POLICY AND POSITION STATEMENT

An American Gastroenterological Association Medical Position Statement on the Clinical Use of Esophageal Manometry

The following guidelines were developed to assist physicians in the appropriate use of esophageal manometry in patient care. They emanate from a comprehensive review of the medical literature pertaining to manometric technique and application.¹ Manometry is widely available, but the limited specificity of manometric data and the low prevalence rates of clinically significant motility disorders in symptomatic patients speak for the necessity of practice guidelines. This position statement is intended to help the clinician apply manometric studies most beneficially within the context of other available tests of esophageal structure and function.

Guidelines

1. Manometry may be requested by any physician in compliance with the remainder of these guidelines.

2. Manometry is indicated to establish the diagnosis of suspected cases of achalasia or diffuse esophageal spasm. Because of the low prevalence of these diagnoses in patients with esophageal symptoms, more common esophageal disorders should be excluded with barium radiographs or endoscopy before manometric evaluation.

3. Manometry is indicated for detecting esophageal motor abnormalities associated with systemic diseases (e.g., connective tissue diseases) if their detection would contribute to establishing a multisystem diagnosis or to other aspects of management.

4. Manometric techniques are indicated for placement of intraluminal devices (e.g., pH probes) when positioning is dependent on the relationship to functional landmarks, such as the lower sphincter.

5. Manometry is possibly indicated for the preoperative assessment of peristaltic function in patients being considered for antireflux surgery and is indicated in this setting if uncertainty remains regarding the correct diagnosis.

6. Manometry is not indicated for making or confirming a suspected diagnosis of gastroesophageal reflux disease.

7. Manometry should not be routinely used as the initial test for chest pain or other esophageal symptoms because of the low specificity of the findings and the low likelihood of detecting a clinically significant motility disorder.

(Approved by the American Gastroenterological Association Patient Care Committee on May 15, 1994. Approved by the American Gastroenterological Association Governing Board on July 15, 1994.)

References

1. Kahrilas PJ, Clouse RE, Hogan WJ. American Gastroenterological Association technical review on the clinical use of esophageal manometry. Gastroenterology 1994;107:1865-1884.

American Gastroenterological Association Technical Review on the Clinical Use of Esophageal Manometry

Manometric recordings from within the gastrointestinal tract were first obtained more than a century ago. However, these first balloon kymograph studies of Kronecker and Meltzer in 1894 were clearly limited to the experimental domain.¹ The era of clinical esophageal manometry dates from the first atlas of esophageal manometry published by Code et al. in 1958.² Since that time, methodological improvements have steadily occurred, and esophageal manometry has evolved to the point that it is now widely used in the clinical evaluation of esophageal contractile activity. Nonetheless, the dichotomy persists between the use of manometry as an investigational technique or as a useful clinical test, leading to pervasive uncertainty regarding the clinical indications for an esophageal manometric evaluation. Thus, the object of this review is threefold. First, our current understanding of esophageal physiology will be summarized, emphasizing aspects evaluated by manometric techniques. Secondly, the technical aspects and limitations of performing an esophageal manometric evaluation will be discussed. Finally, the use of manometric evaluation in terms of patient outcomes will be reviewed. However, note that this review pertains to adult patients, and some conclusions and recommendations might differ for pediatric patients.

What Physiological Data Can be Obtained From Esophageal Manometry?

There are three functional regions of the esophagus: the upper esophageal sphincter (UES), the esophageal body, and the lower esophageal sphincter (LES). Each region has physiological attributes that can be assessed by manometry. In the case of the sphincters, resting tone, timing of relaxation, completeness of relaxation, and response to exogenous stimuli can be measured. In the case of the esophageal body, the presence, propagation, and vigor of peristalsis or the presence of nonperistaltic contractions can be determined. The following sections detail the physiological activity of each esophageal region, emphasizing aspects detectable by manometric recordings.

The UES

The muscles of the UES are striated, consisting of the cricopharyngeus and adjacent portions of the esophagus and inferior constrictor. The cricopharyngeus muscle inserts bilaterally at the inferior-lateral margins of the cricoid lamina, and the zone of maximal intraluminal pressure is ≈1 cm in length at precisely this location.³ The closed sphincter has a slitlike configuration with the lamina of the cricoid cartilage anterior and the cricopharyngeus attached in a "C" configuration, making up the lateral and posterior walls. Because the only insertion of the cricopharyngeus is to cartilage of the larynx, the sphincter and larynx are obliged to move in unison. This axial mobility is facilitated by a posterior tissue fissure lined with adipose tissue.⁴

Resting UES pressure is markedly asymmetric with greater values anteriorly and posteriorly than laterally.^5,6 This asymmetry is understandable in view of the slitlike configuration of the sphincter; indeed, the radial asymmetry disappears after laryngectomy.⁵ Another complicating attribute of intraluminal UES pressure is that the technique of measurement in and of itself stimulates sphincter contraction. The less movement applied to the recording catheter during measurement, the lower the recorded pressures.^6,7 Furthermore, intraluminal UES pressure is comprised of both an active component related to cricopharyngeal contraction and a passive component, on the order of 10 mm Hg, attributable to elasticity.^7-9 With UES pressure measurement so dependent on methodology, it is not surprising that there is little consensus on normal values. Representative studies are summarized in Table 1,^5,6,10-13 most of which allude to the great variability observed in UES pressure values among subjects and among trials for a given subject. Thus, at present, it is impossible to define a meaningful normal range for UES pressure.

NOTE. Time is expressed in minutes as mean ± SEM.

The Tubular Esophagus

The body of the esophagus is a 20-22-cm tube composed of skeletal and smooth muscle. The proximal 5% of the esophagus is striated muscle, the middle 35%-40% is mixed (showing an increasing proportion of smooth muscle distally), and the distal 50%-60% is entirely smooth muscle.^21,22 The bundles of the outer longitudinal muscle arise from the cricoid cartilage and pass dorsolaterally to fuse posteriorly about 3 cm below the cricoid cartilage. The esophagus contains a nerve network, the myenteric plexus, situated between the longitudinal and circular muscle layers. These enteric neurons are the relay neurons between the vagus and the smooth muscle. Although the relationship between morphology and function of the nerve plexuses has yet to be determined, it is apparent that there are two main types of effector neurons within the esophageal myenteric plexus. Excitatory neurons mediate contraction of both longitudinal and circular muscle layers via cholinergic receptors.²³ Inhibitory neurons predominantly affect the circular muscle layer via a nonadrenergic, noncholinergic neurotransmitter.²⁴ Both types of neurons innervate the distal tubular esophagus and the LES. A multitude of recent investigations suggests that the long elusive nonadrenergic, noncholinergic neurotransmitter is nitric oxide.^25-27 Significantly, inhibitors of NO activity have been shown to prevent LES relaxation.^28,29 Before the explosion of research exploring the role of NO as the inhibitory neurotransmitter of the intestine, vasoactive intestinal polypeptide was a leading candidate for this role.³⁰ Vasoactive intestinal polypeptide does colocalize with NO synthase,³¹ and it is still possible that vasoactive intestinal polypeptide and NO collaborate as mediators of LES relaxation.

