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Revista Brasileira de Anestesiologia

Print version ISSN 0034-7094On-line version ISSN 1806-907X

Rev. Bras. Anestesiol. vol.57 no.4 Campinas July/Aug. 2007 



Gastric emptying and chronic renal failure*


Vaciamiento gástrico y la insuficiencia renal crónica



Eunice Sizue Hirata; TSAI; Maria Aparecida MesquitaII; Gentil Alves FilhoIII; Cecilia Hirata TerraIV

IProfessora Doutora do Departamento de Anestesiologia da FCM/UNICAMP
IIProfessora Doutora da Disciplina de Gastroenterologia do Departamento de Clínica Médica da FCM/UNICAMP
IIIProfessor Doutor da Disciplina de Nefrologia do Departamento de Clínica Médica da FCM/UNICAMP
IVAcadêmica de Medicina da FCM/USP

Correspondence to




BACKGROUND AND OBJECTIVES: The first reference to delayed gastric emptying (GE) was made by Grodstein in 1979. Other studies have since been published, not always confirming his work. The importance of GE in anesthesia can be resumed by one of its main aspects, preoperative fasting. Delayed gastric emptying can lead to stasis and increase the risk of vomiting and aspiration. The possibility that uremic patients present delayed gastric emptying is fascinating. Gastric complaints are common in this patient population, and could be explained by the difficulty to empty the stomach. Despite the evidence, there is controversy in the literature regarding this subject. There is no consensus regarding the results. Differences in the methods of the studies could explain the results obtained in clinical and experimental trials. The objective of this study was to review a few important aspects of the dyspeptic syndrome in patients with chronic renal failure (CRF), emphasizing the delayed GE.
CONTENTS: The basic aspects of the physiology of GE, methods used more often to study GE, dyspeptic syndrome and uremia, and gastric emptying in chronic renal failure will be discussed.
CONCLUSIONS: Gastric emptying is a complex physiological process that transfers food from the stomach to the duodenum, whose mechanisms are yet to be fully characterized. Scintigraphy, using meals with radiolabelled drugs, is the exam used more often to study GE. An expressive percentage of the patients with end-stage renal disease also present delayed GE. It is possible that other mechanisms, besides uremia, involved in gastric motor function also play a role in this dysfunction.

Key Words: DISEASES: chronic renal failure; PHYSIOLOGY, Gastrointestinal: gastric emptying.


INTRODUCCIÓN Y OBJETIVOS: La primera referencia de retardo en el vaciamiento gástrico (EG) fue hecha por Grodstein en 1979. Otros estudios fueron publicados posteriormente, y no siempre confirmando esa observación. La importancia del EG en anestesia puede ser resumida un uno de sus aspectos principales, el ayuno preoperatorio. El retardo en el vaciamiento puede causar estasis y aumentar el riesgo de vómito y aspiración pulmonar. La posibilidad de existir retardo del vaciamiento en urémicos nos atrae. Quejas dispépticas son comunes en estos pacientes y podrían ser explicadas por la dificultad de vaciamiento gástrico. A pesar de las evidencias, la literatura es muy controvertida en este aspecto. No existe un consenso en cuanto a los resultados obtenidos. Diferencias en el método de estudio utilizado podrían explicar esos resultados, observados en estudios clínicos y experimentales. El objetivo de este estudio fue ver nuevamente algunos aspectos importantes del síndrome dispéptico en pacientes con insuficiencia renal crónica (IRC) terminal, con énfasis en el retardo del EG.
CONTENIDO: Se abordarán los aspectos básicos relacionados a la fisiología del EG, los métodos más empleados para el estudio del EG, el síndrome dispéptico y la uremia y el vaciamiento gástrico en la insuficiencia renal crónica.
CONCLUSIONES: El EG es un proceso fisiológico complejo de transferencia del alimento del estómago para el duodeno, cuyos mecanismos todavía no se conocen bien. La cintilografía, utilizando comidas con radio fármacos, es el examen más utilizado para el estudio del EG. Un porcentaje expresivo de pacientes con IRC terminal presenta retardo en el EG. Posiblemente otros mecanismos, además de la uremia, involucrando la función motora gástrica, están involucrados en esta disfunción.




