In which of the following clinical situations would you recommend hyperbaric oxygen HBO therapy if available?

Conclusions

HBOT has been both lauded and questioned, primarily because advocates have not generated adequate controlled data to define conclusively its appropriate uses. It is difficult to assess the efficacy of HBOT in infectious diseases, even those for which use is endorsed by the UHMS and reimbursed by third-party payers. In clinical practice nonhealing wounds, including complicated DFUs, have become the most common indications for HBOT. Use of HBOT in clinical practice has increased considerably in the last decade and will likely continue to rise if current modes and extent of reimbursement continue. It is not entirely clear which patients with infections, if any, truly stand to benefit from HBOT, and how they should be selected. Prospective RCTs are needed to provide definitive answers regarding efficacy of HBOT in infectious diseases. Until convincing controlled data appear, each patient and each clinical situation must be evaluated individually. Most important, it is critical to weigh the risks of transport, lack of access to the patient, potential complications, and cost against any potential differential benefit over standard care that the treatment may provide.

Hyperbaric Oxygen Therapy

Hyperbaric oxygen therapy has proved to be successful in the treatment of certain forms of stroke. For example, decompression sickness occurs when nitrogen bubbles form within the bloodstream. The hyperbaric chamber causes the nitrogen bubbles to dissolve and delivers oxygen to ischemic brain tissue. The same treatment may be utilized for air embolism, which occurs as a result of trauma, surgery, or vascular procedures. In each of these cases, the cause of the occlusion (i.e., a bubble) is dissolved by the pressure, while hyperbaric oxygen maintains viability within the ischemic brain areas. Now that thrombolysis and endovascular techniques are available to dissolve, recanalize, or remove an intravascular clot, it is possible that hyperbaric oxygen therapy may be combined with such procedures in the treatment of acute stroke.

Hyperbaric Oxygen Therapy

Wound ischemia is the most common cause of wound-healing failure. HBO therapy uses oxygen as a drug and the hyperbaric chamberas a delivery system to increase po2 at the target area. HBO therapy is used for myriad disease processes, including bacterial infections, decompression sickness, improvement of split-thickness skin graft take, flap survival and salvage, acute thermal burns, necrotizing fasciitis, chronic wounds, hypoxic wounds, osteoradionecrosis, and radiation injuries. There is evidence for treatment of chronic diabetic ulcers and radiation-induced wounds.20,21 Ischemia or tissue hypoxia (po2 <30 mm Hg) significantly impairs normal metabolic activity and decreases wound healing by impairing fibroblast proliferation, collagen synthesis, and epithelialization. HBO therapy involves inhalation of 100% oxygen at 1.9 to 2.5 atm, which can increase tissue po2 10 times higher than usual. A higher Pao2 is sufficient to supply the tissue with all its metabolic requirements, even in the absence of hemoglobin; this elevated level lasts for 2 to 4 hours after termination of HBO therapy and induces synthesis of endothelial cell NO synthase as well as angiogenesis. Oxygen has been reported to stimulate angiogenesis, enhance fibroblast and leukocyte function, and normalize cutaneous microvascular reflexes.

A recent animal study analyzed the effects of HBO therapy on rodent cells metabolism, angiogenesis, and wound healing in diabetic wounds.22 Experiments showed increased proliferation of stem cells, upregulated angiogenesis, and improved wound healing capacity. Additionally, this study demonstrates that a combination of HBO treatment and stem cell therapy has a synergistic effect and may open new horizons in treatment of nonhealing wounds.22

Evaluation of the vascular supply to the target area is essential, and revascularization before HBO therapy is an essential prerequisite to HBO therapy. Patients will likely benefit from adjuvant HBO therapy if improvement in tissue oxygenation can be demonstrated in a hypoxic wound while breathing oxygen under hyperbaric conditions. Transcutaneous oxygen pressure (tcpO2) is used to assess wound perfusion and oxygenation. A wound tcpO2 less than 35 mm Hg in room air indicates a hypoxic wound. An in-chamber tcpO2 of 200 mm Hg or more suggests potential benefit from HBO therapy.

HBO treatments for hypoxic wounds are usually delivered at 1.9 to 2.5 atm for sessions of 90 to 120 minutes each, with the patient breathing 100% oxygen during the treatment. Treatments are given once daily, five to six times per week, and should be given as an adjunct to surgical or medical therapies. Clinical evidence of wound improvement should be noted after 15 to 20 treatments.

