The role of mast cell stabilization in treatment of postoperative ileus: a pilot study.
OBJECTIVE
Although postoperative ileus (POI) is considered multifactorial, intestinal inflammation resulting from manipulation-induced mast cell activation is recognized as an important pathophysiological mechanism. Therefore, mast cell stabilization may represent a new therapeutic approach to shortening POI. The aim of this paper was to study the effect of ketotifen, a mast cell stabilizer, on postoperative gastrointestinal transit in patients who underwent abdominal surgery.


METHODS
In this pilot study, 60 patients undergoing major abdominal surgery for gynecological malignancy with standardized anesthesia were randomized to treatment with ketotifen (4 or 12 mg) or placebo. Patients were treated for 6 days, starting 3 days before surgery. Gastric emptying of liquids, selected as a primary outcome parameter, was measured 24 h after surgery using scintigraphy. Secondary end points were (scintigraphically assessed) colonic transit, represented as geometrical center of activity (segment 1(cecum) to 7(stool)) and clinical parameters.


RESULTS
Gastric retention 1 h after liquid intake was significantly reduced by 12 mg (median 3% (1-7), P=0.01), but not by 4 mg ketotifen (18% (3-45), P=0.6) compared with placebo (16% (5-75)). Twenty-four hour colonic transit in placebo was 0.8 (0.0-1.1) vs. 1.2 (0.2-1.4) colon segments in the 12 mg ketotifen group (P=0.07). Abdominal cramps were significantly relieved in patients treated with 12 mg ketotifen, whereas other clinical parameters were not affected.


CONCLUSIONS
Ketotifen significantly improves gastric emptying after abdominal surgery and warrants further exploration of mast cell stabilizers as putative therapy for POI.
The
Frans O
FO
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Buist
Marrije R
MR
Lei
Aaltje
A
Bennink
Roelof J
RJ
Hofland
Jan
J
van den Wijngaard
René M
RM
de Jonge
Wouter J
WJ
Boeckxstaens
Guy E
GE
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D005833:Genital Neoplasms, Female / Q000601:surgery*; D013509:Gynecologic Surgical Procedures / Q000009:adverse effects*; D006634:Histamine H1 Antagonists / Q000008:administration & dosage*; D006801:Humans; D007418:Intestinal Pseudo-Obstruction / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology*; D007665:Ketotifen / Q000008:administration & dosage*; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D008875:Middle Aged; D010865:Pilot Projects
D006634:Histamine H1 Antagonists; D007665:Ketotifen