This content was published in 2012. We do not recommend that you make any clinical decisions based on this information without first ensuring you have checked the latest guidance.
The role of the pre-operative assessment pharmacy team is, first and foremost, to obtain an accurate medication and allergy history for the patient. From the medication history, it may be necessary to advise on stopping or altering medication before an operation to ensure that the patient can safely undergo anaesthesia and the procedure itself.
Although some medicines should be stopped it is important that others are continued. Examples of those that should be continued include anti-Parkinsonian drugs and beta-blockers, the former because omission may reduce mobility and impede recovery,1,2 and the latter because they may help suppress the tachycardia and increased blood pressure provoked by anaesthesia and surgery.3 Our pharmacy team has developed guidelines based on available papers, summaries of product characteristics, other guidelines, journal articles and consultant anaesthetist and surgeon guidance. These have been used successfully for over four years.
Consideration needs to be given to the pharmacology of agents as well as patient and operation specific factors (eg, surgery grading; grade 1 is minor and grade 4 major complex surgery) when determining whether medication should be stopped or continued. Panel 1 gives some examples.
| Panel 1: Medicines that may need to be stopped|
Cytokine modulators Cytokine modulators could increase risk of infection and delay wound healing.1,4,5 Consider stopping two to four weeks before surgery depending on risk (higher risk includes grade 3+ surgery and patients with diabetes). Consult a rheumatologist if necessary.
Lithium Electrolyte disturbances and reduced renal function can precipitate lithium toxicity.1,2,6,7 In grade 1 or 2 surgery, the drug can be continued with close monitoring of urea and electrolytes. In grade 3 or 4 surgery, it should be omitted 24 hours before the procedure.
Antipsychotics Antipsychotics can potentiate arrhythmias and enhance hypotension due to a1 receptor blockade.2,8 They may be continued but for clozapine, the decision is influenced by the brand. Zaponex can be continued (although there is no information in the SPC) but Clozaril should be discontinued 12 hours before surgery where possible as per the Clozaril Patient Monitoring Service guidance. Where stopped, clozapine should be restarted within 48 hours, at normal dose.
Tracheal intubation and surgical incision can increase heart rate and blood pressure so it is important to continue most cardiac drugs such as anti-anginals and antihypertensives. However, drugs that affect the renin-angiotensin-aldosterone-system (RAAS) are an exception. General anaesthetics cause vasodilation and drugs such as angiotensin-converting enzyme inhibitors can exacerbate the resulting hypotension.9–12 This is more of a problem in major surgery (these patients are more likely to experience fluid losses) and in patients with an epidural in situ because this also causes vasodilation. Panel 2 gives examples of drugs that are stopped.
|Panel 2: Examples of medicines that should be stopped|
Antihypertensives (renin-angiotensin-aldosterone system) Intractable hypotension can develop under anaesthesia, particularly with hypovolaemia and concurrent epidural anaesthesia.9–13 Angiotensin-converting enzyme inhibitor, angiotensin-II receptor blocker (ARB) and direct renin inhibitor (ie, aliskiren) doses should be omitted on the morning of the operation, where taken in the morning, or from the evening before the operation if taken in the evening. If taken twice daily, both evening and morning doses should be omitted. In instances where a patient takes both an ACEI and ARB and is to undergo grade 1 or 2 surgery, the ACEI should be omitted as above. Those undergoing grade 3 or 4 surgery should omit both the ACEI and the ARB.