HYPERBARIC OXYGEN THERAPY

In hyperbaric oxygen therapy (HBOT), commonly used in patients with severe burns or wounds, 100% oxygen is used at controlled pressures (typically 1.5 to 1.75 atm, equivalent to 16.5 to 25 feet below sea level) to increase the amount of oxygen at the cellular level. Treatments usually last 1 hour and are given once or twice daily, 5 to 6 days per week; 40 treatments are typical during the first phase of treatment.

The underlying rationale for HBOT in children with cerebral palsy is the theory that damaged motor areas of the brain are surrounded by so-called “dormant” areas that receive relatively less blood flow and thus less oxygen. By increasing blood oxygen levels, HBOT purportedly “wakes up” the brain cells in the dormant areas and also constricts blood vessels, thus reducing brain swelling and promoting growth of new brain tissue.54 Potential risks include ear discomfort or trauma, pneumothorax, myopia, oxygen-induced convulsions, and fire or explosion.

According to an evidence report,55 one fair-quality observational study and one fair-quality randomized controlled trial demonstrated improved motor and social function in the patients receiving HBOT.56–58 However, in the randomized clinical trial, children who did not receive HBOT showed similar improvements. Overall, the report concluded that “there is insufficient evidence to determine whether the use of HBOT improves functional outcomes in children with cerebral palsy.”55 In a review of CAM therapies for cerebral palsy, the authors also noted that it seems unlikely that a single therapy could benefit as heterogeneous a disorder as cerebral palsy.59

Hyperbaric Oxygen

Hyperbaric oxygen (HBO) therapy involves treating the patient with 100% oxygen at elevated atmospheric pressures in a specially designed chamber (Fig. 115.15). The benefits of increasing the partial pressure of oxygen in the tissues may include improved oxygen supply, reduction of inflammation and edema, and inhibition of infection. HBO is reportedly useful in the treatment of a number of wound problems, including complex diabetic foot ulcers, osteomyelitis, necrotizing fasciitis, and the healing of tissue flaps. Typical treatment protocols for leg ulcers involve one or two treatments daily for a total of 20 to 40 treatments.99

HBO has long been considered a potential treatment modality for ischemic ulcers. Oxygen can stimulate angiogenesis, enhance fibroblast and leukocyte function, and normalize cutaneous microvascular reflexes.100,101 Clinically HBO has been demonstrated to improve tcPO2 in the limbs of some patients with ischemic ulcers. Significant side effects of treatment are uncommon but may be severe, including barotraumatic otitis, hyperoxic seizures, and pneumothorax.

The use of HBO in ischemic leg ulcers remains controversial. This is due to the difficulty in conducting large randomized blinded studies with HBO. The majority of the studies are small and not well controlled, leaving significant doubt concerning the validity of the findings.

Faglia and colleagues randomized 68 patients with ischemic diabetic foot ulcers to standard foot ulcer treatment with or without HBO therapy.102 Amputation was required in 33% of the control group, compared with 8.6% of the HBO treated group (P = .016).

Abidia et al.103 randomly assigned 18 patients with nonhealing ischemic diabetic limb ulcers to 100% oxygen or air at 2.4 atmospheres for 90 minutes in a hyperbaric chamber daily. In this double-blinded study, both groups received 30 sessions, after which the outcome was measured. In the oxygen group, five of eight ulcers were closed completely, compared with one of eight in the control group (P = .027).

In 2004, the Cochrane Collaborative reviewed HBO therapy for chronic wounds and concluded that HBO reduces the risk of amputation for patients with diabetic foot ulcers and increases the chance of healing at 1 year.104 However, it noted that these findings were based on small, underpowered studies, and that further randomized studies are greatly needed to clarify the benefits of this costly therapy.