It is not necessary to emphasize the importance of gastric emptying (GE) in anesthesia. Its relevance can be evaluated by one of its main aspects, preoperative fasting. There is a consensus regarding the minimum length of time of fasting required before the surgery. However, the recommendations are valid for people who supposedly present normal GE 1, and several physiological and pathophysiological factors alter gastric motility and gastrointestinal transit 2.

The so-called physiological factors are not associated with diseases, and usually cause discomfort and indisposition that revert spontaneously. The most important are related with the type of diet 3, exercise 4, stress 5, and smoking 6.

Abnormalities in GE may be present in specific disorders of the gastrointestinal tract or might be complications of systemic diseases, such as diabetes mellitus. However, other diseases, such as systemic lupus erythematosus, progressive systemic sclerosis, and uremia are frequently reported. Diabetic gastroparesis is a complication frequently associated with long-standing insulin-dependent diabetes mellitus, which present autonomic dysfunction and peripheral neuropathy 2. Changes in GE compromise fluids and solids, and are poorly related with signs and symptoms of gastric dyspepsia. On the other hand, it frequently affects asymptomatic patients. Technical improvements in image acquisition by scintigraphy enabled us to demonstrate that these patients also have abnormalities in the intragastric distribution of foods and reduced motility in the antrum 7. In systemic sclerosis, gastric dismotility is not as frequent as that of the esophagus and small bowel. Besides muscular atrophy and collagen deposition in the gastrointestinal tract, the motor disturbance seems to be related with a neurogenic component. The absence of dyspeptic signs and symptoms do not exclude the dysfunction, since gastric retention has already been observed in asymptomatic patients 4.

During the perioperative period, GE is important for three main reasons. First, because the drugs administered by mouth cannot have the same effect when GE is altered, since the speed of absorption of a substance from the intestine is directly influenced by the rate of GE. Second, due to what happens to the therapeutic efficacy of an unstable drug in the acid gastric environment, it can even be decreased if the drug remains longer than expected in the stomach 8. Third, delayed gastric emptying may result in stasis, increasing the risk of postoperative nausea and vomiting. Although this is considered a minor complication, it is very common, unpleasant, and is an important cause of the increased length of hospitalization in surgical patients 9.

One of the most feared complications in anesthesia is the Mendelson syndrome, a chemical pneumonia secondary to silent pulmonary aspiration of gastric contents 10. It is known that emergency surgeries performed in the upper abdomen and in patients with a past medical history suggestive of delayed GE, such as peptic ulcer, pregnancy, obesity, diabetes mellitus, stress and pain, are among the many factors associated with this syndrome 1.

The diagnosis of delayed gastric emptying in patients with chronic renal failure (CRF) is particularly important to anesthesia, because these patients frequently need anesthetic-surgical procedures. In this aspect, kidney transplant is the surgery that has demanded greater reflection by the anesthesiologist due to the increased acceptance of this procedure as the treatment of choice for patients with end-stage renal disease.



Gastric emptying is a complex and improved physiological control process, adapted to the digestive and absorptive needs of the individual, aimed at transferring food contents from the stomach to the duodenum 11. It depends mainly on the coordinated motor function of stomach, pylorus, and duodenum 12. The mechanisms involved have not been fully characterized, mainly due to the lack of techniques that allow the simultaneous evaluation of every event in this process.

The stomach is far from being just a food reservoir. After a meal, it expands according to the amount of food ingested, mixes, grinds, and separates it into smaller particles that will be emptied into the duodenum at a rate compatible with the digestive capacity of the pancreas, absorptive capacity of the bowel, and the physical and emotional condition of the patient 13. Functionally, it is divided in a proximal segment, which includes the fundus and the proximal third of the body of the stomach, and a distal segment, which includes the remaining of the body of the stomach and the antrum 2. This division is better adapted to the electromechanical and muscular activity of the organ, but can also be extended, to a lesser degree, to the secretory activity 14.

The main function of the proximal segment is to store a variable amount of food. It is possible due to the phenomena of receptive and adaptive relaxation, which allow the stomach to receive large amounts of food without significantly increasing the intragastric pressure 2. It also participates in the process of gastric emptying by responding to the control of the pressure gradient between the stomach and duodenum 15.

The distal segment shows a cyclic activity, being responsible for grinding and emptying the food into the duodenum. Peristaltic movements that begin in the smooth muscle cells of the upper portion of the body of the stomach, in the greater curvature, drive the food forward, break it down, and drive the food backwards repeatedly, reducing the size of the food particles until they are small enough to go through the pylorus 2,12.

