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Neostigmine for the Treatment of Acute Colonic Pseudo-Obstruction – Adult - Inpatient

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Neostigmine for the Treatment of Acute Colonic
Pseudo-Obstruction – Adult – Inpatient –
Clinical Practice Guideline
Table of Contents
SCOPE ...................................................................................................................................... 5
METHODOLOGY ...................................................................................................................... 5
DEFINITIONS: ........................................................................................................................... 6
INTRODUCTION ....................................................................................................................... 6
RECOMMENDATIONS .............................................................................................................. 7
UW HEALTH IMPLEMENTATION ............................................................................................. 9
REFERENCES .........................................................................................................................10
CPG Contact for Changes: CPG Contact for Content:
Name: Philip Trapskin, PharmD, BCPS Name: Cindy Gaston, PharmD, BCPS
Phone Number: 608-263-1328 Phone Number: 608-265-8161
Email Address:ptrapskin@uwhealth.org Email Address: cgaston@uwhealth.org
Note: Active Table of Contents
Click to follow link
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Guideline Authors: Barry McClain, PharmD and Tosha Wetterneck, MD
Updated by: Eddu Oparie-Addoh, PharmD, BCPS, CNSC
Coordinating Team Members: Cindy Gaston, PharmD, BCPS
Review Individuals/Bodies: Mark Reichelderfer MD, Tasha Wetterneck, MD
Committee Approvals/Dates:
Medication Use Evaluation Committee February 2015
Pharmacy & Therapeutics Committee March 2015
Release Date: March 2015
Next Review Date: March 2018
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Executive Summary
Guideline Overview
These clinical practice guidelines are intended to guide clinicians and provide appropriate
criteria for the use of intravenous neostigmine in the treatment of acute colonic pseudo-
obstruction (ACPO) or Ogilvie syndrome
Key Practice Recommendations
1. Supportive Therapy
1.1. Supportive therapy is indicated for all patients with ACPO (Class I, Level C)
1.2. Supportive therapy includes nothing by mouth, nasogastric suction, rectal
decompression, intravenous fluid replacement and correction of electrolyte imbalances,
especially hypokalemia and hypomagnesaemia.1 (Class I, Level C)
1.3. Avoid all drugs that can delay gut motility such as opioids, anticholinergics and calcium
channel blockers. Laxatives, particularly osmotic compounds such as lactulose, are
contraindicated as they may promote colonic bacterial fermentation, thereby increasing
gas production.1 (Class IIa, Level C)
2. Intravenous Neostigmine
2.1. Intravenous neostigmine is safe and effective in the treatment of ACPO in patients who
fail supportive therapy (Class I, Level A)
2.2. Standard dose based on randomized controlled trails (RTCs): 2 mg IV over 3-5 min.2,3
(Class I, Level A)
2.3. Administration of polyethylene glycol electrolyte – balanced solution via nasogastric
tube has been shown to significantly decrease the rate of relapse of ACPO.4 The
recommended dose of polyethylene glycol 29.5g daily.4 (Class I, Level B)
2.4. A second dose of neostigmine 2 mg IV over 2 – 3 min may be considered in patients
who fail to respond to the initial dose.2,5,6 (Class I, Level C) Although the timing of the
second dose of neostigmine is not well established5, one RCT successfully used a
second dose of neostigmine in non-responders 3 hours after the initial dose.2 (Class IIa,
Level B)
2.5. Doses of 0.4 - 0.8 mg/hr. IV over 24 hours or 2 - 5 mg IV over 30 minutes have been
successfully used in RTCs (Class IIb, Level B). 7,8
2.6. Oral neostigmine is not recommended because of its erratic absorption in the GI tract (1
- 2%).9,10 (Class III, Level C)
3. Administration of Intravenous Neostigmine and Monitoring
3.1. Neostigmine 2 mg IV push is administered over 3 - 5 minutes.2,3 (Class I, Level A)
3.2. Continuous presence of a physician knowledgeable in ACLS on the unit and a nurse in
patient's room for 30 minutes after dose administration is required. (Class I, Level C)
3.3. Continuous telemetry monitoring for 30 minutes after dose administration is required to
