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Szczupak M, Jankowska M, Jankowski B, Wierzchowska J, Kobak J, Szczupak P, Kosydar-Bochenek J, Krupa-Nurcek S. Prokinetic effect of erythromycin in the management of gastroparesis in critically ill patients-our experience and literature review. Front Med (Lausanne) 2024; 11:1440992. [PMID: 39314225 PMCID: PMC11416996 DOI: 10.3389/fmed.2024.1440992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 08/26/2024] [Indexed: 09/25/2024] Open
Abstract
Introduction Gastroparesis is a disorder characterized by impaired gastric emptying and the accumulation of food in the intestines without any clear mechanical cause. Gastroparesis in critical care patients is a prevalent issue in the intensive care unit. The disruption of normal gastrointestinal motility in critically ill patients is linked to a significant risk of intolerance to enteral feeding, colonization of the gastrointestinal tract with pathogenic bacterial strains, increased permeability of the intestinal wall, translocation of the intestinal microbiota, leading to progressive malnutrition, and potential development of bacterial infection. Materials and methods The literature was reviewed to assess the benefits and risks associated with the use of this medication. Aim The aim of the study was to treat the symptoms of gastroparesis and stimulate gastrointestinal motility. Consequently, the aim was to reduce the amount of backed-up food content in the stomach, accelerate gastrointestinal motility, and return to intestinal feeding. Results Gastroparesis is a frequent issue among patients in the intensive care unit. Critical illness can lead to gastrointestinal motility disorders, causing slowed gastric emptying. This increases the risk of problems such as intolerance to enteral feeding, regurgitation, and aspiration of gastrointestinal contents into the respiratory tract, as well as colonization of the gastrointestinal tract by pathogens. Over time, impaired intestinal absorption can result in malnutrition, necessitating the initiation of parenteral nutrition. Conclusion After analysis of the literature and published scientific reports, as well as considering their own research, it is evident that erythromycin, as a prokinetic drug, effectively enhances gastrointestinal motility. This contributes to stimulating gastric emptying in critically ill patients with gastroparesis who are hospitalized in an intensive care unit. The use of erythromycin in combination with metoclopramide and/or itopride hydrochloride allows for a synergistic effect, leading to the quickest possible return to enteral feeding.
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Affiliation(s)
- Mateusz Szczupak
- Department of Anesthesiology and Intensive Care, Copernicus Hospital, Gdansk, Poland
| | - Magdalena Jankowska
- Department of Anesthesiology and Intensive Care, Copernicus Hospital, Gdansk, Poland
| | - Bartłomiej Jankowski
- Department of Anesthesiology and Intensive Care, Copernicus Hospital, Gdansk, Poland
| | - Jolanta Wierzchowska
- Department of Anesthesiology and Intensive Care, Copernicus Hospital, Gdansk, Poland
| | - Jacek Kobak
- Department of Otolaryngology, Medical University of Gdansk, Gdansk, Poland
| | - Paweł Szczupak
- Department of Electrical Engineering and Computer Science, Rzeszow University of Technology, Rzeszow, Poland
| | - Justyna Kosydar-Bochenek
- Institute of Health Sciences, College of Medical Sciences of the University of Rzeszow, Rzeszow, Poland
| | - Sabina Krupa-Nurcek
- Department of Surgery, Institute of Medical Sciences, Medical College of Rzeszow University, Rzeszow, Poland
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Crone V, Møller MH, Baekgaard ES, Perner A, Bytzer P, Alhazzani W, Krag M. Use of prokinetic agents in hospitalised adult patients: A scoping review. Acta Anaesthesiol Scand 2023; 67:588-598. [PMID: 36847067 DOI: 10.1111/aas.14222] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 02/09/2023] [Indexed: 03/01/2023]
Abstract
BACKGROUND Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinetic agents in hospitalised patients. We hypothesised, that the body of evidence would be limited and derive from heterogeneous populations. METHODS We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement. We searched Medline, Embase, Epistemonikos and the Cochrane Library for studies assessing the use of prokinetic agents on any indication and outcome in adult hospitalised patients. We used a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence. RESULTS We included 102 studies with a total of 8830 patients. Eighty-six studies were clinical trials (84%), and 52 (60%) of these were conducted in the intensive care unit, with feeding intolerance as the main indication. In the non-intensive care setting the indications were wider; most studies assessed use of prokinetic agents before gastroscopy to improve visualisation. The most studied prokinetic agent was metoclopramide (49% of studies) followed by erythromycin (31%). In total 147 outcomes were assessed with only 67% of the included studies assessing patient-centred outcomes, and with gastric emptying as the most frequently reported outcome. Overall, the data provided no firm evidence on the balance between the desirable and undesirable effects of prokinetic agents. CONCLUSIONS In this scoping review, we found that the studies addressing prokinetic agents in hospitalised adults had considerable variations in indications, drugs and outcomes assessed, and that the certainty of evidence was judged to be low to very low.
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Affiliation(s)
- Vera Crone
- Department of Intensive Care, Holbaek Hospital, Holbaek, Denmark
| | - Morten Hylander Møller
- Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | | | - Anders Perner
- Department of Intensive Care, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Peter Bytzer
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
- Department of Gastroenterology, Zealand University Hospital, Køge, Denmark
| | - Waleed Alhazzani
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
- Department of Critical Care Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Mette Krag
- Department of Intensive Care, Holbaek Hospital, Holbaek, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Aziz M, Haghbin H, Gangwani MK, Weissman S, Patel AR, Randhawa MK, Samikanu LB, Alyousif ZA, Lee-Smith W, Kamal F, Nawras A, Howden CW. Erythromycin Improves the Quality of Esophagogastroduodenoscopy in Upper Gastrointestinal Bleeding: A Network Meta-Analysis. Dig Dis Sci 2023; 68:1435-1446. [PMID: 36112271 DOI: 10.1007/s10620-022-07698-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/12/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND/AIM Upper gastrointestinal bleeding (UGIB) usually requires esophagogastroduodenoscopy (EGD) for diagnostic and-potentially-therapeutic purposes. However, blood within the gastric lumen may hinder the procedure. Administration of prokinetics like erythromycin has shown efficacy. This network meta-analysis investigates the efficacy of this intervention prior to EGD. METHODS We performed a systematic literature search of Embase, PubMed/Medline, and other databases through March 8, 2022 to include randomized controlled trials (RCTs) comparing prokinetic use in EGD for UGIB. We used the DerSimonian-Laird approach to pool data and compare outcomes including need for repeat endoscopy and blood transfusion. Pooled prevalence of proportional outcomes, 95% confidence interval (CI), and p-values were calculated. RESULTS We included eight RCTs with four distinct intervention groups (erythromycin, placebo to erythromycin, nasogastric (NG) lavage and NG lavage + erythromycin) published between 2002 and 2020 with a total of 721 patients (mean age 60.0 ± 3.1 years; 73.2% male). The need for second look endoscopy was significantly lower with erythromycin than placebo (relative risk: 0.42, CI 0.22-0.83, p = 0.01). Using the frequentist approach, the combination of NG lavage and erythromycin (92.2) was rated highest, followed by erythromycin alone (73.1) for higher rates of empty stomach. Erythromycin was rated highest for lower need for packed red blood cell transfusion (72.8) as well as mean endoscopy duration (66.0). CONCLUSION Erythromycin improved visualization at EGD, reduced requirements for blood transfusion and repeat EGD, and shortened hospital stay. The combination of erythromycin and NG lavage showed reduced mortality.
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Affiliation(s)
- Muhammad Aziz
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA.
| | - Hossein Haghbin
- Division of Gastroenterology, Ascension Providence Southfield, Southfield, MI, USA
| | | | - Simcha Weissman
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Arti R Patel
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Manraj K Randhawa
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | - Luke B Samikanu
- Department of Medicine, Hackensack Meridian Health Palisades Medical Center, North Bergen, NJ, USA
| | | | - Wade Lee-Smith
- University of Toledo Libraries, University of Toledo, Toledo, OH, USA
| | - Faisal Kamal
- Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA
| | - Ali Nawras
- Division of Gastroenterology and Hepatology, University of Toledo, Toledo, OH, USA
| | - Colin W Howden
- Division of Gastroenterology, University of Tennessee College of Medicine, Memphis, TN, USA
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Adão D, Gois AF, Pacheco RL, Pimentel CF, Riera R. Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage. Cochrane Database Syst Rev 2023; 2:CD013176. [PMID: 36723439 PMCID: PMC9891197 DOI: 10.1002/14651858.cd013176.pub2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Upper endoscopy is the definitive treatment for upper gastrointestinal haemorrhage (UGIH). However, up to 13% of people who undergo upper endoscopy will have incomplete visualisation of the gastric mucosa at presentation. Erythromycin acts as a motilin receptor agonist in the upper gastrointestinal (GI) tract and increases gastric emptying, which may lead to better quality of visualisation and improved treatment effectiveness. However, there is uncertainty about the benefits and harms of erythromycin in UGIH. OBJECTIVES To evaluate the benefits and harms of erythromycin before endoscopy in adults with acute upper gastrointestinal haemorrhage, compared with any other treatment or no treatment/placebo. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 15 October 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs) that investigated erythromycin before endoscopy compared to any other treatment or no treatment/placebo before endoscopy in adults with acute UGIH. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were 1. UGIH-related mortality and 2. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. visualisation of gastric mucosa, 3. non-serious adverse events, 4. rebleeding, 5. blood transfusion, and 5. rescue invasive intervention. We used GRADE criteria to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 11 RCTs with 878 participants. The mean age ranged from 53.13 years to 64.5 years, and most participants were men (72.3%). One RCT included only non-variceal haemorrhage, one included only variceal haemorrhage, and eight included both aetiologies. We defined short-term outcomes as those occurring within one week of initial endoscopy. Erythromycin versus placebo Three RCTs (255 participants) compared erythromycin with placebo. There were no UGIH-related deaths. The evidence is very uncertain about the short-term effects of erythromycin compared with placebo on serious adverse events (risk difference (RD) -0.01, 95% confidence interval (CI) -0.04 to 0.02; 3 studies, 255 participants; very low certainty), all-cause mortality (RD 0.00, 95% CI -0.03 to 0.03; 3 studies, 255 participants; very low certainty), non-serious adverse events (RD 0.01, 95% CI -0.03 to 0.05; 3 studies, 255 participants; very low certainty), and rebleeding (risk ratio (RR) 0.63, 95% CI 0.13 to 2.90; 2 studies, 195 participants; very low certainty). Erythromycin may improve gastric mucosa visualisation (mean difference (MD) 3.63 points on 16-point ordinal scale, 95% CI 2.20 to 5.05; higher MD means better visualisation; 2 studies, 195 participants; low certainty). Erythromycin may also result in a slight reduction in blood transfusion (MD -0.44 standard units of blood, 95% CI -0.86 to -0.01; 3 studies, 255 participants; low certainty). Erythromycin plus nasogastric tube lavage versus no intervention/placebo plus nasogastric tube lavage Six RCTs (408 participants) compared erythromycin plus nasogastric tube lavage with no intervention/placebo plus nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin plus nasogastric tube lavage compared with no intervention/placebo plus nasogastric tube lavage on all-cause mortality (RD -0.02, 95% CI -0.08 to 0.03; 3 studies, 238 participants; very low certainty), visualisation of the gastric mucosa (standardised mean difference (SMD) 0.48 points on 10-point ordinal scale, 95% CI 0.10 to 0.85; higher SMD means better visualisation; 3 studies, 170 participants; very low certainty), non-serious adverse events (RD 0.00, 95% CI -0.05 to 0.05; 6 studies, 408 participants; very low certainty), rebleeding (RR 1.13, 95% CI 0.63 to 2.02; 1 study, 169 participants; very low certainty), and blood transfusion (MD -1.85 standard units of blood, 95% CI -4.34 to 0.64; 3 studies, 180 participants; very low certainty). Erythromycin versus nasogastric tube lavage Four RCTs (287 participants) compared erythromycin with nasogastric tube lavage. There were no UGIH-related deaths and no serious adverse events. The evidence is very uncertain about the short-term effects of erythromycin compared with nasogastric tube lavage on all-cause mortality (RD 0.02, 95% CI -0.05 to 0.08; 3 studies, 213 participants; very low certainty), visualisation of the gastric mucosa (RR 1.19, 95% CI 0.79 to 1.79; 2 studies, 198 participants; very low certainty), non-serious adverse events (RD -0.10, 95% CI -0.34 to 0.13; 3 studies, 213 participants; very low certainty), rebleeding (RR 0.77, 95% CI 0.40 to 1.49; 1 study, 169 participants; very low certainty), and blood transfusion (median 2 standard units of blood, interquartile range 0 to 4 in both groups; 1 study, 169 participants; very low certainty). Erythromycin plus nasogastric tube lavage versus metoclopramide plus nasogastric tube lavage One RCT (30 participants) compared erythromycin plus nasogastric tube lavage with metoclopramide plus nasogastric tube lavage. The evidence is very uncertain about the effects of erythromycin plus nasogastric tube lavage on all the reported outcomes (serious adverse events, visualisation of gastric mucosa, non-serious adverse events, and blood transfusion). AUTHORS' CONCLUSIONS We are unsure if erythromycin before endoscopy in people with UGIH has any clinical benefits or harms. However, erythromycin compared with placebo may improve gastric mucosa visualisation and result in a slight reduction in blood transfusion.
