Critically ill patients are especially prone to developing gastroesophageal reflux and related complications, particularly erosive esophagitis, which is one of the leading causes of inpatient upper gastrointestinal tract hemorrhage in mechanically ventilated patients, after stress-related mucosal disease [2,3]. GERD is particularly prevalent in the critically ill patient for several important reasons (Fig. 93.1). First, critically ill patients are often in the recumbent position, which promotes acid reflux [4,5,6] and reduces acid clearance from the esophagus. Second, many critically ill patients are intubated, sedated, or too ill to report symptoms of acid reflux. Significant reflux can thus go unrecognized until significant complications occur. This prolonged acid exposure is exacerbated in patients who are nihil per os (nothing by mouth), in whom decreased swallowing leads to poor clearance of esophageal contents. Third, critically ill patients are more likely to have increased transient relaxation of the lower esophageal sphincter (LES), due to use of drugs (e.g., morphine, atropine, theophylline, barbiturates) and to the frequent use of indwelling nasogastric tubes [7,8,9]. Fourth, mechanically ventilated patients are prone to acid reflux and microaspiration, at least in part due to mechanical deformities of the upper esophageal sphincter created by the pressure of the endotracheal tube cuff [4]. Fifth, critically ill patients often develop concomitant gastroparesis (see following discussion) from a host of factors, which, in turn, favors retrograde flow of gastric contents toward the distal esophagus. Taken together, these multiple mechanisms concur to clinically significant acid reflux and to its related complications.

Several steps can be taken in the critical care setting to minimize complications of acid reflux in the critically ill patient. First, patients should be kept in the semirecumbent or upright position as often as possible. This maneuver can minimize acid stasis in the distal esophagus and improve emptying of stomach contents, thereby reducing complications of acid reflux [4,5]. The effectiveness of this maneuver in patients who are mechanically ventilated remains controversial [5,6]. Nevertheless, as positional changes are generally a low risk and easy to enact measure, it seems prudent to position patients in a semirecumbent or upright position when feasible and be wary when patients remain in the supine position for prolonged periods.

Another step is to minimize the use of nasogastric tubes. Data indicate that indwelling nasogastric tubes promote GERD and subsequent microaspiration of bacterially contaminated contents into the lower airways [7,8,9]. Thus, gastroesophageal reflux also can lead to nosocomial pneumonia [10,11]. Results from a small (n = 17) randomized trial suggests that the nasogastric tube size (i.e., 2.85 mm vs. 6.0 mm) does not appear to reduce GERD [9], although clearly this study was not powered to demonstrate statistically significant differences in clinically relevant outcomes (such as bleeding or pneumonia). Placement of a gastrostomy tube in mechanically ventilated patients may reduce GERD and potentially its complications, although such intervention is not without its own risks and side effects [12].

A final step is to minimize the use of medications known to relax the LES. Many of these agents (Table 93.1) are commonly used in the intensive care setting. It should be noted that while these agents are known to decrease LES resting pressure, the clinical significance on the development of complication of GERD including erosive esophagitis or upper gastrointestinal hemorrhage is unknown. Thus, the agents listed in Table 93.1 should not be avoided on the basis of theoretical concerns alone, assuming their use is otherwise medically justified.

Pharmacological therapy is often necessary especially in the intensive care unit (ICU) to reduce the potential complications of GERD. Treatment relies primarily on acid suppression. Traditionally, intravenous (IV) histamine-2 receptor antagonists (H2RAs) have served as the mainstay antisecretory therapy in the critical care setting. H2RAs are particularly useful for prophylaxis against stress-related mucosal disease [13] and are therefore primarily used for stress ulcer prophylaxis (as opposed to GERD prophylaxis) (see Chapter 92). However, IV
proton pump inhibitors (PPIs) (pantoprazole, esomeprazole) have since replaced H2RAs as the antisecretory of choice in the hospital setting. IV PPIs have excellent effectiveness in reducing recurrent hemorrhage following endoscopic hemostasis for bleeding peptic ulcer [14]. Although there are limited data regarding their use for erosive esophagitis, experimental data have shown that IV PPIs produce potent and longer-lasting acid inhibition [15], making them the preferred antisecretory medication in patients at risk for GERD-related complications [16].

Gastroparesis, or delayed gastric emptying in the absence of mechanical obstruction, may lead to several complications in critically ill patients, including malnutrition, erosive esophagitis (as previously noted), and aspiration of gastric contents with resulting nosocomial pneumonia.

As with GERD, gastroparesis arises from a confluence of several common factors (Table 93.2) in the critically ill patient, including medications (especially narcotics and anticholinergic agents), autonomic dysfunction, postsurgical states, and endocrine abnormalities, among others.

Patients with gastroparesis typically present with nausea, vomiting, abdominal pain, early satiety, and postprandial bloating. In patients receiving tube feeding, high gastric residuals are a common early sign of delayed gastric emptying. Because the symptoms of gastroparesis are often nonspecific, the clinician should maintain a low threshold for considering the diagnosis. A combination of physical examination findings and imaging studies confirm gastroparesis and exclude competing diagnoses, including mechanical obstruction and mucosal diseases. On examination, patients with gastroparesis may demonstrate epigastric distention with tenderness but typically lack abdominal rigidity or guarding, signs of a potentially more ominous and acute diagnosis. The examiner should evaluate for a succussion splash by placing the stethoscope over the left upper quadrant while gently shaking the abdomen laterally by holding either side of the pelvis. A positive test occurs when a splash is heard over the stomach and favors the diagnosis of mechanical gastric outlet obstruction over gastroparesis. Of note, the maneuver is only valid if the patient has not ingested solids or liquids within the previous 3 hours.

