Combined Hyperbaric Oxygen Partial Pressure at 1.4 Bar with Infrared Radiation: A Useful Tool To Improve Tissue Hypoxemia?

Tissue hypoxia contributes to the pathogenesis of several acute and chronic diseases. Hyperbaric oxygen therapy (HBO) and whole-body warming using low-temperature infrared technology (LIT) are techniques that might improve hypoxemia. Combining HBO and LIT as hyperbaric oxygen therapy combined with low-temperature infrared radiation (HBOIR) might be an approach that results in positive synergistic effects on oxygenation. LIT increases blood flow and could reduce HBO-induced vasoconstriction, and hyperoxia could compensate for the increased metabolic oxygen requirements mediated by LIT. Both LIT and HBO increase the oxygen diffusion distance in the tissues. HBOIR at 0.5 bar has been shown to be safe and feasible. However, physiological responses and the safety of HBOIR at an increased oxygen (O2) partial pressure of 1.4 bar or 2.4 atmospheres absolute (ATA) still need to be determined. The hope is that should HBOIR at an increased oxygen partial pressure of 1.4 bar be safe, future studies to examine its efficacy in patients with clinical conditions, which include peripheral arterial disease (PAD) or wound healing disorders, will follow. The results of pilot studies have shown that HBOIR at an overload pressure is safe and well tolerated in healthy participants but can generate moderate cardiovascular changes and an increase in body temperature. From the findings of this pilot study, due to its potential synergistic effects, HBOIR could be a promising tool for the treatment of human diseases associated with hypoxemia.

Background

Hyperbaric oxygen therapy (HBO) has been widely implemented as primary or adjunctive therapy for conditions ranging from cardiovascular disorders to the management of wound healing [1,2]. Breathing 100% oxygen at an elevated environmental pressure increases oxygen tension in tissues. An increase in pressure from normobaric conditions to 3 atmospheres absolute (ATA) enables an increase in the physically dissolved oxygen in arterial blood from 0.3 mL/dL to approximately 6 mL/dL [3]. Therefore, breathing under hyperbaric conditions raises the diffusion gradient between dissolved oxygen in plasma and tissue [4,5]. According to the Krogh tissue cylinder model of oxygen transport, oxygen diffusion distance in tissue improves under hyperbaric conditions, resulting in an increase in diffusion distance from the capillary at 3 ATA by a calculated factor of 4 [6,7]. As a consequence, the supply of oxygen to tissue regions suffering from hypoxia is facilitated. Tissue hypoxia is known to negatively impact on the course of several chronic diseases [8-11]. Therefore, HBO provides an efficient adjunct treatment strategy in a variety of chronic diseases with an underlying deficiency in tissue oxygenation.

Why Combine HBO with Low-Temperature Infrared Technology (LIT)?

Standard pressure chambers are expensive and are currently only accessible to a small number of patients. Also, detrimental effects of HBO have been shown to include reactive vasoconstriction in organs and tissues induced by hyperoxia [12-14]. An increase in the oxygen diffusion gradient may compensate for this potential disadvantage. However, it remains unclear if reactive vasoconstriction could negatively affect the treatment outcome in different medical conditions. Therefore, the effectiveness of HBO may be substantially increased if the administration of oxygen at higher pressure is combined with a method that increases metabolism and oxygen diffusion distance, and induces vasodilation at the same time as increasing local blood flow and tissue perfusion.

An approach to improving the effectiveness of HBO is to use low-temperature infrared technology (LIT). During LIT, only a small area of skin is irradiated under thermo-neutral conditions (ambient temperature of 28–37°C) [15]. Hyperbaric oxygen therapy combined with low-temperature infrared radiation (HBOIR) technology using the Sensocare® system (Physiotherm, Thaur, Austria) automatically regulates the intensity of infrared radiation according to the registered temperature of the skin on the back, which is measured continuously and is contactless. Therefore, regulation of the heat input is independent of any subjective pain response to heat. The signal from the temperature sensors is transferred to the control system, which, in turn, automatically regulates radiation intensity and heat input to the body. The desired target temperature is reached after between 12–15 minutes, which enables the core temperature to increase slightly within a sub-febrile range at the onset of treatment due to the heat defense mechanisms of the body. Therefore, the central circulation is not disturbed. Heat is dispersed from the core to the body surface, inducing moderate whole-body warming with only a slight increase in core temperature [16,17].

