gms | German Medical Science

Principles and working mechanisms (thermal and thermic effects, non-thermal and non-thermic effects) of water-filtered infrared-A (wIRA) related to wound healing and fundamental recommendations for the clinical use of wIRA and safety aspects are presented in detail in [1] and [2], see especially review [1].

The typical main clinical effects of wIRA (both true in acute and in chronic wounds) are:

wIRA increases

• tissue temperature
• tissue oxygen partial pressure
• tissue perfusion.

wIRA decreases

• pain (and consequently the required dose of pain medication)
• inflammation
• hypersecretion.

wIRA has

• positive immunomodulatory effects.

wIRA improves and advances

• wound healing (even the normal wound healing process).

wIRA shortens

• time till complete wound healing and hospital stay.

And especially in chronic wounds:

• wIRA can enable wound healing in non-healing wounds.

Tissue temperature [3], [4], [5], [6], tissue oxygen partial pressure [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], and tissue perfusion are decisive factors for a sufficient tissue supply with energy and oxygen and consequently as well for wound healing and infection defense, see review in [1], [2].

wIRA can increase tissue temperature [5], [6], [18], [19], [20], [21], [22], [23], tissue oxygen partial pressure [5], [24], and tissue perfusion [21], [22], [23], [24], [25], see review in [1], [2].

wIRA in clinical use at appropriate irradiances has been described as helpful and safe [5], [6], [10], [18], [19], [20], [21], [22], [23], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], review in [1], [2], and with possible protective cellular effects [45], [46], [47], [48], [49], [50].

Acute wounds and especially chronic wounds, non-healing wounds or infected problem wounds should be irradiated with wIRA ideally once or twice per day for (20-)30 minutes each (longer irradiation times per day are possible and often helpful), at least three times per week for (20-)30 minutes [1], [2]. wIRA does not replace other sensible/necessary therapeutic procedures but complementes them. Correspondingly the therapy with wIRA has to be embedded in an overall therapeutic concept. wIRA can be used independently from therapy preferences concerning wound management (e.g. moist wound management). Typically for wIRA irradiation the wound has to be uncovered, as most bandages or wound dressings (with the exception of e.g. some tested transparent foils) are not adequately permeable for wIRA [1], [2].

According to modern concepts [51] for the assessment of wound healing also other end-points and variables of interest aside from a complete wound closure have to be used like reduction of pain, improvement of quality of life, improvement of the cosmetic result, reduction of scars, clinically relevant shortening of the time of wound healing and improved quality of healing [2]. Nowadays great importance is placed on the reduction or avoidance of pain in order to improve the wound healing and to avoid the formation of a pain memory with chronification of the pain [52], [53] associated with the application of management strategies of common acute and chronic wounds.

Up to now 6 prospective clinical studies with wIRA concerning wound healing have been performed, 3 with acute wounds (presented here), 3 with chronic wounds (presented in [54]).

A prospective, randomized, controlled, double-blind study with 111 patients (94 were finally included) after major abdominal surgery at the University Hospital Heidelberg, Germany, Department of Surgery, showed with 20 minutes irradiation twice a day (starting on the second postoperative day) in the group with wIRA and visible light VIS (wIRA(+VIS), approximately 75% wIRA, 25% VIS) compared to a control group with only VIS a significant and relevant pain reduction combined with a markedly decreased required dose of analgesics: Remarkably during 230 single irradiations with wIRA(+VIS) the pain decreased without any exception (median of decrease of pain on postoperative days 2-6 was 13.4 on a 100 mm visual analog scale VAS 0-100), while pain remained unchanged in the control group (p<0.001, significant) (see Figure 1 [Fig. 1]). The required dose of analgesics was 57-70% lower in the subgroups with wIRA(+VIS) compared to the control subgroups with only VIS (median 598 versus 1398 ml ropivacaine, p<0.001, for peridural catheter analgesia; 31 versus 102 mg piritramide, p=0.001, for patient-controlled analgesia; 3.4 versus 10.2 g metamizole, p=0.005, for intravenous and oral analgesia, see Figure 2 [Fig. 2]) [5].

