Intra-operative locally injected pharmacotherapy as a novel strategy for adhesion prophylaxis

Pharmacotherapy for peritoneal adhesion prophylaxis has been a focus for intensive research. Previous strategies included intravenous and intraperitoneal application of suitable pharmaceutical agents. However, success of these strategies in humans has been limited. Here we describe intra-operative local injection of pharmaceuticals as a novel strategy for adhesion prophylaxis.

N=208 peritoneal lesions were created in 26 adult Wistar rats. In each animal, lesions on one flank were randomly chosen for treatment with locally injected prednisolone whereas the contralateral side was injected with normal saline. Half of the animals were randomly selected for early adhesion scoring after 3 days. Adhesions were scored after 10 days in the other animals.

One animal randomized into the late group died peri-operatively. In the early analysis group, 27% (14/52) of treated lesions were affected by adhesions, whereas 50% (26/52) of control lesions were affected by adhesions. This difference was statistically significant (p=0.02). In the late analysis group, 52% (25/48) of treated lesions were affected by adhesions, whereas 60% (29/48) of control lesions were affected by adhesions. This difference did not reach statistical significance.

These experiments provide proof of principle that intra-operative local injection of pharmaceutical agents is a promising strategy for adhesion prophylaxis. Once sutiable agents become available this could become as common as local anesthesia for pain reduction. However, the effect of injected prednisolone diminishes before the vulnerable time-frame for adhesion formation closes. Therefore slow-release formulations and other agents with longer effect will need to be investigated in the future.