Therefore, combining HBO and LIT could have a synergistic effect. In addition to HBO, whole-body warming also increases the diffusion distance of oxygen, and the augmented peripheral perfusion generated by LIT could attenuate hyperoxia-induced vasoconstriction. Also, increased metabolism, induced by LIT, with its associated rise in oxygen consumption, might be compensated for by hyperoxia, and the standard duration of HBO therapy could be reduced, resulting in improved patient safety.

Because a major part of healthcare costs arise from the management of chronic diseases, efficient and cost-effective innovative approaches, which are easily accessible and have no, or few, side effects are becoming increasingly important. Therefore, and for the first time, we recently evaluated the safety and feasibility of the combined application of HBO and LIT or hyperbaric oxygen therapy combined with low-temperature infrared radiation (HBOIR) used for 45 minutes at a low working pressure of 0.5 bar, or 1.5 atmosphere absolute (ATA), on healthy participants. We have previously reported clinically insignificant increases in heart rate and skin temperature (+3°C), elevations in core temperature within the desired range (+0.2°C), and unchanged arterial blood pressure, without adverse effects or impairment of participant well-being, indicating that HBOIR at 0.5 bar in a healthy study population to be safe and feasible [18]. However, physiological responses at a working pressure equivalent to commonly used HBO pressures (1.4 bar) have not previously been assessed.

Because the evaluation of the safety and feasibility of HBOIR at 1.4 bar (for 45 minutes) might provide the basis to examine the efficacy of HBOIR in patients with chronic diseases, a pilot study was performed to test the effects of HBOIR at a pressure of 1.4 bar (2.4 ATA) on physiological parameters that included heart rate, blood pressure, core temperature, skin surface temperature, and oxygen saturation, and to assess the safety of HBOIR in healthy participants and their tolerance of the treatment.

In this study, a total of six healthy participants received ten consecutive HBOIR treatments at 1.4 bar. Pure oxygen was administered using a re-breather technology for 30 minutes. Infrared radiation transferred heat to the back region via the automated Sensocare® system. Physiological and ambient parameters were continuously recorded. Also, perceived well-being was assessed before, and after each HBOIR session. The main findings of this study were that the ten consecutive HBOIR treatments at 1.4 bar were well tolerated by all participants, and no significant side effects or complications were reported by the six study participants. The heart rate (75±12 bpm to 82±13 bpm) (p<0.001) and core body temperature (37.3±0.3 to 37.5±0.3°C) (p<0.001) increased slightly, but not significantly. Systolic blood pressure decreased (121±15 to 110±10 mmHg) (p<0.001). The findings of this pilot study in six healthy volunteer participants generated moderate cardiovascular and thermal responses with good well-being scores during treatment (see Attachment).

