In addition to being essential for adequate nutrient absorption, normal gastrointestinal motility is crucial for maintaining an appropriate balance of microorganisms and proper function within the gut.¹ It also serves as a major defense mechanism against infection of the gut, and limits the propagation of bacteria to pathologic levels.¹ Gastric atony, also referred to as gastroparesis, can be defined as the inability of the stomach to contract normally, causing a delay in the movement of food out of the stomach. Causal factors for gastric atony can be classified as either medical or idiopathic. The most common medical cause is diabetes mellitus, whereas less common medical conditions include neurologic disorders, connective tissue disorders, critical illness, and surgery.

In the nonsurgical patient with medical comorbidities, disruption of the normal motility can lead to atony, resulting in often devastating symptoms that severely impact nutrition and quality of life. Diabetic gastroparesis is thought to be the result of the dysregulation of the autonomic nervous system, a system that is intimately related to the neural functioning of the stomach. Similarly, the impact of neurologic disorders on gastric motility is often a consequence of the parallel functioning of neurotransmitters within the central nervous system and those found in enteric neurons. Disturbance of the former can lead to disruption of the latter and gastric atony. With connective tissue disorders, gastric atony is of critical importance, given the tendency of these patients to develop severe and complicated reflux resulting from lower esophageal sphincter hypotension and significantly impaired esophageal peristaltic amplitude. Critical illness greatly impairs the use of enteral nutrition and results in a sustained catabolic state that depletes the patient’s caloric reserves, leading to decreased immune function, impaired wound healing, and ultimately increased morbidity and mortality.² This disruption can further result in bacterial overgrowth, translocation, pneumonia, and sepsis. While multiple therapeutic options exist for medical gastric atony, patients may often spend a majority of their life with discomfort and in search of the appropriate management.

In the postoperative setting, gastric atony, or failure of the stomach to empty, must, by definition, not be related to any other common postsurgical complication such as wound infection, intraperitoneal abscess, electrolyte disturbances, pancreatitis, thromboembolic disorders, pneumonitis, or cardiovascular complications. While a variety of factors may cause postoperative ileus, the specific categorization of atony must include “dysfunction causing a prolonged postoperative course defined as more than 14 days elapsing between the primary surgical intervention and planned discharge of the patient from the hospital.”³

In general, there are a variety of techniques employed to treat gastric atony including medical management, endoscopic techniques, and surgical intervention. Future directions will focus on greater development of these treatment strategies either alone or in combination to improve the daily functioning of these patients. The purpose of this chapter is to review the biology, physiology, diagnosis, treatment options, and persistent clinical challenges that describe this often complex and debilitating disorder.

Research investigating the specific mechanisms through which the intestinal tract functions has revealed a well-designed balance between management of the intestinal microbiome and intestinal motility.

Historical Perspective

The role of the stomach in nutrient digestion and health maintenance has interested man since early times.^4-6 The ancient Greeks often detailed the “bitter-sour” nature of gastric contents, and in the 16th century, both Paracelsus⁷ and van Helmont⁸ believed acid to be present in the stomach and a necessity for digestion. Subsequent observations by Reaumur⁹ and Spallanzani¹⁰ further described the “solvent” effects of gastric juices. However, the role of gastric acid was not well understood until 1823 when William Prout published his work on the effects of gastric acid secretion.⁴ Three years later, observations made by William Beaumont of his patient afflicted with a gastrocutaneous fistula, Alexis St Martin, were published in 1826.¹⁰ His detailed observations over almost a decade of the gastrocutaneous fistula described gastric digestion in a human during normal life experiences including the effects of stress.

In the early 20th century, the multifaceted nature of the control of gastric acid secretion was explored by experiments using ablation of the celiac axis and vagotomy as therapeutic intervention for peptic ulcer disease. This led to a rapid increased interest in gastric acid secretion and spurred the work of Dale and Laidlaw on histamine.¹² This seminal research led to the critical discovery by Popielski of histamine’s effect on gastric secretion,¹³ Bayliss and Starling’s discovery of secretin,¹⁴ and Edkins’ discourse on gastrin.¹⁵ These discoveries ushered in a new era in our understanding of gastric disease and specifically led to remarkable advances in the pharmacologic management of peptic ulcer disease starting with the discovery of the H₂-receptor antagonists by Sir James Black in 1972.¹⁶

