Perioperative medication management Flashcards
:) How does aspirin work & what are the implications preoperatively?
irreversibly inhibits plt COX so may increase periop blood loss & haemorrhagic complications but may help prevent periop thromboembolic complications
:) What’s the risk of pre-op aspirin withdrawal in CABG patients? what type of studies this from?
increased in-hospital mortality, observational studies
:) What does POISE-2 tell us about periop aspirin & non cardiac surgery? What are the clinical implications of this? What is an issue with pt exclusion for this trial?
aspirin increases bleeding risk but doesn’t improve CV or mortality outcomes, sub-study showed no benefit at reducing AKI risk & no benefit for VTE prevention (but 2/3 of the pts also received VTE prophylaxis & there were low overall VTE rates).
Withold aspirin 7/7 in pts taking it for primary or secondary prevention prior to non-cardiac surgery (however if secondary prevention, discussion btwn cardiologist, neurologist, surgeon & pt) & recommence postop once surgical bleeding risk passed EXCEPT pts undergoing CABG, CEA, popliteal artery aneurysm repair or those who are 6/12 after a BMS or DES or those who are having cataract surgery/minor dental/dermatologic procedures.
Many neurosurgical, where bleeding may be highest risk of severe adverse outcomes, were not enrolled in POISE-2, so optimal strategy for periop aspirin for these pts unknown.
:) What’s the benefit of aspirin for CABG? does dose matter? what can be given to attenuate risk?
A systematic review from the Antiplatelet trialist’s collaboration showed that anti-platelets (esp if given early) are associated with improved graft patency @ an average of 1 year after CABG, similar benefit with low- vs high-dose aspirin. Antacids & PPIs often given preoperatively to attenuate risk.
ACC/AHA 2021: If patients are already taking aspirin, continue up until the time of surgery to reduce ischaemic events (*unless redo OT or bleeding dyscrasias or other risks of sig bleeding). If pt is undergoing elective CABG but not already on aspirin, don’t initiate it <24hrs pre-op (no benefit).
+ What does the ATACAS trial tell us about prep aspirin 1-2 hours prior to CABG (in pts who had newly commenced aspirin or who hadn’t been on it for at least 5 days pre-op)
no difference in death/nonfatal MI/stroke/PE/renal failure or bowel infarct, major haemorrhage & no difference in cardiac tamponade. No sig difference in death or severe disability at 1 year.
Issues included short follow-up (phone call 30 days), half the pts receiving aspirin also had TxA, a large number of pts were eligible but not enrolled, stopped early due to higher event rates than anticipated but the composite end-point included biomarker elevation only- not equivalent in weight against other outcomes
ACC/AHA 2021: further trial showed that if aspirin initiated the night before surgery, incr major bleeding & transfusion rates but no difference in early or late MACE cf placebo.
Therefore, DON’T initiate aspirin for the first time <24hrs prior to CABG.
:) What are the benefits of aspirin after CABG?
mortality benefit
:) How should aspirin be managed perioperatively for CABG?
if already on it, continue pre-op including day of surgery unless v high bleeding risk. Recommence it 6hrs after surg or extubation (whichever first). The deleterious effects of aspirin on post-op bleeding & transfusion requirement can be attenuated by antifibrinolytic therapy.
:) How should aspirin be managed preoperatively for CEA patients? why? does dose matter?
should be started prior to CEA & continued indefinitely, unless contraindications, in both symptomatic & asymptomatic CEA due to reduced stroke risk. Low-dose (81-325mg) aspirin is more effective than high-dose
:) How should aspirin be managed for pts undergoing peripheral artery surgery (including large artery aneurysms)? What is the timing & dosing pre- & postoperative for popliteal artery aneurysms?
All pts should have it (commence if not already on it) as it reduces risk of early stent-graft thrombosis following endovascular repair of popliteal artery aneurysms. For repair popliteal artery aneurysms, should start at least 48hrs before the procedure (325-650mg), if within 48hrs give 650mg loading (unless contraindication). Should have postop DAPT for at least 4/52 if bleeding risk low.
:) How long should pts be on DAPT after DES or BMS?
for ACS, at least 12/12 but may consider discontinuation of aspirin after 1-3 months & discontinuation of P2Y12 @ 6/12 could be considered if high risk bleeding. For SIHD: BMS at least 1/12 DAPT. DES at least 6/12 DAPT but 1-3 months could discontinue aspirin & at 3/12 if high bleeding risk may discontinue P2Y12.
