Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Ileus and Pseudo-Obstruction Syndromes


Ileus and pseudo-obstruction refer to intestinal dysmotility syndromes that have signs, symptoms, and the radiologic appearance of obstruction (i.e., a dilated viscus) in the absence of a mechanical cause. These conditions—which may be acute, chronic, or acute on chronic—affect the small intestine or colon, and infrequently both organs. By convention, acute dysmotility of the small intestine, which most frequently occurs after abdominal surgery, is referred to as ileus whereas chronic dysmotility is termed chronic intestinal pseudo-obstruction (CIPO). The corresponding terms for the colon are acute colonic pseudo-obstruction , or Ogilvie syndrome, and chronic megacolon or megarectum. Acute colonic pseudo-obstruction occurs most often in older adults with severe underlying disorders that may be responsible for the acuteness of the situation. Acute colonic pseudo-obstruction is characterized by massive dilatation of the cecum and right colon, with simultaneous, yet less severe, dilatation of the left colon and distal small intestine, without evidence of mechanical obstruction. With early aggressive treatment, the massive dilatation usually resolves and intestinal function returns to normal. Megacolon and megarectum are terms applied to radiologic images or the intraoperative appearance of a chronically dilated colon or rectum that can develop as a result of pseudo-obstruction, inflammation, infection, spinal trauma, and metabolic or congenital disorders. The most common cause of congenital megacolon and megarectum is Hirschsprung disease (HD).

Ileus

Postoperative ileus (POI) refers to the impaired GI motility that occurs in all patients who undergo GI surgery. In most patients, POI is benign and self-limited. Gastric and small intestinal activity generally reappear within hours of surgery whereas colonic activity returns by postoperative day 2 or 3.

Prolonged (or pathologic ) POI is defined by delayed recovery of intestinal function in the absence of mechanical intestinal obstruction. It manifests as failure to pass flatus or intolerance of an oral diet. The definition of an acceptable recovery time depends on the type of surgery and has varied among studies. An international consensus panel recommended that normal or obligatory POI be defined as the period of time, lasting fewer than 4 days, from surgery until the passage of flatus or stool and tolerance of an oral diet. The same panel defined prolonged POI as the occurrence of 2 or more of the following signs and symptoms (i.e., nausea or vomiting, inability to tolerate an oral diet over the preceding 24 hours, absence of flatus over the preceding 24 hours, abdominal distention, and radiologic features of ileus) on postoperative day 4 or after. However, some of these features (e.g., intestinal distention) are not objective and may be confounded by other factors (e.g., nausea or constipation related to medications). The severity of POI ranges from delayed passage of flatus to severe paralytic ileus.

Epidemiology

Whereas transient or physiologic ileus is common, perhaps inevitable, after abdominal surgery, prolonged or pathologic POI occurs less frequently. In general, the risk of POI is lower after abdominal surgery with smaller incisions and minimal visceral manipulation (e.g., cholecystectomy) but greater after lower abdominal surgery with large incisions and with intestinal manipulation (e.g., colorectal or gynecologic procedures). In large studies, which used varying definitions of prolonged POI, the incidence of POI was approximately 3% after abdominal hysterectomy, 10% after radical cystectomy, 13% to 24% after elective colonic resection, and 15% after bowel resection. Prolonged POI delays patient recovery, increases postoperative morbidity, and increases health care costs. After abdominal surgery, POI is the most common cause of prolonged hospitalization with an estimated annual cost of $1.5 billion in the USA. Indeed, the costs of managing POI are similar to those of managing other major postoperative complications such as wound infections, pulmonary embolus, and deep venous thrombosis.

