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Affiliation(s)
| | - Elaine Ah-Gi Lo
- National University Hospital, National University Health System, Singapore
| | - Siang Fei Yeoh
- National University Hospital, National University Health System, Singapore
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Hedges K, Odunayo A, Price JM, Hecht S, Tolbert MK. Evaluation of the effect of a famotidine continuous rate infusion on intragastric pH in healthy dogs. J Vet Intern Med 2019; 33:1988-1994. [PMID: 31294879 PMCID: PMC6766495 DOI: 10.1111/jvim.15558] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2019] [Accepted: 06/26/2019] [Indexed: 11/29/2022] Open
Abstract
Background Famotidine is sometimes administered as a continuous rate infusion (CRI) to treat gastrointestinal ulceration in critically ill dogs. However, clinical studies have not evaluated the efficacy of a famotidine CRI in dogs. Hypothesis/Objectives To evaluate the efficacy of famotidine at raising intragastric pH when it is administered as a CRI in dogs. We hypothesized that CRI treatment with famotidine would meet clinical goals for raising intragastric pH ≥3 and 4. Animals Nine healthy Beagle dogs. Methods Randomized 2‐way crossover. All dogs received 1.0 mg/kg IV q12h famotidine or CRI famotidine at 1.0 mg/kg IV loading dose and 8.0 mg/kg/d for 3 consecutive days. Beginning on day 0 of treatment, intragastric pH monitoring was used to continuously record intragastric pH. Mean percentage times (MPTs) for which intragastric pH was ≥3 and ≥4 were compared between groups using analysis of variance. Results There was a statistically significant difference (P < .05) in MPT ≥3 and ≥4 between the CRI and IV q12h groups on all treatment days. On days 1, 2, and 3, the MPTs ± SD for which pH was ≥3 were 92.1 ± 8.5, 96.3 ± 6.2, and 90.0 ± 15.7 for the CRI treatment group and 49.3 ± 27.3, 42.2 ± 19.6, and 45.8 ± 10.1, respectively, for the twice‐daily group. Conclusions and Clinical Importance These results suggest that a famotidine CRI, but not standard doses of famotidine, achieves the clinical goals established in people to promote healing of gastric tissue injury and offers an alternative to intravenous treatment with proton pump inhibitors in dogs.
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Affiliation(s)
- Katherine Hedges
- University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee
| | - Adesola Odunayo
- University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee
| | - Josh M Price
- University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee
| | - Silke Hecht
- University of Tennessee College of Veterinary Medicine, Knoxville, Tennessee
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Reilly J, Fennerty MB. Stress Ulcer Prophylaxis: The Prevention of Gastrointestinal Bleeding and the Development of Nosocomial Infections in Critically Ill Patients. J Pharm Pract 2016. [DOI: 10.1177/089719009801100603] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
| | - M. Brian Fennerty
- Section Chief of Gastroenterology, Oregon Health Sciences University, Portland, Oregon
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Abstract
OBJECTIVE To review and summarize the human and veterinary literature regarding stress-related mucosal disease (SRMD) pathogenesis, patient risk factors, and therapeutic options for prophylaxis and treatment. ETIOLOGY SRMD is a common sequela of critical illness in human patients. Development of SRMD results from splanchnic hypoperfusion, reperfusion injury, and exposure of the gastric mucosa to acid, pepsin, and bile acids following breakdown of the gastric mucosal defense system. Human patients with the highest risk of stress ulceration include those with respiratory failure necessitating mechanical ventilation greater than 48 h or coagulopathy. Currently, little is known about the incidence and pathophysiology of SRMD in critically ill veterinary patients. DIAGNOSIS A presumptive diagnosis can be made in high-risk patient populations following detection of occult or gross blood in nasogastric tube aspirates, hematemesis, or melena. Definitive diagnosis is achieved via esophagogastroduodenoscopy. Lesions are localized to the acid-producing portions of the stomach, the fundus, and body. THERAPY Therapy is aimed at optimization of tissue perfusion and oxygenation. Pharmacologic interventions are instituted to increase intraluminal pH and augment natural gastric defenses. Histamine(2)-receptor antagonists, proton pump inhibitors, and sucralfate are the mainstays of therapy. In people, clinically significant bleeding may necessitate additional interventions (eg, packed red blood cell transfusions, endoscopic, or surgical hemostasis). PROGNOSIS Mortality is increased in people with clinically significant bleeding compared to those patients who do not bleed. Institution of prophylaxis is recommended in high-risk patients. However, no consensus exists regarding initiation of prophylaxis, preference of frontline drug class, or indication for discontinuation of therapy. The prognosis of veterinary patients with SRMD remains unknown at this time.
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Affiliation(s)
- Andrea A Monnig
- Department of Emergency and Critical Care, The Animal Medical Center, New York, NY 10065, USA.
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6
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Blouin J, Désaulniers PL, Tremblay L, Poitras P, Dragomir A, Perreault S. Implementation of an Algorithm for Intravenous Pantoprazole: Impact on Prescription Compliance in Quebec University Hospitals. J Pharm Technol 2006. [DOI: 10.1177/875512250602200504] [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] Open
Abstract
Background: Intravenous pantoprazole is used at Centre Hospitalier de l'Université de Montréal (CHUM) for the adjuvant treatment of nonvariceal upper gastrointestinal bleeding (UGB) and for inhibiting acid secretion among patients unable to tolerate oral intake (NPO). Since it was added to the CHUM formulary, the use of intravenous pantoprazole has steadily increased, and at times it has been used without endoscopic documentation of a nonvariceal UGB or even when the patient could have received a proton pump inhibitor orally. Objective: To assess the impact of an algorithm for intravenous pantoprazole on prescription compliance. Methods: Using a pre–post intervention specification, the use of pantoprazole was audited on a retrospective (January 1, 2002, to April 30, 2002) and prospective (January 1, 2003, to April 30, 2003) basis. We reviewed the medical records of all patients having received intravenous pantoprazole during these periods, assessing the compliance of prescriptions as specified by the algorithm. Cost of therapy and the step-down regimen were also reviewed. Results: In total, 150 patients were identified in the retrospective phase and 109patients in the prospective phase. The subjects were organized into 2 groups: UGB and NPO. In the UGB group, rates of compliance with indication, dose, and duration of treatment in the retrospective phase were 8.8%, 76.5%, and 58.8%, respectively; the corresponding rates for the prospective phase were 26.5% (p < 0.01), 80.9% (p = 0.53), and 69.1% (p = 0.78), respectively. The total rates of compliance (including indication, dose, and duration) were 4.4% in the retrospective phase and 11.8% in the prospective phase (p = 0.12). In the NPO group, the rate of compliance at the initiation of pantoprazole was 42.7% in the retrospective phase and 36.6% in the prospective phase (p = 0.51). The cost of noncompliance with the indication in the UGB group was estimated at $12 270 CDN (in the retrospective phase) and $7829 (in the prospective phase). In the NPO group, the cost figures were $8048 (retrospective phase) and $5929 (prospective phase). Conclusions: This study demonstrates that intravenous pantoprazole is being used in a suboptimal manner in our institution. Despite explicit criteria for use, in the prospective phase, we observed only 11.8% total compliance in the UGB group and 36.6% compliance at the initiation of pantoprazole in the NPO group. Even though these results were not statistically significant, in the prospective phase, we saw improvement in most compliance rates.
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Affiliation(s)
- Julie Blouin
- JULIE BLOUIN BPharm MSc, PhD Candidate, Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada
| | - Pierre-Louis Désaulniers
- PIERRE-LOUIS DÉSAULNIERS BPharm MSc, Pharmacist, Department of Pharmacy, Notre-Dame Hospital, Centre Hospitalier de l'Université de Montréal, Montreal
| | - Lydjie Tremblay
- LYDJIE TREMBLAY BPharm MSc, Pharmacist, Department of Pharmacy, Saint-Luc Hospital, Centre Hospitalier de l'Université de Montréal
| | - Pierre Poitras
- PIERRE POITRAS MD, Gastroenterologist, Department of Gastroenterology, Saint-Luc Hospital, Centre Hospitalier de l'Université de Montréal
| | - Alice Dragomir
- ALICE DRAGOMIR MSc, Research Assistant, Faculty of Pharmacy, University of Montreal
| | - Sylvie Perreault
- SYLVIE PERREAULT BPharm PhD, Associate Professor, Faculty of Pharmacy, University of Montreal
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7
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Gisbert JP. Tratamiento farmacológico de la hemorragia digestiva por úlcera péptica. Med Clin (Barc) 2006; 127:66-75. [PMID: 16801006 DOI: 10.1157/13089992] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Affiliation(s)
- Javier P Gisbert
- Servicio de Aparato Digestivo, Hospital Universitario de la Princesa, 28669 Boadilla del Monte, Madrid, Spain.
