The options for the management of blisters are keeping the blister intact, deroofing the blister, aspiration of the blister and recently, using the blister fluid as an adjunct to wound healing.

Burn injuries are a unique type of tissue trauma. They have features not associated with other wounds such as significant oedema, eschar formation and ischaemic changes. Heat applied at a cellular level causes denaturation of proteins and loss of plasma membrane integrity.

The focus of burn fluid resuscitation and burn wound management is to prevent further injury to the zone of stasis and facilitate healing.

Following thermal injury to skin, blisters may form in second degree burns, both superficial and deep partial thickness burns. This occurs as a physiological response to separation of the dermis from the burnt epidermis. In acute burn injury, vasodilatation and increased capillary leakage leads to ultrafiltration of the plasma into the wound. This fluid collects in the space between the epidermis forming a blister. The plasma proteins and proteinaceous cellular debris present in the exudate causes further fluid shift from plasma to into the blister. This fluid shift, in large burns, can cause a pressure effect of the blister on the surrounding tissue.

Intact blisters preclude the ability to accurately assess burn depth and percentage burn. In dark-skinned patients this is can be more challenging as burnt skin is darker rather than red. If blistered and dead skin is not removed, burn size can be miscalculated, which would result in inadequate fluid resuscitation, causing burn wound conversion. Blisters form in both superficial partial thickness and deep partial thickness burns. The blister wall thickness can help in differentiating between them. However, this is not always possible, and as deep partial thickness burns may need grafting. Misdiagnosing the depth of the burn can delay wound healing by treating the wound expectantly. The debate on blister management centres around the effects of blister fluid, pressure of blister and infection.

Fluid in the blister is the ultrafiltrate of the plasma, which is rich in proteins such as immunoglobulins, various cytokines, prostaglandins, interleukins and various growth factors. This fluid is pro-inflammatory, and the evidence regarding its effect on wound healing is varied.

Growth factors such as platelet-derived growth factor (PDGF), interleukin (IL-6) and transforming growth factor (TGF) alpha were found in elevated levels in blister fluid. Adding blister fluid to a culture of keratinocytes enhanced the growth of the cultured cells. However, contrary evidence on the effect of epidermal cell proliferation was found by Garner et al. They found that the cell responses were decreased, suggesting that re-epithelization may be inhibited by intact blisters. Blister fluid was found to not only influence cell division but also cell functioning. Lymphocyte-repressive substances were found in blister fluid, whilst these tend to be transient, they may have negative effects on wound healing. Leukocytes were also found to be affected by having decreased ability for phagocytosis of Pseudomonas aeruginosa. Blister fluid was also found to have decreased opsonisation for Pseudomonas aeruginosa. This gives rise to a debate to the best practise on blister management.

In addition to growth factors for wound healing, blister fluid has also been found to have angiogenic factors such as angiogenin, epidermal growth factor receptor, epithelial cell-derived neutrophil-activating protein-78 (ENA-78), and IL-8. Angiogenin was first discovered from the cell culture medium of colon cancer cells and is a potent inducer of the angiogenic process. Angiogenin in blister fluid was found to be an important for neovascularisation, by independently inducing differentiation of circulating angiogenic cells into endothelial cells.

The successful use of platelet-rich plasma on accelerating wound healing is well documented. Given the similarity of blister fluid to plasma it was thought that blister fluid would enhance wound healing in similar manner. By aspirating the fluid, this would provide an opportunity to study the effects of topical application of sterile blister fluid on wounds. In a case report, this was done on the superficial part of a mixed depth wound, and this area of burn was healed by 11 days. The zone of stasis is an area of focus for prevention of burn wound progression both in terms of depth and size.

It in these areas that the effects of vasoactive metabolites play their role in mitigating against burn wound conversion. The damage to the microcirculation in this zone is greatest between 12-24 hours. This occurs due to gradual release of vasoactive cytokines. Burned tissue release bradykinin and arachidonic acid. Histamine, bradykinin and oxygen free radicals act on capillary venules in the zone of stasis to increase permeability. Bradykinin also stimulates the release of arachidonic acid from cell membrane phospholipids.

Arachidonic acid is converted to vasoactive compounds, some are stable, and some are unstable metabolites. The stable metabolites are prostaglandin E2 and F2, with the former causing vasodilatation and inhibiting platelet adhesion whilst F2 is a vasoconstrictor.

The unstable metabolites, prostaglandin I2 and thromboxane A2, are thought to have a more potent effect. Prostaglandin I2 is a vasodilator whilst thromboxane A2 is a vasoconstrictor and platelet aggregator. Vasoconstriction results when the there is an imbalance between thromboxane and prostaglandin I2.  Vasoconstriction in the zone of stasis can lead to burn wound conversion, increasing depth and size of burn. Thromboxane levels are markedly elevated in burn tissue and blister fluid. This rise in thromboxane begins four hours after the burn. Thromboxane causes vasoconstriction and platelet aggregation, leading to thrombosis in the zone of coagulation and cell death.

Biochemical analysis of blister fluid reveals that blister fluid contains arachidonic acid metabolites, thromboxane A and calmodulin. The vasoconstrictive effects of thromboxane on the zone of stasis are a cause for concern in retention of blister fluid.

Blister fluid may become a gelled blister, this has the potential to create a pressure effect on the surrounding tissue thus create an eschar. This gel-filled blister also is an ideal culture medium for bacteria.

Given the above conflicting research, a prospective randomised trial on patients with blister following burn injury was performed by Hyung-Suk Ro et al. Two groups were compared, in the one group blisters were aspirated and the other group the blisters were deroofed. They found no difference in time to wound healing, but some evidence of improved scar thickness and pain in the aspirated group. The majority of the blisters in this study were between 6-10mm, with only 22% being greater than 10mm. The possible advantaged of keeping blisters intact are prevalent, however this must be weighed against inaccurately assessing burn wound depth and size. In a small wound, in which wound size and depth can be accurately determined, the blister may be aspirated and treated with closely observed moist wound care. In larger burns where the burn size and depth cannot be accurately assessed, the wound should be cleaned, and blisters debrided followed with an appropriate dressing.

*References available on request.