Risk Factors and Pathophysiology

Initially, ileus affects intestinal loops that have been manipulated during the surgery. Later, even non-manipulated sections of the intestinal tract can be involved. The factors that contribute to ileus are listed in Box 124.1 . Abdominal or retroperitoneal surgery is the most common cause of ileus, which invariably occurs after these procedures. In one series of 327 patients undergoing elective colorectal surgery, of whom 27% had prolonged POI, the independent predictors of prolonged POI were male sex, lower postoperative albumin, a larger wound, operative difficulties, bowel handling during surgery, red cell transfusion, administration of IV crystalloids, and delayed first mobilization. By comparison, ileus is probably less common after non-abdominal operations, e.g., occurring in less than 1% of patients who had total joint arthroplasty. In addition to the procedure itself, infection, inflammation, severe pain, medications (especially opioids), general anesthesia, and electrolyte abnormalities contribute to ileus. Activation of μ-opioid receptors (e.g., with μ-opioid receptor agonists such as morphine) inhibits release of acetylcholine from myenteric neurons and delays GI transit.

BOX 124.1
Common Factors That Contribute to Post-Operative Ileus

Surgery

  • Cardiothoracic

  • Colorectal

    • Genitourinary

    • Gynecologic

    • Laparoscopy

    • Laparotomy

    • Orthopedic (e.g., hip and knee surgery) procedures

  • Spinal

Infections

  • Intra-abdominal infections

    • Pneumonia

  • Sepsis

Inflammation

  • Local tissue trauma

    • Pancreatitis

    • Peritonitis

    • Retroperitoneal hemorrhage

Metabolic Disturbances

  • Hypokalemia , hypocalcemia, hyponatremia, or hypomagnesemia

Pharmacologic

  • Anticholinergic agents

  • General anesthetic agents

  • Opioids

Miscellaneous

  • Immobility

  • Pain

Initially, the surgery itself causes ileus via neurogenically mediated spinal reflexes that are activated from the first abdominal incision to just after the surgery is completed ( Fig. 124.1 ). Typically, this phase is relatively brief. The second phase is sustained, attributed to inflammation, begins during surgery, and continues for a variable length of time after surgery (see Fig. 124.1 ). The early studies of POI that were conducted in canine and feline models documented the role of inhibitory neural reflexes mediated by splanchnic pathways. , However, most studies thereafter, and especially those dealing with inflammation, were conducted in murine models in which the intestine was manipulated but not resected or anastomosed. The extent to which these findings are germane to POI in humans is unclear.

Fig. 124.1, Schematic representation of 2 neural pathways triggered by abdominal surgery. The intensity and nature of nociceptive stimuli determine the severity and duration of ileus. Simple laparotomy activates spinal afferents that synapse in the spinal cord where they activate an inhibitory pathway involving prevertebral adrenergic neurons that stops intestinal motility briefly (A). Intestinal manipulation activates additional pathways. Afferent signals are transmitted to the brainstem where they trigger increased autonomic output to the neurons of the intermediolateral column of the thoracic cord, where sympathetic preganglionic neurons that release noradrenaline (NA) are located. Activation of these nerves inhibits the entire GI tract (B). In addition to this adrenergic inhibitory pathway, intense stimulation of splanchnic afferents triggers a vagally-mediated pathway that synapses to inhibitory nitric oxide (NO) and VIP-containing neurons. VIP, vasoactive intestinal peptide.

Early Neurogenic Phase

Bayliss and Starling observed that intestinal handling inhibited intestinal motor activity in intact, unanesthetized dogs, which could be prevented by sectioning the splanchnic nerves. Current concepts suggest that less severe insults, such as skin incision and laparotomy, inhibit motility primarily by activating adrenergic inhibitory pathways that mediate spinal reflexes, which are abrogated by dividing the splanchnic nerves or dorsal root fibers or crushing the spinal cord but not by damaging the ascending and descending pathways in the spinal cord (see Fig. 124.1 A ). By comparison, in rats, more intense stimuli, such as intestinal handling, also engage supraspinal pathways with activation of specific hypothalamic and pontine-medullary neurons such as the nucleus tractus solitarii and the paraventricular nucleus and supraoptic nucleus of the hypothalamus. Intense stimulation of splanchnic afferents in rats also triggers a vagally- mediated pathway, which synapses to inhibitory nitric oxide (NO) and vasoactive intestinal peptide (VIP)-containing neurons located within the intestinal wall.

