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Kumaria A, Kirkman MA, Scott RA, Dow GR, Leggate AJ, Macarthur DC, Ingale HA, Smith SJ, Basu S. A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review. J Neurosurg Anesthesiol 2024; 36:211-217. [PMID: 37188653 DOI: 10.1097/ana.0000000000000918] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 03/21/2023] [Indexed: 05/17/2023]
Abstract
In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.
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Affiliation(s)
| | | | - Robert A Scott
- NIHR Biomedical Research Centre, Nottingham University Hospitals NHS Trust
- Nottingham Digestive Diseases Centre
| | - Graham R Dow
- Department of Neurosurgery, Queen's Medical Centre
| | | | | | | | - Stuart J Smith
- Department of Neurosurgery, Queen's Medical Centre
- Children's Brain Tumour Research Centre, School of Medicine, University of Nottingham, Nottingham, UK
| | - Surajit Basu
- Department of Neurosurgery, Queen's Medical Centre
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Penaud V, Vieille T, Urbina T, Bonny V, Gabarre P, Missri L, Gasperment M, Baudel JL, Carbonell N, Beurton A, Chaibi S, Retbi A, Fartoukh M, Piton G, Guidet B, Maury E, Ait-Oufella H, Joffre J. Prediction of esophagogastroduodenoscopy therapeutic usefulness for in-ICU suspected upper gastrointestinal bleeding: the SUGIBI score study. Ann Intensive Care 2024; 14:28. [PMID: 38361004 PMCID: PMC10869326 DOI: 10.1186/s13613-024-01250-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Accepted: 01/16/2024] [Indexed: 02/17/2024] Open
Abstract
BACKGROUND Suspected upper gastrointestinal bleeding (SUGIB) is a common issue during ICU stay. In the absence of specific guidelines on the indication and timing of esophagogastroduodenoscopy (EGD), there is substantial variability in EGD indication depending on accessibility and clinical presentation. This study aimed to investigate factors associated with the need for per-EGD hemostatic therapy and to create a score predicting therapeutic benefit of emergency bedside EGD in ICU patients with SUGIB. METHODS We conducted a retrospective study in our ICU to identify factors associated with the need for hemostatic procedure during EGD performed for SUGIB. From this observational cohort, we derived a score predicting the need for hemostasis during EGD, the SUGIBI score. This score was subsequently validated in a retrospective multicenter cohort. RESULTS Two hundred fifty-five patients not primarily admitted for GI bleeding who underwent a bedside EGD for SUGIB during their ICU stay were analyzed. The preeminent EGD indication were anemia (79%), melena (19%), shock (14%), and hematemesis (13%). EGD was normal in 24.7% of cases, while primary lesions reported were ulcers (23.1%), esophagitis (18.8%), and gastritis (12.5%). Only 12.9% of patients underwent hemostatic endotherapy during EGD. A SUGIBI score < 4 had a negative predictive value of 95% (91-99) for hemostatic endotherapy [AUC of 0.81; 0.75-0.91 (p < 0.0001)]. The SUGIBI score for predicting the need for an EGD-guided hemostatic procedure was next validated in a multicenter cohort with an AUC of 0.75 (0.66-0.85) (p < 0.0001), a score < 4 having a negative predictive value of 95% (92-97). CONCLUSIONS Our study shows that the therapeutic usefulness of bedside emergency EGD for SUGIB in critically ill patients is limited to a minority of patients. The SUGIBI score should help clinicians stratify the probability of a therapeutic EGD.
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Affiliation(s)
- Victor Penaud
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Thibault Vieille
- Intensive Care Unit, Besançon University Hospital, 25000, Besançon, France
| | - Tomas Urbina
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Vincent Bonny
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Paul Gabarre
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Louai Missri
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Maxime Gasperment
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Jean-Luc Baudel
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Nicolas Carbonell
- Gastroenterology Department, AP-HP, Hôpital Saint-Antoine, Sorbonne University, 75012, Paris, France
| | - Alexandra Beurton
- Intensive Care Unit, Tenon University Hospital, APHP, Sorbonne University, 75020, Paris, France
| | - Sayma Chaibi
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Aurélia Retbi
- Département d'Information Médicale, Hôpital Saint Antoine, Assistance Publique-Hôpitaux de Paris, Sorbonne University, Paris, France
| | - Muriel Fartoukh
- Intensive Care Unit, Tenon University Hospital, APHP, Sorbonne University, 75020, Paris, France
| | - Gaël Piton
- Intensive Care Unit, Besançon University Hospital, 25000, Besançon, France
| | - Bertrand Guidet
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
- Pierre Louis Institute of Epidemiology and Public Health, Inserm U1136, Sorbonne University, Paris, France
| | - Eric Maury
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
| | - Hafid Ait-Oufella
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France
- Paris Cardiovascular Research Center, Inserm U970, Paris Center University, Paris, France
| | - Jérémie Joffre
- Medical Intensive Care Unit, Saint Antoine University Hospital, APHP, Sorbonne University, 75012, Paris, France.
- Centre de Recherche Saint-Antoine, Inserm UMRS-938, Sorbonne University, Paris, France.
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Gastroprotective Effects of Paeonia Extract Mixture HT074 against Experimental Gastric Ulcers in Rats. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:3546258. [PMID: 30906413 PMCID: PMC6398042 DOI: 10.1155/2019/3546258] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 02/03/2019] [Indexed: 12/26/2022]
Abstract
Background Paeonia extract mixture HT074 is a standardized multiherbal mixture comprising extracts from Inula britannica flowers and Paeonia lactiflora roots, which are used to treat digestive disorders in traditional Korean medicine. This study was focused on elucidating the underlying mechanisms of the gastroprotective effects of HT074 in different gastric ulcer models. Methods Gastric lesions were induced in rats by an HCl/EtOH solution, water immersion-restraint stress (WIRS), and indomethacin. Gastric secretions were studied in pylorus-ligated rats, while mucus secretions were assessed by measuring alcian blue-binding capacity of mucus in the rat model of HCl/EtOH-induced gastric ulcer. Additionally, the involvement of nitric oxide (NO) and sulfhydryl compounds in HT074-mediated mucosal protection was elucidated using their inhibitors, i.e., NG-nitro- L-arginine methyl ester hydrochloride (L-NAME) and N-ethylmaleimide (NEM), respectively. Furthermore, the effects on indomethacin-induced cell death and prostaglandin E2 (PGE2) levels were assessed in AGS cells. Results Oral administration of HT074 significantly decreased gastric lesions induced by HCl/EtOH, WIRS, and indomethacin. Furthermore, it significantly decreased the volume, acidity, and total acidity of gastric juice in pylorus-ligated rats and increased the alcian blue-stained gastric mucus in HCl/EtOH-induced gastric ulcer in rats. Pretreatment with NEM abolished the gastroprotective effects of HT074, while L-NAME did not. In AGS cells, HT074 significantly reduced indomethacin-induced cell death and increased the PGE2 levels. Conclusions These findings suggest that HT074 has gastroprotective effects against various ulcerogens, including HCl/EtOH, immersion stress, and NSAIDs. These effects are attributed to the inhibition of gastric secretions and preservation of the gastric mucosal barrier by increased mucus production, which is partially mediated through endogenous sulfhydryl compounds and PGE2. Based on these findings, we propose that HT074 may be a promising therapeutic agent for gastritis and gastric ulcer.
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di Nunzio MR, Douhal Y, Organero JA, Douhal A. Structural and photodynamic properties of the anti-cancer drug irinotecan in aqueous solutions of different pHs. Phys Chem Chem Phys 2018; 20:14182-14191. [PMID: 29761192 DOI: 10.1039/c8cp01134f] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
This work reports on photophysical studies of the irinotecan (IRT) anti-cancer drug in water solutions of different acidities (pH = 1.11-9.46). We found that IRT co-exists as mono-cationic (C1), di-cationic (C2), or neutral (N) forms. The population of each prototropic species depends on the pH of the solution. At pH = 1.11-3.01, the C1 and C2 structures are stabilized. At pH = 7.00, the most populated species is C1, while at pH values larger than 9.46 the N form is the most stable species. In the 1.11-2.61 pH range, the C1* emission is efficiently quenched by protons to give rise to the emission from C2*. The dynamic quenching constant, KD, is ∼32 M-1. While the diffusion governs the rate of excited-state proton-transfer (ESPT) under these conditions, the reaction rate increases with the proton concentration. A two-step diffusive Debye-Smoluchowski model was applied at pH = 1.11-2.61 to describe the protonation of C1*. The ESPT time constants derived for C1* are 382 and 1720 ps at pH = 1.11 and 1.95, respectively. We found that one proton species is involved in the protonation of C1* to give C2*, in the analyzed acidic pH range. Under alkaline conditions (pH = 9.46), the N form is the most stable structure of IRT. These results indicate the influence of the pH of the medium on the structural and dynamical properties of IRT in water solution. They may help to provide a better understanding on the relationship between the structure and biological activity of IRT.