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Affiliation(s)
- Diego Adão
- Department of Medicine, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Aecio Ft Gois
- Cochrane Brazil, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil
| | - Rafael L Pacheco
- Cochrane Brazil, Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde, São Paulo, Brazil
| | | | - Rachel Riera
- Cochrane Brazil Rio de Janeiro, Cochrane Brazil, Petrópolis, Brazil
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Chen Y, Tai K, Lai P, Huang Y. Should we believe the benefit of intravenous erythromycin in critically ill adults with gastric feeding intolerance? Reinspecting the pieces of evidence from a series of meta‐analyses. JPEN J Parenter Enteral Nutr 2022; 46:1449-1454. [DOI: 10.1002/jpen.2352] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Revised: 02/06/2022] [Accepted: 02/10/2022] [Indexed: 11/12/2022]
Affiliation(s)
- Yi‐Ting Chen
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan
| | - Kuan‐Yu Tai
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan
| | - Pei‐Chun Lai
- Education Center, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan
| | - Yen‐Ta Huang
- Department of Surgery, National Cheng Kung University Hospital, College of Medicine National Cheng Kung University Tainan Taiwan
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Vijayaraghavan R, Maiwall R, Arora V, Choudhary A, Benjamin J, Aggarwal P, Jamwal KD, Kumar G, Joshi YK, Sarin SK. Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients. Dig Dis Sci 2022; 67:4223-4233. [PMID: 34392492 PMCID: PMC8364303 DOI: 10.1007/s10620-021-07185-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Accepted: 07/19/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND AIMS Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. METHODS Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. RESULTS Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality. CONCLUSIONS FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.
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Affiliation(s)
- Rajan Vijayaraghavan
- grid.418784.60000 0004 1804 4108Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070 India
| | - Rakhi Maiwall
- grid.418784.60000 0004 1804 4108Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070 India
| | - Vinod Arora
- grid.418784.60000 0004 1804 4108Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070 India
| | - Ashok Choudhary
- grid.418784.60000 0004 1804 4108Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070 India
| | - Jaya Benjamin
- grid.418784.60000 0004 1804 4108Department of Clinical Nutrition, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Prashant Aggarwal
- grid.418784.60000 0004 1804 4108Department of Anaesthesia and Critical Care, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kapil Dev Jamwal
- grid.464746.30000 0004 1761 4703Department of Gastroenterology, Artemis Hospitals, Gurugram, Haryana India
| | - Guresh Kumar
- grid.418784.60000 0004 1804 4108Department of Clinical Research, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Y. K. Joshi
- grid.418784.60000 0004 1804 4108Department of Clinical Nutrition, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv K. Sarin
- grid.418784.60000 0004 1804 4108Department of Hepatology, Institute of Liver and Biliary Sciences, D-1 Vasant Kunj, New Delhi, 110070 India
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Goelen N, Tack J, Janssen P. Erythromycin stimulates phasic gastric contractility as assessed with an isovolumetric intragastric balloon pressure measurement. Neurogastroenterol Motil 2021; 33:e13991. [PMID: 33025716 DOI: 10.1111/nmo.13991] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 08/24/2020] [Accepted: 08/26/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND A novel technique to assess gastric motility by measuring the pressure in a low-volume intragastric balloon was developed to monitor (disordered) motility. We previously showed that this technique allows measuring pharmacologically induced inhibition of motility. In this study, we assessed whether it is possible to measure pharmacologically induced stimulation of gastric motility using 200 mg erythromycin. Erythromycin is a highly effective stimulator of gastric emptying and contractility. METHODS After an overnight fast, a nasogastric balloon catheter was introduced in healthy subjects. After inflation with 120 ml of air, the catheter was connected to a pressure sensor. Intraballoon pressure was continuously recorded for 4 h. After a baseline recording of 2 h, 200 mg erythromycin was infused intravenously over 20 min while the recording continued for 2 h. Epigastric symptoms were surveyed on 100-mm visual analogue scales. Motility was quantified from the pressure recording as a gastric balloon motility index. Wilcoxon signed-rank tests were performed. Data are shown as median (interquartile range). KEY RESULTS Six subjects were enrolled and five completed the procedures (age: 28 (25-29) years, body mass index: 24.0 (23.8-24.5) kg m-2 ). One subject could not tolerate tube placement. Bloating, nausea, and epigastric sensation scores were 0 (0-3), 0 (0-1), and 1 (0-1) mm, respectively. Erythromycin significantly increased the motility index from 0.48 (0.41-0.51) to 0.79 (0.70-0.82) (p = 0.03). CONCLUSIONS AND INFERENCES Gastric motility assessed via pressure measurement in a low-volume intragastric balloon is able to detect pharmacologically stimulated motility in healthy subjects, which further validates this technique.
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Affiliation(s)
- Nick Goelen
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Pieter Janssen
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium.,VIPUN Medical, Mechelen, Belgium
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Shaikh N, Nainthramveetil MM, Nawaz S, Hassan J, Shible AA, Karic E, Singh R, Al Maslamani M. Optimal dose and duration of enteral erythromycin as a prokinetic: A surgical intensive care experience. Qatar Med J 2021; 2020:36. [PMID: 33447536 PMCID: PMC7802089 DOI: 10.5339/qmj.2020.36] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 06/06/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Enteral feeding has various advantages over parenteral feeding in critically ill patients. Acutely ill patients are at risk of developing enteral feeding intolerance. Prokinetic medications improve gastrointestinal mobility and enteral feed migration and absorption. Among the available prokinetic agents, erythromycin is the most potent. Erythromycin is used in different dosages and durations with variable efficacy. Intravenous erythromycin has an early and high rate of tachyphylaxis; hence, enteral route is preferred. Recently, the combination of prokinetic medications has been increasingly used because they accelerate the prokinetic action and decrease the adverse effects. AIM This study aimed to determine the optimal effective prokinetic dose and duration of administering enteral erythromycin in combination with metoclopramide in critically ill patients. PATIENTS AND METHODS This study has a prospective observation design. After obtaining permission from the medical research center of the institution, all patients in the surgical and trauma intensive care unit having enteral feed intolerance and those who were already on metoclopramide for 24 hour (h) were enrolled in the study. Patients' demographic data, diagnosis, surgical intervention, disease severity scores, erythromycin dose, duration of administration, any adverse effects, factors affecting erythromycin response, and outcome were recorded. All patients received 125 mg syrup erythromycin twice daily through a nasogastric tube (NGT). The NGT was clamped for 2 h, and half amount of previous enteral feeds was resumed. If the patient did not tolerate the feeds, the erythromycin dose was increased every 24 h in the increment of 250, 500, and 1000 mg (Figure 1). Statistical significance was considered at P < 0.05. A total of 313 patients were enrolled in the study. Majority of the patients were male, and the mean age was 45 years. RESULTS Majority (48.2%) of the patients (96) with feed intolerance were post laparotomy. Ninety percent (284) of the patients responded to prokinetic erythromycin therapy, and 54% received lower dose (125 mg twice daily). In addition, 14% had diarrhea, and none of these patients tested positive for Clostridium difficile toxin or multidrug resistance bacteria. The mean duration of erythromycin therapy was 4.98 days. The most effective prokinetic dose of erythromycin was 125 mg twice daily (P = 0.001). Erythromycin was significantly effective in patients with multiple organ dysfunction and shock (P = 0.001). Patients with high disease severity index and multiple organ dysfunction had significantly higher mortality (p < 0.05). Patients not responding to erythromycin therapy also had a significant higher mortality (p = 0.001). CONCLUSION Post-laparotomy patients had high enteral feed intolerance. Enteral erythromycin in combination with metoclopramide was effective in low dose and was required for short duration. Patients who did not tolerate feeds despite increasing dose of erythromycin had higher mortality.
