Peptic ulcer disease bleeding

Previous peptic ulcer disease or upper gastrointestinal bleeding Cardiovascular disease and other comorbid conditions Multiple NSAID use (e.g., low-dose aspirin in conjunction with another NSAID)... 

Patients at increased risk of NSAID-induced gastrointestinal adverse effects (e.g., dyspepsia, peptic ulcer formation, and bleeding) include the elderly, those with peptic ulcer disease, coagulopathy, and patients receiving high doses of concurrent corticosteroids. Nephrotoxicity is more common in the elderly, patients with creatinine clearance values less than 50 mL/minute, and those with volume depletion or on diuretic therapy. NSAIDs should be used with caution in patients with reduced cardiac output due to sodium retention and in patients receiving antihypertensives, warfarin, and lithium. 

Gl effects - Do not use ketorolac in active peptic ulcer disease, recent Gl bleeding or perforation, a history of peptic ulcer disease, or Gl bleeding. 

Rare react ions with long-term use include peptic ulcer disease, G1 bleeding, gastritis, a severe hepatic reaction (jaundice), nephrotoxicity (hematuria, dysuria, proteinuria), and a severe hypersensitivity reaction (bronchospasm or angioedema). 

Contraindications Active peptic ulcer disease, chronic inflammation of GI tract, GI bleeding or ulceration, history of hypersensitivity to aspirin or NSAIDs... 

Rare reactions with long-term use include peptic ulcer disease, GI bleeding, gastritis, nephrotoxicity (dysuria, cystitis, hematuria, proteinuria, nephrotic syndrome), severe hepatic reactions (cholestasis, jaundice), and severe hypersensitivity reactions (bronchospasm, angioedema). 

Unlabeled Uses Peptic ulcer disease, active ulcer bleeding (injection), adjunct in treatment of Helicobacter pylori infecfion. 

All NSAIDs have the potential to cause gastric and duodenal ulcers and bleeding through direct (topical) or indirect (systemic) mechanisms. Risk factors for NSAID-associated ulcers and ulcer complications (perforation, gastric outlet obstruction, GI bleeding) include increased age, comorbid medical conditions (e.g., cardiovascular disease), concomitant corticosteroid or anticoagulant therapy, and history of peptic ulcer disease or upper Gl bleeding. 

Contraindications fc>r nonsalicylate NSAID therapy are the same as those for aspirin (see Box 7-I).The formation of a gastric ulcer or erosion that may bleed profusely is a serious potential problem with NSAIDs. Consequently, the nonsalicylate NSAIDs should be avoided or used with great caution in patients with active peptic ulcer disease. NSAIDs may increase the risk of GI complications even when used in conjunction with low-dose aspirin for cardioprotection. In addition, because of potential crosssensitivity to other NSAIDs, the nonsalicylate NSAIDs should not be given to patients in whom aspirin or other NSAIDs have caused symptoms of asthma, rhinitis, urticaria, angioedema, hypotension, bronchospasm, or of symptoms of hypersensitivity reactions. Opioids, tramadol, or acetaminophen may be suitable alternatives for patients with known or suspected susceptibility. 

Levy M Aspirin use in patients widi major upper gastrointestinal bleeding and peptic ulcer disease. New Eng. J. Med. 222 1158, 1974... 

Smalley WE, Ray WA, Daugherty JR, Griffin MR. No association between calcium channel blocker use and confirmed bleeding peptic ulcer disease. Am J Epidemiol 1998 148(4) 350-4. 

Important susceptibility factors include age, endogenous coagulation defects, thrombocytopenia, hypertension, cerebrovascular disease, thyroid disease, renal insufficiency, liver disease, tumors, cerebrovascular disease, alcoholism, a history of gastrointestinal bleeding (peptic ulcer disease alone without past bleeding is not associated with an increased risk of bleeding), and an inability to adhere to the regimen. 

A meta-analysis has helped to clarify this issue (96). The aim was to assess the presence and magnitude of any possible interaction in peptic ulcer disease between these two susceptibility factors, with particular attention to bleeding peptic ulcer disease, the sites of ulceration, and the effect of H. pylori eradication. In all, 61 relevant studies were identified, 36 of which were excluded for various reasons. Thus, 25 studies were left for analysis, of which 16 observational studies (eight cross-sectional studies, seven case-control studies, and one cohort study) provided data on the prevalence of peptic ulcer disease in 1633 NSAID users, with data on H. pylori status for 1625 patients. The pooled frequency of peptic ulcer disease in NSAID users was 42% in those who were H. py/on-positive and 25% in those who were H. py/on-negative (OR = 2.12 95% Cl = 1.68, 2.67). 

Overall, H. pylori infection was diagnosed in 47% of the NSAID users and 46% of the controls, but peptic ulcer disease was significantly more common in the NSAID users (36% versus 8.3% OR = 5.14 Cl = 1.35, 20). Compared with patients who were H. py/ori-negative and were not taking NSAIDs, the risk of ulcer in H. py/ori-infected NSAID users was very high (OR = 61 Cl = 10, 373). H. pylori infection increased the risk of peptic ulcer disease in NSAID users 3.53 times in addition to the risk associated with NSAID use (OR = 19). Similarly, in the presence of a risk of peptic ulcer disease associated with H. pylori infection (OR = 18) the use of NSAIDs increased the risk of peptic ulcer disease 3.55 times. H. pylori infection and NSAID use, respectively, increased the risk of ulcer bleeding 1.79 times and 4.85 times the risk of ulcer bleeding increased to 6.13 when both factors were present. 

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