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8
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Zacny J, Zamakhshary M, Sketris I, Veldhuyzen van Zanten S. Systematic review: the efficacy of intermittent and on-demand therapy with histamine H2-receptor antagonists or proton pump inhibitors for gastro-oesophageal reflux disease patients. Aliment Pharmacol Ther 2005; 21:1299-312. [PMID: 15932360 DOI: 10.1111/j.1365-2036.2005.02490.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
AIM To perform a systematic review on the efficacy of intermittent and on-demand therapy with either histamine H2-receptor antagonists or proton pump inhibitors for patients with erosive oesophagitis or symptomatic heartburn. METHOD We conducted randomized-controlled trials of non-continuous therapy in gastro-oesophageal reflux disease patients. RESULTS Fourteen studies met inclusion criteria. Because of variation in outcome measures statistical pooling of results was not possible. Results were analysed qualitatively. Four studies evaluated intermittent therapy of treatment 3 days a week with omeprazole 20 mg or daily with ranitidine which were not efficacious compared to a daily proton pump inhibitor. Famotidine 10 and 20 mg, ranitidine 75 mg and cimetidine 200 mg were efficacious in five on-demand studies for relief of symptomatic heartburn episodes. In three of four studies, evaluating only non-erosive (endoscopy-negative) gastro-oesophageal reflux disease patients, esomeprazole 20 and 40 mg and omeprazole 10 and 20 mg a day were efficacious using willingness to continue as an endpoint. Lansoprazole 30 mg and omeprazole 20 mg maintained symptom control in 60-70% of healed oesophagitis patients. CONCLUSIONS Intermittent proton pump inhibitor or H2-receptor antagonist therapy is not effective in maintaining control in oesophagitis patients. H2-receptor antagonists are effective for relief of heartburn episodes. On-demand proton pump inhibitor therapy may work in a proportion of non-erosive gastro-oesophageal reflux disease patients.
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Affiliation(s)
- J Zacny
- Division of Gastroenterology, Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada.
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9
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Hsu PI, Lo GH, Lo CC, Lin CK, Chan HH, Wu CJ, Shie CB, Tsai PM, Wu DC, Wang WM, Lai KH. Intravenous pantoprazole versus ranitidine for prevention of rebleeding after endoscopic hemostasis of bleeding peptic ulcers. World J Gastroenterol 2004; 10:3666-9. [PMID: 15534928 PMCID: PMC4612014 DOI: 10.3748/wjg.v10.i24.3666] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
AIM: The role of intravenous pantoprazole in treatment of patients with high-risk bleeding peptic ulcers following endoscopic hemostasis remains uncertain. We therefore conducted the pilot prospective randomized study to assess whether intravenous pantoprazole could improve the efficacy of H2-antagonist as an adjunct treatment following endoscopic injection therapy for bleeding ulcers.
METHODS: Patients with active bleeding ulcers or ulcers with major signs of recent bleeding were treated with distilled water injection. After hemostasis was achieved, they were randomly assigned to receive intravenous pantoprazole or ranitidine.
RESULTS: One hundred and two patients were enrolled in this prospective trial. Bleeding recurred in 2 patients (4%) in the pantoprazole group (n = 52), as compared with 8 (16%) in the ranitidine group (n = 50). The rebleeding rate was significantly lower in the pantoprazole group (P = 0.04). There were no statistically significant differences between the groups with regard to the need for emergency surgery (0% vs 2%), transfusion requirements (4.9 ± 5.9 vs 5.7 ± 6.8 units), hospital days (5.9 ± 3.2 vs 7.5 ± 5.0 d) or mortality (2% vs 2%).
CONCLUSION: Pantoprozole is superior to ranitidine as an adjunct treatment to endoscopic injection therapy in high-risk bleeding ulcers.
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Affiliation(s)
- Ping-I Hsu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan, China
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Bustamante Balén M, Ponce García J. Tratamiento antisecretor de la hemorragia digestiva por úlcera péptica: una aproximación a la evidencia disponible. Rev Clin Esp 2004. [DOI: 10.1016/s0014-2565(04)71423-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Abstract
Two well-controlled trials were carried out to investigate the effectiveness of intravenous proton pump inhibitors (PPIs) to reduce peptic ulcer rebleeding after successful hemostasis. The results demonstrated that the PPI reduced the rate of rebleeding significantly. The recent availability of the first intravenous PPI formulation in the United States, intravenous pantoprazole, represents an alternative to intravenous histamine-2 receptor antagonists. The results of 16 randomized, controlled trials involving a total of >3,800 patients (1,892 receiving PPIs and 1,911 controls) suggest that bolus administration plus continuous infusion of PPIs is a more effective pharmacotherapy than bolus infusion alone in decreasing both rebleeding and the need for surgery. Optimal effect is achieved with an intravenous 80-mg bolus, followed by continuous infusion of 8 mg/hr for 3 days, after which therapy may be continued with an oral PPI. Intermittent bolus administration yielded a minimal benefit. A difference in mortality rates has not yet been demonstrated.
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12
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Gisbert JP, González L, Calvet X, Roqué M, Gabriel R, Pajares JM. Proton pump inhibitors versus H2-antagonists: a meta-analysis of their efficacy in treating bleeding peptic ulcer. Aliment Pharmacol Ther 2001; 15:917-26. [PMID: 11421865 DOI: 10.1046/j.1365-2036.2001.01012.x] [Citation(s) in RCA: 103] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
PURPOSE To evaluate whether proton pump inhibitors are more effective than H2-antagonists (H2-A) for the treatment of bleeding peptic ulcer. DATA SOURCES PubMed database until January 2000. STUDY SELECTION Comparative randomized trials of proton pump inhibitors (omeprazole, lansoprazole, or pantoprazole) vs. H2-A (cimetidine, ranitidine or famotidine). DATA EXTRACTION Meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). OUTCOMES EVALUATED: Persistent or recurrent bleeding, need for surgery, or mortality. DATA SYNTHESIS Eleven studies fulfilled the inclusion criteria and contained data for at least one of the planned comparisons. Persistent or recurrent bleeding was reported in 6.7% (95% CI: 4.9-8.6%) of the patients treated with proton pump inhibitors, and in 13.4% (95% CI: 10.8-16%) of those treated with H2-A (OR 0.4; 95% CI: 0.27-0.59) (chi2-homogeneity test, 18; P=0.09). Surgery was needed in 5.2% (95% CI: 3.4-6.9%) of the patients treated with proton pump inhibitors, and in 6.9% (95% CI: 4.9-8.9%) of the patients treated with H2-A (OR 0.7; 95% CI: 0.43-1.13). Respective percentages for mortality were 1.6% (95% CI: 0.9-2.9%) and 2.2% (95% CI: 1.3-3.7%) (OR 0.69; 95% CI: 0.31-1.57). SUB-ANALYSIS: Five studies evaluated the effect of both therapies given in bolus injections on persistent or recurrent bleeding rate, which was 6% (95% CI: 3.6-8.3%) and 8.1% (95% CI: 5.3-10.9%), respectively (OR, 0.57; 95% CI: 0.31-1.05). Persistent or recurrent bleeding in high risk patients (Forrest Ia, Ib and IIa) occurred in 13.2% (95% CI: 7.9-8%) of the patients treated with proton pump inhibitors and in 34.5% (27-42%) of those treated with H2-A (OR 0.28; 95% CI: 0.16-0.48). In patients not having endoscopic therapy, persistent or recurrent bleeding was reported, respectively, in 4.3% (95% CI: 2.7-6.7%) and in 12% (95% CI: 8.7-15%) (OR 0.24; 95% CI: 0.13-0.43). Less marked differences were observed in patients having adjunct endoscopic therapy: 10.3% (95% CI: 6.7-13.8%) and 15.2% (11.1-19.3%) (OR 0.59; 95% CI: 0.36-0.97). Moreover, the significance disappeared in this group when a single outlier study was excluded. CONCLUSIONS Proton pump inhibitors are more effective than H2-A in preventing persistent or recurrent bleeding from peptic ulcer, although this advantage seems to be more evident in patients not having adjunct sclerosis therapy. This beneficial effect seems to be similar or even more marked in patients with Forrest Ia, Ib or IIa ulcers. However, proton pump inhibitors are not more effective than H2-A for reducing surgery or mortality rates. Nevertheless, the data are too scarce and heterogeneous to draw definitive conclusions, and further comparative trials are clearly warranted.