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Affiliation(s)
- Maria Rosaria di Nunzio
- Departamento de Química Física, Facultad de Ciencias Ambientales y Bioquímica, and INAMOL, Universidad de Castilla-La Mancha, Avenida Carlos III, S/N, 45071 Toledo, Spain.
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Kaplan MM, May JR. The Influence of pH Control on the Prevention and Management of Gastrointestinal Bleeding. J Intensive Care Med 2016. [DOI: 10.1177/0885066690005001s06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Gastrointestinal bleeding from stress-related mucosal damage (SRMD) is caused by a breakdown in the pro cesses that normally protect the gastric mucosa from the corrosive effects of gastric acid and the proteolytic enzyme pepsin. Prostaglandins stimulate some of these protective factors, which include mucus secretion, bi carbonate secretion, rapid cellular repair and rapid blood flow. Acid and pepsin inhibit blood clotting in the stomach by inhibiting platelet aggregation and the func tion of all of the blood clotting factors. The inhibition of blood clotting in the stomach exacerbates bleeding caused by ulcers in the stomach and duodenum. Hence, treatment that will raise intragastric pH (lower acid con centration) should be effective in preventing gastric bleeding from SRMD. Patients in intensive care units are at high risk of developing upper gastrointestinal bleed ing from SRMD. It is easier to prevent SRMD bleeding than to treat it once it starts. Hence, patients in intensive care units should be treated prophylactically to prevent bleeding. Controlled trials and clinical experience indi cate that both antacids and H2 blockers in doses high enough to raise the intragastric pH above 4 are effective forms of prophylaxis. Intravenously administered H2 blockers are more convenient to administer and have fewer side effects than the large doses of antacid re quired to maintain the intragastric pH above 4.
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Affiliation(s)
- Marshall M. Kaplan
- Division of Gastroenterology, New England Medical Center,
Tufts University School of Medicine, Boston, MA
| | - J. Russell May
- Pharmacy for Drug Information and Clinical Services,
The Medical College of Georgia, Augusta, GA
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Abstract
Stress ulcer syndrome refers to gastroduodenal erosions or ulcers that develop acutely in relation to major physi ological stress, usually manifested clinically as upper gastrointestinal (UGI) bleeding. These lesions occur most often in the gastric fundus. Endoscopy has shown gastroduodenal mucosal lesions in 75 to 100% of inten sive care unit (ICU) patients within 72 hours of admis sion. Patients at high risk for stress ulcer include those with large body surface area burns, intracranial lesions associated with coma, fulminant hepatic failure, sepsis, and trauma and abdominal, cardiovascular, and thoracic surgery patients. Also considered high risk are ICU pa tients with superimposed complications such as shock, mechanical ventilation for more than 3 days, coagulopa thy, jaundice, and sepsis. Approximately 15% of ICU pa tients will experience UGI bleeding from stress ulcer. Patients bleeding from stress ulcer have an overall mor tality rate approaching 65% compared with 9 to 22% mortality in patients without stress ulcer. When strati fied according to occult blood loss versus clinically significant bleeding, mortality can be as high as 90% in patients overtly bleeding; 30% of deaths are directly related to bleeding. Both antacids and H2 receptor an tagonists are effective in prophylaxis for stress ulcer bleeding.
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Affiliation(s)
| | - David Cort
- Washington University School of Medicine, St. Louis, MO
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Abstract
In general, the histamine type-2 receptor antagonists (H2RA) enjoy an enviable record of safety. These agents, notably cimetidine, have been studied extensively in clinical trials, case reports, and worldwide drug use reporting systems. Of the available agents (cimetidine, famotidine, nizatidine, and ranitidine) several similarities exist from compound to compound and use data to support that each of the agents is equally safe and efficacious in equipotent dosing. A review of H2RA pharmacology, pharmacokinetics, adverse effects, and drug interactions is included to provide the clinician with a basis for rational selection and use of an H2RA.
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Affiliation(s)
- Edward J. Drea
- Department of Pharmacy Services, Memorial Medical Center, Springfield, IL
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A. Ketuly K, A. Hadi AH, Golbabapour S, Hajrezaie M, Hassandarvish P, Ali HM, Majid NA, Abdulla MA. Acute toxicity and gastroprotection studies with a newly synthesized steroid. PLoS One 2013; 8:e59296. [PMID: 23516624 PMCID: PMC3596355 DOI: 10.1371/journal.pone.0059296] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2012] [Accepted: 02/14/2013] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats. METHODOLOGY/PRINCIPAL FINDING Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes. CONCLUSION/SIGNIFICANCE The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.
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Affiliation(s)
- Kamal A. Ketuly
- Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - A. Hamid A. Hadi
- Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Shahram Golbabapour
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Maryam Hajrezaie
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Pouya Hassandarvish
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Hapipah Mohd Ali
- Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Nazia Abdul Majid
- Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
| | - Mahmood A. Abdulla
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
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Guillaume A, Seres DS. Safety of Enteral Feeding in Patients With Open Abdomen, Upper Gastrointestinal Bleed, and Perforation Peritonitis. Nutr Clin Pract 2012; 27:513-20. [DOI: 10.1177/0884533612450919] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
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10
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CHEN CY, KUO TL, SHEU SY, KUO TF. Preventive Effects of Chinese Herb Chai-Hu-Gui-Zhi-Tang Extract on Water Immersion Restraint Stress-Induced Acute Gastric Ulceration in Rats. J Vet Med Sci 2010; 72:679-85. [DOI: 10.1292/jvms.09-0284] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Chi-Yang CHEN
- Graduate Institute of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University
| | - Tsung-Li KUO
- Department of Forensic Medicine, College of Medicine, National Taiwan University
| | - Shi-Yuan SHEU
- School of Chinese Medicine, China Medical University
- Department of Acupuncture, E-DA Hospital / I-Shou University
| | - Tzong-Fu KUO
- Graduate Institute of Veterinary Medicine, College of Bio-Resources and Agriculture, National Taiwan University
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Lee YC, Wang HP, Wu MS, Yang CS, Chang YT, Lin JT. Urgent bedside endoscopy for clinically significant upper gastrointestinal hemorrhage after admission to the intensive care unit. Intensive Care Med 2003; 29:1723-8. [PMID: 12915940 DOI: 10.1007/s00134-003-1921-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2002] [Accepted: 06/12/2003] [Indexed: 10/26/2022]
Abstract
OBJECTIVE To investigate the sources of hemorrhage and use of endoscopic hemostasis in patients with clinically significant upper gastrointestinal (UGI) hemorrhage after admission to the intensive care unit (ICU). DESIGN AND SETTING Prospective study, 123 beds of ICU in a 1,629-bed medical center. MEASUREMENTS AND RESULTS Of the 9,512 consecutive admissions over a 2-year period 105 UGI hemorrhage patients underwent urgent bedside UGI endoscopy. We compared two groups of these patients, one receiving and the other not receiving endoscopic hemostasis. Ulcers with profusely bleeding stigmata occurred in 31 patients (29.5%), ulcers with clean bases or firmly adherent blood clots in 27 (25.7%), stress-related mucosal diseases in 23 (21.9%), esophageal varices in 5 (4.8%), malignancy in 4 (3.8%), and no detectable bleeding site in 15 (14.3%). Endoscopic hemostasis was attempted in 34 patients (32.4%). Primary hemostasis for them was achieved in 67.6% and the rebleeding rate was 30.4%. In-hospital mortality rate was 77.1% and death related to hemorrhage 6.2%. Length of ICU stay before endoscopic diagnosis was significantly shorter in those who underwent endoscopic hemostasis than those who did not (28.2+/-26.3 vs. 41.2+/-57.5 days). CONCLUSIONS Endoscopic hemostasis may be more beneficial when the period between ICU admission and development of hemorrhage is shorter. Bleeders can be more readily identified and controlled endoscopically in such patients. A significant proportion of bleeding sites cannot be identified by UGI endoscopy. It may indicate higher risk of small bowel hemorrhage in these critically ill patients.
