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Rapid Gastric Emptying Is More Common Than Gastroparesis In American Journal of Gastroenterology ISSN 0002-9270 C 2007 by Am. Coll. of Gastroenterology doi: 10.1111/j.1572-0241.2006.00946.x Published by Blackwell Publishing Rapid Gastric Emptying Is More Common than Gastroparesis in Patients With Autonomic Dysfunction Adeyemi Lawal, M.D.,1 Alexandru Barboi, M.D.,2 Arthur Krasnow, M.D.,3 Robert Hellman, M.D.,3 Safwan Jaradeh, M.D.,2 and Benson T. Massey, M.D.1 1Division of Gastroenterology and Hepatology, 2Department of Neurology, and 3Division of Nuclear Radiology, Medical College of Wisconsin, Milwaukee, Wisconsin OBJECTIVES: Autonomic dysfunction is associated with a wide variety of gastrointestinal symptoms. It is unclear how many patients with autonomic dysfunction have slow or rapid gastric emptying. The aim of this study was to determine the prevalence of rapid and delayed solid phase gastric emptying in patients with autonomic dysfunction referred for evaluation of gastrointestinal symptoms and the association of emptying rate with clinical symptoms. METHODS: Retrospective review of all patients with autonomic dysfunction who had a gastric emptying test from January, 1996 to March, 2005. Demographic data, clinical symptoms, composite autonomic scoring scale (CASS) score, and gastric emptying parameters were analyzed. RESULTS: Sixty-one subjects (women 49, age 42 [16–74] yr) with autonomic dysfunction were reviewed. Patients had mild-to-moderate (mean CASS score 3) autonomic dysfunction. Twenty-seven, 17, and 17 patients had rapid, normal, and delayed gastric emptying t1/2, respectively. In addition, 10 patients had initially rapid emptying in phase 1, with subsequent slowing in phase 2 to produce an overall normal or delayed t1/2. There was no difference in demographic data or CASS score among the three groups. More patients with initial or overall rapid emptying had diarrhea (70%) compared to patients with normal (33%) or delayed (33%) emptying (P = 0.018). CONCLUSIONS: Unexpectedly, more patients with autonomic dysfunction have rapid rather than delayed gastric emptying. The presence of diarrhea in patients with autonomic symptoms should prompt consideration for the presence of rapid gastric emptying. Conversely, the finding of rapid gastric emptying in patients with gastrointestinal symptoms should prompt consideration for the presence of underlying autonomic dysfunction. (Am J Gastroenterol 2007;102:618–623) INTRODUCTION symptoms and gastric emptying time has been frequently re- ported (5–9). Autonomic dysfunction is associated with a wide variety While gastroparesis is a known complication in diabetics of gastrointestinal manifestations. Autonomic dysfunction with autonomic dysfunction, many diabetics actually have may be a consequence of a known disease, such as dia- rapid gastric emptying (10–13). It is unclear how many pa- betes mellitus or large fiber neuropathies, or it can be id- tients with autonomic dysfunction have delayed or rapid gas- iopathic. Idiopathic autonomic dysfunction can have pro- tric emptying. The aim of this study was to determine preva- tean manifestations depending on the predominant output lence of rapid and delayed solid phase gastric emptying in affected—parasympathetic, sympathetic, or panautonomic. patients with autonomic dysfunction referred for evaluation Gastrointestinal signs and symptoms—including nausea, of gastrointestinal symptoms and to determine whether there vomiting, early satiety, bloating, abdominal pain, diarrhea, were clinical features associated with these abnormalities. and constipation—are present in more than 70% of the cases of idiopathic autonomic dysfunction (1). Disturbances in gastric emptying can also be manifesta- METHODS tions of known organic disease or may be idiopathic. Gas- tric emptying abnormalities are also reported in a significant We reviewed medical records of all patients with abnormal fraction of patients with functional gastrointestinal disorders, autonomic function testing who underwent a gastric emp- such as functional dyspepsia, irritable bowel syndrome, and tying test (GET) to evaluate gastrointestinal symptoms be- functional diarrhea (2–4). In patients with functional disor- tween January, 1996 and March, 2005 at the Medical Col- ders or diabetes, poor correlation between gastrointestinal lege of Wisconsin and Froedtert Memorial Lutheran Hospital. 