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Affiliation(s)
- J P Gisbert
- Department of Gastroenterology, University Hospital 'La Princesa', Madrid, Spain.
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13
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Abstract
Mechanical ventilation (MV) can be lifesaving by maintaining gas exchange until the underlying disorders are corrected, but it is associated with numerous organ-system complications, which can significantly affect the outcome of critically ill patients. Like other organ systems, GI complications may be directly attributable to MV, but most are a reflection of the severity of the underlying disease that required intensive care. The interactions of the underlying critical illness and MV with the GI tract are complex and can manifest in a variety of clinical pictures. Incorporated in this review are discussions of the most prevalent GI complications associated with MV, and current diagnosis and management of these problems.
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Affiliation(s)
- G M Mutlu
- Section of Respiratory and Critical Care Medicine, University of Illinois at Chicago, Chicago, IL, USA
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14
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Abstract
In summary, a variety of gastrointestinal processes may occur in the chronically critically ill patient population, usually as consequence of the primary systemic process. The clinical presentation is frequently nonclassic and there often is a substantial delay in diagnosis, resulting in increased morbidity and mortality.
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Affiliation(s)
- S G Sheth
- Haryard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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15
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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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Wolfe MM, Sachs G. Acid suppression: optimizing therapy for gastroduodenal ulcer healing, gastroesophageal reflux disease, and stress-related erosive syndrome. Gastroenterology 2000; 118:S9-31. [PMID: 10868896 DOI: 10.1016/s0016-5085(00)70004-7] [Citation(s) in RCA: 200] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- M M Wolfe
- Section of Gastroenterology, Boston University School of Medicine and Boston Medical Center, Massachusetts 02118-2393, USA.
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18
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Úlceras de estrés. Semergen 2000. [DOI: 10.1016/s1138-3593(00)73588-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Tsai WL, Poon SK, Yu HK, Chang CS, Yeh HZ, Ko CW, Chen GH. Nasogastric lansoprazole is effective in suppressing gastric acid secretion in critically ill patients. Aliment Pharmacol Ther 2000; 14:123-7. [PMID: 10632655 DOI: 10.1046/j.1365-2036.2000.00680.x] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM To evaluate the effect of nasogastric lansoprazole on acid suppression in critically ill patients. METHODS Patients were eligible for the study if they had a nasogastric tube in place and had not received acid-suppressive agents for 3 days prior to enrolment into the study. Patients with active gastrointestinal bleeding or a baseline gastric pH > 4.0 were excluded. Patients served as their own controls during a 24 h lead-in period. Lansoprazole 30 mg was administered once daily with water through a nasogastric tube for 2 days. Intragastric pH was measured by continuous 24 h pH-metry for 3 days. RESULTS Fifteen patients were enrolled into the study. The baseline median 24 h intragastric pH was 2.25 +/- 1.01, and increased to 6.70 +/- 0.82 (P= 0.001) after 2 days of lansoprazole. Mean percentage of time intragastric pH was > or = 4.0 was 25 +/- 13% at baseline, and increased to 84 +/- 14% (P=0. 001) after 2 days of lansoprazole. CONCLUSIONS Nasogastric lansoprazole 30 mg daily is effective in suppressing gastric acid secretion in critically ill patients.
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Affiliation(s)
- W L Tsai
- Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
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Barkun AN, Cockeram AW, Plourde V, Fedorak RN. Review article: acid suppression in non-variceal acute upper gastrointestinal bleeding. Aliment Pharmacol Ther 1999; 13:1565-84. [PMID: 10594391 DOI: 10.1046/j.1365-2036.1999.00623.x] [Citation(s) in RCA: 73] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Abstract
Despite a decreased incidence of ulcer disease and improvements in the management of acute upper gastrointestinal (GI) bleeding, mortality remains at about 6-7%. Although endoscopic haemostatic therapy has been demonstrated to be the mainstay of management, the search continues for less invasive medical modalities that might also improve patient outcome. In vitro data have indicated the important role of acid in impairing haemostasis and causing clot digestion. Therefore, theoretically, maintenance of a high intragastric pH (above 6.0) during management of upper GI bleeding is warranted. Until recently, available agents did not permit such a sustained elevation in gastric pH. Early studies with H2-receptor antagonists have not demonstrated significant improvements in important patient outcomes, such as rebleeding, surgery or mortality. With the availability of intravenous formulations of proton pump inhibitors, it is now possible to aim at maintaining gastric pH above 6.0 for 24 h per day. Recent clinical trial data would appear to support the use of proton pump inhibitors to decrease the rate of rebleeding and the need for surgery. This paper provides a review of non-variceal acute GI bleeding, with special reference to the role of proton pump inhibitors in this clinical setting.
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Affiliation(s)
- A N Barkun
- Division of Gastroenterology, McGill University, Montréal, Québec, Canada
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Liolios A, Oropello JM, Benjamin E. Gastrointestinal complications in the intensive care unit. Clin Chest Med 1999; 20:329-45, viii. [PMID: 10386260 DOI: 10.1016/s0272-5231(05)70145-3] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Pathologic conditions affecting the abdomen are a significant cause of morbidity and mortality in the intensive care unit, but their importance is not widely recognized. This article presents several aspects of abdominal pathology that can occur in intensive care unit patients. This pathology may have a considerable impact on the prognosis and survival of the critically ill patient. The diagnostic contribution of laboratory tests and imaging is discussed. Conditions such as the abdominal compartment syndrome, acute mesenteric ischemia, gastrointestinal bleeding, diarrhea, abdominal sepsis, complications of entereal and parenteral nutrition, and ileus in critically ill patients are also reviewed.
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Affiliation(s)
- A Liolios
- Department of Surgery, Mount Sinai Medical Center, City University of New York, New York, USA
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22
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Netzer P, Gaia C, Sandoz M, Huluk T, Gut A, Halter F, Hüsler J, Inauen W. Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours. Am J Gastroenterol 1999; 94:351-7. [PMID: 10022628 DOI: 10.1111/j.1572-0241.1999.857_y.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE In healthy subjects and patients with bleeding peptic ulcers, ranitidine and omeprazole, given parenterally, achieve high intragastric pH values on the first day of therapy. However, data on the antisecretory effect beyond the first 24 h is scanty. In addition, the superiority of either infusion or injection of omeprazole remains unproven. Thus, we have compared the antisecretory effect of high dose omeprazole and ranitidine infusion and injection over the critical first 72 h. METHODS A total of 34 healthy volunteers were randomized into a double-blind crossover 72 h intragastric pH-metry study (data compared: median pH, percentage of time with pH >4 and pH >6). Omeprazole-infusion: initial bolus of 80 mg + 8 mg/h; omeprazole-injection: initial bolus of 80 mg + 40 mg/6 h; Ranitidine-infusion: initial bolus of 50 mg + 0.25 mg/kg/h; ranitidine-injection: 100 mg/6 h. RESULTS Omeprazole-infusion versus ranitidine-infusion: on day 1: median pH 6.1 vs 5.1 (p = 0.01) and 95% vs 70% was pH >4 (p < 0.01); on day 2: median pH 6.2 vs 3.2 (p < 0.01); and 100% vs 38% was pH >4 (p < 0.01); on day 3: median pH 6.3 vs 2.7 (p < 0.01); 100% vs 26% was pH >4 (p < 0.01). Injections of both drugs were significantly less effective than the infusions on day 1. Thereafter, omeprazole injection was almost as effective as omeprazole infusion, whereas ranitidine injection and infusion were equally effective. CONCLUSION Our study shows, for the first time, that omeprazole infusion was significantly superior to all other regimens by having a high median pH >6 on each day. The tolerance effect of ranitidine, however, led to a rapid loss of antisecretory activity on days 2 and 3, rendering it inappropriate for situations in which high intragastric pH-levels appear to be essential.
