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neostigmine - 0.5-1 mg/hr
continuous.
oral narcan for opioid constipation (Pain 2000;84:105-109)
3-12 mg ngt tid start low to prevent withdrawal observational non-controlled
study of crit care pts.
start with 20% of daily mrophine equivalent; divide in tid dosing
Neostigmine — Several reports have suggested that neostigmine, an
acetylcholinesterase inhibitor, may be effective in producing rapid colonic
decompression [6-8]. In a controlled trial, 21 patients with a cecal diameter of
at least 10 cm who had no response to at least 24 hours of conservative
treatment were randomly assigned to neostigmine (2.0 mg IV) or intravenous
saline [8]. Patients who had no response were eligible to receive open-label
neostigmine. Prompt decompression was observed in 11 patients (91 percent) who
received neostigmine compared to none receiving placebo. Furthermore, seven
patients in the placebo group subsequently were treated with neostigmine with an
immediate clinical response and a significantly greater decrease in proximal
colon diameter relative to placebo.
The median time to response was four minutes (range 3 to 30), and in most
patients the response was durable. Initial treatment was considered to have
failed in three patients; one had a durable response to a second dose and the
others required colonoscopic decompression due to recurrent distension. The most
frequent adverse effect was mild to moderate crampy abdominal pain, which was
transient. Excessive salivation and vomiting were also noted in a few patients.
Symptomatic bradycardia requiring atropine was observed in two patients.
Another report focused on 151 patients with acute colonic pseudoobstruction of
whom 117 (77 percent) had spontaneous resolution of symptoms [9]. Of those who
did not resolve, 18 received neostigmine while 16 were treated with alternative
methods. Of the 16 who did not receive neostigmine, 11 required colonoscopic
decompression, two underwent surgery, and three died of underlying illness.
Sustained clinical response to neostigmine was observed in 11 of 18 patients (61
percent); the others required colonoscopic decompression or surgery. Responders
were significantly more likely to be older (mean age 76 versus 54). Cecal
diameter did not differ between responders and nonresponders The median time to
resolution in spontaneous resolvers was four days compared with two days in
those who received neostigmine. The authors noted that only 1 of the 16 patients
who did not receive neostigmine had a contraindication, suggesting that
neostigmine may be underutilized.
Because of the hemodynamic effects, patients treated with neostigmine should be
instructed to remain supine for at least 60 minutes, receive cardiac monitoring,
and atropine should be available. Those who have underlying bradyarrhythmias or
who are receiving beta adrenergic antagonists may be at increased risk. Clinical
experience suggests that lower doses (1.5 mg) may also be effective and may
possibly decrease abdominal cramping, nausea, and vomiting, which can be severe.
Because of the side effects described above, the drug should be administered
cautiously.
Neostigmine for the treatment of acute colonic
pseudo-obstruction.
AU - Ponec RJ; Saunders MD; Kimmey MB
SO - N Engl J Med 1999 Jul 15;341(3):137-41.
BACKGROUND: Acute colonic pseudo-obstruction -- that is, massive dilation of the
colon without mechanical obstruction -- may develop after surgery or severe
illness. Although it may resolve with conservative therapy, colonoscopic
decompression is sometimes needed to prevent ischemia and perforation of the
bowel. Uncontrolled studies have suggested that neostigmine, may be an effective
treatment. METHODS: We studied 21 patients with acute colonic
pseudo-obstruction. All had abdominal distention and radiographic evidence of
colonic dilation, with a cecal diameter of at least 10 cm, and had had no
response to at least 24 hours of conservative treatment. We randomly assigned 11
to receive 2.0 mg of neostigmine intravenously and 10 to receive intravenous
saline. A physician who was unaware of the patients' treatment assignments
recorded clinical response (defined as prompt evacuation of flatus or stool and
a reduction in abdominal distention), abdominal circumference, and measurements
of the colon on radiographs. Patients who had no response to the initial
injection were eligible to receive open-label neostigmine three hours later.
RESULTS: Ten of the 11 patients who received neostigmine had prompt colonic
decompression, as compared with none of the 10 patients who received placebo
(P<0.001). The median time to response was 4 minutes (range, 3 to 30). Seven
patients in the placebo group and the one patient in the neostigmine group
without an initial response received open-label neostigmine; all had colonic
decompression. Two patients who had an initial response to neostigmine required
colonoscopic decompression for recurrence of colonic distention; one eventually
underwent subtotal colectomy. Side effects of neostigmine included abdominal
pain, excess salivation, and vomiting. Symptomatic bradycardia developed in two
patients and was treated with atropine. CONCLUSIONS: In patients with acute
colonic pseudo-obstruction who have not had a response to conservative therapy,
treatment with neostigmine rapidly decompresses the colon.
Patients were randomly assigned to receive 2.0 mg of neostigmine
intravenously over a period of three to five minutes or identical-
appearing saline placebo. The injections were given by a
physician who was unaware of the patients’ treatment assignments.
All patients were monitored by electrocardiography; atropine
was available at the bedside, and 1.0 mg was given intravenously
as needed for symptomatic bradycardia. Patients were
instructed to remain supine for at least 60 minutes after the injection.
Vital signs were recorded immediately before the injection
and five minutes and three hours afterward.
The physician administering the infusion monitored the clinical
response for 30 minutes after the injection. The maximal abdominal
circumference and the diameter of the cecum, ascending colon,
and transverse colon on plain radiographs were measured before
and three hours after the injection by an investigator who
was unaware of the patients’ treatment assignments.
Three hours after the infusion, patients who did not have a reduction
in colonic distention on both clinical examination and radiographs
were eligible to receive open-label neostigmine (2.0
mg intravenously) administered by a physician who was unaware
of the identity of the study drug. The three-hour period was chosen
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