Nowadays, it has been established that, after a meal, the nutrients are distributed between the proximal and distal regions of the stomach. At first, in larger amounts in the proximal region and, as the stomach is progressively emptied, in the distal region 16.

The characteristics of GE for liquids and solids are different. Solid foods are emptied in a linear fashion. After an initial quiescent phase, in which there is no emptying, the food is broken down, its viscosity changes, and it is redistributed from the proximal to the distal region of the organ. Liquids leave the stomach in bursts, due to the coordinated movement of the pyloric antrum-duodenal contractions. During these contractions, the liquid is swept through the pylorus into the duodenum 13. The emptying of liquids occurs in an exponential manner 4 and is dependent on the pressure gradient between the stomach and duodenum. Since the magnitude of this gradient varies according to the intragastric pressure, which is determined by the tonus of the proximal stomach, it is considered that this region is responsible for emptying fluids from the stomach 12.

Control of GE depends on a complex integration between the central nervous system, intrinsic and extrinsic innervation, and peptides that function as hormones or neurotransmitters. The intrinsic innervation is composed of the myoenteric plexus and has a diversified content of neurotransmitters and hormones. The extrinsic innervation is represented by the vagus nerve and celiac plexus, and its greater role on controlling gastric mobility is patent 14,17.

The afferent pathway of the extrinsic innervation is formed by vagal and splanchnic fibers that received stimuli from chemical and mechanical receptors in the gastric mucous membrane. The efferent pathway is formed by cholinergic, adrenergic, and non-adrenergic non-cholinergic fibers. Every excitatory motor activity of the stomach is a response to the stimulation of cholinergic fibers. On the other hand, the inhibitory activity is a response to the stimulation of adrenergic and non-adrenergic non-cholinergic fibers 18. There is evidence that nitric oxide mediates the inhibitory activity of non-adrenergic non-cholinergic fibers 19.

The GE process begins when food enters the stomach. The distension of the organ activates mechanoreceptors in the mucous membrane and musculature of the stomach 2,12 that, through a vagal non-adrenergic non-cholinergic mechanism, causes the relaxation of the proximal portion of the stomach 20. Contractions of the distal stomach are controlled by electric signals that originate in the pace maker in the greater curvature 21. The continuation of the process depends on the muscular activity, which receives neuronal and hormonal influences of chemical receptors in the small bowel that are sensitive to the constituents of a meal, controlling the rate of emptying according to the substance released 14.

Several intestinal peptides work on the gastric motor activity in the digestive and interdigestive periods. The role of cholecystokinin, motilin, vasoactive intestinal peptide, and substance P, among others, have not been fully determined in the physiologic process of GE 17.

The rate of GE is also influenced by the chemical and physical characteristics of a meal, such as pH 22, volume 23, temperature 23,24, and osmolarity 25.

Gastric emptying has been the focus of several clinical and experimental trials. It is necessary to emphasize that several of those mechanisms are studied separately and not as an integrated process. The absence of a method that can evaluate every aspect of GE together has been a limiting factor to an adequate understanding of this process. In a way, the variety of techniques available reflects this difficulty 26.



The methods used to study GE in human beings have several positive and negative aspects. Intubation, aspiration, and fractionated measurement of gastric contents were often used, and their major contribution is that we started to better understand the physiology of GE in humans. Nowadays, they are still important in experimental research, because much of what is known about GE rates produced by meals with different physical characteristics and nutritional components was obtained from studies that use this method of investigation 26.

The advantage of the paracetamol ingestion and absorption test is that it can be performed with the patient in bed and does not need special equipment. It was widely used to study GE in the perioperative period in pregnant women, but the advent of more accurate techniques supplanted its usefulness. However, an adequate substitute to be used in this critical period is still to be found, and possible changes produced by anesthetics and anesthesia on GE are yet unknown 26.

Currently, the study of GE uses the resources offered by diagnostic imaging techniques more often. Ultrasound allows not only the study of the rate of emptying, but also the visualization of the contents and contractions of the antrum-pyloric-duodenal region. It is useful to study the antrum and it seems to be a good tool to study emptying of liquids 26. However, it demands expensive equipment and a skillful professional. The MRI probably represents the future of the study of GE, because evidence suggest the it is the exam that will allow the simultaneous analysis of motility and gastric secretion, offering the possibility to study gastric function in an integrated fashion and closer to the normal physiology 27.