observe for bradycardia or asystole. (Class I, Level C)
3.4. Monitor blood pressure every 15 minutes x 2 (Class I, Level C)
3.5. Monitor respiratory rate and depth every 15 minutes x 2 (Class I, Level C)
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3.6. Patient should be kept supine for 30 minutes, with a bedpan readily available (Class I,
Level C)
3.7. Crash cart kept immediately outside of patient’s room (Class I, Level C)
3.8. The safety and efficacy of neostigmine injection in the treatment of ACPO has not been
established in children (Class III, Level C)
3.9. The onset of action of intravenous neostigmine is 1 - 20 min, with duration of action of 1
- 2 hours. The average elimination half-life is 80 minutes, which is extended in patients
with renal insufficiency.11,12
4. Contraindications
4. 1 Do not use neostigmine in the following conditions (Class III, Level C)
4.1.1 Hypersensitivity to neostigmine
4.1.2 Baseline heart rate < 60 bpm or systolic blood pressure < 90 mm Hg
4.1.3 Uncontrolled arrhythmias
4.1.4 Mechanical intestinal or urinary tract obstruction
4.1.5 Signs of bowel perforation, ischemia, peritonitis, or acidosis
4.1.6 Renal insufficiency
4.1.7 Pregnancy
4.1.8 Severe bronchospasm
Companion Documents
Not applicable
Pertinent UW Health Policies & Procedures
Not applicable
Patient Resources:
Not applicable
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Scope
Disease/Condition(s):
Adult patients diagnosed with Acute Colonic Pseudo-obstruction (ACPO)
Clinical Specialty:
Gastroenterology, General Surgery, Internal Medicine
Intended Users:
Physicians, Physician Assistants, Advanced Practice Nurses, Pharmacists and Nurses
CPG objective(s):
To provide recommendations and criteria for the use of intravenous neostigmine in
patients with ACPO
Target Population:
Adult inpatients with ACPO
Interventions and Practices Considered:
Use of supportive therapy and intravenous neostigmine in the management of patients
with ACPO
Major Outcomes Considered:
Successful management of patients with ACPO with supportive therapy and intravenous
neostigmine
Avoidance of drug toxicity when using intravenous neostigmine
Guideline Metrics:
1. Successful management of patients with ACPO with supportive therapy and
intravenous neostigmine
2. Avoidance of drug toxicity when using intravenous neostigmine for ACPO
3. Medication use evaluation (MUE) will be performed 2 years after the approval
this this guideline
4. Review of safety concerns related to the use of intravenous neostigmine for the
treatment of ACPO as documented in the Patient Safety Network (PSN)
Methodology
Methods Used to Collect/Select the Evidence:
A literature search was performed using Medline, Cochrane, and PubMed databases,
using the keywords “neostigmine”, “acute colonic pseudo-obstruction” and “Ogilvie
syndrome”
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Methods Used to Assess the Quality and Strength of the Evidence:
A modified Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) developed by the American Heart Association and American College of
Cardiology was used to assess the Quality and Strength of the Evidence in this Clinical
Practice Guideline.13
Definitions:
Acute colonic pseudo-obstruction (ACPO) or Ogilvie syndrome - is characterized by
massive colonic dilation in the absence of mechanical obstruction.5
Introduction
Acute colonic pseudo-obstruction is characterized by abdominal distension, pain,
nausea and/or vomiting, with a failure to pass flatus and stools documented in up to 60
per cent of patients1. Patients with complications present with marked abdominal
tenderness and systemic features such as fever and tachycardia.1
Ischemia and perforation are serious complications of ACPO; spontaneous perforation
has been reported in 3% to 15% of patients with a mortality rate of 50% or higher.5 The
rate of perforation and/or ischemia rapidly increases with cecal diameters >10 to 12
centimeters and when the duration of distention exceeds 6 days.5
The differential diagnosis includes mechanical obstruction and toxic megacolon due to
Clostridium difficile infection. The diagnosis of ACPO depends on accurate clinical
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observations and radiographic evidence to differentiate mechanical obstruction from
pseudo-obstruction in all situations of large bowel obstruction.1
The pathogenesis of ACPO is not well understood. It is thought to occur as a result of
an alteration in the autonomic regulation of colonic motor function.