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Affiliation(s)
- Nissar Shaikh
- Surgical Intensive care, Hamad Medical Corporation, Doha, Qatar E-mail:
| | | | - Shoaib Nawaz
- Surgical Intensive care, Hamad Medical Corporation, Doha, Qatar E-mail:
| | - Jazib Hassan
- Surgical Intensive care, Hamad Medical Corporation, Doha, Qatar E-mail:
| | - Ahmed A Shible
- Clinical Pharmacy, Hamad Medical Corporation, Doha, Qatar
| | - Edin Karic
- Critical Care, Al Wakrah Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Rajvir Singh
- Heart Hospital, Hamad Medical Corporation, Doha, Qatar
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Peng R, Li H, Yang L, Zeng L, Yi Q, Xu P, Pan X, Zhang L. The efficacy and safety of prokinetics in critically ill adults receiving gastric feeding tubes: A systematic review and meta-analysis. PLoS One 2021; 16:e0245317. [PMID: 33428672 PMCID: PMC7799841 DOI: 10.1371/journal.pone.0245317] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 12/28/2020] [Indexed: 12/13/2022] Open
Abstract
Background Intolerance to gastric feeding tubes is common among critically ill adults and may increase morbidity. Administration of prokinetics in the ICU is common. However, the efficacy and safety of prokinetics are unclear in critically ill adults with gastric feeding tubes. We conducted a systematic review to determine the efficacy and safety of prokinetics for improving gastric feeding tube tolerance in critically ill adults. Methods Randomized controlled trials (RCTs) were identified by systematically searching the Medline, Cochrane and Embase databases. Two independent reviewers extracted the relevant data and assessed the quality of the studies. We calculated pooled relative risks (RRs) for dichotomous outcomes and the mean differences (MDs) for continuous outcomes with the corresponding 95% confidence intervals (CIs). We assessed the risk of bias using the Cochrane risk-of-bias tool and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to rate the quality of the evidence. Results Fifteen RCTs met the inclusion criteria. A total of 10 RCTs involving 846 participants were eligible for the quantitative analysis. Most studies (10 of 13, 76.92%) showed that prokinetics had beneficial effects on feeding intolerance in critically ill adults. In critically ill adults receiving gastric feeding, prokinetic agents may reduce the ICU length of stay (MD -2.03, 95% CI -3.96, -0.10; P = 0.04; low certainty) and the hospital length of stay (MD -3.21, 95% CI -5.35, -1.06; P = 0.003; low certainty). However, prokinetics failed to improve the outcomes of reported adverse events and all-cause mortality. Conclusion As a class of drugs, prokinetics may improve tolerance to gastric feeding to some extent in critically ill adults. However, the certainty of the evidence suggesting that prokinetics reduce the ICU or hospital length of stay is low. Prokinetics did not significantly decrease the risks of reported adverse events or all-cause mortality among critically ill adults.
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Affiliation(s)
- Rong Peng
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
- Department of Clinical Nutrition, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Hailong Li
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Lijun Yang
- Department of General Practice Medicine, Affiliated Hospital of Chengdu University, Chengdu, Sichuan, China
| | - Linan Zeng
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Qiusha Yi
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Peipei Xu
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Xiangcheng Pan
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
| | - Lingli Zhang
- Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan, China
- * E-mail:
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10
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Charoensareerat T, Bhurayanontachai R, Sitaruno S, Navasakulpong A, Boonpeng A, Lerkiatbundit S, Pattharachayakul S. Efficacy and Safety of Enteral Erythromycin Estolate in Combination With Intravenous Metoclopramide vs Intravenous Metoclopramide Monotherapy in Mechanically Ventilated Patients With Enteral Feeding Intolerance: A Randomized, Double-Blind, Controlled Pilot Study. JPEN J Parenter Enteral Nutr 2020; 45:1309-1318. [PMID: 32895971 DOI: 10.1002/jpen.2013] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 08/09/2020] [Accepted: 09/04/2020] [Indexed: 12/26/2022]
Abstract
BACKGROUND In this pilot study, we aimed to determine the efficacy and safety of enteral erythromycin estolate in combination with intravenous metoclopramide compared to intravenous metoclopramide monotherapy in mechanically ventilated patients with enteral feeding intolerance. METHODS This randomized, double-blind, controlled pilot study included 35 mechanically ventilated patients with feeding intolerance who were randomly assigned to receive 10-mg metoclopramide intravenously every 6-8 hours in combination with 250-mg enteral erythromycin estolate (study group) or placebo every 6 hours for 7 days. The primary outcome was an administered-to-target energy ratio of ≥80% at 48 hours, indicating a successful feeding. Secondary, prespecified outcomes were daily average gastric residual volume (GRV), total energy intake, administered-to-target energy ratio, hospital length of stay, in-hospital mortality, and 28-day mortality. RESULTS The rate of successful feeding was not significantly different between the study and placebo groups (47.1% and 61.1%, respectively; P = .51). The average daily GRV was significantly lower in the study group than in the placebo group (β = 91.58 [95% Wald CI, -164.35 to -18.8]), determined by generalized estimating equation. Other secondary outcomes were comparable, and the incidence of adverse events was not significantly different between the 2 groups. One common complication was cardiac arrhythmia, which was mostly self-terminated. CONCLUSION Although the combination therapy of enteral erythromycin estolate and intravenous metoclopramide reduced GRV, the successful feeding rate and other patient-specific outcomes did not improve in mechanically ventilated patients with feeding intolerance.
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Affiliation(s)
| | - Rungsun Bhurayanontachai
- Critical Care Medicine Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand
| | - Sirima Sitaruno
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand
| | - Asma Navasakulpong
- Respiratory and Respiratory Critical Care Medicine Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Apinya Boonpeng
- School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand
| | - Sanguan Lerkiatbundit
- Department of Pharmacy Administration, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand
| | - Sutthiporn Pattharachayakul
- Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand
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11
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Abstract
Bowel dysfunction, especially ileus, has been increasingly recognized in critically ill patients. Ileus is commonly associated to constipation, however abnormal motility can also concern the upper digestive tract, therefore impaired gastrointestinal transit (IGT) seems to be a more appropriate term. IGT, especially constipation, is common among patients under mechanical ventilation, occurring in up to 80% of the patients during the first week, and has been associated with worse outcome in intensive care unit (ICU). It is acknowledged that the most relevant definition for constipation in ICU is the absence of stool for the first six days after admission. Concerning the upper digestive intolerance (UDI), the diagnosis should rely only on vomiting and the systematic gastric residual volume (GRV) monitoring should be avoided. IGT results from a complex pathophysiology in which both the critical illness and its specific treatments may have a deleterious role. Both observational and experimental studies have shown the deleterious effect of sepsis, multiorgan failure, sedation (especially opioids) and mechanical ventilation on gut function. To date few studies have reported effect of treatment on IGT and the level of evidence is low. However, cholinesterase inhibitors seem safe and could probably be used in case of constipation but remains poorly prescribed. Prevention with bowel management protocol using osmotic laxatives appears to be safe but did not demonstrate its effectiveness. For patients treated with high posology of opioids during sedation, enteral opioid antagonists may be a promising strategy.
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Affiliation(s)
- Philippe Ariès
- Clermont-Tonnerre Military Teaching Hospital, Brest, France.,Val-de-Grâce French Military Health Service Academy, Paris, France.,Department of Anesthesia and Surgical Intensive Care, Brest Teaching Hospital, Brest, France
| | - Olivier Huet
- Department of Anesthesia and Surgical Intensive Care, Brest Teaching Hospital, Brest, France - .,UFR of Medicine, University of Western Brittany, Brest, France
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12
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Silva DAF, Riera R, Pacheco RL, Pimentel CFMG, Gois AFT. Erythromycin prior to endoscopy for acute upper gastrointestinal haemorrhage. Hippokratia 2018. [DOI: 10.1002/14651858.cd013176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Affiliation(s)
- Diego Adão F Silva
- Universidade Federal de São Paulo; Department of Medicine; Rua Pedro de Toledo, 720 2nd floor São Paulo Brazil 04039-002
| | - Rachel Riera
- Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde; Cochrane Brazil; Rua Borges Lagoa, 564 cj 63 São Paulo SP Brazil 04038-000
| | - Rafael L Pacheco
- Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde; Cochrane Brazil; Rua Borges Lagoa, 564 cj 63 São Paulo SP Brazil 04038-000
| | - Carolina FMG Pimentel
- Universidade Federal de São Paulo; Department of Medicine; Rua Pedro de Toledo, 720 2nd floor São Paulo Brazil 04039-002
| | - Aecio FT Gois
- Centro de Estudos de Saúde Baseada em Evidências e Avaliação Tecnológica em Saúde; Cochrane Brazil; Rua Borges Lagoa, 564 cj 63 São Paulo SP Brazil 04038-000
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13
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Deane AM, Chapman MJ, Reintam Blaser A, McClave SA, Emmanuel A. Pathophysiology and Treatment of Gastrointestinal Motility Disorders in the Acutely Ill. Nutr Clin Pract 2018; 34:23-36. [PMID: 30294835 DOI: 10.1002/ncp.10199] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Gastrointestinal dysmotility causes delayed gastric emptying, enteral feed intolerance, and functional obstruction of the small and large intestine, the latter functional obstructions being frequently termed ileus and Ogilvie syndrome, respectively. In addition to meticulous supportive care, drug therapy may be appropriate in certain situations. There is, however, considerable variation among individuals regarding what gastric residual volume identifies gastric dysmotility and would encourage use of a promotility drug. While the administration of either metoclopramide or erythromycin is supported by evidence it appears that, dual-drug therapy (erythromycin and metoclopramide) reduces the rate of treatment failure. There is a lack of evidence to guide drug therapy of ileus, but neither erythromycin nor metoclopramide appear to have a role. Several drugs, including ghrelin agonists, highly selective 5-hydroxytryptamine receptor agonists, and opiate antagonists are being studied in clinical trials. Neostigmine, when infused at a relatively slow rate in patients receiving continuous hemodynamic monitoring, may alleviate the need for endoscopic decompression in some patients.
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Affiliation(s)
- Adam M Deane
- Intensive Care Unit, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
| | - Marianne J Chapman
- Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.,Department of Critical Care Services, Royal Adelaide Hospital, Adelaide, Australia
| | - Annika Reintam Blaser
- Department of Anaesthesiology and Intensive Care, University of Tartu, Tartu, Estonia.,Center of Intensive Care Medicine, Lucerne Cantonal Hospital, Lucerne, Switzerland
| | - Stephen A McClave
- Department of Medicine, University of Louisville, Louisville, Kentucky, USA
| | - Anton Emmanuel
- Department of Neuro-Gastroenterology, University College London, London, UK
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14
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Fiets RB, Bos JM, Donders A, Bruns M, Lamfers E, Schouten JA, Kramers C. QTc prolongation during erythromycin used as prokinetic agent in ICU patients. Eur J Hosp Pharm 2017; 25:118-122. [PMID: 31157004 DOI: 10.1136/ejhpharm-2016-001077] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 12/12/2016] [Accepted: 12/20/2016] [Indexed: 01/15/2023] Open
Abstract
Background High-dose erythromycin used as antibiotic prolongs QTc interval. Low-dose erythromycin is frequently used as a prokinetic agent, especially in patients in the intensive care unit (ICU). It is unknown whether low-dose erythromycin affects cardiac repolarisation and puts patients at risk for torsades de pointes. Methods In this prospective study, we included ICU patients treated with erythromycin as prokinetic in a dose of 200 mg twice a day. An ECG was performed before, 15 min and 24 hours after the start of erythromycin. Cardiac repolarisation was assessed by rate-corrected analysis of the QT interval (QTc) on the ECG by two independent investigators. Starting or stopping other possibly QTc prolonging drugs during the study period was an exclusion criterion. Wilcoxon signed-rank test and Friedman's test were used for statistical analysis to assess prolongation of QTc. Primary outcome was defined by the prolongation of QTc after 15 min and 24 hours. Results 51 patients were eligible for this study. In these patients, QTc increased significantly from 430 ms at baseline to 439 ms (p=0.03) after 15 min and 444 ms (p=0.01) after 24 hours. After 15 min and 24 hours, the upper limit of 95% CI for prolongation of QTc was well above 10 ms. No QTc-related arrhythmias were seen. Conclusions During treatment with erythromycin in a dose of 200 mg twice a day. QTc prolonged mildly but significantly. Sequential ECG registration should be performed when low-dose erythromycin is prescribed, especially in the presence of other risk factor for QTc prolongation.