The extrinsic innervation of the esophagus is via the vagus nerve. Fibers innervating the striated muscle are axons of lower motor neurons with cell bodies situated in the nucleus ambiguus, whereas the innervation of the smooth muscle is provided by the dorsal motor nucleus of the vagus.^32,33 The vagus nerves also provide sensory innervation; in the cervical esophagus, this is via the superior laryngeal nerve with cell bodies in the Nodose ganglion, whereas the remainder of the esophagus sensory fibers travel via the recurrent laryngeal nerve or, in the most distal esophagus, via the esophageal branches of the vagus. These vagal afferents are strongly stimulated by esophageal distention.

Primary esophageal peristalsis is initiated by swallowing and is evident shortly after the pharyngeal contraction traverses the UES, progressing at a velocity of 2-4 cm/s. Secondary peristalsis can be elicited at any level of the esophagus in response to luminal distension by air, fluid, or a balloon. A key property of the peristaltic mechanism is deglutitive inhibition. A second swallow, initiated while an earlier peristaltic contraction is still progressing, causes complete inhibition of the contraction induced by the first swallow.^34,35 With repeated swallows at short intervals, the esophagus remains inhibited with the LES relaxed. Primary peristalsis occurs after the last swallow in the series. Deglutitive inhibition is intricately involved in sequencing the peristaltic contraction. An elegant experiment using an intraesophageal balloon to quantify the period of deglutitive inhibition at different levels of the esophagus showed that inhibition commences nearly simultaneously but persists progressively longer at more distal esophageal locations.³⁶ Excitation then follows the period of inhibition at each level, resulting in a sequenced peristaltic contraction.

The mechanical effect of peristalsis is a stripping wave that milks the esophagus clean from its proximal to distal end. Progression of the stripping wave corresponds closely with that of the manometric contraction such that the point of the inverted "V" found fluoroscopically at each esophageal locus coincides with the upstroke of the pressure wave.³⁷ However, it is important to note that any intraluminal pressure waveform is potentially either intrabolus pressure or squeeze pressure from within a closed lumen; manometry alone cannot reliably distinguish between these conditions.³⁸ The longitudinal esophageal muscle also contracts at the onset of peristalsis with the net effect of transiently shortening the esophagus by 2-2.5 cm.^39,40 The efficacy of esophageal emptying is inversely related to peristaltic amplitude such that emptying becomes progressively impaired with peristaltic amplitudes <40 mm Hg.³⁷ Failed or feeble peristalsis (<40 mm Hg in the distal esophagus) is not an unusual observation in a normal population. Richter et al. found 4.1% ± 8.3% of swallows in normal volunteers of varied age to result in nonperistaltic contractions.⁴¹ Kahrilas et al. found 10% incidence of peristaltic dysfunction in a young normal population and determined that the 95% confidence interval for peristaltic dysfunction was 50% in that population.⁴²

More than any other peristaltic variable, the amplitude of peristaltic contractions has been the subject of substantial scrutiny during the past decade. Table 3^41-44 shows representative normal data on peristaltic amplitude obtained using modern methodology. The 40-60-year-old patients in the study by Richter et al. had slightly increased peristaltic amplitudes relative to the younger patients. Typical duration of peristaltic contractions in both studies was 4 ± 1 seconds, and typical propagation velocity was 3.0 ± 1 cm/s in the distal esophagus. Occasional double-peaked contractions were noted to occur in 44% of the normal subjects studied by Richter et al.,⁴¹ but these waveforms usually occur with no more than 10%-15% of swallows.⁴⁴ An interesting perspective on double-peaked contractions was provided by a recent topographic analysis of esophageal peristalsis.⁴⁵ That analysis confirmed a consistent pressure trough in the proximal esophagus corresponding to the junction between the striated and smooth muscle. Furthermore, the distal esophagus was separated into two contractile segments divided by another relative pressure trough. Slight malalignment of these distal contractile segments resulted in the most distal segment commencing its contraction late, when the proximal segment was past the peak of its contraction. A double-peaked contraction is then recorded where the slightly staggered contractile segments overlap.

TABLE 3
Normal Values of Primary Peristaltic Contraction Amplitude During Water Swallows

Position of recording site above the LES (cm)
3	6	9	12	15	18	n
98 ± 60	123 ± 55	100 ± 40	89 ± 35	68 ± 29	44 ± 20	3142
91 ± 42	124 ± 67	100 ± 64	87 ± 51	67 ± 49	50 ± 24	4842a
58 ± 9	63 ± 24	65 ± 30	59 ± 18	70 ± 45	38 ± 24	1043
109 ± 45	90 ± 41 (8 cm)		70 ± 32 (13 cm)		109 ± 45	9541
32 or 137 (95% confidence interval for the distal esophagus)						4144

NOTE. Values are expressed as mm Hg (mean ± SEM).

^aPatient controls.

The LES

Liebermann-Meffert provided a detailed description of the muscular anatomy of the human LES, identifying a ring of thickened circular muscle angling obliquely upward from the lesser to the greater curvature of the stomach.⁴⁶ Away from this ring, muscle thickness decreases both toward the esophagus and toward the stomach. Distally, the ring is split into two segments; one forming short transverse muscle clasps around the esophagus and the other forming long oblique loops to the stomach. The LES is normally situated within the diaphragmatic hiatus, typically formed by the right diaphragmatic crus. Recent studies discussed further suggest that a component of LES pressure results from extrinsic compression by the crural diaphragm.

Physiologically, the LES is a 3-4-cm long segment of tonically contracted smooth muscle at the distal end of the esophagus. Resting LES pressure varies among individuals from 10 to 45 mm Hg relative to intragastric pressure. LES pressure is greatest at night and least in the postprandial period.⁴⁷ LES tonic contraction results from both an intrinsic property of the muscle itself and modification of that tone by the nerves affecting the sphincter.⁴⁸ Intra-abdominal pressure, gastric distention, peptides, hormones, various foods, and many drugs modify the LES pressure (Table 4).⁴⁹ The LES is inhibited with swallowing concurrent with and presumably by the same mechanism as deglutitive inhibition in the smooth muscle esophagus. In fact, the sphincter should be viewed as identical to the adjacent circular muscle except that it maintains a tonic contraction by a myogenic mechanism.

