Acute Intestinal Pseudo-obstructionEamonn MM Quigley, MD, FRCP, FACP, FACG

AddressClinical Sciences Building, Cork University Hospital, Cork, Ireland.Email: equigley@ucc.ie

Current Treatment Options in Gastroenterology 2000, 3:273–285Current Science Inc. ISSN 1092-8472Copyright © 2000 by Current Science Inc.

Introduction

Intestinal pseudo-obstruction refers to a syndrome thatrepresents the clinical expression of profoundlydisturbed intestinal motor function [1]. Such motordysfunction may reflect either a myopathic or a neuro-pathic process whose net effect is to severely disrupt theorderly transit of food or digesta along the gastrointesti-nal tract. In clinical terms, pseudo-obstruction is arbi-trarily divided into acute and chronic forms, the latterrepresenting the long-term consequences of injury to, orpathologic change in, the intestinal muscle or its inner-vation. While chronic intestinal pseudo-obstructionmay present in an acute form, the term “acute pseudo-obstruction” is usually reserved for those instances ofacute motor dysfunction consequent upon transientand potentially reversible alterations in motor function[2]. Three clinical presentations may be identified: acutegastroparesis, ileus, and acute colonic pseudo obstruc-tion (also referred to as acute megacolon or Ogilvie’ssyndrome). Each of these is most commonly seen in thepostoperative state, but may also occur in the nonsurgi-

cal patient in the context of metabolic disturbances,electrolyte disorders, and severe acute systemic illnesses,or in relation to exposure to a number of toxic, infec-tive, and pharmacologic agents.

ACUTE GASTROPARESISAcute gastroparesis has been most extensively recognizedamong patients who have recently undergone surgicaland other procedures on the stomach or upper abdomen[3–10,11••] (Table 1). Gastroparesis is a recognized con-sequence of truncal vagotomy, whether combined with anantrectomy or gastro-enterostomy [3,4,8,11••]. It is alsobeen described, albeit less commonly, following highlyselective vagotomy [10] and, more recently, following Nis-sen fundoplication [7]. Kung et al. [8] identified some riskfactors for the development of gastroparesis following agastrojejunostomy. A delayed return of gastric emptyingwas more likely if the patient was over 60 years of age, anda bypass was performed without any gastric resection.Gastroparesis also appears to be particularly common fol-

Opinion statement• Acute pseudo-obstruction may manifest clinically in one of three forms—acute

gastroparesis, ileus, and acute colonic pseudo-obstruction (Ogilvie’s syndrome). Though formerly associated primarily with the postoperative state, these entities are increasingly recognized in association with a wide variety of major medical problems.

• There are few controlled studies to guide the clinician in the management of these disorders. Treatment remains largely empirical, and time-honored, based primarily on “bowel rest,” nasogastric decompression, and supportive care. While a wide variety of pharmacologic approaches have been advocated, few have been subjected to, or survived, the rigors of a properly controlled trial. Neostigmine is a notable exception, and has been shown to be effective in Ogilvie’s syndrome.

• Perforation is a significant threat in megacolon; colonoscopic, or surgical decompres-sion may, therefore, be indicated. Both are associated with significant risks in this context, but may prevent progression to perforation with its attendant mortality.

• New approaches seek to exploit current concepts in the pathophysiology of ileus and megacolon but have not, as yet, achieved efficacy in human studies.