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Affiliation(s)
- P Netzer
- Inselspital, and Department of Mathematical Statistics, University of Berne, Switzerland
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23
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Kress S, Schilling D, Riemann JF. [Concept of stress ulcer prevention. Is re-thinking necessary?]. MEDIZINISCHE KLINIK (MUNICH, GERMANY : 1983) 1998; 93:486-91. [PMID: 9747104 DOI: 10.1007/bf03042598] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND The efficiency of stress ulcer prophylaxis in the prevention of gastrointestinal bleeding in critically ill patients has led to its widespread use. The lower incidence of stress ulcer bleeding, the side-effects and the cost of the prophylaxis have made it necessary targeting this preventive therapy to those patients most likely to benefit. Metaanalysis of studies on patients who received no stress ulcer prophylaxis showed few critically ill patients with important gastrointestinal bleeding. INDICATIONS Patients who benefit most from receiving stress ulcer prophylaxis are critically ill patients with coagulopathy, or those requiring mechanical ventilation for more than two days. In patients with headinjuries, widespread burns or severe hypotension, the effects of stress ulcer prophylaxis have not been fully researched, but we would recommend administering stress ulcer prophylaxis in these cases. TREATMENT Following a recent metaanalysis, stress ulcer prophylaxis is performed either with H2-blockers (ranitidine, famotidine) or sucralfate.
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Affiliation(s)
- S Kress
- Medizinische Klinik C, Klinikum Ludwigshafen
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24
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Lasky MR, Metzler MH, Phillips JO. A prospective study of omeprazole suspension to prevent clinically significant gastrointestinal bleeding from stress ulcers in mechanically ventilated trauma patients. THE JOURNAL OF TRAUMA 1998; 44:527-33. [PMID: 9529184 DOI: 10.1097/00005373-199803000-00020] [Citation(s) in RCA: 91] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To prospectively evaluate the incidence of clinically significant bleeding, side effects, and cost of therapy in mechanically ventilated trauma patients at high risk for stress ulcers who received simplified omeprazole suspension (SOS). METHODS Prospective, evaluative study in a Level I trauma center. Mechanically ventilated trauma patients admitted with at least one additional risk factor for stress ulcer development received SOS for stress ulcer prophylaxis. RESULTS Sixty trauma patients were enrolled. The mean Injury Severity Score was 27.3. After starting SOS, there were no cases of clinically significant upper gastrointestinal bleeding related to stress ulceration. Baseline pH was 3.3, and mean gastric pH after SOS was increased to 6.7 (p < 0.005). There were no adverse effects thought to be related to omeprazole suspension. Incidence of nosocomial pneumonia after beginning SOS was 28.3%. The cost of acquisition plus administration of SOS was $13.13 per day, whereas the cost of drug acquisition alone was $3.83 per day. CONCLUSION In a prospective, evaluative study of 60 trauma patients who required mechanical ventilation and had at least one additional risk factor for stress ulcer development, omeprazole suspension prevented clinically significant gastrointestinal bleeding, maintained excellent control of gastric pH, produced no toxicity, and was the least costly medication alternative.
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Affiliation(s)
- M R Lasky
- Department of Anesthesiology, University of Missouri, Columbia 65212, USA
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25
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Kuusela AL. Long-term gastric pH monitoring for determining optimal dose of ranitidine for critically ill preterm and term neonates. Arch Dis Child Fetal Neonatal Ed 1998; 78:F151-3. [PMID: 9577289 PMCID: PMC1720764 DOI: 10.1136/fn.78.2.f151] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
AIM To determine the optimal doses of ranitidine for both preterm and term infants. METHOD The effect of ranitidine treatment was measured from the long-term intraluminal gastric pH in 16 preterm (gestational age under 37 weeks) and term infants treated in neonatal intensive care. The infants received three different bolus doses of ranitidine: 0.5 mg, 1.0 mg, and 1.5 mg per kilogram of body weight to keep the intraluminal gastric pH above 4 on a 24 hour basis. RESULTS Critically ill neonates, including very low birth weight infants, were capable of gastric acid formation, and ranitidine treatment increased the intraluminal gastric pH. The effect of a single dose lasted longer in preterm than in term infants. The time needed for reaching the maximum gastric pH was significantly longer in preterm than in term infants. The ranitidine given correlated with the duration of increased gastric pH in a dose dependent manner both in preterm and term infants. CONCLUSION Preterm infants need significantly smaller doses of ranitidine than term neonates to keep their intraluminal gastric pH over 4. The required optimal dose of ranitidine for preterm infants is 0.5 mg/kg/body weight twice a day and that for term infants 1.5 mg/kg body weight three times a day.
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MESH Headings
- Analysis of Variance
- Dose-Response Relationship, Drug
- Drug Administration Schedule
- Gastrointestinal Hemorrhage/prevention & control
- Histamine H2 Antagonists/administration & dosage
- Histamine H2 Antagonists/therapeutic use
- Humans
- Hydrogen-Ion Concentration
- Infant, Newborn
- Infant, Premature
- Infant, Premature, Diseases/prevention & control
- Infant, Premature, Diseases/therapy
- Infant, Very Low Birth Weight
- Monitoring, Physiologic
- Ranitidine/administration & dosage
- Ranitidine/therapeutic use
- Respiration, Artificial
- Stomach/physiopathology
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Affiliation(s)
- A L Kuusela
- Department of Paediatrics, University of Tampere Medical School, Finland
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26
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Baumgartner TG, Henderson GN, Fox J, Gondi U. Stability of ranitidine and thiamine in parenteral nutrition solutions. Nutrition 1997; 13:547-53. [PMID: 9263236 DOI: 10.1016/s0899-9007(97)00034-8] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Our objectives were to ascertain the stability of thiamine HCl (3 mg/L) and ranitidine HCl (150 mg/L) at room and refrigeration temperatures in a central vein formula of parenteral nutrition (PN) solution (containing 6% amino acid, 25% carbohydrate, macro- and microminerals, and multivitamins) and to determine the effect of ranitidine on the stability of thiamine. Stability of thiamine and ranitidine in PN solutions was also compared with PN-salt solutions, which contained no amino acids or carbohydrates, to indirectly ascertain the impact of these macronutrients on the stability of these moieties. High-pressure liquid chromatography (HPLC) methods were developed to measure thiamine and ranitidine in the PN mixture. Stability studies were conducted in triplicate and each sample was assayed in duplicate using newly developed HPLC methods. Refrigeration provided stability for both ranitidine and thiamine for extended periods of time. At room temperature, ranitidine was also shown to be stable for about 188 h; there was, however, significant degradation of thiamine at 24 h with, and without, addition of ranitidine. The time required for 10% of thiamine to degrade was calculated to be 12.9 h for the PN mixture containing multivitamins and ranitidine; 11.1 h for the PN mixture containing multivitamins alone; and 33.4 h for the PN mixture containing only thiamine HCl. This work suggests that the concentration of thiamine in this central vein PN formula, with or without ranitidine, falls below the 90% acceptable stability within 24 h.
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Affiliation(s)
- T G Baumgartner
- Shands Hospital, University of Florida, Gainesville 32610-0316, USA
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27
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Phillips JO, Metzler MH, Palmieri MT, Huckfeldt RE, Dahl NG. A prospective study of simplified omeprazole suspension for the prophylaxis of stress-related mucosal damage. Crit Care Med 1996; 24:1793-800. [PMID: 8917027 DOI: 10.1097/00003246-199611000-00006] [Citation(s) in RCA: 98] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVES To determine the efficacy, safety, and cost of simplified omeprazole suspension in mechanically ventilated critically ill patients who have at least one additional risk factor for stress-related mucosal damage. DESIGN Prospective, open-label study. SETTING Surgical intensive care and burn unit at a university tertiary care center. PATIENTS Seventy-five adult, mechanically ventilated patients with at least one additional risk factor for stress-related mucosal damage. INTERVENTIONS Patients received 20 mL of simplified omeprazole suspension (containing 40 mg of omeprazole) initially, followed by a second 20-mL dose 6 to 8 hrs later, then 10 mL (20 mg) daily. Simplified omeprazole suspension was administered through a nasogastric tube, followed by 5 to 10 mL of tap water. The nasogastric tube was clamped for 1 to 2 hrs after each administration. MEASUREMENTS AND MAIN RESULTS The primary outcome measure was clinically significant gastrointestinal bleeding determined by endoscopic evaluation, nasogastric aspirate examination, or heme-positive coffee ground material that did not clear with lavage, which was associated with at least a 5% decrease in hematocrit. Secondary efficacy measures were gastric pH measured 4 hrs after omeprazole was first administered, mean gastric pH after omeprazole was started, and the lowest gastric pH during omeprazole therapy. Safety-related outcomes included the occurrence rate of adverse events and pneumonia. No patient experienced clinically significant upper gastrointestinal bleeding after receiving omeprazole suspension. The 4-hr postomeprazole mean gastric pH was 7.1, the mean gastric pH after starting omeprazole was 6.8, and the mean lowest pH after starting omeprazole was 5.6. The occurrence rate of pneumonia was 12%. No patient in this high-risk population experienced an adverse event or a drug interaction that was attributable to omeprazole. CONCLUSIONS Simplified omeprazole suspension prevented clinically significant upper gastrointestinal bleeding and maintained gastric pH of > 5.5 in mechanically ventilated critical care patients without producing toxicity.