The vast majority of patients with ACPO (> 95%) have the syndrome in association with
one or more of multiple predisposing factors or clinical conditions. 14 The most common
causes of ACPO is associated with surgery 23%, non-operative trauma 11%, and
cardiac disease (10 - 18%).15,16 Other causes include neurological diseases (such as
Parkinson’s and Alzheimer’s), severe infections (particularly those induced by Gram-
negative bacteria), electrolyte imbalance/metabolic alterations (for example
hypokalemia).1 ACPO can be compounded by drugs such as antidepressants,
phenothiazines, antiparkinsonian agents and opioids/narcotics.1,5
Supportive measures are indicated for all patients with ACPO even those in whom an
invasive approach is immediately necessary.1 The duration of supportive therapy should
not exceed 48 - 72 hours.1 A duration of 6 days has been shown to be associated with a
greater risk of complications.5,17
Recommendations
1. Supportive Therapy
1.1. Supportive therapy is indicated for all patients with ACPO (Class I, Level C).
Supportive therapy includes nothing by mouth, nasogastric suction, rectal
decompression, intravenous fluid replacement and correction of electrolyte
imbalances, especially hypokalemia and hypomagnesaemia.1 (Class I, Level C)
1.2. The duration of supportive therapy should not exceed 48-72 hours. A duration of
6 days has been shown to be associated with a greater risk of complications.1
1.3. Avoid all drugs that can delay gut motility such as opioids, anticholinergics and
calcium channel blockers. Laxatives, particularly osmotic compounds such as
lactulose, are contraindicated as they may promote colonic bacterial
fermentation, thereby increasing gas production.1 (Class IIa, Level C)
2. Intravenous Neostigmine
2.1. Intravenous neostigmine is safe and effective in the treatment of ACPO in
patients who fail supportive therapy. 8 (Class I, Level A).
2.2. Standard dose based on randomized controlled trails (RTCs): 2 mg IV over 3-5
min.2,3 (Class I, Level A)
2.3. Administration of polyethylene glycol electrolyte – balanced solution via
nasogastric tube has been shown to significantly decrease the rate of relapse of
ACPO.4The recommended dose of polyethylene glycol 29.5g daily. (Class I,
Level B)
2.4. A second dose of neostigmine 2 mg IV over 2 – 3 min may be considered in
patients who fail to respond to the initial dose.2,5,6 (Class I, Level C)
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2.4.1. Although the timing of the second dose of neostigmine is not well
established, one randomized control trial successfully used a second dose
of neostigmine in non-responders 3 hours after the initial dose.2,5 (Class
IIa, Level B)
2.5. Doses of neostigmine 2 - 5 mg IV over 30 minutes may be considered.7,8 (Class
IIb, Level B)
2.6. Oral neostigmine is not recommended because of its erratic absorption in the GI
tract (1 - 2%)9,10. (Class III, Level C)
3. Administration of Intravenous Neostigmine and Monitoring
3.1 Neostigmine 2 mg IV push is administered over 3 - 5 minutes.2,6 (Class I, Level
B)
3.2 Continuous presence of a physician knowledgeable in ACLS and a nurse in
patient's room for 30 minutes after dose administration is required (Class I, Level
C)
3.3 Continuous telemetry monitoring for 30 minutes after dose administration is
required to observe for bradycardia or asystole (Class I, Level C)
3.4 Keep atropine at bedside (Class I, Level B) Dose of atropine for symptomatic
bradycardia is 1 mg intravenously as needed.2 (Class I, Level B)
3.5 Monitor blood pressure over 15 minutes x 2 (Class I, Level C)
3.6 Monitor respiratory rate and depth every 15 minutes x 2 (Class I, Level C)
3.7 Patient should be kept supine, with a bedpan readily available (Class I, Level C)
3.8 Crash cart kept immediately outside of patient’s room (Class I, Level C)