274 Functional GI Disorders and GI Motility Dysfunction

lowing pylorus-preserving pancreaticoduodenectomy [2].The recent literature has documented a significant inci-dence of gastroparesis among individuals who haveundergone lung and cardiac transplantation [9]. Whilevagotomy may well be relevant to the gastric motor dys-function which occurs in relation to these two procedures,it is more difficult to explain reports of gastroparesisamong patients who have undergone liver and pancreaticallografts. Acute gastroparesis and even gastric dilatationhave also been reported in relation to a number of endo-crine [12–14], metabolic, neurological [15–18] and otherdiseases [19] (Table 1). The development of acute gastro-paresis should always prompt the clinician to search forevidence of “down-stream” obstruction. While gastricoutlet obstruction will usually be sought for, and elimi-nated in this clinical context [20], one should also ensurethat this clinical presentation is not a consequence ofmore distal small bowel obstruction. Thus, instances ofacute “gastroparesis” have been reported in patients withsmall bowel obstruction caused by either adenocarci-noma [21] or leiomyosarcoma. [16] Interestingly, gastro-paresis may also occur as a consequence of such tumors asleiomyosarcoma [22] and pancreatic carcinoma [23]. Insome cases, no cause of acute gastroparesis is found (idio-pathic gastroparesis).

The natural history of acute gastroparesis is not welldefined. Most series in the literature are small and few, ifany, have documented the natural evolution of this syn-drome. The major clinical consequence is, most com-monly, a delay in the patient’s ability to resume oralintake following a surgical procedure. However, instancesof massive gastric dilatation and even perforation have

been reported. Diagnosis rests, first and foremost, on clin-ical awareness; the clinician must recognize the potentialfor its occurrence in the various clinical contexts describedabove. The presence of gastroparesis may be suggested bythe development of upper abdominal distension and dis-comfort, by persistent aspiration of large volumes from anasogastric tube, or even by the development of nauseaand vomiting. In most situations, the diagnosis may beconfirmed by plain abdominal radiographs or upperabdominal ultrasound. Where appropriate, endoscopymay be performed to rule out gastric outlet obstructionbut, for the most part, formal tests of gastric emptying areneither necessary nor indicated.

The pathophysiology of acute gastroparesis hasreceived relatively little attention [11••]. Given the simi-larity of the clinical contexts in which they both occur, itstands to reason that those factors that have been impli-cated in the pathogenesis of acute ileus, describedbelow, may also be relevant to its gastric counterpart. Ithas, for example, been suggested, based on studies in ananimal model, that acute gastroparesis may be relatedto the activation of capasaicin-sensitive splanchnicafferents and corticotrophin-releasing factor (CRF)receptors in the brain [24].

ILEUSIleus, usually a consequence of an operative procedurein the abdominal cavity, is defined as the functionalinhibition of propulsive bowel activity without evi-dence of mechanical obstruction [2,25]. It is tradition-ally divided into two phases; postoperative ileus isdefined as that which immediately follows surgery andresolves spontaneously after 2 to 3 days, whereas para-lytic ileus persists beyond 3 days. It is usually assertedthat the duration of ileus is directly related to the dura-tion and extent of the surgical procedure. Some recentstudies have failed to confirm that relationship[11••,25]. For example, some [26], but not all, havereported that ileus is more prolonged following openrather than laparoscopic procedures [11••,28]. Postop-erative recovery from ileus is most rapid in the smallintestine, less so in the stomach, and slowest of all inthe colon [2,11,25]. Several other factors may contributeto the prolongation of what may be regarded as a physi-ologic response to surgery (ie, postoperative ileus), to apathologic state, namely, paralytic ileus. These includeischemia [28], hypoperfusion, hypoxia, sepsis [29],renal failure, a variety of electrolyte disturbances( inc lud ing hyponat raemia , hypoca l caem ia ,hypokalaemia, hypercalcaemia, and hypomagnesemia),intra-abdominal complications of surgery (includingleak, abscess and vascular injury), retroperitoneal disor-ders (hemorrhage, hematoma, inflammation, andabscess), and perhaps, most commonly of all, medica-tions such as narcotic analgesics, phenothiazines, tricy-clic antidepressants, and any other agent that maysuppress bowel motility [2,11••,25].