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Affiliation(s)
- R B Fiets
- Department of General Internal Medicine, Canisius Wilhemina Hospital, Nijmegen, Nijmegen, The Netherlands.,Department of General Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - J M Bos
- Department of Hospital Pharmacy, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Art Donders
- Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands
| | - M Bruns
- Department of Intensive Care, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - Ejp Lamfers
- Department of Cardiology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - J A Schouten
- Department of Intensive Care, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands
| | - C Kramers
- Department of General Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.,Department of Hospital Pharmacy, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands.,Department of Pharmacology and Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands
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15
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Chapman MJ, Deane AM, O'Connor SL, Nguyen NQ, Fraser RJL, Richards DB, Hacquoil KE, Vasist Johnson LS, Barton ME, Dukes GE. The effect of camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2016; 20:232. [PMID: 27476581 PMCID: PMC4967996 DOI: 10.1186/s13054-016-1420-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/29/2016] [Accepted: 07/20/2016] [Indexed: 02/08/2023]
Abstract
Background The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients. Methods A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19–84), 73 % male, APACHE II score 18 (5–37) with a gastric residual volume ≥200 mL]. Gastric emptying and glucose absorption were measured both pre- and post-treatment after intragastric administration of 50 mg (n = 15) camicinal and placebo (n = 8) using the 13C-octanoic acid breath test (BTt1/2), acetaminophen concentrations, and 3-O-methyl glucose concentrations respectively. Results Following 50 mg enteral camicinal, there was a trend to accelerated gastric emptying [adjusted geometric means: pre-treatment BTt1/2 117 minutes vs. post- treatment 76 minutes; 95 % confidence intervals (CI; 0.39, 1.08) and increased glucose absorption (AUC240min pre-treatment: 28.63 mmol.min/L vs. post-treatment: 71.63 mmol.min/L; 95 % CI (1.68, 3.72)]. When two patients who did not have detectable plasma concentrations of camicinal were excluded from analysis, camicinal accelerated gastric emptying (adjusted geometric means: pre-treatment BTt1/2 121 minutes vs. post-treatment 65 minutes 95 % CI (0.32, 0.91) and increased glucose absorption (AUC240min pre-treatment: 33.04 mmol.min/L vs. post-treatment: 74.59 mmol.min/L; 95 % CI (1.478, 3.449). In those patients receiving placebo gastric emptying was similar pre- and post-treatment. Conclusions When absorbed, a single enteral dose of camicinal (50 mg) accelerates gastric emptying and increases glucose absorption in feed-intolerant critically ill patients. Trial registration The study protocol was registered with the US NIH clinicaltrials.gov on 23 December 2009 (Identifier NCT01039805).
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Affiliation(s)
- Marianne J Chapman
- Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia. .,Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia.
| | - Adam M Deane
- Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia.,Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia
| | - Stephanie L O'Connor
- Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, Australia.,Discipline of Acute Care Medicine, University of Adelaide, Adelaide, Australia
| | - Nam Q Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, Australia.,Discipline of Medicine, University of Adelaide, Adelaide, Australia
| | - Robert J L Fraser
- Department of Gastroenterology and Hepatology, Flinders Medical Centre, Adelaide, Australia
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16
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Rahman R, Nguyen DL, Sohail U, Almashhrawi AA, Ashraf I, Puli SR, Bechtold ML. Pre-endoscopic erythromycin administration in upper gastrointestinal bleeding: an updated meta-analysis and systematic review. Ann Gastroenterol 2016; 29:312-7. [PMID: 27366031 PMCID: PMC4923816 DOI: 10.20524/aog.2016.0045] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Accepted: 04/09/2016] [Indexed: 12/13/2022] Open
Abstract
Background In patients suffering from upper gastrointestinal bleeding (UGIB), adequate visualization is essential during endoscopy. Prior to endoscopy, erythromycin administration has been shown to enhance visualization in these patients; however, guidelines have not fully adopted this practice. Thus, we performed a comprehensive, up-to-date meta-analysis on the issue of erythromycin administration in this patient population. Methods After searching multiple databases (November 2015), randomized controlled trials on adult subjects comparing administration of erythromycin before endoscopy in UGIB patients to no erythromycin or placebo were included. Pooled estimates of adequacy of gastric mucosa visualized, need for second endoscopy, duration of procedure, length of hospital stay, units of blood transfused, and need for emergent surgery using odds ratio (OR) or mean difference (MD) were calculated. Heterogeneity and publication bias were assessed. Results Eight studies (n=598) were found to meet the inclusion criteria. Erythromycin administration showed statistically significant improvement in adequate gastric mucosa visualization (OR 4.14; 95% CI: 2.01-8.53, P<0.01) while reduced the need for a second-look endoscopy (OR 0.51; 95% CI: 0.34-0.77, P<0.01) and length of hospital stay (MD -1.75; 95% CI: -2.43 to -1.06, P<0.01). Duration of procedure (P=0.2), units of blood transfused (P=0.08), and need for emergent surgery (P=0.88) showed no significant differences. Conclusion Pre-endoscopic erythromycin administration in UGIB patients significantly improves gastric mucosa visualization while reducing length of hospital stay and the need for second-look endoscopy.
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Affiliation(s)
- Rubayat Rahman
- Division of Gastroenterology and Hepatology, University of Missouri Health Sciences Center (Rubayat Rahman, Umair Sohail, Ashraf A. Almashhrawi, Imran Ashraf, Matthew L. Bechtold), USA
| | - Douglas L Nguyen
- Gastroenterology and Hepatology, University of California-Irvine (Douglas L. Nguyen), USA
| | - Umair Sohail
- Division of Gastroenterology and Hepatology, University of Missouri Health Sciences Center (Rubayat Rahman, Umair Sohail, Ashraf A. Almashhrawi, Imran Ashraf, Matthew L. Bechtold), USA
| | - Ashraf A Almashhrawi
- Division of Gastroenterology and Hepatology, University of Missouri Health Sciences Center (Rubayat Rahman, Umair Sohail, Ashraf A. Almashhrawi, Imran Ashraf, Matthew L. Bechtold), USA
| | - Imran Ashraf
- Division of Gastroenterology and Hepatology, University of Missouri Health Sciences Center (Rubayat Rahman, Umair Sohail, Ashraf A. Almashhrawi, Imran Ashraf, Matthew L. Bechtold), USA
| | - Srinivas R Puli
- Gastroenterology and Hepatology, University of Illinois-Peoria (Srinivas R. Puli), USA
| | - Matthew L Bechtold
- Division of Gastroenterology and Hepatology, University of Missouri Health Sciences Center (Rubayat Rahman, Umair Sohail, Ashraf A. Almashhrawi, Imran Ashraf, Matthew L. Bechtold), USA
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17
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Hellström PM, Tack J, Johnson LV, Hacquoil K, Barton ME, Richards DB, Alpers DH, Sanger GJ, Dukes GE. The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying. Br J Pharmacol 2016; 173:1768-77. [PMID: 26924243 DOI: 10.1111/bph.13475] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 01/29/2016] [Accepted: 02/14/2016] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND PURPOSE Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis. EXPERIMENTAL APPROACH In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg). Gastric emptying ((13) C-octanoic acid breath test), pharmacokinetics and safety were primary outcomes. KEY RESULTS Nine of the 10 patients enrolled completed the study. Gastric half-emptying time decreased by -95 min (95% CI: -156.8, -34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half-emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure-response relationship was demonstrated across all doses. The effects of camicinal on gastric half-emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose-proportional pharmacokinetic characteristics and a clear exposure-response relationship with gastric emptying. CONCLUSIONS AND IMPLICATIONS Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.
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Affiliation(s)
| | | | | | | | | | | | - David H Alpers
- Washington University School of Medicine, St Louis, MO, USA
| | - Gareth J Sanger
- Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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18
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Kar P, Jones KL, Horowitz M, Chapman MJ, Deane AM. Measurement of gastric emptying in the critically ill. Clin Nutr 2015; 34:557-564. [PMID: 25491245 DOI: 10.1016/j.clnu.2014.11.003] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 11/04/2014] [Accepted: 11/05/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Enteral nutrition is important in critically ill patients and is usually administered via a nasogastric tube. As gastric emptying is frequently delayed, and this compromises the delivery of nutrient, it is important that the emptying rate can be quantified. METHODS A comprehensive search of MEDLINE/PubMed, of English articles, from inception to 1 July 2014. References of included manuscripts were also examined for additional studies. RESULTS A number of methods are available to measure gastric emptying and these broadly can be categorised as direct- or indirect-test and surrogate assessments. Direct tests necessitate visualisation of the stomach contents during emptying and are unaffected by liver or kidney metabolism. The most frequently used direct modality is scintigraphy, which remains the 'gold standard'. Indirect tests use a marker that is absorbed in the proximal small intestine, so that measurements of the marker, or its metabolite measured in plasma or breath, correlates with gastric emptying. These tests include drug and carbohydrate absorption and isotope breath tests. Gastric residual volumes (GRVs) are used frequently to quantify gastric emptying during nasogastric feeding, but these measurements may be inaccurate and should be regarded as a surrogate measurement. While the inherent limitations of GRVs make them less suitable for research purposes they are often the only technique that is available for clinicians at the bedside. CONCLUSIONS Each of the available techniques has its strength and limitations. Accordingly, the choice of gastric emptying test is dictated by the particular requirement(s) and expertise of the investigator or clinician.
