Alvimopan: An oral, peripherally acting, µ-opioid receptor antagonist for the treatment of opioid-induced bowel dysfunctionA 21-day treatment-randomized clinical trial Journal of Pain March 2005 Volume 6 Number 3
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
Constipation and Bowel Regimens for the Critically Ill
Use either lactulose or PEG to decrease length of stay in the ICU (Crit Care Med. 2007 Dec;35(12):2726-31)
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neostigmine – 0.5-1 mg/hr continuous.
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 . 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 . 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
Pharmacologic Management of Constipation in the Critically Ill Patient Posted 07/21/2006
Asad E. Patanwala, Pharm.D.; Jacob Abarca, Pharm.D., M.S.; Yvonne Huckleberry, Pharm.D.; Brian L. Erstad, Pharm.D., FCCP
Abstract and Introduction
Study Objective: To compare the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU).Design: Retrospective medical record review.Setting: MICU of an academic medical center.Patients: Ninety-five patients admitted to the MICU from July 1October 31, 2004.Measurements and Main Results: Fifty patients satisfied the inclusion criteria. Patient-specific data such as age, weight, sex, length of MICU stay, Acute Physiology and Chronic Health Evaluation (APACHE) II score, dietary intake, opioid intake, laxative intake, and bowel movements were recorded during the first 96 hours of admission. Logistic regression analysis was used to compare patients who did and did not have a bowel movement. Of the 50 patients, 25 did not have a bowel movement during the first 96 hours of MICU admission. Patients given a stimulant laxative (senna, bisacodyl) and/or an osmotic laxative (lactulose, milk of magnesia) were more likely to have a bowel movement (odds ratio [OR] 26.6, 95% confidence interval [CI] 3.2221, p=0.002). Opioid intake, expressed as logarithmic morphine equivalents, was negatively associated with occurrence of a bowel movement (OR 0.76, 95% CI 0.590.97, p=0.027). Disease severity, as determined by APACHE II score, was also negatively associated with a bowel movement (OR 0.84, 95% CI 0.70.99, p=0.04).Conclusion: Critically ill patients have a high frequency of constipation, and opioid therapy is a significant risk factor. Routine administration of stimulant or osmotic laxatives should be considered for this patient population.
The epidemiology of constipation in the general population depends on the definition of constipation. In an effort to introduce uniform standards to clinical research, a consensus definition of constipation was developed.[1, 2] This definition incorporates several components, such as straining, hard stools, feelings of incomplete evacuation, and three or fewer bowel movements/ week. United States and British community-based population surveys have estimated that the prevalence of constipation varies from 228% depending on the definition used. However, little data exist regarding prevalence of constipation in critically ill patients. In this population, measurement of bowel consistency is highly subjective, and symptomatic constipation cannot be ascertained accurately.
Constipation has been defined as the lack of a bowel movement for 3 consecutive days, and the frequency has been found to be as high as 83% in critically ill patients. Risk of constipation is increased in critically ill patients due to immobility, inability to act or respond to the urge to defecate, and opioid use, which can result in abdominal distension, vomiting, restlessness, gut obstruction, and perforation. Constipation also has been implicated in prolonged mechanical ventilation and in delayed start of enteral nutrition.
Implementation of an inpatient constipation protocol in nonintensive care patients has reduced the frequency of constipation. This protocol involves risk assessment and dietary interventions that often would not apply to intensive care patients. Little information has been published regarding management of constipation in critically ill patients.
Several therapeutic modalities are available to the intensive care clinician for treating consti-pation. However, due to the lack of published literature, questions still exist regarding the optimal use of laxatives for intensive care patients. Therefore, we compared the effectiveness of common laxatives in producing a bowel movement in patients admitted to a medical intensive care unit (MICU).
Section 1 of 6 Next Page: Methods Department of Pharmacy Practice and Science (Drs. Patanwala, Huckleberry, and Erstad) and the Center for Health Outcomes and PharmacoEconomic Research (Drs. Abarca and Erstad), College of Pharmacy, University of Arizona, Tucson, Arizona. Pharmacotherapy. 2006;26(7):896-902. ©2006 Pharmacotherapy Publications Go to source: Pharmacologic Management of Constipation in the Critically Ill Patient
Start with magnesium citrate (if no renal failure)
Oral PEG has a much longer latency period, but is very effective
if opioid induced, can try methylnaltrexone 8 mg SC QOD if 38 -62 kg and 12 mg SC QOD if 62 – 114 kg
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