Table 1. Causes of acute gastroparesis

SurgicalVagotomyNissen fundoplicationRepair of diaphragmatic herniaCeliac axis blockBotulinum toxin injection for achalasiaSolid organ transplantationPylorus-preserving pancreatico-duodenectomy

MedicalDiabetic ketoacidosisElectrolyte disturbancesThyrotoxicosisMyxedemaHypopituitarismMultiple sclerosisDuchenne muscular dystrophyWaardenburg's syndromeIntensive chemo-radiation therapyCytomegalovirus (CMV) infectionLeiomyosarcomaPancreatic carcinoma

Acute Intestinal Pseudo-obstruction Quigley 275

Ileus is increasingly recognized among non-surgicalpatients, and may complicate virtually any inflamma-tory or infectious process within the abdominal cavity[30,31], as well as a variety of infectious [32,33],systemic [35,36], neurologic [37,38] and iatrogenic[39,42] disorders (Table 2).

In the postoperative state, ileus is diagnosed on thebasis of a failure of return of bowel sounds and activity;in the nonoperated patient the presentation is, typically,one of nausea, vomiting and intestinal distention. In thelatter context, differentiation from intestinal obstructionmay be particularly difficult. It should also be recognizedthat chronic intestinal pseudo-obstruction is frequentlycomplicated by episodes of acute ileus.

The pathophysiology of postoperative ileus hasreceived extensive investigation [2,11••,25,43••].Several studies have examined the intestinal motorresponse to surgery [2,11••,25]. Studies in the smallintestine have revealed that motor activity, especiallyphase three of the migrating motor complex, recoversrapidly following major abdominal surgery in man. Theability to inhibit the migrating motor complex on foodingestion and to convert to a fed pattern is, however,delayed until the second or third post-operative day.Gastric electrical and contractile activity typicallyrecover within 24 to 48 hours postoperatively. Colonicrecovery is slower and occurs gradually over the courseof 3 to 6 days. The return of colonic activity has been

Table 2. Causes of ileus

SurgicalGastrointestinalGynecologicalVascular, especially aortic

MedicalAcute pancreatitisPancreatic pseudocystPeritonitisIntra-abdominal abscessRetroperitoneal diseaseEndotoxemiaCongestive cardiac failurePheochromocytomaChurg-Strauss diseaseVon Recklinghausen's diseaseMitochondrial encephalomyelopathyParkinson's diseaseVincristineVinorelbineImipramineAcarboseStrongyloides stercoralisHerpes Zoster

Table 3. Causes of acute megacolon (Ogilvie's syndrome)

SurgicalGynecologicalOrthopedic (especially hip surgery)Intra-abdominalCholecystectomyGastrectomyTransplantationInguinal herniorraphyCardiothoracicNeurosurgical

laminectomyspinal fusionmyelographyspinal anesthesiaepidural narcotic injection

MedicalAcute myocardial infarctionCongestive cardiac failureChronic obstructive lung diseasePulmonary embolismAcute respiratory failureParkinson's diseaseDysautonomiaAmyloidosisSepticemiaMultiple Endocrine Neoplasia Type 2BBurns

Gastrointestinal disordersacute cholecystitischolantitispancreatitisappendicitisperitonitis (including spontaneous)mesenteric thrombosis

Retroperitoneal disordershemorrhagehematomamalignancychemo-radiation therapy

Medicationstricyclic antidepressantsnarcotic analgesicsclonidinetheophyllinelaxatives

InfectionsCMVHerpes virus

Nonmetastatic manifestation of malignancyPregnancy

276 Functional GI Disorders and GI Motility Dysfunction

associated, clinically, with the passage of flatus or stooland the resolution of the symptoms of ileus, confirmingthe clinical suspicion that the colon is the rate-limitingfactor in the resolution of normal postoperative ileus.[11••,25]. Traditionally, postoperative ileus was pre-sumed to result from a transient, reflex inhibition ofmotility, mediated by overstimulation of extrinsic sym-pathetic nerves [11••,25]. Recent studies have focused,in more detail, on the afferent and efferent limbs of theresponsible neural pathways. On the afferent side, bothcalcitonin gene-related peptide (CGRP)-containing sen-sory neurons and spinal afferents are thought to beinvolved [44], while on the efferent side vasoactiveintestinal peptide (VIP)-(45), nitric oxide (NO)-[29,46,47] and kappa opioid-[48,49] containing fibershave been, variably, implicated. Disturbances of thehypothalamic-pituitary axis have also been invoked insome contexts [50]. Recently, Bauer et al. [51–53] havesuggested an important contribution for peripheralevents in the pathogenesis of motor dysfunction inresponse to surgery and shock. They noted a significantrelationship between the local inflammatory response,neutrophil infiltration and smooth-muscle dysfunction.

