Werner Schwizer

Chicago classification criteria of esophageal motility disorders defined in high resolution esophageal pressure topography.

Background  The Chicago Classification of esophageal motility was developed to facilitate the interpretation of clinical high resolution esophageal pressure topography (EPT) studies, concurrent with the widespread adoption of this technology into clinical practice. The Chicago Classification has been an evolutionary process, molded first by published evidence pertinent to the clinical interpretation of high resolution manometry (HRM) studies and secondarily by group experience when suitable evidence is lacking.

High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry

Background and aims:  High‐resolution manometry (HRM) is a recent development in oesophageal measurement; its value in the clinical setting remains a matter of controversy. (i) We compared the accuracy with which bolus transport could be predicted from conventional manometry and HRM. (ii) The clinical value of HRM was assessed in a series of patients with endoscopy‐negative dysphagia in whom conventional investigations had been non‐diagnostic.

Conscious Sedation for Gastroscopy: Patient Tolerance and Cardiorespiratory Parameters

BACKGROUND/AIMS Most patients receive conscious sedation for gastroscopy. However, the benefit of the most often used combination of low-dose intravenous midazolam and topical lidocaine on patient tolerance remains poorly defined and has not been shown to outweigh cardiorespiratory risks. To respond to these issues, a randomized, double-blind, placebo-controlled prospective study was performed. METHODS Two hundred outpatients undergoing diagnostic gastroscopy were assigned to receive either (1) midazolam (35 micrograms/kg) and lidocaine spray (100 mg), (2) midazolam and placebo lidocaine, (3) placebo midazolam and lidocaine, or (4) placebo midazolam and placebo lidocaine. RESULTS Tolerance (visual analogue scale, 0-100 points; 0, excellent; 100, unbearable) improved as compared with placebo midazolam and placebo lidocaine by 23 points (95% confidence interval, 15-32) in group 1, 15 points (95% confidence interval, 7-24) in group 2, and 10 points (95% confidence interval, 2-18) in group 3. Increasing age (P < 0.001), low anxiety (P < 0.001), and male sex (P < 0.03), but not amnesia, were associated with better patient tolerance. Oxygen desaturation (< 1 minute) occurred in 8.2% and was not more frequent after midazolam treatment. Hypotension was rare (2.1%), and no adverse outcome occurred. CONCLUSIONS Both low-dose midazolam (35 micrograms/kg) and lidocaine spray have an additive beneficial effect on patients tolerance and rarely induce significant alterations in cardiorespiratory monitoring parameters, thus supporting the widespread use of conscious sedation.

Measurement of gastric emptying by magnetic resonance imaging in humans

A new noninvasive radiation-free method to measure gastric emptying in humans was developed. The upper abdomen was recorded with a magnetic resonance imager after administration of a liquid meal containing Gadolinium tetraazacyclododecane tetraacetic acid as a magnetic resonance image (MRI) marker. Meal volumes, total gastric volumes, and secretory rates were measured. The MRI technique was validated simultaneously by the double indicator method in 5 healthy volunteers and in 5 patients with symptoms of disordered gastric emptying applying gamma camera scintigraphy and MRI in randomized order. Similar gastric meal emptying curves were obtained in volunteers and in patients by MRI and the reference methods as assessed by linear (r greater than 0.90; P less than 0.001) and intraclass correlation analysis (r greater than 0.905) for T1/2, areas under the curve, and percent of gastric meal retained. Furthermore, similar total gastric volumes and gastric secretory rates were measured by MRI and the double indicator technique. The new MRI method correctly reflected gastric emptying disorders in patients. Thus for the first time it is possible to combine these measurements of gastric functions in a single method and to relate them to gastric morphology visualized by the generation of three-dimensional images.

Gastric flow and mixing studied using computer simulation

The fed human stomach displays regular peristaltic contraction waves that originate in the proximal antrum and propagate to the pylorus. High–resolution concurrent manometry and magnetic resonance imaging (MRI) studies of the stomach suggest a primary function of antral contraction wave (ACW) activity unrelated to gastric emptying. Detailed evaluation is difficult, however, in vivo. Here we analyse the role of ACW activity on intragastric fluid motions, pressure, and mixing with computer simulation. A two–dimensional computer model of the stomach was developed with the ‘lattice–Boltzmann’ numerical method from the laws of physics, and stomach geometry modelled from MRI. Time changes in gastric volume were specified to match global physiological rates of nutrient liquid emptying. The simulations predicted two basic fluid motions: retrograde ‘jets’ through ACWs, and circulatory flow between ACWs, both of which contribute to mixing. A well–defined ‘zone of mixing’, confined to the antrum, was created by the ACWs, with mixing motions enhanced by multiple and narrower ACWs. The simulations also predicted contraction–induced peristaltic pressure waves in the distal antrum consistent with manometric measurements, but with a much lower pressure amplitude than manometric data, indicating that manometric pressure amplitudes reflect direct contact of the catheter with the gastric wall. We conclude that the ACWs are central to gastric mixing, and may also play an indirect role in gastric emptying through local alterations in common cavity pressure.