TABLE 4
Substances Influencing LES Pressure

	Increase LES pressure	Decrease LES pressure
Hormones	Gastrin Motilin Substance P	Secretin Cholecystokinin Glucagon Somatostatin Gastric inhibitory polypeptide Vasoactive intestinal polypeptide Progesterone
Neural agents	-adrenergic agonists -adrenergic antagonists Cholinergic agonists NO antagonists	-adrenergic antagonists -adrenergic agonists Cholinergic antagonists NO agonists
Foods	Protein	Fat Chocolate Ethanol Peppermint
Miscellaneous	Histamine Antacids Metoclopramide Domperidone Prostaglandin F2 Cisapride	Theophylline Prostaglandins E2 and I2 Serotonin Meperidine Morphine Dopamine Calcium channel blockers Diazepam Barbiturates

Modified and reprinted with permission.⁴⁹

Another complex phenomenon of LES pressure was discovered during investigations into the mechanism of gastroesophageal reflux. Dent et al. and Dodds et al. found that despite having adequate LES pressure, normal volunteers and patients with esophagitis periodically showed gastroesophageal acid reflux by the mechanism of transient LES relaxation.^47,55 Although the proportion of transient LES relaxations accompanied by acid reflux is disputed, it is increasingly clear that the transient LES relaxation is an essential component of the belch reflex.^17,56 Transient LES relaxation frequency is greatly increased by distention of the stomach by gas.^17,57 Cooling of the cervical vagi temporarily eliminates transient LES relaxations in dogs until the vagi recover.⁵⁸

Similar to the case with the UES, a variety of methods have been used for the determination of resting LES pressure. The three most widely used techniques are (1) a sleeve sensor, (2) the rapid pull-through of side-hole sensors across the sphincter during suspended respiration, or (3) a station pull-through of a side-hole sensor recording pressure activity for 30-60 seconds at 1-cm increments as the catheter is withdrawn. Table 5^{11,41,44,47,59} contains normal values obtained by each of these methods using modern equipment. As with the upper sphincter, LES pressure values vary substantially with the method of measurement. A nearly linear relationship exists between the manometric catheter diameter and recorded LES pressure in healthy subjects.^60,61 Varying conventions are to measure either midrespiratory or end expiratory LES pressure. The impact of this seemingly minor detail is evident in the study by Richter et al. in which station pull-through recordings were interpreted at end expiration and end inspiration, yielding values of 15 ± 11 mm Hg vs. 40 ± 13 mm Hg from the same tracings.⁴¹ The extent of the temporal variability of LES pressure is extremely evident in the study by Dent et al. of normal volunteers during continuous 12-hour LES pressure monitoring during two consecutive nights.⁴⁷ The minute-to-minute variation in LES pressure averaged 6 mm Hg with a range of 4-9 mm Hg among subjects. Furthermore, when the data were analyzed in 10-minute epochs, each individual ranged from a low value of 10 ± 5 mm Hg to a high value of 55 ± 10 mm Hg; the lowest values were invariably postprandial, and the highest values were obtained during sleep. Taken together, these data make it very difficult to establish a normal range of LES pressure values. Perhaps the only meaningful statement that can be made regarding isolated measurements of LES pressure is that it is abnormal to have an extremely low value (5 mm Hg).

NOTE. Values are expressed as mm Hg (mean ± SEM).

^aSee text for variability analysis.

^br = 0.71 between methods; no age or sex effect.

Technical Aspects and Limitations of Manometric Recordings

Although the contractile function of each esophageal region has been quickly summarized, a number of issues complicate the performance and interpretation of esophageal manometric recordings. Manometry is by nature a highly technical evaluation, more akin to physiological studies than to endoscopic or radiographic studies. When knowledgeably used, a manometric examination provides an accurate description of esophageal contractile function but only if physical principles and equipment characteristics are respected. In general, manometric data is only as valid as the methodology used to acquire it. In the evaluation of each esophageal region, one must consider the recording accuracy of equipment, the appropriateness of sensor design and configuration, and the technique of data acquisition. The essential principles of each of these methodological issues will be considered in turn.

Recording Accuracy of Manometric Equipment

The frequency content and waveform of esophageal contractile waves define the required characteristics of manometric recording apparatus. To produce a high-fidelity recording, the equipment must be capable of faithfully reproducing these waveforms. Orlowski et al. performed a computer analysis of esophageal peristaltic pressure complexes in normal subjects; the results are summarized in Table 6.⁶² From this analysis, it is evident that the frequency response of manometric systems required to reproduce esophageal pressure waves with 98% accuracy is 0-4 Hz, whereas that required for reproducing pharyngeal pressure waves is 0-56 Hz. Alternatively, manometric system characteristics can be expressed in terms of maximal recordable dP/dt, in which case 300 mm Hg/s will suffice for the mid or distal esophagus vs. 4000 mm Hg/s for the pharynx. Because the characteristics of the manometric system as a whole are only as good as those of the weakest element within that system, each element (pressure sensor, transducer, recorder) must possess these response characteristics if high-fidelity recordings are to be obtained.

Modified and reprinted with permission.⁶²

in which compliance is defined as the change in volume within the recording assembly associated with a given change in pressure.⁶³ The pneumohydraulic infusion pump was a great advance over its predecessors (syringe pumps) because with its low compliance. Accurate recordings of esophageal pressure waves could be made at infusion rates <0.5 mL/min per channel.⁶⁴

Esophageal contractions create circularly oriented forces that tend to seal the catheter recording orifice. Once the orifice becomes sealed, it no longer fully senses the contraction but instead records an inaccurately low pressure. As suggested by the equation above, recording accuracy can be improved by sufficiently increasing the perfusion rate to prevent sealing. However, during the critical period of a rapid pressure transient, recording system compliance reduces the effective catheter infusion rate. Total system compliance includes the compliances of the infusion pump, manometric catheter, and transducer to which the catheter is connected. Because volume displacement pressure transducers have exceedingly low compliance (<0.05 µL/100 mm Hg), catheter compliance is the major source of compliance in the manometric system.⁶⁴ Catheter compliance is minimized by using minimally elastic, thick-walled catheters of the shortest length and smallest internal diameter feasible. When polyvinyl catheters are used in conjunction with a pneumohydraulic infusion pump, the maximal pressure responses that the manometric system is capable of are summarized in Table 7. Proximal occlusion defines the response characteristics of the infusion pump and pressure transducer, whereas distal occlusion adds the length of the recording catheter into the test. Clearly, with perfusion manometry, the catheter is the major limitation of recording fidelity. Nonetheless, adequate response is achieved with a 0.8 mm ID catheter to record esophageal pressure events with high fidelity (see Table 6).

Modified and reprinted with permission.⁶⁴

The main alternative to the water-perfused manometric system described above is a manometric assembly incorporating strain gauge sensors and solid-state electronic elements. In these manometric systems, the manometric probe contains the transducers (strain gauges) at fixed locations along its length. The probe plugs into a small box containing the electronics, which is then connected to the recorder. The advantages of intraluminal strain gauge systems are (1) their vastly expanded frequency response (typically 0-20,000 Hz), making them suitable for recording any intraluminal pressure activity and (2) their less cumbersome nature compared with perfusion pumps, requiring less skilled personnel to perform clinical studies and less equipment maintenance. The main disadvantages of the solid-state systems are (1) the manometric probes are expensive (typically >$1000/channel), sometimes fragile, and unmodifiable; (2) manometric probes are subject to several physical constraints with respect to the number of sensing elements and the proximity of the elements to each other; and (3) there is no equivalent of a sleeve device compatible with these systems (see below).