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Affiliation(s)
- J O Phillips
- Department of Surgery, University of Missouri-Columbia 65212, USA
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28
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Matsui T, Motomura A, Arita M, Takeyama Y, Sakurai T, Yao T. Control of gastric pH with ranitidine in patients with Crohn's disease receiving total parenteral nutrition. Comparison of two intravenous regimens. J Gastroenterol 1996; 31:6-11. [PMID: 8808422 DOI: 10.1007/bf01211180] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Eleven patients with Crohn's disease in remission who were receiving total parenteral nutrition (TPN) underwent continuous intragastric 24-h pH monitoring before and during ranitidine administration. The patients were randomly allocated to receive 200 mg/day (group 1) or 400 mg/day (group 2) of ranitidine by continuous infusion. The mean basal 24-h gastric pH was sustained at a low value. After raintidine administration, the mean pH increased significantly both in group 1 (from 2.13 to 3.28) and in group 2 (from 1.91 to 3.36), with the mean holding-time at pH-3 also increasing significantly in both groups. There were no differences in the mean pH or holding-time at pH-3 between the two groups during ranitidine administration; however, the plasma ranitidine concentration was significantly higher in group 2. These findings indicate that the continuous infusion of a standard dose of ranitidine exerted a maximal inhibitory effect on the sustained hyperacidity induced by TPN, but that this infusion was unable to maintain the intragastric pH level at above 3.5.
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Affiliation(s)
- T Matsui
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Japan
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29
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Kolkman JJ, Meuwissen SG. A review on treatment of bleeding peptic ulcer: a collaborative task of gastroenterologist and surgeon. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1996; 218:16-25. [PMID: 8865446 DOI: 10.3109/00365529609094726] [Citation(s) in RCA: 33] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The majority of patients presenting with acute upper gastrointestinal haemorrhage bleed from peptic diseases erosive gastritis and duodenal or gastric ulcers. Early gastroscopy is essential in order to reach a diagnosis, assess the prognosis, and institute appropriate therapy. In a meta-analysis it was shown that H2-antagonists significantly reduced mortality. However, two large, prospective and placebo-controlled studies with famotidine and omeprazole failed to show reduction of rebleeding or death. The value of endoscopic haemostatic therapy in patients with high-risk peptic ulcers (active bleeding and non-bleeding visible vessel) has been firmly established with 75% decrease in rebleeding and operation rate, and a 40% reduction in mortality. Risk factors for an adverse outcome are: elderly patients, concomitant diseases and large ulcers in the posterior duodenal bulb or on the lesser curvature. The mortality for emergency surgery in upper GI bleeding is still 10-50%. The mortality of elective operations is less than 2%. Some studies have reduced mortality by avoiding emergency surgery through early elective surgery in high-risk patients.
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Affiliation(s)
- J J Kolkman
- Dept. of Gastroenterology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
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30
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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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31
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Baghaie AA, Mojtahedzadeh M, Levine RL, Fromm RE, Guntupalli KK, Opekun AR. Comparison of the effect of intermittent administration and continuous infusion of famotidine on gastric pH in critically ill patients: results of a prospective, randomized, crossover study. Crit Care Med 1995; 23:687-91. [PMID: 7712759 DOI: 10.1097/00003246-199504000-00017] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
OBJECTIVES To compare the effects of intermittent intravenous administration and continuous intravenous infusion of famotidine on gastric pH in critically ill patients. DESIGN A prospective, randomized, crossover study of continuous infusion and bolus administration of famotidine in critically ill patients. SETTING A 14-bed medical intensive care unit (ICU) of a 500-bed county hospital. PATIENTS Medical ICU patients requiring stress ulcer prophylaxis. INTERVENTIONS Patients were randomized to receive an equivalent dose of famotidine by continuous infusion or intravenous bolus for 24 hrs, and then were crossed over to the other arm of the study. MEASUREMENTS AND MAIN RESULTS Critically ill patients who met the inclusion criteria were randomly assigned to receive famotidine 20 mg i.v. over 10 mins, every 12 hrs or a continuous infusion of 1.7 mg/hr for 24 hrs. After a 16-hr washout period, patients crossed over to the other arm of the study. Gastric pH was monitored continuously for 24 hrs. A total of 710 gastric pH measurements were obtained for each phase of the study. The mean area under the pH-time curve for a 24-hr period was higher for continuous infusion than bolus administration (p = .05). Continuous infusion of famotidine maintained a gastric pH of > or = 4 over a longer time period than bolus administration (20.8 hrs vs. 12.6 hrs, respectively; p < .01). Onset of therapeutic gastric pH for continuous infusion was slightly delayed as compared with bolus administration. CONCLUSIONS Continuous infusion of famotidine is more effective than an equivalent dose given by intermittent bolus in maintaining the appropriate gastric pH necessary for prevention of stress ulceration. Delayed onset of effect may warrant a priming dose when famotidine is given by continuous infusion.
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Affiliation(s)
- A A Baghaie
- Department of Pharmacy Practice, Texas Southern University College of Pharmacy and Health Sciences, Houston 77004, USA
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32
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Fisher RL, Pipkin GA, Wood JR. Stress-Related Mucosal Disease: Pathophysiology, Prevention, and Treatment. Crit Care Clin 1995. [DOI: 10.1016/s0749-0704(18)30070-8] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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33
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Burgess P, Larson GM, Davidson P, Brown J, Metz CA. Effect of ranitidine on intragastric pH and stress-related upper gastrointestinal bleeding in patients with severe head injury. Dig Dis Sci 1995; 40:645-50. [PMID: 7895560 DOI: 10.1007/bf02064385] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
We conducted a double-blind, placebo-controlled study to evaluate the effects of ranitidine on intragastric pH and upper gastrointestinal tract bleeding in severe head injury patients. Within 24 hr of the precipitating trauma, 34 adults with Glasgow coma scale scores < or = 10 were randomized to a 6.25 mg/hr ranitidine continuous infusion or placebo for a maximum of 72 hr. Intragastric pH was recorded via an intragastric pH electrode. Patients with hematemesis, hematochezia, bright red blood, or "coffee ground" nasogastric tube aspirates plus a 5% decrease from baseline in hematocrit were considered to have gastrointestinal bleeding. Ranitidine patients maintained a significantly greater mean pH than placebo patients (placebo 2.2, ranitidine 4.1; P < 0.01). All patients had at least two bleeding risk factors at study entry. No ranitidine patients (0/16) developed bleeding compared with five (5/18) placebo patients (P < 0.05). Ranitidine continuous infusion provided consistent intragastric pH control and significant protection from stress-related upper gastrointestinal tract bleeding in a high-risk patient population.
