Neostigmine is commonly used for medical treatment of acute colonic pseudo obstruction, however, the ideal route of administration has not been determined. Though IV push works rapidly, it is likely associated with the most side effects. This study will compare the efficacy and side effect profile of 2 potential routes of administration: IV push and subcutaneous.

Acute colonic pseudo-obstruction (ACPO) is a severe form of colonic ileus seen in patients hospitalized with a variety of medical and surgical conditions. The most serious complication is spontaneous colonic perforation, which occurs in 3% of cases with a mortality rate of up to 50%. The risk of perforation is greater in those patients with a cecal diameter >12 cm, although the duration of dilation might be more important than the cecal diameter. A significant number of patients will respond to the conservative measures enumerated in the abstract.

Endoscopic decompression of the dilated colon is undertaken commonly to prevent spontaneous perforation. However, it is performed under suboptimal conditions (unprepared and distended colon) increasing the risk of complications with a morbidity rate of 3% and a mortality rate of 1%. Furthermore, although effective initially in 69% of cases, 40% of them will have at least one recurrence. To decrease this recurrence rate, endoscopic placement of a drainage tube is now advocated. Patients who fail to respond to conservative therapy and colonoscopic decompression will require surgery, which has a mortality rate of up to 26%.

In an effort to find a more effective, noninvasive therapy, Ponec et al., introduced and highlighted the effect of IV neostigmine (2 mg over 3-5 min). Neostigmine was significantly more effective than placebo in rapidly decreasing colonic dilation in the majority of patients with ACPO. Although it has a short half-life, a single IV dose of 2 mg of neostigmine was sufficient in most cases to restore colonic motility.

It is important to be aware of contraindications to using parasympathetic agents, including bradyarrhythmia and history of bronchospasm. Patients need to be monitored while neostigmine is infused, and atropine should be available in the event of complications. Patients with renal insufficiency might be at higher risk of complications as a significant quantity of the drug is excreted in urine.

In light of these contraindications, administration by the subcutaneous (SQ) route has been utilized intermittently for ACPO. Data for use of SQ administration of neostigmine in adult patients are limited to one multi-institutional observational study, one case series, and two case reports in acute medical and palliative care patients. Although these case reports describe a range of dosing, the SQ route of administration appears to be attractive alternative to IV administration for this indication, with a time to effect of 8 to 10 hours.

This study is a prospective randomized non-inferiority trial that seeks to analyze the success of two different routes of neostigmine administration, sub-cutaneous and IV push, for safety and efficacy in the ACPO patient population.

Inclusion Criteria:

1. Patients with radiologically confirmed acute colonic pseudo obstruction (ACPO).

   1. Plain abdominal radiograph or computed tomography imaging
   2. Cecal diameter of >9 cm or transverse colon diameter of >6 cm

2. Distal obstruction ruled out on imaging (Contrast enema, endoscopy, CT scan)

Exclusion Criteria:

1. Patients with previous neostigmine administration during current hospitalization
2. Patients with prior attempt at endoscopic decompression on this admission.
3. Patients with base-line heart rate of less than 60 beats per minute or on beta blocker medication
4. Patients with systolic blood pressure of less than 90 mm Hg
5. Signs of bowel perforation, with peritoneal signs on physical examination or free air on radiographs
6. Active bronchospasm requiring medication
7. Treatment with prokinetic drugs such as cisapride or metoclopramide in the 24 hours before evaluation
8. A history of colon cancer or partial colonic resection
9. Signs concerning for colonic obstruction
10. Active gastrointestinal bleeding
11. Pregnancy
12. Serum creatinine concentration of more than 3 mg per deciliter (265μmol per liter).