Gastric Emptying in Adults: An Overview Related to Anaesthesia
O. U. Petring MD.
Key Words: GASTROINTESTINAL TRACT stomach emptying
Gastric emptying should be considered by anaesthetists not only because of the risk of pulmonary aspiration, but also to determine the systemic availability of substances given orally. Delayed gastric emptying prevents a return to oral feeding, increases nausea and vomiting and may result in morbidity and mortality.1 The importance of these considerations has increased with recent emphasis on day surgery and shorter admissions. Several papers and editorials have recently re-examined the guidelines for preanaesthetic food and fluid restrictions.2,3
This review describes the physiology of gastric emptying, the methods currently in use for its measurement and the limitations of each method. This information may explain many of the apparent contradictions in published data on gastric emptying in the perianaesthetic period. Factors such as disease states and pharmacological effects which may influence gastric emptying are summarised. Unfortunately, few measurements of gastric emptying have actually been made in patients during the perianaesthetic period, so that data must be extrapolated from studies of healthy volunteers, non-surgical patients or from animal studies. In addition these results may not apply to all types of gastric contents as liquids, digestible solids and indigestible solids empty with different rates and patterns, due to the functional anatomy of the stomach.4
Both neural and humoral influences on gastric emptying must be considered. The extrinsic innervation of the stomach is via the vagus and sympathetic nerves, and both contain afferent and efferent fibres.5 The stomach wall also has an extensive intrinsic nervous system, the most important component being the myenteric plexus.6 The distal stomach reduces digestible solids and semisolids and their subsequent emptying is controlled by the gastric pacemaker (a group of smooth muscle cells in the mid corpus on the greater curvature). Contractions occur at a basal rate of three to four cycles per minute or as peristaltic waves initiated by the entry of solids into the stomach.7 Emptying occurs at a constant rate because the antrum maintains a relatively constant volume.8 Stomach contents induce the release of peptides and neurotransmitters from the gastrointestinal mucosa but, although many hormones alter gastric emptying, their physiological role in disorders of gastric emptying is not clear.9,10
Methods Used To Study Gastric Emptying
Gastric emptying in man has been studied for approximately 160 years and many techniques have been employed:
The methods now most frequently used are the scintigraphic measurement of emptying of radionuclide labelled meals and absorption of orally administered paracetamol.
In scintigraphic studies, radionuclide markers are incorporated into liquid, solid or semisolid (mixed solid and liquid) meals. The gastric emptying of the nuclide is assumed to represent the behaviour of the test meal. Since the liquid and solid phases of a meal empty at different rates, identification of each phase is important.
The use of two radionuclides to measure liquid and solid emptying simultaneously has been described, but the labelling of a solid phase is a cumbersome procedure.11 Liquids are therefore frequently used as test meals, although symptoms of gastric retention or dumping are usually related to the consumption of solids or semisolids.12
In most departments of nuclear medicine only a single gamma camera can be provided. This can result in inaccuracies, due to redistribution of the labelled food from the proximal part to the other parts of the stomach, away from the detector. The magnitude of the error is related to the size and composition of the test meal.13 Accurate emptying patterns can be best obtained from the anterior12 or left anterior oblique14 views using a small volume test meal.15 Data is usually presented as the percentage of the total initial counts remaining in the stomach versus time.
The absorption of many drugs is influenced by gastric emptying rate. Paracetamol absorption from the stomach is negligible, but its rate of absorption from the small intestine is rapid and independent of pH changes.16 The absorption of oral paracetamol is therefore directly related to gastric emptying.17
Gastric emptying can be estimated from serum paracetamol concentrations, the peak concentration (Cmax), the time to reach maximum concentration (Tmax), and the area under the paracetamol concentration curve (AUC). Simultaneous measurement of gastric emptying rate with radionuclide markers has confirmed that the absorption rate of oral paracetamol estimates the liquid phase of gastric emptying.16,17 However, for semisolids and solids no such correlation has been shown.15,18
Serum paracetamol can be measured by high-pressure liquid chromatography19 or by Fluorescence Polarization Immunoassay (TDx Acetaminophen, Abbott Laboratories, North Chicago, USA).18 The technique is safe and acceptable for both patients and volunteers and can be used when transportation of patients to a nuclear medical department is inconvenient, e.g., with anaesthetised or critically ill patients. When only liquid stomach contents are expected it is appropriate to measure gastric emptying by paracetamol absorption. Blood samples may be frozen for later analysis or sent directly for assay.