Both peripheral and central factors may be relevant.There is, for example, evidence to suggest that theresponses to laparotomy, on the one hand and to intes-tinal handling, on the other, may be mediated throughseparate mechanisms [46,48].

ACUTE COLONIC PSEUDO-OBSTRUCTIONAcute colonic pseudo-obstruction, or Ogilvie’s syn-drome, is defined as an acute dilatation of the colonwithout evidence of mechanical obstruction distal to thedilated segment [2,54–57]. Ogilvie’s syndrome is associ-ated with an underlying medical condition, or the post-operative state, in over 90% of cases [58–75] (Table 3). Inone extensive review, over 50% of all instances occurredin relation to surgery, and 45% were associated with a sig-nificant acute or chronic medical disorder [54]. Advanced

age, obesity, immobility, and the use of patient-con-trolled analgesia (PCA) have been identified as risk fac-tors for Ogilvie’s in individual patients [61,62].

Progressive abdominal distention is the clinicalhallmark of this condition [2]. In postoperative cases,distention is, typically, evident by the fourth postoper-ative day. Nausea and vomiting are present in half ofcases and are, usually, not as prominent as in mechan-ical obstruction. Lower abdominal pain is present in60% to 80% and can occur in the absence of eitherischemia or perforation. Most patients are obstipated;it must be stressed that some will continue to pass fla-tus or even stool. A low-grade fever may be present.Physical examination reveals distention and tympany.Only 40% of patients will have hypoactive or absentbowel sounds; the remainder demonstrating eithernormal or hyperactive sounds. The classical radiologi-cal findings feature dilatation of the cecum, ascendingand transverse colon combined with the paucity of gasin the left colon. Distention is limited to that part ofthe colon proximal to the splenic flexure in 70% and90% of cases. In contrast to mechanical obstruction,haustral markings are preserved in Ogilvie’s syndrome.Fluid levels have been reported in 40% of cases. In oneseries, small bowel dilatation was noted in 80% ofcases. A major issue that confronts the clinician in theevaluation or management of patients with Ogilvie’ssyndrome is the risk of perforation, which was recentlyestimated at 3%. The associated mortality fromcolonic perforation is significant, ranging from 43% to50% [76]. Crucial to management decisions in Ogil-vie’s syndrome is the degree of cecal distention. A cecaldiameter in excess of 9 cm is regarded as abnormal andthe risk of perforation becomes significant when itexceeds 12 cm [77]. It has been suggested that theduration, rather than the degree, of cecal distentionbest predicts the risk of perforation; cecal perforationbeing most likely to occur when distention lasted forlonger than 6 days [79].

Treatment

• Upon reviewing the literature on acute intestinal pseudo-obstruction and its various presentations, it immediately becomes obvious that there is a striking lack of truly controlled clinical studies in this area [76–80]. Most information is based on retrospective reviews, or prospective observations on a single technique or intervention without a control comparison.

• For each of these conditions, therapy continues to be based, primarily, on the traditional concept of bowel rest. This approach includes nasogastric suction, nothing by mouth, and the parenteral administration of fluid, electrolytes, and nutrition, as required. Whether this approach has any influence on the natural history of these disorders is unknown [11••,81],

Acute Intestinal Pseudo-obstruction Quigley 277

but upper gastrointestinal decompression will certainly provide symptom-atic relief, and the administration of intravenous fluids will avoid fluid depletion, electrolyte imbalance, and malnutrition.

