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Use of wireless motility capsule to determine gastric emptying and small intestinal transit times in critically ill trauma patients
Journal of Critical Care (2012) 27, 534.e7–534.e12
Use of wireless motility capsule to determine gastric emptying and small intestinal transit times in critically ill trauma patients☆,☆☆,★ Stefan Rauch MD a,⁎, Kristine Krueger MD b , Alparslan Turan MD c , Jing You MS d , Norbert Roewer MD a , Daniel I. Sessler MD c a
Department of Anesthesiology, University of Würzburg, Germany Digestive Health Center, University of Louisville, Louisville, Kentucky c Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio d Departments of Quantitative Health Sciences and Outcomes Research, Cleveland Clinic b
Keywords: Anesthesia; Critical care; Capsule endoscopy; Enteral nutrition; Gastrointestinal transit time; Intestinal motility
Abstract Purpose: The purpose of this study is to use a novel wireless motility capsule to compare gastric emptying and small bowel transit times in critically ill trauma patients and healthy volunteers. Materials and Methods: We evaluated gastric emptying, small bowel transit time, and total intestinal transit time in 8 critically ill trauma patients. These data were compared with those obtained in 87 healthy volunteers from a separate trial. Data were obtained with a motility capsule that wirelessly transmitted pH, pressure, and temperature to a recorder attached to each subject's abdomen. Results: The gastric emptying time was significantly longer in critically ill patients (median, 13.9; interquartile range [IQR], 6.6-48.3 hours) than in healthy volunteers (median, 3.0; IQR, 2.5-3.9 hours), P b .001. The small bowel transit time in critically ill patients was significantly longer than in healthy volunteers (median, 6.7 hours; IQR, 4.4-8.5 hours vs median, 3.8 hours; IQR, 3.1-4.7 hours), P = .01. Furthermore, the capsules passed after 10 (IQR, 8.5-13) days in the critical care group and 1.2 (IQR, 0.9-1.9) days in healthy volunteers (P b .001). Conclusions: Both gastric emptying and small bowel transit were delayed in critically ill trauma patients. © 2012 Elsevier Inc. All rights reserved.
☆
Support: This work was supported by departmental funds. None of the authors has a personal financial interest related to this research. ★ Received from the Department of Anesthesiology, University of Würzburg, Würzburg, University of Louisville, Louisville, Kentucky; and the Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio. ⁎ Corresponding author. Tel.: +49 7161 64 0. E-mail address: [email protected] (S. Rauch). URL: http://www.or.org/ (S. Rauch). ☆☆
0883-9441/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcrc.2011.12.002
1. Introduction Delayed gastric emptying is a well-known problem in critically ill patients [1-7] and is associated with feeding disturbances and inadequate nutrition. However, evaluating gastrointestinal function remains challenging in critically ill patients who are mechanically ventilated. Many tests that are
534.e8 practical and accurate under standardized, controlled conditions often fail in the critical care setting. For example, the consensus recommendations for gastric emptying scintigraphy that have been published recently [8] are impractical in intubated patients because they recommend low-fat, eggwhite meal with imaging at 0, 1, 2, and 4 hours after meal ingestion. Another test, the lactulose hydrogen breath test, relies on prompt bacterial breakdown of lactulose in the colon; however, changes in bacterial flora—which are presumably common in critical care patients—can produce false transit times [9]. The 13C-octanoic acid breath test was reported by Ritz et al [4] as successful when used bedside to measure gastric emptying. However, manometry only assesses the upper gastrointestinal function, mainly esophagus, stomach, and proximal small bowel. Finally, video capsule technology has been used to determine small bowel transit time and pathomorphology in critically ill patients, although inadequate battery lifespan of the capsule (approximately 8-10 hours) could prevent complete examination in some cases [10]. An alternative technique, wireless capsule technology, may be useful for evaluating gastrointestinal motility in critical care patients. There are reports of using wireless capsule technology to measure intestinal temperature, pressure, and pH dating to the 1950s [11-13], but a brief communication in Nature in 2000 by Iddan launched the era of video capsule endoscopy in humans [14]. A newly developed motility capsule for assessing gastric emptying in patients with suspected gastroparesis has been available since 2006 [15-20]. It is a wireless capsule that transmits pH, pressure, and temperature (Fig. 1). We describe the first use of a novel motility capsule to compare gastric emptying and small bowel transit times in critically ill trauma patients with intracranial hemorrhage with times recorded previously in healthy volunteers. Second, we compared critically ill patients and volunteers on whole-gut transit time.
Fig. 1 SmartPill GI Monitoring Capsule; SmartPill, Inc, Buffalo, NY.