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Affiliation(s)
- Yi-Chia Lee
- Department of Internal Medicine, En Chu Kong Hospital, Taipei, Taiwan
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12
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Wassef W, Obando J, Sharma A. Upper Gastrointestinal Bleeding of Nonvariceal Origin in the ICU Setting. J Intensive Care Med 2001. [DOI: 10.1046/j.1525-1489.2001.00105.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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13
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Wassef W, Obando J, Sharma A. Upper Gastrointestinal Bleeding of Nonvariceal Origin in the ICU Setting. J Intensive Care Med 2001. [DOI: 10.1177/088506660101600301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Upper gastrointestinal bleeding (UGI) is a common medical emergency in the intensive care unit (ICU). Although it can be caused by a number of gastrointestinal disorders, its management usually follows a few simple management rules. Prior to endoscopy, the key to management is to resuscitate the patient, to determine the need for airway protection, and to assess the need for transfusions according to the American Society of Gastrointestinal Endoscopy guidelines. During endoscopy, the key to management is to recognize the cause of the bleeding and to achieve hemostasis. Following endoscopy, the key to management is to determine the need for medical therapy and to determine a proper disposition for the patient given his potential risk for rebleeding. Stress-related erosions syndrome (SRES) is a disease that usually develops in the ICU setting and is known to be associated with a high degree of morbidity and mortality. Although it is approached in the same fashion as other causes of UGI bleeding, patients tend to do better if they are recognized early and treated prophylactically. Criteria for proper patient selection and the recommended prophylactic therapy are reviewed.
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Affiliation(s)
- Wahid Wassef
- Division of Digestive Disease and Nutrition, UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, MA
| | - Jorge Obando
- Division of Digestive Disease and Nutrition, UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, MA
| | - Ashish Sharma
- Division of Digestive Disease and Nutrition, UMass Memorial Health Care, University of Massachusetts Medical School, Worcester, MA
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Beejay U, Wolfe MM. Acute gastrointestinal bleeding in the intensive care unit. The gastroenterologist's perspective. Gastroenterol Clin North Am 2000; 29:309-36. [PMID: 10836185 DOI: 10.1016/s0889-8553(05)70118-7] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Although SRES-associated hemorrhage previously constituted a significant cause of bleeding in the ICU, improvements in ICU management and the institution of prophylactic measures in high-risk patients have significantly reduced SRES-associated hemorrhage since the 1980s. Antacids, H2-receptor antagonists, and sucralfate have been shown to be effective in preventing clinically significant bleeding resulting from SRES, particularly when the intragastric pH is maintained at greater than 4. A selective approach should be adopted in SRES prophylaxis: Patients on mechanical ventilation, with coagulopathy, or with two of the other known risk factors should receive prophylaxis. Although the drug of choice depends to some extent on local preferences, an H2-receptor antagonist by continuous intravenous infusion may represent the best option. No pharmacologic therapy is of proven value once hemorrhage begins, but the current interventional techniques are effective in controlling hemorrhage. Gastrointestinal bleeding from NOMV has become less common with improvements in the hemodynamic monitoring of critically ill patients, but this disease must always be considered when lower gastrointestinal bleeding occurs in the context of relative hypoperfusion. For SRES and NOMV, treatment of the underlying disease or diseases is the optimal route to prevention.
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Affiliation(s)
- U Beejay
- Section of Gastroenterology, Boston University School of Medicine, Massachusetts, USA
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Zhu L, Yang ZC, Li A, Cheng DC. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions. World J Gastroenterol 2000; 6:84-88. [PMID: 11819529 PMCID: PMC4723604 DOI: 10.3748/wjg.v6.i1.84] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.
METHODS: A rat model with 30% TBSA full-thickness burn injury w as employed and the gastric acid production, together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48 h postburn.
RESULTS: The gastric acid production in the acute shock period was markedly inhibited after severe burn injury. At the 3rd h postburn, the gas tricjuice volume, total acidity and acid output were already significantly decreased (P < 0.01), and reached the lowest point, 0.63 mL/L ± 0.20 mL/L, 10.81 mmol/L ± 2.58 mmol/L and 2.23 mmol/h ± 0.73 mmol/h respectively, at the 12th h postburn. Although restored to some degree 24 h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, co nsistent with the trend of gastric acid production changes.
CONCLUSION: Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment.
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Cook D, Heyland D, Griffith L, Cook R, Marshall J, Pagliarello J. Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. Crit Care Med 1999; 27:2812-7. [PMID: 10628631 DOI: 10.1097/00003246-199912000-00034] [Citation(s) in RCA: 175] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To evaluate the incidence and risk factors for clinically important upper gastrointestinal bleeding in critically ill patients requiring mechanical ventilation. DESIGN In duplicate, blinded adjudicators determined the presence of clinically important gastrointestinal bleeding using a priori criteria, evaluating relevant clinical, laboratory, and diagnostic data. Cox proportional hazards regression analyses were used to examine baseline and time-dependent risk factors for bleeding. SETTING Sixteen university-affiliated intensive care units (ICUs) in Canada. PATIENTS A total of 1,077 critically ill ICU patients ventilated for at least 48 hrs. INTERVENTIONS Patients were randomized to stress ulcer prophylaxis with intravenous ranitidine or nasogastric sucralfate; otherwise, management was at the discretion of the ICU team. MEASUREMENTS AND MAIN RESULTS Demographic data included patient characteristics, Acute Physiology and Chronic Health Evaluation II score, and multiple organ dysfunction (MOD) score. Each day in the ICU, physiologic measurements including MOD score, feeding, and other treatment variables were recorded. The significant risk factors for upper gastrointestinal bleeding in the univariable analyses were low platelet count, maximum serum creatinine, maximum MOD score, maximum pulmonary component of the MOD score, maximum hepatic component of the MOD score, maximum renal component of the MOD score, enteral nutrition, and stress ulcer prophylaxis with ranitidine. The only independent predictors of bleeding in the multivariable analysis were maximum serum creatinine (relative risk = 1.16 [95% confidence interval = 1.02-1.32]), enteral nutrition (relative risk = 0.30 [95% confidence interval = 0.13-0.67]), and ranitidine administration (relative risk = 0.39 [95% confidence interval = 0.17-0.83]). CONCLUSIONS In critically ill ventilated patients, renal failure was independently associated with an increased risk of clinically important gastrointestinal bleeding, whereas enteral nutrition and stress ulcer prophylaxis with ranitidine conferred significantly lower bleeding rates.
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Affiliation(s)
- D Cook
- Department of Medicine, McMaster University, Hamilton, ON, Canada
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17
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Heyland DK, Cook DJ, Schoenfeld PS, Frietag A, Varon J, Wood G. The effect of acidified enteral feeds on gastric colonization in critically ill patients: results of a multicenter randomized trial. Canadian Critical Care Trials Group. Crit Care Med 1999; 27:2399-406. [PMID: 10579255 DOI: 10.1097/00003246-199911000-00013] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To evaluate the effect of acidified enteral feeds on gastric colonization in critically ill patients compared with a standard feeding formula. DESIGN Randomized, double-blind, multicenter trial. SETTING Eight mixed intensive care units at tertiary care hospitals. PATIENTS We recruited mechanically ventilated critically ill patients expected to remain ventilated for >48 hrs. We excluded patients with gastrointestinal bleeding, acidemia, and renal failure requiring dialysis. We enrolled 120 patients; 38% were female, age (mean +/- SD) was 57.6+/-19.3 yrs, and Acute Physiology and Chronic Health Evaluation II score (mean +/- SD) was 21.6+/-7.6. INTERVENTIONS Vital High Nitrogen (Abbott Laboratories, Ross Products Division, Columbus, OH) was used as the standard feeding formula for the control group (pH = 6.5). Hydrochloric acid was added to Vital High Nitrogen to achieve a pH of 3.5 in the experimental group. MEASUREMENTS AND MAIN RESULTS The main outcome measure was gastric colonization. Secondary outcomes included gastric pH, pneumonia, and mortality. The mean gastric pH in patients receiving acid feeds was lower (pH = 3.3) compared with controls (pH = 4.6; p<.05). One patient (2%) on acid feeds was colonized in the stomach with pathogenic bacteria, compared with 20 patients (43%) in the control group (p<.001). There was no difference in the incidence of pneumonia (6.1% in the acid feeds group vs. 15% in the control group; p = .19). Overall, there were 15 deaths in the acid feeds group and seven in the control group (p = .10); four patients in the acid feeds group and three in the control group died during the study period (p not significant). CONCLUSIONS Acidified enteral feeds preserve gastric acidity and substantially reduce gastric colonization in critically ill patients. Larger studies are needed to examine its effect on ventilator-associated pneumonia and mortality.
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Affiliation(s)
- D K Heyland
- Department of Medicine, Queen's University, Kingston, ON, Canada.
