Proton Pump Inhibitors (PPIs)


 

Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole


  Issues for Surgery


For regular, chronic use – risk of rebound hyperacidity if omitted.

Increased risk of pulmonary aspiration and / or stress-related mucosal disease if omitted.

For investigations of Helicobacter pylori (H. pylori) associated dyspepsia – risk of false negative if continued.


  Advice in the Perioperative period


Elective Surgery

Continue.

Patients who take ‘when required’ PPI should be advised to take a dose of their usual medication on the morning of surgery.

EXCEPT:

  • Investigations for H. pylori – stop 2 weeks prior to investigation1, 2.
  • Combination product VIMOVO® (contains esomeprazole + naproxen) – see Non-Steroidal Anti-Inflammatory Drugs(NSAIDs) including Cyclo-oxygenase-2 (COX-2) Selective Inhibitors (Oral) monograph. Consideration should be given to prescribing the components of this combination as separate medicines perioperatively.

Emergency Surgery

Continue.

Perioperative Considerations

For patients with increased risk factors for aspiration (e.g. pregnancy, obesity, non-fasted state in emergency surgery) consider administration of acid-suppressing medication (oral or intravenous) perioperatively – see Further Information ‘PPIs vs. Histamine H2-Receptor Antagonists [H2RAs]. NB: PPIs are not licensed for prophylaxis of aspiration in relation to anaesthesia.

Post-operative Advice

Patients Undergoing Anti-Reflux Surgery or Total Gastrectomy
Review continued need for PPI therapy following surgery. Consider long-term implications of PPI use if continued – see Further Information.

Use of Post-operative Non-Steroidal Anti-inflammatory Drugs (NSAIDs)
Consider prophylaxis with a PPI for patients commenced on NSAIDs for post-operative pain relief, especially in those that have increased risk factors for gastrointestinal ulceration. Use the lowest possible dose. Discontinue PPI as soon as patient stops NSAID treatment.

H2RAs are an alternative in those patients where PPIs are unsuitable (see Histamine H2-Receptor Antagonists (H2RAs) monograph).


  Interaction(s) with Common Anaesthetic Agents


Benzodiazepines

Increased benzodiazepine effects have been seen after omeprazole has been given with certain benzodiazepines (diazepam, flurazepam, lorazepam)3, 4. Diazepam exposure is slightly increased by esomeprazole3. The clinical significance is unclear, but should be borne in mind should any benzodiazepine adverse effects (drowsiness, sedation, ataxia) occur: consider reducing the benzodiazepine dose if necessary3.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Antimicrobials

Glossitis, stomatitis and black tongue have, very rarely been seen in patients given lansoprazole and certain antimicrobials (amoxicillin, clarithromycin and metronidazole) as part of triple therapy regimens for H. pylori3, 4. Given the wide use of H. pylori regimens containing these drugs it seems unlikely that the interaction is common3.

Whilst single surgical prophylactic doses should not pose a problem, if a prolonged course of antimicrobials is required post-operatively in patients on regular, long-term PPIs, bear in mind the increased risk of Clostridium difficile infection (CDI) in patients taking PPIs (see Further Information).

Hypomagnesaemia
Proton pump inhibitors can cause hypomagnesaemia, which might be additive with the magnesium-lowering effects of aminoglycosides (e.g. gentamicin)3, 4. The risk is highest with those who have been on long-term PPI therapy (usually > 1 year)3, 4. The MHRA have advised that consideration should be given to monitoring magnesium levels3. In patients who develop hypomagnesaemia, oral and parenteral magnesium supplements might not be as effective as anticipated – stopping the PPI, where possible, might be necessary3.


  Further Information


Long-Term use of PPIs

A PPI should be prescribed for appropriate indications at the lowest effective dose for the shortest period; the need for long-term treatment should be reviewed periodically1, 2. Long-term complications of PPI use include electrolyte disturbances (especially hypomagnesaemia), increased risk of fractures and gastro-intestinal infections (including CDI)1 – see below.

Clostridium difficile Infection (CDI)

The risk of CDI for patients taking PPIs is increased in hospitalised patients receiving antibiotics. Public Health England guidelines for managing and treating CDI recommend that consideration be given to stopping or reviewing the need for PPIs in patients with, or at high risk of, CDI5.

PPIs vs. Histamine H2- Receptor Antagonists (H2RAs)

Superiority of either class of acid-suppressing medication given perioperatively to reduce the risk of aspiration has not been definitely proven, although the majority of evidence supports the pre-operative administration of H2RAs in most patients, with PPI therapy being reserved for patients on chronic acid suppression who may have developed some degree of tolerance to such chronic acid suppression6, 7. Also see Histamine H2-Receptor Antagonists (H2RAs) monograph.

 

  References


  1. NICE Clinical Guideline [CG184]. Gastro-oesophageal reflux disease and dyspepsia in adults: investigation and management. www.nice.org.uk. Accessed 22nd June 2019, last updated November 2014
  2. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 22nd June 2019]
  3. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 22nd June 2019]
  4. Omeprazole. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com  [Accessed 22nd June 2019]
  5. UK Medicines Information (UKMi) Medicines Q&As. Clostridium difficile infection – is use of proton pump inhibitors a risk factor? www.sps.nhs.uk [Accessed on 27th June 2019]. Date updated: November 2015
  6. Medscape. Acid Suppression in the Perioperative Setting: Acid-Related Pulmonary Complications. www.medscape.org [Accessed 22nd June 2019]
  7. Aspiration syndromes (Gastrointestinal Drugs – Management of Gastrointestinal Disorders). In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com  [Accessed 22nd June 2019]