During irradiation with wIRA(+VIS) the subcutaneous oxygen partial pressure rose markedly by approximately 30% and the subcutaneous temperature by approximately 2.7°C (both in a tissue depth of 2 cm), whereas both remained unchanged in the control group: after irradiation the median of the subcutaneous oxygen partial pressure was 41.6 (with wIRA) versus 30.2 mm Hg in the control group (p<0.001, significant, see Figure 3 [Fig. 3]), the median of the subcutaneous temperature was 38.9 versus 36.4°C (p<0.001, significant, see Figure 4 [Fig. 4]). There was a trend towards increased subcutaneous oxygen partial pressure, both before and after irradiation, from the second to the tenth postoperative day in the group with wIRA (see Figure 3 [Fig. 3]) as a sign of persistent effects of wIRA on the tissue, at least lasting for more than 12 hours [5].

The overall evaluation of the effect of irradiation, including wound healing, pain and cosmesis, assessed on a VAS (0-100 with 0 representing maximal negative effect, 50 as indifferent point of no effect and 100 representing maximal positive effect) by the surgeon (median 79.0 versus 46.8, p<0.001) or the patient (79.0 versus 50.2, p<0.001) was markedly better in the group with wIRA compared to the control group [5].

This was also true for single aspects:

Wound healing assessed on a VAS by the surgeon (median 88.6 versus 78.5, p<0.001, significant) or the patient (median 85.8 versus 81.0, p=0.040, trend) [5],

Cosmetic result assessed on a VAS by the surgeon (median 84.5 versus 76.5, p<0.001) or the patient (median 86.7 versus 73.6, p=0.001) [5].

In addition there was a trend in favor of the wIRA group to a lower rate of total wound infections (3 of 46, approximately 7%, versus 7 of 48, approximately 15%, p=0.208) including late infections after discharge, caused by the different rate of late infections after discharge: 0 of 46 in the wIRA group and 4 of 48 in the control group [5].

And there was a trend towards a shorter postoperative hospital stay: 9 days in the wIRA group versus 11 days in the control group (p=0.037) [5].

(Regarding the necessity of an alpha error adjustment in multiple testing, in [5] five p-values are presented confirmatively, see e.g. Figure 3 [Fig. 3] and Figure 4 [Fig. 4], and the other p-values in a descriptive sense.)

The principal finding of this study was that postoperative irradiation with wIRA can improve even a normal wound healing process [2], [5], [29], [30].

As both groups received irradiation with visible light and no placebo effects were observed (no acute changes in objective and subjective variables during irradiation in the control group), the acute changes in the wIRA group were attributed to wIRA within the irradiation [5].

In accordance with [1] and [2] the effects of wIRA are explained in [5] as thermal and non-thermal effects (see [1]). wIRA improves factors involved in energy production: tissue oxygen partial pressure, perfusion and temperature. As non-thermal effects are mentioned the direct stimulation of cells causing immunomodulation or improvement of wound healing, and the influence on adhesive interactions between cells and extracellular matrices [55], which have a regulatory role in wound repair processes [5]. Pain relief by wIRA is explained both by thermal and non-thermal effects: increased perfusion allows better elimination of accumulated metabolites, such as pain mediators, lactic acid and bacterial toxins, and increases metabolism; non-thermal effects include direct effects on cells and possibly on nociceptors [5]. Other cross effects are mentioned in [5]: Pain reduction by wIRA leads to a reduced required dose of analgesics and consequently to decreased sedation and to better bowel movement. Pain reduction by wIRA may support its vasodilatory effect and may decrease the risk of wound infection, as adequate control of postoperative pain increases oxygen partial pressure and decreases by this the risk of infection markedly [5], [56], [57]. An increased oxygen partial pressure can influence positively the concentration and receptor density of vascular endothelial growth factor (VEGF) in the wound, resulting in accelerated healing by increased blood vessel growth [5], [58].

