Capnographic monitoring of respiratory activity improves safety of sedation for endoscopic cholangiopancreatography and ultrasonography.

BACKGROUND & AIMS: The Joint Commission on the Accreditation of Healthcare Organizations recommends ventilation monitoring during procedural sedation for gastrointestinal endoscopy. We sought to determine whether intervention, based on a microstream capnography-based ventilation monitoring system that has been shown to function as an early warning system for hypoxemia, would decrease hypoxemia during endoscopy. METHODS: Subjects undergoing elective endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasonography (EUS) under procedural sedation with a combination of opioid and benzodiazepine were randomly assigned to either a study arm in which the endoscopy team was blinded to capnography or an open arm in which the endoscopy team was prompted of capnographic changes. The primary end point was the occurrence of hypoxemia; secondary end points were the occurrences of severe hypoxemia, apnea, and oxygen supplementation. RESULTS: A total of 263 subjects were enrolled; 247 were analyzed for efficacy. The numbers of hypoxemic events in the blinded and open arms were 132 and 69, respectively (P < .001). Thirty-five percent of all hypoxemic events occurred with completely normal ventilation. Hypoxemia developed in 69% of patients in the blinded arm compared with 46% in the open arm (P < .001). Severe hypoxemia percentages in the blinded and open arms were 31% and 15% (P = .004), for apnea were 63% and 41% (P < .001), for oxygen supplementation were 67% and 52% (P = .02), and for recurrent hypoxemia after oxygen supplementation were 38% and 18% (P = .01), respectively. CONCLUSIONS: Capnographic monitoring of respiratory activity improves patient safety during procedural sedation for elective ERCP/EUS by reducing the frequency of hypoxemia, severe hypoxemia, and apnea.

Bispectral index monitoring of conscious sedation with the combination of meperidine and midazolam during endoscopy.

UNLABELLED: background & aims: Current practice guidelines strongly recommend differentiation of deep from moderate sedation during endoscopy. Standard methods of sedation monitoring are labor-intense. Bispectral index monitoring (BIS) is widely used during anesthesia, but its benefits during conscious sedation are controversial. Thus, we performed a prospective observational study to assess its ability for detecting deep sedation during endoscopy. METHODS: Patients presenting for elective outpatient endoscopy were monitored simultaneously with the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) and BIS. A combination of a narcotic and benzodiazepine was used, with the target being moderate sedation and analgesia. Deep sedation was defined by MOAA/S score of 1-2 and BIS score of

Comparison of endoscopic ultrasound chronic pancreatitis criteria to the endoscopic secretin-stimulated pancreatic function test.

Endosonography (EUS) has emerged as a major diagnostic tool in pancreatic imaging. Direct tests of pancreatic function are considered the most sensitive and accurate method to establish a diagnosis of chronic pancreatitis (CP), particularly when imaging studies are inconclusive. The aim of this study was to compare current EUS CP criteria with our newly described, purely endoscopic, secretin-stimulated pancreatic function test (ePFT). Fifty-six patients (25 male, mean age = 44 years) who were referred for evaluation/treatment of chronic abdominal pain with or without CP underwent both EUS and ePFT. The EUS protocol included the following: (1) EUS images were obtained in a standardized fashion from both gastric and duodenal stations, and (2) EUS images were scored independently by one of three therapeutic endoscopists for 0--9 parenchymal/ductal criteria as follows: 0-3 = normal, 4-5 = equivocal, >/=6 = definite CP. Endoscopic pancreatic function test (ePFT) protocol included the following: (1) upper endoscopy, (2) intravenous synthetic porcine secretin (0.2 mcg/kg, ChiRhoClin, Inc.) after test dose, (3) duodenal fluid aspirated every 15 min for 1 h, and (4) autoanalyzed for [HCO3] cutpoint of 80 mEq/L. According to EUS, 33 were normal, 13 equivocal, and 10 definite for CP. The mean peak [HCO3 -] range (in mEq/L) for each group was normal CP (83.7, range = 58-118), equivocal CP (68, range = 30-88), and definite CP (56, range=19-84). Using a peak [HCO3 -] of

Comparison of the secretin stimulated endoscopic pancreatic function test to retrograde pancreatogram.