The emphasis on acid-related disease preoccupied research in the middle and latter half of the 20th century until the groundbreaking discovery of Helicobacter pylori in 1983 by Marshall and Warren.¹⁷ This was counterintuitive to the then current thinking that the stomach was microbiologically sterile, despite the many observations of numerous bacterial populations in gastric secretions described by Jaworski¹⁸ and the Nobel Prize–winning contribution of Metchnikoff in 1908 for his work describing Lactobacillus and gut immunity.¹⁹ As a consequence, the importance of the gastric microbiome and its relationship to H pylori revolutionized our understanding of gastric diseases, specifically cancer, especially in terms of prevention. Current neurohormonal research has led to a better understanding of the control of appetite, food absorption, metabolism and obesity. Furthermore, increasing evidence supports a vital role for gastric motility in the maintenance of the several processes mentioned earlier in completing digestion and ultimately absorbing nutrients.

Current Understanding and the Migrating Motor Complex

Despite these many advances demonstrating the complexity of the stomach, it is still often viewed as “just” the hollow muscular organ that initiates the second phase of digestion⁴ (the first being mastication and transport of the food bolus through the esophagus). However, all ingested materials, specifically nutrients and orally dosed medications, have to negotiate the stomach, and as such, the stomach is now recognized to be one of the most important components within the gastrointestinal (GI) tract. Furthermore, the stomach facilitates many unique functions that are crucial to the continued transport of ingested materials, digestion, and the uptake of nutrition, roles that may also have a secondary purpose of maintaining homeostasis.^1,19,20

It is now confirmed that gastric motility is one of the most important factors necessary for normal digestion. In the interdigestive state, upper GI motility can be described by the recurrent contractility pattern of the migrating motor complex (MMC) (Fig. 30-1).²¹ The MMC is thought to serve a “housekeeping” role by sweeping residual undigested material through the digestive tract, out of the stomach, and into the small intestine. The MMC is a distinct 4-stage pattern of electromechanical activity that takes place in GI smooth muscle between meals. Although well preserved across mammalian species, the specific role of the MMC in humans has remained unclear. However, using manometry, Björnsson and Abrahamsson^22,23 demonstrated that apart from the intestinal contractions migrating in the distal direction observed in phase II, phase III of the MMC also behaves as a retroperistaltic pump in the duodenum, creating intermittent alkalinization of the stomach. While acidity of the stomach has always been a key component of homeostasis, recent observations have also identified a role for this alkalinization in maintaining normal physiologic balance and signaling the return of hunger after meals.^24,25 Conversely, impaired GI motility impedes the absorption of drugs and nutrients introduced into the stomach, decreases the hunger stimulus, and can also be the nidus from which the symptoms of poor digestion, including nausea, vomiting, distention, and early satiety, begin.

GI motility serves as a major means to prevent infection of the intestinal tract. Normally, microorganisms are rarely encountered in the esophagus, stomach, and duodenum because of peristaltic contractions that continually move their contents toward the colon. While fairly low in the esophagus and stomach, the quantity of bacteria increases significantly as the GI contents reach the terminal ileum and eventually the bacterial-laden colon. Multiple “normal” physiologic processes within the gut limit the proliferation of these microorganisms to pathologic levels.²⁶ While gastric acid is directly toxic to bacteria, resulting in minimized overgrowth, inhibiting gastric acid secretion in the face of normal motility does not seem to affect bacterial counts. Conversely, when motility is disrupted, with or without normal acid secretion, small intestinal bacterial overgrowth occurs. Hence, it is now recognized that patients with impaired GI motility are also at risk of bacterial overgrowth in the proximal gut with pathogenic organisms and subsequent translocation of these organisms or their toxins into the bloodstream.

We can conclude that normal GI motility is vital to the initial desire to eat, natural and timely digestion, the specific uptake of nutrients to maintain health and well-being, and the regulation of bacterial flora whose structured concentration is also necessary for digestive stability. Disruption in motility at any step can have major consequences impacting overall health and nutrition in multiple ways.

Gastric atony can arise in multiple situations, including medical, postsurgical, and idiopathic settings, each related to specific derangements in normal motility (Table 30-1). The management of these patients presents several challenges and is best conducted in the context of a dedicated and skilled multidisciplinary team.