The study of gastric emptying using scintigraphy by the incorporation of a radioisotope to a component of the meal is currently the simplest method available in clinical and experimental studies to measure the rate of GE 26. The ingestion of a meal containing the radioactive material, followed by image acquisition of the stomach in different moments, allows the measurement of GE and to follow the amount of a meal present in the stomach over time.

The use of adequate testing meals, the improvement of image acquisition techniques, the introduction of scintigraphy chambers with double heads, and the possibility to use non-absorbable radiolabelled drugs are responsible for the dissemination of this method. Scintigraphy measures the rate of emptying of liquid and solid meals, the intragastric distribution of the meal, and it is also possible to determine the amount of food in the stomach after a certain period of time 26.

The most commonly used parameter to study gastric emptying for solids is the T½ , which represents the length of time necessary for 50% of the meal to leave the stomach 3,16.

The study of GE with scintigraphy is subjected to mistakes that can be minimized by technical refinement and obtaining anterior and posterior images simultaneously. Most recently, gastric dynamic scintigraphy, in which images are acquired every second, made it possible to study the contractility of the antrum, which, in the past, was only possible using gastric manometry 15.



Dyspeptic symptoms are frequent in patients under conservative clinical treatment, undergoing dialysis, and even after renal transplant. The most common complaints include anorexia, nausea, and vomiting, followed by epigastric pain and burning. These problems, associated with nutritional and endocrine disorders, renal osteodystrophy, and anemia, are responsible for the decreased growth and development observed in children with renal disease 28.

Digestive diseases are also frequent in patients with CRF 29,30. Anatomical changes in the gastrointestinal tract in patients with CRF were first described by Jaffé and Laing 31, in 1934, in 136 patients who died in consequence of uremia. The authors described pseudomembranous lesions and diffuse hemorrhage in the gastrointestinal mucosa. With the advent of dialysis, which increased the survival of those patients, and the improvement of diagnostic methods, the pattern, nature, and distribution of gastric changes associated with CRF were modified. Gastritis and duodenitis, diagnosed by upper GI endoscopy, are more common in patients in dialysis 30. The incidence of gastroduodenitis is close to 50% in patients, in dialysis or not, when the histopathologic diagnosis is made 29.

The prevalence of peptic ulcer in patients in dialysis was thought to be higher. These rates decreased with the introduction of endoscopy. The incidence of gastric bleeding has not been determined; however, the mortality associated with this complication is elevated 32.



The possible association of delayed GE and chronic renal failure is fascinating. Several causes could explain the presence of this dysfunction in the uremic patient, since anemia, metabolic acidosis 28, and uremic neuropathy 33, so common in these patients, in theory could affect the rhythm of GE. Signs and symptoms, such as nausea, vomiting, gastric plenitude, early satiety, and epigastric pain, so frequent in uremic patients, could be explained by the presence of uremia 29,34,35.

The first reference to delayed GE in uremic patients was made by Grodstein 36, in 1979, who registered a GE of 700 minutes. Only in 1984 new studies contradicted his data. At first, by Wright et al.34, and later by Soffer et al.35, who studied patients with CRF treated by hemodialysis, with and without symptoms of nausea and vomiting. The results of both studies were very similar. There were no differences in T1/2 between patients with kidney disease and the control group. There were also no differences between patients with nausea and vomiting and asymptomatic patients. New doubts were raised by McNamee et al.37 who studied patients in hemodialysis and patients undergoing conservative clinical treatment, and noticed that there were differences regarding T1/2 and the GE curve only between patients in clinical conservative treatment and healthy individuals. In patients in hemodialysis, GE was similar to the control group. Freeman et al. 38, studying 10 patients in clinical treatment and 6 healthy individuals, did not observe any differences in GE for solids and liquids between both groups, which goes against the observations of McNamee et al.

However, more recent studies demonstrated that some patients with CRF had slower GE. Ravellil et al. 39, using CT scans to study GE in 12 children with end-stage renal disease, demonstrated that 5 had delayed GE for standardized liquid meals. Domitrascu et al. 33 studied 15 patients with CRF on different types of dialysis and conservative treatment. They used ultrasound and a semi-solid standard meal. They observed delayed GE only in patients with concomitant autonomic sympathetic and parasympathetic dysfunction. Finally, Kao et al. 40 verified a high incidence of patients with delayed GE and low incidence of dyspeptic signs and symptoms in 40 Chinese patients with CRF. They did not observe any correlation between delayed GE and signs and symptoms of dyspepsia. The study was done with a meal labeled with a radionucleotide.