Late Inflammatory Phase

The muscularis externa contains a uniquely adapted population of resident macrophages (MΦs). At steady state, these MΦs respond to luminal bacterial infections and interact with enteric neurons to regulate GI motility. In rodents and humans, surgery activates these resident MΦs, which in turn recruit leukocytes, especially monocytes and neutrophils, into the muscularis externa within a few hours after surgery. , These events are associated with impaired muscle contractility and delayed GI transit. Inactivation or depletion of resident MΦs and blocking adhesion molecules on the endothelial surface before surgery prevented leukocyte recruitment and ameliorated GI transit. A similar beneficial outcome was obtained by blocking adhesion molecules on the endothelial surface to prevent leukocyte infiltration. Hence, leukocyte infiltration has been implicated to cause POI.

However, some leukocytes, and in particular monocytes, also have anti-inflammatory effects that offset the pro-inflammatory effects, prevent excessive injury, and facilitate timely resolution of inflammation. Indeed, once recruited, leukocytes reside up to 7 days in the muscularis externa, even beyond the duration of POI. Hence, it is conceivable that the leukocytes recruited to the muscularis externa may initially have pro-inflammatory effects but later facilitate resolution of inflammation. , Confirming this hypothesis, mice with defective monocyte migration (i.e., C-C motif chemokine receptor 2 [Ccr2 −/− mice]) had more neutrophil-mediated inflammation and delayed recovery of GI transit after intestinal manipulation compared with wild type mice. This suggests that activation of resident MΦs, which release cytokines, prostaglandins, and NO, is perhaps more important than the recruitment of monocytes for POI. , The mechanisms responsible for activating resident MΦs are unclear. By contrast, monocytes that enter the muscularis in a CCR2-dependent manner differentiate into mature MΦs which facilitate healing.

Earlier studies with mast cell-deficient mice that lack interstitial cells of Cajal (ICC) and are also immunocompromised, suggested that mast cells contribute to POI. However, subsequent studies in mice with a more selective depletion of mast cells did not confirm these findings. , In humans, POI is associated with intestinal and peritoneal mast cell activation. Whether activated mast cells contribute to POI in humans is unclear. A small pilot study using the mast cell stabilizer/histamine 1 receptor antagonist ketotifen improved postoperative gastric emptying in humans).

Pharmacologic Mechanisms

Anesthesia

GI motility is impaired to a variable degree after anesthesia and general surgery, especially abdominal surgery. Several drugs that are used to induce or maintain general anesthesia, and particularly induce analgesia, reduce GI motility. Among the agents that are used to induce anesthesia, the IV agent propofol has minimal effects on GI or colonic motility and is now one of the most commonly used anesthetics to reduce postoperative nausea. Interestingly, combining propofol with analgesics such as remifentanil promotes GI motility but is seldom used in humans. NO does not seem to have a clinically significant effect on ileus. Administered peripherally, the N-methyl-D-aspartate receptor antagonist ketamine reduced visceromotor responses and motility reflexes, but not at the doses used in anesthesia (1.8 to 2.4 mg/kg/hr). These effects on motility reflexes are likely due to non- N-methyl-D-aspartate receptor actions, possibly on nicotinic receptors. Ketamine also has anti-nociceptive effects, making it an attractive non-opioid option in anesthesia. However, in a double-blind randomized controlled trial that compared saline to ketamine for IV patient-controlled analgesia in 42 patients who underwent bowel resection, the morphine dose and return of bowel function were not significantly different between these groups.

During surgery, the stress response and inhibition of diaphragmatic activity are lower with neuraxial than general anesthesia. Adding neuraxial to general anesthesia is associated with better perioperative outcomes after orthopedic surgery. Similarly, a systematic review observed that there is high-quality evidence to support the inference that an epidural local anesthetic, with or without an opioid, delivered by a mid-thoracic (T6-T8) catheter accelerates the recovery of GI motility. There is moderate evidence that this combination also decreases pain after an abdominal surgery. Although the evidence is limited, an epidural block containing a local anesthetic does not affect the incidence of vomiting or anastomotic leak. For an open operation, there is evidence—of very low quality—that an epidural block containing a local anesthetic would reduce the length of hospital stay.

