Systemic absorption can follow topical application of beta-blockers to the eyes – the advice and cautions as listed within this monograph should still be considered for patients using ocular products containing Timolol.
Issues for surgery
For hypertension – loss of blood pressure (BP) control if omitted.
For arrhythmias – risk of cardiac arrhythmias if omitted.
For ischaemia heart disease (IHD) – rebound worsening of myocardial ischaemia if stopped abruptly.
For prophylaxis of migraine – risk of migraine precipitation if omitted.
For primary open-angle glaucoma (topical) – increased risk of deterioration in eyesight if omitted for a prolonged period.
Risk of rebound tachycardia and hypertension if stopped abruptly.
Risk of bradycardia and hypotension if continued.
Advice in the perioperative period
Elective surgery
Continue (including combination products – see below).
Check BP and heart rate pre-operatively.
The manufacturers of beta-blockers advise ensuring anaesthetist is aware of use of beta-blockers, but this does not need to be done in advance of the day of surgery.
Oral combination products:
- timolol + amiloride + hydrochlorothiazide (also see Amiloride drug monograph)
- timolol + bendroflumethiazide (also see Bendroflumethiazide drug monograph)
Ocular combination products:
- timolol + bimatoprost (also see Bimatoprost drug monograph)
- timolol + brimonidine (also see Brimonidine drug monograph)
- timolol + brinzolamide (also see Brinzolamide drug monograph)
- timolol + dorzolamide (also see Dorzolamide drug monograph)
- timolol + latanoprost (also see Latanoprost drug monograph)
If necessary, consideration should be given to prescribing the components of oral combination products as separate medicines perioperatively. However, some components of combination products do not exist as individual medicines (e.g. hydrochlorothiazide). If there is any doubt about the need to continue or withhold component agents of a combination product, advice should be sought from an anaesthetist.
Consideration of pre-operative omission
See also Further information.
If it is deemed strictly necessary to withdraw oral beta-blocker therapy before surgery please consult product literature for time to stop pre-operatively. In general, beta-blockers should be withdrawn at least 24 hours prior to anaesthesia, sometimes longer. However, where possible, sudden withdrawal should be avoided, especially in patients with IHD as it may result in increased angina; gradual withdrawal should take place over 1-2 weeks. If necessary initiation of replacement therapy to prevent exacerbation of angina pectoris should be considered if the decision is made to stop beta-blocker therapy pre-operatively.
Emergency surgery
Continue (including combination products as above).
The manufacturers of beta-blockers advise ensuring anaesthetist is aware of use of beta-blockers, but this does not need to be done in advance of the day of surgery.
Pre-operative initiation of beta-blockers for patients undergoing non-cardiac surgery
For patients not already on a beta-blocker as part of their regular therapy:
Pre-operative initiation may be considered in patients who are considered high risk for perioperative complications (e.g. undergoing vascular surgery, known IHD or myocardial ischaemia) – for more details see European Society of Cardiology / European Society of Anaesthesiology guidelines on non-cardiac surgery: cardiovascular assessment and management.
Atenolol or bisoprolol are the first choice agents in patients undergoing non-cardiac surgery, and the dose should be slowly up titrated, well before the procedure; and tailored to appropriate heart rate and blood pressure targets.
Post-operative advice
Ophthalmic preparations
Beta-blocker eye drops should be re-commenced when the next dose is due in the post-operative period unless the patient has undergone ophthalmology surgery and the Ophthalmologist requests for them to be withheld.
Oral preparations
For patients who were taking beta-blockers as part of their regular therapy prior to surgery, treatment should be recommenced post-operatively.
For patients commenced on pre-operative beta-blockade due to risk factors (see Pre-operative initiation of beta-blockers above), continue treatment post-operatively. The optimal duration of treatment is not clear. There is potential for delayed cardiac events indicating continuation of therapy may be required for several months. If the patient tested positive for pre-operative stress, beta-blockers should be continued long-term.
Monitor BP and Heart Rate (see Further information).
Interactions with common anaesthetic agents
Anaesthesia in the presence of beta-blockers normally appears to be safer than withdrawal of the beta-blocker before anaesthesia. See Further information.
Bradycardia
See also (see also Sympathomimetics and Local anaesthetics below).
Beta-blockers can increase the risk of bradycardia when used concomitantly with the following:
- alfentanil, fentanyl or remifentanil
- cisatracurium
- neostigmine
Hypotension
Beta-blockers can increase the risk of hypotension when used concomitantly with inhalational or intravenous anaesthetics.
