Periop Meds

Several medications are reviewed for use & disuse perioperatively.

Anticoagulant & Antiplatelet meds

Anticoagulant & antiplatelet agents risk perioperative bleeding.  Management has always had great complexity, now compounded by numerous agents and situations.  As editor, I have decided that the best thing I can do with this material is direct users to good external sources until a single unified and authoritative source of guidance emerges which I could adapt here (if you know of one, let me know).

External links to web & *app resources

MAQI2 Anticoag Toolkit U-Mich
  
 

iPRO's MAPPP
    
 

ACC's Manage Anticoag
    
   
 
ASRA's Coags (reg-neuraxial)
     

Univ. Michigan's MAQI2 Anticoagulation Toolkit and iPRO's MAPPP (managing anticoag in the periprocedure period) give guidance on all of the medications in all situations (VTE, A-fib, heart valve, CAD, DAPT) in which these meds are used; note VTE is covered only by extending PAUSE trial's a-fib DOAC guidance.  ACC's app only covers A-fib.  ASRA Coags (American Society Regional Anesthesia) covers the unique risks involved in neuraxial and regional anesthesia, and ASRA has no web version.
* directly launching each app above would be desirable, but this is no longer technically possible, sorry.

General principles of periop mgmnt

General principles (students, residents)

My summaries (some old!)

Warfarin & bridging Heparins (2012-2015)
 
Aspirin (2015)
 
Clopidogrel/P2Y12-inhibitors (appx. 2015)
 
DOAC guidance from PAUSE trial

Insulin & Diabetic meds

The ICSI guideline offers the following recommendations for the management of insulins and diabetic medications around surgery:

- individualized diabetes mgmt plans should be formulated prior to surgery so as to avoid glycemic extremes (strong, low)

- long-acting insulins (glargine, NPH, etc.) may be decreased by up to 50% preoperatively (strong, low)

- do not administer oral hypoglycemics or short-acting insulins preoperatively (strong, low)

- Short-acting, sliding scale insulin should be used to treat high blood glucose values in patients holding their normal diabetic medications (strong, low)

- GLP-1 agonists (exenatide, liraglutide) should be held perioperatively (strong, low) as these agents slow GI motility and may further delay GI recovery after surgery

- DPP-4 inhibitors (sitagliptin) can be continued perioperatively, if patient desires (strong, low).  But ICSI adds that since they work on glucose for absorption in the GI tract, the agents are safe but unnecessary since surgical patients are NPO

- SGLT-2 inhibitors (not addressed by ICSI) are the subject of case reports regarding euglycemic DKA.  No guideline yet offers advice, including ADA Diabetes Standards 2020.  Experts and case series reviewers suggest withholding SGLT-2’s 24, 48, even 72 hours before surgery, and not resuming until patient is tolerating full diet.  Pay attention for stronger evidence and guidance.

- Glycemic control should be directed at achieving blood glucose levels between 140-180 mg/dL and not be directed at more intensive goal targets (80-110 mg/dL) (strong, high)

Further ICSI pointers:

- mild hyperglycemia is preferable to hypoglycemia

- long-acting or intermediate insulin may be used to cover basal insulin needs; 50-100% of usual dose is reasonable

- insulin pumps should be continued but only to provide basal insulin coverage

- details of insulin recommendations influenced by insulin sensitivity of patient, timing of procedure, length of procedure, and how long patient will need to be NPO following procedure

ACE inhibitor & ARB

ACC reviews the evidence that ACE's and ARB's can cause transient hypotension but then notes that the same large study showed no actual adverse outcomes.  Thus ACC says:

- continuation of ACE inhibitors or ARBs perioperatively is reasonable (IIa, B)

- if ACE inhibitors or ARBs are held before surgery, it is reasonable to restart as soon as clinically feasible

ICSI points out the same issue of hypotension at induction of anesthesia and acknowledges the question as controversial, without making a recommendation.

Be aware that new evidence may prompt reconsideration.  The VISION trial was a large 4,802 patient international cohort study of 45+ yr. olds.  1,245 patients had their ACE/ARB held 24+ hrs before surg vs. 3,557 with med uninterrupted.  The all-bad-outcomes composite of death-stroke-MI occurred in 12.0% with ACE/ARB held vs. 12.9% when continued, p 0.01, and clinically meaningful intraoperative hypotension occurred for 23.3% off ACE/ARB vs. 28.6% when continued p<0.001 (Roshanov Anesth 2017).

The accompanying editorial recommends that the VISION study findings should prompt a large RCT to settle the issue rather than itself change practice.  Pay attention to how this finding is interpreted locally.

Buprenorphine

Guidance on handling buprenorphine (and buprenorphine/naloxone a.k.a Suboxone) peri- and post-operatively is evolving. Guidelines suggest several options:

1) Continue buprenorphine at the patient's maintenance dose, but break the total daily dose into 3-4 smaller more frequent doses. Although used mainly for its craving/withdrawal-suppression effect of 24+ hours duration, Buprenorphine also has a shorter pain-relieving effect on the order of 6-8 hours duration. Thus for mild-to-moderate pain, buprenorphine itself can be used when dosed more frequently.

2) Continue use of buprenorphine but at doses elevated above the patient's maintenance dose, divided every 6 hours, and then tapered post-operatively in both frequency and quantity back down to the original maintenance dose.

3) Continue buprenorphine at the patient's maintenance dose but add strong full opioid agonists (fentanyl, morphine, hydromorphone) at higher than usual doses to overcome buprenorphine binding and provide necessary post-op pain relief. Patients treated with high dose opioids should have closer monitoring and narcan available. Post-operative doses should be tapered until discontinued, leaving the patient once again on just the buprenorphine maintenance dose.