Anticholinesterases Anticholinesterases prolong the action of depolarising neuromuscular blocker agents. Those used to treat dementia (eg, galantamine and rivastigmine) should be stopped the day before surgery. Rivastigmine and galantamine are reversible inhibitors of acetylcholinesterase. Both prolong the effects of suxamethonium and patients would need to be kept anaesthetised for longer — until the paralysis had subsided — before they can be safely woken up and are able to breathe unaided. Rivastigmine also antagonises the effects of non-depolarising muscle relaxants so their muscle relaxant effects are reversed and the patient is difficult to paralyse. Donepezil might enhance the effects of suxamethonium and may antagonise the effects of non-depolarising muscle relaxants. However, it is continued because it would need to be stopped two to three weeks before an operation (due to its long half life) and if the drug is discontinued for three to six weeks patients will not obtain the original level of function that they had with initial treatment when it is restarted. Anticholinesterases used in myasthenia gravis (eg, pyridostigmine and neostigmine) are usually continued to prevent paralysis of the muscles involved in respiration but the anaesthetist should be informed. Sometimes the anaesthetist may request that they are omitted on the day of the procedure.1,2,14 Avoid suxamethonium in these patients.1,2
Antidepressants Hypertensive crisis can occur when monoamine oxidase inhibitors are used with sympathomimetics1–3,6,7,15,16 (eg, noradrenaline). Irreversible MAOIs should be stopped two weeks before an operation but this must be discussed with the anaesthetist and patient’s psychiatrist. It should be noted that recovery of MAOI function with irreversible drugs can take up to three weeks.6,7 Moclobemide, being a reversible MAOI, can be stopped 24 hours before an operation. Its short elimination half-life, means activity returns to normal within 24 hours of stopping.6,7
Herbal remedies Ephedra increases risk of myocardial infarction and stroke from tachycardia and hypertension, echinacea may increase risk of infection and poor wound healing, valerian may increase sedation and garlic can increase bleeding risk.17 The hospital has a list of herbal remedies that we advise patients to stop a week before an operation. This also includes cat’s claw, ginseng, omega fish oils and saw palmetto but we stop any herbal or homoeopathic remedies we are unfamiliar with.
Heparin/low molecular weight heparin The last treatment dose should be given no less than 24 hours before the operation. The last prophylactic dose should be given no less than 12 hours before the operation.
The bleeding risk of surgery depends on the type. For example, major abdominal surgery presents a greater risk than arthroscopy. Any anticoagulant or antiplatelet can increase the risk of bleeding. So, for example, for patients on anticoagulants, we obtain details (indication, dose, international normalised ratio target) and send these to the anticoagulation clinic for advice (which is usually to stop the anticoagulant). Newer oral anticoagulants, such as dabigatran and rivaroxaban, are now available. These are reserved for the post-operative prevention of venous thromboembolism in patients who have undergone a total hip or total knee replacement, but as the indications for these medicines increase, there will be a need to consider them pre-operatively.
When assessing antiplatelet therapy, it is essential to check the indication for therapy and to weigh the risks of stopping (increased cardiovascular risk) against those of continuing (bleeding).18 The pharmacist in the pre-operative clinic checks the patient’s risk factors (ie, coronary stents, myocardial infarction, cerebrovascular accident, transient ischaemic attack, peripheral vascular disease) and considers the type of surgery the patient is to undergo. Operations where we would consider stopping antiplatelet therapy include grade 3 or 4 colorectal surgery, transurethral resection of prostate (TURP) and abdominal aortic aneurysm (AAA) repair.
Aspirin is usually continued unless there is a specific risk of excessive bleeding with a procedure. Patients may still be asked to continue their aspirin if the pre-operative assessment pharmacist identifies a significant cardiovascular risk, for example, coronary artery stent or substantial cardiac history (eg, recent or multiple myocardial infarction or stroke). It is generally considered safe to stop aspirin where it is used for primary prevention. When aspirin is stopped, this should be done seven days before a procedure to allow for new platelets to generate.19,20
Where considered safe, clopidogrel, when used as a single agent, should, ideally, be stopped seven days before an operation where there is potential for the patient to have an epidural or spinal anaesthesia.2 This is because of a possibility of increased risk of haematoma, which could compress the spinal cord. Clopidogrel also presents the same bleeding risk as aspirin for some procedures. For patients who are not allergic to aspirin, it may be possible to switch to aspirin 75mg daily for seven days. This can be considered where the pharmacist has identified a specific cardiovascular risk. The anaesthetist is involved if antiplatelet protection is deemed necessary but the patient is unable to take aspirin.