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18
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Olsen KM, Hiller F, Ackerman BH, Crisp-Landwehr K, San Pedro GS. Effect of single intravenous doses of histamine2-receptor antagonists on volume and pH of gastric acid secretions in critically ill patients. Curr Ther Res Clin Exp 1995. [DOI: 10.1016/0011-393x(95)85059-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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19
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Chan KH, Lai EC, Tuen H, Ngan JH, Mok F, Fan YW, Fung CF, Yu WC. Prospective double-blind placebo-controlled randomized trial on the use of ranitidine in preventing postoperative gastroduodenal complications in high-risk neurosurgical patients. J Neurosurg 1995; 82:413-7. [PMID: 7861219 DOI: 10.3171/jns.1995.82.3.0413] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
To determine the efficacy of ranitidine in preventing clinically acute overt gastroduodenal (GD) complications (bleeding and/or perforation) after neurosurgery, 101 patients with nontraumatic cerebral disease considered at high risk of developing postoperative GD complications were randomized in a standard double-blind manner to receive either ranitidine (50 mg every 6 hours) or placebo medication preoperatively. Postoperative serial GD endoscopy was used to document the occurrence of complications: an overt symptomatic complication was defined as bleeding requiring blood transfusion and/or surgery. Fifty-two patients received ranitidine and 49 received a placebo preoperatively; 30 developed overt GD bleeding; nine of these received ranitidine and 21 received a placebo. Ranitidine significantly reduced the incidence of bleeding (p < 0.05). Multivariate logistic regression analysis revealed three factors of independent significance in predicting overt GD bleeding: use of a placebo drug, a gastric pH of less than 4, and a high daily volume of gastric output. The authors conclude that ranitidine is useful in preventing postoperative GD complications in high-risk neurosurgical patients.
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Affiliation(s)
- K H Chan
- Department of Surgery, Queen Mary Hospital, University of Hong Kong
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20
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Blandizzi C, Gherardi G, Natale G, Marveggio C, Del Tacca M. Protective action of omeprazole against gastric mucosal injury induced by hemorrhagic shock in rats. Dig Dis Sci 1994; 39:2109-17. [PMID: 7924729 DOI: 10.1007/bf02090358] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The efficacy of omeprazole in preventing gastric mucosal injury induced by hemorrhagic shock in rats and the putative mechanisms involved in this effect were investigated in the present study. Omeprazole did not affect mean arterial blood pressure under both basal conditions and induction of hemorrhagic shock, but it evoked a marked increase in Alcian blue recovery from gastric preepithelial mucus. The morphometric analysis of histological sections revealed that omeprazole caused a significant reduction of hemorrhagic shock-induced damage of gastric mucosa. Ranitidine, used as the reference drug, failed to affect mean arterial blood pressure, Alcian blue recovery from gastric mucus, or hemorrhagic shock-induced damage of gastric mucosa. Both omeprazole and ranitidine exerted a significant inhibition of gastric acid output from anesthetized pylorus-ligated rats. Overall, the present results indicate that omeprazole is effective in protecting gastric mucosa from necrotic damage induced by hemorrhagic shock and suggest that an enhancement of gastric mucus secretion contributes to this protective action.
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MESH Headings
- Animals
- Blood Pressure/drug effects
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical
- Gastric Acid/metabolism
- Gastric Mucosa/drug effects
- Gastric Mucosa/pathology
- Male
- Omeprazole/pharmacology
- Omeprazole/therapeutic use
- Ranitidine/therapeutic use
- Rats
- Rats, Wistar
- Shock, Hemorrhagic/complications
- Shock, Hemorrhagic/pathology
- Shock, Hemorrhagic/physiopathology
- Stomach Ulcer/etiology
- Stomach Ulcer/pathology
- Stomach Ulcer/physiopathology
- Stomach Ulcer/prevention & control
- Stress, Physiological/etiology
- Stress, Physiological/pathology
- Stress, Physiological/physiopathology
- Stress, Physiological/prevention & control
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Affiliation(s)
- C Blandizzi
- Institute of Medical Pharmacology, University of Pisa, Italy
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21
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Kayabali M, Hazar H, Gürsoy MA, Bulut T. Free oxygen radicals in restraint-induced stress gastritis in the rat. Surg Today 1994; 24:530-3. [PMID: 7919736 DOI: 10.1007/bf01884573] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
In this experimental study, the role of free oxygen radicals (FOR) in stress gastritis (SG) was investigated in a restraint stress model for rats. Allopurinol, dimethyl sulfoxide (DMSO), and superoxide dismutase (SOD) were tested as single agents in controlled groups. The portal blood pH values, the ratio of the mucosal erosion area to the gastric mucosal area (EA/MA), the ratio of the depth of mucosal erosions to the concomitant gastric mucosal wall (ED/MD), and concentrations of malondialdehyde (MDA)--a lipid peroxidation coproduct--in the gastric mucosa were used as parameters in the experiment. The EA/MA between the treated and untreated control groups were found to have no statistically significant difference (P > 0.05). ED/MD, a crucial determinant for bleeding probability, was found to be decreased in the SOD group (P < 0.05). SOD, allopurinol, and DMSO reduced the mucosal MDA concentration to lower values than the untreated group (P < 0.05). We concluded that although FOR may not play a dominant role in stress-induced gastric lesions, SOD may be a good candidate for a clinical trial on SG prophylaxis.
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Affiliation(s)
- M Kayabali
- Department of Surgery, Istanbul Medical Faculty, Turkey
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22
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Hogan DL, McQuaid KR, Koss MA, Crombie DL, Hunter S, Metz C, Euler AR, Isenberg JI. Gastric acid suppression is greater during intravenous ranitidine infusion versus bolus injections of famotidine. Aliment Pharmacol Ther 1993; 7:537-41. [PMID: 8280822 DOI: 10.1111/j.1365-2036.1993.tb00130.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
It has been proposed that famotidine may be effective in maintaining intragastric pH > or = 4 for up to 12 h with a single i.v. 20 mg bolus injection and thereby prevent acute stress-related mucosal haemorrhage. The present study was designed to compare a ranitidine continuous i.v. infusion (6.25 mg/h) vs. famotidine bolus injection (20 mg every 12 h) on 24-h intragastric pH and gastric acid secretion. Twenty-eight healthy volunteers (15 males, 13 females; 20-56 years) participated in two 24-h treatment periods; each test was in random order separated by 7-10 days. After an overnight fast, subjects were intubated and gastric pH and acid secretion measured hourly. Whereas ranitidine maintained gastric pH above 4 for the entire 24-h period, mean pH steadily decreased to a nadir of 2.9 and 3.7, respectively, 12 h after each famotidine injection (P < 0.01 vs. ranitidine). Furthermore, gastric acid secretion increased to 4.4 +/- 1.2 mmol/h 12 h after famotidine injection compared to 1.1 +/- 0.3 mmol/h with ranitidine (P < 0.01). We conclude that ranitidine delivered as a continuous i.v. infusion (6.25 mg/h) is superior to bolus famotidine injections (20 mg) at 12-h intervals in suppressing gastric acid secretion and maintaining an intragastric pH > or = 4. More frequent famotidine dosing, or delivery by continuous i.v. infusion, may be required to provide prolonged acid suppression.
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Affiliation(s)
- D L Hogan
- Division of Gastroenterology, University of California San Diego
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23
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Benjamin E, Oropello JM, Iberti TJ. Acute mesenteric ischemia: pathophysiology, diagnosis, and treatment. Dis Mon 1993; 39:131-210. [PMID: 8472615 DOI: 10.1016/0011-5029(93)90023-v] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Ischemia has traditionally been viewed as arising only from abnormalities of oxygen dynamics, namely the cellular hypoxia resulting from the imbalances between oxygen supply, consumption, and demand. Recently, it has become clear that such a view is too restrictive. Hypoperfusion may be caused by both anatomic and functional impediments to either inflow or to outflow from an organ. Furthermore, the pathophysiologic consequences are likely to involve not only cellular hypoxia, but also a restricted supply of nutrients and other important molecules and an abnormal elimination of physiologic wastes such as carbon dioxide. Hence the recommendation that ischemia be defined as a dual defect of oxygen deficit and carbon dioxide excess. AMI is, therefore, a severe anatomic or functional impediment to the splanchnic circulation, resulting in a dual defect of intestinal hypoxia and cellular hypercarbia. Although the functional and structural consequences of cellular hypoxia are well known, the pathophysiology of cellular hypercarbia has only begun to be explored. AMI syndromes include three related processes: occlusive mesenteric ischemia, nonocclusive ischemia, and sepsis-induced SI. Leakage of bacteria or bacterial toxins into the circulation during mesenteric ischemia forms the basis of the systemic components of this syndrome. Striving for an earlier diagnosis, treating the systemic (septic) consequences, and taking measures to promptly restore mucosal oxygen balance through aggressive pharmacologic and appropriate surgical intervention have significantly improved the prognosis. About 80% of patients with acute arterial embolism, 60% of those with nonocclusive ischemia, and only 20% of patients with arterial thrombosis are expected to live without significant residual nutritional deficits. The cause of death is usually sepsis and multisystem organ failure, and therefore, further reductions in mortality are likely to occur with the improved prevention and treatment of sepsis.