Earlier guidelines offered additional options of discontinuing buprenorphine altogether in favor of peri & post-op exclusive use of strong opiate agonists. The latest guideline (Kohan, 2021) recommends against such options due to evidence on risks of withdrawal and precipitated withdrawal.

Ideally, management would be coordinated with the patient’s opiate use disorder prescriber and/or hospital pain management experts.

Beta-blocker

ACC says:

- patients chronically on beta-blockers should stay on beta-blockers perioperatively (I, B)

- after surgery use of beta-blocker should be guided by clinical circumstances, regardless of when beta-blocker was started (IIa, B)

- for patients with intermediate- or high-risk myocardial ischemia noted on preop stress testing, it may be reasonable to begin perioperative beta-blockers (IIb, C)

- for patients with 3 or more RCRI risk factors (diabetes, HF, CAD, CKD, CVA), it may be reasonable to begin beta-blockers before surgery (IIb, B)

- for patients with a compelling long-term indication for beta-blocker therapy but no other RCRI risk factors, initiating beta-blockers in the perioperative setting as an approach to reduce perioperative risk is of uncertain benefit (IIb, B)

- for patients in whom beta-blocker therapy is initiated, it may be reasonable to begin perioperative beta-blockers long enough in advance to assess safety and tolerability, preferably more than 1 day before surgery (IIb, B)

- beta-blocker therapy should not be started on the day of surgery (III:H, B)

There is no longer a recommended heart rate titration goal, as evidence is insufficient to guide on this topic. 

What happened to the enthusiasm for perioperative beta-blockade? Several RCT's initially created excitement that periop beta-blockade could protect patients from the risk of myocardial ischemia. But the POISE trial gave untitrated fairly high-dose beta-blockade on the day of surgery, yielding cardiac benefit but stroke harm, which dampened overall enthusiasm. Furthermore, the scientific integrity of some work in this field has been called into question. Thus the ACC recommendations above which were once strong are now more tempered. .

Psychotropics

ESA offers the following guidance:

– Patients chronically treated with TCAs should undergo cardiac eval [details unstated] (D).

– Antidepressant for chronically depressed patients should not be discontinued (B).

– Discontinuation of SSRI perioperatively is not recommended (D).

– Irreversible MAOIs should be discontinued at least 2 weeks prior to anesthesia. In order to avoid relapse of underlying disease, medication should be changed to reversible MAOIs (D).

– The incidence of postoperative confusion is significantly higher in schizophrenic patients if medication was discontinued prior to surgery. Thus, antipsychotic medication should be continued in patients with chronic schizophrenia perioperatively (B).

– Lithium should be discontinued 72 h prior to surgery. It can be restarted if the patient has normal ranges of electrolytes, is hemodynamically stable and able to eat and drink. Blood levels of lithium should be controlled within 1 week (B).

– For minor surgery under local anesthesia, continuation of lithium therapy can be considered (D). 

NSAIDs

When to stop (per ICSI 2014):

Non-COX selective, shorter half-life agents (ibuprofen, indomethacin, etc.): stop 1 day before surgery

Non-COX selective, longer half-life agents (naproxen, sulindac, etc.) stop 3 days before surgery

COX-2 selective agents (celecoxib) stop 2 days before surgery, mainly due to concern for renal effects

With NSAIDs primarily cleared by the kidneys, recommendations above might be adjusted (lengthened) in CKD patients.  But CKD patients should not be taking NSAIDs, so perhaps this proviso won’t arise often.

It is commonly advised that NSAIDs be stopped 7-14 days before surgery.  But this is due to the misconception that NSAIDs inhibit platelets like aspirin.  Aspirin irreversibly inhibits platelets, thus aspirin needs to be stopped long enough prior to surgery for the lifecycle of platelet production to replace old inhibited platelets with new ones.  However, NSAIDs reversibly inhibit platelet function, and thus they only need to be discontinued long enough for roughly 5 half-lives of the agent so that it and it’s platelet inhibitory impact are cleared.  It may not be worth arguing with physicians who demand a lengthy discontinuation period for NSAIDs, but patients should rest assured that inadvertent NSAID use closer to surgery is not an indication to postpone their procedure.

Statins

ACC says:

– patients on statins should continue (I,B)

– perioperative initiation of statin reasonable for all patients having vascular surgery (IIa B)

– perioperative initiation of statin may be considered in patients with clinical indications according to guideline directed medical therapy who are undergoing elevated-risk procedures (IIb, C)

ICSI essentially recommends the same as above.

Alpha-blocker

Systemic a1-antagonists are typically used for BPH and HTN. However, they can complicate cataract surgery by causing intraoperative floppy iris syndrome (IFIS), characterized by sudden intraoperative iris prolapse and pupil constriction. IFIS increases both the difficulty and the risk of cataract surgery. Tamsulosin is associated with higher rates of IFIS than other a-blockers. Few outside of ophthalmology know of this condition.

Stopping the a-blocker does not reduce the risk of IFIS. But having cataract surgery before starting an a-blocker, avoiding Tamsulosin, and certainly alerting eye surgeons to a-blocker use before surgery are all recommended (ASCRS & AAO).

Alpha-2-agonist

ACC reviews the evidence and concludes that perioperative alpha-2 agonists for prevention of cardiac events are not recommended (III:NB, B)

Calcium channel blocker

Several studies done, Diltiazem seems more promising than other agents, but ACC recommends that large scale trials are necessary to define the value of calcium channel blockers perioperative before they can be recommended for use.