Therapeutics/Acute Colonic Pseudo-obstruction

Case

A 63-year-old man developed increasing abdominal distension 3 days after radical prostatectomy with bilateral lymph node dissection for prostate cancer. His postoperative course was complicated by atrial fibrillation with rapid ventricular response requiring intravenous rate control with calcium-channel antagonist medication in the ICU. The patient reported progressive cramping abdominal pain, bloating, and distension over a 3-day period. There was nausea but no vomiting. He was passing flatus but minimal stool. His past medical history was notable only for osteoarthritis and hypertension. His postoperative medications also included morphine administered by patient-controlled analgesia.

Abdominal radiographs revealed gaseous distension of large bowel with a cecal diameter of approximately 10cm. There were no fevers and the leukocyte count was normal. Supportive therapy was instituted but the patient had progressive symptoms and distension despite these measures. Follow-up abdominal radiograph the next day showed persistent, marked cecal distension. Given the significant colonic dilation and non-response to over 24h of supportive therapy, the patient was considered for pharmacologic decompression with neostigmine. Although there had been atrial tachyarrythmias postoperatively, the rate had been adequately controlled and the rhythm had reverted to normal sinus spontaneously. Neostigmine, 2mg intravenously, was administered with prompt evacuation of flatus and stool, and resolution of colonic distension by subsequent radiograph. No adverse reactions to the infusion were noted. He made a full recovery and was discharged home a week later.

Therapeutics

An evidenced-based guideline for the treatment of Acute colonic pseudo-obstruction has been published by the American Society of Gastrointestinal Endoscopy. The clinical dilemma facing the clinician caring for a patient with Acute colonic pseudo-obstruction is whether to treat the patient with conservative measures and close observation versus proceeding with medical orendoscopic decompression of the dilated colon.

Treatment options for Acute colonic pseudo-obstruction include appropriate supportive measures, pharmacologic therapy, colonoscopic decompression, and surgery. Despite extensive literature documenting the clinical features of Acute colonic pseudo-obstruction, there are few controlled clinical trials on the treatment of this condition, and most evidence for efficacy of treatments comes from anecdotal reports, retrospective reviews, or uncontrolled studies.

Supportive Therapy

Supportive therapy (Table Supportive therapy for acute colonic pseudo-obstruction) is the preferred initial management of Acute colonic pseudo-obstruction and should be instituted in all patients. Patients are given nothing by mouth. Intravenous fluids and electrolytes imbalances are corrected. Nasogastric suction is provided to limit swallowed air from contributing further to colonic distension. Laxatives are avoided, particularly lactulose, which provides substrate for colonic bacterial fermentation, resulting in further gas production. A rectal tube should be inserted and attached to gravity drainage.

Medications that can adversely affect colonic motility, such as opiates, anticho-linergics, and calcium-channel antagonists are discontinued if possible. Mobilization and ambulation of patients are encouraged, and the patients’ position in bed should be changed frequently. The knee-hand position has been advocated by some to stimulate motility and promote colonic emptying. Serial physical examinations and daily abdominal radiographs help closely monitor the progress of the patient. The benefits of any particular component of these supportive measures are unknown as these measures have not been studied individually.

Table Supportive therapy for acute colonic pseudo-obstruction

Nothing by mouth

Correct fluid and electrolyte imbalances

Nasogastric suction

Rectal tube decompression

Limit offending medications

Frequent position changes, ambulate if possible

Conservative management is successful as the primary treatment in the majority of patients. Sloyer et al. reported 25 cancer patients with Acute colonic pseudo-obstruction (mostly non-gastrointestinal malignancies). The mean cecal diameter was 11.7cm (range 9-18cm). Of the 24 patients treated conservatively, 23 (96%) improved by clinical and radiologic criteria with the median time to improvement of 1.6 days (mean 3 days). There were no perforations or Acute colonic pseudo-obstruction-related deaths. In another retrospective series of 151 patients, 117 (77%) had spontaneous resolution of Acute colonic pseudo-obstruction with conservative treatment. These studies demonstrate that the initial management of Acute colonic pseudo-obstruction should be directed towards eliminating or reducing factors known to contribute to the problem.