Sensor Configuration and Design

Manometric assemblies are designed to obtain pressure recordings from 3-8 discrete channels simultaneously. Point pressure sensing sites are either small side holes cut into individual lumens of the multilumen tube in the case of perfusion manometry or a laterally oriented strain gauge in the case of solid-state units. The relative positioning of the sensing sites within the esophagus varies with the number of channels to be used and whether or not a sleeve element is to be used. Virtually all designs are adequate for the purpose of recording peristaltic activity in the tubular esophagus. Having a greater number of recording sites is convenient in that it minimizes the need to reposition the tube in the course of the study. Having more closely spaced sensors is desirable in that it minimizes the risk of missing localized events that may occur over a short length of esophagus. Three channel assemblies typically position sensing elements 5 cm apart, thereby spanning a 10-cm length of esophagus. Eight channel assemblies usually have sensing sites at 3-cm intervals spanning 15-18 cm of esophagus, depending on the precise design.

Obtaining a faithful recording of the intraluminal pressure within a sphincter during an extended period of time or during swallowing requires that the pressure-sensing element maintain a constant position relative to the sphincter high-pressure zone. Unfortunately, this is not easily achieved. Both sphincters show orad excursion during swallowing owing to laryngeal elevation during swallowing (UES)³ or contraction of the longitudinal muscle of the esophageal body (LES).^39,40 Each sphincter will move about 2-3 cm orad in the course of the swallow. On the other hand, a transnasally passed manometric assembly will move 1-2 cm orad coincident with soft palate elevation early in the swallow and discordant to the movement of either sphincter.³ If a sensing element is initially positioned at the peak of the sphincter high-pressure zone and the position of the sensing element changes relative to the sphincter high-pressure zone during the swallow, it will register a diminished pressure (sometimes suggestive of complete relaxation) as a result of that movement, regardless of whether or not relaxation actually occurred. This problem decreases the accuracy of a point sensor for detecting dynamic sphincter activity, including the completeness of sphincter relaxation. However, a single point sensor can be used for a static determination of sphincter pressure using a pull-through technique in which the sensing element is pulled across the sphincter in steps, yielding an axial pressure profile.

An ingenious device that circumvents the problem of sphincter movement and provides a time-tested, experimentally validated method for the dynamic recording of intraluminal sphincter pressure is a sleeve sensor.^6,65,66 Typically, a sleeve sensor contains a 6-cm-long silicone membrane under which water is perfused. When pressure is applied anywhere along the length of the membrane, the resistance to water flow beneath that membrane increases and pressure registers on that manometric channel. The physical properties of a sleeve sensor are those of a Starling Resistor in that it measures the highest pressure acting anywhere along its length, making it ideal for "tracking" the contractile activity of a mobile sphincter. Thus, the advantages of a sleeve sensor are that it is the only device presently available that can provide accurate recordings of intraluminal sphincter activity when sphincter movement is anticipated and that it can be easily incorporated into a perfused manometry system. The disadvantages of a sleeve sensor are (1) proper use requires that three recording channels be devoted to the sleeve itself: a side hole at the beginning of the sleeve element, one for the sleeve element, and one at the end of the sleeve element; (2) it has a limited frequency response, making it unsuitable for the recording of brisk contractile activity^3,6; (3) it misrecords the duration of sphincter relaxation because the apparent termination of relaxation registers when the peristaltic contraction arrives at the proximal end of the sleeve; (4) it records from only one radial orientation, making it insensitive to radial pressure asymmetry, and (5) proper use requires skilled personnel well versed in the physical principles and recording characteristics of sleeve sensors. However, it is important to note that despite the apparent advantage of a sleeve sensor for recording dynamic sphincter activity, no published study has compared its efficacy to that of other manometric techniques in identifying disorders associated with incomplete sphincter relaxation, e.g., achalasia.

Techniques of Data Acquisition for Clinical Esophageal Manometry

The clinical use of esophageal manometry is in defining the contractile characteristics of the esophagus in an attempt to identify pathological conditions. Toward this end, physiological information must be obtained in a standardized fashion regarding the peristaltic function of the tubular esophagus and function of the LES. Each of these will be considered in turn. At present, it is less important to study the UES during a clinical manometric evaluation because of the many limitations associated with such measurements as previously described. Even though the measurements can be made, no meaningful normal values exist; at present, manometry lacks the proven sensitivity or specificity required for impact on the need for either medical or surgical therapy of any known disorder of the UES.

A manometric assessment of the tubular esophagus must assess the success rate and vigor of primary peristalsis throughout the length of the esophagus. Partly because of the fact that manometric equipment is not standardized, there is no standardized protocol for assessing peristalsis. Studies can be performed with either orally or nasally passed catheters, but we believe that the studies are better tolerated and fewer recording artifacts occur when the manometric catheter is passed nasally. A swallow marker should be used both to show the occurrence of second swallows (causing deglutitive inhibition) and to provide evidence of failed peristaltic contractions. Adequate results can be obtained from a sensor belt or microphone on the neck, a pressure sensor in the mouth, submental electromyographic recording, or very careful observation and activation of a manual event marker. Water swallows (5 mL) are used because several investigators have determined that a more vigorous and consistent peristaltic response results when water swallows as opposed to saliva swallows are tested.^41,67 More recently, clinicians and investigators have advocated the use of bread bolus swallows in clinical manometry, claiming an increased sensitivity for detecting motor abnormalities.^68,69 However, preliminary data also suggest that failed peristalsis is markedly more frequent in healthy subjects during the swallowing of boluses of solid food.⁷⁰ Hence, the diagnostic potential of bread bolus swallows during manometry needs better definition, and this procedure cannot be recommended at present. A typical evaluation of peristalsis examines the contractile activity of each esophageal region after at least 10 swallows, each separated by 30 seconds or more. With an 8-lumen manometric catheter constructed with closely spaced recording sites, this can be accomplished with a single catheter station; with a 3-lumen catheter, assessing the length of the esophagus requires repositioning the catheter at least once. Multiple swallows must be examined because intermittent failed peristalsis is a common finding and because simultaneous contraction sequences or other spastic events can be notoriously sporadic. Even so, the likelihood of detecting a very low frequency event when only 10 swallows are studied is not very good; the more sporadic the event that is being sought, the lower the sensitivity of the manometric study. Mathematically, the probability of detecting an abnormality (P) under these circumstances can be expressed as P = 1 - (1 - p)ⁿ in which p is the frequency with which the abnormal contraction occurs and n is the number of swallows included in the manometric study. Thus, if a spastic contraction occurs 10% of the time, the likelihood of detecting it during a manometric examination consisting of 10 swallows is only 0.65.

LES pressure is assessed by a rapid pull-through technique, a station pull-through technique, or a sleeve recording. A rapid pull-through is performed by first positioning 3-4 adjacent recording sites within the stomach and then withdrawing them across the LES high-pressure zone at a rate of about 1 cm/s with respiration suspended at midexpiration. Intragastric position is determined by the pressure inversion point (the axial location at which inspiration results in increased as opposed to decreased intraluminal pressure indicative of an intra-abdominal as opposed to an intrathoracic recording). A station pull-through differs from a rapid pull-through in that the recording assembly is withdrawn 0.5 cm at a time and held at each station for 30-60 seconds. Respiration is not suspended during a station pull-through, and one or more swallows are obtained at each station so that deglutitive LES relaxation can be assessed. Sleeve recordings of LES pressure are obtained by first localizing the LES high-pressure zone by a rapid pull-through and then centering the high-pressure zone on the sleeve sensor. A continuous recording of basal LES pressure is obtained for 5-10 minutes, during which swallowing is kept to a minimum. Deglutitive LES relaxation is assessed in association with esophageal peristalsis during water swallows.

