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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!

CCC Pharmacology Series

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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