Issues for surgery
As antiplatelet
For prevention of cardiovascular events – risk of major adverse cardiovascular events (MACE) if omitted.
Risk of bleeding and / or complications of bleeding if continued.
For analgesia
Loss of pain control if omitted.
For gout, inflammatory conditions, migraine, menorrhagia – loss of symptom control if omitted, which may impede post-operative recovery.
Risk of bleeding and / or complications of bleeding if continued.
Advice in the perioperative period
Elective surgery
Check blood pressure (BP) and renal function pre-operatively.
As antiplatelet
Cardiac surgery
Multi-disciplinary team to evaluate if benefit outweighs risk of bleeding and decide if aspirin should be continued or stopped pre-operatively.
Non-cardiac surgery
- High dose (>150mg): Consider reducing to low dose for 7 days pre-operatively (bleeding risk is lower with 75mg-150mg doses and antithrombotic impact is comparable to higher doses).
- Low dose (≤150mg): Continue.
Except:
- procedures associated with high risk of bleeding or complications of bleeding (e.g. spinal surgery, some ophthalmological and neurosurgical procedures)
- individuals who refuse blood transfusion for religious reasons (e.g. Jehovah’s Witness)
In these circumstances consideration should be given to stopping 7 days pre-operatively.
For analgesia
Consider stopping 7 days pre-operatively, especially for high-bleeding risk procedures (see under As antiplatelet above), and using alternative analgesia to minimise the risk of bleeding (including combination products).
Analgesic aspirin combination products:
(Note: there are many different over-the-counter [OTC] analgesic preparations that contain aspirin together with other medicines):
- paracetamol + aspirin + caffeine (e.g Anadin® Extra)
- aspirin + caffeine (e.g. Beechams® Powders)
- aspirin + codeine (e.g. Codis® 500)
- Migramax® (contains aspirin + metoclopramide)
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.
Patient undergoing surgery associated with unacceptably high risk of bleeding
Consider withholding aspirin and delaying surgery for 3 days to allow partial restoration of platelet function (see Further information)
If this is not possible consider platelet transfusion to indirectly reverse the effects of aspirin by increasing the total circulating pool of platelets.
Perioperative considerations
Neuraxial (spinal/epidural) anaesthesia or lumbar puncture
Aspirin, when given in isolation, does not increase the risk of spinal epidural haematoma and is not a contraindication to neuraxial anaesthesia.
However, concomitant use of low molecular weight heparin (LMWH) may have an additive bleeding risk, therefore pre-operative thromboprophylaxis should be prescribed with caution in patients taking aspirin, particularly at analgesic doses, who are likely to receive neuraxial anaesthesia.
Post-operative advice
As antiplatelet
If stopped pre-operatively, restart as soon as possible post-operatively once haemostasis secure.
For analgesia
Avoid using aspirin as an analgesic in the post-operative period.
Interactions with common anaesthetic agents
Thiopental
The anaesthetic dose of thiopental is reduced and its effects prolonged in patients who have been pre-treated with aspirin (at analgesic dose).
Interactions with other common medicines used in the perioperative period
Non-steroidal anti-inflammatory drugs (NSAIDs)
Ideally multiple NSAID use should be avoided, particularly if aspirin is being used at analgesic doses. Short term NSAID use with aspirin at antiplatelet dose may be appropriate.
NSAIDs may have an additive effect on the risk of bleeding (including gastrointestinal bleeding) when given with aspirin; consider gastroprotection if other risk factors for gastrointestinal bleeding are present.
Concomitant administration of standard NSAIDs, which are non-selective reversible cyclooxygenase (COX)-1 inhibitors (e.g. naproxen, ibuprofen), may lead to impaired efficacy of aspirin through competition for binding sites. The Commission on Human Medicines advises there may be a small increased risk of thrombotic events with non-selective NSAIDs, particularly when used at high doses and for long-term treatment.
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.
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
- daptomycin (see Antimicrobials below)
- trimethoprim
- vancomycin
Hyperkalaemia and hyponatraemia
Concomitant use of aspirin with the following medications can increase the risk of hyperkalaemia:
- LMWH / UFH
- trimethoprim (see Nephrotoxicity above)
Concomitant use of aspirin 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).
Metoclopramide
Metoclopramide can be used to increase the rate of absorption, and may possibly speed up the onset of analgesic effect.
Low Molecular Weight Heparin (LMWH) / Unfractionated Heparin (UFH)
LMWHs and UFH are predicted to increase the risk of bleeding events when given with aspirin; manufacturer advises use with caution.
Further information
Mode of action
Aspirin exerts its antiplatelet effect by inhibiting cyclo-oxygenase (COX) thus preventing prostaglandin-mediated production of thromboxane A2, which is responsible for platelet activation and aggregation. The irreversible inhibition of cyclo-oxygenase means the pharmacological effects persist until platelets are regenerated. After discontinuation of aspirin intake platelet function can be expected to increase by 10-15% a day as a result of new platelet formation. Within 3-4 days more than 30% of irreversibly inhibited platelets will be replaced; in patients with a normal platelet count this is usually sufficient to return haemostasis to normal.
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.
Aspirin irreversibly affects COX-1, leading to inhibition of platelet aggregation and vasoconstriction for the entire life cycle of the platelet.
Renal toxicity
Adequate fluid intake should be ensured during treatment with aspirin to prevent dehydration and possible associated increased renal toxicity. Caution should be taken when initiating treatment with aspirin in patients with considerable dehydration.
Hypertension
Due to inhibition of prostaglandin synthesis, aspirin (at analgesic doses) can cause fluid retention, oedema, and hypertension. BP should be routinely monitored with all other NSAIDs.
Risk of major adverse cardiovascular events (MACE)
Non-adherence or withdrawal of aspirin in non-surgical patients is associated with a three-fold increase in MACE; this rises to an 89-fold increased incidence in patients with coronary artery stents. This increased incidence is thought to be due to rebound increases in thromboxane A2 activity leading to increased platelet aggregation. Patients with diabetes, acute coronary syndrome or undergoing cardiac surgery are associated with high platelet reactivity. The time between aspirin withdrawal and adverse event was found to be 8.5 days for acute coronary syndrome and 14.3 days for cerebrovascular events. It is possible that the risk of discontinuation is further increased in the perioperative period as surgery promotes an inflammatory state that increases platelet reactivity.
Risk of bleeding
Pre-operative aspirin continuation increases the baseline rate of bleeding by fifty percent in a large meta-analysis of pooled data from several underpowered studies. However, whilst the prevalence of bleeding was higher in patients who continued aspirin the severity of bleeding and bleeding associated mortality was not increased, apart from in a study of patients undergoing transurethral resection of the prostate (TURP). With recent changes in surgical technique, and the use of isotonic saline rather than glycine irrigation, bleeding complications from TURP may now be lower than in 2005 when this meta-analysis was conducted.
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