S. Rauch et al.
2. Materials and methods This prospective cohort study (NCT01159002) was approved by the Human Studies Committee of the University of Louisville, and authorized representatives of participating patients provided written informed consent. All hospital intensive care units (ICUs) were screened for patients twice daily by the principal investigator. Patients were enrolled within 36 hours of ICU admission. Eligible patients were intubated, ventilated, and had an Acute Physiology, Age, Chronic Health Evaluation score of greater than 25. All had major trauma and had an intracranial hemorrhage. Patients were excluded if they were younger than 18 years, had open abdominal trauma or inflammatory bowel disease, had a history of complicated (eg, total or partial gastrectomy, colectomy) or unknown abdominal surgery, or presented with clinical evidence of ileus or suspected obstruction. Patients with a pacemaker were also excluded because the capsule we used is not recommended for use in these patients. We enrolled 8 patients who were sedated with propofol (25-50 μg·kg−1 ·min−1 ) or midazolam and were given intravenous morphine/fentanyl intermittently. Patients were maintained supine, with the head of the bed elevated 30°. Positioning of the motility capsule (SmartPill GI Monitoring Capsule; SmartPill, Inc, Buffalo, NY) was coupled with the medically necessary feeding tube placement 2 days after patients were admitted to an ICU. The capsule was inserted with a delivery device (AdvanCE, Mentor, Ohio) into the esophagus using a laryngoscope to overcome the narrowing of the hypopharynx caused by the endotracheal tube and then advanced blindly into the stomach. The capsule was deployed into the stomach, and its position was confirmed radiographically. Intestinal feeding was delayed for 12 hours after capsule insertion. Data were transmitted to a recorder attached to the patient over a 5-day period. MotiliGI software (MotiliGI 1.3.1; SmartPill, Inc) (Fig. 2) was used to calculate gastric emptying. The transition from stomach to small bowel was marked by an abrupt pH rise (N3 pH units) from gastric baseline to a pH greater than 4 as well as a change in pressure patterns before emptying [21-23]. Pressure recordings showed high-amplitude phasic contractions just before the capsule's emptying from the stomach. The pH change marked the end of the gastric pressure analysis window and the beginning of the small bowel pressure analysis window. Small bowel transit time was calculated from the time the capsule entered the duodenum until it reached the cecum characterized by a drop in pH and pressure changes. Pressure patterns are characterized as high-amplitude phasic gastric contractions, mean peak amplitude, and mean contractions per minute. Mean peak amplitude (between 10 and 300 mm Hg) is the sum of amplitudes/number of contractions. The control group consisted of 87 healthy volunteers with no history of major abdominal surgery. They were studied in a separate, multicenter trial, NCT001282884, which was approved by the local institutional review board. Each subject gave informed consent before enrollment. After an overnight
Use of wireless motility capsule
534.e9
Fig. 2 SmartPill pH, pressure and temperature tracing. The green tracing and axis on the right show the pH tracing. The red tracing and axis on the left show pressure profile as recorded by the capsule. Temperature is shown in blue. Gastric emptying time is marked with a solid vertical line. Before emptying from the stomach, there are high-amplitude pressure contractions and a rapid rise in pH.
fast, volunteers ingested a monitoring capsule with 50 mL of water and afterward drank 250 mL Ensure (Abbott Laboratories, Abbott Park, Ill) with an additional 120 mL water. They then fasted for approximately 8 hours after capsule ingestion. Volunteers were asked to remain seated for the first 8 hours but were then permitted nonstrenous ambulatory activity. Total gastrointestinal transit time was calculated from the time the capsule was placed until it passed from the body.
2.1. Statistical analysis Demographics were summarized using means and standard deviations or frequencies and were compared for balance by Student t or Fisher exact test, as appropriate. Primary outcomes of gastric emptying time and small bowel transit time were compared between the critically ill patients and the healthy volunteers with Wilcoxon rank sum tests. To account for simultaneous testing on 2 outcomes while maintaining a type I error of 0.05, we used a significance criterion of P b .025 for each of the 2 primary outcomes (Bonferroni adjustment). The corresponding median differences between critically ill patients and healthy volunteers were estimated with the corresponding 97.5% confidence interval (CI). With 8 critically ill patients and 87 controls, the study had approximately 85% power at the .025 significance level to detect a difference of 2.5 or more hours in gastric emptying and small bowel transit times between critically ill patients and volunteers, assuming a standard deviation of 2 hours. 2.1.1. Secondary outcome We also compared critically ill patients and healthy volunteers on the whole-gut transit time using the Wilcoxon rank sum test. In addition, the median difference and 95% CI were estimated.
SAS software version 9.2.2 for Windows (SAS Institute, Cary, NC) was used for the power analysis. R software version 2.12.0 for Windows (The R Foundation for Statistical Computing, Vienna, Austria) was used for all the other analyses. Values were expressed as median and interquartile range (IQR), unless otherwise specified.
3. Results Demographic characteristics were well balanced between critically ill patients and healthy volunteers (Table 1). Analgesia, sedation, and vasopressor requirements were similar among the intensive care patients. None of the patients were given proton-pump inhibitor or prokinetic medication. They only received H2 blockers per hospital protocol.
Table 1 Demographic and morphometric characteristics, and illness scores
Sex, male/female Age (y) Height (cm) Weight (kg) APACHE III score Glasgow Coma Scale score
Critical care (n = 8)
Healthy (n = 87)
P⁎
6/2 40 ± 11 176 ± 12 82 ± 20 41 ± 8 8±2
48/39 37 ± 12 172 ± 11 77 ± 16 NA NA
.46 ⁎⁎ .51 .32 .60 – –
APACHE III, Acute Physiology, Age, Chronic Health Evaluation prognostic system; NA, not applicable. Data are presented as mean ± SD or frequency. ⁎ Student t test, unless specified. ⁎⁎ Fisher exact test.