Since the publication of the aforementioned Cochrane review, several studies have focused on the use of tcPO2 to select patients for HBO treatment. Grolman et al.105 measured tcPO2 in the ischemic limb of 36 patients breathing room air, followed by 100% oxygen. They found that a greater than 10 mm Hg increase in tcPO2 in the ischemic foot was associated with a healing rate of 70%, compared with a healing rate of 11% in those with an increase of less than 10 mm Hg. Others have reported that the improvement in foot tcPO2 obtained during a trial session of HBO is also predictive of wound healing.106

IV.I Experimental Therapies

Hyperbaric oxygen therapy has proved to be successful in the treatment of certain forms of stroke. For example, decompression sickness occurs when nitrogen bubbles form within the bloodstream. The hyperbaric chamber causes the nitrogen bubbles to dissolve and delivers oxygen to ischemic brain tissue. The same treatment may be utilized for air embolism, which occurs as a result of trauma, surgery, or vascular procedures. In each of these cases, the cause of the occlusion (i.e., a bubble) is dissolved by the pressure, while hyperbaric oxygen maintains viability within the ischemic brain areas. Now that thrombolysis and endovascular techniques are available to dissolve, recanalize, or remove an intravascular clot, it is possible that hyperbaric oxygen therapy may be combined with such procedures in the treatment of acute stroke. Currently, this hypothesis is under investigation.

By forcing oxygenated arterial blood backward through the venous system, ischemic areas may be supplied with needed oxygen even when the arterial supply is occluded. This technique, called retrograde transvenous neuroperfusion (RTN), is being actively studied to measure its effectiveness as an acute stroke intervention. In a small clinical trial involving eight subjects, RTN has shown promise for the management of acute stroke. Its effect may be almost immediate, in contrast to the effect of thrombolytic therapy, and it may be further increased by simultaneously employing hypothermia to reduce cerebral metabolic demands.

Neuroprotective drugs are under active development. The idea is to arrest the pathophysiologic mechanisms that lead to tissue damage and irreversible injury. If CBF or oxygen delivery could then be restored, a larger volume of intact and viable brain tissue would be available to promote functional recovery. Although the core region of infarction is not likely to be impacted by such an approach, the surrounding “ischemic penumbra” could in theory be rescued completely. Animal studies have shown the feasibility of this approach, but to date there are no effective neuroprotective drugs available for use in humans.

Advanced imaging techniques are being developed and promoted faster than they can be evaluated. Many of these techniques (FLAIR, MRA, MRV, etc.) have rapidly revealed their clinical utility, whereas others (MR spectroscopy and CBF PET) have limited clinical utility due to lack of availability, complexity, expense, or other factors. Despite these limitations, advanced brain imaging techniques enable brain areas at risk of permanent damage to be identified (Fig. 3) quickly and efficiently. This ensures that future research will be able to combine neuroimaging with clinical interventions to demonstrate the relative potencies of various medical therapies for acute stroke, neuroprotective interventions, endovascular techniques, or surgical procedures.

Hyperbaric Oxygen

Hyperbaric oxygen (HBO) therapy refers to exposure to a contained environment with 100% oxygen at increased atmospheric pressure. HBO increases oxygen delivery to the tissues of the body by increasing the volume of oxygen dissolved in the blood and is, therefore, a useful treatment in ischemic conditions such as poor wound healing, carbon monoxide poisoning, and burns. TBI shares many similarities with these ischemic conditions. Primary injury leads to vessel damage, hypotension from autoregulatory failure, and prostaglandin-induced vasoconstriction resulting in cerebral hypoperfusion and ischemia (Werner and Engelhard, 2007). The use of HBO following TBI results in relief of hypoxia, reduction in cerebral edema and intracranial pressure via vasoconstriction, and improvement in microcirculation.32 HBO has also been shown to provide additional antiapoptotic and antiinflammatory effects. Following administration of HBO, animal models demonstrated increased expression of antiapoptotic bcl-2 mRNA with increased ratio of bcl-2 to bax and reduced apoptotic caspase-3 mRNA levels.32 Matrix metalloproteinases, which are responsible for tissue remodeling and inflammation, were also found in reduced quantities in HBO treated animals.33

Clinical trials with HBO in mTBI have shown mixed results. In a study of 56 mTBI patients with prolonged postconcussive syndrome 1–5 years after injury, researchers demonstrated significant improvements in cognitive function following HBO compared to control therapy, indicating that HBO may be a useful treatment even years after trauma.34 This is a significant finding as this information would substantially increase the window period in which patients may benefit from treatment. In contrast, other studies have shown inconclusive results. In one study of 50 military service members with mTBI, HBO had no effect on postconcussive symptoms.35 A recently published study by the Department of Defense (DOD) also suggests that HBO is no better than sham air compression treatment. Approximately 72 military service members with persistent postconcussion symptoms were randomized to HBO, sham sessions with room air, or no supplemental chamber procedures, and found that both intervention groups showed improved outcomes compared to standard care and any improvements are likely attributed to placebo effect.36 A larger confirmatory trial by the DOD is currently underway, although additional military studies have shown similar results.37 Furthermore, despite some results suggesting that HBO reduces the risk of death and improves GCS, evidence has not shown any improvement in quality of life, resulting in more individuals surviving mTBI, but with greater deficits.38,39