Support for the Safety and Expected Benefits of Combining HBO and LIT

Despite the significant increase in working pressure and the high number of consecutive applications, the effects on the cardiovascular system in the pilot study were comparable to those observed in our previous study that applied a working pressure of 0.5 bar [18]. Known hemodynamic and circulatory changes in both healthy and unhealthy people during HBO include bradycardia and increased arterial blood pressure, reduced heart rate at rest and during exercise, which have been mainly attributed to the elevated oxygen pressure [19]. However, a decrease in arterial blood pressure and normal heart rate at rest and during exercise have also been recorded during normobaric oxygen administration and can, therefore, be independent of additional increases in hyperbaric pressure [20]. It has been proposed that a bradycardic effect is mediated by baroreflex activation due to a hyperoxia-induced increase in arterial blood pressure, as a result of increased parasympathetic activity [21]. Also, hyperoxia decreases catecholamine levels [22,23], as well as sympathetic activity, which reinforces parasympathetic activity [21]. The increased peripheral vascular resistance due to hyperoxic vasoconstriction tends to induce arterial hypertension [12,13]. This finding is in contrast to the reduction in systolic blood pressure observed in this pilot study. A possible explanation for this reduction in systolic blood pressure is that the increased blood flow induced by LIT reduced peripheral vascular resistance. If this was the case, then LIT might offset the potential vasoconstriction induced by the physiological effects of increased oxygen during HBOIR.

During standard HBO therapy, an increase in heart rate is primarily considered to be a warning sign of oxygen toxicity [24], which is a concern in HBO studies [25]. However, when using HBOIR, an increase in heart rate is interpreted to be a compensatory response to the vasodilatory effect induced by the thermal application [26]. The moderate observed increase in heart rate at 1.4 bar is comparable to that observed in our previously published study, where a lower pressure of 0.5 bar was used [18]. During diving, exposure to a pO2 greater than 1.6 bar is known to be a risk factor for acute oxygen toxicity [27]. However, a higher pO2 can be tolerated during HBO therapy, but oxygen toxicity may arise at lower levels when exposure is prolonged.

In this pilot study, heart rate responses below and above a pO2 of 1.6 bar were similar, and the exposure time was limited to approximately 30 minutes, and oxygen toxicity was not expected, as exposures to hyperbaric oxygen were performed at rest in a hyperbaric chamber and not underwater, which is known to decrease the time of onset of oxygen toxicity [28]. Also, in this pilot study, changes in pO2 did not correlate with those in heart rate and systolic blood pressure, and heart rate and blood pressure changes were moderate, indicating that the applied levels of pO2 did not adversely affect heart rate or blood pressure, which are two physiological variables that are sensitive indicators of the acute onset of hyperoxia. Therefore, the findings of this pilot study of the use of HBOIR in six individuals, and under the conditions of the study, were that the treatment was acceptable.

The slight increase in core temperature observed in the pilot study was within the sub-febrile range (≤38°C), and was necessary to achieve a synergistic effect of HBO and LIT. The increase in temperature was facilitated by the special heating system with irradiation of only a small area of the body (<15% of the overall skin surface) [18], used in combination with a moderate environmental air temperature (thermoneutral temperature) in the chamber. Heat input to the body was raised slowly and adjusted in response to the heat-induced alteration in blood circulation. Heat transfer to the skin by infrared radiation was expected to be reduced during increased atmospheric pressures. However, the sensors used regulated the skin temperature independent of the changes in atmospheric pressure. The automatic regulation of heat input might have important implications for the future of the safe application of this system on patients suffering from chronic diseases, who may also have sensory disorders and who may be taking medication. Also, as the HBOIR system is contactless and records in real time, skin temperature is prevented from rising to above 43° for more than 3 minutes, which means that any effect on the heat defense reaction of the skin is marginal and thermal damage to the skin from a burn or heat can be avoided [29-31]. It is also important to note that the erythema observed on the backs of the participants immediately after treatments disappeared within one hour after leaving the chamber. In the pilot study, changes in heart rate, blood pressure and core temperature during HBOIR did not differ between treatments, which indicated that consistent physiological reactions could be achieved over ten consecutive HBOIR treatments with a 24-hour time interval between treatments.

The physiological responses recorded in this study contrast with those observed during conventional thermal treatments, such as sauna applications. During HBOIR, only marginal increases in core temperature are observed. However, during sauna applications (80–100°C) ambient temperatures are higher and thermal absorption by the body exceeds heat dissipation, resulting in an altered thermoregulation. Hence, blood supply to the inner body initially decreases to prevent a fever. After a certain exposure time, relative central volume depletion occurs, followed by a rapid increase in core temperature up to 39°C, as the blood flow to the inner body is enhanced [32,33]. Therefore, the cardiovascular strain can be high during sauna applications [26].