:) What are some surgeries where the risk of major bleeding may outweigh risk of stent thrombosis if urgent surg required within 4-6/52 of BMS or DES placement?
neurosurgery, posterior eye or prostatic
:) For how many days is clopidogrel generally stopped before surgery?
5
:) For how many days is prasugrel generally stopped before surgery?
7
:) For how many days is ticagrelor stopped before surgery?
3-5
:) What is a systems consideration for pts within 6/12 of BMS or DES insertion requiring an antiplatelet to be ceased for non-cardiac surgery?
Perform the surgery @ a centre with 24-hour interventional cardiology coverage
:) For how many days do pts require DAPT after balloon angioplasty without stenting? How common is this?
14 days. <5% of PCIs are performed in this manner.
:) For how many days after balloon angioplasty should urgent surgery ideally be deferred (if can’t wait 14 days)?
48hrs, to confirm stable PCI result
:) Does using aspirin impact on the placement of neuraxial block?
No, but consider impact if combined with other meds impacting coagulation eg. NSAIDs
:) How long should clopidogrel be withheld prior to placing a neuraxial block?
5-7 days
:) What are the 3 types of acute coronary syndromes?
STEMI, NSTEMI & unstable or crescendo angina
:) What is the approach to a patient who requires urgent or emergency surgery but who has known or suspected coronary artery disease (or ACS!), heart failure or severe valvular heart disease?
urgent cardiology consult for suggestions re: monitoring & medication management (& rarely additional cardiovascular testing)
+2021 ACC/AHA coronary revascularisation guidelines:
What are some situations where myocardial revascularisation BEFORE non cardiac surgery may improve perioperative outcomes?
What is the cornerstone of therapy for prevention of thrombotic complications with PCI?
What is clopidogrel?
For pts undergiong urgent CABG, for how long should clopidogrel & ticagrelor be discontinued? and elective?
and CABG?
For how long should DAPT be continued after PCI?
If a pt has AF & undergoas PCI, what should happen with their anticoagulants?
-pts with significant CAD undergiong high-risk surgery have incr incidence periop CV events but routine prophylactic revascularisation does not reduce risk of death or CV events. Studies excluded pts with high-risk anatomy (unprotected L) main, multivessel CAD, solid organ transplant); for such pts, heart team approach for risk:benefit analysis.
If pts are symptomatic with other clinical indications for revascularisation, consider in accordance with recommendations but not solely to reduce periop complications.
-consider if: unstable CAD (ACS) who are candidates for emerg or urgent revasc, significant L) main disease, pts with high-risk features on noninvasive testing (eg. reversible large anterior wall defect, extensive stress-induced wall motion abnormalities).
Downsides to re-vascularisation are the durations of recovery from CABG or duration of DAPT required prior to proceeding with non-cardiac surgery.
Evidence not robust & suggests pts w stable CAD don’t benefit from prophylactic revascularisation before non-cardiac surgery.
DAPT with aspirin & an oral P2Y12 inhibitor (clopidogrel, ticagrelor or prasugrel)
a prodrug with an active thiol metabolite (CYP2C19>CYP2C9) which irreversibly blocks P2Y12 platelet ADP receptor, reducing platelet aggregation
Genetic polymorphisms may –> poor metabolism of prodrug & inadequate effect, increasing CV risk
The half-life of the parent drug is 6 hours, half-life of active thiol metabolite 30mins
The effect on platelets is irreversible, lasting the lifetime of the platelet (7-10 days); platelet aggregation/bleeding time returns to baseline after 5 days.
Compared to the other P2Y12 inhibitors, clopidogrel is the least potent, requiring longer time to plt (-) after a loading dose. Therefore, the more potent ticagrelor or prasugrel (or clopidogrel) should be used for PCI in ACS. For pts with SIHD undergoing PCI, prasugrel & ticagrelor haven’t been studied for long-term clinical outcomes so use aspirin & clopidogrel. Also, for pts who are undergoing PCI immediately after anti-fibrinolytics, use clopidogrel (others not studied). ?older pts having ACS w PCI clopidogrel may be better than potent ones (lower bleeding risk). Prasugrel is contraindicated in pts w previous TIA or CVA, caution advised in pts <60kg or age >=75kg.