The decision to intervene with medical therapy, colo-noscopy, or surgery is dictated by the patient’s clinical status. Knowing that the risk of colonic perforation is greatest with cecal diameter greater than 12 cm and when distension has been present for more than 6 days, patients with marked cecal distension (>10cm) of significant duration (>3-4days) and those not improving after 24-48 h of supportive therapy are candidates for further intervention. In the absence of signs of overt peritonitis or perforation, medical therapy with neostigmine should be considered the initial therapy of choice.

Medical Therapy

Neostigmine

The only randomized, controlled therapeutic trial for Acute colonic pseudo-obstruction involves intravenous neostigmine. Neostigmine, a reversible acetylcholinesterase inhibitor, indirectly stimulates muscarinic receptors, thereby enhancing colonic motor activity, inducing colonic propulsion, and accelerating transit. The rationale for using neostigmine stems from the imbalance in autonomic regulation of colonic function that is proposed to occur in Acute colonic pseudo-obstruction. Neostigmine, administered intravenously, has a rapid onset of action (l-20min) and short duration (l-2h). The elimination half-life averages 80min, which is prolonged in patients with renal insufficiency.

A randomized, double-blind, placebo-controlled trial evaluated neostigmine in patients with Acute colonic pseudo-obstruction with a cecal diameter of greater than 10 cm and no response to 24h of conservative therapy. Exclusion criteria were suspected ischemia or perforation, pregnancy, severe active bronchospasm, cardiac arrhythmias, and renal failure. Patients were randomized to receive neostigmine, 2mg, or saline by intravenous infusion over 3-5 min. A clinical response was observed in 10 of 11 patients (91%) randomized to receive neostigmine compared to 0 of 10 receiving placebo. The median time to response was 4 min. Eight patients not responding to initial infusion (seven placebo, one neostigmine) were administered open-label neostigmine, and all had prompt decompression. Of the 18 patients who received neostigmine, either initially or during open-label treatment, 17 (94%) had a clinical response. The recurrence of colonic distension after neostigmine decompression was low (11%). The most common side effects observed with neostigmine were mild abdominal cramping and excessive salivation. Symptomatic bradycardia requiring atropine occurred in two of 19 patients.

Neostigmine was also evaluated in a double-blinded, placebo-controlled trial involving 24 critically ill, ventilated patients with ileus (denned as absence of stools for 3 days). No details of the extent and duration of colonic distension were provided. Neostigmine was administered as a continuous infusion (0.4mg/h for 24h). Of the 13 patients receiving neostigmine, 11 passed stools, whereas none of the placebo-treated patients passed stools (p < 0.001). No acute serious adverse events occurred but three patients had ischemic colonic complications 7-10 days after treatment.

There are also several non-controlled, open-label and retrospective series supporting the use of neostigmine in this condition. Collectively, rapid decompression of colonic distension was observed in 87% of patients with a recurrence rate of approximately 10% (Table Neostigmine for colonic decompression in patients with acute colonic pseudo-obstruction). In the prospective series reported by Mehta et al., a response to neostigmine was more likely in the postoperative setting (11 of 15 (73%) vs. 1 of 4 (25%), P = 0.07), and less likely in those with electrolyte imbalance or receiving antimotility agents (3 of 15 (20%) vs. 4 of 4, P = 0.003). This study highlights the importance of correcting electrolyte abnormalities and limiting exacerbating medications.

Repeated infusions or more prolonged treatment with neostigmine have not been fully evaluated. There have been reports of patients with Acute colonic pseudo-obstruction receiving repeated infusions and prolonged treatment with resolution.

