Issues for surgery
Loss of pain control if omitted.
For gout and inflammatory conditions – loss of symptom control if omitted, which may impede post-operative recovery.
Increased risk of bleeding if continued.
Advice in the perioperative period
Elective surgery
Check blood pressure (BP) and renal function pre-operatively.
Low bleeding risk procedures
Continue.
High bleeding risk procedures
The risk benefit of stopping sulindac pre-operatively should be considered, weighing up potential loss of pain control versus risk of bleeding. It may be beneficial to continue sulindac use until the day of surgery, ensuring that the Surgeon and Anaesthetist are aware of continued use.
If the decision is made to stop sulindac pre-operatively, the optimal time for cessation is to stop 4 days before surgery. Consider switching to a short-acting NSAID (e.g. ibuprofen) if pain / symptom control is a concern. See Further Information.
Emergency surgery
For high-risk bleeding procedure: If there is insufficient time to follow the advice above be aware of the potential for increased bleeding if patient has taken doses in the days leading up to surgery.
Perioperative considerations
Neuraxial anaesthesia (see Further Information): Although sulindac can affect platelet function, there is no increased risk of epidural haematoma and therefore there are no contraindications to patients having either regional anaesthesia or neuraxial blockade.
Post-operative advice
NSAIDs are a valuable option for post-operative pain relief in patients for whom their use is not contraindicated. They may be useful alternatives or adjuncts to opioids; however, in surgery with high risk of bleeding or where bleeding can result in catastrophic outcome, such as ophthalmic or neurosurgery, the decision to prescribe NSAIDs should be made on a case-by-case basis. Furthermore, NSAIDs may be associated with increased risk of gastrointestinal (GI) anastomotic leak and caution is recommended when using NSAIDs after GI surgery.
An intravenous NSAID should not be used to manage immediate post-operative pain (including pain after dental surgery) unless the patient cannot take oral medicines.
Monitor renal function – there is an increased risk of acute kidney injury (AKI) in patients with use of NSAIDs after surgery (especially in patients undergoing emergency surgery or intraperitoneal surgery).
NSAIDs may mask fever and other signs of inflammation or infection - close monitoring for post-operative infection is advised.
NSAIDs should be prescribed at the lowest effective dose and for the shortest duration possible to minimise adverse effects, particularly in those at increased risk of serious adverse reactions (e.g. elderly, impaired renal, cardiovascular or hepatic function). If the surgery has addressed the cause of the pain, NSAID analgesia should be weaned post-operatively with a view to stopping completely.
Interactions with common anaesthetic agents
None relevant.
Interactions with other common medicines used in the perioperative period
Multiple NSAID use
Multiple NSAID use should be avoided.
Ketorolac is an NSAID that is often used as an adjunctive pain relief perioperatively; hence there is an increased risk of NSAID related adverse effects if ketorolac is used concomitantly with another NSAID.
Bleeding risk
Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and oral anticoagulants (warfarin, direct oral anticoagulants [DOACs]) are predicted to increase the risk of bleeding events when given with NSAIDs (see also Hyperkalaemia and Hyponatraemia below).
Gastrointestinal ulceration and bleeding
Corticosteroids may increase the incidence and/or severity of ulceration associated with NSAIDs, and increases the possibility of gastrointestinal bleeding.
Caution with concomitant use and consider the use of gastroprotection such as histamine-2 receptor antagonist or proton pump inhibitor. This interaction is unlikely to be an issue where corticosteroids are used as single doses to reduce post-operative nausea and vomiting or as cover for patients at risk of adrenal insufficiency.
Nephrotoxicity
There is an increase in the risk of nephrotoxicity if NSAIDs are used concurrently with the following antimicrobials:
- aminoglycosides (e.g. gentamicin) (see Antimicrobials below)
- cephalosporins
- co-trimoxazole (see Antimicrobials below)
- daptomycin (see Antimicrobials below)
- trimethoprim
- vancomycin
Hyperkalaemia and hyponatraemia
Concomitant use of NSAIDs with the following medications can increase the risk of hyperkalaemia:
- co-trimoxazole (see Nephrotoxicity above)
- LMWH / UFH
- trimethoprim (see Nephrotoxicity above)
Concomitant use of NSAIDs and trimethoprim can increase the risk of hyponatraemia.
Antimicrobials
NSAIDs potentially increase the risk of seizures when given with quinolones (e.g. ciprofloxacin). Seizures are rare, so in most patients concurrent use should be without problem. Avoid concurrent use or monitor closely those patients with epilepsy or who are predisposed to seizures; however, due to the increased risk of seizure associated with quinolones, they are generally avoided in those who are predisposed to seizures.