Analysis of Clinical Esophageal Manometric Recordings

Despite the seeming complexity of the examination, the interpretation of clinical manometric examinations is relatively simple. Manometric diagnoses are established by analysis of esophageal body and LES contractility. Although several diagnostic schemes have been suggested, none are universally used. Furthermore, by their nature, manometric findings are not specific for disease because virtually any pattern may be produced by more than one underlying condition. The following discussion on the interpretation of manometric tracings assumes that artifacts that may complicate the study (e.g., repeated swallows, cough, Valsalva) have been sought and that swallows associated with such artifacts were eliminated from analysis (see Weihrauch⁷¹ and Castell et al.⁷² for potential recording artifacts and practical aspects of manometric technique).

Peristaltic function is characterized by its success rate, the rate of progression of the contractile complex, and characteristics of the contractile complex (amplitude, duration, repetitive contractions). For the peristaltic success rate to be assessed, both the occurrence of a swallow and the occurrence of a propagated contraction in the distal esophagus need to be known. Failed peristalsis is present either when no esophageal contraction occurs after a swallow, when the propagated contraction proceeds part way down the esophagus and then disappears, or when the contraction proceeds part way and then ends with a simultaneous contraction in the distal esophagus.⁴² Each of these outcomes results in impaired esophageal emptying of the ingested fluid.³⁷ The progression rate of a peristaltic contraction is measured by identifying the timing of the initial upstroke of the peristaltic contraction (not the peak pressure) at adjacent recording sites and knowing the distance between these recording sites. Fluoroscopic studies have shown that the initial upstroke of a contraction correlates with luminal closure of the esophagus at that recording site, making this the most physiologically relevant time.³⁷ Fluoroscopic studies have also shown that if the rate of progression is faster than 6.25 cm/s, poor esophageal emptying occurs, in essence making this a simultaneous contraction.⁷³ Contractile amplitude is scored relative to the baseline esophageal pressure, and the duration of the contraction is the interval from the initial upstroke until the return to baseline at a given recording site. A pressure complex in the distal esophagus is scored as hypotensive if the amplitude is <35 mm Hg.^41,42,44 A typical convention for scoring hypertensive peristalsis is that the mean amplitude of contractile complexes exceed 180 mm Hg,⁴¹ but this upper limit has varied among investigators depending on the definition of normal and has no fluoroscopic counterpart for validation. Repetitive contractions are multipeaked contractile complexes. By convention, a contraction is scored as multipeaked if the "valley" between the peaks is at least 10 mm Hg less than and at least 1.0 second after the preceding peak.⁷⁴

Both the axial location of the LES and the magnitude of LES pressure are determined from the manometric study. The proximal margin of the LES is the distance from the nares or incisors at which intraesophageal (as opposed to intrasphincteric or intragastric) pressure is first recorded. The convention for measuring LES pressure is that it be determined relative to intragastric pressure. With rapid pull-throughs, the peak pressure obtained from each side hole is measured and an average value computed. With station pull-throughs, the station recording the highest pressure is identified and the mean end expiratory or midrespiratory value determined; again, values among side holes are averaged. When a sleeve is used to measure resting LES pressure, the average end expiratory value (excluding swallow-related relaxations and contractions) is determined for a 5-10-minute period. Deglutitive LES relaxation can be assessed with a sleeve recording, during a station-pull through, or after repositioning the catheter side hole at the optimal position. In the case of side hole measurements, data is obtained from either the station recording the greatest pressure or one of the stations proximal to that (because of esophageal shortening). A sleeve is ideal for assessing LES relaxation. In either case, the absolute value of the residual pressure during relaxation is determined relative to intragastric pressure. Surprisingly, there are no validated standards for the timing of normal deglutitive LES relaxation, making this interpretation somewhat subjective. Typical criteria for discriminating between artifact and deglutitive LES relaxation are the demonstration of a reproducible temporal relationship of relaxation to deglutition and a persistence of the residual or near residual pressure for a period of 3-10 seconds.^71,75

Role of Esophageal Manometry in Clinical Practice

Manometry can potentially aid in the diagnosis and management of esophageal syndromes involving dysphagia, chest pain, or gastroesophageal reflux and in defining multisystem diseases that have esophageal dysmotility as one component. However, it has become increasingly clear that, along with pathophysiologically important abnormalities, manometry detects insignificant aberrations of esophageal motility that have no proven relevance to the symptoms or management of patients with esophageal syndromes. These minor manometric abnormalities may represent subclinical forms of motor dysfunction or insignificant deviations from normal, and their detection is of questionable clinical value. Thus, our objective in this section is to critically evaluate the use of esophageal manometry in the above clinical scenarios. In each case, we will attempt to define the associated, pathophysiologically significant motility abnormalities, assess the potential for identifying afflicted patients on the basis of manometric findings, and determine the effect of detecting manometric abnormalities on clinical management decisions.

This critical assessment was accomplished by retrieving and reviewing data reported in the medical literature. For each syndrome, relevant key words were used to search the National Library of Medicine database for the period from 1980 to July 1993. The key word combination of gastroesophageal reflux disease and surgery located 401 citations, gastroesophageal reflux in conjunction with diagnosis or manometry located 453 citations, chest pain and esophageal motility disorders located 189 citations, and deglutition disorders in conjunction with diagnosis or manometry located 217 citations. Reports were included in the discussion only if they met rather stringent criteria: (1) they were designed to address one of the clinically relevant objectives enumerated above, (2) the manometric findings under discussion were of potential physiological relevance as outlined in the first section of this report, (3) the manometric methodology used was valid and consistent with the methodological principles outlined above, and (4) reported findings were based on an appropriate experimental design with an adequate number of subjects and controls when necessary. In no case was there a sufficient number of comparable reports addressing clinical use found to allow combined statistical analyses of results.

Manometry for Gastroesophageal Reflux Disease

Potential of using manometric abnormalities for identifying patients with gastroesophageal reflux disease.

Perhaps nowhere more than in the case of gastroesophageal reflux disease is the dichotomy between the use of manometry as a diagnostic technique as opposed to as an investigational method more evident. Countless investigations have shown a plethora of aberrations in gastroesophageal reflux disease, leading to the conclusion that clinically significant reflux is the common final pathway of a multifactorial pathophysiological process, some elements of which are evident manometrically. Proposed manometric abnormalities include impaired peristalsis⁴² and LES dysfunction secondary to hypotension,⁷⁶ short length,⁷⁷ or excessive transient relaxations.^47,55 However, there has not yet been any demonstration that the detection of any of these manometric aberrations predicts the occurrence of clinically significant gastroesophageal reflux disease.

Impact of manometry on management decisions in gastroesophageal reflux disease.