Table Neostigmine for colonic decompression in patients with acute colonic pseudo-obstruction

Number	Design	Dose	Decompression
21(neostigmine 11, placebo 10)	RCT(OL in non-responders)	2.0mg intravenous over 3-5 min	10/11 in RCT 17/18 total
11	OL	2.5mg intravenous in 1 min	8/11
12	OL	2.5mg intravenous over 1-3min	12/12(2 patients required 2 doses)
16	OL	2.5mg intravenous over 60min	12/16
28	OL	2.5mg intravenous over 3min	26/28
11	OL	2.5mg intravenous over 60min	10/11(2 patients required 2 doses)
8	Retrospective	2.0mg intravenous	6/8(2 patients required 2 doses)
18	Retrospective	2.0mg intravenous	16/18
19	Prospective	2.0mg intravenous	16/19
141			123 (87%)

Table Suggested protocol for administration of neostigmine in acute colonic pseudo-obstruction

Neostigmine, 2mg, intravenous infusion over 3-5 min

Atropine available at bedside

Patient kept supine, on bedpan

Continuous electrocardiographic monitoring with vital signs for 30min

Continuous physician assessment for 15-30 min

This experience suggest that cautious repeated infusions can be successful and merits further study in patients with persistent or recurrent pseudo-obstruction.

Although neostigmine was associated with a favorable safety profile in the reported clinical trials, caution should be used when administering the medication. Neostigmine should be given with the patient kept supine in bed with continuous electrocardiographic monitoring, physician assessment, and vital signs for 15-30 min following administration. Contraindications to its use include mechanical obstruction, presence of ischemia or perforation, pregnancy, uncontrolled cardiac arrhythmias, severe active bronchospasm, and renal insufficiency (serum creatinine >3mg/dL).

The cost of neostigmine for a 2 mg ampule for paren-teral use is approximately $3. The cost to the patient after storage and handling fees are included is approximately $15.

Thus, neostigmine appears to be an effective, safe, and inexpensive method of colonic decompression in Acute colonic pseudo-obstruction. The published data support its use as the initial therapy of choice for patients not responding to conservative therapy if there are no contraindications to its use. In patients with only a partial response or recurrence after an initial infusion, a second dose is reasonable and often successful. If the patient fails to respond after two doses, proceeding with colonoscopic decompression is advised.

Other Pharmacologic Therapy

Administration of polyethylene glycol electrolyte solution in patients with Acute colonic pseudo-obstruction after initial resolution may decrease the recurrence rate of colonic dilation. Sgouros etal. evaluated polyethylene glycol electrolyte in a randomized, controlled trial in Acute colonic pseudo-obstruction patients who had initial resolution of colonic dilation. The study enrolled 30 patients with cecal diameter 10 cm or greater that had resolution of the colonic dilation with either neostigmine (22 patients) or endoscopic decompression (eight patients). Patients were then randomized to receive daily polyethylene glycol electrolyte 29.5g or placebo. Recurrence was defined as a cecal diameter of 8 cm or greater with a concomitant 10% increase after the initial successful decompression. Five (33%) patients in the placebo group had recurrent cecal dilation compared with none in the polyethylene glycol electrolyte group (P = 0.04). Therapy with polyethylene glycol electrolyte resulted in a significant increase in stool and flatus output, decrease in colonic distension on radiographic measurements, and improvement in abdominal girth.

There are few data on strategies to prevent the development of Acute colonic pseudo-obstruction. A recent randomized controlled clinical study evaluated whether lactulose or polyethylene glycol electrolyte were effective in promoting defecation in critically ill patients, whether either of the two is superior, and whether the use of enteral laxatives is related to clinical outcome. Three hundred and eight consecutive patients with multiple organ failure were included. Acute colonic pseudo-obstruction occurred in 4.1% of patients in the placebo group, 5.5% of patients in the lactulose group, and 1.0% of patients in the polyethylene glycol group. Thus, it appears that the use of polyethylene glycol electrolyte in critically ill patients to promote defecation may prevent the development of Acute colonic pseudo-obstruction, and that its use following a pseudo-obstruction episode decreases the recurrence rate.