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Affiliation(s)
- Palash Kar
- Discipline of Acute Care Medicine, University of Adelaide, South Australia, Australia; Intensive Care Unit, Royal Adelaide Hospital, South Australia, Australia.
| | - Karen L Jones
- Centre for Research Excellence, University of Adelaide, South Australia, Australia; Discipline of Medicine, University of Adelaide, South Australia, Australia
| | - Michael Horowitz
- Centre for Research Excellence, University of Adelaide, South Australia, Australia; Discipline of Medicine, University of Adelaide, South Australia, Australia
| | - Marianne J Chapman
- Discipline of Acute Care Medicine, University of Adelaide, South Australia, Australia; Intensive Care Unit, Royal Adelaide Hospital, South Australia, Australia; Centre for Research Excellence, University of Adelaide, South Australia, Australia
| | - Adam M Deane
- Discipline of Acute Care Medicine, University of Adelaide, South Australia, Australia; Intensive Care Unit, Royal Adelaide Hospital, South Australia, Australia; Centre for Research Excellence, University of Adelaide, South Australia, Australia
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19
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van Zanten ARH, van der Meer YG, Venhuizen WA, Heyland DK. Still a Place for Metoclopramide as a Prokinetic Drug in Critically Ill Patients? JPEN J Parenter Enteral Nutr 2015; 39:763-6. [PMID: 25567783 DOI: 10.1177/0148607114567711] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 11/20/2014] [Indexed: 12/26/2022]
Affiliation(s)
| | - Y Gert van der Meer
- Department of Hospital Pharmacy, Gelderse Vallei Hospital, Ede, The Netherlands
| | - Willem A Venhuizen
- Department of Hospital Pharmacy, Gelderse Vallei Hospital, Ede, The Netherlands
| | - Daren K Heyland
- Clinical Evaluation Research Unit, Kingston General Hospital, Kingston, Ontario, Canada
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Prokinetic drugs for gastric emptying in critically ill ventilated patients: Analysis through breath testing. J Crit Care 2015; 30:655.e7-13. [PMID: 25746849 DOI: 10.1016/j.jcrc.2014.12.019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 11/28/2014] [Accepted: 12/30/2014] [Indexed: 12/26/2022]
Abstract
PURPOSE The prupose was to identify, through the BreathID automatic breath-testing device, the best prokinetic therapy to enhance gastric-emptying rate (GER) in ventilated intensive care unit patients. MATERIALS AND METHODS This was a prospective, crossover, nonrandomized study. Consecutive ventilated patients who could be fed enterally and expected to require 5 days of ventilation were included. (13)C-labeled-acetate in 100 mL Osmolite (BreathID; Exalenz Bioscience Ltd, Jerusalem, Israel) was administered intragastrically and followed by a 4-hour continuous recording of expiratory (13)CO2 by the BreathID. Prokinetics were changed daily: (1) baseline (no prokinetic), (2) intravenous (IV) metoclopramide (10 mg every 6 hours), (3) IV metoclopramide (10 mg every 6 hours) and continuous low-dose erythromycin (10 mg/h), (4) IV continuous low-dose erythromycin alone (10 mg/h), and (5) IV bolus erythromycin (200 mg every 12 hours). Gastric-emptying rate was assessed by the percentage dose recovered (PDR)-change from time 0 of the recording in the ratio of (13)CO2/(12)CO2 in exhaled gases (%/h). We used PDR peak values and time to peak (minutes to reach PDR peak) to express GER. RESULTS In the first 17 patients (group A), baseline GER measurements preceded prokinetic therapy. In the subsequent 14 patients (group B), 2 prokinetic regimens preceded baseline. No order-time effect was observed, justifying pooled analysis of all 31 patients. Combined metoclopramide-continuous low-dose erythromycin yielded significantly higher PDR peak and shorter time to peak vs baseline (P = .0001, P = .005, respectively). The PDR peak was also significantly higher from baseline during continuous low-dose administration of erythromycin alone (P = .004). Metoclopramide alone did not improve GER significantly. CONCLUSIONS Combined metoclopramide-continuous low-dose erythromycin was found to be the best protocol in the current study to increase GER in ventilated patients. It should be tested as a first-line prokinetic therapy in ventilated patients with poor gastric emptying in further randomized controlled studies. The breath-test device presented in this study can be a user-friendly and practical method to monitor GER, enabling individual tailoring of prokinetic therapy. Further studies to explore its utility are warranted.
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van der Meer YG, Venhuizen WA, Heyland DK, van Zanten ARH. Should we stop prescribing metoclopramide as a prokinetic drug in critically ill patients? Crit Care 2014; 18:502. [PMID: 25672546 PMCID: PMC4331179 DOI: 10.1186/s13054-014-0502-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Regulatory agencies in North America and Europe recently re-evaluated the safety of metoclopramide. This re-evaluation resulted in recommendations and restrictions in order to minimise the risk of neurological and other adverse reactions associated with the use of metoclopramide. In the ICU, off-label prescription of metoclopramide is common. We have reviewed the evidence for safety, effectiveness and dosing of metoclopramide in critically ill patients. Furthermore, tachyphylaxis is addressed and alternatives are summarised. Finally, recommendations are presented not to abandon use of metoclopramide in ICU patients, because metoclopramide is considered effective in enhancing gastric emptying and facilitating early enteral nutrition.
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Affiliation(s)
- Y Gert van der Meer
- />Department of Hospital Pharmacy, Gelderse Vallei Hospital, Willy Brandtlaan 10, Ede, 6716 RP the Netherlands
| | - Willem A Venhuizen
- />Department of Hospital Pharmacy, Gelderse Vallei Hospital, Willy Brandtlaan 10, Ede, 6716 RP the Netherlands
| | - Daren K Heyland
- />Clinical Evaluation Research Unit, Angada 4, Kingston General Hospital, 76 Stuart Street, Kingston, ON K7L 2 V7 Canada
| | - Arthur RH van Zanten
- />Department of Intensive Care, Gelderse Vallei Hospital, Willy Brandtlaan 10, Ede, 6716 RP the Netherlands
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Nguyen NQ, Yi Mei SLC. Current issues on safety of prokinetics in critically ill patients with feed intolerance. Ther Adv Drug Saf 2014; 2:197-204. [PMID: 25083212 DOI: 10.1177/2042098611415567] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Feed intolerance in the setting of critical illness should be treated promptly given its adverse impact on morbidity and mortality. The technical difficulty of postpyloric feeding tube placement and the morbidities associated with parenteral nutrition prevent these approaches being considered as first-line nutrition. Prokinetic agents are currently the mainstay of therapy for feed intolerance in the critically ill. Current information is limited but suggests that erythromycin or metoclopramide (alone or in combination) are effective in the management of feed intolerance in the critically ill and not associated with significant cardiac, haemodynamic or neurological adverse effects. However, diarrhoea is a very common gastrointestinal side effect, and can occur in up to 49% of patients who receive both erythromycin and metoclopramide. Fortunately, the diarrhoea associated with prokinetic treatments has not been linked to Clostridium difficile infection and settles soon after the drugs are ceased. Therefore, prolonged or prophylactic use of prokinetics should be avoided. If diarrhoea occurs, the drugs should be stopped immediately. To minimize avoidable adverse effects the ongoing need for prokinetic drugs in these patient should be reviewed daily.
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Affiliation(s)
- Nam Q Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia
| | - Swee Lin Chen Yi Mei
- Departments of Gastroenterology and Hepatology, Royal Adelaide Hospital; Adelaide, SA, Australia
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Jun BY, Choi MG, Lee JY, Baeg MK, Moon SJ, Lim CH, Kim JS, Cho YK, Lee IS, Kim SW, Choi KY. Premedication with erythromycin improves endoscopic visualization of the gastric mucosa in patients with subtotal gastrectomy: a prospective, randomized, controlled trial. Surg Endosc 2014; 28:1641-7. [PMID: 24380989 DOI: 10.1007/s00464-013-3364-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2013] [Accepted: 11/24/2013] [Indexed: 12/30/2022]
Abstract
BACKGROUND Food residue in the remnant stomach after subtotal gastrectomy (STG) interferes with endoscopic observation. We investigated whether intravenous erythromycin improves gastric mucosa visualization in patients with STG. METHODS This study was conducted from April 2012 to October 2012 as a double-blinded, placebo-controlled, randomized trial. Patients who received STG with complete resection (stage T1-2N0M0) were included. Exclusion criteria were diabetes mellitus, neurologic disease, myopathy, recent viral enteritis history, concomitant therapy influencing gastrointestinal motility and severe comorbidity. Patients were instructed to consume a soft diet for dinner between 1800 and 2000 h, and endoscopies were performed between 0900 and 1200 h. Patients were assigned randomly to receive either erythromycin (125 mg in normal saline 50 cc) or placebo saline. The endoscopy was performed 15 min after infusion. Grade of residual food was rated as follows: G0, no residual food; G1, a small amount of residual food; G2, a moderate amount of residual food; G3, a moderate amount of residual food that hinders observation of the entire surface, even with body rolling; G4, a great amount of residual food such that endoscopic observation is impossible. RESULTS When good visibility was defined as G0+G1, visibility was significantly better in the erythromycin group (61 + 19 %) than in the placebo group (38 + 12 %, p < 0.001). However, this effect was not seen in patients within 6 months after gastrectomy. The risk factor for food stasis in the placebo group (n = 58) was food stasis at last endoscopy. The only factor predicting erythromycin response in the erythromycin group (n = 56) was elapsed time since surgery. Adverse effects included nausea [11 (19.7 %)] and vomiting [1 (1.8 %)] in the erythromycin group and vomiting [3 (5.2 %)] in the placebo group. However, they were transient and tolerable. CONCLUSIONS Premedication with erythromycin improves mucosal visualization during endoscopy in patients with STG. ( CLINICAL TRIALS REGISTRATION NUMBER NCT01659619).
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Affiliation(s)
- Byoung Yeon Jun
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Republic of Korea,
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Abstract
Gastroesophageal reflux (GER) is a common occurrence in critically ill, mechanically ventilated patients. Reflux can lead to pulmonary aspiration of gastric contents and subsequent pneumonia. Several characteristics of patients, interventions provided in the intensive care unit setting, and factors associated with feeding increase a patient's risk for reflux. Critical care nurses and clinical nurse specialists can identify patients at highest risk for GER by utilizing the patient's history, reviewing the medications, and assessing the current status to provide interventions to reduce the risk of GER and its sequelae of aspiration pneumonia. This article reviews the physiology of GER, risk factors, and interventions to decrease GER in the critically ill patient.
