Gastric exercise tonometry: The key investigation in patients with suspected celiac artery compression syndrome

Gastric exercise tonometry: The key investigation in patients with suspected celiac artery compression syndrome Peter B. F. Mensink, MD, a Andre S. van Petersen, MD, b Jeroen J. Kolkman, MD, PhD, a Johannes A. Otte, MD, a Ad B. Huisman, MD, c and Robert H. Geelkerken, MD, PhD, b Enschede, the Netherlands Introduction: Controversy continues about the mere existence of the celiac artery compression syndrome. Earlier results of treatment of unselected patients groups showed varying, mostly disappointing, results. The recently introduced gastric exercise tonometry test is able to identify patients with actual gastrointestinal ischemia. We prospectively studied the use of gastric exercise tonometry as a key criterion for revascularization treatment in patients with otherwise unexplained abdominal complaints and significant stenosis of the celiac artery by compression of the arcuate ligament. Methods: Patients were prospectively selected using abdominal artery angiography and gastric exercise tonometry. Patients with a significant compression of the celiac artery, typical abdominal complaints, and abnormal tonometry were considered for revascularization. Results: Over a 7-year period, 43 patients with significant celiac artery compression were included in this study, and 30 patients were diagnosed as ischemic. Twenty-nine patients had revascularization, 22 (76 %) had a trunk release only. After a median follow-up of 39 months, 83% of patients were free of symptoms. The repeated tonometry after treatment improved in 100% of patients free of symptoms, compared with 25% in patients with persistent complaints after revascularization. Conclusions: The results of this study suggest that the celiac axis compression syndrome exists and that the actual ischemia can be detected by gastric exercise tonometry and treated safely, with success. (J Vasc Surg 2006;44:277-81.) In 1972, Szilagyi et al 1 reviewed all available literature on stenosis of the celiac artery and concluded that no objective facts have been uncovered and published to prove or even strongly suggest that isolated stenosis of the celiac artery has any pathophysiological effect on the function of the organs supplied by this vessel. They therefore deemed treatment unnecessary, for which three main arguments were used. 1 First, it was generally assumed that the abundant collateral splanchnic circulation prevents development of symptomatic ischemia in most subjects. Second, surgical treatment consisted of dissecting the crural ligament, which probably resulted in neurolysis of the adjacent nerve plexus, and thus pain relief. Third, many authors treated these patients and noted variable and often disappointing results. 2-12 Nevertheless, there remains alack of definitive evidence of a causal relation between treatment and the disappearance of symptoms, and the debate has still not been settled. A randomized trial comparing sham treatment with crural dissection would be ideal. In light of the rarity of the syndrome and the doubts on its mere existence, this seems an impracticable and unethical undertaking. An alternative is to compare outcome and pain relief with vessel patency, preferably in combination with a physiologic marker of From the Departments of Internal Medicine and Gastroenterology, a Vascular Surgery, b and Radiology, c Medisch Spectrum Twente. Competition of interest: none. CME article 0741-5214/$32.00 Copyright 2006 by The Society for Vascular Surgery. doi:10.1016/j.jvs.2006.03.038 ischemia. The latter has become clinically available with gastrointestinal tonometry. This technique is based on the constant relation between increased carbon dioxide in the mucosa and lumen of the ischemic stomach or bowel. Initially, the goal was to measure carbon dioxide after a testmeal, butthisprovedinaccurate. 13,14 Wedeveloped a gastric exercise test, using a 10-minute bicycle test, which enables a diagnosis of gastrointestinal ischemia that is 86% accurate. 15,16 In this study, we prospectively assessed the results of revascularization in patients in which gastrointestinal ischemia was suspected based on the celiac artery compression syndrome. Gastric exercise tonometry was used as one of the key criteria for treatment, and repeated tonometry after treatment was used to evaluate treatment success. METHODS After institution of a multidisciplinary team on gastrointestinal ischemia in 1996, all patients referred to our center for unexplained abdominal complaints were prospectively analyzed and observed. This team, consisting of a gastroenterologist, a vascular surgeon, and an interventional radiologist, reviewed and discussed the symptoms, medical history, physical examination, and all diagnostic evaluations. All patients were included who had pain related to meals or exercise, or weight loss, or a combination of these. All previous investigations were reviewed to exclude more prevalent disorders. If these were sufficiently excluded, an intra-arterial digital substraction multiplane 277