Opioids

Opioids alleviate pain but predispose to ileus. Of the 3 main classes of opiate receptors (μ, λ, Κ), opioid drugs mainly target μ receptors to cause analgesia via effects in the brain and spinal cord, and to inhibit propulsive motility via effects in the GI tract. , By releasing the intestinal circular muscle from inhibition, morphine increases resting contractile tone and induces rhythmic contractions with occasional high-amplitude, non-propulsive phasic contractions in the circular muscle of the small and large intestine. This activity is non-propulsive because the neural integration required for coordinated, propulsive, motor activity is lost. In addition, activation of Κ and ä receptors inhibits submucosal secretomotor neurons to reduce active Cl secretion and passive water movement into the colonic lumen.

Clinical Features

The clinical features of ileus are similar to those of mechanical obstruction. Typical symptoms of ileus include abdominal pain (which usually is poorly localized), abdominal distention, inability to tolerate solid food, and obstipation; nausea and vomiting also may occur. Physical examination reveals reduced bowel sounds. Symptoms range from mild to severe; some patients resume daily activities within 1 or 2 days, whereas others require prolonged, intensive monitoring, hydration, and pain management. Abdominal plain films show air-filled small intestine, often with air-fluid levels at various levels that raise the question of SBO. Differential air-fluid level may be seen with ileus as well as SBO, although it is more common with the latter. Distention often extends up to the stomach and down to the colon. Abdominal CT can confirm unobstructed distension or identify mechanical obstruction and its various causes. Importantly, ileus in the early postoperative period does not require diagnostic evaluation. Prolonged POI exceeds 7 days’ duration and is independently associated with perioperative blood loss and total narcotic dose. Early postoperative bowel obstruction has a similar presentation to POI, although the consequences can be more serious; it is a complication of surgery that affects 0.7% to 10% of surgical patients. Postoperative bowel obstruction is diagnosed if, within 30 days of surgery after resolution of POI and return of normal bowel function, abdominal pain, vomiting, and radiologic evidence consistent with SBO are present. CT can help distinguish POI from early postoperative SBO and identify other complications.

Treatment

Historically, treatment for POI has included bowel rest, NG tube decompression, and IV fluid therapy. These interventions were thought to shorten recovery time by lowering the incidence of complications and improving outcomes. However, a critical review of the evidence does not support such conclusions. Bowel rest neither shortens the time to first bowel movement nor decreases the time to oral intake. Carbohydrate loading prior to surgery and early postoperative feeding are now used to hasten recovery. Regular use of NG tube decompression beyond surgery and abdominal drains is no longer recommended; similarly, urinary catheters are discontinued within 24 to 48 hours because their use does not hasten recovery. The advent of laparoscopic surgery, regional anesthesia, opioid-sparing analgesics, and several evidence-based treatments that hasten recovery from ileus has led to improved care of patients who undergo abdominal surgery. First described in the 1990s, ERPs (Enhanced Recovery Programs/Pathways, also known as Enhanced Recovery After Surgery Programs [ERAS]) combine treatment modalities, detailed subsequently, that individually improve outcome following major surgery ( Table 124.1 ). An overarching goal of fast-track surgery is to lower rates of organ dysfunction, thereby reducing morbidity, hastening recovery, and shortening hospital stay. Some benefits of ERPs are listed in Box 124.2 . The concept has proved valid across all surgical specialties, but the most data are available for colonic surgery. Fast-track surgery has been shown to enhance recovery from POI. Most patients have a normal oral intake and defecate within 48 hours, and have a hospital stay of 2 to 4 days (reduced from 5 to 10 days) after uncomplicated open colonic surgery. Although only some ingredients of the ERAS programs reduce the incidence and/or severity of ileus, all recommendations are comprehensively discussed later.