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Affiliation(s)
- E Benjamin
- Mount Sinai School of Medicine, New York, New York
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24
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Ephgrave KS, Kleiman-Wexler RL, Adair CG, Skaar LM. Cholecystokinin does not mediate glucose's cytoprotective effects. J Surg Res 1992; 53:145-51. [PMID: 1405602 DOI: 10.1016/0022-4804(92)90026-v] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Cold restraint stress produces acute gastric mucosal injury in association with altered gastric motility. Enteral nutrients prevent this injury in conjunction with inhibition of gastric emptying. Because cholecystokinin (CCK) is released by nutrients known to be cytoprotective and is thought to inhibit gastric emptying, we performed three experiments to see if CCK contributes to the gastric mucosal protection afforded by enteral nutrients. Our data show that enteral glucose protects the gastric mucosa and increases gastric volume, gastric luminal pH, and gastric mucin. Neither physiologic nor pharmacologic doses of CCK protected the mucosa. None of the other significant effects of glucose on gastric function during cold restraint were affected by exogenous CCK. Furthermore, antagonism of CCK receptors with L-364,718 did not have any independent effects, nor did it diminish the protection associated with enteral glucose. We conclude that enteral glucose protects the gastric mucosa from cold restraint injury in association with a number of potentially beneficial effects on gastric physiology, but none of the effects of glucose in this model appear to be mediated by CCK.
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Affiliation(s)
- K S Ephgrave
- Department of Surgery, University of Iowa College of Medicine, Iowa City 52246
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25
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Abstract
Bleeding from stress erosive gastritis continues to be a potential problem in critically ill and injured patients, but fortunately its incidence has decreased dramatically over the last decade. The explanation for this circumstance is probably multifactorial, but clearly relates to our increased knowledge of its pathophysiology. This understanding has led to the routine use of measures to reduce intragastric acidity (luminal acid being a prerequisite for stress ulcer to occur), coupled with improved techniques for the treatment of shock and the accompanying gastric mucosal hypoperfusion (another prerequisite for the formation of stress ulcers). A number of measures have been used to lower intragastric acidity with H2 receptor blockers emerging as the agents of choice to accomplish this goal. In the unlikely event that bleeding occurs despite these prophylactic measures, aggressive medical management will result in cessation of hemorrhage in over 80% of patients. In those few individuals requiring surgery to control bleeding, no operation has emerged as the recognized procedure of choice. Thus, we believe that a conservative operative approach is indicated in this setting and recommend vagotomy and pyloroplasty with oversewing of the bleeding erosions as appropriate therapy for most patients requiring surgical intervention.
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Affiliation(s)
- T A Miller
- Department of Surgery, University of Texas Medical School, Houston
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26
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Ekman T, Bagge U, Bylund-Fellenius AC, Soussi B, Risberg B. Changes in gastric mucosal microcirculation and purine nucleotide metabolism during hemorrhagic shock in rats. Scand J Gastroenterol 1991; 26:652-60. [PMID: 1862303 DOI: 10.3109/00365529109043640] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Intravital fluorescence microscopy and morphometry were used to study the microcirculation in the rat gastric mucosa during and after hemorrhagic shock. Under control conditions the circulation appeared homogeneous and unaffected by superfusion with 0.1 N HCl. During hemorrhagic shock, scattered areas of the mucosa lost circulation. Morphometry showed that the number of perfused mucosal vessels decreased significantly in the abluminal part of the mucosa both in perfused and ischemic areas, the reduction being most pronounced in the ischemic areas, where the number of perfused luminal vessels also decreased significantly. During reperfusion, bleedings occurred from the mucosa. A key finding was that the bleedings always had their origin at the border zone between ischemic and perfused areas. After hemorrhagic shock adenosine triphosphate and energy charge levels dropped significantly in both perfused and ischemic areas but with significantly lower levels in the ischemic areas. The hypoxanthine levels increased in both perfused and ischemic areas. The experiments show that local mucosal ischemia and accelerated nucleotide degradation are of pathogenetic importance in the development of stress ulcers after hemorrhagic shock. The border zone between circulated and ischemic areas seems to be an area of special interest.
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Affiliation(s)
- T Ekman
- Dept. of Medicine, Wallenberg Laboratory, University of Gothenburg, Sweden
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27
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Lebovics E, Lee SS, Dworkin BM, Heier SK, Casellas A, Reed G, Rosenthal WS. Upper gastrointestinal bleeding following open heart surgery. Predominant finding of aggressive duodenal ulcer disease. Dig Dis Sci 1991; 36:757-60. [PMID: 2032517 DOI: 10.1007/bf01311233] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
We reviewed our experience with endoscopically evaluated severe upper gastrointestinal hemorrhage following open heart surgery. Of 4892 patients undergoing open heart surgery, 18 (0.4%) sustained upper gastrointestinal hemorrhage requiring endoscopic evaluation. Endoscopy identified the source of bleeding in all cases. No significant complications of endoscopy were observed. Duodenal ulcers (DUs) were found in 16 (89%) of cases and were felt to be the source of bleeding in 15 (83%). Aggressive features, such as multiplicity, large size, or distal location were associated with 13 (81%) of the DU cases. Complications necessitated endoscopic or surgical therapy in eight (44%) patients with DUs. We conclude that aggressive DU disease accounts for the majority of severe upper gastrointestinal bleeding following open heart surgery.
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Affiliation(s)
- E Lebovics
- Department of Medicine, New York Medical College, Valhalla 10595
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28
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Morris RW, Boyle M, Jacobs S, Torda T. A graded combination regimen for maintenance of gastric pH above 3.5 in critically ill patients. Anaesth Intensive Care 1991; 19:79-83. [PMID: 2012300 DOI: 10.1177/0310057x9101900114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Prophylaxis of acute upper gastrointestinal bleeding by control of gastric pH has been widely advocated for intensive care patients. H2-blockers and antacids have been used and demonstrated to be incompletely effective at maintaining gastric pH above 4. A study of 100 patients measured the efficacy of two-hourly gastric pH measurement and titrated therapy consisting of five levels: 1. no therapy 2. ranitidine 50 mg 8 hourly intravenously 3. ranitidine plus Mylanta 30 ml 2 hourly by nasogastric tube 4. ranitidine plus Mylanta 60 ml 2 hourly and 5. ranitidine 100 mg 8 hourly intravenously plus Mylanta II 60 ml 2 hourly. The level of treatment required by proportions of the total study group were (1) 15%, (2) 71%, (3) 96%, (4) 100%. Head-injured and intubated patients generally fell in the more resistant group while patients having had major elective surgery required lower levels of therapy. If control of gastric pH is to be uniformly achieved, a technique of titrated therapy based on gastric pH measurements is supported as cheaper and more effective than other standardised treatment regimens.
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Affiliation(s)
- R W Morris
- Department of Anaesthesia and Intensive Care, Prince Henry Hospital, Sydney, New South Wales, Australia
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29
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Sandborn WJ, Forland SC, Cutler RE, Strong RM. Pharmacokinetics and pharmacodynamics of oral and intravenous cimetidine in seriously ill patients. J Clin Pharmacol 1990; 30:568-71. [PMID: 2355107 DOI: 10.1002/j.1552-4604.1990.tb03622.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
This study was done to determine if the pharmacokinetics and gastric pH response of intravenous cimetidine are superior to oral dosing in seriously ill patients. A paired study of intravenous followed by oral liquid cimetidine was given to eight men and two women who were inpatients in a VA Hospital. Treatment was prescribed for either upper gastrointestinal (GI) bleeding or prophylaxis against GI bleeding. All patients received cimetidine 300 mg every 6 hours intravenously on day 1 and orally on day 2. After the fourth dose each day, venous blood samples and gastric pH measurements were taken serially for 6 hours. Peak serum cimetidine concentration was 2.0 +/- 0.5 mg/L for the intravenous dose and 1.5 +/- 0.3 mg/L for the oral dose (P = .001). Area under the curve (AUC) of cimetidine concentration was 3.81 +/- 1.1 mg/hr/L for the intravenous dose and 4.19 +/- 1.22 mg/hr/L for the oral dose (P greater than .30). Bioavailability (AUCpo/AUCiv) was 1.13 +/- 0.25, demonstrating complete oral absorption. The time during a 6-hour dosing interval that the gastric pH remained above 3.0 was 3.3 +/- 2.1 hours for the intravenous dose and 2.5 +/- 2.3 hours for the oral dose, P = .171). The time that the serum cimetidine concentration remained above 0.5 mg/L was 2.0 +/- 0.9 hours for the intravenous dose and 2.7 +/- 1.0 hours for the oral dose (P = .055). We concluded that bioavailability, time that gastric pH is maintained greater 3.0, and time that the serum cimetidine concentration is greater than 0.5 mg/L for intravenous cimetidine are not significantly different from oral cimetidine in seriously ill patients.
