What are the Contraindications, Complications and Side Effects?

Hyperbaric oxygen therapy is one of the most benign medical treatments routinely carried out in hospitals; it has few side effects that are generally easily dealt with during treatment. Notwithstanding this, certain pre-existing conditions or concurrent therapies may give rise to absolute or relative contraindications and/or complications. This is why it so important for us to review the patient's medical records and, if necessary, discuss the patient with you as part of our initial assessment prior to acceptance into the program. The information concerning absolute and relative contraindications given below has been summarized for this document; it is also subject to change as more data become available (Kindwall and Whelan, 2002). If there are any uncertainties concerning individual patients please contact the facility for more information or talk to one of our hyperbaric physicians. Contact information is given on the title page at the beginning of this document.

Absolute contraindications

Untreated Pneumothorax - An untreated pneumothorax is considered the only absolute contraindication. In a monoplace chamber this is because it can develop into a tension pneumothorax and make depressurization dangerous and potentially life-threatening. Based on emerging clinical need such patients should be transferred to a multiplace facility. A chest drain should always be established before the patient enters the chamber. Treatment should be delayed in elective patients with a pre-existing pneumothorax until the latter has been resolved.

Relative Contraindications

Bleomycin - This drug is widely documented for its action against a variety of tumors. Studies indicated that pulmonary toxicity is a dose limiting factor and several had indicated that even moderate increases in FIO2 may cause severe interstitial pneumonitis or even death in patients undergoing surgery years after Bleomycin therapy. (Goldiner et al, 1978, 1979; Gilson & Sahn, 1985) A personal communication from Dr. Eric Kindwall advises that newly emerging data suggest patients with a history of Bleomycin therapy may be treated with caution. The status of Bleo has been changed in the third edition of Hyperbaric Medicine Practice published in 2012.

Cis-Platinum - This drug is used in a number of cancers because it disrupts DNA synthesis. It also delays fibroblast proliferation and collagen synthesis. A study to see if HBO2 might mitigate this effect actually found that the breaking strength of wounds was adversely affected. (Nemiroff,1988). Patients with chronic wounds who are receiving cis-platinum will not be helped and could be made worse by HBO2. If wound strength is not an issue, such as in emergent carbon monoxide poisoning, then HBO2 treatment may be administered based on the emergency indication.

Doxorubicin (Adriamycin®) - Research has shown that when combined with HBO2 this chemotherapeutic drug caused 87% mortality in rats, possibly due to cardiac toxicity. While doxorubicin is probably inactivated and cleared from the tissues within 24 hours it is prudent to wait for several days before beginning hyperbaric therapy. Once the drug therapy has been halted, HBO2 has been successfully used as an adjunct to help heal tissue necrosis secondary to doxorubicin extravasation (Upton et al, 1986).

Disulfiram (Antabuse®) - This drug has been shown to block both pulmonary and central nervous system toxicity. It has also been shown to block the production of the free radical scavenger superoxide dismutase (SOD), which is the primary defense against oxygen toxicity. A single exposure in an emergency situation such as carbon monoxide poisoning can be carried out safely, however, subsequent treatments in the absence of SOD would have unknown consequences. While there have been no reports of negative reactions to Disulfiram and HBO2 in humans, it is nonetheless considered to be contraindicated in patients having multiple treatments (Heikkila et al, 1976)

Mafenide Acetate (Sulfamylon®) - This antibacterial drug was developed for topical application and is still widely used in burns patients. It is a carbon anhydrase inhibitor, which tends to cause a build-up of CO2 and consequent peripheral vasodilatation. When used with HBO2, which is a vasoconstrictor, the results are worse than with either agent alone. Mafenide cream must be carefully and thoroughly removed from the patient prior to hyperbaric treatment. Silver sulfadiazene (Silvadene®) can be safely substituted.

Conditions formerly contraindicated

There are a number of conditions previously listed as contraindications that current research has shown are in fact treatable. Unless new data show otherwise, the conditions listed below are no longer considered to be contraindicated.