24hrs to reduce major bleeding complications (ACC/AHA 2021) (CABG <5 days after discontinuation of clopidogrel ass’d w major bleeding risks- tamponade or re-operation)
Elective: clopidogrel 5 days, ticagrelor 3 days, prasugrel 7 days (reduce major bleed, product transfusion).
For SELECT patients undergoing PCI, shorter-duration DAPT (1-3 months) is reasonable, with subsequent transition to P2Y12 inhibitor monotherapy to reduce risk of bleeding events, without significant difference in MACE (but these trials were not powered to assess differences in stent thrombosis).
After DES for stable IHD, should have at least 6/12 aspirin + clopidogrel BUT may discontinue aspirin & continue clopidogrel monotherapy after 1-3 months. After 3 months if the patient has high risk of bleeding on DAPT, may discontinue P2Y12 (-).
After 6/12 if no high risk bleeding, may continue DAPT up to max 12/12.
After BMS for stable IHD, should have at least 1 month of aspirin + clopidogrel. if no high risk bleeding, may continue DAPT >1 month, up to max 12/12.
After PCI for ACS, @ least 12/12 aspirin + a P2Y12 (-); it may be reasonable to continue for >1yr if no significant bleeding risk, but may consider discontinuation of aspirin @ 1-3 months & proceed with P2Y12(-) monotherapy. If high risk of overt bleeding, discontinuation of P2Y12(-) @ 6/12 may be reasonable.
After CABG, lifelong aspirin. in selected pts, DAPT w aspirin & ticagrelor or clopidogrel for 1 year may be reasonable (different pathophys; to prevent vein graft occlusion).
If a pt with AF on an oral anticoagulant undergoes PCI, discontinue aspirin after 1-4 weeks & maintain P2Y12 inhibitor along with NOAC or warfarin. NOAC may have lowerste bleeding risk than warfarin.
Rates of stent thrombosis with modern DES is similar or lower than BMS; BMS are rarely used, may be considered if: the patient won’t be able to take DAPT for at least 30 days or high risk of bleeding.
:) Should pts undergoing cataract surgery have aspirin withheld?
no since the risks associated with either continuing or discontinuing aspirin are very small
:) What’s dipyridamole & what’s the half-life of it’s MR preparation? Evidence for periop cessation? if decide to, how long?
Has vasodilator (phosphodiesterase and adenosine deaminase inhibitor) & anti-platelet activity, usually used after CVA or TIA, 10 hrs.
No data on safety of continuing dipyridamole perioperatively, consider balance of bleeding & ischemic events, withheld 2 days if decide to- if combo aspirin & dipyridamole, withheld 7-10 days prep.
:) What’s cilostazol & what’s it’s half-life? How long stop preop?
Selective PDE-3 enzyme inhibitor, weaker reversible anti platelet activity than P2Y12 receptor blockers. Used for claudication symptoms. 21hrs. Should stop for at least 3 days (manufacturer says at least 5 days). Claudication symptoms may recur then cease again once the medication recommenced.
:) How do COX-1 (nonselective) & COX-2 selective NSAIDs impact platelets? How long should they be held prior to surgery?
COX-1 inhibitors reduce levels of TxA2 hence reduce platelet aggregation. COX-2 inhibitors don’t impact platelets but have negative cardiovascular effects.
Should withhold NSAIDs at least 3/7 before surgery (platelet function does normalise within 24hrs of ibuprofen, after holding most other NSAIDs platelet function normalises within 3 days).
:) What is bridging anticoagulation & it’s purpose?
The administration of a short-acting anticoagulant, typically LMWH, during the interruption of a longer-acting agent, to minimise the time the patient isn’t anticoagulant, minimising their risk of peri-operative thromboembolism.
:) In which patients is bridging required?
- Those taking warfarin with a mechanical mitral valve or a mechanical aortic valve with additional stroke risk factors.
- Embolic stroke within the previous 3/12 or very high stroke risk (CHADS2-vasc score 7-9)
- VTE within the previous 3/12 (since diagnosis- except if calf DVT with no evidence of calf DVT on repeat US)
- Selected pts who have had recent coronary stenting
- Previous thromboembolism during interruption of chronic anticoagulation
:) What are the elements of the CHA2DS2-Vasc score?
CHF (1)
HTN (1)
Age >=75 (2)
DM (1)
prior TIA/CVA/thromboembolism (2)
Vascular disease (peripheral artery disease, MI, aortic plaque) (1)
female sex (1)
age 65-74 (1)
:) What are the 3 major risk factors for thromboembolism?