278 Mensink et al JOURNAL OF VASCULAR SURGERY August 2006 Table. Patient characteristics of celiac artery compression syndrome and nonischemic patients* All patients CACS Nonischemic Number 43 30 13 Age (years) 38 (14-73) 36.6 (18-61) 41.2 (14-73) Male/female 10/33 7/23 3/10 Duration of complaints (months) 30 (3-192) 35 (4-192) 18 (3-120) BMI 21.8 (15.7-33.5) 21.4 (15.7-28.4) 22.5 (16.8-33.5) BMI 20 16 (37) 12 (40) 4 (30) Reporting weight loss 29 (67) 23 (77) 6 (46) Weight loss (kg/month) 2.0 (0.1-9.0) 1.8 (0.1-9.0) 2.8 (0.7-7.3) Postprandial pain 32 (74) 24 (80) 8 (62 %) Exercise-induced pain 19 (44) 12 (40) 7 (57 %) Abdominal bruit 15 (35) 7 (23) 8 (54 %) Cardiovascular history 5 (12) 2 (6) 3 (23 %) Smoking 21 (49) 19 (63) 2 (23 %) CACS, Celiac artery compression syndrome; BMI, body mass index. *All values are expressed in numbers (%) or as mean (with range). P.03. History of systemic vascular disease (clinical evidence of atherosclerosis). P.006. abdominal angiography (DSA) and gastric exercise tonometry was performed. Angiography. The DSA consisted of an anteroposterior and two or more lateral abdominal exposures with aortic injections to visualize the origin of the splanchnic vessels in expiration and inspiration. Thereafter, a selective injection of the celiac, the superior mesenteric, and the inferior mesenteric arteries was performed. A significant stenosis was defined as a luminal reduction of 70%. A compression of the celiac artery by the arcuate ligament was defined as a stenosis varying with the respiratory cycle, mostly asymmetric. All angiographies were reviewed by two independent investigators (A. B. H. and R. H. G.). In case of discrepancy, the DSA was re-evaluated by both, and a definitive consensus was reached. Patients with angiographic evidence of significant celiac axis compression and who had not received prior treatment were selected for this study. Gastric exercise tonometry. Gastric exercise tonometry testing was performed using a standardized protocol with measurement of gastric and arterial PCO 2 before, during, and after 10 minutes of submaximal exercise, as describedpreviously. 17 Inshort,afteracidsuppressionwith an H2-receptor antagonist (ranitidine; first 20 patients), or proton pump inhibitor (omeprazole; last 23 patients), baseline measurements of gastric PCO 2 and arterial blood gases were taken. Thereafter, a 10-minute bicycle test at submaximal exercise intensity was performed, followed by a 20-minute recovery period. Blood gases and gastric PCO 2 were measured at peak exercise and twice during recovery. The criteria for a positive, pathologic test result were established earlier and consist of (1) a gastric-arterial PCO 2 difference (gradient) 0.8 kpa after exercise, (2) an increase in gastric PCO 2 from baseline to peak exercise, and (3)anarteriallactatelevel 8mmol/L. 16 Allthreecriteria had to be met to define a test result as abnormal. Diagnosis and treatment. After completion of the investigations, the multidisciplinary team on gastrointestinal ischemia discussed all of the data. For each patient, a consensus diagnosis was made and treatment advice was given. Patients with significant celiac artery compression, a history consistent of chronic gastrointestinal ischemia (abdominal pain related to meals or exercise, or both, and weight loss), and abnormal tonometry results were advised to have treatment. We considered release of the celiac artery by cleaving the arcuate ligament as the treatment of first choice. After cleaving, the flow in the celiac artery was assessed peroperatively by duplex ultrasound imaging. A persistent stenosis was treated by a celiac artery inflow reconstruction. Follow-up. All treated patients visited our clinic every 6 months for an assessment of clinical status and duplex ultrasound scanning of the splanchnic arteries. A postintervention tonometry was scheduled 3 to 6 months after treatment. The patients who were diagnosed as nonischemic, and who were therefore not treated, were discharged from follow-up. The clinical status of these subjects was thoroughly assessed, and an inquiry was sent to the referring physician or primary care physician. Statistical analysis. Data were expressed as mean and standard deviation or median and range, when appropriate. The various group comparisons were performed using unpaired t test, Fisher s exact test, or Wilcoxon rank sum testing. P.05 was considered significant. RESULTS Between July 1996 and July 2003, 320 patients were evaluated for possible chronic gastrointestinal ischemia. All patients had unexplained abdominal complaints, postprandial pain, exercise-related pain, or weight loss, or a combination. DSA of the splanchnic arteries. In 43 patients, DSA was compatible with compression of the isolated celiac artery by the median arcuate ligament. These 43 patients had chronic abdominal complaints with a mean duration of 30 months (range, 3to 192 months) (see Table). Asignif-