• Pharmacologic, endoscopic, and surgical approaches have been variably attempted to relieve gastroparesis, ileus and megacolon, and will be discussed in the following sections. Such approaches have included the administration of prokinetic drugs [80], colonoscopic decompression of megacolon [76••], placement of gastrostomy/enterostomy tubes to decom-press the upper gastrointestinal tract [82], pacing [4], and surgery.[83].

• Given the nature of these conditions, dietary and lifestyle interventions are not typically employed in the actual management of acute intestinal pseudo-obstruction, but a variety of dietary manipulations have been attempted to prevent the development of ileus, in particular.

• Early enthusiasm for early postoperative feeding waned when subsequent studies failed to show that this approach had any effect on the prevalence or duration of ileus [78••]. There is, however, some evidence to suggest that a high-fiber diet, administered in the preoperative period, may be beneficial [78••].

• Considerable attention has been paid to the identification of factors that might predispose to postoperative gastroparesis, ileus, or megacolon; here again, attempts at interventions have proven disappointing. For example, it is unclear as to whether the additional administration of thoracic epi-dural analgesia or anesthesia as part of the anesthetic regime will reduce postoperative ileus [84•–86], though there is some evidence that the epi-dural administration of a local anaesthetic agent is associated with less ileus than is an opiate [11••]. It is certainly wise to eliminate, or at least minimize, the use of pharmacologic agents that are known to suppress motility and also, wherever possible, to correct electrolyte abnormalities that, in and of themselves, are likely to cause ileus. While nasogastric suc-tion has become a standard component of therapy, there is inconclusive evidence that the prophylactic placement of a nasogastric tube will prevent, or shorten, the duration of postoperative ileus [78••, 81].

• Patient positioning has been shown to promote resolution of toxic mega-colon [87], and has been suggested for idiopathic megacolon. [75, 88].

• Finally, there is some evidence that a program that prepares patients psychologically for surgery and for its likely sequelae shortens the interval to resumption of oral intake following the surgical procedure [78••].

• Metabolic, electrolyte, or endocrine abnormalities that may have a primary role in the pathogenesis of the problem should be defined and treated appropriately. In particular, the patient’s medications should be carefully reviewed and any agents that can induce or aggravate ileus eliminated.

• The most difficult issue here is usually that of pain control. Opiates are especially problematic, and there is experimental evidence to indicate that nonsteroidal anti-inflammatory drugs (NSAIDs), and ketorolac, in particular, can reverse laparotomy-induced ileus in animal models [89,90]. The use of this agent is complicated, however, by a significant risk of upper gastrointestinal ulceration and bleeding [91,92].

Diet and Lifestyle

Pharmacologic treatment

278 Functional GI Disorders and GI Motility Dysfunction

• While several prokinetic, and other pharmacologic agents have been tested in these disorders, few have been subjected to prospective, randomized clinical trials [2,93]. Given the clinical context, these agents will, of necessity, usually need to be administered by the parenteral route or by rectal administration.

• Cholinergic agonists are the original pro-motility agents. Their effect is mediated primarily through stimulation of muscarinic M2-type receptors on smooth muscle cells.

• Recently, anticholinesteresases have been used for the same reason. While there have been sporadic reports of the use of these agents in gastroparesis and ileus, the best evidence for efficacy is in acute colonic pseudo-obstruc-tion [94,95••]. Ponec et al. [94] administered neostigmine in a dose of 2 mg intravenously to 11 patients with acute colonic pseudo-obstruction, and com-pared their outcome to that of 10 who received intravenous saline.

• Ten of the 11 patients who received neostigmine had prompt colonic decompression, as compared with none of the 10 patients who received placebo. The median time to response was just 4 minutes. Two patients who had an initial response to neostigmine required colonoscopic decom-pression for recurrence of colonic distension; one eventually underwent subtotal colectomy. In contrast, seven patients in the placebo group, and the one patient in the neostigmine group without an initial response all required colonic decompression.