Laboratory testing may help determine the underlying cause of the decreased motility. Serum electrolyte levels, serum glucose level, serum cortisol level, thyroid-stimulating hormone level, amylase, and white blood cell count (screen for infection) should be measured. A host of other tests can be used in the outpatient setting to investigate chronic gastroparesis (e.g., erythrocyte sedimentation rate [scleroderma, myopathies, lupus], urinary protein [amyloidosis], chest radiography [lung cancer with gastroparesis as a paraneoplastic syndrome], and antineuronal or anti-Hu antibodies [paraneoplastic gastroparesis]), but these are rarely useful in the critically ill patient.

Plain films of the abdomen should be obtained to evaluate for evidence of gastric distention and to screen for overt evidence of gastric obstruction. Upper endoscopy should be considered if there is suggestion of gastric outlet obstruction,
because significant amounts of retained food, feedings, and secretions can be found in the stomach even in the absence of an obstruction to the pyloric outlet. Additional imaging tests for the investigation of gastroparesis in the ICU setting are infrequently indicated. If the problem is suspected by the presentation, becomes a primary issue, and is not easily linked to other disorders in the ICU patient, then confirming the diagnosis by other methods may be merited once the patient leaves the ICU. The most accepted diagnostic test, usually performed in the outpatient setting, is a scintigraphic emptying study. Most centers use a 4-hour gastric emptying test, with a ⁹⁹Tc-labeled-egg meal. In health, gastric retention of more than 10% at 4 hours suggests delayed gastric emptying [17]. Alternative diagnostic tests include stable isotope-labeled breath tests, magnetic resonance imaging, catheter-based manometry, and newly developed wireless capsule-based manometry. Still, the simple finding of persistent high gastric tube residuals should be sufficient to formulate a presumptive diagnosis in the critically ill patient.

Once diagnosed, gastroparesis is treated by reversing known underlying causes of decreased motility, providing adequate nutritional support, and employing medical therapies to promote gastric motility and reduce gastric acid to prevent complications of GERD. Principles of nutritional support include using smaller volume, low-fat, and low-fiber meals or tube feeds [18]. Consultation with the nutrition or metabolic support services is often warranted to help select between available liquid caloric supplements. In general, parenteral nutrition should be avoided if possible. Rather, patients who need long-term nutrition support due to gastroparesis should be considered for a percutaneous endoscopically or radiologically placed jejunostomy tube [19], often placed in conjunction with a gastrostomy tube for venting of the stomach [20]. Surgical interventions should only be used as a last resort in patients with intractable nausea, vomiting, and malnutrition, and this has no place in the critically ill patient.

The currently available medications are unfortunately limited in both number and efficacy. With the removal of cisapride and tegaserod from the menu of available promotility agents, clinicians have limited options. Most authorities recommend metoclopramide, despite its neurologic side effects (e.g., akathisia) that impact up to 30% of users [21]. Reducing the rate of IV infusion may reduce frequency of neurological side effects. Metoclopramide has multiple actions, including coordination of antral, duodenal, and pyloric muscle function while simultaneously serving as a centrally acting antiemetic [22,23]. Metoclopramide can be administered orally, intravenously, rectally, and subcutaneously. In the critically ill patient, metoclopramide typically is dosed at 10 to 20 mg IV every 6 hours. The major disadvantage of IV bolus dosing is that plasma levels are often erratic, largely because levels peak rapidly and the half-life is short. Subcutaneous dosing (two to four times per day in 2-mL aliquots) has been promoted as an alternative route, as it is associated with more stable plasma levels [24]. Although the tardive dyskinesia side effects have been known for decades, the Food and Drug Administration (FDA) recently issued a “black box” warning in reference to metoclopramide, which indirectly has put some pressure on clinicians toward less use of this medication.

Erythromycin, an antibiotic with motilin-receptor agonist properties, also has promotility effects. Oral tablets generally have poor efficacy in gastroparesis [25], the preferred route of oral administration being liquid suspension at low doses of 125 to 250 mg twice daily. Erythromycin may be used in combination with metoclopramide for patients with an incomplete response to either agent alone. IV dosing of erythromycin (100 to 200 mg every 6 hours) improves gastric contractility by invoking high-amplitude gastric contractions [26]. It is particularly effective in diabetic patients and has also shown benefits in reducing high tube feed residuals [27]. Unfortunately, long-term use of erythromycin leads to tachyphylaxis from downregulation of motilin receptors [25] and also is associated with antimicrobial resistance.

Nonpharmacologic therapies include gastric pacing and pyloric botulin toxin injection [28]. These options are currently available at limited centers but rarely used in critically ill patients.

Any disease state affecting neurohormonal mediators, vascular perfusion, electrolyte balance, and muscular contraction has the potential to affect the coordinated propulsive small and large intestinal motility, resulting in ileus. Virtually all causes of ileus can present in the critically ill patient. The postoperative state, inflammation, metabolic derangement, neurogenic impairment, and drug-induced aperistalsis are all common occurrences in the ICU. As a result of decreased impaired propulsive activity, patients develop obstipation and, eventually,
inability to tolerate enteral intake. Patients typically present with abdominal distention, nausea, vomiting, abdominal pain, and high tube feed residuals.