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Affiliation(s)
- W J Sandborn
- Section of Gastroenterology, Jerry L. Pettis Memorial Veterans Medical Center, Loma Linda, CA 92357
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30
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Siepler JK, Trudeau W, Petty DE. Use of continuous infusion of histamine2-receptor antagonists in critically ill patients. DICP : THE ANNALS OF PHARMACOTHERAPY 1989; 23:S40-3. [PMID: 2573209 DOI: 10.1177/1060028089023s1007] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Certain clinical situations require the use of a histamine2 (H2)-receptor antagonist to reduce gastric-acid volume and concentration or an antacid to act as a buffering agent. Presently, there are three H2-receptor antagonists available for iv use: cimetidine, ranitidine, and famotidine. Conventional therapy dictates that the H2-receptor antagonist be given by intermittent intravenous infusion, resulting in peaks and valleys of acid secretory control. Antacids, although capable of providing adequate gastric acidity control, must be administered frequently, often hourly, and thus require excessive nursing time. Presented here is a review of the rationale for the use of an H2-receptor antagonist by continuous infusion.
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Affiliation(s)
- J K Siepler
- University of California, Davis School of Medicine, Sacramento, 95817
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31
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Martyn JA, Greenblatt DJ, Hagen J, Hoaglin DC. Alteration by burn injury of the pharmacokinetics and pharmacodynamics of cimetidine in children. Eur J Clin Pharmacol 1989; 36:361-7. [PMID: 2737228 DOI: 10.1007/bf00558296] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
We have studied the mechanisms of the increased dosage requirements of the H2-receptor antagonist cimetidine in paediatric burned patients in a pharmacokinetic and pharmacodynamic study. Cimetidine (10-15 mg.kg-1) was given to 21 burned children and multiple blood samples were obtained for determination of plasma cimetidine concentrations and pharmacokinetic analysis. The relation of gastric pH to plasma cimetidine concentrations was studied in five of these children who had nasogastric tubes. In an additional four patients the effects of cimetidine on gastric pH were studied during a continuous infusion of cimetidine, which maintained steady-state plasma cimetidine concentrations above 0.5 microgram.ml-1. The mean (SEM) clearance of cimetidine in burned children was 16.22 ml.kg-1 and cimetidine half-life was 1.06 h. The cimetidine clearance and half-life values were significantly higher in burned children compared with our previously reported values for normal adult patients, 8.2 ml.min.kg-1 and 2.21 h respectively. Endogenous creatinine clearance normalized to 70 kg in burned children was 190 ml.min-1. In burned children 41% of the dose of intact cimetidine was excreted during 8 h of the study compared with 45% excretion during 24 h in healthy adult controls previously reported. The correlation coefficient between creatinine and cimetidine clearances was 0.93 (r2 = 0.85). The plasma concentration of cimetidine needed to increase gastric pH to greater than or equal to 4.0 was greater than or equal to 1.0 micron.ml-1, which contrasts with the value of greater than 0.5 micron.ml-1 required for adult burned patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Affiliation(s)
- J A Martyn
- Department of Anesthesiology, Harvard Medical School, Boston, MA
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32
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Chan KH, Mann KS. Failure of cimetidine prophylaxis in neurosurgery. THE AUSTRALIAN AND NEW ZEALAND JOURNAL OF SURGERY 1989; 59:133-6. [PMID: 2784050 DOI: 10.1111/j.1445-2197.1989.tb01483.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Three hundred and eight-one patients who underwent major neurosurgical procedures were given cimetidine prophylaxis against stress ulceration. Nine patients (2.4%) developed acute gastrointestinal complications; two patients had perforation and bleeding from gastroduodenal ulcers, and seven patients had bleeding alone. Six of these patients, all above the age of 70 years, died as a consequence of the complication. Univariate analysis showed that four variables--state of consciousness, syndrome of inappropriate secretion of antidiuretic hormone, nature of surgery, and age--were significant factors in predicting cimetidine failure. Multivariate analysis revealed that a patient's pre-operative state of consciousness and the presence of inappropriate secretion of antidiuretic hormone were of independent significance in predicting cimetidine failure. The risk was 52% and 0.07%, respectively, when both factors were either present or absent.
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Affiliation(s)
- K H Chan
- Department of Surgery, University of Hong Kong, Queen Mary Hospital
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Abstract
The purpose of this study was to evaluate the early appearance and incidence of stress gastritis following severe head injury. We performed upper esophagogastroduodenoscopy in 44 patients within 24 hours of a head injury. All patients were comatose and required ventilatory support. Forty of the patients (91%) had gastritis at esophagogastroduodenoscopy. The lesions were distributed in the fundus and corpus of the stomach (77% of the patients), in the esophagus (30% of the patients), in the antrum (25% of the patients), and in the duodenum (7% of the patients). The grade of gastritis at esophagogastroduodenoscopy did not correlate with the severity of the head injury, the type of head injury sustained, the timing of esophagogastroduodenoscopy after head injury, or the presence of shock on admission. However, patients with grade III gastritis had a greater injury Severity Score than patients with grade 0 gastritis (normal mucosa). Gastroduodenal mucosal damage is common after severe head injury and occurs soon after the event.
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Affiliation(s)
- T H Brown
- Department of Surgery, University of Louisville, Kentucky 40292
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34
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Malledant Y, Tanguy M, Saint-Marc C. [Digestive stress hemorrhage. Physiopathology and prevention]. ANNALES FRANCAISES D'ANESTHESIE ET DE REANIMATION 1989; 8:334-46. [PMID: 2573302 DOI: 10.1016/s0750-7658(89)80075-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Lesions of the gastroduodenal mucosa are seen very early on in virtually 100% of patients suffering from organ failure. Bleeding, even if it is only occult, defines acute stress-induced gastrointestinal tract bleeding (SGIB). The rates of SGIB vary according to the inclusion criteria: 13 to 100% microscopic SGIB, 2.3 to 9.5% haemorrhage with blood transfusion and/or shock. Gastrointestinal bleeding does not really influence the death rate of patients with SGIB (0 to 5% increase). Damage to the gastric mucosa may be due to an intraluminal aggression, and/or decreased mucosal and mural defence mechanisms. H+ ions and bile salts are mostly responsible for the former. Physiological quantities of H+ ions may be sufficient, as their abnormal diffusion into the gastric mucosa will reduce the mucosal pH (pHm), which is itself sensitive to microcirculatory modifications and systemic acidosis. There is a good correlation between bleeding and pHm. Bile salts are involved because of the usual increase in frequency and volume of gastric biliary reflux due to stress. Surfactant, mucosal alkaline layer and the microcirculation are all involved in gastric protection. The PGE2 synthetized by the gastric mucosa have a favourable influence on these 3 mechanisms. Changes in microcirculation and hypoxia are the predominant factors involved in stress-induced mucosal damage. The prevention of SGIB relies on the treatment of risk factors, a reduction of intraluminal aggression, and the support and/or stimulation of gastric defence mechanisms. Antacids and anti-H2 drugs aim to neutralize most of the H+ ions, being more efficient than placebo in increasing gastric pH greater than 4, although anti-H2 agents are responsible of a greater number of failures. The non-homogenous character of the patient groups studied and the diagnostic methods, as well as the increasing lack of placebo groups in the published studies make the interpretation of the results rather risky. Antacids and anti-H2 drugs are more efficient than placebo, and equally efficient, in preventing overt SGIB. Efficiency is increased by giving anti-H2 drugs continuously, and antacids hourly. Other agents are thought to protect mucosal cells, probably increasing mucosal defences. Amongst them are the prostaglandins, the most interesting of which are still being investigated, and sucralfate. The latter molecule is as efficient as antacids and anti-H2 drugs, and does not alter gastric pH, so reducing the number of nosocomial pneumonias. Its reduced cost and easy administration make it, at the present time, the treatment of choice of SGIB. The few rare contraindications of sucralfate will justify the infusion of anti-H2 drugs in those patients at risk.