There are many aspects of HBO therapy, including a standardized protocol, that must be addressed before it can serve as an effective treatment option for mTBI. In one animal model of TBI, researchers found that HBO given within 3–12 hours reduced neurologic deficits and neuronal loss, but had fewer neuroprotective effects when given at 24–72 hours.32 Animal models also benefitted from repeated HBO treatments for 3–5 days.32 Most human studies, however, vary in the time from injury to HBO initiation, as well as in the total treatment time.38,40 Length of treatment in clinical trials has varied from 35 minutes to 1 hour daily and can last for 3–188 treatments, or until the patient is awake.41 Studies have also been inconsistent in pressurization used during HBO treatment. Subsequent clinical trials have ranged from 1 to 2.5 atmospheres, possibly contributing to an increased risk for side effects and the conflicting results that have been seen in the literature. These controversies suggest that further work is needed to identify the optimal therapeutic window, frequency, length of treatment, and pressure for HBO in TBI. Although more work needs to be done in this area, there is currently insufficient evidence to support the use of HBO for mTBI.

Clinical Trials of HBOT for Traumatic Brain Injury

Animal modeling has been very important in demonstrating preliminary effectiveness of HBOT. Previous animal studies of HBO therapy for TBI have shown that increases in PO2 immediately after injury can enhance mitochondrial redox potential and increase brain tissue O2 consumption (Daugherty et al., 2004). Investigators at the University of Minnesota recently completed a preliminary animal study, using a cognitive water maze test 11–15 days after the animals had experienced TBI. Rats were given TBI by lateral fluid percussion impact and then exposed to normobaric 30% or 100% O2 alone for 4 h, or 1 h of HBO followed by 3 h of normobaric 100% O2. The HBO therapy consisted of 100% O2 pressurized to 1.5 ata. They found that injured animals receiving only 30% O2 took a significantly longer time to reach the goal platform (90.5 s) compared with rats in the other groups (100% normobaric O2 treatment, mean time 77.4 s; HBOT treatment, mean time 65.5 s; and sham-injured group treated with 30% O2, mean time 42.2 s). The ANOVA analysis of goal latencies revealed a significant main effect of the group. These results demonstrate that HBO therapy can extensively reduce cognitive deficits associated with TBI in rats (Personal communication, 2014).

Another animal study demonstrated that HBOT suppressed microglial activation, TNF-α expression, and neuronal apoptosis in rats in both groups treated either 1 or 8 h after fluid-percussion-induced TBI (Lim et al., 2013). A study completed by Chen and colleagues demonstrated that interleukin-10 (IL-10) plays a role in the neuroprotection of mouse brain affected by TBI. Their study showed that after only 1 h at 2.0 ata HBOT, the brains showed reductions in lesion volume, cerebral edema, apoptosis (decreased ratio of caspase-3 to pro-C3 and decreased Bax expression), inflammation, and improved neurological status. They also noticed an improvement in the blood–brain barrier and unregulated expression of tight junction proteins. From these results, they concluded that IL-10 had a significant role in the protection of tissue (Chen et al., 2014). Vlodavsky and colleagues demonstrated a reduction in neuroinflammation and expression of matrix metalloproteinase-9 in 10 rats that underwent two sessions of 2.8 ata 45-min HBOT treatments. They discovered that animals treated with HBOT had a significant decrease of apoptotic cells as determined by TUNEL analysis and had a substantial reduction of neutrophilic inflammatory infiltration. Animals in the control group (normobaric oxygen) showed no significant changes (Vlodavsky, Palzur, & Soustiel, 2006).