Neostigmine

Standard dosage 2 mg intravenously.Contraindications Intestinal obstruction, urinary obstruction, cardiac conduction defects.

Main drug interactions Depolarizing muscle relaxants, cyclopropane, halothane.Main side effects Related to cholinergic stimulation, ie, nausea, salivation, diarrhea, colic, bradycardia.

Special points Good evidence for efficacy in acute colonic pseudo-obstruction.Cost-effectiveness In the United States, the approximate cost for a single dose of neostigmine is $15.

This is highly cost-effective in comparison to colonoscopic decompression [95].

• Until recently, the most widely used prokinetic agent was metoclopramide, a dopamine antagonist with central and peripheral effects. Recently, domp-eridone, a dopamine antagonist that does not cross the blood-brain barrier, and, therefore, operates primarily through peripheral (DA2) receptors, has become available for use throughout most of the world. It is not as yet available in the United States.

• Metoclopramide alone is available for parenteral administration. While there is no convincing evidence for efficacy influencing the natural history of gastroparesis, ileus, and megacolon, parenteral metoclopramide may reduce the severity of associated nausea and vomiting [78••,96].

Pharmacologic treatment: cholinergic agonists

Pharmacologic treatment: dopamine antagonists

Acute Intestinal Pseudo-obstruction Quigley 279

Metoclopramide

Standard dosage 10 mg t.i.d. sc, IM, IV.Contraindications Parkinson’s disease, pheochromocytoma, hyperprolactinemic states.

Main drug interactions Butyrophenones, anticholinergics, phenothiazines.Main side effects Extra-pyramidal reactions, gynecomastia, galactorrhea.

Special points Little evidence for efficacy in the small intestine and colon. May reduce severity of nausea and vomiting. Though unproven in clinical trials, experience in chronic gastroparesis suggests that it could shorten the duration of acute gastroparesis [97]. Up to 25% of patients may experience side effects.

Cost-effectiveness Cheap, available in generic form.

• In this group, cisapride is the prototype. It facilitates acetylcholine release from myenteric neurons through a 5HT4 receptor-mediated effect.

• Important warning: Because of reports of serious cardiovascular side effects, the manufacturer of cisapride (Janssen Pharmaceutica, Titusville, NJ) has voluntarily pulled the drug from the US market as of July 14, 2000. Physicians who believe that cisapride may still be beneficial for certain patients can contact Janssen at 1-800-JANSSEN for eligibility guidelines.

• Among the commonly available oral agents, cisapride appears to have the most diffuse gastrointestinal effects. While there is some evidence that intravenous cisapride is effective in ileus [78••] and that oral cisapride may attenuate acute gastroparesis [6], rectal administration of cisapride has proven disappointing in the management of ileus. [78••]. There is, how-ever, some experimental evidence that oral cisapride may limit the duration of ileus in neonates [98]. Cisapride is not, and will not be, available for parenteral administration.

Cisapride

Standard dosage 10–20-mg q.i.d. or b.i.d. PO.Contraindications Patients with a history of irregular heartbeats; abnormal electrocardiogram (ECG or

EKG); heart disease; kidney disease; lung disease; low blood levels of potassium, calcium, or magnesium; eating disorders; sudden dehydration; or persistent vomit-ing; concomitant use of drugs that inhibit cisapride metabolism or prolong the QT interval (see below); history of prolonged QT interval or related arrhythmias; hypokalaemia; hypomagnesaemia; and respiratory failure. Not for use in patients who might experience a rapid reduction in plasma potassium or who suffer from intestinal obstruction, gastrointestinal hemorrhage, or perforation.

Main drug interactions Antibiotics: erythromycin, clarithromycin, troleandomycin; antidepressants: nefazodone; antifungals: fluconazole, itraconazole, ketoconazole; protease inhibi-tors: indinavir, ritonavir. These drugs inhibit cytochrome P450 3A4 and may lead to elevated cisapride blood levels and provoke cardiac arrhythmias. The following agents may also predispose to cardiac arrhythmias when given concomitantly with cisapride by independently prolonging the QT interval. These include: anti-arrhyth-mics: quinidine, procainamide, sotalol; anti-psychotics: certain phenothiazines, sertindole; antidepressants: maprotiline and the following drugs: astemizole, bepri-dil, sparfloxacin, terodiline, potassium-wasting diurectics, insulin (when given in acute settings), anti-cholinergics, cimetidine and oral anti-coagulants.