If hypotension occurs, bear in mind the response to antimuscarinic drugs (e.g. glycopyrrolate and atropine) may be reduced.
Sympathomimetics
The interactions between beta-blockers and sympathomimetics (e.g. adrenaline / epinephrine) are complex and depend on the selectivity of both drugs. Concomitant use may lead to an increase in BP, due to alpha-mediated vasoconstriction, and reflex bradycardia. They have been reports of marked and serious BP rises and severe bradycardia occurring in some patients. The same interaction could possibly occur with noradrenaline / norepinephrine (although there does not seem to be any case reports to support this theory).
Lidocaine
Studies have found that some beta-blockers increase the levels of lidocaine (reduced clearance), but the evidence is conflicting. There is no evidence to confirm this is a problem with timolol.
Concurrent use of beta-blockers with lidocaine may increase the risk of myocardial depression (e.g. bradycardia).
Interactions with other common medicines used in the perioperative period.
Hypotension
Beta-blockers can increase the risk of hypotension when used concomitantly with antiemetics droperidol and prochlorperazine.
Corticosteroids
Corticosteroids can decrease the antihypertensive effect of beta-blockers due to water and sodium retention.
These interactions are 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. However, bear the interaction in mind should continued corticosteroid treatment be necessary.
Further information
Perioperative use of beta-blockers
Perioperative use of beta-blockers is controversial. There is some evidence that continuing or starting beta-blockers perioperatively may be of benefit in patients at risk of cardiovascular events. The main rationale for perioperative beta-blocker use is attenuation of the stress response. In patients undergoing general anaesthesia beta-blockers reduce the risk of myocardial ischaemia and arrhythmias (reduction in heart rate and decreased myocardial contractility) during induction and intubation and the post-operative period; however, there is a risk of attenuation of reflex tachycardia and hypotension (due to the reduced ability of the heart to respond to beta-adrenergically mediated sympathomimetic reflex stimuli).
The risk-benefit of stopping beta-blockade should be made for each patient. If treatment is continued, an anaesthetic with little negative inotropic activity should be selected to minimise the risk of myocardial depression.
Current recommendations and evidence base
2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management
Beta-blockers should be continued when prescribed for IHD or arrhythmias. For treatment of hypertension, the absence of evidence for a perioperative cardioprotective effect with other antihypertensive drugs does not support a change in therapy. Beta-blockers should not be withdrawn in patients with stable heart failure due to left ventricular (LV) systolic dysfunction.
If a patient has unstable cardiac disease, non-cardiac surgery should be deferred if possible, so that patients’ medical therapy can be optimised.
Cochrane Review: Perioperative beta-blockers for preventing surgery-related mortality and morbidity
Cardiac Surgery: Perioperative beta-blockers play a pivotal role in cardiac surgery, as they substantially reduce the high burden of supraventricular and ventricular arrhythmias post-operatively. Their influence on mortality, stroke, acute MI, congestive heart failure, hypotension and bradycardia remains unclear.
Non-cardiac Surgery: In non-cardiac surgery, evidence shows an association of beta-blockers with increased all-cause mortality and stroke. As the quality of data is low to moderate, more evidence is needed before a definitive conclusion can be drawn. The substantial reduction in supraventricular arrhythmias and acute MI in this setting seems to be offset by the potential increase in mortality and stroke.
References
Anaesthetics, general + Beta blockers. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 14th September 2019]
Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 14/09/2019]
Beta-Blockers. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 14th September 2019]
Blessberger H, Kammler J, Domanovits H, Schlager O, Wildner Brigitte, Azar D, Schillinger M, Wiesbauer F, Steinwender C. Perioperative beta-blockers for preventing surgery-related mortality and morbidity. Cochrane Systematic Review – Intervention. Published 2018. Available at at www.cochranelibrary.com [Accessed 14th September 2019]
Lidocaine. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 14th September 2019]
Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press http://www.medicinescomplete.com [Accessed 14th September 2019]
Summary of Product Characteristics – Timolol Eye Drops 0.5%. FDC International Ltd. Accessed via www.medicines.org.uk 14/09/2019 [date of revision of the text January 2016]
Sympathomimetics. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 14th September 2019]
The Joint Task Force on non-cardiac surgery: cardiovascular assessment and management of the European Society of Cardiology (ESC) and the European Society of Anaesthesiology (ESA). 2014 ESC/ESA Guidelines on non-cardiac surgery: cardiovascular assessment and management. European Heart Journal. 2014; 35:2383-2431