618 Gastric Emptying in Autonomic Neuropathy 619 Demographic data, the presence of clinical symptoms (nau- collected over the stomach immediately after completion of sea, vomiting, diarrhea, constipation, bloating, belching, meal ingestion (time 0), and then every 10 min with the sub- chest pain, abdominal pain/dyspepsia, dysphagia, dizziness, ject standing apposed to the collimator until greater than 50% palpitations, sweats, headache, and weight change), auto- emptying had occurred, up to maximum of 3 h. A γ -camera nomic function test results, and gastric emptying parameters interfaced to a nuclear medicine computer was used. The were recorded. region of interest (ROI) corresponding to the stomach was Patients with prior gastric surgery were excluded. The Hu- identified and counts were corrected for radioactive decay. man Research Review Committee of the Medical College of After correcting for tissue attenuation and decay, each count Wisconsin approved the study. rate over the ROI was converted to percentage of the initial (or near maximum) count rate recorded. Gastric emptying Autonomic Function Test was evaluated using a two-component model as previously Autonomic function testing at the Medical College of described (16), and the slopes for both components were cal- Wisconsin includes the following components measured ac- culated. b1 is the slope of the first phase of gastric emptying, cording to published methods (14): b2 is the slope of the second phase of gastric emptying, and c is the time when the slope changes from b to b . In addi- 1. The quantitative sudomotor axon reflex test evaluates the 1 2 tion, the gastric emptying half-time (GET1/2) was obtained function of the postganglionic sympathetic sudomotor by fitting the data points from ROI to linear components by axon. Recordings were obtained from four sites: forearm, least squares regression analysis until the value of C, yield- proximal leg, distal leg, and foot, using the standard pub- ing the smallest sum of residual mean squares (16). These lished techniques (14). three parameters of gastric emptying were determined to be 2. The thermoregulatory sweat test used in conjunction with normal, rapid, or slow, based on previously obtained results the quantitative sudomotor axon reflex test gives infor- in normal subjects at our institution and adjusted for gen- mation about preganglionic sudomotor function. The per- der. The normal ranges (mean ± 2 SD) of the parameters centage of anterior body sweating was estimated after vi- for men: b (phase 1) = –0.70 (±0.56)%/min, b (phase 2) sual inspection of digital images that captures the sweat- 1 2 = –0.80 (±0.52)%/min, c = 36 (±38.2) min, and T1/2 = induced color change of alizarin red. The patient spends 66.2 (±27.2) min. The normal ranges for women: b = –0.17 enough time in the sweat chamber to raise oral tempera- 1 (±0.58)%/min, b = –0.67 (±0.26)%/min, c = 45 (±32.8) ture by 1◦C provided that the resting core temperature is 2 min, and T1/2 = 103.6 (±28) min. Previous studies have 36.5◦C. shown comparable result of T1/2 values obtained by either 3. Cardiovagal function was measured from the heart rate re- the power exponential or the two-line fit method (17). sponse to deep breathing and the Valsalva ratio, which are calculated as the ratio of maximal to minimal heart rate recorded in two consecutive trials. A Finometer (Finapres Statistical Analysis Medical System, Amsterdam, The Netherlands)—a con- For statistical analysis, patients were divided into those with tinuous noninvasive blood pressure monitor—was used to / rapid, normal, and delayed GET1 2. In addition, a separate record the beat-to-beat blood pressure and heart rate. analysis was performed grouping those patients with overall 4. Vasomotoradrenergic function was evaluated by measure- or first phase rapid emptying into a rapid emptying category. ment of blood pressure responses during the Valsalva ratio The χ 2 test was used to assess possible association between and from blood pressure and heart rate responses during the different symptoms and rapid versus slow gastric emp- head up tilt table testing. tying. Analysis of variance (ANOVA) was used to compare Normal values for the above test components were deter- the mean age and weight among patients with rapid, normal, mined from a study of 75 healthy controls at the Medical or slow gastric emptying. The Kruskal-Wallis test was used College of Wisconsin. The results of the autonomic func- to assess the differences in median CASS score among the tion testing were used to calculate the composite autonomic patients with rapid, normal, and slow emptying. A P value scoring scale (CASS) (14, 15). This scale consists of sudo- of <0.05 was considered statistically significant. Data are motor, cardiovagal, and adrenergic subscores. Each score was expressed as mean ± SEM unless otherwise stated. normalized for age and gender. Using the sum of the score from these three subsets, patients with autonomic dysfunc- tion were graded as follows: 1–3, mild; 4–6, moderate; and RESULTS 7–10, severe autonomic dysfunction. Gastric emptying studies from 61 subjects (women 49, age Gastric Emptying Test 42 [16–74] yr) with autonomic dysfunction were available
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