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Affiliation(s)
- P Burgess
- Department of Surgery, University of Louisville, School of Medicine, Kentucky 40292
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Teyssen S, Chari ST, Scheid J, Singer MV. Effect of repeated boluses of intravenous omeprazole and primed infusions of ranitidine on 24-hour intragastric pH in healthy human subjects. Dig Dis Sci 1995; 40:247-55. [PMID: 7851185 DOI: 10.1007/bf02065405] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
The aim of this study was to identify dosage regimens using intravenous omeprazole and ranitidine that would elevate and consistently maintain intragastric pH > 6 in the first 24 hr of therapy. In 19 healthy, fasting human subjects using continuous 24-hr gastric pH-metry, we studied two dosages of primed infusions of ranitidine (50 mg bolus followed by infusion of either 3 or 6 mg/kg body wt/24 hr) and six regimens of intravenous omeprazole (80-200 mg in 24 hr in two to five boluses). Only the two ranitidine infusions and high doses of omeprazole (> or = 160 mg/day as four or five boluses) raised the intragastric median pH above 5.4. There was no significant difference in the median intragastric pH after high dose ranitidine and high doses of omeprazole. Considerable interindividual variation in intragastric pH was observed after omeprazole therapy. The percentage of intragastric pH > 6.0 during the 24-hr study was lower after omeprazole (35-42%) than after high-dose ranitidine (58%). We conclude that it is possible to raise intragastric pH > 6.0 by use of either primed ranitidine infusion or by repeated boluses of omeprazole. However, maintenance of this high pH in the first 24 hr is difficult with both, more so with omeprazole.
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Affiliation(s)
- S Teyssen
- Department of Medicine IV (Gastroenterology), University Hospital of Heidelberg at Mannheim, Germany
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35
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Amsden GW, Goss TF, Harrison NJ, D'Andrea DT, Schentag JJ. Pharmacodynamics of bolus famotidine versus infused cimetidine, ranitidine, and famotidine. J Clin Pharmacol 1994; 34:1191-8. [PMID: 7738215 DOI: 10.1002/j.1552-4604.1994.tb04731.x] [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: 01/26/2023]
Abstract
A four-way crossover pilot study was conducted to compare the pharmacodynamic response of intermittent famotidine (20 mg every 12 hr) to continuous infusions of cimetidine (1200 mg/24 hr), ranitidine (150 mg/24 hr), and famotidine (40 mg/24 hr) in six normal male volunteers. Intragastric pH was monitored continuously for 24 hours. Comparisons included percent time during the 24-hour period that gastric pH was greater than pH 4.0, and pH 5.0, and also for the steady-state period of each regimen (12-24 hr). Although no statistically significant difference was observed for any of these comparisons, a clinically relevant trend was observed. In crossover experiments, famotidine intermittent infusions provided gastric pH readings above 4.0 and 5.0 for a longer duration than any of the continuous infusion regimens. Famotidine intermittent infusion regimens (20 mg every 12 hr) are at least equivalent to continuous infusions of cimetidine, ranitidine, and famotidine. Based on these findings, comparative studies in an appropriate critical care population would be beneficial, but any such studies must use a crossover design because of the even higher degree of intersubject variance in pH control. For this reason, the normal volunteer crossover model used here may provide important comparative information for the various regimens used in suppression of gastric acidity.
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Affiliation(s)
- G W Amsden
- Clinical Drug Research Center, Saint Vincent Hospital, Worcester, Massachusetts 01604
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Abstract
OBJECTIVE To present recent advances in stress gastritis prophylaxis in the critically ill and review considerations in selection of a prophylactic agent. DATA SOURCES Information was obtained from MEDLINE search, reference lists from articles identified in search, and from review articles. STUDY SELECTION Emphasis was placed on controlled trials conducted within the last 5 years. DATA EXTRACTION All literature was assessed for methodology, results, and conclusions. Results of prospective, randomized trials, and meta-analyses are summarized. DATA SYNTHESIS Histamine2-receptor antagonists, antacids, and sucralfate appear equally effective in preventing stress gastritis in the critically ill. A definitive cause-effect relationship between histamine2-receptor antagonists and increased incidence of nosocomial pneumonia has not yet been established. The indications for using a prophylactic agent and consideration in selecting an agent should include an evaluation of the following: risk factors for gastritis including the type of intensive care patient, comparative efficacy, adverse effects, drug interactions, cost, and ease of administration. The least expensive, safest agent requiring minimal monitoring is sucralfate. Prevention of stress gastritis has never been shown to reduce morbidity or mortality significantly. CONCLUSIONS Controversies still exist regarding the need to provide prophylaxis, the choice of an agent, and the relative importance of previously identified risk factors. Further well-designed studies are needed before consensus can be reached.
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Affiliation(s)
- M A Smythe
- Department of Pharmacy Practice, Wayne State University, Detroit, MI 48202
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Hatton J, Luer M, Hirsch J, Westrich T, Holstad S. Histamine receptor antagonists and lipid stability in total nutrient admixtures. JPEN J Parenter Enteral Nutr 1994; 18:308-12. [PMID: 7933436 DOI: 10.1177/014860719401800405] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Drug stability and compatibility studies should be performed for all medications added to total nutrient admixtures (TNAs) before administration to patients. The stability of TNA components will vary depending on product selection and final concentrations. This variability prohibits generalizing published study results generically to TNAs containing untested products or combinations. Histamine receptor antagonists (H2RAs) are commonly administered by continuous infusion via nutrient solutions. When the delivery vehicle is a TNA, comparative stability and compatibility studies performed under similar test conditions are lacking. The stability of marketed parenteral H2RAs and of the investigational H2RA, nizatidine was analyzed in TNA solutions containing either Liposyn II or Intralipid at differing concentrations. All H2RAs remained at more than 90% of initial concentration at 24 hours. After 48 hours, only ranitidine concentrations fell to less than 90% in all study solutions. Each TNA containing an H2RA was within pH stability ranges for lipid products, and no change in particle size was detected during the 48-hour period. This is the first report determining H2RA compatibility and stability in TNA solutions with both 3% and 5% Intralipid and Liposyn II and using similar methodology for all standard H2RA concentrations. Results suggest that these drugs are stable for 24 hours in TNAs containing either lipid product. Beyond this time, administration of ranitidine may be unreliable because of poor stability under the conditions tested.
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Affiliation(s)
- J Hatton
- Department of Pharmacy, University of Kentucky Medical Center, Lexington 40536-0084
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Jones LA, Gonzalez ER, Reines HD, Venitz J. Assessment of 24-hour gastric pH measurements in trauma patients receiving intravenous famotidine by intermittent bolus versus continuous infusion administration. Ann Pharmacother 1994; 28:841-4. [PMID: 7949496 DOI: 10.1177/106002809402800702] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
OBJECTIVE To compare the effects of intermittent bolus versus continuous infusion intravenous famotidine on gastric pH in critically ill trauma patients. DESIGN Twenty patients were randomized to receive famotidine by intermittent bolus or continuous infusion for 24 hours. Patients fasted during the study period. Hourly gastric pH measurements were made using an indwelling sensor/sump tube. SETTING The study was conducted in a university teaching hospital. PARTICIPANTS Adult patients admitted to the neurosurgical or surgical/trauma intensive care unit within 72 hours of traumatic injury were enrolled in the study if they had two consecutive hourly gastric pH readings of < 4 without receiving antacids, sucralfate, or histamine2-antagonists. MAIN OUTCOME MEASURES Groups were compared with regard to (1) total dose of famotidine received/24 hours, and (2) number of dosage changes required to maintain a gastric pH value of > or = 4. RESULTS The median dose of famotidine required to maintain a gastric pH > or = 4 was 50 mg/24 h (25th-75th percentiles = 40-55 mg) in the intermittent bolus group compared with 42 mg/24 h (25th-75th percentiles = 42-52 mg) in the continuous infusion group (p = 0.9577). A dosage increase was required by 5 of 8 patients (62 percent) receiving intermittent bolus therapy, whereas only 2 of 8 patients (25 percent) in the continuous infusion group required a dosage adjustment (p = 0.315, power = 0.318). CONCLUSIONS Intravenous famotidine (40-50 mg/d) effectively controlled gastric pH in critically ill trauma patients. Patients treated with intermittent bolus therapy required slightly more drug and more frequent dosage adjustments to achieve a gastric pH > or = 4. These differences did not reach statistical significance.