Dual antiplatelet therapy
Aspirin and clopidogrel are co-prescribed following acute coronary syndromes (ACS) and following percutaneous coronary intervention involving stent insertion. Patients who have ACS should continue the combination for one year, after which the clopidogrel can be stopped and the aspirin continued. Dual antiplatelet therapy should be continued for a minimum of three months after insertion of a bare metal stent and for a minimum of 12 months following insertion of a drug-eluting stent.21
Patients with a coronary stent present our greatest challenge. As for ACS we would always try to delay surgery until it was safe to stop the clopidogrel. However, it may not always be feasible to delay surgery (eg, urgent cancer cases). In these cases the pharmacist discusses the best plan of action with a consultant anaesthetist and the patient’s consultant surgeon. Aspirin is continued but the clopidogrel is stopped five days pre-operatively and tirofiban (short-acting) is used as a bridging agent in these patients.22,23
At the time of writing, a new antiplatelet agent — prasgurel — has become available. We are treating this as we treat clopidogrel.
Dipyridamole does not alter bleeding times or laboratory platelet aggregation. As a single agent, it can be safely continued but, because it is regularly used with other antiplatelet agents, surgeons and anaesthetists are concerned about possible additive effects. When other antiplatelet agents are continued pre-operatively, dipyridamole is stopped 24 hours pre-operatively.18,24
Neuromuscular blocking agents used for anaesthesia work by interfering with acetylcholine (ACh) at the neuromuscular junction. Neuromuscular blockade results in muscle relaxation and short-term paralysis.
ACh is normally broken down by cholinesterase enzyme. Patients on anticholinesterases can present a problem because these medicines reduce the effect of depolarising neuromuscular blockers (eg, suxamethonium) by increasing levels of ACh at the neuromuscular junction (due to reduced enzymatic breakdown). The increased ACh competes with the suxamethonium. At the same time the duration of action of suxamethonium is prolonged because it is also normally broken down by cholinesterase.
Non-depolarising neuromuscular blocking agents, such as atracurium, act by competitively blocking the binding of ACh at receptor sites, prolonging depolarisation and so causing blockade. Anticholinesterases antagonise the effect of these drugs; they increase the level of ACh at the neuromuscular junction and so increase competition for receptor sites. If it is possible, the use of anticholinesterases should be avoided peri-operatively (see Panel 2).
Patients with acid reflux
Patients who have acid reflux are at risk of acid aspiration under general anaesthesia. Proton pump inhibitors or H2 antagonists help to increase gastric pH and lower gastric acid volume, and reduce the risk of acid aspiration so they should be continued.25,26
Patients with diabetes
Under anaesthesia, the signs and symptoms of hypoglycaemia are masked and this can lead to fatal brain damage.27,28 Patients with diabetes are advised on pre-operative medication changes in order to avoid hypoglycaemia. The hospital has a guideline for managing these patients but the pharmacy team is currently reviewing this in line with the recent NHS document “Management of adults with diabetes undergoing surgery and elective procedures: improving standards.” This document, released in April 2011, should have prompted hospitals to review their protocols for patients with diabetes.
Guidelines in use
Ensuring that medication is dealt with appropriately pre-operatively is a pivotal part of the role of the pharmacy team. Our pre-operative medication guidelines have evolved as new evidence and new drugs become available. In the future, they will be available on the trust intranet so other healthcare professionals can access them outside the pre-operative assessment clinic.
Wrexham Maelor Hospital’s pre-operative assessment unit has trained technicians who are able to give certain medication advice. The technicians follow specific referral criteria that direct them to refer the patient to the pharmacist for advice when it is necessary.
Thanks to Neil Agnew, consultant anaesthetist, Wrexham Maelor Hospital.
- British National Formulary March 2011. BMJ Group and Pharmaceutical Press, 2011.
- www.medicines.org.uk. The electronic medicines compendium. <Accessed between August 2006 – January 2011>
- Weisbauer F et al. Perioperative beta-blockers for preventing surgery related mortality and morbidity (Protocol). The Cochrane Collaboration. The Cochrane Library 2008, Issue 3.