In theory, the combination of abnormalities leading to gastroesophageal reflux disease in an individual patient might lead to customized treatment to correct the specific defects. However, there has not yet been any demonstration that the detection of any of these manometric aberrations predicts the appropriateness of a particular therapeutic agent. Instead, medical therapy has centered on antisecretory drugs, and the best predictor of the level of antisecretory therapy required for a given patient is the severity of mucosal disease found at index endoscopic examination.⁷⁸ Although frequently detectable, coexisting manometric abnormalities do not modify the choice of therapeutic agent. Thus, at present, published reports have not shown any significant influence of a manometric assessment on the diagnosis, staging, or pharmacological treatment algorithms of gastroesophageal reflux disease.

Refractory reflux disease is an accepted indication for antireflux surgery, although there is no universal agreement on what constitutes refractory disease. Generally, this physician-specific determination is based on the antisecretory therapy requirements necessary to obtain or maintain an adequate symptomatic response or on a poor response, regardless of the level of antisecretory therapy. At present, there are no findings from a manometric assessment that define an indication for antireflux surgery. However, manometry does have a place in the preoperative assessment of patients being considered for antireflux surgery in whom there is any uncertainty regarding the diagnosis of gastroesophageal reflux disease. Antireflux surgery will only compound a patient's problems if inadvertently performed for achalasia or non-reflux-induced esophageal spasm, entities that may be detected by preoperative manometric assessment. On the other hand, preoperative assessment of LES tone, a factor that participates in the pathogenesis of gastroesophageal reflux disease for some patients, has not proven useful in patients selected for surgery by the usual indications and has a poor predictive value of clinical outcome.⁷⁹

A more difficult issue is the relationship between preoperative manometric findings and postoperative dysphagia (experienced by up to 25% of patients undergoing fundoplication^79,80). Reasoning that the etiology of dysphagia in this setting is the combination of poor peristaltic function and the relative obstruction caused by the fundoplication, several prominent investigators have considered impaired peristaltic function to be a relative contraindication to antireflux surgery.⁸¹ However, no controlled data could be found in this review to support that opinion and, in fact, the available data contradict it. The only relevant prospective, controlled, blinded series analyzed the clinical outcome of 126 consecutive patients undergoing fundoplication who underwent the operation without prior knowledge of preoperative manometric findings.⁷⁹ Although these patients showed the usual array of peristaltic dysfunction preoperatively, including 14 with >50% failed peristalsis (it is not stated if any had 100% failure), there was no correlation between the manometric findings and a poor surgical outcome for reason of dysphagia. Of the 14 patients with the worst peristaltic function preoperatively, 10 had a good to excellent surgical outcome; the poor outcome in the other 4 was unrelated to dysphagia. Furthermore, none of the 6 patients experiencing severe postoperative dysphagia were among the high-risk group suggested by the preoperative manometry. In fact, the investigators could find no manometrically definable risk factor that indicated a group of patients prone to postoperative problems.

Another surgical series examined peristaltic function prefundoplication and postfundoplication in 26 unselected patients and found that both failed peristalsis and hypotensive peristalsis were significantly improved after antireflux surgery.⁸² In that report, the 3 patients with the most severe peristalsis preoperatively (85%, 90%, and 100% failed peristalsis) improved dramatically, showing that 12%, 8%, and 0 failed peristalsis postoperatively. Thus, despite widespread opinion to the contrary, available data suggest that the preoperative manometric assessment of LES and peristaltic function does not predict surgical outcome either in terms of antireflux efficacy or the occurrence of postoperative dysphagia. That conclusion must remain somewhat guarded, both because it so strongly contradicts "accepted practice" and because only scant data exist on surgical outcome in patients with the most severe impairment, i.e., aperistalsis with or without underlying connective tissue disease. In view of these limitations, it is wisest to acknowledge that insufficient data presently exist to evaluate the benefit of the preoperative assessment of peristaltic function.

Although not the subject of this review, ambulatory esophageal pH monitoring has become an increasingly common diagnostic test in the evaluation of reflux disease. The convention for performing pH monitoring studies is to position the pH probe 5 cm above the proximal margin of the LES. Suggested methodologies for pH probe placement include defining the LES by the location of the pH increase during pH electrode withdrawal, endoscopy, fluoroscopy, calculation according to subject height, or manometry. Of these methods, the manometric definition of the sphincter is the most accurate,^83,84 except perhaps in the very young pediatric population in which subject height correlates well with esophageal length.⁸⁵ Recently, a single probe "LES locator" has been shown to be equally effective to bedside manometry for the purposes of pH probe placement.⁸⁶

Manometric Findings in the Evaluation of Chest Pain and/or Dysphagia

Abnormal esophageal motility can potentially cause chest pain and/or dysphagia. An esophageal etiology of chest pain should be considered after careful consideration of potential cardiopulmonary etiologies. However, even within the spectrum of esophageal diseases, neither chest pain nor dysphagia is specific for a motility disorder because both are also characteristic of common esophageal disorders, including peptic or infectious esophagitis. After these more common diagnostic possibilities have been excluded by appropriate radiographic and/or endoscopic evaluation, motility disorders should be considered as the potential cause of the still unexplained symptoms. Available data regarding the use of esophageal manometry in this clinical situation will be addressed.

Manometric abnormalities are prevalent in patients with chest pain, dysphagia, or both, as shown by the findings from the 16 studies listed in Table 8, which includes representative studies with at least 30 subjects.^87-101 Asymptomatic volunteers (usually younger than the patients) were evaluated for definition of normal values in five of these studies,^88,91-94 but other types of control groups have not been reported. The manometric pattern of achalasia was not detected in any volunteer, suggesting that this finding is truly more prevalent in symptomatic subjects. Diffuse esophageal spasm (DES) is more variably defined than is achalasia,¹⁰¹ but simultaneous contractions after 30% of swallows were not found in any volunteer, again suggesting that this finding is truly more prevalent in symptomatic subjects. However, achalasia and DES account for only a small minority of patients in Table 8. Achalasia is probably found in <1% of subjects when chest pain is the principal symptom. Likewise, DES is found on average in 5% of patients with chest pain. Achalasia is more common in patients with other symptoms of esophageal dysfunction and in patients with dysphagia as the predominant complaint. The prevalence rate of DES is less influenced by clinical presentation.

Functionally significant abnormalities in patients with chest pain or dysphagia.

The functional significance of the manometric findings typifying achalasia is of poor bolus transit as determined by radiography or scintigraphy. Pathologically, these findings are indicative of either idiopathic achalasia characterized by depletion of NO or other inhibitory nerves in the smooth muscle esophagus¹⁰⁴ or "pseudoachalasia," in which distal esophageal obstruction (e.g., from tumor) precipitates motor dysfunction indistinguishable from that of idiopathic achalasia.^102,105 Similar to achalasia, the simultaneous contractions typifying DES also impair bolus transit through the esophagus, potentially explaining the associated dysphagia.^73,106 At least 10% of patients with DES have impaired LES relaxation,⁹¹ a functionally important manometric finding that may also explain symptoms. In a few cases, DES has been associated with neuromuscular pathology of the esophagus, but no characteristic lesion has been described.^107,108