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Affiliation(s)
- L A Jones
- University of Texas Health Science Center at San Antonio
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39
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40
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Merki HS, Wilder-Smith CH. Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing? Gastroenterology 1994; 106:60-4. [PMID: 8276209 DOI: 10.1016/s0016-5085(94)94341-9] [Citation(s) in RCA: 115] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
BACKGROUND/AIMS Prolonged infusions of H2-antagonists are commonly used in intensive care units, although little is known about their antisecretory efficacy beyond the initial 24 hours of dosing. The aim of this study was to assess the antisecretory effects of infusions of ranitidine and omeprazole for a period of 72 hours. METHODS Twelve healthy volunteers received individually titrated 72-hour intravenous infusions of omeprazole, ranitidine, or placebo in a double-blind, crossover study. Gastric pH and dosing requirements were compared. RESULTS The median percentage of time with pH > 4 (interquartile range) was 93% (88%-95%) on day 1 and 96% (94%-99%) on day 3 with omeprazole and 67% (56%-78%) and 43% (31%-51%), respectively, with ranitidine (both P < 0.001 vs. omeprazole). The mean doses (+/- SD) required on days 1 and 3 for omeprazole were 235.8 +/- 44 mg and 134.0 +/- 37 mg (P < 0.0001), and ranitidine doses were 502.5 +/- 76 mg and 541.8 +/- 25 mg, respectively (P = 0.05). CONCLUSIONS Omeprazole infusions consistently maintained gastric pH above 4 over a period of 72 hours with progressively lower doses. Significant tolerance to the antisecretory effect of ranitidine infusion developed in 72 hours, which was not overcome despite individually titrated doses of more than 500 mg/24 hours. Consequently, application of pharmacodynamic results of single-day H2-blocker and proton-pump inhibitor studies to prolonged infusion trials for stress ulcer-related bleeding is inappropriate.
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Affiliation(s)
- H S Merki
- Department of Medicine, Inselspital, University of Bern, Switzerland
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41
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Thomson AB, Kirdeikis P, Simon K, Zuk L, Pinchbeck B, Wasarab-Rolland D, Kersey K. Effect of intravenous infusion of ranitidine on intragastric acidity in fasting subjects: comparison with bolus or Gastrojet (pH-stat-adjusted) infusion. Aliment Pharmacol Ther 1993; 7:649-53. [PMID: 8161672 DOI: 10.1111/j.1365-2036.1993.tb00147.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
This study was undertaken in nine fasting healthy volunteers to compare the effect of intravenous continuous infusion versus bolus injection of ranitidine on 12-h intragastric pH, and to compare the efficacy of these two modes of administration of pH-stat-adjusted infusion of ranitidine using the Gastrojet. Each volunteer had three study sessions with 12-h pH measurements. In the ranitidine infusion treatment arm (RAN-INF), ranitidine was continually infused intravenously using an IVAC-pump at a dose of 0.125 mg mg.kg over a 12-h period. In the ranitidine bolus treatment arm (RAN-BOL), ranitidine bolus 50 mg was given over 10 min, every 6 h. When ranitidine infusion was given by the pH stat method using the Gastrojet (RAN-JET), sufficient ranitidine was given to maintain a present value of pH > or = 5. The study was analysed with a 3 x 3 Latin square cross-over design with multiple measurements of each phase of the cross-over. No difference was found between RAN-INF and RAN-BOL in 12-h or in daytime (10.00-18.00 h) mean pH, median pH, or percentage of pH > or = 5. Using RAN-JET, 89.5% of the pH values were > or = 5., compared with 39.7% and 40.0% with RAN-INF or RAN-BOL. RAN-JET also gave higher (P < 0.05) mean and median 12-h or daytime pH values, as compared with RAN-INF or RAN-BOL. The mean doses of ranitidine given in the 12-h infusion periods were 100 mg, 109 mg and 112 mg (RAN-BOL, RAN-INF and RAN-JET, respectively). Thus, this superior inhibition of acid inhibition achieved with Gastrojet does not require higher mean doses of ranitidine. These findings cannot necessarily be applied to persons with duodenal ulcer disease or to patients in an intensive-care unit setting. However, the data do raise the possibility that much greater inhibition of acid inhibition can be achieved by individualizing the dose of ranitidine using the Gastrojet.
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Affiliation(s)
- A B Thomson
- Department of Medicine, University of Alberta, Edmonton, Canada
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42
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Wilson P, Clark GW, Anselmino M, Welch NT, Singh S, Perdikis G, Hinder RA. Comparison of an intravenous bolus of famotidine and Mylanta II for the control of gastric pH in critically ill patients. Am J Surg 1993; 166:621-4; discussion 624-5. [PMID: 8273840 DOI: 10.1016/s0002-9610(05)80667-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
The effects of the intravenous bolus administration of famotidine versus the administration of Mylanta II liquid every 2 hours on the pH of the gastric antrum, body, and fundus for 24 hours were compared in 10 critically ill patients admitted to the intensive care unit with isolated cranial trauma. Patients received 30 mL of Mylanta II every 2 hours via nasogastric tube for 24 hours, followed by administration of 20 mg of intravenous bolus famotidine every 12 hours for the subsequent 24-hour period. pH of the gastric antrum, body, and fundus was monitored continuously using a three antimony pH electrode/nasogastric tube assembly. Gastric pH data were analyzed for the percentage of time pH was less than 4 and median pH for the antrum, body, and fundus for each 24-hour period. The percentage of time pH was less than 4 was significantly less in the antrum and body of the stomach during famotidine therapy (8.9% +/- 3.6% and 24.9% +/- 6.9%, respectively) compared with Mylanta II (39.1% +/- 6.7% and 57.6% +/- 8.5%, respectively, both p < 0.005), but was not significantly different in the fundus (famotidine: 25.3% +/- 7.8%; Mylanta II: 28.3% +/- 6.5%). Median gastric pH for 24 hours was significantly greater in the antrum and body of the stomach during famotidine therapy (7.8 +/- 0.2 and 6.8 +/- 0.6, respectively) compared with Mylanta II (4.5 +/- 0.6 and 3.7 +/- 0.9, respectively, p < 0.005 and p < 0.01, respectively), but was not significantly different in the fundus (famotidine: 5.9 +/- 0.8; Mylanta II: 5.4 +/- 0.7). The data indicate that an intravenous bolus of famotidine every 12 hours is more effective than Mylanta II liquid every 2 hours administered via a nasogastric tube in maintaining gastric pH above 4 in critically ill patients. Famotidine produces a uniform increase in gastric pH throughout the stomach, whereas Mylanta II controls only proximal gastric pH, probably related to fundic pooling of antacid in the supine position.
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Affiliation(s)
- P Wilson
- Department of Surgery, Creighton University, Omaha, Nebraska 68131
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43
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Bachmann K, Sullivan TJ, Jauregui L. A controlled comparison of continuous ranitidine and intermittent famotidine infusions on gastric pH. J Clin Pharmacol 1993; 33:1219-24. [PMID: 7907348 DOI: 10.1002/j.1552-4604.1993.tb03923.x] [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
Continuous infusions of any given H2-blocking drug have uniformly been found to be superior to intermittent infusions of the same H2-blocking drug in sustaining elevations in gastric pH. Comparisons of intermittent and continuous infusions among different H2-blocking drugs have heretofore not been made. Owing to its greater potency and longer half-life, the authors were interested in determining whether intermittent infusions of famotidine might be as effective as continuous infusions of ranitidine in sustaining elevations of gastric pH. The effectiveness of a continuous intravenous infusion of ranitidine (6.25 mg/hr) was compared with the effectiveness of intermittent intravenous infusions of famotidine (20 mg every 12 hours) in sustaining gastric pH above 4.0 in 18 young, healthy adult male subjects using a randomized two-way cross-over design. Gastric pH was continuously monitored for 24 hours. The intermittent famotidine regimen was determined to be as effective as the continuous ranitidine regimen with respect to the following parameters: (1) the percentage of the 24-hour dosing period during which gastric pH exceeded 4.0; (2) the area under the pH > or = 4 versus time curve; and (3) median gastric pH.