534.e10
S. Rauch et al.
The gastric emptying time was significantly longer in critically ill patients (median, 13.9 hours; IQR, 6.6-48.3 hours; range, 4.3-74.3 hours) than in healthy volunteers (median, 3.0 hours; IQR, 2.5-3.9 hours; range, 1.7-17.1 hours), P b .001; the corresponding median difference was estimated as 10.9 hours (97.5% CI, 2.8-69.3). The small bowel transit time in critically ill patients (median, 6.7 hours; IQR, 4.4-8.6 hours; range, 3.4-13.8 hours) was significantly longer than in healthy volunteers (median, 3.8 hours; IQR, 3.1-4.7 hours; range, 1.8-13.5 hours), P = .01; the estimated median difference was 2.7 hours (97.5% CI, 0.2-5.1). Furthermore, the capsules passed after 10 (IQR, 8.5-13) days in the critical care group and 1.2 (IQR, 0.9-1.9) days in healthy volunteers (median difference, 8.8 days; 95% CI, 6.9-11.0; P b .001) (Table 2). The mean high-amplitude phasic gastric pressure in critical care patients was 66.5 mm Hg (IQR, 15.1-102 mm Hg). The mean pressure in the small bowel (ileum) before entering the cecum was 17.5 mm Hg (IQR, 14.2-24.2 mm Hg). The mean pressure in the cecum was 2.3 mm Hg (IQR, 1.3-2.8 mm Hg). The mean peak amplitude was 8.0 mm Hg (IQR, 5.3-9.2 mm Hg) in the stomach, 14.6 mm Hg (IQR, 9.5-18.9 mm Hg) in the small bowel, and 11.8 mm Hg (IQR, 10.0-12.5 mm Hg) in the colon. The mean number of contractions per minute was 1.4 (IQR, 0.8-1.8) in the stomach, 3.2 (IQR, 2.5-3.5) in the small bowel, and 1.6 (IQR, 1.2-1.9) in the colon. The mean high-amplitude phasic gastric pressure in the healthy volunteers was 30 mm Hg (IQR, 5.0-43.0 mm Hg). The mean pressure in the small bowel (ileum) before entering the cecum was 19.1 mm Hg (IQR, 16.0-23.1 mm Hg). The mean pressure in the cecum was 37.6 mm Hg (IQR, 30.444.8 mm Hg). The mean peak amplitude in the healthy volunteers was 21.3 mm Hg (IQR, 19.4-25.0 mm Hg) in the stomach, 18.3 mm Hg (IQR, 16.8-20.1 mm Hg) in the small bowel, and 41.1 mm Hg (IQR, 38.5-45.5 mm Hg) in the colon. The mean number of contractions per minute was 1.1 (IQR, 0.7-1.6) in the stomach, 3.4 (IQR, 2.4-4.3) in the small bowel, and 0.7 (IQR, 0.4-0.9) in the colon. In the critical care patients, the average gastric pH before the capsule's emptying was 2.9 (IQR, 2.1-3.9). The average pH in the small bowel after pyloric passage was 6.7 (IQR,
Table 2 Gastric emptying time, small bowel and whole-gut transit time
Gastric emptying time (h) Small bowel transit time (h) Whole-gut transit time (d)
Critical care (n = 8)
Healthy (n = 87)
P
13.9 [6.6-48.3]
3.0 [2.5-3.9]
b.001
6.7 [4.4-8.6]
3.8 [3.1-4.7]
.01
10 [8.5-13]
1.2 [0.9-1.2]
b.001
Data presented as median [IQR].
6.2-7.1). The pH at the end of the small bowel transition before entering the cecum was 7.7 (IQR, 7.5-8.2). Cecal pH was 6.6 (IQR, 6.3-7.0). The average pH over the entire recording time was 5.1 ± 1.7 in the stomach, 7.8 ± 0.5 in the small bowel, and 7.7 ± 0.5 in the colon. In the volunteers, the average gastric pH before the capsule's emptying was 1.61 ± 0.63. The pH in the small bowel (duodenum) was 6.6 ± 1.7. The pH in the ileum was 7.9 ± 2.2, and in the cecum, 6.8 ± 0.3. The average pH over the whole recording time was (mean ± SD) 3.0 ± 0.9 in the stomach, 7.0 ± 0.5 in the small bowel, and 6.9 ± 0.7 in the colon. There were no complications associated with the insertion of the capsules or any other aspect of the study.