With regard to the findings in the pilot study, which involved six study participants, we did not expect any positive changes in participant well-being, as the treatments were performed on a group of healthy participants. However, the scores for perceived well-being increased overall, and quite significantly during some of the treatments. Importantly, well-being did not decrease during any of the treatments. These findings, together with the positive ratings during the treatments obtained by the VAS regarding pain, anxiety, and comfort indicate that HBOIR is not an unpleasant treatment. As for the climate in the chamber, increases in ambient temperature are as expected so the heat dissipation in the participants was not disturbed.

Future Perspectives

HBOIR at an overload pressure of 1.4 bar results in moderate changes to the cardiovascular system and generates whole-body warming induced by small core temperature increases in a group of healthy participants. Aside from appearing to be a safe approach, HBOIR is very well tolerated and does not impair well-being during repeated exposures. These positive findings provide the basis for further studies to examine the efficacy of the HBOIR system in patients with medical conditions such as peripheral arterial occlusive diseases or wound healing disorders. We consider HBOIR to be a promising alternative means to improve hypoxemia in various conditions with the potential to be easier accessible than standard HBO.

Table 1

Cardiovascular, respiratory, and thermal changes during hyperbaric oxygen therapy combined with low-temperature infrared radiation (HBOIR) at treatment (tr) days 1–10.

	tr 1	tr 2	tr 3	tr 4	tr 5	tr 6	tr 7	tr 8	tr 9	tr 10
Heart eate (b/min)
Baseline	78±11	74±14	73±13	80±11	74±12	74±13	74±13	77±12	73±7	76±11
End of treatment	90±13*	81±12*	79±15	86±16	80±15*	82±15*	82±13*	81±9	80±13	82±11
Systolic blood pressure (mmHg)
Baseline	125±15	113±17	108±15	118±12	124±19	121±18	119±14	120±18	121±18	117±16
End of treatment	110±9*	113±12	107±13	115±11	115±18	110±16	110±9*	110±11*	108±12*	108±10
Diastolic blood pressure (mmHg)
Baseline	82±13	77±10	69±8	78±4	80±12	77±11	76±8	77±9	76±13	79±10
End of treatment	78±9	75±10	70±5	79±10	81±18	76±11	76±11	75±9	76±12	77±9
Oxygen saturation (%)
Baseline	98±0.7	98±0.5	99±0.5	98±0.5	98±0.6	99±0.5	98±0.6	98±0.7	98±0.5	98±0.6
End of treatment	99±0.3	99±0.5	99±0.1	99±0.2*	99±0.1	99±0.3	99±0.5	99±0.5	99±0.2	99±0.5
Core temperature [C°]
Baseline	37.2±0.3	37.2±0.3	37.2±0.3	37.3±0.2	37.3±0.4	37.2±0.4	37.2±0.3	37.2±0.2	37.2±0.2	37.4±0.3
End of treatment	37.5±0.4*	37.4±0.3	37.4±0.3	37.5±0.3*	37.4±0.4*	37.4±0.3	37.4±0.3*	37.5±0.1*	37.4±0.2	37.5±0.2
Skin temperature (back) (°C)
Baseline	36.8±2.9	36.2±2.4	34.5±1.2	34.5±1.5	37.9±2.0	36.4±0.8	36.0±2.2	36.2±1.0	36.5±1.9	35.8±1.6
End of treatment	42.3±0.5	42.3±0.5*	42.2±0.5**	42.2±0.6**	42.2±0.4*	42.4±0.1**	42.0±0.5*	42.2±0.5**	42.2±0.5*	42.2±0.5*

Data are presented as mean ±SD.

p≤0.05,

p≤0.001: significant changes from baseline to the end of treatment during each treatment (tr).