- AF (if CHA2DS2-Vasc 7-9 or if TIA/stroke within 3/12 or if rheumatic valvular heart disease)
- Prosthetic heart valves (mechanical MVR or AVR with additional risk factors (LVEF <=30%, hypercoaguable (infection or cancer surgery), AF, previous thromboembolism) or if stroke or TIA within 6/12)
- recent (within 3/12) venous or arterial thromboembolism or VTE with severe thrombophilia
:) Has the CHA2DS2-Vasc score been prospectively validated in the perioperative setting?
No
:) What dose of vitamin K, given the day before surgery if the INR is >1.5, should reduce the INR to 1.4 on day of surgery? how long via K take (orally vs IV) to work?
1-2.5mg PO
oral 6-10hrs, IV 1-2hrs
:) Why should patients with mechanical valves NOT routinely have high-dose vitamin K given before invasive procedures?
those with mechanical valves since this will delay & reduce the effects of re-anticoagulation with a vitamin K antagonist after the procedure
:) For how long after mitral valve replacement or repair should elective non-cardiac surgery be delayed, where possible?
3 months, since the risk of thromboembolism is highest within that timeframe
:) For how long is VKA therapy generally recommended after placement of bioprostetic MVR or AVR?
3/12 (INR goal 2.5)
:) How to approach a patient with mechanical valve on a VKA having dental extraction, minor derm surgery or anterior eye surgery (minor procedures in which bleeding easily controlled) or PPM/ICD insertion?
can generally continue the VKA for procedure as long as INR not supra therapeutic (based on 2014 AHA/ACC valve guidelines)
:) How to approach a pt at low thromboembolic risk who’s on a VKA?
withhold warfarin 3-5 days
:) What is the anticoagulant regimen for pts with TAVR (bioprosthetic)?
aspirin & clopidogrel for 6/12
:) Which patients with mechanical valves require bridging with UFH or SC LMWH?
Those with mechanical MVR or TVR, mechanical AVR with risk factors or an older generation mechanical AV (such pts will be on warfarin with INR goal 3 & long-term daily aspirin)
:) What are some additional thromboembolic risk factors which would prompt requirement for bridging in a pt with mechanical AVR requiring surgery where INR must be <1.5?
> 1 valve, LVEF <30, AF, previous thromboembolism, hypercoaguable condition (eg. cancer surgery or infection), older generation mechanical valve
:) How to bridge?
Admit the pt (safety of bridging at home hasn’t been established). Cease warfarin 5 days before procedure & commence IV UFH or LMWH, generally 3 days before procedure, when the INR falls below therapeutic range (aim <1.5 for OT).
discontinue LMWH 24hrs before procedure; if BD LMWH is given, omit the evening dose night before. if once-daily, give half the dose the morning of the day before. This is based on biologic half-life of LMWHs of 3-5hrs, the fact that some residual anticoagulant effect of therapeutic LMWH may be present at 24hrs.
discontinue UFH 4-5hrs before procedure (biologic half-life 45mins)
Recommence heparin asap after surgery & continue it until INR in goal therapeutic range for 2 consecutive days.
:) Pros & cons of LMWH vs UFH?
more convenient, may result in more predictable anticoagulation but cannot reverse as rapidly/reliable if severe bleeding occurs
:) Should aspirin be continued during bridging?
Yes, unless risk major bleeding (neurosurgeon, prostate, posterior eye) in which case withhold aspirin 5/7 prep
:) What doses of LMWH given during bridging? or UFH?
1mg/kg LMWH 12-hourly, 18 units/kg/hr UFH adjusted to APTT 1.5-2x control
:) How long stop bridging LMWH or UFH prior to surg?
LMWH 24hrs pre procedure, UFH 4-6 hrs
:) What agent should be used to emergently reverse VKA in pt w mechanical valve?
4-factor PCC or FFP with low-dose oral vitamin K- vit K has slower onset but longer half-life than PCC or FFP so slower to get therapeutic VKA postop if use high-dose vit K
:) How to manage a pt within 3/12 of a VTE?
delay surgery if possible until 3/12 have passed- no clear evidence for when thromboembolic risk declined to baseline. If Emerg surgery, bridging anticoagulation may be used.
:) What’s the risk of recurrent early VTE if not anticoagulated? how about if receive warfarin therapy
50%, declines to 5% after 3/12 warfarin therapy