Duodenal intubation techniques with hormonal stimulation are the most accurate at diagnosing early chronic pancreatitis. Pancreatography (ERCP), the radiologic gold standard, can accurately diagnose chronic pancreatitis, but is expensive, may expose the patient to radiation, and/or induce acute pancreatitis. We have developed an endoscopic pancreatic function test (ePFT) that can assess pancreatic secretory function during upper endoscopy. We sought to determine the accuracy of the endoscopic secretin pancreatic function test using retrograde pancreatogram as the gold standard. Patients referred to The Pancreas Clinic for the evaluation and management of chronic abdominal pain and suspected chronic pancreatitis who had both endoscopic function testing and pancreatic duct imaging (ERCP) were studied. Pancreatograms were scored for duct morphologic characteristics (Cambridge classification) and compared to peak bicarbonate concentration in secretin stimulated duodenal juice. The ePFT consisted of a test dose of intravenous synthetic porcine secretin (0.2 microg), full-dose intravenous secretin (0.2 microg/kg) over 1 min, (3) upper endoscopy with moderate sedation, (4) gastric fluid aspirated and discarded, (5) duodenal fluid aspirations at 0, 15, 45, and 60 min after secretin injection, and (6) fluid analysis with lab autoanalyzer for bicarbonate concentration (historical normal cutpoint >80 mEq/L). Thirty-six patients had both the endoscopic function test and ERCP. Seventeen had chronic abdominal pain with normal pancreatograms, and nineteen had chronic abdominal pain with abnormal pancreatograms, consistent with chronic pancreatitis. The sensitivity and specificity of the endoscopic function test were 94% and 79%, respectively. The positive and negative predictive values were 80% and 94%, respectively. Overall agreement with ERCP was 86%. The ePFT with synthetic porcine secretin has excellent correlation with abnormal pancreatogram (chronic pancreatitis). Furthermore, a normal bicarbonate (negative function test, HCO(3) >80 mEq/L) essentially rules out chronic pancreatitis as a diagnostic cause of abdominal pain. Endoscopic pancreatic function testing may decrease the need for ERCP in patients with chronic abdominal pain.

The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT).

BACKGROUND: We have developed a purely endoscopic collection method for the assessment of pancreatic secretory function (ePFT). The pancreatic secretory effects of sedation medications utilized during endoscopic procedures are not completely known. AIMS: To study the effect of moderate sedation on the exocrine pancreas gland in a prospective, randomized trial. METHODS: Healthy volunteers were randomized by computers to one of two treatments (A-no sedation, B-sedation) in period 1 and crossed-over to the other treatment in period 2 with a minimal washout interval of 7 days. Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram. Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope every 5 min for 1 h and sent on ice to our hospital laboratory for the measurement of pancreatic secretory electrolyte concentrations by autoanalyzer. RESULTS: A total of 17 healthy volunteers were enrolled. Sixteen subjects (8 males and 8 females) completed the randomized prospective trial. Median intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg, respectively. Maximum pancreatic juice flow occurred during the early phase of secretion and maximum bicarbonate concentration occurred during the late phase of secretion. Analysis of the electrolyte composition of the endoscopically collected duodenal drainage fluid revealed a constant cation concentration for both sodium and potassium over the 1 h collection period. The anions, chloride and bicarbonate, exhibited a reciprocal relationship identical to that seen in traditional gastroduodenal tube collection studies. There was no statistical difference observed between the sedation and no sedation groups. The estimated total bicarbonate output (area under curve, AUC) for the sedated and non-sedated groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range 4,323-6563) respectively (p= 0.0656). The mean peak bicarbonate concentrations for sedated (n = 8) versus non-sedated (n = 8) groups were 103 +/- 11 meq/L (range 78-125) and 106 +/- 11 meq/L (range 87-138), respectively (p= 0.1346). There was excellent correlation of peak bicarbonate concentrations when sedation and no sedation groups were compared (r= 0.744, p < 0.05; Spearman rank correlation). There were no episodes of pancreatitis. CONCLUSIONS: (a) Moderate sedation used for upper endoscopy does not effect the clinical diagnostic parameters (peak bicarbonate concentration or total bicarbonate output) utilized to diagnose pancreatic insufficiency. (b) Analysis of duodenal drainage fluid collected endoscopically after synthetic secretin stimulation produces an identical pancreatic secretory curve described with traditional gastroduodenal tube collection methods.

Endoscopic ultrasound errors in esophageal cancer.