4. Discussion Gastric emptying of the monitoring capsules took significantly longer in trauma patients than in the healthy volunteers. Our results are thus generally consistent with previous work suggesting that gastric emptying is delayed in ventilated critically ill patients. For example, Ritz et al [4] found that halfgastric emptying time was significantly delayed in 45% of unselected ICU patients (median, 155 minutes; IQR, 130-220) using the 13C-octanoic acid breath test. Nguyen et al [24] found that 78% of their study population had impaired gastric emptying (median, 102 minutes; IQR, 62-258) measured by scintigraphy. In a study of paracetamol absorption, 16 (59%) of 27 patients had prolonged gastric emptying [25]. Kao et al [2] reported an 80% incidence of abnormal gastric emptying halftime of a liquid meal (57 ± 21 minutes) in 35 patients with traumatic brain injury. Unlike gastric emptying, which can be evaluated with various approaches, little is known about small intestinal motility in severely injured patients because the small bowel is relatively inaccessible to examination because of length, location, and tortuosity. Small bowel transit time was significantly prolonged in our critically ill patients: 6.7 vs 3.8 hours. Furthermore, the variability was greater in the ICU patients (IQR, 4.1 hours vs 1.6 hours), and 1 subject in each group had a small bowel transit time greater than 13 hours. The current results differ from those in our previous study in which small bowel transit time (median, 5.1 hours; IQR, 3.97.7 hours) was not significantly delayed in ventilated patients with isolated intracranial hemorrhage compared with healthy patients [10]. The difference could be explained by the fact that we did not include patients with severe brain injuries (Glasgow Coma Scale b6) or severe blunt abdominal injuries and shock. These are clinical situations that are associated with higher gastrointestinal complications (eg, ileus) and delayed transit times. Motility capsule technology has been validated when comparing gastric emptying in gastroparetic and healthy subjects. Kuo et al [19] showed in their study that there is a correlation (r = 0.73) between the gastric emptying of the
Use of wireless motility capsule capsule and transit of a radiolabeled meal (gastric scintigraphy). The study from Cassilly et al [16] compared the emptying of the capsule to the traditional measurements of gastric function assessed with gastric emptying scintigraphy and antroduodenal manometry. They demonstrated in healthy subjects that the emptying of the capsule correlated with scintigraphy (r = 0.98). It emptied from the stomach with the occurrence of high-amplitude antral contractions. Antral phase III seems to be important for moving capsules from the stomach. It also depends on the size of the nondigestible solid (eg, capsule). Markers that are smaller than 4 mm are more likely independent from antral phase III motor activity [16,18]. The influence of food and nondigestible solids on gastric emptying has been evaluated in different studies. Studies in healthy subjects have shown that emptying of the capsule occurred faster while fasting, without meals [22]. Further studies have shown that gastric emptying is more delayed with a meal than with water [16,26]. In general, gastric emptying of the capsules remains physiologically despite the influence of different feeding regimens in healthy volunteers. Our results are limited by the small number of critically ill patients, although the population was relatively homogeneous. Another limitation was that we excluded patients with increased intraabdominal pressure, open abdominal injury, and exploratory laparotomies. Although it would be interesting to study those pathologic entities that are associated with more gastrointestinal complications and disturbed motility, we did not because a lodged capsule—which is more likely in these patients—would have required surgical removal. We measured gastric emptying and small bowel transit time only once during the ICU stay because it is not possible to start a new capsule examination until the previous one has passed from the body. Although delayed gastric emptying is most common in the first 3 days after ICU admission [27, 28], we cannot exclude disturbance of intestinal motility later in the critical care course. Of course, both enteral feeding and antiacid therapies can alter intraluminal pH, complicating identification of the capsule's transition from the stomach to small intestine. Despite the use of H2 blockers, all of our patients had a distinct pH pattern to identify the passage of the capsule. Nguyen et al [24] has shown in a retrospective study that morphine/midazolam and propofol can alter gastric emptying. It seems that patients under propofol-based sedation have a lower incidence of delayed gastric emptying. Although sedation and analgesia requirements were similar among the critically ill group, we cannot exclude that the pharmacologic effect of propofol/midazolam and fentanyl/morphine could have contributed to the prolonged gastric emptying time and small bowel transit time.
5. Conclusions Gastric emptying and small bowel transit times were markedly prolonged in critically ill trauma patients with
534.e11 intracranial hemorrhage, compared with normal volunteers. Physicians caring for critically ill patients should consider small intestinal dysfunction, along with delayed gastric emptying.
Acknowledgments The investigators also thank Nancy Alsip, PhD, for editing the manuscript (Office of Clinical Research Services and Support, University of Louisville).
References [1] Heyland DK, Tougas G, King D, et al. Impaired gastric emptying in mechanically ventilated, critically ill patients. Intensive Care Med 1996;22:1339-44. [2] Kao CH, ChangLai SP, Chieng PU, et al. Gastric emptying in headinjured patients. Am J Gastroenterol 1998;93:1108-12. [3] Ott L, Young B, Phillips R, et al. Altered gastric emptying in the headinjured patient: relationship to feeding intolerance. J Neurosurg 1991;74:738-42. [4] Ritz MA, Fraser R, Edwards N, et al. Delayed gastric emptying in ventilated critically ill patients: measurement by 13 C-octanoic acid breath test. Crit Care Med 2001;29:1744-9. [5] Ritz MA, Fraser R, Tam W, et al. Impacts and patterns of disturbed gastrointestinal function in critically ill patients. Am J Gastroenterol 2000;95:3044-52. [6] Cook D, Heyland D, Griffith L, et al. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.[see comment]. Crit Care Med 1999;27:2812-7. [7] Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994;330:377-81. [8] Abell TL, Camilleri M, Donohoe K, et al. Consensus recommendations for gastric emptying scintigraphy: a joint report of the American Neurogastroenterology and Motility Society and the Society of Nuclear Medicine. J Nucl Med Technol 2008;36:44-54. [9] Simren M, Stotzer PO. Use and abuse of hydrogen breath tests. Gut 2006;55:297-303. [10] Rauch S, Krueger K, Turan A, et al. Determining small intestinal transit time and pathomorphology in critically ill patients using video capsule technology. Intensive Care Med 2009;35:1054-9. [11] Farrar JT, Zworykin VK, Baum J. Pressure-sensitive telemetering capsule for study of gastrointestinal motility. Science 1957;126: 975-6. [12] Mackay RS, Jacobson B. Endoradiosonde. Nature 1957;179:1239-40. [13] Nöller HG. Die Endoradiosonde. Dtsch Med Wochenschr 1960;85: 1707-13. [14] Iddan G, Meron G, Glukhovsky A, et al. Wireless capsule endoscopy. Nature 2000;405:417. [15] Camilleri M, Thorne NK, Ringel Y, et al, Wireless pH-motility capsule for colonic transit: prospective comparison with radiopaque markers in chronic constipation. Neurogastroenterol Motil 22:874-882, e233, 2010. [16] Cassilly D, Kantor S, Knight LC, et al. Gastric emptying of a nondigestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil 2008;20:311-9. [17] Kloetzer L, Chey WD, McCallum RW, et al, Motility of the antroduodenum in healthy and gastroparetics characterized by wireless motility capsule. Neurogastroenterol Motil 22:527-533, e117, 2010
534.e12 [18] Kuo B, Maneerattanaporn M, Lee AA, et al: Generalized transit delay on wireless motility capsule testing in patients with clinical suspicion of gastroparesis, small intestinal dysmotility, or slow transit constipation. Dig Dis Sci, Epub Date 2011/06/01. [19] Kuo B, McCallum RW, Koch KL, et al. Comparison of gastric emptying of a nondigestible capsule to a radio-labelled meal in healthy and gastroparetic subjects. Aliment Pharmacol Ther 2008;27:186-96. [20] Rao SS, Kuo B, McCallum RW, et al. Investigation of colonic and whole-gut transit with wireless motility capsule and radiopaque markers in constipation. Clin Gastroenterol Hepatol 2009;7:537-44. [21] Evans DF, Pye G, Bramley R, et al. Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 1988;29: 1035-41. [22] Mojaverian P, Chan K, Desai A, et al. Gastrointestinal transit of a solid indigestible capsule as measured by radiotelemetry and dual gamma scintigraphy. Pharm Res 1989;6:719-24.