NSAIDs may reduce excretion of aminoglycosides (e.g. gentamicin) which may lead to accumulation and increased risk of adverse effects (see Nephrotoxicity above).
NSAIDs may reduce excretion of daptomycin – monitor the patient for possible daptomycin adverse effects.
NSAIDs are highly protein bound, hence concomitant administration with other highly protein-bound drugs such as sulphonamide antibiotics (e.g. co-trimoxazole) should be done with caution and overdose symptoms carefully monitored (see Hyperkalaemia and Hyponatraemia above).
Further information
COX-1 vs. COX-2 inhibition and bleeding risk
The COX enzymes are responsible for the production of prostaglandins. There are two types of COX enzymes: COX-1 and COX-2. Both enzymes produce prostaglandins that promote inflammation, pain and fever; however, only COX-1 produces prostaglandins that activate platelets and protect stomach and intestinal lining.
Standard NSAIDs (e.g. ibuprofen) reversibly inhibit the COX enzyme. NSAIDs vary in their selectivity for inhibiting COX-1 and COX-2 and thus their effects on platelet activity. Due to their reversible action, the bleeding risk is reduced on cessation of therapy (see Evidence base for discontinuing NSAIDs pre-operatively).
Evidence base for discontinuing NSAIDs pre-operatively
Recommendations on when to stop NSAIDs pre-operatively can sometimes be without the appropriate evidence-base. Discontinuation of NSAIDs should be based on the pharmacokinetics of the drug, COX selectively, patient factors (i.e. renal/hepatic function, pain level and tolerability) and the overall bleeding risk associated with the surgery. Sulindac is a long-acting NSAID with a half-life of approx. 16-18 hours; if sulindac is to be stopped pre-operatively, the recommendation is to stop five half-lives before the procedure (i.e. approx. 4 days). Consideration should be given to switching to a short-acting NSAID pre-operatively if necessary and following the advice above. In general, levels of active drug reach an acceptably low level within 5 half-lives of stopping therapy.
Renal toxicity
Adequate fluid intake should be ensured during treatment with NSAIDs to prevent dehydration and possible associated increased renal toxicity. Caution should be taken when initiating treatment with NSAIDs in patients with considerable dehydration.
Hypertension
Due to inhibition of prostaglandin synthesis, NSAIDs can cause fluid retention, oedema, and hypertension. BP should be routinely monitored.
Regional anaesthesia
NSAIDs, when used alone, are not a contraindication to regional anaesthesia. However, consideration should be given to patients receiving other agents, which may increase the risk of bleeding (e.g. LMWH, aspirin), if regional anaesthesia is planned.
References
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 10th October 2021]
Davies G and Checketts MR. Regional anaesthesia and antithrombotic drugs. Continuing Education in Anesthesia, Critical Care & Pain 2012; 12(1):11-16
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 9th October 2021]
National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management. Clinical guideline 148. Accessed via www.nice.org.uk 01/08/2021. Published: 18 December 2019.
National Institute for Health and Care Excellence. Clinical Knowledge Summaries. NSAIDs – prescribing issues. Accessed via www.cks.nice.org.uk 01/08/2021. Last revised August 2018
National Institute for Health and Care Excellence. Perioperative care in adults. NICE guideline 180. Accessed via www.nice.org.uk 02/07/2021. Published: 19th August 2020
Nonsteroidal Anti-inflammatory Drugs. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 9th October 2021]
Summary of Product Characteristics – Sulindac® (sulindac) 200mg Tablets. Mylan. Accessed via www.medicines.org.uk 10/10/2021 [date of revision of the text September 2014]
Summary of Product Characteristics – Warfarin 0.5mg Tablets. ADVANZ Pharma. Accessed via www.medicines.org.uk 20/06/2021 [date of revision of the text 11th April 2018]
Summary of Product Characteristics – Xarelto® (rivaroxaban) 10mg film-coated tablets. Bayer plc. Accessed via www.medicines.org.uk 20/06/2021 [date of revision of the text January 2021]
The Association of Anaesthetists of Great Britain & Ireland, The Obstetric Anaesthetists’ Association and Regional Anaesthesia UK. Regional Anaesthesia and Patients with Abnormalities of Coagulation. Anaesthesia. 2013; 68:966 – 72
Younan M, Atkinson TJ, Fudin J. A Practical Approach to Discontinuing NSAID Therapy prior to a Procedure. Volume 13, Issue 10. November/December 2013. Available at www.PracticalPainManagement.com [Accessed 9th October 2021]