Implanted Pacemakers - Early pacemakers had void spaces; consequently they did not tolerate pressure change well, and became unstable and unreliable. Modern devices appear to be more pressure tolerant and many are function-tested under pressure, although the test pressures and procedures vary. The maximum pressure used in clinical hyperbaric oxygen therapy is 3 atm abs, with 2.5 atm being the typical maximum for elective wound-care patients. Details of pressure testing should be provided on the manufacturer safety data sheets (MSDS) supplied with the pacemaker. It is important that the manufacturer, type and serial number of the pacemaker fitted is clearly identified in the patient's notes. When data is available attesting to pressure testing and functional stability within the maximum 3 atm abs pressure range, treatment is no longer contraindicated. If, however, no data is readily available treatment cannot proceed until suitability has been confirmed.

Known Malignancies - It has long been a concern that occult metastases which had outgrown their blood supply would be stimulated by the growth of new blood vessels following exposure to HBO2. As hyperbaric units began treating increasing numbers of patients with radionecrosis, some were found to have residual tumor. In these patients, it was discovered that while the radionecrotic areas improved dramatically, zones containing tumor were unchanged. Subsequent studies have shown that HBO2 does not increase the rate of tumor growth (Granström et al, 1990; Marx & Johnson, 1988; Nemiroff et al, 1988; Sklizovic et al, 1993). Following thorough review of the literature Feldmeier and colleagues have reported that HBO2 does not enhance tumor growth and, in some cases actually produced a reduction in growth or rates of metastases (Feldmeier et al, 1994; Feldmeier, 2001; Feldmeier et al, 2003).

Pregnancy - Since the early 1950's it has been known that extended exposure to high concentrations of oxygen produces retrolental fibroplasia or retinopathy in newborns treated in incubators. In addition, as closure of the patent ductus arteriosus is stimulated by increased arterial PO2, there were concerns that potentially fatal intrauterine closure of the ductus could occur. Based on these concerns it was considered that short-term exposure of pregnant women to HBO2 should be contraindicated.

Research carried out in Russia on more than 700 women treated during all stages of gestation for hypoxemia secondary to conditions such as congenital heart defects, mitral insufficiency, habitual abortion, diabetes and toxemia; and subsequent clinical experience, has shown no maternal or fetal complications or mortality. Some babies have also been delivered in a hyperbaric chamber. (Aksenova et al, 1979; Molzhaninov et al, 1981, Pobedinsky et al, 1981, Stepanyants et al, 1981; Vanina et al, 1981; Proshina 1983). Further, it has now been established that 12 continuous hours of elevated PO2 is required to initiate closure of the patent ductus. On this basis, HBO2 is no longer considered to be contraindicated in the emergent treatment of the pregnant patient (VanHoesen et al, 1989). In addition, while premature infants may still be at increased risk, treatment of full-term babies has been shown to be safe.

It is important to be aware of the difference between HBO2 and scuba diving. As described in section 11.4, the volume of dissolved nitrogen carried by a patient undergoing hyperbaric oxygen therapy is being reduced throughout an exposure whereas the scuba diver is taking it up. Nitrogen forms bubbles in the bloodstream even during normal decompression, it is believed similar bubbling might also occur in the fetus. While current research is limited, it points to an increased risk of birth defects in infants whose mothers have continued to dive during pregnancy.

Relative Complications

A history of any one or more of the following complications is considered a red flag to possible problem occurring during treatment.

Upper Respiratory Infections and Chronic Sinusitis - Infections of the upper respiratory system and chronic sinusitis make it difficult for a patient to clear his/her ears. For emergent conditions, decongestants may be used or, if necessary, a bilateral myringotomy. With elective patients, it is usually better to withhold treatment for the few days needed to clear the infection.

Seizure Disorders - Patients with a history of seizures or a low seizure threshold may be at greater risk of developing an oxygen seizure during treatment. Based on clinical judgement concerning the need for treatment, this can be managed with anticonvulsants. It is worth noting that our standard treatment protocols include "Air Breaks" which are brief periods during which the concentration of oxygen breathed by the patient is reduced. This significantly reduces the potential for seizure in at-risk patients.