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Affiliation(s)
- Y Malledant
- Département d'Anesthésie-Réanimation, Hôpital Pontchaillou, Rennes
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35
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Cheung LY. Thomas G Orr Memorial Lecture. Pathogenesis, prophylaxis, and treatment of stress gastritis. Am J Surg 1988; 156:437-40. [PMID: 3059833 DOI: 10.1016/s0002-9610(88)80522-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
In the last decade, significant progress has been made in understanding the basic mechanisms involved in the development of acute stress gastritis. Many of the experimental observations have been applied in our clinical approaches to patients at high risk. A strong impression exists among investigators that efforts to improve ventilatory support, correct abnormalities in cardiac output and intravascular volume, and maintain adequate nutrition in critically ill patients may have contributed to the decreased incidence and prevalence of stress gastritis over the past decade. In addition, reduction of intragastric acidity, either by titration with antacids or administration of H2 antagonists, further prevented stress gastritis in these patients. We have every reason to believe that progress will continue at the same rate in the decades before us in this area of investigation.
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Affiliation(s)
- L Y Cheung
- Department of Surgery, University of Kansas Medical Center, Kansas City 66103
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Kleiman RL, Adair CG, Ephgrave KS. Stress ulcers: current understanding of pathogenesis and prophylaxis. DRUG INTELLIGENCE & CLINICAL PHARMACY 1988; 22:452-60. [PMID: 3293957 DOI: 10.1177/106002808802200602] [Citation(s) in RCA: 28] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Stress-related gastrointestinal bleeding is known to occur in approximately 25 percent of untreated seriously ill patients, but with appropriate prophylaxis is largely preventable. Since the treatment of stress bleeding is generally unsatisfactory and has a high mortality, routine prophylaxis should be instituted for susceptible patients. Multiple mechanisms contribute to stress ulcer formation, the most important of which appear to be mucosal ischemia and the inability to control back-diffused hydrogen. Antacids and histamine2-blocking agents are presently the cornerstone of effective prophylaxis, but because they have been implicated as contributors to nosocomial pneumonias due to bacterial overgrowth in the stomach, investigation is ongoing into such alternative prophylactic agents as sucralfate and prostaglandins that do not alter the normal gastric acidity. This article presents a review of the literature on the development and prevention of stress ulcer disease.
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Affiliation(s)
- R L Kleiman
- Department of Clinical/Hospital Pharmacy, College of Pharmacy, University of Iowa, Iowa City 52242
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Piqué JM, Yonei Y, Whittle BJ, Leung FW, Guth PH. Indomethacin potentiates endotoxin-induced blood flow reduction and histological injury in rat gastric mucosa. Br J Pharmacol 1988; 93:925-31. [PMID: 3390661 PMCID: PMC1853906 DOI: 10.1111/j.1476-5381.1988.tb11481.x] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
1. The effect of the intravenous administration of lipopolysaccharide from Salmonella typhosa endotoxin on arterial blood pressure (BP), gastric mucosal blood flow (GMBF) and gastric damage was studied in anaesthetized rats. The effect of the inhibition of endogenous prostaglandin generation by indomethacin on these parameters was also investigated in this model of endotoxin shock. 2. A similar and dose-dependent percentage of reduction in BP and GMBF was observed 5 min after a bolus injection of 20 or 30 mg kg-1 endotoxin. A transient recovery in GMBF at 15 min was observed followed by a second fall at 30 min, at a time when BP was slowly increasing. 3. Pretreatment with indomethacin (5 mg kg-1, s.c.) one hour before the administration of 30 mg kg-1 endotoxin, significantly augmented the reduction in GMBF without affecting the reduction in BP. 4. The gastric damage, assessed histologically, was similar and confined to the superficial mucosa 30 min after the administration of 20 or 30 mg kg-1 endotoxin. The histologically-assessed damage was significantly greater in indomethacin pretreated rats injected with 30 mg kg-1 endotoxin. 5. These findings suggest that endogenous prostaglandin generation plays a protective role in endotoxin-induced gastric mucosal microcirculatory disturbances and mucosal damage.
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Affiliation(s)
- J M Piqué
- West Los Angeles, VA Medical Center, California
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Lancaster JR. Upper Gastrointestinal Bleeding. Prim Care 1988. [DOI: 10.1016/s0095-4543(21)01056-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Abstract
During the last 15 years, there has been a dramatic decline in the incidence of bleeding from stress-related mucosal damage. This decrease probably relates to an increased understanding of those mechanisms responsible for the pathogenesis of stress-related mucosal damage and the application of this knowledge to prophylaxis and treatment. Stress-related bleeding has become less of a clinical problem, in part, because of the development of improved techniques for the treatment of shock and its accompanying gastric mucosal hypoperfusion. The nearly routine use of prophylactic antacid and/or histamine (H2)-receptor antagonist therapy to adequately buffer intragastric acidity is another factor that has minimized the development of stress-related damage. As continued understanding of the mechanisms responsible for stress damage is obtained and therapy applied appropriately, this disease should become a disorder of only historical interest in years to come.
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Affiliation(s)
- T A Miller
- Department of Surgery, University of Texas Medical School, Houston 77030
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40
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Abstract
Stress ulceration, a disease associated with the stress of severe injury, sepsis, and organ failure, has declined in frequency during the last decade. Factors contributing to this decrease include more rapid transport of trauma patients, early resuscitation, avoidance and treatment of complications, and prophylactic maintenance of increased gastric mucosal pH. The pathophysiology of these lesions remains to be elucidated completely; however, both aggressive factors (acid, duodenal reflux, etc.) and a deficiency in defensive mechanisms (gastric mucosal blood flow, gastric mucosal barrier, mucus, bicarbonate, etc.) play a role in their inception. The hemorrhagic complication of stress ulcer, which is usually seen between the fifth and tenth days after admission, remains a sequela associated with a significant rate of mortality.
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Affiliation(s)
- B A Levine
- Department of Surgery, University of Texas Health Science Center, San Antonio 78284-7842
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Bailey RW, Bulkley GB, Hamilton SR, Morris JB, Haglund UH, Meilahn JE. The fundamental hemodynamic mechanism underlying gastric "stress ulceration" in cardiogenic shock. Ann Surg 1987; 205:597-612. [PMID: 3592803 PMCID: PMC1493091 DOI: 10.1097/00000658-198706000-00001] [Citation(s) in RCA: 35] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Acute hemorrhagic ulceration of the gastric mucosa is seen frequently in patients with hypovolemic or cardiogenic shock. Although such lesions clearly are related to regional gastric ischemia, little attention has been directed at the underlying mechanism(s) mediating the ischemia itself. To this end, anesthetized pigs were subjected to sustained cardiogenic shock (mild hemorrhage and pericardial tamponade) such that cardiac output was reduced to 38 +/- 1% of the baseline level for 4 hours, followed by release of the tamponade, reinfusion of the shed blood, and resuscitation for 2 hours. During the period of shock, there was profound regional gastric ischemia, resulting from severe and disproportionate gastric vasoconstriction. "Blinded" gross and microscopic evaluation of the stomachs removed after the experiment revealed severe mucosal ischemic necrosis, hemorrhage, and ulceration, whereas sham-operated pigs showed no lesions. The characteristics of this model therefore mimic the essential features of the gastric "stress ulceration" syndrome. Prior confirmed total alpha-adrenergic blockade with phenoxybenzamine failed to alter these features significantly. In contrast, prior ablation of the renin-angiotensin axis, whether by angiotensin-converting enzyme inhibition with teprotide or by bilateral nephrectomy, significantly and substantially ameliorated the ischemia, vasospasm, and mucosal injury. In this model of cardiogenic shock, acute gastric mucosal "stress ulceration" is caused by a disproportionately severe regional gastric ischemia resulting from selective splanchnic vasospasm that is unaffected by sympathetic blockade but abolished by prior ablation of the renin-angiotensin axis. Like nonocclusive small bowel ischemia, ischemic colitis, and the "shock liver" syndrome, gastric "stress ulceration" is yet another component of the multiple splanchnic organ failure syndrome that appears to be mediated primarily by the remarkable sensitivity of the splanchnic vascular bed to the renin-angiotensin axis.
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Abstract
Focal gastric mucosal blood flow was studied during aspirin injury by hydrogen gas clearance in a chambered segment model of canine gastric corpus. Measurements were made simultaneously every 15 minutes at ulcerated and nonulcerated areas 1.5 hours before, during (20 mM of aspirin in 150 mM of HCl for 1 hour), and 2 hours after exposure of the mucosa to topical aspirin. There was a highly significant decrease (p less than 0.001) in flow at the ulcerated areas 30 minutes after exposure to aspirin, coinciding with the appearance of focal mucosal pallor followed by subsequent hemorrhagic foci and ulceration. This was not followed by recovery to basal flow values. Blood flow to the non-ulcerated areas was significantly but less severely reduced than in the ulcerated areas (p less than 0.05) 90 minutes after exposure to aspirin. This was followed by recovery to basal levels. It is proposed that aspirin induces reduction of focal mucosal blood flow of varying degrees and that mucosal areas with flow reduced to below a "critical value" develop gross damage.
