Ranitidine

CLASS

• H2 receptor antagonist

MECHANISM OF ACTION

• competitive blockade of H2 receptors -> decrease in secretion
• also decreases action of gastrin and acetylcholine

PHARMACEUTICS

• injection: 25mg/mL
• tablets: 150, 300mg
• syrup: 15mg/mL

DOSE

• IV: 50mg QID
• PO: 150mg bd

INDICATIONS

1. peptic ulder disease
2. GORD
3. Zollinger-Ellison syndrome
4. prevention of stress ulceration in ICU
5. prior to GA in aspiration risk

ADVERSE EFFECTS

• LFTs derangement
• rash
• anaphylactoid reaction
• confusion
• thrombocytopenia
• leukopenia

PHARMACOKINETICS

• Absorption – bioavailability = 50%
• Distribution – 15% protein bound, Vd = 1.5 L/kg
• Metabolism – hepatic
• Elimination – t ½ = 2 hrs

EVIDENCE

Cook, D et al (1998) “A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation” Canadian Critical Care Trials Group, NEJM, 338:791-7

• MRCT
• placebo vs ranitidine vs sucralfate
  -> GIH: placebo ( ), ranitidine (1.7%), sucralfate (3.8%) – P < 0.05 -> pneumonia incidence: ranitidine (19.2%), sucralfate (16.2%) – P > 0.05
  -> no change in LOS or mortality

Mariki, P. E. et al (2010) “Stress ulcer prophylaxis in the new millennium: A systematic review and meta-analysis” Critical Care Medicine: Volume 38 – Issue 11 – pp 2222-2228

Background

• stress ulceration uncommon (1%)
• prophylaxis may be unwarranted if feeding can be established early
• prophylaxis may increase risk of hospital-acquired pneumonia and Clostrodium difficile infection

• meta-analysis of RCT’s
• histamine-2 receptor blockers vs placebo
• 17 studies (1836 patients)
• primary end point: clinically significant GIH
• secondary end points: incidence of HAP and hospital mortality.
• sub group analysis performed by grouping studies by enteral nutrition or no enteral nutrition

-> significant decrease in risk of gastrointestinal bleeding (OR 0.47, p < 0.02) -> BUT only noted in a subgroup of patients who did not receive enteral nutrition (OR 1.26, CI 0.43-3.7)
-> if patients fed, prophylaxis did not alter the risk of GI bleeding
-> no increase in risk of HAP overall
-> BUT, those who were fed had an increased risk of HAP (p 0.02, or 2.81)
-> stress ulcer prophylaxis did not change mortality
-> the subgroup who received stress ulcer prophylaxis AND enteral feeding had a elevated HAP rate (? both increasing gastric pH and thus allowing gastric multiplication of bacteria and subsequent aspiration)

Internal Validity

• clinically significant GIH was defined by each individual study
• if there wasn’t a definition of clinically significant bleeding then endoscopic bleeding was used.
• used H2 antagonists: cimetidine, ranitidine, famotidine
• varying doses
• some studies ran infusions
• only 3 studies looked at enteral nutrition

External Applicability

• many ICUs use omeprazole
• those who were fed may have been sicker than those that weren’t which may explain increase in HAP and death (confounding)

AN APPROACH

• feed early unless contraindicated
• don’t use prophylaxis if feeding established
• if unable to establish enteral feed, risk assess for GIH: if high risk -> use prophylaxis
• if develops stress ulcers treat
• vigilance for the development of hospital acquired pneumonia
• may need to take ulcer prophylaxis out of FASTHUG sticker!