Emphysema with CO2 Retention - Often hypoxemia is the only stimulus to breathe in patients with severe emphysema and COPD because sensitivity to normal levels of CO2 is lost. Such patients may have dramatic reductions in respiratory rate when blood PO2 levels increase as they are pressurized in the hyperbaric chamber. There is currently minimal experience to support treating these patients unless they are intubated and ventilated. Thus, it is a matter of clinical judgement on the risk/benefit of treating elective patients with such respiratory complications.

>High Fevers - Patients with uncontrolled high fevers may have a reduced seizure threshold. In emergent cases, such as gas gangrene or necrotizing fasciitis, where the patient must be treated promptly, fever reducing drugs and hypothermia blankets may be used, with prophylactic anti-convulsants where appropriate. For elective patients there is no clinical justification for commencing treatment until the patient's condition has been resolved.

History of Spontaneous Pneumothorax - While a history of spontaneous pneumothorax is an absolute contraindication to scuba diving, it does not present a major risk in clinical hyperbaric oxygen therapy. Nevertheless, the physician and chamber operators should be aware of the patient's history and be prepared to manage the problem should it develop during treatment. While this most commonly occurs during periods of exercise, particularly that involving the upper body, it can also occur spontaneously during sleep; thus the patient remains at risk even though they are at rest in the chamber.

History of Thoracic Surgery - This is of considerable concern in scuba diving. In hyperbaric oxygen therapy, however, it is less a contraindication and more of a red flag to the fact that potential complications do exist. The primary concern is in patients who have recently had thoracic surgery, such as a pneumonectomy, which has left air trapped in the space formerly occupied by the lung. Typically, such cases would be transferred to multiplace chamber which will make patient management easier. The size of the trapped air space will be reduced during the pressurization phase of the treatment and return to its original size on depressurization to atmospheric pressure, therefore, a chest tube should be inserted to prevent distortion of the thorax and manage changes in gas volume. Over time, the space left by the excised lung fills with fluid which then consolidates. Once the air space is completely cleared there is no longer a risk to treatment.

History of Surgery for Otosclerosis - Current practice is to use a plastic or wire strut to replace the middle ear ossicular conduction chain in preference to stapes mobilization. Failure to equalize the middle ear in these patients may displace or distort the strut with consequent hearing loss, possibly necessitating surgical correction. Prudent practice requires that such patients have pressure equalization tube(s) fitted by an ENT specialist. A history of mastoid or other kinds of ear surgery, or perforated ear drums do not usually present a problem.

Viral Infections - Some authorities suggest that acute viral infections may be exacerbated by HBO2 while clinical experience reported by others suggests no adverse affects. Animal studies have indicated that pulmonary infections may be potentiated by HBO2, perhaps because the pure oxygen further irritates the already inflamed lung. It has been noted that other viral infections such as herpes zoster and herpes simplex types 1 & 2 are not exacerbated by HBO2. Current data suggest that the immune system is not negatively influenced by HBO2 (Feldmeier, 1987); indeed several studies have reported benefit in HIV and AIDS patients. For elective patients it is suggested that treatment be delayed until the viral infection has been cleared.

Congenital Spherocytosis - It has been shown that severe hemolysis may occur when the fragile red cells are exposed to elevated levels of oxygen. Patients have been successfully treated, so this should not deter the treatment of emergent life-threatening conditions such as gas gangrene or necrotizing fasciitis but preparations should be made to manage potential complications.

History of Optic Neuritis - Rarely there have been anecdotal reports of blindness associated with HBO2 in patients with a history of optic neuritis, including some in which the optic neuritis was not active at the time of treatment. These are reported to have recovered spontaneously although there is one case where blindness was permanent. Concern over this condition may be over stated; there have been many thousands of treatments administered to multiple sclerosis patients with a history of optic neuritis, over several years in some cases, with no reports of ophthalmological complications (Kindwall, 1991). Visual changes are not unusual in patients undergoing long-term serial treatment and generally reverse when treatment is stopped for a short time. If changes are detected or reported in patients with a history of optic neuritis, however, HBO2 should be stopped immediately and the patient referred for ophthalmological examination.