Table 2

Participant well-being during hyperbaric oxygen therapy combined with low-temperature infrared radiation (HBOIR) at treatment (tr) days 1–10.

	tr 1	tr 2	tr 3	tr 4	tr 5	tr 6	tr 7	tr 8	tr 9	tr 10
Well-being
Before treatment	8±16	71±20	79±25	84±15	76±22	94±15	86±18	82±16	81±26	81±27
After treatment	91±15*	94±11*	91±8	88±15	89±11	97±9	95±14	97±10*	95±17	98±19*

Ratings of the general condition of the pilot study participants two hours before and one hour after each treatment (tr). Data are presented as mean ±SD.

p≤0.05 indicates a significant change.

N=6 for each time point.

Table 3

Changes in chamber parameters during hyperbaric oxygen therapy combined with low-temperature infrared radiation (HBOIR) at treatment (tr) days 1–10.

	tr 1	tr 2	tr 3	tr 4	tr 5	tr 6	tr 7	tr 8	tr 9	tr 10
Air temperature (°C)
Minute 5	32.4±2	32.3±3	30.3±1	29.8±1	34.5±2	30.5±2	30.9±2	30.3±2	30.8±2	30.3±2
End of treatment	36.2±2*	35.9±2*	35.6±1*	34.7±2*	30.1±2*	35.2±2*	35.5±2*	34.5±2*	35.0±2*	34.6±1*
Air humidity (%)
Minute 5	61±9	62±10	54±7	54±8	51±5	45±8	51±9	52±8	49±8	53±5
End of treatment	72±10*	73±7*	71±4*	74±6*	69±9*	69±7*	69±10*	73±8*	69±10*	72±8*
Carbon dioxide:
Minute 5	583±102	706±105	611±96	618±72	536±142	645±73	679±127	617±50	594±143	603±46
End of treatment	1328±1758	321±285*	448±594	644±1079	548±896	475±606	443±279	477±506	274±200*	325±194*
Oxygen concentration (%)
Minute 5	20.5±0.1	20.4±0.2	20.4±0.3	20.3±0.2	20.2±0.2	20.4±0.2	20.5±0.2	22.4±0.1	20.4±0.4	20.2±0.2
End of treatment	22.2±0.2*	22.3±0.2*	22.5±0.2*	22.6±0.5*	22.8±0.6*	22.6±0.3*	22.7±0.5*	22.8±0.5*	22.4±0.4*	22.7±0.4*
(min–max)	20.6–23.9	20.7–23.6	20.6–23.1	20.7–23.2	20.6–23.4	20.6–23.3	20.7–23.9	20.6–23.4	20.6–23.3	20.7–23.4
Chamber pressure (mbar)
Minute 5	1334±138	1360±78	1382±35	1384±30	1382±33	1380±36	1378±41	1380±34	1377±41	1378±45
End of treatment	1396±11	1402±4	1405±6	1402±4	1402±7	1403±6	1403±5	1403±5	1400±6	1402±5
Partial oxygen pressure [bar]
minute 15	1.22±0.2	1.33±0.3	1.45±0.2	1.58±0.2	1.55±0.3	1.54±0.2	1.52±0.2	1.53±0.2	1.51±0.2	1.58±0.2
End of treatment	1.56±0.3	1.73±0.2#	1.80±0.2#	1.92±0.2#	1.90±0.3#	1.83±0.4	1.73±0.2	1.71±0.3	1.90±0.1	1.72±0.2
(min–max)	1.03–1.88	0.76–2.10	1.21–2.16	1.44–2.25	1.24–2.19	1.17–1.86	1.20–1.99	1.28–2.07	1.26–2.01	1.33–1.80

Data are presented as mean ±SD.

p≤0.05 indicates significant changes from the time when the chamber was pressurized (minute 5) to the end of treatment.

p≤0.05 indicates significant changes from the time when oxygen administration had started in all participants (minute 15) to the end of treatment.