TABLE 124.1
Evidence-Based Components of Enhanced Recovery Pathways
Preoperative Intraoperative Postoperative
Preoperative assessment; verbal explanation and written material provided on ERP; preset criteria for discharge and readmission reviewedCarbohydrate loading by solution or solids up to 2-6 hr, respectively, before surgery
Avoidance of mechanical colon preparation
Prophylaxis of postoperative nausea and vomiting
Reduction of the stress response		 Goal-directed fluid therapy
Laparoscopy, or midline or transverse laparotomy incision with C6-8 epidural anesthesia
Opioid-sparing anesthesia and analgesia		 Avoidance of NG tubes and drains; removal of urinary catheter within 24 hr
Early mobilization and ambulation
Continuous epidural low-dose local anesthetic and opioid-sparing combinations or IV patient-controlled analgesia; NSAID and/or acetaminophen use as baseline analgesic
Early enteral feeding
Early withdrawal of IV fluid
Use of chewing gum
Use of laxatives
Early scheduled follow-up
ERP, Enhanced Recovery Pathways.

BOX 124.2
Benefits of Enhanced Recovery Pathways for Colorectal Surgery

  • Accelerated recovery

  • Cost containment

  • Improved resource utilization

  • Low morbidity

  • Low readmission rate

  • Safe reduction in length of stay

  • Standardized health practice

Prevention

Preoperative

Nutrition

Multiple randomized controlled clinical trials have supported the ingestion of clear liquids less than 2 hours before elective surgery. These studies have shown that ingestion of clear liquids within 2 to 4 hours of surgery versus more than 4 hours is associated with smaller gastric volume and higher gastric pH at the time of surgery. By comparison, the quality of evidence and strength of recommendation for preoperative oral carbohydrate loading is lower. Although this approach reduced length of stay after major abdominal surgery, differences for length of stay and rate of complications were significant compared with fasting but not with water or placebo. Hence, allowing clear liquids before surgery may be comparable to carbohydrate loading.

Reducing the Stress Response

Pre- and early postoperative nutritional support, epidural anesthesia, adequate analgesia including non-opioid pain management with NSAIDs and acetaminophen, and use of ERPs reduce the stress response to surgery, which has been associated with prolonged POI, delayed wound healing, fatigue, wound infections, and longer suppression of immune function.

Mechanical Bowel Preparation

Used in isolation, mechanical bowel preparation prior to elective colonic surgery offers no benefit. However, oral antibiotic preparation, which was mostly administered together with mechanical bowel preparation, reduced the risk of surgical site infections, and in some studies also reduced anastomotic leakage and intra-abdominal infections.

Prophylaxis of Postoperative Nausea and Vomiting

In post-anesthesia care units, the overall incidence of postoperative nausea and vomiting (PONV) is approximately 30%. Preoperative screening can reliably identify patients who have a higher risk (e.g., up to 80%) of PONV and is recommended in all patients. The risk of PONV ranges from 10% for patients with no risk factors to approximately 79% for patients with 4 risk factors (i.e., female sex; nonsmoker status; a history of PONV or motion sickness; and expected postoperative opioid use); that risk assessment did not compare various anesthetic agents. Other studies have observed that the incidence of PONV, need for antiemetic medications, and unplanned admissions to the hospital after surgery are all lower after total IV anesthesia with propofol and alfentanil, which is a short-acting opioid, than with inhalational maintenance with NO and enflurane. Among inhalational agents, there is no difference between halothane, enflurane, isoflurane, and desflurane, all of which are associated with less nausea than opioids. Among muscle relaxants, the incidence is greater with pancuronium than with vecuronium, atracurium, or alcuronium.

The 2017 Clinical Practice Guidelines for Enhanced Recovery after Colon and Rectal Surgery from 2 American professional societies recommend that all at-risk individuals should receive PONV prophylaxis with dexamethasone sodium phosphate at induction and ondansetron or another 5-hydroxytryptamine 3 antagonist at closure. Dexamethasone also has analgesic effects with reduced pain, fatigue, and opioid consumption, while increasing patient-reported quality of recovery during the first postoperative day after laparoscopic surgery for suspected acute appendicitis. IV acetaminophen given either before surgery or before arrival in the post-anesthesia care unit reduced the risk of nausea and pain provided it was given before the onset of pain. A meta-analysis shows that the pooled relative risk of PONV is lower in patients who receive preoperative gabapentin.