S. Rauch et al. [23] Mojaverian P, Ferguson RK, Vlasses PH, et al. Estimation of gastric residence time of the Heidelberg capsule in humans: effect of varying food composition. Gastroenterology 1985;89:392-7. [24] Nguyen NQ, Chapman MJ, Fraser RJ, et al. The effects of sedation on gastric emptying and intra-gastric meal distribution in critical illness. Intensive Care Med 2008;34:454-60. [25] Tarling MM, Toner CC, Withington PS, et al. A model of gastric emptying using paracetamol absorption in intensive care patients.[see comment]. Intensive Care Med 1997;23:256-60. [26] Smith HJ, Feldman M. Influence of food and marker length on gastric emptying of indigestible radiopaque markers in healthy humans. Gastroenterology 1986;91:1452-5. [27] Mentec H, Dupont H, Bocchetti M, et al. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med 2001;29:1955-61. [28] Nguyen NQ, Chapman MJ, Fraser RJ, et al. Erythromycin is more effective than metoclopramide in the treatment of feed intolerance in critical illness. Crit Care Med 2007;35:483-9.
Use of wireless motility capsule to determine gastric emptying and small intestinal transit times in critically ill trauma patients☆,☆☆,★ Stefan Rauch MD a,⁎, Kristine Krueger MD b , Alparslan Turan MD c , Jing You MS d , Norbert Roewer MD a , Daniel I. Sessler MD c a
Department of Anesthesiology, University of Würzburg, Germany Digestive Health Center, University of Louisville, Louisville, Kentucky c Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio d Departments of Quantitative Health Sciences and Outcomes Research, Cleveland Clinic b
Keywords: Anesthesia; Critical care; Capsule endoscopy; Enteral nutrition; Gastrointestinal transit time; Intestinal motility
Abstract Purpose: The purpose of this study is to use a novel wireless motility capsule to compare gastric emptying and small bowel transit times in critically ill trauma patients and healthy volunteers. Materials and Methods: We evaluated gastric emptying, small bowel transit time, and total intestinal transit time in 8 critically ill trauma patients. These data were compared with those obtained in 87 healthy volunteers from a separate trial. Data were obtained with a motility capsule that wirelessly transmitted pH, pressure, and temperature to a recorder attached to each subject's abdomen. Results: The gastric emptying time was significantly longer in critically ill patients (median, 13.9; interquartile range [IQR], 6.6-48.3 hours) than in healthy volunteers (median, 3.0; IQR, 2.5-3.9 hours), P b .001. The small bowel transit time in critically ill patients was significantly longer than in healthy volunteers (median, 6.7 hours; IQR, 4.4-8.5 hours vs median, 3.8 hours; IQR, 3.1-4.7 hours), P = .01. Furthermore, the capsules passed after 10 (IQR, 8.5-13) days in the critical care group and 1.2 (IQR, 0.9-1.9) days in healthy volunteers (P b .001). Conclusions: Both gastric emptying and small bowel transit were delayed in critically ill trauma patients. © 2012 Elsevier Inc. All rights reserved.