Main side effects Diarrhea, abdominal cramps, constipation, and headache. The main concerns with the use of cisapride have been instances of cardiac arrhythmias. These have included torsades de pointes, ventricular tachycardia, and fibrillation, which have, on occasion, been fatal. As a consequence, in addition to the action taken in the United States (see important warning above), several countries have restricted

Pharmacologic treatment: substituted benzamides

280 Functional GI Disorders and GI Motility Dysfunction

cisapride use to very specific indications, and have also requested the performance of an electrocardiograph before cisapride administration. There also have been rare reports of convulsions.

Special points Overall, there is little evidence for efficacy of cisapride in acute gastroparesis, ileus, or megacolon. Furthermore, its use is limited by its exclusive availability in most countries in oral formulation, and perhaps most importantly, by the likelihood that patients with these problems may be at increased risk for the development of cardiac toxicity related to cisapride.

Cost-effectiveness No real data; relatively expensive.

• Erythromycin, and other macrolides are motilin analogs. They are, there-fore, potent prokinetics that exert effects on gastric emptying, and antral and duodenal contractility, in particular.

• There is also some evidence for efficacy in the small intestine and colon. Though there are some reports of efficacy [99], these agents have not been formally tested in the context of acute gastroparesis, ileus ,or megacolon. However, erythromycin has been shown to be effective in severe diabetic gastroparesis, and in chronic post-surgical gastroparesis [96]. It is more effective when given by the intravenous rather than the oral route [97,99].

Erythromycin

Standard dosage IV: 50–200 mg t.i.d. PO 250 mg t.i.d.Contraindications Liver disease.

Main drug interactions Theophylline, oral anticoagulants, cisapride.Main side effects Nausea, vomiting, abdominal pain, antibiotic-related effects.

Special points Currently, erythromycin is the only macrolide available as a prokinetic. In the acute situation, intravenous erythromycin may be commenced in a dose of 3 mg per kg every 8 hours and should be considered in patients with severe acute gastroparesis.

Cost-effectiveness IV therapy is very expensive.

• In the management of acute gastroparesis, upper gastrointestinal endo-scopy may play a diagnostic role in eliminating gastric outlet obstruction, and a therapeutic one by assisting in the placement of nasogastric or nasoduodenal tubes.

• If gastroparesis becomes prolonged, endoscopy may also assist by facilitat-ing the placement of percutaneous endoscopic gastrostomy (PEG) or jejunostomy (PEJ) tubes [82,101–103].

• The main role of endoscopy, however, is in the management of megacolon [6,104–107]. Given the risk of spontaneous perforation, with its high associated mortality, colonoscopy has, for some time, played an important role in the management of patients with megacolon and significant cecal distension.

• By definition, the colon will not be prepared in these patients and the pro-cedure may, therefore, be technically difficult. An overall success rate of approximately 70% has been reported in achieving a reduction in cecal diameter, but the recurrence rate has been as high as 40% [76]. Some have advocated the placement of a decompression tube at the time of colonos-copy and have reported that this reduces the recurrence rate [106].

Pharmacologic treatment: macrolides

Endoscopic therapy

Acute Intestinal Pseudo-obstruction Quigley 281

• This involves the placement of a guidewire through the biopsy channel of the colonoscope and the subsequent insertion of the decompression tube over the guidewire, under fluoroscopic control, following withdrawal of the colonoscope.

• Colonoscopy is not without risk in Ogilvie’s syndrome, however. Given the recent reports of success with intravenous neostigmine, it seems appro-priate that colonoscopy should be reserved for those who fail conservative therapy and the administration of neostigmine [77].