In 2012, Harch and colleagues conducted a preliminary study on the efficacy of only 1.5 ata HBOT on military patients with blast-induced mild to moderate TBI and posttraumatic stress disorder. Sixteen subjects received the entire round of treatment. After just a few weeks of treatment, patients experienced significant improvements in full-scale IQ, working and delayed memory, impulsivity, PCS symptoms, PTSD symptoms, depression, anxiety, and quality of life. In addition, there were extensive improvements in physical exam findings and SPECT scan abnormalities. Fig. 3.4 shows areas of the cortex that experienced increased regional cerebral blood flow (Harch et al., 2012).

A meta-analysis involving seven HBOT studies and over 500 patients found HBOT to be associated with a decrease in unfavorable outcomes 1 month after treatment using the Glasgow Coma Scale (GCS) (Bennett, Trytko, & Jonker, 2012). The same study revealed that the relative risk of death with HBOT was 0.69 (NNT = 7) compared to normal treated controls.

It is not surprising that both location and severity of brain damage can make a significant difference in the level of recovery. As one 2004 study points out, “In young patients with brainstem contusion, significantly more regained consciousness at 1 month with HBOT (67%) than control (11%)” (McDonagh, Helfand, Carson, & Russman, 2004). The study also pointed out that “patients with an intracranial pressure (ICP) greater than 20 mm Hg or a Glasgow Coma Scale score of 4 to 6 had significantly lower mortality at 1 year with HBOT than with the control group.” The researchers noted that HBOT could be used to actually reduce ICP in patients with TBI. With further regards to the GCS, a 2008 study found that out of 44 patients, 22 enrolled in HBOT versus control and improved from 11.1 to 13.5 on average. The control group averaged an increase of 10.4–11.5 (Lin et al., 2008).

A clinical analysis in the United Kingdom showed that patients who have TBI and received 30 sessions of HBOT in addition to standard treatment had a better outcome than those who were only given standard treatment. The research group found that those with a Disability Rating Scale (DRS) score of 22–24 (vegetative state) showed the most improvement. Following the treatment, a larger portion of patients who received HBOT versus those who did not exhibited a stronger recovery in cognitive functions (Sahni, Jain, Prasad, Sogani, & Singh, 2012).

Dr. Shai Efrati of Tel Aviv University’s Sackler Faculty of Medicine has demonstrated significant preservation of neurological function in brain tissue thought to be chronically damaged even years after initial injury. Theorizing that high levels of oxygen could reinvigorate dormant neurons, Dr. Efrati and his fellow researchers, including Professor Eshel BenJacob of TAU’s School of Physics and Astronomy and the Sagol School of Neuroscience, recruited poststroke patients for HBOT. Analysis of brain imaging showed significantly increased neuronal activity after a 2-month period of HBOT treatment compared to control periods of nontreatment, as reported by Dr. Efrati in PLoS ONE. Patients experienced improvements such as a reversal of paralysis, increased sensation, and renewed use of language. Seventy-four participants spanning 6–36 months poststroke were divided into two groups. The first treatment group received HBOT from the beginning of the study, and the second received no treatment for 2 months, then received a 2-month period of HBOT treatment. Treatment consisted of 40 2-h sessions five times weekly in an HBO tank. The results indicated that HBOT treatment can lead to significant improvement in brain function in poststroke patients even at chronically late stages, helping neurons strengthen and build new connections in damaged regions (Efrati et al., 2013). It was also suggested that while there is no agreed-upon effective metabolic intervention for TBI, HBOT appears to be an invaluable tool in repairing and maintaining metabolic function of the brain after TBI (Efrati & Ben-Jacob, 2014).

In 2006, a group of Chinese scientists conducted a study on 310 patients exhibiting neuropsychiatric ailments resulting from mild TBI. After receiving only two treatments of HBOT, 70% of the patients did not show any signs of brain damage on SPECT scan. The patients had also improved significantly on their neuropsychiatric tests (Shi, Tang, Sun, & He, 2006).

Because TBI occurs in children as well due to sport and recreational injuries, it is important to gain a baseline understanding of whether HBOT has the same effect on a child’s body. Prakash and colleagues conducted an HBOT study on 56 pediatric patients with head injury, in which 28 received HBOT, all of whom had GCS scores below 8. The results showed significant improvement in patients who received treatment over control patients, for duration of hospitalization, GCS (average increase of 5 points), disability reduction, and social behavior (Prakash et al., 2012).

