FLUCTUATIONS IN THE SECRETION OF PANCREATIC-ENZYMES BETWEEN CONSECUTIVE DOSES OF OCTREOTIDE - IMPLICATIONS FOR THE MANAGEMENT OF FISTULAS

Objective: To determine whether variations in pancreatic enzyme secretion between consecutive subcutaneous administrations of octreotide explain why octreotide takes longer than somatostatin to facilitate the closure of gastrointestinal fistulae. Methods: Pancreatic enzyme secretion was studied over a 3-day period in a patient with a catheter left in the pancreatic duct postoperatively. On days 1 and 3 the patient did not receive octreotide (control days) but on day 2 he received subcutaneous octreotide 100 mug every 8 h. Pancreatic juice was collected at 2-h intervals over the 3-day period. Results: On the day of octreotide treatment, the patient's pancreatic secretory volume and protein output were significantly reduced (P < 0.001, Mann-Whitney U-test) compared with the 2 control days. The pancreatic secretory volume decreased markedly after the first injection of octreotide and remained low for the duration of the treatment period. The enzyme concentration of the pancreatic juice was also markedly reduced after the first injection of octreotide. However, approximately 4h after each octreotide injection the protein concentration of the pancreatic juice began to rise progressively, peaking approximately 6h after each administration of the analogue. Conclusion: Subcutaneous administration of octreotide produces a sustained decrease in the volume of pancreatic juice secreted, but enzyme secretion rises progressively between consecutive administrations of the analogue. The net effect is therefore the production of low volumes of pancreatic juice with a high enzyme concentration between consecutive injections of octreotide, which may delay the healing of the fistula tract. This may explain why longer treatment periods are required to achieve fistula closure with octreotide than with somatostatin, particularly in the case of pancreatic fistulae.