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Affiliation(s)
- K Bachmann
- Center for Applied Pharmacology, University of Toledo, Ohio
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44
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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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45
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Geus WP, Vinks AA, Smith SJ, Westra P, Lamers CB. Comparison of two intravenous ranitidine regimens in a homogeneous population of intensive care unit patients. Aliment Pharmacol Ther 1993; 7:451-7. [PMID: 8218759 DOI: 10.1111/j.1365-2036.1993.tb00119.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Primed continuous infusion and repeated intravenous injections of ranitidine (daily dose 200 mg) were compared in a homogeneous population of post-operative intensive care unit patients in a randomized fashion. Intragastric pH was measured continuously for 72-96 h with combined glass electrodes positioned in the gastric corpus. Patients whose intragastric acidity fell below pH 4.0 for 70% of a 24-h period within 48 h after the operation (baseline period) were considered 'at risk' of developing stress-related lesions. From the 26 patients screened, 18 fulfilled this criterion. Nine received the continuous infusion regimen (50 mg bolus + 0.125 mg.kg/h) and nine received repeated boluses (50 mg ranitidine every 6 h). A consistent decrease of intragastric acidity was shown in each group by a rise in 24-h median pH from 1.4 (1.3-1.7; 26th-75th percentile) during the baseline period to 4.2 (1.9-5.4, P < 0.01) for the continuous infusion and from 1.55 (1.1-2.2) to 2.65 (2.1-3.5, P < 0.02) for the repeated boluses during the final 24 h of the therapy period. During that period intragastric pH was maintained above 4 for 52% of time by continuous infusion and for 40% of time for repeated boluses compared with 10.8% (P = 0.01) and 6.2% (P = 0.008) of time, respectively, in the baseline period. In conclusion, although no statistically significant differences between the two regimens could be detected, the continuous infusion regimen tended to show slightly better results in percentages of time that pH values were above 1 to 7, and in median 24-h pH values.
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Affiliation(s)
- W P Geus
- Department of Intensive Care and Internal Medicine, Leyenburg Hospital, The Hague, The Netherlands
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Moore JG, Clemmer TP, Taylor S, Bishop AL, Maggio S. Twenty-four-hour intragastric pH patterns in ICU patients on ranitidine. Dig Dis Sci 1992; 37:1802-9. [PMID: 1473427 DOI: 10.1007/bf01308071] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Thirty critically ill patients with mixed diagnoses underwent continuous intragastric pH monitoring for 72 hr while confined to a shock/trauma intensive care unit. The first 24 hr were monitored under no specific acid-suppressing therapy (placebo control). During the second and third consecutive 24-hr periods, patients received continuous infusion of intravenous ranitidine in the dose of 6.25 mg/hr and 12.5 mg/hr, respectively. Results of the placebo-control 24-hr study revealed that one third (N = 10) of the patients were gastric acid hyposecretors (24-hr median intragastric pH values above pH 4.0). In the normosecreting group (N = 20), both ranitidine schedules significantly elevated 24-hr median pH values, when compared to placebo (placebo 24-hr median intragastric pH 1.75; ranitidine 6.25 mg/hr 24-hr median intragastric pH 4.625, P < 0.0001; ranitidine 12.5 mg/hr 24-hr median intragastric pH 6.29, P = 0.0099). Five patients (18%) failed to adequately respond to the ranitidine 12.5 mg/hr dose (24-hr median intragastric pH < 4.0). These findings suggest that a significant percentage of intensive care unit patients are not in need of acid-suppressing therapy as prophylaxis against stress-induced ulceration. Conversely, other patients may require more intensive acid-suppressing regimens because of failure to respond to high dose H2-antagonist therapy.
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Affiliation(s)
- J G Moore
- Department of Medicine, LDS Hospital, University of Utah School of Medicine, Salt Lake City
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Wilder-Smith CH, Halter F, Häcki W, Merki HS. pH-feedback controlled infusions of ranitidine are no more effective than fixed-dose infusions in reducing gastric acidity and variability in antisecretory responses. Br J Clin Pharmacol 1992; 33:487-93. [PMID: 1524960 PMCID: PMC1381434 DOI: 10.1111/j.1365-2125.1992.tb04075.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
1. The antisecretory responses to pH-feedback controlled (maximum dose 800 mg 24 h-1) and fixed-dose (0.25 mg kg-1 h-1) continuous infusions of ranitidine were compared in a randomised, placebo-controlled, cross-over study in 10 healthy male volunteers. 2. To assess tolerance during repeated dosing with ranitidine, the same infusion regimens were given before and after 6 days oral dosing with ranitidine 300 mg four times daily. 3. With the pH-feedback controlled infusion of ranitidine the median % time (interquartile range) with pH greater than 4 in the 24 h period was 57% (45-76) before and 23% (17-34) after 6 days oral dosing (P less than 0.001). The respective values with fixed-dose infusion were 51% (38-63) and 26% (15-32) (P less than 0.002). 4. The median 24 h doses (interquartile range) of ranitidine given by feedback-controlled infusion before and after 6 days oral dosing were 675 mg (542-728) and 749 mg (709-760), respectively (P less than 0.01). The dose of ranitidine given by fixed-rate infusion was 423 mg (393-502) on both study days (P less than 0.001 vs feedback infusion). 5. Plasma gastrin concentrations remained slightly elevated after 6 days of oral ranitidine dosing, whereas pancreatic polypeptide plasma levels remained unchanged. 6. The antisecretory efficacy of infusions of ranitidine is significantly decreased by circadian stimuli and tolerance. Individually-adapted infusions of high doses of ranitidine were not superior to fixed-dose infusion of 0.25 mg kg-1 h-1 in overcoming this variability.
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48
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Wilder-Smith CH, Merki HS. Tolerance during dosing with H2-receptor antagonists. An overview. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1992; 193:14-9. [PMID: 1363254 DOI: 10.3109/00365529209096000] [Citation(s) in RCA: 39] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Diminution of antisecretory effect of H2-receptor antagonists with repeated oral dosing, termed tolerance, has been established in healthy volunteers. Anecdotal evidence indicates the development of tolerance with intravenous dosing. These findings demonstrate that tolerance may be clinically relevant in diseases where tight control of acidity is required. Patients with duodenal ulcer disease, however, do not develop significant tolerance, according to the sparse investigations available. Tolerance will, at most, only be of minor clinical significance in failures of DU to heal. The mechanisms implicated in the development of tolerance remain unclear.
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Affiliation(s)
- C H Wilder-Smith
- Dept. of Medicine, Inselspital, University of Berne, Switzerland
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49
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Sanders SW, Moore JG. Gastrointestinal chronopharmacology: physiology, pharmacology and therapeutic implications. Pharmacol Ther 1992; 54:1-15. [PMID: 1528953 DOI: 10.1016/0163-7258(92)90049-6] [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: 12/27/2022]
Abstract
This chapter discusses the influence of ultradian and circadian rhythms of gastrointestinal motor and secretory function on the action of orally administered drugs. Most drugs exhibit more rapid absorption in the morning compared to the evening due, in part, the circadian alterations in gastric emptying. Gastric acid secretion and gastrointestinal toxicity to oral drugs also display circadian rhythmicity. These observations provide a rationale for use or avoidance of drugs based on time-of-day dosing considerations. The chronopharmacological behavior of a drug may thus play an important role in the effectiveness of any oral medication treatment schedule.
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Affiliation(s)
- S W Sanders
- University of Utah School of Medicine, Salt Lake City 84148
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50
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Geus WP, Vinks AA, Lamers CB. Pharmacokinetics of ranitidine in a homogeneous population of intensive care unit patients during intermittent and continuous administration. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY. SUPPLEMENT 1992; 194:55-8. [PMID: 1298048 DOI: 10.3109/00365529209096027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
The pharmacokinetics of ranitidine during two different modes of intravenous administration was studied in a homogeneous group of postoperative intensive care unit patients (n = 18). Patients at risk of developing stress-related lesions were randomized to receive repeated injections, 50 mg every 6 h (group A), or a continuous infusion, 50-mg bolus followed by 0.125 mg/kg/h (group B). Before treatment all patients received a single 50-mg ranitidine dose. Serum ranitidine concentrations were measured for 12 h after the single dose and during the treatment period, to calculate individual pharmacokinetic variables. From the single-dose study the calculated half-life, volume of distribution, and clearance were 3.14 +/- 0.61 h, 1.45 +/- 0.42 l/kg, and 0.40 +/- 0.14 l/kg/h for group A and 3.33 +/- 1.08 h, 1.16 +/- 0.20 l/kg, and 0.35 +/- 0.21 l/kg/h, for group B, respectively. Ranitidine pharmacokinetics after the single dose was comparable in the two groups. No statistically significant differences could be detected between the ranitidine pharmacokinetics after the first single dose and the multiple dose or continuous infusion.
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Affiliation(s)
- W P Geus
- Dept. of Gastroenterology, Leyenburg Hospital, The Hague, The Netherlands
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