Side Effects

In addition to the contraindications and complications mentioned above there are several side effects to treatment. The most prominent of these are trouble with ears during compression, oxygen seizures, and occasional confinement anxiety. The hyperbaric physician responsible for the unit is aware of these and will take them into consideration when screening your patient prior to acceptance into the program. The complications and side effects listed below range from common to extremely rare; all are included for completeness.

We ask that patients advise clinic personnel of any changes in their general health that have occurred since the last treatment. Problems that develop during the course of the treatment program such as influenza, fever, sinusitis, ear infections or colds, may require special attention or cause us to temporarily exclude the patient from treatment.

Barotitis - This is a potentially painful but easily prevented problem. It can lead to barotrauma with extreme pain, progressive damage to the eardrum and possible rupture. Also known as an ear squeeze, it is the most common complication encountered in hyperbaric oxygen therapy. It is caused by an excessive pressure differential across the tympanic membrane during the pressurization phase of treatment. The inner ends of the Eustachian tubes have slit-like openings and they tend to close tightly if the patient does not actively equalize the pressure in the middle ear. The patient should start actively equalizing pressure right from the start of treatment, once the Eustachian tubes close it is impossible to open them using any of the standard techniques. In such a situation the pressure in the chamber will need to be reduced to "pop" them open before continuing the pressurization. Usually, competent patients can easily control this and keep their Eustachian Tubes open simply by swallowing, or executing a Toynbee, Frenzel or Modified Valsalva maneuver to "clear" their ears.

When your patient attends for the first treatment they will be instructed on the management of pressure change including how to execute the equalization maneuvers. Our chamber operators remind them of these simple procedures at the start of each ensuing treatment and work with the patient throughout the compression phase to help avoid problems resulting from the pressure change. Hyperbaric oxygen therapy should be a totally painless procedure and we go out of our way to make sure it is.

There are a number of reasons why otherwise competent patients may be unable clear their ears. It might simply be an inability to learn how to clear their ears, or an inability to open the Eustachian Tube(s) due to scarring (typically in irradiated head and neck patients), allergic rhinitis, or the presence of nasal polyps. It is worth noting that most patients with in-dwelling endotracheal or tracheostomy tubes have difficulty clearing their ears.

There are options in such cases. A myringotomy will be adequate for short-term emergency treatments such as Gas Gangrene, CO Poisoning or Gas Embolism. For longer term elective treatments a tympanostomy may be indicated. Either procedure must be done bi-laterally, a unilateral procedure will be of no help.

A third, non-invasive, option exists for elective patients which will work for most individuals. They are known as "Ear Planes" and are simple silicone inserts that significantly reduce sensitivity to pressure change. They are most commonly used by airline passengers who have equalization problems but work extremely well for hyperbaric patients. They are inexpensive and freely available in most pharmacies. One set will last the patient for as long as he/she needs them. It is always worth trying the Ear Plane inserts before moving to a tympanostomy.

Round Window Blowout - This complication is caused by excessive vigor when executing the Modified Valsalva maneuver during pressurization. It has been associated with divers but there are no reported cases of it occurring during hyperbaric oxygen therapy. Increased pressure in the perilymph and endolymph tends to force the round and oval windows into the relative vacuum of the middle ear, maintaining the effort may cause a window to rupture. This can cause deafness, tinnitus and vestibular dysfunction. Instructing patients in the methods of managing pressure change seems sufficient to prevent the occurrence of round window blowout in clinical patients.

Sinus Squeeze - This is caused if any of the sinus openings in the head are blocked by mucus, edema or tissue overgrowth. It should not occur in clinical patients screened on acceptance into a hyperbaric program and daily prior to treatment. A squeeze of the frontal sinus brings extreme pain which cannot be tolerated and should be relieved by decongestants or very slow depressurization. Pain from a sphenoid sinus squeeze is referred into the occiput or vertex of the skull. A maxillary sinus squeeze may be confused with a squeeze of one of the maxillary teeth. If an elective patient contracts a cold or sinusitis during the course of therapy it is best to delay further treatments until it can be cleared up.