☆
Support: This work was supported by departmental funds. None of the authors has a personal financial interest related to this research. ★ Received from the Department of Anesthesiology, University of Würzburg, Würzburg, University of Louisville, Louisville, Kentucky; and the Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio. ⁎ Corresponding author. Tel.: +49 7161 64 0. E-mail address: [email protected] (S. Rauch). URL: http://www.or.org/ (S. Rauch). ☆☆
0883-9441/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcrc.2011.12.002
1. Introduction Delayed gastric emptying is a well-known problem in critically ill patients [1-7] and is associated with feeding disturbances and inadequate nutrition. However, evaluating gastrointestinal function remains challenging in critically ill patients who are mechanically ventilated. Many tests that are
534.e8 practical and accurate under standardized, controlled conditions often fail in the critical care setting. For example, the consensus recommendations for gastric emptying scintigraphy that have been published recently [8] are impractical in intubated patients because they recommend low-fat, eggwhite meal with imaging at 0, 1, 2, and 4 hours after meal ingestion. Another test, the lactulose hydrogen breath test, relies on prompt bacterial breakdown of lactulose in the colon; however, changes in bacterial flora—which are presumably common in critical care patients—can produce false transit times [9]. The 13C-octanoic acid breath test was reported by Ritz et al [4] as successful when used bedside to measure gastric emptying. However, manometry only assesses the upper gastrointestinal function, mainly esophagus, stomach, and proximal small bowel. Finally, video capsule technology has been used to determine small bowel transit time and pathomorphology in critically ill patients, although inadequate battery lifespan of the capsule (approximately 8-10 hours) could prevent complete examination in some cases [10]. An alternative technique, wireless capsule technology, may be useful for evaluating gastrointestinal motility in critical care patients. There are reports of using wireless capsule technology to measure intestinal temperature, pressure, and pH dating to the 1950s [11-13], but a brief communication in Nature in 2000 by Iddan launched the era of video capsule endoscopy in humans [14]. A newly developed motility capsule for assessing gastric emptying in patients with suspected gastroparesis has been available since 2006 [15-20]. It is a wireless capsule that transmits pH, pressure, and temperature (Fig. 1). We describe the first use of a novel motility capsule to compare gastric emptying and small bowel transit times in critically ill trauma patients with intracranial hemorrhage with times recorded previously in healthy volunteers. Second, we compared critically ill patients and volunteers on whole-gut transit time.
Fig. 1 SmartPill GI Monitoring Capsule; SmartPill, Inc, Buffalo, NY.
S. Rauch et al.
2. Materials and methods This prospective cohort study (NCT01159002) was approved by the Human Studies Committee of the University of Louisville, and authorized representatives of participating patients provided written informed consent. All hospital intensive care units (ICUs) were screened for patients twice daily by the principal investigator. Patients were enrolled within 36 hours of ICU admission. Eligible patients were intubated, ventilated, and had an Acute Physiology, Age, Chronic Health Evaluation score of greater than 25. All had major trauma and had an intracranial hemorrhage. Patients were excluded if they were younger than 18 years, had open abdominal trauma or inflammatory bowel disease, had a history of complicated (eg, total or partial gastrectomy, colectomy) or unknown abdominal surgery, or presented with clinical evidence of ileus or suspected obstruction. Patients with a pacemaker were also excluded because the capsule we used is not recommended for use in these patients. We enrolled 8 patients who were sedated with propofol (25-50 μg·kg−1 ·min−1 ) or midazolam and were given intravenous morphine/fentanyl intermittently. Patients were maintained supine, with the head of the bed elevated 30°. Positioning of the motility capsule (SmartPill GI Monitoring Capsule; SmartPill, Inc, Buffalo, NY) was coupled with the medically necessary feeding tube placement 2 days after patients were admitted to an ICU. The capsule was inserted with a delivery device (AdvanCE, Mentor, Ohio) into the esophagus using a laryngoscope to overcome the narrowing of the hypopharynx caused by the endotracheal tube and then advanced blindly into the stomach. The capsule was deployed into the stomach, and its position was confirmed radiographically. Intestinal feeding was delayed for 12 hours after capsule insertion. Data were transmitted to a recorder attached to the patient over a 5-day period. MotiliGI software (MotiliGI 1.3.1; SmartPill, Inc) (Fig. 2) was used to calculate gastric emptying. The transition from stomach to small bowel was marked by an abrupt pH rise (N3 pH units) from gastric baseline to a pH greater than 4 as well as a change in pressure patterns before emptying [21-23]. Pressure recordings showed high-amplitude phasic contractions just before the capsule's emptying from the stomach. The pH change marked the end of the gastric pressure analysis window and the beginning of the small bowel pressure analysis window. Small bowel transit time was calculated from the time the capsule entered the duodenum until it reached the cecum characterized by a drop in pH and pressure changes. Pressure patterns are characterized as high-amplitude phasic gastric contractions, mean peak amplitude, and mean contractions per minute. Mean peak amplitude (between 10 and 300 mm Hg) is the sum of amplitudes/number of contractions. The control group consisted of 87 healthy volunteers with no history of major abdominal surgery. They were studied in a separate, multicenter trial, NCT001282884, which was approved by the local institutional review board. Each subject gave informed consent before enrollment. After an overnight
Use of wireless motility capsule
534.e9
Fig. 2 SmartPill pH, pressure and temperature tracing. The green tracing and axis on the right show the pH tracing. The red tracing and axis on the left show pressure profile as recorded by the capsule. Temperature is shown in blue. Gastric emptying time is marked with a solid vertical line. Before emptying from the stomach, there are high-amplitude pressure contractions and a rapid rise in pH.
fast, volunteers ingested a monitoring capsule with 50 mL of water and afterward drank 250 mL Ensure (Abbott Laboratories, Abbott Park, Ill) with an additional 120 mL water. They then fasted for approximately 8 hours after capsule ingestion. Volunteers were asked to remain seated for the first 8 hours but were then permitted nonstrenous ambulatory activity. Total gastrointestinal transit time was calculated from the time the capsule was placed until it passed from the body.
