areas with otherwise disturbed oxygen care, on the basis of lack blood circulation or increase of the diffusion opposition (e. g. desolate-conditioned), a normal oxygen care of the cells

cent in the extravasations of fluid in the first 24 post- burn-hours. HBO was also able to reduce the generalized edema that occurs in burns [6]. Similarly biopsies of burned animals have shown progression to full-thickness injury in controls, while there is preservation of capillary patency and dermal elements in animals treated with HBO [6–8].

Main criticism has been that intermittent rise of O2 offers in best-case only transient improvements. However, recent findings demonstrate a more sophisticated basis that is focused on oxidative stress. Whereas toxicity of O2 is based on overshooting free radical formation appropriate intracellular levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a vital role in regulating many biological processes [9 –11]. ROS are generated as natural by-products of metabolism and it is generally accepted that agents such as superoxide, hydrogen peroxide, and hydroxyl are elevated in tissues as a consequence of exposure to HBO. RNS such as nitric oxide (·NO) and products generated by reactions between ROS and ·NO, or its oxidation products such as nitrite, are as well elevated by HBO. HBO is able to activate nitric oxide synthase enzymes and it can also increase pro-

Fig. 2. HBO Treatment Table for burn wounds

duction of RNS capable of nitrosylation reactions through involvement of enzymes such as myeloperoxidase [12 –14].

Moreover, HBO seems to have ideal properties for the treatment of burned patients as it reduces circulating levels of proinflammatory cytokines under stress conditions (e. g. endotoxin challenge), without altering circulating levels of insulin, insulin-like growth factors, or proinflammatory cytokines [15, 16]. Consequently HBO is reported to decrease the inflammatory response while significantly improving the microvasculature [7].

HBO therapy has been claimed to be effective in burn-wound sepsis in which the chief offending pathogen is Pseudomonas aeruginosa [17–19].

In a large non-randomized study Niu et al. found that in patients with 35 to 75 percent total body surface area burns, 6.8 percent of the 117 patients in the hyperbaric oxygen group died versus 14.8 percent deaths in the 169 controls (p = 0 028). The investigators also noted that fluid resuscitation could be achieved more rapidly, nasogastric feeding could be initiated in the second 24 hours or earlier, and there was an acceleration of reepithelialization. The average number of hospital days in the same high-risk group was 47 in the hyperbaric oxygen-treated group and 59 in the controls. However, this difference was not statistically significant [20].

In a small control study in humans, Hart et al. 61 found that using a two-way (air versus oxygen) fact-

orial analysis of variance, the mean healing time in the controls was 43.8 days, whereas it was 19.7 days in a HBO group (p > 0 005) [21].

More recently, Cianci et al. [22] demonstrated that adjunctive hyperbaric oxygen therapy reduced the mean length of hospitalization in patients with 18 to 39 percent total body surface area bums from 33 to 20.8 days (p = 0 012). In another study published by Cianci et al., the average cost savings per patient was $10,850 when using hyperbaric oxygen. Hyperbaric oxygen costs averaged $8200, which is included in the total hospital charge [23].

Cianci et al. also looked into the effect of hyperbaric oxygen on the number of surgeries required in bum treatment. In patients burned over 40 to 80 percent of their total body surface area, matched for age and also percentage and thickness of burn, the number of surgeries required fell from 8 to 3.7 when hyperbaric oxygen was used (p = 0 041) [24].

In a negative clinical study by Waisbren et al. in which hyperbaric oxygen treatment of severe burns failed to reveal either a deleterious or salutary effect on mortality, grafting was reduced by 75 percent in the HBO group (p > 0.01) [25].

In a case series Baiba et al. published the course of ten patients suffering from burns and severe COintox showing major complications during the course of treatment:

two patients suffered from eustachian tube occlusion, two patients had episodes of aspiration, one patient had seizure activity, and severe hypocalcemia developed in another. Progressive hypovolemia was seen in three patients; respiratory acidosis was evident in four [26]. However in a letter to the editor Noble et al. explained the probable reason for these findings: “However, when critically ill patients are transported to a chamber outside the hospital and left without physician supervision for up to five hours as in the Heimbach series, these toxicities and complications are more likely co be experienced” [27].

Contraindications for the use of HBO

Untreated pneumothorax is an absolute contraindication to hyperbaric oxygen, as is concurrent therapy with doxorubicin (Adriamycin), cis-platinum, and disulfiram (Antabuse). Doxorubicin has been shown

to produce a high mortality when combined with hyperbaric oxygen in animals. Cis-Platinum given concomitantly with hyperbaric oxygen decreases the strength of healing incisions, while disulfiram blocks production of superoxide dismutase. Superoxide dismutase is protective against damage from high partial pressures of oxygen. All other contraindications are relative, such as upper respiratory infections, which make clearing the ears and sinuses difficult, low seizure threshold, which can be mitigated by anticonvulsants, emphysema with CO2 retention, where low arterial PO2 triggers breathing, high fevers, which lower seizure threshold, and congenital spherocytosis, which may provoke hemolysis [28].

Understanding the pathophysiology of burns and HBO is necessary to choose the right patient and the right time for treatment. In case both is available there is still the need for a team capable of providing the same level of care during the HBO treatment like on the intensive care unit (ICU). This limits the number of centers worldwide being currently able to provide a benefit for critically burned patients by administering adjuvant HBO therapy. However patients suffering from minor burns but having concomitant diseases like diabetes or other microvascular diseases leading to a delayed wound healing are likely to profit from adjuvant HBO therapy as they do not need special intensive care during the HBO treatment.

Conclusion

Being aware of the small number of centers being able to maintain the level of treatment in critically burned patients during the HBO session and the large number of patients necessary to conduct a prospective randomized controlled study we must be aware that such a study will probably not be conducted within the next future. On the other hand HBO has been shown to promote wound healing and everybody treating burned patients is aware of the fact that the time until burn wounds are closed is critical – specially in patients with major burns (Figs. 3 and 4). Therefore burned patients will profit from every intervention shortening healing time. However it must be granted that the intervention itself does not put any harm to the patient. Therefore the right time for treatment and the right environment to ensure optimal transport-

Fig. 3. Burn patient with additional inhalation injury treated in a HBO chamber

conditions and level of care during the HBO session is crucial – otherwise the overall effect will be similar to the Heimbachs series cited above.

As we had good results treating burned patients with HBO we can recommend adjunctive HBO therapy in patients with thermal injury.

At the burn center in Vienna the HBO program was initiated in 2003 starting with non-burned patients – mildly burned patients and finally after 1 year training severely burned patients. Assistant Professor Andrew Donner MD (+ 2005) who contributed substantially to the HBO-program also played an important role in the successful implementation of this therapeutic option – therefore we want to dedicate this chapter to him.

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Fig. 4. Burn patient treated in multiplace HBO chamber

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Correspondence: Harald Andel, M. D., Ph. D., M. Sc., Department of Anaesthesie and General Intensive Care, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria, E-mail: harald-lothar.andel@meduniwien.ac.at