Simultaneous determination of gastric emptying by scintigraphic and paracetamol absorption methods may be useful. If only one isotope can be studied at a time, simultaneous gastric emptying of both liquid and solid phases can be determined by using a radionuclide labelled solid meal together with paracetamol estimation of the liquid phase of emptying.
Interpretation of measurements - physiologic considerations
The emptying of liquids is controlled by the proximal stomach. It is directly related to the gastroduodenal pressure gradient,20 unless the function of the pyloric ring has been disturbed by surgery.21 Noncaloric liquids such as sodium chloride empty from the stomach in a mono-exponential pattern, the rate decreasing as intragastric volume and pressure decrease. If the intragastric fluid is caloric, acidic or nonisotonic, initial emptying is retarded and then follows a more linear pattern.22 These patterns may be monitored by paracetamol absorption.
Scintigraphic studies show that there is a lag period between ingestion of food and the first appearance of activity in duodenum.23 This probably reflects the time necessary for food to be ground into sufficiently small particles. Increased lag period can be the main feature of a prolonged gastric emptying. Pro-motility drugs can improve gastric emptying by shortening the lag period.24
Larger, non-digestible solid particles (more than 1 mm) are not emptied from the stomach by the process described above. They are emptied during fasting by a cycle of activity which begins in the proximal stomach after the digestible contents are emptied and migrates distally through the small intestine. The duration of the cycle in man ranges from 80 to 150 minutes and is called the "migrating motor complex" (MMC), or the "inter-digestive myoelectric complex".25 During total parenteral alimentation MMCs continue for as long as 12 weeks in the empty stomach, but immediately cease after oral food intake. When the stomach has emptied most of its digestible contents, there is a gradual transition to the motility pattern of the MMC,6 but whether or not this has significance for gastric emptying in the fasting patient is unknown.
Factors Influencing Gastric Emptying
Various studies have found similar factors to have contradictory effects on gastric emptying. The differences are difficult to explain but could be attributed to the measurement technique, various inclusion criteria, size, pre-existing drug treatment; and also composition and caloric content of test meals.
The rate of gastric emptying of either liquids or solids varies widely between healthy subjects, but under controlled situations is relatively reproducible. Reproducibility of gastric emptying in pathological conditions has not been studied satisfactorily. The volume and composition of ingested food determines the rate of gastric emptying.26 Gastric emptying of liquids is rapid (half-time is about 12 minutes so that 95 % is emptied within one hour).2 An increase in caloric content generally slows gastric emptying so that the rate of delivery of calories into the duodenum is relatively constant.27 It is estimated that nearly 50% of a solid meal remains in the stomach after two hours.
The temperature of the ingested meal is not important for liquids, which conduct heat rapidly, but may delay the emptying of hot or cold semisolid or solid meals, which have a higher thermal inertia. Gastric emptying occurs more rapidly in the morning than in the evening,29 so that longer fasting may be needed to obtain an empty stomach later in the day.
Gastric emptying is slightly slower in healthy older subjects (over 70 years of age) of both sexes,30 even though the absorption of oral drugs does not seem to vary with age.30,31
The results of studies of the effect of body weight on gastric emptying of solids and liquids are inconsistent. Accelerated,32 delayed33 and unchanged gastric emptying34 have all been reported. The differences in emptying rates are difficult to explain, but it appears that moderate obesity is not a major modifying factor, although the emptying of solids may be delayed in obese subjects who are at least 63 % in excess of ideal weight.33 Whether changes in gastric emptying are a primary cause of obesity is unknown.