Medically Related Atony

DIABETES MELLITUS

Even though the relationship between diabetic gastroparesis and other complications of longstanding diabetes mellitus (DM) is incompletely understood, it has been established that there is an association with autonomic neuropathy.²⁷ Additionally, although acute hyperglycemia delays gastric emptying,²⁸ the relationship between long-term control of glycemia and gastric emptying is unclear, and results from investigation have been conflicting at best. For example, although increased glycosylated hemoglobin (HbA1c) levels have been associated with GI symptoms in people with type 2 DM (T2DM),²⁹ HbA1c levels were not found to be significantly different among patients with T2DM with GI symptoms and delayed gastric emptying, patients with T2DM with GI symptoms and normal gastric emptying, and patients with T2DM without GI symptoms. In addition, improved glycemic control did not improve gastric emptying in subjects with delayed gastric emptying and type 1 DM or patients with T2DM and delayed gastric emptying.³⁰ These findings are in contrast to those of the Diabetes Control and Complications Trial (DCCT),³¹ in which 6.5 years of intensive insulin therapy reduced the risk of other complications such as diabetic retinopathy, nephropathy, and peripheral and cardiac autonomic neuropathy by 40% to 60% when compared with conventional insulin therapy. Furthermore, the differences between the former intensive and conventional treatment groups persisted for as long as 14 years despite the loss of glycemic separation.^32-34 In the only community-based study, symptoms of peripheral or autonomic neuropathy were not associated with diabetic gastroparesis.³⁵ Nevertheless, despite uncertainty in the causal factors for gastric atony, diabetic patients are still the cohort most commonly afflicted with medically related gastric atony, and are often most afflicted with gastric atony–related symptoms second only to patients with postsurgical gastric atony.³⁶

NEUROLOGIC DISORDERS

As populations age, the prevalence of neurologic disease continues to increase and consultations involving GI motility problems in the patient diagnosed with a neurologic disorder become ever more common. The high prevalence of gastric atony and other disturbances of gut motor function in neurologic diseases is based on similarities in morphology and function of the neuromuscular apparatus of the gut and that of the somatic nervous system.³⁶ Furthermore, the basic organization of the enteric nervous system (ENS) (neurons, ganglia, glia, and ENS-blood barrier) and the ultrastructure of its components are similar to those of the central nervous system (CNS). Almost all neurotransmitters identified within the CNS are also found in enteric neurons. Thus, the concept of ENS involvement in neurologic disease should not come as a great surprise.

Dysfunction of the autonomic nervous system (an important modulator of enteric neuromuscular function) can be commonly seen in several neurologic syndromes. In addition to the presence of several primary and secondary disorders of autonomic function, disturbed autonomic modulation of gut motor function, in some cases, may be an important factor that contributes to symptom development. It is also evident that the gut has important sensory functions. Sensory input is fundamental to several reflex events in the gut, such as the viscerovisceral reflexes that coordinate function along the gut. Even though these functions are usually subconscious, gut sensation may be relayed to and perceived within the CNS. Because the role of sensory dysfunction in the mediation of common symptoms such as abdominal pain and nausea in the patient with CNS disease with GI manifestations has not been extensively investigated, this does offer a future area of study.³⁶

The two predominant neurologic disorders often encountered in GI practice are cerebrovascular disease and parkinsonism. In addition, patients with multiple sclerosis, autonomic and peripheral neuropathies including that associated with diabetic autonomic neuropathy, Guillain-Barré syndrome, myotonic dystrophy, and Duchenne muscular dystrophy have all been shown to demonstrate signs and symptoms suggestive of gastric atony. Regardless of the specific neurologic diagnosis, the use of a multidisciplinary team that is aware of the wishes and needs of the family and mindful of the nature and the natural history of the underlying disease process is best practice. Together, the team, including a neurologist and/or neurosurgeon, nutritionist, gastroenterologist, and specialty nurse, can assess and manage gastric atony and other GI problems in the patient with neurologic disease.³⁶