Wolf and colleagues from the US Air Force School of Aerospace Medicine conducted an HBOT study on 50 military service people who had suffered at least one combat-related mild TBI. After receiving either 30 sham-controlled (room air at ata 1.3) or HBO (ata 2.4) treatments, the investigators concluded that HBO therapy did not make a significant difference on their symptoms measured by the Posttraumatic Disorder Check List-Military Version (PCL-M). The results suggested that HBOT may not have as dramatic effects on milder forms of TBI, whereas the real benefit may come in individuals with more severe injury (Wolf, Cifu, Baugh, Carne, & Profenna, 2012). Paul Harch later stated that the study was not sham-controlled (placebo implied), and thus did not meet the criteria to serve as a valid study. Rather it was mischaracterized as sham-controlled but in fact included a group that received a lower dose of therapy. Moreover, Harch classified Wolf’s work as a Phase II comparative dosing study of two composite doses of hyperbaric therapy (Harch, 2013).

Hyperbaric Oxygen Therapy (HBOT)

Among other brain abnormalities that have been identified, numerous studies using PET and SPECT have shown cerebral hypoperfusion in autism (George, Costa, Kouris, Ring, & Ell, 1992; Mountz, Tolbert, Lill, Katholi, & Liu, 1995; Ohnishi et al., 2000; Starkstein et al., 2000; Zilbovicius et al., 2000), leading to the hypothesis that hyperbaric oxygen therapy (HBOT) may be beneficial in the treatment of autism (Rossignol & Rossignol, 2006). HBOT involves the inhalation of 100% oxygen in a pressurized chamber, usually above one atmosphere absolute (ATA). It has been shown that HBOT can lead to improved functioning in various neurological populations that show cerebral hypoperfusion including stroke (Nighoghossian, Trouillas, Adeleine, & Salord, 1995), cerebral palsy (Montgomery et al., 1999), chronically brain injured (Golden et al., 2002), and even a teenage male with Fetal Alcohol Syndrome (Stoller, 2005). It has been suggested that the increased oxygen delivered by HBOT could counteract the hypoxia caused by hypoperfusion, and lead to a reduction in symptoms of autism.

In a retrospective case study of six children with autism who had undergone low-pressure HBOT at 1.3 ATA and 28–30% oxygen over the course of 3 months, Rossignol and Rossignol (2006) found an average improvement of 22.1% based on ratings from the ATEC. An average improvement of 12.1% was reported based on the CARS, and a 22.1% improvement on the SRS. All children in this study, however, continued all other therapies they were previously receiving, and were also able to initiate new therapies during the study. Furthermore, the study was retrospective, parents were not blinded to the treatment, and there was no control group.

Rossignol, Rossignol, James, Melnyk, and Mumper (2007) treated 18 children with autism with 40 sessions of HBOT at either 1.5 atm at 100% oxygen, or at 1.3 atm and 24% oxygen. They reported a trend toward improvement in C-reactive protein measurements (a marker of inflammation) and no significant increase in oxidative stress. Parental reports revealed statistically significant improvements in irritability, social withdrawal, hyperactivity, motivation, speech, and sensory/cognitive awareness. However, parents were not blinded as to the type of therapy their children were receiving and there was no placebo or control group. These results remain preliminary and further studies are needed with more rigorous experimental designs (blinded, placebo-controlled, randomized). This study does suggest, however, that it is a relatively safe treatment, as no adverse events were reported and all children were able to complete the 40 treatment sessions.

In summary, this review of the autism treatment literature reveals there are no treatments, except possibly behavior therapy, that have been well validated or that have exhibited favorable long term results. In addition, many forms of intervention include the possibility of adverse effects, require long-term use, or were not developed specifically for Autistic Spectrum Disorders. Neurofeedback represents an alternative that may have the potential to decrease symptomatology on a long-term basis with little risk of harm.

Treatment

As noted previously in this chapter under Biomarkers of CO Exposure, the half-life of COHb when breathing room air is 4–6 hours. The half-life decreases to 40–60 minutes when breathing 100% oxygen and further decreases to 15–30 minutes when HBO therapy is administered.

The cornerstone of treatment for CO poisoning is 100% normobaric oxygen using a tight-fitting mask for > 6 hours to treat hypoxia, for blood pressure support, and to address any cardiac issues if present.