Intraoperative

Nature of Surgery

In appropriate cases, and when performed by trained personnel, laparoscopic surgery is better than open surgery for treating colorectal conditions. The benefits include better short-term outcomes (e.g., quicker return of bowel function, less blood loss, less postoperative pain, shorter hospital lengths of stay) and less perioperative morbidity, including total morbidity, wound morbidity, and nonsurgical morbidity. Patients undergoing laparoscopy have decreased time to pulmonary recovery, receive fewer narcotics, and have improved short-term quality of life.

Anesthesia

Regional anesthesia largely prevents the neuroendocrine stress response to surgery by preventing afferent neural transmission from reaching the CNS and by blocking efferent activation of the sympathetic nervous system; its use preserves immune function while reducing the need for opiates. Epidural anesthesia and analgesia is recommended for open colorectal surgery, and for laparoscopy if patients have significant respiratory disease , ; it also has been shown to enhance colonic blood flow and improve return of GI function. Among 45 patients who underwent elective abdominal aortic surgery, the duration of POI was shorter in patients who received thoracic epidural neostigmine than placebo.

Hemodynamic Management

During major abdominal surgery, a maintenance infusion of 1.5 to 2 mL/kg/hr of balanced crystalloid solution is sufficient to cover insensible fluid losses and maintenance needs. IV fluid overload or excessive fluid restriction can impair organ function, increase postoperative morbidity, and prolong hospital stay. Balanced chloride-restricted crystalloid solutions are preferred because they are associated with a lower risk of hyperchloremic metabolic acidosis than with normal saline. In high-risk patients, fluid therapy should be guided by more objective measures of volume status (e.g., cardiac output). A double-blinded clinical trial observed that the average duration of ileus was significantly shorter in patients who were resuscitated with colloids (73.4 ± 20.8 hours) than with crystalloids (86.7 ± 23.6 hours) during and after small or large intestinal resection and anastomosis. The incidence of vomiting was also lower in patients who were resuscitated with colloids.

Postoperative NG Tubes, Drains, and Catheters

NG tubes should be reserved for patients who develop POI refractory to more conservative management. Routine use of NG tubes delays resumption of oral nutrition. Urinary catheters should be removed within 24 hours of surgery.

Gum Chewing and Laxative Use

A Cochrane review observed that in patients who chewed gum (i.e., sugar-free gum for 10 minutes or longer 3 to 4 times per day) after surgery, the return of bowel sounds, passage of flatus, and bowel movements occurred earlier than in those who did not chew gum. There was a small difference in hospital length of stay but no differences in complications or cost of care between people who did or did not chew gum.

Early Oral Intake and Nutrition

Liquids are started immediately in the postoperative period with no restrictions on dietary intake starting 24 hours after laparotomy and laparoscopic surgery. , Early feeding accelerates GI recovery, decreases the hospital length of stay, prevents complications, and is associated with lower mortality.

Postoperative Pain Management

Opioid-sparing analgesia (including thoracic epidural analgesia) provides the best analgesia postoperatively. , Additional effective postoperative pain relief methods include patient-controlled analgesia, intrathecal analgesia, wound infusion and infiltration, systemic lidocaine infusion, and transversus abdominis plane (TAP) block. NSAIDs and acetaminophen often are used to achieve multimodal analgesia; however, there are reports of an increased risk of anastomotic leakage with use of cyclooxygenase 2 inhibitors.

Early Mobilization

Effective pain management is key to early mobilization, as has been shown with ambulatory epidural analgesia. , Ambulation improves pulmonary function and tissue oxygenation; it also reduces insulin resistance, risk of pulmonary embolism, and muscle loss while improving muscle strength. In one regimen, patients are advised to ambulate out of their room 5 times on the day after surgery and sit in a chair for 6 hours a day. Nursing and physical therapy support is helpful.