JOURNAL OF VASCULAR SURGERY Volume 44, Number 2 Mensink et al 279 Fig 1. Flow chart for decision-making and results of treatment. CGI, chronic gastrointestinal ischemia; CA, celiac artery; CACS, celiac artery compression syndrome; GET, gastric exercise tonometry; MT-GI, multidisciplinary team on gastrointestinal ischemia; FU, follow-up; no-rep GET, no repeated gastric exercise tonometry. icant stenosis was found during expiration in 36 patients and during inspiration in seven patients. Gastric exercise tonometry and diagnosis. Tonometry could be performed without difficulty in all 43 patients. In 29 (67%), the gastric exercise tonometry indicated ischemia by using the aforementioned criteria. After the multidisciplinary team discussed all the results, gastric ischemia from celiac artery compression was diagnosed in 30 patients (70%), including 29 with abnormal results on tonometry. In one patient with normal results on tonometry, the clinical history was extremely characteristic for gastrointestinal ischemia (postprandial pain 10 to 15 minutes after meals, exercise-induced upper abdominal pain, and weight loss) that the gastric exercise tonometry was considered false-negative. The remaining 13 patients were considered nonischemic (see Fig 1). Patient characteristics. Clinical characteristics of the patients with gastric ischemia and those without ischemia did not differ significantly. Complaints were similar, and the only significant differences were the frequency of abdominal bruit and smoking incidence (Table). Interventions. An intervention was performed in 29 (97 %) of 30 patients defined a having gastric ischemia from celiac artery compression. One patient diagnosed with asymptomatic celiac axis compression was treated by a revascularization procedure elsewhere. In one patient diagnosed with gastric ischemia, no intervention was performed because the patient preferred conservative treatment. The surgical procedures were a celiac trunk release in 22 patients, venous patching of the celiac artery inflow in five, and an end-to-side antegrade autologous aortic-celiac bypass in two. The mean hospital stay was 8.6 days (range, 5 to 11 days). No patients died, and no early major complications occurred. Late complications occurred in three patients after surgical treatment. Severe gastroesophageal reflux disease (GERD) developed 3 to 12 months after treatment in two patients after a celiac trunk release and in one patient after an arterial bypass reconstruction. Two patients responded well on proton-pump inhibition, and one patient underwent antireflux surgery with good results. Symptoms after treatment. After a median 39 months (range, 10 to 106 months) of follow-up, 24 (83%) of the 29 patients were asymptomatic; 27 (93 %) had a normal celiac artery, and in one patient the vessel could not be visualized on duplex ultrasonography. Of the five patients with persistent complaints after treatment, four had a normal celiac artery, and one had a 50% to 70% celiac artery stenosis on repeated duplex ultrasonography. The one patient who decided not to have the intervention had persisting complaints after an anatomically successful celiac artery release. Postintervention tonometry. In 22 (76 %) of the 29 treated patients, tonometry was repeated postintervention. In two patients, the results of the postintervention tonometry could not be interpreted (both patients were free of symptoms). Five of the other seven patients refused repeated tonometry, one patient had normal results preintervention, and one patient was pregnant at the time of planned repeated tonometry and this was therefore cancelled. The results on repeated tonometry improved in all 16 patients (100%) free of symptoms and in one (25%) of the four patients with persistent complaints (P.0008). The maximal PCO 2 gradient measured with tonometry in the patients free of symptoms decreased from 1.5 0.4 to 0.7 0.3 postintervention (P.0001) (see Fig 2). Nonischemic group follow-up. Follow-up (mean, 32 months; range, 9 to 80 months) was available in all 13 patients with celiac artery compression who were diagnosed as nonischemic. In none of these patients were symptoms or signs of worsening of ischemic complaints seen. DISCUSSION This study provides evidence for the existence of the celiac axis compression syndrome, defined as celiac axis compression with symptomatic gastric ischemia, and that this can be treated successfully in most patients. Gastric