The influence of gender on gastric emptying is controversial. Some authors have found similar gastric emptying rates for men and women,18,30 others have found slower gastric emptying in women than in men.35,36 The difference could be attributed to the phase of the menstrual cycle at the study time, as the rate of solid gastric emptying decreases linearly during the menstrual cycle towards the luteal phase (19-28th day). The emptying of liquids does not differ between the two phases of the cycle.18,37
Factors such as age, sex and body weight may be significant for the pharmacokinetics of oral drugs; however it is less likely that they influence the volume of remaining perioperative gastric contents.
Pregnancy is believed to delay gastric emptying, and anaesthetic technique is modified accordingly. However, the majority of studies have not shown delayed gastric emptying of liquids in women presenting during the first or second trimester for terminations of pregnancy, at elective caesarean section,38 and at first and third postpartum day.39 These results indicate that guidelines for fasting of fluids in elective pregnant patients need not be different from those in nonpregnant patients.
Gastric emptying of solids has not been studied satisfactorily in pregnancy as use of the scintigraphic method is unacceptable . Recently, high-resolution ultrasonography, presumably capable of noninvasively identifying the stomach contents, found delayed gastric emptying of solids during active labor.40
Pain and emotional stress are believed to cause delay in gastric emptying, but it is difficult to quantify the effect.41,42 Other factors such as body temperature, noise, light and previous experience may modify the response. Inducing vertigo or immersion of a hand in ice cold water produces elevations of plasma betaendorphin, sympathetic stimulation, and causes a delay in gastric emptying in volunteers.42 However, the gastric intubation used in these studies could in itself delay gastric emptying because it unfortunately combines the effects of physical stimulus with emotional stress. Ischaemic pain induced by the submaximal effort tourniquet test also delays gastric emptying of semisolids as assessed by the scintigraphic method.43
In contrast, pain may have less effect on the emptying of liquids as intermittent immersion of the feet in ice water did not influence absorption of paracetamol in healthy volunteers.44 Additionally, paracetamol absorption in patients with pain awaiting emergency orthopaedic surgery was almost identical both to that observed in the same patients before discharge from hospital and to that observed in healthy volunteers.45,46
The perception of pain intensity is influenced by personality variables and other sociocultural factors.42 Accordingly, preoperative delay in gastric emptying occurred only in patients who became apprehensive, while less anxious patients did not show any change in paracetamol absorption.47 However, other studies in patients with pain are needed.
The patient's mobility and posture prior to anaesthesia may also be significant. Lying on the left side delays gastric emptying of liquids.48 Movement between sitting and standing position produces the most rapid gastric emptying of both liquids and solids.49
Abstinence from smoking has no major effect on gastric emptying of liquids in habitual smokers.50 Intubation-aspiration studies performed with a double-lumen gastric tube found no difference in the aspirated gastric volume in smokers refraining from smoking in the fasting period compared with either patients smoking cigarettes in the fasting period51 or nonsmokers.52
The influence of premedication
Premedication can be the most important factor responsible for changing the rate of gastric emptying in patients awaiting anaesthesia. Sedative drugs may delay gastric emptying as drowsiness and sleep is accompanied with decrease in gastrointestinal motility. The most striking delay in gastric emptying occurs with the administration of opioid analgesics,45,53 including short-acting drugs such as alfentanil,54 but the mechanism by which this occurs is not understood. The existence of opioid receptors in both the brain and gastrointestinal tract makes it difficult to determine whether the effect is central or peripheral. It was originally postulated that agonist/antagonist opioids (kappa(k) agonists, and mu(m) antagonists) such as buprenorphine and nalbuphine might not delay gastric emptying; however, this has been disproved by several paracetamol absorption and scintigraphic studies.55,56 The action of opioids on gastric emptying is reversed by naloxone,1 but a large dose of naloxone induces a paradoxical, inhibitory effect on basal gastric emptying.51 Consequently, when possible, preanaesthetic sedation should be with non-opioid drugs.