CONNECTIVE TISSUE DISORDERS

Gastric atony is also seen with scleroderma, one of the most common causes of pseudo-obstruction. Gastric involvement in scleroderma tends to parallel the same clinical course as the esophagus.³⁷ In the Olmstead County study,^38,39 10.8% of all cases of definite gastric atony were associated with the presence of a connective tissue disorder. In scleroderma, gastric involvement has been documented in anywhere from 10% to 75% of all patients, and delayed gastric emptying has been seen in 50% to 75% of those patients with scleroderma who demonstrated GI symptoms.³⁶ Gastric atony in itself has important clinical consequences in scleroderma, including exacerbation of gastroesophageal reflux and malnutrition. The former is of critical importance, given the tendency of these patients to develop severe and complicated reflux resulting from significantly impaired esophageal peristaltic amplitude and lower esophageal sphincter hypotension. Using the relatively noninvasive ¹³C-octanoic acid breath test, Marie et al⁴⁰ documented delayed gastric emptying in 47% of 57 consecutive patients with scleroderma. Furthermore, they described a close correlation between GI symptoms and a delay in gastric emptying.⁴⁰

Using the same approach, Hammar et al⁴¹ discovered atony in 29% of their 28 patients with primary Sjögren syndrome. Most recently, a reported association between Ehlers-Danlos syndrome type III (the joint hypermobility syndrome) and a variety of functional GI symptoms, including those that may be based on gastric emptying delay, have begun to emerge,^42-44 with the frank documentation of gastric atony in some of the studies.⁴²

CRITICAL ILLNESS

The prevalence of delayed gastric emptying in the intensive care unit (ICU) setting has been estimated to range from 38% to 57%, depending on the method used to define it.^45,46 Using the ¹³C-octanoate acid breath test and measuring ¹³CO₂ in end-expiratory breath samples, Ritz et al,⁴⁷ found that 40% to 45% of the patients in an intensive care setting had delayed gastric emptying. Factors that can contribute to delayed gastric emptying in critical care patients include the supine position, coughing, suctioning, obesity, and advanced age, and the extent of the delay is directly related to the severity of critical illness. Nguyen et al⁴⁸ found that, after controlling for other factors, admission diagnoses had only a modest impact on the risk for gastric atony in the ICU, with those at the highest risk being patients with head injuries, multisystem trauma, sepsis, and burns. That being said, a number of comorbid conditions may increase gastric emptying time, including raised intracranial pressure, hiatal hernia, gastric cancer, gastric resection, liver cirrhosis, and chronic pancreatitis. Interestingly, Lam et al⁴⁹ observed in a retrospective study that a history of diabetes was not an independent risk factor for gastric emptying delay in critically ill patients despite its high prevalence in modern hospital populations. Additionally, proximal gastric motor responses to feeding were similar in diabetic patients to those of healthy individuals.⁵⁰ Nevertheless, hyperglycemia does impair gastric contractility and, along with electrolyte disturbances, may lead to gastric atony.^51,52 Hence, in the critically ill setting, the continued need for optimization of both of these parameters is vital. Treatment has thus focused on the correction of electrolyte disturbances, withdrawal of medications that may impair gut motility, hypoglycemic monitoring, the addition of prokinetics, and the placement of feeding tubes (gastrostomy or jejunostomy) as needed.

Postsurgical Atony

Although many surgical procedures originally associated with gastroparesis or gastric atony are less commonly performed today, several more recently developed upper abdominal procedures may be complicated by the development of gastric atony (Table 30-1). Acute gastric atony may be the result of the “ileus syndrome,” which can complicate many surgical procedures. Most often, it is a transient event that usually resolves in a short period of time. Occasionally, this gastric dysmotility can become chronic and result in significant symptoms. In contrast to chronic medical gastric atony, whose pathophysiology is often poorly understood, in the acute form of postsurgical atony, inflammatory processes seem central to the inhibition of motility. The frequency of postsurgical gastric atony can vary widely depending on many factors including the site and nature of the surgical procedure.³⁶ Again citing the prominent Olmstead County studies of the community prevalence of gastric atony, 7.2% of all cases were related to prior gastrectomy or fundoplication.³⁹ More specifically, Dong and colleagues⁵³ noted that the rates of atony ranged from 0.4% to 5% after gastrectomy, 20% to 50% after pylorus-preserving pancreaticoduodenectomy, and 50% to 70% after cryoablation therapy for pancreatic cancer.