Preset Discharge Criteria

ERPs include standardized discharge criteria: patients must be able to tolerate solid food for 3 consecutive meals, have passed gas or stool, have adequate analgesia with a low pain score on a visual analog scale, and also feel ready for discharge with adequate social support.

Drug Therapy

Opioid-Sparing Analgesia

Minimizing opioid use facilitates earlier return of bowel function and reduces length of stay. , Analgesic agents (acetaminophen, nonselective or selective NSAIDs [and COX- 2 inhibitors]) should be administered on schedule rather than on an as-needed basis. These agents improve postoperative analgesia, and reduce systemic opioid consumption and some of their dose-dependent adverse effects. Experimental and observational clinical studies suggest that NSAIDs may increase the risk of anastomotic leakage. However, one recent meta-analysis observed that the risk of anastomotic leakage was not significantly increased in patients receiving one or more doses of NSAIDs in the first 48 hours after surgery. This risk may be more pronounced in patients receiving NSAIDs for a period of more than 3 days after surgery and in patients who have emergency, but not elective, colorectal surgery. Wound infiltration and abdominal trunk blocks with liposomal bupivacaine have shown promising results in patients undergoing open and laparoscopic colorectal surgery. In addition, limited data demonstrate that administering a local anesthetic into the TAP is associated with decreased length of stay compared with systemic opioids in laparoscopic colorectal surgery. TAP blocks performed before surgery appear to provide better analgesia than TAP blocks performed at the end. Although many centers start a multimodal analgesic regimen preoperatively, the efficacy of preemptive analgesia remains controversial and mainly limited to epidural blockade and TAP blocks.

Opioid Antagonists

Alvimopan is a peripherally acting μ-opioid receptor antagonist that ameliorates the inhibitory intestinal motor effect of opioids without compromising the analgesic effects. , In patients undergoing open colonic resection, postoperative administration of alvimopan (12 mg) reduced the duration of POI by 15 to 18 hours, hospital stay by 1 day, , and the incidence of prolonged hospital stay (>7 days) from 6.8% to 2.1% by lowering POI-related morbidity. Alvimopan is approved by the FDA to accelerate the time to upper and lower GI recovery following partial small or large bowel resection surgery with primary anastomosis. The approved dose is 12 mg administered 30 minutes to 5 hours prior to surgery, followed by 12 mg twice daily for up to 7 days for a maximum of 15 doses. Another study assessed the long-term safety and tolerability of alvimopan (0·5 mg twice daily) in 805 patients taking opioids for chronic non-cancer pain and opioid-induced bowel dysfunction. The proportion of adverse effects was similar for alvimopan (13%) and placebo (11%) groups. More patients treated with alvimopan had a variety of common neoplasms, e.g., colon polyps, skin lesions (2.8% vs . 0.7%), and myocardial infarctions (1.3% vs . 0.0%) but differences were not statistically significant and a causal relationship was not established. Hence, only hospitals that have registered in and met the requirements for the Entereg (alvimopan) Access Support and Education program may use the drug. In contrast to open colorectal surgery, the utility of alvimopan after laparoscopic surgery is less clear, especially when the cost of the drug is taken into consideration. ,

Methylnaltrexone is a peripherally acting μ-opioid receptor antagonist that is not approved by the FDA for treating POI. It had variable effects on the opioid-induced delay in GI transit time in healthy patients. In a small phase II clinical trial of 65 patients who underwent segmental colectomy, methylnaltrexone reduced POI and reduced hospital stay by one day compared with placebo. However, in 2 phase III placebo-controlled trials of 1048 patients undergoing open colectomy, methylnaltrexone (12 mg and 24 mg) did not improve POI or discharge parameters.