The effects of wIRA (increased oxygen partial pressure) and antibiotics are presumably synergistic, as antibiotics are less effective in hypoxic tissue [5], [59], [60].

The shorter postoperative hospital stay with the application of wIRA and the tendency towards lower infection rates are expected to lead to substantial reductions in average hospital costs [5].

The reduced degree of pain during wIRA treatment, the decreased need for pain medication, better wound healing, and shorter hospital stay might explain the markedly better overall assessment for the entire treatment period recorded before discharge by patients treated with wIRA, reflecting a better quality of life [5].

A prospective, randomized, controlled, double-blind study with 45 severely burned children at the Children’s Hospital Park Schönfeld, Kassel, Germany, Department of Pediatric Surgery, showed with 30 minutes irradiation once a day (starting on the first day, day of burn as day 1) in the group with wIRA and visible light VIS (wIRA(+VIS), approximately 75% wIRA, 25% VIS) compared to a control group with only VIS a markedly faster reduction of wound size [32]. On the fifth day (after 4 days with irradiation) decision was taken, whether surgical debridement of necrotic tissue was necessary because of deeper (second degree, type b) burns (11 of 21 in the group with wIRA, 14 of 24 in the control group) or non-surgical treatment was possible (second degree, type a, burns) (10 of 21, 47%, in the group with wIRA; 10 of 24, 42%, in the control group). The patients treated conservatively were kept within the study and irradiated until complete cutaneous regeneration (complete reepithelialization) occurred.

The relative change of the wound size is presented in Figure 5 [Fig. 5]: over the whole period of time at any day the relative reduction (in %) of the wound area (related to the size at the beginning) was larger in the group with wIRA compared to the control group, which means the patients in the group with wIRA showed a markedly faster reduction of wound area: a median reduction of wound size of 50% was reached in the group with wIRA already after 7 days compared to 9 days in the control group, a median reduction of wound size of 90% was already achieved after 9 days compared to 13 days in the control group, which are relevant advantages concerning time [32]. In addition the group with wIRA showed superior results till 3 months after the burn in terms of the overall surgical assessment of the wound, cosmesis, and assessment of effects of irradiation compared to the control group [32]. E.g. the median of the assessed effect of irradiation (VAS 0-100 with 0 representing maximal negative effect, 50 as indifferent point of no effect and 100 representing maximal positive effect) on days 7-9 was 58 versus 50 (no placebo effect in the control group), after 3 months 65 versus 56. The hospital stay was slightly shorter in the group with wIRA compared to the control group. These results are in accordance with the findings of the above described study of the University Hospital Heidelberg, Department of Surgery.

Examples of rapid improvement of wound healing with wIRA are presented in Figure 6 [Fig. 6] and Figure 7 [Fig. 7].

In a prospective, randomized, controlled study with 12 volunteers at the University Medical Center Charité, Berlin, Germany, Department of Dermatology, Center of Experimental and Applied Cutaneous Physiology, within each volunteer 4 experimental superficial wounds (5 mm diameter) as an acute wound model were generated by suction cup technique, removing the roof of the blister with a scalpel and a sterile forceps (day 1). 4 different treatments were used and investigated during 10 days: no therapy, only wIRA(+VIS) (approximately 75% wIRA, 25% VIS; 30 minutes irradiation once a day), only dexpanthenol (= D-panthenol) cream once a day, wIRA(+VIS) and dexpanthenol cream once a day.

Healing of the small experimental wounds was from a clinical point of view excellent with all 4 treatments. Therefore there were only small differences between the treatments with slight advantages of the combination wIRA(+VIS) and dexpanthenol cream and of dexpanthenol cream alone concerning relative change of wound size and assessment of feeling of the wound area. However laser scanning microscopy with a scoring system as described in [61] revealed differences between the 4 treatments concerning the formation of the stratum corneum (from first layer of corneocytes to full formation) especially on the days 5-7: fastest formation of the stratum corneum was seen in wounds treated with wIRA(+VIS) and dexpanthenol cream, second was wIRA(+VIS) alone, third dexpanthenol cream alone and last were untreated wounds.