VAGOTOMY

Although vagotomy is now infrequently performed for the management of peptic ulcer disease, the effect of inadvertent vagal injury underscores the continued relevance of a complete understanding of the complex effects of vagotomy on gastric motor function.³⁶ Loss of vagally mediated reflexes impairs receptive relaxation of the gastric fundus, leading to acceleration of the early phase of liquid emptying. This acceleration causes rapid emptying of hyperosmolar solutions into the proximal small intestine and may result in dumping syndrome. Conversely, and as a consequence of impaired antropyloric function, vagotomy prolongs the later phases of liquid and solid emptying. Other motility effects of vagotomy include impairment of the motor response to feeding, which contributes to the pathophysiologic mechanisms of postvagotomy diarrhea, and a suppression of the antral component of the MMC, which is particularly common among individuals with symptomatic postvagotomy gastroparesis.^36,46,52,53

Currently, standard practice includes the addition of a drainage procedure, such as a pyloroplasty or gastroenterostomy, which tends to only negate the effects of vagotomy and results in little alteration in the gastric emptying of liquids or solids. Interestingly, prolonged postoperative gastroparesis (ie, lasting longer than 3-4 weeks) is, in fact, rare (<2.5% of patients after either vagotomy and pyloroplasty or vagotomy and antrectomy).⁵⁴ In contrast, significant postoperative gastric atony may occur in patients who have a prior history of prolonged gastric outlet obstruction. In these cases, normal gastric emptying may not return for several weeks. That being said, longitudinal studies suggest that vagotomy-related gastroparesis trends toward resolution over time. One study has suggested gastric emptying in those who had undergone either a truncal or a highly selective vagotomy (previously thought to have very different long-term results) being similar in clinical features by 12 months after the procedure.⁵⁵

When postsurgical gastric motor dysfunction persists, it can often present an arduous management challenge. Responses to medical therapies such as prokinetic agents have proved particularly disappointing in this group, and in these resistant cases, a completion gastrectomy may be the best alternative. It should be noted, however, that this intervention may still lead to frustration, as results in a large series deemed this approach successful in only 43% of patients.⁵⁶

ANTIREFLUX OPERATIONS

Multiple studies have documented that fundoplication affects sensorimotor function of the proximal stomach.^57-59 Furthermore, most, but not all,⁶⁰ studies have demonstrated that following fundoplication, there is impaired relaxation of the proximal stomach in response to meal ingestion. Instances of gastric atony have been described following antireflux surgery and endoscopic antireflux procedures,⁶¹ even though the usual effect of fundoplication is to accelerate, rather than delay, gastric emptying.⁵⁸ It should come as no surprise that Nissen fundoplication was the most common cause of postsurgical gastroparesis in the audit conducted by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Gastroparesis Consortium. Despite the high frequency with which this procedure is now performed,⁶² the pathophysiologic process leading to postfundoplication gastroparesis remains unclear. It has been proposed that some cases of postsurgical gastric atony have been secondary to an unrecognized preoperative disorder. In other cases, there is compelling evidence to implicate vagal nerve injury, which also has a higher occurrence in redo procedures and may contribute to persistent gas and bloating symptoms.⁶³

In rare instances, postfundoplication gastric atony may be severe and persistent. Although gastric resection does not seem to offer much help for these situations,⁶⁴ some success has been reported with an approach that combines pyloroplasty with the conversion to a partial fundoplication.⁶⁵ In an uncontrolled trial, endoscopic injection of the pylorus with botulinum toxin A produced symptomatic improvement in a small series of patients with postvagotomy gastroparesis, which in the vast majority was thought to result from fundoplication.⁶⁶

ROUX-EN-Y SYNDROME, OR ROUX SYNDROME

Patients undergoing creation of a Roux-en-Y gastroenterostomy can develop severe symptoms of postprandial abdominal pain, bloating, and nausea. This has often been associated with a specific clinical entity referred to as the Roux syndrome.⁶⁷ Studies have inconsistently described impaired gastric motor function⁶⁸ and a functional obstruction within the roux limb as a result of motor asynchrony,^67,69 with the latter demonstrated by manometry. Regardless of these associations, for the most part, the overall impact of these motility patterns in the pathophysiologic processes of this syndrome still remains unclear.⁷⁰

BARIATRIC SURGERY

Ardila-Hani and Soffer⁷¹ comprehensively reviewed the impact of bariatric (or metabolic) surgical procedures on GI motor function and found that esophageal problems were by far, the most common. Gastric emptying did not appear to be affected by laparoscopic adjustable gastric banding, whereas Roux-en-Y gastric bypass and sleeve gastrectomy tended to accelerate gastric emptying. The few instances of gastric atony reported have often been described as severe and persistent and likely secondary to an anastomotic stricture, small bowel obstruction due to anastomotic edema of either the gastrojejunostomy (most common) or jejunojejunostomy, hernia, or behavioral problems such as disordered eating. Medical therapy appears to be the first-line approach; however, this too can result in lackluster alleviation of symptoms. Interestingly, Salameh et al⁷² described successful treatment using gastric electrical stimulation in 6 patients with intractable gastroparesis following Roux-en-Y gastric bypass for morbid obesity. More investigation will be needed before consistent solutions to this rare problem can be offered.