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Sanger GJ, Wang Y, Hobson A, Broad J. Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists. Br J Pharmacol 2013; 170:1323-32. [PMID: 23189978 PMCID: PMC3838679 DOI: 10.1111/bph.12075] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2012] [Revised: 10/26/2012] [Accepted: 11/15/2012] [Indexed: 12/11/2022] Open
Abstract
UNLABELLED The gastrointestinal hormone motilin has been known about for >40 years, but after identification of its receptor and subsequent development of new tools and methods, a reappraisal of its actions is required. Firstly, it is important to note that motilin and ghrelin receptors are members of the same family (similar genomic organization, gastrointestinal distribution and abilities to stimulate gastrointestinal motility), yet each fails to recognize the ligand of the other; and whereas ghrelin and ghrelin receptors are widespread outside the gastrointestinal tract, motilin and its receptors are largely restricted to the gastrointestinal tract. Secondly, although some studies suggest motilin has activity in rodents, most do not, and receptor pseudogenes exist in rodents. Thirdly, motilin preferentially operates by facilitating enteric cholinergic activity rather than directly contracting the muscle, despite the relatively high expression of receptor immunoreactivity in muscle. This activity is ligand-dependent, with short-lasting actions of motilin contrasting with longer-lasting actions of the non-selective and selective motilin receptor agonists erythromycin and GSK962040. Finally, the use of erythromycin (also an antibiotic drug) to treat patients requiring acceleration of gastric emptying has led to concerns over safety and potential exacerbation of antibiotic resistance. Replacement motilin receptor agonists derived from erythromycin (motilides) have been unsuccessful. New, non-motilide, small molecule receptor agonists, designed to minimize self-desensitization, are now entering clinical trials for treating patients undergoing enteral feeding or with diabetic gastroparesis. Thus, for the translational pharmacologist, the study of motilin illustrates the need to avoid overreliance on artificial systems, on structural information and on animal studies. LINKED ARTICLES This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.
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Affiliation(s)
- G J Sanger
- Neurogastroenterology Group, Blizard Institute, Barts & The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Luttikhold J, de Ruijter FM, van Norren K, Diamant M, Witkamp RF, van Leeuwen PAM, Vermeulen MAR. Review article: the role of gastrointestinal hormones in the treatment of delayed gastric emptying in critically ill patients. Aliment Pharmacol Ther 2013; 38:573-83. [PMID: 23879699 DOI: 10.1111/apt.12421] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Revised: 12/27/2012] [Accepted: 07/01/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Delayed gastric emptying limits the administration of enteral nutrition, leading to malnutrition, which is associated with higher mortality and morbidity. Currently available prokinetics have limitations in terms of sustained efficacy and side effects. AIM To summarise the mechanisms of action and to discuss the possible utility of gastrointestinal hormones to prevent or treat delayed gastric emptying in critically ill patients. METHODS We searched PubMed for articles discussing 'delayed gastric emptying', 'enteral nutrition', 'treatment', 'gastrointestinal hormones', 'prokinetic', 'agonist', 'antagonist' and 'critically ill patients'. RESULTS Motilin and ghrelin receptor agonists initiate the migrating motor complex in the stomach, which accelerates gastric emptying. Cholecystokinin, glucagon-like peptide-1 and peptide YY have an inhibiting effect on gastric emptying; therefore, antagonising these gastrointestinal hormones may have therapeutic potential. Other gastrointestinal hormones appear less promising. CONCLUSIONS Manipulation of endogenous secretion, physiological replacement and administration of gastrointestinal hormones in pharmacological doses is likely to have therapeutic potential in the treatment of delayed gastric emptying. Future challenges in this field will include the search for candidates with improved selectivity and favourable kinetic properties.
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Affiliation(s)
- J Luttikhold
- Department of Surgery, VU University Medical Center, Amsterdam, the Netherlands.
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Theivanayagam S, Lim RG, Cobell WJ, Gowda JT, Matteson ML, Choudhary A, Bechtold ML. Administration of erythromycin before endoscopy in upper gastrointestinal bleeding: a meta-analysis of randomized controlled trials. Saudi J Gastroenterol 2013; 19:205-10. [PMID: 24045593 PMCID: PMC3793471 DOI: 10.4103/1319-3767.118120] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
BACKGROUND/AIM Erythromycin infusion before endoscopy in upper gastrointestinal bleeding (UGIB) has been hypothesized to aid in visualization and reduce the need for second-look endoscopy; however, the results have been controversial. To evaluate further, we performed a meta-analysis comparing the efficacy of erythromycin infusion before endoscopy in acute UGIB. METHODS Multiple databases were searched (March 2013). Only randomized controlled trials were included in the analysis. A meta-analysis for the effect of erythromycin or no erythromycin before endoscopy in UGIB were analyzed by calculating pooled estimates of primary (visualization of gastric mucosa and need for second endoscopy) and secondary (units of blood transfused, length of hospital stay, duration of the procedure) outcomes. Statistical analysis was performed using RevMan 5.1 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration). RESULTS Six studies (N = 558) met the inclusion criteria. Erythromycin infusion before endoscopy in UGIB demonstrated a statistically significant improvement in visualization of the gastric mucosa [odds ratio (OR) 3.43; 95% confidence interval (CI): 1.81 to 6.50, P < 0.01] compared with no erythromycin. In addition, erythromycin infusion before endoscopy resulted in a statistically significant decrease in the need for a second endoscopy (OR 0.47; 95% CI: 0.26 to 0.83, P = 0.01), units of blood transfused (WMD - 0.41; 95% CI: -0.82 to -0.01, P = 0.04), and the duration of hospital stay (WMD - 1.51; 95% CI: -2.45 to -0.56, P < 0.01). CONCLUSIONS Erythromycin infusion before endoscopy in patients with UGIB significantly improves visualization of gastric mucosa while decreasing the need for a second endoscopy, units of blood transfused, and duration of hospital stay.
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Affiliation(s)
- Shoba Theivanayagam
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA
| | - Roxanne G. Lim
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA
| | - William J. Cobell
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA
| | - Jayashree T. Gowda
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA
| | - Michelle L. Matteson
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA
| | - Abhishek Choudhary
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA
| | - Matthew L. Bechtold
- Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA,Address for correspondence: Prof. Matthew L. Bechtold, Division of Gastroenterology and Hepatology, CE405, DC 043.00, University of Missouri Health Sciences Center, Five Hospital Drive, Columbia, MO 65212, USA. E-mail:
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Javid FA, Bulmer DC, Broad J, Aziz Q, Dukes GE, Sanger GJ. Anti-emetic and emetic effects of erythromycin in Suncus murinus: role of vagal nerve activation, gastric motility stimulation and motilin receptors. Eur J Pharmacol 2012. [PMID: 23201066 DOI: 10.1016/j.ejphar.2012.11.035] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3 ± 1.8 to 4.0 ± 1.1 emetic episodes at 5mg/kg) or by nicotine (from 9.5 ± 2.0 to 3.1 ± 2.0 at 5mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.
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Affiliation(s)
- Farideh A Javid
- School of Applied Sciences, Division of Pharmacy and Pharmaceuticals Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK
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Pinto TF, Rocha R, Paula CA, de Jesus RP. Tolerance to enteral nutrition therapy in traumatic brain injury patients. Brain Inj 2012; 26:1113-1117. [PMID: 22571511 DOI: 10.3109/02699052.2012.666369] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To evaluate the tolerance to enteral nutrition (EN) and the effects of pro-kinetic drugs in critical traumatic brain injury (TBI) patients. METHODS Transversal observational study. A total of 32 out of 45 TBI patients of both genders receiving EN were evaluated in a trauma referral hospital intensive care unit (ICU). Data from each patient were collected for a period of 10 consecutive days after initiation of enteral feeding: gastric residue, presence of vomiting, abdominal distension, Glasgow coma scale and the use of pro-kinetic agents. RESULTS In 20 of the 32 patients high levels of gastric residue were found. Of these 20 patients, half could not tolerate the diet within the first 72 hours following infusion. However, no association was found between disease severity and occurrence of gastrointestinal complications (p > 0.05). Feeding intolerance was observed in 75.0% (n = 24) of patients, even with the systematic use of metaclopramide from the outset of nutritional therapy. All patients with feeding intolerance who used erythromycin by nasogastric tube showed improvement. CONCLUSIONS The high level of gastric residue was the most common feeding intolerance and the delivery of erythromycin by nasogastric tube seems to control gastrointestinal disorders in TBI patients.
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Affiliation(s)
- Tatiana Fuchs Pinto
- Department of Sciences of Nutrition, School of Nutrition, Federal University of Bahia, Brazil
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Chapman MJ, Nguyen NQ, Deane AM. Gastrointestinal dysmotility: clinical consequences and management of the critically ill patient. Gastroenterol Clin North Am 2011; 40:725-39. [PMID: 22100114 DOI: 10.1016/j.gtc.2011.09.003] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Gastrointestinal dysmotility is a common feature of critical illness, with a number of significant implications that include malnutrition secondary to reduced feed tolerance and absorption, reflux and aspiration resulting in reduced lung function and ventilator-associated pneumonia, bacterial overgrowth and possible translocation causing nosocomial sepsis. Prokinetic agent administration can improve gastric emptying and caloric delivery, but its effect on nutrient absorption and clinical outcomes is, as yet, unclear. Postpyloric delivery of nutrition has not yet been demonstrated to increase caloric intake or improve clinical outcomes.
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Affiliation(s)
- Marianne J Chapman
- Department of Critical Care Services, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia.
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Plasma erythromycin concentrations predict feeding outcomes in critically ill patients with feed intolerance. Crit Care Med 2011; 39:868-71. [PMID: 21297459 DOI: 10.1097/ccm.0b013e318206d57b] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVE Motilin receptors are rapidly down-regulated by exposure to erythromycin, and its progressive loss of clinical prokinetic effect may relate to higher plasma drug concentrations. This study aimed to evaluate the relationship between plasma erythromycin concentrations and feeding outcomes in critically ill patients. DESIGN Observational comparative study. SETTING Tertiary critical care unit. PATIENTS Twenty-nine feed-intolerant (gastric residual volume >250 mL) mechanically ventilated, medical critically ill patients. INTERVENTIONS Patients received intravenous erythromycin 200 mg twice daily for feed intolerance. MEASUREMENTS Plasma erythromycin concentrations were measured 1 and 7 hrs after drug administration on day 1. Success of enteral feeding, defined as 6-hourly gastric residual volume of ≤ 250 mL with a feeding rate ≥ 40 mL/h, was recorded over 7 days. RESULTS At day 7, 38% (11 of 29) of patients were feed tolerant. Age, Acute Physiology and Chronic Health Evaluation scores, serum glucose concentrations, and creatinine clearance were comparable between successful and failed feeders. Both plasma erythromycin concentrations at 1 and 7 hrs after drug administration were significantly lower in successfully treated patients compared to treatment failures (1 hr: 3.7 ± 0.8 mg/L vs. 7.0 ± 1.0 mg/L, p = .02; and 7 hr: 0.7 ± 0.3 mg/L vs. 2.8 ± 0.6 mg/L, p = .01). There was a negative correlation between the number of days to failure of feeding and both the 1-hr (r = -.47, p = .049) and 7-hr (r = -.47, p = .050) plasma erythromycin concentrations. A 1-hr plasma concentration of >4.6 mg/L had 72% sensitivity and 72% specificity, and a 7-hr concentration of ≥ 0.5 mg/L had 83% sensitivity and 72% specificity in predicting loss of response to erythromycin. CONCLUSIONS In critically ill feed-intolerant patients, there is an inverse relationship between plasma erythromycin concentrations and the time to loss of clinical motor effect. This suggests that erythromycin binding to motilin receptors contributes to variations in the duration of prokinetic response. The use of lower doses of erythromycin and tailoring the dose of erythromycin according to plasma concentrations may be useful strategies to reduce erythromycin tachyphylaxis.
