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Page 8 of 11                                           Kumar et al. Plast Aesthet Res 2020;7:29  I  http://dx.doi.org/10.20517/2347-9264.2019.71

               protocol or as required. The minimum required effective negative pressure produces folds of plastic of
               LAD that lie snuggly over the wound or skin under LAD; higher pressures are guided by pain complaints
               by the patient and bleeding from the wound. Physiotherapy and occupational therapy may be started at
               the earliest. Obviously dead tissues are removed surgically and a new LAD is reapplied every 5-7 days. The
               LAD may be changed if significant leakage occurs. Daily LAD wash with saline and antimicrobial (Betadine)
               solution is performed. A secondary, elective procedure is performed (e.g., split skin graft/flap etc.) as and
               when required. Physiotherapy may be required after satisfactory healing [25,30,37] .

               Role of LAD
               LAD provides limited access of wound pathogens to the hospital environment and vice versa. LAD is
               helpful in preventing and treating secondary damage in trauma by reducing edema and removing harmful
                                                                 [37]
               enzymes, toxins and other chemicals from the open wound .
               Effects of LAD on oncosis (cellular swelling)
               Cellular swelling due to sodium and potassium pump failure obstructs the microcvasculature, leading to
               cell death and necrosis of the affected tissue. Intermittent negative pressure of LAD produces intermittent
               compression of the part under LAD leading to reduction in edema. This intra LAD compression, if
               combined with early intra LAD physiotherapy, effectively controls edema. Edema reduction thus improves
                                           [37]
               the circulation of adjacent tissues .
               Effects of LAD on pH
                                              [38]
               In a RCT (randomized control trial) , 42 patients with chronic wounds in each group (LAD, conventional
               dressing) were studied for wound surface pH. On the 10th post-operative day, the LAD group showed a
               significant (P = 0.048) reduction in pH as compared to the conventional dressing group (LAD group 0.41 ±
               0.26 vs. conventional group 0.83 ± 0.52) with the mean wound surface pH (± SD) in the LAD group 7.5 ± 0.43.

               Following trauma, the release of lysosomal enzymes is responsible for secondary damage. Lysosomal
               enzyme activity (lysosomal digestion) is optimal in acidic pH (< 5), reduced at near neutral pH, and
                                                [39]
               is nearly de-activated at a pH of 7.2 . Lysosomal enzymes are not only removed by LAD but also
               deactivated, or its activity reduced by a change in pH under LAD. Hence, LAD may prove to be an effective
               tool to control secondary damage following trauma.


               LAD provides a safe environment during waiting or temporization
               during the waiting period, infection and SIRS may pose a difficult problem but is controlled effectively with
               LAD.

               1. Control of infection. LAD controls infection in the following ways [37,40] : wound isolation and safe disposal
               of drainage. The important feature of LAD design helps to control infection.

               Prevention of wound invasion: negative pressure of LAD provides an alternate channel for the movement
                                                                                                        5
               of microorganisms. Intermittent or continuous negative pressure reduces bacterial concentrations (< 10 /g
               tissue) to a level that prevents invasion.

               Mechanical disruption of quorum sensing by negative pressure occurs as negative pressure prevents the
               desired concentration of bacterial chemicals through intermittent/continuous removal.

               Mechanical disruption of biofilm: Higher intra-LAD negative pressure can cause disruption of the biofilm
               and expose bacteria in the niche environment to negative pressure.
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