2.1. Statistical analysis Demographics were summarized using means and standard deviations or frequencies and were compared for balance by Student t or Fisher exact test, as appropriate. Primary outcomes of gastric emptying time and small bowel transit time were compared between the critically ill patients and the healthy volunteers with Wilcoxon rank sum tests. To account for simultaneous testing on 2 outcomes while maintaining a type I error of 0.05, we used a significance criterion of P b .025 for each of the 2 primary outcomes (Bonferroni adjustment). The corresponding median differences between critically ill patients and healthy volunteers were estimated with the corresponding 97.5% confidence interval (CI). With 8 critically ill patients and 87 controls, the study had approximately 85% power at the .025 significance level to detect a difference of 2.5 or more hours in gastric emptying and small bowel transit times between critically ill patients and volunteers, assuming a standard deviation of 2 hours. 2.1.1. Secondary outcome We also compared critically ill patients and healthy volunteers on the whole-gut transit time using the Wilcoxon rank sum test. In addition, the median difference and 95% CI were estimated.
SAS software version 9.2.2 for Windows (SAS Institute, Cary, NC) was used for the power analysis. R software version 2.12.0 for Windows (The R Foundation for Statistical Computing, Vienna, Austria) was used for all the other analyses. Values were expressed as median and interquartile range (IQR), unless otherwise specified.
3. Results Demographic characteristics were well balanced between critically ill patients and healthy volunteers (Table 1). Analgesia, sedation, and vasopressor requirements were similar among the intensive care patients. None of the patients were given proton-pump inhibitor or prokinetic medication. They only received H2 blockers per hospital protocol.
Table 1 Demographic and morphometric characteristics, and illness scores
Sex, male/female Age (y) Height (cm) Weight (kg) APACHE III score Glasgow Coma Scale score
Critical care (n = 8)
Healthy (n = 87)
P⁎
6/2 40 ± 11 176 ± 12 82 ± 20 41 ± 8 8±2
48/39 37 ± 12 172 ± 11 77 ± 16 NA NA
.46 ⁎⁎ .51 .32 .60 – –
APACHE III, Acute Physiology, Age, Chronic Health Evaluation prognostic system; NA, not applicable. Data are presented as mean ± SD or frequency. ⁎ Student t test, unless specified. ⁎⁎ Fisher exact test.
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S. Rauch et al.
The gastric emptying time was significantly longer in critically ill patients (median, 13.9 hours; IQR, 6.6-48.3 hours; range, 4.3-74.3 hours) than in healthy volunteers (median, 3.0 hours; IQR, 2.5-3.9 hours; range, 1.7-17.1 hours), P b .001; the corresponding median difference was estimated as 10.9 hours (97.5% CI, 2.8-69.3). The small bowel transit time in critically ill patients (median, 6.7 hours; IQR, 4.4-8.6 hours; range, 3.4-13.8 hours) was significantly longer than in healthy volunteers (median, 3.8 hours; IQR, 3.1-4.7 hours; range, 1.8-13.5 hours), P = .01; the estimated median difference was 2.7 hours (97.5% CI, 0.2-5.1). Furthermore, the capsules passed after 10 (IQR, 8.5-13) days in the critical care group and 1.2 (IQR, 0.9-1.9) days in healthy volunteers (median difference, 8.8 days; 95% CI, 6.9-11.0; P b .001) (Table 2). The mean high-amplitude phasic gastric pressure in critical care patients was 66.5 mm Hg (IQR, 15.1-102 mm Hg). The mean pressure in the small bowel (ileum) before entering the cecum was 17.5 mm Hg (IQR, 14.2-24.2 mm Hg). The mean pressure in the cecum was 2.3 mm Hg (IQR, 1.3-2.8 mm Hg). The mean peak amplitude was 8.0 mm Hg (IQR, 5.3-9.2 mm Hg) in the stomach, 14.6 mm Hg (IQR, 9.5-18.9 mm Hg) in the small bowel, and 11.8 mm Hg (IQR, 10.0-12.5 mm Hg) in the colon. The mean number of contractions per minute was 1.4 (IQR, 0.8-1.8) in the stomach, 3.2 (IQR, 2.5-3.5) in the small bowel, and 1.6 (IQR, 1.2-1.9) in the colon. The mean high-amplitude phasic gastric pressure in the healthy volunteers was 30 mm Hg (IQR, 5.0-43.0 mm Hg). The mean pressure in the small bowel (ileum) before entering the cecum was 19.1 mm Hg (IQR, 16.0-23.1 mm Hg). The mean pressure in the cecum was 37.6 mm Hg (IQR, 30.444.8 mm Hg). The mean peak amplitude in the healthy volunteers was 21.3 mm Hg (IQR, 19.4-25.0 mm Hg) in the stomach, 18.3 mm Hg (IQR, 16.8-20.1 mm Hg) in the small bowel, and 41.1 mm Hg (IQR, 38.5-45.5 mm Hg) in the colon. The mean number of contractions per minute was 1.1 (IQR, 0.7-1.6) in the stomach, 3.4 (IQR, 2.4-4.3) in the small bowel, and 0.7 (IQR, 0.4-0.9) in the colon. In the critical care patients, the average gastric pH before the capsule's emptying was 2.9 (IQR, 2.1-3.9). The average pH in the small bowel after pyloric passage was 6.7 (IQR,
Table 2 Gastric emptying time, small bowel and whole-gut transit time
Gastric emptying time (h) Small bowel transit time (h) Whole-gut transit time (d)
Critical care (n = 8)
Healthy (n = 87)
P
13.9 [6.6-48.3]
3.0 [2.5-3.9]
b.001
6.7 [4.4-8.6]
3.8 [3.1-4.7]
.01
10 [8.5-13]
1.2 [0.9-1.2]
b.001
Data presented as median [IQR].