Bacterial counts of the wounds were taken every 2 days until day 9 (4 follow-up samples per wound): wIRA(+VIS) and the combination of wIRA(+VIS) with dexpanthenol cream were able to inhibit the colonisation with physiological skin flora up to day 5 when compared with the two other groups (untreated group and group with dexpanthenol cream alone). All groups developed colonisation peaks at day 7 and an ensuing decline of colonisation at the time of wound closure (day 9). At any investigated time, the amount of colonisation under therapy with wIRA(+VIS) alone was lower (interpreted as more suppressed) compared with the group with wIRA(+VIS) and dexpanthenol cream. It can be interpreted, that among the tested therapies wIRA(+VIS) led to disadvantageous conditions for bacteria.

The investigation of a preliminary group ahead of a formerly planned prospective randomized, controlled, blinded study concerning wIRA during rehabilitation after hip and knee endoprosthetic operations revealed both clinically and sonographically a faster resorption of wound seromas and wound hematomas and a reduction of pain by irradiation with wIRA(+VIS) [2], [62].

Independently from this a well documented case of a 64 year old female patient who had relapsing wound seromas and wound hematomas (without infection) after a hip operation (replacement of the acetabulum part of a 15 years old endoprosthesis) is remarkable: even after an additional operation with the only intention to stop the wound seromas and after approximately 8 aspirations of seroma fluid (up to approximately 90 mL within one aspiration) within 2 months, the wound seromas kept on recurring and a third operation was seriously considered. At that situation wIRA(+VIS) irradiation was started, beginning with 30 minutes twice a day and increasing up to 3 times one hour per day. Within a few days the seroma did no longer increase as usual, after approximately one week a slight decrease of seroma size was noticed clinically, and after approximately 2 months the seroma had resolved completely (both clinically and sonographically) without any aspiration of seroma fluid or operation since starting with wIRA(+VIS) irradiation, see Figure 8 [Fig. 8]. The situation continued to keep stable further on (up to now approximately 1 year follow-up) with full mobility and being able to do sports. This experience is in accordance with the well known effect, that wIRA decreases hypersecretion and inflammation.

wIRA can be used successfully for persistent postoperative pain:

After a thoracotomy with a successful coronary bypass operation sternal pains persisted for 9 months in a female patient, especially all movements, which expanded the thorax (like bringing the arms to the side backwards), caused an increase of pain – the two parts of the sternum showed a dehiscence on magnetic resonance tomography of 7 mm in spite of the cerclages –, three times 300 mg tramadol per day and in addition several times 25 mg tramadol per day (in total approximately 350-400 mg tramadol per day) (and for a period of time in combination with amitryptilin in analgesic indication) were necessary. Within 6 weeks of irradiating with wIRA(+VIS) 30-45 minutes per day led to a marked reduction of pain and only 100 mg tramadol per day were sufficient. During each irradiation the subjective state improved from 30 to 80-90 on a VAS (0-100, 0 representing extremely bad, 100 extremely good). After a few additional weeks pain was further decreased and analgesic medication could be stopped completely.

As positive effects both of preoperative [3] and of postoperative [4], [5] warming have already been shown, it seems clinically prudent to use wIRA both pre- and postoperatively, e.g. in abdominal and thoracic operations.

wIRA can be used preoperatively (e.g. during 1-2 weeks) to precondition donor and recipient sites of skin flaps, transplants or partial-thickness skin grafts, and postoperatively to improve wound healing and to decrease pain, inflammation and infections at all mentioned sites.

wIRA can be used to support routine pre- or intraoperative antibiotic administration or it might even be discussed to replace this under certain conditions by wIRA [5].

Aspects to use wIRA in combination with a photodynamic therapy PDT to prevent or decrease wound infections are presented in [54].