BACKGROUND: Previous assessments of endoscopic ultrasound (EUS) classification of esophageal cancer are dominated by symptomatic patients with advanced stage disease. Fewer data exist on EUS errors in a cohort balanced between early and advanced disease. PURPOSE: Assess EUS errors in classification of esophageal cancer in a more balanced cohort, and identify clinical and tumor characteristics associated with EUS errors. METHODS: A total of 266 patients underwent EUS and esophagectomy without preoperative chemoradiotherapy. Pathologic classification of disease extent: 108 (41%) tumors were confined to the esophageal wall (pTis-pT2, pN0, pM0); 158 (59%) were advanced beyond (pT3-pT4, pN1, or pM1). Logistic regression analysis was performed to identify correlates of error in T classification and disease extent using 10 clinical and tumor characteristics (gender, age, dysphagia, weight loss, tumor length, location, traversability, morphology, histopathologic type, and histologic grade). RESULTS: EUS erroneously predicted pathologic T (pT) in 119 patients (45%). When T classification was dichotomized into tumors whose depth of invasion was not beyond the muscularis propria (pTis-pT2) and those beyond (pT3-pT4), errors occurred in 42 patients (16%). EUS erroneously predicted N classification in 67 patients (25%), and was insensitive to the presence of distant metastases. EUS misclassified disease extent in 40 patients (15%). Logistic regression analysis indicated that weight loss and tumor length were the only clinical and tumor characteristics correlated with EUS errors; more weight loss was associated with decreased odds of misclassification, while the odds of misclassification were four to six times greater for intermediate length tumors than for shorter tumors. CONCLUSIONS: EUS errors, particularly in predicting pT, are more frequent than previously reported. Weight loss and tumor length are the only clinical and tumor characteristics correlated with EUS errors.

In vivo colonoscopic optical coherence tomography for transmural inflammation in inflammatory bowel disease.

BACKGROUND & AIMS: Transmural inflammation, a distinguishing feature of Crohn's disease (CD), cannot be assessed by conventional colonoscopy with mucosal biopsy. Our previous ex vivo study of histology-correlated optical coherence tomography (OCT) imaging on colectomy specimens of CD and ulcerative colitis (UC) showed that disruption of the layered structure of colon wall on OCT is an accurate marker for transmural inflammation of CD. We performed an in vivo colonoscopic OCT in patients with a clinical diagnosis of CD or UC using the previously established, histology-correlated OCT imaging criterion. METHODS: OCT was performed in 40 patients with CD (309 images) and 30 patients with UC (292 images). Corresponding endoscopic features of mucosal inflammation were documented. Two gastroenterologists blinded to endoscopic and clinical data scored the OCT images independently to assess the feature of disrupted layered structure. RESULTS: Thirty-six CD patients (90.0%) had disrupted layered structure, whereas 5 UC patients (16.7%) had disrupted layered structure (P < .001). Using the clinical diagnosis of CD or UC as the gold standard, the disrupted layered structure on OCT indicative of transmural inflammation had a diagnostic sensitivity and specificity of 90.0% (95% CI: 78.0%, 96.5%) and 83.3% (95% CI: 67.3%, 93.3%) for CD, respectively. The kappa coefficient in the interpretation of OCT images was 0.80 (95% CI: 0.75, 0.86, P < .001). CONCLUSIONS: In vivo colonoscopic OCT is feasible and accurate to detect disrupted layered structure of the colon wall indicative of transmural inflammation, providing a valuable tool to distinguish CD from UC.

Ex vivo histology-correlated optical coherence tomography in the detection of transmural inflammation in Crohn's disease.

BACKGROUND AND AIMS: Distinguishing Crohn's disease (CD) from ulcerative colitis (UC) can be difficult. Transmural inflammation, a key feature of CD, cannot be assessed by conventional colonoscopy with biopsy. Optical coherence tomography (OCT) provides high-resolution, cross-sectional images of the gut wall and might become a new diagnostic tool. The aims of this study were to perform histology-correlated OCT on surgical specimens of CD and UC and to determine its diagnostic accuracy. METHODS: Colectomy specimens from patients with a preoperative diagnosis of CD (N = 24) or UC (N = 24) were studied with OCT in the operating room. OCT and histopathology were assessed blindly, and diagnostic accuracy of OCT was assessed. RESULTS: Eight preoperatively identified UC patients (33%) with transmural inflammation on postoperative histology were diagnosed with CD, and all 8 had a disrupted layered structure on OCT, a characteristic feature of transmural disease. Sixteen UC patients (67%) had superficial inflammation on histology; of them, 13 (81%) had an intact layered structure on OCT. All 24 preoperative CD patients had transmural inflammation on histology, and 23 (96%) had a disrupted layered structure on OCT. Of 585 histology-OCT image sets from the 48 patients, 152 sets (26%) had transmural inflammation on histology. The sensitivity and specificity for OCT to detect transmural disease were 86% and 91%, respectively. CONCLUSIONS: Transmural inflammation, as characterized by disruption of the layered structure of colon wall on OCT, is an accurate marker for the diagnosis of CD. Ex vivo OCT predicted transmural inflammation on postoperative histopathology.