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James Sarfeh I, Rypins EB. Physiology and Pathophysiology of the Digestive Organs in Critical Illness. Crit Care Clin 1987. [DOI: 10.1016/s0749-0704(18)30551-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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44
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Chervyak PI, Keisevich LV, Khokholya VP. Impaired epithelial regeneration in the mucosa as a factor in the pathogenesis of acute gastric and duodenal ulcer. Bull Exp Biol Med 1987. [DOI: 10.1007/bf00840583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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Bailey RW, Bulkley GB, Hamilton SR, Morris JB, Haglund UH. Protection of the small intestine from nonocclusive mesenteric ischemic injury due to cardiogenic shock. Am J Surg 1987; 153:108-16. [PMID: 3799886 DOI: 10.1016/0002-9610(87)90210-8] [Citation(s) in RCA: 113] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
In a pericardial tamponade model of cardiogenic shock in pigs, we had previously shown that acute reductions in cardiac output produce severe mesenteric ischemia due to disproportionate splanchnic vasoconstriction. In this study, we extended the period of cardiogenic shock in order to investigate the pathogenesis of ischemic injury to the small intestinal wall. Four hours of tamponade produced sustained changes in splanchnic hemodynamics, similar to those observed in the prior short-term experiments. The resultant mesenteric ischemia caused necrotic lesions of the small intestine which were characteristic of those seen in nonocclusive mesenteric ischemia in human subjects. Prior alpha-adrenergic blockade failed to prevent either sustained mesenteric vasospasm or ischemic injury. In contrast, prior blockade of the renin-angiotensin axis, whether by nephrectomy or angiotensin-converting enzyme inhibition, blocked the splanchnic vasoconstriction, and thereby protected the small intestine from ischemic injury. The primary hemodynamic and pathologic features of this model of nonocclusive mesenteric ischemia appear to be mediated by the renin-angiotensin axis.
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46
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Arvidsson S, Fält K, Haglund U. Gastric mucosal damage in sepsis--effects of pretreatment with a synthetic prostaglandin E1 analogue. Gut 1985; 26:1025-31. [PMID: 3932138 PMCID: PMC1432948 DOI: 10.1136/gut.26.10.1025] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
An experimental model was used which includes intragastric instillation of 80 mM HCl and 0.6 ml bile/kg followed by intravenous infusion of live E coli in cats for up to three hours. This procedure regularly induces gastric mucosal ulcerations. Mucosal blood flow was measured by microspheres before, early, and late in sepsis. Total gastric blood flow was recorded electromagnetically. Mucosal regeneration capacity as reflected by the RNA/DNA ratio was measured. Misoprostol (a PGE1 analogue) was infused iv (5 micrograms/kg X h) or given locally in the stomach (10 micrograms/kg) before bacteriemia. Misoprostol did not influence the haemodynamic response to bacteria. The gastric mucosal damage was assessed either as an index representative for the entire corpus-fundus region or as the number of areas with intact surface epithelium within the series. Misoprostol iv protected the mucosa from ulceration compared with untreated septic controls while misoprostol intragastrically significantly reduced the number of damaged areas only. Topical misoprostol increased total gastric and mucosal blood flows early in sepsis compared to iv or no pretreatment while no difference was seen during late sepsis. The protective effect of misoprostol was thus not dependent on increased gastric mucosal blood flow. Nor was it mediated through effects on mucosal nucleic acid concentrations or ratio.
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Moscona R, Kaufman T, Jacobs R, Hirshowitz B. Prevention of gastrointestinal bleeding in burns: the effects of cimetidine or antacids combined with early enteral feeding. Burns 1985; 12:65-7. [PMID: 3933770 DOI: 10.1016/0305-4179(85)90185-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The efficacy of prophylactic therapy with cimetidine or antacids combined with early enteral feeding to prevent gastrointestinal bleeding in patients with severe burns was evaluated. Fifty patients with burns exceeding 30 per cent of the total body surface area (TBSA) were divided into two groups, each of them treated by one of these agents in combination with early feeding. Bleeding was not encountered in either group. It is assumed that the combination of either agent with enteral feeding early in the post-burn course equally protected against gastrointestinal bleeding. Because of the ease and lack of side-effects of cimetidine in this series, its use was preferable.
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48
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Abstract
Stress ulceration is usually considered a mucosal abnormality of the oesophagus, stomach or duodenum in the critically ill. It is found to a varying degree in all such patients. Only about one-quarter of lesions are associated with blood loss and less than 5% need resuscitation and treatment. However, because treatment of established bleeding is unsatisfactory, and associated with a high mortality, prophylactic measures are usually employed. These include optimising gastric mucosal blood flow and oxygen delivery, correcting coagulation abnormalities and treating underlying infection. Enteral feeding should also be employed whenever possible. Other prophylactic measures currently used involve raising gastric pH above 4, with either antacids or H2 receptor antagonists. This is best achieved by measuring the gastric pH hourly and titrating it against an appropriate dose of either type of drug or a combination of both. Newer drugs, such as omeprazole, sucralfate and prostaglandins, are proving very successful in the treatment and prevention of gastric and duodenal ulcers and may prove even more effective than currently available agents.
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Sakamoto T, Swierczek JS, Ogden WD, Thompson JC. Cytoprotective effect of pentagastrin and epidermal growth factor on stress ulcer formation. Possible role of somatostatin. Ann Surg 1985; 201:290-5. [PMID: 2858183 PMCID: PMC1250666 DOI: 10.1097/00000658-198503000-00005] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
This study was designed to test the effects of pentagastrin and epidermal growth factor (EGF) on stress-induced ulceration and on the antral content of gastrin and somatostatin (SLI) in rats. Four groups of 14 to 15 rats had been prepared for 7 days by one of the following methods: saline injection (control); injection of pentagastrin (250 micrograms/kg, 3 times/day); injection of EGF (10 micrograms/kg, 3 times/day); or injection of EGF plus pentagastrin. At the end of the treatment period, half of each group of rats were sacrificed (nonstress group). There were no ulcers in the nonstress control groups of rats. Stress was applied by water immersion in the remaining half of the rats. The injections of pentagastrin and/or EGF resulted in substantial increase in antral content of SLI. After 20 hours of stress, the ulcer index was 40.5 +/- 3.3 in the controls, compared to 6.4 +/- 1.2 and 16.2 +/- 2.3 in rats that received pentagastrin or EGF, respectively. Injections of both pentagastrin and EGF resulted in an ulcer index of 26.2 +/- 2.0, which was significantly lower than that in controls, but higher than that in rats treated with either peptide alone. The stress resulted in significant decrease in antral SLI in all groups of rats, whereas SLI content in rats treated with pentagastrin and/or EGF remained significantly higher than that of controls. Antral content of gastrin did not differ significantly in the four groups tested. The ulcer index was inversely correlated with antral SLI content. We confirm and extend previous observations that pentagastrin and EGF prevent stress ulcer formation, and suggest that endogenous SLI may account, at least in part, for their antiulcer activity.
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Ashley SW, Sonnenschein LA, Cheung LY. Focal gastric mucosal blood flow at the site of aspirin-induced ulceration. Am J Surg 1985; 149:53-9. [PMID: 3966642 DOI: 10.1016/s0002-9610(85)80009-x] [Citation(s) in RCA: 69] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Focal gastric mucosal blood flow as measured by the hydrogen gas clearance method was compared with total gastric blood flow as determined by venous outflow in an isolated segment of canine stomach before, during, and after exposure to aspirin. Despite an increase in total gastric blood flow from 10.8 +/- 1.6 ml/min per chamber to 17.4 +/- 1.9 ml/min per chamber and mucosal blood flow at nonulcerated sites from 29.5 +/- 4.3 ml/min per 100 g to 83 +/- 14.4 ml/min per 100 g, mucosal blood flow at the site of aspirin-induced ulceration was significantly reduced from 29.5 +/- 4.3 ml/min per 100 g to 12.5 +/- 2.5 ml/min per 100 g. After the removal of aspirin, mucosal blood flow returned to control levels. Such a redistribution of mucosal blood flow in response to aspirin is consistent with the localized nature of acute aspirin-induced injury. The findings also explain the inability of previous methods measuring blood flow of the entire stomach to demonstrate mucosal ischemia during such injury.
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