Pyridostigmine Efficacy and Safety for Treatment of Ileus After Colorectal Surgery

Inclusion Criteria:

1. Adult (age 18 and over) patients with benign or malignant colonic or rectal diseasewho have undergone elective laparoscopic, robotic, or open colorectal resectionswith or without ostomy construction at our center, and subsequently developed POI,defined as symptoms of bloating with or without nausea and vomiting, with absence ofpassage of flatus or stool for at least 48 hours postoperatively and require returnto NPO status after initial diet attempts with or without placement of an NGT.

2. Radiographic confirmation of POI diagnosis either via abdominal radiography (KUB),computed tomography abdomen/pelvis (CT A/P), or both

3. ECOG Performance status < 4

4. Laboratory evidence of normal organ function, defined as:

5. Hemoglobin ≥ 7.0 g/dL

6. WBC ≤ 20,000/mcL and ≥ 4,000/mcL

7. Platelet count ≥ 100,000/mcL or ≤ 100,000,000/mcL

8. AST (SGOT) ≤ 2.5 times the institutional upper limit of normal

9. ALT (SGPT) ≤ 2.5 times the institutional upper limit of normal

10. Total bilirubin within the upper limit of institutional normal range

11. Serum Creatinine within the upper limit of institutional normal range

Exclusion Criteria:

1. Radiographic evidence of bowel obstruction

2. Documented intraabdominal septic complications (IASC, such as abdominopelvicabscess, peritonitis, anastomotic leak) at any time prior to or after enrollment

3. Isolated small bowel or ostomy surgery without colon or rectal resection

4. ASA score 5

5. Pregnant or breastfeeding females as PYR is classified by the FDA as a pregnancyrisk category C medication with the potential for teratogenic or abortifacienteffects and demonstrated secretion into breastmilk with an unknown but potentialrisk for adverse effects in the nursing infants

6. Current use of any other investigational agents including: neostigmine or otheracetylcholine esterase inhibitors, alvimopan, metoclopramide, erythromycin,methylnaltrexone, naloxegol, cisapride, and laxatives or cathartics (i.e. milk ofmagnesia, polyethylene glycol)

7. History of allergic reactions attributed to PYR or other acetylcholine esteraseinhibitors

8. Patients with any of the following uncontrolled, concurrent illnesses: active orlatent MG, bronco-constrictive disease (asthma/reactive airway disease), chronicobstructive lung disease (COPD), symptomatic congestive heart failure (CHF),unstable angina pectoris, cardiac arrhythmia including bradycardia, renal failure,hepatic failure, gastroparesis, short bowel syndrome (small bowel < 200cm),preexisting short or large bowel dysmotility or pseudo-obstruction, chronicconstipation/laxative use, peritoneal carcinomatosis, and psychiatric illness/socialsituations that would limit compliance with study requirements