Other Agents

Dexmedetomidine is a highly selective α 2 -adrenoceptor agonist that possesses hypnotic, sedative, and sympatholytic properties without effect to depress respiration. Similar to clonidine, which is another α 2 agonist, its sympatholytic effect maintains hemodynamic stability by reducing norepinephrine release. Among 92 patients having laparoscopy, dexmedetomidine administered from the time of insufflation of the peritoneum to the end of surgery, at a dose that is lower than that approved by the FDA, facilitated bowel movements and reduced the length of hospital stay after laparoscopic gastrectomy; however, dexmedetomidine is not approved for managing POI by the FDA.

There is insufficient evidence to recommend the use of prokinetic agents such as dopamine antagonists, erythromycin, cisapride, propranolol, vasopressin, neostigmine, and cholecystokinin-like drugs for managing POI. The local anesthetic lidocaine reduces inflammation and perception of pain and can promote GI motility by blocking the afferent and/or efferent arms of the sympathetic inhibitory spinal and prevertebral reflexes, which are involved in ileus. Lidocaine also decreases sympathetic nervous system activity and has a direct excitatory effect on intestinal smooth muscle. In 6 clinical trials that included 116 patients, IV lidocaine given over 4 hours or 24 hours after surgery reduced the time until return of bowel function one day sooner than saline and reduced the length of hospital stay, depending on the type of resection and surgical approach. In most studies, lidocaine shortened the duration of POI and length of hospital stay; in a few trials (e.g., laparoscopic cholystectomies), improvement was not significant. Ghrelin is an orexigenic and prokinetic hormone that stimulates the migrating motor complex (MMC) and gastric motility and emptying and coordinates patterns of smooth muscle propulsive activity. In 2 phase 3 trials that enrolled 662 patients, the ghrelin receptor agonist TZP101 (ulimorelin) did not shorten the duration of POI after partial small bowel resection. 5-Hydroxytryptamine receptor-4 (5-HT ) agonists are potent prokinetic agents that promote enhanced intestinal contractility in the upper and lower GI tract. Cisapride improved POI but was removed from the market because of cardiovascular adverse events. Prucalopride is a high-affinity 5-HT molecule that is approved for treating chronic constipation in Europe, Mexico, and Canada but not in the USA. In a randomized clinical trial of 110 patients undergoing elective GI surgery, excluding total or subtotal colectomy, prucalopride shortened the time to passage of flatus and defecation and the postoperative length of stay by one day.

Acute Colonic Pseudo-Obstruction

Acute colonic pseudo-obstruction (ACPO) or Ogilvie syndrome is characterized by acute massive colon dilatation in the absence of mechanical obstruction and usually occurs in older adults or hospitalized or institutionalized patients with serious underlying medical or surgical conditions ( Table 124.2 ). ACPO is estimated to occur in 0.1% of all surgical patients, and patient outcome depends on the severity of underlying illness, age, maximum diameter of the cecum, delay until colonic decompression, and the presence or absence of colonic ischemia.

TABLE 124.2
Conditions Associated With Acute Colonic Pseudo-Obstruction (400 Cases)
Adapted from Vanek VW, Al-Salti M. Acute pseudo-obstruction of the colon (Ogilvie’s syndrome): an analysis of 400 cases. Dis Colon Rectum 1986; 29:203-10. Modified from Saunders MD, Kimmey MB. Systematic review: acute colonic pseudo-obstruction. Aliment Pharmacol Ther 2005; 22:917-25.
Health Condition (Most Common) Cases (%)
Trauma (non-operative) 11.3
Infection (pneumonia, sepsis) 10.0
Cardiac (myocardial infarction, heart failure) 10.0
Gynecologic surgery 9.8
Abdominal/pelvic surgery 9.3
Neurologic (Parkinson disease, spinal cord, multiple sclerosis, Alzheimer disease) 9.3
Orthopedic surgery 7.3
Miscellaneous medical conditions (metabolic, cancer, respiratory failure, kidney failure) 32.0
Miscellaneous surgical conditions (urologic, thoracic, neurosurgical) 11.8
Some patients had more than one risk factor; hence percentages exceed 100%.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here

Related Posts