An endoscopic pancreatic function test with synthetic porcine secretin for the evaluation of chronic abdominal pain and suspected chronic pancreatitis.

BACKGROUND: Pancreatic function tests are the most reliable methods for the diagnosis or exclusion of chronic pancreatitis in patients without obvious radiologic changes, but they are cumbersome, time consuming, and unavailable in clinical practice. Synthetic porcine secretin, a 27 amino acid peptide identical to the biologic form, is available for exocrine function testing. This study examined the utility of a simple, newly developed, purely endoscopic pancreatic function test with synthetic porcine secretin. METHODS: Three groups of patients were studied: patients with chronic abdominal pain with and without risk factors for chronic pancreatitis, and patients with advanced chronic pancreatitis. All patients with abdominal pain had "pancreatic type" pain for greater than 6 months and negative radiographic imaging studies. All patients with chronic pancreatitis had advanced disease based on retrograde pancreatography and/or CT findings. Participants underwent the following protocol: (1) standard endoscopy to the descending duodenum with the patient under conscious sedation; (2) intravenous administration of secretin (0.2 microgram/kg); (3) endoscopic duodenal fluid collection at 0, 15, 30, 45, and 60 minutes after secretin injection; and (4) fluid analysis for bicarbonate concentration. RESULTS: Eighteen patients were studied (5 abdominal pain without risk factors, 7 abdominal pain with risk factors, and 6 advanced chronic pancreatitis). Median peak (interquartile range) bicarbonate concentrations in meq/L for each group were, respectively, 87 (6, range 84-108), 72 (10, range 68-90), and 35 (27, range 18-88). Median peak bicarbonate concentration values for the 3 groups are significantly different (p = 0.010; Kruskal-Wallis test). Bicarbonate secretion in patients with chronic pancreatitis was markedly reduced compared with that in patients with abdominal pain without risk factors (p = 0.038; the Fisher exact test). The secretory function curve for patients with abdominal pain with risk factors was markedly abnormal, resembling the attenuated secretory curve seen in patients with chronic pancreatitis. The test was safe and well tolerated. CONCLUSIONS: A simple endoscopic pancreatic function test with synthetic porcine secretin appears to distinguish patients with known chronic pancreatitis from those with chronic abdominal pain without chronic pancreatitis. This simple, practical endoscopic test can be performed during upper endoscopy and may decrease the need for invasive procedures in patients with abdominal pain and normal radiographic imaging studies.

An endoscopic pancreatic function test with cholecystokinin-octapeptide for the diagnosis of chronic pancreatitis.

BACKGROUND & AIMS: Current pancreatic function tests are cumbersome and unavailable to the clinical gastroenterologist. We have developed a function test that can be modified to a purely endoscopic collection method (ePFT). The aim of this study was to compare the endoscopic and traditional Dreiling tube collection methods. METHODS: Two separate groups of healthy subjects and patients with chronic pancreatitis underwent pancreatic function testing. One group underwent the endoscopic collection method (ePFT). Intravenous cholecystokinin (CCK 40 ng x kg(-1) x h(-1)) was started in preprocedure area. Duodenal fluid was collected with upper endoscope during endoscopy at 30, 40, 50, and 60 minutes during infusion. Another group underwent the traditional Dreiling collection method. Intravenous CCK was started in postprocedure area after endoscopic tube placement. Duodenal fluid was collected at 0, 20, 40, 60, and 80 minutes during infusion. Lipase concentration was determined (IU/L) on laboratory autoanalyzer. RESULTS: Seventy-three patients were studied. Thirty-four underwent endoscopic collection and 39 underwent Dreiling collection. The mean peak lipase concentrations (+/- standard deviation) for healthy subjects and patients with chronic pancreatitis in the endoscopic collection method group were 1612500 +/- 556152 IU/L and 369594 +/- 281624 IU/L, respectively (P < 0.001). The mean peak lipase concentrations (+/- standard deviation) for healthy subjects and patients with chronic pancreatitis in the Dreiling tube collection method group were 1670324 +/- 786731 IU/L and 478956 +/- 406061 IU/L, respectively (P < 0.001). There was no statistical difference between collection methods at distinguishing healthy subjects and patients with chronic pancreatitis. Receiver operating characteristic curves (ROC) for the endoscopic and Dreiling collection methods were 0.993 (standard error of mean, 0.009) and 0.921 (standard error of mean, 0.041). A lipase concentration cut point of 810600 IU/L distinguishes healthy subjects from patients with chronic pancreatitis with a sensitivity and specificity of 92% and 95%, respectively. The ePFT was safe, short in duration, minimized costs (US dollars 1890 vs. US dollars 2659), required small amounts of fluid for analysis (1-3 mL), and eliminated radiation exposure. CONCLUSIONS: Analysis of timed endoscopic aspirations of pancreatic juice after hormonal stimulation can distinguish healthy subjects from patients with chronic pancreatitis. This new endoscopic collection method (ePFT) is less cumbersome and more time efficient, when compared to traditional collection methods. The ePFT broadens the availability of function testing to the practicing clinical gastroenterologist.