Sedation and analgesia for colonoscopy : patient tolerance, pain, and cardiorespiratory parameters

BACKGROUND Colonoscopy is generally performed with the patient sedated and receiving analgesics. However, the benefit of the most often used combination of intravenous midazolam and pethidine on patient tolerance and pain and its cardiorespiratory risk have not been fully defined. METHODS In this double-blind prospective study, 150 outpatients undergoing routine colonoscopy were randomly assigned to receive either (1) low-dose midazolam (35 micrograms/kg) and pethidine (700 micrograms/kg in 48 patients, 500 micrograms/kg in 102 patients), (2) midazolam and placebo pethidine, or (3) pethidine and placebo midazolam. RESULTS Tolerance (visual analog scale, 0 to 100 points: 0 = excellent; 100 = unbearable) did not improve significantly more in group 1 compared with group 2 (7 points; 95% confidence interval [-2-17]) and group 3 (2 points; 95% confidence interval [-7-12]). Similarly, pain was not significantly improved in group 1 as compared with the other groups. Male gender (p < 0.001) and shorter duration of the procedure (p = 0.004), but not amnesia, were associated with better patient tolerance and less pain. Patient satisfaction was similar in all groups. Oxygen desaturation and hypotension occurred in 33% and 11%, respectively, with a similar frequency in all three groups. CONCLUSIONS In this study, the combination of low-dose midazolam and pethidine does not improve patient tolerance and lessen pain during colonoscopy as compared with either drug given alone. When applying low-dose midazolam, oxygen desaturation and hypotension do not occur more often after combined use of both drugs. For the individual patient, sedation and analgesia should be based on the endoscopists clinical judgement.

Scintigraphic validation of a magnetic resonance imaging method to study gastric emptying of a solid meal in humans

Background We have previously used a magnetic resonance imaging (MRI) method to study gastric emptying of liquids. So far, however, it has not possible to assess solid gastric emptying with this technique. Aims To validate scintigraphically MRI as a method for measuring emptying of a mixed solid/liquid meal. Methods In eight healthy subjects, gastric emptying of a solid/liquid (SM) and a liquid meal (LM) of identical energy content and macronutrient composition was studied by scintigraphy and MRI for 120 minutes. Results MRI and scintigraphy agreed with respect to emptying profiles (intraclass correlation coefficient (RI) SM: 0.988, RI, LM: 0.917), t1/2 (SMMRI: 129 (9), SMScinti: 123 (11) minutes, NS; LMMRI: 100 (7), LMScinti: 110 (8) minutes, NS) and AUC (SMMRI: 8999 (232), SMScinti: 8788 (277) min%, NS; LMMRI: 8819 (368), LMScinti: 8891 (321) min%, NS). Conclusions MRI can be used to measure reliably gastric emptying not only of liquid but also of mixed solid/liquid meals in humans.

Role of cholecystokinin in the regulation of liquid gastric emptying and gastric motility in humans: studies with the CCK antagonist loxiglumide

Background—Exogenous cholecystokinin (CCK) inhibits antral motility and slows gastric emptying (GE) but the effect of endogenous CCK on the gastric motor mechanisms responsible for GE remains unclear. Methods—The effect of the CCK-A antagonist loxiglumide (LOX) on GE and motility was studied using magnetic resonance imaging in six healthy volunteers after ingestion of 500 ml Intralipid 10% (550 kcal). Subjects were studied in the supine position on two occasions during intravenous infusion of LOX (66 μmol/kg/h for 10 min followed by 22 μmol/kg/h) or placebo. GE was determined every 15 minutes using transaxial abdominal scans and motility was studied by means of 120 coronal scans, 1.2 seconds apart. For each coronal image the proximal and distal (antral) diameters were measured at a fixed point in the stomach to determine contraction frequency (ACF) and amplitude (AMP). Results—GE was faster during LOX infusion than placebo (t1/2 31 (22) versus 115 (67) minutes, p<0.03). There was little variation in the diameter of the proximal stomach with either LOX or placebo. In the distal stomach marked contractile activity was observed during LOX (ACF 2.9 (0.2) versus 1.5 (2.9) during placebo, p<0.01). AMP also increased during LOX compared with placebo (56 (22)% versus 27 (16)%, p<0.001). Conclusion—The increases in antral motility are likely to contribute to the acceleration of GE and suggest that CCK may regulate GE by acting on the distal stomach although an effect on the proximal stomach cannot be excluded.

Optimized and combined T1 and B1 mapping technique for fast and accurate T1 quantification in contrast-enhanced abdominal MRI

Fast T1 mapping techniques are a valuable means of quantitatively assessing the distribution and dynamics of intravenously or orally applied paramagnetic contrast agents (CAs) by noninvasive imaging. In this study a fast T1 mapping technique based on the variable flip angle (VFA) approach was optimized for accurate T1 quantification in abdominal contrast‐enhanced (CE) MRI. Optimization methods were developed to maximize the signal‐to‐noise ratio (SNR) and ensure effective RF and gradient spoiling, as well as a steady state, for a defined T1 range of 100–800 ms and a limited acquisition time. We corrected B1 field inhomogeneities by performing an additional measurement using an optimized fast B1 mapping technique. High‐precision in vitro and abdominal in vivo T1 maps were successfully generated at a voxel size of 2.8 × 2.8 × 15 mm3 and a temporal resolution of 2.3 s per T1 map on 1.5T and 3T MRI systems. The application of the proposed fast T1 mapping technique in abdominal CE‐MRI enables noninvasive quantification of abdominal tissue perfusion and vascular permeability, and offers the possibility of quantitatively assessing dilution, distribution, and mixing processes of labeled solutions or drugs in the gastrointestinal tract. Magn Reson Med 57:568–576, 2007.

Non-invasive measurement of gastric accommodation in humans

Gastric accommodation describes the reduction in gastric tone and increase in compliance that follows ingestion of a meal and involves at least two responses: “receptive relaxation” which allows the stomach to accept a volume load without a significant rise in gastric pressure and “adaptive relaxation” which modulates gastric tone in response to the specific properties of the meal ingested. However, there are considerable technical difficulties in measuring the accommodation process. The current standard barostat studies, and other methods such as conventional and three dimensional ultrasound, or single photon emission computed tomography have significant disadvantages. Preliminary findings from the development and validation of a new magnetic resonance imaging technique that addresses many of the deficiencies of previous methods are presented.