3.9 The safety and efficacy of neostigmine injection in the treatment of ACPO has
not been established in children
3.10 The onset of action of intravenous neostigmine is 1 - 20 minutes, with duration
of action of 1 - 2 hours. The average elimination half-life is 80 minutes, which is
extended in patients with renal insufficiency.11,12
4. Contraindications
4.1 Do not use neostigmine in the following conditions (Class III, Level C)
4.1.1. Hypersensitivity to neostigmine
4.1.2. Baseline heart rate < 60 bpm or systolic blood pressure < 90 mm Hg
4.1.3. Uncontrolled arrhythmias
4.1.4. Mechanical intestinal or urinary tract obstruction
4.1.5. Signs of bowel perforation, ischemia, peritonitis, or acidosis
4.1.6. Renal insufficiency, serum creatinine > 3 mg/dl
4.1.7. Pregnancy
4.1.8. Severe bronchospasm
4.2 Use with caution in the following conditions (Class IIb, Level C)
4.2.1. History of asthma or COPD
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4.2.2. Epilepsy
4.2.3. Hyperthyroidism
4.2.4. History of cardiac arrhythmia such as atrial fibrillation and atrioventricular
block
4.2.5. Recent myocardial infarction (within the past 30 days)
4.2.6. Current beta blocker use
4.2.7. History of colon cancer
4.2.8. History of colon resection
4.2.9. Peptic ulcer
4.2.10. Vagotonia
5. Other Pharmacologic Agents
5. 1 There are anecdotal reports of success using traditional prokinetic agents such
as erythromycin, metoclopramide, and cisapride. The response rates were
inconsistent for these agents, with only gradual improvement over 12 to 24
hours of therapy.5 (Class IIb, Level B)
6. Endoscopic Decompression
6. 1 Should supportive and pharmacologic treatment fail, colonoscopic
decompression has been successful in approximately 80% of patients with
ACPO.1,5 (Class I, Level C)
UW Health Implementation
Potential Benefits:
1. Successful management of patients with ACPO with supportive therapy and
intravenous neostigmine
2. Avoidance of complications of ACPO including colonic ischemia and perforation and
associated morbidity
3. Avoidance of drug toxicity when using intravenous neostigmine
Potential Harms:
1. Safety information from using neostigmine for the treatment of ACPO is favorable8;
however, there are serious cautions to consider. Current clinical trials have required
the presence of a physician for 30 minutes after the administration of injectable
neostigmine for ACPO.2
1.1. Serious Complications
1.1.1. Cardiovascular: Sinus cardiac arrhythmias (including atrioventricular
block, bradycardia, nodal rhythms, and nonspecific electrocardiogram
changes), cardiac arrest and hypotension
1.1.2. Pulmonary: Bronchospasm, increased bronchial secretions, and
respiratory depression
1.1.3. Hypersensitivity: anaphylaxis
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1.1.4. Neurological: Seizures
1.2. Common Adverse Events
1.2.1. Cardiovascular: flushing and syncope
1.2.2. Gastrointestinal: emesis and nausea
1.2.3. Musculoskeletal: muscle cramps and spasms
1.2.4. Neurological: dizziness, drowsiness, dysarthria, headache, loss of
consciousness, miosis, visual changes and weakness
Implementation Plan/Tools
This guideline has been developed based on best evidence recommendations. By
implementing the parameters set forth in the guideline, patients will received
intravenous neostigmine appropriately and safely
1. Dosing guidelines will be built into Health Link to be visible upon order entry of
intravenous neostigmine for ACPO
2. Education will be provided to health care providers as necessary
3. Guideline is available on “UConnect”
4. Education will be provided through Drug Policy Program (DPP) update
Disclaimer
This Clinical Practice Guideline provides and evidence-based approach for the
treatment of ACPO. It is understood that the occasionally patients will not match the
conditions considered in the guideline.