Symptomatic “dumping” may occur in up to 50% of patients after Billroth I or II gastrectomy. By removing the antral mill, antral resection often renders the stomach incontinent to solids, leading to accelerated emptying.⁷³ Late dumping symptoms occur 90 to 120 minutes after a meal and are a consequence of reactive hypoglycemia. In addition, the accommodation reflex is impaired among symptomatic patients.⁷⁴ Delayed gastric emptying sometimes occurs after a Billroth II gastrectomy as a result of a large atonic gastric remnant.⁷³ Meng et al⁷⁵ reported a 6.9% frequency of gastric atony among 563 patients who underwent radical gastrectomy for gastric cancer in their hospital in Shanghai, China. The principal risk factors for the occurrence of atony included preoperative gastric outlet obstruction and anastomotic function following reconstruction. While others have proposed laparoscopy-assisted, pylorus-preserving gastrectomy as a less radical operative approach to early gastric cancer, gastric atony was still the most common complication of this procedure, occurring in 6.2% of cases.⁷⁶ Interestingly, Meng et al⁷⁵ also observed a similar rate of gastric atony (3.7%) among a smaller group of patients who underwent a laparoscopic gastrectomy. Reassuringly, in contrast to the previously mentioned experience with completion gastrectomy following vagotomy, completion gastrectomy has been shown to result in significant symptomatic improvement among subjects with postgastrectomy gastric atony.⁷⁷

PANCREATECTOMY

Pancreatectomy, pancreas transplantation,⁷⁸ and pylorus-preserving pancreaticoduodenectomy, in particular, have been associated with a high incidence of postoperative gastric atony. Over time, it has been concluded, that while operative technique generally seems to be of less importance, the principal predictor of gastric emptying delay after these operations is the occurrence of other postoperative complications.^79,80 Parmar et al,⁸¹ in what has been the largest series (N = 711) to date, documented an overall rate of delayed gastric emptying specifically following pancreaticoduodenectomy of 20%. Furthermore, they observed that the occurrence of gastric atony was associated with complications such as fistula formation, postoperative sepsis, and reoperation, and did not seem to be influenced by technical factors such as pylorus preservation or whether the gastrojejunostomy was antecolic or retrocolic. In contrast, results of a prior systematic review⁸² found that an antecolic reconstruction was in fact linked to lower rates of gastroparesis. Others have suggested that the use of a Billroth II rather than a Roux-en-y gastrojejunostomy for reconstruction following this procedure may reduce the risk of gastric emptying delay.⁸³ Either way, decreasing the complication rate while paying attention to surgical technique may be helpful in decreasing postsurgical atony. Interestingly, the presence of preoperative diabetes has also been identified as an additional risk factor for this postsurgical cohort.⁸⁴

OTHER PROCEDURES

It has been demonstrated that virtually any procedure that can affect upper GI motor function or compromise the vagus nerve can result in gastric atony. Clinically significant atony or gastroparesis has been reported not only in association with a wide range of gastric procedures but also in relation to esophageal procedures including botulinum toxin injection for achalasia⁸⁵ and esophageal resection,⁸⁶ lung transplantation, and even hepatic surgery. Sutcliffe et al⁸⁶ noted a 12% rate of gastric conduit emptying delay in a series of patients following esophagectomy. In another report, gastric atony was more commonly seen after minimally invasive than open esophagectomy.⁸⁷ Gastric atony in the setting of lung transplantation is especially worrisome, as its presence preoperatively has been associated with an increased risk for the development of bronchiolitis obliterans syndrome.⁸⁸ Although common even before surgery,⁶⁹ new-onset gastric atony has also been observed in up to 6% of subjects after transplantation^88,89 and may trigger or exacerbate gastroesophageal reflux from which these patients have no protection. For this reason, there is a low threshold in this patient population to proceed with fundoplication in combination with gastric electrical stimulation to address concomitant gastric atony.⁹⁰