Considerable attention has been directed at determining the functional significance of nonspecific motility disturbances, particularly the "nutcracker esophagus." However, esophageal bolus transit is usually normal in this condition,¹⁰⁹ and associated neural or muscular pathology is not generally recognized. A few instances have been reported in which patients with "nutcracker esophagus" are subsequently diagnosed with achalasia.^110,111 However, considering the rarity of this observation and the high prevalence of "nutcracker esophagus," any association between the motor disturbances could most likely be explained by chance. A cross-sectional study failed to correlate the severity of nonspecific abnormalities with the severity of symptoms, although there was a trend toward an association with dysphagia.¹¹² Long-term observations have shown neither a parallel in clinical course with manometric findings nor consistency in manometric diagnosis during a period of time.^113,114 A double-blinded, crossover treatment trial with nifedipine in patients with chest pain showed that significant reduction of wave amplitude in patients with "nutcracker esophagus" was not accompanied by a significant reduction in chest pain.¹¹⁵ A double-blinded, controlled trial of trazodone for symptomatic patients with a variety of nonspecific disturbances produced significant symptomatic improvement but no change in manometric findings.¹¹⁶ Only one controlled trial using diltiazem showed an association of improvement in symptoms with improvement in manometry within treatment groups, but the correlation for individual subjects was not reported.¹¹⁷ Other proposed treatments, including long-acting and short-acting nitrates and surgical myotomy, have not been tested in any kind of controlled fashion, and their success remains at the anecdotal level.¹⁰² A study of therapeutic vs. sham bouginage for patients with "nutcracker esophagus" showed similarly good benefits of both "treatments."¹¹⁸ Provocation of nonspecific abnormalities with cholinergic stimulation has not established their importance. Controlled studies have found only minimal differences in the manometric response among symptomatic patients with provoked pain, symptomatic patients without pain, and asymptomatic patients with no pain response,^119,120 and provoked pain rarely correlates with meaningful changes in bolus transit.¹²¹ In summary, it has been difficult to determine a direct relevance of nonspecific motility disturbances to either symptoms or function, making their detection of no generalizable value.

Potential of manometry for identifying patients with symptomatic motility disorders.

In cases of achalasia that are established by all available clinical criteria, the defining manometric features (aperistalsis and incomplete LES relaxation) are present in >90% of patients. Other manometric features (increased intraesophageal baseline pressure or isobaric waveforms) provide supportive evidence to improve the suspicion rate.¹⁰² Failure of diagnosis results from inability to intubate the LES in 10% of cases¹²² and seemingly normal peristalsis or LES relaxation in occasional cases.¹²³ Impairment of LES relaxation could be underestimated by a catheter with side-hole sensors as opposed to a sleeve for the reasons mentioned earlier, but the general experience has been that any LES assessment technique successfully detects achalasia. It is important to emphasize that the manometric features of achalasia are not specific for idiopathic achalasia or achalasia associated with Chagas disease; tumor-related pseudoachalasia accounts for up to 5% of cases with manometrically defined achalasia, being more common with progressive age.¹⁰⁵ Nonetheless, it is likely that manometry will correctly identify the majority of patients with achalasia. One prospective study showed that achalasia was suggested by the radiologist in only 21 of 33 patients who were given this diagnosis at manometry; endoscopists prospectively suggested the correct diagnosis in less than one third of the patients.¹²⁴

Diffuse esophageal spasm is principally defined by manometry; consequently, the manometric detection rate is very high. However, the true sensitivity of manometry in the detection of DES is unknown because of potential underdetection related to the sporadic occurrence of contractile events as alluded to earlier. The "nonspecific motor disorders" are presently defined solely by esophageal manometry.

Provocative testing with intravenous edrophonium sulfate was developed as a technique to increase the potential of manometry for identifying patients with symptomatic motor disorders. The test is most commonly performed by administering edrophonium (80 µg/kg body wt) by rapid intravenous push followed by ten 5-mL water swallows during a 5-minute period.¹²⁵ A prior injection of saline is sometimes used for patient blinding. Edrophonium can induce motor abnormalities and symptoms, but the motor abnormalities that develop resemble nonspecific motor disturbances that in either the provoked or nonprovoked setting do not differentiate symptomatic from asymptomatic subjects.^119,120 Thus, the principal response is pain. Although the test is often performed in conjunction with clinical esophageal manometry, manometry is not required for its interpretation. Provocation of symptoms, particularly pain, is also the relevant outcome when using intraluminal infusion of 0.1N HCl¹²⁶ or an intraluminal balloon distention device.¹²⁷ Although also performed in conjunction with manometry, these tests do not rely on the manometric recording for interpretation. Manometric localization of the LES, as for placement of pH probes, is commonly used to standardize position of the perfusion port or balloon for the test.

Impact of identifying patients with motility disorders on management decisions.

Treatments of achalasia (pneumatic dilation or myotomy) result in both symptomatic and functional improvement, making its identification of obvious clinical significance. Furthermore, limited data suggest that the efficacy of pneumatic dilation in symptom relief and in promoting esophageal emptying is directly related to the postdilation LES pressure with a value <10 mm Hg being an optimal result.¹²⁸ Unfortunately, the same study could not show that pretreatment manometric characteristics were predictive of outcome. No study over the period of literature review directly addressed the value and outcome of making the manometric diagnosis of DES in symptomatic patients. However, the consensus established in older literature holds that the findings have some specificity for symptoms when corroborated by radiographic evidence linking them with abnormal transit. In contrast to the nonspecific motility disorders, the diagnosis of DES seems to have some constancy over time.^114,129 Unfortunately, long-term outcome studies of the medical treatment of DES with smooth muscle relaxants are not available, and this therapy remains at an anecdotal level.¹⁰² Likewise, there are no controlled studies of treatment of well-defined patients with DES with pneumatic dilation or myotomy. Some patients with DES develop achalasia, a disorder with defined treatment strategies.¹³⁰ Thus, at least in some instances, the manometric evaluation of the patient with chest pain or dysphagia will affect therapy if achalasia or DES is detected.

The relationship of nonspecific motility disorders to symptoms is not established, and there is presently no merit to basing therapy on their detection. Only the study by Hsia et al.⁹⁷ suggested a benefit of diltiazem in "nutcracker esophagus," but statistical analyses were insufficient to determine if the marginal treatment effect on symptoms was related to group differences at baseline. More impressive has been the finding that reflux disease is often responsible for explaining symptoms of esophageal dysfunction whether nonspecific motor abnormalities are present or not. Bancewicz et al. found that aggressive antireflux therapy was the most useful treatment approach in the large subset of referred symptomatic patients without a specific motor disorder at initial evaluation.⁹² More recently, Achem et al. showed that antireflux therapy benefited patients with unexplained chest pain, regardless of the presence or absence of nonspecific motor abnormalities.¹³¹ With the cost-benefit question in mind, Meshkinpour et al. also showed that manometry was of little benefit except in the detection of achalasia.⁸⁷ More than 10 years have passed since that report, but successful specific treatments directed by manometric abnormalities that fall short of those required to define achalasia, DES, or similarly severe disturbances have not surfaced.