References
1. De Giorgio R, Knowles CH. Acute colonic pseudo-obstruction. The British journal
of surgery. 2009;96(3):229-239.
2. Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute
colonic pseudo-obstruction. The New England journal of medicine.
1999;341(3):137-141.
3. Amaro R, Rogers AI. Neostigmine infusion: new standard of care for acute
colonic pseudo-obstruction? The American journal of gastroenterology.
2000;95(1):304-305.
4. Sgouros SN, Vlachogiannakos J, Vassiliadis K, et al. Effect of polyethylene glycol
electrolyte balanced solution on patients with acute colonic pseudo obstruction
after resolution of colonic dilation: a prospective, randomised, placebo controlled
trial. Gut. 2006;55(5):638-642.
5. Harrison ME, Anderson MA, Appalaneni V, et al. The role of endoscopy in the
management of patients with known and suspected colonic obstruction and
pseudo-obstruction. Gastrointestinal endoscopy. 2010;71(4):669-679.
6. Abeyta BJ, Albrecht RM, Schermer CR. Retrospective study of neostigmine for
the treatment of acute colonic pseudo-obstruction. The American surgeon.
2001;67(3):265-268; discussion 268-269.
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 03/2015CCKM@uwhealth.org

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7. van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ,
Zandstra DF. Neostigmine resolves critical illness-related colonic ileus in
intensive care patients with multiple organ failure--a prospective, double-blind,
placebo-controlled trial. Intensive care medicine. 2001;27(5):822-827.
8. Valle RG, Godoy FL. Neostigmine for acute colonic pseudo-obstruction: A meta-
analysis. Annals of medicine and surgery (2012). 2014;3(3):60-64.
9. De Giorgio R, Barbara G, Stanghellini V, et al. Review article: the
pharmacological treatment of acute colonic pseudo-obstruction. Alimentary
pharmacology & therapeutics. 2001;15(11):1717-1727.
10. Neostigmine Bromide Tablet (Package Insert) 2013, Aliso Viejo, CA: Valeant
Pharmaceuticals North America.
11. Aquilonius SM, Hartvig P. Clinical pharmacokinetics of cholinesterase inhibitors.
Clinical pharmacokinetics. 1986;11(3):236-249.
12. Cronnelly R, Stanski DR, Miller RD, Sheiner LB, Sohn YJ. Renal function and the
pharmacokinetics of neostigmine in anesthetized man. Anesthesiology.
1979;51(3):222-226.
13. Goff DC, Jr., Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the
assessment of cardiovascular risk: a report of the American College of
Cardiology/American Heart Association Task Force on Practice Guidelines.
Circulation. 2014;129(25 Suppl 2):S49-73.
14. Saunders MD, Kimmey MB. Systematic review: acute colonic pseudo-
obstruction. Alimentary pharmacology & therapeutics. 2005;22(10):917-925.
15. Batke M, Cappell MS. Adynamic ileus and acute colonic pseudo-obstruction. The
Medical clinics of North America. 2008;92(3):649-670, ix.
16. Wegener M, Borsch G. Acute colonic pseudo-obstruction (Ogilvie's syndrome).
Presentation of 14 of our own cases and analysis of 1027 cases reported in the
literature. Surgical endoscopy. 1987;1(3):169-174.
17. Johnson CD, Rice RP, Kelvin FM, Foster WL, Williford ME. The radiologic
evaluation of gross cecal distension: emphasis on cecal ileus. AJR. American
journal of roentgenology. 1985;145(6):1211-1217.
Copyright © 2015 Univ ersity of Wisconsin Hospitals and Clinics Authority
Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 03/2015CCKM@uwhealth.org