From 2008 to 2010, 87 hyperbaric facilities reported information on 864 patients who received treatment for CO poisoning (Clower et al., 2012), of which 353 required hospitalization (median COHb 25%, range 1–77%) and 475 were discharged after treatment (median COHb 21%, range 0.1–46%). The most common symptoms were headache (66%), dizziness (51%), nausea/vomiting (46%), loss of consciousness (44%), and confusion (30%). Twenty-one patients reported no symptoms. Thirty-eight percent had loss of consciousness for ≤ 10 minutes, while for 49% the duration was unknown.

Since the indications of when to use HBO therapy for CO poisoning have remained controversial (Raphael et al., 1989; Weaver et al., 1996), Ernst and Zibrak (1998) published guidelines in 1998. These included: (1) coma; (2) any period of unconsciousness; (3) any abnormal score on the CO Neuropsychological Screening Battery; (4) COHb > 40%; (5) pregnancy and COHb level > 15%; (6) signs of cardiac ischemia or arrhythmia; (7) history of ischemic heart disease and COHb level > 20%; (8) recurrent symptoms for up to 3 weeks; and (9) symptoms that do not resolve with normobaric oxygen after 4–6 hours. As discussed in the section on neuropsychologic effects, above, if the only finding was an abnormal score on one of the tests in the CO Neuropsychological Screening Battery, this should not warrant treatment with HBO.

The Undersea and Hyperbaric Medical Society recommends HBO treatment for CO-poisoned patients regardless of COHb levels when there is transient or prolonged unconsciousness, neurologic signs, cardiovascular dysfunction, or severe acidosis, or if their age is ≥ 36 years, or if the CO exposure duration interval is ≥ 24 hours. They agree that the role of neuropsychologic testing to determine need for HBO therapy is not clear. The optimal protocol for HBO treatment with CO poisoning has not been determined and whether clinical improvement or reduced rate of neurocognitive sequelae occurs when HBO is administered beyond 6 hours from poisoning is unknown (Weaver, 2008). These recommendations are made in the absence of well-designed randomized control studies or appropriate study design to allow for meaningful interpretation of the results.

The controversy over HBO treatment for CO poisoning continues as the American College of Emergency Physicians subcommittee could not reach a consensus on any variable for which HBO was indicated with CO poisoning (Wolf et al., 2008). Two Cochrane reviews critiqued multiple randomized controlled trials and concluded that the evidence did not support that HBO therapy for CO poisoning reduced the persistence of adverse neurologic outcomes (Juurlink et al., 2005; Buckley et al., 2011). In light of marked variability in patient selection and CO poisoning in these studies, a more conservative recommendation suggested one HBO treatment at 2 atmosphere within 12 hours of CO exposure for comatose patients with acute nonsuicidal CO poisoning and COHb greater than 25%.

Any pregnant woman with CO poisoning should receive HBO therapy (Guzman, 2012) because CO exposure in pregnant women is dangerous, as there may be a lag time for CO uptake, but eventually the COHb level in the fetus is higher than in the mother (Long and Hill, 1977). The fetal hemoglobin releases less oxygen to the tissues, resulting in significant hypoxia (Farrow et al., 1990).

To test the hypothesis that HBO therapy is needed to prevent the development of DNS, Thom et al. (1995) treated patients with CO poisoning with HBO: none developed DNS while 23% developed DNS after treatment with ambient-pressure oxygen. There was a problem with case definition for DNS. None of these patients had loss of consciousness and their level of function (going to work) with persistent symptoms of headache, dizziness, and difficulty concentrating is not commonly used to define DNS. In this study differences in performance on the neuropsychologic battery between the two treatment groups could be attributed to premorbid abilities as the ambient pressure oxygen group had fewer years of education and this was not taken into account in the analyses (Thom et al., 1995).

There is concern that advocates for HBO treatment are located at facilities that offer this treatment. Some believe further randomized controlled trials are unnecessary, as withholding HBO treatment in CO-poisoned patient is unethical, while others feel further trials are unethical given the absence of data showing the effectiveness of HBO treatment and the expense of transferring patients to such facilities (Kao and Nanagas, 2006).

HBO is not free of side-effects; some include painful barotrauma, decompression sickness, pulmonary edema and hemorrhage, seizures, and oxygen toxicity. The presence of a pneumothorax is an absolute contraindication for HBO treatment (Kao and Nanagas, 2006).