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Dive AM. Prokinétiques chez le patient de réanimation : quand et lesquels ? MEDECINE INTENSIVE REANIMATION 2011. [DOI: 10.1007/s13546-011-0281-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Altraif I, Handoo FA, Aljumah A, Alalwan A, Dafalla M, Saeed AM, Alkhormi A, Albekairy AK, Tamim H. Effect of erythromycin before endoscopy in patients presenting with variceal bleeding: a prospective, randomized, double-blind, placebo-controlled trial. Gastrointest Endosc 2011; 73:245-50. [PMID: 21145052 DOI: 10.1016/j.gie.2010.09.043] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2010] [Accepted: 09/27/2010] [Indexed: 12/11/2022]
Abstract
BACKGROUND Blood in the stomach and esophagus in patients with variceal bleeding often obscures the endoscopic view and makes endoscopic intervention difficult to perform. Erythromycin, a motilin agonist, induces gastric emptying. OBJECTIVE To assess the effect of erythromycin on endoscopic visibility and its outcome in patients with variceal bleeding. DESIGN Randomized, double-blind, placebo-controlled trial. SETTING Tertiary care hospital. PATIENTS Adult patients with liver cirrhosis presenting with hematemesis within the previous 12 hours. INTERVENTION Either 125 mg erythromycin or placebo administered intravenously 30 minutes before endoscopy. MAIN OUTCOME MEASUREMENTS Endoscopic visibility during index endoscopy and mean duration of procedure. SECONDARY OUTCOME MEASUREMENTS: Need for repeat endoscopy and blood transfusions within 24 hours, endoscopy-related complications, and length of hospital stay. RESULTS A total of 102 patients received either erythromycin or placebo (53 erythromycin and 49 placebo). Forty-seven patients in the erythromycin group and 43 in the placebo group had variceal bleeding and were considered for final analysis. A completely empty stomach was seen in 48.9% of the erythromycin group versus 23.3% of the placebo group (P<.01). Mean endoscopy duration was significantly shorter in the erythromycin group than in the placebo group (19.0 minutes vs 26.0 minutes, respectively; P<.005). Length of hospital stay was significantly shorter in the erythromycin group than in the placebo group (3.4 days vs 5.1 days, respectively; P<.002). The need for repeat endoscopy and the mean number of units of blood transfused did not differ significantly in the 2 groups. No adverse events were observed with erythromycin. LIMITATIONS Sample size not sufficient to measure the need for repeat endoscopy and survival benefit. CONCLUSIONS Erythromycin infusion before endoscopy in patients with variceal bleeding significantly improves endoscopic visibility and shortens the duration of the index endoscopy. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01060267.).
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Affiliation(s)
- Ibrahim Altraif
- Department of Clinical Pharmacy, King Abdul-Aziz Medical City, Riyadh, Saudi Arabia.
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Deane AM, Zaknic AV, Summers MJ, Chapman MJ, Lange K, Ritz MA, Davidson G, Horowitz M, Fraser RJ. Intrasubject variability of gastric emptying in the critically ill using a stable isotope breath test. Clin Nutr 2010; 29:682-686. [PMID: 20409622 DOI: 10.1016/j.clnu.2010.03.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2009] [Revised: 03/03/2010] [Accepted: 03/11/2010] [Indexed: 02/07/2023]
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Fraser RJL, Bryant L. Current and future therapeutic prokinetic therapy to improve enteral feed intolerance in the ICU patient. Nutr Clin Pract 2010; 25:26-31. [PMID: 20130155 DOI: 10.1177/0884533609357570] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Malnutrition is associated with poor outcomes in critically ill patients, and providing enteral feeding to those who cannot eat is considered best practice. Enteral feeding is often unsuccessful when there is delayed gastric emptying. Recent research has given additional insight into the mechanisms underlying delayed gastric emptying. Pharmacological strategies to improve the success of feeding include prokinetic drugs such as metoclopramide and erythromycin alone or in combination. When drug treatment fails, either parenteral nutrition or direct small intestinal feeding is indicated. Simpler methods to access the duodenum and distal small bowel for feed delivery are under investigation. This review summarizes current understanding of the mechanisms underlying enteral feeding intolerance in critical illness, together with the evidence for current treatment practices. Areas requiring further research are also described.
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Affiliation(s)
- Robert J L Fraser
- Repatriation General Hospital, Daws Road, Daw Park, Adelaide 5041, South Australia.
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Deane AM, Chapman MJ, Fraser RJL, Summers MJ, Zaknic AV, Storey JP, Jones KL, Rayner CK, Horowitz M. Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia. Crit Care Med 2010; 38:1261-1269. [PMID: 20228679 DOI: 10.1097/ccm.0b013e3181d9d87a] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To determine the acute effects of exogenous glucagon-like peptide-1 on gastric emptying, glucose absorption, glycemia, plasma insulin, and glucagon in critically ill patients. DESIGN Randomized, double-blind, crossover study. SETTING Intensive care unit. SUBJECTS Twenty-five mechanically ventilated patients, without known diabetes, studied on consecutive days. INTERVENTIONS Intravenous glucagon-like peptide-1 (1.2 pmol/kg/min) or placebo was infused between -30 and 330 mins. At 0 min, 100 mL liquid nutrient (1 kcal/mL) including 100 microg of 13C-octanoic acid and 3 grams of 3-O-methyl-glucose was administered. MEASUREMENTS AND MAIN RESULTS Blood glucose, serum 3-O-methyl-glucose (as an index of glucose absorption), insulin and glucagon concentrations, as well as exhaled 13CO2 were measured. The gastric emptying coefficient was calculated to quantify gastric emptying. Data are presented as mean (sd). There was a nonsignificant trend for glucagon-like peptide-1 to slow gastric emptying (gastric emptying coefficient) (glucagon-like peptide-1, 2.45 [0.93] vs. placebo, 2.75 [0.83]; p = .09). In 11 of the 25 patients, gastric emptying was delayed during placebo infusion and glucagon-like peptide-1 had no detectable effect on gastric emptying in this group (1.92 [0.82] vs. 1.90 [0.68]; p = .96). In contrast, in patients who had normal gastric emptying during placebo, glucagon-like peptide-1 slowed gastric emptying substantially (2.86 [0.58] vs. 3.41 [0.37]; p = .006). Glucagon-like peptide-1 markedly reduced the rate of glucose absorption (3-O-methyl-glucose area under the curve(0-330), 37 [35] vs. 76 [51] mmol/L/min; p < .001), decreased preprandial glucagon (at 0 min change in glucagon, -15 [15] vs. -3 [14] pmol/L; p < .001), increased the insulin/glucose ratio throughout the infusion (area under the curve(-30-330), 1374 [814] vs. 1172 [649] mU/mmol/min; p = .041), and attenuated the glycemic response to the meal (glucose area under the curve(0-330), 2071 [353] vs. 2419 [594] mmol/L/min; p = .001). CONCLUSIONS Exogenous glucagon-like peptide-1 lowers postprandial glycemia in the critically ill. This may occur, at least in part, by slowing gastric emptying when the latter is normal but not when it is delayed.
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Affiliation(s)
- Adam M Deane
- Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
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38
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Dickerson RN, Mitchell JN, Morgan LM, Maish GO, Croce MA, Minard G, Brown RO. Disparate response to metoclopramide therapy for gastric feeding intolerance in trauma patients with and without traumatic brain injury. JPEN J Parenter Enteral Nutr 2010; 33:646-55. [PMID: 19892902 DOI: 10.1177/0148607109335307] [Citation(s) in RCA: 65] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Patients with traumatic brain injury (TBI) have delayed gastric emptying and often require prokinetic drug therapy to improve enteral feeding tolerance. The authors hypothesized that metoclopramide was less efficacious for improving gastric feeding tolerance for trauma patients with TBI compared to trauma patients without TBI. A retrospective analysis was conducted of patients admitted to the trauma or neurosurgical intensive care unit who received gastric feeding from January 2006 to April 2008. Gastric feeding intolerance was defined by a gastric residual volume >200 mL or emesis with abdominal distension or discomfort. Patients with gastric feeding intolerance were given metoclopramide 10 mg intravenously every 6 hours, followed by a dose escalation to 20 mg, and then combination therapy with metoclopramide and erythromycin 250 mg intravenously every 6 hours if intolerance persisted. In total, 882 trauma patients (49% with TBI) were evaluated. TBI patients had a higher incidence of gastric feeding intolerance than those without TBI (18.6% vs 10.4%, P < or = .001). Efficacy rates for metoclopramide 10 mg, metoclopramide 20 mg, and metoclopramide-erythromycin were 55%, 62%, and 79%, respectively (P < or = .03). Metoclopramide failure occurred in 54% of patients with TBI compared to 35% of patients without TBI, respectively (P < or = .02), due to a greater prevalence of tachyphylaxis. Single-drug therapy with metoclopramide was less effective for TBI trauma patients compared to trauma patients without TBI. Combination therapy with erythromycin as first-line therapy for TBI trauma patients with gastric feeding intolerance is indicated if there are no contraindications or significant drug interactions.
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Affiliation(s)
- Roland N Dickerson
- Department of Clinical Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
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Libert N, De Rudnicki S, Cirodde A, Janvier F, Leclerc T, Borne M, Brinquin L. [Promotility drugs use in critical care: indications and limits?]. ACTA ACUST UNITED AC 2009; 28:962-75. [PMID: 19910155 DOI: 10.1016/j.annfar.2009.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2009] [Accepted: 08/20/2009] [Indexed: 02/08/2023]
Abstract
Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.
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Affiliation(s)
- N Libert
- Département d'anesthésie réanimation, hôpital d'instruction des armées du Val-de-Grâce,74, boulevard de Port-Royal, 750005 Paris, France.