- British Society for Rheumatology/British Health Professionals in Rheumatology. BSR/BHPR guideline for disease-modifying anti-rheumatic drug (DMARD) therapy in consultation with the British Association of Dermatologists. Rheumatology. April 2008.
- Royal College of Nursing. Assessing, managing and monitoring biologic therapies for inflammatory arthritis: Guidelines for rheumatology practitioners. April 2003.
- Rahman M, Beattie J. Medication in the pre-operative period. The Pharmaceutical Journal 2004;272:287–9.
- Drugs in the peri-operative period. 1 – Stopping or continuing drugs around surgery. DTB 1999;37(9):62–4.
- Clozapine Monitoring Service correspondence. August 2003
- Raja SG, Fida N. Should angiotensin converting enzyme inhibitors/angiotensin II receptor antagonists be omitted before cardiac surgery to avoid postoperative vasodilation? Interactive CardioVascular and Thoracic Surgery, 2008;7:470-6.
- Comfere T et al. Angiotensin System Inhibitors in a General Surgical Population. Anesth Analg 2005;100:636–44.
- Brabant SM et al. The Hemodynamic Effects of Anesthetic Induction in Vascular Surgical Patients Chronically Treated with Angiotensin II Receptor Antagonists. Anesth Analg 1999;88:1388–9.
- Bertrand M et al. Should the Angiotensin II Antagonists be Discontinued Before Surgery? Anesth Analg 2001;92:26–3.
- Rahman MH, Beattie J. Peri-operative medication in patients with cardiovascular disease. The Pharmaceutical Journal 2004;272:352– 4.
- Novartis Medical Information Officer. Email correspondence – Exelon (rivastigmine) patches in patients scheduled for surgery. 23rd March 2011.
- Luck JF et al. Monoamine Oxidase Inhibitors and Anaesthesia. The Royal College of Anaesthetists 2003;Bulletin 21:1029–34.
- Taylor D, Paton C, Kerwin R. The Maudsley Guidelines Prescribing Guidelines. 9th Edition. The South London and Maudsley NHS Foundation Trust and Oxleas NHS Foundation Trust, 2007.
- Ang-Lee, Moss J, Yuan C. Herbal Medicines and Perioperative Care. JAMA 2001;286(2):208–1.
- Chassot PG, Delabays A, Spahn DR. Perioperative antiplatelet therapy: the case for continuing therapy in patients at risk of myocardial infarction. Br J Anaesth 2007;99(3):316–28.
- Rahman MH, Beattie J. Per-operative medication in patients with cardiovascular disease. The Pharmaceutical Journal 2004;272:352–4.
- Drugs in the peri-operative period. 4 – Cardiovascular drugs. DTB 1999;37(12):89–92.
- AHA/ACC/SCAI/ACS/ADA Science Advisory. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. Circulation 2007;11.
- Broad L et al. Case Report. Successful management of patients with a drug-eluting coronary stent presenting for elective, non-cardiac surgery. Br J Anaesth 2007;98:19–22.
- Savonitto S et al. Urgent surgery in patients with a recently implanted coronary drug-eluting stent: a phase II study of ‘bridging’ antiplatelet therapy with Tirofiban during temporary withdrawal of clopidogrel. Br J Anaesth 2010;104(3):285–91.
- Boehringer Ingelheim. Correspondence via fax. Asasantin/Persantin Retard – Surgery. 26th November 2007.
- Ng A, Smith G. Gastroesophageal reflux and aspiration of gastric contents in anesthetic practice. Anesth Analg 2001; 93: 494-513.
- Clark K, Lam L, Gibson S, Currow D. The effect of ranitidine versus proton pump inhibitors on gastric secretions: a meta-analysis of randomised control trials. Anaesthesia 2009; 64: 652-7.
- Rahman MH, Beattie J. Peri-operative care and diabetes. The Pharmaceutical Journal 2004;272:323–5.
- Drugs in the peri-operative period: 2 – Corticosteroids and therapy for diabetes mellitus. DTB 1999;37(9):68–70.