It appears that anxiolytic drugs do not delay gastric emptying. Gastric emptying measured by paracetamol absorption is unchanged following a single dose of diazepam.58,59 A study using oral diazepam even showed enhanced gastric emptying.60
The anticholinergic activity of certain antihistamines (e.g., diphenhydramine) delays gastric emptying. However, a single, modest but sedative intravenous dose of chlorpromazine does not alter gastric emptying of liquids.61
Gastric contents at induction of anaesthesia
Measurements of the pH and volume of gastric aspirate at anaesthesia induction have been used to determine the risk of developing pulmonary damage in the event of pulmonary aspiration. The traditional criteria used, a pH less than 2.5 and a volume greater than 0.4 ml.kg-1, were derived from animal experiments, and comparable studies in humans could not be performed. Extrapolation of data from more recent animal studies suggest that approximately 0.8 ml.kg-1 instilled directly into the trachea is necessary to reproduce the aspiration pneumonitis.2 The residual gastric volume needed to produce this volume of tracheal aspiration is unknown."Nil orally after midnight" does not ensure an empty stomach in preoperative patients62 nor does it take into account the difference between gastric emptying of solids and liquids.
Using the gastric intubation method (which underestimates the remaining gastric contents) more than fifty per cent of elective patients assumed to have normal gastric emptying have acid stomach contents exceeding 30 ml.45 A consistent finding has been that the recovered aspirate is independent of the duration of the fluid fast beyond two hours, provided that only clear liquids such as water,63 coffee or orange juice64 are consumed. Even a light breakfast (a slice of buttered toast and one cup of tea or coffee with milk) two to four hours before an elective operation did not increase the number of patients at risk of pulmonary aspiration at the time of tracheal intubation.65 There is some evidence that additional clear fluids two to three hours preoperatively may actually reduce residual gastric volume by a stimulation of gastric peristalsis.66
In the absence of other factors known to delay gastric emptying, the available evidence suggests that elective preoperative patients should have access to clear fluids until two to three hours before surgery. Conversely, the variation in time required for gastric emptying of solids (up to 12 hours) mandates that patients should have no solid food on the day of surgery.2, 3,67,68
Gastric emptying following induction of anaesthesia and surgery
Gastric emptying may be abolished or delayed for up to 24 hours after abdominal surgery, although this is less than the duration of ileus (about 48-72 hours). Both anaesthetic and surgical factors contribute to this delay. Surgical factors include handling of the gut and exposure to air,69 peritoneal irritation,70 general body disturbance such as cold, hypoxia or electrolyte disorders,71 and surgical trauma.72 Inhibitory sympathic and vagal efferents are activated via a spinal reflex from afferents originating in the area of trauma.73 However, blockade of these afferents by spinal anaesthesia does not abolish the inhibition of gastric emptying.72 As an epidural bupivacaine anaesthetic itself does not influence gastric emptying (studied in volunteers by paracetamol absorption), factors other than these spinal reflexes must predominate.74 Both epidural morphine and epidural bupivacaine combined with fentanyl do delay paracetamol absorption.74-76 This effect of epidural opioids is independent of systemic action, indicating that direct activation of CNS opioid receptors can influence gastric motility.
Although anaesthetic drugs may delay gastric emptying,77 the gastric emptying of liquids is normal after a short period of general anaesthesia (mean 6 min) with etomidate, halothane and N2O 67% in oxygen for non-abdominal surgery.78 Extending the anaesthesia time to a mean of 75 min (thiopentone, halothane, pancurium and N2O 67%) delayed the immediate postoperative gastric emptying. Following cholecystectomy there was no correlation between the postoperative gastric emptying and age, plasma potassium, choice of anaesthetic agent or duration of surgery.79 The effects of perioperative opioid administration outweigh changes due to other anaesthetic drugs;54,79 even taking into account a wide intersubject variation in the rate of postoperative gastric emptying. In gynaecological patients, gastric emptying was only delayed by alfentanil or fentanyl given immediately prior to induction of anaesthesia. Ketamine (0.5 mg.kg-1 IM)80 and droperidol (30-55 mg.kg-1 IV)81 have been tested in volunteers and do not delay gastric emptying of liquids.