6.2-7.1). The pH at the end of the small bowel transition before entering the cecum was 7.7 (IQR, 7.5-8.2). Cecal pH was 6.6 (IQR, 6.3-7.0). The average pH over the entire recording time was 5.1 ± 1.7 in the stomach, 7.8 ± 0.5 in the small bowel, and 7.7 ± 0.5 in the colon. In the volunteers, the average gastric pH before the capsule's emptying was 1.61 ± 0.63. The pH in the small bowel (duodenum) was 6.6 ± 1.7. The pH in the ileum was 7.9 ± 2.2, and in the cecum, 6.8 ± 0.3. The average pH over the whole recording time was (mean ± SD) 3.0 ± 0.9 in the stomach, 7.0 ± 0.5 in the small bowel, and 6.9 ± 0.7 in the colon. There were no complications associated with the insertion of the capsules or any other aspect of the study.
4. Discussion Gastric emptying of the monitoring capsules took significantly longer in trauma patients than in the healthy volunteers. Our results are thus generally consistent with previous work suggesting that gastric emptying is delayed in ventilated critically ill patients. For example, Ritz et al [4] found that halfgastric emptying time was significantly delayed in 45% of unselected ICU patients (median, 155 minutes; IQR, 130-220) using the 13C-octanoic acid breath test. Nguyen et al [24] found that 78% of their study population had impaired gastric emptying (median, 102 minutes; IQR, 62-258) measured by scintigraphy. In a study of paracetamol absorption, 16 (59%) of 27 patients had prolonged gastric emptying [25]. Kao et al [2] reported an 80% incidence of abnormal gastric emptying halftime of a liquid meal (57 ± 21 minutes) in 35 patients with traumatic brain injury. Unlike gastric emptying, which can be evaluated with various approaches, little is known about small intestinal motility in severely injured patients because the small bowel is relatively inaccessible to examination because of length, location, and tortuosity. Small bowel transit time was significantly prolonged in our critically ill patients: 6.7 vs 3.8 hours. Furthermore, the variability was greater in the ICU patients (IQR, 4.1 hours vs 1.6 hours), and 1 subject in each group had a small bowel transit time greater than 13 hours. The current results differ from those in our previous study in which small bowel transit time (median, 5.1 hours; IQR, 3.97.7 hours) was not significantly delayed in ventilated patients with isolated intracranial hemorrhage compared with healthy patients [10]. The difference could be explained by the fact that we did not include patients with severe brain injuries (Glasgow Coma Scale b6) or severe blunt abdominal injuries and shock. These are clinical situations that are associated with higher gastrointestinal complications (eg, ileus) and delayed transit times. Motility capsule technology has been validated when comparing gastric emptying in gastroparetic and healthy subjects. Kuo et al [19] showed in their study that there is a correlation (r = 0.73) between the gastric emptying of the
Use of wireless motility capsule capsule and transit of a radiolabeled meal (gastric scintigraphy). The study from Cassilly et al [16] compared the emptying of the capsule to the traditional measurements of gastric function assessed with gastric emptying scintigraphy and antroduodenal manometry. They demonstrated in healthy subjects that the emptying of the capsule correlated with scintigraphy (r = 0.98). It emptied from the stomach with the occurrence of high-amplitude antral contractions. Antral phase III seems to be important for moving capsules from the stomach. It also depends on the size of the nondigestible solid (eg, capsule). Markers that are smaller than 4 mm are more likely independent from antral phase III motor activity [16,18]. The influence of food and nondigestible solids on gastric emptying has been evaluated in different studies. Studies in healthy subjects have shown that emptying of the capsule occurred faster while fasting, without meals [22]. Further studies have shown that gastric emptying is more delayed with a meal than with water [16,26]. In general, gastric emptying of the capsules remains physiologically despite the influence of different feeding regimens in healthy volunteers. Our results are limited by the small number of critically ill patients, although the population was relatively homogeneous. Another limitation was that we excluded patients with increased intraabdominal pressure, open abdominal injury, and exploratory laparotomies. Although it would be interesting to study those pathologic entities that are associated with more gastrointestinal complications and disturbed motility, we did not because a lodged capsule—which is more likely in these patients—would have required surgical removal. We measured gastric emptying and small bowel transit time only once during the ICU stay because it is not possible to start a new capsule examination until the previous one has passed from the body. Although delayed gastric emptying is most common in the first 3 days after ICU admission [27, 28], we cannot exclude disturbance of intestinal motility later in the critical care course. Of course, both enteral feeding and antiacid therapies can alter intraluminal pH, complicating identification of the capsule's transition from the stomach to small intestine. Despite the use of H2 blockers, all of our patients had a distinct pH pattern to identify the passage of the capsule. Nguyen et al [24] has shown in a retrospective study that morphine/midazolam and propofol can alter gastric emptying. It seems that patients under propofol-based sedation have a lower incidence of delayed gastric emptying. Although sedation and analgesia requirements were similar among the critically ill group, we cannot exclude that the pharmacologic effect of propofol/midazolam and fentanyl/morphine could have contributed to the prolonged gastric emptying time and small bowel transit time.
5. Conclusions Gastric emptying and small bowel transit times were markedly prolonged in critically ill trauma patients with
534.e11 intracranial hemorrhage, compared with normal volunteers. Physicians caring for critically ill patients should consider small intestinal dysfunction, along with delayed gastric emptying.
Acknowledgments The investigators also thank Nancy Alsip, PhD, for editing the manuscript (Office of Clinical Research Services and Support, University of Louisville).
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