There are only anecdotal case reports using other pro-kinetic agents, such as erythromycin, in Acute colonic pseudo-obstruction.

There are no data in Acute colonic pseudo-obstruction on the use of other newly-developed prokinetic agents such as the selective chloride channel activator, lubiprostone, or opioid antagonist, alvimopan.

Endoscopic Decompression

Procedural Aspects

Non-surgical approaches to mechanical decompression have included radiologic placement of decompression tubes, colonoscopy with or without placement of a decompression tube, and percutaneous cecostomy performed through a either an endoscopic or radiologic approach. Colonoscopic decompression is preferred among these invasive, non-surgical options given the reported experience in the literature, now totaling many hundreds of patients.

Colonic decompression is the initial invasive procedure of choice for patients with marked cecal distension (>10cm) of significant duration (>3 — 4 days), not improving after 24-48 h of supportive therapy, and who have contraindications to or fail neostigmine. Colonoscopy is performed to prevent bowel ischemia and perforation. It should not be performed if overt peritonitis or perforation are present.

There is no well-defined standard of care regarding the use of colonoscopy in Acute colonic pseudo-obstruction. Colonoscopic decompression can be helpful in Acute colonic pseudo-obstruction, but it is associated with a greater risk of complications, is not completely effective, and can be followed by recurrence. Oral laxatives and bowel preparations should not be administered prior to colonoscopy. Enemas can be given but the stool is usually already liquefied and whether their use facilitates colonoscopy in this setting is uncertain. Patients are often debilitated and bed-bound, thus making the administration of enemas impractical. Conscious sedation is achieved using primarily benzodiazepines, titrated to patient comfort. One should limit or use only low doses of narcotic analgesics given their deleterious effects on colonic motility.

The necessary materials needed for colonoscopic decompression are detailed in Table Recommended materials for colonoscopic decompression in acute colonic pseudo-obstruction. Colonoscopes with large-diameter accessory channels (3.8mm) or the dual channel colonoscope (Olympus® CF-2T160C), are preferable for optimal suctioning of stool and gas. The dual-channel scope with its 3.7mm and 3.2 mm accessory channels has the advantage of not only superior suctioning capability but also in allowing continued suctioning during placement of the decompression tube.

Table Recommended materials for colonoscopic decompression in acute colonic pseudo-obstruction

Equipment	Comment
Colonoscope
Olympus® CF-Q160AL	Large therapeutic channel (3.8mm)
Olympus® CF-2T160C	Dual-channel (3.7 mm, 3.2 mm); insertion tube outer diameter 13.7mm
Guidewire
Wilson-Cook®	0.035inch, 480cm length;included in decompression kit
Savary or American guidewire	Length 210cm
Decompression tube
Wilson-Cook® Colon	14 French; length 175cm
Decompression kit
Levin tube	18 French; length 80 cm

The colonoscope should be advanced as far as possible. Prolonged attempts at cecal intubation are not necessary because reaching the hepatic flexure usually suffices. Air insufflation should be minimized and the entire colon need not be examined. Gas should be aspirated and the viability of the mucosa assessed during slow withdrawal of the endoscope.

A tube for decompression should be placed in the right colon with the aid of a guidewire and fluoroscopic guidance. Commercially available, disposable, over-the-wire colon decompression tubes are available (Wilson-Cook® 14 French Colon Decompression Set). This disposable kit includes a guiding catheter (6 French, 181cm length), guidewire (0.035 inch, 480cm length), and decompression catheter (14 French, 175 cm length). The cost for this kit is $129 (USD). The drainage catheter consists of 10 elongated side ports for faster drainage.

Alternatively, one can use a “home-made” model consisting of an 18 French Levine tube with the tip cut off and passed over a Savary or American guidewire (210 cm). The cost of this home-made model is approximately $160 (Levine tube $20; guidewire $140). The length of the Levine tube (80 cm) is shorter than the commercially-available catheters but placement into the right colon is usually feasible. The larger size of the Levine tube (18 versus 14 French) is advantageous.

