Ogilvie’s syndrome

BOX 22.1 Supportive therapy for acute colonic pseudo-obstruction

Nil per os
Correct fluid and electrolyte imbalances
Nasogastric tube suction
Rectal tube to gravity drainage
Limit offending medications (especially narcotics)
Frequent position changes, ambulate if possible

Management

Treatment options for ACPO include appropriate supportive measures, medical therapy, colonoscopic decompression, and surgery. Despite extensive literature documenting the clinical features of ACPO, there are very few randomized controlled clinical trials on the treatment of this condition, and most evidence for efficacy of treatments comes from uncontrolled studies.

Supportive therapy

Supportive therapy (Box 22.1) should be instituted in all patients as it appears to be successful as the primary treatment in the majority of patients [7]. B4 Patients are given nothing by mouth. Intravenous fluids are administered and electrolyte imbalances are corrected. Nasogastric suction is provided to limit swallowed air from contributing further to colonic distension. A rectal tube should be inserted and attached to gravity drainage. Medications that can adversely affect colonic motility, such as opiates, anti-cholinergics and calcium channel antagonists are discontinued if possible. Ambulation and mobilization of patients are encouraged. The knee-chest position with hips held high has been advocated as aiding in evacuation of colonic gas [8]. None of these supportive measures has been studied in a randomized trial. C5

The reported success of supportive management is variable, with pooled rates from several retrospective series of approximately 85% [7, 9–13]. In these combined series, 111 patients were treated conservatively, of which 95 (86%) had resolution of the pseudo-obstruction. B4 Sloyer et al. reported outcomes of 25 cancer patients with ACPO (mostly non-gastrointestinal malignancies) [7]. 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 ACPO-related deaths. The authors concluded that early endoscopic or surgical decompression is not necessary in patients with ACPO. B4 In another recent retrospective series of 151 patients reported by Loftus et al., 117 (77%) had spontaneous resolution of ACPO with conservative treatment [14]. B4 These studies demonstrate that the initial management of ACPO should be directed towards eliminating or reducing the factors known to contribute to the problem.

Patient outcome

The clinical dilemma facing the clinician caring for a patient with ACPO is whether to treat the patient with conservative measures and close observation versus proceeding with medical or endoscopic decompression of the dilated colon. The outcome of patients with ACPO is determined by multiple factors. The severity of the underlying illness appears to exert the greatest influence on patient outcome. ACPO often afflicts debilitated patients, which explains the significant morbidity and mortality even with successful treatment of the colonic dilatation. Other factors that appear to influence outcome are increasing age, maximal cecal diameter, delay in decompression and status of the bowel [2]. The risk of spontaneous colon perforation in ACPO is low but clearly exists. Rex reviewed all available reports in the literature and estimated the risk of spontaneous perforation to be approximately 3% [15]. The mortality rate in ACPO is approximately 40% when ischemia or perforation are present, compared with 15% in patients with viable bowel [2]. Retrospective analyses of patients with ACPO [2,13] have attempted to identify clinical factors that predict which patients are more likely to have complications such as ischemia or perforation. The risk of colonic perforation has been reported to increase with cecal diameter greater than 12 cm and when distension has been present for more than six days [13]. In the large series reported by Vanek and Al-Salti, no cases of perforation were seen when the cecal diameter was less than 12 cm [2]. However, at diameters greater than 12 cm, there was no clear relationship between risk of ischemia or perforation and the size of the cecum. The duration and progression of colonic distension may be more important. Johnson and Rice reported a mean duration of distension of six days in patients who perforated compared with two days in those who did not [13]. A two-fold increase in mortality occurs when cecal diameter is greater than 14 cm and a five-fold increase when delay in decompression is greater than seven days [2]. Thus, the decision to intervene with medical therapy, colonoscopy or surgery is dictated by the patient’s clinical status. On the basis of the limited available evidence patients with marked cecal distension (>10cm) of significant duration (>3–4 days) and those not improving after 24–48 hours of supportive therapy are considered to be candidates for further intervention. B4 In the absence of signs of ischemia or perforation, medical therapy with neostigmine should be considered the initial therapy of choice.

Medical therapy

Neostigmine

The only randomized controlled trial of an intervention for ACPO involves the use of neostigmine [16]. Neostigmine, a reversible acetylcholinesterase inhibitor, indirectly stimulates muscarinic receptors, thereby enhancing colonic motor activity, inducing colonic propulsion and accelerated transit [17]. The rationale for using neostigmine stems from the imbalance in autonomic regulation of colonic function that is proposed to occur in ACPO. Neostigmine was first used for manipulation of the autonomic innerva-tion to the gastrointestinal tract by Neely and Catchpole over 30 years ago in studies on small bowel paralytic ileus [18]. Neostigmine, administered intravenously, has a rapid onset (1–20 minutes) and short duration (1–2 hours) of action [19]. The elimination half-life averages 80 minutes, but is more prolonged in patients with renal insufficiency [20].

A randomized double-blind, placebo-controlled trial evaluated neostigmine in patients with ACPO with a cecal diameter of >10cm and no response to 24 hours of conservative therapy [16]. Exclusion criteria were suspected ischemia or perforation, pregnancy, severe active bron-chospasm, cardiac arrhythmias and renal failure. Patients were randomized to receive neostigmine, 2 mg, or saline by intravenous infusion over 3–5 minutes. The primary end-point was the clinical response to infusion, defined as a prompt reduction in abdominal distension by physical examination. Secondary endpoints included the change in measurements of colonic diameter on radiographs and abdominal girth. Patients not responding within three hours to initial infusion were eligible for open label neostigmine. A clinical response was observed in 10 of 11 patients (91%) randomized to receive neostigmine compared to 0 of 10 receiving placebo. Ald The median time to response was four minutes. Median reduction in cecal diameter (5 cm vs 2cm) and abdominal girth (7cm vs 1 cm) were significantly reduced in neostigmine-treated patients. Open-label neostigmine was administered to eight patients who failed to respond to the initial infusion (seven placebo, one 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 rate of colonic distension after neostigmine decompression was low (11%). The most common adverse effects observed with neostigmine were mild abdominal cramping and excessive salivation. Symptomatic bradycardia requiring atropine occurred in 2 of 19 patients.

Neostigmine was also evaluated in a double-blinded, placebo-controlled trial involving 24 critically ill, ventilated patients with ileus (defined as absence of stools for three days) [21]. No details of the extent and duration of colonic distention were provided. Neostigmine was administered as a continuous infusion (0.4mg/hour for 24 hours). 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 to 10 days after treatment.

There are also several uncontrolled observational studies supporting the use of neostigmine in this condition [14, 22-27]. Collectively, rapid decompression of colonic distension was observed in 88% of patients with a recurrence rate of 7% (Table 22.2). B4 In the case series reported by Mehta and colleagues [28], a response to neostigmine was more likely in the postoperative setting (11 of 15 patients (73%) versus one of four patients (25%), p = 0.07), and less likely in those with electrolyte imbalance or receiving anti-motility agents (3 of 15 (20%) versus 4 of 4, p = 0.003). This study suggests that it may be important to correct electrolyte abnormalities and to limit potentially exacerbating medications.

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