Idiopathic Atony

Among patients who do not have underlying disorders or have not undergone any of the surgical procedures described above, the pathogenesis of idiopathic gastric atony is poorly understood, but often still has some link to illness or remote surgery. In a tertiary referral series of patients with idiopathic gastric atony, it was observed that the onset of symptoms was consistent with a viral origin in 23% of participants.⁹¹ In the NIDDK Gastroparesis Clinical Research Consortium, approximately 19% of participants with idiopathic gastric atony and 14% with either type 1 DM or T2DM and gastric atony demonstrated symptoms of an infectious prodrome before diagnosis.⁹² Although cholecystectomy, per se, has not been incriminated as a cause of gastric atony,³⁶ a prior cholecystectomy seems to negatively affect the natural history of both diabetic and idiopathic gastroparesis. The previously mentioned tertiary study found that gastroparesis symptoms began after a cholecystectomy in 8% of participants,⁹³ and 36% of patients with idiopathic or diabetic gastric atony had undergone a cholecystectomy in the NIDDK study.⁹² Whether cholecystectomy is an independent risk for atony is unclear; however, patients with cholecystectomy had more comorbidities, particularly chronic fatigue syndrome, fibromyalgia, depression, and anxiety.

Hospitalization and Economic Burden

Hospitalizations with gastroparesis as the primary diagnosis increased from 3977 in 1995 to 10,252 in 2004 (+158%), whereas hospitalizations with gastroparesis as the secondary diagnosis increased from 56,726 to 134,146 (+136%).⁹⁴ In contrast, smaller changes were seen in diabetes-related hospitalizations (+53%), all hospitalizations (+13%), and hospitalizations with gastroesophageal reflux disease (GERD), gastric ulcer, gastritis, or nonspecific nausea/vomiting as the primary diagnosis (–3% to +76%).⁹⁴ Furthermore, comparing 4 of the most common GI conditions (GERD, gastric ulcers, gastritis, and nonspecific nausea/vomiting), when gastric atony or gastroparesis was listed as the primary diagnosis, the length of stay was longer (increase of 15.4%-66.2%; all conditions vs gastroparesis, P < .001) and had the highest or second highest total charges (–7.2% to +60.6%, all P < .01) in 2004, with similar results in 1995.⁹⁴ Although more recent trends have yet to be published, similar trends for gastric atony versus other diagnoses have been previously observed.^66,95

Bielefeldt et al⁹⁶ pointed at an indirect economic impact of the chronic illness with high rates of un- or underemployment and likely, as a result, a high number of patients with low household incomes. Parkman et al⁹⁷ more recently published a study of nearly 400 patients demonstrating that while patients reported median household incomes close to the national average, less than half of the patients were employed at the time of enrollment and nearly one-third had high rates of work absenteeism due to their disease.

Signs and Symptoms

As previously mentioned, the symptoms of gastric atony can be frustrating and debilitating for the patient. While some are able to find intermittent relief, others may toil for years, resulting in a substantial decrease in quality of life.

NAUSEA AND VOMITING

Regardless of the etiology, nausea and vomiting are the most common symptoms in patients with gastric atony, with over 40% of patients reporting that these symptoms are among the most bothersome.⁹⁸ Accordingly, the pathogenesis of these symptoms is heterogeneous and often multifactorial. It is known that the receptor site for vomiting is centrally located in the area postrema at the base of the fourth ventricle in the brain (chemoreceptor trigger zone). Peripheral receptor sites include the vagus nerve and vestibular apparatus. Stimulation of the vagal afferents from either gastric distention or deregulated gastric motility triggering emesis⁹⁹ can lead to a repeated cycle of vomiting following the first episode.

EARLY SATIETY AND FULLNESS

Early satiety and fullness are common symptoms among patients with both idiopathic and diabetic gastric atony, especially in those with T2DM.⁹¹ Impaired gastric accommodation, known as the reduction in gastric tone and increase in compliance that follows ingestion, has been found in 43% of patients with idiopathic gastric atony, and it contributes to patients’ inability to completely tolerate a normal meal.¹⁰⁰ Similarly, impaired gastric accommodation was found in 40% of patients with functional dyspepsia.¹⁰¹ A smaller study of 10 diabetic gastroparesis patients, who were refractory to prokinetic therapy, found that 90% of these patients had impaired gastric accommodation.¹⁰²