The study of GE in animals should be mentioned, because it is possible to reproduce CRF in rats by a nephrectomy. Rigatto 41 did not observe any differences in GE after liquid and solid meals between rats with moderate CRF and the control group.

Despite these considerations, studies of GE in CRF are rare and the results controversial. These studies involve a small number of patients and between groups with few control variables, such as duration of renal failure; type of treatment: hemodialysis, peritoneal dialysis, or conservative clinical treatment; type of evaluation used to study GE; and type of test meal. Those trials do not consistently exclude patients who develop chronic renal failure secondary to diseases that are also associated with reduced GE, such as diabetes mellitus and systemic lupus erythematosus, making it very difficult to analyze and compare the results reported in the literature. Most of the studies in patients with CRF use T1/2 as a measure of GE. There are no references to the use of other parameters in the study of gastric motility, such as the intragastric distribution of foods, an important parameter that, in certain clinical situations, such as functional dyspepsia, T1/2 could be normal and the intragastric distribution of foods is altered 16.

Over the last 25 years, gastric scintigraphy has been the method used most often to evaluate GE in patients with dysfunction of gastric motility and to study the pharmacodynamics of pro-gastro kinetic drugs. It has restrictions when looking for more detailed information on gastric physiology and pathophysiology 15. However, it is a safe exam when the proper isotope is used, such as 99m-technesium 2. It does not have restrictions, except for pregnant women, being considered the most reliable and sensitive method to study GE 42,43.

The majority of the studies that measure GE in patients with CRF uses T1/2 as the main parameter because very few, at the time they were conducted, had access to the most recent acquisitions in the imaging field that are used in the study of gastric functions. Under certain circumstances, such as in functional dyspepsia and diabetic gastroparesis, these developments allowed researchers to study the changes in the intragastric distribution of foods that reflect disorders of accommodation of food in the proximal stomach or in contractility in the distal portion of the stomach in patients with normal T1/2.

More recently, Hirata et al. 44 measured the T½ and introduced the study of the intragastric distribution of a standard solid meal in the proximal and distal portions of the stomach and in the entire organ in patients with end-stage renal disease treated conservatively and in patients with CRF in hemodialysis. They used scintigraphy in their study. The GE curves in both groups were similar to normal individuals, and they did not find any evidence to suggest the presence of partial or total GE dysfunction. Compensatory mechanisms developed during the evolution of the renal disease might explain the results, since delayed GE has been observed in rats with acute renal failure induced by bilateral nephrectomy 45. The possibility of producing CRF in animals has been very helpful in the study of GE because in experimental trials, the variables that are so difficult to be limited in clinical trials are easier to control 41.

It is important to mention that it is not difficult to find in the literature higher T1/2 in patients with CRF 35,38,40. Hirata et al. 44 identified 9 of 30 patients with higher T1/2. Alimchandani and Pai-dhungat 46 observed the same in 22 out of 32 patients and Strid H et al. 47 in 14 out of 39 patients. The same tendency was observed in other studies: elevated T1/2 in isolated groups of patients with CRF. These patients tend to increase the mean T1/2 of the group, but not enough to be statistically significant. A more detailed nutritional, neuroendocrine, and histopathologic study of these patients could be enlightening and help to identify in uremic patients, and not in the uremia itself, some risk factor that predisposes to delayed GE.



Gastric emptying is a complex physiological process that transfers the food from the stomach to the duodenum, whose mechanisms are not completely characterized. Scintigraphy, using radiolabeled meals, is the exam used more often to study GE. An expressive percentage of patients with end-stage renal disease have delayed GE. It is possible that other factors, besides uremia, involving motor gastric function play a role in this dysfunction.



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Correspondence to:
Dra. Eunice Sizue Hirata
Rua Dona Presciliana Soares, 195/71, 7° andar – Cambuí
13025080 Campinas, SP

Submitted em 19 de maio de 2006
Accepted para publicação em 27 de abril de 2007



* Received from Departamento de Anestesiologia da Faculdade de Ciências Médicas da UNICAMP (FCM/UNICAMP), Campinas, SP

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