Cholecystokinin-stimulated peak lipase concentration in duodenal drainage fluid: a new pancreatic function test.

OBJECTIVE: Hormonal stimulation with secretin or cholecystokinin (CCK) is the most sensitive means of assessing pancreatic function. Secretin is not available, and current CCK tests are cumbersome, requiring dual tube intubation and marker perfusion techniques. The aim of this study was to test the efficacy of a new CCK-stimulated pancreatic function test measuring peak lipase concentration. METHODS: A Dreiling gastroduodenal tube was inserted to the ligament of Treitz, and fluid was collected on ice for 80 min in four 20-min aliquots. CCK was infused i.v. at a constant rate of 40 ng/kg/h. Gastric aspirations were discarded. Duodenal aspirates were analyzed for volume and enzyme concentration with a clinical laboratory autoanalyzer. RESULTS: Nineteen healthy volunteers and 18 chronic pancreatitis patients were studied. Lipase concentration and secretory volume showed a peak response by 40 min of stimulation, whereas amylase response was variable. The mean peak lipase concentrations (+/-SEM) for normal volunteers and mild, moderate, and advanced chronic pancreatitis patients were 16.9+/-1.9, 7.9+/-1.7, 3.7+/-1.2, and 2.1+/-0.6 x 10 5 IU/L, respectively. Lower peak lipase concentrations were significantly associated with more advanced chronic pancreatitis (p < 0.001). The receiver operating characteristic curve area for all chronic pancreatitis patients was 0.944 (95% CI = 0.825-0.985). A peak lipase concentration of 780,000 IU/L provided a sensitivity and specificity of 0.833 and 0.867, respectively. This CCK test was well tolerated and without complications. CONCLUSIONS: Lipase concentration in duodenal fluid increases nearly 3-fold from baseline after CCK stimulation in healthy volunteers but is markedly reduced in patients with chronic pancreatic disease. Peak lipase concentration is a significant predictor of chronic pancreatitis and correlates with severity of pancreatic disease. Aspiration of duodenal drainage fluid with a Dreiling tube and analysis with a laboratory autoanalyzer are less cumbersome than marker perfusion and back titration techniques. Measurement of enzyme concentration instead of output could lead to the development of an endoscopic or through-the-scope screening method for assessing patients with suspected chronic pancreatitis or chronic abdominal pain.

Gastroenterologist-administered propofol versus meperidine and midazolam for advanced upper endoscopy: a prospective, randomized trial.

BACKGROUND & AIMS: Propofol is increasingly used for gastrointestinal endoscopy because of its rapid recovery profile. There has been no prospective, randomized comparison of gastroenterologist-administered propofol to meperidine and midazolam for endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. Additionally, its cost-effectiveness has not been studied. METHODS: Seventy-five randomized patients received either gastroenterologist-administered propofol (n = 38) or meperidine/midazolam (n = 37) for endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. Monitoring with capnography allowed for rapid titration of propofol at the earliest signs of respiratory depression. Visual analogue scales measured tolerance and satisfaction. A cost-effectiveness analysis was performed by using return to baseline for both activity and food intake 24 hours after the procedure as the effectiveness measure. RESULTS: The groups had similar physiological outcomes and satisfaction. Patients receiving propofol had shorter recovery times (P < 0.001) and a higher recovery of both baseline activity level and dietary intake 24 hours after the procedure (P = 0.028). With incremental cost-effectiveness analysis, gastroenterologist-administered propofol cost an additional $403.00 per additional patient at 100% of baseline for both activity level and food intake when compared with standard sedation and analgesia. Sensitivity analysis indicated that the only model in which propofol administration would become the dominant strategy was with its administration by a registered nurse. CONCLUSIONS: Gastroenterologist-administered propofol using monitoring with capnography is similar to meperidine/midazolam for both physiological outcomes and patient/endoscopist satisfaction. Propofol leads to significantly improved recovery of baseline activity and food intake 24 hours after the procedure. Our model suggests that propofol would be more cost-effective than meperidine and midazolam for endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography if registered nurse administration were possible.