• Surgical intervention has no role to play in the management of acute gas-troparesis and ileus, though there are several reports of the performance of a subtotal or a completion gastrectomy for patients with prolonged post-surgical gastroparesis [83,108,109].

• In the same situation, good results have been reported by laparoscopic placement of gastrostomy and jejunostomy tubes, permitting simultaneous gastric decompression and enteral feeding [102].

• Surgical intervention, and the placement of a tube cecostomy in particular, may become necessary in the patient with megacolon who appears at high risk of perforation and has failed pharmacological and colonoscopic attempts at decompression. This may sometimes be done laparascopically or even percutaneously.

• Clearly, surgery will also be necessary in those who, unfortunately, progress to ischemia or perforation. In all of these situations, surgery has been asso-ciated with high morbidity and mortality rates [54–57,76,77].

• Given the prevailing opinion with regard to the pathophysiology of ileus, it should come as no surprise that a variety of adrenergic blocking agents and parasympathomimetics have been employed in this situation, but have not provided much evidence of efficacy.

• Other agents evaluated in experimental animal models, and which do show promise, include kappa opioid agonists, [48,49], prostagladin analogs [110], and novel substituted benzamides [111]. The opiate antagonist nalox-one has been used clinically in constipation [112], but whether it is effec-tive in gastroparesis, ileus, or megacolon has not been established.

• It has also been suggested that electrical pacing of the stomach or intestine may be of value in acute gastroparesis and ileus, respectively, but this approach has not, as yet, been validated in clinical practice [4]. Hyperbaric oxygen has shown some promise in toxic megacolon, related to ulcerative colitis [113], but has not been evaluated in Ogilvie’s syndrome [4].

• Finally, a recent review suggested that homeopathic approaches may be beneficial in ileus [114].

Editor’s Note: Dr. Quigley’s excellent review of Chronic Intestinal Pseudo-obstruction can be found in Current Treatment Options in Gastroenterology, Volume 2, Number 3, June, 1999.For more information on acute idiopathic gastroparesis, please refer to “Unexplained Nausea and Vomiting,” by Kenneth L. Koch, MD, in this issue.

Surgery

Emerging therapies

282 Functional GI Disorders and GI Motility Dysfunction

References and Recommended ReadingPapers of particular interest, published recently, have been highlighted as:• Of importance•• Of major importance

1. Quigley EMM: Chronic intestinal pseudo-obstruction. CTO Gastroenterol 1999, 2:239–230.

2. Quigley EMM: Post-surgical motility problems. In Gastrointestinal Motility Disorders—Issues in Evaluation and Treatment; Gastrointestinal Motility. A Multi-Media Guide. Edited by Quigley, EMM. Los Angeles; AMV productions, 1999:103–114.

3. Ramirez B, Eaker EY, Drane WE, et al.: Erythromycin enhances gastric emptying in patients with gastro-paresis after vagotomy and antrectomy. Dig Dis Sci 1994, 39:2295–2300.

4. Hocking MP, Vogel SB, Sninksy CA: Human gastric myoelectric activity and gastric emptying following gastric surgery and with pacing. Gastroenterology 1992, 103:1811–1816.

5. Gutierrez-Galiana E, Botoman VA, Bech H: Symptom-atic gastroparesis in a patient with achalasia. J Clin Gastroenterol 1998, 27:166–168.

6. Iftikhar S, Loftus EV Jr.: Gastroparesis after celiac plexus block. Am J Gastroenterol 1998, 93:2223–2225.

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10. Tobi M, Holtz, Carethers J, Owyang C: Delayed gastric emptying after laparoscopic anterior highly selective and posterior truncal vagotomy. Am J Gastroenterol 1995, 90:810–811.

11.•• Resnick J, Greenwald DA, Brandt LJ: Delayed gastric emptying and postoperative ileus after nongastric abdominal surgery: Part 1. Am J Gastroenterol 1997, 92:751–762.

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