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41
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Poulard F, Dimet J, Martin-Lefevre L, Bontemps F, Fiancette M, Clementi E, Lebert C, Renard B, Reignier J. Impact of not measuring residual gastric volume in mechanically ventilated patients receiving early enteral feeding: a prospective before-after study. JPEN J Parenter Enteral Nutr 2009; 34:125-30. [PMID: 19861528 DOI: 10.1177/0148607109344745] [Citation(s) in RCA: 132] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND Monitoring of residual gastric volume (RGV) to prevent aspiration is standard practice in mechanically ventilated patients receiving early enteral nutrition (EN). No data are available to support a correlation between RGV and adverse event rates. We evaluated whether not measuring RGV affected EN delivery, vomiting, or risk of nosocomial pneumonia. METHODS Two hundred and five eligible patients with nasogastric feeding within 48 hours after intubation were included in a 7-day prospective before-after study. Continuous 24-hour nutrition was started at 25 mL/h then increased by 25 mL/h every 6 hours, to 85 mL/h. In both groups, intolerance was treated with erythromycin (250 mg IV/6 h) and a delivery rate decrease to the previously well-tolerated rate. RGV monitoring was used during the first study period (n = 102), but not during the subsequent intervention period (n = 103). Intolerance was defined as RGV >250 mL/6 h or vomiting in the standard-practice group and as vomiting in the intervention group. RESULTS Groups were similar for baseline characteristics. Median daily volume of enteral feeding was higher in the intervention group (1489; interquartile range [IQR], 1349-1647) than in the controls (1381; IQR, 1151-1591; P = .002). Intolerance occurred in 47 (46.1%) controls and 27 (26.2%) intervention patients (P = .004). The vomiting rate did not differ between controls and intervention group patients (24.5% vs 26.2%, respectively; P = .34), and neither was a difference found for ventilator-associated pneumonia (19.6% vs 18.4%; P = .86). CONCLUSION Early EN without RGV monitoring in mechanically ventilated patients improves the delivery of enteral feeding and may not increase vomiting or ventilator-associated pneumonia.
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Affiliation(s)
- Fanny Poulard
- Medical-Surgical Intensive Care Unit, District Hospital Center, La Roche-sur-Yon, France
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sanger GJ, westaway SM, barnes AA, macpherson DT, muir AI, jarvie EM, bolton VN, cellek S, näslund E, hellström PM, borman RA, unsworth WP, matthews KL, lee K. GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil 2009. [DOI: 10.1111/j.1365-2982.2009.01270.x] [Citation(s) in RCA: 59] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/19/2023]
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Gómez-Garrido M, Martínez González E, Botella Romero F, Gómez-Garrido J. [Enteral feeding of critical patients]. ACTA ACUST UNITED AC 2009; 56:31-42. [PMID: 19284126 DOI: 10.1016/s0034-9356(09)70318-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Artificial nutrition support forms part of the basic care of critical patients. Enteral feeding has been shown to be better than total parenteral nutrition at improving morbidity (infectious complications) and reducing the length of hospital stays, number of days with mechanical ventilation, and costs. As with any other treatment, enteral feeding has associated complications and side effects which should be understood and treated in order to obtain the greatest benefit from it and reduce possible adverse effects. In this review, we attempt to provide a practical summary of the use of enteral feeding in critical patients. We cover the management of the most frequent associated complications, based on new studies and current scientific evidence. The review is intended to serve as a practice guide for the routine care of severely ill patients.
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Affiliation(s)
- M Gómez-Garrido
- Area de Anestesiología y Reanimación, Complejo Hospitalario Universitario de Albacete.
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Grant K, Thomas R. Prokinetic Drugs in the Intensive Care Unit: Reviewing the Evidence. J Intensive Care Soc 2009. [DOI: 10.1177/175114370901000110] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Delay in gastric emptying is common in the critically ill, and can lead to abdominal distension, diarrhoea or constipation, and vomiting, and may contribute to increased incidence of reflux and nosocomial infection. Prokinetic agents increase the rate of luminal transit as well as the force of contraction, and are commonly used in the intensive care unit. This article summarises the current state of knowledge about the use of prokinetics and explores potential agents which might be used in the future in this group of patients.
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Affiliation(s)
- Katherine Grant
- Trainee Doctor in Anaesthetics, North Hampshire Hospital, Basingstoke
| | - Richard Thomas
- Consultant in Anaesthesia and Intensive Care, Royal Hampshire County Hospital, Winchester
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Andreis U, Américo MF, Corá LA, Oliveira RB, Baffa O, Miranda JRA. Gastric motility evaluated by electrogastrography and alternating current biosusceptometry in dogs. Physiol Meas 2008; 29:1023-31. [PMID: 18698113 DOI: 10.1088/0967-3334/29/9/002] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Association techniques could be the answer for evaluating electromechanical coupling and gastric emptying under basal conditions and after administration of drugs. Electrogastrography (EGG) and alternating current biosusceptometry (ACB) emerged due to their interesting nature, noninvasiveness and low cost. The aims were to examine in dogs the effect of erythromycin on gastric emptying by ACB and electrical and motor responses to erythromycin and propranolol by ACB and EGG respectively. Twelve beagle dogs ingested a solid test meal on separate days. Under anesthesia, gastric motility was evaluated by EGG and ACB after erythromycin and propranolol administration. Without anesthesia, gastric emptying was assessed under basal conditions and after erythromycin by ACB. ACB and EGG showed a strong temporal correlation. Erythromycin and propranolol presented the same profile with different power ratios; the amplitude increased whereas frequency decreased. Also, erythromycin administration hastened gastric emptying while reducing the orocaecal transit time. There is a demand for reliable, easy-to-perform and comfortable techniques to record gastric emptying and gastric activity in medicine and veterinary practice. In summary, the association of ACB with EGG accompanied by an appropriate animal model is promising for evaluating effects of drugs in gastric myoelectrical and contractile activity.
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Affiliation(s)
- Uilian Andreis
- Departamento de Física e Biofísica, IBB, São Paulo State University-UNESP, Botucatu, São Paulo, Brazil
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MacLaren R, Kiser TH, Fish DN, Wischmeyer PE. Erythromycin vs Metoclopramide for Facilitating Gastric Emptying and Tolerance to Intragastric Nutrition in Critically Ill Patients. JPEN J Parenter Enteral Nutr 2008; 32:412-9. [DOI: 10.1177/0148607108319803] [Citation(s) in RCA: 79] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Robert MacLaren
- From the Department of Clinical Pharmacy, School of Pharmacy, and the Department of Anesthesiology, School of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
| | - Tyree H. Kiser
- From the Department of Clinical Pharmacy, School of Pharmacy, and the Department of Anesthesiology, School of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
| | - Douglas N. Fish
- From the Department of Clinical Pharmacy, School of Pharmacy, and the Department of Anesthesiology, School of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
| | - Paul E. Wischmeyer
- From the Department of Clinical Pharmacy, School of Pharmacy, and the Department of Anesthesiology, School of Medicine, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
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Ladanyi S, Elliott D. Traumatic brain injury: an integrated clinical case presentation and literature review part II: the continuum of care. Aust Crit Care 2008; 21:141-53. [PMID: 18387814 DOI: 10.1016/j.aucc.2008.02.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2007] [Revised: 01/30/2008] [Accepted: 02/07/2008] [Indexed: 01/15/2023] Open
Abstract
The following paper continues the presentation of a case scenario outlining the assessment, interventions and outcome of a person who sustained multiple trauma with a focus on traumatic brain injury (TBI). Part I explored assessment and initial management of the patient from pre-hospital care through to the emergency department and operating theatre. Part II describes the intensive care period as an integral component of the continuum of care. Key issues in the case are presented sequentially with relevant theory integrated and applied to the clinical case throughout the discussion with a focus on the complex physiological, psychological, and spiritual needs of the patient and their family.
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Affiliation(s)
- Suzy Ladanyi
- Faculty of Nursing, Midwifery and Health, University of Technology, Sydney, NSW, Australia.
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48
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Sanger GJ, Lee K. Hormones of the gut-brain axis as targets for the treatment of upper gastrointestinal disorders. Nat Rev Drug Discov 2008; 7:241-54. [PMID: 18309313 DOI: 10.1038/nrd2444] [Citation(s) in RCA: 77] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The concept of the gut forming the centre of an integrated gut-brain-energy axis - modulating appetite, metabolism and digestion - opens up new paradigms for drugs that can tackle multiple symptoms in complex upper gastrointestinal disorders. These include eating disorders, nausea and vomiting, gastroesophageal reflux disease, gastroparesis, dyspepsia and irritable bowel syndrome. The hormones that modulate gastric motility represent targets for gastric prokinetic drugs, and peptides that modify eating behaviours may be targeted to develop drugs that reduce nausea, a currently poorly treated condition. The gut-brain axis may therefore provide a range of therapeutic opportunities that deliver a more holistic treatment of upper gastrointestinal disorders.
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Affiliation(s)
- Gareth J Sanger
- Immuno Inflammation Centre of Excellence for Drug Discovery, GlaxoSmithKline, Stevenage, Hertfordshire SG1 2NY, UK.
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Sanger GJ. Motilin, ghrelin and related neuropeptides as targets for the treatment of GI diseases. Drug Discov Today 2008; 13:234-9. [PMID: 18342799 DOI: 10.1016/j.drudis.2007.10.024] [Citation(s) in RCA: 66] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2007] [Revised: 10/26/2007] [Accepted: 10/29/2007] [Indexed: 12/14/2022]
Abstract
Motilin and ghrelin are released from the upper gut during fasting, to stimulate gastric motility. Additional actions of ghrelin (e.g. changes in appetite, nausea or endocrine functions) improve the possibility of using ghrelin receptor agonists to treat complex disorders such as functional dyspepsia. However, changes in endocrine functions increase the risk of unacceptable side effects. By comparison, the more restricted prokinetic activity of motilin limits the therapeutic possibilities but improves the risk:benefit ratio. Compounds targeting both receptors are in development. Recently, additional peptides have been identified from preproghrelin (obestatin) and prepromotilin. These exert biological activity but their pathophysiological significance is unknown.
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Affiliation(s)
- Gareth J Sanger
- ImmunoInflammatory-CEDD, GlaxoSmithKline, Stevenage, Herts, UK.
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50
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Herbert MK, Holzer P. Standardized concept for the treatment of gastrointestinal dysmotility in critically ill patients--current status and future options. Clin Nutr 2007; 27:25-41. [PMID: 17933437 DOI: 10.1016/j.clnu.2007.08.001] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2007] [Accepted: 07/20/2007] [Indexed: 12/22/2022]
Abstract
Inhibition of gastrointestinal motility is a major problem in critically ill patients. Motor stasis gives rise to subsequent complications including intolerance to enteral feeding, enhanced permeability of the atrophic intestinal mucosa and conditions as severe as systemic inflammatory response syndrome, sepsis and multiple organ failure. Although the diagnosis of motility disturbances in critically ill patients is difficult, the type and site of the disturbance are important to consider in the analysis of the condition and in the choice of therapeutic approach. The pharmacological treatment of impaired gastrointestinal motility is difficult to handle for the clinician, because the underlying mechanisms are complex and not fully understood and the availability of pharmacological treatment options is limited. In addition, there is a lack of controlled studies on which to build an evidence-based treatment concept for critically ill patients. Notwithstanding this situation, there has been remarkable progress in the understanding of the integrated regulation of gastrointestinal motility in health and disease. These advances, which largely relate to the organization of the enteric nervous system and its signaling mechanisms, enable the intensivist to develop a standardized concept for the use of prokinetic agents in the treatment of impaired gastrointestinal motility in critically ill patients.
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Affiliation(s)
- Michael K Herbert
- Department of Anaesthesiology, University of Wuerzburg, Oberduerrbacher Str. 6, 97080 Wuerzburg, Germany.
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