The guidewire is advanced through the accessory channel of the colonoscope into the cecal pole or ascending colon. The endoscope is then removed from the patient as the guidewire is inserted, using fluoroscopy to make sure the wire tip remains in place. Following endoscope removal, the decompression tube is passed over the guidewire, using fluoroscopy to prevent loop formation and ensure tube placement into the right colon. The guidewire is removed and the tube connected to gravity drainage.

The decompression tube should be flushed every 6h with saline to prevent clogging. The tube generally passes spontaneously over 3 days as peristalsis improves. If it has not passed spontaneously after 72 h, the tube is removed.

Efficacy

The efficacy of colonoscopic decompression has not been established in randomized clinical trials. However, successful colonoscopic decompression has been reported in many retrospective series (Table Colonoscopic decompression in acute colonic pseudo-obstruction), now totaling many hundreds of patients. Rex reviewed the available literature of patients with Acute colonic pseudo-obstruction treated with colonoscopy. Among 292 reported patients, 69% were estimated to have a successful initial decompression, determined by a reduction in radiographically measured cecal diameter. Forty percent of patients treated without decompression tube placement had at least one recurrence, requiring an additional colonoscopy.

Thus, an initial decompression colonoscopy without tube placement can be considered to be definitive therapy in less than 50% of patients. To improve the therapeutic benefit, decompression tube placement at the time of colonoscopy is strongly recommended. The value of decompression tubes has not been evaluated in controlled trials, but anecdotal evidence suggests that it may lower the recurrence rate. In the series reported by Geller et al., the overall clinical success of colonoscopic decompression was 88%. However, in procedures where a decompression tube was not placed the clinical success was poor (25%).

Safety

The complication rate of decompression colonoscopy in Acute colonic pseudo-obstruction ranges from approximately 1 to 5%, with perforation being the most feared adverse event, occurring in approximately 3%.

Table Colonoscopic decompression in acute colonic pseudo-obstruction

Number of patients	Successful initial decompression (%)	Overall colonoscopic success (%)	Complications (%)
22	68	73	<1(no perforations)
44	61	73	2(1 perforation)
22	68	77	4.5(1 perforation)
45	84	36	<1(no perforations)
41	95	88	5(2 perforations)

Percutaneous Cecostomy

Percutaneous cecostomy, performed either radiologically or endoscopically, can be considered in high surgical risk patients. A small case series described five patients with Acute colonic pseudo-obstruction in which percutaneous endoscopic cecostomy was the definitive treatment. This approach is modeled after the percutaneous endoscopic gastrostomy pull technique. There were no complications reported with tube placement in Acute colonic pseudo-obstruction patients in these small series. It is uncertain when percutaneous endoscopic cecostomy should be considered over other forms of mechanical decompression, such as colonoscopy with decompression tube placement or surgical cecostomy. At the present time, percutaneous endoscopic cecostomy should be reserved for patients failing neostigmine and colonoscopic decompression who have no evidence of ischemia or perforation and who are felt to be at high risk for surgery.

Surgical Therapy

Surgical management is reserved for patients with signs of colonic ischemia or perforation or who fail endoscopic and pharmacologic efforts. Surgical intervention is associated with significant morbidity and mortality, likely related to the severity of the patients’ underlying medical condition. In a large retrospective series, 179 patients underwent surgery for Acute colonic pseudo-obstruction with resulting morbidity and mortality rates of 6 and 30%, respectively. The type of surgery performed depends on the status of the bowel. Without perforated or ischemic bowel, cecostomy is the procedure of choice because the success rate is high, morbidity is relatively low, and the procedure can be performed under local anesthesia. In cases of ischemic or perforated bowel, segmental or subtotal resection is indicated, with either exteriorization or primary anastomosis.