Manometry for the Diagnosis of Multisystem Disease

Manometrically evident abnormalities of peristalsis and LES function can be associated with systemic diseases that affect smooth muscle or the autonomic nervous system. The pattern of dysfunction evident in scleroderma and other collagen vascular diseases is of diminished or absent peristalsis in the distal half to two thirds of the esophagus and diminished or absent LES pressure.¹³² Clinically, this often results in dysphagia and gastroesophageal reflux disease along with its complications. Diabetes has been associated with more varied manometric abnormalities ranging from aperistalsis to nonspecific disturbances,^133-135 but the findings are not used clinically to define diabetes. Because substantial clinical data regarding the incidence, pathogenesis, sensitivity, and specificity of manometric findings have been reported only in the case of the collagen vascular diseases, this discussion will be limited to them.

The findings of aperistalsis in the smooth muscle esophagus and hypotension of the LES are so characteristic of scleroderma that this manometric pattern has been labeled "scleroderma esophagus."⁹¹ Although the exact prevalence of these findings in scleroderma is not known, 74% of patients with typical skin manifestations of scleroderma had histological evidence of esophageal involvement at autopsy.¹³⁶ Atrophy and fibrosis of the smooth muscle esophagus are evident with light microscopy.¹³⁷ However, "scleroderma esophagus" is not specific for scleroderma; similar esophageal features are found with lesser frequency in other connective tissue diseases, especially those that overlap with typical scleroderma (CREST syndrome, polymyositis, dermatomyositis, mixed connective tissue disease). Esophageal abnormalities are most commonly found when Raynaud's phenomenon is present.^132,138 Furthermore, from a diagnostic standpoint, the pattern is not specific for collagen vascular disease. In a study of 39 consecutive patients, collagen vascular disease accounted for <40% of patients identified at a motility laboratory with findings of "scleroderma esophagus."¹³⁹ The remainder of the patients in that study had reflux symptoms but no evidence of rheumatic disease (including Raynaud's phenomenon) either at the time of the study or during a 60-month follow-up period. Thus, although manometry is able to show esophageal involvement in known cases of collagen vascular disease, the manometric findings of "scleroderma esophagus" lack the specificity to establish any diagnosis.

No reports were found indicating a reversal of esophageal involvement as a result of specific therapy for collagen vascular disease. Similarly, there are no reported data showing that early diagnosis and treatment alters the clinical course of esophageal involvement in collagen vascular disease. Thus, the clinical outcome of "scleroderma esophagus" is entirely dependent on the severity of ensuing reflux disease and, as previously discussed, published reports have not shown any significant influence of a manometric assessment on the diagnosis, staging, or pharmacological treatment algorithms of gastroesophageal reflux disease. The most difficult therapeutic issue in the treatment of scleroderma patients with esophagitis is the role of surgery because these patients commonly have dysphagia, show severely defective peristalsis preoperatively, and will not show recovery of peristalsis as a result of antireflux surgery. Thus, scleroderma patients are thought to be at the greatest risk of all for severe postoperative dysphagia, and many investigators caution against antireflux surgery. The issue of dysphagia is even more complicated in this group because many patients have symptomatic strictures as well. However, the only substantial reported series on the topic suggests that the surgical outcome in scleroderma is comparable with that of other patients with reflux.¹⁴⁰ Of 100 scleroderma patients referred for evaluation, 37 underwent an operation with a Collis gastroplasty (esophageal lengthening) and fundoplication (Belsy or Nissen). Eighty-nine percent of patients that underwent the operation had good control of their reflux symptoms, and only 38% had symptomatic dysphagia postoperatively (vs. 81% preoperatively). A bias in surgical technique obviously occurred because the operating surgeon was aware of the underlying disease as well as the preoperative peristaltic dysfunction and modified the procedure accordingly. Nevertheless, the impact of the manometric findings on clinical outcome remains to be determined.

Conclusions And Clinical Recommendations

This review analyzed the capabilities and present clinical use of esophageal manometry. The first two sections of the report provided a current description of esophageal physiology, emphasizing aspects detectable by manometric techniques, followed by a discussion of the methodological issues that must be confronted to accurately make these determinations. In essence, these sections defined the set of valid findings potentially determined by esophageal manometry. The final section of the report examined recently reported clinical data to determine how manometric findings can be applied in the diagnosis and management of esophageal syndromes.

An initial observation is that the elegance of manometry is most evident when sophisticated, carefully controlled evaluations are obtained using relatively high level, often customized, instrumentation and study protocols. Under these circumstances, the manometric evaluation can be tailored to answer specific physiological questions on a case-by-case basis or to compare the physiological responses among groups of individuals. This usage is generally reserved for research settings in specialized centers. On the other hand, when used in a clinical setting, esophageal manometry is usually used to assess very limited aspects of esophageal physiology: the integrity of primary peristalsis and LES function. The potential yield of the examination is thereby limited to a few possible pathological observations, e.g., weak or absent peristalsis, disordered peristalsis, or impaired LES relaxation. Although these findings are sensitive for detecting esophageal motor disorders, they are by nature nonspecific, each potentially occurring in more than one clinical setting.

In view of the limited specificity of esophageal manometry and the low prevalence rates of significant disorders in symptomatic patients, it is not possible to use it as the sole basis for establishing diagnoses, and it has no identified use as a screening test. Thus, manometry should rarely, if ever, be used as an initial diagnostic evaluation. In fact, in many instances, manometry will prove unnecessary after mucosal or structural abnormalities (e.g., strictures, rings, esophagitis) are detected by endoscopy and/or a carefully performed air contrast esophagram. When these conditions are detected, the additional information gained by a manometric evaluation has not been shown to impact on the therapy rendered or the clinical outcome. However, after these common conditions have been excluded, esophageal manometry is a useful diagnostic tool for detecting motor dysfunction that may be directly associated with symptoms, particularly if achalasia or DES is a diagnostic possibility. However, current data do not support the use of manometry in the performance or interpretation of currently used provocative tests except for the positioning of a catheter or test device in relation to the LES.

With respect to gastroesophageal reflux disease, our review suggests that manometry presently has little role in diagnosis or management. Exceptions relate to the recognized value of manometry in the placement of intraluminal diagnostic devices, such as pH probes or acid perfusion catheters, and in instances that there is doubt in diagnosis. The importance of preoperative manometry in patients being considered for antireflux surgery is unproved. Sufficient data to determine the actual prognostic value of manometric findings with regard to postoperative outcome are not presently available. However, manometric screening for severe peristaltic dysfunction remains reasonable despite the lack of data because of the strong clinical impression that patients with these findings are at greater risk of poor outcome and might benefit from alternative management approaches.

Clinical guidelines that are developed from this technical review will need to consider the limited use of esophageal manometry when compared with other tests of esophageal structure and function in clinical use today. Regardless, manometry remains an important research tool because of the physiological data that manometric measurements provide. New clinical uses of manometry may surface because researchers continue to explore the relationship of symptoms and disorders to the results from an analytical manometric investigative approach.

(Approved by the American Gastroenterological Association Patient Care Committee on February 26, 1994.)

PETER J. KAHRILAS

Section of Gastroenterology
Department of Medicine
Northwestern University
Chicago, Illinois

RAY E. CLOUSE

Section of Gastroenterology
Department of Medicine
Barnes Hospital
St. Louis, Missouri

WALTER J. HOGAN

Section of Gastroenterology
Department of Medicine
Medical College of Wisconsin
Milwaukee, Wisconsin

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