280 Mensink et al JOURNAL OF VASCULAR SURGERY August 2006 Max PCO2 gradient 3.0 2.5 2.0 1.5 1.0 0.5 0.0 GET 1 GET 2 Fig 2. Results of initial (GET 1) and repeated gastric exercise tonometry (GET 2) in the treatment patients group. On the left (A) the patients with successful treatment (free of complaints) and on the right (B) the patients with persistent complaints. Max PCO 2 gradient, maximal gradient between gastric and arterial blood carbon dioxide level (in kpa). Dotted line, cutoff point of 0.8 kpa ( 0.8 kpa is considered abnormal). exercise tonometry is the first test to prove actual gastric ischemia, thereby guiding treatment. Moreover, the results of follow-up tonometry showed improvement in all symptom-free patients, and improvement in only a minority of patients with persistent symptoms. One of the shortcomings in earlier studies on treatment of celiac artery compression was the lack of a diagnostic tool for the assessment of gastrointestinal ischemia. The tonometric measurement of PCO 2 has been shown to detect ischemia. The relation between an increased PCO 2 gradient (difference between luminal and arterial PCO 2 ) and ischemia has been established in numerous studies. 18,19 Nevertheless the clinical impact of tonometry has been limited so far. By introducing the gastric exercise test, we recently showed that (submaximal) exercise triggers gastric ischemia in patients who have asignificant splanchnic stenosis with an accuracy of 86%. 16 The use of tonometry enables us to objectively identify patients with actual gastrointestinal ischemia, thereby selecting patients who are most likely to benefit from treatment. As shown in this study, almost one third of the patients with a significant compression of the celiac artery and abdominal complaints have no evidence for gastrointestinal ischemia. Adding to this notion is the significant difference in outcome of repeated tonometry after intervention: normalized in 100% of patients free of symptoms and in only 25% of the patients with persistent complaints. The mean follow-up of just over 3 years in this study is relatively short compared with other studies showing relapse of symptoms at 15 years follow-up. Although a longer follow-up of these patients is needed, our mid-term results seem very promising. 5 The latter is emphasized by the fact that all patients with recurrence of symptoms have their relapse in the first 6 months after treatment. Since we only treated patients in whom the diagnosis chronic gastrointestinal ischemia was made, a possible beneficial effect of revascularization in the nonischemic group cannot be excluded. The combination of introducing a multidisciplinary team and tonometry as the key investigation has probably a synergistic effect on the outcome of these patients. In three patients with persistent complaints after anatomically successful revascularization, the postintervention tonometry results remained abnormal. The findings on tonometry in these patients might be considered false-positive results. An explanation of these false-positive findings could be active acid production before and during tonometry. Persistent stomach acid production is one of the pitfalls of tonometry: the hydrogen (H ) in the stomach acid reacts with the bicarbonate (HCO 3 ) in the stomach mucosal layer and produces carbon dioxide, irrespective of the presence of mucosal ischemia. The H2-receptor antagonist, used in the first 20 patients in this study, is known not to suppress acid production completely in all patients, and this might explain the persistent elevated gradient in these patients. 20 Three patients in the surgical intervention group had newly diagnosed, severe GERD complaints after surgery. This GERD probably resulted from dissection of the left crus of the diaphragm, as the right and left crus of the diaphragmhaveastabilizingfunctioninthissphincter. 21 It may well be that clinical failures in other earlier studies are patients with severe reflux disease after surgical revascularization. 21 CONCLUSION This study suggests that a significant compression of the celiac artery can give rise to ischemic complaints: the celiac artery compression syndrome. The availability of gastric exercise tonometry, a physiologic test that detects gastric ischemia, enables identification of these patients. We thank Job van der Palen for his advice on statistical matters and Joyce Kuiper for her advice on English grammar. AUTHOR CONTRIBUTIONS Conception and design: JJK, RHG, PBF Analysis and interpretation: JJK, PBF Data collection: PBF Writing the article: PBF, ASP, AH, RHG, JJK Critical revision of the article: JJK, RHG Final approval of the article: JJK, RHG, ASP, AH, PBF, JHO Statistical analysis: PBF Obtained funding: Not applicable Overall responsibility: JJK, RHG REFERENCES 1. Szilagyi DE, Rian RL, Elliot JP, Smith RF. The celiac artery compression syndrome: does it exist? Surgery 1972;6:849-63.

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