Patients undergoing minor elective surgery can safely continue to receive their medications orally without risk of drug accumulation, unless opioids are given in the postanaesthetic period. Anticholinergic agents, such as atropine and glycopyrrolate,1,82 also temporarily delay gastric emptying.
Reducing Residual Gastric Volume
Complete removal of gastric contents is difficult if not impossible using gastric aspiration.83,84 The Salem double-lumen tube is more effective for removal of liquids than the conventional gastric tube.83,85 Leaving a nasogastric tube in situ itself delays gastric emptying because it mechanically disturbs the gastrointestinal mucosa.86 Other adverse effects of this intubation procedure are mechanical injury to oesophagus, stomach or larynx, interference with ventilation, gastric haemorrhage and even cardiac arrest.87 As there is no scientific evidence confirming the benefit of preoperative gastric intubation and aspiration, this procedure cannot be recommended.
Bethanechol, an acetylcholine analogue, and neostigmine have been used to accelerate gastric emptying and to relieve postoperative ileus.88 However, the need for parenteral administration, parasympathetic and other side effects make these drugs unsuitable for routine use.
Agonists of dopamine D2-receptors of the chemoreceptor trigger zone such as apomorphine and bromocriptine are potent emetic drugs and also delay gastric emptying. Metoclopramide and domperidone are antagonists at both central89 and peripheral90 dopamine receptors and are used to enhance gastric emptying. Metoclopramide has three actions which make it useful in anaesthesia. It increases the lower oesophageal sphincter pressure, accelerates gastric emptying preoperatively and has antiemetic properties.91,92 It has no direct effect on gastric fluid pH. Domperidone has proprieties similar to those of metoclopramide, but lacks cholinergic activity and does not cross the blood brain barrier in significant amounts.93 Administration of domperidone decreases adaptive relaxation, and increases gastric emptying in both normal subjects and in subjects with esophageal reflux.94,95 Unfortunately, human and experimental studies show that the effect of metoclopramide is blocked by atropine, prostaglandins, opioids and peptide hormones.
Dopamine receptor antagonistic activity is not a prerequisite for the gastrointestinal action of promotility drugs.96 An example is cisapride.97 It acts by directly facilitating acetylcholine release from the myenteric plexus, without muscarinic or nicotinic receptor stimulation.98 It appears that cisapride may have a more potent effect on gastric emptying than metoclopramide.
Composition of gastric contents, pH, temperature and osmotic pressure all determine the rate of normal physiological gastric emptying. Liquids are rapidly emptied from the stomach, while emptying of solids requires an unpredictable period of time. Generally, with increasing volume or caloric content, the emptying time is delayed. In patients without known predisposing factors, gastric emptying is close to normal and routine attempts to reduce gastric contents are not required. The experimental data summarised here suggests that the guidelines for preoperative fasting in elective patients with no identified cause of delayed gastric emptying should be as follows: 1. no solid food on the day of surgery, 2. unrestricted clear fluids until two to three hours before scheduled surgery.
A wide variety of medical conditions and pharmacologic treatment may delay gastric emptying in the perianaesthetic period. Since opioids including the agonist-antagonist opioid buprenorphine are the most significant factor, the maintenance of normal gastric emptying requires the use of other analgesics. The oral route of drug administration is inappropriate for patients receiving opioids in the perianaesthetic period. In patients "at risk", pharmacological acceleration of gastric emptying provides additional safety. Clear antacids may be used to buffer the acid already contained in the stomach and histamine, blockers will prevent further generation of gastric acid.