Confinement Anxiety - While true claustrophobia is not actually a common problem, we do find that most patients exhibit some level of anxiety about being confined in the chamber for the first time, and this is quite understandable. We take special care during our initial patient presentation to describe what is going to happen in detail, and our chamber operators' work with patients as necessary to provide support and reassurance during treatment. In our experience, by the second or third treatment any concerns have evaporated. Rarely, it may be appropriate to prescribe a relaxant to help calm the patient during the initial treatment(s).

Ocular Effects - Reports have shown benefit in treating serious eye disorders such as central retinal artery occlusion and diabetic retinopathy, although conclusive studies remain to be done. That said some patients undergoing prolonged periods of daily hyperbaric treatment may develop myopia, which is usually reversible (Palmquist, 1984). Although the mechanism remains obscure, it is thought to be due to an increased refractive index of the lens. Studies have shown that within the usual maximum 20-30 HBO2 treatments given for problem wounds in the United States, no patient who started with a clear lens developed any opacity (Lyne, 1978). In patients presenting with opacities at the commencement of treatment, the opacities became no worse. Patients, particularly those with a history of optic neuritis, exhibiting or reporting ocular changes should be referred to an ophthalmologist for a consult. There are several reports in the literature of permanent damage occurring after hyperbaric exposures, it should be noted, however, that in all cases the exposure times and pressures used were well in excess of any that would ever be used in clinical hyperbaric oxygen therapy (Kobayashi & Murakami,1972; Margolis,1966; Noell, 1955; Noell,1958)

Numb Fingers - Rarely patients will report numbness and tingling in the fingers. This does not normally occur until they have had more than 20 treatments. There is no known mechanism and reassurance is the only treatment. The parathesias disappear at four to six weeks following cessation of treatment and there are no reported residual effects. Numb fingers have occurred as a side effect in divers using elevated oxygen pressures to increase the rate of decompression.

Dental Problems - This is a rare problem that results from the presence of an air space beneath a filling. It can occur during pressurization or depressurization. If an air space is left under a filling, pulp is forced into the space causing great pain. Unfilled teeth or teeth with obvious caries are not affected. Having the filling temporarily removed or replaced is the only solution. If this occurs in the maxillary teeth it may be confused with a maxillary sinus squeeze.

Pulmonary and CNS Oxygen Toxicity - These are commonly, but incorrectly, cited as major concerns. The treatment protocols used in hyperbaric oxygen therapy all fall within well defined safe limits for oxygen exposure.

Pulmonary symptoms are the result of chronic exposure and are rarely seen during the maximum 20-30 treatment programs used for problem wounds in the United States. In the unlikely event a patient develops symptoms; they are reversed by stopping treatment for a few days.

CNS toxicity, which gives rise to oxygen seizures, results from acute exposure. At 2.4 atm abs, the pressure commonly used for elective problem wound therapy, the incidence of oxygen seizure is less than 1.3/10,000 treatments for all patients (Davis, 1988). This number is based on data gathered over many years in the hyperbaric laboratory at the USAF School of Aerospace Medicine. A retrospective review of the data indicates that many of these patients were hypoglycemic and that the seizures were likely due to low blood sugar. If these patients are excluded the incidence drops to approximately 0.7/10,000 treatments.

Unlike the side effects seen with many pharmaceutical drugs, an oxygen seizure passes quickly and recurrence is prevented by simply switching the breathing medium to air or to a lower inspired PO2. An oxygen seizure has no residual effects and the patient will have no memory of it. It should also be noted that in most cases of oxygen seizure there are other contributing factors such as fever, closed head injury or underlying diabetes, which may sensitize the patient to oxygen. It is common practice to interrupt periods of oxygen breathing with "air breaks" which significantly reduces the likelihood of O2 seizure.

When we review the patient's notes as part of our initial assessment, we look for indications that he/she may be at increased risk of seizure. Blood sugar can drop during treatment, thus in our diabetic patients, we monitor blood sugar on treatment days to make sure it is within threshold values and take remedial action prior to treatment as necessary. It is not uncommon to find that insulin requirements reduce during the course of treatment.

Copyright Life Support Technologies Group Inc, Sept 2012